October 10, 2024 • 40 mins
*Or at least, sort of bringing back mammoths and dodos.
Beth Shapiro is the chief scientific officer at Colossal Biosciences and the author of How to Clone a Mammoth: The Science of De-Extinction. Beth's problem is this: How do you use the tools of modern biology – and hundreds of millions of dollars – to bring back species that have been extinct for centuries? And on another level, Beth’s problem is explaining to the world what it really means (and doesn’t mean) to bring back an extinct species.
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Episode Transcript
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Speaker 1 (00:15):
Pushkin. There's a company called Colossal Biosciences that has raised
over two hundred million dollars and its stated aim is
to bring back the wooly mammoth and also the dodo bird,
as well as a considerably less famous but equally extinct
(00:38):
animal called the thylacine aka the Tasmanian tiger. I have
questions like, why why are private investors putting hundreds of
millions of dollars into this company? And really mostly how
how do you bring back a species that has been
(00:59):
extinct for centuries. I'm Jacob Goldstein, and this is What's
problem the show where I talk to people who are
trying to make technological progress. My guest today is Beth Shapiro.
She's the chief scientific officer at Colossal Biosciences, a company
(01:21):
that is in the business of d extinction. BET's problem
is this, how do you use the tools of modern
biology to bring back species that have been extinct for
hundreds or thousands of years. Also, on kind of a
more subtle level, BET's problem is just defining for the
world what de extinction really means. Before Beth joined Colossal,
(01:44):
she spent decades in academia. She helped to pioneer the
field of paleogenetics, studying the genes of ancient organisms, and
she spent a lot of time studying the Dodo bird.
Tell me about your life with the Dodo.
Speaker 2 (02:00):
I guess my first exposure to the Dodo was in
nineteen ninety nine when I started my PhD at Oxford.
The ancient DNA lab that we were using with in
the back of the Oxford University Museum of Natural History,
and that is so we had to pass by the
Dodo every time we were going to the lab. And
(02:21):
I was, you know, in this field ancient DNA where
we could extract DNA from things, no one was sure
what exactly a Dodo was, what kind of bird it
was most closely related to, And so I thought it
would be really cool if I could use these really
new tools and technologies to be able to solve this
question answer what sort of bird a Dodo is? So
I ask if I could extract DNA from the Dodo.
If they said no, because it is a very specials special,
(02:44):
precious specimen and you have not proven that you are
good at this yet, And so I proved myself. You know,
I extracted DNA from other birds and other things, and
I was having pretty good success with this, and they said, okay,
you can take some grungey bits out of the inside
of the skull of this dodo with these long forceps.
Speaker 1 (03:03):
They have this one Dodo that's an actual Dodo, and
you're like, look, I could I could tell you whatever
the genome of that bird if you just let me
at it.
Speaker 2 (03:12):
Yep, that's well, maybe not the genome, but I wanted
to know at the time what type of bird it was.
And at the time we were the field of ancient
DNA was focusing on extracting mitochondrial DNA, which is a
type of DNA that is inherited maternally, so it doesn't
tell you everything about a species. So there's lots and
(03:32):
lots of mitochondrial DNA in every cell, and there's only
two copies of every nuclear locus that's in the cells.
And so in the early days of ancient DNA, when
we really weren't very good at recovering DNA, we were
focusing on mitochondria. So I wanted to get mitochondria from
this Dodo specimen. So why I could answer this outstanding
taxonomic question, what type of bird is or was a dodo?
Speaker 1 (03:54):
Uh huh, because people were just trying to guess based
on the morphology, based on what it looked like.
Speaker 2 (04:00):
Essentially, Yeah, I mean, taxonomy before DNA really was that
people are comparing the shapes of things. But DNA is
a really unbiased way of reconstructing evolutionary history and it's
really powerful, and so I wanted to be able to
apply that in addition to the morphological data that people
have been collecting for hundreds of years.
Speaker 1 (04:18):
And so they eventually let you at the bird, and
what do you figure out?
Speaker 2 (04:24):
They first let me take some long force ups to
try to scrape some gunk out of the inside of
its skull, and that led to nothing because there wasn't
any DNA and the gunked up bits of gunk from
the inside of the cell. And then they finally let
me cut a tiny little piece of bone out of
its leg and I was able to extract mitochondrial DNA
from that and compare that to all other types of
(04:44):
birds that were hypothesized to potentially be a dodo, and
we discovered that the dodo is a type of pigeon.
It falls within the diversity of pigeons. Most closely related
to a pigeon called the nicobar pigeon, which is a
very strong flyer, very beautiful bird, different a lot different
from a dodo.
Speaker 1 (05:02):
So you figure out that the dodo was a pigeon
that was relatively early in your career, right, and then
spend a long time doing scholarly work, doing academic work.
You eventually sequence the whole Dodo genome, right, and then
eventually what last year you get to Colossal? What made
(05:24):
you want to join Colossal?
Speaker 2 (05:27):
Well, I mean you summarized twenty five years of my
academic history.
Speaker 1 (05:34):
You want to give me a high point along the way.
Speaker 2 (05:37):
Well, you know, I've been working in this field of
ancient DNA, trying to develop tools to be able to
get more DNA out of things, to look at the
nuclear genomes of different species, develop computational approaches to be
able to use the genetic information that we've extracted to
tell us when populations are growing and shrinking, To look
at replacements, to get DNA directly from ancient sediments so
(05:58):
that we can look at what whole ecosystems look like.
And all of this really driving toward understanding how we
can use the past as a sort of completed evolutionary
experiment to try to make more informed decisions of what
we can do to protect and preserve species and habitats
and ecosystems moving forward. I mean, now, when we're deciding
what we're going to do from a conservation perspective, we
(06:19):
look around, we see things are in trouble, and we
use science we make educated guesses about what the best
things are going to be to restore missing ecological interactions
to help make these different communities more resilient or more
robust in the face of these changes. And ancient DNA
lets us do this by showing us how things responded
in the past to massive perturbations to their habitat, whether
(06:42):
that's an ice age or a really warm interglacial, or
the introduction of people or a predator, a different type
of predator into that into that ecosystem. And every time
we would publish this work that we would want to
tell people about it, we would we would want to
explain to people what it is that we're excited about,
But often the only question that people wanted answered was
(07:04):
what does this mean about how close we are to
bringing these species back to life?
Speaker 1 (07:09):
Kind of fighting that right, like you write about it
like there's I was reading the twenty twenty edition of
your book How to Clone a Mammoth, where you said
the present focus on bringing back particular species, whether that
means mammoths, Dodo's passenger pigeons, or anything else, is misguided, right,
which seems tell me about that? Is there a point
(07:32):
where you stop thinking it's misguided?
Speaker 2 (07:34):
You know, there's a lot of complications. There a biological, technical,
and ethical challenges associated with bringing extinct species back to life,
And so you ask what is misguided? When people hear
about de extinction or the word de extinction, or think
(07:54):
about bringing mammoths back to life, what they imagine is
recreating something that is identical in every way to a
mammoth that used to be alive. But that isn't possible, right,
And I think that is where I find the push
to this to be misguided. As I said at the time,
(08:15):
it's a little bit more nuanced than just as explained.
So what is misguided is this idea that de extinction
is a solution to the extinction crisis. Right, once a
species is gone, we can't bring it back. That species
is gone. What we can bring back are some of
these core phenotypes, whatever it was that was about that
(08:40):
species that made it unique in their habitat some way
of replacing that missing ecological interaction. But it's not by
resurrect something that's identical to the species that used to
be there, but by taking species that are alive today
and tweaking them using the tools of genetic engineering, so
that they can fit into that ecosystem, so they can
play some of those roles ecological roles that the extinct
(09:04):
species once had. Does that make sense?
Speaker 1 (09:07):
It does? It seems somewhat at odds with the sort
of public messaging of Colossal Right, Like I was reading
your writing on all of what you're saying makes sense
and we can talk more about it. But it is
the case that like the homepage of Colossal Right Now says,
we endeavor to jumpstart nature's ancestral heartbeat to see the
(09:30):
wooly mammoth thunder upon the tundra once again, right, which
is not to see the Asian elephant with some phenotypical
traits of the wooly mammoth. Like, so, I don't know,
like how do you reconcile those? Is it? Just like
there's sort of a public story that needs to be simplified,
just because that's the nature of public stories and then
(09:50):
a more complex technical story.
