Scientists are making progress in efforts to revive an extinct giant

(CNN) — A bold plan to genetically create a version of the woolly mammoth, a toothed Ice Age giant that disappeared 4,000 years ago, is moving forward, according to the scientists involved.

The long-term goal is to create a living elephant-mammoth hybrid that is visually indistinguishable from its extinct ancestor, which, if released into the wild in sufficient numbers, could help restore the fragile Arctic tundra ecosystem.

The resurrection of this extinct species has been the central project of Harvard University 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 an investment of money and subsequent promotion later that year.

There are still many challenges ahead, such as developing an artificial uterus capable of carrying baby elephants. But Colossal Biosciences announced Wednesday that it has taken a “significant step.”

Ariona Hisoli, head of biological sciences at Church and Colossal, revealed that they had reprogrammed the cells of an Asian elephant, the mammoth’s closest living relative, in the embryonic stage – the first time stem cells have been obtained 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 The team plans to publish the work in a scientific journal, but the research has not yet been peer-reviewed.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 grow into any type of elephant cell in the laboratory, allowing researchers to model, test, and refine a number of genetic changes. There is an important equipment that they have to introduce to provide the Asian elephant. Genetic traits necessary for survival in the Arctic. These include a woolly coat, a layer of insulating fat, and small ears.

“The beauty of cells is that they can renew themselves indefinitely and differentiate into any type of cell in the body,” explains Hisoli, the company’s lead scientist on the Mammoth project.

The stem cells will also make it easier for scientists to study the unique biology of the Asian elephant. Due to their size, these organisms are particularly resistant to cancer, for reasons that are not yet well understood. A major hurdle for the team in creating the elephant cell lines was disrupting the genes that confer cancer resistance.

Oliver Ryder, director of conservation genetics for the Wildlife Alliance at the San Diego Zoo, says the cellular research techniques pioneered by Colossal have opened a new path to saving endangered elephants.

“The idea of ​​creating iPSCs from elephants has been around for years. It is difficult to achieve,” said Ryder, who was not involved in the research. “The impact on conservation will be in the areas of genetic rescue and assisted breeding,” he said.

For obvious reasons, natural elephant embryos are difficult to study. The stem cells will allow scientists to create model elephant embryos that will provide information about how an elephant develops into an embryo, a “very valuable asset,” Ryder said.

A row of Asian elephant stem cells colored in different colors to highlight different elements.  (Courtesy of Colossal)

A row of Asian elephant stem cells colored in different colors to highlight different elements. (Courtesy of Colossal)

Creation of woolly mammoth hybrids

Elephant stem cells are also key to the mammoth’s regeneration. Once edited to have the same genetic properties as the mammoth, the elephant’s cells could be used to create eggs and sperm and an embryo that could be implanted into some type of artificial womb. However, this will take years of work.

Given the initial six-year timeline set by Colossal, the team plans to first employ existing cloning techniques, similar to those used to create Dolly the sheep in 1996, using gene-edited cells from a donated Will be inserted into the egg which will be fertilized by an elephant. However, although this technology has been around for a long time, results have been inconsistent. And many wonder whether it is ethical to use endangered animals for this purpose, given the likelihood that the efforts will fail.

“I think the first engineered elephant will be the biggest milestone and it may match Ben (Lam)’s six-year prediction from 2021,” Church said. Church says, “The second thing that would make us happy is that it’s really cold resistant. And the third thing is can we do it in a way that’s scalable, that doesn’t involve options. That’s right now is still unknown.” ,

The Colossal research team has already analyzed the genomes of 53 woolly mammoths using ancient DNA obtained from fossils. The wide variety of samples from animals that lived in different places at different times in the past helped scientists understand exactly which genes make a mammoth unique.

“We’ve 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 Hisoli did not say 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 create a toothless mammoth so that it does not become prey to hunters.

Church, who has been at the forefront of genetic engineering of pigs with organs compatible with the human body for transplant, said it is possible to make 69 modifications to pigs at once. The number of modifications needed to make the Asian elephant cold-resistant would be very similar, he said.

Possible role of revived mammoths

Colossal has long argued that if mammoths returned in sufficient numbers to the grasslands of the northernmost part of the planet, they would help slow the melting of permafrost.

Some scientists believe that before their extinction, grazing animals such as mammoths, horses, and bison kept the land beneath them frozen by trampling grass, cutting down trees, and freezing snow.

A small study conducted in Siberia and published in 2020 showed that the presence of large mammals such as horses, bison, yak and reindeer led to lower soil temperatures in the protected area where they were kept, compared to the land outside them. Compared to. That limit. However, it is difficult to imagine that a herd of cold-adapted elephants would have a significant impact in a region that is warming faster than any other part of the world, other experts have said.

Colossal also announced plans to revive the Tasmanian tiger in 2022 and the dodo in 2023, but its work on the mammoth has been in progress the longest.

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