The Saad Truth with Dr. Saad - De-Extinction of the Dire Wolf! Modern Day Jurassic Park？ (The Saad Truth with Dr. Saad_832)

00:00:00.900 Hi, everybody. Today, I've got two, I seldom have two guests in one shot. I've got Dr.

00:00:06.620 Beth Shapiro, and I'll introduce her in a second, and Matt James. First, welcome. How

00:00:10.800 are you guys doing?

00:00:12.620 Great. Thanks for having us.

00:00:15.060 I wanted to introduce you. First of all, Beth, if I may address you guys by your first

00:00:20.240 names, congratulations on a big award that you just received. I read it. Member of the

00:00:26.740 National Academy of Sciences, so congratulations for that.

00:00:31.060 Thank you. Thank you.

00:00:32.760 I'm sure I must have some other guests because I've had a lot of incredible, illustrious guests,

00:00:38.580 but I'm sure you're among a very few people on my show who hold that title. So you are

00:00:44.160 traditionally a professor at UC Santa Cruz. You've taken a leave to work at Colossal Biosciences,

00:00:52.440 which that's what we're going to talk about today. Matt James, you are the Chief Animal

00:00:56.040 Officer at Colossal. So maybe we'll, did I miss anything in terms of an intro that you

00:01:03.560 guys would like to add?

00:01:06.160 No, it's perfect.

00:01:07.540 All right, let's do it. Okay, so I mean, I first heard of you guys, I don't know if it,

00:01:13.380 I mean, I don't know if you guys know, but Joe Rogan and I are, you know, pretty, pretty

00:01:17.640 tight guys. And I saw Ben Lamb on, and I said, what the hell is this? And that's how I kind

00:01:26.200 of got into it. So tell us what the company is about. Tell us what you're doing so much,

00:01:31.020 so many exciting things to talk about. Take it away.

00:01:34.540 Matt, why don't you do that? You can do the overview.

00:01:37.160 Sure. So I mean, Colossal Biosciences is a biotechnology company that launched, you know,

00:01:43.000 in 2021 with the, originally with this goal of restoring the woolly mammoth from extinction.

00:01:48.800 But what Colossal has really become is this de-extinction and species preservation company

00:01:53.880 that is building technologies today, whether that's from the genetic engineering and cell

00:01:59.100 engineering, genome sequencing side, or reproductive sciences and, and assisted reproduction in order

00:02:05.620 to bring species back from extinction and prevent future extinctions. So we're working on everything

00:02:11.900 from woolly mammoths, thylacins and dodos. And most recently, you know, in the news, the dire wolf

00:02:17.320 to how can we apply our technologies in meaningful ways to prevent the extinction of American red wolf

00:02:23.600 of the Northern white rhino, the Mauritian pink pigeon and tons of others. So it's been an amazing

00:02:29.540 sort of three and a half, four year journey. And now, you know, we've sort of made the big splash

00:02:34.180 recently with the dire wolf news that shows that the de-extinction pipeline is a full technology

00:02:39.140 set that works today.

00:02:40.900 How much of the de-extinction, you know, project involved new technology that just came about

00:02:49.140 since the founding of Colossal versus it existed, but it just needed somebody to ignite the process.

00:02:55.600 Walk us through that.

00:02:56.740 It's a good question. You know, we're obviously standing on the shoulders of lots of work that's been done

00:03:04.200 in lots of different fields simultaneously. We're reaching from ancient DNA extraction and analysis,

00:03:10.240 computational biology, evolutionary biology inference, gene editing technology, all the way through,

00:03:16.540 you know, our assisted reproductive technologies and animal husbandry approaches. This is a pretty wide

00:03:22.800 ranging. There are a couple of things that we used for the dire wolf project that were developed that

00:03:27.660 were ours. The one that's gotten the most attention is this idea that we can clone cells that can be

00:03:33.600 isolated directly from a simple blood draw. And we used that approach to clone the wolves that we,

00:03:39.660 that we, you know, cloned in this process. And this is really cool. It's a, it's a cell type. People have

00:03:45.600 taken blood draws before and attempted to, to use cloning this process that most famously brought us

00:03:51.120 dolly the sheep with those different cell types, but they haven't used the cell type that we isolated

00:03:55.940 the endothelial progenitor cells. These are cells that will eventually become the lining of the blood

00:04:01.320 vessels and things like that. Um, we hypothesize that the reason that they are so robust is that

00:04:07.860 they aren't as far down the pathway to, we call terminal differentiation, the, where a cell gets to,

00:04:14.920 where it only has the instructions to be whatever type of cell it ends up being. Cause there are

00:04:19.100 different genes that are on or off or turned up or turned down if you're a skin cell or a liver cell

00:04:23.920 or a heart cell. So they all have specific instructions about how to be that type of cell.

00:04:28.340 The cells that we're cloning from don't really have all of those instructions yet. And so they're

00:04:33.240 further back toward the type of cell that we want to start with. If we're going to clone something,

00:04:38.100 a type of cell that can become every type of cell that makes up an organism's body. And we found that

00:04:44.020 these cells are not only really good for cloning, but they're also great for just growing up in

00:04:49.660 culture, which is really useful for conservation. So we can grow up these huge, happy, healthy

00:04:55.460 plates of cells that we can then store and bank that we can go back to later and turn them back

00:05:01.900 on, bring them back to life, if you will, by thawing them in a, in a careful way. And then they can

00:05:06.500 divide and differentiate and be used for cloning 40 years from now, which would be really great for

00:05:11.800 conservation. So, well, this, this is not quite what you're talking about, but I'm a huge Belgian

00:05:17.760 shepherd guy way before it was cool to talk about the Belgian Malinois. This has been something that

00:05:24.720 I've had my whole life. And when our first Belgian, we've had two, I always say that our children have

00:05:31.420 grown up with these two majestic, I mean, literally they look like wolves, maybe even more vicious if

