Colossal Biosciences

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<p>Employees say:</p><p>"This organization is one of the very few outside of academia that focuses directly on biodiversity remediation and applied research. It is unique to be part of a company that dedicates itself to such a critical mission. Having the opportunity to work on projects with direct environmental and conservation impacts makes this a very meaningful place to work."</p>

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Colossal Biosciences | Fortune

Colossal Biosciences Company Profile, Stock Price, News, Rankings | Fortune

Presenter: Beth Shapiro, Chief Science Officer, Colossal Biosciences 

Brainstorm Tech 2024: How AI can bring back extinct species

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We have this field called the extinction. We are correcting our intervention in nature. Absolutely critical. Hello. So I'm an evolutionary biologist and a recovering academic until three months ago. I was a professor at UC Santa Cruz where I'm standing there beneath a blue whale at our blue whale skeleton at our southern, at our coastal campus. I ran a lab for the last 20 years where we were innovating and revolutionizing a field called ancient DNA. We'd travel out to cold places in the world and collect the remains of things like mammoths and mastodons and giant bears and wooly rhinos and extract their DNA. The goal of my research was to use that DNA to understand how species and communities and ecosystems evolve and change. With a goal to use the past as a kind of completed evolutionary experiment to make more informed decisions about how to protect living species by understanding what makes certain species more robust than others. But when you extract DNA from million year old mammoths, the conversations you have about your work often tend to go in a slightly different direction. And so in 2015, I wrote this book really laying out all of the steps that one would need to overcome if one were to bring a mammoth or some other extinct species back to life. My goal was to lay out the technical ethical ecological regulatory challenges that we would have to solve, but also to highlight how transformative this technology would be for the conservation of living endangered species. And then about seven years after I published this book, Ben Lamb and George Church co founded a company called Colossal with the goal to do exactly what I had played out in the book. And so of course, Ben called me and said you should join us. You wrote the playbook and I was a little hesitant, I joined as a consultant, I wanted to see how far they could get in pushing along this technology. And I was immediately surprised, excited, really enthusiastic by, by how far they able to get in such a short amount of time. And then a few months ago, I decided to take the D and I am now colossal s Chief Scientific Officer. Colossal goal is to make extinction a thing of the past to use the tools of gene editing genetic engineering to replace missing components of ecosystems, to help these ecosystems to become more robust and resilient. Given the dramatic upheavals that are happening to habitats across the world. Today, we've launched three de extinction projects. Mammoth Dodo and Thylacine, which is also sometimes called the Tasmanian Tiger. The choice of these three species is purposeful. We have a marsupial mammal, a placental mammal and a bird. And as we develop the technologies to bring these species back to life, these technologies will have immediate applications to helping species pretty much across this animal diversity to survive and adapt in the climate of today. Core to the core to colossal s mission is this idea of de extinction. And when most people think of the extinction, one very specific image comes to mind, but this is not what we're doing. First of all, I'm a scientist, so I have to break down the science a little bit. Dinosaurs went extinct more than 65 million years ago. The oldest DNA that we've so far is somewhere between one and 2 million years old, but most DNA degrades away by about 10 or 20,000 years. Dinosaur fossils are rocks and rocks don't have DNA. It is also not possible to recover DNA from mosquitoes preserved in amber. I've tried it, it doesn't work amber. It turns out is a really poor environment for DNA preservation. It forms in very hot places which encourages speeding up of DNA decay. And also it's porous, which means that microbes can get in there and chew up the DNA really quickly making it disappear. There's no DNA in mosquitoes in amber. There's no DNA in dinosaur fossils. Dinosaur distinction is not going to happen. I'm very sorry. Right. Sorry. But this is not the plan. The other thing that the scientists, the Jurassic Park did was they took these tiny little short fragments of DNA and then they filled in the missing bits that they could get with frog DNA, which is a weird choice given that even at the time, we already knew that birds are dinosaurs, right? But whatever, and then they put the dinosaurs in habitats that they were completely maladapted to and chaos ensued. This is not what we want to do instead, what colossal is doing is rebuilding extinct species. For the present day, we will identify these core traits that make these animals unique and important components of their ecosystems. In some cases, we will augment these traits because ecosystems of today are different from the past. And when necessary, we will add additional evolutionary adaptations to these animals. Lots of habitats right now and species are suffering because of introduced diseases or introduced predators. And we can use the tools of genome editing to make these species resistant and resilient, creating different spec see in the form of these extinct species. This is our definition of de extinction. If we look at the mammoth project, for example, all we're going to do is start with something that already exists. An Asian elephant is the closest living relative of a mammoth. They shared a common ancestor about 6 million years ago. Their genomes are already 98% identical. So when we have an Asian elephant cell growing in a dish in a lab. We already have 98% of a mammoth. We just have to engineer the remaining 2%. So how do we do that? This is a bit of an oversimplification. Pretty good for a walk through. We go out into the fields. My sites in Siberia, Alaska, Yukon, we collect mammoth DNA. We've done this already. We have hundreds of mammoth genomes. We can line them up on a computer next to each other. Collect a bunch of Asian elephant genomes, line them up against the mammoth genomes and identify where they are different from each other and yet where all of those mammoths are the same as each other. These are the portions of the mammoth