Speaker 2 (09:53):
If you dive into the website on Colossal, it does
explain that the idea of the extinction includes resurrecting extinct
traits using extinct genomes, but also engineering that we are
taking Asian elephants and engineering them to have and express
some of these mammoth trades. On the website, they're even
called Arctic adapted elephants in several places. So I think
(10:14):
it depends on what you're willing to accept as a mammoth. Right,
if you are only ever going to accept something that
is ecologically, genetically and physiologically one identical to a species
that used to be alive, then that's not what we're doing,
because that's not possible. But if you are willing to
accept an elephant that has longer hair, slightly larger back,
(10:37):
the longer curved tusks, that is capable of living in
the habitat that mammoths once lived in and playing the
roles that mammoths once played, then that is Colossal's goal,
and that is what we are we are saying that
we are making.
Speaker 1 (10:51):
Has your view on sort of what scientists should try
and do, or how they should talk about it, or
anything along those lines changed over time, like this idea
of the extinction, which I don't want to get too
caught up in the semantics, right. I understand that it
can mean different things different people, and that there's a
kind of subtle meaning of it, but like, has your
(11:13):
view in fact changed it all over time?
Speaker 2 (11:16):
My view is that the idea of de extinction is
exciting because it allows us to write down a long
list of all of these challenges that we would need
to be able to solve if we were going to
do this, and along the way we come up with
new technologies and new ideas and new associations that have
application to present day conservation work as well as to
(11:39):
extinction work. My idea of whether de extinction, if you
define it as bringing something back that is one hundred
percent identical to a species that used to be alive,
is impossible, has not changed, right. I don't like the
idea that people would say that that is what we're doing,
because I think then that gives people license to imagine
that extinction isn't a problem. But extinction is a problem,
(12:02):
and this is not a solution to that problem. But
am I willing to say that we shouldn't try this,
that we shouldn't develop these tools that may have application
to helping species not become extinct because we're worried that
somebody is going to get tied up in the semantics
of something and accuse us of something we're not. No.
Am I sad that Ben Lamb has been able to
(12:23):
raise two hundred and twenty five million dollars to be
able to invest into developing these tools that I hope,
I imagine are going to dramatically impact the way that
we do by diversity conservation moving forward. No, I think
this is amazing. I think it's a fantastic opportunity that
we should celebrate.
Speaker 1 (12:43):
Great since you mentioned that that Ben Lamb, the CEO
of the company, has raised two hundred and twenty five
million dollars, Like, what what is the business model? You know,
it's a it's a private company, right, it's not a nonprofit.
So how are the investors going to make a profit?
Speaker 2 (13:02):
You know, this is that's a Ben question. It's not
a me question. I'm the chief science officer. But you know,
some of the ways that the company will make money
is along the path toward the extinction. There are a
ton of technologies that are going to be developed, things
like multiplex genomediting, different approaches to driving genetic changes. We're
working on an artificial womb as one of the tools,
(13:23):
and all of these will drive patents that will be
useful for things outside of the extinction landscape. Ben has
promised that any technology that we develop for conservation can
be applied to conservation without having to pay for that.
So he's promised that that tools that we develop will
go to conservation at no cost. But the path toward
(13:44):
toward bringing in investment return for investors really is in
the space of being at the absolute cutting edge of
genetic engineering and that sort of science.
Speaker 1 (13:53):
Right, And a company was already spun out sort of
in that way, right, is it form Bio that's spun
out of a spun out of Colossal and is a
sort of kind of platform genetics, Like, yes, it's.
Speaker 2 (14:05):
A software company's sort of developing tools that we really
need to be able to track what we're doing all
the different experiments that are going on in Colossal that
have to do with a different species, so that we're
not repeating experiments, but it's super useful for being able
to refine experimental designs. And so that is a spinout
company that's working on developing software platforms for other industries
(14:27):
including drug development, etc.
Speaker 1 (14:29):
So let's talk about how it works and sort of
what you've figured out and what you still have to
figure out. And I know how it works is different
for different species. So tell me about the plan with
the mammoth.
Speaker 2 (14:42):
Sure, So, there are lots of different steps toward figuring
out how to take an Asian elephant and turn it
into an Arctic adapted elephant that we would let's call
a mammoth, defending on whether you're willing to say that.
The first step is to figure out the link between
the genotype, the a's and c's and g's and t's
that make up on organism's genome and the phenotype or
(15:06):
the way that organism looks and acts. For this, we
collect a lot of information, go out into the field,
collect a lot of mammoth bones, sequence high quality whole
coverage genomic data. We have academic collaborators who are helping
with that, Luvo de Lens Lab and Stockholm is a
major advisor to this group. We have now more than
fifty high coverage genome sequences from mammoths, and we can
(15:30):
compare these to genome sequences from Asian elephants and African
elephants and other afrotherorians, so they differentiate all mammoths from
everything else that's there. As a way to start to look,
we can get information from doing experiments like looking and
see what genes are being expressed during tusk development, or
what genes are being expressed in the follicles that produce
(15:51):
long hair. As another way of narrowing down where our
fosi should be as far as identifying these genes that
we want to change. Once we have a panel, we
then have to engineer those and so for this we
take cells from elephants that are growing in a dish
in a lab. A few months ago we released a
pre print and now we have the paper under revision
(16:11):
where we were able to derive induced play potent stem
cells from elephants. This is something people have been trying
to do for a long time and our mammoth team
was successful in doing this. This is really cool and
useful for us because it means that we have cell
lines that are healthy and happy and survive in a
dish that we can transform into different tissue types. So
(16:32):
if we have hypotheses about whether this particular DNA sequence
change causes changes in hair growth, we can make a
type of organoid where we can test that hypothesis. So
we don't have to make an elephant in order to
test our hypothesis. We do this in culture.
Speaker 1 (16:48):
So, dumb question, in that particular example you gave, would
there actually be like hair growing out of the dish
in the lab?
Speaker 2 (16:57):
Yes?
Speaker 1 (16:59):
That's rad okay, So you have that, which is a
useful sort of platform, right, A useful tool certainly to
test hypotheses about, well, what genetic changes lead to what
phenotypical changes right? Go on? Right?
Speaker 2 (17:15):
So then after you do that, you have your your
cells growing in addition to lad that you've engineered all
of your edits into. So I've probably skipped over there.
Lots of very difficult challenging biology. Identify what genes we're
interested in, figure out how to edit these the genomes
and cells to get all those changes in them. And
we have teams of people who are working on multiplex
(17:36):
genome editing, replacing large chunks of DNA rather than just
making single edits to the DNA sequence lots of different
approaches that are developing new tools, new ways of doing
genome engineering that of course have application outside of the
field of the extinction or mammoth or any of these
other cells. Then once you have your edited cell, you
(17:56):
do cloning, sematic cell nuclear transfer, the same process that
brought us Dolly the sheep. You have planted that into
a host, and then eventually your animal is born. So
all of that is very hard. I have summed cross
very hard, difficult, challenging things, and in elephants in particular,
one of the one of the groups that we have
at Colossal is an EXODEV group or artificial boom group,
(18:18):
with the idea of eventually being able to do all
of this without needing a surrogate hoast, without needing to
use a female elephant to get there. The mammoth project
obviously has a very long timeline.
Speaker 1 (18:31):
In terms of the sort of macro side. So that
was a description of the cellular level for the most part. Right, Like,
you're starting with an Asian elephant, which I understand is
quite similar genetically to the mammoth, Right, like more than
ninety nine percent the same genetically, is that? Right?
Speaker 2 (18:52):
That's right?
Speaker 1 (18:53):
How different does an Asian elephant look from a mammoth?
Speaker 2 (18:57):
I don't think I've quantified that.
Speaker 1 (18:58):
What do you think? I don't have any idea. I mean,
how much bigger is a mammoth at the same size?
Speaker 2 (19:04):
The size is not a is not one of the changes.
I mean, a mammoth has a slightly different shape, but
has a different, different tusk shape, and it's obviously harrier.
Speaker 1 (19:16):
And how far along is that project? I suppose one
kind of milestone is implanting some genetically modified elephant that's
a little bit more mammoth like into an Asian elephant.
When do you think that might happen?
Speaker 2 (19:33):
I always tell Ben and also the comms team here
that I am not going to answer timing questions. I
would love to be able to predict the timing of
scientific innovation, but I want my teams to be able
to do good scientific work and to think hard about
the experiments that they're doing, rather than to work against
an externally imposed deadline. Now, George and Ben and Ariona
(19:57):
have said that they plan to have this happen before
twenty twenty eight, and I, as far as I know,
this team is on goal to being able to do this.