00:05:37.940 you, if you mess with our family, but in any case, when our first one passed away, I was so heartbroken

00:05:43.900 that before he had passed away, we had extracted some, you know, sperm from him and which is still

00:05:49.940 stored somewhere with the hope that eventually he'll be, you know, brought back to earth, so to speak,

00:05:55.940 not quite in the way you guys are doing it. Where do you get the, the DNA or any material that you're

00:06:02.020 using for these projects? Are they historically, if you, I know you probably don't like Jurassic Park

00:06:08.600 analogy, but. Love it. Oh yeah. Run with Jurassic Park. Go for it. Okay, good. You know, it's the,

00:06:15.840 you know, the mosquito that's stuck in the amber that you, you pull out. Maybe that's probably not

00:06:21.000 how you're getting it. Is there a particular source where all the stuff you're hoping to get for all of

00:06:27.280 these different, the extinction projects? The ancient, I come from the field of ancient DNA.

00:06:33.320 I've been working in that field for a really long time. This is the idea that we can pick up a sample

00:06:37.280 from somewhere in the world, from an animal that used to be alive, and we can extract DNA. So we take

00:06:43.140 a bit of that bone powder or hair, and we chemically dissolve all the stuff and release the DNA. And then

00:06:49.680 we can use that DNA in a standard DNA sequencing. I say standard, it's a little bit different because

00:06:55.480 the fragments that we can recover are really short and have damaged bits to them. But we understand

00:07:01.420 how DNA decays over time. And so we can use computational approaches to piece those short

00:07:06.400 fragments together to reconstruct the whole genomes. We can get DNA from skin, from teeth, from hair,

00:07:12.760 from muscle tissue. We know that DNA survives longer when the bone or whatever material it is,

00:07:19.580 is preserved in a cold place. So most of the work that's been done to date in the field of ancient DNA

00:07:24.760 focuses on animals that lived in the Arctic. But we can also get high quality DNA from places that

00:07:30.280 are consistently cool and dark. UV radiation will damage DNA. That's why we put on sunblock when we

00:07:35.960 go outside. Freezing and thawing damages DNA because the water molecules expand and physically break the

00:07:41.440 DNA. And then probably the thing that damages DNA the most is just microbial action. Bungus and bacteria

00:07:49.180 chewing up the DNA to turn it into the next generation of organisms, right?

00:07:53.700 How do you do that?

00:07:54.700 Oh, sorry, go ahead. Go ahead.

00:07:55.900 No, go ahead. What's the question?

00:07:57.280 I was going to say, so, you know, in forensic science, in criminology at least, when you enter

00:08:04.360 someone's DNA into the database, if that person is not already in the database for another crime that

00:08:11.180 they've committed, I know their DNA profile, but I don't know who they are. So now you can see where I

00:08:16.520 might be going with your question. If you pick up some ancient DNA that is ostensibly of some species,

00:08:23.280 how can you know out of all the species that have become extinct that that DNA morsel stems from

00:08:31.020 species XYZ?

00:08:33.520 That's a really good question. Part of it comes from extracting DNA from bones that we have identified.

00:08:40.180 So I know that that's a mammoth bone and the DNA that DNA that I get out of it creates an organism

00:08:46.200 that if you compare it to all of the sequences of animals that are alive today is near elephants.

00:08:52.620 And we know that that's a mammoth bone. So now I have a template for what I can say is mammoth like

00:08:57.660 DNA. So when I get tiny little fragments of bone that I don't know what it is, or we can even extract

00:09:03.100 DNA directly from sediments. You can go and take a plug, like a long core and suck out a bit of dirt

00:09:08.680 and extract DNA and find all of the plants and animals that were alive in that spot at that time.

00:09:14.280 Ice to do that with, right?

00:09:15.800 Yeah, you could do it and dirt as well, just sediments. So we, I have colleagues who work in

00:09:20.080 the Arctic who will just take plugs out of a, out of a wall and we can radiocarbon date bits of plants

00:09:25.440 so we know how old it is and then extract DNA and amplify, we call them barcode regions. So parts of the

00:09:31.520 genome where everybody's different than each other. All of the different species out there

00:09:36.000 are different from each other, but in a way that we already know what it is. So we can say, oh,

00:09:40.000 that's a mammoth and that's a bison and that's a horse. And then we can get some idea of the

00:09:45.260 relative abundance of these different animals in that landscape and also what that community looked

00:09:49.680 like. It's actually really cool. I was involved in a project a while ago where we went to St. Paul

00:09:54.480 Island in the Bering Sea, which is the second last place mammoths ever lived. Mammoths survived on

00:10:00.800 Rangel Island off the northeastern coast of Siberia until just about 3,000 years ago. So there were

00:10:06.480 people building pyramids at the same time as there were mammoths in the Arctic. But they also lasted

00:10:12.760 until about 5,000, 6,000 years ago on St. Paul Island, which is in the Bering Sea. St. Paul was

00:10:19.500 connected to Alaska. And then at the end of the ice age, as the sea level rose, it got disconnected and

00:10:24.300 a population of mammoths got trapped there. And we wanted to know when they went extinct and why they

00:10:29.260 went extinct. But we didn't have that many bones. So we went to the only source of fresh water on

00:10:34.060 the island, which is a volcanic caldera that is filled with water where the people who live there

00:10:39.200 now go swimming during the summer. And we went out during the winter when it was frozen over the top

00:10:43.420 and shoved a long metal core into the bottom of that freshwater lake and then sucked out all of the

00:10:49.480 dirt. And then because the oldest stuff is at the bottom and the youngest stuff is at the top,

00:10:53.740 we could get an age profile of how old stuff was. And we could extract DNA from all of it and see

00:10:59.360 what happened. Did the plant community change? Did something else change that might have made

00:11:04.580 mammoths go extinct? We knew it wasn't people because people weren't present on St. Paul Island

00:11:09.740 at the time. We actually found that what happened was probably there was a massive drought. And the water

00:11:16.560 of that lake became really salty and had different types of organisms that could only live in salty

00:11:23.260 water because the seawater will have introgressed. And that was the only source of fresh water on the

00:11:27.480 island. And they probably just ran out of stuff to drink. And that's why mammoths died 5,600 years

00:11:32.900 ago on St. Paul Island. But we learned that just by looking at DNA preserved in sediment, which is

00:11:38.340 pretty fascinating.

