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Bringing Back Mammoths and Dodos* · What's Your Problem?

0:15
Speaker 1: Pushkin. There's a company called Colossal Biosciences that has raised
0:24
Speaker 1: over two hundred million dollars and its stated aim is
0:28
Speaker 1: to bring back the wooly mammoth and also the dodo bird,
0:34
Speaker 1: as well as a considerably less famous but equally extinct
0:38
Speaker 1: animal called the thylacine aka the Tasmanian tiger. I have
0:44
Speaker 1: questions like, why why are private investors putting hundreds of
0:50
Speaker 1: millions of dollars into this company? And really mostly how
0:57
Speaker 1: how do you bring back a species that has been
0:59
Speaker 1: extinct for centuries. I'm Jacob Goldstein, and this is What's
1:09
Speaker 1: problem the show where I talk to people who are
1:11
Speaker 1: trying to make technological progress. My guest today is Beth Shapiro.
1:16
Speaker 1: She's the chief scientific officer at Colossal Biosciences, a company
1:21
Speaker 1: that is in the business of d extinction. BET's problem
1:25
Speaker 1: is this, how do you use the tools of modern
1:28
Speaker 1: biology to bring back species that have been extinct for
1:31
Speaker 1: hundreds or thousands of years. Also, on kind of a
1:35
Speaker 1: more subtle level, BET's problem is just defining for the
1:39
Speaker 1: world what de extinction really means. Before Beth joined Colossal,
1:44
Speaker 1: she spent decades in academia. She helped to pioneer the
1:47
Speaker 1: field of paleogenetics, studying the genes of ancient organisms, and
1:52
Speaker 1: she spent a lot of time studying the Dodo bird.
1:55
Speaker 1: Tell me about your life with the Dodo.
2:00
Speaker 2: I guess my first exposure to the Dodo was in
2:03
Speaker 2: nineteen ninety nine when I started my PhD at Oxford.
2:05
Speaker 2: The ancient DNA lab that we were using with in
2:09
Speaker 2: the back of the Oxford University Museum of Natural History,
2:12
Speaker 2: and that is so we had to pass by the
2:16
Speaker 2: Dodo every time we were going to the lab. And
2:21
Speaker 2: I was, you know, in this field ancient DNA where
2:24
Speaker 2: we could extract DNA from things, no one was sure
2:26
Speaker 2: what exactly a Dodo was, what kind of bird it
2:29
Speaker 2: was most closely related to, And so I thought it
2:31
Speaker 2: would be really cool if I could use these really
2:33
Speaker 2: new tools and technologies to be able to solve this
2:35
Speaker 2: question answer what sort of bird a Dodo is? So
2:38
Speaker 2: I ask if I could extract DNA from the Dodo.
2:40
Speaker 2: If they said no, because it is a very specials special,
2:44
Speaker 2: precious specimen and you have not proven that you are
2:47
Speaker 2: good at this yet, And so I proved myself. You know,
2:51
Speaker 2: I extracted DNA from other birds and other things, and
2:55
Speaker 2: I was having pretty good success with this, and they said, okay,
2:57
Speaker 2: you can take some grungey bits out of the inside
3:00
Speaker 2: of the skull of this dodo with these long forceps.
3:03
Speaker 1: They have this one Dodo that's an actual Dodo, and
3:06
Speaker 1: you're like, look, I could I could tell you whatever
3:08
Speaker 1: the genome of that bird if you just let me
3:11
Speaker 1: at it.
3:12
Speaker 2: Yep, that's well, maybe not the genome, but I wanted
3:15
Speaker 2: to know at the time what type of bird it was.
3:18
Speaker 2: And at the time we were the field of ancient
3:22
Speaker 2: DNA was focusing on extracting mitochondrial DNA, which is a
3:25
Speaker 2: type of DNA that is inherited maternally, so it doesn't
3:29
Speaker 2: tell you everything about a species. So there's lots and
3:32
Speaker 2: lots of mitochondrial DNA in every cell, and there's only
3:35
Speaker 2: two copies of every nuclear locus that's in the cells.
3:38
Speaker 2: And so in the early days of ancient DNA, when
3:41
Speaker 2: we really weren't very good at recovering DNA, we were
3:43
Speaker 2: focusing on mitochondria. So I wanted to get mitochondria from
3:46
Speaker 2: this Dodo specimen. So why I could answer this outstanding
3:50
Speaker 2: taxonomic question, what type of bird is or was a dodo?
3:54
Speaker 1: Uh huh, because people were just trying to guess based
3:57
Speaker 1: on the morphology, based on what it looked like.
4:00
Speaker 2: Essentially, Yeah, I mean, taxonomy before DNA really was that
4:04
Speaker 2: people are comparing the shapes of things. But DNA is
4:07
Speaker 2: a really unbiased way of reconstructing evolutionary history and it's
4:11
Speaker 2: really powerful, and so I wanted to be able to
4:12
Speaker 2: apply that in addition to the morphological data that people
4:16
Speaker 2: have been collecting for hundreds of years.
4:18
Speaker 1: And so they eventually let you at the bird, and
4:22
Speaker 1: what do you figure out?
4:24
Speaker 2: They first let me take some long force ups to
4:27
Speaker 2: try to scrape some gunk out of the inside of
4:29
Speaker 2: its skull, and that led to nothing because there wasn't
4:31
Speaker 2: any DNA and the gunked up bits of gunk from
4:34
Speaker 2: the inside of the cell. And then they finally let
4:36
Speaker 2: me cut a tiny little piece of bone out of
4:38
Speaker 2: its leg and I was able to extract mitochondrial DNA
4:41
Speaker 2: from that and compare that to all other types of
4:44
Speaker 2: birds that were hypothesized to potentially be a dodo, and
4:47
Speaker 2: we discovered that the dodo is a type of pigeon.
4:50
Speaker 2: It falls within the diversity of pigeons. Most closely related
4:54
Speaker 2: to a pigeon called the nicobar pigeon, which is a
4:58
Speaker 2: very strong flyer, very beautiful bird, different a lot different
5:01
Speaker 2: from a dodo.
5:02
Speaker 1: So you figure out that the dodo was a pigeon
5:06
Speaker 1: that was relatively early in your career, right, and then
5:09
Speaker 1: spend a long time doing scholarly work, doing academic work.
