Bringing Extinct Species Back to Life | Dr. Beth Shapiro
Guests: Beth Shapiro
Full transcript · Read the full conversation in order, with its original context.
§01Transcript — part 1
So our direwolves, they have 20 edits that we picked and we sequenced genomes from fossil
direwolves. 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 direwolf. You know, I often get the question of why are you thinking about bringing
extinct species back to life? Why aren't you thinking about helping living species not become extinct?
And the answer is, we are doing both.
It is the same tools.
It's the same technology.
It's the same needs.
And when we excite people with the idea of mammoths and dodos and thylacines,
we get more engagement and enthusiasm and investment in developing the technology
that we can use to stop living species from becoming extinct.
Welcome to the Huberman Lab podcast,
where we discuss science and science-based tools for everyday life.
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
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
public. In keeping with that theme, today's episode does include sponsors. And now for my
discussion with Dr. Beth Shapiro. Dr. Beth Shapiro, welcome. Thank you. Long time fan of your work.
Same. Love animals, love stories about animals that aren't around anymore. Heard that you're
going to bring back the woolly mammoths, the dodo bird, and that you might have already done
something to contribute to the proliferation of the black-footed ferret. I'm a big fan of
mustelids of which ferrets are. We're going to talk about all of that today, including the
ethical implications and so on. But I have a very basic question, which is how do you decide
what a species is? Because you have a degree in zoology. I always wanted to get a degree in
zoology. But a few years ago, we got this thing called DNA sequencing. We can look at ancient DNA,
can look at skeletons. People have done that for a long time. And my understanding is that it's
completely revised the understanding of the relationship between different animals and the
number of branches in these phylogenetic trees. So what have we learned that I think people might
appreciate understanding about taxonomy and like, is my dog as a bulldog mutt really the same as a
chihuahua? Are they really the same species? Right. That's a really fascinating way to put it.
And I think the most important thing that most people probably don't think about is that
Biology doesn't care what species you are. Species is a human concept. We have this incredible
proclivity to want to put things into boxes so that we can talk about them, so that we can have
conversations or share stories or share memories. In order to share something, we have to know what
to call it. That's one of the reasons language has been so fundamental to the evolution of our
species and our social structures. So what is a species? Probably when you learned about species
biology class when you were in middle school. You learned about Ernst Mayr's biological species
concept. Kingdom, phylum, order, genus, species, like this kind of thing, clade, you know?
That's the taxonomy, right? So we have Linnaeus came up with this idea of doing taxonomy, right?
So here's an interesting taxonomy story. I've spent a lot of my career working on bison for
unfortunate reasons, probably, or fun reasons or whatever, but a lot of time working on bison.
And bison were called buffalo, right?
We think of American bison as buffalo.
It's the same thing.
It's the same thing.
But bison is the taxonomic name that was given to American buffalo by Carl Linnaeus.
Because when Europeans were going around the world and finding for the first time, Europeans had seen all these different animals.
If they saw a big animal that looked like it would make a good coat, that was called a bouff 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.
That's the Latin name bison, bison, bison.
Bison, bison, bison.
It's almost as humorous as I think it's gorilla, gorilla.
Yes, gorilla, gorilla.
And llama, llama.
That's one of my favorites too.
Love it.
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 at 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.
Which seems like a good place to start.
It's a good place to start.
Because even in my understanding from my fly biologists friends,
is that you can't mate Drosophila with another species of fly and get a fertile offspring.
there's some restriction. And what's wild is that flies and mammals of all sorts seem to know.
Like they actually don't try to mate. In most cases, they don't try to mate
with other species, which is fascinating in its own right.
We might beg to disagree there. I mean, if you've seen your dog tries, your dog probably tries to
mate anything it comes across.
He just hit seven months. I've not seen him hump a single time. He's still intact.
This time I'm keeping my dog intact. We can talk about the reasons for that health reasons. I might
get them a vasectomy. People, we never talk about this, right? You can keep your dog intact and just
give them a vasectomy if you don't want them to breed. Right. Yeah. Right. A guest on this podcast
said that an animal expert from the Karolinska. That makes so much sense. She said, you know,
in Scandinavia, it's actually, she claims, and I believe her, that it's illegal to neuter a male
dog unless there's a health reason. In Scandinavia and Australia, the inverse is true. Of course,
they're upside down, but we'll forgive them for that. But yeah, they need their hormones for
proper brain development.
Right.
And we worry about them running around and breeding.
There is this thing called a vasectomy, which is actually less invasive a procedure than
the full neuter.
Anyway, we don't want to digress too much.
But my dog doesn't try and mate.
I didn't see my previous dog try and mate with cats or even chihuahuas.
Do you think Neanderthals and humans are a different species?
I don't know.
But I want to know if we are all the same species.
This is an edgy topic, right?
If it's somewhat based on nomenclature and if there's enough genetic variation out there,
is it the case that people that we call people are actually divergent enough in terms of their DNA
that two people are not necessarily both homo sapiens, that there's some homo sapiens with an asterisk?
I'm not trying to cast any hierarchy.
They could just be different.
So you're referring to a different species concept, which is the genetic species concept,
where an organism is classified based on some threshold of sequence similarity.
And that is a species concept that is as valid and valuable a species concept
as the biological species concept, which says you can't interbreed.
If you're interested in conserving species,
you might use a geographic species concept that says if you live here,
you're a Florida panther, but if you live in Texas, you're a Texas panther.
We're going to call you different species.
Biology doesn't care about your species concept.
concept is something that you have adopted to have a conversation with another person about a
particular topic. Educate us on this Neanderthal piece. I know this is a topic very close to home,
given that your husband works on these issues and we can, maybe we'll get him on here separately,
but feel free to steal his thunder in any way that you feel. 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, if we start
there with what's going on with Neanderthals, is we now know, based on studying DNA, both from
Neanderthals that used to be alive and a different lineage of human called Denisovan, we call it
this, that was first isolated again by Svante 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 want to call them.
They met groups of Neanderthals and they bred with them.
So if they were a different species, they were violating the biological species concept at this point.
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.
Many questions about this.
First of all, and try not to laugh, the silhouette diagram that we've seen of apes gradually in sort of time sequence working their way to bipedal and upright.
When we see that diagram, is that substantiated by the fossil record?
It is, yes.
We know that the lineage that eventually became us evolved in Africa.
We can trace ancestry back to apes and then to primates or primates and then to apes and then eventually to us.
The fossil record in Africa is very fragmentary. One thing that's been really fun about working in ancient DNA is the field of paleoanthropology 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.
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
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,
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§02Transcript — part 2
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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
point, but to non-genetically similar, I don't want to say identical because they're not twins,
right? So I don't have a language here, forgive me, but you can get breeding across species and
get reproductively viable offspring. That has to be the way this happened, right? It couldn't have
just been through spontaneous mutations that suddenly took animals from quadrupeds to bipeds.
No, this is a very long and slow evolutionary process. It's actually a really good question,
And I think it's an open question in evolutionary biology.
And it's probably different.
Evolution does happen because of random mutations that accumulate in a genome.
And if you think about what might happen if two lineages are isolated from each other for a really long time and in different habitats, say, this lineage is adapting to the habitat that it's in.
Maybe it's, 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 contact with each other?
I think it will really depend on what those mutations that arose over that time was.
It could be that there's a very short evolutionary time, but a mutation has arisen that means the sperm can't fertilize the egg or the egg can't subdivide properly if you have a hybrid ancestry.
Or it could be that nothing really has happened over a really long evolutionary time and admixture can happen.
Humans and Neanderthals diverged somewhere 300,000 to 500,000 years ago.
That's not very long ago in evolutionary time. Brown bears and polar bears diverged about half a million years ago,
and we know that they can readily interbreed and do whenever they overlap in habitat. Yeah.
They're called grolar bears or pizzly bears, depending on which direction. I know they're
terrible names, right? You want a different name for this really cool name. Yeah, especially if
you're a bear. Yeah. 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 a polar bear off the coast
that probably lived more than 100,000 years ago.
And it had ancestry that we see in brown bears everywhere in the world,
suggesting that that bear's ancestors at some point,
or that bear's descendants had hybridized with brown bears,
and that DNA got passed around.
We know that during the last ice age,
there were polar bears that got trapped on the ABC Islands in southeast Alaska.
And when brown bears expanded from the mainland,
they interbred with those polar bears.
And brown bears all alive in North America today have polar bear ancestry that is because of that interbreeding 20,000 years ago or so.
Wow.
Yeah.
So in that case, a half a million years had gone by.
They're really adapted to different habitats, and yet they can interbreed.
But what's most interesting and I think is relevant to your question is that those hybrid bears only ever live and survive as brown bears.
We see no evidence of brown bear DNA getting into polar bears.
And that is, again, because of how evolution has worked.
And it's especially interesting because it only really happens in the direction where the mom is a polar bear and the dad is a brown bear.
Polar bears are induced ovulators.
So the presence of a male will cause them to ovulate.
it caused 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
that we see that have polar bear ancestry are brown bears, not polar bears.
We were working with some polar bear biologists.
We were doing this analysis many years ago,
and their hypothesis was simply that if you have brown bear ancestry,
you don't have perfectly white fur and you cannot successfully hunt seals.
So it is just adaptation that means that that admixture doesn't work, right?
So even though there's no problem with the sperm and egg mixing and the animal is born,
they cannot survive as polar bears.
separate from brown bear in that way.
I'm going to bring up dogs again, but in the back of my mind is a conversation about humans
and this question about different species of prior to Homo sapiens or Homo sapiens and
nearby species having reproductively competent offspring.
So in the dog world, it's well known that the English bulldog, which has a big head,
small hips, is the byproduct of many crossings, but it's basically the bull mastiff and the
pug.
generate an animal with a short snout so it could clamp down for bull baiting, which fortunately is
an illegal sport now, to clamp down and not get shaken off by the bull very easily. The floppy
faces associated with lack of pain receptors. So a bunch of things in the bull mastiff lineage that
they want, but they wanted a low center of gravity. So they took the pug. But when you cross them,
of course, the females can't give birth because the birth canal just doesn't allow for it.
