#681 - Ben Lamm - The Man Bringing Extinct Creatures Back To Life episode artwork

EPISODE · Sep 16, 2023 · 1H 9M

#681 - Ben Lamm - The Man Bringing Extinct Creatures Back To Life

from Modern Wisdom · host Chris Williamson

Ben Lamm is an entrepreneur, CEO of Colossal and a founder. What if Jurassic Park's dream of bringing extinct creatures back to life was possible? Well it kind of is. And Ben's company is forging ahead in the new frontier of de-extinction, starting with some of the most legendary animals from history. Expect to learn why Ben is bringing Wooly Mammoths back to life, how you give birth to an animal that died out thousands of years ago, where Ben gets the genetic material from, how bringing back Mammoths could fix climate change, whether artificial wombs will actually work, if we can make humans as strong as Neanderthals using their DNA, why we should bring back the Dodo bird and much more... Sponsors: Get the Whoop 4.0 for free and get your first month for free at https://join.whoop.com/modernwisdom (discount automatically applied) Get 5 Free Travel Packs, Free Liquid Vitamin D and more from AG1 at https://drinkag1.com/modernwisdom (discount automatically applied) Get 15% discount on Mud/Wtr at https://mudwtr.com/mw (use code MODERNWISDOM) Extra Stuff: Get my free Reading List of 100 books to read before you die → https://chriswillx.com/books/ To support me on Patreon (thank you): https://www.patreon.com/modernwisdom - Get in touch. Instagram: https://www.instagram.com/chriswillx Twitter: https://www.twitter.com/chriswillx YouTube: https://www.youtube.com/modernwisdompodcast Email: https://chriswillx.com/contact/ Learn more about your ad choices. Visit megaphone.fm/adchoices

Ben Lamm is an entrepreneur, CEO of Colossal and a founder. What if Jurassic Park's dream of bringing extinct creatures back to life was possible? Well it kind of is. And Ben's company is forging ahead in the new frontier of de-extinction, starting with some of the most legendary animals from history. Expect to learn why Ben is bringing Wooly Mammoths back to life, how you give birth to an animal that died out thousands of years ago, where Ben gets the genetic material from, how bringing back Mammoths could fix climate change, whether artificial wombs will actually work, if we can make humans as strong as Neanderthals using their DNA, why we should bring back the Dodo bird and much more... Sponsors: Get the Whoop 4.0 for free and get your first month for free at https://join.whoop.com/modernwisdom (discount automatically applied) Get 5 Free Travel Packs, Free Liquid Vitamin D and more from AG1 at https://drinkag1.com/modernwisdom (discount automatically applied) Get 15% discount on Mud/Wtr at https://mudwtr.com/mw (use code MODERNWISDOM) Extra Stuff: Get my free Reading List of 100 books to read before you die → https://chriswillx.com/books/ To support me on Patreon (thank you): https://www.patreon.com/modernwisdom - Get in touch. Instagram: https://www.instagram.com/chriswillx Twitter: https://www.twitter.com/chriswillx YouTube: https://www.youtube.com/modernwisdompodcast Email: https://chriswillx.com/contact/ Learn more about your ad choices. Visit megaphone.fm/adchoices

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#681 - Ben Lamm - The Man Bringing Extinct Creatures Back To Life

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Just as a headline here, you're trying to fix global warming by bringing woolly mammoths back to life amongst a number of other extinct creatures. Right. Well, I don't think that one company can fix global warming. I think that we are at the brink of a major biodiversity crisis which will lead to ecosystem collapse.

And restoring ecosystems like the Arctic tundra is something that we're very focused on. So I hope that we are one of many people working on biodiversity loss and combating climate change. But I think it's maybe a little bold to say that we are solving ourselves. I understand.

Okay, so somebody comes up to you at cocktail party and says, what do you do? What is your answer for your day to day work? So my general answer is I say I'm in technology. If they die deeper, I'm in biotechnology.

If they die deeper, I tell them that we're working to bring back extinct species and preserve all life on Earth. And it kind of unravels from there. Right. Okay, talk to me about de extinction then.

What even is that? Yeah, so de extinction is not necessarily a new concept. Everything from books and movies and some other movements in the world have talked about the concept of de extinction and the way we do de extinction is the de extinction of core genes to build proxy species or genetics that have been lost to time, whether that was due to solely climate change events or towards or due to the fact of man's implications. Right.

And so fundamentally, we are de extinct the core genes that make all of these species, those unique species. And so recently I was on a podcast where someone wanted to debate semantics over the dodo. That. And they're like, dodo is just going to be a silly looking pigeon.

And I hated to inform them that a johto was a silly looking pigeon. Jonas were pigeons. And so the things that made it a different flightless pigeon were the genes that were de extincting. And so it definitely brings out different groups have different perspectives on the work that we're doing, but fundamentally we're bringing back these lost species to increase biodiversity and we're using all those technologies for conservation, which is pretty cool.

Okay, nuts and bolts. How the fuck do you bring a dead animal back to life? So you can't, you can't clone a dead animal. You don't have living cells.

So what you have to do is you have to look for its closest living relative. So in case of the mammoth, that's the Asian elephant. Mammoths are actually closer related to Asian elephants than Asian elephants are to African elephants, which is like that Blew my mind when I learned that because I was also the first to pick extinction when I was working on this. And what was interesting is you actually have to then go look at the DNA sequences.

So we actually had to assemble 54 mammoth genomes to build out kind of a reference genome that would do all the comparative genomics to that of the Asian elephant. And they're about 99.6% the same genetically. And so then in that difference of 0.4%, so long genes, we, we then started to isolate what are the genes that really made a mammoth. Of the mammoth, you know, the jo cranium, the curved tusk, the shaggy coat, these extra fat layer, how they produce oxygen at some freezing temperatures.

And so we then have to spend a lot of time doing compositional analysis to really understand that. And then we take and engineer those genes into that of an Asian elephant cell. Then we go through the cloning process. Kind of like what they did with Daly Dashi back in the 90s, only it's way more efficient now and it uses like lasers and stuff like that.