00:11:39.820 Amazing. I mean, if there are young people watching today's show, if this doesn't excite

00:11:46.900 you about science, I don't know what would, right? How do you decide the order? So right now you've

00:11:53.300 only de-extinctified, or I'm probably using the wrong verb, one species, the dire wolf. Then you

00:12:00.580 mentioned the dodo bird, maybe others. As someone who my doctoral dissertation was actually in psychology

00:12:06.360 of decision making. So I'm interested in all things related to how do people make decisions. So what is the

00:12:12.540 decision making process out of all possible species that you could de-extinctify? How do you choose which

00:12:20.780 ones to go first, second, fourth one?

00:12:23.480 You know what's so funny? I'm going to answer the question. But first, I have to just acknowledge, I have

00:12:27.520 always said that I really hate the word de-extinction, because I cannot figure out how to conjugate it, which is the

00:12:34.020 problem that you're having right now. I don't want to say you de-extincted, it just sounds terrible, but

00:12:40.280 is de-extinctified any better? I don't know, maybe not, whatever. I think, you know, the decision-making

00:12:48.260 process about picking the original ones is really about, well, there's a bunch of different things.

00:12:54.540 I mean, as you point out, there's going to be some social idea here. What do you want? People want

00:12:58.300 dinosaurs. As soon as they figure out we can't have dinosaurs, because no dinosaur DNA survives,

00:13:02.960 the next thing people think about is mammoths. That's why my first book was called How to Clone

00:13:07.260 a Mammoth. If I'd written a book about how to clone the Christmas Island kangaroo rat, nobody

00:13:12.100 would have cared, right? So it's partly that. And then there's my side and Matt's side. So

00:13:18.980 from my side, the challenges are, can we actually get DNA from this animal, right? Is there sufficient

00:13:27.660 information preserved that we could understand what it is about the DNA code that makes that animal

00:13:32.800 different from whatever animal we're using as the surrogate species, right? So, and then can we

00:13:38.180 learn what those differences actually are and choose edits that we can make in a way that we know are

00:13:43.640 going to be safe in a genetic background of a different species? Because we know we can't make 0.98

00:13:48.000 all of the changes that were there. So how can we, is there a scientifically rigorous, ethical,

00:13:53.780 careful path that we can choose to make the decisions about what we're going to do? And then the other

00:13:58.400 technologies, we've launched Dodo, but right now there isn't really a mechanism to transfer edited

00:14:07.180 DNA sequences between generations of birds, because you can't clone birds using the process

00:14:13.060 that brought us Dolly the sheep. So there are teams internationally that have been working on

00:14:16.700 different approaches and our team is also working on a different approach to do this, but that's a

00:14:21.220 blocking aspect of that de-extinction project that's on our end. And then I'll pass it over to Matt,

00:14:26.860 but there's lots of problems after we have cells as well. So I mean, the reproductive science plays a

00:14:33.140 huge role in this, right? You know, to best point, you can edit cell lines all the way to a point where

00:14:37.720 suddenly you need to create an embryo, which is sort of our challenge on the avian side. But with every

00:14:42.900 mammal species we work with, we also have a unique set of challenges, whether that's elephant anatomy

00:14:48.480 required for mammoth restoration is really difficult. And their reproductive physiology is still quite a

00:14:53.960 mystery to us to resource availability. How many oocytes or eggs can you get for this cloning

00:15:00.100 process, which is still not a very efficient process. So it takes a number of eggs to create

00:15:07.140 a single embryo. So those are, those are a lot of the challenges that we face along the way. And then

00:15:11.920 the question is, if you bring it back, how do you take care of it? Can it, can it be gestated within a

00:15:18.480 living animal today? Or do we need to create a synthetic solution for gestation, like an artificial

00:15:23.000 womb? And if once it's born, how do you take care of it? And where does it go in the wild? And most

00:15:28.160 importantly, is the why? Why are we bringing it back? What purpose does it serve to science, conservation,

00:15:34.280 to humanity? And so those are some of the discussions we have. So as you might imagine,

00:15:38.580 you put 20 people around a table, and we'll have 20 different opinions on what should be first and why it

00:15:43.100 should be first. Do you take a vote? Is it a majority vote? Is it a democracy? Is there an

00:15:48.840 autocratic dear leader? How, how do you navigate through the 20 choices? I would say we live

00:15:54.300 somewhere between an autocracy and a meritocracy in our decision making here, right? Yeah, I think

00:15:59.440 Ben and Beth have a significant amount of sway, I get to have a significant amount of sway in terms of

00:16:06.060 how I think it could be a conservation impact. And so that's what, that's sort of how we focus. But

00:16:11.280 then there's also, all of that is sort of interwoven with this, with this level of opportunity. What is

00:16:18.300 the opportunity to get to that DNA to, to use this animal in a meaningful way? And, and then that's

00:16:23.820 sort of how the cream rises to the top. And, and sort of what happened to us with dire wolf, it was when

00:16:29.220 we launched, we were a mammoth based company, right? We were only focused on that. And then we suddenly

00:16:33.960 spread to several species. And then dire wolf became the obvious choice to be the first to roll out

00:16:39.140 publicly. I think there are several reasons for that. I mean, the, the, the, it was an obvious

00:16:43.680 choice because we have a gray wolf and we can leverage so much scientific information about gray