5:13
Speaker 1: You eventually sequence the whole Dodo genome, right, and then
5:17
Speaker 1: eventually what last year you get to Colossal? What made
5:24
Speaker 1: you want to join Colossal?
5:27
Speaker 2: Well, I mean you summarized twenty five years of my
5:31
Speaker 2: academic history.
5:34
Speaker 1: You want to give me a high point along the way.
5:37
Speaker 2: Well, you know, I've been working in this field of
5:39
Speaker 2: ancient DNA, trying to develop tools to be able to
5:41
Speaker 2: get more DNA out of things, to look at the
5:44
Speaker 2: nuclear genomes of different species, develop computational approaches to be
5:48
Speaker 2: able to use the genetic information that we've extracted to
5:51
Speaker 2: tell us when populations are growing and shrinking, To look
5:54
Speaker 2: at replacements, to get DNA directly from ancient sediments so
5:58
Speaker 2: that we can look at what whole ecosystems look like.
6:00
Speaker 2: And all of this really driving toward understanding how we
6:04
Speaker 2: can use the past as a sort of completed evolutionary
6:07
Speaker 2: experiment to try to make more informed decisions of what
6:10
Speaker 2: we can do to protect and preserve species and habitats
6:14
Speaker 2: and ecosystems moving forward. I mean, now, when we're deciding
6:17
Speaker 2: what we're going to do from a conservation perspective, we
6:19
Speaker 2: look around, we see things are in trouble, and we
6:21
Speaker 2: use science we make educated guesses about what the best
6:24
Speaker 2: things are going to be to restore missing ecological interactions
6:28
Speaker 2: to help make these different communities more resilient or more
6:31
Speaker 2: robust in the face of these changes. And ancient DNA
6:35
Speaker 2: lets us do this by showing us how things responded
6:38
Speaker 2: in the past to massive perturbations to their habitat, whether
6:42
Speaker 2: that's an ice age or a really warm interglacial, or
6:45
Speaker 2: the introduction of people or a predator, a different type
6:48
Speaker 2: of predator into that into that ecosystem. And every time
6:51
Speaker 2: we would publish this work that we would want to
6:55
Speaker 2: tell people about it, we would we would want to
6:58
Speaker 2: explain to people what it is that we're excited about,
7:00
Speaker 2: But often the only question that people wanted answered was
7:04
Speaker 2: what does this mean about how close we are to
7:06
Speaker 2: bringing these species back to life?
7:09
Speaker 1: Kind of fighting that right, like you write about it
7:12
Speaker 1: like there's I was reading the twenty twenty edition of
7:18
Speaker 1: your book How to Clone a Mammoth, where you said
7:20
Speaker 1: the present focus on bringing back particular species, whether that
7:24
Speaker 1: means mammoths, Dodo's passenger pigeons, or anything else, is misguided, right,
7:28
Speaker 1: which seems tell me about that? Is there a point
7:32
Speaker 1: where you stop thinking it's misguided?
7:34
Speaker 2: You know, there's a lot of complications. There a biological, technical,
7:38
Speaker 2: and ethical challenges associated with bringing extinct species back to life,
7:43
Speaker 2: And so you ask what is misguided? When people hear
7:50
Speaker 2: about de extinction or the word de extinction, or think
7:54
Speaker 2: about bringing mammoths back to life, what they imagine is
7:57
Speaker 2: recreating something that is identical in every way to a
8:02
Speaker 2: mammoth that used to be alive. But that isn't possible, right,
8:06
Speaker 2: And I think that is where I find the push
8:11
Speaker 2: to this to be misguided. As I said at the time,
8:15
Speaker 2: it's a little bit more nuanced than just as explained.
8:19
Speaker 2: So what is misguided is this idea that de extinction
8:24
Speaker 2: is a solution to the extinction crisis. Right, once a
8:27
Speaker 2: species is gone, we can't bring it back. That species
8:31
Speaker 2: is gone. What we can bring back are some of
8:35
Speaker 2: these core phenotypes, whatever it was that was about that
8:40
Speaker 2: species that made it unique in their habitat some way
8:43
Speaker 2: of replacing that missing ecological interaction. But it's not by
8:46
Speaker 2: resurrect something that's identical to the species that used to
8:49
Speaker 2: be there, but by taking species that are alive today
8:52
Speaker 2: and tweaking them using the tools of genetic engineering, so
8:56
Speaker 2: that they can fit into that ecosystem, so they can
9:00
Speaker 2: play some of those roles ecological roles that the extinct
9:04
Speaker 2: species once had. Does that make sense?
9:07
Speaker 1: It does? It seems somewhat at odds with the sort
9:12
Speaker 1: of public messaging of Colossal Right, Like I was reading
9:17
Speaker 1: your writing on all of what you're saying makes sense
9:20
Speaker 1: and we can talk more about it. But it is
9:22
Speaker 1: the case that like the homepage of Colossal Right Now says,
9:26
Speaker 1: we endeavor to jumpstart nature's ancestral heartbeat to see the
9:30
Speaker 1: wooly mammoth thunder upon the tundra once again, right, which
9:35
Speaker 1: is not to see the Asian elephant with some phenotypical
9:39
Speaker 1: traits of the wooly mammoth. Like, so, I don't know,
9:43
Speaker 1: like how do you reconcile those? Is it? Just like
9:45
Speaker 1: there's sort of a public story that needs to be simplified,
9:48
Speaker 1: just because that's the nature of public stories and then
9:50
Speaker 1: a more complex technical story.
9:53
Speaker 2: If you dive into the website on Colossal, it does
9:56
Speaker 2: explain that the idea of the extinction includes resurrecting extinct
9:59
Speaker 2: traits using extinct genomes, but also engineering that we are
10:03
Speaker 2: taking Asian elephants and engineering them to have and express
10:07
Speaker 2: some of these mammoth trades. On the website, they're even
10:10
Speaker 2: called Arctic adapted elephants in several places. So I think
10:14
Speaker 2: it depends on what you're willing to accept as a mammoth. Right,
10:17
Speaker 2: if you are only ever going to accept something that
10:20
Speaker 2: is ecologically, genetically and physiologically one identical to a species
10:25
Speaker 2: that used to be alive, then that's not what we're doing,
10:29
Speaker 2: because that's not possible. But if you are willing to
10:31
Speaker 2: accept an elephant that has longer hair, slightly larger back,
10:37
Speaker 2: the longer curved tusks, that is capable of living in
10:40
Speaker 2: the habitat that mammoths once lived in and playing the
10:43
Speaker 2: roles that mammoths once played, then that is Colossal's goal,
10:47
Speaker 2: and that is what we are we are saying that
10:50
Speaker 2: we are making.
