Colossal Biosciences revived the dire wolf by extracting 72,000-year-old ancient DNA and editing gray wolf genomes to match key extinct traits. Restoring apex predators like this can stabilize entire ecosystems — just as wolves reshaped Yellowstone's rivers, forests, and wildlife.
Everyone likes to talk about the climate crisis, but we are actually in a biodiversity crisis, and that's absolutely critical to our way of life. So, if all of these species go extinct, then we'll have full ecosystem collapse. Some scientists have estimated that by 2050, half of all species that are alive today will be extinct. The truth is that extinction happens. Extinctions have happened throughout evolutionary history, but right now the rate of extinction is estimated to be 1000 to 10,000 times faster than the base rate in the fossil record. And a lot of that is our fault. We need a solution. Colossal is the world's first de-extinction company, and we combine de-extinction with species preservation, and our goal is to make extinction a thing of the past. People think it's a scary word: de-extinction. They immediately put up with Jurassic Park, and it's not. We're trying to develop these new techniques in order to save animals, in order to bring back animals that, in some cases, were our fault that we don't have them any longer. It wasn't a climate problem, it was a human problem. I think we all share the deep concern about what's happening to biodiversity, what's happening to the planet, what's happening to people whose lives have been intertwined with wild nature since before time began. And so coming together is so exciting because I think that's how we can really drive change. We're finding solutions to restore a species back to the wild. The purpose of that is to serve an ecological function. As we lose species within an ecosystem, if you think of a Jenga puzzle, you're sort of pulling blocks out of there. Those blocks that are creating the instability in the ecosystem is literally the function that animal plays. If we can find ways to restore animals that provide that specific function, we can create more stability within an ecosystem. We've announced three species: the wooly mammoth, the thylacine and the dodo. But one of the things that's absolutely critical to ecosystems is predators, as we've seen with what's happened in Yellowstone, with the reintroduction of wolves back into the park. They've shown that they've even reshaped the river systems. They’ve brought back beavers, they’ve brought back songbirds. And so we felt that it was very important for us to bring back the dire wolf, dire wolf, dire wolf. The dire wolf is the first species that we're bringing back at colossal. So the dire wolf, which most people think is just a mythical creature, was actually a keystone species that was not only endemic to the United States and most of the America's, but it was actually culturally important to some of the biggest indigenous early tribes in America. So we thought if we could use it as an opportunity where we can also develop technologies that can help wolves, we thought it was the right first project, given how important wolves are to ecosystems. One of the challenges when we started working on the dire wolves was that we knew of only two dire wolf specimens in the world that contained some usable DNA. One of our dire wolf samples was a single tooth, and then another was a 72,000 year old skull. So we were able to use these specimens and isolate this ancient DNA out of them. For the dire wolf, there was a massive study that did many samples across multiple institutions, and Colossal took two of those samples and was able to generate whole genome sequences from each. And so this is incredible for any species, let alone species that have been extinct. So what you can do is you can map that to its closest living relative. So at Colossal we're using the gray wolf, and we've been able to generate such a high quality genome that we can map back to create our own dire wolf reference genome. When we edit different lines of genetically diverse gray wolves, we'll create a set of genetically diverse dire wolves with similar edits, but the basis of their diversity already existed within the gray wolf. Gray wolves are on the endangered species list, and that means you can’t just go in and collect the samples that we want. Typically, people have to take an ear punch or a skin biopsy, and sometimes it's a very invasive process for the animal. We've developed a technology where you can take a simple blood draw, isolate these specific cells in the blood, and then clone from it. We're changing the genome of this living animal partially into the genome of the extinct animal. For those genes that matter, for the traits and characteristics that we want to see in that animal. Discovering which parts of the genome make an animal look and act like that animal is one of the hardest problems in biology. It is unsolved and something that we have to solve. If we want to know which parts of the genome we want to edit to make a