Humans realize this pretty quickly and they learn cesarean section. So I could imagine a situation,
I don't tend to think like this.
Today, I'm imagining a situation where Homo sapiens
and some other non-Homo sapien human-ish species
were having sex, sometimes getting pregnant,
but the babies would always die
because the birth canal and the structure of the pelvis
wasn't quite right to allow the head size through,
which, you know, there are a lot of,
I hear a lot of arguments that, you know,
humans sort of have optimized for just enough space
so that the large brain humans, you know,
we love to talk about how big our brains are, right?
through, but no larger and not much smaller in most cases. One of the reasons that giving birth
is one of the ways that women have died in our evolutionary history. Right. And cesarean sections,
I probably have changed human evolution in that sense, as has aseptic conditions and things like
that. Absolutely. For me, my child was cesarean birth. Right. So I like to think you would have
survived. But I could imagine a mutation that was an adaptive mutation where suddenly this other
species, which maybe had a smaller pelvis, a female could deliver this child live. The mother
survived as well. And then that DNA propagates so that there are now humans, maybe it's been
bred out, but that there are or were humans walking around who are not completely homosapien.
Or is it not possible? I don't know about what's known about hip size or anything like this,
But it is true that humans and our archaic cousins, Neanderthals, interbred, and that people walking around today have Neanderthal DNA.
Two to five percent, you said.
Two to five percent.
What's interesting about that, and it touches a little bit on the adaptation component that you raised, is that I think most people or a lot of people have heard this number.
We have two to five percent Neanderthal DNA.
Less well understood is that it's a different two to five percent.
Like the 2% Neanderthal that is in my genome is different from the 2% or maybe 5% Neanderthal that's in your genome is different than the next person.
So it could be heart, liver, skeleton, and spleen for me, and it could be some other constellation for you.
It 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.
We don't know what happened in the other direction, right?
We see Neanderthal bones and there hasn't really been any evidence of humans admins with Neanderthals.
There has been evidence of hybrids between Neanderthals and Denisovans.
This is really one of the most exciting things that ancient DNA has been able to contribute, I think, to understanding human disease and human medicine and what it means to be human.
Because before we had the Neanderthal genome, if we wanted to know what in our DNA makes us human, we would have to compare all the humans that are alive today with our closest living relative, which is a chimpanzee or a bonobo.
So there's three to five million years of time between when we shared a common ancestor.
And a lot of change happens in three to five million years in your DNA.
And some of it is useful.
Some of it is what makes us human.
And most of it is just not.
It's just change because copying errors during copying cells.
And that's what happens.
That's how we're different.
Every child that's born has about 100 differences compared to their parents because of copying
error in the process of making the sperm and making the eggs that made that kids.
When we got the Neanderthal genome, that 3 million to 5 million year long branch leading to us was shortened to 300,000 to 500,000 years by an order of magnitude.
So now if we want to know what it is that makes us human, we have a much smaller list of mutations or variants that we can look at.
And because we now know that 95%, say, of the Neanderthal genome exists in people today, we've narrowed that list down even further to that other 5%.
What's going on in that 5% of the genome where no living person has Neanderthal DNA?
That is where the stuff that the baby had to have the human version in order for that baby to survive.
That's where we look to see what it is that made us human.
A few years back when 23andMe and these other companies started making genomics in humans easier and more affordable, a lot of guys boast about Neanderthal DNA being vigor genes, whereas women try and downplay the amount of Neanderthal DNA that they have when they get their results.
I found that interesting.
Is there any evidence that the Neanderthal genes are, quote unquote, vigor genes, that they allow for more durability of human, male or female?
It's an interesting question.
look at that 2% to 5% of Neanderthal DNA that we all have, most of it is not anything that is
under selection. So you see it at about 3% frequency or so in different populations.
What is interesting is when a piece of Neanderthal DNA is suddenly much more common in a population
of humans, because that would suggest I got some DNA from my Neanderthal ancestry, and that bit of
DNA suddenly made me more fit. Because I had that bit of Neanderthal DNA, I was able to survive and
have more kids than everybody else. And so it increases in frequency compared to average.
And this has been a really interesting thing to learn when you think about Neanderthal DNA.
There are a couple of things that have come out. There are genes that are common in Latin
American populations that come from Neanderthals that predispose to type 2 diabetes. There is
another gene that I think was, again, in a Latin American population that makes people feel,
I can't remember if it was more pain or less pain, but it did have to do with pain sensation.
And I remember there was a trial of people in Colombia where they got to feel pain in some way.
And there's a Neanderthal gene associated with this.
But most of the really interesting ones have been in immune-related genes.
During the pandemic, one of the first alleles that was discovered to be associated with negative risk or bad outcomes of COVID was a gene that came from Neanderthals.
So it's a Neanderthal-derived gene that was at something like 50% frequency.
So way above the 3% average frequency in Asian populations. And it made people more susceptible to the virus
entering your lungs. Presumably, it only became that high frequency because it was protective
against some other disease that was circulating in the past. But the trade-off of that is that
it, of course, made them more susceptible to COVID. There was another Neanderthal-associated
allele that was actually protective against COVID. So I think our ancestors have been subjected to
different diseases and pandemics and things that have happened throughout life.
And we see the traces of that in ancient DNA.
We can now go into graveyards in Europe
and actually isolate plague from dirt and from bones
from people who died of plague
and look and see how their immune systems and genes
have responded to exposure to things like this.
It's really fascinating.
Wow.
My redhead friends like to claim that they have more Neanderthal
and therefore more vigor and pain resistance.
guessing the study probably said more pain resistance. We have pain experts on here that
verify that indeed, on average, that redheads tend to require more anesthesia on average.
So that tracks. But were Neanderthals, were a lot of them gingers?
Yes. This comes from studying an MC1R, a gene that's associated with the red melanin. Mammoths
as well. They had, I mean, you can see mammoth, you can see mammoth mummies with the actual hair
and you can see that they're kind of, I don't know if it's because they all bleach to red,
some evidence from their genome that they had reddish colored hair.
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? This almost sounds like some eugenics
thing, but that's not why I'm asking. You also see a lot about how true green-eyed people are
quite rare. Was there a time when the population of humans on earth had a lot more green-eyed people?
I think all of the colors, if you look at African populations, mostly it's like me,
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 to mate that has blue eyes.
You really think that it was selected for at the level of mating?
I think probably eye color was sexual selection. I don't know what other benefits blue eyes could
have other than looking very, you know, stoic and cool as you're like trying to hunt down something.
Oh, geneticists are so much fun because they're willing to just go there.
ask you this question later, but I'll ask now because it relates to what we're onto now. You
know, we tend to think of our lives in the time bin of our lives, you know, roughly a hundred years
if we're lucky, right? You know, at this stage of human evolution for about a hundred years,
maybe 80, maybe, you know, if we're fortunate, 90, a hundred. 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
§03Transcript — part 3
everything 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 it could focus on? I'm going to focus at this time
bin, right? It's a, it's an interesting way to live. And I'm just curious how you pick 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 completely? Why not both?
Right. But in terms of just, you know, where to focus, like why bring back things from way back
when, as opposed to, you know, maybe we could name a few species that disappeared in the last 200
years. I'm guessing there are quite a few. Yeah. You know, how do you pick? And when you're making
that decision, what's guiding it at the ethical level? What's guiding it at the practical level?
Like what really are you trying to accomplish? Because the stuff about humans is fun place to
play and put in the backdrop. We'll return to it. But your work's really focused on de-extinction.
And like dinosaurs are one option, woolly mammoths are another. And, you know, just making sure that
we don't lose any species that we've got right now also seems like a very, very important,
indeed noble pursuit. Yes, that's a very complicated set of questions there. I think I'll start with
what is motivating? And I think what's motivating is what drives the selection of the species.
In fact, it's funny, I wrote a book a long time ago now called How to Clone a Mammoth,
and the first chapter was how to pick a species. What are you going to do? How are you going to
choose a species to bring back. And there are technical, ethical, ecological, and social reasons
to pick any of the species that you can. Technical, these are the easiest, right? We can't bring a
dinosaur back to life because we don't have dinosaur DNA. The oldest DNA that we have ever
recovered from a bone is from a mammoth bone. A mammoth bone probably dates to around one to two
million years ago. It's hard to know how old it is in that time range because there's not a really clean way of dating something
within that time range. But it's old. Dinosaurs went extinct more than 66 million years ago. So
that's far outside of where we're going to get recoverable DNA. And that's because the skeletons
just don't... They're fossilized. They've turned into rock, right? There's no shred of DNA left.
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 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. 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 going to be able to recover DNA from any of the fragments that are on Mauritius Island.
And I have tried, like, hundreds of bones from Mauritius.
We have a great dodo genome, but it's from a bird that went to Europe alive on a ship and is part of the collection at the Danish 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 going to do.
You probably should know what caused that species to go extinct in the first place so that you don't bring something back that becomes the first species to be de-extinct and then the first species to be re-extinct.
Or bring back something really nasty that knocks out a bunch of other species.
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.
Could you give me an example of that?
So if you were to bring back woolly mammoths, I'm guessing that's not going to save the Amazon forest, but probably is going to do something useful based on what you just said.
Yeah. So if you think about what large animals, large herbivores do in their ecosystem, they turn the soil by walking around. They knock down things. Elephants knock down trees. Mammoths probably lived places above trees, so that wasn't what they were doing. But they were distributing seeds and nutrients.
Have you heard of Pleistocene Park? This is up in northeastern Siberia. There are these two scientists. It's actually Sergei Zimov, who's a Russian Academy scientist, and his son Nikita. They've been running this park up in northeastern Siberia for a long time.
