De-Extinction of the Dire Wolf! Modern Day Jurassic Park？ (The Saad Truth with Dr. Saad_832)
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Summary
In this episode, Dr. Beth Shapiro and Matt James, the Chief Animal Officer at Colossal Biosciences, join Dr. Kelly to talk about their work in the field of cell engineering and stem cell research.
Transcript
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Hi, everybody. Today, I've got two, I seldom have two guests in one shot. I've got Dr.
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Beth Shapiro, and I'll introduce her in a second, and Matt James. First, welcome. How
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I wanted to introduce you. First of all, Beth, if I may address you guys by your first
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names, congratulations on a big award that you just received. I read it. Member of the
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National Academy of Sciences, so congratulations for that.
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I'm sure I must have some other guests because I've had a lot of incredible, illustrious guests,
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but I'm sure you're among a very few people on my show who hold that title. So you are
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traditionally a professor at UC Santa Cruz. You've taken a leave to work at Colossal Biosciences,
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which that's what we're going to talk about today. Matt James, you are the Chief Animal
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Officer at Colossal. So maybe we'll, did I miss anything in terms of an intro that you
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All right, let's do it. Okay, so I mean, I first heard of you guys, I don't know if it,
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I mean, I don't know if you guys know, but Joe Rogan and I are, you know, pretty, pretty
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tight guys. And I saw Ben Lamb on, and I said, what the hell is this? And that's how I kind
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of got into it. So tell us what the company is about. Tell us what you're doing so much,
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so many exciting things to talk about. Take it away.
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Matt, why don't you do that? You can do the overview.
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Sure. So I mean, Colossal Biosciences is a biotechnology company that launched, you know,
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in 2021 with the, originally with this goal of restoring the woolly mammoth from extinction.
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But what Colossal has really become is this de-extinction and species preservation company
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that is building technologies today, whether that's from the genetic engineering and cell
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engineering, genome sequencing side, or reproductive sciences and, and assisted reproduction in order
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to bring species back from extinction and prevent future extinctions. So we're working on everything
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from woolly mammoths, thylacins and dodos. And most recently, you know, in the news, the dire wolf
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to how can we apply our technologies in meaningful ways to prevent the extinction of American red wolf
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of the Northern white rhino, the Mauritian pink pigeon and tons of others. So it's been an amazing
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sort of three and a half, four year journey. And now, you know, we've sort of made the big splash
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recently with the dire wolf news that shows that the de-extinction pipeline is a full technology
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How much of the de-extinction, you know, project involved new technology that just came about
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since the founding of Colossal versus it existed, but it just needed somebody to ignite the process.
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It's a good question. You know, we're obviously standing on the shoulders of lots of work that's been done
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in lots of different fields simultaneously. We're reaching from ancient DNA extraction and analysis,
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computational biology, evolutionary biology inference, gene editing technology, all the way through,
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you know, our assisted reproductive technologies and animal husbandry approaches. This is a pretty wide
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ranging. There are a couple of things that we used for the dire wolf project that were developed that
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were ours. The one that's gotten the most attention is this idea that we can clone cells that can be
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isolated directly from a simple blood draw. And we used that approach to clone the wolves that we,
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that we, you know, cloned in this process. And this is really cool. It's a, it's a cell type. People have
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taken blood draws before and attempted to, to use cloning this process that most famously brought us
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dolly the sheep with those different cell types, but they haven't used the cell type that we isolated
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the endothelial progenitor cells. These are cells that will eventually become the lining of the blood
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vessels and things like that. Um, we hypothesize that the reason that they are so robust is that
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they aren't as far down the pathway to, we call terminal differentiation, the, where a cell gets to,
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where it only has the instructions to be whatever type of cell it ends up being. Cause there are
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different genes that are on or off or turned up or turned down if you're a skin cell or a liver cell
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or a heart cell. So they all have specific instructions about how to be that type of cell.
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The cells that we're cloning from don't really have all of those instructions yet. And so they're
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further back toward the type of cell that we want to start with. If we're going to clone something,
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a type of cell that can become every type of cell that makes up an organism's body. And we found that
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these cells are not only really good for cloning, but they're also great for just growing up in
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culture, which is really useful for conservation. So we can grow up these huge, happy, healthy
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plates of cells that we can then store and bank that we can go back to later and turn them back
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on, bring them back to life, if you will, by thawing them in a, in a careful way. And then they can
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divide and differentiate and be used for cloning 40 years from now, which would be really great for
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conservation. So, well, this, this is not quite what you're talking about, but I'm a huge Belgian
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shepherd guy way before it was cool to talk about the Belgian Malinois. This has been something that
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I've had my whole life. And when our first Belgian, we've had two, I always say that our children have
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grown up with these two majestic, I mean, literally they look like wolves, maybe even more vicious if
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you, if you mess with our family, but in any case, when our first one passed away, I was so heartbroken
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that before he had passed away, we had extracted some, you know, sperm from him and which is still
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stored somewhere with the hope that eventually he'll be, you know, brought back to earth, so to speak,
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not quite in the way you guys are doing it. Where do you get the, the DNA or any material that you're
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using for these projects? Are they historically, if you, I know you probably don't like Jurassic Park
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analogy, but. Love it. Oh yeah. Run with Jurassic Park. Go for it. Okay, good. You know, it's the,
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you know, the mosquito that's stuck in the amber that you, you pull out. Maybe that's probably not
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how you're getting it. Is there a particular source where all the stuff you're hoping to get for all of
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these different, the extinction projects? The ancient, I come from the field of ancient DNA.
