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 greywolf 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 thyloines, 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 opthalmology 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

deextincting species such as the woolly

mammoth, the dodo bird, and the

direwolf, meaning bringing them back to

life. But that entire initiative is also

about species preservation more broadly

and how genomics can be used to improve

the global ecosystem. In this episode,

we discuss what it means to use ancient

DNA to bring back extinct species, which

then led us to a broader discussion

about genetic engineering in human

health, both of which, by the way, are

happening right now. So, this is not

just a projection into what's coming in

the future. As you'll see, Dr. Beth

Shapiro is truly a one-of-a-kind

thinker. And today, you'll learn the

science, the ethical implications, and

the positive potential of using genetics

to de-extinct species and using genetic

selection and genetic tools to change

humans. And no, Dr. Beth Shapiro is not

planning to bring back dinosaurs. And

today, you'll learn why. Before we

begin, I'd like to emphasize that this

podcast is separate from my teaching and

research roles at Stanford. It is

however part of my desire and effort to

bring zero cost to consumer information

about science and science related tools

to the general public. In keeping with

that theme, today's episode does include

sponsors. And now for my discussion with

Dr. Beth Shapiro. Dr. Beth Shapiro,

welcome.

>> Thank you.

>> Longtime 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

blackfooted ferret. I'm a big fan of

muselids, 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 phoggenetic trees.

So, what have we learned that you think

people might appreciate understanding

about taxonomy and like a is my dog as a

bulldog mut [clears throat]

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 a human concept. We

have this incredible proclivity to want

to put things into boxes so that we can

talk about them so that we can have

conversations or share stories or share

memories. In order to share something,

we have to know what to call it. That's

one of the reasons language has been so

fundamental to the evolution of our

species and our social structures. So,

what is a species? probably when you

learned about species in biology class

when you were in middle school you

learned about Ernst Mar's biological

species concept

>> kingdom film order genus species like

this kind of thing clay you

>> know that's the taxonomy right so we

have a lanaeus came up with this idea of

doing taxonomy right so here's an

interesting taxonomy story I've I've

spent a lot of my career working on

bison for unfortunate reasons probably

or fun reasons or whatever but a lot of

time working on bison and bison were

called buffalo buffalo right we think of

American bison as buffalo it's the same

thing the same thing but bison is the

taxonomic name that was given to

American buffalo by Carl Lanaeus 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 boof coat they called

it a buffalo or a buffalo right so we

have African buffalo buffalo, an Asian

buffalo, an 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 Carlaeus

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 for the gorilla.

>> 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 Erns May 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. So even

among flies, there's some restriction.

And what's wild is that flies and

mammals of all sorts seem to know. Like

they actually don't try to mate in most

cases. They don't try to mate with other

species, which is fascinating in its own

right.

>> Beg to disagree there. I mean, if you

seen your dog tries, your dog probably

tries to mate anything it comes across.

>> Just hit seven [laughter] 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 him a vasectomy. People we

never talk about this, right? You can

keep your dog intact and just give him 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 the vasectomy

which is actually less invasive a

procedure than the the full neuter.

Anyway, we don't want to digress too

much but my dog doesn't try and mate I'

I didn't see my previous dog try and

mate with cats or

>> or even Chihuahua, you know.

>> Do you think Neanderls 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? But if humans I mean

if 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 spec species concept where an

organism is classified based on some

threshold of sequence similarity and

that is a species concept that is as

valid and valuable a species concept as

the biological species concept which

says you can't interbreed. If you're

interested in conserving species, you

might use a geographic species concept

that says, if you live here, you're a

Florida panther. But if you live in

Texas, you're a Texas panther. We're

going to call you different species.

Biology doesn't care about your species

concept. Your species concept is

something that you have adopted to have

a conversation with another person about

a particular topic.

