Kind: captions
Language: en
How do you get informed consent from a
Neanderl to be brought back to life?
>> Simple. You bring them back to life and
ask them.
>> And if they say no,
>> that question answers itself. [laughter]
[music]
Hello everyone. Ever wonder if we could
bring back a woolly mammoth? Well, our
next guest, Beth Shapiro, is hoping to
make that sci-fi dream a reality. She's
an evolutionary biologist and chief
scientist at Colossal, the folks who
recently made headlines for the
deextinction of the direwolf. No biggie,
just bringing ancient predators back to
life. Now, let's get into it. Dr.
Shapiro, welcome to Particles of
Thought.
>> I'm excited to be here.
>> Thank you so much for coming. I know
it's you're really busy. um you know
bringing all these species back to life.
So [laughter] thank you for
>> I had to step out of the lab for a
minute. You know it's it's a it's a
tough job.
>> So let's talk about your baby wolves. So
how old are they now? The three
>> well Romulus and Remis will be one
pretty soon. They're they were born in
October and Klesi was born in the end of
January. So and they're approaching
their first birthdays. What are their
personalities like? Or, you know, I have
a a dog that just turned one. Uh, and
this animal has chewed up everything in
the house. Okay. And [laughter] it can
jump unlike any dog I've ever seen.
Right. So, is there anything in their
personality that you can say, "Oh, this
seems more direwolf than it does
greywolf." [laughter]
>> Well, you know, they're still young. And
the all three of these animals have
lived with people for much of their
lives. The last time that I was able to
see them was a couple of months ago and
it was the first time that I'd been in
an enclosure with Ramulus and Remis and
felt a little nervous. So they are
definitely way more wolflike in their
behavior than they were even five six
months ago. They they really don't want
to get close to you, but they're they
are different from each other. It used
to be in the very beginning um Romulus
was more likely to come up to you and
and hang out and see you. And he has
become really like I don't I don't trust
you. I don't like you. And he's really
big. They're they're they're about 115
pounds now. And so it's a little bit ter
I'm 115 lbs. So this is not something
that I'm very excited about hanging out
with. And so like you walk in there and
you think, "Oh,
>> they are direwolves. I am probably not
supposed to be here." But when I was
there a few months ago, you klesi still
a bit in that puppy phase and she wasn't
yet in the large expansive enclosure
with her brothers. She was still kept a
little bit separate from them. You know,
we've since started to introduce them
and that's that's going really well. But
I walked right in and the first thing
she does is jump up on you and put her
giant giant wolf paws on your shoulder.
And she started chewing on my collar and
I'm [laughter]
>> Boy.
Oh man, that's those are fangs right
next to your neck. [laughter] That's
You're a brave researcher.
>> Yeah. So she at some point will will
have more of these behaviors, but she's
still still kind of a puppy. So it's
she's she's lovely though. And you know,
it's just it's such um it's so inspiring
to see this. You spend so much of your
time in the lab staring at a dish,
staring at things you can't see. To
actually be able to see these wolves, to
to see the direwolves running around in
this secure and expansive ecological
preserve has just been
>> that is amazing.
>> I don't know. It it it makes me
emotional just thinking about it. It's a
it's it was it's and also to know that I
the thing is the the traits that we
modified the size and and and the
musculature were they're obviously not
things that are immediately obvious when
they're born. I mean they were large
puppies but at the same time that could
be because there were there weren't that
many of them in the litter and so
they're larger because of that and now
they're they're definitely large and we
can see the impact of the edits. But
when they were born they were white.
They were white and most wolves when
they're born are dark colored and so you
could look at them and you could go it
worked. We did it. Like we modified the
sequence of their DNA and that phenotype
is what we see. We have made these
direwolves using ancient DNA and very
precise genome modification. And this is
an incredible step forward for synthetic
biology for conservation, synthetic
biology for de-extinction and using a
combination of deextinction and
synthetic biology, genetic rescue for
real rewing, for real sort of ecosystem
scale conservation.
>> Okay. So let's do two things now. Let's
define some things for our audience. Um
so the two things that I I want to
define or describe from you. One is, you
know, what does it really mean to
deextinct? And the second thing I want
you to get into is like how do you do
it, right? Like, you know, yeah, what
what is what what's happening in the
lab?
>> How long is this podcast? [laughter]
>> As long as you want it cuz I'm
interested. How often do I get this
opportunity? You know, I got [laughter]
Dr. Beth Shapiro. I'm asking you.
I want to know, you know, I
>> So, our goal with deextinction is to be
able to create um versions of these
extinct species that are able to thrive
in habitats of today that resurrect
using DNA, using ancient DNA, extinct
traits. And by creating these extinct
species, by bringing extinct species
back to life, our goal is to restore
missing ecological interactions so that
we can make ecosystems more robust and
more resilient. So Romulus, Remis, and
Kesi, we intended to bring back traits
including the size and the musculature.
And we really liked the the the light
colored coat. This was we didn't know
that direwolves were light colored until
we sequenced the ancient DNA and were
able to see in the sequence of their DNA
that the animals whose genomes we'd
sequenced both had light colored coats.