And they have been really interested in understanding what happens when you restore all of the species that used to live on the tundra to the tundra ecosystem.
And they have bison that they've brought in from Canada and wild horses and several species of deer and muskox.
And they've seen that having the animals on the landscape that they've fenced off actually causes the plants to come back with more ferocity.
animals, they have to eat during the winter. So in order to find food, they scrape the snow off of
the surface of the dirt. In the absence of these animals, the snow stays on the surface and snow
is a very efficient insulator. So it traps the summer heat in that frozen sediment, causes the
sediment to melt faster. And when the plants come back, it's a particular type of plant that can
live in that moist sediment. With the animals, you get a mosaic landscape where there's some parts
that are moist and wet. There are other parts that have been exposed and they're dry and colder,
and you get broader diversity of plants that are coming back where these animals are. So they are
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Okay, so you're picking, you don't have to pick a species, but you got to pick something of, you know, two or three.
Right, right.
I can't say we're going to bring back everything from a given era.
So we did technical, ethical, ecological.
I think another answer is what is going to make an impact, right?
When I joined Colossal, we didn't have a bird program, but I really wanted there to be a bird de-extinction program because 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.
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.
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 and 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 any other bird for the first one?
Cool beak.
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,
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.
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.
It was in Alice in Wonderland.
Most of what we know about the dodo
is from cartoonish drawings of this animal.
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.
You didn't choose to bring back like a 75 foot long python.
Thank goodness.
But there may be virtue in doing that.
There might be.
Although I think there are plenty of pythons in Florida Everglades right now.
I'm not a snake fan.
No disrespect to the snake lovers.
But talk about bird developmental genetics for a second, not to scare anyone away, but hang in there.
A few years ago, I saw something that two female condors can reproduce.
Crazy.
Right?
And this, of course, for-
It actually wasn't two female condors reproducing.
It was one female condor.
One female condor.
Just having an egg all on her own.
Yeah.
And because of the sociopolitical implications, it's got people in what we're in from Northern
California pretty excited.
They were like, okay, we don't need men after all, right?
That was the, that's always, that was the, you know-
That's funny because what I heard was life finds a way.
one female condor who we trust her when she says that she never mated with a male condor
or a female condor, we believe her, was able to reproduce.
My scientific explanation is that meiosis didn't fully separate and she ended up having a fertilized
egg or-
We should explain meiosis.
So the separating of the-
Of the cells during the very early phase when you're making eggs or making sperm.
You're trying to duplicate your cell, but instead of that, you make two versions of
one copy each of your chromosomes. So when normally in normal reproduction, an egg that has one copy
of the set of chromosomes and a sperm that has one copy of the set of chromosomes come together,
they're fertilized. The resulting eventually embryo has two copies, one from mom and one from
dad. In this case, there was no sperm. There was an egg that had both copies, probably because of
a mistake during meiosis. Like they didn't separate out properly and that was able to develop full
term. Was the offspring viable? Yes. What's weird about that, yes. I mean, it's very, very cool and
very clear the way you described it, how that could happen because you need the two sets of
chromosomes. So both sets came from mom in this case and only mom, but in humans where that happens
and it does happen on certain chromosomes, these homozygosity effects, they happen under certain
conditions. Like there are these paternal or maternal imprinted conditions like Prader-Willi
syndrome where paternal DNA gets kicked off and you have two copies from mom, which doesn't sound
like a bad thing unless there are things on the paternal chromosome that are required for
development. And the reverse also happens, like in Angelman syndrome, I think it is,
that all the genes, everyone healthy walking around out there, you and me, and have genes
that only came from our mom and only from dad. And so if you get two copies from mom of a chromosome
or two copies from dad, you end up with like pretty severe deficits in brain development and
other things. In some things. And you also could never be a boy because the one gene that turns on
that cascade of male development is called SRY. It's on the Y chromosome. So without that gene,
you would never be a boy. You would always be a girl. Trisomies where you get two copies from mom
and one copy from dad, those can also be bad because of different levels of gene expression.
Is Down syndrome.
Trisomy 21.
Down syndrome is trisomy 21.
And there are a few other trisomies that are compatible with life.
Trisomy 21 is the most common one because those people can live, obviously, with some challenges, additional challenges because it's an additional chromosome, but they can live full lives till relatively middle age.
Is there a way of looking back at the ancient DNA of different species and knowing if they reproduce the way we imagine they reproduce?
I'm not talking about the actual verb sex.
I'm talking about the, like somehow sperm and egg met, but, or there was something more like the condor.
You were just describing where the females were able to reproduce through these kind of unusual meiotic events.
I think because, well, obviously sex has evolved a bunch of different times on the animal or the tree of life, right?
And so different ways of doing sex have evolved.
So we have this XY process where the males are what we call the heterogametic sex.
And females have two X's and they don't have a Y.
But birds do it differently.
They have the WZ.
And it's the females that have the two different chromosomes, the males that don't.
And then there are alligators and crocodiles.
And they do sex determination based on the temperature at which the egg is sitting during a very critical period during development.
Yeah, there are communities online I've learned that actually believe this kind of stuff for humans.
§04Transcript — part 4
There are all these theories about how to get a male or a female offspring based on position of intercourse, temperature, location, food.
None of it beats chance.
Right.
Or if you really want ICSI, right, which is the process by which you take an egg and you take a particular sperm that you know whether it's carrying the Y chromosome or not and use that to fertilize the egg.
Can you actually determine the XX or XY of the sperm?
They can do that now?
You can do it.
You can select, so you can do true sexual selection.
Because the Y chromosome is teeny, teeny tiny compared to the X.
And so you can centrifuge them.
And because they're smaller, they sort out.
Got it.
So you can spin sperm around.
Don't do this at home.
And then based on how the different things of different weights basically spin out to different depths.
And so you can bias the likelihood that you'll get a XY carrying sperm or an XX carrying sperm.
Or you can use cloning like we are at Colossal.
And like we're thinking about in synthetic biology where you actually know the sex
because you're starting with an actual somatic cell, a tissue cell of that animal instead of using a sperm and an egg.
So let's 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 create more cells that become the embryo, right?
And so in these other species, I guess you know how many chromosomes there are.
And I must use the woolly mammoth because it's a fun one.
And birds are complicated.
As a developmental neurobiologist in my past, the bird stuff gets tricky, reptile stuff.
Birds are tricky.
They're really tricky.
Some birds are trickier than others.
I did not know until I joined Colossal that there are some birds that have what's called a germline restricted chromosome,
which doesn't exist in any of their cells except for the germline.
Germline or the sperm and eggs.
And it comes into being this chromosome just in the germline, and then it disappears.
Wow.
I know. Biology is amazing.
But birds have these mini microchromosomes that are a pain to assemble.
And if you're sequencing DNA from 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 like a tweezers or anything like that.
Yeah, birds are really cool animals.
They, from reproductive biology standpoint, it's tricky.
So with the woolly mammoth was a mammal.
Yes.
Okay.
And you know that because, I mean, people can say, well, duh, because people normally
think, oh, it has fur and must be a mammal.
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?
Using its genome.
So we've been able to sequence whole genome sequences, high quality whole genome sequences
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.
Okay. So if you get 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.
That's the epigenome.
Right. But the menu is there.
The menu is there.
Are you growing up DNA in a laboratory?
No.
That is the mammoth sequence?
So this is what comes, I think, from Jurassic Park. And this is why I love talking about Jurassic Park, because I think everybody has an idea of how we're doing this because they saw Jurassic Park or they've thought about this movie. And what happened in Jurassic Park? And I should just say, it was not a documentary. So let's not get carried away here. Right? Okay.
What happened in Jurassic Park was scientists found mosquitoes preserved in amber.
They stuck a needle into those mosquitoes, preserved an animal.
They sucked out a bit of stuff that happened to be blood, and it had dinosaur DNA.
And then they had the little dancing DNA thing tells you about how they piece it together,
and you can see the little pieces of dinosaur DNA lining up next to each other.
And then there's holes and they fill in those holes with frog DNA, which was a weird choice even at the time because we already knew that birds are dinosaurs, right?
So why they pick frogs?
I don't know.
But anyway, they filled in.
Maybe they talked to Richard Harland at Berkeley or something.
That's another biology joke.
Look it up.
But that's not actually how we're doing this.
What we're doing is somehow easier than that because we know that Asian elephants are the closest living relative of mammoths.
We also can, by sequencing a bunch of Asian elephant DNA and sequencing a bunch of mammoth DNA,
we can see that they already have almost exactly the same genome sequence.
How similar?
They're about 99% similar.
It depends on how you calculate the percentage and things like that.
As a point of reference, how similar are we to the chimpanzees in terms of percentage similarity of DNA?
In that counting, it's about the same.
But some people might say, we don't look at anything like chimpanzees.
Well.
Sounds like so similar, like you're going to get the same thing.
Yeah, well, there have been people calculate this in lots of different ways.
There's some statistic online that we're 85% the same as a banana or something like that.
Like a lot of our DNA is, I don't know if that's true, right?
Is the goal to recreate the ancient mammoth or is it to create a pseudo hybrid of the ancient mammoth?
The goal is to think about a mammoth in terms of what it does and what it looks like.
And this gets back to this idea that you brought up in the beginning about a species concept.
You know, this is one of the most common things that we hear. If you are going by a strictly genetic species concept where you're
saying that a species, an organism is classified just by some threshold of similarity, sequence
similarity to something else, that's the only way you can call it that thing. That isn't what we're
doing in de-extinction. That's not what anyone doing synthetic biology is thinking about when
they're designing or engineering things to solve problems, engineering animals or engineering
plants to solve problems that we have in the future. The genetic species concept is an idea
that was proposed to classify organisms that evolve over a very long evolutionary bifurcating
phylogenetic tree process where accumulation of changes is over many generations over a long time.