>> Educate us on this Neanderthal piece. I

know this is a 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 that

you feel

>> uh my husband Ed Green was part of

spontabo's group when they were

assembling the Neanderl genome and so he

spent a lot of time thinking about

Neanderl I think what's interesting from

a species concept if we start there with

what's going on with Neanderls is we now

know based on studying DNA both from

Neanderls that used to be alive and a

different lineage of human called uh

Denisven we we call it this that was

first isolated again by Swonte Pabo's

research group from a tiny little finger

bone that they found in a cave Denise of

a cave in Russia that's why they're

called Denisvens we know that there were

multiple different species or lineages

or whatever you want to call them of

humanike 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 Neanderls and they bred with them. So

if they were a different species, they

were violating the biological species

concept at this point. So again, species

concepts are just what we make of them.

And today most people have somewhere

between 2 and 5% of their DNA that is

from this ad mixture event, this

hybridization event between anatomically

modern humans dispersing out of Africa

and the Neandertols 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 bipeedal and

upright. When we see that diagram, is

that substantiated by the fossil record?

>> It is. Yes. Um, we know that the the

lineage that eventually became us

evolved in Africa. We can trace ancestry

back to apes and then to primates or

primates and then to apes and then

eventually to us. The fossil record in

Africa is very fragmentaryary. One thing

that's really been really fun about

working in ancient DNA is the field of

paleo anthropology 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 Denisa, right? And I can

get DNA from that. I know that my bone

has ancestors, right? If I have a bone

that might be somewhere on that lineage

to human evolution, I don't know that

that bone has descendants. I don't know

that that bone is part of our actual

family tree or if it's another one of

the dead ends that went in a different

direction and eventually became extinct.

But that is one of the coolest things

about being able to sequence one of

these bones because now you know what it

is and now you can line it up against

all the DNA from all of the people that

are alive today and discover things like

we all have ancestry because there was

breeding between these lineages because

they could and because I think that if

they can they do.

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to save up to $200. 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 or two, some at some some

point, but two non- genetically similar,

I don't want to say identical because

they're not twins, right? So, I don't

have a language here, forgive me, but

you can get breeding across species and

get reproductively viable offspring.

That that has to be the way this

happened, right? It couldn't have just

been through spontaneous mutations that

suddenly took animals from quadripeds 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's it it's in. Maybe

it's, you know, very rainy and there's a

lot of water and there's a lot of floral

plants and over here it's drier and

there's really scrubby plants. There's

different selective environments and as

mutations arise in that genome,

different ones will go to fixation. The

size of the population also matters. If

a population is really small, even

mutations that arise that are bad can

become fixed in that population just

because the population is small and it

just happens by chance. And so over time

these two will become more and more

different from each other. So what

happens when they come back in in

contact with each other? I think it will

really depend on what those mutations

that arose over that time was. It could

be that there's a very short

evolutionary time but a mutation has

arisen that means the sperm can't

fertilize the egg or the egg can't

subdivide properly if you have a hybrid

ancestry. Or it could be that nothing

really has happened over a really long

evolutionary time and ad mixture can

happen.

>> Humans in the anderls diverged somewhere

300 to 500,000 years ago. That's not

very long ago in evolutionary time.

Brown bears and polar bears diverged

about half a million years ago. And we

know that they can readily interbreed

and do whenever they overlap in habitat.

Yeah, they're called grer bears or

pizzly bears depending on which

direction. I know they're terrible

names, right? You want a different name

for this really

>> especially if you're a bear. [laughter]

>> 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 um a polar

bear off the coast of Alaska that

probably lived more than 100,000 years

ago. And it had ancestry that we see in

brown bears everywhere in the world,

suggesting that that bear's ancestors 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 call them to ovulate,

cause them to ovulate. So you can

imagine situation where a brown bear

wakes up from hibernation, goes on to

polar bear habitat to scavenge for food,

comes across a polar bear female,

induces ovulation and they mate. The

other way around where a polar bear male

finds a seasonally ovulating brown bear

female probably wouldn't happen because

the timing of overlap wouldn't be right

and also he would probably kill her

rather than mate her because of the size

difference and difference in what

they're doing. So why is it then that

since bears live with their moms, all

the brown bears that we see that have

polar bear ancestry are brown bears, not

polar bears? We were working with some

polar bear biologists when we were doing

this analysis many years ago and their

hypothesis was simply that if you have

brown bear ancestry, you don't have

perfectly white fur and you cannot

successfully hunt seals. So it is just

adaptation that means that that ad

mixture doesn't work, right? So even

though there's no problem with the sperm

and egg mixing and the animal is born,

they cannot survive as polar bears and

so polar bear stays separate from brown

bear in that way.

