#394 — Bringing Back the Mammoth

Sam Harris speaks with Ben Lamm about his work at Colossal Biosciences. They discuss his efforts to de-extinct the woolly mammoth, the Tasmanian tiger, and the dodo; the difference between Colossal's approach and Jurassic Park; the details of resurrecting the mammoth; the relevance of this work to human health; the role of artificial intelligence; reintroducing mammoths, Tasmanian tigers, and dodos back into the wild; the environmental and business case for de-extinction; and other topics. If the Making Sense podcast logo in your player is BLACK, you can SUBSCRIBE to gain access to all full-length episodes at samharris.org/subscribe http://samharris.org/subscribe. Learning how to train your mind is the single greatest investment you can make in life. That's why Sam Harris created the Waking Up https://www.wakingup.com/makingsense app. From rational mindfulness practice to lessons on some of life's most important topics, join Sam as he demystifies the practice of meditation and explores the theory behind it.

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

• 0:06Sam Harris?

  Welcome to the Making Sense Podcast. This is Sam Harris. Just a note to say that if you're hearing this, you are not currently on our subscriber feed and will only be hearing the first part of this conversation. In order to access full episodes of the Making Sense Podcast, you'll need to subscribe at samharris.org. There you'll find our private RSS feed to add to your favorite podcatcher, along with other subscriber-only content. We don't run ads on the podcast, and therefore it's made possible entirely through the support of our subscribers. So if you enjoy what we're doing here, please consider becoming one. Welcome to the Making Sense Podcast. This is Sam Harris.

• 0:51Sam Harris?

  Today I'm speaking with Ben Lamm. Ben is a technology and software entrepreneur who has been featured in many publications, The Wall Street Journal, New York Times, Forbes, discussing topics related to innovation and technology. He's also the co-founder and CEO of Colossal Biosciences, a company he started with biologist George Church for the purpose of resurrecting extinct species like the woolly mammoth and the Tasmanian tiger and the dodo, and they aim to reintroduce them into the wild. Ben is also a fellow of the Explorers Club and serves on the Scientific Advisory Board of the Planetary Society. But we focus on his work at Colossal.

• 1:34Sam Harris?

  We discuss the difference between their approach and Jurassic Park, the details of resurrecting the mammoth and other species, the relevance of this work to human health, the role of artificial intelligence here, what it would take to reintroduce mammoths and Tasmanian tigers and dodos back into the wild, the environmental and business case for doing this, and other topics. Anyway, the future appears to be almost here. And now I bring you Ben Lamm.

• 2:08Sam Harris?

  I am here with Ben Lamm. Ben, thanks for joining me.

• 2:12Speaker 01

  Thanks so much for having me.

• 2:13Sam Harris?

  So we're going to talk about some amazing stuff that you're doing over there at Colossal, your biotech company. But before we get there, how do you summarize your career and interests at this point? Or how did you give me the potted bio that gets us to the topic at hand?

• 2:32Speaker 01

  Well, I'm definitely insatiably curious. And so I'm always, you know, I'm not really a technologist. I'm not really an engineer. I try to look at things from a systems design perspective. And I'm always fascinated with how things work and how things can be improved. And I always like to find new, interesting projects. And so I've been in everything from mobile gaming before that was quite big. I built some precursors to large language models that we were actually calling conversational operating systems at the time. My last company was actually satellite software and defense. So we actually built a common operating picture to understand and track everything in the sky, all the way, actually in low Earth orbit, all the way down to the surface of the sea, and worked closely with the US Air Force and

• 3:16Speaker 01

  Space Force and some of our global partners on that. And then I met George Church. And, you know, I actually kind of fell into the extinction. I reached out to him because I'm curious. And I thought that the intersection of synthetic biology and AI and computational biology and, you know, quantum, which I hear is only two years away every two years, will eventually, you know, kind of give us dominion to engineer life and do directed evolution on a scale that, you know, is unprecedented for, you know, human advancement. And so I got massively excited about the opportunities there. And then I asked George the question, and I said, if you had one project with unlimited capital that you could focus on for the rest of your life, you know, what would it be, George?