Before the implantation, and that that would be fascinating. Now
it is not going to be all of the genetic changes, right,
It's not going to be absolutely everything, but you're writing
(20:18):
that it is an important first step to try to
get there. We have a separate team called our Animal
ops team, who's really it's made of people from the
veterinarian zoo community who are working with the animals, who
are working to try to really learn what these animals
need to be physically and psychologically healthy and captive environments
to learn about processes like OPU, which means ovum pick up.
(20:41):
This is how do we get eggs from these animals
that are going to be the surrogate hosts for somatic
cell nuclear transfers. We're also working with the community of
people who are doing the Northern white Rhino Southern White
Rhino project because you know, what we learn in one
species we can apply to other species. But there are
lots of very hard problems to solve there, but they're
also important problems for the future of those species. So
(21:04):
remember that anything that we learn as we push toward
a mammoth is also something that we can apply to
elephant conservation and to rhino conservation. So this is all
work that is hard, but I appreciate that we have
the opportunity and the finances to be able to put
the energy into it.
Speaker 1 (21:25):
And so, setting aside the understandably sensitive question of specific timelines,
talk about the sort of happy outcome for the mammoth
project in whatever timeframe it may happen, If it sort
of works, what does that look like in the world.
Speaker 2 (21:45):
The long term happy outcome to me is that we
have structured communities of animals that are able to live
in an environment that is really similar to the wild
environment to replace whatever ecological interactions are missing because of
their extinction. And this happy outcome to me, where we
(22:05):
have grandparents and parents and offspring that are all living
in a wild habitat somewhere. This is not a near
term solution. Elephants have twenty two months gestation. They reach
sexual maturity when they're teenagers. So this is something that
I can tell you isn't going to be by twenty
twenty eight or twenty thirty, right. This happy outcome of
(22:26):
an entire population or community of animals living in the
wild is.
Speaker 1 (22:31):
That is a sort of kind of human lifetime's time
scale this's a one hundred years story, absolutely, And what
I mean would that be Siberia? Is it basically the tundra.
Speaker 2 (22:41):
It wouldn't necessarily have to be Siberia, wouldn't necessarily have
to be Alaska or the Yukon. Remember, mammoths lived everywhere
from temperate to subtropical zones. They live throughout warm intervals
and they live throughout cold intervals. But where these ecosystems
have been most changed by their absence is the Arctic
and places where the plant community has changed a lot.
(23:03):
There are lots of missing animal species. We know elephants
are engineers of their ecosystems. There's no and to suspect
mammoths wouldn't have similarly been engineers of their ecosystem in
the past.
Speaker 1 (23:16):
In a minute, why bringing back the dodo maybe even
harder than bringing back the mammoth. Tell me about the dodo.
Give me like a dodo one on one.
Speaker 2 (23:35):
Well, based on sort of written records from the first
people who saw them, So dodos lived on this island.
They were a flightless bird, so about the sides of
a really big chicken, and they probably ate fruit. They
had a big beak that was probably able to crush
fruits and seeds and things like that. We don't know
much about their color. The people who drew them, they're
(23:57):
very Some of them looked like they couldn't have actually
stood up according to the to the way that they've
been drawn. It's funny because most people who drew a
dodo never saw one, because dodos went extinct within a
couple of decads after the first person set foot on
Borucius Island. And it wasn't because people ate them. There
are some written records that suggests that they didn't taste
very good, but because when people arrived in Mauritius, they
(24:20):
brought things like cats and pigs and rats, and dodos
laid a single egg and a nest on the ground
because they couldn't fly, and the things that we brought
with us, that people brought with us just ate all
the eggs. And if you can't, you can't have offspring,
then you're not going to survive.
Speaker 1 (24:37):
Yeah, a single egg and a nest on the ground
is like a perfect I mean, it's not a metaphor
because it's real. It's just so wildly vulnerable, right, it's
just so vulnerable. So okay, so you're trying to bring
back the Dodo or something like the Dodo, and I
understand that one particular challenge there is you actually can't
(24:57):
use the same cloning technology that people have been using
for decades for mammals. Right, tell me about that.
Speaker 2 (25:04):
It's not possible to clone birds the same way that
we clone mammals because of the intricacies of their reproductive system.
So the way that Colossal is working on this problem
with birds and is similar to way that other teams
have been doing this. There's a person called Mike McGrew
who's in Edinburgh, the Roslin Institute, who's developed a lot
of this technology for chickens, but that's the only bird
(25:26):
species so far for with this technology exists, and we're
working on that now for pigeons for the Dodo project.
So the idea is when the egg is laid, the
cells that are called primordial germ cells. These are the
cells that will eventually become germ cells, either sperm or eggs,
depending on the biological sex of the animal. They are
(25:46):
circulating throughout the bloodstream of the developing embryo. They're on
their way to the gonads, which don't exist yet because
it's not that stage of development yet, and at that
point you can stick a needle into the egg very carefully.
I've actually seen our DODO lead do this a few times.
It's pretty impressive how you do this. And you can
suck out a little bit of that circulating blood without
harming the embryo, and you can put that in a
(26:08):
dish in a lab and if you understand what the
right culture conditions are for those cells, you can keep
those cells alive. Then they'll start to grow and make
lots more of themselves, and then you can edit those cells.
And then because those are edited, you can inject them
into an embryo at that same developmental stage and they
will circulate around the bloodstream established in the gonads, and
(26:31):
that chick will be chimeric. Right. It will not be
edited itself, but it's sperm or it's eggs will be edited.
And then you can, if it's a female, you will
fertilize it with edited sperm and then when it lays eggs,
those eggs will hatched into the edited offspring.
Speaker 1 (26:49):
And so I mean is that I don't know if
it's a dumb question to ask, Is that the hardest
part of the DODO like project that whole idea, or
there's so many.
Speaker 2 (27:00):
Hard parts, oh the hardest part. Yeah, though, there are
a lot of hard parts. But you know, this is
a situation where we currently don't have any way of
driving gene edits into bird species. The birds are among
the most endangered species on the planet, especially on islands,
and if we can develop these technologies of being able
to keep these germ cells alive and different species in
(27:21):
addition driving these edits into them, and show that we
can do this, then this is a tool that we
could use, for example, to help make Kawaiian honeycreepers resistant
to avian malaria, or drive resistance to diseases of other
bird species that are impacted by changes to their habitat,
a lot of which have been caused by changes in
the way that people have used the landscape.
Speaker 1 (27:44):
And then talk about the long happy story for the dono, like,
how does that story go?
Speaker 2 (27:53):
We have collaborations with the Russian government and Russian Wildlife Foundation.
This is an island country that is very proud and
very excited about doing conservation work and have an incredible
track record of success there as well. They have several
islands that are off of them mainland that they've been
doing removal of invasive species and replacements sometimes with proxy species.
(28:15):
For example, one of the species that went extinct at
the same time as the dodo is a giant tortoise,
and they have replaced on some of these islands. There's
an island called Round Island, another called eulok Agret where
they've put giant tortoises from Seychelles, And what they've seen
is that having these giant tortoises on the landscape have
(28:36):
been able to help out with their invasive species removal
programs and really change the shape and face of that
floral and faunal community. So it turns out that ebony
trees germinate better after they've passed through the digestive system
of a giant tortoise and many of the other endemic
plant species because they evolved alongside tortoises. They have anti
(28:56):
tortoise or bivory like really sharp little baby leaves for example,
that tortoises can't eat. So the tortoises are consuming all
of the non native species, the species that have been
introduced and leaving behind the endemics species that are now
coming back because of the replacement of this animal on
the landscape, and they hope that by replacing this other
key member of that extinct foneal community, a forgivorous bird
(29:21):
that had a very strange shaped face that's able to
move around and consume fruits and do similar things, I mean,
maybe not even things that we've imagined yet, that this
will will really help them to help them in their
restoration projects. One thing that's clear though, is that even
the idea that there might be a Dodo at some
(29:41):
point has caused a reinvigoration of the excitement of other
people for their conservation programs, and they've seen renewed investments
in creating habitats that dodos might someday be in. They
are really excited about working with us on setting up
places where we can have aviaries for some of these
early birds, because obviously we would love to have them
back there. They're Marsian animals, so they should they should
(30:02):
be there, And so yeah, this is it's been a
it's been I've got to go to Murcius in June
this year and interact with see some of these sites
and interact with some government officials, and the excitement for
having a Dodo and Mauritius is really palpable. It's it's
exciting to be part of.
Speaker 1 (30:19):
What you're trying to do is wildly hard. It's like
kind of amazing, as you alluded that somebody was able
to raise two hundred million dollars for this very hard,
not obviously commercial project. And so I don't know, you're
in a really interesting spot, right, Like you've been studying
this at an academic setting for twenty ish years. Now
(30:40):
you're at this company that's that strangely amazingly has raised
hundreds of millions of dollars to do this hard thing.