>> I'm going to bring up dogs again, but in

the back of my mind is a conversation

about humans and this question about

different species of prior to homo

sapiens or homo sapiens and nearby

species having reproductively competent

offspring. So in the dog world, it's

well known that the English bulldog,

which has a big head, small hips, is the

byproduct of many crossings, but it's

basically the bullmastiff and the pug.

And this was an attempt to generate an

animal with a short snout so it could

clamp down for bull baiting, which

fortunately is an illegal sport now, and

to clamp down and not get shaken off by

the bull very easily.

>> Uh the floppy face is associated with

lack of pain receptor. There's a bunch

of things in the bullmastive 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,

>> right?

>> Humans realize this pretty quickly and

they learn cescareian section. So, I

could imagine a situation, although I

don't tend to think like this today. I'm

imagining a situation where homo sapiens

and some other non-hom homo sapien

humanish species were having sex

sometimes getting pregnant but the

babies would always die because the

birth canal and that structure of the

pelvis wasn't quite right to allow the

head size through which you know there a

lot of I hear a lot of arguments that

you know humans sort of optimized for

just enough space so that the large

humans you know we love to talk about

how big our brains are right could pass

through but no larger and and not much

smaller in most cases.

>> One of the reasons that giving birth is

one of the ways that women have died in

our evolutionary history.

>> Right. And and cesareian sections I

probably have changed human evolution in

that sense as has a aseptic you know

conditions and things like that.

>> Absolutely. For me my child was cesarian

birth. So

>> right. So, I like to think you would

have survived anyway, but the um but I

could imagine a mutation that was an

adaptive mutation where suddenly this

other species which maybe had a smaller

pelvis, a female could deliver this

child live. The the mother survived as

well and then that DNA, you know,

propagates so that there are now humans,

maybe it's been bred out, but that there

are or were humans walking around who

are not completely homo sapien or is it

not not possible? I don't know about

what's known about hip size or anything

like this, but but it is true that

humans and our archaic cousins Neanderls

interbred and that people walking around

today have Neanderl DNA.

>> 2 to 5% you said

>> two to 5%. What's interesting about that

and it touches a little bit on the

adaptation component that you you raised

is that I think most people or a lot of

people have heard this number. We have 2

to 5% Neanderl DNA. less well understood

is that it's a different 2 to 5%. Like

the 2% Neanderl that is in my genome is

different from the 2% or maybe 5%

Neanderl that's in your genome is

different than the next person.

>> So it could be heart, liver, skeleton

and uh spleen for me and it could be

some other constellation for you.

>> Could be anything. And if we were to go

around the world today and pick out all

of the pieces of Neanderl DNA that exist

in humans today, we would put together

more than 90% possibly more than 95% of

the Neanderl genome just from people who

are alive today. And that tells us that

most of the Neanderl genome was not

maladaptive for people that pretty much

all of it could get passed on and live

in healthy humans today.

>> Interesting. We don't know what happened

in the other direction, right? We we see

Neanderl bones and there hasn't really

been any evidence of humans admins with

Neanderls. There has been evidence of

hybrids between Neanderls and Denisven.

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 Neanderl 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

chimpanzeee or a bonobo. So there's 3 to

5 million years of time between when we

shared a common ancestor. And a lot of

change happens in 3 to 5 million years

in your DNA. And some of it is useful

and some of it is what makes us human.

And most of it is just not. It's just

changed cuz copying errors during

copying cells and that's what happens.

That's how we're different. Every child

that's born has about a hundred

differences compared to their parents

because of copying error in the process

of making the sperm and making the eggs

that made that kids. So when we got the

Neanderl 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 Neanderl 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 Neanderl DNA? That

is where the stuff that the baby had to

have the human version in order for that

baby to survive. And that's where we

look to see what it is that made us

human.

