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Colossal Begins Ambitious De-Extinction Plan With Elephant Sequencing Project, Despite Critics


NEW YORK – Bioscience and genetics startup Colossal made headlines around the world last month when it revealed its intentions to bring the woolly mammoth back from extinction. But underneath that sensational plan lies a mission that's slightly more nuanced, beginning with the goal of genetically preserving endangered species for the benefit of future generations.

Last week, Colossal said it has partnered with and will fund the Vertebrate Genomes Project on the world's first effort to sequence, assemble, and annotate the genomes of all three species of the existing elephant lineage: the Asian elephant (Elephas maximus), the African elephant (Loxodonta africana), and the Forest elephant (Loxodonta cyclotis). These high-quality genome assemblies will be as complete and error-free as possible, and will be made publicly available.

Colossal said that this will be the first of many species preservation and extension efforts it plans to engage in. In addition to funding previously non-sequenced species in collaboration with the VGP and other groups, the company will pursue and fund the sequencing and resequencing of individuals from select species that are categorized as endangered or critically endangered by the environmental preservation group, the International Union for Conservation of Nature.

Indeed, behind Colossal's announcement last month was a plan to develop a practical, working model of de-extinction, with the goal of returning extinct species to their original habitats so they can revitalize lost ecosystems for a healthier planet.

With respect to the mammoth, the company said that once it has enough of the ancient animals, it plans to repopulate the tundra with them. Company cofounders — technology and software entrepreneur Ben Lamm and Harvard geneticist George Church — believe this could potentially revitalize the Arctic grasslands, which in turn could help combat climate change through carbon sequestering, methane suppression, and light reflection.

"We're very passionate about the application of the technologies that we're building for thoughtful, disruptive conservation and captive breeding, protecting habitats, and anti-poaching [efforts]," Lamm said. "The reason why we wanted to start with the mammoth is there's a close-enough living relative — the Asian elephant — that we can get samples from. The Asian elephant is 99.6 percent mammoth already. So, our goal is not to necessarily bring back the woolly mammoth — we're bringing back a functional woolly mammoth."

The idea, Lamm said, is to take existing mammoth DNA samples and put those genes into Asian elephant cell lines to create a functional mammoth species that exhibits not only the phenotypes that are associated with the mammoth — long shaggy fur, the woolly fat packs, and the tusks — but also, importantly, have the mammoth's cold tolerance.

He described the method as using synthetic biology to express the mammoth genes of interest inside an Asian elephant's genome, calling it "genetic reconciliation."

This would have the benefit of creating a new, possibly stronger mammoth, as the ancient genes would essentially be grafted onto those of a modern descendant species. It would also benefit the elephant, Lamm said, which itself is endangered.

"If you look at what we're calling species extension, we're allowing the elephant lineage to now exist in [what was] its ancestral domain," Lamm said. "The byproduct of that, because elephants are incredibly efficient at knocking down trees, traversing large distances, and being geoengineers to their environment, they also have this halo effect being incredibly helpful to Arctic rewilding and restoring the Arctic grasslands."

One of the company's major goals is to bring awareness, new interest, and new funding to conservation efforts, he added. Declaring an intent to repopulate the Arctic with the woolly mammoth certainly does get people talking. Whether it will bring conservation groups more money has yet to be seen, but it did bring Colossal $15 million in seed funding.

Lamm said the firm will use that money to further develop and scale the new tools it needs to fulfill its "mammoth hybrid" and de-extinction missions. As part of its collaboration with the VGP, Colossal is aiming to produce population sequence data on 100 African and Asian elephants to record and understand extant elephantid population genomes.

Colossal will also sponsor research in Church's lab at Harvard Medical School, with the aim of creating the elephant-mammoth hybrid. The partners are hoping that the project will also yield technological advances in multiplexed genetic engineering, synthetic biology, and other emerging areas of research.

Those new tools, once fully developed and put into regular practice, have the potential to benefit other species that are currently on the brink of disappearing, like the northern white rhinoceros — of which there are only two left in the world — or the Sumatran rhinoceros — whose numbers are down to about 30 to 80.

According to Eriona Hysolli, Colossal's head of biological sciences, the tools Colossal needs largely already exist. "We have genome engineering tools, we have cloning and somatic cell nuclear transfer protocols, we have artificial wombs, and we have in vitro development and stem cell biology," she said.

Hysolli worked as a postdoctoral fellow in the Church lab from 2015 to 2021, where she focused on developing and optimizing novel genetic tools for multiplex mammalian genome engineering, including mammoth de-extinction and building a virus-resistant human cell line.