And this is a actually really important
way of of really showcasing how we are
concentrating on deextinction but also
on animal welfare. So we knew that we
wanted to make these light colored
animals. the gene variants that were in
our ancient direwolf fossils were in a
gene that in modern greywolves, if
individuals have variants in those
genes, they can sometimes be blind or
deaf. It's not the same variant that we
saw in the direwolf fossils, but it's in
the same gene. And we thought that's a
little bit risky. But since our goal is
to bring back phenotypes, we know that
we can make a greywolf background into a
white animal because there are white
greywolves today. So we will use those
variants to bring back to de-extinct
this direwolf light colored coat. And in
this way we are ensuring that we are
bringing back we are deextincting
direwolf traits in the safest most
ethical way possible. So how do we do
it?
>> Wait wait wait let me let me ask a
question about that. So I I I've heard
this in with respect to the human
genome, but you can
map specific physical characteristics to
specific genes and you can say okay this
particular gene you know like for
example light skin occurring in in
humans in Anatolia or something like
that. We know what gene created that.
Um, so is it the case that you take a
existing genome of say a greywolf oh you
know what I'm getting to the question
I'm about to ask you and then you say
okay let me add the particular genes
that give me the direwolf
characteristics to that existing
existing one or do you say hey I have
this direwolf incomplete direwolf DNA
profile and let me fill in the gaps with
living greywolf which
>> you know what That is the Jurassic Park
versus the way we're actually doing it
conversation, right? Which you had said.
So I think that's why people are
confused because Jurassic Park, which I
can I just remind everyone who's
watching right now that Jurassic Park
was not a documentary that uh this was a
a science fiction. I think sometimes
people get a little confused and they
think this is what we're doing. And I'm
also going to admit that um I am an
ancient DNA scientist who has attempted
to extract DNA from insects preserved in
amber. And the hardest because of course
I did. And the hardest part about that
was actually smashing the amber cuz it's
so sticky. I had to freeze it really
hard and then take a sledgehammer and
whack the crap out of it so it would
shatter and then try to find the pieces
with the Anyway, there is no authentic
insect ancient DNA or authentic dinosaur
ancient DNA in amber. Amber is actually
a really bad
material for for the long-term
preservation of DNA because it forms in
really hot places and that's terrible
for DNA preservation. It's also super
porous, so microbes can get into those
pores and they'll just chew up the DNA
that's in there, and that is also
terrible for DNA preservation. The
oldest DNA that has been recovered so
far is from mammoth bones
>> uh that were preserved in in Siberia in
perafrost, frozen dirt. So, the the
bones were defl
predators and then buried and then
frozen solid. and they are probably
around 1 to two million years old, which
is really old. Most of the DNA we have
is dates to within the last 50,000 years
or so. There's actually DNA that's been
isolated from dirt directly from
sediment from Greenland called Cap
Copenhagen, which is potentially
slightly older, plyiosine in age, just
before the ice ages started. It's really
hard to know exactly how old things are
around that time point, but that could
be the oldest DNA. Still, dinosaurs have
been extinct for more than 66 million
years. And so we do not have DNA that is
that is that old. So in Jurassic Park,
they got dinosaur DNA, which isn't
possible, out of amber, which doesn't
have DNA. And they pieced it together,
and then they saw that there were holes
in this, not surprising, giant holes as
in none of it was real. But we're going
here because this is this is like it's a
it's a movie. All right. So these things
were there, and then they thought, there
are holes in DNA. I'm going to use frog
DNA to fill in those gaps, which was a
weird choice even then, right? Because
we already knew that birds are
dinosaurs, right? But whatever. Frogs
shoved in the middle and that meant that
somehow they turned into girls. Is that
what happened? I can't really remember
the
>> So, [laughter] so set it up, right? This
is how it had to happen. So now when
people imagine what we're doing, they're
thinking, "Oh, you're going out. You're
getting these DNA sequences directly
from these bones and you're like somehow
holding on to them maybe with a really
tiny pipeter and then you have another
one with another tiny pipeter and you're
super gluing those things together and
you still can't do it. So you're and
that just that it's it's not going to
work. The the the DNA is is broken in a
way and it's also really hard. We
actually have a much easier way
>> to be successful doing deextinction.
Think about the the mammoth project for
example. We know that mammoths and Asian
elephants, that's their closest living
relative. Hey, fun fact, mammoths and
Asian elephants are more closely related
to each other than Asian elephants and
African elephants are related to each
other,
>> right? All right. So, we have mammoths
and Asian elephants that are only about
5 million years diverged from each
other. That means that they share a lot
of their DNA. In fact, they share more
than 99% of the DNA sequence between
them. They're identical to each other,
but it's somewhere around 99 and a half%
depending on how you count. Which means
if you want to change an Asian elephant
into a mammoth, that is a lot easier of
a task than piecing together a mammoth
by taking little tiny fragments of DNA
with little tiny tweezers and shoving
them together, which is also impossible.
So now you have this great great
shortcut that you can use where you can
start with Asian elephant cells growing
in a dish in a lab and you can use the
tools of genome editing. The most famous
one that most people have heard about
now is crisper because it allows us some
really nice precision to be able to make
these changes. And then if you can think
about it like this, gradually go in and
cut out the version of the elephant DNA
and paste in its place the mammoth
version. So we're cutting and pasting
our way to a mammoth starting with this
template that is already 99.5%
mammoth. Right? So that is way easier
than piecing it together.