• 4:00Speaker 01

  And you know, didn't know what I would get out of George. Is it going to, you know, another star system or what? And his feedback was I would bring back woolly mammoths and help reintroduce them back into the ecosystem to help biodiversity in the ecosystem as well as develop technologies for both human healthcare and species preservation. And at that moment, I was pretty hooked.

• 4:20Sam Harris?

  Hmm. Yeah. George is a very impressive scientist. I've met him, I think it might've only been once, maybe, maybe twice at a conference, but he's, is he still at Harvard?

• 4:30Speaker 01

  He's still at Harvard. So I do get to monopolize a decent amount of his time, but I do, we do share him with Harvard and a handful of other initiatives he's co-founded.

• 4:39Sam Harris?

  So the company is Colossal Biosciences. Is that the, the full name?

• 4:44Speaker 01

  Correct.

• 4:45Sam Harris?

  And so what are you doing over there at Colossal?

• 4:48Speaker 01

  Yeah. So we decided that we wanted to build the world's first de-extinction and species preservation company, because if you look at some of these stats and kind of the trend line that we're seeing for biodiversity loss and what the impacts to ecosystems can, will and will be, especially from a keystone perspective, it's pretty terrifying. And when we started the company, our original pitch deck, all the data we could find showed that if without massive human intervention or massive new technologies, that we could lose up to 15, 1-5% of biodiversity between now and 2050. What's terrifying is in 2024, that number's been upped to 50%, 5-0. So that's not a very good trend line. And so

• 5:31Speaker 01

  George had this vision, and I just feel like I'm kind of the steward and helper with it, of we could go build a company that could, you know, one, build tools and technologies that could be capable of bringing back lost species, as well as applying those technologies and innovation to conservation, giving that to the world for free. And all these species have direct applications, those technologies like genetic engineering and others to human healthcare. So we really had this interesting opportunity to build a company that hopefully could inspire people, create true impact, but also create massive value creation around the way.

• 6:06Sam Harris?

  And which species are you focused on first?

• 6:10Speaker 01

  So we've announced three species to date. The woolly mammoth, which George was actually working on for about eight years before I showed up, collecting samples in Siberia, working on computational analysis in elephants. The Tasmanian tiger, also known as the thylacine, which went extinct in 1936 in Tasmania and lower Australia due to human hunting. The Australian government actually put a bounty on eradicating the species. And then, you know, we wanted a bird species. We wanted to recruit Beth Shapiro, who's our chief science officer. So we did the dodo because there's probably not a more iconic species than the dodo that symbolizes de-extinction.

• 6:48Sam Harris?

  So how is this different from Jurassic Park? I mean, you know, I don't think anyone would really associate it with Jurassic Park until you bring in the mammoth and then all of a sudden we the we're talking about charismatic megafauna and we're we're hoping for a T-Rex. To what degree does that vision account for some of your enthusiasm around this? And I mean, obviously there's a difference between reintroducing animals to the wild and and setting up a theme park. Are you I mean, was Jurassic Park a formative idea for you? Or is that or you arrived where you are by a different path?

• 7:24Speaker 01

  So we get the Jurassic Park question quite a bit as you as that may not surprise you. Like occasionally when I go on stage to speak, they'll play the music. You know, we've seen every meme with like George's face on it or my face on it. So we we've heard this a time or two. George will tell you, so I think George and I have slightly different perspectives on it. George will tell you that in a weird way, he thinks that Michael Crichton was actually inspired and Jurassic Park was actually inspired by him. Because if you go look in the original Jurassic Park novel, there's actually a DNA sequence early in the in the work in in the novel. And it actually is George's work with only one letter changed. And George will argue that statistically.

• 8:08Sam Harris?

  That's still plagiarism?