10:51
Speaker 1: Has your view on sort of what scientists should try
10:55
Speaker 1: and do, or how they should talk about it, or
10:58
Speaker 1: anything along those lines changed over time, like this idea
11:03
Speaker 1: of the extinction, which I don't want to get too
11:06
Speaker 1: caught up in the semantics, right. I understand that it
11:08
Speaker 1: can mean different things different people, and that there's a
11:10
Speaker 1: kind of subtle meaning of it, but like, has your
11:13
Speaker 1: view in fact changed it all over time?
11:16
Speaker 2: My view is that the idea of de extinction is
11:20
Speaker 2: exciting because it allows us to write down a long
11:25
Speaker 2: list of all of these challenges that we would need
11:28
Speaker 2: to be able to solve if we were going to
11:30
Speaker 2: do this, and along the way we come up with
11:32
Speaker 2: new technologies and new ideas and new associations that have
11:35
Speaker 2: application to present day conservation work as well as to
11:39
Speaker 2: extinction work. My idea of whether de extinction, if you
11:43
Speaker 2: define it as bringing something back that is one hundred
11:46
Speaker 2: percent identical to a species that used to be alive,
11:49
Speaker 2: is impossible, has not changed, right. I don't like the
11:53
Speaker 2: idea that people would say that that is what we're doing,
11:55
Speaker 2: because I think then that gives people license to imagine
11:58
Speaker 2: that extinction isn't a problem. But extinction is a problem,
12:02
Speaker 2: and this is not a solution to that problem. But
12:06
Speaker 2: am I willing to say that we shouldn't try this,
12:08
Speaker 2: that we shouldn't develop these tools that may have application
12:12
Speaker 2: to helping species not become extinct because we're worried that
12:15
Speaker 2: somebody is going to get tied up in the semantics
12:17
Speaker 2: of something and accuse us of something we're not. No.
12:20
Speaker 2: Am I sad that Ben Lamb has been able to
12:23
Speaker 2: raise two hundred and twenty five million dollars to be
12:26
Speaker 2: able to invest into developing these tools that I hope,
12:30
Speaker 2: I imagine are going to dramatically impact the way that
12:34
Speaker 2: we do by diversity conservation moving forward. No, I think
12:37
Speaker 2: this is amazing. I think it's a fantastic opportunity that
12:41
Speaker 2: we should celebrate.
12:43
Speaker 1: Great since you mentioned that that Ben Lamb, the CEO
12:48
Speaker 1: of the company, has raised two hundred and twenty five
12:51
Speaker 1: million dollars, Like, what what is the business model? You know,
12:55
Speaker 1: it's a it's a private company, right, it's not a nonprofit.
12:59
Speaker 1: So how are the investors going to make a profit?
13:02
Speaker 2: You know, this is that's a Ben question. It's not
13:05
Speaker 2: a me question. I'm the chief science officer. But you know,
13:08
Speaker 2: some of the ways that the company will make money
13:10
Speaker 2: is along the path toward the extinction. There are a
13:13
Speaker 2: ton of technologies that are going to be developed, things
13:16
Speaker 2: like multiplex genomediting, different approaches to driving genetic changes. We're
13:20
Speaker 2: working on an artificial womb as one of the tools,
13:23
Speaker 2: and all of these will drive patents that will be
13:26
Speaker 2: useful for things outside of the extinction landscape. Ben has
13:30
Speaker 2: promised that any technology that we develop for conservation can
13:34
Speaker 2: be applied to conservation without having to pay for that.
13:37
Speaker 2: So he's promised that that tools that we develop will
13:41
Speaker 2: go to conservation at no cost. But the path toward
13:44
Speaker 2: toward bringing in investment return for investors really is in
13:48
Speaker 2: the space of being at the absolute cutting edge of
13:51
Speaker 2: genetic engineering and that sort of science.
13:53
Speaker 1: Right, And a company was already spun out sort of
13:56
Speaker 1: in that way, right, is it form Bio that's spun
13:58
Speaker 1: out of a spun out of Colossal and is a
14:02
Speaker 1: sort of kind of platform genetics, Like, yes, it's.
14:05
Speaker 2: A software company's sort of developing tools that we really
14:09
Speaker 2: need to be able to track what we're doing all
14:11
Speaker 2: the different experiments that are going on in Colossal that
14:14
Speaker 2: have to do with a different species, so that we're
14:15
Speaker 2: not repeating experiments, but it's super useful for being able
14:19
Speaker 2: to refine experimental designs. And so that is a spinout
14:23
Speaker 2: company that's working on developing software platforms for other industries
14:27
Speaker 2: including drug development, etc.
14:29
Speaker 1: So let's talk about how it works and sort of
14:32
Speaker 1: what you've figured out and what you still have to
14:34
Speaker 1: figure out. And I know how it works is different
14:37
Speaker 1: for different species. So tell me about the plan with
14:41
Speaker 1: the mammoth.
14:42
Speaker 2: Sure, So, there are lots of different steps toward figuring
14:47
Speaker 2: out how to take an Asian elephant and turn it
14:51
Speaker 2: into an Arctic adapted elephant that we would let's call
14:53
Speaker 2: a mammoth, defending on whether you're willing to say that.
