WEBVTT - Bringing Back Mammoths and Dodos* 0:00:15.356 --> 0:00:24.436 Pushkin. There's a company called Colossal Biosciences that has raised 0:00:24.476 --> 0:00:28.796 over two hundred million dollars and its stated aim is 0:00:28.836 --> 0:00:33.716 to bring back the wooly mammoth and also the dodo bird, 0:00:34.356 --> 0:00:38.276 as well as a considerably less famous but equally extinct 0:00:38.316 --> 0:00:44.396 animal called the thylacine aka the Tasmanian tiger. I have 0:00:44.556 --> 0:00:50.716 questions like, why why are private investors putting hundreds of 0:00:50.756 --> 0:00:56.716 millions of dollars into this company? And really mostly how 0:00:57.556 --> 0:00:59.716 how do you bring back a species that has been 0:00:59.796 --> 0:01:09.036 extinct for centuries. I'm Jacob Goldstein, and this is What's 0:01:09.316 --> 0:01:11.316 problem the show where I talk to people who are 0:01:11.356 --> 0:01:15.796 trying to make technological progress. My guest today is Beth Shapiro. 0:01:16.276 --> 0:01:21.116 She's the chief scientific officer at Colossal Biosciences, a company 0:01:21.156 --> 0:01:25.516 that is in the business of d extinction. BET's problem 0:01:25.596 --> 0:01:28.476 is this, how do you use the tools of modern 0:01:28.476 --> 0:01:31.556 biology to bring back species that have been extinct for 0:01:31.836 --> 0:01:35.636 hundreds or thousands of years. Also, on kind of a 0:01:35.676 --> 0:01:39.476 more subtle level, BET's problem is just defining for the 0:01:39.516 --> 0:01:44.596 world what de extinction really means. Before Beth joined Colossal, 0:01:44.716 --> 0:01:47.556 she spent decades in academia. She helped to pioneer the 0:01:47.556 --> 0:01:52.116 field of paleogenetics, studying the genes of ancient organisms, and 0:01:52.156 --> 0:01:55.076 she spent a lot of time studying the Dodo bird. 0:01:55.756 --> 0:01:58.116 Tell me about your life with the Dodo. 0:02:00.316 --> 0:02:02.876 I guess my first exposure to the Dodo was in 0:02:03.196 --> 0:02:05.756 nineteen ninety nine when I started my PhD at Oxford. 0:02:05.916 --> 0:02:09.436 The ancient DNA lab that we were using with in 0:02:09.476 --> 0:02:12.716 the back of the Oxford University Museum of Natural History, 0:02:12.756 --> 0:02:16.196 and that is so we had to pass by the 0:02:16.276 --> 0:02:20.396 Dodo every time we were going to the lab. And 0:02:21.796 --> 0:02:24.556 I was, you know, in this field ancient DNA where 0:02:24.556 --> 0:02:26.756 we could extract DNA from things, no one was sure 0:02:26.836 --> 0:02:29.396 what exactly a Dodo was, what kind of bird it 0:02:29.476 --> 0:02:31.636 was most closely related to, And so I thought it 0:02:31.636 --> 0:02:33.436 would be really cool if I could use these really 0:02:33.476 --> 0:02:35.596 new tools and technologies to be able to solve this 0:02:35.676 --> 0:02:38.156 question answer what sort of bird a Dodo is? So 0:02:38.156 --> 0:02:40.236 I ask if I could extract DNA from the Dodo. 0:02:40.316 --> 0:02:44.076 If they said no, because it is a very specials special, 0:02:44.356 --> 0:02:47.636 precious specimen and you have not proven that you are 0:02:47.716 --> 0:02:51.316 good at this yet, And so I proved myself. You know, 0:02:51.356 --> 0:02:54.756 I extracted DNA from other birds and other things, and 0:02:55.636 --> 0:02:57.916 I was having pretty good success with this, and they said, okay, 0:02:57.956 --> 0:03:00.076 you can take some grungey bits out of the inside 0:03:00.116 --> 0:03:02.956 of the skull of this dodo with these long forceps. 0:03:03.116 --> 0:03:06.116 They have this one Dodo that's an actual Dodo, and 0:03:06.156 --> 0:03:08.796 you're like, look, I could I could tell you whatever 0:03:08.956 --> 0:03:11.676 the genome of that bird if you just let me 0:03:11.716 --> 0:03:11.996 at it. 0:03:12.316 --> 0:03:15.396 Yep, that's well, maybe not the genome, but I wanted 0:03:15.396 --> 0:03:18.236 to know at the time what type of bird it was. 0:03:18.316 --> 0:03:22.156 And at the time we were the field of ancient 0:03:22.236 --> 0:03:25.756 DNA was focusing on extracting mitochondrial DNA, which is a 0:03:25.876 --> 0:03:29.476 type of DNA that is inherited maternally, so it doesn't 0:03:29.516 --> 0:03:32.396 tell you everything about a species. So there's lots and 0:03:32.396 --> 0:03:34.996 lots of mitochondrial DNA in every cell, and there's only 0:03:35.036 --> 0:03:38.916 two copies of every nuclear locus that's in the cells. 