EP 141 Ben Lamm (Founder & CEO, Colossal Biosciences) On The Breakthroughs Making De-Extinction Actually Possible

Ben Lamm, founder and CEO of Colossal Biosciences, joined the show to talk about the science (and business) of bringing extinct species back to life. Backed by top scientists and investors, Colossal is using advanced gene editing and synthetic biology to recreate animals like the woolly mammoth and dire wolf. Ben walks us through the technology, ethical considerations, and commercialization paths, including tech spinouts and conservation credits. It’s a wild conversation at the intersection of Jurassic Park and deep tech.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:01Speaker 00

  No one has ever taken ancient DNA, put it in a living species, and also done it through multiplex editing and got 100% efficiency.

• 0:08Speaker 01

  I view it as like forced evolution.

• 0:10Speaker 00

  I love that idea.

• 0:11Speaker 01

  You're forcing the gray wolf to become a dire wolf through like little tweaks in the DNA.

• 0:15Speaker 00

  We're now making over 50 edits at once right now, which is insane.

• 0:19Logan Bartlett?

  How do you think through the PR side versus the practicality side?

• 0:23Speaker 00

  Mammals are closer related to Asian elephants than Asian elephants are to African elephants. I suppose people's minds.

• 0:32Logan Bartlett?

  Ben, thanks for doing this.

• 0:33Speaker 00

  Yeah, thanks for having me.

• 0:34Logan Bartlett?

  So for people that don't know, can you use just a quick primer on what Colossal is?

• 0:39Speaker 00

  Yeah, so Colossal is the world's first de-extinction and species preservation company. We use a lot of genetic engineering, computational biology, solve some pretty hard challenges in genotype-to-phenotype relationships, and we open source all the technology for conservation.

• 0:53Logan Bartlett?

  And you've been at it for how long?

• 0:54Speaker 00

  Since 2021, so nearly four years.

• 0:56Logan Bartlett?

  And raised?

• 0:57Speaker 00

  Four, uh, we raised $435 million for the company, and then we have a foundation where we raised $50 million.

• 1:03Logan Bartlett?

  And so as you thought about this, we'll get into the background and how all this stuff came to be, but...

• 1:09Speaker 00

  Complete accident, too.

• 1:10Logan Bartlett?

  Yeah, well, so maybe give that short version of like how you how you sort of fell into this.

• 1:15Speaker 00

  So I'm a software guy, and I've only known how to build like teams of software. I try to hire a bunch smarter women and men than me, and I've always just thought about like the system, right? You know, you've been in software, right? You invest in software. So it's all it's all just system design, right? So I think that really good software engineers and really good system designers can really just figure out how to ask the right questions. Like, I don't have to be an expert in biology. I just know how to kind of ask the right questions and hire people that can answer them at least better than I can, right? And so I reached, I thought that, you know, looking at kind of access to compute, AI, and synthetic biology, this idea that we can engineer life, that we can do directed evolution, that we can do accelerated evolution was going to be really interesting. And then if you layer on quantum, which I hear is... Only two years away every two years. That's gonna be really crazy. And I think we're gonna

• 1:59Speaker 00

  enter this whole new world. So I reached out to George Church, who's the father of synthetic biology. He's had genetics at Harvard. Some of the core read write technologies that exist in the world were all invented by him in his lab, as well as David Lu up at Harvard. So I thought I'd reach out to him halfway into the conversation. I was like, what else are you working on? Cause I'm weird and curious. And he started going down this path of like all these different projects he was working on. And it was, it was a little overwhelming. And then I asked, you know, the probably the most interesting question of my life, which is if you had unlimited capital, what was you gonna work on and why? And it was the mammoth. He's like, I'd work to bring back existing species, make technologies for human healthcare, make technologies for eventually for conservation.

• 2:38Logan Bartlett?

  It was the mammoth, just like, forgive the guess colloquialism, but a pet project of his? Or was there some like derivative consideration of?

• 2:46Speaker 00

  No, he thought that we had like the amalgamation of all the tech, right? It's also majorly not efficient right now. So you need to innovate on all this stuff. But there wasn't any major like science gaps, right? We could get ancient DNA, we could do comparative genomics, you could build sequencing, you could make edits, even if you only make one edit at a time. And then you could figure out kind of the embryology. So there's some things to figure out on the gestational side. But for the most part, like we had all the core tech. And so his vision was at the time, he raised a hundred thousand dollars for his lab from Peter Thiel, who just gave him a donation. And he is stretching that out over the course of 10 years. So he wasn't very far.

• 3:23Logan Bartlett?

  It turns out it's a lot more expensive. Yeah, I can imagine. Well, I guess to that end, like as you, as you set out to go do this, did you have some business that it could ultimately be? Because when you, when you talk about this and you start to unpack it, it sounds almost like a, a research project in a lot of ways.

• 3:40Speaker 00

  Yeah, but like a lot of academic research projects, they result in papers and not products. Not that there's anything wrong with papers. I get a lot of feedback on my views of papers, right? Because at the end of the day, you can't ship a paper to anyone except the scientific community. And so I felt like there was, there's got to be a way. Our first pitch deck was pretty shitty. It was, you know, George thinks he can bring back a mammoth. We are pretty confident we know how to build teams. We're pretty sure there's value there, right? Like that, that literally was the first pitch deck. So I guess the short answer in the beginning was no. Over time, we realized that, you know, to really make this work at the speed we want it to work, the impact we want it to work, and the scale we want it to work, we had to innovate on a lot of technologies. There's a little bit we didn't invent, but for the most part, we had to innovate. And all those created,

• 4:23Speaker 00

  you know, massive opportunities, both human healthcare and to some industrial use cases. So we thought that like, kind of that Apollo-esque model to start would be interesting. Over time, there's been other business models that have arisen that we think are even equally interesting.

• 4:38Logan Bartlett?

  I want to dive into the process and all, all of that stuff as well. But so recently, you announced the de-extinction of dire wolves.

• 4:48Speaker 00

  Yeah, dire wolves.

• 4:49Logan Bartlett?

  And you have three?

• 4:51Speaker 00

  So we have three. Yeah. So we got two males and one female.

• 4:54Logan Bartlett?

  Maybe we can dive into, yeah, like the actual process of how to.

• 4:57Speaker 01

  Also, the shirt is awesome.

• 4:59Logan Bartlett?

  Yeah, it's like.

• 5:00Speaker 00

  Yeah, we do. We don't, we make all of our own stuff and we just like, we wanted, we work with a lot of top designers and we don't sell it. We just give it to our team. And so when you come to the lab, you guys should come see, check out the lab, because lab's way cooler than talking to me. And it's literally, it's like a hodgepodge of all these people wearing cool colossal shirts. So we'll send you one.

• 5:16Speaker 01

  That's awesome. Yeah. I was going to mug you afterwards for the shirt. So I'm glad you gave it.

• 5:19Speaker 00

  I don't have an undershirt, so please don't. Travesty to the world.

• 5:22Speaker 01

  I thought just, you know, as a, as a non-scientist in science as well.

• 5:26Speaker 00

  Yeah, same. Yeah. You've done well in, as a non-scientist in science.

• 5:30Speaker 01

  Yeah. So I pretend I understand, but I just kind of memorized the phrases. But.

• 5:34Speaker 00

  I feel like I had to do that for every species. Like I had to learn a lot about elephants. And it's like the ultimate like college cram, right? Where it's like, okay, I've learned everything about marsupial gestation. I have to learn everything about this. So it's cool because you actually get to learn a lot.

• 5:47Speaker 01

  Yeah, I find the same. It's like, okay, I'm going to go learn about like biologics today and try and remember the words.

• 5:52Speaker 00

  Yeah. It's its own nomoclass. So it's so weird.

• 5:55Logan Bartlett?

  So maybe to try and keep it like somewhat high level, but in the science.

• 6:00Speaker 00

  Yeah.

• 6:00Logan Bartlett?

  When I think about this step by step and curious to learn like how you do this, we will start with a dire wolf.

• 6:06Speaker 00

  Yeah.

• 6:06Logan Bartlett?

  So you've got.

• 6:08Speaker 01

  Old dire wolf DNA.

• 6:10Speaker 00

  Right.

• 6:10Speaker 01

  Let's say, so we kind of know the underlying DNA of the dire wolf.

• 6:13Speaker 00

  Which is hard in itself.

• 6:14Speaker 01

  To find it.

• 6:14Speaker 00

  Yeah, to find it. So like in like La Brea Tar Pits, they have thousands of dire wolf skulls, but they've all been stressed due to heat and acidification. So there's no DNA, at least no recoverable DNA.

• 6:26Speaker 01

  No recoverable DNA.

• 6:27Speaker 00

  So there's kind of this like, before it all starts, there's like this search, like you've got to have something to start. And we found that you need about 6X coverage to be able to do this. So that means that you have to have, you probably know this, but for everyone else is like, you need to be able to read the full genome about six times. You need to get enough destructive sampling that you can get about six passes of the full genome to get enough of the of the core regions to assemble it.

• 6:51Speaker 01

  Yeah. So let's say, and we can simplify, you know, this is what we're aiming for.

• 6:55Speaker 00

  Yeah.

• 6:55Speaker 01

  If you will. So you've got kind of like that DNA. And then on the other side of it, you've got an existing live species.

• 7:01Speaker 00

  Yes.

• 7:01Speaker 01

  That is close enough.

• 7:03Speaker 00

  Close enough.

• 7:04Speaker 01

  But not the same.

• 7:05Speaker 00

  Not the same.

• 7:05Speaker 01

  So walk us through, how do you determine where in the DNA the differences that matter?

• 7:12Speaker 00

  Yep.

• 7:12Speaker 01

  Lie, right? Because there's lots of differences, I assume.

• 7:15Speaker 00

  Yeah, yeah. So yeah, that point, like people sometimes get confused and they're like, well, an Asian elephant's 99.6% a mammoth. But they're like, but that point, that point four is quite, quite large, as you know. What was interesting though about certain species, like mammoths are closer to real, mammoths are closer related to Asian elephants than Asian elephants are to African elephants. I suppose people's mind, right? And so, so we look for the closest living relatives because I think if you think about it, both from a reproductive tract perspective and from a kind of evolutionary biology perspective, they will have the highest likelihood of less number of impactful edits. And so what we try to do is very much like software, so I think it's nice to talk to someone about this in software. We think of this as like functional, the extinction. We're not trying, we've always said this, we are not trying to clone an extinct species.

• 8:00Speaker 00

  There's no living cells for dire wolves or mammoths or anything, regardless of what like. Weird TikTok someone occasionally sees about like Or like Jurassic Park. Yeah, there's dinosaur cells. I see that. And then like, I get a flurry of like, people sending me DMs are like, they found dinosaur cells. They did not find dinosaur cells. Or the dinosaur embryo you guys are surprised seeing on Instagram. It's like, that's not, that's fossilized. It's not real. It's real. It's not viable. And so what you do is you look for the closest living relative. And then we're really looking for the genes that are fixed and conserved across it. Now, if you can get multiple samples. So on the mammoth, we have about 65 mammoth genomes, right? Ranging from about 1.2 million years old to about 4,000 years old.

• 8:42Speaker 00

  Which is great, because then we can really identify what truly made a mammoth. The mammoth is, as you know, a lot of that's like genetic diversity, genetic drift and whatnot. But what are the core things that drive core phenotypes? And so we think of ourselves as more of an engineering company. The more computational biology we can do, the smarter we can be about the edits, the lettuce edits we can make with the highest impacts. You know, if you can write something, you write software with 3,000 lines of code, and you write software that's six lines of code, you want the second one every day of the week for efficiency, for bug detection, for all of these things. We think of it the same way. And so we spend a lot of time trying to identify what genes are fixed and what are in the regions that we already know from literature that drive like

• 9:21Speaker 00

  size, hair phenotypes, coloration, and whatnot. And, you know, like on the mammoth, it's about 85 genes. So there's about 85. It's still a lot, but it's not like, you don't have to make, you know, 2 million changes to get the core phenotypes that really made a mammoth a mammoth.

• 9:37Logan Bartlett?

  Before we go into like the specifics on making the two things work together, but so, so did you start top down, like, hey, we want to make a woolly mammoth and a dire wolf and then figure out the ways to do it? Or did you have like 15 different things and what's viable that we could actually do?