14:57
Speaker 2: The first step is to figure out the link between
14:59
Speaker 2: the genotype, the a's and c's and g's and t's
15:02
Speaker 2: that make up on organism's genome and the phenotype or
15:06
Speaker 2: the way that organism looks and acts. For this, we
15:10
Speaker 2: collect a lot of information, go out into the field,
15:12
Speaker 2: collect a lot of mammoth bones, sequence high quality whole
15:16
Speaker 2: coverage genomic data. We have academic collaborators who are helping
15:20
Speaker 2: with that, Luvo de Lens Lab and Stockholm is a
15:22
Speaker 2: major advisor to this group. We have now more than
15:25
Speaker 2: fifty high coverage genome sequences from mammoths, and we can
15:30
Speaker 2: compare these to genome sequences from Asian elephants and African
15:34
Speaker 2: elephants and other afrotherorians, so they differentiate all mammoths from
15:37
Speaker 2: everything else that's there. As a way to start to look,
15:41
Speaker 2: we can get information from doing experiments like looking and
15:45
Speaker 2: see what genes are being expressed during tusk development, or
15:48
Speaker 2: what genes are being expressed in the follicles that produce
15:51
Speaker 2: long hair. As another way of narrowing down where our
15:54
Speaker 2: fosi should be as far as identifying these genes that
15:57
Speaker 2: we want to change. Once we have a panel, we
15:59
Speaker 2: then have to engineer those and so for this we
16:02
Speaker 2: take cells from elephants that are growing in a dish
16:06
Speaker 2: in a lab. A few months ago we released a
16:08
Speaker 2: pre print and now we have the paper under revision
16:11
Speaker 2: where we were able to derive induced play potent stem
16:14
Speaker 2: cells from elephants. This is something people have been trying
16:16
Speaker 2: to do for a long time and our mammoth team
16:19
Speaker 2: was successful in doing this. This is really cool and
16:22
Speaker 2: useful for us because it means that we have cell
16:25
Speaker 2: lines that are healthy and happy and survive in a
16:28
Speaker 2: dish that we can transform into different tissue types. So
16:32
Speaker 2: if we have hypotheses about whether this particular DNA sequence
16:36
Speaker 2: change causes changes in hair growth, we can make a
16:39
Speaker 2: type of organoid where we can test that hypothesis. So
16:42
Speaker 2: we don't have to make an elephant in order to
16:44
Speaker 2: test our hypothesis. We do this in culture.
16:48
Speaker 1: So, dumb question, in that particular example you gave, would
16:53
Speaker 1: there actually be like hair growing out of the dish
16:56
Speaker 1: in the lab?
16:57
Speaker 2: Yes?
16:59
Speaker 1: That's rad okay, So you have that, which is a
17:04
Speaker 1: useful sort of platform, right, A useful tool certainly to
17:07
Speaker 1: test hypotheses about, well, what genetic changes lead to what
17:12
Speaker 1: phenotypical changes right? Go on? Right?
17:15
Speaker 2: So then after you do that, you have your your
17:17
Speaker 2: cells growing in addition to lad that you've engineered all
17:20
Speaker 2: of your edits into. So I've probably skipped over there.
17:23
Speaker 2: Lots of very difficult challenging biology. Identify what genes we're
17:27
Speaker 2: interested in, figure out how to edit these the genomes
17:31
Speaker 2: and cells to get all those changes in them. And
17:33
Speaker 2: we have teams of people who are working on multiplex
17:36
Speaker 2: genome editing, replacing large chunks of DNA rather than just
17:40
Speaker 2: making single edits to the DNA sequence lots of different
17:43
Speaker 2: approaches that are developing new tools, new ways of doing
17:47
Speaker 2: genome engineering that of course have application outside of the
17:51
Speaker 2: field of the extinction or mammoth or any of these
17:53
Speaker 2: other cells. Then once you have your edited cell, you
17:56
Speaker 2: do cloning, sematic cell nuclear transfer, the same process that
18:00
Speaker 2: brought us Dolly the sheep. You have planted that into
18:03
Speaker 2: a host, and then eventually your animal is born. So
18:06
Speaker 2: all of that is very hard. I have summed cross
18:09
Speaker 2: very hard, difficult, challenging things, and in elephants in particular,
18:12
Speaker 2: one of the one of the groups that we have
18:15
Speaker 2: at Colossal is an EXODEV group or artificial boom group,
18:18
Speaker 2: with the idea of eventually being able to do all
18:21
Speaker 2: of this without needing a surrogate hoast, without needing to
18:24
Speaker 2: use a female elephant to get there. The mammoth project
18:28
Speaker 2: obviously has a very long timeline.
18:31
Speaker 1: In terms of the sort of macro side. So that
18:34
Speaker 1: was a description of the cellular level for the most part. Right, Like,
18:41
Speaker 1: you're starting with an Asian elephant, which I understand is
18:44
Speaker 1: quite similar genetically to the mammoth, Right, like more than
18:49
Speaker 1: ninety nine percent the same genetically, is that? Right?
18:52
Speaker 2: That's right?
18:53
Speaker 1: How different does an Asian elephant look from a mammoth?
18:57
Speaker 2: I don't think I've quantified that.
18:58
Speaker 1: What do you think? I don't have any idea. I mean,
19:01
Speaker 1: how much bigger is a mammoth at the same size?
19:04
Speaker 2: The size is not a is not one of the changes.
19:07
Speaker 2: I mean, a mammoth has a slightly different shape, but
19:09
Speaker 2: has a different, different tusk shape, and it's obviously harrier.
19:16
Speaker 1: And how far along is that project? I suppose one
19:23
Speaker 1: kind of milestone is implanting some genetically modified elephant that's
19:28
Speaker 1: a little bit more mammoth like into an Asian elephant.
19:31
Speaker 1: When do you think that might happen?
19:33
Speaker 2: I always tell Ben and also the comms team here
19:36
Speaker 2: that I am not going to answer timing questions. I
19:38
Speaker 2: would love to be able to predict the timing of
19:42
Speaker 2: scientific innovation, but I want my teams to be able
19:46
Speaker 2: to do good scientific work and to think hard about
19:49
Speaker 2: the experiments that they're doing, rather than to work against
19:52
Speaker 2: an externally imposed deadline. Now, George and Ben and Ariona
19:57
Speaker 2: have said that they plan to have this happen before
20:00
Speaker 2: twenty twenty eight, and I, as far as I know,
20:03
Speaker 2: this team is on goal to being able to do this.
20:06
Speaker 2: Before the implantation, and that that would be fascinating. Now
20:11
Speaker 2: it is not going to be all of the genetic changes, right,
20:15
Speaker 2: It's not going to be absolutely everything, but you're writing
20:18
Speaker 2: that it is an important first step to try to
20:21
Speaker 2: get there. We have a separate team called our Animal
20:24
Speaker 2: ops team, who's really it's made of people from the
20:26
Speaker 2: veterinarian zoo community who are working with the animals, who
20:29
Speaker 2: are working to try to really learn what these animals
20:33
Speaker 2: need to be physically and psychologically healthy and captive environments
20:37
Speaker 2: to learn about processes like OPU, which means ovum pick up.