00:16:48.320 wolves to make this easier, but also, and what we, I mean, we should highlight is that for each of

00:16:52.620 these species, we have community partners who are willing to be involved as stakeholders who

00:16:57.900 ultimately steward these species, right? So we have to have people on the field, on the ground,

00:17:02.740 and it was actually interacting with community partners, with our indigenous conservation board,

00:17:07.780 where the idea of the gray, gray of the dire wolf was first, first floated. But the science then,

00:17:13.960 you know, the idea that we know so much about gray wolves, that we can make these decisions in a way

00:17:17.980 that we know is going to be safe. We have protocols for making sure that the surrogacy can take place

00:17:22.320 in, in domestic dogs, and they're all going to be safe and healthy. You know, this is all a very,

00:17:27.020 if we're going to have this as a technology, that's expanding beyond this, that we can really use for,

00:17:32.420 as a new tool for conservation to stop species from becoming extinct,

00:17:35.980 we have to be able to evaluate how we've done. We have to know if there are any unintended

00:17:41.660 consequences to the animals. We have to be able to learn how they're interacting with the habitats.

00:17:45.660 And there's a very small list of species where we have enough information that we can use as a

00:17:50.500 control to really understand what we've done. And dire wolf, gray wolf is a fantastic species pair

00:17:55.500 to get this, I think, foundational data that we need moving forward.

00:17:59.800 Okay, a couple of questions. One, I know that some people, when, you know, the beautiful images of the dire

00:18:05.000 wolves running around were released, but that's not really true. They're not really dire wolves.

00:18:09.060 So let me ask you this. So when we had the, I think they call them spider goats, where they breed

00:18:16.980 goats to be able to produce spider silk, right? So you're doing this synthetic kind of solution.

00:18:24.340 I mean, without confusing all of our lay listeners, is this what's happening in that, you know, the dominant

00:18:33.380 expressive, you know, phenotype looks like a dire wolf for whatever, you know, black magic you've done 0.84

00:18:41.020 in the background. But the reality is, it's not indistinguishable from the dire wolf that would

00:18:47.460 have existed X years ago, or is it indistinguishable?

00:18:51.920 I think, I think it probably is distinguishable. We focused on specific phenotypes, right? And we

00:18:57.540 have, we're doing functional de-extinction, right? We're bringing back animals that we think we can

00:19:02.300 slot into a landscape, and they're going to perform some of the ecological roles that those animals

00:19:07.600 once played. It's impossible to make all of the changes right now. Maybe it's never, maybe it's, I mean,

00:19:12.760 probably in the future, we'll be able to synthesize whole genomes, we'll be able to bring something

00:19:16.360 back that is identical to the animals that were there. But given existing technologies, we have

00:19:21.180 to work within these constraints, and we still want to be able to generate these animals that can fill

00:19:25.680 these ecological niches. And that's what it means to do functional de-extinction. Taxonomically, whether

00:19:31.760 it's assigned a taxonomic name that's the same as something else, that's for systematists to argue

00:19:36.400 about, and they can. And the spider goats, which are a regular goat, but have some DNA that allows them

00:19:42.140 to create the protein to make the spider silk. They have DNA that comes from a different part of the

00:19:47.000 evolutionary tree, and systematists will also fight about how you should actually name them.

00:19:51.660 That's not important to us. I mean, it's important when you have a conversation. The conversation that

00:19:56.920 we're having is about whether these animals can fill the niche of a direwolf, and if they can,

00:20:01.720 then we should call them direwolves.

00:20:02.960 That's very interesting. Actually, I'm looking right now here at a book that I bought about two months

00:20:07.880 ago, The Man Who Organized Nature. It's about the original taxonomist, the Swedish, Linus.

00:20:15.280 Linus, is that how you pronounce it?

00:20:16.600 Linus, yes.

00:20:17.840 Linus, thank you. So I haven't read it yet. One of the big stresses in my life is that I've got a

00:20:22.720 gigantic personal library, and every time that I walk into my study and think about all the books that

00:20:28.100 I've yet to read, am I running out of time in terms of my lifespan? God willing, I've got many

00:20:33.160 more years to read the entire library. All right, here's a bit of a technical question. I hope you

00:20:38.820 like it. So I'm an evolutionary behavioral scientist, which basically means I apply principles

00:20:43.940 from evolutionary biology and evolutionary psychology to study human behavior in general,

00:20:49.360 consumer and economic behavior in particular. So one of the things that I learned early in my

00:20:54.980 training with evolutionary psychology is the mismatch hypothesis, right? Which, are you

00:21:01.260 familiar with this? Even though you're an evolutionary paleobiologist, you may not know the term. No,

00:21:06.700 that doesn't ring a bell?

00:21:07.980 No.

00:21:08.420 So the mismatch hypothesis was originally proposed by people in evolutionary medicine, whereby they

00:21:14.720 argued that many of the diseases that we currently suffer from, actually, I think the top eight or

00:21:20.360 nine are due to a mismatch between the ancestral environment where we would have had some adaptations

00:21:29.120 that would have been beneficial then, but in the current environment, they become maladaptive. So for

00:21:34.900 example, our preference for fatty foods and to gorge on fatty foods would make perfect evolutionary

00:21:40.580 sense in an environment of caloric scarcity and caloric uncertainty. It doesn't make as much

00:21:45.680 evolutionary sense when I can just go down to the local fast food place and gorge and then I'll get

00:21:51.500 colon cancer and diabetes and heart disease and so on and so forth and high blood pressure. So there's

00:21:57.480 this mismatch that causes many of the ailments that we face today. Can we apply that principle

00:22:04.580 to some of the de-extinction programs that you're doing, whereby whether it be the dire wolf or any other

00:22:11.580 species that you bring back, it occupied an evolutionary niche where it made sense for it to be there,

00:22:19.760 it's mismatched with today, here ensued the disasters.