• 9:52Speaker 00

  So we started with this system, right? We're like, how'd you, we started with the mammoth. And then we said, how do you make a mammoth, right? So we've kind of like built out like that core system. It has ancient DNA extraction. It has DNA assembly. It has comparative genomics. It's got tissue culture. It's got cellular engineering, genetic engineering, embryology. Some axillary cloning is effectively, it's got all embryology, like IVF. Elephants, so we had to go figure out the whole system. And where'd you actually find the DNA of the mammoths? So we actually worked with, so two, uh, uh, twofold. One is I'm on the board of trustees of the Explorers Club. And so they actually have people that go out into the Arctic and have expeditions. George Church has actually been to Siberia and Churchkey and all these and brought back samples.

• 10:32Speaker 00

  Um, most of our samples actually come from, uh, University of Stockholm. So we work with, uh, Lou Vidalin, who's the number one mammoth researcher in the world. And he actually provides us with, uh, DNA and samples, right? And is it preserved in a way that's actually replicable? It, it, it depends, right? So it's all, and it comes in all shapes and sizes. So, um, you know, what's great about, you know, mammoths is a lot of them died in cold places. So it was preserved on some level, but most of it comes not from that fleshy tissue. People think that that's it or mummification. Most of it comes from like teeth and the petrisbone, which is like an inner ear bone that's really, really like condensed. And it doesn't change a lot after you're born. So it's a great DNA storage vessel. It's, Amber is not the best DNA storage fill. If you've seen a movie about it.

• 11:14Speaker 01

  Yeah. And I think this nuance, especially like when I've talked about this, this idea with people, cause I had, it's, you know, it's cool.

• 11:19Speaker 00

  Yeah.

• 11:20Speaker 01

  That, that maybe people miss in the beginning is you're not actually trying to take the mammoth DNA or the dire wolf DNA.

• 11:27Speaker 00

  And ram it in.

• 11:27Speaker 01

  And there's like stick it into, and grow it. And, and, and that's actually, I think what everybody thinks at first.

• 11:32Speaker 00

  I know. We have the same, yeah.

• 11:33Speaker 01

  Cause it's Jurassic Park. You're like, I'll just grow the dinosaur. And that's, that's not how it works. But what you're actually trying to do is take the closest living relative to a dire wolf in this case, what, what's the name of the species?

• 11:44Speaker 00

  Oh, it's for a dire wolf. It's a gray wolf.

• 11:46Speaker 01

  Gray wolf, gray wolf. That's what I was missing. And you're saying, all right, if I make a few changes in the gray wolf DNA, I'm going to get things that look like dire wolves. Maybe not an exact copy, but inching closer to it.

• 11:57Speaker 00

  And they are the, and like, so if you were to take the, uh, if you were to take like, uh, for example, L coral, it's a gene that drives size. If you take, if you take L coral from the dire wolf and L coral from, uh, a gray wolf, and you were to take them out, right? To this Jurassic Park example and, um, and then stick them back in, what we've done is we take out the, the, um, well, in this case, we actually synthesized. We synthesize L coral with the same code. Cause the, what people don't realize is like, or what some people don't realize is that the DNA. Those cells are dead. So we're basically getting the code, right? We're getting what are the right letters in the right order?

• 12:34Speaker 01

  It's code, but not actually viable DNA.

• 12:36Speaker 00

  It's not actual viable DNA. It's not like we're taking blood out and injecting blood. We're reading the code and then we're either changing what's in there or synthesizing a piece and swapping it in. So if, if, you know, if, if you had blinders on and you then cut that exact gene out, it is the dire wolf gene. It's just been synthesized, right? Cause you can't move it over there. Sometimes people think we've got like the smallest like scissors and the smallest like little tweezers and we move shit. And that's just not, that's just not the case.

• 13:03Logan Bartlett?

  And this is maybe a stupid like definitional thing, but when you announced this, there were so many people that were parsing like the, the language, kind of to what Zach is saying.

• 13:12Speaker 00

  Semantics, yeah.

• 13:12Logan Bartlett?

  Of like, you didn't actually, you didn't bring them back from extinction. You, and so I guess, how did you think about what the appropriate end state was to get to?

• 13:22Speaker 00

  No, it's, it's a great question. So we've said from day one, in fairness to semantic, semantic arguments is that like, we've been very transparent and clear with what we're doing from day one. Like we say, we made this many edits. These are the edits we made. These are what they do. They're like, we didn't say, hey, we made a mammoth. We promise it's a secret and we don't like, we, we said all of that, right? When we made our woolly mouse, we're like, here's every edit we made in every single region. And here's about like, we've been very clear about it, right? So there's, make no mistake on that. But what's been interesting is we've also talked about functional de-extinction. We've said, we cannot clone mammoths. We're not cloned these, these cells don't exist. We've been very, very clear about it, right? Uh, but you know, there's a, a group called the IUCN, which is like the, you know, it's in the Species Survival Commission, which is like the UN of Species.

• 14:07Speaker 00

  And they came out five years before we started the business and said, here are the things that you have to do in order to make an extinct species, right? It's be classified as extinct species. And what other people don't know is there's actually like 31 different ways. I didn't know this because I'm not a biologist or paleontologist. There's 31 ways, uh, kind of like Baskin Robbins of like how you define a species, right? So we were probably taught, or I was taught, uh, in, in my schools, the biological species concept where it's like, if things can't interbreed, then they're unique species. But if you see a polar bear. And a brown bear, guess what? They're a unique species. They have a different species, same genus, but separate species names. Most wolves and canids fall in that same category as well as most bears. But by like the biological definition of species, which is one of the 31,

• 14:52Speaker 00

  they're not the same. They should be classified as the same species. If you ask most paleontologists, they will agree that they should be not separate species. You know, morphologically, one's white, one's archi-adapted and one's aquatic. But they have babies that are super healthy all the time. There's tons of interbreeding that happens there. And I think that what people don't always realize is that speciation is a human construct that we're trying to put on these things, right? And so for us, you know, we've been very clear that we're doing functional de-extinction. We've been very clear, you can't clone an extinct species. We've always said that we're trying to identify the core genes that make a species a species and bring those back, right? To make proxies for that. So we've been super clear on that. And what's been, the two things that one's sad, one's funny.

• 15:36Speaker 00

  What's been sad about some of the reaction to the dire wolf is that, yes, while it broke the internet, the people that spent hundreds of hours, like Time Magazine and The New Yorker and Rolling Stone, that spent hundreds of hours with our teams, went to our labs, talked to external validators, talked to us, their conclusion was, yeah, this is about, this is as dire wolf as we're ever going to get, right? Because to your point, 99.5% was the same. So they came to that conclusion, right? Like, we didn't write those headlines. You know, there will always be people that debate semantics. But the sad thing is, they kind of missed the bigger picture here, right? Like, that, you know, we're inspiring kids, we're bringing technology to conservation, and we've done genetic feats that no one else has done. No one has ever taken ancient DNA, put it in a living species, and also done it through multiplex editing and got 100% efficiency.

• 16:21Speaker 00

  I mean, you know, from your back, like, that's insane. And so they've kind of like, the Seinfeld, they're like yada, yada, yadded over the science, and they just want to argue the name. And it's like, if the worst thing that happens in our dire wolf is that people want to argue the semantics of how to classify it, then I think we've done okay.

• 16:36Speaker 01

  I think I view it as like forced evolution is the method you're using.

• 16:40Speaker 00

  I love that idea.

• 16:41Speaker 01

  Right? Because you're not, you're not kind of like, I mean, you're working backwards in the logic, but the actual way the science happens is you're, you're forcing the gray wolf.

• 16:49Speaker 00

  Yeah.

• 16:49Speaker 01

  To become a dire wolf through like little tweaks in the DNA.

• 16:52Speaker 00

  Yeah.

• 16:52Speaker 01

  And that's, that's how you get there. By the way, that's probably how the dire wolf evolved.

• 16:55Speaker 00

  Well, so, so, so three, so three things on that. What I, you're, I love forced evolution. It's a great way. I always say accelerated, that's, that is forced evolution. But what's interesting is that people don't realize this, but we have a 13,000 year old tooth. And we have a 63,000 year old or 62,000 or 72,000 year old skull. So we have 60,000 years of genetic divergence. There's more genetic divergence between our two dire wolf samples than the living wolf cells and our other, and our tooth. People forget that part, right? So from an evolutionary distance perspective, there's actually more evolutionary distance between our two dire wolf samples than our dire wolf and gray wolf sample, right? And so people kind of forget that. And then the other thing is I love to ask people like,

• 17:38Speaker 00

  did you see Jurassic? Because we get the, believe it or not, we get the Jurassic Park question.

• 17:41Speaker 01

  I can imagine.

• 17:41Speaker 00

  And.

• 17:42Speaker 01

  That's actually page two.

• 17:44Speaker 00

  Okay, it's all page.

• 17:45Speaker 01

  Photos as well.

• 17:47Speaker 00

  And so we always get the question and I always ask people, did you watch Jurassic Park? And they're like, yeah, what's the movie about? Some people get cute and they're like about human hubris, but, but what is the movie really about?

• 17:56Speaker 01

  Dinosaurs.

• 17:57Speaker 00

  Fucking dinosaurs, right? And so in that, I'm like, well, are they? Because they're genetically modified birds with ancient DNA and with frog DNA. And then the latest one, they've got everything under the sun in it, right? And so they are synthetic biology genetically modified organisms. So are they dinosaurs or are they that? So it's like, if you classify what you see in Jurassic Park as dinosaurs going by Jurassic Park tech, right? Which is, which is similar to what we do, then you know, our dire wolves are dire wolves. If you want to argue that our mammoths are going to be cold adapted elephants with mammoth alleles, then say that.

• 18:31Speaker 01

  It's actually the perfect example of like the well, actually of the internet.

• 18:34Speaker 00

  Yeah.

• 18:34Speaker 01

  It's like, it's just people want to, it's, it's the super cool thing that has never been possible happens. And people are, well, actually.

• 18:42Speaker 00

  Yeah, yeah.

• 18:42Speaker 01

  It's not quite as cool as you think. It's not exactly.

• 18:45Speaker 00

  It's an amazing achievement from a science. I feel bad for the scientists, right? Because people are like, I've been asked, it's like, does this upset you? And I was like, I was just did this thing in the LA Times and they were writing, they were writing an editorial that was quite negative. And I was like, they're like, are you frustrated with that? I was like, no. I was like, what? Story besides tariffs in the world, three weeks later, you're still talking about it. I was like, what, what the people that hate colossal the most about that are these like armchair scientists, right? That are not at the top of their field. Remember, we have, people love to say, well, scientists disagree. I have 95 of the top scientific advisors and Nobel laureates in the world, right? I've got all the top ancient DNA experts are working with colossal. And then I have 170 people with 140 of those being scientists that we pulled from the top universities. So

• 19:29Speaker 01

  What do they disagree with, the little

• 19:31Speaker 00

  They want the classification, classification.

• 19:33Speaker 01

  Ah, the branding.

• 19:34Speaker 00

  They, they want, you can't call them dire wolves. So I'm like, well, then call them whatever you want. And people hate when I say that, but I was like, I, if you want to

• 19:39Speaker 01

  Just call it dire wolf 2.0.

• 19:41Speaker 00

  Yeah, or call, or call, how about this colossal dire wolf.

• 19:43Speaker 01

  There you go.

• 19:44Speaker 00

  And they're like, ah, and I was like, no, no, but that's fine. If you want to keep arguing the semantics on this, what you're doing is you're just driving more attention to my company.

• 19:52Speaker 01

  Yeah.

• 19:53Speaker 00

  So I couldn't be happier with people arguing the debate on what to call them.

• 19:58Speaker 01

  I'm sorry, I'm going to go back to the, the methodology.

• 20:00Speaker 00

  Yeah.

• 20:01Speaker 01

  Cause I find it fascinating. So you take the gray wolf DNA, if you will. And we'll talk about like, what, what are you actually taking? Like, is it a cell line? Do you synthesize it? But

• 20:10Speaker 00

  We take cell lines.

• 20:11Speaker 01

  You take the cell lines?

• 20:11Speaker 00

  Yeah. And, and what we found is that there's, cause these are all non-model species, meaning they're not a mouse or a pig. These are species that really aren't that well studied, right? And so we find that different cell types and different species work better. With specifically, uh, the wolves, a lot of the cells were sinessing and they just couldn't, we weren't, we, we didn't go through the process of making pluripotent sub cells, making basically reprognable cells back to their most nascent state. We actually, uh, discovered a new type and it's not, we didn't discover the cell. We discovered a new way to use a cell, like the inner lining of like our, our veins. They, they kind of schluff off this, uh, these things called EPCs, endothelial progenitor cells, which are not fully differentiated because you can't clone from blood because there's no nucleus and red blood cells.