20:41
Speaker 2: This is how do we get eggs from these animals
20:44
Speaker 2: that are going to be the surrogate hosts for somatic
20:46
Speaker 2: cell nuclear transfers. We're also working with the community of
20:50
Speaker 2: people who are doing the Northern white Rhino Southern White
20:52
Speaker 2: Rhino project because you know, what we learn in one
20:55
Speaker 2: species we can apply to other species. But there are
20:58
Speaker 2: lots of very hard problems to solve there, but they're
21:01
Speaker 2: also important problems for the future of those species. So
21:04
Speaker 2: remember that anything that we learn as we push toward
21:07
Speaker 2: a mammoth is also something that we can apply to
21:10
Speaker 2: elephant conservation and to rhino conservation. So this is all
21:14
Speaker 2: work that is hard, but I appreciate that we have
21:20
Speaker 2: the opportunity and the finances to be able to put
21:23
Speaker 2: the energy into it.
21:25
Speaker 1: And so, setting aside the understandably sensitive question of specific timelines,
21:34
Speaker 1: talk about the sort of happy outcome for the mammoth
21:38
Speaker 1: project in whatever timeframe it may happen, If it sort
21:41
Speaker 1: of works, what does that look like in the world.
21:45
Speaker 2: The long term happy outcome to me is that we
21:48
Speaker 2: have structured communities of animals that are able to live
21:54
Speaker 2: in an environment that is really similar to the wild
21:58
Speaker 2: environment to replace whatever ecological interactions are missing because of
22:02
Speaker 2: their extinction. And this happy outcome to me, where we
22:05
Speaker 2: have grandparents and parents and offspring that are all living
22:09
Speaker 2: in a wild habitat somewhere. This is not a near
22:13
Speaker 2: term solution. Elephants have twenty two months gestation. They reach
22:17
Speaker 2: sexual maturity when they're teenagers. So this is something that
22:20
Speaker 2: I can tell you isn't going to be by twenty
22:22
Speaker 2: twenty eight or twenty thirty, right. This happy outcome of
22:26
Speaker 2: an entire population or community of animals living in the
22:29
Speaker 2: wild is.
22:31
Speaker 1: That is a sort of kind of human lifetime's time
22:34
Speaker 1: scale this's a one hundred years story, absolutely, And what
22:38
Speaker 1: I mean would that be Siberia? Is it basically the tundra.
22:41
Speaker 2: It wouldn't necessarily have to be Siberia, wouldn't necessarily have
22:45
Speaker 2: to be Alaska or the Yukon. Remember, mammoths lived everywhere
22:49
Speaker 2: from temperate to subtropical zones. They live throughout warm intervals
22:52
Speaker 2: and they live throughout cold intervals. But where these ecosystems
22:57
Speaker 2: have been most changed by their absence is the Arctic
23:00
Speaker 2: and places where the plant community has changed a lot.
23:03
Speaker 2: There are lots of missing animal species. We know elephants
23:06
Speaker 2: are engineers of their ecosystems. There's no and to suspect
23:10
Speaker 2: mammoths wouldn't have similarly been engineers of their ecosystem in
23:14
Speaker 2: the past.
23:16
Speaker 1: In a minute, why bringing back the dodo maybe even
23:20
Speaker 1: harder than bringing back the mammoth. Tell me about the dodo.
23:33
Speaker 1: Give me like a dodo one on one.
23:35
Speaker 2: Well, based on sort of written records from the first
23:39
Speaker 2: people who saw them, So dodos lived on this island.
23:42
Speaker 2: They were a flightless bird, so about the sides of
23:45
Speaker 2: a really big chicken, and they probably ate fruit. They
23:48
Speaker 2: had a big beak that was probably able to crush
23:51
Speaker 2: fruits and seeds and things like that. We don't know
23:54
Speaker 2: much about their color. The people who drew them, they're
23:57
Speaker 2: very Some of them looked like they couldn't have actually
24:00
Speaker 2: stood up according to the to the way that they've
24:02
Speaker 2: been drawn. It's funny because most people who drew a
24:04
Speaker 2: dodo never saw one, because dodos went extinct within a
24:08
Speaker 2: couple of decads after the first person set foot on
24:11
Speaker 2: Borucius Island. And it wasn't because people ate them. There
24:15
Speaker 2: are some written records that suggests that they didn't taste
24:17
Speaker 2: very good, but because when people arrived in Mauritius, they
24:20
Speaker 2: brought things like cats and pigs and rats, and dodos
24:24
Speaker 2: laid a single egg and a nest on the ground
24:26
Speaker 2: because they couldn't fly, and the things that we brought
24:30
Speaker 2: with us, that people brought with us just ate all
24:32
Speaker 2: the eggs. And if you can't, you can't have offspring,
24:35
Speaker 2: then you're not going to survive.
24:37
Speaker 1: Yeah, a single egg and a nest on the ground
24:39
Speaker 1: is like a perfect I mean, it's not a metaphor
24:42
Speaker 1: because it's real. It's just so wildly vulnerable, right, it's
24:46
Speaker 1: just so vulnerable. So okay, so you're trying to bring
24:50
Speaker 1: back the Dodo or something like the Dodo, and I
24:53
Speaker 1: understand that one particular challenge there is you actually can't
24:57
Speaker 1: use the same cloning technology that people have been using
25:01
Speaker 1: for decades for mammals. Right, tell me about that.
25:04
Speaker 2: It's not possible to clone birds the same way that
25:07
Speaker 2: we clone mammals because of the intricacies of their reproductive system.
25:11
Speaker 2: So the way that Colossal is working on this problem
25:15
Speaker 2: with birds and is similar to way that other teams
25:17
Speaker 2: have been doing this. There's a person called Mike McGrew
25:21
Speaker 2: who's in Edinburgh, the Roslin Institute, who's developed a lot
25:23
Speaker 2: of this technology for chickens, but that's the only bird
25:26
Speaker 2: species so far for with this technology exists, and we're
25:29
Speaker 2: working on that now for pigeons for the Dodo project.