Like where are you right now?
Speaker 2 (30:49):
What I like about this project is that, as we've said,
as you've said here, everything that we're doing is really hard.
Speaker 1 (30:56):
Right.
Speaker 2 (30:57):
But as we look around the planet today, what we
see are ecosystems, species, and populations and communities that are
in trouble, And what we have is decision anxiety. What
do we do? How can we help? Where do we
even start? Right? But this project, what it forces us
(31:17):
to do is write down all of the steps that
we need to do to answer this really hard problem,
to get to the end of this really hard solution.
And that now that we've had them written down, means
that we can just go and start knocking them down. Right,
here's problem we have to solve. Here's a problem that
has to do with rewilding and restoration that we have
to solve. In order to solve that, there are all
(31:38):
of these other problems that have to do with invasive
species on the landscape that are going to eat the
dodo's eggs on the ground. How do we solve those?
Who do we partner with to solve those? It's not
all Colossal's job, right, but we do want to enable
it because we want to create an environment where we
can be successful and our partners can be successful. And
our partners are nonprofit conservation groups and governments and local
(32:01):
communities who want these things to happen. But by saying
we're going to do it, we've enforced you got to
write down the problem, We got to figure out how
to solve them.
Speaker 1 (32:11):
And I love that.
Speaker 2 (32:12):
I think that this motivation to get there is going
to solve is going to help so much as we
try to figure out what we can do as a
global community to try to stem the biodiversity loss crisis
that we're facing today.
Speaker 1 (32:28):
We'll be back in a minute with the lightning round.
I have read that you have a tattoo of a dodo.
First of all, is that correct?
Speaker 2 (32:48):
It is yes.
Speaker 1 (32:49):
If you are going to get a tattoo of another
animal extinct or not, what would it be.
Speaker 2 (32:55):
I promised our thylacine lead Sarah that when she delivered
a thylacine I would get a thilocine tattoo. I haven't
decided what it will look like or where it will be,
but that's that's.
Speaker 1 (33:07):
Probably what's the thylacine look like?
Speaker 2 (33:10):
Well look it up. It looks like it looks like
a weird stripey large marsupial wolf.
Speaker 1 (33:17):
I've heard it called the Plasmanian tiger. I know us Okay,
that seems like a cool animal to get a to
get a tattoo of. What's the most dangerous or sketchy
thing you did to get a piece of ancient DNA?
Speaker 2 (33:41):
The most dangerous or sketchy thing I did? You know?
I try not to do any dangerous or sketchy things.
Let's see, I have written on Russian helicopters. That's pretty
dangerous and sketchy to try to get out into the field.
We did once time one time get left in the
field for an extra couple of weeks because these same
helicopters got a better deal taking some wealthy people fishing
(34:03):
for a little while rather than pick up some scientists
that they were supposed to pick up.
Speaker 1 (34:08):
Were you out getting mammoth DNA? What were you doing.
Speaker 2 (34:11):
We're collecting just fossils from Arctic species. I've worked a
lot on muskogs and bison and horses and species like that.
So we were out just in the field collecting bones
for future work. Yep.
Speaker 1 (34:25):
Yeah, we haven't talked all about dinosaurs. Are you tired
of people asking you about dinosaurs? No?
Speaker 2 (34:30):
I mean it's something that people are excited about. There's
no DNA in dinosaurs, right, So the oldest DNA that's
been recovered could be escas escaviller Slav's ancient plant DNA,
which is from sediment that might be about two and
a half million years old. The oldest DNA from bones
are mammoth bones that were frozen in permafrost for more
than a million years, maybe as long as two million years.
(34:52):
But dinosaurs have been extinct for more than sixty five
million years. There is no dinosaur bone out there that
still is organic. They're all fossils that organic material has
been replaced. So we're not going to get dinosaur DNA.
Speaker 1 (35:05):
And there's not even like a theoretical way. It's sort
of like a laws of physics of problem, like fundamental
laws of biology say, we're just not going to get it.
Speaker 2 (35:12):
We're not going to get dinosaur DNA. Yeah, I've tried
even the amber thing like smashing stuff up and getting
because I answer that, yeah, of course. You know why.
You can only be asked that question at least four
hundred or five hundred times before you're like, well, you know,
I'm just.
Speaker 1 (35:28):
Gonna just try it. Time some asshole asked me, I
could say I did it. It didn't work. What's the
oldest DNA that you have ever retrieved?
Speaker 2 (35:39):
Me, personally working in a lab touching samples, the oldest
DNA that I've recovered is from a horse that's probably
around eight hundred thousand years old, somewhere between seven hundred
and eight hundred thousand years old, horse like animal. In fact,
we thought it was a horse, but it turns out
that it is a type of extinct donkey. Well not
even really, that it's slightly more closely related to donkeys
(36:01):
than it is to horses. It's in that lineage, but
it's a species that really hasn't been known to paleontology,
but now we have a whole genome from it.
Speaker 1 (36:08):
So that's fun. Was one surprising thing about the Dodo.
Speaker 2 (36:13):
Surprising thing about the Dodo, I guess I was mostly
surprised very early in the beginning of my experience with
the Dodo that it's a pigeon.
Speaker 1 (36:27):
Well, that's a sign of a good paper, right the
side of a good finding. What's the worst thing about
winning a MacArthur Genius Grant That.
Speaker 2 (36:36):
People ask you what you're going to do with the money,
Like everybody expected you're going to have something really profound
to do with the money that they give you over
the course in the next few years.
Speaker 1 (36:47):
The real answer, just stop writing grants all the time
for the next three years.
Speaker 2 (36:51):
No, do you know what I did with it? I
used it for childcare.
Speaker 1 (36:55):
You know.
Speaker 2 (36:56):
It actually made it possible for me to be a
very young mom trying to run a lab and get
myself off the ground, you know, if I was able
to use it to help my kids.
Speaker 1 (37:08):
So that's actually a really interesting answer, Like it's a
really that's a really interesting answer. I know you might
not be the right person asked this question, but you're
the one I'm talking to, so you know, it was
interesting to me looking at that at the last round
of funding that Colossal got that it came part of
it came from you know what I'm gonna say, part
(37:29):
of it came from in q TEL, the venture capital
fund set up by the CIA. What does I know
it's not actually the CIA, But what does this CIA
VC fund want with you?
Speaker 2 (37:41):
I don't think this is things I can talk about.
And actually I think you know, inq TELL are just
really interested in knowing what's happening, and they like to
be involved in things that are really at the cutting
edge of any sort of new discipline, and I think
their interest is just, you know, we want to know
what you're doing.
Speaker 1 (37:57):
Fair Enough, I'm going to mix metaphors on this one.
Do you have a white whale? Like, is there some
particular species or even just technique or something? Is there
so thing you've been trying to figure out how to
do that you haven't figured out yet that you really
want to figure out.
Speaker 2 (38:16):
Figure out how to make a mammoth? Now, well, I mean.
Speaker 1 (38:22):
All of this. Can I end on that? Could I
end on that? Please?
Speaker 2 (38:28):
We're gonna do it. We're I think we're on the path,
but it's there are definitely a lot of things to
solve still, So yeah, it's a white whale. Isn't a
white whale something that you think you're not going to solve?
I don't, I don't.
Speaker 1 (38:40):
I don't really know the I mean it's from Moby
Dick and Ahab is like his whole thing is he's
got to get the white whale. I mean, it ends
up killing him, but we don't have to think about
that part. It's the thing that he has driven to
get but that he has not yet gotten.
Speaker 2 (38:53):
I guess that's the right answer, you know, let's get there.
Speaker 1 (38:57):
Is it a dodo?
Speaker 2 (38:57):
Though for me? It might be a dodo for me?
Speaker 1 (38:59):
Do you think do you think? I mean? Well, I
I We're going to get back to the semantic question.
And that's a dumb thing to end on, but I
do want to ask, like, do you think you're gonna
make it? And I know it's a dumb question, but
it's also not a dumb question, right, like one wants
to ask it.
Speaker 2 (39:16):
Absolutely, you know there's and I accept something that looks
and acts like a dodo, that can fit into that environment, that.
Speaker 1 (39:23):
Can do like a do and it quacks. Though, do
we know did a dodo quack? Problem? Cool? It was
a pigeon.
Speaker 2 (39:29):
It cools, right, it coos yeah.
Speaker 1 (39:36):
Beth Shapiro is the chief Scientific Officer at Colossal Biosciences.