0:03:38.916 --> 0:03:41.316 And so in the early days of ancient DNA, when 0:03:41.596 --> 0:03:43.836 we really weren't very good at recovering DNA, we were 0:03:43.836 --> 0:03:46.956 focusing on mitochondria. So I wanted to get mitochondria from 0:03:46.956 --> 0:03:49.676 this Dodo specimen. So why I could answer this outstanding 0:03:50.516 --> 0:03:54.676 taxonomic question, what type of bird is or was a dodo? 0:03:54.876 --> 0:03:57.756 Uh huh, because people were just trying to guess based 0:03:57.796 --> 0:04:00.676 on the morphology, based on what it looked like. 0:04:00.796 --> 0:04:04.636 Essentially, Yeah, I mean, taxonomy before DNA really was that 0:04:04.756 --> 0:04:07.916 people are comparing the shapes of things. But DNA is 0:04:07.956 --> 0:04:11.076 a really unbiased way of reconstructing evolutionary history and it's 0:04:11.076 --> 0:04:12.836 really powerful, and so I wanted to be able to 0:04:12.876 --> 0:04:16.356 apply that in addition to the morphological data that people 0:04:16.356 --> 0:04:18.076 have been collecting for hundreds of years. 0:04:18.636 --> 0:04:21.716 And so they eventually let you at the bird, and 0:04:22.796 --> 0:04:23.716 what do you figure out? 0:04:24.796 --> 0:04:27.316 They first let me take some long force ups to 0:04:27.316 --> 0:04:29.396 try to scrape some gunk out of the inside of 0:04:29.436 --> 0:04:31.876 its skull, and that led to nothing because there wasn't 0:04:31.916 --> 0:04:34.356 any DNA and the gunked up bits of gunk from 0:04:34.356 --> 0:04:36.876 the inside of the cell. And then they finally let 0:04:36.876 --> 0:04:38.596 me cut a tiny little piece of bone out of 0:04:38.596 --> 0:04:41.836 its leg and I was able to extract mitochondrial DNA 0:04:41.876 --> 0:04:44.956 from that and compare that to all other types of 0:04:44.956 --> 0:04:47.956 birds that were hypothesized to potentially be a dodo, and 0:04:47.996 --> 0:04:50.516 we discovered that the dodo is a type of pigeon. 0:04:50.716 --> 0:04:54.436 It falls within the diversity of pigeons. Most closely related 0:04:54.476 --> 0:04:58.076 to a pigeon called the nicobar pigeon, which is a 0:04:58.156 --> 0:05:01.556 very strong flyer, very beautiful bird, different a lot different 0:05:01.556 --> 0:05:02.116 from a dodo. 0:05:02.596 --> 0:05:05.596 So you figure out that the dodo was a pigeon 0:05:06.756 --> 0:05:08.956 that was relatively early in your career, right, and then 0:05:09.196 --> 0:05:13.396 spend a long time doing scholarly work, doing academic work. 0:05:13.476 --> 0:05:17.596 You eventually sequence the whole Dodo genome, right, and then 0:05:17.636 --> 0:05:24.436 eventually what last year you get to Colossal? What made 0:05:24.476 --> 0:05:26.436 you want to join Colossal? 0:05:27.596 --> 0:05:31.036 Well, I mean you summarized twenty five years of my 0:05:31.076 --> 0:05:34.476 academic history. 0:05:34.756 --> 0:05:36.996 You want to give me a high point along the way. 0:05:37.276 --> 0:05:39.356 Well, you know, I've been working in this field of 0:05:39.396 --> 0:05:41.876 ancient DNA, trying to develop tools to be able to 0:05:41.916 --> 0:05:43.956 get more DNA out of things, to look at the 0:05:44.076 --> 0:05:48.516 nuclear genomes of different species, develop computational approaches to be 0:05:48.516 --> 0:05:51.636 able to use the genetic information that we've extracted to 0:05:51.716 --> 0:05:54.396 tell us when populations are growing and shrinking, To look 0:05:54.396 --> 0:05:58.196 at replacements, to get DNA directly from ancient sediments so 0:05:58.196 --> 0:06:00.476 that we can look at what whole ecosystems look like. 0:06:00.956 --> 0:06:04.516 And all of this really