25:32
Speaker 2: So the idea is when the egg is laid, the
25:36
Speaker 2: cells that are called primordial germ cells. These are the
25:39
Speaker 2: cells that will eventually become germ cells, either sperm or eggs,
25:43
Speaker 2: depending on the biological sex of the animal. They are
25:46
Speaker 2: circulating throughout the bloodstream of the developing embryo. They're on
25:50
Speaker 2: their way to the gonads, which don't exist yet because
25:53
Speaker 2: it's not that stage of development yet, and at that
25:55
Speaker 2: point you can stick a needle into the egg very carefully.
25:59
Speaker 2: I've actually seen our DODO lead do this a few times.
26:01
Speaker 2: It's pretty impressive how you do this. And you can
26:03
Speaker 2: suck out a little bit of that circulating blood without
26:06
Speaker 2: harming the embryo, and you can put that in a
26:08
Speaker 2: dish in a lab and if you understand what the
26:12
Speaker 2: right culture conditions are for those cells, you can keep
26:14
Speaker 2: those cells alive. Then they'll start to grow and make
26:17
Speaker 2: lots more of themselves, and then you can edit those cells.
26:21
Speaker 2: And then because those are edited, you can inject them
26:24
Speaker 2: into an embryo at that same developmental stage and they
26:28
Speaker 2: will circulate around the bloodstream established in the gonads, and
26:31
Speaker 2: that chick will be chimeric. Right. It will not be
26:35
Speaker 2: edited itself, but it's sperm or it's eggs will be edited.
26:39
Speaker 2: And then you can, if it's a female, you will
26:41
Speaker 2: fertilize it with edited sperm and then when it lays eggs,
26:44
Speaker 2: those eggs will hatched into the edited offspring.
26:49
Speaker 1: And so I mean is that I don't know if
26:54
Speaker 1: it's a dumb question to ask, Is that the hardest
26:56
Speaker 1: part of the DODO like project that whole idea, or
26:59
Speaker 1: there's so many.
27:00
Speaker 2: Hard parts, oh the hardest part. Yeah, though, there are
27:03
Speaker 2: a lot of hard parts. But you know, this is
27:05
Speaker 2: a situation where we currently don't have any way of
27:08
Speaker 2: driving gene edits into bird species. The birds are among
27:12
Speaker 2: the most endangered species on the planet, especially on islands,
27:15
Speaker 2: and if we can develop these technologies of being able
27:18
Speaker 2: to keep these germ cells alive and different species in
27:21
Speaker 2: addition driving these edits into them, and show that we
27:23
Speaker 2: can do this, then this is a tool that we
27:25
Speaker 2: could use, for example, to help make Kawaiian honeycreepers resistant
27:30
Speaker 2: to avian malaria, or drive resistance to diseases of other
27:34
Speaker 2: bird species that are impacted by changes to their habitat,
27:37
Speaker 2: a lot of which have been caused by changes in
27:39
Speaker 2: the way that people have used the landscape.
27:44
Speaker 1: And then talk about the long happy story for the dono, like,
27:51
Speaker 1: how does that story go?
27:53
Speaker 2: We have collaborations with the Russian government and Russian Wildlife Foundation.
27:56
Speaker 2: This is an island country that is very proud and
28:00
Speaker 2: very excited about doing conservation work and have an incredible
28:05
Speaker 2: track record of success there as well. They have several
28:07
Speaker 2: islands that are off of them mainland that they've been
28:10
Speaker 2: doing removal of invasive species and replacements sometimes with proxy species.
28:15
Speaker 2: For example, one of the species that went extinct at
28:18
Speaker 2: the same time as the dodo is a giant tortoise,
28:21
Speaker 2: and they have replaced on some of these islands. There's
28:26
Speaker 2: an island called Round Island, another called eulok Agret where
28:29
Speaker 2: they've put giant tortoises from Seychelles, And what they've seen
28:32
Speaker 2: is that having these giant tortoises on the landscape have
28:36
Speaker 2: been able to help out with their invasive species removal
28:39
Speaker 2: programs and really change the shape and face of that
28:43
Speaker 2: floral and faunal community. So it turns out that ebony
28:46
Speaker 2: trees germinate better after they've passed through the digestive system
28:49
Speaker 2: of a giant tortoise and many of the other endemic
28:52
Speaker 2: plant species because they evolved alongside tortoises. They have anti
28:56
Speaker 2: tortoise or bivory like really sharp little baby leaves for example,
29:00
Speaker 2: that tortoises can't eat. So the tortoises are consuming all
29:03
Speaker 2: of the non native species, the species that have been
29:06
Speaker 2: introduced and leaving behind the endemics species that are now
29:09
Speaker 2: coming back because of the replacement of this animal on
29:12
Speaker 2: the landscape, and they hope that by replacing this other
29:16
Speaker 2: key member of that extinct foneal community, a forgivorous bird
29:21
Speaker 2: that had a very strange shaped face that's able to
29:24
Speaker 2: move around and consume fruits and do similar things, I mean,
29:28
Speaker 2: maybe not even things that we've imagined yet, that this
29:31
Speaker 2: will will really help them to help them in their
29:35
Speaker 2: restoration projects. One thing that's clear though, is that even
29:38
Speaker 2: the idea that there might be a Dodo at some
29:41
Speaker 2: point has caused a reinvigoration of the excitement of other
29:45
Speaker 2: people for their conservation programs, and they've seen renewed investments
29:48
Speaker 2: in creating habitats that dodos might someday be in. They
29:51
Speaker 2: are really excited about working with us on setting up
29:54
Speaker 2: places where we can have aviaries for some of these
29:56
Speaker 2: early birds, because obviously we would love to have them
29:59
Speaker 2: back there. They're Marsian animals, so they should they should
30:02
Speaker 2: be there, And so yeah, this is it's been a
30:06
Speaker 2: it's been I've got to go to Murcius in June
30:09
Speaker 2: this year and interact with see some of these sites
30:12
Speaker 2: and interact with some government officials, and the excitement for
30:14
Speaker 2: having a Dodo and Mauritius is really palpable. It's it's
30:18
Speaker 2: exciting to be part of.