>> A few years back when 23 and me and

these other uh 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 vi vigor genes that they allow

for more durability of human male or

female?

>> It's an interesting question. If you

just look at that 2 to 5% of nano 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 Neanderl

DNA is suddenly much more common in a

population of humans because that would

suggest I got some DNA from my Neanderl

ancestry and that bit of DNA suddenly

made me more fit because I had that bit

of Neanderl 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 Neanderl DNA. There are

a couple of things that have come out.

There are genes that are common in Latin

American populations that come from

Neanderls 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 Neandertol gene associated with this.

But most of the really interesting ones

have been at inimmune related genes

during the pandemic. One of the first

alals that was discovered to be

associated with negative risk or bad

outcomes of COVID was a gene that came

from Neanderls. So it's a Neandertol

derived gene that was at something like

50% frequency. So way above the 3%

average frequency in Asian populations.

And it it made people more susceptible

to the virus entering your lungs. And

presumably it only became that high

frequency because it was protective

against some other disease that was

circulating in the past. But the

trade-off of that is that it of course,

you know, made them more susceptible to

CO. There was another Neanderl

associated alil that was actually

protective against CO. So I think our

ancestors have been subjected to

different diseases and pandemics and

things that have happened throughout

life and we see the traces of that in in

ancient DNA. We can now go into

graveyards in Europe and and actually

isolate plague from dirt and from bones

from people who died of plague and look

and see how their immune systems and

genes have responded to exposure to to

things like this. It's really

fascinating.

>> Wow. My red head friends like to claim

that they have more Neanderthal and

therefore more vigor and pain

resistance. So I'm guessing the study

probably said more pain resistance. It

we have pain experts on here that verify

that indeed on average

>> that red heads tend to require more uh

anesthesia on average. So that tracks

but were neanderthalss were a lot of

them gingers.

>> Yes. This comes from studying at 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 bleached

to red, but there definitely is a um

some evidence from their genome that

they had reddish colored hair. Yes.

>> 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.

Um, you also see a lot about how true

greeneyed people are are quite rare. Was

there a time when the population of

humans on Earth had a lot more greeneyed

people?

>> I think all of the colors, if you if you

look at um 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 a mate that has blue eyes

and stuff. really think that that it was

selected for it.

>> Probably eye color was was sexual

selection. I I don't know what other

benefits blue eyes could have other than

looking very, you know, stoic and cool

as you're like trying to hunt down

something on them. [laughter]

>> Oh, geneticists are so much fun because

they're they're willing to just go

there. I was going to ask you this

question later, but I'll ask now because

it relates to what we're on to now. You

know, we tend to think of our lives in

in the time bin of our lives, you know,

roughly 100 years if we're lucky, right?

You know, at this stage of human

evolution for about 100 years, maybe 80,

maybe, you know, if we're fortunate, 90,

[clears throat] 100. But as somebody who

studies long periods of time and what's

happened to our species and other

species across long periods of time,

>> I'm always curious about this. I know

you have to make your coffee in the

morning and do every 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 I could focus on I'm going

to focus at this time bin right it's a

it's an interesting way to live now I'm

just curious how you pick the problems

that you choose to work on because we'll

talk about deextinction but you know why

the woolly mammoth why not like get the

Florida Panthers rebooted um completely.

Maybe 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 uh 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 what really are you trying to

accomplish? Cuz 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 the extinction.

>> Mhm.

>> 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, there's that's a very complicated

set of questions there. Um, I think I'll

start with

what is motivating. And I think what's

motivating is what drives the selection

of the species. In fact, it's funny. I I

wrote a book a long time ago now called

How to Clone a Mammoth. And the first

chapter was how to pick a species. What

are you going to do? How are you going

to choose a species to bring back? And

there are technical, ethical,

ecological, and social reasons to pick

any of the species that you can.

Technical. These are the easiest, right?