driving toward understanding how we 0:06:04.556 --> 0:06:07.756 can use the past as a sort of completed evolutionary 0:06:07.916 --> 0:06:10.636 experiment to try to make more informed decisions of what 0:06:10.756 --> 0:06:13.996 we can do to protect and preserve species and habitats 0:06:14.036 --> 0:06:17.156 and ecosystems moving forward. I mean, now, when we're deciding 0:06:17.156 --> 0:06:19.196 what we're going to do from a conservation perspective, we 0:06:19.236 --> 0:06:21.636 look around, we see things are in trouble, and we 0:06:21.836 --> 0:06:24.596 use science we make educated guesses about what the best 0:06:24.636 --> 0:06:28.236 things are going to be to restore missing ecological interactions 0:06:28.236 --> 0:06:31.396 to help make these different communities more resilient or more 0:06:31.756 --> 0:06:35.036 robust in the face of these changes. And ancient DNA 0:06:35.116 --> 0:06:38.316 lets us do this by showing us how things responded 0:06:38.316 --> 0:06:42.276 in the past to massive perturbations to their habitat, whether 0:06:42.316 --> 0:06:45.316 that's an ice age or a really warm interglacial, or 0:06:45.396 --> 0:06:48.196 the introduction of people or a predator, a different type 0:06:48.236 --> 0:06:51.596 of predator into that into that ecosystem. And every time 0:06:51.596 --> 0:06:55.396 we would publish this work that we would want to 0:06:55.436 --> 0:06:57.396 tell people about it, we would we would want to 0:06:58.276 --> 0:07:00.756 explain to people what it is that we're excited about, 0:07:00.756 --> 0:07:04.396 But often the only question that people wanted answered was 0:07:04.636 --> 0:07:06.116 what does this mean about how close we are to 0:07:06.156 --> 0:07:08.316 bringing these species back to life? 0:07:09.316 --> 0:07:12.436 Kind of fighting that right, like you write about it 0:07:12.476 --> 0:07:18.156 like there's I was reading the twenty twenty edition of 0:07:18.196 --> 0:07:20.356 your book How to Clone a Mammoth, where you said 0:07:20.916 --> 0:07:24.116 the present focus on bringing back particular species, whether that 0:07:24.156 --> 0:07:28.556 means mammoths, Dodo's passenger pigeons, or anything else, is misguided, right, 0:07:28.596 --> 0:07:32.196 which seems tell me about that? Is there a point 0:07:32.196 --> 0:07:33.956 where you stop thinking it's misguided? 0:07:34.156 --> 0:07:38.196 You know, there's a lot of complications. There a biological, technical, 0:07:38.236 --> 0:07:43.276 and ethical challenges associated with bringing extinct species back to life, 0:07:43.516 --> 0:07:50.436 And so you ask what is misguided? When people hear 0:07:50.796 --> 0:07:54.476 about de extinction or the word de extinction, or think 0:07:54.516 --> 0:07:57.836 about bringing mammoths back to life, what they imagine is 0:07:57.916 --> 0:08:02.636 recreating something that is identical in every way to a 0:08:02.716 --> 0:08:06.796 mammoth that used to be alive. But that isn't possible, right, 0:08:06.876 --> 0:08:10.996 And I think that is where I find the push 0:08:11.076 --> 0:08:15.396 to this to be misguided. As I said at the time, 0:08:15.476 --> 0:08:19.396 it's a little bit more nuanced than just as explained. 0:08:19.436 --> 0:08:23.596 So what is misguided is this idea that de extinction 0:08:24.116 --> 0:08:27.516 is a solution to the extinction crisis. Right, once a 0:08:27.556 --> 0:08:31.276 species is gone, we can't bring it back. That species 0:08:31.396 --> 0:08:35.116 is gone. What we can bring back are some of 0:08:35.156 --> 0:08:40.636 these core phenotypes, whatever it was that was about that 0:08:40.676 --> 0:08:43.636 species that made it unique in their habitat some way 0:08:43.676 --> 0:08:46.716 of replacing that missing ecological interaction. But it's not by 0:08:46.796 --> 0:08:49.836 resurrect something that's identical to the species that used to 0:08:49.836 --> 0:08:52.396 be there, but by taking species that are alive today 0:08:52.756 --> 0:08:56.276 and tweaking them using the tools of genetic engineering, so 0:08:56.316 --> 0:09:00.196 that they can fit into that ecosystem, so they can 0:09:00.556 --> 0:09:04.436 play some of those roles ecological roles that the extinct 0:09:04.436 --> 0:09:07.076 species once had. Does that make sense? 