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I've been working in that field for a really long time. This is the idea that we can pick up a sample
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from somewhere in the world, from an animal that used to be alive, and we can extract DNA. So we take
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a bit of that bone powder or hair, and we chemically dissolve all the stuff and release the DNA. And then
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we can use that DNA in a standard DNA sequencing. I say standard, it's a little bit different because
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the fragments that we can recover are really short and have damaged bits to them. But we understand
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how DNA decays over time. And so we can use computational approaches to piece those short
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fragments together to reconstruct the whole genomes. We can get DNA from skin, from teeth, from hair,
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from muscle tissue. We know that DNA survives longer when the bone or whatever material it is,
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is preserved in a cold place. So most of the work that's been done to date in the field of ancient DNA
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focuses on animals that lived in the Arctic. But we can also get high quality DNA from places that
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are consistently cool and dark. UV radiation will damage DNA. That's why we put on sunblock when we
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go outside. Freezing and thawing damages DNA because the water molecules expand and physically break the
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DNA. And then probably the thing that damages DNA the most is just microbial action. Bungus and bacteria
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chewing up the DNA to turn it into the next generation of organisms, right?
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I was going to say, so, you know, in forensic science, in criminology at least, when you enter
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someone's DNA into the database, if that person is not already in the database for another crime that
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they've committed, I know their DNA profile, but I don't know who they are. So now you can see where I
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might be going with your question. If you pick up some ancient DNA that is ostensibly of some species,
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how can you know out of all the species that have become extinct that that DNA morsel stems from
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That's a really good question. Part of it comes from extracting DNA from bones that we have identified.
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So I know that that's a mammoth bone and the DNA that DNA that I get out of it creates an organism
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that if you compare it to all of the sequences of animals that are alive today is near elephants.
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And we know that that's a mammoth bone. So now I have a template for what I can say is mammoth like
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DNA. So when I get tiny little fragments of bone that I don't know what it is, or we can even extract
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DNA directly from sediments. You can go and take a plug, like a long core and suck out a bit of dirt
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and extract DNA and find all of the plants and animals that were alive in that spot at that time.
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Yeah, you could do it and dirt as well, just sediments. So we, I have colleagues who work in
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the Arctic who will just take plugs out of a, out of a wall and we can radiocarbon date bits of plants
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so we know how old it is and then extract DNA and amplify, we call them barcode regions. So parts of the
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genome where everybody's different than each other. All of the different species out there
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are different from each other, but in a way that we already know what it is. So we can say, oh,
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that's a mammoth and that's a bison and that's a horse. And then we can get some idea of the
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relative abundance of these different animals in that landscape and also what that community looked
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like. It's actually really cool. I was involved in a project a while ago where we went to St. Paul
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Island in the Bering Sea, which is the second last place mammoths ever lived. Mammoths survived on
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Rangel Island off the northeastern coast of Siberia until just about 3,000 years ago. So there were
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people building pyramids at the same time as there were mammoths in the Arctic. But they also lasted
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until about 5,000, 6,000 years ago on St. Paul Island, which is in the Bering Sea. St. Paul was
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connected to Alaska. And then at the end of the ice age, as the sea level rose, it got disconnected and
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a population of mammoths got trapped there. And we wanted to know when they went extinct and why they
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went extinct. But we didn't have that many bones. So we went to the only source of fresh water on
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the island, which is a volcanic caldera that is filled with water where the people who live there
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now go swimming during the summer. And we went out during the winter when it was frozen over the top
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and shoved a long metal core into the bottom of that freshwater lake and then sucked out all of the
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dirt. And then because the oldest stuff is at the bottom and the youngest stuff is at the top,
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we could get an age profile of how old stuff was. And we could extract DNA from all of it and see
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what happened. Did the plant community change? Did something else change that might have made
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mammoths go extinct? We knew it wasn't people because people weren't present on St. Paul Island
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at the time. We actually found that what happened was probably there was a massive drought. And the water
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of that lake became really salty and had different types of organisms that could only live in salty
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water because the seawater will have introgressed. And that was the only source of fresh water on the
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island. And they probably just ran out of stuff to drink. And that's why mammoths died 5,600 years
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ago on St. Paul Island. But we learned that just by looking at DNA preserved in sediment, which is
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Amazing. I mean, if there are young people watching today's show, if this doesn't excite
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you about science, I don't know what would, right? How do you decide the order? So right now you've
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only de-extinctified, or I'm probably using the wrong verb, one species, the dire wolf. Then you
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mentioned the dodo bird, maybe others. As someone who my doctoral dissertation was actually in psychology
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of decision making. So I'm interested in all things related to how do people make decisions. So what is the
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decision making process out of all possible species that you could de-extinctify? How do you choose which
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You know what's so funny? I'm going to answer the question. But first, I have to just acknowledge, I have
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always said that I really hate the word de-extinction, because I cannot figure out how to conjugate it, which is the
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problem that you're having right now. I don't want to say you de-extincted, it just sounds terrible, but
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is de-extinctified any better? I don't know, maybe not, whatever. I think, you know, the decision-making
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process about picking the original ones is really about, well, there's a bunch of different things.