Versus back in the 90s they were kind of just jamming stuff together, which was weird, but it kind of worked. And now actually it really works because it's way more precise. And then you actually implant that embryo into the closest looking relative being the Asian elephant. From a cerepesy perspective, where do you get the genomics of a animal that's not.

When did they. When was the last Boyganothali? So the last one's actually around 3500 BC. So they were up in Wrangel Island.

So they've been extinct for quite some time. Ironically though, during the building of the pyramids, the last mammoths were still alive. So it's kind of weird. It kind of blows my mind.

A lot of people think that mammoths were like around the time the dinosaurs, since they're like 65 million years old, it's not. And a lot of the DNA comes from the permafrost. As animals will die up there, they will instantly start to freeze layers of snow and ice. Layers of snow and ice.

And so there's tons of preserved species up in the permafrost. And so, you know, over the last 15 years there's been incredible researchers like George Shirts and Luba Dala and Vespero and teams, these things I work with that actually gone on expeditions to the permafrost to extract ancient DNA. So it's a little bit of science fiction in Jurassic Parking. It's a little bit of Indiana.

It's really interesting how it kind of all comes together in the extinction science today. So you have, is it entire animals or is it bones of animals? What's preserved? Yeah, preserved in frost, right?

Yeah, lots of shit can be preserved in frost, but it depends. So in the case of the dodo burn, some of it is just. Some of the DNA is actually just taken from the bone or the inner beak that they've actually drilled into. In the case of the thylacine, you know, signal, in 1936, hunters actually preserved one of the pups that they killed in alcohol that ended up being a museum.

And so that was really well preserved in case the permafrost. With mammoths, you know, sometimes you get actual flesh, sometimes you get actual, you know, errors, sometimes you get actual meat. It's very old and very disgusting. It's got lots of bacteria, so I won't even eat it.

Some people have, which is crazy. But a great place to get ancient DNA is. You mentioned it's teeth. So some teeth do a great job of preserving it.

And there's an inner ear bone called Petrospone where you actually get great DNA from species that are 10,000 years or older. What do you mean when you say great DNA? Is this an error? Wait, it's not degraded over time.

There's a high density, there's massive. There is things like heat and sun and radiation are all very, very bad for DNA. So DNA starts to degrade the minutes outside your body. So it is definitely degraded DNA, but you can get more and more of it if it's in these well preserved spots like teeth, like the pector spone, or really well frozen.

We got all over the tops. And we're actually doing a project right now with the University of Alaska and this program we put together called Dr. Mammoth. But we're actually taking teeth samples and we're giving them from universities, from the museum in Alaska, giving them and loaning them to school kids, showing them how you extract ancient DNA.

And we're doing a whole both radiocarbon dating and population genomic study and sequencing all of these Alaska mammoths. So the way to bring kids into it, promote education, you know, because these things are pretty cool, right? But then also it's an incredible way for us to get tons of data that we can use to understand populations of American mammoths. Because a lot of the mammoths that we have are actually from Siberia.

So the Russian mammoths. Oh, interesting. And you mentioned 53 different samples that was taken and all of those are combined. Presumably the goal Here is if we have, you know, like 98% degradation of the genome, but we get tons of them, like 50 of them, you can build that up over time and hopefully we get somewhere close to actually seeing a full sequence.

You'll never get to fully 100%. I mean, you just won't. Right? And so some of the stuff happens in the regulatory regions, some of the non regulatory regions, you don't even really need as much as you may think.

There's an area that I learned about when we started working on this about kind of DNA coverage and the number of reads that the system does, because even these sequencers aren't perfect, right? So they're basically giving you a probability score of what that letter is in terms of the individual nucleotides in the DNA sequence. And so what's interesting is the more DNA you get and the more reads you can do, the higher probability, right? Because if you go through 20 to 50x coverage, that means that they've gone through the whole genome 20 to 50 times.

So that means that there's a higher likelihood that they're going to be correct, that the genes will be correct in telling you what that specific letter is. And so anytime you get 25x up, sometimes as low as, you know, teens up, you typically get enough of the genome that you get pretty precise. Okay, so let's say that you now have compared the African elephant, Asian elephants, you've compared the Asian elephants to these 53 AI enhanced sequenced differences. There's this 0.4% or 0.6% which is the difference.

We've got this. Now what? Now you get a 3D printer mammoth, like what are we doing here? So you actually do molecular and functional assays and tests to understand what do those genes do.

And what's interesting from both a convergent evolution and a general evolution perspective, you can start to see in different species how certain hair, for example, grows. So we know this is not mammals, which is really interesting. I always thought that mammals just have long hair, right? They actually have five different types of hair.

And so different genes and different pathways do that. And so one of the things that we're doing with, with Colossal, which we find interesting, is we're not only looking at what were the genes and single gene and additional genes that work together to produce that phenotype or physical attribute of that species. We're also, we have an entire genotype to phenotype team RTPTeam that looks in leverages AIs and we create newer technologies to actually try to understand how do things like size, how do things appear, how does that work across a million species? Right.

Even with different genes, like what are the different stages of development? So we're doing a lot of work in kind of general genotypic things like around big core things like, you know, everything from size to cranial facial shapes, you know, to fat patterns to patterns of actual kind of fur. And then as well as, you know, looking at things like hair and fur length and different regulatory things like that. So it's really interesting because for our perspective, because we're on multiple species, we have our individual teams that's trying to solve the individual challenge of each species.

And then we've got this functional team that's trying to look for trends that can be applied to other mammals. Right. And that can be really helpful for like drought resistant cattle in UP species. Okay.

Moving forward, how do we make a mammoth? Yeah. So the way you do it, you have the competition analysis. First you get DNA, simple the DNA.

Then you actually do that competition analysis. And once you have your targeted gene list, you then go through the actual process of editing Asian elephant cells. Right. Because they're the closest living.

So we did, you mentioned African elephants. We did a work with the genome project to do a full reference genome of the African elephant. More for conservation than really for our project. We did find some interesting differences between animus Asian elephants and African elephants that we were starting to explore.