00:22:25.860 It's an interesting question. When I think about this, it's similar to an argument that I make about

00:22:31.720 why we need genetic engineering technologies for biodiversity conservation, because I like to point

00:22:38.080 out that habitats around the world are changing faster than evolution can keep up, which places

00:22:43.800 these animals in a situation where they are mismatched with their current environment. And if

00:22:48.580 we can find solutions to that in different parts of the evolutionary tree, if we can make animals that

00:22:54.720 are better able to resist, plants, animals that are better able to resist drought, or that can capture

00:22:58.880 carbon at a different rate, or that have genetic resistance to diseases that have been introduced to

00:23:04.500 their habitats. The black-footed ferret project is a really great example of that, where plague has

00:23:10.320 been introduced into their habitat. They didn't evolve with plague, so they are susceptible to it.

00:23:14.880 But their evolutionary cousins, the domestic ferret, did evolve with plague. They are not susceptible to it.

00:23:21.060 So if we can take that genetic resistance to plague from the domestic ferret and give it, using gene

00:23:27.360 engineering, to the black-footed ferret, we've created a better match to that habitat for those animals

00:23:32.800 using these tools. So it's really interesting to think about it that way. As far as mismatch to the current

00:23:38.820 environments, one of the reasons that we argue that we probably shouldn't just take wholesale ancient

00:23:45.300 genomes and stick them into an animal today is exactly because of this mismatch with pathogens. If we have a

00:23:51.860 habitat that is, not that we have any intention to release dire wolves into the wild, where they will

00:23:58.520 interact with gray wolves. We don't intend to do that. But let's say we did. And then we had dire wolves

00:24:03.860 that were more dire wolfy because they had all of the extinct dire wolf DNA. They would not have that

00:24:09.880 evolved susceptibility to whatever diseases are circulating in that gray wolf population, and they

00:24:13.900 would be immediately unfit in that environment of today. So by focusing just on traits that we feel

00:24:19.980 do have the capacity to augment ecosystems by restoring missing links between species and focusing just on

00:24:27.780 those and doing functional de-extinction, we're hoping to avoid this while using these tools to

00:24:33.980 help stabilize these ecosystems and restore missing functionality to make those ecosystems more

00:24:39.300 resilient.

00:24:40.960 Wow, incredible. This next question is more to Matt, but of course you can weigh in also, Beth.

00:24:45.540 So let me start with a personal story. Back in 2006, I had been invited to the University of New Mexico.

00:24:52.740 They had, I think a lot of the guys have retired since, they had a great evolutionary behavioral

00:24:58.140 sciences group, some anthropologists, some psychologists, some economists. And when I was

00:25:03.940 going there to give a talk on my first book that was about to come out, now close to Albuquerque,

00:25:10.200 where the University of Mexico is, there was a wolf sanctuary. I think it's actually called the

00:25:14.860 wolf sanctuary, if I'm not mistaken. And I had started communicating with them because it had always

00:25:19.540 been a dream of mine to actually maybe interact with wolves. And once they trusted me and saw that

00:25:24.980 I was kind of a reasonably cool guy, they actually allowed me first to enter an enclave with some

00:25:30.520 puppy wolves. And then later I asked them, I had the temerity of asking them, there was a male or female

00:25:36.660 who have since passed away, but you could still go on their website and see them, Raven and Cheyenne.

00:25:41.720 They were full adult wolves. I said, do you think I can go in there? And they said, are you sure you

00:25:49.520 can handle it? Now, I come from a Belgian shepherd's background. And so maybe I had the chutzpah to think

00:25:54.800 that it wouldn't be too scary. I actually went in there. And then I even convinced my wife to go in

00:26:00.260 there. We have photos of it. It was one of the most mystical experiences I've ever had. They actually

00:26:05.380 started howling right in front of me. So my next question, maybe more to Matt than to you, Beth,

00:26:12.920 am I going to be allowed to interact and play with the doctor?

00:26:18.340 I think, yeah, I think we can figure out an arrangement. Obviously we're not playing and

00:26:23.880 interacting with them. We get close. We do at times need to share space with them. They're in a very

00:26:29.500 large preserve. So they're used to their very small subset of caretakers being around them.

00:26:35.460 If somebody they'd never seen would show up, it's most likely that they would hightail it to the other

00:26:40.880 end of the habitat. And eventually they would habituate and come back.

00:26:45.540 But right now there is a, I don't want to say domesticated, but there is a bond that is developed

00:26:52.580 between a few keepers and existing dire wolves. Okay. They've been habituated with a, with a small

00:26:59.300 team of caretakers that help manage them every day, help check on their health, feed them. So

00:27:04.120 there's an association with food comfort reward for them to be around people. And that's really

00:27:09.560 important in the way that we manage animals under human care, because we need these animals to

00:27:13.460 participate in their healthcare, right? Just like you and I go to the doctor, they need to go see the

00:27:17.460 doctor on occasion so that, and the least stressful way to do that is to have a certain level of

00:27:22.460 habituation to a small group of people that they can, that they trust. And they'll allow us to do,

00:27:27.180 you know, very basic observations, exams, if there's something more intervention,

00:27:32.380 you know, more significant intervention needed, then that requires anesthesia. But, you know,

00:27:37.160 right now, you know, I unfortunately think if you walked in today, their first instinct would be

00:27:41.120 to run to the other side of the habitat. Well, that's already better than them eating.

00:27:44.840 Well, now they're only seven months old today. So if we waited until they were two years old and

00:27:51.060 these males that had the full time to mature, and they had a territory, and they had the testosterone

00:27:55.040 needed to be old wolves, they'd most likely come up and mark and make a very clear,

00:28:03.640 they clearly communicate that this is my territory, and you shouldn't be here.

