Resurrecting dire wolves is just the beginning for Colossal Biosciences’ Ben Lamm

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1:35It's about the storybook like resurrection of the long extinct dire wolf with the CEO of Colossal Biosciences, Ben Lamb. Enjoy it. If people don't know what a dire wolf was, it wasn't just in Game of Thrones. They're a wolf that existed in North America, and they went extinct about 12 ,500 years ago until recently. We took a 13 ,000-year-old tooth in a 72 ,000-year-old skull, and then through a process called somatic cell nuclear transfer, aka cloning, you get an embryo. You put it into a domestic dog. 60 days later, we had our first hour wolf puppies. What do you say to people who say, like, oh, it's wrong to mess with nature.

2:20It's plain God. I think that, you know, given that we're going to lose up to 50 % of biodiversity between now and 2050, we have a moral obligation to do something.

2:36That's Ben Lam, co-founder and CEO of Colossal Biosciences, the startup behind the recent viral return of the formerly extinct dire wolf. The story has garnered a lot of excitement, but equally sparked a debate about whether these dire wolves are the real thing and whether it's ethical to birth and rewild extinct animals. I asked Ben about all of this, plus how the startup attracted a roster of celebrity investors and what other animals Colossal is working on bringing back next. Whether it's lessons from Jurassic Park, cutting edge genetic science or the need to build your own ethical framework, Ben is provocative and compelling.

3:15So let's get to it. I'm Bob Safian, and this is Rapid Response.

3:26I'm Bob Safian. I'm here with Ben Lamb, co-founder and CEO of Colossal Biosciences. Ben, thanks for being here. Yeah, thanks so much for having me. Excited to be here. So Colossal first came onto my radar through news about trying to resurrect the woolly mammoth. Colossal managed to produce some woolly mammoth traits in a mouse that was dubbed the woolly mouse. But nothing has gotten attention like the announcement that you've brought back, the long extinct dire wolf. Now, for people who aren't fans of Game of Thrones or Dungeons and Dragons or thought dire wolves only existed in fantasy, what is a dire wolf?

4:05And of all the creatures that have disappeared. Why did you focus on this one? So we started, the dire wolf just kind of happened. You know, most people know us about the woolly mammoth, the Tasmanian tiger, and the dodo, and we still are pursuing those. We give updates every, you know, probably every half a year, we have a big update on what we're doing on those projects. But if people don't know what a dire wolf was, it wasn't just in Game of Thrones. They weren't the size of cars. They're a wolf that existed in North America, only in North America, with like 90 % of the fossil record being found here in the continental United States.

4:39They were about 20 to 25 % bigger than existing gray wolves. They had a thicker jaw. They had a stronger kind of craniofacial structure. They were also heavier from a weight perspective, at least from what we expect from the bone density. And they went extinct about 12 ,500 years ago until recently. You obtained, found sort of ancient 12 ,000-year-old DNA that you bred these creatures from. Can you walk me through how you undertook this? Yeah. So Colossal focuses on what we call functional de-extinction, right? It's not possible to clone an extinct species. There's no living cells. It's not possible to completely just like take a cell like you do with all the sheep and just clone.

5:29That is part of the process, but you actually have to start with something, right? And so we've actually identified that dire wolves' closest living relatives were gray wolves. And so the process of functional de-extinction is you do a lot of AI and computer analysis of the ancient genomes. And we took a 13 ,000-year-old tooth and a 72 ,000-year-old skull, and we took that, we took all the ancient DNA that we can find out of that. And a lot of times it comes up empty. We put it into a machine. It gives us a genome and we compare it to that closest living relative being the gray wolf. And with that, we can actually identify what genes really made a direwolf a direwolf in terms of the physical attributes or phenotypes that existed.

6:14And with that, we then use a combination of genome engineering tools to take those genes, engineer that DNA into the closest living cells, which are gray wolves. And then through a process called somatic cell nuclear transfer, aka cloning, you get an embryo, you put it into a domestic dog. 60 days later, we had our first owl wolf puppies. So it's not that everything comes from the DNA that you found in these bones. It's that you're sort of tweaking the DNA of existing gray wolves to more closely mimic or mirror the DNA that you found in these ancient bones. Am I explaining that the right way? Yeah.