But once you do that, you go through the process of understanding what that gene list is. You can start making edits and you start with looking for the edits that you think are going to be the highest impact. You then do a bunch of tests to make sure those ed. And once you get to the point that you feel like you've got a cell with the edits that you feel comfortable with, you do sequencing just up at the beginning on those cells to make sure that the edits are there.

They didn't create what's called off target effects, meaning things that you didn't mean to break in the genome. And so once you feel like you're comfortable there, you then go into a user process called somatic cell nuclear transfer or cloning. And that's where we take the nucleus of a somatic cell and we put it into that of a germ cell. What's a somatic cell?

For people that don't know, somatic cells are basically all the cells in your body that are ordinary in animal's body that are not sluromatics. Those are like skin cells. Different types of tissue cells. So we take the nucleus or that brain out of a somatic cell and we put it into that of a germ cell or an egg cell.

And then effectively you got, you know, the basis of an embryo. You then use a process of slight electrification and some other media and it starts to divide. And once you get to the right stage of division, you then implant that into a surrogate. In the case of the woolly mammoth, that's the Asian elephant.

So that's how it works in mammals. How it works in birds is slightly different. It's a little bit different of a process, but it's a much easier gestation process. So that's interesting for Dodo as we talk about that or.

Yeah, yeah, I want to know how. I want to know how birds are even. What's interesting to me about birds is the gestational side because we're not going through this maximum transfer or that cloning step in birds. Birds are harder on the front end, but they're so much easier currently on the back end.

Right. Because you don't have to work. We don't have to work on the surrogacy side. You don't have to do the embryo transfer, you don't have to do the nucleus transfer.

So what's great about birds is while we can't clone birds currently in the world, meaning that we can keep find the nucleus at the right time of development to move it, you can't clone birds yet. Maybe one day you can. There's debate on whether it's possible, but, you know, everything is impossible. It's not right.

And so. But what's interesting is what we are doing is we're actually using chickens as our host. And so this blew my mind. Kind of like how close were.

When you take. If you can cultivate what's called primordial germ cells. So the precursors to egg and sperm. Right.

And then you edit those. You can then use that and build a. An edited chicken with these edited primordial germ cells. So this is where it's crazy.

I mean, at least for me being a de extinction, you can then have edited primordial germ cells, chicken A and edited primordial germs. Those chickens can fall in love and depending on her worldviews, they get married or whatever and then they have a baby and they have an egg. When that egg hatches, it is based on what you put into the promotional germs. So they've done this and created transgenic ducks where they put edited duck cells in PGCs in a chicken one, they done it in chicken two.

Those chickens grow up, those chickens fall in love. They, whatever they have, they have a baby, an egg, the egg hatches and it's a duck. And so what's amazing is that chickens will actually be the surrogates for our first dodos, which as we talked about briefly earlier, are kitchens. So our state invested.

It's an interesting, it's an interesting world. And now we're even exploring. I don't know if it's possible, but I'm happy to share with you. We are exploring bird cloning, right.

Because we were told this is how you have to do it, using these, using these types of primordial germ cells. So that was the process that we followed. But then, you know, we're like, well, why doesn't bird cloning work? And we got lots of feedback like, huh, maybe we'll try that.

So we are working on bird cloning. Not sure it's going to work, but if not, we'll go down this PGC route. That seems pretty plausible. Okay, so getting back to the mammoth, there's an unclosed loop about that one.

We have this Asian elephant, this unsuspecting mother Asian elephant who is going to give birth to what. What will ultimately come out of this elephant? Yeah, so it's a great question. It'll be our kind of mammoth 1.0s.

Right. So we take it's an Asian elephant that has been edited. So I come from software citing things like software. So our 1.0s will produce all the core phenotypes that we know and love in a woolly mammoth.

So we're de extincting all the core hair genes, the cranial facial shape, the dome cranium, the tusk morphology in terms of the curved tusks as well as like short tails, smaller ears. And then there's some stuff kind of under the hood, like how, you know, how the mammoths are more cold toler with certain fat layers, with the ability for their neuroendinks not to fry at suffrage and temperatures, the ability to produce hemoglobin and oxygen laseriz. There are no laser eyes. That's a we thought ask if we can make a thylacine laser eyes.

So we get a lot of interesting requests, believe it or not. Right. So is it accurate to say that it's a mammoth or is it accurate to say that it's an entirely new species? It's really not.

So the IUCN, in the Species Survival Commission, we'll show it at the ufcc, which is amazing. We'll work close with them, defines a new species of something that gave rise in nature. So it's not really a new species. At least how it's.

How it's also not a mammoth, right. Because it has all the core. I mentioned this earlier, right. You know, whether you think dodo is a silly looking pigeon or a mammoth is an elephant.

A mammoth was an elephant. Like that's just what they were. They're practicing that. That's what they were.

And so I don't know, like my dogs are mutts. Right. And I would argue that most species are hybrids and that's hybridization gives rise to newer species. Right.

And so, you know, if some people aren't happy unless we clone a hundred percent of the mammoth, then I would argue that, you know, it's a cold adjusted, genetically modified elephant with extinct mammoth alleles from a series of biodiversity gaps of, you know, three to five or 10,000 years. Right. So much less sexy as a name. Yeah.

I mean that's what you want to call it. That's what you want to call it. I mean for you and me, or at least for me when I see it, if we are successful, you know, it has all the core phenotypes and it's called adapted. If we de extinct to the core genes that made a mammoth a mammoth, then to me that's a mammoth.

Right. You know, our goal is not to create. There's a lot of infrastructure in the genome that's just. It doesn't produce any real effects.

So I mean we could add thousands upon thousands of edits to our mammoths that don't have any true meaningful effects. But from a purist perspective, some of them say, oh, that's closer to a mammoth. That's at least how we do it functionally. It's a mammoth, right?

So it's a functional mammoth. It looks like a mammoth, it drives like a mammoth. Yeah, right. At least that's, that's how we think about it.

There is a small percentage of folks that disagree with us, but you know, you mean the mammoth purists out there? If the mammoth purists want to go a step further, they can and we welcome them to. Okay, what about like gestation and stuff? Because there's got to be differences and inter utro bullshit.