• 20:54Speaker 00

  But you can capture from blood, these cells, which is awesome for cloning because they're highly efficient to clone. They're super easy to bio bank. And from an animal welfare perspective, you just take a blood draw. And so you don't have to take like skin biopsies or liver tissue. You don't have to anesthetize the animal. And so for our dire wolves, we actually use EPCs.

• 21:13Speaker 01

  EPCs. Yeah. So just to translate for, for people, or at least the way I, I think about it is there are, you know, in a gray wolf, there's how many cell types?

• 21:21Speaker 00

  A lot.

• 21:21Speaker 01

  A lot.

• 21:22Speaker 00

  Yeah.

• 21:22Speaker 01

  And, you know, They don't love to be messed with.

• 21:25Speaker 00

  No.

• 21:26Speaker 01

  Right? Like you start messing with the cells, they, they, they, they're not happy.

• 21:29Speaker 00

  Yeah, they die.

• 21:30Speaker 01

  They die. Yeah, exactly. And so there's only a certain, it depends on the animal, I assume, but like certain type of cell that you can even like tweak.

• 21:37Speaker 00

  Yeah. And somewhere in, so a lot of times it's, uh, so getting to pluripotent stem cells is typically the best. Embryonic stem cells are great, but in the pluripotent stem cells are great because we can differentiate different tissue types. So we can test the edits before you even have to make the animal.

• 21:51Speaker 01

  Yeah, that's where I was gonna go with. So, you know, you're, you're in, in the beginning, I assume you're, you're kind of like guessing at the edits.

• 21:56Speaker 00

  Yeah.

• 21:56Speaker 01

  Like you think based on whatever various studies and wolves and you kind of know are roughly, this looks like it's the hair and this looks like it's the sun.

• 22:03Speaker 00

  Yeah.

• 22:04Speaker 01

  So before you ever kind of commit to the new, the new embryo, if you will.

• 22:07Speaker 00

  Yeah.

• 22:08Speaker 01

  You do edits in the gray wolf, so, so whatever, whichever cell line you're using.

• 22:13Speaker 00

  Yeah.

• 22:13Speaker 01

  And you can, you can generate tissue from that cell line?

• 22:16Speaker 00

  You can, you can generate tissue from the cell line. So I'll give you the best example that I think people understand is, wait, did you see our woolly mouse?

• 22:22Speaker 01

  Yeah, yeah, yeah, yeah.

• 22:23Speaker 00

  So fan favorite, kid favorite. Uh, people, by the way, we got negative feedback from the scientific community, uh, when we launched the dire wolf and they're like, we thought they were only working in mice. Cause they were, we got some negative feedback when we launched woolly mouse is like, they'll never get to a mammoth because these idiots are only working in mice. And they're, they're not very far. They're never gonna, and then, and they were frustrated at us because while we were taking this negative feedback, we had these dire wolves that were already been born. And so, which are obviously not much harder project. But, but with, but to that example, there's three ways that we can really test, uh, whether the edits that we make in a mammoth and an elephant will be a mammoth. Right? You can grow one, which is risk.

• 23:03Speaker 01

  Time expensive.

• 23:03Speaker 00

  22 months of, 22 months of gestation, quite a long time. That's option one. Option two is you can do some, you can do some modeling and some like molecular test. And is it exuding the right protein? Like you can do that test. I guess there's four. The third is you can grow organoids as a tissue. So we actually have grown, uh, we've created elephant pluripotent stem cells and we've differentiated them into organoids for hair. So we have. Like, kinda creepy, it's super sciencedified. So we actually have like hair growing in, in

• 23:29Speaker 01

  Like a petri dish.

• 23:30Speaker 00

  Yeah, which, which, which is alive, but it's not a full animal. But then you can use mouse models, right? So what we've done is we took, we didn't just take the mammoth genes and ram them into a, a mouse, because there's about 200 million years of genetic divergence. We, we then looked at, okay, what are the specific, uh, uh, variants in mice that are in the same genes? We're looking at those same gene families in the, in the sub pathways. And then let's make those edits. And then we did eight edits in seven genes. Once again, all using multiplex with 100% efficiency. We screened for off targets. So this is, this is pretty amazing science, like just that in itself, that, that delivery mechanism was incredible. Uh, so, so we did that. And then 21 days later, we got our woolly mice that had the color, the coat type, the,

• 24:13Speaker 00

  the hair length, the, the way the hair is growing different ways, the thickness. And so we were able to visibly see those phenotypes. So in longer gestational species, we can do that. Now, the good things about wolves and dire wolves is they're dogs. So we, we've done a lot of genetics on dogs. So we went to Brigitte Von Holt, who's the number one, uh, uh, wolf, uh, expert, specifically around red wolves, which is one of the closest living relatives to, to the dire wolves, which is critically endangered. The most endangered wolf on the planet is the red wolf here in America. And then we went to the Broad Institute in Eleanor Carls. And we, and she's the number one Canid expert, geneticist in Canids. So then we could look at doing all of that comparative genomics so that we weren't making choice, uh, gene target effects that could have negative impact.

• 24:56Speaker 01

  Yeah. So translated, I think for, for, for people, you think you know what in the DNA you need to edit based on a variety of different, like ways you can research it. You're not 100% sure you're right.

• 25:07Speaker 00

  Yeah.

• 25:09Speaker 01

  And so you have to kind of make the edit and see what happens. There's only so much see what happens you can do before you actually grow one.

• 25:16Speaker 00

  Yes.

• 25:16Speaker 01

  So you're looking for proxies like skin and I assume hair color, stuff like that.

• 25:21Speaker 00

  So, so on the hair color, I'll give you, I'll give you an interesting one. And, and once again, this goes back to this whole. Stupid, I think stupid purist perspective, right? So we found out, so before we brought back the dire wolves, here's what the world knew about dire wolves. We knew roughly where they lived. We knew roughly when they went extinct. We knew they were roughly 20 to 25% bigger. And we knew that based on muscle and they had a larger, a slightly larger skull. And then we knew based on the bone density, we think they were heavier.

• 25:47Speaker 01

  What's the defining characteristic you think that gets normal people to believe it's a dire wolf?

• 25:52Speaker 00

  I think it's size. No, I think it's size. I think it's size and they did know dire wolf. It's it's size, muscle structure and cranial facial, the bigger snout.

• 26:02Speaker 01

  The snout.

• 26:02Speaker 00

  Yeah, those are, those are things that we, that's what we knew.

• 26:05Speaker 01

  Yeah.

• 26:05Speaker 00

  Right before this. Now, what we found out, and this is the good and annoying thing about science. Five years ago, there was a paper about dire wolves, right? And a misconception. So the result of that paper was, are they, what are they, where do they fall in the Canid lineage? The results of that paper, not our paper, but that paper, which Beth Shapiro, our chief science officer, and many of our scientists were on that paper, came out to, we don't know. We don't have data. They had 0.15x of the genome. That means that they had less than a full read of the full genome. We have 13x reads. We have 500 times more data. We've got a lot, we've, and then we have, sorry, we have two specimens out. So what's interesting about that, that was, you know, once again, the press cycles because of Game of Thrones. You know, people in the paper, it mentioned jackals because they were somewhere in the Canid lineage.

• 26:50Speaker 00

  So the paper, there were stories that came out five years ago that said dire wolves weren't wolves, they were jackals. And then there's paleo artists that drew them to look like jackals. So they're red. So when we launched our thing, people were like, no, no, they're not wolves. They're closer related to jackals. By the way, the original paper doesn't even say that. And with the paleo artists that we all see in our minds from that original paper, they were red. So what we also found out when we did the resampling was, one, they are closer to wolves. So we put out a paper about that. We also found out they were white because there's no dire wolf DNA. There's no dire wolf hair laying around. So we didn't know that. So we found that. And going back to your gene question, here's what we found. The specific edit in the, or sorry, the specific variant that causes white hair, white hair in Canids,

• 27:33Speaker 00

  so in all dogs, the specific truncation in the variant, the, the, the, the specific one has been known that dire, that, that at least our two dire wolves had with 60 million years genetic divergence. So we know that they're white, but it does sometimes cause blindness and deafness in some wolf and dog breeds.

• 27:54Speaker 01

  Yeah.

• 27:54Speaker 00

  So this goes back to choice. So if we're rebuilding dire wolf 2.0 or rebuilding extinct species for today, like we think about, a purist perspective is just go stick that gene and see what happens. Let's roll the dice, right?

• 28:07Speaker 01

  Yeah.

• 28:07Speaker 00

  From an animal welfare perspective, because we're sort of by American Humane Society, the oldest humane organization in the world. That's a terrible idea, not just because of our certification, but because of like just true animal welfare. So what we didn't, what we then did is we worked with the brood and other people and said, what is the same gene that causes the same coloration that we can put in that we know has no negative impacts?

• 28:28Speaker 01

  So when you're, when you think, and I have a note here, it's like roughly 20 edits across 14 genes.

• 28:32Speaker 00

  Roughly, it was 20 edits.

• 28:34Speaker 01

  Are the, like, talk to me about the edits themselves. Are these like individual base pair edits? Are you inserting?

• 28:40Speaker 00

  Well, a combination. So these were all, these were all snippets. So these were all individual base chair, base, base, uh, individual base pair edits.

• 28:48Speaker 01

  And sorry, are you doing this in gray wolves?

• 28:51Speaker 00

  We're doing this in, on the gray wolf. We call it the genetic donors.

• 28:55Speaker 01

  But then the validation process, you use the woolly mouse as an example of getting to the woolly mammoth. What are you doing?

• 29:00Speaker 00

  So we didn't, we didn't do a woolly mouse type project for this because we know so much about dog genetics and wolf genetics, right?

• 29:08Speaker 01

  Because we've been doing this for a long time.

• 29:09Speaker 00

  Right? So it's just like, it's.

• 29:11Speaker 01

  You make, you make the edits. Let's, there's some validation that, okay, we think these are gonna, these are gonna work. How do you handle like the actual editing itself?

• 29:18Speaker 00

  Yep.

• 29:19Speaker 01

  The tech, do you do it in-house, out of-house? And then there's, there's this concept of like off-target.

• 29:24Speaker 00

  Yeah, yeah.

• 29:24Speaker 01

  And it's what we're all gonna talk about. It's just like, you edit here, but also something happens over here and you didn't realize.

• 29:29Speaker 00

  Consequences are off-target effects.

• 29:30Speaker 01

  Yeah, yeah.

• 29:30Speaker 00

  So these are awesome questions. So a lot of times, a lot of these editing tools, uh, essentially have like 15 to like 20% efficiency. And I think that's a good day in some of these cases, right? We're seeing 90 plus percent efficiency before we do monoclonal screening, meaning we screen all the cells, which we'll get to in a second. This answers your off-target effect. So what we do is we edit a lot of cells. One of the things that colossal has done, I think that is novel is we've. Really focused in two categories. DNA synthesis, so synthesizing big blocks that we can swap in safely, number one. And number two, multiplex editing. And I would argue, and I think that our investors would all argue that we're probably the number one company in the world in terms of multiplex editing. Being able, and what that means in kind of layman's terms is instead of making one change, we're making a bunch of change.

• 30:16Speaker 00

  Now, where we're getting pretty interesting is we're clustering all of that. So we're building arrays to deliver not just multiplex editing of single nucleotides or knockouts, knock-ins, or even, and then these large cargo inserts. We're wrapping all that and we've got a novel way of delivering a lot of edits at once. So we're now making over 50 edits at once right now, which is, which is insane.

• 30:39Speaker 01

  Yeah, the thing I think is sometimes hard to understand is like the more stuff you're trying to change in a single cell, the more chances it goes wrong.

• 30:48Speaker 00

  Yeah, the more chances it goes wrong, causes breaks, causes unintended consequences like off-target effects. It's also the higher probability that the cell just, I mean, you're, you're hitting the cell, right? Think about it, you're punching the cell.

• 30:59Speaker 01

  And it's just like a CRISPR-driven.

• 31:01Speaker 00

  It's a combination. So CRISPR is one from a knockout perspective. We're doing single, we're doing some, using some of the work. We've got licenses to the Basin Prime editing from the Broad and from, and from David Lu's lab. And so we're using a combination of all these tools. And then we're packaging all of it in different ways. And I think one of the things that's interesting about colossal is our packaging and our delivery mechanisms are creating very high degrees of efficiency with how we're delivering.

