A bold plan to genetically create a version of the woolly mammoth, the tusked giant of the Ice Age 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 that, if released into the wild in sufficient numbers, could help restore the fragile Arctic tundra ecosystem.
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 infusion of money and subsequent publicity later that year.
There are still many challenges ahead, such as developing an artificial uterus capable of carrying an elephant calf. But Colossal Biosciences declared Wednesday that it had taken a “momentous step.”
Church and Eriona Hysolli, head of biological sciences at Colossal, revealed that they had reprogrammed cells from an Asian elephant, the closest living relative of the mammoth, in an embryonic state – 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 The team plans to publish the work in a scientific journal, but the research has not yet been peer-reviewed.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 continue to develop in the laboratory into any type of elephant cell, an important tool for researchers to model, test, and refine the numerous genetic changes they must introduce to provide the Asian elephant with the genetic traits it needs to survive in the Arctic. These include a woolly coat, a layer of insulating fat, and smaller ears.
“The beauty of cells is that they can renew themselves indefinitely and differentiate into any type of cell in the body,” explains Hysolli, 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. Because of their size, these creatures are especially resistant to cancer, for reasons that are not yet well understood. A key hurdle for the team in making the elephant cell lines was inhibiting the genes thought to confer cancer resistance.
The cellular research techniques pioneered by Colossal have opened a new avenue for saving the endangered elephant, says Oliver Ryder, director of conservation genetics for the Wildlife Alliance at the San Diego Zoo.
“The intention to produce iPSCs from elephants has been around for years. It’s been difficult to achieve,” said Ryder, who was not involved in the research. “The impact on conservation will occur in the field of genetic rescue and assisted reproduction,” she added.
Elephant stem cells are also key to the mammoth’s rebirth. Once edited to have genetic traits similar to those of the mammoth, the elephant cells could be used to make eggs and sperm and an embryo that could be implanted in some type of artificial womb. However, that 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 in 1996 to create Dolly the sheep, inserting gene-edited cells into a donated egg that would be gestated by an elephant. However, although this technology has been around for a long time, the results are inconsistent. And many wonder whether it is ethical to use endangered animals for this purpose, given the likelihood that attempts will fail.
“I think the first engineered elephant will be the biggest milestone and that may match Ben (Lamm’s) prediction of six years from 2021,” Church said. “The second thing that’s going to make us happy is having one that’s really cold-resistant. And the third thing is whether we can do it in a way that’s scalable, that doesn’t involve substitutes. That’s a distant unknown,” Church says.
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.
Church and Hysolli did not say how many genetic changes they hope to introduce into the Asian elephant’s DNA to create a mammoth-like creature capable of withstanding Arctic temperatures. Geneticists also want to engineer a tuskless mammoth so that it will not fall prey to poachers.
Colossal has long argued that mammoths, if returned to the grasslands of the planet’s northernmost reaches in sufficient numbers, 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 beneath them by trampling on grass, felling trees, and compacting snow.
A small study conducted in Siberia and published in 2020 suggested that the presence of large mammals such as horses, bison, yaks, and reindeer led to lower soil temperatures in the protected area where they were kept, compared to lands outside that limit. However, it is difficult to imagine cold-adapted elephant herds having 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 resurrect the Tasmanian tiger in 2022 and the dodo in 2023, but its work on the mammoth has been the longest in progress.