There's definitely intra utero bullshit. So it's about 22 months of gestation. So it's a very long gestational cycle. Right.

Which you know, I try to think of things from A systems design perspective. Right. And so for me, that's one reason why I love the thylacine. So if I can dumb down the process.

Once a thylacine, Tasmanian tiger, it's a large heart, it's the largest carnivores, arsenic. Wow. It kind of looks like a wolf. From a.

It's genetically related to wolf, but from a convergent evolution perspective, meaning that in the isolated population, it kind of looks like wolf. And if you look at a thylacine and a wolf skull, I say 99 out of 100 times, people would say, oh, that's the same. There's only one small difference on the inside, but really interesting is that the perk conversion illusion also looks like a wolf. But going back to your question, from a gestational perspective, you got 22 months with the mammoth.

With the thylacine, you have 13 and a half days now. So that's the end of the process. The beginning of the process. Compatibility.

Right. Like the symbol reference genome. With the mammoth, we have 54m genomes. You do a lot of work to your points, very degraded.

You do so much work on it. On the thylacine, we get over 92% complete read on the first read. Right. So that's easier.

But then in the middle on the editing, lots of more edits that are required in the file scene than in the mammoth. So it's like hard, easier, hard. And this one was easy, harder, easy. So what's interesting from a systems perspective looking at this is you can look at the entire kind of like system in mammalian de extinction and build a system that kind of has to work for both.

And so that's what we're spending a lot of time. I will say that it is a lot easier to gestate the pilot scene than the mammoth. Yeah, I guess that one Asian elephant is looked at very, very carefully for 22 months. Do not let it out of your sight.

If it goes missing, you're in trouble. All right, so what could go wrong during this process? Are there anything? I mean, there's a lot.

Anytime you're doing something that's hard from a science perspective, things can go wrong. Right. Like, you could not fully get all of the right edits made. You could.

Not only that, we can test for whether we made them. Right. But do all of the edits produce the phenotypes or core physical bottoms that we're looking for? Right.

How does the SOMAT cell transfer process work in elephant versus bovine versus pig versus dog versus mouse? Right. And so there's still nuances to that. Right.

And then gestationally. You know, the thing that's really interesting is that I don't think there's been this whole concept of xenotransfer. Right. Of like or xenotransplantation of taking something from one to another.

You know, sounds like crazy, but we see it all the time. People get xenotransplantation pieces of pigs in their hearts and go live normal lives. Right. We also see that, you know, we also see that that species like a mammoth, which is closer related to an Asian elephant than it is to a.

Than an Asian elephant is an African elephant. African elephant. An Asian elephant is actually going to bring. And so these are two genetically distant species that are further apart than these two.

And remember to your point earlier, we're not making exactly this one. We can somewhere between. Right. So we're even closer to nation of it.

So we believe there's a high degree of confidence in that interspecies transfer and in that, in that. Sergio. But people ask me all time where the name. Due to the 22 month gestation, I think it's highly likely there'll be another species.

Oh, it's gonna get pipped at the. It's start off on the race first and it's gonna end up coming in last. It's got 22 months of gestation. I mean that's just, that's.

That's hard to. It's time to grow a mammoth. Yeah. There are people, there's other species that can do a picture lap before.

Yeah, you've got an entire army of those things that look like wolves. All right, what else? Actually, here's a question. So it seems to me, with my extensive knowledge of how genomic sequencing works, that the main limiting factor is the quality of the DNA that you can get from whatever the sample is of the animal.

Is that right? I think that that's overcome. I don't think that's. That's the limited thing.

I think that the obvious. I think that what you just said is overcome with more samples. Right. And so we've got incredible partners like Lubadalin in Stockholm.

Lubadoll is arguably one of the most knowledgeable people in the world of the genes that came in with the nano. And he's constantly just finding, sequencing more nanos. So I think that we can probabilistically get through what you just suggested. I think the biggest issue and I think different for species, but you know, it's just editing.

Right. What's amazing is that we Have a lot of incredible editing technologies. People kind of just clump all genome editing as one thing. But there's a lot of different technologies.

There's editing individual letters in kind of that twisted letter, right? Each one of those rungs, you can edit individual ones. You can knock out pieces of it. You can edit multiple things at the same time all over the genome.

That's called multiplex editing. That's where we're spending a lot of time and we're trying to be the most innovative copy in the world. Being able to edit a lot of parts of the genome at one time so you don't have to be so precise. You can edit that same level of precision all over.

And we've had, you know, over 90% efficacy already proven internally, which is amazing for edits and trying to stack those. And then you come to DNA synthesis where it's like to your. If you can get to your point earlier, if you can get that right amount of, you know, letters in the right order, you have high degree of confidence in it. You can synthesize a big piece of that and then just swap it in.

So in areas where there's lots of edits, instead of doing lots of edits, you know, either using kind of some of these individual editing tools or even editing multiplex or even synthesizing pieces of full pieces of DNA and swapping it in. Because that may have, you know, 20 different edits that we have to make because we really only had to synthesize and then swap it one. So I think that depending on how far we want to push editing, I think that the rate at which editing, the rate at which editing technologies progress will probably be the limiting factor. Not on our success, but on the number of edits that can be made.

When it comes to other animals, if we were to try and get more exotic, I mean, the Jurassic park means, right? Themselves with their tail, Right? We've heard that before. Yeah, it doesn't surprise me with those.

What's the limiting factor there? Why is it the case that you. Maybe you can, but why is it the case that you can't do something which is a little bit more exotic? Well, I mean, I would argue that no one to my knowledge, has seen a mammoth.

So it's pretty exotic. More exotic, you know, Older. Older. Let's not call it more exotic.

I'm gonna value judgment on your mammoth. Older. Yeah, so, I mean, Catholic is pretty exotic. Mauritius is very exotic place.

Beautiful dodos. So, you know, great limiting. And you can't, you know, harvest DNA from Bone. You know, Kenneth Lacovara, who's incredible, is one of the top paleontologists in the world.

He discovered Dreadnoughtus. He's also one of the most interesting people in the world. The largest dinosaur ever, Dreadnought. He's actually been able to demineralize bones, dinosaur bones and get pieces of amino acids, right?

