UCSC biologist part of team that brought version of dire wolf back to life

UC Santa Cruz evolutionary biology professor Beth Shapiro is in awe of the three healthy dire wolf pups she helped bring to life after they went extinct more than 12,500 years ago. 

Popularized in George R.R. Martin’s series of fantasy novels, “A Song of Ice and Fire,” and the series’ television adaptation, “Game of Thrones,” the dire wolf isn’t just a mythical wolf, but in fact used to roam North America. 

Shapiro, as the chief science officer for Colossal Biosciences, helped the organization, which describes itself as a de-extinction company, successfully bring the dire wolf — or a version of it — back from extinction.

Her science team and Colossal’s staff extracted DNA from ancient dire wolf fossils, edited 20 genes in a cell taken from a gray wolf to match dire wolf DNA, implanted the edited embryos into dogs, which gave birth to them, and watched the pups very closely as they’ve grown. 

“It feels like a dream,” said Shapiro from her Santa Cruz home. “George R.R. Martin said that what we’ve done is indistinguishable from magic. I don’t really agree with that, because I’ve been on the ground actually watching these people work really hard to make it happen. But if you just look at it from the outside … I get it.”

Shapiro, who is still a professor at UCSC, has been on leave from her teaching position since last March to focus on her work with Colossal but is still involved in her lab and supports her students. She said she’s not certain how long her leave will last but she could continue it through the end of 2027. 

The first dire wolves, brothers Romulus and Remus, were born on Oct.1, 2024, and a third, Khaleesi – named after a “Game of Thrones” character – was born on Jan. 31. In Roman mythology, Romulus and Remus were brothers who founded Rome after they were left for dead by their father and briefly cared for by a she-wolf. 

The dire wolves live on a 2,000-acre ecological preserve whose location is being kept secret to safeguard the wolves, Shapiro said. The animals won’t be released into the wild and they’re given hormones intentionally that prevent them from being able to reproduce. Shapiro added there’s a lot of security and the wolves have trackers on them so Colossal knows where they are at any time. 

“They can’t get a splinter without us noticing,” she said. 

In 2012, Shapiro joined her husband, bioengineering professor Ed Green, at UC Santa Cruz, where they co-founded the Paleogenomics Lab, an ancient DNA research center. They have two children, who aren’t sure if they want to follow in their parents’ footsteps, Shapiro said.

“I think they mostly want us to step quieter” when it comes all the recent attention, she joked, adding that she took her 12-year-old son on a work trip with her to Mauritius, off the east coast of Africa, last year. 

Their lab focuses on the DNA of ancient species to explore how they’ve evolved over time. The pair create new methods of extracting small amounts of ancient DNA from fossils and generate genomes from bones that scientists were previously unable to work with because of how old they were. They’ve worked on the ancient long-horned bison, for example, which went extinct more than 100,000 years ago. They’ve also used this research to contribute to conservation efforts. 

While at UCSC, Shapiro has published several books and academic papers that helped bring her to this point, including the 2020 book “How to Clone a Mammoth: The Science of De-Extinction” and a 2021 scientific article entitled “Dire wolves were the last of an ancient New World canid lineage” in the publication Nature. 

She says it was the book on mammoth cloning that caught the attention of Colossal Biosciences CEO Ben Lamm, who asked her to run the company’s science team.

Colossal Biosciences is focused on creating technology to restore extinct species and conserve critically endangered ones with the aim of improving biodiversity on the planet. The company was founded by Lamm, a software entrepreneur, and geneticist George Church. In an interview with news outlet Semafor, Lamm said Colossal has the potential to bring in money through licensing its technology, eco-tourism and other government partnerships –  such as possibly working with the Mauritian government to bring back the extinct dodo and increase the country’s tourism revenue. 

Shapiro describes Colossal as a species preservation company. “Ultimately, the goal of this company is to develop new tools that we can use to stop species from becoming extinct and to help invigorate existing ecosystems, and some of that is through de-extinction,” she said. 

Shapiro joined the company as an advisor in 2022, working to help obtain genetic samples, generate data of ancient DNA and launching the Dodo and Avian Genomics Group. The group sequenced the genome of the large bird, which went extinct around 1690 after humans arrived to the dodo’s native island of Mauritius and brought other species like goats and pigs, which all ate dodo eggs.   

In early 2023, the idea of dire wolf de-extinction came up in conversation among Colossal staff. Shapiro was at the Colossal Biosciences headquarters in Texas when Lamm asked her and other advisors which extinct animals they should consider adding to a list to bring back to life. 

Suggestions included the Steller’s sea cow, which roamed the northern Pacific Ocean and went extinct around 1768, and the giant sloth, which lived across the Americas and went extinct around 11,000 years ago, potentially due to human hunters. But Shapiro said they would be impossible to revive because there are no close living relatives that could be surrogates – which Shapiro said is necessary for the safety of the animals. 

Then someone suggested looking into species that used to live in America that are now extinct. 