• 31:29Speaker 01

  So you get, yeah, well, maybe we can make some numbers up, but you got your cell line.

• 31:33Speaker 00

  Yeah.

• 31:33Speaker 01

  You make a bunch of edits. You hope, obviously that the edits work.

• 31:37Speaker 00

  But then you screen all.

• 31:37Speaker 01

  Screen after the edits.

• 31:38Speaker 00

  You screen all the edits. And then one of the things that we do is we then do, we do full genome, we do full gene sequencing, right? On all, on the edited cells. And then, once we go through the somacel nucleotransfer or cloning process, once we transfer the nucleus, we then resequence them all, which, which is a lot of.

• 31:58Speaker 01

  In the fertilized, roughly, if you call it that, fertilized new cell. Yeah. So step by step, basically like you've got your cells, the gray wolf cells.

• 32:07Speaker 00

  Yeah.

• 32:08Speaker 01

  You've got a bunch of cool technology to go and edit them. That is actually very hard to do successfully at any scale because you just get like errors and issues along the way. Making 20 edits is not an easy thing to do.

• 32:19Speaker 00

  I mean, it's ever been, there's only one other group that's ever done 20 edits that we've seen. I mean, maybe there's one that we haven't seen that's made 20 edits and they were just, they were random knockouts.

• 32:30Speaker 01

  Right.

• 32:30Speaker 00

  So they weren't, they weren't really what we call precision editing, right? They weren't like, let's change this letter to this letter.

• 32:36Speaker 01

  Yeah, or like take this whole thing out and swap a new piece of DNA in, which is like a big change.

• 32:40Speaker 00

  Yeah.

• 32:41Speaker 01

  You then have the like.

• 32:42Speaker 00

  We've actually done over a hundred KB swaps, which is crazy.

• 32:45Speaker 01

  It's very long.

• 32:46Speaker 00

  Yeah.

• 32:46Speaker 01

  Swap.

• 32:46Speaker 00

  Very long swap.

• 32:47Speaker 01

  So it's got to be real precise of like, where do you start and where do you stop? And there's a bunch of like new technologies, let's call it, that allow you to do this. I mean, 10 years ago, impossible?

• 32:55Speaker 00

  10 years ago, yeah, probably.

• 32:59Speaker 01

  Probably impossible, yeah. So timing as well.

• 33:01Speaker 00

  Yeah.

• 33:01Speaker 01

  And then what's the big change in the, like, what do you think has allowed this?

• 33:04Speaker 00

  So I'd say, I'd say there's the, the, the three things. One, AI and AI and access to compute is definitely, like, this would be impossible without that for us.

• 33:13Speaker 01

  Which part of it?

• 33:14Speaker 00

  So all the, all of the DNA synthesis work would be impossible. All of the comparative genomics work, some of the ancient DNA assembly, we've built some proprietary tools around it.

• 33:23Speaker 01

  To like know what to change and the analysis there.

• 33:25Speaker 00

  Yeah, we actually, we actually have a tool that's pretty cool. So we use, we do a lot of interesting things. When you come from a software background, you try to, oh, we'd solve everything with software, right?

• 33:34Speaker 01

  Not here.

• 33:34Speaker 00

  No, I, no, but I, but I naively thought that. So everything, you know, it's like you have software hammers, everything looks like a software nail. So, um, but we have done some pretty cool stuff. Like, we have one thing that is not interesting to probably anyone else, but we now, we've fed it enough data over enough editing with different types of editing modalities that we can now effectively say, we're going to go make this change in this part of the genome, which is the best tool? And it tell, it actually relevance ranks the tools for us of what we should use, which will, which, which have the highest likelihood of less off-target effects.

• 34:06Speaker 01

  Yeah, those, those, I assume the answer would be the actual editing technology to like go into the cell, into the nucleus and swap DNA in the spot that you want is reasonably new?

• 34:16Speaker 00

  Yeah, it's reasonably new, like last five years.

• 34:18Speaker 01

  Yeah. So to do, maybe you could do like a single base pair swap.

• 34:21Speaker 00

  But people are still doing that. I mean, people are claiming victory, which is great. I'm, I'm all about this for. A small knockout for just a single change. Like, people are doing that all the time. Like, you know, like, when, when the one of the negative feedbacks we got when we launched the William Mouse Project, which I would say is pretty objectively cute project, they, one of the feedbacks was like, well, people have made eight changes in a mouse. And I was like, not at once.

• 34:46Speaker 01

  Yeah, individually.

• 34:47Speaker 00

  Yeah, they've done it over eight generations of mice, right? And so, so we, like, the, these are the things that I, and I think that, I believe that, I don't know what the current upper limit is. I don't.

• 35:00Speaker 01

  Of changes.

• 35:02Speaker 00

  Of changes.

• 35:02Speaker 01

  Yeah, before something and it just goes wrong.

• 35:05Speaker 00

  We're just doing, we're doing, we're hollering it so well, that we're doing 50-plus edits right now. And so this like, this goes back to your point of, of risk, right? Like, one of the feedbacks that we got on the classification of dire wolves, like, why didn't they make a thousand changes? It's not going to make, on a percentage basis of three and a half billion base pairs, guess what?

• 35:24Speaker 01

  It may not matter.

• 35:25Speaker 00

  It's not going to make it more dire wolf, and it's not going to change the phenotypes anymore. So the physical attributes, it's not going to make it look more like a dire wolf. And it's not going to make it more dire wolf from a percentage basis, right? And, and all you're doing is, is doing more, you're just creating more risk for what? So that you can show the strength of genome engineering? Well, I can show that in a cell. I don't have to take the risk with a live animal.

• 35:46Speaker 01

  So in the new cell, you take some of them, you sequence them, you make sure you didn't have off-target issues, meaning like, hey, we thought we were going to edit this thing.

• 35:52Speaker 00

  And we did.

• 35:53Speaker 01

  But, oh, well, we also edited over here.

• 35:55Speaker 00

  Yeah.

• 35:56Speaker 01

  Because DNA is complicated, and it's not as simple as just, you know, it doesn't, doesn't work that way. And so the notion of like, off-target can be really bad.

• 36:03Speaker 00

  Yeah, exactly.

• 36:04Speaker 01

  Right? Either because like, it just makes the cells not viable, or...

• 36:07Speaker 00

  And so that's where we spend a lot, we, we spend a lot of money and time on sequencing. We, we kind of like...

• 36:13Speaker 01

  But it gets cheap now.

• 36:14Speaker 00

  Yeah, but it, but it's belts, it's belts and suspenders, right? Like, I think from a, when you're living, doing not just cell work, but your goal is to have a living, healthy animals, like, I think you have a responsibility to do that. And so, people are like, oh, you raised so much money. It's like, well, one, we have to build a whole system. Two, we have to have the best people in the world. This technology is really expensive. Oh, and by the way, like, we, we're adding in layers of safety protocols throughout the whole thing. Because the last thing we want is some, like, you know, stillborn animal or something, because we made the wrong change and we, and we didn't screen for it.

• 36:43Speaker 01

  Yeah, you get a wolf with... Mental issues or behavioral issues or physical issues.

• 36:49Speaker 00

  And that, I mean, that happens all the time. I won't say which one, but there is a zoo in the United States that recently had a stillborn giraffe that had multiple heads and multiple legs and they weren't gene editing. That's just biology. Biology goes wrong, right? It's not perfect. And so, so we have, I think we have a responsibility when we're taking in that forced evolution, right? That, that we need to actually overprotect to ensure that the things we're doing won't have negative.

• 37:16Speaker 01

  By the way, and this is like probably a longer conversation for another day, but the whole like biology goes wrong thing, I think is like for normal people who aren't in science day today, which was me, you know, as of like three years ago. Now I get it a little bit better. But you forget that like the, the ability for biology to go wrong is also what enables evolution in the first place. And so you need a little bit of like, nope, that's not good. That's not good to catch the one that, that is.

• 37:40Speaker 00

  That is, that, that, that advances the ball for the.

• 37:43Speaker 01

  All right. So you get the, you get, let's call it like the clean new.

• 37:45Speaker 00

  Yeah.

• 37:46Speaker 01

  DNA.

• 37:46Speaker 00

  The cells you're super stoked about.

• 37:48Speaker 01

  Now you gotta get them into essentially, you could think, I think of it as kind of like into like an egg, right? If you will.

• 37:53Speaker 00

  Yeah. It's a great way to look at it. So this is the same thing that we did, we as Humane, not colossal, did with Dolly the sheep, right? Only they were using like archaic tools like jamming stuff together. We use a combination of robotics. We actually have a laser drill. We have a hole system that use computer vision to drill into a hole into the, the outer shell so that we're not just hitting and like literally physically just jamming the.

• 38:15Speaker 01

  You take the whole nucleus out and pop it in?

• 38:17Speaker 00

  Yes. So we take the whole and we cut, it's pretty interesting what, what.

• 38:20Speaker 01

  Can you explain that one in like kind of simple, I mean, dumb it down, but like.

• 38:24Speaker 00

  So instead of like, like before we like, like they would have needles in kind of, kind of blunt instruments that are just like jamming the nucleus to extract the DNA. We aren't doing that. So we actually cut a hole in the outer shell, the Zona pulusa. We go in, we actually fabricate our own, we actually fabricate our own removal devices as well. Because there was nothing that could do exactly what we wanted to. And different species have different things. Like for example, we needed to build a, one made out of quartz. The only way that we could do get into the get past the zone of pelusa in that we vibrated at insanely high frequency to get into the zone of pelusa for marsupial cells.

• 39:07Speaker 00

  And it sounds weird because you're like, oh, big giant elephant, little tiny marsupial. But their outer shell is insanely hard that that we hit it as hard as we could with a laser and it wouldn't even burst.

• 39:16Speaker 01

  Wouldn't open.

• 39:17Speaker 00

  Yeah, so it's crazy. So we do that. And we take out that middle kind of brain. And then we put it into that of an egg cell where we kind of do the exact same process. In reverse, suck it out and kind of make space for it. And then we drop it in. And then essentially you have an embryo, right? You have the precursor to to an embryo, which is pretty, which is pretty awesome.

• 39:32Speaker 01

  And you take that and implant it back into a gray whale?

• 39:35Speaker 00

  So you grow it. So you grow it in in culture for a little bit, right? So once you get to a little bit further, you put it, we use domestic dogs. So we put them in in domestic dogs.

• 39:45Speaker 01

  So like it's the actual growth, what percentage of the from like the actual embryo to growth is in the dog versus in the in the lab?

• 39:53Speaker 00

  Oh, 99% is in the dog.

• 39:55Speaker 01

  In the dog.

• 39:55Speaker 00

  Yeah.

• 39:56Speaker 01

  And in that process.

• 39:57Speaker 00

  Weekly ultrasounds, we do. Yeah, it's pretty involved. And why do a dog versus a wolf? Well, wolves are endangered. Yeah. And so. Oh, really? Yeah. And so you and so one of the things that colossal, we do have a 17 person team to get, we talk about this get weirder in a minute. We have a 17 person team working on artificial womb. So long term, we'd love to grow everything exhaust, just like through kind of extraterrestrial development systems. But short term, we're still using surrogates, right? And so we have to get good at for many reasons at interspecies somatocyanic transfer. So.

• 40:31Speaker 01

  Well, yeah, if you're growing, I didn't realize they were extinct or not extinct, endangered.

• 40:34Speaker 00

  Yeah.

• 40:35Speaker 01

  And so you've got to go to like a slightly adjacent species to grow. In that whole process, anything in there where you felt like this is just insanely complicated? We couldn't do it and you figured it out. I assume there's tooling and.

• 40:48Speaker 00

  Oh, yeah, it's all like, I mean, delivering the number of edits is really hard. Getting culture conditions is really hard and different projects have different issues. So so for example, You do a different process with birds than you do mammals because there's not a clear way to do semiotics, like do the cloning stuff in birds. So you have to use generational birds. So you actually, instead of editing like, um, uh, stem cells, you are editing like EPCs with wolves, we're editing what's called primordial germ cells, the precursor to egg and sperm. But just to get the culture, like this is the media, it's like getting just the media conditions for those, what they're called PGCs, to grow outside of a

• 41:29Speaker 00

  bird body is insanely hard. It's only been done publicly in chickens. Um, we're very close to having it done in pigeons because dodos were pigeons. Um, and so it's very, very hard just to get the media conditions correct on that stuff. So we have to innovate across the entire spectrum. But once again, it's like, it's not like, we know, like, well, like when you do reprogramming, we know the cellular program, we know that there's a cocktail of transcription factors. We just have to get the right cocktail.

