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A view of a life-size woolly mammoth is on display at The Box museum in Plymouth, UK.
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A bold plan to genetically engineer a version of the woolly mammothThe fanged ice age 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 elephant-mammoth hybrid that is visually indistinguishable from its extinct predecessor and, if released into the wild in sufficient quantities, could help restore the fragile Arctic tundra ecosystem.
Resurrecting 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 glowing publicity later that year.
Many challenging tasks remain, such as developing an artificial uterus capable of carrying an elephant calf. But Colossal Biosciences said Wednesday it had taken a “momentous step” forward.
Church and Eriona Hysolli, director of life sciences at Colossal, revealed that they had reprogrammed cells from an Asian elephant, the closest living relative of the mammoth, 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 The team plans to publish the work in a scientific journal, but the research has not yet been peer-reviewed.
These engineered cells, known as induced pluripotent stem cells or iPSCs, can be teased in the lab to become any type of elephant cell, an important tool as researchers model, test and refine the genetic changes they need to make. to 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.
John Davidson
Geneticist Eriona Hysolli is head of biological sciences at Dallas-based Colossal Biosciences.
“So the beautiful thing about cells is that they can potentially renew themselves indefinitely and differentiate into any type of cell in the body,” said Hysolli, who is 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 exceptionally resistant to cancer, for reasons that are not well understood. A key hurdle for the team in creating elephant cell lines was inhibiting genes thought to confer that cancer resistance.
The cellular research techniques Colossal pioneered have opened a new avenue for saving the endangered elephant, said Oliver Ryder, director of conservation genetics for the San Diego Zoo Wildlife Alliance.
“The intention to produce iPSCs from elephants has existed for years. It’s been difficult to achieve,” said Ryder, who was not involved in the research. “The impact on conservation will be in the field of genetic rescue and assisted reproduction,” he added.
For obvious reasons, it is difficult to study naturally occurring elephant embryos. 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.
Colossal courtesy
A line of Asian elephant stem cells dyed in different colors to highlight different elements.
Elephant stem cells also hold the key to mammoth rebirth. Once edited to have mammoth-like genetic traits, the elephant’s cells could be used to produce eggs, sperm, and an embryo that could be implanted in some type of artificial womb. However, that will take years of work.
Given an initial Within Colossal’s six-year time frame, the team plans to first employ existing cloning techniques similar to those used in 1996 to make doll the sheep, inserting gene-edited cells into a donated egg that would be gestated by a surrogate mother elephant. However, while that technology has been around for some time, the results are unpredictable. And many wonder if it is ethical to use endangered animals as substitutes given the likelihood of failed attempts.
Christopher P. Michel
Harvard University geneticist George Church is co-founder of Colossal Biosciences.
“I think the first designed elephant will be the most important milestone and that may 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 is really cold resistant. Then the third will be whether we can do it in a way that is scalable, that doesn’t involve substitutes. “That’s an unknown distance,” Church said.
The Colossal research team has already analyzed the genomes of 53 woolly mammoths using ancient DNA recovered from fossils. The wide variety of animal specimens that lived in different places at different times in the past helped scientists understand exactly what 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 extracted from) humans,” Church said.
Church and Hysolli did not say exactly how many genetic changes they hope to make to the Asian elephant’s DNA to create a mammoth-like creature capable of withstanding arctic temperatures. Geneticists also want to engineer a mammoth without tusks, so that the animals will not fall prey to poachers.
Church, who has been leading the work to genetically modified pigs with organs compatible with the human body for transplants, stated that it is possible to carry out 69 editions at the same time in pigs. The number of modifications needed to make an Asian elephant cold-hardy would be very similar, he said.
Colossal has long claimed that mammoths, if returned in sufficient numbers to the grasslands in the northernmost reaches of the planet, 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 by trampling grass, felling trees and compacting snow.
One small studio in Siberia published in 2020 suggested 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 that boundary. However, it is difficult to imagine herds of cold-adapted elephants having a significant impact in a region that is warming faster than anywhere else in the world. other experts have said.
Colossal also announced plans to resurrect the Tasmanian Tiger in 2022 and the dodo in 2023, but their work on the mammoth takes longer.