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Episode: #394 — Bringing Back the Mammoth

Author: Sam Harris
Duration: 00:23:12

Episode Shownotes

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. 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 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.

Full Transcript

00:00:06 Speaker_00
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.

00:00:18 Speaker_00
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00:00:30 Speaker_00
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

00:00:51 Speaker_00
Today I'm speaking with Ben Lamb. 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.

00:01:05 Speaker_00
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.

00:01:22 Speaker_00
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.

00:01:34 Speaker_00
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,

00:01:47 Speaker_00
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 Lamb.

00:02:08 Speaker_00
I am here with Ben Lamb. Ben, thanks for joining me.

00:02:12 Speaker_01
Thanks so much for having me.

00:02:13 Speaker_00
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?

00:02:27 Speaker_00
Give me the potted bio that gets us to the topic at hand.

00:02:32 Speaker_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.

00:02:38 Speaker_01
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.

00:02:49 Speaker_01
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.

00:03:00 Speaker_01
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 lower the orbit all the way down to

00:03:12 Speaker_01
the surface of the sea and worked closely with the U.S. Air Force and Space Force and some of our global partners on that. And then I met George Church and I actually kind of fell into de-extinction.

00:03:24 Speaker_01
I reached out to him because I'm curious and I thought that the intersection of synthetic biology and AI and computational biology and quantum, which I hear is only two years away every two years, will eventually kind of give us dominion to engineer life and do directed evolution on a scale that

00:03:42 Speaker_01
You know is unprecedented for you know human advancement and so i got massively excited about the opportunities there and and then i asked george the question and i said if you had one.

00:03:54 Speaker_01
Project with unlimited capital that you can focus on for the rest of your life you know what would it be george. and didn't know what I would get out of George. Is it going to another star system or what?

00:04:04 Speaker_01
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.

00:04:18 Speaker_01
And at that moment, I was pretty hooked.

00:04:20 Speaker_00
Yeah. George is a very impressive scientist. I've met him, I think it might've only been once, maybe twice at a conference, but is he still at Harvard? He's still at Harvard.

00:04:31 Speaker_01
So I do get to monopolize a decent amount of his time, but we do share him with Harvard and a handful of other initiatives he's co-founded.

00:04:40 Speaker_00
So the company is Colossal Biosciences, is that the full name? Correct. And so what are you doing over there at Colossal?

00:04:48 Speaker_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 and will be, especially from a Keystone perspective, it's pretty terrifying.

00:05:09 Speaker_01
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.

00:05:24 Speaker_01
What's terrifying is in 2024, that number has been upped to 50%, five zero. So that's not a very good trend line. And so George had this vision and I just feel like I'm kind of the steward and helper with it.

00:05:36 Speaker_01
of we could go build a company that could, 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.

00:05:57 Speaker_01
So we really had this interesting opportunity to build a company that hopefully could inspire people, true impact but also create massive value creation around the way.

00:06:07 Speaker_00
And which species are you focused on first?

00:06:10 Speaker_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.

00:06:23 Speaker_01
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.

00:06:38 Speaker_01
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.

00:06:48 Speaker_00
So how is this different from Jurassic Park? I mean, 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're talking about charismatic megafauna and we're hoping for a T-Rex.

00:07:04 Speaker_00
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 setting up a theme park.

00:07:15 Speaker_00
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?

00:07:25 Speaker_01
So we get the Jurassic Park question quite a bit, as that may not surprise you. Occasionally when I go on stage to speak, they'll play the music. We've seen every meme with George's face on it or my face on it. So we've heard this a time or two.

00:07:40 Speaker_01
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 and Jurassic Park was actually inspired by him,

00:07:52 Speaker_01
Because if you go look in the original Jurassic Park novel, there's actually a DNA sequence early in the work, in the novel, and it actually is George's work with only one letter changed.

00:08:05 Speaker_01
And George will argue that statistically, it wouldn't be- That's still plagiarism. It's it's still and George loves, you know, many of Crichton's novels. Right. And it's very inspiring author that he was.

00:08:17 Speaker_01
And but George will tell you that, you know, he laughs and says, maybe I inspire Jurassic Park because a lot of his original work in yeast is actually shows up in the book.

00:08:26 Speaker_01
I will tell you from my perspective, you know, growing up, you know, born in the 80s, you know, a child, the 80s and 90s, you know, I think one, you know, I love science fiction. I love Jurassic Park.