Today's show was produced by Gabriel Hunter Chang. It was
edited by Lyddy Jean Kott and engineered by Sarah Bruger.
You can email us at problem at Pushkin dot fm.
I'm Jacob Boldstein and we'll be back next week with
another episode of What's Your Problem As
Pushkin. There's a company called Colossal Biosciences that has raised
over two hundred million dollars and its stated aim is
to bring back the wooly mammoth and also the dodo bird,
as well as a considerably less famous but equally extinct
(00:38):
animal called the thylacine aka the Tasmanian tiger. I have
questions like, why why are private investors putting hundreds of
millions of dollars into this company? And really mostly how
how do you bring back a species that has been
(00:59):
extinct for centuries. I'm Jacob Goldstein, and this is What's
problem the show where I talk to people who are
trying to make technological progress. My guest today is Beth Shapiro.
She's the chief scientific officer at Colossal Biosciences, a company
(01:21):
that is in the business of d extinction. BET's problem
is this, how do you use the tools of modern
biology to bring back species that have been extinct for
hundreds or thousands of years. Also, on kind of a
more subtle level, BET's problem is just defining for the
world what de extinction really means. Before Beth joined Colossal,
(01:44):
she spent decades in academia. She helped to pioneer the
field of paleogenetics, studying the genes of ancient organisms, and
she spent a lot of time studying the Dodo bird.
Tell me about your life with the Dodo.
Speaker 2 (02:00):
I guess my first exposure to the Dodo was in
nineteen ninety nine when I started my PhD at Oxford.
The ancient DNA lab that we were using with in
the back of the Oxford University Museum of Natural History,
and that is so we had to pass by the
Dodo every time we were going to the lab. And
(02:21):
I was, you know, in this field ancient DNA where
we could extract DNA from things, no one was sure
what exactly a Dodo was, what kind of bird it
was most closely related to, And so I thought it
would be really cool if I could use these really
new tools and technologies to be able to solve this
question answer what sort of bird a Dodo is? So
I ask if I could extract DNA from the Dodo.
If they said no, because it is a very specials special,
(02:44):
precious specimen and you have not proven that you are
good at this yet, And so I proved myself. You know,
I extracted DNA from other birds and other things, and
I was having pretty good success with this, and they said, okay,
you can take some grungey bits out of the inside
of the skull of this dodo with these long forceps.
Speaker 1 (03:03):
They have this one Dodo that's an actual Dodo, and
you're like, look, I could I could tell you whatever
the genome of that bird if you just let me
at it.
Speaker 2 (03:12):
Yep, that's well, maybe not the genome, but I wanted
to know at the time what type of bird it was.
And at the time we were the field of ancient
DNA was focusing on extracting mitochondrial DNA, which is a
type of DNA that is inherited maternally, so it doesn't
tell you everything about a species. So there's lots and
(03:32):
lots of mitochondrial DNA in every cell, and there's only
two copies of every nuclear locus that's in the cells.
And so in the early days of ancient DNA, when
we really weren't very good at recovering DNA, we were
focusing on mitochondria. So I wanted to get mitochondria from
this Dodo specimen. So why I could answer this outstanding
taxonomic question, what type of bird is or was a dodo?
Speaker 1 (03:54):
Uh huh, because people were just trying to guess based
on the morphology, based on what it looked like.
Speaker 2 (04:00):
Essentially, Yeah, I mean, taxonomy before DNA really was that
people are comparing the shapes of things. But DNA is
a really unbiased way of reconstructing evolutionary history and it's
really powerful, and so I wanted to be able to
apply that in addition to the morphological data that people
have been collecting for hundreds of years.
Speaker 1 (04:18):
And so they eventually let you at the bird, and
what do you figure out?
Speaker 2 (04:24):
They first let me take some long force ups to
try to scrape some gunk out of the inside of
its skull, and that led to nothing because there wasn't
any DNA and the gunked up bits of gunk from
the inside of the cell. And then they finally let
me cut a tiny little piece of bone out of
its leg and I was able to extract mitochondrial DNA
from that and compare that to all other types of
(04:44):
birds that were hypothesized to potentially be a dodo, and
we discovered that the dodo is a type of pigeon.
It falls within the diversity of pigeons. Most closely related
to a pigeon called the nicobar pigeon, which is a
very strong flyer, very beautiful bird, different a lot different
from a dodo.
Speaker 1 (05:02):
So you figure out that the dodo was a pigeon
that was relatively early in your career, right, and then
spend a long time doing scholarly work, doing academic work.
You eventually sequence the whole Dodo genome, right, and then
eventually what last year you get to Colossal? What made
(05:24):
you want to join Colossal?
Speaker 2 (05:27):
Well, I mean you summarized twenty five years of my
academic history.
Speaker 1 (05:34):
You want to give me a high point along the way.
Speaker 2 (05:37):
Well, you know, I've been working in this field of
ancient DNA, trying to develop tools to be able to
get more DNA out of things, to look at the
nuclear genomes of different species, develop computational approaches to be
able to use the genetic information that we've extracted to
tell us when populations are growing and shrinking, To look
at replacements, to get DNA directly from ancient sediments so
(05:58):
that we can look at what whole ecosystems look like.
And all of this really driving toward understanding how we
can use the past as a sort of completed evolutionary
experiment to try to make more informed decisions of what
we can do to protect and preserve species and habitats
and ecosystems moving forward. I mean, now, when we're deciding
what we're going to do from a conservation perspective, we
(06:19):
look around, we see things are in trouble, and we
use science we make educated guesses about what the best
things are going to be to restore missing ecological interactions
to help make these different communities more resilient or more
robust in the face of these changes. And ancient DNA
lets us do this by showing us how things responded
in the past to massive perturbations to their habitat, whether
(06:42):
that's an ice age or a really warm interglacial, or
the introduction of people or a predator, a different type
of predator into that into that ecosystem. And every time
we would publish this work that we would want to
tell people about it, we would we would want to
explain to people what it is that we're excited about,
But often the only question that people wanted answered was
(07:04):
what does this mean about how close we are to
bringing these species back to life?
Speaker 1 (07:09):
Kind of fighting that right, like you write about it
like there's I was reading the twenty twenty edition of
your book How to Clone a Mammoth, where you said
the present focus on bringing back particular species, whether that
means mammoths, Dodo's passenger pigeons, or anything else, is misguided, right,
which seems tell me about that? Is there a point
(07:32):
where you stop thinking it's misguided?
Speaker 2 (07:34):
You know, there's a lot of complications. There a biological, technical,
and ethical challenges associated with bringing extinct species back to life,
And so you ask what is misguided? When people hear
about de extinction or the word de extinction, or think
(07:54):
about bringing mammoths back to life, what they imagine is
recreating something that is identical in every way to a
mammoth that used to be alive. But that isn't possible, right,
And I think that is where I find the push
to this to be misguided. As I said at the time,
(08:15):
it's a little bit more nuanced than just as explained.
So what is misguided is this idea that de extinction
is a solution to the extinction crisis. Right, once a
species is gone, we can't bring it back. That species
is gone. What we can bring back are some of
these core phenotypes, whatever it was that was about that
(08:40):
species that made it unique in their habitat some way
of replacing that missing ecological interaction. But it's not by
resurrect something that's identical to the species that used to
be there, but by taking species that are alive today
and tweaking them using the tools of genetic engineering, so
that they can fit into that ecosystem, so they can
play some of those roles ecological roles that the extinct
(09:04):
species once had. Does that make sense?
Speaker 1 (09:07):
It does? It seems somewhat at odds with the sort
of public messaging of Colossal Right, Like I was reading
your writing on all of what you're saying makes sense
and we can talk more about it. But it is
the case that like the homepage of Colossal Right Now says,
we endeavor to jumpstart nature's ancestral heartbeat to see the
(09:30):
wooly mammoth thunder upon the tundra once again, right, which
is not to see the Asian elephant with some phenotypical
traits of the wooly mammoth. Like, so, I don't know,
like how do you reconcile those? Is it? Just like
there's sort of a public story that needs to be simplified,
just because that's the nature of public stories and then
(09:50):
a more complex technical story.
Speaker 2 (09:53):
If you dive into the website on Colossal, it does
explain that the idea of the extinction includes resurrecting extinct
traits using extinct genomes, but also engineering that we are
taking Asian elephants and engineering them to have and express
some of these mammoth trades. On the website, they're even
called Arctic adapted elephants in several places. So I think
(10:14):
it depends on what you're willing to accept as a mammoth. Right,
if you are only ever going to accept something that
is ecologically, genetically and physiologically one identical to a species
that used to be alive, then that's not what we're doing,
because that's not possible. But if you are willing to
accept an elephant that has longer hair, slightly larger back,
(10:37):
the longer curved tusks, that is capable of living in
the habitat that mammoths once lived in and playing the
roles that mammoths once played, then that is Colossal's goal,
and that is what we are we are saying that
we are making.