• 8:09Speaker 01

  It's it's still and George loves, you know, many of Crichton's novels, right? And it's a very inspiring author that he was. And but George will tell you that, you know, he laughs. And says, maybe I inspired Jurassic Park because a lot of his original work in yeast is actually shows up in the book. I will tell you from my perspective, you know, growing up, you know, born in the eighties, you know, a child of the eighties and nineties, you know, I think one, you know, I love science fiction. I love Jurassic Park. That's not necessarily why I got into this, but it sure makes it a lot easier to connect with people because even though we have the memes and all the jokes that come around colossal versus Jurassic Park, at least, you know, Jurassic Park, which was this dystopian movie, at least it taught people about there's this

• 8:53Speaker 01

  thing called DNA and there's this thing called genetic engineering. And so like moms in Iowa know that there's this ability to manipulate the genome because of Mr. DNA, right? And so we also, we a lot of times use Jurassic Park as an example of how we're doing it exactly inverse, meaning that we're not trying to fill the gaps in a ancient DNA that with the holes that you get from, you know, frogs or whatnot. We're trying to truly understand the genomes so that we could selectively choose the genes that we then want to engineer into that of a living species. So it's almost like reverse Jurassic Park. And when we say that to the kind of average

• 9:35Speaker 01

  public and that we're in, in, in, in some journalists and whatnot, when we're explaining the process and the science, they really resonate with it because I think that movie does have such a had was the right movie with the right technology and the right story at the right time that really connects with people.

• 9:50Sam Harris?

  Well, so let's go over those details again. So what was being proposed as the scientific, you know, bioengineering basis for Jurassic Park? And what exactly are you doing with, you know, paleogenomics and going out into the wild and getting DNA samples, however imperfectly preserved and integrating them with living species? How, what is your approach and how is it different from what was being? I, it's been a long time since I, I saw the film. I actually never read the novels. I don't know if the films depart from the novel in their logic. And I, I know nothing about any of the.

• 10:30Sam Harris?

  You know, errors that Crichton might have made and with respect to his molecular biology, if he made any. So what was proposed there and what are you guys actually doing?

• 10:39Speaker 01

  So in Jurassic Park, they proposed that you could go find pieces of like amber, which by the way is a very porous material. It is not a good DNA store, not that we've tried. But then magically in amber, you'd get insects and specifically mosquitoes that had been trapped for over 65 million years. And while that's true, there isn't DNA from that amber, as I mentioned, is a very porous material. It is not, it's not a great DNA store. Typically, the best DNA stores for us for ancient DNA are cold, dry places. So animals that passed away in a cave and a very dry cave that stayed consistent without other animals in it. That's kind of optimal for us.

• 11:22Speaker 01

  And so then they would take this DNA that they extracted from a mosquito that lived, you know, 100 million years ago and bit a dinosaur and they would extract in the movie actual blood, which also is impossible. And then they would take that blood, use computers, which is very similar to what we do, which I'll get into, and then fill in the holes of the, of the ancient DNA, because ancient DNA is very, very fragmented with that of in the movie frog DNA and amongst some other, many other things. But the problem with that, number one is there isn't ancient dino DNA. You know, the oldest DNA that we're able to collect is, you know, a little bit over a million years. There's some fragments and stuff that are older, but you know, for the most part, we're working in thousands and tens of thousands of years, not, you know,

• 12:07Speaker 01

  millions of years, because DNA degrades very, very quickly. It starts to break down the minute it leaves your body. And so when you layer in like radiation, heat, acidification, other animals' defecation, other animals dying on it, it starts to break down and it also gets massively contaminated. It's not truly endogenous at that point, right? And so what we do is instead of going and taking a bunch of different pieces of a mammoth, assembling it and saying, what's missing? And how do we plug that with a frog or elephant DNA? We do it almost exactly in reverse. So the first thing that we did is we went out and we looked at phylogenetically. So on that tree of life that we've all seen, some version of it, you know, in science textbooks and today on the internet.

• 12:52Speaker 01

  We say, what is the closest living relative to the mammoth in this case? And that's actually the Asian elephant. It's 99.6% the same genetically. It's actually closer genetically to an Asian elephant than an Asian elephant is to an African elephant. And that's kind of a fun party trivia for you. And then we spent a lot of time trying to do comparative genomics, truly use a bunch of software, use AI, some of our custom models to understand what is the difference even from an African elephant to an Asian elephant? What is the difference from a population level? So we actually sequenced a lot of different Asian elephants. So what is truly Asian elephant versus population diversity in those genomes? Cause not all genomes are obviously exact copies of each other.