We can't bring a dinosaur back to life

because we don't have dinosaur DNA. The

oldest DNA that we have ever recovered

from a bone is from a mammoth bone. A

mammoth's bone probably dates to around

1 to2 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? So

>> there's 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 and

thawing is water molecules expand and

will physically break the DNA fragment.

So that's bad for DNA preservation. And

most importantly, just microbial decay.

The fungi, the bacteria that get into an

organism when it's decaying. and chew it

up to transform that carbon and nitrogen

into the next generation of organisms,

right? And so that process is slower in

some environments than others. Exactly

in the same way that your sandwich will

rot faster if you leave it in the sun

versus in the shelf versus in the fridge

versus in the freezer. DNA will preserve

for longer in the cold Arctic where

things are rapidly buried in frozen dirt

and they stay that way for a million

years. like this mammoth bone that we

were able to recover DNA from. But if

you die in a very hot, wet, swampy place

like Maitius, 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 Maitius Island. And I have

tried like hundreds of bones from

Maitius. 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

wellpreserved 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 deextinct. 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 of that?

So, if you were to bring back woolly

mammoths, I'm guessing that's not going

to save the Amazon forest. But what what

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 Pletoine

Park? This is up in northeastern

Siberia. There are these two scientists.

It's actually Sergey 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 verocity. So these

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 a mosaic

landscape where there's some parts that

are moist and 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

essentially recreating their ecosystem

just by being there.

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subscription. Okay? So, you're picking,

look, you don't have to pick a species,

but you got to pick something if you

know two or three, right? I can't say

like we're going to bring back

everything from a given era. So,

>> 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 deextinction program

because all of the tools that we are

developing for deextinction 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. Right? All of that is applicable

across the board. So the stack that

we're building for de-extinction for

synthetic biology stack applies to

synthetic biology for conservation. So

when I joined Colossal and there wasn't

a bird program, they had launched the

mammoth program which is a placental

mammal and the thyloine 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

sematic 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

thyloine and the other mamalian 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

that drawing mammoths and bioines 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.

>> Well, it was in Alice in Wonderland.

Most of what we know about the dodo is

from cartoonish drawings of this animal.

There are some and of course there's

skeletons that we can piece together

using the many many bones in Maitius

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. Oh,

but there may be virtue in doing that.

>> There might [clears throat] 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 uh bird

developmental genetics for a second. Not

to scare anyone away, but hang in there.

A few years ago, I saw something that um

two female condors can reproduce.

>> Crazy, right?

>> And this, of course, for

>> it actually wasn't two female condors

reproducing. It was one female condale

just having an egg all on her own.

>> Yeah. And because of the socopolitical

implications, this got people in well,

we're 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 cuz what I heard was life

finds a way. So, how did 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

>> of the cells during 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 the cell that only have

one copy each of your [clears throat]

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 and um 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 uh 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 praater willy 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 that everyone healthy

walking around out 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

>> and 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. Tricomemes 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.

>> Down syndrome is tricome 21 and there

are a few other tricomemes that are

>> compatible with life. Try 21 is the most

common one because those people can live

obviously with some challenges

additional challenges because the

additional chromosome but they can live

full lives till relatively middle age.

Right? 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 repro 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

[clears throat] myiotic events.

>> Um I think because well obviously sex

has evolved a bunch of different times

on the 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 heterogimedic sex. So the males

have an X and a Y and the females have

two X's and they don't have a Y. But do

it differently. They have the WZ and

it's the the females that have the two

different chromosomes. The males that

don't. And then there are, you know,

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. And so,

>> yeah, there's like there are communities

online

>> I've learned that actually believe this

kind of stuff for humans. There all

these theories about how to get a male

or female offspring based on position of

intercourse, temperature, location,

food. None of it beats chance,

>> right? Um

>> or if you really want ixxie 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

>> can you actually determine the XX or XY

of the sperm and they can do that now

you can do it

>> you can select so you can do true sexual

selection

>> you can and it's 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

>> caring.

>> 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 sematic 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 or the cuz it's a fun

one. Birds [clears throat] are

complicated. As a developmental

neurobiologist in my past, the bird

stuff gets tricky. Reptiles

>> birds are tricky and there's really

tricky.