But amino acids and even some proteins and some collagens. But that does not. That's not a big chunk of DNA. Right.

So we get the amber question, we get the dino DNA question. So I guess there is technically dinosaur collagen and dinosaur amino acids and maybe some proteins here and there. But that is so. So that the pieces of confetti.

You're now making pieces of confetti, a pieces of DNA confetti of confetti. To try a dinosaur. It does not maketh. It does not.

And so right now we can go back about a million years. I haven't seen the latest in terms of what's been sequenced, but I know we've been able to sequence 700,000 two to a million years and get viable DNA. But at some point, you know, so, so that there's a lot of exotic stuff between then and now Also, you know, cold, dry environments are great for DNA. You know, hot.

A lot of people love to talk about the lower tarp. We get a lot of questions about. And you know, hot acid filled places are not great for DNA. There's been some really cool animals that have gone extinct in warm, wet, in climates that you know, aren't great for DNA.

So you can't make those. A big fan favorite is the giant sloth people. There used to be a giant sloth. It was the size of a tree.

A giant ground sloth that would literally. And there's like some. I've read some stories about how they loved avocados and how they propagated avocados. I don't know if there's any truth to that.

It's one of the recent things I've read about. So there are lots of kind of different species that you know, are interesting. I think that a lot of the Pleistocene species lately species make of sense because there is great or there is as great as preservation as you could probably get because early humans weren't sticking them in some freezing temperature freezers at the time. Right.

Okay, what else from the last million years? If you were to have a hit list atop of the pops, aside from your mammoth and your dodo, what else is in there for. I would like to bring this Back? Well, I mean, I think you have to have a reason why.

No, no, no, Ben, this is. We are completely liberated from resources, ethics or a service of humanity. What do you want to bring back? I think it's hard to fully liberate ourselves from service of humanity or ethics.

There's a couple species that I find very interesting. I think the great auk is really interesting. It was like the American penguin. It's super cool.

I think that it served a purpose. I think that there's a whale sized manatee or dugong called the Stellar Sea Dao. We can't bring it back. We actually did it for it.

There's nothing adjusted. It's too big. Unless we get extraordinary development devices to work, which we do have 17% working on. You know a fan favorite is Sabertooth cat, which there were several, but there were two that were pretty prominent, one being Homotherium and one being Smilon.

Spylon have the bigger tusk, you know, the big canines that we think of. So I think all of those are pretty interesting candidates. You know, I don't, we can't do this largely count. I think that'd be incredible to see.

Like you know, blue whale sized, you know, manatee, like you'd be like. And apparently they're like incredibly helpful to the count. Forest of the Pacific Northwest. And so they're also big carbon sticks like elephants.

So those are all really cool species. We're not working on any of them currently. All right, so what's. Aside from the mammoth, the mammoth being very useful one and I want to get onto why it's particularly useful.

And aside from these other ones that are like the sexy ones, what else would you just don't think that mammoth is sexy. I think mammoths are pretty sexy. I'm not a hairy. That much hair is too much for me.

What else is particularly useful from the last 1 million years like I said, with these very specific use cases of certain animals. So I'll hit the use cases of the two non mammoth species and then kind of I guess probably another species. But so specifically with the dodo. Bringing back the dodo doesn't like fix the ecosystem of Mauritius.

But bringing back the dodo, which is a symbol of man caused extinction, will force us and the Mauritian government, who we're working very closely with on removing the invasive species that actually led to the dodo's extinction. So a lot of people love to just say that dodos were dumb and people just ate them. There's actually not as much data suggesting that as that because they were a ground dwelling species of flightless bird and they laid their eggs on the ground one time a year. Longer gestation cycles.

When you bring in, you know, invasive species like pigs and rats and other things and they eat the stuff that's on the ground because they can concentrate for the most part. And so the process of bringing back the dodo in collaboration with, you know, local people like governments, indigenous people groups and whatnot, if we do want to successfully revolve them in Mauritius and in the neighboring islands, then we actually have to do a process of ecosystem restoration. So it's forcing us to undo some of the sins of the past of introducing these invasive species. Right.

So a lot of the wastes of the dodo, it doesn't really solve a pure ecological impact, besides forcing us to undo that, which also could help other species that are native to those islands. In the case of thylacine or Tasmanian fiber, some people call it Tasmanian wool, but more commonly Tasmanian tiger, you know, it was the largest apex predator in Tasmania and lower Australia. And what people don't realize is people just think, oh, predators, easy life, top of the food chain. It's like, no, those are actually the bigger, those are easier lives, you know, because they're eating grass.

There's a lot of energy expenditure that happens in carnivores to go make a kill, right? And so if you're a carnivore and you're driving and if you're an animal carnivore, I should say, and you're out in the field and you have to go actually like make a kill versus just get it from your local Whole Foods, you actually have to do the work. You're going to be very strategic. You're going to spend that energy expenditure very wisely.

You're going to look for either the small, old, weak or sick animals to pick them off. And so what people don't realize is that a lot of these carnivores have tremendous help in kind of securing the balance of the ecosystem. Not just because they're thinning herds, because they're also eating a lot of the stuff that, you know, in killing off the weak, the young or the sick. And so one of the animals that the Tasmanian tigers probably preyed on was the Tasmanian devil.

It was smaller in the sack. And now due to this whole facial tumor disease and they don't have any natural predators anymore, they're actually spreading this terrible facial tumor cancer to each other when they eat. I've been with Tanyan devils in the wild and it's very interesting, they're very aggressive and so when they're doing that they're fighting each other, clawing each other and they actually pretty deep up during that kind of feed and friendly process and they actually pass that disease. Well if biologist things around or a larger animal that preyed on them they would most likely thin out a lot of those animals that can't walk through a large sea bird to the fish.

So then there's less that can actually produce that. So that'll affect isotropic downgrading when you, when you have a predator that actually can remove that from the wild and that helps balance the ecosystem. Right. So you know, Dr.

Andrew Cass is one of our partners on the biosing wilding restoration or rotten project has been very adamant on their demise has led to the potential demise of the devils which is terrible. So those would be non mammoth species impacts. Okay, so why the mammoth is kind of a. It holds a particularly good cultural position.