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I mean, as you point out, there's going to be some social idea here. What do you want? People want
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dinosaurs. As soon as they figure out we can't have dinosaurs, because no dinosaur DNA survives,
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the next thing people think about is mammoths. That's why my first book was called How to Clone
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a Mammoth. If I'd written a book about how to clone the Christmas Island kangaroo rat, nobody
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would have cared, right? So it's partly that. And then there's my side and Matt's side. So
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from my side, the challenges are, can we actually get DNA from this animal, right? Is there sufficient
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information preserved that we could understand what it is about the DNA code that makes that animal
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different from whatever animal we're using as the surrogate species, right? So, and then can we
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learn what those differences actually are and choose edits that we can make in a way that we know are
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going to be safe in a genetic background of a different species? Because we know we can't make
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all of the changes that were there. So how can we, is there a scientifically rigorous, ethical,
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careful path that we can choose to make the decisions about what we're going to do? And then the other
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technologies, we've launched Dodo, but right now there isn't really a mechanism to transfer edited
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DNA sequences between generations of birds, because you can't clone birds using the process
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that brought us Dolly the sheep. So there are teams internationally that have been working on
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different approaches and our team is also working on a different approach to do this, but that's a
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blocking aspect of that de-extinction project that's on our end. And then I'll pass it over to Matt,
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but there's lots of problems after we have cells as well. So I mean, the reproductive science plays a
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huge role in this, right? You know, to best point, you can edit cell lines all the way to a point where
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suddenly you need to create an embryo, which is sort of our challenge on the avian side. But with every
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mammal species we work with, we also have a unique set of challenges, whether that's elephant anatomy
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required for mammoth restoration is really difficult. And their reproductive physiology is still quite a
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mystery to us to resource availability. How many oocytes or eggs can you get for this cloning
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process, which is still not a very efficient process. So it takes a number of eggs to create
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a single embryo. So those are, those are a lot of the challenges that we face along the way. And then
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the question is, if you bring it back, how do you take care of it? Can it, can it be gestated within a
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living animal today? Or do we need to create a synthetic solution for gestation, like an artificial
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womb? And if once it's born, how do you take care of it? And where does it go in the wild? And most
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importantly, is the why? Why are we bringing it back? What purpose does it serve to science, conservation,
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to humanity? And so those are some of the discussions we have. So as you might imagine,
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you put 20 people around a table, and we'll have 20 different opinions on what should be first and why it
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should be first. Do you take a vote? Is it a majority vote? Is it a democracy? Is there an
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autocratic dear leader? How, how do you navigate through the 20 choices? I would say we live
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somewhere between an autocracy and a meritocracy in our decision making here, right? Yeah, I think
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Ben and Beth have a significant amount of sway, I get to have a significant amount of sway in terms of
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how I think it could be a conservation impact. And so that's what, that's sort of how we focus. But
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then there's also, all of that is sort of interwoven with this, with this level of opportunity. What is
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the opportunity to get to that DNA to, to use this animal in a meaningful way? And, and then that's
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sort of how the cream rises to the top. And, and sort of what happened to us with dire wolf, it was when
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we launched, we were a mammoth based company, right? We were only focused on that. And then we suddenly
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spread to several species. And then dire wolf became the obvious choice to be the first to roll out
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publicly. I think there are several reasons for that. I mean, the, the, the, it was an obvious
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choice because we have a gray wolf and we can leverage so much scientific information about gray
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wolves to make this easier, but also, and what we, I mean, we should highlight is that for each of
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these species, we have community partners who are willing to be involved as stakeholders who
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ultimately steward these species, right? So we have to have people on the field, on the ground,
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and it was actually interacting with community partners, with our indigenous conservation board,
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where the idea of the gray, gray of the dire wolf was first, first floated. But the science then,
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you know, the idea that we know so much about gray wolves, that we can make these decisions in a way
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that we know is going to be safe. We have protocols for making sure that the surrogacy can take place
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in, in domestic dogs, and they're all going to be safe and healthy. You know, this is all a very,
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if we're going to have this as a technology, that's expanding beyond this, that we can really use for,
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as a new tool for conservation to stop species from becoming extinct,
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we have to be able to evaluate how we've done. We have to know if there are any unintended
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consequences to the animals. We have to be able to learn how they're interacting with the habitats.
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And there's a very small list of species where we have enough information that we can use as a
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control to really understand what we've done. And dire wolf, gray wolf is a fantastic species pair
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to get this, I think, foundational data that we need moving forward.
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Okay, a couple of questions. One, I know that some people, when, you know, the beautiful images of the dire
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wolves running around were released, but that's not really true. They're not really dire wolves.
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So let me ask you this. So when we had the, I think they call them spider goats, where they breed
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goats to be able to produce spider silk, right? So you're doing this synthetic kind of solution.