• 13:35Speaker 01

  And then how do we compare that to the mammoth? And then we can identify, okay, where are these regions of the genome that are vastly different? And what do we know about that from scientific research, from other peer reviewed papers? You know, from actually doing molecular and functional assays, actually growing stem cells and testing our hypothesis. So you have to do a lot of work to then kind of verify what we think the core genes that made a mammoth a mammoth were. So that then we can engineer them into that of an Asian elephant cell. And that's not just taking pieces and pushing it in there. That's actually just changing existing code. So we fundamentally don't need long-term pieces of these DNA. We don't need all of these dead samples. We just need the code in the computer.

• 14:20Sam Harris?

  So do we have the complete genome of the woolly mammoth? I mean, is that something that's disputed or did we get enough samples of sufficient integrity such that we just know we've got the full mammoth genome?

• 14:34Speaker 01

  We have enough. So we have, we have about 65 mammoth genomes. Most of those aren't published. Most of those are Siberian and Russian mammoth samples. We're now doing a lot of work with Alaskan mammoths as well. And we work with about 17 universities across the world, one of which is the University of Stockholm. And Luvva Dolan's work and Luvva is arguably the number one mammoth researcher in the world. And so we've taken all of his different samples and it's about a 700,000 year difference between all the different samples. To kind of fill that in, but we have enough of the protein coding regions of it as well as Colombian mammoths, step mammoths and others. And we have a pretty cool paper that I hope will come out mid next year about this. That shows the comparative genomics that we know enough of the mammoth genome.

• 15:18Speaker 01

  That we can identify the core areas around cold tolerance, fat, hair, curved tusk. So we actually have enough to do our work. It is not as complete as our, our thylacine genome. Which we recently announced is 99.5% complete, or no, sorry, 99.9% complete. Which is, which is truly incredible for any genome, let alone ancient DNA.

• 15:38Sam Harris?

  That's the Tasmanian tiger?

• 15:40Speaker 01

  Correct.

• 15:41Sam Harris?

  So are you using CRISPR technology to insert mammoth code into the, an Asian elephant zygote? Or what is the step there that would produce a living mammoth?

• 15:53Speaker 01

  Yeah. So we start with an Asian elephant cell, right? And we actually had to spend a lot of time getting the culture conditions right. Actually immortalizing those cells. One of the things that, you know, before we get into the genetic engineering side. Uh, one of the things that's interesting about elephants and blue whales and a handful of other species. Is they actually get cancer a fraction of what we do, based on age and body weight of which they grow to. And the leading theory of that, and we're seeing this also being verified in our lab. Is they have an overexpression of a protein called P53, about seven times more than we have in, in mice have. Uh, which I'm sure you're, you're familiar with. And what's interesting is we've actually had to learn how to regulate that. Because anytime we went to go make those changes, which, which we'll get into, the cell would just senesce.

• 16:37Speaker 01

  So not only do we have to build immortalization constructs to keep the cells growing and living and healthy. We also had to figure out how we Can quote unquote, turn down P53 so that we could edit the cells and then be able to turn it back up because you don't want to produce, you know, cancer in elephants, right? And so we had, there's a lot of prep work before we even get to the point that we can do the engineering itself. And as you can probably guess, you know, because you, your deep background in science, you know, CRISPR has become a catchall for all genetic engineering. They're like, oh, it's just CRISPR, right? We just, we just CRISPR it. But what's interesting is we use a combination of tools, some of which are proprietary,

• 17:16Speaker 01

  some of which are, have been invented by other organizations and universities, and then we layer new techniques on it. So in some cases, we're changing the individual nucleotides, the individual letters on, on that double helix. In other cases, we're knocking out certain genes. And in other cases, we're actually synthesizing big blocks of DNA. Where if there's like a bunch of changes along one kind of strand, it's actually more efficient for us to synthesize that block, knock that block out and then insert this new block so that you have less likelihoods of off-target effects or unintended consequences from your editing. And I'd say the last thing that we're doing that on the editing front that is, is our kind of,

• 17:59Speaker 01

  I, I think the thing that sets us apart from a, from a genomics perspective is we're trying to become the biggest pioneer of multiplex editing, meaning editing all over the genome at the same time. So instead of making one edit, maybe you can make 20 edits, 50 edits, a thousand edits, all with a very high degree of efficiency versus having to synthesize entire giant blocks. I do believe that technology will get here, being able to synthesize even full chromosomes at some point. But we're not, we as humanity aren't quite there yet. So editing is the most efficient kind of current modality that, that we've been pursuing.

