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We're going to do the de-extinction pipeline. That is a little carnivore. That little guy there. Electropre-ation? Electroporation. -poration. This is a way to absolutely make sure that we never lose any other species ever again. Today I'm at Colossal Biosciences. I'm going to meet up with my good friend and CEO Ben Lamm to learn about some of the amazing projects they have in the works. And I'm even going to get face to face with one of their creations. And this is not a real mammoth. It's not a real mammoth. is not actually cold. Okay. I mean,
talk about an entrance. And then I look over there and I see something else that we got to build. So, this is so we do not actually have direwolves in our labs. We actually built animatronic direwolf. So, that are actually to scale of what Remus was when he was about 18 months, which is great. And then we even do projection mapping about how wolves are helping with ecosystem and and how wolf re-wilding actually helps turn the ecosystem back into a more flourishing environment and work with the animals there. Even the lighting is based on the phylogenetic tree of like
how species evolved and how they're related to each other. What I'm hoping to be able to do today is take an elaborate behind-the-scenes tour and learn about some of the things that your team is working on. Now you guys have multiple projects in the works. Right. We sometimes people think it's it's all under one team. It's actually in multiple species teams. Now when it comes to the labs and the different projects, where is the best entry point for me to get in and see where all the magic is? So the magic happens. You've got to go through our PPE. We've got to get you
in the right attire to get you on the tour. And Sarah Ord is going to take you through all of it. Hello. Welcome. Come on in to Colossal Lab. We're going to get you all suited up first. Okay. And then we're going to go on in. We're going to do the de-extinction pipeline, but stop through all of our major species so you can hear a little bit about where we are with each of them. What's our closest living relative? It's the Asian elephant. 99.6% similar to the woolly mammoth. That's actually closer than the Asian elephant. and the African elephant. Okay, two of the extent species.
So, let me ask this question real quick. With the mammoth, similar to the direwolf, it's not so much that you're reconstructing this animal from scratch. You're editing a genome sequence to change the physical characteristics of a genome sequence that currently exists to be closer to this and only off by.4%. That's right. That's crazy to think that even.4% makes the difference between a naked looking elephant and a fully woolly mammoth. So, we're going to head over to our second species. We announced we're being back from extinction. This is going to be the thylacine, also known as the Tasmanian tiger. Oh, yeah. So, this is a more
recent extinction in the early 1900s. Um, this is one that we actually do have really nice DNA from. All of our thylacine samples come from museum samples. For whatever reason, in the early 1900s, there were a couple museum curators that decided to store some samples in ethanol instead of formaldehyde. Isn't that's a no? It's a yes. Oh, it's a yes. We've actually been able to generate a high quality reference genome for the thylacine. It's going to be as complete as the human genome telomere to telomere. It's actually the most complete genome of any extinct species
and it's more complete than most living species today. Wow. Yes. We are starting with a marsupial mouse called the fat-tailed dunnart and we are engineering it into a marsupial wolf which is the thylacine. So wait, you're telling me this is genetically closely linked to the thylacine? Yes, that is a little carnivore. That little guy there. He that is a meat eater. That cute little thing. Meat eater and a marsupial. Yeah. And a marsupial. So you're like, okay, eats meat. Got a pouch. Why not start there? Yeah. But also genetically super similar. But how did you know to think about
looking at that? So we know that they're all in the same group of marsupials. This is called the dasyuridae. So they're all in that same the same as a numbat, Tasmanian devils, voles. They're all part of that meat-eater group. And so that's why we sequenced all of them and then figured out which one was the closest. That makes sense. Okay. So biggest challenge that we have to face is number edits, right? Because this the huge distance between them is going to is accumulated lots and lots and lots of differences between as genomes, right? On the order of millions of differences. So once we've
built all the components we need in the bacteria and I have all the DNA that I need to then get into the cells, then I hand that over to the cell team. And now you're going to talk to Cory. The challenge here is that the cell membrane, the outer cell membrane is not able to allow things that are large like our editors to get through passively. So we need to kind of help these editors along. To do this, we use a process called electroporation. Electropre-ation? Electroporation. Poration. Yes. Okay. And this is how we get the cells to become edited. We're not coming
in with like tiny scissors or tweezers. It's using these molecular tweezers called enzymes. Wow. I'm ready for what's next. Awesome. Well, thank you, Cory and Jonathan. Thank you guys. Wonderful to meet you. Thanks. That was a crazy education all at once. Hopefully you guys understood that. But there is so much incredible genetic sciences happening here at Colossal. It is truly groundbreaking. Now, we're going to head to the avian side of things. So, we're going to ditch the mammals and we're going to go to our newer species that we've announced, such as the dodo and
the moa. So, you may know the dodo was a pigeon. So, we work a lot with pigeon eggs. Those are pigeon eggs. They are. Dang, they're bigger than I thought they'd be. I can hold that. Yep. Wow. Careful. Now, pigeon egg. It's amazing that big egg comes out that tiny bird. So, we incubate these for about 3 days. Okay. And then what we're going to do is collect the primordial germ cells from those. The primordial germ cells are what will form eggs and sperm in adult birds. So those are the cells that we need to edit to get our dodo or moa edits into a living bird.
That makes sense. Okay. Wow. And Emily is going to demonstrate exactly how we collect primordial germ cells from embryos. You can see up on screen a zoom. Whoa, is that its heartbeat? It is. Yeah, that's the heart tube. Yeah. So, one of the cool things about bird embryos is that those cells that I was just talking about are born in one area of the embryo and then they pop into the bloodstream and they move around until they get to the gonads. So, what that means is we can take advantage of that and she can collect a blood sample and it'll grab those PGC's around. Is that a tiny little needle you're using? extremely tiny needle. Yes.