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I mean, without confusing all of our lay listeners, is this what's happening in that, you know, the dominant
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expressive, you know, phenotype looks like a dire wolf for whatever, you know, black magic you've done
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in the background. But the reality is, it's not indistinguishable from the dire wolf that would
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have existed X years ago, or is it indistinguishable?
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I think, I think it probably is distinguishable. We focused on specific phenotypes, right? And we
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have, we're doing functional de-extinction, right? We're bringing back animals that we think we can
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slot into a landscape, and they're going to perform some of the ecological roles that those animals
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once played. It's impossible to make all of the changes right now. Maybe it's never, maybe it's, I mean,
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probably in the future, we'll be able to synthesize whole genomes, we'll be able to bring something
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back that is identical to the animals that were there. But given existing technologies, we have
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to work within these constraints, and we still want to be able to generate these animals that can fill
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these ecological niches. And that's what it means to do functional de-extinction. Taxonomically, whether
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it's assigned a taxonomic name that's the same as something else, that's for systematists to argue
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about, and they can. And the spider goats, which are a regular goat, but have some DNA that allows them
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to create the protein to make the spider silk. They have DNA that comes from a different part of the
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evolutionary tree, and systematists will also fight about how you should actually name them.
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That's not important to us. I mean, it's important when you have a conversation. The conversation that
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we're having is about whether these animals can fill the niche of a direwolf, and if they can,
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That's very interesting. Actually, I'm looking right now here at a book that I bought about two months
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ago, The Man Who Organized Nature. It's about the original taxonomist, the Swedish, Linus.
00:20:17.840
Linus, thank you. So I haven't read it yet. One of the big stresses in my life is that I've got a
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gigantic personal library, and every time that I walk into my study and think about all the books that
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I've yet to read, am I running out of time in terms of my lifespan? God willing, I've got many
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more years to read the entire library. All right, here's a bit of a technical question. I hope you
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like it. So I'm an evolutionary behavioral scientist, which basically means I apply principles
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from evolutionary biology and evolutionary psychology to study human behavior in general,
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consumer and economic behavior in particular. So one of the things that I learned early in my
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training with evolutionary psychology is the mismatch hypothesis, right? Which, are you
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familiar with this? Even though you're an evolutionary paleobiologist, you may not know the term. No,
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So the mismatch hypothesis was originally proposed by people in evolutionary medicine, whereby they
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argued that many of the diseases that we currently suffer from, actually, I think the top eight or
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nine are due to a mismatch between the ancestral environment where we would have had some adaptations
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that would have been beneficial then, but in the current environment, they become maladaptive. So for
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example, our preference for fatty foods and to gorge on fatty foods would make perfect evolutionary
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sense in an environment of caloric scarcity and caloric uncertainty. It doesn't make as much
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evolutionary sense when I can just go down to the local fast food place and gorge and then I'll get
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colon cancer and diabetes and heart disease and so on and so forth and high blood pressure. So there's
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this mismatch that causes many of the ailments that we face today. Can we apply that principle
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to some of the de-extinction programs that you're doing, whereby whether it be the dire wolf or any other
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species that you bring back, it occupied an evolutionary niche where it made sense for it to be there,
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it's mismatched with today, here ensued the disasters.
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It's an interesting question. When I think about this, it's similar to an argument that I make about
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why we need genetic engineering technologies for biodiversity conservation, because I like to point
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out that habitats around the world are changing faster than evolution can keep up, which places
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these animals in a situation where they are mismatched with their current environment. And if
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we can find solutions to that in different parts of the evolutionary tree, if we can make animals that
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are better able to resist, plants, animals that are better able to resist drought, or that can capture
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carbon at a different rate, or that have genetic resistance to diseases that have been introduced to
00:23:04.500
their habitats. The black-footed ferret project is a really great example of that, where plague has
00:23:10.320
been introduced into their habitat. They didn't evolve with plague, so they are susceptible to it.
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But their evolutionary cousins, the domestic ferret, did evolve with plague. They are not susceptible to it.
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So if we can take that genetic resistance to plague from the domestic ferret and give it, using gene
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engineering, to the black-footed ferret, we've created a better match to that habitat for those animals
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using these tools. So it's really interesting to think about it that way. As far as mismatch to the current
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environments, one of the reasons that we argue that we probably shouldn't just take wholesale ancient
00:23:45.300
genomes and stick them into an animal today is exactly because of this mismatch with pathogens. If we have a
00:23:51.860
habitat that is, not that we have any intention to release dire wolves into the wild, where they will
00:23:58.520
interact with gray wolves. We don't intend to do that. But let's say we did. And then we had dire wolves
00:24:03.860
that were more dire wolfy because they had all of the extinct dire wolf DNA. They would not have that
00:24:09.880
evolved susceptibility to whatever diseases are circulating in that gray wolf population, and they
00:24:13.900
would be immediately unfit in that environment of today. So by focusing just on traits that we feel
00:24:19.980
do have the capacity to augment ecosystems by restoring missing links between species and focusing just on
00:24:27.780
those and doing functional de-extinction, we're hoping to avoid this while using these tools to
00:24:33.980
help stabilize these ecosystems and restore missing functionality to make those ecosystems more
00:24:40.960
Wow, incredible. This next question is more to Matt, but of course you can weigh in also, Beth.