Our mammoths, our dire wolves are not created by that process. And so that concept really doesn't
apply. I think that's where a lot of the disinformation comes. I'm going to just push
back a little bit on this because what I don't want is for this sort of definitional gatekeeping
to really take over and become the whole story. It's important. It's a question, but it's a
narrow one. And I think it crowds out the real discussion about what it is that we're doing,
how the technologies that we're developing can be applied to ecosystem health, to help stop species
from becoming extinct, even as synthetic biology for human medicine. So we're not trying to make
something that is identical to a particular individual that used to be alive. Our mammoths
are millions of letters of DNA code different from each other. So even which one to use would
be an open question. Instead, what we're doing is focusing on where all of those mammoths are the
same as each other, but different from elephants and thinking that those places, like we were talking about with humans,
Those are the places that are important to make a mammoth a mammoth.
And that is where I'm going to focus my energy in bringing back a mammoth, which will be an elephant that is capable of living in the habitats that a mammoth lived in.
Mammoths will have to live in habitats that exist today and tomorrow.
So the mammoths will have to be genetically capable of living with the pathogens and the microbes and the food sources and the microbiome that the elephants that will birth them can survive in today.
When you mentioned species nomenclature gatekeeping, I have a feeling this is based on the publicity around the dire wolf.
Yes.
Okay.
I like to just address things very directly.
I want to be very clear.
I'm not arguing for species gatekeeping here.
That's not what I do.
After all.
It's not even that.
It's that.
It's 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 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 want to call it a dire wolf, just don't.
Right. It's like, I think like, like all things media and Hollywood, you know, 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.
But didn't we just say that these dinosaurs were some dinosaur DNA and a whole bunch of frog DNA?
Nobody looks at them and goes, no, they're not a dinosaur.
Well, you're a scientist and I am too.
Actually, it's funny that you mentioned 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 to the barista in Brooklyn, you know, and people like to
bridge those concepts and they think, oh, that's so cool.
as we say, but he was rolling his eyes. He's like, okay, that's not how these things work.
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? And my experience in doing what I do is that the public,
if they just have the knowledge in hand and the way you described it, great. So-
So our direwolves, they have 20 edits that we picked and we sequenced genomes from
fossil direwolves. 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 direwolf. If it looks like a direwolf and it's able to fill the niche of a
direwolf, I'm happy to call it a direwolf. So the direwolf was a very interesting choice.
Clearly you were successful in creating this animal. It sounds like you were very intentional
and picking which genes.
It wasn't like, oh, we're going to take a couple of genes from the dire wolf and throw
them into this other wolf and create what we call is the dire wolf.
If I were to look at the dire wolf and you said a gray wolf?
Yes.
Side by side, is the dire wolf larger?
They are.
On average at the same age.
Are there any other features that are visibly different or the other features more adaptive
in terms of gut and ability to live in certain environments and this kind of thing?
They're muscular.
The fur is longer and more full, and it's also light colored.
I think it's an important thing to understand about how we're selecting these because we are very deliberate about what we're doing.
And it's both because we want to, with some fidelity, bring back these extinct traits so that the animals can eventually be released.
Now, we're not planning on rewilding dire wolves.
We will study the animals and learn about the effect of their genes on their lifespan.
Yeah, I'm sorry.
But the other animals, the ultimate goal is to eventually have populations of free living animals that local people are stewarding as they might like to.
And so we want to understand how healthy they are, how they're going to interact with the habitat that's there.
And we want to make sure that because we, with synthetic biology, have the power to engineer them in a very deliberate way, that we can do that in a way that's safe.
So the hair color is a really interesting example of this and the strategy that we use.
So when we sequenced the genomes of the fossil direwolves, we found that they both had variants, the same variants, in two genes that would have made them have light colored coats.
But in living gray wolves and dogs,
variants in those genes,
not the same ones that we saw in dire wolves,
but close enough to where we would need to do the edits
that you have some concern
that you would have bystander edits
that might cause a problem,
can lead to oculocutaneous albinism.
So blindness or deafness in these dogs.
And we decided that
because we're not changing the whole genome,
they have to be safe on a gray wolf genetic background.
we wouldn't make the trait that way.
It just wasn't passing the bar of animal welfare safety.
And so instead we brought back the dire wolf light colored coat using different edits that we know are safe in a gray wolf background
because there are light colored domestic dogs and gray wolves.
So we use the edits that we know are safe because they exist in living dogs.
Oh, that's cool.
So we were able to engineer using all the tools of synthetic biology,
this light colored coat that is the dire wolf light colored coat,
is safe. And this is the way that we think about all of our projects. We have to take an Asian
§05Transcript — part 5
elephant and turn it into a woolly animal. That trait requires changing not just the structure of
the hair, but of the skin itself. We have to make room for more follicles, sebaceous glands,
different approaches to be able to support that woolly coat, right? And we need to be able to do
that in a way that results in a healthy animal, because these are very long-lived animals,
It takes 22 months for gestation.
They reach sexual maturity at 14, and it's a lot of work.
So how many dire wolves are walking around right now in some location?
Right now there is Romulus and Remus, and they're almost two years old.
Male and female or male-male?
Romulus and Remus are boys, and Khaleesi is a girl.
She is about 18 months old or so.
Is the intention to mate them?
No, they're too closely related.
We're stopping them using hormones, so rather than castration.
But they live together.
She was reared by herself.
The boys had each other and she had just her.
So she's a little bit on the like, I mean, you would never look at these animals and say, this is the way a wild wolf behaved.
They were hand reared, right?
But she's a little bit on the specially goofy side.
But she's the best.
She's adorable.
Do you feel safe interacting with them?
Oh, no.
We have interacted with them.
But the people who work with them a lot that they know feel safe interacting with them.
But as they got older, it was very clear that they're wild animals.
These are not domestic dogs.
Remus is a little bit less skittish than Romulus.
He will eventually, if you sit in the middle of where they are, he will eventually kind of sniff around and maybe come near you.
Romulus wants nothing to do with you, which is funny because they're identical twins, but they're slightly different interacting with people.
But it's very clear that these are wild.
They're also huge, right?
Yeah, how big are they?
I don't have the latest measurements on how big they are.
And of course, it's seasonal for all these different things.
But I know that they were, at some point, they were at least like 120 pounds, which is big for a gray wolf.
Yeah, that's a big animal.
So everything you just said about these dire wolves, would you also say about gray wolves?
Like you wouldn't want to be alone with one.
Some can be skittish.
Some can be calm.
You know, I have good friends who are somebody you should think about having on.
Actually, if you're interested in dog behavior and what we've learned about domestic dogs, I know you have a dog and it's very exciting.
Elinor Karlsson is at the Broad Institute and at UMass.
And she's done a lot of work with wolf-dog hybrids and then also with domestic dogs and trying to map genes to behavior and all these things.
showed that breed stereotypes are just not real, that you really can't map genes to behavior,
except for chihuahuas. They're just terrible. I'm just kidding.
No, it's okay. We had Cesar Millan on the podcast. He'll be the first to say that in
almost every decade in the United States, there was the demonized dog breed. It was actually
German Shepherds post-World War II. Then it was Dobermans, same reason. Then it was the Bulldog,
the English Bulldog, which having had English Bulldog is hilarious to me.
I went to Georgia, so that's never going to be my least favorite dog.
And now it's pit bulls, right?
And statistically, actually, I think most bites come from chow.
At least my uncle, who's a vet, tells me that.
But chow owners, I met some nice chows.
The blue tongue is pretty cool.
And that's a particular variant.
You can imagine, yeah, there's color is one of the things that's best understood, I think,
especially in domestic dogs.
There's so many genomes and all these things have been mapped.
And that's part of what we have to do in all these cases is how do we figure out what it
is that causes the thylacine to have the stripes that it has or causes the particular types of hair development that happen on a woolly mammoth.
These are all huge open problems in evolutionary biology that I get to work on every day in my job.
Clearly you have the right job.
So you have these three dire wolves.
They're not mating.
Is the plan to make more of them, to mate them?
What's the ultimate goal and intermediate goal?
We will have another pack so that hopefully they will all be born more of them at the same time.
So 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.
This is really the next rational, logical step in any de-extinction project.
I often hear rumors and what are you doing?
You're just going to take, get an elephant and make a mammoth and just release it into Alaska.
No. First of all, no, because it's going to be so hard to make that first mammoth that I'm going to want to make sure that it is safe and cared for and has access to all.
Well, this is the Jurassic Park thing again. It's that they break out. Right.
But also, you know, you can't do that. We exist in the regulatory environment of anywhere that these animals are.
It's not that we're some crazy scientists on an island like in Jurassic Park.
We work here. We have IACUC protocols. And 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.
And the 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. It took a decade, and a billion trees died.
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 to my
residence.
Do you know about this?
No, but I'm scared.
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 container, just thin, an envelope.
And I had a little note, and it said, free seeds for gardening.
And I was like, this is really odd.
And I started 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 is 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.
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 grows.
And this is how you can decimate important populations of trees and plants.
It was the first time I really thought about vegetation on vegetation warfare.
Is that actually what was happening?
Is it 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 dog park.
I wouldn't put the wolves out because 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 think people, we as a lineage, have been messing with the evolution of the stuff around us for as long as we've existed, right?
Initially, just by driving things extinct.
Not deliberately, right?
Just like maybe this wasn't a deliberate attempt to have some plants that would outcompete other things.
No, maybe they like those particular flowers, yeah.
But we did.
And we changed ecosystems by going into them and getting rid of all the largest animals that were there.
Or the trappers.
Because we were hunting them.
you know, our ancestors in, you know, 50,000 years ago in Australia, 30,000 years ago in Asia.
And then we domesticated things and now we conserve things. And when people think about
conservation, a lot of people have this idea that it's this beautiful thing where you're just
leaving everything alone. But that's not what we're doing. We are deciding how many of them
get to live, what they get to eat. We vaccinate them. We protect them from predators. We,
I'm not saying that is bad, but I think it's naive to say that it's not us determining what the future of these animals are.