I really like that thing about the dodo that it's not about what it does functioning but what it does symbolically. Look guys, we went through all of this effort to bring this thing back because of how top turby the ecology of this particular location. You've got to fix this. I think that's just a really smart way of playing with human psychology.

The mammoth also kind of is symbolic in some regards. I don't know if we actually do know why it went extinct. Was it hunted until extinction? Was.

Yeah, there's a lot of different. It depends on who you ask. Right. Like there's scientific peer reviewed papers that say early man hunted into extinction.

There's other papers that show, and other research that shows that you know, it was, it was climate and the evolving climate that pushes further north. And then there's genetic bottleneck and Rainbow island, the last mammoth side inbreeding. But most likely what most people don't realize, I think the absurd somewhere in between because I think there's data, I mean we have, you know, proof of early man hunting mammoths. We have, you know there's, there's spear marks and stuff like that in some mammoths.

There's actually mammoth tools that have been used. Right. And so I do think that were designed built at that time. I think more than likely, you know, with elephants specifically 22 months just they need about 6 years to get to the point that they are truly adult elements.

And then there's about a 12 to 13 year sexual maturity process. So if you want to kill all of this, you actually don't have to eradicate elements, you don't have to eradicate all of them. You just have to eradicate enough of them because of that cycle. You know, whether it's the environment or predator, someone will thin them off at the time to get to extinction.

From a reproduction perspective and from a fertility perspective, elephants generally are a fragile creature. Long gestation, long time as a relatively useless unprotected infant, still relatively useless sexually. Finally we can do. There's a lot of opportunity to be dead in that before you get to the point to pass on routines.

One thing about elephants though, and we are working on this as it relates to mammoth extinction, we're not looking at it from a cancer perspective. But one thing that's interesting about elephants and I believe also blue whales, is they have an over expression of this person called P53, you and I and mice, we have about one expression of it, they have seven. And what's interesting is if you look at elephants for both body weight and body weight and size and longevity of life, they get cancer a fraction of what they should based on like cancer mutation curves of most mammals. And it is believed that a lot of that is due to P53.

Right. And it's just something that's not as well studied as probably should be because most people work in mice and in pig. So one of the things that's interesting what we're doing with colossal outside the extinction or species preservation efforts, it's a point of if it's an option, but, but finding because we are working in so many non model organisms, we're starting to see really interesting things and learning a lot about species that there's just not enough research into at least at the genetic level. And so I'm not saying that P53 or elephants have to cure to cancer, but they may.

And so we are working like for us to do our editing about that for us for us to create what's called induced pluripotent stem cells, the most naive state of stem cells that then you can reprogram into any type of tissue, which is very helpful for us. What we're trying to do, you know, we've achieved that in our marsupial species, the fat tiltanar, it's our model words for thylacine. But in the case of the mammoth, in the agent that we're very, very close, we have not that quite yet we've gotten to IPSCs, but we want to get to further differentiation of them so that we can really characterize them as the most Purest form of IPSC stomach grading scale. And we've achieved that kind of first step.

Now we progressing, but we actually had to isolate and build a construct around P53 and learn how to regulate it. Because think about what do mutations look like? They look like cancer, right? So when you're introducing mutations into the genome, it looks like it looks like a form of cancer.

So we're learning a lot about, you know, how cellular regulation works around P53, which is really, really fascinating. One of our advisors, Fritz of Ulrathis is one of the top p53 researchers, are very helpful to us. But, but fundamentally that's an area where some of these species are not massively redirected. Bibles as you just stated, could be really helpful if we understand more about their genetics.

Okay, so dodo bird. Symbolic. Useful not being gone for that long. Tasmanian tiger would be good to stop Tasmanian devils from getting a space tumor.

Also symbolic because they're only extinct because the Australian government put a bounty on their heads and paid people to eradicate them. So also very small, 100% man caused the extinction. All of that being said, woolly mammoths functionally do some cool stuff. What cool stuff do they do?

How do they help the planet? Yeah. So there's a group called Pleistocene park that George has been working with for the last 10 years in Northern Siberia. And what they found, they've done this in ethnic publishing.

Eight different peer review papers that if you can build, if you can do two things, if you can remove these carnivore trees, this taiga forest, that is not the best carbon sink. They're also very dark bark. They almost are like heat lightning rods that permeate, that permeate the heat down into the ground. If you remove those and if you get to the right level of cold tolerant, dense, cold tolerant, dense species, the right level of density, you can actually lower ground temperatures by up to 80 degrees.

Now why not on top of it? Why is that important? Well, there's more carbon and more methane in methane. It's about 30 times worse of the atmosphere.

That's what kind of Venus's apspominately made of. There's more carbon and more methane stored in the permafrost in that tundra area than anywhere else on the planet. It's more than double within release in the atmosphere. So we're truly nutrich times of carbon in methane, which is there.

It's more than the Amazon rainforest. Right. The Amazon and the rainforest have a carbon oxygen cycle that it just repeats not in The Arctic, it frees something. Diesel freezes, dies, freezing just piles up, right.

So there's all this condensed biomass there and you know, if it really, if it releases, it could be pretty bad. I was actually with the Army Corps of Engineers up there outside of Fairbanks in the permafrost research tunnels and it's just, it's absolutely amazing, but also kind of terrifying if it does smell. And so what's interesting is there's been studies shown about how effective elephants are, specifically forest elephants in Africa at doing a couple things. They actually make the ground temperatures cooler because they pack the ground and they let the wind actually come down and hit the ground during the cooler months.

Especially makes the ground cooler. Number one, number two, elephants love knocking down trees. And I know that sounds like, but I thought trees were good. Does Colossal have a war on trees?

We do not have war on trees. We just don't want the non efficient, carnivorous, dark bark trees in the Arctic that aren't helpful. The grasslands, the Arctic grasslands at that time were about two to three times more efficient and what's called the albino effect, light reflection. So anything that wasn't absorbed for those absorbed in those grasses is not only is reflected back to space, up to three times more efficient than trees and as well as about six times more efficient at storing carbon down into our root structures.

