Explainer: How stem cells might see woolly mammoth de-extinction

Sometimes it takes the smallest thing to undertake a mammoth task.

That’s what researchers behind the attempts to de-extinct the woolly mammoth are hoping as they announced what they believe to be a step forward in their efforts.

One Texas-based company has made de-extinction its business. It is looking at not only de-extinction of the woolly mammoth, but also dodos and Australia’s thylacine – both hunted to extinction within the last 500 years.

The key is an announcement this week from researchers with Colossal Biosciences who say they’ve derived induced pluripotent stem cells (iPSCs) from Asian elephants (Elephas maximus).

These iPSCs are reprogrammed to be able to give rise to any cell type in the body.

It means the researchers might be able to investigate the genetic differences between the woolly mammoth (Mammathus primigenius) and their closest living relatives – the Asian elephant. They can also test gene edits without needing tissue from living animals.

First they went extinct

Woolly mammoths roamed Earth for nearly 800,000 years.

They diversified from the steppe mammoth (Mammuthus trogontherii) at the beginning of the Middle Pleistocene (770,000–126,000 years ago). They were closely related to the North American Columbian mammoth (Mammathus columbi) and DNA studies show they occasionally interbred.

Woolly mammoths were up to 3.5 metres tall at the shoulder and could weigh as much as 8 metric tons. (By contrast the Asian elephant is 2-3m and weights up to 5t.)

Mammoths are synonymous with the last Ice Age which ended about 12,000 years ago. It’s believed that a combination of a warming climate and human hunting saw woolly mammoth numbers decline.

They died out so recently that some mammoth bodies have been recovered extremely well preserved in ice and snow.

The last stronghold of the woolly mammoth was the Siberian island of Wrangel where they lived until as recently as 4,000 years ago.

When these last mammoths died, the Great Pyramids of Giza were already 600 years old. Stonehenge had been around for 1,000 years and Sumerian poets had begun compiling the works that would over the next 800 years be brought together into the Epic of Gilgamesh.

In the great scheme of geological time, we are tantalisingly close to these remarkable creatures.

A cell which might be equal to the “tusk”

The successful formation of Asian elephant iPSCs in the lab is critical to understanding how the woolly mammoth’s genetic code sets it apart from its modern counterparts.

Which bits of DNA come together to produce features like their shaggy hair, curved tusks, fat deposits and dome skulls? These are the kinds of questions scientists at Colossal now feel they can answer.

It is also possible that the iPSCs can lead to producing elephant sperm and egg cells in the lab. Anyone who’s had the “birds and the bees” chat doesn’t need to be told why that’s important in de-extinction.

Being able to create these cells in a lab is particularly important given the precariousness of Asian elephant populations.

Fewer than 50,000 Asian elephants remain in the wild according to the World Wildlife Fund. They are listed as “endangered” on the IUCN’s Red List. Attempts to retrieve egg and sperm cells from Asian elephants would be difficult and potentially adverse.

Making elephant iPSCs has been so difficult because of complex gene pathways unique to these animals. Colossal’s genetic engineers overcame this by suppressing core genes called TP53 which regulate cell growth and halt the duplicating process.

The plan from here

But the work doesn’t stop.

They’re still looking at alternative methods to create iPSCs and maturing the ones they’ve already made.

There’s also a lot still to learn about the complex 22-month gestation period of elephants if a healthy woolly mammoth calf is to be produced through in vitro fertilisation of a modern elephant.

Colossal’s plan is to have a living, breathing woolly mammoth by 2028.

For that to happen, the company is also looking into restoring suitable tundra steppe habitats in Canada and the US where the reborn mammoth population can settle.

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