0:09:07.516 --> 0:09:12.396 It does? It seems somewhat at odds with the sort 0:09:12.436 --> 0:09:17.436 of public messaging of Colossal Right, Like I was reading 0:09:17.476 --> 0:09:19.596 your writing on all of what you're saying makes sense 0:09:20.076 --> 0:09:21.996 and we can talk more about it. But it is 0:09:22.076 --> 0:09:26.356 the case that like the homepage of Colossal Right Now says, 0:09:26.796 --> 0:09:30.316 we endeavor to jumpstart nature's ancestral heartbeat to see the 0:09:30.356 --> 0:09:34.836 wooly mammoth thunder upon the tundra once again, right, which 0:09:35.356 --> 0:09:39.516 is not to see the Asian elephant with some phenotypical 0:09:39.556 --> 0:09:42.556 traits of the wooly mammoth. Like, so, I don't know, 0:09:43.436 --> 0:09:45.396 like how do you reconcile those? Is it? Just like 0:09:45.436 --> 0:09:48.116 there's sort of a public story that needs to be simplified, 0:09:48.276 --> 0:09:50.636 just because that's the nature of public stories and then 0:09:50.676 --> 0:09:52.956 a more complex technical story. 0:09:53.596 --> 0:09:56.236 If you dive into the website on Colossal, it does 0:09:56.316 --> 0:09:59.796 explain that the idea of the extinction includes resurrecting extinct 0:09:59.876 --> 0:10:03.756 traits using extinct genomes, but also engineering that we are 0:10:03.756 --> 0:10:07.076 taking Asian elephants and engineering them to have and express 0:10:07.156 --> 0:10:10.396 some of these mammoth trades. On the website, they're even 0:10:10.396 --> 0:10:14.436 called Arctic adapted elephants in several places. So I think 0:10:14.476 --> 0:10:17.396 it depends on what you're willing to accept as a mammoth. Right, 0:10:17.556 --> 0:10:20.436 if you are only ever going to accept something that 0:10:20.636 --> 0:10:25.596 is ecologically, genetically and physiologically one identical to a species 0:10:25.636 --> 0:10:29.116 that used to be alive, then that's not what we're doing, 0:10:29.156 --> 0:10:31.796 because that's not possible. But if you are willing to 0:10:31.836 --> 0:10:36.916 accept an elephant that has longer hair, slightly larger back, 0:10:37.116 --> 0:10:40.276 the longer curved tusks, that is capable of living in 0:10:40.316 --> 0:10:43.596 the habitat that mammoths once lived in and playing the 0:10:43.676 --> 0:10:46.956 roles that mammoths once played, then that is Colossal's goal, 0:10:47.076 --> 0:10:50.316 and that is what we are we are saying that 0:10:50.356 --> 0:10:50.996 we are making. 0:10:51.876 --> 0:10:55.876 Has your view on sort of what scientists should try 0:10:55.876 --> 0:10:57.956 and do, or how they should talk about it, or 0:10:58.996 --> 0:11:03.236 anything along those lines changed over time, like this idea 0:11:03.236 --> 0:11:06.076 of the extinction, which I don't want to get too 0:11:06.076 --> 0:11:08.236 caught up in the semantics, right. I understand that it 0:11:08.236 --> 0:11:10.156 can mean different things different people, and that there's a 0:11:10.236 --> 0:11:12.956 kind of subtle meaning of it, but like, has your 0:11:13.036 --> 0:11:15.276 view in fact changed it all over time? 0:11:16.316 --> 0:11:20.316 My view is that the idea of de extinction is 0:11:20.396 --> 0:11:25.156 exciting because it allows us to write down a long 0:11:25.276 --> 0:11:28.076 list of all of these challenges that we would need 0:11:28.116 --> 0:11:30.196 to be able to solve if we were going to 0:11:30.236 --> 0:11:32.236 do this, and along the way we come up with 0:11:32.276 --> 0:11:35.156 new technologies and new ideas and new associations that have 0:11:35.236 --> 0:11:38.596 application to present day conservation work as well as to 0:11:39.396 --> 0:11:43.316 extinction work. My idea of whether de extinction, if you 0:11:43.396 --> 0:11:46.436 define it as bringing something back that is one hundred 0:11:46.436 --> 0:11:48.716 