And so there's been a lot of really great modeling done that if you could return the Arctic back to a more biodiverse with these like Pleistocene creatures area where you have these natural herding animals during the winter, they'll pack the snow down deeper or pack the snow down so that the winter months can actually like lower the temperatures. And we've seen that work in Siberia already. Mammoths, like elephants, are natural, they love knocking down trees, right? So then you don't have to use tractors and other equipment like they're doing in Siberia to knock down those trees again.

Just building up that biodiversity in that area will lead to a better oxygen nitrogen cycle so that they, you know, with their defecation, more of the grasslands that are more efficient in the summer months. Right? So, so it's really interesting, put all puzzles together. Outside of mammoths, it's about 8 degrees lower, which is pretty important when we're looking at probably surpassing that 1.5 degrees that we talked about in the Paris.

Right. It's pretty important to keep all that tracking and that the model is that mammoth can be the massive accelerant and can push those numbers even higher. Little hairy farmers, big hairy farmers, walking all over the place. So I went to.

Yeah. When I went to Thailand seven years ago, I volunteered at a conservation center that was reclaiming land from monocrop, monoculture stuff. I want to say soybeans maybe do they do kind of the recipe Anyway, somewhere that had been just one thing. And this guy had bought tons and tons of hectares of land, had also bought two elephants.

He'd saved two elephants that had been carrying mother and daughter, they'd been carrying tourists uphills, one of those classic like mystery animal stories and then brought them in. I remember asking at the time, I was like, why you would like is the elephant, is it just for fun or whatever they were? Oh no, the elephants, they keep the trees to a certain level, they help to rotate the crops and the different. To ensure that manure from one side goes to another side and then there's fertilizer and do all this other stuff as well.

And yeah, I realized that elephants are basically nature's farmers in a way. Yeah, you're 100% spot on. And there was a study that came out that we can get just in you if you find it interesting to read it. I think I will.

Where I think that they defined just for elephants in Asia preserve the equivalent of half a trillion dollars of carbon credits. That's amazing. And so people breed more relevant, breed more elephants. Yeah.

And we want to do that right. With this part of our goals. How do you. Have you considered.

I know you haven't got one yet. What is the game plan upon? Right. We can now produce elephants or we can produce mammoths at the pace about one every 22 months.

And then we can like scale it. What do you do? Fly them in. Fly them in on a big level of the C130 plane.

C130? Yeah. No, no. We work closely with the US government.

I don't know if they're going to see 130 transports. So the idea is kind of twofold. One, let me talk about scaling briefly and we'll talk about rewilding. So on the scaling function, you know, to your point, breeding elephants is a long tedious process.

Right. You're not going to make thousands of mammoths the old fashioned way. It's just gonna take a long time. Right.

But fundamentally, so we have a group. And once again, what's so weird about my day to day life today is, is that de extinction no longer seems like science fiction to me because I took closer. Right. It's like I see where I see a lot more than the world sees.

And we Try to talk about everything as much as we can. But I see how close some things are and how far other things are. And so de extinction to me doesn't seem like science fiction anymore. The science fiction part of my job is we have an exterior development artificial womb team that we're really, you know, investing heavily in.

And I do think that there's no major science gates there, it's just engineering challenges, right? You have to know enough about the species, you have to build the right environment, you have to ensure that you have the right placental interface for the placenta. But you can really build out a extra development. That's where you can get scale, right?

And this is before we talk about, about where you put them back. But you know, our long term goal is to be able to produce many, many mammoths in, you know, a facility, right? Like where you're not even using surrogates. And I think that interestingly enough, some of the rig for conservation is a game changer for building.

But then separately, I think this artificial womb, if we are to be successful in it, it will have more impact even than all this other work we're doing on species preservation. Because if you think about it, if you grow, you know, we talk about the northern white rhinos, there's only two blacker functioning, extinct, there's only two females. But if you could grow 100 northern white rhinos, different engineered in genetic diversity and work with three wild teams for the back of the wild, you change conservation forever, right? And so I do think there's some things that we're working on that are more science fiction.

But if we are successful, we'll have kind of the scale functions that you're talking about. But long term is to actually have those breeding centers in the Arctic, in Alaska, in our allied nations, in the Arctic circ and actually, you know, do that work there and then work really well, slap them on the ass and send them out into the world, give them a treat and hope for the best while you don't can mammoths produced by you? Are you just allowed to let them have sex and proliferate and then you get mammoths out the other side or does something weird happen? You do get mammoths out the other side.

There's actually data to suggest that mammoths and Asian elites did integrate, which is interesting separate conversation. So we work very closely with every nation. Every state has slightly different rules. We work very close with the US government, we're working with the Australia Russian government and then working with a couple state governments.

The US government Actually invested one of the cruises in Astro Colossal. And so for us, you know, it's really important to be inclusive. Not when we get mammoths and slap them on the button and hope for the best. It's important to do it now.

Right. So we spend a lot of time with the government, we spend a lot of time with regulatory agencies, we spend a lot of time with indigenous people groups, private landowners. And that's important, right, because it's not just about government regulation and support like the EPA and other. You also have indigenous people groups, you have private landowners.

So we've been, we've taken the stance that the rewilding process is going to be as long as the engineering process. So why don't we start that now? And so just because we don't want approval, we want true collaboration. And it's, that's one thing I think that we've done, done really right.

We have a team that works with these governments and indigenous people groups and public town hall forums to have conversations with the local public, both from education and a feedback perspective. You can actually learn a lot from a critic if you listen. And so I think we've done a good job of taking a wide range of feedback that we've been given. More so on the critical side, less so on the please make a dinosaur side.

Understood. Rolling the clock forward, the next question evidently is what does this mean for humans? Does this mean that we can change our DNA to survive space flight? Can we give us the strength of Neanderthals?

Can we do work with Chris Mason? He had that thought experiment in about if you're able to make humans do photosynthesis and you'd only need three tennis fields worth of skin and you'd be able to survive just on the sun like some crazy butterfly of space. Yeah. Plants are the original solar power.