Speaker 1 (10:51):
Has your view on sort of what scientists should try
and do, or how they should talk about it, or
anything along those lines changed over time, like this idea
of the extinction, which I don't want to get too
caught up in the semantics, right. I understand that it
can mean different things different people, and that there's a
kind of subtle meaning of it, but like, has your
(11:13):
view in fact changed it all over time?
Speaker 2 (11:16):
My view is that the idea of de extinction is
exciting because it allows us to write down a long
list of all of these challenges that we would need
to be able to solve if we were going to
do this, and along the way we come up with
new technologies and new ideas and new associations that have
application to present day conservation work as well as to
(11:39):
extinction work. My idea of whether de extinction, if you
define it as bringing something back that is one hundred
percent identical to a species that used to be alive,
is impossible, has not changed, right. I don't like the
idea that people would say that that is what we're doing,
because I think then that gives people license to imagine
that extinction isn't a problem. But extinction is a problem,
(12:02):
and this is not a solution to that problem. But
am I willing to say that we shouldn't try this,
that we shouldn't develop these tools that may have application
to helping species not become extinct because we're worried that
somebody is going to get tied up in the semantics
of something and accuse us of something we're not. No.
Am I sad that Ben Lamb has been able to
(12:23):
raise two hundred and twenty five million dollars to be
able to invest into developing these tools that I hope,
I imagine are going to dramatically impact the way that
we do by diversity conservation moving forward. No, I think
this is amazing. I think it's a fantastic opportunity that
we should celebrate.
Speaker 1 (12:43):
Great since you mentioned that that Ben Lamb, the CEO
of the company, has raised two hundred and twenty five
million dollars, Like, what what is the business model? You know,
it's a it's a private company, right, it's not a nonprofit.
So how are the investors going to make a profit?
Speaker 2 (13:02):
You know, this is that's a Ben question. It's not
a me question. I'm the chief science officer. But you know,
some of the ways that the company will make money
is along the path toward the extinction. There are a
ton of technologies that are going to be developed, things
like multiplex genomediting, different approaches to driving genetic changes. We're
working on an artificial womb as one of the tools,
(13:23):
and all of these will drive patents that will be
useful for things outside of the extinction landscape. Ben has
promised that any technology that we develop for conservation can
be applied to conservation without having to pay for that.
So he's promised that that tools that we develop will
go to conservation at no cost. But the path toward
(13:44):
toward bringing in investment return for investors really is in
the space of being at the absolute cutting edge of
genetic engineering and that sort of science.
Speaker 1 (13:53):
Right, And a company was already spun out sort of
in that way, right, is it form Bio that's spun
out of a spun out of Colossal and is a
sort of kind of platform genetics, Like, yes, it's.
Speaker 2 (14:05):
A software company's sort of developing tools that we really
need to be able to track what we're doing all
the different experiments that are going on in Colossal that
have to do with a different species, so that we're
not repeating experiments, but it's super useful for being able
to refine experimental designs. And so that is a spinout
company that's working on developing software platforms for other industries
(14:27):
including drug development, etc.
Speaker 1 (14:29):
So let's talk about how it works and sort of
what you've figured out and what you still have to
figure out. And I know how it works is different
for different species. So tell me about the plan with
the mammoth.
Speaker 2 (14:42):
Sure, So, there are lots of different steps toward figuring
out how to take an Asian elephant and turn it
into an Arctic adapted elephant that we would let's call
a mammoth, defending on whether you're willing to say that.
The first step is to figure out the link between
the genotype, the a's and c's and g's and t's
that make up on organism's genome and the phenotype or
(15:06):
the way that organism looks and acts. For this, we
collect a lot of information, go out into the field,
collect a lot of mammoth bones, sequence high quality whole
coverage genomic data. We have academic collaborators who are helping
with that, Luvo de Lens Lab and Stockholm is a
major advisor to this group. We have now more than
fifty high coverage genome sequences from mammoths, and we can
(15:30):
compare these to genome sequences from Asian elephants and African
elephants and other afrotherorians, so they differentiate all mammoths from
everything else that's there. As a way to start to look,
we can get information from doing experiments like looking and
see what genes are being expressed during tusk development, or
what genes are being expressed in the follicles that produce
(15:51):
long hair. As another way of narrowing down where our
fosi should be as far as identifying these genes that
we want to change. Once we have a panel, we
then have to engineer those and so for this we
take cells from elephants that are growing in a dish
in a lab. A few months ago we released a
pre print and now we have the paper under revision
(16:11):
where we were able to derive induced play potent stem
cells from elephants. This is something people have been trying
to do for a long time and our mammoth team
was successful in doing this. This is really cool and
useful for us because it means that we have cell
lines that are healthy and happy and survive in a
dish that we can transform into different tissue types. So
(16:32):
if we have hypotheses about whether this particular DNA sequence
change causes changes in hair growth, we can make a
type of organoid where we can test that hypothesis. So
we don't have to make an elephant in order to
test our hypothesis. We do this in culture.
Speaker 1 (16:48):
So, dumb question, in that particular example you gave, would
there actually be like hair growing out of the dish
in the lab?
Speaker 2 (16:57):
Yes?
Speaker 1 (16:59):
That's rad okay, So you have that, which is a
useful sort of platform, right, A useful tool certainly to
test hypotheses about, well, what genetic changes lead to what
phenotypical changes right? Go on? Right?
Speaker 2 (17:15):
So then after you do that, you have your your
cells growing in addition to lad that you've engineered all
of your edits into. So I've probably skipped over there.
Lots of very difficult challenging biology. Identify what genes we're
interested in, figure out how to edit these the genomes
and cells to get all those changes in them. And
we have teams of people who are working on multiplex
(17:36):
genome editing, replacing large chunks of DNA rather than just
making single edits to the DNA sequence lots of different
approaches that are developing new tools, new ways of doing
genome engineering that of course have application outside of the
field of the extinction or mammoth or any of these
other cells. Then once you have your edited cell, you
(17:56):
do cloning, sematic cell nuclear transfer, the same process that
brought us Dolly the sheep. You have planted that into
a host, and then eventually your animal is born. So
all of that is very hard. I have summed cross
very hard, difficult, challenging things, and in elephants in particular,
one of the one of the groups that we have
at Colossal is an EXODEV group or artificial boom group,
(18:18):
with the idea of eventually being able to do all
of this without needing a surrogate hoast, without needing to
use a female elephant to get there. The mammoth project
obviously has a very long timeline.
Speaker 1 (18:31):
In terms of the sort of macro side. So that
was a description of the cellular level for the most part. Right, Like,
you're starting with an Asian elephant, which I understand is
quite similar genetically to the mammoth, Right, like more than
ninety nine percent the same genetically, is that? Right?
Speaker 2 (18:52):
That's right?
Speaker 1 (18:53):
How different does an Asian elephant look from a mammoth?
Speaker 2 (18:57):
I don't think I've quantified that.
Speaker 1 (18:58):
What do you think? I don't have any idea. I mean,
how much bigger is a mammoth at the same size?
Speaker 2 (19:04):
The size is not a is not one of the changes.
I mean, a mammoth has a slightly different shape, but
has a different, different tusk shape, and it's obviously harrier.
Speaker 1 (19:16):
And how far along is that project? I suppose one
kind of milestone is implanting some genetically modified elephant that's
a little bit more mammoth like into an Asian elephant.
When do you think that might happen?
Speaker 2 (19:33):
I always tell Ben and also the comms team here
that I am not going to answer timing questions. I
would love to be able to predict the timing of
scientific innovation, but I want my teams to be able
to do good scientific work and to think hard about
the experiments that they're doing, rather than to work against
an externally imposed deadline. Now, George and Ben and Ariona
(19:57):
have said that they plan to have this happen before
twenty twenty eight, and I, as far as I know,
this team is on goal to being able to do this.
Before the implantation, and that that would be fascinating. Now
it is not going to be all of the genetic changes, right,
It's not going to be absolutely everything, but you're writing
(20:18):
that it is an important first step to try to
get there. We have a separate team called our Animal
ops team, who's really it's made of people from the
veterinarian zoo community who are working with the animals, who
are working to try to really learn what these animals
need to be physically and psychologically healthy and captive environments
to learn about processes like OPU, which means ovum pick up.