The researchers are planning to analyze genome sequences from elephants and woolly mammoths in order to model what a self-sustaining population of cold-tolerant elephants or functional mammoths could look like. She noted that they're fortunate enough that the permafrost is full of mammoth DNA samples, giving them a lot of starting material. The researchers will also have an entire range of genome editing tools to make specific changes in the mammoth genes for more efficient insertion into the elephant cells.

Finally, she noted, artificial wombs will allow the company to move towards a model of non-in vivo gestation.

"In order to actually be able to restore an ecosystem, we need to grow a lot of woolly mammoths," Hysolli said. "So we're hoping to grow these animals into gestation in vitro rather than using closely related relatives."

Indeed, Lamm said, the company now largely faces issues of scale and engineering challenges. "Really, the hard engineering is how do we produce and get to the point that we have herds of 500-plus mammoths that we can successfully rewild, and how do we do that in a way that is effective for an Arctic rewilding? So those are more engineering challenges in hardware and software, rather than true science challenges."

Skeptics have their say

Those aren't the only issues Colossal is facing — there's also the question of whether what they're doing is ethical. After all, the mass revival of a long-dead species (whether it's a pure mammoth or an amalgamation of mammoth and elephant) could have consequences for the entire planet. And if Colossal's mission with the mammoth does indeed go to plan, what animal will they revive next?

(Lamm did note that although the company has received several letters from people who are scared of Colossal's intentions to reinterpret the movie Jurassic Park, the company has no intentions to bring back dinosaurs.)

NYU bioethics professor Arthur Caplan, for example, is highly skeptical of Colossal's plan. He was particularly leery of the idea of putting the mammoth back into the Arctic, as the habitat may not be able to sustain a large herd of mammoth in terms of the diet they'd need to survive. "Just because it's cold, doesn't mean that's where they used to live," he said.

Caplan also called out the company's idea of creating a hybrid of the mammoth and Asian elephant, saying it would change the nature of the animal altogether. He worried that this might have a psychological impact on the animals — elephants are known to be particularly smart, so changing their nature and isolating them in the Arctic might be harmful to them, he said.

But he was most skeptical about the idea of using the new animal as a kind of stop-gap to climate change, calling it "ridiculously silly," and speculating that the small number the company might be able to produce would likely have no impact on the climate at all.

Colossal would do better in helping the environment by applying its tools to developing something like an effective gene drive, Caplan said.

"If you really want to do some good for the climate, you might find [that] it's possible to get rid of malaria by gene drives, and then have people go back to work more and stop spending so much of their economy sick and in bed and wasting potential industrial output."

He also said that the company's de-extinction mission would be more convincing if it was aimed at reviving species that are currently critically endangered or have recently gone extinct. In any case, it's critically important for the company to seek out and listen to the advice of ethicists who aren't paid by it, aren't on its advisory board, and aren't connected to it in any way, he added.

Lamm said Colossal hasn't currently set any hard limits on itself as to how far back in time it would go to de-extinct any given species, preferring to think of how it would choose a species for de-extinction more in terms of the value that species could provide to the environment if it were brought back. However, he added, the firm has sought, and continues to seek, the advice of several bioethicists, one of whom is on its scientific advisory board and some of whom are adamantly against de-extinction. It has also had internal conversations about the parameters it would use.

Lamm noted that the firm is very focused on the unintended consequences of its work. The good news is, he added, is that at the speed and scale at which Colossal is working, there's plenty of time to have those conversations, and nothing is going to happen overnight. Colossal is also committed to listening to negative feedback and learning from it.

Hysolli added that multiple questions must be asked before a decision is made on the revival of any given species. For example, not only should a species have ecological and geo-engineering value for the planet, but its habitat must also essentially still exist.

Some species no longer have a functioning ancestral habitat, so questions would have to be asked where those animals would live if they were brought back, and how they might disrupt the natural ecosystem. And for other species, like those that died out millions of years ago, there may not be any DNA to sequence, "for people who always would like to think about bringing back Jurassic Park," she added.

But while Tyrannosaurus rex isn't in Colossal's plans, Lamm is already considering another ancient species for possible revival once the mammoth project is done: the ancient woolly rhino, which he said is genetically and phylogenetically closely related to the Sumatran rhino.

"Once we're successful with the mammoths, we can apply some of the lessons learned in cold tolerance to other species, like rhinos," Lamm said. "It may be possible."