• 41:56Logan Bartlett?

  On the surrogate side, like, how do you ensure across species compatibility of?

• 42:01Speaker 00

  So, so we typically use the egg cell from that species, right? And so the, the further genetic distance you get, you could run into mitochondrial rejection issues of the, not of the parent, but of the host, uh, of the host egg, right? And so we use- Of the dog in this case. Of the dog in this case. And so, so one of the things that, that we are working on in addition to artificial wombs is we are working on, and we're not there yet on artificial wombs, and we're not there on this other concept, but we are working on a universal egg concept of like, how do you map, how do you have like, which I think has weird, interesting applications to mitochondrial health, applications outside of colossal, but how do you map, uh, and change mitochondrial, basically have a universal egg that you could

• 42:45Speaker 00

  accept any type of nucleus in it and you have a low probability of mitochondrial rejection.

• 42:51Logan Bartlett?

  Like the simplest form of an egg that you possibly can-

• 42:53Speaker 00

  Yeah.

• 42:54Logan Bartlett?

  That will be transferable, the primitives of an egg.

• 42:58Speaker 01

  So the wolf shows up.

• 42:59Speaker 00

  Yeah.

• 42:59Speaker 01

  And now I assume there's like a whole bunch of optimization work to make sure that, you know, the throughput and the yield, if you will, this whole process just like inches up and up.

• 43:07Speaker 00

  Yeah.

• 43:07Speaker 01

  You're probably wasting money.

• 43:09Speaker 00

  Yeah, exactly.

• 43:09Speaker 01

  In a lot of areas.

• 43:10Speaker 00

  I mean, the biggest thing, the biggest thing now for us is, I'd say the two biggest areas for us from an innovation perspective that we are, is delivering DNA, you know, how do we expand DNA synthesis and delivery? How do we also deliver multiplex more and more edits at a high degree of efficiency? Because we can screen in the sequencing that that allows us to know what we did wrong, right?

• 43:33Speaker 01

  Why do you think you need more edits? I mean, the wolf looked pretty, pretty wolf-like.

• 43:37Speaker 00

  I mean, it looked just like a dire wolf.

• 43:38Speaker 01

  Yeah.

• 43:39Speaker 00

  So at least at this stage, morphological, I mean, they're 85 pounds right now and they're six months old, right? A typical wolf is like 75 to 100 pounds, right? So we're on the trajectory, the wolves grow for about 18 months, we're on the trajectory for these to be 140, 150 pounds, which is roughly what dire wolves were. So, and then, and also this now, everything, their stock here, if you go look at a five month old, if you go to the internet, look at a five month old wolf pup and you look at ours, you're like, yeah, those don't look the same. You can, like, ours look like linebacker, the linebackers of the, of the wolf world. Well, it's just different species, right? So like on the thylacine or Tasmanian tiger, there's 70 million years of genetic divergence between the thylacine and, and the fat-tailed dunnar, which is, it's a marsupial carnivorous mouse. We're turning a marsupial mouse into a carnivorous wolf.

• 44:24Speaker 00

  Well, it's not a wolf, but it's a, it's a wolf-shaped body.

• 44:27Speaker 01

  So different species are going to require more edits essentially.

• 44:29Speaker 00

  Yeah. And so now the better we do at CompBio, we think that it's about 500 edits for cranial facial morphology. So we get that hypercarnivism skull, like the thylacine is a super, it was a super hypercarnivore. So it's about, we think it's about 500 edits, which we've made in a, in one cell line, which is great. But some of the, the work on sizing and some of the patterning could be, could be more. And so I think the thylacine project, it's hard to say, but it'll be thousands of edits.

• 44:59Speaker 01

  It may be a controversial question, so. Business model for a second, right? And obviously, there'll be some pieces of this, which is like, we made a technology. It's cool.

• 45:08Speaker 00

  And we spun it out.

• 45:09Speaker 01

  We spin it out.

• 45:10Speaker 00

  So we spun out three companies so far. A computational biology platform for human healthcare, a company called Breaking, which is a plastic degradation company. So we've accelerated, there's a microbe that makes this enzyme that literally breaks the chemical bonds of plastics. And so that's why we call it Breaking. And that's now, we've raised capital for both those businesses. We spun out another company we haven't announced yet that's valued at way over a hundred million dollars, which is great. So spin out technologies is.

• 45:35Speaker 01

  And each of those carry their own unique esoteric risks of like classic startups. You've got to, the jack has to work, you've got to scale it, someone has to pay for it.

• 45:43Speaker 00

  Yeah, some of them are right, I don't run them.

• 45:44Speaker 01

  Yeah, find a CEO.

• 45:46Speaker 00

  But I'm.

• 45:47Speaker 01

  I try to stay on the board as little as time as possible. It's also a lot of work. On the core business itself, do you view this as like, people will actually buy the wolves as pets? I mean, they're not going to buy a woolly mammoth as a pet, I don't think.

• 46:00Speaker 00

  So we got, so we got a tremendous amount of ask for everyone ranging from, the requests on the woolly mouse were ranging for kids' pets, school pets, a large household named, I don't want to throw out them, but museums want them. We've even had some museums reach out and say, well, mice don't live forever. Can we taxidermy them and put them in a display? And so like, so we've gotten all kinds of those types of requests, right? We get the apparel requests, we get all these types of requests. You know, I do think that there's lots of people that would love to buy our animals. That is not our business model. Our business model, and it's, we're learning. If you ask us, when we started, it's like, nonexistent. If you asked us two years ago, it was technology spin outs, because we thought, hey, we can create enough option value that,

• 46:45Speaker 00

  you know, if you innovate across all these things, and if we can deliver thousands of edits with zero off-target effects, that company alone is worth a hundred billion dollars, just that spin out.

• 46:52Speaker 01

  Oh, your cash runs out, which is a challenge in that model, right? Because you've got core cash and.

• 46:56Speaker 00

  And you spin them out, yeah.

• 46:57Speaker 01

  You spin them out, and then they need their own money.

• 46:59Speaker 00

  They need their own money. We don't, we don't take, we don't fund them, right? They go out.

• 47:03Speaker 01

  Oh, I just mean without like a core revenue stream.

• 47:05Speaker 00

  No, without core revenue stream, yeah. So we are raising money. So that's, that was kind of model one. There's a huge. Huge economic driver and you've probably heard about carbon credits, seen the carbon credit model, right? Yeah, mostly fraud, but. Yeah, just like crypto, like crypto, like I. Well, no, I mean, well. I would argue crypto is more of a religion than a currency, but that's another argument. I meant more like a lot of the carbon credit businesses. No, no, no. Beneath them are fraudulent. Yes, and so, so just like the early days of crypto. But what you've seen in that market, a couple of things that you've seen in that market. One is you've seen this move to biodiversity credits because it's highly trackable versus like. So that's like saying, there's now been studies that have been peer reviewed that says an elephant in Gabon has this annual ecosystem restoration and carbon impact, right?

• 47:50Speaker 00

  So you have people that aren't like, hey, like the fraud that you're talking about is that people are like, oh, like, I'm gonna go buy a bunch of forest and I'm gonna keep all the animals alive. And they like wink at you and then, and it's like, that's worth a trillion dollars of carbon. Or like, here's this forest, we didn't cut down and either the forest never existed in the first place, or they did cut it down and they just didn't tell you. No, exactly. It's been wrought with that. But what you found is that if you look at like, you know, the Paris Agreement, 66% of people's agreements say that they have to move to nature based solutions like rewilding, like some of these things. So if you look at things like rewilding elephants, if you look at kind of like the, the, the total economic value, and I'm not talking about anyone that's currently monetizing it,

• 48:29Speaker 00

  but from peer reviewed papers shows that there is over $500 billion of, of value that's being added to the African, and they take into ecotourism, take all these things into it to protect, to, to, to essentially protect the forest elephant, which is critically endangered, right? And so what we're seeing, if you look at now PWC entering the game, you see TPG, you know, raising a $9 billion fund around this. You see, who else did, oh, Lloyds of London's now certifying it. You're now seeing people saying, yeah, this market was nascent, lots of people running around. But here's the other thing, we know that ExxonMobil and we know that, you know, in this extractive economy that we live in,

• 49:10Speaker 00

  we know that like Sumitomo Corporation, Mitsubishi, in strip mining and where do you think lithium comes from? It doesn't like magically grow on trees, right? And so synthetic biology does not solve the, the house plant that makes lithium problem, right?

• 49:21Speaker 01

  No.

• 49:21Speaker 00

  And so.

• 49:22Speaker 01

  Nor is it likely.

• 49:24Speaker 00

  Nor is it very, very likely. And so I, I, I think that those companies, whether it's social pressures, ESG or government regulations like in, in the EU, they, they have to buy these offset credits, right? And so regardless of where the market was, there's now this maturation of the market. So for us, it's a perfect market timing because, you know, a lot of these pioneers got arrows in the back, which is great. Now you've got people that are actually coming in and having to certify and really understand it. So if we can go in and say, hey, we're going to return the thylacine back into Tasmania. We think the tropic cascading effects could be this. Let's go measure it. Let's bring in ecologists and conservationists. Let's then bring in Lloyd's. Let's certify it. And then let's also get government subsidies for.

• 50:06Speaker 01

  This is the most progressive left business model I've ever heard. I love it.

• 50:09Speaker 00

  Yeah, it's interesting. So we have both sides of the aisle. Yeah.

• 50:13Speaker 01

  So it's not a domestic safari that's like really expensive to visit because that I think I, I would go for that.

• 50:19Speaker 00

  Everyone would go for that, right? And so.

• 50:21Speaker 01

  Is that like an ethical consideration? I mean, like a fancy zoo sounds awesome.

• 50:25Speaker 00

  Yeah. I mean, look, I am not.

• 50:27Speaker 01

  Five star hotel.

• 50:30Speaker 01

  Sengita brings.

• 50:32Speaker 00

  No, but, but two things, like if you look at like on the eco tourism front, like we talked to, we talked to the Ministry of Tourism from Mauritius where the dodo was. And he's like, you're in a five XR tourism, right? And I said, well, look, we would love for you to give us land that goes on our balance sheet. We would love to get the carbon and biodiversity credits that we can go sell that we can get certain that we can, that isn't just like, hey, we promise you there's dodos there's wink, wink, but like, let's actually measure it. Let's have third party verifications. Let's go sell it. And the other thing about the carbon and biodiversity market is based on the sexy factor, like the, the carbon, the credits try to add a higher value, right? Because ExxonMobil wants to show that they're doing stuff with like, you know, alternative things like ethanol or algae, right? So they do trade at a higher premium. So, so if we can do

• 51:17Speaker 00

  all that, and then if we can, if we can say, oh, well, let's have a four seasons or a one and only earn a mon, be there and they do an eco lodge and we get a cut of that, then that's great, right? But also the local people get a cut of it and whatnot. And if, and if it causes people in Mauritius to clean up the environment and remove the invasive species that led to the dodo's demise, then that's a win also for conservation. And so, so I think that you can find a way to put a value on nature. Don't you remember forever? People were like, well, if we, if we charge a hundred thousand dollars to kill a lion, then we're putting a value. That was like the argument for like hunting lions. But what they, what regardless of how you feel about hunting. What they were right about is if an animal has some value and isn't just seen as some random animal that doesn't have value, someone will at least think about that, right?

• 51:59Speaker 00

  And so, and so if we can do it in the opposite way where you're not killing them, you're encouraging them to have an ecosystem function, I think that's, that's pretty interesting. And to your zoo question, we're not against zoos. Like, we, we think like people like the AZA and people that have great zoos like San Diego Zoo, they do a lot of stuff for conservation, they do really good stuff. We, we work and collaborate with some of them on different projects. You know, I, I think that bringing back extinct species just to put them in zoos seems like a weird optics.

• 52:26Speaker 01

  Yeah, it's one business line of, you know, many. Yeah. I, I was gonna go to, to maybe the-

• 52:31Speaker 00

  But, but we think that, that we really do believe the restoration work, the biodiversity credits, where we think it's gonna go is certified nature credits plus ecotourism. We think, we think that's billions of dollars in ARR for us.

• 52:43Speaker 01

  I mean, the tourism appeal is, is likely massive, right? Just given the-

• 52:47Speaker 00

  And government subsidies.