>> Some birds are trickier than others. I

did not know until I joined Colossal

that there are some birds that have a

what's called a germline restricted

chromosome which doesn't exist in any of

their cells except for the germline.

>> Germ line or the sperm and eggs.

>> Sperm and eggs. And it comes into being

this chromosome just in the germ line

and then it disappears.

>> Wow.

>> I know. Biology is amazing. The birds

have these like mini mic chromosomes

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

our with like a tweezers or anything

like that. But

>> yeah, the birds are really cool animals,

but they from reproductive biology

standpoint, it's it's tricky. So with

the woolly mammoth was a mammal.

>> Yes.

>> Right. Okay. And you know that because I

mean people can say well duh because

people normally think oh it has fur 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 sequence 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. Okay, so if you get this 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

that is that 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. [laughter]

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

>> talk 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 sequenced.

>> 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 anything like chimpanzees."

>> Well,

>> 99 just sounds like so similar, like

you're going to get the same thing.

>> Yeah. Well, there I mean, 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. Yeah. Is the goal to recreate the

ancient mammoth or is it to create a 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 deextinction. 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 a an idea that was proposed to

classify organisms that evolve over a

very long evolutionary bifurcating

filogenetic tree process where

accumulation of changes is over many

generations over a long time. Our

mammoths, our direwolves are not created

by that process. And so that concept

really doesn't apply. I think that's

where a lot of the 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 it's

important. It's it's a question, but

it's a narrow one. And I think it crowds

out the 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 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 um species

nomenclature gatekeeping, I have a

feeling this is based on the publicity

around the dire wolf.

>> Yes.

>> Okay. I just I like to just address

things very directly. I want to be very

clear. I'm not arguing for species

gatekeeping here. Uh that's not what I

do. I have I own a mut after all.

>> It's not even that. It's it's that um

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 have, but if people

don't want to call it a direwolf, just

don't, right? Like,

>> well, 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."

>> You're a scientist and I am, too.

Actually, it's funny that you 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 you use the

example of like a butterfly flaps its

wings in Patagonia and then this thing

happens in the to the barista in in

Brooklyn, you know, and people like to

bridge those concepts and they think,

"Oh, that's so cool." Like, so it's it's

it's sticky, as we say. But that's but

he 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? in 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 um and we 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

greywolf 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.

>> Sounds like you were very intentional in

picking which genes. It wasn't like, oh,

we're going to take a couple genes from

the direwolf and throw them into this

this other wolf and create what we call

as the direwolf.

>> If I were to look at the direwolf

and a you said a greywolf.

>> Yes. Side by side, is the direwolf

larger?

>> They are

>> on average at the same age. Are there

any other features that are 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 uh longer

and more full and it's also light

colored. I 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

rewing direwolves and we will study the

animals and learn about the effect of

their genes on their lifespan.

>> Yeah, sorry. [laughter]

But the other other animals, the

ultimate goal is to to eventually have

populations of freeling

as as they would like to. And so we 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 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 variance, the same variance in

two genes that would have made them have

light colored coats, but in living

greywolves and dogs, variance in those

genes, not the same ones that we saw in

direwolves, 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 oculaneous

albinism. Um, 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 greywolf 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 direwolf

light colored coat using different edits

that we know are safe in a greywolf

background because there are light

colored domestic dogs and greywolves.

So, we used 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 direwolf

light colored coat, but using a path

that we know is safe. And this is the

way that we think about all of our

projects. We have to take an Asian

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 longived animals. Takes

22 months for gestation. They reach

sexual maturity at 14 and it's a lot of

work.

>> So, how many dire wolf wolves are

walking around right now in some

location? Right now there is Romulus and

Reheis and they are almost two years

old. And

>> male and female or male?

>> Romulus and Remis are boys and Klesia 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

>> But they live together.

>> 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? Um, but she's a little

bit on the specially goofy side, but

she's the 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. Remis 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 and

maybe come near you. Romulus wants

nothing to do with you, which is funny

because they're they're identical twins,

but they're slightly different

interacting with people, but it's very

clear that they these are wild. They're

also huge, right? So,

>> 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 lbs, which

is big for a grey wolf.