So, she'll push that needle into the blood vessel and pull out a little bit of blood and then that blood contains hundreds of primordial germ cells, millions of red blood cells, and then we'll culture those, grow up more of the primordial germ cells, and then we can do the precise genome editing. So now that we have this special embryo, this special tissue where we put it is in our bio- bank. Oo. So any tissue that we work with from a species, we want to be able to have a backup and that's going to go in here. So this is the place where we go out, we find species that are
maybe on the brink of extinction. We can collect samples from those animals. We bring those samples back here. We grow up cells from those specimens. So we have all the equipment here that we need to do it. These are all incubators that are right now full of cells from all sorts of different species. Once those cells are growing and dividing, we can then freeze them down at an ultra low temperature, which is what I'll show you next. Okay? And when we do that, those cells will stay alive forever. So, real quickly, how cold is this thing? So, you can see here it's currently at - 145° C.
So, that's about -250° F. Well, you're going to open up just like that. Okay. Whoa. So, if you want to grab out this rack in the front here, you kind of have to Can I lean over it? I'm afraid to like breathe it in. That's it. Whoa. And you can just set it up on these other racks. Wow. So, in here we have all these uh racks of tubes. And each one of these tubes represents a species that we have now put into the BioVault. So, this is a species that's either endangered or there's a small population of them. We've grown up the cells. We've frozen those cells. And now
we've dropped it into this suspended animation. So, there are hundreds of species inside of this BioVault. Yes. What is your favorite species that you have in here? Is there one that for you're like, "Yes, we caught that one genetic information." I'm an Aussie, so I love all of the Australian species. We have so many critically endangered marsupials. So, we're doing a lot of work on biobanking a lot of those particular specimens. And this is just one bio- bank of many that we have across the globe. So there's going to be a complete global network where we're trying to
biobank local species but also make sure that when we've got incredibly precious samples in these BioVault that we have them across multiple different sites so that if anything ever happens at one of these facilities, we've got backups of those all over the place. So that way we can ensure that we never lose any other species ever again. Okay. So then your favorite one is I would have to go numbat for me as a living animal. Yeah. Okay, that's a good choice. Do you guys have komodo dragon yet? No komodos yet. Okay. Today one of the most important things we could
be doing globally is more bio- banking. This is a way to absolutely make sure that we never lose not just species but the diversity in those species. And you've been through the whole de-extinction pipeline now. And so if we have a living cell frozen from any of our species, you don't have to re-engineer that animal back into existence, which is what we do with the de-extinction. So by doing a BioVault like this, we make sure that we don't have to de-extinct anything ever again. We can use cells and we can actually clone that animal. So it's a lot better process. It's a lot faster process
and it just ensures that we really don't lose any other animals. That's really cool. So from the conservation perspective, this is future proofing. Any species on the planet that you can get into the vault means it will never go extinct again. I mean that's a big thing for everyone to understand that this is the true miracle that Colossal Biosciences is really achieving at this point. I mean it's amazing to think about the direwolves and giant moa and woolly mammoth, but it's the animals that are currently living on our planet. They're on the brink of extinction
that's most important to protect at this point. Absolutely. There we go. Whoa, that was uh vapor-y. This thing is so cool. It's important to know for anybody that didn't quite understand that all you need is a very tiny sample of an animal. So, you guys aren't actually killing animals and taking pieces of them. You're taking live samples from live animals to be able to store that genetic information. Yeah, absolutely. Well, we've got one more stop to make. The big payoff for this tour. I'm very excited because this is something you guys are not gonna want to miss.
Okay, I have no idea what I'm walking into. They said they've they've got a surprise for me in this room. Oh, it's underneath a blanket. Um, cameras rolling. Reveal the surprise. All right. So, I'm Katie. I'm our animal care specialist here at Colossal. So, that might give you a hint at what your surprise is. Is there a mammoth in here? Oh, I wish. A baby one. Oh, it's close. This woolly mouse. What? This is it. Wow. Look at the woolly coat. That is unbelievable. So, we are looking at a genetically altered mouse. Correct. And you guys figured out how to change that genome sequence to have
the cutest, woolliest fur ever. Yes, our scientist definitely did. The base mouse that he came from had a much shorter brown, a very dark brown coat. So, you can definitely see the difference here. I'm sure everybody out there watching wants to know, how did we get to this point of being able to genetically alter a mouse to look like a woolly mammoth? Yeah. So, our scientists really wanted to prove in an animal with a shorter gestation, obviously, than an elephant where our animals would be healthy um with edits that were made. So, they chose a mouse, which we know a lot
about their genome, and to make the same edits in the same places. There are 11 adaptations here, focusing on fur color, fur length, um, and metabolism to have that cold tolerance, just like we're going to do in the elephants for the mammoth. And as you can see, um, it worked. Wow. Pocket-sized. Cutest little mouse I think anybody's ever seen. You Sometimes mice get a bad reputation. People are like, "There's a mouse in the house." And freak out like, mice this cute, I think we would probably welcome them into our lives. I hope so.
I hope people welcome mice and understand that they're not all bad. Um, they got kind of a bad rap in the media from a really long time ago, but I'm hoping our woolly mice can kind of help change that perspective a little. Well, it was so much fun getting to tour behind the scenes here today, see all the cool stuff that you guys are doing, and thank you for introducing us to the woolly mouse, cutest mouse on the face of the planet. Bye, buddy. We'll see you later. How cool is that? the woolly mouse. Getting to learn about the mammoth, the thyloine, and the aven projects here at Colossal Biosciences was incredible. Big thanks
to all the experts that took us behind the scenes to learn about the projects that they have in the works. And if you want to follow along with their projects, just follow Colossal's YouTube channel. I'm Coyote Peterson. Be brave. Stay wild. We'll see you on the next adventure.