00:28:08.380 As you were, as I'm hearing you speak, I've been, I was thinking about possible projects that

00:28:14.880 one can do at research projects, behaviorally speaking, I'm a behavioral scientist. So for

00:28:20.840 example, you probably have seen the studies with wolves, where when you compare, you know, the

00:28:26.920 pointing paradigm, so, so you basically just point to where the food could be. Dogs pass that test very

00:28:36.180 easily, because they have sort of co-evolved to take cues from their human partners, whereas

00:28:42.260 wolves do very, very poorly on the pointing task. I mean, for reasons that we can surmise.

00:28:49.220 So I'm wondering, have you guys thought, maybe it's too early in the process, but have you thought

00:28:53.520 eventually of conducting, you know, ethological, zoological, behavioral studies with some of these

00:29:00.600 de-extinctified animals that you're bringing back to life? Yeah, absolutely. I think there's a long

00:29:07.800 list of questions that we have that people in our network have, and it ranges from everything from

00:29:13.940 what are the genetic, epigenetic effects of cloning and gene editing, and, you know, epigenetic

00:29:19.380 aging, to what are the behavioral impacts? What are the, you know, what are some of the social

00:29:24.580 ecology questions we could answer? So the short answer is yes, we have, and we're very focused on

00:29:31.260 things that impact health directly today, but we want to begin to expand that as we're sort of getting

00:29:35.980 our legs under us here. Wow. So this is a question for Beth. So you're, you're, you're, much of your

00:29:41.720 career, most of your career has been in academia. Now you've taken a sabbatical, you've gone to

00:29:46.540 industry. We often hear, and certainly I've said so, that in academia, regrettably, oftentimes

00:29:54.000 universities is where innovation goes to die, because you have to spend 74,000 years going through all

00:30:01.220 of the hoops. For me to run the most innocuous study ever, I have to go through six months of

00:30:05.840 institutional review boards and blah, blah, blah. So it is, has that been true as you've segued from

00:30:12.720 academia to your current position where things move much more quickly because you don't have the same

00:30:18.720 sort of bureaucratic oversight over you? You know, it's, we still have bureaucratic oversight. You know, we do not

00:30:26.480 get to operate in a regulatory vacuum. We still have external IACUCs and review boards and every

00:30:32.100 experiment that we do has to be approved by somebody outside. And then everything that we do is

00:30:36.460 regulated within the existing regulatory frameworks of the country in which we're operating. So, you know,

00:30:41.600 we have oversight by the FDA and the USDA for the animal facilities. And, and it's, people imagine,

00:30:47.440 I think some of the fears that we've been is like, oh my goodness, like in Jurassic Park, they just got to do

00:30:51.340 whatever the hell they wanted with these things, which is just, it's just not true. And it's good that it's not

00:30:55.960 true, right? I mean, we want things to be correct and safe and, and to operate within this framework

00:31:01.320 and the framework exists for that purpose. So we're not, we're not pushing against it or we're not,

00:31:06.560 we're not outside of the regulatory framework in a way that would make our lives completely easy,

00:31:11.580 but I also am a little bit relieved by that. You know, my scientific reputation is staked on that

00:31:17.240 we're doing this in a transparent way that is accurate, correct within these regulatory frameworks.

00:31:21.840 That said, I do not have to go to faculty meeting, which is great.

00:31:28.380 And that certainly takes,

00:31:30.420 I was going to say, I don't think you have to worry about your scientific

00:31:33.160 reputation having been just inducted into the

00:31:37.480 National Academy of Sciences. I think you can move past that concern.

00:31:42.060 Where are you guys located? Or at least more importantly, where are the dire wolves

00:31:45.920 located? Is it, are you guys? So, so our company is based out of Dallas, Texas. The wolves are in a

00:31:52.260 secret location. That's really, we're only keeping it under a veil of secrecy, mostly for the protection

00:31:57.040 and the safety of those wolves and the people that care for them. Because, you know, even, you know,

00:32:01.460 funny story, even when we announced the woolly mouse a month prior to the dire wolf announcement,

00:32:06.540 we had people coming to the front door of this office building right here saying, I want to see

00:32:10.220 the woolly mice. I want to see the woolly, and you go, this is not how this works. This is not a zoo.

00:32:14.820 This is not exhibition. This is a professional working environment.

00:32:18.940 So, you know, we were, we're very sensitive about their, their location and their safety.

00:32:24.660 Gotcha. I wanted to read for you. This is, I think the tagline of your company,

00:32:28.740 the science of genetics, the business of discovery. The reason why I, it kind of caught my attention

00:32:34.000 because I operate in my academic career at, at that exact intersection and that I apply

00:32:39.960 evolutionary psychology while housed in the business school, right? So I'm trying to,

00:32:47.020 for much of my career, I've, I've, I've been a professor now for 31 years to Darwinize the

00:32:51.960 business school. The idea being that you can't study entrepreneurship or personnel psychology

00:32:57.000 or organizational behavior or consumer behavior somehow completely detached from the fact that

00:33:03.000 all of these human agents are, are shaped by an evolutionary set of mechanisms. But yet most of

00:33:10.460 my social science colleagues think it is the most heretical thing to ever state that, you know,

00:33:15.920 biology and evolutionary biology apply to every species on earth, except one called Homo sapiens.

00:33:24.660 Maybe I'll start by asking this to Beth. Then Matt, of course, you can also weigh in. Are you familiar

00:33:31.060 with this incredible obstacle to try to get scientists to accept that evolutionary principles

00:33:38.040 also apply to the species called Homo sapiens? Yes. In fact, I, in my most recent book, which is

00:33:45.260 called Life As We Made It, I talk a bit about this and how I say humans are, are, are a new type of

00:33:50.540 evolutionary force. We're shaping absolutely everything around us and the decisions that we

00:33:54.760 make shape everything around us. And I think a lot of the ethical slash moral questions that people

00:33:59.840 ask us about the work that we're doing, um, try to put humans outside of what we're doing. And, and I,

00:34:05.860 it's a, it's fun to talk about, right? But if you stand back and think about it, it's also a little

00:34:11.780 bit frustrating. Like this idea of how it's too scary to try to do this, you know, we can't do this.