And we've also been moving stuff around forever.
Like we have English birds all over the place here and in New Zealand that were brought by people because they liked them, right?
They liked them where they were.
And I think it's a mistake to imagine that the only good ecosystem is the one that you know right now, because you're claiming a particular slice of history as the thing that is better than everything else.
And I think it's more important to think in terms of robustness.
And you said, go back to the beginning, you said something about how when we have multiple things happening, multiple species in an ecosystem that are all doing different things, you end up with more biodiversity and richer environments.
When there's an overlap in ecological niches, there's some redundancy there.
And that redundancy is really good for that ecosystem because it means that bad stuff can happen and it can weather that bad stuff.
So maybe we shouldn't always think in terms of bringing in something new is bad.
I should have planted the seeds.
No, I'm totally on board with what you're saying.
I don't mean to plant the seeds.
No, no, no, no.
I'm totally on board with what you're saying.
It touches on an important theme that we've certainly never discussed on this podcast,
but it's very relevant to today's discussion and that people should think about,
which is, you know, who gets to decide?
It's interesting because there's both a kind of like massive ego inserted into the notion
that like we know best about everything, 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,
was better in the past is because a most people never experienced that they have no concept i
think there's a great book that i had to read years ago called uh the good old days they were
terrible but we hear the good old days 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 dark side of that right but the other one is that
we don't have a window into the future right 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 Anacapa Island and Santa Rosa Island and all these islands 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 a lot of tourists
walking around out there. We want to protect that. But humans brought those out. But the fact that it
was Native Americans and it was some time ago leads to our percept like it was good, right?
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.
Right.
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 they are serving other populations of animals and plants.
There's new interactions that are benevolent interactions that are pro-evolution as opposed to devolution.
think the challenge for people is we don't know what that looks like. And it feels like 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 when you're thinking about what you do.
I'm thinking in terms of helping ecosystems to become more resilient. 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 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
declared as one of our de-extinction targets.
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?
Yeah, this came up on a few podcasts ago because we had Jared Rutter,
who's another Hughes biologist, or some mitochondria.
We're talking about there are no transmissible cancers,
but these Tasmanian devils have wound-induced cancer-like problems.
So they fight, they scratch each other up, they get cancers,
and that population is suffering as a consequence.
And they're so closely related to each other that they can pass them between each other.
Oh, so it's the genetic similarity that allows that to happen.
§06Transcript — part 6
The point is that I, yes, this is terrible, but if we had had the top predators,
those sick individuals would have been weeded out of that population,
and we might not have this problem.
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. It is the
same tools. It's the same technology. It's the same needs. And when we excite people with the
idea of mammoths and dodos and thylacines, we get more engagement and enthusiasm and investment
in developing the technology that we can use to stop living species from becoming extinct.
There's a really great story. Our Colossal Australia partners have been working on a
project to try to stop the northern quoll from becoming extinct. Have you ever heard of this guy?
I'm familiar with the quoll. Most people won't.
It's Q-U-O-L-L. So it's a little guy. They're adorable little.
They're super cute.
carnivorous marsupials, and they eat amphibians. And in Australia, there is an introduced amphibian
called a cane toad that is toxic. It's toxic to dogs. When dogs eat them, they die. It's toxic
to everything. When a quoll eats a cane toad, it dies. And that's terrible. And there is a very
strong chance in the next few decades that northern quoll is going to become extinct.
However, there is a synthetic biology solution to this, and it's one that has actually already been made, right?
There are mammals that eat toxic toads that live on the other side of the planet, even that eat cane toads, right?
And they have a single letter change that changes one amino acid in one gene that allows them to eat that toxic cane toad and not die.
Our Australia, Colossal Australia partners, have made those changes in a quoll.
And when you measure in a dish the ability of that toxin to break down the cane toad, that single letter change to that quoll's genome could allow that quoll not only to avoid becoming extinct, but to eat cane toads, which currently nothing really can in Australia.
So now we can see the real benefit of this massive comparative biology framework.
I know which gene it is that I need to change.
The stack that allows us to develop the tools to be able to make that change, just that change,
and then show that that's the only change that's there.
You've made what you wanted to do.
And then put that in a living animal can stop a species from becoming extinct.
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membership. Again, that's functionhealth.com slash Huberman. As someone who does a lot of
public science, health, education interaction, there are a couple of things that get the public
really worried and that they need reassurance on. Honestly, I think it dates back to the pandemic.
There's a lot of distrust about scientists. There is this belief that some scientists
are only concerned with themselves.
It's an important myth, in my opinion,
to dispel the idea that most scientists
are not 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 they're not so careerist
that they're willing to overlook that.
Independent of the IRB boards and the thing,
the constraints that force them to do that.
But that is the era we're living in, right?
So I think that some people think more now
Scientists are like doing stuff because 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 scared.
But I totally agree with what you're saying.
And I want to talk about two species to try and highlight this and how it can be done
right.
Because I think it's clear that you're trying to do this right.
Which means for the best possible outcomes for humans and other species.
And the first are mosquitoes.
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 it turns out bugs find mates and find things to suck blood from and et cetera by odors and pheromones, but odors.
And so there was this idea, oh, mosquitoes have malaria.
This wasn't Leslie's idea, but it was like, mosquitoes have malaria.
Let's just get rid of all the mosquitoes.
And the biologists were like, no, you can't do that because then the birds are going to suffer because they eat the mosquitoes and on and on and on.
I mean, this stuff can really domino.
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 in half of them, right?
There were these ideas just kind of thrown out there that with genetics, you can do that.
release a few of these little suckers into the wild, then 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 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 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? Maybe the mosquito
would be, I hope, a simple example of this. Mosquitoes are a hard one. And I think that
they do cause a lot of death and disease, but not all mosquitoes. So the 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. 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 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 I've spent a lot of time in my life.
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.
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 synthetic drive into the wild.
And then it passes on to the next generation.
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.
Anything that breaks a gene drive and lets something reproduce is going to be favored in a population, right?
So gene drives are going to 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.
You talk about your plants that you got.
In this part of the world, there's cheatgrass everywhere.
And it's highly flammable.
And it grows alongside the rose.
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 cheatgrass for a few generations. Do you think this is one of the reasons there's so many
fires? They're very flammable and they also don't have very deep roots. So in California,
it's very dry, right? 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
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 because it causes
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
system. 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
cryptorchidism. Their testicles didn't descend and they were going to become extinct. This was an
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, sometimes to good ends and sometimes to bad ends. 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 biodiverse than the present.
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.
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 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.
Right.
People need to hear from a group, including the dissenters in that group, and why they
arrived at a particular decision.
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 to talk about what the future might look like well before we have a thylacine to be able to release anywhere.
Our MOA project is led by the Naitahu Research Center 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, it's their decision.
in consultation with other people who will be impacted by this.
And I think that's really important.
§07Transcript — part 7
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 even get yelled at for this.
Why is Colossal always talking about what Colossal is doing?
Well, would you rather we not tell you?
I mean, I think the education piece is the critical piece.
I think it's great that the colossal is doing this.
I mean, it is true.
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 are like, wow, I can't believe you learn from a bone and actually use the tools of synthetic biology to engineer extinct traits into a living animal.
And now you have living dire wolves, right?
And there were people who were scared of it and people who loved it.
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.
And they were talking about it as if they had some agency in the world that they were inheriting.
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 direwolves 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. As long as we're wading into deep water here,
Let's talk about the really deep water, which is humans.
Okay.
So we have this thing called IVF, where people can make embryos and select what are deemed at this point healthy versus unhealthy.
So people are doing genetic selection in humans 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 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.
One story is that they did it for benevolent reasons to prevent these babies from getting HIV from either an infected parent or to just protect them against HIV.
The father was HIV positive.
The other story that was running in parallel was that this modification might have some impact on hippocampal or other brain circuit function that might make them hyperintelligent in one dimension.
So this was kind of more of like a eugenics experiment.
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 going to win a Nobel Prize and be celebrated or was going to be put in prison.
Yeah, I remember this.
It was Antonio Regalado broke the story about a week before the big CRISPR conference.
There were these emails that suddenly came out.
And it was very clear, like people were kind of tap dancing around this guy.
Like, what's going to 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?
He's like, he's blacklisted.
It turns out it was the latter, right?
And the Chinese government said, yeah, we're going to shut down his lab.
He's going to 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 this was so interesting, right?
Because since then, there's been no fewer than four major companies launched for deep
sequencing of embryos, 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 going to have the
highest IQ and which of them is going to be tallest and which of them is going to be this
and which one and that.
And so some of these companies are geared towards ruling out disease.
Right.
Others are geared towards trying to optimize for best possible outcome.
Right.
Now, this gets people riled up because it's very expensive at this point.
So that has other implications.
Right.
And it's easy to say, oh, well, that's like eugenics.
But when people select who, assuming they do it voluntarily, who to have children with, they're selecting on the basis
of a number of features, some physical, some emotional, some resource related, some cognitive,
you know. And so there's a lot of this happening, happens in the animal kingdom. And in humans,
it's happening now at the level of genetic sequencing. And I think we're headed for
big discussions about ethics, about changing quote unquote ecosystems through genetic selection of
it. It's happening. There's a really fascinating story that comes partly out of ancient human DNA
literature and speaks directly to this, this idea that I think we feel uncomfortable with things.
We feel comfortable with new technologies initially because there's kind of this reptile
brain thing going on where first we have to decide if we're scared of it before we can decide if we're
curious of something, right? So there's initial pushback there. But we are doing, as you say,
genetic selection on humans by choosing our mates. And it makes us uncomfortable even to think about
that. But here is a relatively benign example to show that that's true. And it has to do with human
height, right? So we know, unlike IQ, which is very difficult to pin down which bits of your
genome mean IQ, and IQ as measured by what, and what are you at? And it's different in different cultures, and so that's hard.