00:08:37 Speaker_01
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.

00:08:47 Speaker_01
At least Jurassic Park, which was this dystopian movie, at least it taught people about there's this thing called DNA, and there's this thing called genetic engineering.

00:08:57 Speaker_01
And so moms in Iowa know that there's this ability to manipulate the genome because of Mr. DNA, right? And so 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

00:09:16 Speaker_01
ancient dna that with the holes that you get from no frogs or what not we're trying to truly understand the genome so that we can selectively choose the jeans that we didn't want to engineer into that of a living species is almost like reverse dress park and when we say that to the average public and that were in

00:09:37 Speaker_01
in some journalists and whatnot when we're explaining the process and the science, they really resonate with it.

00:09:42 Speaker_01
Because I think that movie does have such a, was the right movie with the right technology and the right story at the right time, that really connects with people.

00:09:50 Speaker_00
So let's go over those details again. So what was being proposed as the scientific bioengineering basis for Jurassic Park?

00:09:59 Speaker_00
And what exactly are you doing with paleogenomics and going out into the wild and getting DNA samples, however imperfectly preserved, and integrating them with living species? How

00:10:15 Speaker_00
what is your approach and how is it different from what was being... It's been a long time since I saw the film. I actually never read the novels. I don't know if the films depart from the novel in their logic.

00:10:26 Speaker_00
And I know nothing about any of the errors that Crichton might have made with respect to his molecular biology, if he made any. So what was proposed there and what are you guys actually doing?

00:10:39 Speaker_01
JS So in Jurassic Park, They propose that you would go find pieces of amber, which by the way is a very porous material. It is not a good DNA store, not that we've tried.

00:10:52 Speaker_01
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's not a great DNA store.

00:11:09 Speaker_01
Typically, the best DNA stores for us for ancient DNA are cold, dry places. So animals that passed away in a cave, in a very dry cave that stayed consistent without other animals in it, that's kind of optimal for us.

00:11:22 Speaker_01
And so then they would take this DNA that they extracted from a mosquito that lived a hundred million years ago and

00:11:29 Speaker_01
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 ancient DNA, because ancient DNA is very, very fragmented, with that of, in the movie, frog DNA, amongst many other things.

00:11:51 Speaker_01
But the problem with that, number one, is there isn't ancient dino DNA. The oldest DNA that we're able to collect is a little bit over a million years.

00:11:59 Speaker_01
There's some fragments and stuff that are older, but for the most part, we're working in thousands and tens of thousands of years, not millions of years, because DNA degrades very, very quickly.

00:12:11 Speaker_01
It starts to break down the minute it leaves your body, and so when you layer in radiation, heat, acidification, other animals defecation, other animals dying on it, it starts to break down and it also gets massively contaminated.

00:12:25 Speaker_01
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

00:12:34 Speaker_01
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.

00:12:42 Speaker_01
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 in science textbooks and today on the internet, we say what is the closest living relative to the mammoth in this case?

00:12:56 Speaker_01
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.

00:13:10 Speaker_01
And then we spend 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 sequence a lot of different Asian elephants, so what is truly Asian elephant versus population diversity

00:13:31 Speaker_01
in those genomes, because not all genomes are obviously exact copies of each other. And then how do we compare that to the mammoth?

00:13:38 Speaker_01
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?

00:13:49 Speaker_01
you know, from actually doing molecular and functional assays, actually growing stem cells and testing our hypothesis.

00:13:55 Speaker_01
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.

00:14:10 Speaker_01
That's actually just changing existing code. So we fundamentally don't need long-term pieces of these DNA. We don't need all these dead samples. We just need the code in the computer.

00:14:20 Speaker_00
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?

00:14:34 Speaker_01
We have enough. So 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.

00:14:47 Speaker_01
And we work with about 17 universities across the world, one of which is the University of Stockholm. and Luva Dahlin's work, and Luva is arguably the number one mammoth researcher in the world.

00:14:55 Speaker_01
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.

00:15:04 Speaker_01
But we have enough of the protein coding regions of it, as well as Colombian mammoths, steppe mammoths, and others, and we have a pretty cool paper that I hope will come out mid-next year about this.

00:15:14 Speaker_01
that shows the comparative genomics that we know enough of the mammoth genome that we can identify the core areas around cold tolerance, fat, hair, curved tusks. So we actually have enough to do our work.