00:24:45.540
So let me start with a personal story. Back in 2006, I had been invited to the University of New Mexico.
00:24:52.740
They had, I think a lot of the guys have retired since, they had a great evolutionary behavioral
00:24:58.140
sciences group, some anthropologists, some psychologists, some economists. And when I was
00:25:03.940
going there to give a talk on my first book that was about to come out, now close to Albuquerque,
00:25:10.200
where the University of Mexico is, there was a wolf sanctuary. I think it's actually called the
00:25:14.860
wolf sanctuary, if I'm not mistaken. And I had started communicating with them because it had always
00:25:19.540
been a dream of mine to actually maybe interact with wolves. And once they trusted me and saw that
00:25:24.980
I was kind of a reasonably cool guy, they actually allowed me first to enter an enclave with some
00:25:30.520
puppy wolves. And then later I asked them, I had the temerity of asking them, there was a male or female
00:25:36.660
who have since passed away, but you could still go on their website and see them, Raven and Cheyenne.
00:25:41.720
They were full adult wolves. I said, do you think I can go in there? And they said, are you sure you
00:25:49.520
can handle it? Now, I come from a Belgian shepherd's background. And so maybe I had the chutzpah to think
00:25:54.800
that it wouldn't be too scary. I actually went in there. And then I even convinced my wife to go in
00:26:00.260
there. We have photos of it. It was one of the most mystical experiences I've ever had. They actually
00:26:05.380
started howling right in front of me. So my next question, maybe more to Matt than to you, Beth,
00:26:12.920
am I going to be allowed to interact and play with the doctor?
00:26:18.340
I think, yeah, I think we can figure out an arrangement. Obviously we're not playing and
00:26:23.880
interacting with them. We get close. We do at times need to share space with them. They're in a very
00:26:29.500
large preserve. So they're used to their very small subset of caretakers being around them.
00:26:35.460
If somebody they'd never seen would show up, it's most likely that they would hightail it to the other
00:26:40.880
end of the habitat. And eventually they would habituate and come back.
00:26:45.540
But right now there is a, I don't want to say domesticated, but there is a bond that is developed
00:26:52.580
between a few keepers and existing dire wolves. Okay. They've been habituated with a, with a small
00:26:59.300
team of caretakers that help manage them every day, help check on their health, feed them. So
00:27:04.120
there's an association with food comfort reward for them to be around people. And that's really
00:27:09.560
important in the way that we manage animals under human care, because we need these animals to
00:27:13.460
participate in their healthcare, right? Just like you and I go to the doctor, they need to go see the
00:27:17.460
doctor on occasion so that, and the least stressful way to do that is to have a certain level of
00:27:22.460
habituation to a small group of people that they can, that they trust. And they'll allow us to do,
00:27:27.180
you know, very basic observations, exams, if there's something more intervention,
00:27:32.380
you know, more significant intervention needed, then that requires anesthesia. But, you know,
00:27:37.160
right now, you know, I unfortunately think if you walked in today, their first instinct would be
00:27:41.120
to run to the other side of the habitat. Well, that's already better than them eating.
00:27:44.840
Well, now they're only seven months old today. So if we waited until they were two years old and
00:27:51.060
these males that had the full time to mature, and they had a territory, and they had the testosterone
00:27:55.040
needed to be old wolves, they'd most likely come up and mark and make a very clear,
00:28:03.640
they clearly communicate that this is my territory, and you shouldn't be here.
00:28:08.380
As you were, as I'm hearing you speak, I've been, I was thinking about possible projects that
00:28:14.880
one can do at research projects, behaviorally speaking, I'm a behavioral scientist. So for
00:28:20.840
example, you probably have seen the studies with wolves, where when you compare, you know, the
00:28:26.920
pointing paradigm, so, so you basically just point to where the food could be. Dogs pass that test very
00:28:36.180
easily, because they have sort of co-evolved to take cues from their human partners, whereas
00:28:42.260
wolves do very, very poorly on the pointing task. I mean, for reasons that we can surmise.
