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A bold plan to genetically engineer a version of the woolly mammal, the tusked ice age giant that disappeared 4,000 years ago, is progressing, according to the scientists involved.
The long-term goal is to create a living walking elephant-mama hybrid that would be visually indistinguishable from its extinct predecessor and – if released into its natural habitat in sufficient numbers – could help the fragile Arctic ecosystem restoring tundra.
Resurrecting the extinct species has been a pet project of Harvard University geneticist George Church for more than a decade. The plan gained traction in February 2021 when Church co-founded Dallas-based Colossal Biosciences with entrepreneur Ben Lamm and received an infusion of cash and subsequent publicity glare later in the year.
Many challenging tasks remain, such as developing an artificial womb capable of carrying a baby elephant. But Colossal Biosciences said on Wednesday it had made a “significant step” forward.
Church and Eriona Hysolli, Colossal’s leader in biological sciences, demonstrated that they had reprogrammed cells from an Asian elephant, the mammal’s closest living relative, to an embryonic state — the first time stem cells had been derived from elephant cells. The team plans to publish the work in a scientific journal, but the research has not yet been peer-reviewed.
These modified cells, known as induced pluripotent stem cells or iPSCs, can be further encapsulated in the laboratory to grow into any type of elephant cell – an important tool as researchers model, test and control scores of genetic changes. to refine. giving the 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.
“So the beautiful thing about the cells is that they can renew indefinitely and differentiate into any cell type of the body,” said Hysolli, who is the company’s lead scientist on the massive 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 key hurdle for the team in making the elephant cell lines was blocking genes thought to confer that cancer resistance.
Cellular research techniques developed by Colossal have opened a new way to save the endangered elephant, said Oliver Ryder, director of conservation genetics at the San Diego Zoo Wildlife Alliance.
“The intention to produce iPSCs from elephants has been there for years. It was hard to get it done,” said Ryder, who was not involved in the research. “The impact on conservation will be in the area of genetic rescue and assisted reproduction,” he said.
For obvious reasons, naturally occurring elephant embryos are difficult to study. 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.
Woolly mammoth hybrid engineering
The elephant’s stem cells also hold the key to the mammal’s rebirth. Once the genetic traits of mammoths were edited, the elephant’s cells could be used to make eggs and sperm and an embryo that could be implanted into some sort of artificial womb. However, that will take years of work.
Given Colossal’s initial six-year deadline, the team plans to use existing cloning techniques similar to those used in 1996 to make Dolly the sheep, placing genetically edited cells in an egg a donor who would be carried by a surrogate mother elephant. However, while that technology has been around for a while, the results have been hit and miss. And many question the ethicality of using endangered animals as surrogates given the likelihood of failed attempts.
“I think the first engineered elephant will be a big milestone and that could be in line with Ben (Lamm’s) prediction six years from 2021,” Church said. “The second thing that will make us happy is that we have one that is very cold resistant. Then the third one will be if we can do it in a way that’s scalable, doesn’t involve surrogates. That’s an unknown distance out,” Church said.
The research team at Colossal has already analyzed the genomes of 53 woolly mammoths from ancient DNA recovered from fossils. The wide range of specimens from animals that lived in different places at different points in the past helped scientists understand exactly which genes make a mammal unique.
“We’ve come a long way. The quality of giant DNA is almost as good as the elephant and both of them are almost as good as (DNA extracted from) humans,” Church said.
Church and Hysolli did not say exactly how many genetic changes they expect to make to the Asian elephant’s DNA to make a mammoth-like creature that can withstand Arctic temperatures. The geneticists also want to engineer a mammoth without tusks, so that the animals do not fall prey to poachers.
Church, who has been at the forefront of work to genetically engineer pigs with organs compatible with the human body for transplant, said 69 edits can be made at one time on pigs. The number of modifications needed to make the Asian elephant cold-resistant would be more or less the same, he said.
The possible role of the resurrected mammoth
Colossal has long claimed that returning mammoths to the grasslands in the northernmost reaches of the planet would help slow the melting of the permafrost.
Some scientists believe that grazing animals such as mammoths, horses and bison kept the frozen world below before they died, as they poured down the grass, felled trees and compacted snow.
One small study in Siberia published in 2020 suggested that large mammals such as horses, bison, gecko and reindeer had lower soil temperatures in the protected area where they were kept compared to land outside that boundary. Still, it’s hard to imagine cold-adapted elephant herds making a big impact in a region that’s warming faster than anywhere else in the world, other experts said.
Colossal also announced plans to resurrect the Tasmanian tiger in 2022 and the dodo in 2023, but its work on the mammal took longer.
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