percent identical to a species that used to be alive, 0:11:49.116 --> 0:11:53.356 is impossible, has not changed, right. I don't like the 0:11:53.436 --> 0:11:55.636 idea that people would say that that is what we're doing, 0:11:55.676 --> 0:11:58.916 because I think then that gives people license to imagine 0:11:58.956 --> 0:12:02.596 that extinction isn't a problem. But extinction is a problem, 0:12:02.636 --> 0:12:05.556 and this is not a solution to that problem. But 0:12:06.156 --> 0:12:08.756 am I willing to say that we shouldn't try this, 0:12:08.876 --> 0:12:12.196 that we shouldn't develop these tools that may have application 0:12:12.356 --> 0:12:15.676 to helping species not become extinct because we're worried that 0:12:15.756 --> 0:12:17.836 somebody is going to get tied up in the semantics 0:12:17.836 --> 0:12:20.276 of something and accuse us of something we're not. No. 0:12:20.716 --> 0:12:23.756 Am I sad that Ben Lamb has been able to 0:12:23.916 --> 0:12:26.596 raise two hundred and twenty five million dollars to be 0:12:26.676 --> 0:12:30.196 able to invest into developing these tools that I hope, 0:12:30.276 --> 0:12:33.996 I imagine are going to dramatically impact the way that 0:12:34.036 --> 0:12:37.956 we do by diversity conservation moving forward. No, I think 0:12:37.996 --> 0:12:41.276 this is amazing. I think it's a fantastic opportunity that 0:12:41.316 --> 0:12:42.196 we should celebrate. 0:12:43.796 --> 0:12:48.756 Great since you mentioned that that Ben Lamb, the CEO 0:12:48.836 --> 0:12:51.276 of the company, has raised two hundred and twenty five 0:12:51.316 --> 0:12:55.476 million dollars, Like, what what is the business model? You know, 0:12:55.596 --> 0:12:58.316 it's a it's a private company, right, it's not a nonprofit. 0:12:59.156 --> 0:13:01.276 So how are the investors going to make a profit? 0:13:02.796 --> 0:13:05.036 You know, this is that's a Ben question. It's not 0:13:05.116 --> 0:13:08.876 a me question. I'm the chief science officer. But you know, 0:13:08.916 --> 0:13:10.796 some of the ways that the company will make money 0:13:10.836 --> 0:13:13.716 is along the path toward the extinction. There are a 0:13:13.756 --> 0:13:16.156 ton of technologies that are going to be developed, things 0:13:16.236 --> 0:13:20.556 like multiplex genomediting, different approaches to driving genetic changes. We're 0:13:20.596 --> 0:13:23.196 working on an artificial womb as one of the tools, 0:13:23.276 --> 0:13:26.876 and all of these will drive patents that will be 0:13:26.956 --> 0:13:30.676 useful for things outside of the extinction landscape. Ben has 0:13:30.756 --> 0:13:34.156 promised that any technology that we develop for conservation can 0:13:34.196 --> 0:13:37.556 be applied to conservation without having to pay for that. 0:13:37.836 --> 0:13:41.116 So he's promised that that tools that we develop will 0:13:41.116 --> 0:13:44.036 go to conservation at no cost. But the path toward 0:13:44.476 --> 0:13:48.396 toward bringing in investment return for investors really is in 0:13:48.516 --> 0:13:51.276 the space of being at the absolute cutting edge of 0:13:51.436 --> 0:13:53.436 genetic engineering and that sort of science. 0:13:53.596 --> 0:13:56.236 Right, And a company was already spun out sort of 0:13:56.316 --> 0:13:58.836 in that way, right, is it form Bio that's spun 0:13:58.876 --> 0:14:01.996 out of a spun out of Colossal and is a 0:14:02.036 --> 0:14:05.756 sort of kind of platform genetics, Like, yes, it's. 0:14:05.596 --> 0:14:09.876 A software company's sort of developing tools that we really 0:14:09.876 --> 0:14:11.476 need to be able to track what we're doing all 0:14:11.476 --> 0:14:13.996 the different experiments that are going on in Colossal that 0:14:14.076 --> 0:14:15.876 have to do with a different species, so that we're 0:14:15.876 --> 0:14:19.196 not repeating experiments, but it's super useful for being able 0:14:19.196 --> 0:14:23.156 to refine experimental designs. And so that is a spinout 0:14:23.156 --> 0:14:27.316 company that's working on developing software platforms for other industries 0:14:27.356 --> 0:14:28.716 including drug development, etc. 0:14:29.676 --> 0:14:32.636 So let's talk about how it works and sort of 0:14:32.676 --> 0:14:34.676 what you've figured out and what you still have to 0:14:34.676 --> 0:14:37.836 figure out. And I know how it works is different 0:14:37.916 --> 0:14:41.676 for different species. So tell me about the plan with 0:14:41.716 --> 0:14:42.196 the mammoth. 