Back From Oblivion?

Once Matt James caught a glimpse of the newborn wolf’s white coat, he knew the years of experiments had paid off. His company had successfully bred three pups with genes from dire wolves, animals that went extinct some 13,000 years ago.

“That first flash of white was a real slap in the face,” says James, the chief animal officer at Colossal Biosciences. “It’s going to stick in my memory forever.”

For more than a decade, scientists have chased the idea of reviving extinct species, a process sometimes called de-extinction. Now Colossal Biosciences appears to have done it—or something close. In April, it announced that it had used ancient DNA from dire wolves to make 20 modifications to 14 gray wolf genes. The result is three healthy wolves—two males and one female—with dire wolf traits. They have uniquely dense, pale coats and are about 20 percent larger than gray wolves.

Beth Shapiro, the chief scientific officer of Colossal, describes the wolf pups as the first successful case of de-extinction.

“We’re creating these functional copies of something that used to be alive,” she says.

Matt James knew his company’s experiments had paid off when he caught a glimpse of the newborn wolf’s white coat. His team had successfully bred three wolf pups using genes from dire wolves, animals that went extinct some 13,000 years ago.

“That first flash of white was a real slap in the face,” says James, the chief animal officer at Colossal Biosciences. “It’s going to stick in my memory forever.”

For more than a decade, scientists have chased the idea of reviving extinct species. The process is sometimes called de-extinction. Now Colossal Biosciences appears to have done it—or something close. In April, it announced that it had used ancient DNA from dire wolves to make 20 modifications to 14 gray wolf genes. The result is three healthy wolves with dire wolf traits. The two males and one female have uniquely dense, pale coats. They are about 20 percent larger than gray wolves.

Beth Shapiro, the chief scientific officer of Colossal, describes the wolf pups as the first successful case of de-extinction.

“We’re creating these functional copies of something that used to be alive,” she says.

Over the years, scientists have proposed various ways of reviving a lost species, such as cloning a cell from the frozen carcass of an ancient animal like the woolly mammoth. The entrepreneurs and scientists who started Colossal in 2021 decided to take a different path. They’d analyze ancient DNA to identify the key mutations that made extinct species different from living relatives. The researchers would then edit the DNA of a living relative and use those genes to reproduce the extinct species. The revived animals wouldn’t be genetically identical to the extinct ones, but they’d be alike in crucial ways.

Colossal initiated high-profile experiments on the woolly mammoth and the dodo, a flightless bird that went extinct three centuries ago. But the team soon realized that dire wolves would be an easier target species. Dire wolves are related to dogs, so scientists could take advantage of years of research on cloning dogs and implanting embryos in female dogs.

For thousands of years, dire wolves dominated what’s now southern Canada and the United States. They had thick white coats, massive teeth, and jaws that allowed them to hunt horses, bison, and possibly mammoths. When many of those prey species drastically declined or became extinct, the gray wolf swept down from northern Canada and Alaska and became the dominant wolf species.

Last year, Shapiro and her team discovered a wealth of dire wolf genetic material in two fossils—a 13,000-year-old tooth from Ohio and a 72,000-year-old skull from Idaho. The dire wolf genomes allowed Shapiro and her colleagues to reconstruct the history of the species in greater detail.

With a list of dire wolf genes in hand, the scientists at Colossal started this latest de-extinction project. First, they isolated cells from the blood of gray wolves and grew them in a dish. There, they introduced dire wolf mutations to the gray wolf genes. The researchers then transferred the edited DNA from the gray wolf blood cells into an empty dog egg. They created dozens of these eggs, which they implanted into large dogs that served as surrogate mothers.

Over the years, scientists have proposed various ways of reviving a lost species. This includes cloning a cell from the frozen carcass of an ancient animal like the woolly mammoth. The entrepreneurs and scientists who started Colossal in 2021 decided to take a different path. They’d analyze ancient DNA. They’d look to identify the key mutations that made extinct species different from living relatives. The researchers would then edit the DNA of a living relative. The edited genes would be used to reproduce the extinct species. The revived animals wouldn’t be genetically identical to the extinct ones, but they’d be alike in crucial ways.

Colossal initiated high-profile experiments on the woolly mammoth and the dodo, a flightless bird that went extinct three centuries ago. But the team soon realized that dire wolves would be an easier target species. Dire wolves are related to dogs. Scientists could take advantage of years of research on cloning dogs and implanting embryos in female dogs.

For thousands of years, dire wolves dominated what’s now southern Canada and the United States. They had thick white coats, massive teeth, and powerful jaws. They hunted horses, bison, and possibly mammoths. When many of those prey species drastically declined or became extinct, the gray wolf swept down from northern Canada and Alaska. It then became the dominant wolf species.

Last year, Shapiro and her team used two fossils—a 13,000-year-old tooth from Ohio and a 72,000-year-old skull from Idaho—to discover a wealth of dire wolf genetic material.  The dire wolf genomes allowed Shapiro and her colleagues to reconstruct the history of the species in greater detail.

Then the scientists at Colossal started this latest de-extinction project. First, they isolated cells from the blood of gray wolves and grew them in a dish. There, they introduced dire wolf mutations to the gray wolf genes. The researchers then transferred the edited DNA from the gray wolf blood cells into an empty dog egg. They created dozens of these eggs. These eggs were then implanted into large dogs that served as surrogate mothers.

That process led to the birth of three wolf pups: Romulus and Remus, named for the mythical founders of Rome, who were raised by a wolf; and Khaleesi, named after a leading character in the TV series Game of Thrones, which helped make dire wolves famous. Colossal is keeping the wolves at a 2,000-acre facility in an undisclosed location in the northern U.S.

Some scientists, however, don’t consider the pups to be truly resurrected dire wolves. Adam Boyko, a geneticist at Cornell University, says that while the 14 dire wolf genes the animals carry might reveal something about the extinct species, it’s possible many other genes helped set them apart from other wolves.

“We don’t know what that number is,” he says. “It could be 20, or it could be 2,000.”

He also notes that the animals won’t learn the behavior of their species, since they’re not being raised in packs.

As the wolves grow, Colossal researchers have an eye out for any unexpected changes to the animals’ biology. Shapiro says the animals are unlikely to reveal much about the behavior of dire wolves, given their captive upbringing.

“I would love to know the natural behavior of a dire wolf,” she says. “But they are essentially living the Ritz-Carlton lifestyle of a wolf. They can’t get a splinter without us knowing about it.”

That process led to the birth of three wolf pups. Romulus and Remus were named for the mythical founders of Rome, who were raised by a wolf. Khaleesi was named after a leading character in the TV series Game of Thrones, which helped make dire wolves famous. Colossal is keeping the wolves at a 2,000-acre facility in an undisclosed location in the northern U.S.

Some scientists, however, don’t consider the pups to be truly resurrected dire wolves. Adam Boyko, a geneticist at Cornell University, says that while the 14 dire wolf genes the animals carry might reveal something about the extinct species, it’s possible many other genes helped set them apart from other wolves.

“We don’t know what that number is,” he says. “It could be 20, or it could be 2,000.”

He also notes that since the animals aren’t being raised in packs, they won’t learn the behavior of their species.

As the wolves grow, Colossal researchers will watch for any unexpected changes to the animals’ biology. Shapiro says the animals are unlikely to reveal much about the behavior of dire wolves since they are being raised in captivity.

“I would love to know the natural behavior of a dire wolf,” she says. “But they are essentially living the Ritz-Carlton lifestyle of a wolf. They can’t get a splinter without us knowing about it.”

Carl Zimmer covers science for The Times.

Carl Zimmer covers science for The Times.