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So here's a question now. So are you in
is this DNA manipulation happening
outside the context of a cellular
nucleus? It's it's free floating in some
medium.
>> No, it is happening in the nucleus of
living cells that are growing in media
in a dish in a lab. Yes.
>> But we've missed a really important part
that you actually highlighted earlier,
right? which is how do we know what to
change, right? Um, being 99.5% the same
is great, but that.5% difference is
still a lot of genetic differences
between a mammoth and an Asian elephant.
And we can't make hundreds of millions
or tens of millions or even millions of
changes right now. The technology isn't
there yet. It it will get there
eventually. So, you're limiting the
number of changes you can make.
>> We're limited. And at Colossal, we're
really trying to push the limit of that.
How many edits can we make
simultaneously? Um, can we cut and paste
large pieces of DNA, maybe even to the
scale of whole chromosome arms at some
point so we can make lots of changes at
the same time? Because every time we go
into that nucleus of the cell with the
machinery that we need to make the
edits, we stress that cell out and the
cell has to be able to recover after
that before it can do something else. So
we have to focus on keeping cells
healthy on maximizing the number of
changes we can make at the same time so
that the number of times we stress out
the cell can be really limited. So these
are all the technologies that we're
pushing forward here. And I like to
point this out as we make these changes
as we figure out how to do multipplex
genome editing which is just making lots
of changes at the same time or replacing
whole genes. These are technologies that
can be immediately applied to human
health, to animal health. Once we figure
out how we can edit birds and pass those
DNA changes down between generations of
birds, we could do things like modify
genomes in Hawaiian honey creepers so
that they can be resistant, resilient to
aven malaria so that these species may
not become extinct. These technologies
are critical tools in what should be an
advanced toolkit for biodiversity
preservation and those tools are being
developed right now on the path to a
mammoth and a dodo and a moa and a
thyloine. And I it to me it's such an
exciting environment to be part of but
we still haven't gotten to a very hard
thing that you pointed out at the
beginning which was how do I know what
to change?
>> Yeah.
>> And that is where these ancient genomes
come in handy. So we can go out into
Siberia and we can collect hundreds,
thousands of mammoth bones and extract
DNA from them and piece together using
these tiny fragments and computers
sequences of mammoth genomes. And we can
compare all of these to each other and
compare them to elephant genomes and ask
where are all the mammoth genomes the
same as each other but different from
elephants? Because if they're the same
as each other, then that means that
they're probably important to making
them a mammoth. You and I, for example,
share a lot of our genomes, 99.9 blah
blah blah blah blah percent, because
we're both anatomically monitored
humans, right? We have we're pretty much
identical genetically, right?
>> Yeah. Yeah. But you could compare our
our genomes to Neandertols and to uh any
other of Denisven the other archaic
commonin that's our cousin that has
genome sequence that's been and you
could ask where are we the same as each
other and different from them and that
will start to narrow it down what it is
that makes all of us what it is that
makes anatomically modern humans
distinct as a lineage. One thing we can
also do there that's very useful for us
is we can look at where you are
different from me and where we are
different from anybody else that we
encounter and we can say those aren't
important changes to being a human
because they're not shared by all
humans. So we can throw those out and
that is important because that means we
can throw out a whole bunch of places in
the genome where the mammoths are all
different from each other because those
aren't things we have to change. We know
that they're not important to making a
mammoth a mammoth. When you start
thinking of a species to de-extinct, are
there certain criteria like is any
extinct species capable of being
de-extincted or is it a matter of
particular characteristics of that
species particular states of our
technology as a interface or even and I
imagine DNA quality and quantity impact
somehow what you can do.
>> Yes. Um and this is a really important
point. Uh, I think you know eventually
it will be possible to to deextinct or
to resurrect some phenotypes or traits
associated with any species. But there
there are definitely hurdles that span
the gamut and you bring up many of them
there. from a social perspective,
regulatory perspective, technical
perspective, ecological perspective,
every species that is a candidate for
deextinction will face a different suite
of tech technical challenges, ethical
challenges, ecological challenges across
the board. Um, for example, one of my
favorite species to think about is the
stellar sea cow. This was a shipsized
manatee.
>> Wow.
>> Uh that lived off the coast of
California all the way around the around
the Alaskan Illutian Islands and into
Siberia. They became extinct within just
a few decades of western people first
discovering them because they would feed
a crew of 30 dudes for 30 days because
they were so giant and and and they were
really docile just like manatees and
dugongs are today. Um, they lived in the
kelp forests that were around that area
and probably were doomed to extinction
even if we hadn't over hunted them
because we over hunted the furs seals
which were controlling the urchins that
were also so this is really complicated
really beautiful cascading ecosystem
that has to do with otter and furs seals
and urchins and these kelp forests and
and once you get rid of otter that are
eating the urchins the urchin population
explodes and They eat all of the kelp
forest. And without the kelp forest, the
stellar sea cow wouldn't have been able
to survive because they hid in and and
and lived in that in that land. But um
before we had a chance for that
ecological cascade to destroy them, we
hunted them to death. Now, would we like
to bring them back? I think it would be
a really brilliant thing to bring them
back. However, there's a problem. Their
closest living relative is the dong,
which is much smaller, lives off the
coast of Australia. And if the the same
ratio of the size of the mom to the size
of a newborn baby were to hold, then if
we used a dong as a surrogate mom to
de-extinct the stellar sea cow, the
newborn baby would be slightly larger
than its mom,
>> which probably wouldn't work.