“I was like, ‘Well, there’s the dire wolf. And Ben’s like, ‘Wait, what? Dire wolf? That’s not a real thing. That’s from “Game of Thrones,”‘” she recalled. “I was like, ‘No, it was a real wolf.’” 

Shapiro said that Lamm mentioned he had recently had conversations with the Mandan, Hidatsa and Arikara (MHA) Nation in North Dakota about reviving an extinct species and Indigenous leaders had talked about the cultural significance of the wolf.

“The de-extinction of the dire wolf is more than a biological revival. Its birth symbolizes a reawakening – a return of an ancient spirit to the world. The dire wolf carries the echoes of our ancestors, their wisdom, and their connection to the wild,” MHA Nation Tribal Chairman Mark Fox said in a statement. 

Shapiro says that de-extinction is just one tool to help with conservation work. By bringing back species, or versions of them, she says Colossal can reintegrate some of the traits that were previously lost into an ecosystem and help stabilize it by adding more diversity and resilience.

Biologists estimate that the world could lose up to half of its species by 2050 due to the impacts of human development and agriculture, pollution from chemicals and plastics and global warming on their environments. Biodiversity among plants and animals helps maintain ecosystems, like wetlands that help filter freshwater, and offers a wide range of other benefits for humans and the environment.

For example, after gray wolves were reintroduced in Yellowstone National Park 30 years ago, scientists discovered they contributed to a range of ecological changes that have helped improve biodiversity in the park. Since the wolves’ reintroduction, the number of beaver colonies increased from one to nine, as a result of the predatory wolves’ impact on the environment. And, with more beavers and beaver dams, the rivers in the park have also changed significantly, for example contributing to more cold, shaded areas for fish.

Similarly, by reintroducing extinct species, Colossal Biosciences hopes it can improve dying ecosystems and the loss of biodiversity. 

When the dire wolf was added to the company’s list of species for de-extinction in 2023, Shapiro and the Colossal staff went through questions about how it would technically work, what ethical issues they would have to navigate and the regulatory and ecological challenges they would encounter. 

Among the questions they wrestled with were how editing some gray wolf genes could negatively affect the animal. For example, they realized changes to the gray wolf’s genes that give it a white fur coat, would, when done to a gray wolf’s genes, lead to deafness and blindness. So they used a different technique affecting different genes to ensure the pups would be healthy. 

Shapiro said the dire wolf is closely related to gray wolves or coyotes. That means there are decades of science and knowledge on wolves and dogs that the scientists can draw from to help them take on the de-extinction of the dire wolf. 

“There are companies out there that clone dogs … veterinary protocols, even ethics review boards that are already established to work with these animals. We don’t have any of that for elephants or mammoths,” she said. “So there is a lot to say in favor of having a dire wolf be this first species” to be made de-extinct.

As part of the announcement of the dire wolf, Colossal Biosciences said some of its work on the wolf’s de-extinction has led to major implications for the preservation of the critically endangered red wolf, which currently lives in the wild only in North Carolina.

As of February, there were only about 16 to 19 wild red wolves left, along with another 270 in a captive breeding program, according to the U.S. Fish and Wildlife Service. After the federal agency ended a breeding program in 2015, the wolves’ numbers crashed to just seven, which significantly reduces their genetic diversity. Genetic diversity within a species gives animals more traits that can help them adapt and survive in a range of ecosystems.

The breeding program was revived in 2021 and has gradually increased the number of wolves. The wolves alive today come from just 12 founder individuals, which doesn’t give the species a wide variety of genetic diversity in order to be more resilient. 

Using similar technology to develop the dire wolves, Colossal cloned red wolves to birth four pups for the captive breeding population. Colossal used red wolf DNA that was previously thought lost from the living red wolf population but was discovered in a coyote-like population that only roams the Gulf Coast of Louisiana and Texas. Some of the red wolf DNA found in those “red ghost wolves” isn’t present in the 12 founder individuals. 

The company says by adding these four pups, from three different lineages taken from the ghost wolves’ red wolf DNA, it will be increasing the number of founding lineages by 25% – from 12 founding individuals to 15. Two of the four pups come from the same lineage.  

In addition to the dire wolf and the red wolf, the company is also working on the de-extinction of the mammoth, the dodo and the thylacine, commonly referred to as the Tasmanian tiger. The mammoth went extinct about 4,000 years ago and the thylacine in 1936. 

Shapiro said since the news of the de-extinction came out earlier this month, she’s been talking nonstop and doing interviews with media all over the world. She’s also heard a lot of criticism from fellow scientists about the news being “overhyped” as the pups aren’t 100% dire wolves. Some have questioned whether the work can truly be called a de-extinction, or if the pups can actually be called dire wolves. Those criticisms and Shapiro’s own personal thoughts about the project have left her with these takeaways. 

“I don’t care if you call it a dire wolf,” she said. “De-extinction is never going to be about creating perfect copies of something. De-extinction is not a silver bullet for the extinction crisis, but this is a tool that we should be really considering adding to what should be a growing toolbox in our kit that we have to be able to stop species from becoming extinct.” 

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