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A daring plan to genetically engineer a version of the woolly mammoth, the Ice Age tusk giant that disappeared 4,000 years ago, is making some progress, according to the scientists involved.
The long-term goal is to create a living, walking hybrid of elephant and mammoth that is visually indistinguishable from its extinct ancestor and that – if released in sufficient numbers into its natural habitat – could potentially help protect the fragile ecosystem of restore the Arctic tundra.
Reviving the extinct species has been a pet project of Harvard University geneticist George Church for more than a decade. The scheme gained traction in February 2021 when Church co-founded Dallas-based Colossal Biosciences with entrepreneur Ben Lamm and received a flood of money and resulting publicity later that year.
Many challenging tasks remain, such as developing an artificial womb that can produce a baby elephant. But Colossal Biosciences said Wednesday it had taken a “momentous step” forward.
Church and Eriona Hysolli, Colossal’s head of biological sciences, revealed that they had reprogrammed cells from an Asian elephant, the mammoth’s closest living relative, to an embryonic state – the first time stem cells have been derived from elephant cells. The team plans to publish the work in a scientific journal, but the research has not yet undergone peer review.
These modified cells, known as induced pluripotent stem cells or iPSCs, can be further teased in the laboratory to grow into any kind of elephant cell – an important tool as researchers model, test and refine the scores of genetic changes they need to make. Give an Asian elephant the genetic traits it needs to survive in the Arctic. These include a woolly coat, a layer of insulating fat and smaller ears.
“The great thing about the cells is that they can potentially renew indefinitely and differentiate into any cell type in the body,” says Hysolli, the company’s lead scientist on the mammoth project.
The stem cells will also make it easier for conservation scientists to study the unique biology of the Asian elephant. Because of their size, the creatures are uniquely resistant to cancer – for reasons that are not well understood. A major obstacle for the team in creating the elephant cell lines was inhibiting genes thought to confer cancer resistance.
Cellular research techniques developed by Colossal have opened a new path to saving the endangered elephant, says Oliver Ryder, director of conservation genetics at the San Diego Zoo Wildlife Alliance.
“The intention to produce iPSCs from elephants has been around for years. It was difficult to achieve this,” said Ryder, who was not involved in the study. “The impact on conservation will be in the areas of genetic rescue and assisted reproduction,” he added.
For obvious reasons, it is difficult to study naturally occurring elephant embryos. The stem cells would allow scientists to create model elephant embryos that will lift the curtain on how an elephant develops into a fetus — a “very valuable asset,” Ryder said.
Development of a woolly mammoth hybrid
Elephant stem cells also hold the key to the mammoth’s rebirth. Once edited to have mammoth-like genetic traits, the elephant’s cells could be used to make eggs and sperm, and an embryo that could be implanted in a kind of artificial womb. However, that will take years of work.
Given an initial deadline of six years set by Colossal, the team plans to first apply existing cloning techniques similar to those used in 1996 to create Dolly the sheep, in which genetically modified cells are inserted into a donor egg that would be carried by a surrogate mother of an elephant. But even though that technology has been around for a while, the results have been mixed. And many wonder whether it is ethical to use endangered animals as surrogates, given the likelihood of failed attempts.
“I think the first elephant constructed will be the key milestone and that could be consistent with Ben (Lamm)’s prediction of six years from 2021,” Church said. “The second thing that will make us happy is that we have one that can really withstand the cold. The third is whether we can do it in a scalable way, without any surrogates involved. That’s an unknown distance,” Church said.
Colossal’s research team has already analyzed the genomes of 53 woolly mammoths based on ancient DNA recovered from fossils. The diverse specimens of animals that lived in different places and at different times in the past helped scientists understand exactly which genes make a mammoth unique.
“We have come a long way. The DNA quality of mammoths is almost as good as that of the elephant and they are both almost as good as (DNA extracted from) humans,” Church said.
Church and Hysolli haven’t said exactly how many genetic changes they expect to make to the DNA of Asian elephants to create a creature that resembles a mammoth and is able to withstand Arctic temperatures. The geneticists also want to create a mammoth without tusks, so that the animals do not fall prey to poachers.
Church, who is at the forefront of genetically engineering pigs with organs compatible with the human body for transplants, said it is possible to perform 69 operations simultaneously on pigs. The number of adaptations needed to make an Asian elephant resistant to the cold would be broadly similar, he said.
The potential role of resurrected mammoths
Colossal has long argued that if mammoths returned in sufficient numbers to the grasslands in the planet’s northern reaches, they would help slow the thaw of permafrost.
Some scientists believe that before their extinction, grazing animals such as mammoths, horses and bison kept the earth frozen by kicking down grass, knocking down trees and compacting snow.
A small study in Siberia, published in 2020, suggested that the presence of large mammals such as horses, bison, yak and reindeer resulted in lower soil temperatures in the protected area where they were kept compared to land outside that boundary. However, it’s hard to imagine that herds of cold-adapted elephants will have a significant impact on a region that is warming faster than anywhere else in the world, other experts say.
Colossal also announced plans to revive the Tasmanian tiger in 2022 and the dodo in 2023, but work on the mammoth has already taken the longest.
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