00:15:26 Speaker_01
It is not as complete as our thylacine genome, which we recently announced is 99.9% complete, which is truly incredible for any genome, let alone ancient DNA.

00:15:38 Speaker_00
That's the Tasmanian tiger? Correct. So are you using CRISPR technology to insert mammoth code into an Asian elephant zygote, or what is the step there that would produce a living mammoth?

00:15:53 Speaker_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.

00:16:00 Speaker_01
One of the things that, you know, before we get into the genetic engineering side, 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.

00:16:15 Speaker_01
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 MICEhab, which I'm sure you're familiar with.

00:16:28 Speaker_01
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 we'll get into, the cell would just senesce.

00:16:37 Speaker_01
So not only do we have to build immortalization constructs to keep the cells

00:16:40 Speaker_01
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 cancer in elephants, right?

00:16:54 Speaker_01
And so 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 cuz you you're the background science.

00:17:04 Speaker_01
You know crisper has become a catch all for all genetic engineering there like it's just crisper right we just. We just crisper it but what's interesting is we use a combination of tools some of which are proprietary some of which are.

00:17:18 Speaker_01
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 that double helix.

00:17:31 Speaker_01
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.

00:17:45 Speaker_01
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 our kind of

00:17:59 Speaker_01
I think the thing that sets us apart 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.

00:18:16 Speaker_01
50 edits, 1,000 edits, all with a very high degree of efficiency versus having to synthesize entire giant blocks.

00:18:24 Speaker_01
I do believe that technology will get here, being able to synthesize even full chromosomes at some point, but we as humanity aren't quite there yet. So editing is the most efficient kind of current modality that we've been pursuing.

00:18:38 Speaker_00
So at what point did this actually become technically feasible? What year would you say this became something that you could actually start on and it ceased to be just a piece of science fiction?

00:18:52 Speaker_01
Yeah, so I think people have been talking about CRISPR in some version of genetic engineering from the 80s, right?

00:19:00 Speaker_01
But it was like, I don't remember the exact year, but it was like what, 2012, 2014, somewhere around there where we had the true kind of discovery around CRISPR and the idea that you could target a part of the genome, successfully knock it out, and have it repair itself.

00:19:20 Speaker_01
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.

00:19:27 Speaker_01
You've seen kind of this like pre-Cambrian explosion, you know, to use our Jurassic, use some of our Jurassic fun terms, of genetic engineering tools and technologies, 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.

00:19:47 Speaker_01
But I think that really in the last 10 years has been where those technologies have been viable. I don't believe before that kind of 2012-2015 time frame of that CRISPR race with Fang and

00:20:03 Speaker_01
And down and all of them right there is there in george included which were all incredible scientist i don't believe that this would have been a viable undertaking.

00:20:13 Speaker_01
And in that after that it became viable but it you know you soft compute you saw the ai there's a lot of other components to it and it just becomes very very costly.

00:20:22 Speaker_01
The goal to really make this where it's possible and scalable, 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.

00:20:34 Speaker_00
So is AI a necessary component of the process?

00:20:38 Speaker_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.

00:20:50 Speaker_01
Like we actually have a tool that we built internally that we've been giving it this feedback loop.

00:20:55 Speaker_01
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 that's over 90% accurate of what tool we should use for the specific edit that we're going after.

00:21:10 Speaker_01
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 cells, you gotta wait a couple weeks,

00:21:24 Speaker_01
in some cases, if you don't have sequencing cores internally, to get that data back.

00:21:27 Speaker_01
And so the feedback loop, if you've made the wrong edit using the wrong tool, or at least the most efficient tool, can be months of lost scientific experiment time, both costly in terms of go-to-market and in terms of your research.

00:21:43 Speaker_01
and all the reagents and stuff that you had to go use in that, right? And so we're now using AI not just for comparative genomics, but even in selection of what editing tool we should use for the editing job that we're trying to go pursue.

00:21:58 Speaker_00
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.

00:22:09 Speaker_00
What have you produced in the lab and is it all still in vitro or do you have a pregnant Asian elephant that has a name?

00:22:19 Speaker_01
There is no secret pregnant Asian elephant mammoth, unfortunately. I would be the first. I couldn't be more excited to share it with you if there was. So, de-extinction is a systems problem, right? There's computational analysis, or there's ancient DNA.

00:22:34 Speaker_00
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00:22:51 Speaker_00
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