00:28:49.220
So I'm wondering, have you guys thought, maybe it's too early in the process, but have you thought
00:28:53.520
eventually of conducting, you know, ethological, zoological, behavioral studies with some of these
00:29:00.600
de-extinctified animals that you're bringing back to life? Yeah, absolutely. I think there's a long
00:29:07.800
list of questions that we have that people in our network have, and it ranges from everything from
00:29:13.940
what are the genetic, epigenetic effects of cloning and gene editing, and, you know, epigenetic
00:29:19.380
aging, to what are the behavioral impacts? What are the, you know, what are some of the social
00:29:24.580
ecology questions we could answer? So the short answer is yes, we have, and we're very focused on
00:29:31.260
things that impact health directly today, but we want to begin to expand that as we're sort of getting
00:29:35.980
our legs under us here. Wow. So this is a question for Beth. So you're, you're, you're, much of your
00:29:41.720
career, most of your career has been in academia. Now you've taken a sabbatical, you've gone to
00:29:46.540
industry. We often hear, and certainly I've said so, that in academia, regrettably, oftentimes
00:29:54.000
universities is where innovation goes to die, because you have to spend 74,000 years going through all
00:30:01.220
of the hoops. For me to run the most innocuous study ever, I have to go through six months of
00:30:05.840
institutional review boards and blah, blah, blah. So it is, has that been true as you've segued from
00:30:12.720
academia to your current position where things move much more quickly because you don't have the same
00:30:18.720
sort of bureaucratic oversight over you? You know, it's, we still have bureaucratic oversight. You know, we do not
00:30:26.480
get to operate in a regulatory vacuum. We still have external IACUCs and review boards and every
00:30:32.100
experiment that we do has to be approved by somebody outside. And then everything that we do is
00:30:36.460
regulated within the existing regulatory frameworks of the country in which we're operating. So, you know,
00:30:41.600
we have oversight by the FDA and the USDA for the animal facilities. And, and it's, people imagine,
00:30:47.440
I think some of the fears that we've been is like, oh my goodness, like in Jurassic Park, they just got to do
00:30:51.340
whatever the hell they wanted with these things, which is just, it's just not true. And it's good that it's not
00:30:55.960
true, right? I mean, we want things to be correct and safe and, and to operate within this framework
00:31:01.320
and the framework exists for that purpose. So we're not, we're not pushing against it or we're not,
00:31:06.560
we're not outside of the regulatory framework in a way that would make our lives completely easy,
00:31:11.580
but I also am a little bit relieved by that. You know, my scientific reputation is staked on that
00:31:17.240
we're doing this in a transparent way that is accurate, correct within these regulatory frameworks.
00:31:21.840
That said, I do not have to go to faculty meeting, which is great.
00:31:30.420
I was going to say, I don't think you have to worry about your scientific
00:31:37.480
National Academy of Sciences. I think you can move past that concern.
00:31:42.060
Where are you guys located? Or at least more importantly, where are the dire wolves
00:31:45.920
located? Is it, are you guys? So, so our company is based out of Dallas, Texas. The wolves are in a
00:31:52.260
secret location. That's really, we're only keeping it under a veil of secrecy, mostly for the protection
00:31:57.040
and the safety of those wolves and the people that care for them. Because, you know, even, you know,
00:32:01.460
funny story, even when we announced the woolly mouse a month prior to the dire wolf announcement,
00:32:06.540
we had people coming to the front door of this office building right here saying, I want to see
00:32:10.220
the woolly mice. I want to see the woolly, and you go, this is not how this works. This is not a zoo.
00:32:14.820
This is not exhibition. This is a professional working environment.
00:32:18.940
So, you know, we were, we're very sensitive about their, their location and their safety.
00:32:24.660
Gotcha. I wanted to read for you. This is, I think the tagline of your company,
00:32:28.740
the science of genetics, the business of discovery. The reason why I, it kind of caught my attention
00:32:34.000
because I operate in my academic career at, at that exact intersection and that I apply
00:32:39.960
evolutionary psychology while housed in the business school, right? So I'm trying to,
00:32:47.020
for much of my career, I've, I've, I've been a professor now for 31 years to Darwinize the
00:32:51.960
business school. The idea being that you can't study entrepreneurship or personnel psychology
00:32:57.000
or organizational behavior or consumer behavior somehow completely detached from the fact that
00:33:03.000
all of these human agents are, are shaped by an evolutionary set of mechanisms. But yet most of
00:33:10.460
my social science colleagues think it is the most heretical thing to ever state that, you know,
00:33:15.920
biology and evolutionary biology apply to every species on earth, except one called Homo sapiens.
00:33:24.660
Maybe I'll start by asking this to Beth. Then Matt, of course, you can also weigh in. Are you familiar
00:33:31.060
with this incredible obstacle to try to get scientists to accept that evolutionary principles
00:33:38.040
also apply to the species called Homo sapiens? Yes. In fact, I, in my most recent book, which is
00:33:45.260
called Life As We Made It, I talk a bit about this and how I say humans are, are, are a new type of
00:33:50.540
evolutionary force. We're shaping absolutely everything around us and the decisions that we
00:33:54.760
make shape everything around us. And I think a lot of the ethical slash moral questions that people
00:33:59.840
ask us about the work that we're doing, um, try to put humans outside of what we're doing. And, and I,
00:34:05.860
it's a, it's fun to talk about, right? But if you stand back and think about it, it's also a little
00:34:11.780
bit frustrating. Like this idea of how it's too scary to try to do this, you know, we can't do this.
00:34:16.300
What is it? It's our, it's not our role to bring species back to life or to help species adapt to
00:34:21.220
the changing climates. Well, why not? Why isn't it our role? I mean, we, we, we evolved to have this
00:34:26.180
big brain and the ability to make decisions and to recognize that we might want to stop doing such
00:34:31.000
damage in the rest of the world. We developed, we evolved enough to be able to develop the
00:34:35.200
technologies to do this. And we should apply that to being able to make a difference. Standing back and
00:34:40.340
doing nothing is also a decision. It also has consequences, right? And so we should think about these
00:34:45.960
things rather than just wring our hands about how scared we are.