• 52:48Speaker 01

  Yeah. So. Human embryo editing.

• 52:50Speaker 00

  We are not doing that.

• 52:52Speaker 01

  I assume we, it's someone, someone's brought it up.

• 52:54Speaker 00

  Yeah, we, we do have that question. Oh, yeah.

• 52:55Speaker 01

  So what's the, the reason I ask is, you know, theoretically, and tell me where I'm wrong, a lot of the underlying technology is to do like safe editing here. There's no reason why those technologies don't also apply to editing-

• 53:09Speaker 00

  Well, it goes into germline editing, right? And there's a general more-

• 53:11Speaker 01

  On the germline side, yes, yes, yes.

• 53:13Speaker 00

  So, I would say that, um, so colossal does not work on anything that is human, uh, Neanderthal, like precursor to human, or, um, non-human primates. Just, there, there's just, like, we already get enough, you know, Incutel's an investor. We, we get a lot of conspiracy stuff already, right? We don't need more of that, right? So we're like, there's enough for us to do, we're not gonna do some of that stuff. And then if there's applications of our technologies, whether it's artificial wombs or multiplex editing or computational biology, we'll spin those out. Other people can go through the FDA, they can do all that process. That's not our problem, right? We can benefit from it, but that's not our problem. Um, all of the technologies that we're developing, you know, the work that we, uh, we're also looking at different delivery mechanisms.

• 53:57Speaker 00

  So outside of doing somatic cell nuclear transfer for, uh, which we're doing- For the cloning, we did micro injection in the embryo for for the woolly mice. So we actually are editing. So we're delivering a way that also doesn't create chimeras. So you're actually getting all of the delivery in. So it's really cool tech. And so all of that could be applied to embryo editing. We aren't doing that.

• 54:19Logan Bartlett?

  Wait, at what point, like the prioritization in all of this is probably an interesting thing. There's, there's probably, I don't know how many novelty animals you can work on. I don't know if that's the right phrase. Yeah. Just like continuing to do stuff that's sick and like would get me excited about it. But at some point, the dodo is like a little bit more practical or has more practical considerations. How do you think through the, the PR side versus the practicality side?

• 54:43Speaker 00

  The three, our three like flagship projects, right? Mammoth, Thylacine and Dodo all have, Thylacine has a, have applications to rewilding and to, and ecosystem restoration, right? So, so that, so that, those are our three flagship projects, the highest staff projects is the ones we're working on the most. Number one. Number two is we pair each one of those with the critically endangered species, right? So with elephants, it's, it's the mammoth, it's the pink pigeon with the dodo and it's the northern quoll with the, with the Thylacine. And what's interesting is like, you know, while we made three dire wolves, we also, we use that same EPC technology to clone four red wolves. There's only 15 red wolves left in the wild. It's the most endangered wolf in the world and it's the only wolf that's only endemic to America.

• 55:28Logan Bartlett?

  And you think you can grow it in a dog?

• 55:30Speaker 00

  I already have.

• 55:31Logan Bartlett?

  We have.

• 55:31Speaker 00

  I have four.

• 55:32Logan Bartlett?

  There's four?

• 55:33Speaker 00

  I have four red wolves, yeah.

• 55:35Logan Bartlett?

  Is that public or?

• 55:36Speaker 00

  Yes, probably. Yeah. Just no one cared.

• 55:37Logan Bartlett?

  That's amazing.

• 55:38Speaker 00

  Yeah. So.

• 55:39Logan Bartlett?

  And I guess as you think about.

• 55:41Speaker 00

  I shouldn't say that. No one cared in a relative, in a relative number. Last, we did bring, we did increase by a hundred thousand fold Google searches because we, I'm a data guy, so I look at all data. And there were seven billion media hits alone on red wolves. And there was, I think, 398 or 498 stories on just red wolves. So people cared, but you know, there's 180 billion impressions on, on dire wolves. So, so relatively speaking, they didn't care as much. But then a week later, after we were on the Today Show, a week later, the Today Show just ran a special on red wolves. I don't think they would have done that with without us. So, so, so we are building technologies to help conservation, right? Because another business line that we're finding, while we

• 56:24Speaker 00

  open source, I mean, the open source software is a great example, right? So you build a community, you build some tech, you build a community, you do it, people use it and whatnot, that's all great. But then you have the enterprise use cases, right? Where you've got someone like Microsoft or someone saying, hey, cool, this is cute. Our developers have used this technology. We love your technology. We don't want our developers to implement this for the Department of Defense. We need you guys invented the technology. You guys need to do it, right? So a lot of these open source communities will then have their private instincts. So while we open source all of our technologies for conservation, so like, you know, we're cloning red wolves, we're open sourcing all of that technology to make it more efficient, better for cloning. You know, I think we could productionize endangered species, which I think is an interesting concept. So how do we get species off the endangered species list because we're actually recovering them? You know, we're not just

• 57:07Speaker 00

  saving their habitat, which is saving their habitat is critical, and it has to be done. So this isn't a replacement for this. This is an and. But then how do we also make more of them? But now governments are coming to us on a new business line where they're saying, hey, we're using all, we love some of the papers you put out. We love some of the concepts that our team are working on. But this one government, for example, has a specific type of cat. And they were like, we want, we need to get to 50 breedable females. Well, it's going to take them at their best rate, based on the male to female ratio that they, their breeding cycle, the male to female that are born, it's going to take them 23 years to get there. It's going to cost about $300 million to get to their 50 genetically diverse females.

• 57:51Speaker 00

  We can do that because we can select for females, we can engineer in genetic diversity, we can do that in three years. And we, if they paid us $100 million, we'd still be making a fortune on that $100 million. So we could save them hundreds of millions of dollars. But more importantly, we could save them, we could deliver a better product because we can engineer in more genetic diversity, and we can do it in two years.

• 58:09Logan Bartlett?

  Isn't preservation versus de-extinction like pretty separate in terms of like potential implications? Bringing back more red wolves, we know how they do in the wild, we know generally why they've decreased in number versus bringing back a woolly mammoth. I guess we don't, do we, do we know why they went extinct and do we know like the implications of bringing them back into the wild?

• 58:31Speaker 00

  Yeah, so it's a great, it's a great question. We know a lot about rewilding because we know, and we know rewilding works because we've done it. It's a very systematic process that has indigenous people groups, private landowners, governments, you know, local, private landowners. So it's a very staged gated process. Like, nobody just like, you know, like in the Yellowstone wolf rewilding, right? No one just made a bunch of wolves and opened the gates and like crossed their fingers and rolled the die, right? Like, no one did that. It's a very thoughtful staged gated process where you're in a managed care facility, you're in less managed care, you're in less managed care, and then eventually the wild, right? So that's a very, it's a very measured process that, that I think's well documented and, and it's very inclusive of the community to do that. So we do know, we've also, there's also been studies that show what the reintroduction of cold tolerant megafauna back into the Arctic looks like

• 59:15Speaker 00

  and how it revitalizes the ecosystem and kind of makes this mosaic landscape, which is, which is actually really good for adding biodiversity flora and fauna, as well as carbon sequestration. And so, so we know all that because there's been, people have done this and tested it, obviously not with mammoths, but other species. So, so I will say that, you know, from a conservation perspective, you know, we think that, that this is not a replacement for these technologies. This is just a new set of tools, like bio banking, genetic engineering, engineering in genetic diversity, cloning. These could all just be new tools in the tool belt because it's forecasted that we're going to lose about 50% of all biodiversity between now and 2050. So we need new tools. Like, we're, we, we as the world are failing loss of biodiversity.

• 59:57Speaker 01

  Why no non-human primates, monkeys essentially?

• 1:00:01Speaker 00

  Yeah, I mean, it, it just, it's just one step closer, right? Like, what, we're going to make giant apothecus? Like, that's everyone, it seems to be a fan favorite. It's like a small King Kong. It's like, we're not going to do that, so.

• 1:00:12Speaker 01

  The use case actually I'm curious about, and we can talk offline about it actually, is, is in animal testing for new therapeutics, for new drugs.

• 1:00:19Speaker 00

  Yeah.

• 1:00:20Speaker 01

  And.

• 1:00:21Speaker 00

  Do you think that AI and, do you think AI will get to the point from a simulation design perspective that it can simulate all of that?

• 1:00:28Speaker 01

  No, not even close. I would, I would put that at a. Fifty plus years.

• 1:00:32Speaker 00

  I, I think it's one of the hardest things.

• 1:00:33Speaker 01

  Because the data to know.

• 1:00:35Speaker 00

  Yeah, on, on a nail.

• 1:00:37Speaker 01

  What, what happens in a live bot, like, human system, animal system is insane. There's no data.

• 1:00:43Speaker 00

  People, I, I, I'm a hundred percent with you. Like Fusion and so many other technologies are so much closer than that.

• 1:00:48Speaker 01

  Yes.

• 1:00:49Speaker 00

  Yeah, I, I think that's a, I think that is a very, very hard problem. So when I read these things about, oh, well, AI, you're eventually going to be able to do simulation design. I was like, I think you're going to be able to do local simulation design. But I don't think you're going to be able to do it on a system, a full system.

• 1:01:01Speaker 01

  I mean, the, one of my co-founders at Curie, he, because I was asking these same questions of like, you know, why can't we do it with computers as a computer? And, and at one point he said to me, you know, a Petri dish is not a human.

• 1:01:12Speaker 00

  Yeah.

• 1:01:13Speaker 01

  And I think like just that.

• 1:01:14Speaker 00

  And a mouse model is not a human.

• 1:01:14Speaker 01

  A mouse model is not a human, you know, a monkey is not a human.

• 1:01:17Speaker 00

  You see all that in, in, in these therapeutics, so.

• 1:01:20Speaker 01

  Yeah, and, and all the training data for a lot of these biology systems are on a Petri dish, which is a piece of plastic.

• 1:01:27Speaker 00

  Yeah.

• 1:01:27Speaker 01

  And so it's as close as we can get to a human, but it's not a live system. It's like, you know, a cell and a piece of plastic.

• 1:01:32Speaker 00

  Yeah, yeah, totally agree. I totally agree.

• 1:01:34Speaker 01

  So when you look at animal testing, if you think about, we would call them non-human primate testing, right? So essentially monkey test is an absolutely required step for many new drugs.

• 1:01:44Speaker 00

  I bet you could build a large language model for a, a large, like, animal model for non-human primates, though.

• 1:01:50Speaker 01

  Well, I think the non-human primate thing that could be really interesting with the, with the editing side of this is you want non-human primates that have human-like disease.

• 1:01:59Speaker 00

  Yep.

• 1:01:59Speaker 01

  Because that's going to give you a better data set.

• 1:02:02Speaker 00

  Yeah.

• 1:02:02Speaker 01

  And you, you know, the way you can give a non-human primate disease post-birth is limited.

• 1:02:09Speaker 00

  Yep.

• 1:02:09Speaker 01

  Versus if you could edit.

• 1:02:11Speaker 00

  Yep.

• 1:02:12Speaker 01

  And grow, you know, in a, in an HP that is more likely to develop X, Y, and Z disease. And while that sounds, you know, rough from like an animal standpoint, it saves human lives.

• 1:02:22Speaker 00

  Yeah.

• 1:02:22Speaker 01

  Uh, because now you can actually test and get more predictive data on, on a.

• 1:02:26Speaker 00

  And you, you also don't have to have, uh, infinite cycles of that. That is a somewhat contained loop where it's like, you do enough, you get enough training data that you feel confident, at least in this species of monkey that you can.

• 1:02:38Speaker 01

  Maybe give a literal example, like some cancer or. I mean, the one that I would, now, we don't know what causes, from, from what we can tell, you cannot give a, a monkey, uh, an NHP Alzheimer's or dementia at this point.

• 1:02:50Speaker 00

  Yeah.

• 1:02:51Speaker 01

  At least no one's figured out how to do it. I mean, in theory, you could kind of like try and have them live forever and see if they naturally develop it, but you can't. As of today.

• 1:02:58Speaker 00

  You can't give it to it artificially. Can you monitor to the point of showing signs?

• 1:03:03Speaker 01

  They die too fast. And like, that's an oversimplification, but basically, they don't get it. They don't get it. And so, and you can't give a mouse dementia.

• 1:03:12Speaker 00

  Yeah.

• 1:03:12Speaker 01

  And so, when you're developing a new dementia drug, or a new Alzheimer's drug, the only point in which you get any real data on whether this thing works is when you put it into a person.