>> Here's the thing I saw in recent years
is there was either a sheep or a goat
that was grown in a bag.
>> Yes. Yeah. So this is really fascinating
research and and it's grown in a bag but
not throughout the entire duration of
the pregnancy. So right now we can do
the very earliest stages and we can do
the very latest stages but the middle
parts of pregnancy can't be done outside
of an actual of a of a mammal can't be
done outside of a of a of a of a mom
surrogate mom. We do have a team here at
Colossal who is working on a fully
exogenous artificial womb. Um, starting
of course with something much smaller,
starting on on mice and dunerts, which
is a a marsupial mouse, a little little
tiny carnivorous marsupial
>> to see if we can develop the technology
to take them all the way from
fertilization to birth. The goal of that
team is to eventually be able to do this
for elephants and for mammoths so that
we can have a fully exogenous artificial
scenario that we could use for our
mammoth deextinction project. But you
know this is going to be some time off.
So our first mammoth will have to be
born from an elephant surrogate.
>> Oh my god.
>> But this is a really important stop.
>> Can you define some time off because my
you know talk about science fiction.
[laughter]
Are we talking?
>> A really great project though,
>> a century like
>> No, for a mouse I think we'll we'll get
to a mouse within the next year or so.
Um, and that's the first step. You know,
the one thing that's really interesting
that I didn't know until I started
working with this team is that there are
multiple different styles of placenta
even within mammals and all of these
have really different needs. And so
there will be different pathways that we
take for these different placental
types. Who knew? Biology is amazing and
confusing and really hard.
>> So that's what you said just addressed
the next question I was going to ask you
is why do you have to match the species?
Why can't you put the giant sea cow
inside of a blue whale?
>> Oh, a blue whale. That would be an
interesting idea. Yeah. Well, there are
a lot of reasons and they're mostly
biological which means mostly we don't
understand them. of this. It's one of
the really hard things about even
conservation work is to to use a
surrogate host and they call it
intraecies surrogacy or interspecies
surrogacy. So if we use the same species
as a surrogate, we often have better
outcomes than if we use different
species. And this is even for species
that are relatively closely related to
each other and is just one of the
complicated things about speciation. And
how does this happen? And what does it
mean that suddenly two lineages that
were the same that could interbreed
suddenly at some point in evolutionary
time some change has happened which
means they can no longer interbreed.
Bison and cattle are a great example of
this. We know that they diverged only
around a million or so years ago. That's
not very long ago in terms of, you know,
how long ago species shared a common
ancestor or were the same thing. And
yet, it is very difficult to make hybrid
crosses of bison and cattle. And this is
something that people have tried
desperately to do since the beginning of
the 20th century. Um, there were people
working in agriculture at the turn of
the 20th century who wanted to make
cattle that could be as hardy as North
American bison and therefore live in
pasture land, grazing land in the middle
of North America during really cold cold
winters. And so they thought, this is a
great idea. We'll just breed them
together and we'll make a mixture and
that mixture that hybrid animal will
definitely be able to survive, but also
they'll be chill enough for us to be
able to deal with them because bison
aren't particularly chill, right? But
cattle, they're bred to be chill, right?
>> So, we wanted hardy bison but chill
cattle. And so, they decided to make
hybrids.
>> And it just rarely worked. Just
absolutely most of the time it didn't
work. If there was an animal that was
born, they often weren't fertile or they
weren't very fit. I'm just showing that
these two species are at the edge of
being able to reproduce. Some things had
happened in the course of their separate
evolutionary history that made them not
able to reproduce. But then there are
things like brown bears and polar bears.
They can readily reproduce and make
hybrid offspring. Humans in the we know
that they readily interbred and made
hybrid offspring. So, you know,
evolution is interesting, but it also
makes our lives hard. And so, there's a
lot of of learning that goes into this.
But actually, that's one of the really
brilliant things about working in
colossal in this space of deextinction
is that we are learning things about
biology. We're developing tools. We're
developing computational pipelines that
we can directly apply to living species
to apply these new technologies so that
they don't become extinct. And I love
that part of our mission. It's really
what motivates me um daytoday.
>> Wonderful. Wonderful. So it it sounds
like what you're learning here can
result in understanding general
principles. So what do those numbers
look like today for like the the the
best you can do uh in terms of you know
so for every time I attempt to bring
back or or
take a embryo and implant it into a
womb, what percentage of those tend to
be viable and birthed? And then if it's
something that results from a
manipulation of sorts, what percentage
of those are fit enough to live to
adulthood? And what of those are fit
enough to reproduce or is that, you
know, are we too early to have good
statistics on that kind of
>> Yeah, this is a really great question
and it's something that we're really
going to need to figure out. What's
difficult about that question is that
this hasn't been done a lot. Um, a lot
of the data that we have comes from
mouse models, in which case the the the
ultimate goal is not always necessarily
to have healthy animals, but instead
just to see the consequences of a
genetic manipulation. And so that's not
the path that we would be taking. And so
you can't really take those numbers and
and and fit them directly into what
we're doing. What our path does is
really tries to maximize the potential
that when the animals are born, they're
going to be healthy and they're going to
have the edits, the phenotypes that
we're driving. And you could see this in
our our direwolf work. So we um we had
so many different QC steps, quality
control steps along the path to do this.