gray wolf more like a dire wolf. To analyze our genomes, to compare direwolves with gray wolf genomes, we use our tools on a platform built by FormBio, it’s a bioinformatics company that's spun out of Colossal. They built this whole suite of analysis tools and algorithms that allow us to find the differences between the dire wolf genome and the gray wolf genome and filter out these differences that we actually want to edit. And so we aligned our dire wolf reads to the gray wolf genome, that allowed us to know exactly where the gray wolf differed from the dire wolf. One of the most exciting differences that we found in the dire wolf genome is that there is a change in the LCORL gene, and LCORL is a key regulator of animal size. Next, we have to use gene editing technologies. We have cells growing in a dish in a lab that belong to a gray wolf. And so these have gray wolf genomes. And we've decided which part of that genome we want to change. So one at a time we take our gene editing tools and we go into that cell and we cut out the bit of DNA that looks like a gray wolf and paste in its place the DNA that looks like a dire wolf. Each time you edit a gene in a cell, you put a lot of stress on that cell because you have to get your gene editing tools in these cells, and then these changes are made. So what we do instead is we try to make dozens or hundreds of changes at once. It's called multiplex gene editing. So now we have cells growing in a dish in a lab that have DNA that makes them a little bit more dire wolf-like than gray wolf-link. We have to transform these living cells into actual pups. And for that, we use a process called cloning or somatic cell nuclear transfer. This is the same process that most famously brought us Dolly, the sheep. You take an egg, an oocyte from a wolf or a dog, you take out its own DNA and you stick that direwolf cell in it. That cell becomes an embryo that's a dire wolf. It's no longer a domestic dog, which sounds totally science fiction. And with the help of a vet team, we then are able to surgically put this embryo back inside to the surrogate dog. We have to find an appropriate dog that can carry our dire wolf. Everyone is thinking very critically about each step so that when that pup is finally born, we know there aren't any issues. The safety of all of our surrogates for any of our species is the highest priority. We have an overemphasis on our animal husbandry team to secure their safety, as well as our pursuing on the science side, our own exogenous development team, so that one day we won't have to use surrogates. The most exciting part is when the vet team comes in, they do their ultrasound and they say, yeah, congrats, you're going to be a puppy mom. or, you know, you're going to have a cub on the ground in a couple of weeks. After the pups are delivered, there's a care team in place. They're there to make sure that our dire wolf pups are happy and healthy and that mom has gone through delivery without any problems. And then we have another team that will ensure that our pups have the right dynamics, they have the right social structures. We're working actively right now with partners today to make sure that there are solutions in place for these animals to go in the future. And it's really important to say that all of this is done in this massive network. It's critical to work with private landowners, local governments, indigenous people groups and the public at large to do that in a way that's safe and publicly accepted, but also what's good for the ecosystem and the animals themselves. What we're doing is having all of this collaboration in place well before we have these animals, and this is absolutely critical to making this work successful. We're a part of the evolutionary stream of the planet. We're kin to every other species out there. And so because we have the ability to shape the world, I think we have a responsibility to correct our mistakes from the past. What we do today is, I think, what the hope for the future is for biodiversity and for nature. And so to be on sort of the ground floor of creating the tool that will be the solution for our biodiversity crisis, is the most motivating thought that I could ever have. What we're doing at Colossal has never been done before. I hope everyone around the world is leveraging the technologies that we develop here, and I hope that biodiversity loss and extinction is just a thing of the past. The idea of being able to have dire wolves again is tremendously personally exciting, and I think it's going to be exciting to a lot of people. The first time I see a dire wolf, oh my God. Dire wolf’s a big fluffy dog that I probably wouldn't pet. I think it's going to be amazing in a lot of ways. I'm really excited to see the birth of this dire wolf pup, and all the hard work that all of the teams have contributed to. There's so many people that have had their hand in this that it's just fulfilling for us to see, okay, we did it. We produced something that is magnificent and science fiction at its finest.