A Mammoth Disappointment?

Tempering expectations of the deextinction project—how about a woolly rhino?

A woolly mammoth replica / Wikimedia Commons
March 7, 2021

"Scientist plans to clone mammoth," said CNN in 2011. National Geographic ran a series of confident headlines, including 2017's "We Could Resurrect the Woolly Mammoth. Here's How." In 2018, reported, "Scientists Say They Could Bring Back Woolly Mammoths Within Two Years." It's more than two years later, and the mammoths have not returned. So how close are we to seeing a species brought back from extinction?

Source: Kazuhiro Nogi/AFP via Getty Images

The short answer: Mammoths are likely as far away as they've ever been. But global efforts to bring them back continue, fueled by the same fervor that launched efforts over a decade ago. And labs continue to make scientific breakthroughs, from assembling almost the entire mammoth genome to growing hair and fat out of petri dishes.

Although the project of bringing back megafauna to roam vast tracts of Siberian tundra sounds grandiose, deextinction work is actually proceeding on shoestring budgets. Many researchers commit unpaid time. The Woolly Mammoth Revival Team consists of five folks at the Wyss Institute for Biologically Inspired Engineering at Harvard, led by George Church, a titan (physically and mentally) of genomics. A grab bag of American, European, Japanese, and Korean scholars collaborates on trips to northern Siberia to retrieve mammoth carcasses.

But the closest thing deextinction has to a powerful backer is Stewart Brand, whose Long Now Foundation has supported the Church Lab through its Revive & Restore organization. Eriona Hysolli, a research fellow in the lab, says that a few anonymous donors help support deextinction work but that the cost of lab equipment and reagents scares most off.

As for methods of deextinction, several have been bandied about. Quite a few animals, including sheep, pigs, cattle, mice, and dogs, have been cloned. But it would be exponentially more difficult to clone an extinct creature. The two "successful" cases cited in the literature have been a type of Pyrenean ibex, known as a bucardo, in 2009 and the aptly named Lazarus frog in 2013. Both had gone extinct fairly recently: The bucardo was cloned from tissue of the last living bucardo, captured in 1999, while 40-year-old frozen frog tissue was used for the Lazarus. Alas, the ibex suffered a major lung deformity and died within minutes, and no frog embryos survived beyond a few days. Cloning animals is hard, Michael Crichton's Jurassic Park notwithstanding.

The technique used in those cases is the same as in the cloning of Dolly the sheep—somatic cell nuclear transfer. One takes the nucleus of the creature to be cloned and plants it in a different, "denucleated" egg cell, then zaps it with electricity to begin the embryonic process.

Akira Iritani, researcher at the Kyoto University in Japan and cofounder of the Mammoth Creation Project, planned to perform this procedure with the nucleus of a woolly mammoth cell and the egg of a female elephant, but mammoth cells in good condition were needed.

Lo and behold, a well-preserved mammoth was found in 2010. Yuka spent two years stored in the permafrost until scientists from the Mammoth Museum in Yakutsk could venture out to assess her. She is now on display in Moscow, and a small sample of her skin was used by Iritani's team.

"Yuka" (Source: Kazuhiro Nogi/AFP via Getty Images)

The team managed to pull nucleus-like structures from the deep-frozen remains, planted them into mouse cells, and watched as some activity occurred. But cell division didn't occur: You couldn't grow a full, living creature from these ancient nuclei. Hysolli explains that all cells undergo radiation damage over time, meaning it would take a miracle to find a mammoth cell whole enough to survive the traditional cloning process. Considering Iritani is now 91, it will be up to the next generation of deextinction researchers to find a path forward.

Scientists are left with a plan that's not cloning, exactly: Rather, they're working on "elephants with mammoth characteristics," or what Hysolli likes to call an "elemoth." It's on this front that the successful advances have come.

Mammoths and elephants share more than 99 percent of their DNA, which means researchers can play around with the two to try and develop mammoth traits in an otherwise all-elephant genome. Theoretically, one can splice Asian elephant DNA with lab-engineered DNA that mimics certain features of a mammoth.

Church's lab has already succeeded in engineering cells for thicker fat reserves and hair growth: The sight of petri dishes overflowing with mammoth hair is perhaps the most disturbing feature of the project. Church says his current focus is on genes for smaller external ear size, cold-tolerant hemoglobin genes, shorter tusks, and resistance to elephant herpes (evidently a scourge among captive elephants).

The difficulty is that the impressive efforts to sequence the mammoth genome only cover the sections that overlap with an elephant genome: They use the elephant's as a structure on which to hang the broken snippets of ancient mammoth DNA in the correct order. There is no way to piece together mammoth DNA that doesn't match an elephant’s.

"To get these parts, we need long reads" of the mammoth genome, says Beth Shapiro, researcher and author of How to Clone a Mammoth. "Because no long reads are preserved in mammoth remains, we will never be able to get there."

This means the Church lab's attempts to cook up mammoth traits are fundamentally shots in the dark. And though the hair growth and fat pad projects catch the eye, genes are expressed differently in different environments. The specter of a genetically perfect elemoth that still cannot adjust to its new surroundings looms over the deextinction project. How will the elemoth's gut microbiome adjust to a 21st century diet, for instance?

Of course, if one had the embryo ready to go, it would have to gestate somewhere. The womb of an elephant would be the most obvious option, but elephants are an endangered species, and it could take hundreds of eggs to get one successful. Elephant fetuses also take almost two years in the womb. George Church tells me he expects it will be at least five years before we're ready to try in vitro fertilization. Hysolli is more reserved: "It's unclear to me how much work has been done at the animal level that would let us achieve this." And while Church talks about artificial wombs regularly in public appearances, such a device would require far greater technical innovation than any other component in the deextinction process

Deextinction requires serious thought about a host of issues beyond the genetic miracles. For instance, the first elemoth will necessarily be the only one of its kind. Elephants are tremendously intelligent and social creatures who suffer in captivity: Will elemoths notice they're different or get lonely? A fresh elemoth pelt or tusks would presumably fetch a fortune—who will deter poachers?

If the Church Lab ever produces a living, breathing "elephant with mammoth characteristics," it will have a ready home in Pleistocene Park, a massive plot of grassland in Siberia maintained by Russian scientist Sergey Zimov and his son Nikola. The pair have dedicated their lives to preparing the ecosystem for a mammoth and generated mountains of press for their maverick vision. But even Zimov has admitted, sotto voce, that he at this point would prefer woolly rhinos to mammoths: The mammoth would take 15 years to breed, the rhino 5.

Source: Wikimedia Commons

The technical and practical roadblocks to mammoth deextinction explain Hysolli's frankness about the current priorities of the Church Lab. Deextinction is "on the back burner. It's hard to join academia with this work," she says. She emphasizes that more support is needed, for ongoing projects and for the technologies still needed. The project is less than 1 percent of the lab's funding.

Other mammoth researchers are even less hopeful. Love Dalén, author of a fascinating new paper that revealed million-year-old mammoth DNA, says in an email he is not optimistic that deextinction of mammoths will ever work.

These days, says Hysolli, the Church Lab focuses on the medical applications for genome editing and hopes that those more practical applications will spur increased interest and drive down costs for deextinction tech. Despite breathless headlines predicting an imminent return of the species, it will take further generations of visionary academics, and a lot more cash, to make the mammoth dream a reality.

Published under: Cloning , Science