• 1:03:24Speaker 00

  Yeah.

• 1:03:24Speaker 01

  And that could be a hundred million dollars just to get to that point, and the chances of it working are really low. Because there's no feedback loop, right? Like, there's no ability to-

• 1:03:32Speaker 00

  It's also a long feedback loop, isn't it?

• 1:03:34Speaker 01

  Well, you have to wait for the human.

• 1:03:35Speaker 00

  Yeah.

• 1:03:35Speaker 01

  So, it's even longer than you think. And so, you know, you test it in cell lines, you test it in mice, but like, it's not really predictive.

• 1:03:43Speaker 00

  We need the woolly mouse of-

• 1:03:45Speaker 01

  Well, this is gonna sound insane, but like, if you had a non-human primate edited so that it develops something like dementia or Alzheimer's, well, not great for the primate, great for the people, because now you can get feedback on your new potential drug faster and cheaper. And it's not like 5% faster and cheaper. It's like 90% faster and cheaper.

• 1:04:08Speaker 00

  Or zero to never cheaper, or faster.

• 1:04:12Speaker 01

  I mean, the amount of things that we simply don't do, or don't test, because getting a drug into a human for Alzheimer's and dementia, you know, essentially clinical trials is so expensive and time-consuming that you just-

• 1:04:25Speaker 00

  What do you think about, what is, absolute tangent, but what do you think about the whole notion that like, like Alzheimer is, you know, type 3 diabetes?

• 1:04:37Speaker 01

  I mean, there's a lot of cool theories. I think the reality of biology-

• 1:04:40Speaker 00

  On information and sure.

• 1:04:41Speaker 01

  It's probably all of the above, would be my guess, but like, what do I know? I mean, this is the single most complicated organ in the history of the world.

• 1:04:48Speaker 00

  Yeah.

• 1:04:48Speaker 01

  Right? The human brain. We barely understand how it works. So like, what drives this kind of stuff? It could be like nine things all at once. Wouldn't it be nice to be able to study it in a monkey?

• 1:04:59Speaker 00

  Yeah.

• 1:05:00Speaker 01

  And that would accelerate, you know, research faster. So that's why I was asking about it. And it's not just Alzheimer's and dementia, but there are probably edits you could make. Now, I'm speaking a little bit out of my ass, but like, I bet you there are edits you could make in a monkey. That are predictive of disease.

• 1:05:16Speaker 00

  Yeah, I mean, you're seeing that with like PGT testing. Like I just had a kid and we used Orchid Health to look at where they actually do full genome sequencing. And so outside of the specific, you know, major things people screens for and specific things we were screening for, there was also, there's also a, they also kind of give you this in somewhat, I don't know if it's controversial, I think not everyone subscribes to it, but they give you a distributed kind of like bell curve of like, of what you could have predisposition, what your child could have the, or that embryo could have a predisposition to, including, you know, early on, early on site, Alzheimer's and others and things like diabetes and whatnot. So you're at least understanding, because to your point, we don't know all of the things, but at least we know that there are

• 1:06:01Speaker 00

  specific genes and specific mutations that had, that created a higher likelihood within environmental factors.

• 1:06:08Speaker 01

  Yeah, it's great. It's just, you know, to drug it.

• 1:06:10Speaker 00

  Yeah.

• 1:06:11Speaker 01

  Is incredibly challenging.

• 1:06:12Speaker 00

  I'm glad I don't have to make that decision because we made this decision not to be in therapeutics. Because I think those are hard, I think those are really hard decisions, right? I think, I think from where I, do I think that people should explore all ways to make human life better? If you've ever had anyone that has gone through dementia or Alzheimer's, you don't wish it on your worst enemies in the world. So you don't, you don't. And so, so if there are ways to achieve it, I think that's something that we should, we as humanity should, you know, if we achieve longevity, escape velocity, but we don't solve that, well then, what's the point?

• 1:06:42Logan Bartlett?

  Yeah.

• 1:06:42Speaker 01

  Logan just wants to base at it so his kids are Knicks fans.

• 1:06:45Logan Bartlett?

  Yeah, exactly.

• 1:06:46Speaker 01

  Is there a Knicks gene there somewhere?

• 1:06:48Logan Bartlett?

  He's already watched two, two games in five days of life. So he's moving along pretty well on Knicks fandom.

• 1:06:53Speaker 01

  Yeah. Playoff basketball.

• 1:06:55Logan Bartlett?

  Playoff basketball. I'm curious, like you bump into religious zeal, you bump into regulatory considerations, like you're sort of in the Petri dish, I guess, to, you know, use a cute term of like. Society's third rails, it feels like in so many different ways. Not to mention the PR storm that you guys get caught up in or benefit from depending on the day, probably.

• 1:07:18Speaker 00

  Actually, before dire wolf, we were at 98% positive or neutral.

• 1:07:21Logan Bartlett?

  Is that right?

• 1:07:22Speaker 00

  Crazy.

• 1:07:22Logan Bartlett?

  Willie Mouse, people love it.

• 1:07:23Speaker 00

  Well, even before that, mammoth, I see, yeah.

• 1:07:25Speaker 01

  Yeah.

• 1:07:26Speaker 00

  Yeah. And if you extract out, because we, once again, data, if you, if you extract out classification of dire wolves, 98% positive also.

• 1:07:34Logan Bartlett?

  And what was it that was the dire wolf that just sort of set off such a storm?

• 1:07:38Speaker 00

  Can't call dire wolf.

• 1:07:39Logan Bartlett?

  It was really just that. It was that simple.

• 1:07:41Speaker 00

  Yeah, silly argument.

• 1:07:42Speaker 01

  I think the look too. It's a vet, like just the look of it gets national attention because it's folklore, right? Like they're in Game of Thrones, and others, which I think it just causes people to be interested in it. Maybe I guess more so than the, what was it, the red wolf?

• 1:07:58Logan Bartlett?

  Was it a step function in PR too as well? Like, did it just reach a different scape?

• 1:08:02Speaker 00

  We kind of got fucked because we, we spent a lot of time with, what we do is hard and it's complicated, right? We spent a lot of time educating, like, sometimes we get these, these articles where they're like, you know, the, the most annoying was, was we, we launched our foundation, right? So we make all these technologies available for, for, for conservation. We then, we then open source all of that technology. We then also pick a species that we help. So, so for example, 20, the number one killer of elephants in the world is, is a, is a herpes virus, EHEV. 20% of elephants, more than poaching, human elephant conflict combined. It's terrible. We have actually worked with Baylor College of Medicine, some of these AZA accredited zoos to actually get, in, they're in trials in elephants.

• 1:08:45Speaker 00

  That's conferring resistance using an mRNA approach that, that we helped design.

• 1:08:49Logan Bartlett?

  You're vaccinating elephants.

• 1:08:50Speaker 00

  Yeah, and so, but check this out.

• 1:08:51Logan Bartlett?

  It's great.

• 1:08:52Speaker 00

  If colossal does nothing else, and we just saved, we'll, we'll save more if that works, which it is against the number one strain of EHEV. There's, I think there's five strains, but this is the one that takes like 75% of, it kills baby elephants. It's just like fucking awful. That alone will save more elephants than all elephant conservation combined, right? And so, so we have to deal with, so even, even with all of that, right? You know, most people, like, there's still articles out there that, like, we launch, we then launched the foundation, we raised $50 million separately. For the foundation, just to fund other people to use our tech because maybe you don't have the money that you want to use our tech or you don't have labs or whatnot. So we'll fund you to do it if it's helping a species or if you're developing new tech as long as it's open source. So we're doing all that, right? And then, and then like we launched that in London and CNN was one of our launch partners.

• 1:09:34Speaker 00

  Like then we launched the bully mouse and in one of the lines in the same article by the same journalist is like, they should do stuff for conservation. I was like, but you, you know, we do stuff for conservation because we launched our foundation with you.

• 1:09:46Logan Bartlett?

  Yeah.

• 1:09:47Speaker 00

  Um, and so, so there's always an education thing and the, the, the problem with, with colossal times is it's highly nuanced, right? Like everyone's busy, every, our, every PR company or every like media company is looking for clickbait. And so it's like, you know, dire, like there was an article that was like, George R. Martin, George R. R. Martin hasn't finished the last, uh, book of, of his, uh, a song and I series because of colossal. That's literally the title. There was another title in Bloomberg, right? So that the launch title with Bloomberg was, uh, colossal brought back dire wolves because we spent, you know, 20 hours with Bloomberg. They got deep in the science. They really understood it and their result was, oh yeah, we're not going to argue classification. This is a dire wolf. It's closest approximate thing. We're going to call it dire wolf. Same thing with time, same thing with New Yorker, same thing with, with, um, uh, with many others.

• 1:10:32Speaker 00

  But then what happens is then you get wave two, which is all the clickbaity stuff, which is like, there was, there was actually an article that was one of my favorite titles by someone else at Bloomberg, uh, later that's like, the terror, uh, colossals, uh, dire wolves and terrorists, uh, have one thing in common. It's like, this is the weirdest. So you're starting to get stuff like,

• 1:10:51Logan Bartlett?

  What was that?

• 1:10:52Speaker 00

  I didn't read the, I don't read the articles. Like there's billions of articles.

• 1:10:55Logan Bartlett?

  What's a bigger risk for the business, uh, funding and they're not mutually exclusive, I guess, but funding or PR?

• 1:11:01Speaker 00

  I think neither. I really don't. I, I don't. I think there's, there's a huge app. We've been very fortunate. We have huge appetite for funding. Um, you know, we, uh, we're not announcing new funding at this time, but you know, we,

• 1:11:15Speaker 00

  publicly to this date, we've raised $435 million. I think that's highly likely to change in the future.

• 1:11:19Logan Bartlett?

  Yeah. So you have more than enough interest on the funding side and then,

• 1:11:22Speaker 00

  There's unlimited interest.

• 1:11:24Logan Bartlett?

  And do you, you don't worry then about,

• 1:11:26Speaker 00

  And the PR side isn't, the PR thing is really just about education, not persuasion, right? Cause we, we take this attitude, like some of our biggest critics in the world, like my chief science officer, best your hero, number one ancient DNA expert in the world. She joined the, cause she was the most, one of the most negative person when we started coming. And we just reached out to her. You know why? She's the number one, she's the number one in her field. So regardless of whether she likes us or not, we would be fools not to reach out to her. So we've had that attitude, right? We, we don't have an attitude. Are we ever going to fix the clickbaity stuff? No.

• 1:11:53Logan Bartlett?

  Yeah, but I, I guess the question I was more getting at is the clickbaity stuff can often lead to derivative consideration on the policy side. That might be.

• 1:12:03Speaker 00

  We work really closely. It's a great question. We work with both sides of the aisle. Like, you know, you, you said that we had the less, most left.

• 1:12:08Speaker 01

  Well, I was joking about the carbon credits.

• 1:12:10Speaker 00

  Yeah, yeah. But what I'm saying is like, we, we work with both sides. Like one of the things that we found on the Hill is that, that loss, regardless of how people feel about climate change and some of these other things, loss of biodiversity is a, is a bipartisan issue. Everyone agrees losing animals is bad. They may have different motivations behind it, but nobody, neither side seems to really want to lose animals. Right? So like, we have a great relationship with the left. We have a great relationship with the right. We, we, you know, the Department of Interior and Secretary Burgum of this administration acknowledged our work and, um, you know, thought this was one of the most innovative things that's ever happened, uh, which is a really kind statement. And also said that the technologies, that, that de-extinction technologies now need to be a tool in conservation. Now that was weaponized in the press and said, oh, well now, now we don't have to save species. He's like, that's not what he said.

• 1:12:55Logan Bartlett?

  Trump's pick for, you know.

• 1:12:56Speaker 01

  I'll give, I'll give you another business model. Uh, maybe this works, maybe it doesn't. But, you know, while I agree, a lot of groups are interested in like keeping animals around.

• 1:13:04Speaker 00

  Yeah.

• 1:13:05Speaker 01

  Uh, there's obviously a bunch of like environmental review for rare species that we find on some like giant development. And we spent three years arguing about like whether we care about the species. And then the development doesn't happen, which harms people. Yeah. Right? It makes houses more expensive. Could you work with developers to say, look, you find some rare species that you need to protect? We'll just make more of them and move them elsewhere.

