Colossal Biosciences’ 2028 goal: Bringing back the woolly mammoth

Based in Austin, Texas, biotech Colossal Biosciences is at the forefront of de-extinction, critically endangered species protection and the repopulation of critical ecosystems. 

Its mission is to use CRISPR technology to bring back extinct animals, such as the mammoth, the thylacine, and the dodo.

Since DNA was recovered in 2021 from mammoths frozen in the Arctic tundra, the company has been working on splicing bits of the recovered DNA into the genome of its closest relative, the Asian elephant, as it shares 99.6% of its DNA. 

Ben Lamm, co-founder and CEO of Colossal Biosciences spoke with us about the company’s plans.

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    About Colossal Biosciences

    The seeds for Colossal Biosciences were sewn when Lamm met molecular engineer and geneticist George Church. 

    “I called him to reach out to talk about the applications to software for synthetic biology. I thought that could be my next area of interest,” Lamm said. 

    “I’m a curious person, so I did ask the question, George, if you had unlimited capital in one project that you would have to focus the rest of your life on, what would it be and why? And he said, I would bring back the woolly mammoth, reintroduce it back into the Arctic, as well as build systems that can be applied to both human health care and to conservation to save critically endangered species.”

    Lamm and Church decided to pursue the creation of a new company in late 2019, and started raising capital.  

    “Nobody had ever built a for-profit species preservation company or a de-extinction company. So, it was definitely a unique pitch to investors,” Lamm explained.

    Recreating extinct species

    Lamm said recent developments in computing, automation and artificial intelligence will transform science, pushing it toward engineering.

    “We’re not trying to synthesize full genomes. There is some DNA synthesis in what we’re doing. There’s single nucleotide editing, there’s multiplex editing, where we’re editing multiple parts all over the genome. And then the DNA synthesis and enlarged cargo swaps is something that we’re getting much, much better at. 

    “We looked at the problem first as a software problem. Colossal Biosciences is on the path to building out de-extinction while we will build some technologies for conservation, we’ll also build some technologies for human health care. And in that, we will try to monetize those companies if we feel there’s the right product market fit.”

    The first entity to be spun out of Colossal Biosciences was the gene therapy development company Form Bio. 

    Lamm said Colossal Biosciences started looking at the ancient DNA assembly that was needed. They also looked to improve the pipelines for ancient DNA, which is a different process to non-ancient and massively degraded DNA.

    Harnessing computational tools

    The company’s team used computational analysis to start to understand the differences between the closest living relatives to the extinct species being worked on, to map genotype to phenotype expressions. 

    “We saw a large need for computational analysis in the workflows that we were starting to attempt. The better we could approach the problem from an automation and AI perspective, and a data perspective was key.

    “We probably over-indexed on data in terms of the number of sequences we’ve done. But once we get to this first set of edits that we start doing, we’re using a combination of different editing tools that we do in somatic cells. We have different types of processes that we’re putting in place to test both molecular and functional assays. You know, iPSC, induced pluripotent stem cell work, is a big focus across the various species that we’re working on in our mammalian work.” 

    Lamm continued: “We are working to try to also cultivate primordial germ cells in the right media conditions in our avian work. And then once we are successful in these processes and the editing and getting the editing efficiencies and all the edits in that we want, and we’ve done the right level of testing through different tissue type derivation from stem cells. Then we go through a somatic cell nuclear transfer process to transfer the nucleus into an egg cell and then into surrogacy.” 

    What are the challenges faced by Colossal Biosciences?

    Lamm said Colossal Biosciences is working on a variety of approaches. However, as the subject is so new, there are challenges.

    “We almost think of Colossal Biosciences as a free research and development arm for conservation.”

    Ben Lamm, co-founder and CEO of Colossal Biosciences

    “There’s not exactly a playbook to work with elephants. There’s not a playbook to work with marsupials. We are working in these very interesting non-model species, so we have to optimize so much of the process for each one of these species. So cellular health is one that we’ve had to spend a lot of time on to ensure that we can get the right number of edits. 

    “Another area of challenge, but we see it as a real opportunity, is in both DNA synthesis and multiplex editing. From what we’ve seen in peer-reviewed literature, we have vastly surpassed what we’ve seen out there from a multiplex editing perspective. Being able to make multiple edits all over the genome that are not just linear repeats or knockouts, we think that has massive application to disease state, attacking different types of disease states in humans and in animals.”

    Lamm said it is important for the company to not work in a linear fashion, which would add too much time to the work they are doing.

    “We’re trying to parallel path. That’s why we have so many people. That’s why we’ve raised so much capital. We have entire embryology teams that are trying to increase everything from like cloning efficiencies in model and non-model organisms, to leveraging computer-aided and robotic-assisted somatic-cell nuclear transfer, to looking to also optimize what our throughput rate could be on editing cells, and then getting those cells into embryos and trying to optimize that as well. 

    “While we’re looking at the entire system problem, we’re tackling each one of those components of it in parallel.”

    Revolutionizing conservation through ex-utero development

    The ex-utero team at Colossal Biosciences could also have implications for future companies. 

    “If we can really crack the code on that, not only will it allow us to make more potential species, or as well as more of them so that you’re not leveraging animals, you’re leveraging ex-utero development systems. We think it’ll be a game changer for conservation. 

    “If we have the ability to grow 50 northern white rhinos ex-utero in warehouses and labs, and then work with tier one conservation and rewilding partners, put the animals back into their natural habitat, we think that’s really interesting.”

    Lamm said the fusion of synthetic biology with conservation is needed given the current biodiversity crisis that exists. 

    The importance of forging partnerships

    Partnerships are also key to moving the projects forward.

    Colossal Biosciences is working with indigenous people groups, private landowners, governments, conservation groups, and other NGOs to prepare for the potential re-introduction of species. The company recently announced a partnership with Re:wild.

    It is also working with the Mauritian Wildlife Foundation to clean up the ecosystem. This includes the removal of some invasive species. This not only helps with the reintroduction of the dodo, but also the current endemic species. 

    “The Mauritian government’s almost using the dodo as a rallying cry to update and fix the ecosystem, which we find really helpful from a conservation perspective, not just rewilding extinct species like the dodo to Mauritius and the neighboring islands, but also helping those endemic species that live there.” 

    Colossal Biosciences has similar partnerships in place with countries and organizations in the Arctic Circle, where the mammoth can be reintroduced, and in Tasmania, the original habitat of the thylacine.

    “I think that having people that are so focused on the application of our technologies to conservation is a real blessing. But I think it’s something that the conservation community needs. We almost think of Colossal Biosciences partly as a free research and development arm for conservation,” Lamm said.

    What are Colossal Biosciences’ future goals?

    Lamm explained that the company is on track for its first woolly mammoth calves in 2028.

    However, he noted: “With a 22-month gestation, it’s more than likely you would see a species before the mammoth. We’re not making any commitments to what that could or couldn’t be, but 22 months is quite some time. So, I think it’s highly likely before 2028 we’ll see something before the mammoth.”

    Explore other topics: CRISPRSynthetic biologyUSA

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