Yeah, yeah, yeah. So I think so just to be transparent, we are not working in humans, we are working in mammals. I think a lot of the technologies that we're developing web applications to humans, in the case that that occurs, we spin that out as technology. We did that last year with Born Bio, our first AI based computational biology platform.

But I think as we get better at computational biology and as we get better at editing, I think the sky's the limit. Right. And that's why you need to spend a lot of time on the ethics side of it. So.

So, you know, I do believe that from a technology perspective, you know, it's not possible or it's not allowed to do germline editing. So the Editing that we're doing currently with Colossal, you can't do that in humans, so it's not allowed. But I do think that as that changes, I think that'll be a societal change over time with more and more strict policies and not quite strict, but better regulation around gene editing. Because right now it's like, sounds scary, we shouldn't do these limited cases, but it's incredible.

So let me do a real world example today and I'll tell you about tomorrow. So they're not probably screwed up because I'm not a biologist, but they found that like, you know, I don't know what your cholesterol is. Right. But my cholesterol is pretty great.

But part of it is because I actually use a drug that limit that stops and blocks one of the genes in my body called PTS9. And so what's interesting is there's these, these PTS9 inhibitors, PCPS9 inhibitors that, that literally block how your body produces LDL. So some people, genetically, if you're vegan, during thousand miles a day, you'll produce too much ldl, right. It will build up in your system and this lowers it by, you know, 40 to 70%.

It's incredible. And it's not, I've not edited my genome, but I take a drug that blocks that. So what about a world where we can edit out that gene where no one, you know, like, like I believe that diabetes, heart disease right now are 100% trivial. They're true.

I'm just talking about through lifestyle, through medications that exist today. Right. And so from a human perspective, we are, I take a shot twice a month in order to achieve that. Right?

To block that. But fundamentally I do believe that that's something that could be genetic at some point. Right. And so I think in the near term there will be applications of gene editing and gene therapies that cure that.

I think in the long term, I don't think Chris Mason's wrong. I think that we could become more radiation tolerant and with more radiation tolerant that people think about. Oh, that allows us to be a spacefaring species. It also allows less breakdown of our DNA and lets us probably live longer on Earth.

And so, you know, the sun is not always our best friend in that. Right. And so, so I do think that that from, you know, we already know about genes like myostatin. Myostatin.

Have you seen the Belgian blue cows? You know, we can double muscle mass. That's one at one knockout, like I'm saying somebody else. But, but fundamentally, to your point, you Know, I think that, you know, we live in a really interesting time and from an ethical framework perspective and a regulation perspective, I think that we just have to be mindful of ethics regulation.

But I do think from a technology perspective, we are surpassing the rate limits of regulation and ethics in terms of what's possible. More is possible today than we as humans are allowed to do. Yeah. Yeah.

I had a really interesting conversation with Jonathan Anomaly, who is out here in Austin, and he is about to release at some point a company that has been ready for a long time which does embryo selection. It does embryo selection based on risk for all manner of different things. But he can also select for iq and he doesn't select for iq, but it gives you a risk profile. Where does eugenics start and stop?

Right. I asked him this question. I think it's very interesting is what's the difference between embryo selection, which you could do right now, like, you just be like, if you don't have the actual samples, you're like closing your eyes and going IVF number five or whatever, right? Is there a difference, is there a fundamental ethical difference between embryo selection and genetic enhancement?

Is there? And his argument is no. I would argue the answer is no, because people are like, but we can't create like GMOs or genetic miformism or bad. Like we've been creating GMOs with crops for thousands of years.

We've just been doing it very inefficiently. We've been crossbreeding shit and crossing our fingers. Right. And like that.

We've been doing that with dogs. We have dogs that are all different shapes and sizes, that aren't even very. Some of them are genetically exposed to cancer because of the decisions that we made through selective breeding. The selective breeding is a form of genetic engineering.

And so I would argue no, it's really not at its core. And so before, I don't know what exactly his tech is, but another company I'm not affiliated with, but it's called Orchid Health, George also co founded it. And they actually, you know, in when couples have a baby, they'll get a genetic testing to see if they're compatible. Some people do some tests, you know, for down syndrome in womb, right.

Sometimes people don't like that people do it. And then what's interesting though now to your idea point, is once you have those embryos to your point, you can crush your negligurize and pick one. But what's really interesting is now they're doing a risk score where they're saying, this, you know, this may be like the absolute best looking gene or best looking embryo, but you know, we do full genome sequencing on it. Now we can tell you that, you know, this has a predisposition to late stage Alzheimer's.

Right. So even though everything else about is healthy, do you want to insert that one or do you want to take the gamble that. And we're going to. I mean this ultimately is the most interesting part of what I learned from Jonathan, which is at the moment what we do is we roll the dice, right?

We roll the dice with whichever is the fastest sperm, whichever is the egg that was timed at the right time of the month or whatever, whatever the right particular month that is rolling. And it seems like there are a number of defense mechanisms. I learned that around about 50% of all fertilized eggs are cast out of a woman's body without her realizing within the first four. But it's just, you don't even miss anything at all.

And there is, you know, you can imagine why that would be adaptive, that there's something that's not gone quite right here. Perhaps it's an early warning system that just ejects this particular egg. Is that a miscarriage if you weren't aware of it, kind of. And so they.

So I don't know if this stats right, but I believe this is in the ballpark. I think George May told me this. But natural birth is about an 8% success rate, which is kind of crazy because there's so many of these early stage ejections that you don't know about. And so it's really interesting, you know, because like even IVF only shifts 50, 50.

Right. And so like it's crazy to me. And part of the reason why I think some of those only 50, 50 is because they're not doing full genome sequencing embryos. So you can have a developing embryo that, that, that looks great in microscope, but it has a genetic defect that at a certain point will not work.

Oh, you just say nope. Yeah. So you're starting to your point. It takes like this is gonna be embryos.

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This episode was published on September 16, 2023.

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Ben Lamm is an entrepreneur, CEO of Colossal and a founder. What if Jurassic Park's dream of bringing extinct creatures back to life was possible? Well it kind of is. And Ben's company is forging ahead in the new frontier of de-extinction, starting...

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