But height is relatively easy, and we know that it's heritable.
So we know that there's bits in your DNA that can mean that you're tall or short.
I'm five feet tall, so I didn't get any of the tall genes, right?
I'm little.
But we know now, by looking at the ancient human DNA, that in Europe, at least, where
there's a lot of very tall people in Northern Europe, right?
The Dutch are extremely tall.
I remember going to the Netherlands and imagining that I was going to be like speciating there,
where I would be walking in between people as they were above me, you know?
Like driving a tiny car with a lot of big trucks on the highways.
Anyway, that's kind of what I feel like when I walk around the Netherlands.
The Dutch are very tall.
Very kind, but very tall.
Very tall.
But we know that a lot of these genes were first introduced into Europe with the steppe
people at about 4,700 years ago at the Yamnaya, and that originally they were migrating.
And for a long time, we thought that people were just getting taller because of environment.
They were learning more about health.
They're learning more about what they should eat.
And yes, there is some true to that.
But height in Northern Europe has kind of plateaued now.
And people have reached what seems to be the tallest you can be with this set of genes that exist in people today.
But it is there.
It's in Northern Europe.
It's not in other parts of the world, right?
And so there is human genetic selection for a trait that we can visibly see that makes people look different from each other.
That isn't because somebody's picking an embryo and a sperm in a dish.
So we would be naive to imagine that it doesn't happen, that it hasn't happened throughout our evolutionary history, or that we can control it.
But I think what offends us about it, this innate reptilian brain part of us, is that while we don't care that a chihuahua and a boxer, we pick, we engineer to have different traits because they have different roles in the society because we have created the roles for them in society.
We created them.
They were once gray wolves.
We like to think of people as not having niches to fill, as having some freedom of choice to be able to pick what they want to do and what they want to be.
And this idea that one generation might do something to take that away from the next generation just sits really uncomfortably with us.
It's wonderful that you're doing public education on these things because I think people really need to understand that there are well-meaning scientists who are not just trying to figure out what would happen if.
that it's clear that there are going to be more things like this, right? And so we have to navigate
forward with that. Similar to AI, it's not going anywhere, just like smartphones aren't going
anywhere. And the question is, what is the best use of this, the safest uses? And where can it
evolve our thinking in our lives in really unforeseen ways, unforeseen positive ways?
We're really only just beginning to see this. I mean, you know, the story of baby KJ, the first
child who was cured of a genetic disease using the tools of synthetic biology. This was a child
that was born with a urea cycle deficiency. His blood was building up in ammonia. And because
people, scientists, had done a ton of research on this particular condition and really understood a
lot of what was happening, they were able to identify the cause of this genetic disease.
And then it was a collaboration between academic, industry, NIH, the Children's Hospital Philadelphia
This huge collaboration came together, took six months, designed a base editor, CRISPR base editor, to target his particular cells, come up with a delivery mechanism to get it into his liver, do all of the testing that you need to do to make sure that it's safe, and then give him a CRISPR medicine, a bespoke CRISPR medicine as a six-month-old kid three times, and he is cured of this disease and will live a normal life.
Amazing.
And no one accuses those doctors of playing God.
Right. That's what's so funny. I mean, here, I guess we're sort of exploring in the background,
like what establishes the line?
How is that not playing God in the same way that anything is playing God? I think we play God
every day. And in Judaism, there's actually the idea that you're supposed to take care of the
natural world out there. So you're actually playing human in this case, instead of playing
God when you're using the tools available to you to actually make the world and the people around
you better and healthier. When we took a gray wolf and decided we were going to let its puppies live
in our campsite as hunter-gatherers 30,000 years ago, we were making a decision that impacted
another species. As we took teosinte and turned it into corn, every decision that we make about
which populations of species to protect and which not to protect, to decide to allow quolls to have
this genetic modification so they can survive in the habitat that we changed by introducing cane
toads. These are all decisions we make that fall into that category of exerting human influence on
the world. But the world today is a human world. And the species that live today and thrive today
are those that have figured out how best to do that in the niches that we have created for it.
And we need to just deal with that and get better at it. Use the tools at our disposal.
Can I ask you about ferrets?
You can.
And I also want to 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 we're going to 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 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 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 because they're
cute. And my understanding is that it was one ferret, Scarface, who sired like 300 litters
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 male siring all these litters and so you get a bunch of kits and they're mating.
But 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.
And then if you have most people are dominant alleles where you only need one copy, okay, that's a separate matter.
But with normally many mutations, you need two copies, recessive alleles.
But if you get genes that are very similar between brother and sister, you're likely to have two recessive alleles and you get bad mutations.
And you can get deformities and sterilities and low IQ.
It's a very interesting thing that throughout all species, inbreeding is bad.
To a point, 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.
And they have almost identical genomes.
They have almost no genetic diversity, and they are perfectly healthy.
Wow.
I don't know if something happened to that habitat, if they wouldn't be able to survive,
because there's no diversity.
If a disease came in, they would all be susceptible rather than some versus not.
And that's a very protected region.
I know that because my college girlfriend was an environmental studies major, and they used to go out there, and it's very protective.
You can't just, like, take a boat and, like, stomp around those islands.
But it's fascinating.
It is fascinating.
It's fascinating.
It is fascinating.
But in general, my understanding is that reading with close relatives is really bad, certainly for humans, which is why in Iceland and Scandinavia, there's these incredible genetic records dating back to when there were fewer foreign opportunities to mate with foreigners, right?
Yes.
We're going to be blunt about it.
deal with these black-footed ferrets because it's an example of this dynamic tension between
trying to reestablish a population and wanting enough genetic diversity.
Yeah. And it's also a great example of how we can use multiple tools that we have for genetic
rescue simultaneously to help a species. I should say that the black-footed ferret project is not
something that I was personally involved with. This is a project that's been a collaboration
of U.S. Fish and Wildlife and the San Diego Frozen Zoo and Revive and Restore, which is a
nonprofit conservation organization. I was on their board for a long time. And they're doing
really fun work. But the story is interesting. The story is that the prairie dogs, which black-footed
ferrets eat, were a real pain in the butt for farmers. And so they wanted to get rid of prairie
dogs. And so they set out all these ways of just trying to kill a whole bunch of prairie dogs. And
it killed a couple of prairie dogs, but it killed almost all of the black-footed ferrets instead.
§08Transcript — part 8
And so we ended up with a situation where black-footed ferrets were nearly extinct in the wild. People brought them
into captivity, but they could not figure out how to get them to breed in captivity. And eventually,
the last captive animal died, and then the last wild animal died, and they thought the species
was extinct. It was actually on the, I think it's the class of 1966, the first list of endangered
species when the Endangered Species Act first passed, black-footed ferret was. But then,
like a decade later, Shep, the family dog of a family that lived outside of Matitsi, Wyoming,
killed a black-footed ferret while it was out one night.
And the story is that the family took it in to a taxidermist,
and they were like, we want this because it's kind of cool.
Like, what is this?
And the dude was like, I'll be back.
And he went back and called somebody and was like,
I think we have this extinct species here.
And it was proven that it was a black-footed ferret.
So there was a population that persisted around Matitsi, Wyoming.
People started studying this population again,
And they went and they collected a whole bunch more individuals, brought them into captive breeding and knew more about this.
It was a real international push to figure out how to make these animals breed in captivity.
But then they noticed that the animals in the wild started to get sick.
And in a last ditch effort to save them, they went and collected every individual that they could find in the wild.
And I believe one of them was Scarface, who is the one that eventually like bred with everybody and ended up having a bunch of diversity.
Scarface, he had a scar on his little black footed ferret.
are so cute. I recommend everyone who's hearing this, look them up. Don't get one as a pet,
trust me. So this is a successful captive breeding program. And every year they can
release about 500 black-footed ferrets into the wild. But there are two problems. The one is what
you mentioned, and that is that there's not that much genetic diversity. There were a handful of
founders in this population. All of them were from the same population near Matitsi, Wyoming. So
they're already closely related to each other. And over time, the amount of diversity in that
population is going to decline. So a few years ago, this collaboration of organizations got
together and said, there's a solution to this. In the frozen zoo in San Diego, there are tissue
samples from that original captive breeding population, unrelated to the individuals that
were in Matitsi, Wyoming. So different genetic diversity. If we could use cloning, the tools
that we will use to make mammoth, that we use to make our direwolves, that most famously was used
like Dolly the sheep, we can take those skin cells and turn them into a living black-footed ferret.
So revert them to stem cells?
Not in this case.
You just take an egg that you've harvested from another one and you inject the cell into the egg.
And the proteins in the egg itself can do that epigenetic reprogramming, which is kind of like reverting,
but you don't need the Yamanaka factors.
You just need the egg to do this.
So it becomes a cell that starts to divide and become all the different types of cells that make up an animal.
Elizabeth Ann was born.
Elizabeth Ann was the first clone of 40-year-old tissues from an animal that had lived decades earlier.
She was not reproductive, unfortunately.
She was never able to have offspring.
By behavior or there was some biological wiring issue?
There was some wiring issue.
Her ovaries weren't releasing the eggs or something.
I can't remember.
Ferrets have this induced ovulation thing, too.
They have a kind of funny, funny.
I mean, to us, it's funny.
To them, it's perfectly normal.
But they did make another one.
And from the same line, and that animal has reproduced and there were offspring from that that can be able to be
introduced. So here we have a solution to introducing genetic diversity into a population
that had lost genetic diversity on the path to extinction. But there's another problem.
And that is that the thing that's actually killing the black-footed ferrets in the wild
is plague. Bubonic plague? Plague. Yes. That's another reason you don't want to have a ferret
as a pet.
Well, definitely not a black-footed ferret.
I mean, the European, you don't want to send me off on a thing.
