Scientists are moving forward in their efforts to revive an extinct giant

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A bold plan to engineer a genetic copy of… Woolly mammothThe Ice Age giant, which disappeared 4,000 years ago, is making some headway, according to participating scientists.

The long-term goal is to create an elephant-mammoth hybrid that is visually indistinguishable from its extinct ancestor and, if released into its natural habitat in sufficient numbers, could potentially help restore the fragile Arctic tundra ecosystem.

Reviving extinct species has been a pet project of Harvard geneticist George Church for more than a decade. The plan gained momentum in February 2021 when Church co-founded Dallas-based Colossal Biosciences with entrepreneur Ben Lamm and received a cash infusion and the glow of publicity that followed later that year.

Many challenging tasks remain, such as developing an artificial womb capable of carrying an elephant baby. But Colossal Biosciences said on Wednesday it had taken an “important step” forward.

Church and Ariona Hesoli, head of biosciences at Colossal, revealed that they had reprogrammed cells from an Asian elephant, the closest living relative of the mammoth, to an embryonic state – a first. The stem cells were extracted from elephant cells. The team plans to publish the work in a scientific journal, but the research has not yet been subject to peer review.

These modified cells, known as induced pluripotent stem cells or iPSCs, can be developed in the laboratory to grow into any type of elephant cell — an important tool for researchers to use in designing, testing and improving the outcomes of the genetic changes they need to make to give the Asian elephant the genetic traits it needs to survive. Alive in the Arctic. These include a woolly coat, a layer of insulating fat, and smaller ears.

“So the nice thing about cells is that they can renew indefinitely and differentiate into any type of cell in the body,” said Hesoli, the company's lead scientist on the massive project.

The stem cells will also make it easier for conservation scientists to study the unique biological characteristics of the Asian elephant. Due to their size, these creatures have a unique resistance to cancer, for reasons that are not well understood. The team's main hurdle in making the elephant cell lines was inhibiting genes thought to confer that resistance to cancer.

Colossal's cellular research techniques have opened a new path to saving the endangered elephant, said Oliver Ryder, director of genetics at the Wildlife Alliance at the San Diego Zoo.

“The intention to produce iPSCs from elephants has been around for years. It has been difficult to achieve,” said Ryder, who was not involved in the research. “The impact on conservation will be in the area of ​​genetic rescue and assisted reproduction.”

For obvious reasons, naturally occurring elephant embryos are difficult to study. Rader said the stem cells would allow scientists to create model elephant embryos that would lift the curtain on how an elephant develops into a fetus — an “extremely valuable asset.”

Woolly mammoth hybrid architecture

Elephant stem cells also hold the key to the rebirth of the mammoth. Once elephant cells are modified to have mammoth-like genetic traits, they can be used to make eggs, sperm and an embryo that can be implanted in some kind of artificial womb. However, this will take years of work.

Initial given With a six-year deadline set by Colossal, the team plans to use existing cloning techniques similar to those used in 1996 first. Dolly the sheep, inserting genetically modified cells into a donor egg that will be carried by a surrogate elephant mother. However, although this technology has been around for a while, the results have been both hit and miss. Many wonder whether its use is ethical Endangered animals as alternatives due to the possibility of failed attempts.

“I think the first engineered elephant will be a milestone and that could be consistent with Ben (Lam’s) six-year forecast from 2021,” Church said. “The second thing that would make us happy is that we have a product that is truly cold-resistant. Then the third question will be if we can do it in a way that is scalable, that doesn't involve alternatives. That's an unknown distance,” Church said.

The research team at Colossal has already analyzed the genomes of 53 woolly mammoths from ancient DNA extracted from fossils. Extensive sampling of animals that lived in different places and at different points in the past has helped scientists understand the genes that make mammoths unique.

“We've come a long way. The quality of mammoth DNA is almost as good as elephant and both are almost as good as DNA extracted from humans,” Church said.

Church and Hessoli did not say exactly how many genetic changes they expect to make to the Asian elephant's DNA to make a mammoth-like creature capable of withstanding Arctic temperatures. Geneticists also want to engineer mammoths without tusk, so that the animals do not fall prey to poachers.

Church, which has been at the forefront of work for Genetically engineered pigs With human-compatible organs for transplantation, he said it is possible to make 69 modifications simultaneously in pigs. The number of modifications needed to make the Asian elephant resistant to cold would be broadly similar, he said.

Possible role of resurrected mammoths

Colossal has long claimed that mammoths, if they returned to the planet's northernmost grasslands in sufficient numbers, would help slow the thawing of permafrost.

Some scientists believe that before their extinction, grazing animals such as mammoths, horses, and bison kept the ground frozen beneath them by trampling grass, falling trees, and compressing snow.

One Small study In Siberia, published in 2020, notes that the presence of large mammals such as horses, bison, yaks and reindeer resulted in lower soil temperatures in the protected area where they were kept compared to the land outside those boundaries. However, it is difficult to imagine cold-adapted elephant herds having a major impact on a region that is warming faster than anywhere else in the world. Other experts said.

Colossal also announced plans for a revival Tasmanian Tiger in 2022 and the dodo in 2023, but work on the mammoth continued much longer.

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