(20:41):
This is how do we get eggs from these animals
that are going to be the surrogate hosts for somatic
cell nuclear transfers. We're also working with the community of
people who are doing the Northern white Rhino Southern White
Rhino project because you know, what we learn in one
species we can apply to other species. But there are
lots of very hard problems to solve there, but they're
also important problems for the future of those species. So
(21:04):
remember that anything that we learn as we push toward
a mammoth is also something that we can apply to
elephant conservation and to rhino conservation. So this is all
work that is hard, but I appreciate that we have
the opportunity and the finances to be able to put
the energy into it.
Speaker 1 (21:25):
And so, setting aside the understandably sensitive question of specific timelines,
talk about the sort of happy outcome for the mammoth
project in whatever timeframe it may happen, If it sort
of works, what does that look like in the world.
Speaker 2 (21:45):
The long term happy outcome to me is that we
have structured communities of animals that are able to live
in an environment that is really similar to the wild
environment to replace whatever ecological interactions are missing because of
their extinction. And this happy outcome to me, where we
(22:05):
have grandparents and parents and offspring that are all living
in a wild habitat somewhere. This is not a near
term solution. Elephants have twenty two months gestation. They reach
sexual maturity when they're teenagers. So this is something that
I can tell you isn't going to be by twenty
twenty eight or twenty thirty, right. This happy outcome of
(22:26):
an entire population or community of animals living in the
wild is.
Speaker 1 (22:31):
That is a sort of kind of human lifetime's time
scale this's a one hundred years story, absolutely, And what
I mean would that be Siberia? Is it basically the tundra.
Speaker 2 (22:41):
It wouldn't necessarily have to be Siberia, wouldn't necessarily have
to be Alaska or the Yukon. Remember, mammoths lived everywhere
from temperate to subtropical zones. They live throughout warm intervals
and they live throughout cold intervals. But where these ecosystems
have been most changed by their absence is the Arctic
and places where the plant community has changed a lot.
(23:03):
There are lots of missing animal species. We know elephants
are engineers of their ecosystems. There's no and to suspect
mammoths wouldn't have similarly been engineers of their ecosystem in
the past.
Speaker 1 (23:16):
In a minute, why bringing back the dodo maybe even
harder than bringing back the mammoth. Tell me about the dodo.
Give me like a dodo one on one.
Speaker 2 (23:35):
Well, based on sort of written records from the first
people who saw them, So dodos lived on this island.
They were a flightless bird, so about the sides of
a really big chicken, and they probably ate fruit. They
had a big beak that was probably able to crush
fruits and seeds and things like that. We don't know
much about their color. The people who drew them, they're
(23:57):
very Some of them looked like they couldn't have actually
stood up according to the to the way that they've
been drawn. It's funny because most people who drew a
dodo never saw one, because dodos went extinct within a
couple of decads after the first person set foot on
Borucius Island. And it wasn't because people ate them. There
are some written records that suggests that they didn't taste
very good, but because when people arrived in Mauritius, they
(24:20):
brought things like cats and pigs and rats, and dodos
laid a single egg and a nest on the ground
because they couldn't fly, and the things that we brought
with us, that people brought with us just ate all
the eggs. And if you can't, you can't have offspring,
then you're not going to survive.
Speaker 1 (24:37):
Yeah, a single egg and a nest on the ground
is like a perfect I mean, it's not a metaphor
because it's real. It's just so wildly vulnerable, right, it's
just so vulnerable. So okay, so you're trying to bring
back the Dodo or something like the Dodo, and I
understand that one particular challenge there is you actually can't
(24:57):
use the same cloning technology that people have been using
for decades for mammals. Right, tell me about that.
Speaker 2 (25:04):
It's not possible to clone birds the same way that
we clone mammals because of the intricacies of their reproductive system.
So the way that Colossal is working on this problem
with birds and is similar to way that other teams
have been doing this. There's a person called Mike McGrew
who's in Edinburgh, the Roslin Institute, who's developed a lot
of this technology for chickens, but that's the only bird
(25:26):
species so far for with this technology exists, and we're
working on that now for pigeons for the Dodo project.
So the idea is when the egg is laid, the
cells that are called primordial germ cells. These are the
cells that will eventually become germ cells, either sperm or eggs,
depending on the biological sex of the animal. They are
(25:46):
circulating throughout the bloodstream of the developing embryo. They're on
their way to the gonads, which don't exist yet because
it's not that stage of development yet, and at that
point you can stick a needle into the egg very carefully.
I've actually seen our DODO lead do this a few times.
It's pretty impressive how you do this. And you can
suck out a little bit of that circulating blood without
harming the embryo, and you can put that in a
(26:08):
dish in a lab and if you understand what the
right culture conditions are for those cells, you can keep
those cells alive. Then they'll start to grow and make
lots more of themselves, and then you can edit those cells.
And then because those are edited, you can inject them
into an embryo at that same developmental stage and they
will circulate around the bloodstream established in the gonads, and
(26:31):
that chick will be chimeric. Right. It will not be
edited itself, but it's sperm or it's eggs will be edited.
And then you can, if it's a female, you will
fertilize it with edited sperm and then when it lays eggs,
those eggs will hatched into the edited offspring.
Speaker 1 (26:49):
And so I mean is that I don't know if
it's a dumb question to ask, Is that the hardest
part of the DODO like project that whole idea, or
there's so many.
Speaker 2 (27:00):
Hard parts, oh the hardest part. Yeah, though, there are
a lot of hard parts. But you know, this is
a situation where we currently don't have any way of
driving gene edits into bird species. The birds are among
the most endangered species on the planet, especially on islands,
and if we can develop these technologies of being able
to keep these germ cells alive and different species in
(27:21):
addition driving these edits into them, and show that we
can do this, then this is a tool that we
could use, for example, to help make Kawaiian honeycreepers resistant
to avian malaria, or drive resistance to diseases of other
bird species that are impacted by changes to their habitat,
a lot of which have been caused by changes in
the way that people have used the landscape.
Speaker 1 (27:44):
And then talk about the long happy story for the dono, like,
how does that story go?
Speaker 2 (27:53):
We have collaborations with the Russian government and Russian Wildlife Foundation.
This is an island country that is very proud and
very excited about doing conservation work and have an incredible
track record of success there as well. They have several
islands that are off of them mainland that they've been
doing removal of invasive species and replacements sometimes with proxy species.
(28:15):
For example, one of the species that went extinct at
the same time as the dodo is a giant tortoise,
and they have replaced on some of these islands. There's
an island called Round Island, another called eulok Agret where
they've put giant tortoises from Seychelles, And what they've seen
is that having these giant tortoises on the landscape have
(28:36):
been able to help out with their invasive species removal
programs and really change the shape and face of that
floral and faunal community. So it turns out that ebony
trees germinate better after they've passed through the digestive system
of a giant tortoise and many of the other endemic
plant species because they evolved alongside tortoises. They have anti
(28:56):
tortoise or bivory like really sharp little baby leaves for example,
that tortoises can't eat. So the tortoises are consuming all
of the non native species, the species that have been
introduced and leaving behind the endemics species that are now
coming back because of the replacement of this animal on
the landscape, and they hope that by replacing this other
key member of that extinct foneal community, a forgivorous bird
(29:21):
that had a very strange shaped face that's able to
move around and consume fruits and do similar things, I mean,
maybe not even things that we've imagined yet, that this
will will really help them to help them in their
restoration projects. One thing that's clear though, is that even
the idea that there might be a Dodo at some
(29:41):
point has caused a reinvigoration of the excitement of other
people for their conservation programs, and they've seen renewed investments
in creating habitats that dodos might someday be in. They
are really excited about working with us on setting up
places where we can have aviaries for some of these
early birds, because obviously we would love to have them
back there. They're Marsian animals, so they should they should
(30:02):
be there, And so yeah, this is it's been a
it's been I've got to go to Murcius in June
this year and interact with see some of these sites
and interact with some government officials, and the excitement for
having a Dodo and Mauritius is really palpable. It's it's
exciting to be part of.
Speaker 1 (30:19):
What you're trying to do is wildly hard. It's like
kind of amazing, as you alluded that somebody was able
to raise two hundred million dollars for this very hard,
not obviously commercial project. And so I don't know, you're
in a really interesting spot, right, Like you've been studying
this at an academic setting for twenty ish years. Now
(30:40):
you're at this company that's that strangely amazingly has raised
hundreds of millions of dollars to do this hard thing.
Like where are you right now?
Speaker 2 (30:49):
What I like about this project is that, as we've said,
as you've said here, everything that we're doing is really hard.