7:01I mean, it's pretty close, right? It gets super nuanced, right? Because gray wolves are 99.5 % dire wolves already. So you don't mess with any of that, right? It's the same body plan, same canine lineage, same reproductive organs, same placental types. All of that is the exact same, right? So you just kind of leave that alone, right? Because you know it produces a wolf. Very much like Jurassic Park. A lot of people have seen Jurassic Park, right? When people see Jurassic Park, it's very similar. Like they took ancient DNA, they took bird DNA, they took in some movies frog DNA and the later movies, they put everything in the kitchen sink in it to essentially bring back these phenotypes.

7:41Right. But just like in the movie, it's not possible to clone a dinosaur. Those were genetically modified birds with dinosaur alleles. That's the same thing with our direwolves. That's the same thing with the mammoths we're working on and everything. And so it is the closest approximation, but it isn't just engineered to look like a direwolf. It is actually using the direwolf specific genes that drove those traits. Right. And so one of the things that's pretty cool is that we had no idea that direwolves were white until we got all this ancient DNA. People thought that they were red or, you know, orange or some kind of khaki color because they've seen paleo art that depicts them of that color.

8:23But in reality, based on the data that we got from the genome, they were white. And so that was pretty cool. So that so we learned a lot of stuff from the genome that, you know, people didn't even know about dire wolves to begin with. There's been some controversy, right, about whether these are truly dire wolves rather than gray wolves that have been sort of genetically engineered to share some dire like traits. Are those criticisms reasonable? Because it is does sound a little bit like it's a new species, right? It's not really a new species. Right. And part of that. So I'm a big believer in personal choice and freedom.

9:00Right. And so people are like, doesn't it bother you that like some of the scientific community is pushed back? And I was like, no, I think that's the beauty of science. Right. And and some people, though, are quite mad about it. But the reality is, is that we've done things in this project that no one's ever done. No one's ever taken, you know, an edited 15 genes with ancient genomes that have been lost to time for 12 ,000. No one's ever done that. And so the problem with the argument isn't one. It doesn't bother me. But my issue with it is I think it overshadows the incredible science of the women and men that have done this.

9:39Right. Like they took 12 ,000 year old DNA and made puppies. That's incredible. That is that's the moon landing of genetics. Right. And so my argument is, is that if people want to call them dire wolves, call them dire wolves. If they want to call them colossal dire wolves, call them dire colossal. They want to call them genetically modified wolves, call them that. But it's still amazing. It's like, if you go to Jurassic Park and you believe that movie is about dinosaurs, then our dire wolves are dire wolves. If you go to Jurassic Park and say, those are genetically modified birds with dinosaur alleles and frog DNA.

10:12Well, then ours are genetically modified wolves with dire wolf alleles to it. Right. And so it's really a semantics issue. But what's crazy, and I didn't know this because I'm not a biologist or a scientist, is that there's actually over 30 ways to classify a species. And, you know, while some of the scientific community push back, we have over 95 of some of the top scientific, you know, minds in the world, right? We've got people like George Church and Louva Dahlin and Tom Gilbert and, you know, Andrew Pask and Bess Shapiro, who's arguably the number one ancient DNA expert in the world who wrote a book saying how to clone a mammoth.

10:47And it is with you can't because you cannot clone an extinct species, but you can engineer one. And that's exactly what we're doing. We're trying to rebuild extinct species for today using data from the past. And, you know, my only the only thing that annoyed me about the argument was it's a semantic argument. And it's a semantic argument that overshadowed a lot of the great scientists that people put their blood, sweat, and tears in. And, you know, I think over time that'll die down and people will just like look at the science, which is truly amazing in what it can do for not just human healthcare, but also for, you know, endangered species.

11:26You mentioned that you're not a scientist. Your background is not in bioscience. You've been a tech entrepreneur and you got excited about this idea because of the business opportunities. Like, Like, I mean, Colossal is a for-profit business, right? Yes, we are a for-profit business. You know, the reality is I had built a handful of software companies. I liked building technology businesses. I didn't mean to start this business. I reached out to George Church. He's the number one geneticist in the world, maybe of all time, at Harvard. And he's definitely the father of synthetic biology. and I reached out to him and I just asked him, you know, with the proliferation of access to compute, AI, automation, synthetic biology, like what are the opportunities?