I had a pet ferret, I believe, many years ago, and I don't recommend them.
But you were going exactly where I'm going.
It was a domesticated ferret.
It was not the black-footed ferret.
Domestic ferrets are not susceptible to plague.
And that susceptibility must have some genetic underpinning.
So if we can figure out what that is, and there are several hypotheses
working on right now, we could use the tools of synthetic biology, genetic engineering,
to edit the genome of these black-footed ferrets and make them resistant to plague. So not only
use cloning, a form of genetic rescue, but then also synthetic biology to create animals that are
able to survive in this habitat, despite that people have mucked with that habitat in a way
that makes their survival hard. We can use these same tools for lots of different things. We have
a project related to our dodo project with the Mauritian pink pigeon.
Is it actually pink?
It's pink.
It's very pink.
You pick cool animals to wear.
You're like, woolly mammoth dodo bird pink pigeon.
You know, like, you know, you guys know how to, you know, get-
It's part of it, right?
Oh, a dire wolf, 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 was like a piece.
If you weren't going to make a dragon, you might as well make a very large wolf because
it has these kind of connotations.
When I was working on the first direwolf genomes way before I was involved with Colossal, but the very first time we published direwolf DNA, we were desperate to sync the publication with some editor in some science journal to the Game of Thrones coming out.
We were like, we can get this genome done.
Surely they'll want our paper because then they can have some press attention to the direwolf paper.
We never got the DNA finished in time to do that.
It was so poorly preserved.
They lived in warmer parts of the world, and so it was really hard to find samples that had high-quality DNA to be able to get.
It was a fun project, though.
Were the babies cute?
Yes.
Yeah, okay.
They didn't come out ferocious.
Yeah.
No, they were extremely adorable.
Just putting a plug in for the dire wolf here.
Extremely adorable.
I bet.
I bet.
Everyone loves a baby animal.
Yeah, well, that's how we got dogs, I'm pretty sure.
They were hanging around outside, cleaning up after us, giving us a little bit of an advantage,
because if something scary came, like a giant cave bear or something,
they would howl and our ancestors would know.
But I'm pretty sure that that was just commensal.
We could have lived for a long time with them living around us
and us living around them, but I think their puppies were cute.
Yeah.
And you make a really good point.
I mean, you know this notion of like the eyes of the getting rounder,
like in dog breeds, you know, because people like them.
I mean, all the doodle breeds, the hypoallergenic breeds, they don't have fur.
I think about that sometimes because I have two Labradors
permanently coated in at least one layer of dog shed hair.
We're so comfortable as humans to modify species for our immediate convenience.
But sometimes that's obviously detrimental to entire populations.
You're talking about reintroducing a species that have not been there in a long time or
expanding their numbers.
I would like to think that with AI or other modeling tools that you could make predictions,
predictions about, okay, let's model in the mosquito population, where the swamps are,
what the seasons are like, what the quoll population looks like. And you could put,
you could model as many things that you're aware of. There's no graduate student, no matter how
brilliant, or professor, no matter how brilliant that can mathematically model all the different
influences of all these different plant and animal species. But AI can run it 24 hours a day,
seven days a week. This idea of digital twins. Can we create a digital twin of an ecosystem and
then perturb it in lots of different ways and see what happens? I think this is totally within the
realm of feasibility. It's a big foundational model, but I know there are groups of people
who are working on this for smaller systems, like individuals to think about human medicine,
what happens in this system, this particular organ system, if you perturb it in this way and using
AI to be able to narrow down the window of what edits might be reasonable to make and what might
We're doing other things. We have a completely independent group of people that make what we're calling our care reports, which are deep dives into the ecosystems where we would be releasing any future de-extinct animal.
We release these when we have them with the blue buck. We have a blue buck care report that people can read to figure out what we've thought about in terms of the impact of the ecosystem over short, medium and long term.
And it involves conversations with local stakeholders and conservation biologists and people who are thinking about it from all sorts of different perspectives.
So it's absolutely, as you say, critically important to think hard before doing things, but also be willing eventually after you understand as best you can what that risk was.
Yeah. Along those lines, I predict in probably three to five years, not 10, the technology that we were talking about earlier of mutating the HIV receptor, that sort of thing will be very commonplace in the context of fertility.
I mean, if we knew a certain constellation of disease genes inevitably led to a disease or a high probability of disease, and there was a way to use gene editing to rule those out,
Once that had been established a number of times, I'm willing to bet even outside the
Bay Area that people would want that.
Nobody wants a harder life for their child.
Right.
You know, it could also come, I've thought about this, my last book is called Life As
We Made It.
And it's all about how we've been messing with the species that we encounter for as
long as we exist.
In the last chapter, I think about how we might turn our editing technology on ourselves,
really asking the question, what is it that will push us over that edge, right?
One of the possible scenarios is that we have a pandemic, a crisis, and we learn that there are certain people who
have a particular genetic variant that means that they will die. And suddenly the most morally
reprehensible thing that we could imagine doing becomes the actual only ethical solution. And that
is the thing that pushes us over the edge. You mean, so you're talking about more people dying
or rescuing that through gene editing? Gene editing ourselves. And now we're talking more
about public perception, scientists and implementation and where those intersect.
And I think that one thing that I've learned
is that a lot of it is about the delivery method.
So when we hear about gene editing
and you're taking a cell and you're putting in a dish
or even ICSI, what you described before,
like in a dish of basically injecting a sperm cell
into an egg as opposed to running a sperm race, right?
People are a little more comfortable with that
than they are like the ICSI.
It's like this one, we're taking this one already
because you're biasing an outcome in a strong way, right?
You're not letting the system decide.
But people are okay with this if, for example, you have a man with a very low sperm count or with very few healthy sperm where you can take a healthy sperm and put it in the egg.
Yeah.
No, I think people are comfortable with it now because it's been around for a while.
It's this every new technology you have your first, is it scary?
Right.
Like, why do I hate this before?
Let me be curious.
Yeah.
I mean, in a different conversation, but one that is relevant, you know, it's fortunately we're not talking about it today, but, you know, I get asked about peptides like every
five minutes these days and not the peptides of the GLP sort. But what's happened in the health
space is that the GLP drugs have de-stigmatized and taken away needle phobia by putting the,
it's still a needle, but it's on a pen. And so now people are like, which peptide should I take?
And I'm like, how do you get it? No one's saying like, is there a capsule version anymore? That
was a big thing. And now if you're like, because it turns out it's the hypodermic part, not the
needle that freaks people out. The needle kind of freaks people out, but people have no problem taking a pen and going
But they don't like using a plunger and a needle.
So now people, needle phobia has plummeted and people are willing to explore things that some of which there's good data on and some of which there's like no data.
And people are pinning themselves all over the country, right?
And so it turns out that something, this couldn't have been predicted, that there was this other thing that was getting in the way.
It wasn't really the thing about taking the peptide that may or may not have enough data.
There are a lot of data on the GLPs, but it really was the delivery method.
computers, right? They were big clunky things. Everyone had to use the same one. Then all of a
sudden you turn it into a phone that's also a camera. And the next thing you know, you kind of
forget that it's a computer. Same thing with brain machine interface. As long as people think you
need to drill into the skull or put something, a wire behind the ear, pretty soon this will be
non-invasive. And then people aren't thinking about, oh, it's going to control my brain.
So that big fear wall tends to come down to zero through these things that are hard to predict.
and it's often a combination of the messaging
and kind of like,
like maybe everyone should pet a dire wolf just once,
§09Transcript — part 9
just a little bit.
Would you like to pet a dire wolf?
I would love to pet a dire wolf,
especially the little ones, but yeah.
You should come visit us in the lab
and you'll see some of the really cool stuff we're doing.
The artificial wombs are really cool artificial eggs.
You know, there's a-
You have artificial wombs?
We have one of our-
You realize this is going to terrify people.
I'm a biologist, but okay,
so describe to me an artificial womb
and what that looks like.
Right now we're thinking about mice, right?
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 mammoths. We need a way to be able to birth multiple
mammoths simultaneously without using elephants. Elephants should be allowed to make elephants,
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 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?
It is wild. One of the most incredible things that I've witnessed is a NICU. 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 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 kind.
But the NICU technology has come a long, long way.
It's far from perfect, but that's essentially what you're talking about.
Yes, a more sophisticated NICU where 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, 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. There seems to be a theme lately in
where people come on this podcast
and they're talking about revolutionizing education.
We had someone, 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.
Cool, I need that.
Two hours a day.
Then they go learn how to farm, start businesses.
It was interesting that public reaction is very divided on that.
People usually say, great, and then other people say,
oh yeah, but it costs a lot, so it's only for rich kids.
It turns out they're starting scholarship programs.
But the idea there is to figure out the best way to educate humans,
and then wick it out to everybody.
But there has to be this pioneering spirit,
and that's always going to stimulate concern,
and there's going to be the haves and have-nots things in people's minds.
I think thinking about your work in a different but similar vein,
where being a pioneer is hard because you have to tolerate people saying,
and sometimes the assumption that 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?
Why are we doing this?
And I don't have any great solutions for you on this, but I think that public education is clearly a big part of it.
And I think the humanizing it at the level of who's doing it, like it's very clear that you love biology.
It's very clear that you like hard problems in biology.
And it's very clear that if I may, it seems like you're not afraid of, but you rather enjoy the fantasy positive outcome part of it.
It's not all doom and gloom.
I mean, this is similar.
This example works for me.
Hopefully it works for you.
You know, like Elon wants to go to Mars.
And I have guests on the podcast that say like, no, he should be curing humanity here.
And I told that person, that's like telling, you know, the Metallica they should be the Grateful Dead.