0:14:42.916 --> 0:14:47.876 Sure, So, there are lots of different steps toward figuring 0:14:47.916 --> 0:14:51.236 out how to take an Asian elephant and turn it 0:14:51.276 --> 0:14:53.836 into an Arctic adapted elephant that we would let's call 0:14:53.876 --> 0:14:56.196 a mammoth, defending on whether you're willing to say that. 0:14:57.396 --> 0:14:59.836 The first step is to figure out the link between 0:14:59.876 --> 0:15:02.596 the genotype, the a's and c's and g's and t's 0:15:02.636 --> 0:15:06.556 that make up on organism's genome and the phenotype or 0:15:06.596 --> 0:15:10.076 the way that organism looks and acts. For this, we 0:15:10.156 --> 0:15:12.396 collect a lot of information, go out into the field, 0:15:12.796 --> 0:15:16.796 collect a lot of mammoth bones, sequence high quality whole 0:15:16.796 --> 0:15:20.196 coverage genomic data. We have academic collaborators who are helping 0:15:20.196 --> 0:15:22.876 with that, Luvo de Lens Lab and Stockholm is a 0:15:22.916 --> 0:15:25.716 major advisor to this group. We have now more than 0:15:25.756 --> 0:15:30.276 fifty high coverage genome sequences from mammoths, and we can 0:15:30.556 --> 0:15:34.116 compare these to genome sequences from Asian elephants and African 0:15:34.156 --> 0:15:37.756 elephants and other afrotherorians, so they differentiate all mammoths from 0:15:37.836 --> 0:15:40.356 everything else that's there. As a way to start to look, 0:15:41.196 --> 0:15:44.996 we can get information from doing experiments like looking and 0:15:45.036 --> 0:15:48.436 see what genes are being expressed during tusk development, or 0:15:48.436 --> 0:15:51.076 what genes are being expressed in the follicles that produce 0:15:51.156 --> 0:15:54.156 long hair. As another way of narrowing down where our 0:15:54.316 --> 0:15:57.036 fosi should be as far as identifying these genes that 0:15:57.076 --> 0:15:59.596 we want to change. Once we have a panel, we 0:15:59.676 --> 0:16:02.316 then have to engineer those and so for this we 0:16:02.396 --> 0:16:06.156 take cells from elephants that are growing in a dish 0:16:06.156 --> 0:16:08.836 in a lab. A few months ago we released a 0:16:08.876 --> 0:16:11.356 pre print and now we have the paper under revision 0:16:11.396 --> 0:16:14.636 where we were able to derive induced play potent stem 0:16:14.676 --> 0:16:16.956 cells from elephants. This is something people have been trying 0:16:16.996 --> 0:16:19.316 to do for a long time and our mammoth team 0:16:19.396 --> 0:16:22.716 was successful in doing this. This is really cool and 0:16:22.796 --> 0:16:25.396 useful for us because it means that we have cell 0:16:25.396 --> 0:16:28.436 lines that are healthy and happy and survive in a 0:16:28.476 --> 0:16:32.036 dish that we can transform into different tissue types. So 0:16:32.076 --> 0:16:36.196 if we have hypotheses about whether this particular DNA sequence 0:16:36.276 --> 0:16:39.396 change causes changes in hair growth, we can make a 0:16:39.476 --> 0:16:42.316 type of organoid where we can test that hypothesis. So 0:16:42.316 --> 0:16:44.956 we don't have to make an elephant in order to 0:16:44.996 --> 0:16:47.356 test our hypothesis. We do this in culture. 0:16:48.916 --> 0:16:53.916 So, dumb question, in that particular example you gave, would 0:16:53.916 --> 0:16:56.476 there actually be like hair growing out of the dish 0:16:56.476 --> 0:16:56.996 in the lab? 0:16:57.556 --> 0:16:57.756 Yes? 0:16:59.076 --> 0:17:04.116 That's rad okay, So you have that, which is a 0:17:04.196 --> 0:17:07.756 useful sort of platform, right, A useful tool certainly to 0:17:07.796 --> 0:17:12.436 test hypotheses about, well, what genetic changes lead to what 0:17:12.636 --> 0:17:14.836 phenotypical changes right? Go on? Right? 