Um we wouldn't in in mouse work, for
example, maybe you don't sequence all of
the embryos that you go to implant
because it doesn't matter. there's a
really high throughput and it doesn't
really matter for us. We were absolutely
focused on animal health, animal welfare
and deextinction. And so we spent a lot
of time really carefully looking at
everything we possibly could with what
we had done. We scanned um the
literature to understand what the
potential impacts of the edits that we
wanted to make might be and with any
sort of risk profile we would throw them
out and move on to something else. We
were deeply sequencing the cell lines
throughout the process of of first
isolating them from blood. So we
isolated cells from a blood draw and we
were able to characterize the health of
those cell lines and if they don't look
healthy because normally what happens in
culture is cells because they're
dividing really rapidly, they sometimes
lose chromosomes or lose parts of
chromosomes. And this is just completely
normal. It happens all the time in cell
culture across the board. But of course,
we want to make sure that if we're using
a cell to make an animal, it's a healthy
cell. So, we have to sequence them and
look at them every time they divide. Not
every time, but almost every time they
divide. And then when we have animals,
or not animals yet, but a fertilized
cell, we want to make sure that that
cell is very healthy. So, we sequence
that and make sure that there are only
the edits that we want to make and no
other edits and that as the cell has
been dividing, other strange things
haven't arisen. So, um, we had a very
high success rate, pretty much on par
with other success rates, but it's
partly because we we were so very
adamant about making sure that we were
putting the healthiest cell lines
through that the the decisions that we
were making had the highest chance of
leading to healthy animals at the end.
And and obviously, Romulus, Remis, and
Khesi are are are healthy animals that
are thriving and doing well. and we can
see that they have these traits, these
phenotypes that we intended them to have
and that we were able to drive using
genome engineering.
>> There are certain things that you can
see where the push back is going to come
from before you even take on the work,
right? And you know, it's not for
everybody. What what gives you the
courage to step into this arena and you
know do what you're doing? That's a
great question and you know it's a
question I haven't been asked. I I think
for me the motivation is the future.
It's biodiversity. It's the fact that we
are in the midst of a biodiversity
crisis, an extinction crisis, a crisis
of arable land, of our ability to feed
the people that are alive on the planet
today. And we are doing whatever we can.
All the solutions we have at our
fingertips, we're trying to employ. But
there are new tools. There are tools of
synthetic biology, of genetic rescue, of
cloning, of all sorts of exciting new
developments that we've come up with,
people have invented that we are just on
the cusp of being able to use. And and I
want to step up and say, "Yes, these
things might frighten some people
because they're new, but we can evaluate
risks. We can make informed decisions.
We can perform very slow and very
careful and very deliberate experiments,
and we can develop these tools that we
can use to make sure that in the future,
this planet is both biodiverse and
filled with people." And that's what
keeps me going. Now, let me ask you a
question because this is a thought that
came to my mind some years ago. I might
be the first person to have ever had it
[laughter]
because it's kind of dumb. I'm going to
be honest. All right. But it what it
gets to is I always try to draw a line
between what I actually know and what I
don't know. And here's a thought I had.
I don't know that a planet that is made
up of just humans and the animals that
we eat utilize is gonna result in
everything falling apart. Right? I don't
really know that that's true. But do you
as a scientist in this field know that
that's true? That this loss of
biodiversity really will have an
horrible outcome?
>> That's an interesting way of putting it.
I don't I don't know. I think we don't
fully understand the interconnectedness
between organisms in habitats if we get
rid of everything except for
domesticated species. Do we still have
the structure of these ecosystems that
they need to be able to survive? Are we
forgetting about the stuff that we don't
pay attention to? And I think yes,
obviously we do not fully understand how
animals and plants and microorganisms in
an ecosystem are connected with each
other, how they rely on each other, the
ecological services that they provide,
but we know that these things are
foundationally important. And as we
start pulling them apart, it's like a a
Jenga game. We can take so many of these
pieces out, but eventually everything
crumbles. And and I don't want to get to
that spot.
>> Yeah. Yeah. It would be the equivalent
of living on a starship, [laughter]
right?
>> Yeah. If we could have teleportation and
also one of those devices that makes
whatever we want to eat, that'd be cool,
though. I love that. Yeah.
>> Right. Right. So, uh, as I've studied
ancient life, you know, after a ma after
a major extinction, you know, how
mammals took over the niches that were,
um, you know, no longer occupied by
dinosaur species. So the question I have
is, is there some part of conservation
science where you can actually take an
ecosystem and examine it and recognize
where there are species miss missing in
the niche and then say okay here's what
we need to um do to fill that niche
because another element that I think
might interfere is the fact that you
know a lot of these animals and plants
will evolve together right
simultaneously so they become really
specialized with each other. So is there
some element of that niche
engineering or first niche evaluation
then engineering?
>> Absolutely. And I think this is a really
important point that is often missed. Um
the the Dodo project for example the
we've been working with the Mishian
Wildlife Foundation and Derell's
conservation organization and they've
been working in Maitius for a while.
