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A bold plan to genetically engineer a version of the woolly mammoth, the tusked ice age giant that disappeared 4,000 years ago, is making some progress, according to scientists involved.
The long-term goal is to create a living, walking elephant-mammoth hybrid that would be visually indistinguishable from its extinct precursor and — if released into enough habitats — could potentially help restore the fragile Arctic tundra ecosystem.
Resurrection of 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, with plenty of cash and the publicity sheen that followed later that year.
Many challenging tasks remain, such as developing an artificial womb that can impregnate a baby elephant. But Colossal Biosciences said in a statement Wednesday that it had taken a “significant step” forward.
Church and Colossal’s head of biological sciences, Eriona Hysolli, announced that they had reprogrammed cells from the Asian elephant, the mammoth’s closest living relative, into an embryonic state; This marks the first time stem cells have been derived from elephant cells. The team plans to publish the study in a scientific journal, but the research has not yet been peer-reviewed.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 studied in the laboratory to develop into any type of elephant cell; This is an important tool for researchers to 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, an insulating layer of fat, and smaller ears.
“So the nice thing about cells is that they can potentially regenerate indefinitely and differentiate into any cell type in the body,” said Hysolli, the company’s lead scientist on the massive project.
Stem cells will also make it easier for conservation scientists to study the unique biology of the Asian elephant. For reasons that are not fully understood, creatures of their size have a unique resistance to cancer. The key obstacle to the team’s creation of elephant cell lines was blocking genes thought to provide resistance to cancer.
The cellular research techniques pioneered by Colossal open a new path to save the endangered elephant, said Oliver Ryder, director of conservation genetics for the San Diego Zoo Wildlife Alliance.
“The intention to generate iPSCs from elephants has been evident for years. “This 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 breeding,” he added.
For obvious reasons, naturally occurring elephant embryos are difficult to study. Stem cells will 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.
Designing a woolly mammoth hybrid
Elephant stem cells also hold the key to the rebirth of the mammoth. When the elephant’s cells are edited to have mammoth-like genetic characteristics, they can be used to make eggs, sperm and an embryo that can be implanted into a type of artificial womb. However, this will require years of work.
Given the initial six-year window set by Colossal, the team plans to use existing cloning techniques similar to those first used to make Dolly the sheep in 1996 and insert the genetically edited cells into a donor egg that will be impregnated by the surrogate elephant mother. However, although this technology has been around for a while, the results are hit and miss. And many people question whether it is ethical to use endangered animals as surrogate mothers, given the possibility of failed attempts.
“I think the first engineered elephant would be a significant milestone, and that would 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 a grain that is really resistant to cold. The third would be if we can do this in a scalable way that doesn’t require proxies. This is 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 samples taken from animals that lived at different points in time in different places have helped scientists understand exactly which genes make a mammoth unique.
“We have come a long way. The quality of mammoth DNA is almost as good as elephant DNA, and both are almost as good as (DNA from) humans,” Church said.
Church and Hysolli did not say exactly how many genetic changes they expected to make to the Asian elephant’s DNA to create a mammoth-like creature that could withstand Arctic temperatures. Geneticists also want to design a mammoth without tusks to prevent the animals from falling prey to poachers.
Church, who is at the forefront of genetic engineering studies for organ transplantation of pigs compatible with the human body, said that it is possible to make 69 edits in pigs at a time. The number of changes needed to make an Asian elephant cold-hardy would be broadly similar, he said.
Potential role of resurrected mammoths
Colossal has long claimed that if mammoths returned to the planet’s northernmost grasslands in sufficient numbers, they would help slow the melting of the permafrost.
Some scientists believe that before their extinction, grazing animals such as mammoths, horses and bison froze the earth by trampling grass, felling 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 led to lower soil temperatures in the protected area compared to land outside the boundary. But other experts said it was hard to imagine that cold-adapted elephant herds would have a significant impact on a region that is warming faster than anywhere else in the world.
Colossal also announced plans to resurrect the Tasmanian tiger in 2022 and the dodo in 2023, but its work on the mammoth took the longest.
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