• 1:13:28Speaker 00

  That's the argument that, that I think was weaponized by, um, uh, so, so part of, uh, we, we cut, we got, uh, Washington Post wrote, uh, by other people's standards, not mine. A moderately unfair thing because something like that, that exact example was brought up in a cabinet meeting, right? And that was just a discussion, right? It's, I view it as it's okay to have these conversations. And the response to that was, that means we don't need the Endangered Species Act. Nobody's saying that we don't need, like, halosplis, you need the Endangered Species Act, right? It's like, but at the same time, like, there are certain times where you take, like, there's been numerous cases where there's been a population of frogs, they put a rodent, there are now two populations of frogs, and this population's smaller, they are now classified as two different species because there's

• 1:14:13Speaker 00

  a geographic species definition. There's one of your Baskin Robbins 31. And so there's a difference. So, so what I, I think, what I think a better model is to that is, we should, regardless of why we're losing species, we do need to protect habitats, and we know that current conservation works, which doesn't work at the speed at which we're eradicating species. So I think we have to continue to protect land, right? Even, even at some

• 1:14:38Speaker 01

  Cost to humans.

• 1:14:39Speaker 00

  Cost to humans. So I think that we have to do that, and I think we just have to balance that, right? Yeah. And then, at the same time, we also have to look at, what are opportunities for us to also biobank species? Because no matter how good we are at conserving land, there's going to be some trade off to humans, where land development's going to move forward, land development's not going to move forward. So we have to biobank everything, because we know overfishing and all these other things are going to continue to eradicate some of our species. So, so I think that, that having, like, we have insurance policies for everything, yet, you know, like, the, the government and military is like, one of their number one things is like readiness. How ready are they for a conflict? It's like one of the, the core metrics that the military judges itself on. Why don't we have that for biodiversity? And so, sometimes I'm a very big advocate for having, like, the

• 1:15:23Speaker 00

  seed vault, like, in, in Northern Europe for species, like, we need biovault, a nationalized biobalt program. But then people say, well, then you're just trying to build an insurance program, so that we can do with everything species. And that's not what we're saying. I, I think this is an "and" conversation, not an "or" conversation.

• 1:15:37Speaker 01

  I mean, you could make the argument that if this technology works at, at any scale...

• 1:15:40Speaker 00

  But it's expensive.

• 1:15:42Speaker 01

  Totally.

• 1:15:42Speaker 00

  And it's time consuming.

• 1:15:43Speaker 01

  So is endangered species.

• 1:15:44Speaker 00

  Yeah.

• 1:15:45Speaker 01

  Uh, you know, I think that argument of like...

• 1:15:47Speaker 00

  But if you can productionize endangered species, and you can put, and you, and you Can serve land and do if you could take modern conservation and layer on the ability to productionize, then that's that could be a win for everybody, right? And and I think what sometimes people, what people recently have said was, well, if you could productionize a nature species, then you don't need the land. It's like, that's not what we're saying. That's not, you know, other, other people say that that's not, I can't control the world of what they say or what they choose to interpret the technologies. It's kind of like for a while where everyone hated computer vision because people were in in China were using computer vision to segregate populations based on specific profile. Like, yeah, that's bad. That doesn't mean computer vision is bad or facial recognition is bad. That means it was bad. It was a bad application of that technology.

• 1:16:31Speaker 00

  And so, so I do think, though, if we can, like, if we can get animals off the endangered species list because we have one conserve land done existing, maybe it's the same land, maybe it's different lands, right? But if we can conserve that land and do modern conservation and then productionize and make a thousand or 2,000 or however many you need, red wolves that have engineered in genetic diversity so that they have a population that won't go through a bottleneck, that should be a win for everybody.

• 1:16:56Speaker 01

  Yeah, then you don't need the actual endangered species act in the long run, or you just need it in certain geographical areas.

• 1:17:01Speaker 00

  But you still need it. You still need to protect species because you're you're going to have, you're going to have areas, both foreign and domestic, where people don't care, right? I think like, we all care, right? But it's like, we all want to figure out the, the hard thing is always figuring out human progress and and our balance.

• 1:17:18Speaker 01

  Oh, to be clear, I don't care. I don't. I get why people care. I don't believe in the endangered species act. I think nature takes species extinct and has been doing it for four billion years.

• 1:17:26Speaker 00

  Nature does. We have been accelerating it, right? And so I will say.

• 1:17:30Speaker 01

  But so, you know, like lions accelerated, you know.

• 1:17:33Speaker 00

  I would say humans are on a different pace.

• 1:17:36Speaker 01

  That's just how it works. Earth has survived, you know, we go up and we go down.

• 1:17:39Speaker 00

  I think it's forced extinction.

• 1:17:42Speaker 01

  I get why people care. I don't.

• 1:17:45Speaker 00

  But I'm saying, what I'm saying is, is regardless of what you're, I think there's, I think that if every, I think if both sides of the argument open the aperture and look at technological solutions, look at exists, like, what currently works? We know conserving land works. We do know that works. 100%.

• 1:17:59Speaker 01

  Absolutely.

• 1:17:59Speaker 00

  But we also know that sometimes. can come at a cost. So where are the balances? And I think those are important questions. But what I have found, the only decisiveness I've found on the biodiversity topic is this is like, is that we have different, there's different opposing views on, on how to save them. But generally speaking, people are mostly in favor of figuring out how to save them. And what we're saying is we are not the solution. We're just one new tool. So throw our, throw our tool in this whole conversation and see how it happens. Yeah, you guys with the right land could pull it off. There's, but it is still, I will tell you, and once again, I run the D extinction company, right? I will tell you, it is way more expensive, at least today, to bring back a species

• 1:18:42Speaker 00

  than to just say, hey, let's keep it alive here. It is, it is, it is more expensive.

• 1:18:48Logan Bartlett?

  From, from a regulatory standpoint, are there things that you've bumped up against that are just feel nonsensical? And if you could wave your magic wand or, you know, do something. It's like, gosh, this is just rooted in 1900s prohibition.

• 1:19:04Speaker 00

  I think there's different, different things like we, we, we work very closely with all the organizations, like, like we were very transparent about it. The, the intelligence committee or community is an investor in the business. North Dakota is an investor in the business. We have other states that have expressed.

• 1:19:20Logan Bartlett?

  North Dakota like pension?

• 1:19:21Speaker 00

  Yeah, they're economic and commerce development fund. And then there's other vehicles within the United States government that's interested in, in supporting the efforts, right? We work closely with Fish and Wildlife. So we're working with all these different things, right? I think that, you know, I do think that sometimes there are things that could be changed and accelerated. You know, one thing in particular is there was this moratorium for a long time on GMOs. Now, we aren't creating genetically modified organisms for consumption, even though we do get asked if people could eat our mammals, which is weird. But I do think that, that, that we got that question quite often when we watched.

• 1:19:58Logan Bartlett?

  It's kind of a great question. I mean, whether you want to do it or not, it's an interesting question.

• 1:20:01Speaker 00

  Yeah. But, but so I understand the need from a USDA and FDA perspective to look at the classifications of genetically modified organisms for consumption. But for example, So we aren't doing this, but let me give you an answer that goes straight to regulation. The FDA has historically taken the stance that if anything has an edit and it should be treated as a drug. Right? Well, okay. Well, man, that's not going to go through clinical trials. And the other thing is like, there's a process. We're not in the cattle industry, but there are people that are in the cattle industry and a lot of times they have a pretty unhumane model of dehorning cows because when they put them, they're not like running around like Yellowstone National Park. Right? When they put them in these large things, they, they have horns, they spear each other.

• 1:20:45Speaker 00

  That leads to infection, that leads to disease, that's, that can create all kinds of bad stuff for downstream for human healthcare. That could kill off the cattle. It's really, really bad. So they, so they dehorn them, right? Which is a pretty inhumane process if you really, really look at it, but in the whole, it's good for the herd. It's not good for the individual animal, but there's actually some researchers that have identified making, I think it's either one or a couple edits that make it where they just don't grow horns. Right? Way more humane for the cows or whatever, but I don't, I, from my, and I'm not in it, but from my conversations with people that are in that field, that hasn't gotten through because it's classified as a drug. Well, that's silly. Like, like we have been doing genetic modifications to animals and plants for years. We've just done it inefficiently and we've been doing it the old fashioned way. Crossbreeding.

• 1:21:30Speaker 00

  Yeah, yeah. And so I would say we're just doing, to your forced evolution perspective, we're just doing it way more efficiently. Can you get the cows that don't release methane? You know, there was a study, we, we were, I don't know where this went. There was a study that was, that happened in Australia where they were trying. I don't know where this went, so I'm only giving you a half truth on this, but marsupials give different levels of, of milk because so much of the gestation happens outside. So they give you like high fat, then they give you like 2% and then they give you like skim. So the marsupial body is incredible. So they, they, the moms produce these different tiers of milk, which is really cool. And so there was a study, I don't know if it went anywhere. We, we didn't work on it, but some, one of our Australian partners at the University of Melbourne

• 1:22:11Speaker 00

  told me about this where they actually were trying to figure out how you engineer that into cows so that you could have like 2% milk cows. Oh, the one I always think about is. No, I know your time. Cow, cow farts. Yeah, I know. Which everyone laughs at, but it's like a greater.

• 1:22:23Speaker 01

  Contributor to emissions than, you know. Climate change. Yeah, because you need the cows and they, you know, they fart methane.

• 1:22:29Speaker 00

  Yeah, and there's a lot of cows.

• 1:22:30Logan Bartlett?

  Yeah, what about, I mean, there's a ton of super ones probably like that, but what about the religious element of like playing God and altering?

• 1:22:39Speaker 00

  I think, I think we have a pretty, once again, I, we, we try to engage with everyone, right? You know, so we go on the most conservative shows, we go on the most liberal shows. Um, we try to be pretty bipartisan and, and, and pretty inclusive, right? We've got some of the strongest atheists behind us. We, uh, we also have some of the strongest, you know, Christians and, and people from various religions and Jews. And so it's, it's, so for us, I, I think that, you know, we have a tack that, and this goes to you probably where you fall, it's like, we've been playing God for quite some time. Like we're eradicating forests, we're fishing the ocean, we're polluting shit. We're like, like I take drugs, is that a form of playing God? Like I, I like, I like, I lower my cholesterol with a shot twice a year or twice a month. So does that, does that mean?

• 1:23:20Logan Bartlett?

  And we screen human embryos for disease already.

• 1:23:22Speaker 00

  Yeah, I did that with my son. So it's like, so is that a form of playing God? I built a distributed, uh, uh, risk matrix for, uh, embryo selection for our kid. And we chose him because he came out on top from a weighted average that I made. So, um, based on a polygenic risk score, right? So it's a, um, so I think we do that all the time, right? And it's like, you know, I view it as, you know, there's not enough money going into conservation. We open source all the time. We look, I look at, this is like a free research and development arm for conservation, right? Like, we're doing all this stuff as industrial and human application and other things that will make a lot of money on. We do think we'll make money from an ARR perspective on rewilding and carbon credits and biodiversity credits, eco tourism.

• 1:24:06Speaker 00

  But separately, we're just giving all this stuff away for conservation. So anyone that's been a research and development knows it's a huge fucking R and a very small D, right? Very little goes actually into development. So we're, we're burdening that cost and risk for the entire community. And so, so, so I, I think that, you know, we're definitely not going to do everything right. But I think that we're trying to do everything and work with critics that are at least informed to the point that we can get where, you know, people are, uh, excited about it. But the, the playing God one doesn't, um, come up as much as I think one would think. We get asked the question, do you get that question a lot? But, but for the most part, I think people realize that, you know, the intentionality behind what we're doing. Like if we weren't open sourcing stuff for conservation and we're just like, yeah, we're just making whatever we want, F off, then I could see how that could.

• 1:24:51Speaker 01

  I found that logic can be totally orthogonal to sentiment oftentimes.

• 1:24:56Speaker 00

  Yes. Yeah, that's a great point.

• 1:24:59Speaker 01

  It's really cool. I mean, just leaving the business model stuff aside for a second, just the, the underlying technologies to do this without like, you know, insane failure rates up and down the stack are going to be used in a bunch of other settings as you guys, you know, bring the tech to market. So it's very cool.

• 1:25:14Speaker 00

  And it's much harder to do with ancient DNA than existing. So we're making the tools like super hardened.

• 1:25:18Speaker 01

  Yeah.

• 1:25:19Speaker 00

  So.

• 1:25:19Speaker 01

  Thanks for doing this.

• 1:25:20Speaker 00

  Yeah, thanks for having me. This is awesome.