>> Yeah. So, everything you just said about

these direwolves, would you also say

about grey wolves? Like, you wouldn't

want to be alone with one. Some can be

skittish, some can be calm. like you

>> you know I have good friends who are

somebody you should think about having

on actually that if you're interested in

dog behavior and what we've learned

about domestic dogs and I know you have

a dog and it's very exciting. Ellen

Carlson 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 and

basically showed that breed stereotypes

are just not real. The that you really

can't map genes to behavior except for

Chihuahua. They're just terrible. I'm

just kidding. No, it's okay. We had

Caesar Milan on the podcast. [laughter]

He'll be the first to say that in 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 [clears throat] Doberman's.

>> 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.

>> Right. Exactly. And then now it's

pitbulls. Right. And statistically,

actually, I think most bites come from

chow.

>> At least my uncle who's a vet tells me

that. But um 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 a 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.

Um and that's part of what we have to do

in all these cases is is how do we

figure out what it is that causes the

thyloine 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 in evolutionary biology that

I get to work on every day in my job.

>> Clearly you have clearly you have the

the the [laughter] right job. So you

have these three direwolves. They're not

mating. Is the plan to make more of them

to mate them? What's what's the ultimate

goal and intermediate goal?

>> We will have another pack so that

hopefully they will all be born more of

them at the same time so that 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

deextinction project. I often hear

rumors that what are you doing? You're

just going to take get an elephant and

uh make a mammoth and just release it

into Alaska? And you're like no. Um

first of all, no. cuz 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 the

>> Jurassic Park thing again. [laughter]

It's that they break out, right?

>> But also, you know, you can't do that.

We exist in the reg regulatory

environment of anywhere that these

animals are. It's it's not that we're

some crazy scientists on an island like

in Jurassic Park. You know, we we work

here. We have Ayakok protocols and um if

you're doing anything that is releasing

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 geneedited

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 [clears throat] biology uses a

tool to make these things better. The

chestnut tree is one of these stories

like the passenger pigeon where the

American chestnut was the most prolific

tree across the eastern forests of North

America all the way through North

America until the early part of the 20th

century when a disease was introduced

believed to be on an import of a Chinese

chestnut tree that caused a fungus to

get into these trees and they all died.

But it took a decade and a billion trees

died.

>> 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

>> So there was a So I was living in the

East Bay, California, and I get this

envelope and it contains a little kind

of like looks like a small quarter size

plastic like container just thin an

envelope and I had a little note and it

said free seeds for gardening. Oh

>> and I was like this is really odd and I

started you know fishing around on the

internet. Turns out the idea was that

massive amounts of seeds were being

shipped from China and sent here. Now,

this isn't a conspiracy, right? Like, if

you look at this, there are these this

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. Yeah, I know some plant

biologists. They were like, "Whatever

you do, do not put that into the ground

outside because these things travel,

birds eat them, birds poop, and then

stuff gets grows. And this is how you

can decimate important populations of

trees and plants." It was the first time

I really thought about vegetation on

vegetation warfare. Is that what is

actually what was happening? Is it was

this the Chinese trying to do this? We

don't know. But what is very important

is that anytime you plant something, you

actually want to talk to the people who

understand how different ecosystems of

plants coexist in the same way that you

wouldn't put your wolves out into the,

you know, into the dog park.

>> I wouldn't put the wolves out because if

if we release direwolves, they would

compete with greywolves. And greywolves

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 greywolves into the habitat and

so we can use them to study these. But

if you think about what you just said,

right, I I think

>> people we as a lineage have been messing

with the evolution and of the stuff

around us for as long as we've existed,

right? Initially just by driving things

extinct. Not deliberately, right? like

just like maybe this wasn't a deliberate

attempt to

>> have some plants that would out compete

other things,

>> but we did and we changed ecosystems by

going into them and and getting rid of

all the largest animals that were there

because we were hunting them. I'm

thinking about, 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 and now

we we conserve things. And when people

think about conservation, a lot of