Doddos have been extinct for you know
several hundred years. They went extinct
within a few decades of people first
appearing on Maitius. And they didn't go
extinct because people hunted them,
which is most commonly believed reason
why they went extinct, but because they
couldn't fly. And they laid a single egg
in a nest on the ground. And when people
arrived, they brought things with them.
Some of them on purpose, like cats and
pigs and later monkeys, and some of them
by accident, rats coming on boats. And
those rats and cats and pigs made an
easy meal of that egg in a nest on the
ground. And because they couldn't
reproduce, they rapidly became extinct.
>> Wow.
>> And so one of the things that we're
trying to do is identify places in
Maitius where we can remove the types of
species that led to the extinction in
the first place to make it a healthy,
safe place for these animals to go back.
And there has been an incredible amount
of work done already in Maitius to this
end. And one of the one of the the
really important projects that they've
been involved with um speaks exactly to
what you're saying. At the same time as
dodos became extinct, they lost an
endemic giant tortoise.
>> Oh. And um they decided many years ago
to reintroduce giant tortoises to some
of these places where they're trying to
reestablish habitat and remove some of
these invasive rodents in particular.
And they brought giant tortoises from
say shells, transllocated giant
tortoises. And they saw that these
tortoises are doing really well. but
also these cascading benefits that they
hadn't predicted that are there because
of as you say these interactions between
plants and animals in an ecosystem. A
lot of plant species had established in
these parts that weren't from Maitius.
But when these tortoises were put back
on the land, those plants had not
evolved alongside tortoises and they did
not have any mechanism to avoid being
eaten by tortoises when they were little
baby plants. But the native plants did.
>> And so you put the tortoises back on the
landscape and all of a sudden the
non-native species started getting eaten
by the tortoises and you saw those
endemic maritian plants come back. Even
ebony trees, they discovered they grew,
they germinated better after passing
through the digestive system of a giant
tortoise. So reinstating, reestablishing
this missing component of this ecosystem
reestablished all of these different
ecological connections that didn't even
imagine were there before they had
actually done this. It's really
impressive and it also tells us right
back to the beginning like how how
intricately interwoven are components of
ecosystems that we don't fully
understand. And to me, this is one of
the reasons why we really do have to
care about biodiversity loss. And not
just biodiversity loss of large mammals,
but biodiversity loss of every component
of these ecosystems, right down to the
microbes that are in the soils.
>> Hey everyone, if you're loving this
podcast, please go ahead and like us or
leave a comment. And also make sure to
subscribe so you never miss an episode.
Your support [music] means everything
and helps us reach more curious minds
like yours. Now back to the show.
You mentioned not just the extinction
but also modifying the species via this
genetic engineering or genetic
modification.
So you know I remember reading somewhere
you know okay we have this percentage of
you know non-African humans have a small
percentage of Neanderthal DNA. Well, I
want to say this one thing because it's
cool and it fascinates me and I'm just
going to leave it there as a little
tidbit for you because I think you'll
find it interesting, too. We're all
pretty familiar with this idea that
everybody out there has somewhere
between 1 and 4% Neanderl DNA in their
genomes. What's less well understood is
that it's a different one to 4%. And if
we go around the world and we grab up
all of the parts of the Neanderl genome
that exist in one person at any part in
the world and we piece them together,
our study, which used this thing called
an ancestral recombination graph, showed
that we could piece together around 93%
of the Neanderl genome, almost all of
it. And that's super fascinating because
it means that if we want to know what it
is that makes humans different, we have
to look in the other 7%. That's the part
of the genome that either people don't
have because of chance, because of
genetic drift, it was lost, or because a
person living with an anatomically
modern human family who had that bit of
Neanderl DNA could not survive as an
anatomically modern human. That is the
part of the genome that we need to find
if we want to know what it is that makes
humans distinct. We also know that there
are some parts that we some DNA that we
inherited from Neandertols that have
gone to higher frequency than would be
expected by chance in human populations.
And the only way that that can happen is
if there is some benefit, right?
>> We inherit DNA either by chance,
mutation or whatever that makes us more
fit. And then that DNA which just means
we have more babies and then that DNA
gets passed on to the next generation.
>> For example, um the people who live at
high altitude who have the capacity to
have the blood flow more easily at high
altitude that is DNA that was inherited
from Neandertols and Denisven that lived
at high altitude and went to high
frequency in those populations. And that
is just a natural way that evolution by
natural selection works. The goal is to
learn all of these things that might
lead to different phenotypes and to be
able then to pick and choose and say I
want um an animal that is resistant to
aven malaria. I want an animal that is
resistant to plague. You know the work
that's going on with the blackfooted
ferret project and this is led by um the
Smithsonian and revive and restore and
um San Diego frozen zoo. The blackfooted
ferret was nearly extinct. It probably
you know it's still endangered. It's
it's it's one of the they call it the
class of 1966. The first species that
were put on the endangered species list
when it was first legislated because it
was thought to be extinct. It's in
trouble today. It's a really successful
captive breeding program. So, they're
doing well, but we introduced plague
into their populations. Plague, the
plague, right? And when they eat a
prairie dog, which is what they do, they
get plague and they die. So, we can
vaccinate them and that sort of thing,
but that that's not, you know, a
long-term conservation strategy.