genome that are important to make a mammoth look and act like a mammoth. Then we use the tools of genome editing to gradually tweak those Asian elephant cells growing. In addition, a lab to be more mammoth like. Then we have our mammoths, Asian elephant cells in addition to a lab. Then we use somatic cell nuclear transfer. A process commonly known as cloning that most famously brought us dolly the sheep to transform those cells into an embryo. And then we implant that embryo into a surrogate maternal host that embryo develops and builds into a beautiful, wonderful little mammoth size Asian elephant and it is born and it looks and acts like a mammoth and it lives happily ever after pretty straightforward right. What's exciting to me about all of this? Clearly, this is hard and there are a lot of hard problems that are here. But the core technologies exist for each of these steps and as we improve on these technologies and make them applicable to non model organisms, things that aren't mice or fruit flies, we will develop and innovate across all sorts of disciplines that have clear application to other biological disciplines. Advances in bioinformatics that allow us to map a DNA sequence or genotype to the way an animal looks or acts of phenotype. Advances in multiplex genome editing or the assembly and insertion of long synthetic DNA constructs, advances in animal reconduct animal reproductive biology and cloning. These all have application to agriculture, to livestock engineering, to animal husbandry and to human health. If we just think about the mammoth team, for example, this team has already made more stably integrated edits into a cell line that is stereotypically normal and therefore capable of being cloned than any publication in the academic literature. To date. A few months ago, they announced that they had generated induced pluripotent stem cells for elephants. A global first. This is important both for elephant conservation and for de extinction. It means that we can take these induced pluripotent stem cells and transform them into all different types of tissues and organoids and use these to test hypotheses about the edits that we're making without having to use animal models. We may even be able to grow our own elephants eggs to use for cloning. Another innovation that is along our path to elephants. The extinction is to eventually have an artificial womb that we can use to avoid the use of elephants as surrogate hosts. This requires developing platforms for fully exogenous embryonic development. And our teams of engineers and developmental biologists have been building several platforms to work with both placental and marsupial mammals. As we discover all of the cues, hormonal physiological environmental that are responsible and necessary for the development of different tissue types and organs throughout the process of embryonic development. This will also have application to regenerative medicine to personalized medicine. Imagine we can grow your own kidney from your own cells and of course, to understanding the biology of pregnancy, our animal operations team is already making incredible discoveries that are helping endangered species. Today, collaboration with the nonprofit bio rescue. We are working to save the Northern white Rhino from becoming extinct. Today, only two northern white rhinos are alive. A mother daughter pair, both females. Obviously, this would make it difficult for northern white is to reproduce. However, by isolating egg cells from these females and fertilizing them with sperm from northern white rhinos that died some 10 to 20 years ago, we've created embryos that are being used for embryo transfer into Southern white rhinos as surrogate hosts, creating a path for northern white rhinos to reproduce even though there are no males alive today. Our conservation team is also sitting in the development of a vaccine to help save baby elephants from a virus, elephant, endothelial tropic and herpes virus. That is the leading cause of death of Asian elephants, juvenile Asian elephants in captivity and increasingly in the wild. And a few weeks ago, our partners at the Houston Zoo administered this vaccine to a baby elephant for the first time, a huge win for conservation and also for elephants in general. But this is not all that the tools of de extinction can do for the conservation of living animals. A few weeks ago, I was in Mauritius, the island's home of the extinct dodo and the critically endangered Mauritian pink pigeon. Discussing what we might do using the tools of the extinction to help save the and pink pigeon from becoming extinct. Pink pigeons are in trouble because they nearly went extinct and have been managed heavily since that time. They are suffering from the consequences of inbreeding the lost of genetic diversity that's caused by breeding with close relatives where there aren't that many individuals left. You really don't have a choice. What we can do is we can use our bioinformatics tools to discover where in the pink pigeon genome, these mutations that are reducing the fitness of these birds are, we can go to museum collections and sequence genomes of pink pigeons that used to be alive and then replace the parts of the genome that are making these animals less fit with extinct diversity that will actually help them to become more robust and healthy. This is just some of the ways that the tools of the extinction can be applied both to resurrecting extinct diversity and extinct species, restoring missing components of ecosystems and making these ecosystems and communities more robust. It is clear that we are in the midst of a biodiversity loss and extinction crisis around the world. The rate of extinction today is more than 1000 times greater than the baseline rate of extinction in the fossil record. The acute problem that species and habitats are suffering today is that the pace of change is faster than evolution is capable of keeping up with. Ideally, we could all take a step back and give the species and communities and habitats of the world, the space and time that they need to catch up and adapt. But we can't, it's too late and the human footprint is too big. But the tools of the extinction provide hope we can engineer missing diversity, we can replace missing components of ecosystems, we can bring back, we can be extinct, missing phenotypes, missing interactions, even missing entire species creating robust and healthy habitats. It is obvious to all of us that extinction is a colossal problem. It's obvious to me and hopefully now to you that the tools of the extinction will be part of the solution.

Colossal Biosciences

Colossal Biosciences in Fortune Rankings

Colossal Biosciences in Fortune Rankings

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