12:14Is there an opportunity to build software for synthetic biology and directed evolution? What are the opportunities? And I asked him if he had one project with unlimited capital that he thought could change the world, what would it be? And it was this one. I'm not a biologist, but I like to learn new things. And I know how to build teams of women and men much smarter than me. and I thought this would be something that's cool. And now that I have a nine-month-old son, I'm pretty stoked that like we're working on something that can have a huge application to conservation as well as advanced science.

12:44And it's also something that can inspire generations. And we don't get a lot of credit for this. And I think it's our fault. We don't do a good job. But like every single week we get like pictures from like kids talking about like their favorite animals. And like we have whole classrooms that send us like thank you videos and stuff. And so it's cool, right? Like, yes, there's a conservation element. Yes, there's a deep science element, but there's this kind of cool inspiration element to it. And so I can just go build another software company, but to one end, right? To make a little bit better of a chat platform, to make a little bit better of a defense software, to make more money.

13:21Like at some point, I think there's gotta be more to it. And this is something that, you know, I was really passionate about. And this de-extinction is the idea that bringing back these species, what, puts our environment into better balance? Or is it just like they're cool to have these creatures around? Well, it's kind of threefold, right? It is cool. If a kid sees that using genetics, you could make a woolly mammoth, I do think that inspires kids. I know a lot of scientists that don't want to make dinosaurs, but they saw Jurassic Park and they became geneticists because they thought it was cool.

13:57So there is a cool factor to your point. Secondly is conservation. Like it's forecasted that we're going to lose up to 50 % of all biodiversity between now and 2050 if we don't do anything about it. We know conservation works. This is not a substitute for conservation. It just doesn't work at the speed of which we're eradicating species and changing our planet, right? So we need new tools in all of the technology that Colossal makes on the path to de-extinction that has an application to conservation. We make available for free to our conservation partners, right? And if that wasn't enough, we then went and raised$50 million separate of our business to start the Colossal Foundation to fund even other academics working on technologies that can help conservation.

14:38And the third thing is, and this will take time, is once you get enough species, our goal is to work with indigenous people groups, private landowners, governments, ecologists to rewild those species because certain species can have a tremendous impact on the environment. You mentioned sort of sharing your research and your software with others. Like Colossal has only been around a few years. It is a private company. Yeah, we're three years. It's valued at like$10 billion. I mean, you don't sell a product, do you? Or do you? Like, do you have revenue? No, we just, we have no revenue and we're really good at losing money because science is hard and expensive, right?

15:21Most people don't realize this, but for research and development, it's a giant R, but very little of it makes it into development. So it's a little d, right? And so we've spun out three companies. One is called FormBio, which is a computational biology platform. Surprise, a bunch of software people built a software platform that could be used specifically for manufacturability of drugs, understanding where different products fail in the drug discovery market using CRISPR and AI. And so we spun that company out. It's worth over$100 million today. We spun out a second company, which is called breaking.

15:57And the reason we named it breaking is actually breaking the chemical bonds of plastic and just producing biomass. Right. And so even if we change hearts and minds tomorrow about plastic use or single plastic use, we still have a lot of plastic. We still have to figure out how we do with this. Right. So we're very interested in that. And then we have a third one that we have not announced publicly. That's that is worth over a hundred million dollars as well. So that is the business model that like the research that you're doing is going to throw off ideas that will then, you know, be able to be used for things that you don't even know what they are yet?

16:33Well, that's one, right? The second one is actually in long-term rewilding. And so you've probably heard about carbon credits. You've probably heard about, there's a newer thing called biodiversity credits. It's much more valuable to keep an elephant alive than to sell its location to poachers, right? Because of the application of what it does to the environment and the carbon store. So now you actually have entire markets. And like a lot of these newer markets, like crypto, everything, it takes a while for them to mature. We do believe that the long-term rewilding impacts of species back in their natural habitats will create a combination of government subsidies, carbon credits, biodiversity credits.

17:12But think about that, making species, putting them back, helping the environment, and then getting long-term annuities for them is also pretty interesting when you think about the long scale. So you kind of have short-term technology development in longer-term applications to rewilding. And a$10 billion valuation. Wow. I mean, in three years, pretty good. I think we're massively undervalued. I think, you know, we're a$100 billion company, but we are where we are today. Whether or not Colossal is really undervalued at$10 billion, it's impressive how Ben has managed to reach substantive results in just a few years, including Colossal's spun-out businesses.