30:19
Speaker 1: What you're trying to do is wildly hard. It's like
30:22
Speaker 1: kind of amazing, as you alluded that somebody was able
30:25
Speaker 1: to raise two hundred million dollars for this very hard,
30:29
Speaker 1: not obviously commercial project. And so I don't know, you're
30:34
Speaker 1: in a really interesting spot, right, Like you've been studying
30:37
Speaker 1: this at an academic setting for twenty ish years. Now
30:40
Speaker 1: you're at this company that's that strangely amazingly has raised
30:43
Speaker 1: hundreds of millions of dollars to do this hard thing.
30:46
Speaker 1: Like where are you right now?
30:49
Speaker 2: What I like about this project is that, as we've said,
30:53
Speaker 2: as you've said here, everything that we're doing is really hard.
30:56
Speaker 1: Right.
30:57
Speaker 2: But as we look around the planet today, what we
31:00
Speaker 2: see are ecosystems, species, and populations and communities that are
31:04
Speaker 2: in trouble, And what we have is decision anxiety. What
31:09
Speaker 2: do we do? How can we help? Where do we
31:11
Speaker 2: even start? Right? But this project, what it forces us
31:17
Speaker 2: to do is write down all of the steps that
31:20
Speaker 2: we need to do to answer this really hard problem,
31:22
Speaker 2: to get to the end of this really hard solution.
31:25
Speaker 2: And that now that we've had them written down, means
31:28
Speaker 2: that we can just go and start knocking them down. Right,
31:31
Speaker 2: here's problem we have to solve. Here's a problem that
31:34
Speaker 2: has to do with rewilding and restoration that we have
31:36
Speaker 2: to solve. In order to solve that, there are all
31:38
Speaker 2: of these other problems that have to do with invasive
31:40
Speaker 2: species on the landscape that are going to eat the
31:42
Speaker 2: dodo's eggs on the ground. How do we solve those?
31:44
Speaker 2: Who do we partner with to solve those? It's not
31:47
Speaker 2: all Colossal's job, right, but we do want to enable
31:51
Speaker 2: it because we want to create an environment where we
31:54
Speaker 2: can be successful and our partners can be successful. And
31:57
Speaker 2: our partners are nonprofit conservation groups and governments and local
32:01
Speaker 2: communities who want these things to happen. But by saying
32:04
Speaker 2: we're going to do it, we've enforced you got to
32:08
Speaker 2: write down the problem, We got to figure out how
32:10
Speaker 2: to solve them.
32:11
Speaker 1: And I love that.
32:12
Speaker 2: I think that this motivation to get there is going
32:15
Speaker 2: to solve is going to help so much as we
32:18
Speaker 2: try to figure out what we can do as a
32:20
Speaker 2: global community to try to stem the biodiversity loss crisis
32:24
Speaker 2: that we're facing today.
32:28
Speaker 1: We'll be back in a minute with the lightning round.
32:42
Speaker 1: I have read that you have a tattoo of a dodo.
32:46
Speaker 1: First of all, is that correct?
32:48
Speaker 2: It is yes.
32:49
Speaker 1: If you are going to get a tattoo of another
32:52
Speaker 1: animal extinct or not, what would it be.
32:55
Speaker 2: I promised our thylacine lead Sarah that when she delivered
33:01
Speaker 2: a thylacine I would get a thilocine tattoo. I haven't
33:03
Speaker 2: decided what it will look like or where it will be,
33:06
Speaker 2: but that's that's.
33:07
Speaker 1: Probably what's the thylacine look like?
33:10
Speaker 2: Well look it up. It looks like it looks like
33:13
Speaker 2: a weird stripey large marsupial wolf.
33:17
Speaker 1: I've heard it called the Plasmanian tiger. I know us Okay,
33:23
Speaker 1: that seems like a cool animal to get a to
33:25
Speaker 1: get a tattoo of. What's the most dangerous or sketchy
33:36
Speaker 1: thing you did to get a piece of ancient DNA?
33:41
Speaker 2: The most dangerous or sketchy thing I did? You know?
33:45
Speaker 2: I try not to do any dangerous or sketchy things.
33:48
Speaker 2: Let's see, I have written on Russian helicopters. That's pretty
33:52
Speaker 2: dangerous and sketchy to try to get out into the field.
33:55
Speaker 2: We did once time one time get left in the
33:57
Speaker 2: field for an extra couple of weeks because these same
34:00
Speaker 2: helicopters got a better deal taking some wealthy people fishing
34:03
Speaker 2: for a little while rather than pick up some scientists
34:06
Speaker 2: that they were supposed to pick up.
34:08
Speaker 1: Were you out getting mammoth DNA? What were you doing.
34:11
Speaker 2: We're collecting just fossils from Arctic species. I've worked a
34:15
Speaker 2: lot on muskogs and bison and horses and species like that.
34:19
Speaker 2: So we were out just in the field collecting bones
34:22
Speaker 2: for future work. Yep.
34:25
Speaker 1: Yeah, we haven't talked all about dinosaurs. Are you tired
34:28
Speaker 1: of people asking you about dinosaurs? No?
34:30
Speaker 2: I mean it's something that people are excited about. There's
34:33
Speaker 2: no DNA in dinosaurs, right, So the oldest DNA that's
34:36
Speaker 2: been recovered could be escas escaviller Slav's ancient plant DNA,
34:41
Speaker 2: which is from sediment that might be about two and
34:42
Speaker 2: a half million years old. The oldest DNA from bones
34:45
Speaker 2: are mammoth bones that were frozen in permafrost for more
34:49
Speaker 2: than a million years, maybe as long as two million years.
34:52
Speaker 2: But dinosaurs have been extinct for more than sixty five
34:55
Speaker 2: million years. There is no dinosaur bone out there that
34:58
Speaker 2: still is organic. They're all fossils that organic material has
35:02
Speaker 2: been replaced. So we're not going to get dinosaur DNA.
35:05
Speaker 1: And there's not even like a theoretical way. It's sort
35:07
Speaker 1: of like a laws of physics of problem, like fundamental
35:10
Speaker 1: laws of biology say, we're just not going to get it.
35:12
Speaker 2: We're not going to get dinosaur DNA. Yeah, I've tried
35:15
Speaker 2: even the amber thing like smashing stuff up and getting
35:18
Speaker 2: because I answer that, yeah, of course. You know why.
35:21
Speaker 2: You can only be asked that question at least four
35:25
Speaker 2: hundred or five hundred times before you're like, well, you know,
35:27
Speaker 2: I'm just.