• 18:37Sam Harris?

  So at, at what point did this actually become technically feasible? And what, what year would you say this became something that you could actually start on? And it ceased to be just a, a piece of science fiction?

• 18:52Speaker 01

  Yeah, so I think, you know, people have been talking about, you know, CRISPR, you know, in some version of genetic engineering from the 80s, right? But it was like, it was, I don't remember the exact year, but it was like, what, 2012, 14, somewhere around there, where we had the true kind of discovery around, you know, CRISPR and the idea that you could, you know, target a part of the genome, successfully knock it out and have it repair itself. And I think from there, you've seen work like David Lu's work in Prime and Base Editing, where you can change individual letters. You've seen kind of this like pre-Cambrion explosion, you know, to use our Jurassic, use our, some of our Jurassic fun terms, of genetic engineering tools and technologies.

• 19:37Speaker 01

  Because we've all been promised from the 80s and 90s, gene therapies and genetic engineering capabilities that allow us to do all kinds of stuff, right? That have never really manifested. But I think that that really, in the last, you know, 10 years, has been where those technologies have been viable. I don't believe before that kind of 2012, 2015 timeframe of like that CRISPR race with, you know, Fang and

• 20:02Sam Harris?

  Jennifer Doudna.

• 20:03Speaker 01

  And Doudna and all of them, right? That are just, they're, and George included, which were all incredible scientists. I don't believe that this would have been a viable undertaking. And now, after that, it became viable, but it, you know, you still have compute, you still have AI, there's a lot of other components to it, and it just becomes very, very costly. The goal to really make this where it's possible and scalable, I think is, I think we're still a little bit early, but we're in kind of the right kind of five years to truly be able to deliver.

• 20:34Sam Harris?

  So is AI a necessary component of the process?

• 20:37Speaker 01

  It is, and, you know, we're learning every day, new ways that we can apply, you know, my background has been mostly in software, right? And so, you know, we're finding every day, new ways to apply these technologies around it. Like, we actually have a tool that we built internally, that we've been giving it this feedback loop. So we built a cool little model, that probably doesn't apply to most people, but for us, we find it fascinating, that will actually give us The right recommendation with that's over 90% accurate of what tool we should use for the specific edit that we're going after. And that's awesome. When you think about biology, because if you're going to make an edit, you then have to go see if that edit worked, you then have to grow those cells, those cells have to live, then you have to sequence those

• 21:22Speaker 01

  cells. You got to wait a couple of weeks is in some cases, if you don't have sequencing cores internally to get that data back. And so the feedback loop, if you've make some, if you've made the wrong edit using the wrong tool, or at least the not the most efficient tool, you know, can be months of lost scientific experiment time, both costly in terms of go to market and in terms of your research and in all the reagents and stuff that you had to go use in that, right? And so we're, we're now using AI, not just for comparative genomics, but even in what selection of what editing tool we should use for the editing job that we're trying to go pursue.

• 21:58Sam Harris?

  So now, how far have you gotten? And now I'm not asking just about the mammoth, but you can talk about the dodo or the Tasmanian tiger or anything else you've experimented with. What have you produced in the lab? And is it, is it all still in vitro? Or what? Do you have a pregnant Asian elephant that has a name?

• 22:19Speaker 01

  There is, there is no secret pregnant Asian elephant mammoth, unfortunately. I would be the first, I couldn't be more excited to share with you if there was. So, so de-extinction is a systems problem, right? There's computational analysis, or there's HDV.

• 22:34Sam Harris?

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