00:34:16.300 What is it? It's our, it's not our role to bring species back to life or to help species adapt to

00:34:21.220 the changing climates. Well, why not? Why isn't it our role? I mean, we, we, we evolved to have this

00:34:26.180 big brain and the ability to make decisions and to recognize that we might want to stop doing such

00:34:31.000 damage in the rest of the world. We developed, we evolved enough to be able to develop the

00:34:35.200 technologies to do this. And we should apply that to being able to make a difference. Standing back and

00:34:40.340 doing nothing is also a decision. It also has consequences, right? And so we should think about these

00:34:45.960 things rather than just wring our hands about how scared we are.

00:34:49.300 Yeah. I was going to say, I always find it interesting when people have this, the question

00:34:54.920 around, are you playing God? Because I think there is a real selective focus there is that they are

00:35:02.280 selecting to focus on this action and ignore the 99% of other actions in which we assert our humanity

00:35:09.840 on nature every single day. But they go, well, this is the one I have questions on. Well, you know,

00:35:14.540 you, you went to go visit your family and vacation on a jet plane that consumed dino juices to get you

00:35:21.480 there, right? Like there was a lot of activity in there that impacted nature. And you never thought

00:35:25.880 about that as a decision, but that too is a, is a decision every day.

00:35:29.800 In terms of interdisciplinarity. So one of the other things that has defined my career,

00:35:35.320 some might say it was detrimental for my career. I would argue opposite, you know, in academia,

00:35:40.200 you're supposed to be a hyper specialist, right? A stay in your lane guy, you know, you train in a

00:35:45.100 particular methodology in a particular framework, and then keep pumping out papers plus delta within

00:35:50.720 this thing. Well, life is too short for me to only do that. And so I've published papers in,

00:35:55.220 you know, in psychology and in marketing and in economics and in medicine and in bibliometrics.

00:35:59.940 I don't care where I publish as long as I have hopefully something interesting to say.

00:36:05.040 So universities always say yes, yes, interdisciplinarity. But then when you try to

00:36:09.160 implement something that is interdisciplinary, then they all become sort of territorial over their

00:36:13.340 little fiefdoms. And so from this side, I'm interdisciplinary from that side, I'm not.

00:36:17.920 But I can only imagine that the projects that you guys are doing now at Colossal Biosciences is

00:36:23.380 by nature, by definition, greatly interdisciplinary. So can you maybe talk a bit about that?

00:36:30.880 Yeah, I think, you know, one of the first questions that you asked was sort of what are

00:36:35.100 the new technologies that led to this discovery? I've always sort of described Colossal as an

00:36:41.020 intersection of technologies, an intersection of emerging technologies. And we're sort of combining

00:36:45.580 those to create a suite, a toolkit that allows this to happen. So I think, you know, I'm always

00:36:51.620 amazed at how many things Beth is involved in, in terms of the various sciences that she's

00:36:57.020 needing to direct. And then we're weaving that into things like, how do you create an animal

00:37:03.340 care strategy and a management strategy for a species that's never existed before, had

00:37:08.360 existed in 12,000 years, right? And so we're always trying to weave our different expertise

00:37:13.300 in our sciences together in a really interesting way. And so I like to think of Colossal as this

00:37:18.660 sort of amazing, the world's most interesting intersection.

00:37:22.620 Wow. You want to add anything, Beth?

00:37:24.380 Well, I was just going to say, this is to your point about how you're publishing in marketing,

00:37:28.480 and you're publishing in business, and you're publishing in evolutionary psychology. I mean,

00:37:31.300 one of the reasons that I decided to take this leave and join Colossal is because, you know,

00:37:36.060 we only get a certain number of rotations around the star at the center of our universe. And we want to be

00:37:41.100 doing things that are actually impactful. And you want to be doing things that require you to learn

00:37:44.920 something new and interact with people that you've never interacted with before, and figure out where

00:37:49.540 you're wrong, right? Because good scientists want to know where they're wrong so that they can figure

00:37:54.480 out how to not be wrong, right? And if you're just operating in that little lens of your own world

00:37:59.580 forever, you're probably hardly ever going to be wrong. And that means you're never going to learn

00:38:03.780 anything, and you're probably not going to make a big impact. So I love the fact that we're at the

00:38:07.920 center of everything, and that we're doing all sorts of things at the same time and pushing as

00:38:12.340 hard as we can in lots of different directions simultaneously.

00:38:15.700 And sort of the leg that's missing in this three-legged stool that is Beth and me and is Ben,

00:38:21.000 is, you know, what Ben's able to bring to this is really interesting for me coming from a

00:38:25.280 nonprofit conservation background to this, the way we market, the way we communicate, the way we want

00:38:30.120 to build economics around sustainable conservation initiative is amazing. So it's just,

00:38:35.380 it's all the sciences, and then there's the business, the marketing, the comms,

00:38:38.680 all that's layered into, I think, one of the most, I hope, is one of the most interesting

00:38:43.020 companies to have emerged in the last decade or so.

00:38:47.240 Incredible.

00:38:47.800 Actually, what we're forgetting, though, is just that it's also just cool, right? It's freaking cool.

00:38:53.380 And people, and because of the marketing and the comms, we have like kids reaching out to us. My kids

00:38:59.140 came back from school, both of them, and said, in my science class today, they talked about this,

00:39:03.440 because it was on the news. My colleagues at Santa Cruz were saying the undergrads were coming in

00:39:07.700 and talking about it in class, feeling inspired that there was something that they could do about

00:39:12.120 the conservation crisis. And as we think about all of the, oh, people scared, I'm scared of this,

00:39:16.840 where's it going to go? Is it too scary? We also have to remember the number of people that,

00:39:21.640 because of the dire wolf announcement, thought about extinction and biodiversity loss and ecosystems

00:39:27.260 and genetic engineering for the very first time ever in their whole lives is huge.