0:17:15.436 --> 0:17:17.596 So then after you do that, you have your your 0:17:17.596 --> 0:17:20.196 cells growing in addition to lad that you've engineered all 0:17:20.236 --> 0:17:23.476 of your edits into. So I've probably skipped over there. 0:17:23.956 --> 0:17:27.516 Lots of very difficult challenging biology. Identify what genes we're 0:17:27.516 --> 0:17:31.916 interested in, figure out how to edit these the genomes 0:17:31.916 --> 0:17:33.756 and cells to get all those changes in them. And 0:17:33.796 --> 0:17:36.036 we have teams of people who are working on multiplex 0:17:36.116 --> 0:17:40.156 genome editing, replacing large chunks of DNA rather than just 0:17:40.276 --> 0:17:43.956 making single edits to the DNA sequence lots of different 0:17:43.956 --> 0:17:47.796 approaches that are developing new tools, new ways of doing 0:17:47.876 --> 0:17:51.196 genome engineering that of course have application outside of the 0:17:51.236 --> 0:17:53.556 field of the extinction or mammoth or any of these 0:17:53.596 --> 0:17:56.676 other cells. Then once you have your edited cell, you 0:17:56.756 --> 0:18:00.476 do cloning, sematic cell nuclear transfer, the same process that 0:18:00.596 --> 0:18:02.996 brought us Dolly the sheep. You have planted that into 0:18:03.036 --> 0:18:06.316 a host, and then eventually your animal is born. So 0:18:06.396 --> 0:18:08.956 all of that is very hard. I have summed cross 0:18:09.156 --> 0:18:12.796 very hard, difficult, challenging things, and in elephants in particular, 0:18:12.876 --> 0:18:15.556 one of the one of the groups that we have 0:18:15.596 --> 0:18:18.956 at Colossal is an EXODEV group or artificial boom group, 0:18:18.956 --> 0:18:21.516 with the idea of eventually being able to do all 0:18:21.596 --> 0:18:24.476 of this without needing a surrogate hoast, without needing to 0:18:24.556 --> 0:18:28.996 use a female elephant to get there. The mammoth project 0:18:28.996 --> 0:18:31.556 obviously has a very long timeline. 0:18:31.396 --> 0:18:34.516 In terms of the sort of macro side. So that 0:18:34.636 --> 0:18:40.076 was a description of the cellular level for the most part. Right, Like, 0:18:41.276 --> 0:18:43.756 you're starting with an Asian elephant, which I understand is 0:18:44.396 --> 0:18:49.116 quite similar genetically to the mammoth, Right, like more than 0:18:49.196 --> 0:18:52.596 ninety nine percent the same genetically, is that? Right? 0:18:52.756 --> 0:18:53.156 That's right? 0:18:53.796 --> 0:18:57.156 How different does an Asian elephant look from a mammoth? 0:18:57.396 --> 0:18:58.756 I don't think I've quantified that. 0:18:58.916 --> 0:19:01.796 What do you think? I don't have any idea. I mean, 0:19:01.836 --> 0:19:04.476 how much bigger is a mammoth at the same size? 0:19:04.556 --> 0:19:07.276 The size is not a is not one of the changes. 0:19:07.316 --> 0:19:09.316 I mean, a mammoth has a slightly different shape, but 0:19:09.356 --> 0:19:15.596 has a different, different tusk shape, and it's obviously harrier. 0:19:16.516 --> 0:19:23.476 And how far along is that project? I suppose one 0:19:23.596 --> 0:19:28.036 kind of milestone is implanting some genetically modified elephant that's 0:19:28.076 --> 0:19:30.876 a little bit more mammoth like into an Asian elephant. 0:19:31.396 --> 0:19:32.716 When do you think that might happen? 