A proxy for the mammoth would be created by editing the DNA of an endangered relative, the Asian elephant. (Photograph by Claudia Legge)

Bringing Back the Woolly Mammoth Has Already Had an Unintended Consequence

But it’s positive.

There has been no shortage of buzz about George Church’s work to bring back the woolly mammoth using CRISPR-Cas9 gene-editing. It has been the subject of articles and books and soon will be in a feature film. But well before we learn whether Church’s team can pull off the feat, they’ve already produced a surprising unintended consequence. They could save some of today’s endangered elephants from following their hairy cousins into extinction.

In order to reverse the extinction of the mammoth, the scientists need to edit cells from a fairly close living relative, Asian elephants. When Church’s team looked into elephant biology, they learned that a strain of herpes — called elephant endotheliotropic herpesvirus, or EEHV — is killing young calves in captivity and in the wild. EEHV is the leading cause of death for captive elephants between ages 1 and 8 in North America and Europe. More than a dozen cases of infection have been identified in India, Thailand, and Cambodia, but the incidence could be even higher, as it can be difficult to monitor infections in the wild, where the number of Asian elephants has been cut in half in the past century. Unlike in humans, herpes kills young elephants within a few days to a week. Once in the bloodstream it starts breaking blood vessels, causing organs to bleed until the hemorrhaging turns fatal.

Virologist Paul Ling directs a leading research center for EEHV at Baylor College of Medicine. He and his colleagues monitor elephants at the neighboring Houston Zoo on a weekly basis by looking for viral particles in their blood and trunk mucous. If discovered early enough, it can be treated with antiviral drugs. Not all treatments are successful, so they’re looking to develop a vaccine. Ling has sequenced the genome of one strain, EEHV1, the one causing 90 percent of the elephant deaths. But development of a vaccine could be accelerated if scientists can culture it — get it to replicate — in a lab so they can better study how EEHV1 makes elephants susceptible to it. That work had not yet happened, though, until Church’s team followed their interest in de-extinction right to Ling’s lab door.

Bobby Dhadwar, a post-doctoral researcher in Church’s lab, is assembling EEHV1 particles that Ling gave him from infected elephants in order to culture it in the lab. The assembly is nearly completed. If he can get the virus to culture in a dish, he’ll use CRISPR-Cas9 to modify it. The change he wants to make: disable the genes that create proteins that lead to infection. Elephants could then be inoculated with a dose of this doctored virus, if proven safe.

Ling has his eye on other approaches for treatment as well, but if anyone cultures the virus, “it would be fantastic,” he says. He’d be able to use cells in a dish to assess the effectiveness of different herpes drugs and vaccines directly rather than relying on indirect tests in elephants.

Dhadwar, meanwhile, is already looking beyond the zoo and investigating similar CRISPR-Cas9 possibilities for the human herpes virus, which affects billions worldwide. He chalks the new direction in the Church lab up to a fortunate surprise: “Without the woolly mammoth work and the de-extinction work, I would not be doing this. It wouldn’t have crossed my desk at all.”

Britt Wray is the author of Rise of the Necrofauna: The Science, Ethics and Risks of De-Extinction, co-host of the BBC podcast “Tomorrow’s World,” and a PhD Candidate in science communication at the University of Copenhagen.

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