00:34:49.300
Yeah. I was going to say, I always find it interesting when people have this, the question
00:34:54.920
around, are you playing God? Because I think there is a real selective focus there is that they are
00:35:02.280
selecting to focus on this action and ignore the 99% of other actions in which we assert our humanity
00:35:09.840
on nature every single day. But they go, well, this is the one I have questions on. Well, you know,
00:35:14.540
you, you went to go visit your family and vacation on a jet plane that consumed dino juices to get you
00:35:21.480
there, right? Like there was a lot of activity in there that impacted nature. And you never thought
00:35:25.880
about that as a decision, but that too is a, is a decision every day.
00:35:29.800
In terms of interdisciplinarity. So one of the other things that has defined my career,
00:35:35.320
some might say it was detrimental for my career. I would argue opposite, you know, in academia,
00:35:40.200
you're supposed to be a hyper specialist, right? A stay in your lane guy, you know, you train in a
00:35:45.100
particular methodology in a particular framework, and then keep pumping out papers plus delta within
00:35:50.720
this thing. Well, life is too short for me to only do that. And so I've published papers in,
00:35:55.220
you know, in psychology and in marketing and in economics and in medicine and in bibliometrics.
00:35:59.940
I don't care where I publish as long as I have hopefully something interesting to say.
00:36:05.040
So universities always say yes, yes, interdisciplinarity. But then when you try to
00:36:09.160
implement something that is interdisciplinary, then they all become sort of territorial over their
00:36:13.340
little fiefdoms. And so from this side, I'm interdisciplinary from that side, I'm not.
00:36:17.920
But I can only imagine that the projects that you guys are doing now at Colossal Biosciences is
00:36:23.380
by nature, by definition, greatly interdisciplinary. So can you maybe talk a bit about that?
00:36:30.880
Yeah, I think, you know, one of the first questions that you asked was sort of what are
00:36:35.100
the new technologies that led to this discovery? I've always sort of described Colossal as an
00:36:41.020
intersection of technologies, an intersection of emerging technologies. And we're sort of combining
00:36:45.580
those to create a suite, a toolkit that allows this to happen. So I think, you know, I'm always
00:36:51.620
amazed at how many things Beth is involved in, in terms of the various sciences that she's
00:36:57.020
needing to direct. And then we're weaving that into things like, how do you create an animal
00:37:03.340
care strategy and a management strategy for a species that's never existed before, had
00:37:08.360
existed in 12,000 years, right? And so we're always trying to weave our different expertise
00:37:13.300
in our sciences together in a really interesting way. And so I like to think of Colossal as this
00:37:18.660
sort of amazing, the world's most interesting intersection.
00:37:24.380
Well, I was just going to say, this is to your point about how you're publishing in marketing,
00:37:28.480
and you're publishing in business, and you're publishing in evolutionary psychology. I mean,
00:37:31.300
one of the reasons that I decided to take this leave and join Colossal is because, you know,
00:37:36.060
we only get a certain number of rotations around the star at the center of our universe. And we want to be
00:37:41.100
doing things that are actually impactful. And you want to be doing things that require you to learn
00:37:44.920
something new and interact with people that you've never interacted with before, and figure out where
00:37:49.540
you're wrong, right? Because good scientists want to know where they're wrong so that they can figure
00:37:54.480
out how to not be wrong, right? And if you're just operating in that little lens of your own world
00:37:59.580
forever, you're probably hardly ever going to be wrong. And that means you're never going to learn
00:38:03.780
anything, and you're probably not going to make a big impact. So I love the fact that we're at the
00:38:07.920
center of everything, and that we're doing all sorts of things at the same time and pushing as
00:38:12.340
hard as we can in lots of different directions simultaneously.
00:38:15.700
And sort of the leg that's missing in this three-legged stool that is Beth and me and is Ben,
00:38:21.000
is, you know, what Ben's able to bring to this is really interesting for me coming from a
00:38:25.280
nonprofit conservation background to this, the way we market, the way we communicate, the way we want
00:38:30.120
to build economics around sustainable conservation initiative is amazing. So it's just,
00:38:35.380
it's all the sciences, and then there's the business, the marketing, the comms,
00:38:38.680
all that's layered into, I think, one of the most, I hope, is one of the most interesting
00:38:43.020
companies to have emerged in the last decade or so.
00:38:47.800
Actually, what we're forgetting, though, is just that it's also just cool, right? It's freaking cool.
00:38:53.380
And people, and because of the marketing and the comms, we have like kids reaching out to us. My kids
00:38:59.140
came back from school, both of them, and said, in my science class today, they talked about this,
00:39:03.440
because it was on the news. My colleagues at Santa Cruz were saying the undergrads were coming in
00:39:07.700
and talking about it in class, feeling inspired that there was something that they could do about
00:39:12.120
the conservation crisis. And as we think about all of the, oh, people scared, I'm scared of this,
00:39:16.840
where's it going to go? Is it too scary? We also have to remember the number of people that,
00:39:21.640
because of the dire wolf announcement, thought about extinction and biodiversity loss and ecosystems
00:39:27.260
and genetic engineering for the very first time ever in their whole lives is huge.