We need individuals who are thinking in a different way steeped in really good ethics and are excited
about the problem to evolve this thing that we call life on earth. Sure and I'm good with that
if people say to me oh why are you working on this you should be curing cancer those are two
different things although you know there's things that weird. You know what quit this I don't know
you but quit this and go cure cancer. Well I mean we are learning things from elephants for example
that we have to know about and that is actually relevant to curing cancer but that's not our main
I'm not focusing on curing cancer, but people who say you should do this instead of saving living species, I just really have to push back on that.
We are doing both.
There is not enough money in conservation.
There just isn't.
The idea that we're developing tools that are immediately applicable to existing conservation problems using new funding, new resources, bringing in new investment ideas, excitement, enthusiasm, excitement from students.
I mean, why is this not embraced?
Why is it always the, well, you must not be doing that.
We are doing that.
The dire wolves, when we announced the dire wolves, we announced that we had cloned red wolves, which is the most endangered species of wolf in North America, an endemic wolf that, again, is living in a very small population, captive breeding in the Carolinas.
We had colleagues, Bridgett vonHoldt, who is at Princeton, who had discovered a population of coyote-like animals that have a bunch of red wolf ancestry, some on the order of more than 75% red wolf ancestry.
And so we've cloned these wolves as a means to introduce new red wolf genetic diversity into the existing red wolf population using the same toolkit that we used to be able to clone and generate our dire wolves.
Have you heard about our red wolves?
No, they were announced at the same time though. So all these people who are like, you should be doing this instead of this,
pay attention. We are. They've saved the ginger wolves. I love it.
There's something that I think people need to understand about scientists and probably
technologists too, but that's not my area, which is the person matters. Like the person doing the
work has to be really, really drawn to almost obsessed with the project. Because you could
sort of ask like for any scientists 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 go like sometimes those to get funded
sometimes not but but that's the kind of science that certain people do they want to turn a crank
and then there are certain scientists who really want to 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 but with this going to Mars thing and I don't think
he's got a bunch of other stuff going on clearly, but you can't really draw them off target by saying, hey, 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 can't get Metallica to play the Grateful Dead happily.
They're just not going to do it.
It's not in their spirit.
It's not in their soul to do it that way.
And so I think that like 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 can't convince people like, oh, you should be saving the coral reefs. Someone else should be saving
the coral reefs, but they need to be obsessed with coral reefs. I mean, I'm stating the obvious,
but I think from the inside, I relate. Yeah. 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 going to get way less done. You're not
going to make an impact. It's so interesting. People love to tell other people what to do,
But I will say there are people out there, I know this because of this podcast, 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.
So where are the public education efforts outside of podcasting and whatnot?
How many people are at Colossal?
There are about 120 scientists, and then there's other people involved.
We have a huge social media team who put a lot of science bits out for the world,
targeting different audiences with different types of information.
We work with a lot of podcasters, and we work with other teams of people making documentaries and films.
We publish papers using the 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 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 take part in the National Geographic Live series.
So I've gone and just talked to communities about conservation and genetic rescue and de-extinction and a future that can be both biodiverse and filled with people.
So in junior high, high school, graduate school, were you sitting there thinking, I'm in a department of zoology at Oxford University, and there's a picture of some old dude on the wall.
This is how I felt when I went to Cambridge.
I'm like, that's Darwin's house.
There are two ways to be in that kind of environment.
like, whoa, that's so-and-so and there's this history,
or was it, we can do this all much, much better?
Because I get the sense that you like to break the mold,
but I don't want to kind of lead the witness here.
So what were you like as a kid and in graduate school,
were you thinking, you know, this field,
this whole zoology thing feels kind of steeped in old stuff
and I want to break it open?
Or, you know, like maybe just tell us a little bit
about your mindset in these kinds of environments.
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 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
I had to be at work at four o'clock in the morning to write and cut the news so I could be on the
drive time show. Do you remember these from the 90s? 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 archaeology
and it was a nine-week class and we started off on the East Coast and learned about minerals,
and 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 U.S., right?
And I thought to myself, as I was watching this,
you could see the scars on the landscape from glaciers.
And we went to all of these archaeological 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 want to tell.
Maybe I want to be a science journalist instead of just a regular journalist.
The idiocy of people who think they're an expert because 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.
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 I 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 project that I could do as a PhD student where we were going to study the type of wasp that switches back and forth between inbreeding and outbreeding.
So the question was, is the switch to inbreeding something that is intended to purge your genome of those deleterious alleles like the Channel Island foxes?
Like if we inbreed, we'll get rid of all that bad stuff that's accumulated.
Then we can go back to outbreeding.
It's a pressure test.
Yeah.
So we designed this experiment.
I went back to the University of Georgia.
I was like, I'm going to go to Edinburgh.
This is going to be great.
Help me apply for these scholarships.
And they said, cool, because I couldn't afford to go overseas for grad school.
And I said, cool, you can apply.
But you have to apply for all of the scholarships that we have for our honors program people together because it's just one big package.
So I applied for the Marshall Scholarship to go to Edinburgh and the Rhodes.
And I did not get a first round interview for the Marshall.
So I ended up not obviously being able to go to Edinburgh, but I got a Rhodes scholarship.
§10Transcript — part 10
So I ended up at Oxford.
So you are a true, I think you're our first Rhodes scholar, you know.
I got Rhodes.
I ended up at Oxford.
I had no idea what I wanted to do or who I was going to work with.
And I met on my first few days there, this guy called Alan Cooper, who's a Kiwi.
He was setting up an ancient DNA lab.
This was one of the few labs at the time that was going to be built to be able to process these old samples.
And I was really excited about the idea of ancient DNA because it brought together geology and paleontology and storytelling.
If I'm reading DNA sequences from entire ecosystems that used to be alive, I can tell a story about how the environment changed when people first arrived or how the environment changed with rapid warming out of the last ice age.
And I was like, this is the science I want to do.
Plus, it was brand new.
Nobody was doing it.
There were a couple of dinosaur DNA papers that had been published and proven to be false.
And it was really an opportunity to bring stuff together that hadn't been done before and just do something entirely new.
If I joined his lab, I could go to Siberia.
And that was enough for me.
I signed on the line.
I was like, I'm in.
So that's my origin story.
And I think it is because it was new, because it was an opportunity to bring together lots of different disciplines that, you know, otherwise really hadn't been thought of together.
I got into de-extinction because everyone who works in ancient DNA is asked as the first question whenever they publish a paper.
This is, you're working in ancient DNA.
We're doing stuff that's high profile. We get high profile papers. It's normal in science for this thing to happen. You get
interviewed by somebody from the media and the first thing they want to know is,
so what does this mean about how close we are to bringing dinosaurs back to life?
Every time, every time. I'm more concerned about the black-footed ferrets, frankly.
When I was researching my second book, I was using the New York Times Wayback Machine,
which is amazing. Love the Wayback Machine. And I was reading the very first article
about the very first ancient DNA publication.
In 1984, researchers from Berkeley
in what was called the Extinct Species Study Group
had managed to isolate using molecular cloning,
because this was pre-PCR days,
a tiny little fragment of DNA
from the skin of a preserved quagga,
which is an extinct type of zebra,
and show that it was related to a zebra.
So the scientific finding was not that illuminating,
but the fact that DNA survived after death,
first discovery of that. So it wasn't a big deal. It really set off all of the stuff that became
the dinosaur DNA days of ancient DNA. Could lead to forensics.
All of the forensic stuff. Yeah. All of that came out of this too. But when the journalist
interviewed Alan Wilson as the very first ancient DNA researcher, publishing the very first ancient
DNA paper, he got to be the first person to ask the dinosaur question. The dinosaur question. Yes.
I mean, it is true that if you walk into the life sciences building at Berkeley, there's a full size T-Rex skeleton.
It's cool.
It's very cool.
People love that.
I've never been dinosaur obsessed.
I can think of many more animals and human diseases that to me are more interesting.
But this is like the why don't you cure cancer thing.
Yes.
Well, but I think we get to mammoth because as soon as people hear that and understand that we can't have dinosaurs because there's no dinosaur DNA, they tend to settle on mammoth.
Either mammoth or saber tooth cat.
Those are the two things that we get after that.
it's just because they're big. You know, it's this big thing. We know they're extinct because
our ancestors hunted them. We know they're relatively recent. We can imagine what they
looked like. They're in popular culture a bit. And so it's a matter of awe, of interest.
I think it's the size and scope that is, they make us feel small.
Yeah.
Yeah.
People don't like to feel small, but mammoths make us feel small too, I think, but in a
way that we can appreciate.
Yeah. There's something about the psychology around this in terms of public perception
I'm going to go with that people want the best for our species and other species on average.
They're a little scared based on, for reasons that make perfect sense to me,
based on what they know and what they don't know.
For that reason and many other reasons,
I'm just grateful that you'd come out here and talk about this stuff today
and that you're doing what you do.
I thought the dire wolf thing was super cool.
I still do.
You should come see that.
I got it.
I'm not saying that, you know, as a biologist, I got it.
As a, you know, developmental biologist, I was like, I got it.
This is not like taking some human cells from the cortex and putting them into a mouse cortex. Like those are cutesy experiments.
Frankly, I thought those experiments were more like cutesy derivative. They didn't really
inform or anything in my opinion, but what you guys did, I thought was really cool. And then as
I started learning more about what you're trying to accomplish, like repair ecosystems, make better
ecosystems, I'm all for progress. So thank you for doing what you do, for continuing to do what you
do. I didn't even get into the fact that you walked away from a fully thriving lab in academia,
Howard Hughes Investigator, which is this thing that very few attain. And so to do this, so clearly
you're on a mission and I have every anticipation that it's going to work out and work out for the
best for animals and for people. I'm excited to see what you guys do. Thank you for the opportunity
to have this conversation. Yeah, it's a lot of fun for me. I rarely can I talk about ferrets,
woolly mammoths, dinosaurs, and human gene editing
all in one conversation.
Thanks so much.
Thank you.
Appreciate you.
Thank you for joining me for today's discussion
with Dr. Beth Shapiro.
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