00:39:31.800 And if we're going to have a future that is both filled with people and lots of other

00:39:36.080 biodiverse species, we need people to be more engaged than they naturally would be. And this

00:39:40.680 is a way to do it. And we owe that to this sort of crazy strategy that Ben brings to the table,

00:39:46.860 along with obviously how just cool it is.

00:39:49.320 Well, I mentioned, yeah, I mentioned earlier that I first learned about you guys through

00:39:54.800 seeing Ben on Joe Rogan, which kind of brings me to a point that I referred to earlier about

00:40:01.080 stay in your lane. When I first went on Joe Rogan, which would have been now many, many years ago,

00:40:05.660 I think I might've been maybe the first professor to ever go on. It was looked with great derision that,

00:40:11.560 you know, I come from the lofty ivory tower to speak to the great unwashed. And I tell a story in one 0.99

00:40:18.100 of my books, how, when I had gone to Stanford business school to give a talk, they were really

00:40:22.020 not into the fact that I was going on Joe Rogan. Whereas now they all write to me and say,

00:40:26.040 oh, please, can you introduce me to Joe Rogan? Because, because it speaks to the fact that if we are

00:40:31.260 doing really valuable science in any field, you do want people to be inspired by it. I don't want to

00:40:38.540 only speak to 13 people who are going to read my peer reviewed article. I want millions. So for me,

00:40:43.960 I started this show for no other reason than I thought I had some interesting things that I

00:40:49.380 could say. I thought I could bring some really cool guests on the show. Let's open it up to

00:40:54.340 everybody. And luckily I've been able to, to build a, you know, a pretty big platform. So I love the

00:40:59.440 fact that you guys are doing this. I mean, I always say life is marketing and marketing is life. I mean,

00:41:04.300 animals communicate what to one another, advertise their mating, you know, attraction through

00:41:11.460 marketing, right? I mean, sexual signaling is a form of marketing. So, so I love that you guys

00:41:16.480 are doing this. Maybe you could tell us in the few minutes that we have left, what are some,

00:41:20.360 if you're, if you're willing to, to promote the stuff, what are some downstream projects

00:41:25.520 that you're working on that we're all going to be excited to hear about at some not too distant

00:41:30.580 future? I hope. Well, we have the three flagship projects, the mammoth, the thylacine,

00:41:37.280 which is also the Tasmanian tiger and our dodo project. And we'll be announcing another project

00:41:44.080 coming up in a, in a month or so, which I'm not going to say what it is yet, but stay tuned. It'll

00:41:49.140 be exciting to hear about it. And then we have a bunch of conservation projects. Matt, you want to

00:41:54.040 highlight some of the, some of the coolest things that are coming up? Yeah. I would say if you're

00:41:57.720 really interested in maybe what our next day extinction project might be, you should also pay

00:42:02.360 attention to Joe Rogan coming up because I think Beth is going to be making an appearance with Joe to 1.00

00:42:06.380 talk about. Is this your inaugural? But on the conservation front, we're, we're, you know,

00:42:17.340 we launched it. So we have Colossal Biosciences, which is the company we launched, but last November,

00:42:21.880 we also launched the Colossal Foundation. The Colossal Foundation is our 501c3 conservation

00:42:27.000 organization that's focused on applying our technologies that we create from Colossal Biosciences

00:42:32.220 to the conservation world. We give these tools away for free. We want to engage with conservation

00:42:37.120 NGOs. So we're working on things like the American Red Wolf. How can we help support the key to 0.77

00:42:42.080 conservation in the Sea of Cortez, which is the most critically endangered porcus in the world?

00:42:46.320 You know, how can we use genetic rescue as a tool to save populations of animals like Northern 0.97

00:42:52.420 White Rhino and Mauritian Pink Pigeon that are, that have gone through these enormous population

00:42:57.120 bottlenecks. And then also, can we use genetic engineering as a tool to confer toxicity resistance

00:43:02.840 to the Northern Quill to confer, you know, adaptive qualities to other, you know, like drought

00:43:09.400 resistance, maybe to some other species that are on the brick. So if you, we'll keep pounding these

00:43:14.840 out, as you might imagine, our comms team is constantly working on a cadence of announcements to

00:43:18.780 show and highlight the amazing conservation work we're doing that sort of comes in between our

00:43:23.800 key extinction announcements. Very, very exciting. I can't imagine how excited you guys must be to

00:43:29.680 every day walk into those offices. What an adventure. I, in one of my, my last book I talk

00:43:35.480 about, so it's a book on happiness and I have an entire chapter on life as a playground. And I argue

00:43:40.780 that science is the ultimate form of playground, right? I mean, it's puzzle making. There's a bunch

00:43:45.280 of variables and I'd like to see which variable is associated with which other one in a meaningful

00:43:49.640 way. And I guess, I guess you guys get to do this from eight in the morning till eight

00:43:54.640 at night every day. So maybe one day I'll come and visit you out there and you'll tell me what

00:43:58.960 my wolves are. That'd be great. That would be amazing. Yeah. Either you come visit us at the

00:44:03.500 labs or one day I'll, I'll take you to the wolves. Oh, that'd be amazing. Thank you. Hey guys,

00:44:07.080 stay on the line so I can say goodbye offline. Thank you so much for coming on. Anything I can do to

00:44:11.620 help promote your projects, always reach out. Thank you so much for agreeing to come on the show.

00:44:16.520 Thank you. So thank you. It was fun.

The Saad Truth with Dr. Saad - May 05, 2025

De-Extinction of the Dire Wolf! Modern Day Jurassic Park？ (The Saad Truth with Dr. Saad_832)

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