>> But their evolutionary cousin, the
domestic ferret, evolved alongside
plague and is naturally immune.
>> So, the goal of this project is to
figure out what it is that makes a
domestic ferret naturally immune to
plague in their DNA and then use the
tools of genome engineering to transfer
that genetic resistance to the to
blackfooted ferret. There is an online
database of all the DNA sequences that
have ever been published. It's called
NCBI and there's one in Europe called
Ensemble. They exist. They're publicly
open. They're searchable. But it's not
as easy as look up the gene for plague
resistance or look up the gene you
brought up skin color. There isn't a
gene for skin color. There's a family of
genes that are distributed all across
the genome. Otherwise, we would have two
skin colored people. But we don't. We've
got this whole range and diversity of
skin. What you're doing is you're you're
you're messing with my words because
when I heard it, it it they use a word
like alil, right? And I use the word
gene. So we talk gene, chromosome, mal.
Us regular folks don't know the
difference in these things.
>> Oh [laughter] no, us people who work in
the field don't know the difference. Oh
no, we do kind of know the difference,
but it's all very confusing and and yes,
and they're important, too. So sitting
back, you know, a gene is just one place
in the genome that codes for a
particular protein. though and an alil
will be a version of that gene. But with
the skin color, it's not even a
difference of alals. And there might be
lots of different circulating versions
of a particular gene, but there's also
lots of different genes in the genome
that contribute to what we think of as
skin color or hair color or height. Any
sort of trait that we have that isn't A
or B,
>> um, is going to be something that's
controlled by lots of different genes in
the family. So if you look at people,
it's not just people who are my size.
I'm 5 foot tall and your size. I'm
assuming by looking at you, you are much
taller than 5t tall.
>> 8 foot n. Wow. There's not just 5 foot
tall and 8 foot tall people, but there's
a whole range of people and you are an
outlier. [laughter]
>> 10 sigma. All right. So here
that's a nerd joke if there ever was
one. So in terms of conservation, in
terms of the phrase you use, frozen zoo,
you know, I'm aware of this seed bank in
the Arctic, right? That's there's been a
lot of documentaries talking about this
where they are preserving seeds. Are do
we have a similar DNA bank so that we
could preserve any species for which we
could obtain its DNA?
>> That is a brilliant and extremely timely
question. There are the very first one
of these was in San Diego. was founded
in the 1970s as a way of preserving
cells that potentially someday in the
future could be used to help species
come back. And in fact, there have been
two clones that have been born. Two
species have been cloned from the cells
that are in the frozen zoo in San Diego.
One is a Pzorki's horse and the other is
a blackfooted ferret. There was a
blackfooted ferret that was cloned after
being preserved for almost 40 years in
this tissue culture. And it's a way of
introducing genetic diversity into a
population that has been lost because
that population was big and became
really small. And when it was small, it
loses a ton of diversity. And if you
have an animal that lived back here in
time, they have diversity that's been
lost, we can put it back in that
population. So this sort of we call them
biioanks now. And there are biioanks
that are emerging all across the world.
And they should have backups because you
don't want to lose all your diversity
because there's a power outage
somewhere. should be able to regrow your
cells and share all these things. And
there's been a tremendous push recently,
an international p push to create more
biioanks and to bioank more of the
diversity that's out there. And I think
this is really going to be important as
these new tools for conservation come
online. Having these resources available
to use is going to be fundamentally
important in the future. So let's
collect them now. Bio banks.
>> So here's another question. You
mentioned synthetic life. So what about
synthetic DNA? Is it the case that maybe
we don't even need in the future? Like
this is related to two questions. One is
where where is this all going? Where is
it going generally in you know for the
next century? Where is it going as it
relates to humans? And in terms of the
DNA technologies,
could it be the case that in the future
we could build an entire DNA sequence
from, hey, here's what I want it to be
and just go and make it happen, you
know? So, so instead of saving the
actual DNA samples, you just save some
information about it, right? So, now you
don't need refrigeration.
>> Yeah, that's interesting question. And
and right now the answer is is no. And
that's because biology is complicated in
ways that we don't understand yet. Um,
when when we synthesize DNA, when I talk
about synthetic DNA, I'm not really
talking about synthetic life. I'm
talking about a strand of DNA that we
know the sequence of the letters, the
the A's and C's and G's and T's and how
they stick together and we can like put
them together, stitch them together in a
lab using a machine. So, we're just
making a string of DNA. Now, that string
of DNA is not alive. It is not a life
form, right?
>> I mean,
>> it's information storage. But what's
interesting about cells and also what
makes my job hard is that there is more
information than just the sequence of
those letters. There's information in
sort of they call it epigenetics. It's
the nicks that are around the letters
that tells us where
>> where the chromatin which is what what
sort of protects the DNA is open which
means you can make genes from here or
closed which means you can't make
proteins from here and it's different
during different parts of development.