35:28
Speaker 1: Gonna just try it. Time some asshole asked me, I
35:31
Speaker 1: could say I did it. It didn't work. What's the
35:36
Speaker 1: oldest DNA that you have ever retrieved?
35:39
Speaker 2: Me, personally working in a lab touching samples, the oldest
35:42
Speaker 2: DNA that I've recovered is from a horse that's probably
35:45
Speaker 2: around eight hundred thousand years old, somewhere between seven hundred
35:48
Speaker 2: and eight hundred thousand years old, horse like animal. In fact,
35:52
Speaker 2: we thought it was a horse, but it turns out
35:55
Speaker 2: that it is a type of extinct donkey. Well not
35:58
Speaker 2: even really, that it's slightly more closely related to donkeys
36:01
Speaker 2: than it is to horses. It's in that lineage, but
36:03
Speaker 2: it's a species that really hasn't been known to paleontology,
36:07
Speaker 2: but now we have a whole genome from it.
36:08
Speaker 1: So that's fun. Was one surprising thing about the Dodo.
36:13
Speaker 2: Surprising thing about the Dodo, I guess I was mostly
36:21
Speaker 2: surprised very early in the beginning of my experience with
36:24
Speaker 2: the Dodo that it's a pigeon.
36:27
Speaker 1: Well, that's a sign of a good paper, right the
36:29
Speaker 1: side of a good finding. What's the worst thing about
36:33
Speaker 1: winning a MacArthur Genius Grant That.
36:36
Speaker 2: People ask you what you're going to do with the money,
36:38
Speaker 2: Like everybody expected you're going to have something really profound
36:42
Speaker 2: to do with the money that they give you over
36:46
Speaker 2: the course in the next few years.
36:47
Speaker 1: The real answer, just stop writing grants all the time
36:50
Speaker 1: for the next three years.
36:51
Speaker 2: No, do you know what I did with it? I
36:54
Speaker 2: used it for childcare.
36:55
Speaker 1: You know.
36:56
Speaker 2: It actually made it possible for me to be a
36:59
Speaker 2: very young mom trying to run a lab and get
37:04
Speaker 2: myself off the ground, you know, if I was able
37:05
Speaker 2: to use it to help my kids.
37:08
Speaker 1: So that's actually a really interesting answer, Like it's a
37:11
Speaker 1: really that's a really interesting answer. I know you might
37:16
Speaker 1: not be the right person asked this question, but you're
37:19
Speaker 1: the one I'm talking to, so you know, it was
37:22
Speaker 1: interesting to me looking at that at the last round
37:24
Speaker 1: of funding that Colossal got that it came part of
37:27
Speaker 1: it came from you know what I'm gonna say, part
37:29
Speaker 1: of it came from in q TEL, the venture capital
37:32
Speaker 1: fund set up by the CIA. What does I know
37:36
Speaker 1: it's not actually the CIA, But what does this CIA
37:38
Speaker 1: VC fund want with you?
37:41
Speaker 2: I don't think this is things I can talk about.
37:43
Speaker 2: And actually I think you know, inq TELL are just
37:45
Speaker 2: really interested in knowing what's happening, and they like to
37:48
Speaker 2: be involved in things that are really at the cutting
37:50
Speaker 2: edge of any sort of new discipline, and I think
37:53
Speaker 2: their interest is just, you know, we want to know
37:55
Speaker 2: what you're doing.
37:57
Speaker 1: Fair Enough, I'm going to mix metaphors on this one.
38:00
Speaker 1: Do you have a white whale? Like, is there some
38:04
Speaker 1: particular species or even just technique or something? Is there
38:08
Speaker 1: so thing you've been trying to figure out how to
38:11
Speaker 1: do that you haven't figured out yet that you really
38:13
Speaker 1: want to figure out.
38:16
Speaker 2: Figure out how to make a mammoth? Now, well, I mean.
38:22
Speaker 1: All of this. Can I end on that? Could I
38:24
Speaker 1: end on that? Please?
38:28
Speaker 2: We're gonna do it. We're I think we're on the path,
38:31
Speaker 2: but it's there are definitely a lot of things to
38:34
Speaker 2: solve still, So yeah, it's a white whale. Isn't a
38:37
Speaker 2: white whale something that you think you're not going to solve?
38:39
Speaker 2: I don't, I don't.
38:40
Speaker 1: I don't really know the I mean it's from Moby
38:42
Speaker 1: Dick and Ahab is like his whole thing is he's
38:45
Speaker 1: got to get the white whale. I mean, it ends
38:48
Speaker 1: up killing him, but we don't have to think about
38:50
Speaker 1: that part. It's the thing that he has driven to
38:52
Speaker 1: get but that he has not yet gotten.
38:53
Speaker 2: I guess that's the right answer, you know, let's get there.
38:57
Speaker 1: Is it a dodo?
38:57
Speaker 2: Though for me? It might be a dodo for me?
38:59
Speaker 1: Do you think do you think? I mean? Well, I
39:02
Speaker 1: I We're going to get back to the semantic question.
39:05
Speaker 1: And that's a dumb thing to end on, but I
39:06
Speaker 1: do want to ask, like, do you think you're gonna
39:08
Speaker 1: make it? And I know it's a dumb question, but
39:11
Speaker 1: it's also not a dumb question, right, like one wants
39:15
Speaker 1: to ask it.
39:16
Speaker 2: Absolutely, you know there's and I accept something that looks
39:20
Speaker 2: and acts like a dodo, that can fit into that environment, that.
39:23
Speaker 1: Can do like a do and it quacks. Though, do
39:26
Speaker 1: we know did a dodo quack? Problem? Cool? It was
39:29
Speaker 1: a pigeon.
39:29
Speaker 2: It cools, right, it coos yeah.
39:36
Speaker 1: Beth Shapiro is the chief Scientific Officer at Colossal Biosciences.
39:42
Speaker 1: Today's show was produced by Gabriel Hunter Chang. It was
39:45
Speaker 1: edited by Lyddy Jean Kott and engineered by Sarah Bruger.
39:49
Speaker 1: You can email us at problem at Pushkin dot fm.
39:53
Speaker 1: I'm Jacob Boldstein and we'll be back next week with
39:55
Speaker 1: another episode of What's Your Problem As