Startup plots unlikely plan to resurrect mammoths – 08/26/2023 – Science

George Church has already helped found nearly 50 companies based on experiments carried out in his genetics laboratory, with goals ranging from finding cures for diseases linked to aging to creating pig organs to be used in human transplants.

But his most recent project, Colossal Biosciences, is his most bizarre yet. The Texas-based startup plans to launch companies and license technologies to fund the resuscitation of the extinct woolly mammoth, Tasmanian wolf and dodo.

The plan is to use gene editing to modify embryos of known animals until they resemble extinct species. By 2028, the company wants to create its first version of a woolly mammoth — an elephant embryo, born from an elephant mother but gene-edited. For Church, the timeline is ambitious but not unfeasible.

Since the company was co-founded by Church in 2021, it has raised $225 million (R$1.1 billion) from big investors and celebrities including venture capitalist Peter Thiel, entrepreneur Thomas Tull and Paris Hilton.

The company already spawned a spinoff last year, biotech software firm Form Bio, raising $30 million, and hopes to capitalize on other technologies developed along the way to help fund his monumental project.

It envisions cashing in on partnerships with media outlets that will tell the story of a project that is drawing comparisons to “Jurassic Park.”

But, according to Church, the main objective is not to work with endangered species. “We might even donate a lot of this technology in the interest of conservation and goodwill. I think the main objective is technology development.”

Church spent years saying he didn’t think anyone would want to fund his heart project — the resurrection of the woolly mammoth. But in 2015, over breakfast, Peter Thiel, co-founder of PayPal and Palantir, offered him $100,000 (R$ 498,000) for the work.

“He asked, ‘What are your three biggest dreams?’

In 2018 Church traveled to the Pleistocene Park experimental nature reserve in Siberia, where he was working with Russian scientist Sergey Zimov on a plan for mammoths to be eventually released into the wild.

Colossal believes that resuscitating mammoths could help restore the Arctic tundra by preventing thawing and the release of stored greenhouse gases.

The project faces two particular huge challenges. The first is to increase the number of genetic edits that can be done simultaneously, a process known as “multiplex editing”, to get as close as possible to creating a mammoth from an elephant embryo.

The second challenge is to create a system to incubate mammoths in artificial wombs. Matt James, Colossal’s director for animals, who joined the project after a professional career in zoos, where he specialized in caring for elephants, said the number of reproductive females in a population is always the limiting factor when looking to increase populations. endangered species populations.

“If we have an artificial uterus, suddenly we can increase the population and help it recover in a very short time,” he said.

Critics say the challenges make the project virtually impossible, or not environmentally friendly.

Matthew Cobb, professor of zoology at the University of Manchester (ING), said plans involved creating “an elephant that vaguely resembles a mammoth or a pigeon that vaguely resembles a dodo”.

“They are not reversing the extinction of any animal: they are using the power of genetic engineering, they claim, to create a strange hybrid,” he said.

Colossal said it is not trying to generate exact clones, but to create a species that has specific characteristics that make it unique.

Cobb added that it would also be difficult to build a population that reproduces, as that would require at least a few hundred animals, enough to ensure genetic diversity.

Stuart Pimm, an ecologist at Duke University in North Carolina who studies current-day extinctions, said a single woolly mammoth would struggle to survive — and a herd with enough animals would need a huge amount of space.

“If you had an isolated woolly mammoth, the only thing you could do would be put it in an enclosure. It would be revolting — you would have gone to all that effort to create something just for a peep show,” he said. “So otherwise, how many woolly mammoths would you need? You’d need 50, possibly a hundred, and you’d need a thousand square kilometers to put them on.”

James agreed that mammoths would be “highly sociable” and would need “a strong herd structure”; for that very reason, Colossal plans to create herds of genetically diverse mammoths to provide this structure. He said the company is looking to identify locations with enough space for a herd and is having discussions with some US state governments.

Colossal said it is also working with governments on ideas for preserving endangered species.

Ben Lamm, the serial entrepreneur who is Colossal’s co-founder and chief executive, said Form Bio is just the first of the company’s spinout opportunities.

Colossal created the software behind Form Bio to operate its own labs and then sold it to other biotechnology and academic labs. Lamm, who sits on its board of directors, said Form Bio is working with other companies on projects such as using machine learning to create drugs, with the opportunity to join joint ventures and share recipes.

Lamm thinks Colossal could partner with the pharmaceutical or biotechnology industry to use the new multiplex editing tools it is developing with humans. Using gene-editing techniques like Crispr, treatments are being developed for diseases caused by a single defective gene, such as sickle cell anemia. Multiplex gene editing could allow treatment of conditions caused by multiple genes.

Eriona Hysolli, director of biological sciences at Colossal, mentioned some of the possibilities of gene editing: “With multiplex editing, perhaps we can act directly on diseased cells or tissues. Perhaps we can work with multiple genes at the same time — not just single-gene diseases , but multigenic diseases like diabetes or Alzheimer’s.”

Lamm hopes the 17-person team working on the artificial wombs will create technology that can be licensed or given away to another company to help with human reproduction. “It’s a bit like Mars. A lot of people are working on it, and it’s believed that one day they will get there. I think about the same thing about extrauterine development.”

Meanwhile, Colossal is working on ways to further publicize its project and earn revenue from media partnerships.

Lamm said every major entertainment studio has approached Colossal to express interest in filming his work. Several of the company’s investors have professional media backgrounds, including Tull, former chairman and chief executive of Legendary Entertainment.

“We want to educate and inspire by creating mammoths and dodos,” Lamm said.

There may be opportunities to meet Colossal-raised animals, but James said the company has yet to decide how much access it wants to give the public.

He rejected comparisons to “Jurassic Park”. “I don’t like that comparison, because I think we’re doing this work for purposes that are not frivolous. I also think we’re probably taking more ethical considerations into account.”

But Church thinks the film did scientists a favor by encouraging people to think about what could go wrong. “He vaccinated us against certain scenarios. We are unlikely to make the same mistakes that were made in ‘Jurassic Park’. First of all because I’m not in a hurry to create colossal carnivores.”

^{Translated by Clara Allain}