00:39:31.800
And if we're going to have a future that is both filled with people and lots of other
00:39:36.080
biodiverse species, we need people to be more engaged than they naturally would be. And this
00:39:40.680
is a way to do it. And we owe that to this sort of crazy strategy that Ben brings to the table,
00:39:49.320
Well, I mentioned, yeah, I mentioned earlier that I first learned about you guys through
00:39:54.800
seeing Ben on Joe Rogan, which kind of brings me to a point that I referred to earlier about
00:40:01.080
stay in your lane. When I first went on Joe Rogan, which would have been now many, many years ago,
00:40:05.660
I think I might've been maybe the first professor to ever go on. It was looked with great derision that,
00:40:11.560
you know, I come from the lofty ivory tower to speak to the great unwashed. And I tell a story in one
00:40:18.100
of my books, how, when I had gone to Stanford business school to give a talk, they were really
00:40:22.020
not into the fact that I was going on Joe Rogan. Whereas now they all write to me and say,
00:40:26.040
oh, please, can you introduce me to Joe Rogan? Because, because it speaks to the fact that if we are
00:40:31.260
doing really valuable science in any field, you do want people to be inspired by it. I don't want to
00:40:38.540
only speak to 13 people who are going to read my peer reviewed article. I want millions. So for me,
00:40:43.960
I started this show for no other reason than I thought I had some interesting things that I
00:40:49.380
could say. I thought I could bring some really cool guests on the show. Let's open it up to
00:40:54.340
everybody. And luckily I've been able to, to build a, you know, a pretty big platform. So I love the
00:40:59.440
fact that you guys are doing this. I mean, I always say life is marketing and marketing is life. I mean,
00:41:04.300
animals communicate what to one another, advertise their mating, you know, attraction through
00:41:11.460
marketing, right? I mean, sexual signaling is a form of marketing. So, so I love that you guys
00:41:16.480
are doing this. Maybe you could tell us in the few minutes that we have left, what are some,
00:41:20.360
if you're, if you're willing to, to promote the stuff, what are some downstream projects
00:41:25.520
that you're working on that we're all going to be excited to hear about at some not too distant
00:41:30.580
future? I hope. Well, we have the three flagship projects, the mammoth, the thylacine,
00:41:37.280
which is also the Tasmanian tiger and our dodo project. And we'll be announcing another project
00:41:44.080
coming up in a, in a month or so, which I'm not going to say what it is yet, but stay tuned. It'll
00:41:49.140
be exciting to hear about it. And then we have a bunch of conservation projects. Matt, you want to
00:41:54.040
highlight some of the, some of the coolest things that are coming up? Yeah. I would say if you're
00:41:57.720
really interested in maybe what our next day extinction project might be, you should also pay
00:42:02.360
attention to Joe Rogan coming up because I think Beth is going to be making an appearance with Joe to
00:42:06.380
talk about. Is this your inaugural? But on the conservation front, we're, we're, you know,
00:42:17.340
we launched it. So we have Colossal Biosciences, which is the company we launched, but last November,
00:42:21.880
we also launched the Colossal Foundation. The Colossal Foundation is our 501c3 conservation
00:42:27.000
organization that's focused on applying our technologies that we create from Colossal Biosciences
00:42:32.220
to the conservation world. We give these tools away for free. We want to engage with conservation
00:42:37.120
NGOs. So we're working on things like the American Red Wolf. How can we help support the key to
00:42:42.080
conservation in the Sea of Cortez, which is the most critically endangered porcus in the world?
00:42:46.320
You know, how can we use genetic rescue as a tool to save populations of animals like Northern
00:42:52.420
White Rhino and Mauritian Pink Pigeon that are, that have gone through these enormous population
00:42:57.120
bottlenecks. And then also, can we use genetic engineering as a tool to confer toxicity resistance
00:43:02.840
to the Northern Quill to confer, you know, adaptive qualities to other, you know, like drought
00:43:09.400
resistance, maybe to some other species that are on the brick. So if you, we'll keep pounding these
00:43:14.840
out, as you might imagine, our comms team is constantly working on a cadence of announcements to
00:43:18.780
show and highlight the amazing conservation work we're doing that sort of comes in between our
00:43:23.800
key extinction announcements. Very, very exciting. I can't imagine how excited you guys must be to
00:43:29.680
every day walk into those offices. What an adventure. I, in one of my, my last book I talk
00:43:35.480
about, so it's a book on happiness and I have an entire chapter on life as a playground. And I argue
00:43:40.780
that science is the ultimate form of playground, right? I mean, it's puzzle making. There's a bunch
00:43:45.280
of variables and I'd like to see which variable is associated with which other one in a meaningful
00:43:49.640
way. And I guess, I guess you guys get to do this from eight in the morning till eight
00:43:54.640
at night every day. So maybe one day I'll come and visit you out there and you'll tell me what
00:43:58.960
my wolves are. That'd be great. That would be amazing. Yeah. Either you come visit us at the
00:44:03.500
labs or one day I'll, I'll take you to the wolves. Oh, that'd be amazing. Thank you. Hey guys,
00:44:07.080
stay on the line so I can say goodbye offline. Thank you so much for coming on. Anything I can do to
00:44:11.620
help promote your projects, always reach out. Thank you so much for agreeing to come on the show.