0:19:33.716 --> 0:19:36.356 I always tell Ben and also the comms team here 0:19:36.356 --> 0:19:38.996 that I am not going to answer timing questions. I 0:19:38.996 --> 0:19:41.996 would love to be able to predict the timing of 0:19:42.036 --> 0:19:46.076 scientific innovation, but I want my teams to be able 0:19:46.116 --> 0:19:49.876 to do good scientific work and to think hard about 0:19:49.916 --> 0:19:52.436 the experiments that they're doing, rather than to work against 0:19:52.956 --> 0:19:57.436 an externally imposed deadline. Now, George and Ben and Ariona 0:19:57.636 --> 0:20:00.396 have said that they plan to have this happen before 0:20:00.476 --> 0:20:03.356 twenty twenty eight, and I, as far as I know, 0:20:03.516 --> 0:20:06.716 this team is on goal to being able to do this. 0:20:06.796 --> 0:20:11.356 Before the implantation, and that that would be fascinating. Now 0:20:11.436 --> 0:20:15.876 it is not going to be all of the genetic changes, right, 0:20:15.916 --> 0:20:18.476 It's not going to be absolutely everything, but you're writing 0:20:18.556 --> 0:20:20.836 that it is an important first step to try to 0:20:21.076 --> 0:20:24.516 get there. We have a separate team called our Animal 0:20:24.556 --> 0:20:26.596 ops team, who's really it's made of people from the 0:20:26.676 --> 0:20:29.596 veterinarian zoo community who are working with the animals, who 0:20:29.636 --> 0:20:33.316 are working to try to really learn what these animals 0:20:33.356 --> 0:20:37.236 need to be physically and psychologically healthy and captive environments 0:20:37.276 --> 0:20:41.636 to learn about processes like OPU, which means ovum pick up. 0:20:41.676 --> 0:20:44.796 This is how do we get eggs from these animals 0:20:44.836 --> 0:20:46.796 that are going to be the surrogate hosts for somatic 0:20:46.836 --> 0:20:50.436 cell nuclear transfers. We're also working with the community of 0:20:50.436 --> 0:20:52.676 people who are doing the Northern white Rhino Southern White 0:20:52.716 --> 0:20:55.356 Rhino project because you know, what we learn in one 0:20:55.396 --> 0:20:58.036 species we can apply to other species. But there are 0:20:58.036 --> 0:21:01.036 lots of very hard problems to solve there, but they're 0:21:01.036 --> 0:21:04.556 also important problems for the future of those species. So 0:21:04.596 --> 0:21:07.356 remember that anything that we learn as we push toward 0:21:07.636 --> 0:21:10.396 a mammoth is also something that we can apply to 0:21:10.596 --> 0:21:14.476 elephant conservation and to rhino conservation. So this is all 0:21:14.956 --> 0:21:20.436 work that is hard, but I appreciate that we have 0:21:20.476 --> 0:21:23.836 the opportunity and the finances to be able to put 0:21:23.836 --> 0:21:24.676 the energy into it. 0:21:25.156 --> 0:21:31.996 And so, setting aside the understandably sensitive question of specific timelines, 0:21:34.236 --> 0:21:38.036 talk about the sort of happy outcome for the mammoth 0:21:38.036 --> 0:21:41.156 project in whatever timeframe it may happen, If it sort 0:21:41.196 --> 0:21:44.116 of works, what does that look like in the world. 0:21:45.196 --> 0:21:48.356 The long term happy outcome to me is that we 0:21:48.516 --> 0:21:54.236 have structured communities of animals that are able to live 0:21:54.596 --> 0:21:58.516 in an environment that is really similar to the wild 0:21:58.596 --> 0:22:02.316 environment to replace whatever ecological interactions are missing because of 0:22:02.356 --> 0:22:05.156 their extinction. And this happy outcome to me, where we 0:22:05.236 --> 0:22:09.356 have grandparents and parents and offspring that are all living 0:22:09.876 --> 0:22:13.156 in a wild habitat somewhere. This is not a near 0:22:13.276 --> 0:22:17.116 term solution. Elephants have twenty two months gestation. They reach 0:22:17.156 --> 0:22:20.076 sexual maturity when they're teenagers. So this is something that 0:22:20.156 --> 0:22:22.436 I can tell you isn't going to be by twenty 0:22:22.476 --> 0:22:25.876 twenty eight or twenty thirty, right. This happy outcome of 0:22:26.636 --> 0:22:29.796 an entire population or community of animals living in the 0:22:29.836 --> 0:22:31.076 wild is. 0:22:31.076 --> 0:22:34.076 That is a sort of kind of human lifetime's time 0:22:34.156 --> 0:22:37.876 scale this's a one hundred years story, absolutely, And what 0:22:38.036 --> 0:22:41.596 I mean would that be Siberia? Is it basically the tundra. 0:22:41.716 --> 0:22:44.996 It wouldn't necessarily have to be Siberia, wouldn't necessarily have 0:22:45.076 --> 0:22:49.036 to be Alaska or the Yukon. Remember, mammoths lived everywhere 0:22:49.076 --> 0:22:52.876