There's information in the way the
chromosomes fold around each other in
cells. There's information when when we
talk about um developmental biology and
surrogacy. There's a lot of information
about the timing and nature of gene
expression during development that comes
from mom rather than from the developing
embryo in a mammal. And so there's so
much out there that we don't fully
understand that we will understand that
we we have now the computational power
and the the the sequencing power to get
to this. We're beginning to build these
cell atlases and developmental biology
atlases and large databases of DNA. And
we have, you know, large language models
that we can sick on this stuff and say
kind of makes sense of this because my
human brain too small for that, you
know, but uh but so we will eventually
understand way more than we do right
now.
>> But just preserving on a computer
somewhere the genome sequence of an
animal is not as good as preserving that
cell because we can't take that sequence
yet and turn that into a cell that has
all the magic that we need to make that
into an animal or into a plant.
>> Wow. Wow. AI is gonna help us. Well,
[laughter]
>> I mean, it sounds so lame, but it is.
[laughter]
>> Well, I mean, that's what we're saying
about everything now, right? So, that's
the
>> I know.
>> I'm I'm sure I'm not the first person to
think about this, but we have extinct
human cousins. Are we going to bring
them back?
>> I think I think I mean, and this is this
isn't the realm of of reality. This is
the realm of like where is my ethical
line, right? And and I think
>> Neanderls are people, right? And you
can't bring a person back without
getting their consent. I mean, there's a
whole regulatory framework for doing
research on animals compared to doing
research on humans. And it just doesn't
pass that regulatory muster. You know,
we do use regulatory framework for all
the research that we're doing. We have
external independent committees on
animal use and care that we consult with
with for every one of the experiments
that we do.
>> Working on a human, you have to get
what's called informed consent. So, how
do you get informed consent from a
Neanderl to be brought back to life,
right?
>> Simple. You bring them back to life and
ask them.
>> And if they say no,
>> that question answers itself.
[laughter]
>> All right. All right.
Wait, there's only there's one other
answer because you also said we have
dead cousins or all this kind of stuff
and are you going to bring back and I
also get that you're going to bring back
bad guys from history kind of thing.
Wouldn't this be terrible if you do
this?
>> No.
>> But the thing about it is we are a
combination of the letters of our DNA,
the A's and C's and G's and T's that
make up the genes in our genomes and the
environments in which we live. Right? A
and somebody who lived in the past, even
if we could bring them back, so they
were just a clone of who they were in
the past, wouldn't be that person
because the experience, the environment,
everything about it from gestation
onward would be something different. And
anyway, we all know human clones
>> because
>> yeah, identical twins are human clones
and they're not the same person. You you
have friends who are twins. You can't
just replace one for the other when you
want to go have a conversation or you
want to they they are different people
and the same would be true even more so
for clones of over time.
>> So um here's another philosophical
question regarding ethics. You know, I
believe that human intervention isn't
necessarily a bad thing, but generally
that whole idea of using technology to
intervene in natural
um processes, what do you think about
that? You know, I see building a dam as
geoengineering, right?
>> We have been manipulating life around us
since we have existed as a species.
We've been manipulating our habitats,
geoengineering, since we existed as a
species. These new technologies that we
have allow us to do this at a different
rate, perhaps at a different scale. And
so it requires more consideration and
more thought, more evaluation of risks
and rewards. But it is an intervention
just like other interventions have been
in the past. Stuart Brand when he wrote
the forward of the whole earth catalog,
he wrote famously, "We are as gods, so
we may as well get good at it." And I
kind of think there is some truth to
that, right? Like we when when we
decided that we would pick plants at a
particular time and only pick those that
had a certain characteristic, we were
changing the shape of what things were
more likely to survive and get passed on
to the next generation. We think of
conservation as standing aside and
giving things the space away from humans
to be able to survive. But that's not
what it is. Instead, we decide where
things get to live, how many of them get
to live. We we control access to food.
We control predators access to them. We
have extended our control over most
living things on this planet. And the
things that survive and reproduce are
the things that are better able to
survive and reproduce in a world that
has a lot of people.
>> Right?
>> I do say, you know, we talk about risks
and there are always going to be risks
that are associated with technologies
that are new that are not fully
understood, but we can also try to
understand what those risks are and come
up with plans for mitigating risks that
are there. We also though need to
understand the risk of not allowing
ourselves to at least think through
evaluate and consider strongly
implementing some of these new
technologies whether it's biological
engineering synthetic biology or
geoengineering because that decision
also carries risk that we sometimes
ignore. We sometimes pretend that not
doing anything is not making a decision,
but it is making a decision and we know
the consequences of those decisions.
>> Yeah. Yeah. The the the responsibility
of inaction.
Dr. Beth Shapiro, your work is
fascinating and amazing. You are amazing
and fascinating and I just love talking
to you [laughter] anytime you want to
buy me a beer or a coffee.
You're on beer, I think. Let's go for
beer. Yeah, I'll be in DC in a few
weeks. Uh, you know, let me know where
you are and let's do it.
>> Let's do it. I would love [laughter]
that. I'm sorry, but you know, I'm just
curious to no end. And you're what
you're [laughter] doing is really so
amazing.
>> And I get to ask the questions next
time, too, cuz I have a lot of questions
and, you know, turning the tables here
would be a little bit of fun for me.
>> Hey, listen. [laughter] I You got me.
Whatever you want, it's yours. Thank you
so much for joining Particles of Thought
and I know that our listeners are going
to love this. Take care.
>> Thank you for the invitation. I'm really
This has been great. Thank you so much.
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