Reprogramming elephant cells into stem cells. Scientists have been trying for years. Without success. The team at Colossal Biosciences has just succeeded. And this could advance their project to resurrect woolly mammoths.
De-extinction. That’s the somewhat crazy goal pursued by the American Colossal Biosciences startup. That of resurrecting an extinct species. The woolly mammoth (Mammuthus primigenius), in this case. An animal that no one has seen alive for thousands of years. And their scientists have just announced a “significant step” towards success.
To understand, it is useful to specify that Colossal’s real goal is to give life to an Asian elephant (Elephus maximus) hybrid resistant to the cold. An elephant with small ears, a domed head, a thick coat, and a little more fat. Like a woolly mammoth. And to achieve this, a key step: successfully reprogramming elephant skin cells to behave like embryonic cells. These cells, which scientists call induced pluripotent stem cells (iPS), can differentiate into any type of cell in an animal.
Years of Work to Obtain Elephant Stem Cells
Almost 20 years ago, researchers showed that it was possible with mice. Then, they created induced pluripotent stem cells from white rhinos, monkeys, snow leopards, and ptarmigans. But of all the teams that tackled the elephant problem, none succeeded. The complex genetics of the animal was the issue. The challenge was therefore significant. And this is the one that Colossal announces today to have overcome.
The scientists explain their process. First by treating elephant cells with a chemical cocktail used to reprogram human and mouse cells. Then, by adding four key reprogramming factors identified by another team long ago. Finally, by reducing the expression of an anticancer gene that prevents cells from replicating indefinitely. This last operation was not simple. But that’s how the researchers obtained four lines of induced pluripotent stem cells that could form cells that make up the three “germ layers” that compose all vertebrate tissues.
According to Colossal, that is. The work has not yet been peer-reviewed. And other scientists remain skeptical. They are waiting for proof that these iPS cell lines develop stably. That they can actually be transformed into different types of tissues. Like hair or blood.
Also a Significant Step for the Asian Elephant
And Colossal’s researchers are counting on it. These induced pluripotent stem cells they obtained must first help them identify and study the genetic changes necessary to give birth to Asian elephants with mammoth traits. Because the sequencing obtained as early as 2015 is not enough to understand everything.
In the end, the idea is to merge ancient mammoth DNA with Asian elephant cells. Having iPS cells capable of evolving into sperm and eggs to create embryos would avoid having to—for at least the duration of trials—take such cells from living elephants. Especially as they are also threatened with extinction. That is why researchers are also considering producing artificial wombs. “To avoid using Asian elephant surrogate mothers and not interfere with the species’ natural reproduction,” says Colossal Biosciences.
A Desirable Resurrection?
It is understood that if the challenge of producing induced pluripotent stem cells from elephants was significant, it may ultimately be one of the simplest steps in the woolly mammoth de-extinction program. Colossal had promised to bring the first one back in 2028. But given the amount of technology needed—some of which may not even exist yet—observers doubt its feasibility. They also question the relevance of allocating so many resources to such a project.
They also point out that the gestation of elephants is long and complicated. And they wonder who will teach the first resurrected woolly mammoth how to behave… as a woolly mammoth. Because an animal in general and a mammal in particular is defined not only by its genetics but also by complex social and cultural interactions.