17:51So might Colossal's tech be used one day to revolutionize human health? We'll talk about that, plus Colossal's roster of celebrity investors and more after the break. Stay with us.

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21:12property investors, and more. Let's dive back in. So you've got a few of these direwolves. I understand you spent some time with these creatures. Were you scared when you met them? Well, I mean, I met Romulus when he was this big, so I wasn't very scared, right? And I bottle-fed Romulus as a pup, right? We have them in a 2 ,000 acre secure, expansive ecological preserve, and then a subset of that's about six and a half acres where we have an advanced storm shelter in case something bad to happen, we can put them in. We've got an animal hospital on site that we built and we have an animal husband doing where we can feed them to check up some of them and stuff like that, right?

21:54And so I was actually in that six acre preserve with them, I guess some three or four weeks, no, four weeks ago. And Remus came out to me and I saw, and I actually pet Remus, because remember they're not dogs, they're wolves. And they're starting to become more and more like wolves every day. I thought, yeah, this is probably the last time I will be in. I'm going to put myself in the preserve. Where we go from here is we're certified by American Humane Society, so we constantly give them updates to do vet checks. I think the goal from here is to monitor them, take care of them. We'll probably make another three to five more because we want to get the right pack dynamics.

22:32We're not going to breed them. Now, I will say that we do have really close indigenous partners that they have a connection to the dire wolf, and several of them think it could have been the great wolf in some of their oral traditions. And so there could be a season or a time when we actually rewild them back into secure, expansive ecological preserves. They're even larger on indigenous land in collaboration with them, right? But that'll take a long time. So what creatures are we likely to see next from colossal? Woolly mammoths, as I understand, there's a lot of science still to be done, long gestation periods yeah long long gestation so 22 months gestation but we're in the editing phase right so we think it's about 85 genes so more edits than obviously the the the direwolves we've edited about 25 of those we're doing quite well i will say though that one of the things that we care a lot about is the system and so we try to parallel path these things so we are working on elephant idf we're working on rhino idf we're the exclusive genetic rescue partner for uh the Northern White Rhino Project, which is pretty cool.

23:39And so we're trying to develop new what's called assisted reproductive technologies that anyone can use to help save species. That's pretty awesome. You know, I think that what's next, it's hard to guess, but mammoth, thylacine, and dodo are all, you know, chugging along. They're kind of all generally on track somewhere a little ahead of schedule. And then I think you'll also be able to see big conservation winds. Like many people aren't talking about this, but the most endangered wolf in the world is the red wolf. It's an American wolf. There's only 15 left in the wild from 12 founder lines. And we actually made four.

24:12We actually made more red wolves than we did dire wolves. But because they're not in Game of Thrones and movie stars, they are not getting as much feedback. But we actually developed a new technique to clone from blood. And so typical cloning, you have to sometimes anesthetize the animal. You've got to take skin biopsies, ear punches, got to do a lot of stuff, right? and from an animal welfare perspective, this is now just simply a blood draw and you can isolate these specific cells in the blood and then clone from them. And they're pretty cloning efficient. And so, you know, I think most likely what you'll see is more endangered species being worked on from colossal probably before you see the next extinct species.

24:51I see. So not necessarily de-extinction, but maintaining species that are dwindling. Yeah, we think de-extinction goes hand in hand with species preservation. Mm-hmm. It sounds a little bit like the animals you choose to focus on for de-extinction. It's sort of it's in part science and in part on on cultural appeal. Like you want attention, right? I mean, you've got celebrity investors, Tom Brady, Peter Jackson, so on. Is all that a strategic plan to try to make the science more more sexy, more glamorous, more accessible? Well, I don't I don't know how the science could be more sexy. And like we didn't reach out to Tom Brady.

25:31we didn't reach out to Peter Jackson these people reached out to us right and so we aren't out there pursuing Hollywood Hollywood's been pursuing us Peter Jackson got excited about it when he was a kid he read comic books and sci-fi novels and he thought we'd be like vacationing on Venus and we got flying cars and he's like none of that happened he said he literally says that the reason why invested in Colossal was it was the first time you saw a company trying to do something that like as a kid, like sparked his imagination and whatnot in sci-fi. And so, so I, you know, we don't, we don't look for attention.