Speaker 1 (30:56):
Right.
Speaker 2 (30:57):
But as we look around the planet today, what we
see are ecosystems, species, and populations and communities that are
in trouble, And what we have is decision anxiety. What
do we do? How can we help? Where do we
even start? Right? But this project, what it forces us
(31:17):
to do is write down all of the steps that
we need to do to answer this really hard problem,
to get to the end of this really hard solution.
And that now that we've had them written down, means
that we can just go and start knocking them down. Right,
here's problem we have to solve. Here's a problem that
has to do with rewilding and restoration that we have
to solve. In order to solve that, there are all
(31:38):
of these other problems that have to do with invasive
species on the landscape that are going to eat the
dodo's eggs on the ground. How do we solve those?
Who do we partner with to solve those? It's not
all Colossal's job, right, but we do want to enable
it because we want to create an environment where we
can be successful and our partners can be successful. And
our partners are nonprofit conservation groups and governments and local
(32:01):
communities who want these things to happen. But by saying
we're going to do it, we've enforced you got to
write down the problem, We got to figure out how
to solve them.
Speaker 1 (32:11):
And I love that.
Speaker 2 (32:12):
I think that this motivation to get there is going
to solve is going to help so much as we
try to figure out what we can do as a
global community to try to stem the biodiversity loss crisis
that we're facing today.
Speaker 1 (32:28):
We'll be back in a minute with the lightning round.
I have read that you have a tattoo of a dodo.
First of all, is that correct?
Speaker 2 (32:48):
It is yes.
Speaker 1 (32:49):
If you are going to get a tattoo of another
animal extinct or not, what would it be.
Speaker 2 (32:55):
I promised our thylacine lead Sarah that when she delivered
a thylacine I would get a thilocine tattoo. I haven't
decided what it will look like or where it will be,
but that's that's.
Speaker 1 (33:07):
Probably what's the thylacine look like?
Speaker 2 (33:10):
Well look it up. It looks like it looks like
a weird stripey large marsupial wolf.
Speaker 1 (33:17):
I've heard it called the Plasmanian tiger. I know us Okay,
that seems like a cool animal to get a to
get a tattoo of. What's the most dangerous or sketchy
thing you did to get a piece of ancient DNA?
Speaker 2 (33:41):
The most dangerous or sketchy thing I did? You know?
I try not to do any dangerous or sketchy things.
Let's see, I have written on Russian helicopters. That's pretty
dangerous and sketchy to try to get out into the field.
We did once time one time get left in the
field for an extra couple of weeks because these same
helicopters got a better deal taking some wealthy people fishing
(34:03):
for a little while rather than pick up some scientists
that they were supposed to pick up.
Speaker 1 (34:08):
Were you out getting mammoth DNA? What were you doing.
Speaker 2 (34:11):
We're collecting just fossils from Arctic species. I've worked a
lot on muskogs and bison and horses and species like that.
So we were out just in the field collecting bones
for future work. Yep.
Speaker 1 (34:25):
Yeah, we haven't talked all about dinosaurs. Are you tired
of people asking you about dinosaurs? No?
Speaker 2 (34:30):
I mean it's something that people are excited about. There's
no DNA in dinosaurs, right, So the oldest DNA that's
been recovered could be escas escaviller Slav's ancient plant DNA,
which is from sediment that might be about two and
a half million years old. The oldest DNA from bones
are mammoth bones that were frozen in permafrost for more
than a million years, maybe as long as two million years.
(34:52):
But dinosaurs have been extinct for more than sixty five
million years. There is no dinosaur bone out there that
still is organic. They're all fossils that organic material has
been replaced. So we're not going to get dinosaur DNA.
Speaker 1 (35:05):
And there's not even like a theoretical way. It's sort
of like a laws of physics of problem, like fundamental
laws of biology say, we're just not going to get it.
Speaker 2 (35:12):
We're not going to get dinosaur DNA. Yeah, I've tried
even the amber thing like smashing stuff up and getting
because I answer that, yeah, of course. You know why.
You can only be asked that question at least four
hundred or five hundred times before you're like, well, you know,
I'm just.
Speaker 1 (35:28):
Gonna just try it. Time some asshole asked me, I
could say I did it. It didn't work. What's the
oldest DNA that you have ever retrieved?
Speaker 2 (35:39):
Me, personally working in a lab touching samples, the oldest
DNA that I've recovered is from a horse that's probably
around eight hundred thousand years old, somewhere between seven hundred
and eight hundred thousand years old, horse like animal. In fact,
we thought it was a horse, but it turns out
that it is a type of extinct donkey. Well not
even really, that it's slightly more closely related to donkeys
(36:01):
than it is to horses. It's in that lineage, but
it's a species that really hasn't been known to paleontology,
but now we have a whole genome from it.
Speaker 1 (36:08):
So that's fun. Was one surprising thing about the Dodo.
Speaker 2 (36:13):
Surprising thing about the Dodo, I guess I was mostly
surprised very early in the beginning of my experience with
the Dodo that it's a pigeon.
Speaker 1 (36:27):
Well, that's a sign of a good paper, right the
side of a good finding. What's the worst thing about
winning a MacArthur Genius Grant That.
Speaker 2 (36:36):
People ask you what you're going to do with the money,
Like everybody expected you're going to have something really profound
to do with the money that they give you over
the course in the next few years.
Speaker 1 (36:47):
The real answer, just stop writing grants all the time
for the next three years.
Speaker 2 (36:51):
No, do you know what I did with it? I
used it for childcare.
Speaker 1 (36:55):
You know.
Speaker 2 (36:56):
It actually made it possible for me to be a
very young mom trying to run a lab and get
myself off the ground, you know, if I was able
to use it to help my kids.
Speaker 1 (37:08):
So that's actually a really interesting answer, Like it's a
really that's a really interesting answer. I know you might
not be the right person asked this question, but you're
the one I'm talking to, so you know, it was
interesting to me looking at that at the last round
of funding that Colossal got that it came part of
it came from you know what I'm gonna say, part
(37:29):
of it came from in q TEL, the venture capital
fund set up by the CIA. What does I know
it's not actually the CIA, But what does this CIA
VC fund want with you?
Speaker 2 (37:41):
I don't think this is things I can talk about.
And actually I think you know, inq TELL are just
really interested in knowing what's happening, and they like to
be involved in things that are really at the cutting
edge of any sort of new discipline, and I think
their interest is just, you know, we want to know
what you're doing.
Speaker 1 (37:57):
Fair Enough, I'm going to mix metaphors on this one.
Do you have a white whale? Like, is there some
particular species or even just technique or something? Is there
so thing you've been trying to figure out how to
do that you haven't figured out yet that you really
want to figure out.
Speaker 2 (38:16):
Figure out how to make a mammoth? Now, well, I mean.
Speaker 1 (38:22):
All of this. Can I end on that? Could I
end on that? Please?
Speaker 2 (38:28):
We're gonna do it. We're I think we're on the path,
but it's there are definitely a lot of things to
solve still, So yeah, it's a white whale. Isn't a
white whale something that you think you're not going to solve?
I don't, I don't.
Speaker 1 (38:40):
I don't really know the I mean it's from Moby
Dick and Ahab is like his whole thing is he's
got to get the white whale. I mean, it ends
up killing him, but we don't have to think about
that part. It's the thing that he has driven to
get but that he has not yet gotten.
Speaker 2 (38:53):
I guess that's the right answer, you know, let's get there.
Speaker 1 (38:57):
Is it a dodo?
Speaker 2 (38:57):
Though for me? It might be a dodo for me?
Speaker 1 (38:59):
Do you think do you think? I mean? Well, I
I We're going to get back to the semantic question.
And that's a dumb thing to end on, but I
do want to ask, like, do you think you're gonna
make it? And I know it's a dumb question, but
it's also not a dumb question, right, like one wants
to ask it.
Speaker 2 (39:16):
Absolutely, you know there's and I accept something that looks
and acts like a dodo, that can fit into that environment, that.
Speaker 1 (39:23):
Can do like a do and it quacks. Though, do
we know did a dodo quack? Problem? Cool? It was
a pigeon.
Speaker 2 (39:29):
It cools, right, it coos yeah.
Speaker 1 (39:36):
Beth Shapiro is the chief Scientific Officer at Colossal Biosciences.
Today's show was produced by Gabriel Hunter Chang. It was
edited by Lyddy Jean Kott and engineered by Sarah Bruger.
You can email us at problem at Pushkin dot fm.
I'm Jacob Boldstein and we'll be back next week with
another episode of What's Your Problem As
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