A Colossal Biosciences "de-extinct" dire wolf, 1 month after being born. (Photo credit: Colossal Biosciences.)

Dire wolves have not walked this Earth for over 10,000 years; the closest they’ve come to being seen by people has been through the popular “Game of Thrones” series by HBO. In other words, they’re extinct. 

At least, they were.

Colossal Biosciences, a genetic engineering company started in 2021, has been dominating headlines and social media this month for achieving a feat that immediately brings Jurassic Park to mind: the alleged de-extinction of the dire wolf.

“On October 1, 2024, for the first time in human history, Colossal successfully restored a once-eradicated species through the science of de-extinction. After a 10,000+ year absence, our team is proud to return the dire wolf to its rightful place in the ecosystem,” said the company in an announcement on their website in early April, when news of the feat hit the world.

Though the news is recent, the animals themselves were born in October of 2024. Now over six months old, three dire wolves live on a reserve in an unknown location somewhere in the U.S.

The de-extinction has captured the attention of researchers and laypersons alike, with much debate into whether this is a true de-extinction or not.

We can, but should we?

“Your scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should,” reads one of the most iconic lines from the original Jurassic Park movie, when Jeffery Goldblum’s character first learns about the research reviving dinosaurs from ancient DNA trapped in sap.

The concept of the dire wolf revival likely sounds familiar to anyone who has seen the popular “Jurassic Park” franchise, which, at its core, is about scientists who have achieved scientific novelty and wield power in the biodiversity of the planet like never before.

Does this quote apply to Colossal Biosciences? Opinions vary  — especially since many argue these are not true dire wolves at all but rather imitations based on modern-day gray wolves engineered to look like what we think dire wolves looked like. These dire wolves may have distinct genetic differences from the gray wolves whose base genome was edited to create the dire wolves — and one could make an argument that they are decidedly not modern-day wolves — but that does not make them actual dire wolves. These are, for all intents and purposes, just gray wolves edited to look like dire wolves.

Two of the de-extinct dire wolves from Colossal Biosciences. (Photo credits: Colossal Biosciences.)

This line of thinking would render the de-extinct dire wolves as legitimate as two species who experienced convergent evolution — a concept where two species are evolutionary distant and only evolved to look similar to one another but have no actual connection.

Still, others argue that with the resources available today, this is the closest we’ll get to reviving such lost species.

Questions remain, too, on what will happen with the animals themselves regardless of how they are classified. Can they be reintroduced into the wild? If not, are they going to serve anything beyond a marketing or tourism gimmick?

These questions and more should be answered, especially if the company will build off this success towards its long-term goal: reviving the wooly mammoth.

Advancing conservation techniques

Genetic engineering for conservation — as has all research in genetics, really — has been making great strides in short timeframes.

In 1996, Dolly the Sheep became the first mammal to be successfully cloned from an adult cell. In April of 2003, the Human Genome Project completed its first full sequence of a human genome — about 92 percent complete. In 2022, years of work aided by better equipment and computing building on that 2003 stepping stone led to the first full human genome without any gaps.

In short, the last two or three decades have been monumental in the field of genetics research. Moreover, genetics research for conservation existed before Colossal Biosciences. One example is the black-footed ferret. 

The black-footed ferret is North America’s only native ferret species. The species was once believed to be extinct until a discovery in the 1980s proved that to be untrue — though their numbers were just shy of total extinction. 

Focused conservation and breeding efforts over decades helped restore the species population; today, around 500 ferrets have been reintroduced into the wild. However, all known black-footed ferrets — at least until 2020 — were descended from just seven ferrets found in the 80s.

In recent years, efforts like those from Revive & Restore, a conservation organization founded in 2012 focused on the “genetic rescue of endangered and extinct species,” have been implemented to further advance genetic diversity within the population. One of the tools to accomplish this? Cloning.

Using cryopreserved cells from a ferret in the 1980s with no descendants, scientists were able to successfully clone Elizabeth Ann, the first U.S. native endangered species to be cloned.

A chart in the paper “First endangered black-footed ferrets, Mustela nigripes, cloned for genetic rescue” (Credit: Novak et. al)

Ben Novak, lead scientist for Revive & Restore and a key player in making the milestone happen, said the milestone was important for increasing the genetic diversity that was lost due to the species on the brink of extinction.

“Until 2020, every living black-footed ferret that had been born from 1989 to 2020 was descended from just seven individuals,” Novak said. “In 2020, through our program, we produced Elizabeth Ann — a clone. She’s cloned from essentially an eighth ferret from the 1980s. So she’s technically descended from that eighth one, but she’s a copy.

While Elizabeth Ann was the first, she was later accompanied by two “siblings,” one of which started a lineage of her own.

“We made three copies of that ferret from 1988, and then in 2024, one of those clones named Antonia had her first babies, and those two babies have become the very first, since before 1985, that can trace their lineage to [outside] of those seven animals. They can trace it now to eight.”

From a “survival of the fittest” point of view, one might argue the ferrets were simply not the fittest and, thus, should have been left to die out. That argument, Novak said, is not fully informed.

Disease and lack of immunity had a large part to do with the ferrets’ decimation. Sylvatic plague, caused by bacteria found in the bacteria Yersinia pestis, was introduced to the West Coast of the U.S. around the year 1900 from Europe or Asia, Novak said. It has since spread across the country.

The black-footed ferret, North America’s only native ferret species. (Photo credit: U.S. Fish and Wildlife Mountain-Prairie.)

Essentially, it’s not that the black-footed ferret simply does not occupy a niche in its ecosystem anymore, but rather, they faced a disease that they had no chance of fighting. It’s also why genetic diversity efforts and selective cloning and breeding of certain traits to be resistant to the plague are critical in their long-term success.

“What can we do to make this resistant to sylvatic plague, caused by the bacteria we’re seeing in Y. pestis,” Novak said. “Black-footed ferrets, being the only endemic ferret to North America, didn’t evolve with plague as their Eurasian counterparts did, and they have no immunity to it whatsoever.”

Beyond disease, the rate at which the species went extinct was faster than a species experiencing natural extinction would undergo. The culprit? Look no further than ourselves.

“Black-footed ferrets are one such species of basically all the species today that are going extinct because of human activities in the environment,” Novak said. “Not just the fact that there has been a disease introduced that they’ve never dealt with — which probably would not have ever gotten to North America for hundreds of thousands or millions of years — but also the fact that we have fragmented their habitat and taken it up for agriculture.”

With only pockets of available habitat for the ferrets, disease outbreaks are all the more deadly because the ferrets don’t really have any alternative places.

Beyond the black-footed ferrets, Revive & Restore is working on bringing back another well-known species: the passenger pigeon.

Once the most abundant bird on Earth with populations between three and five billion, the passenger pigeon went extinct in the wild in a little more than 40 years due to human activity like overhunting and deforestation. The organization hopes to bring the species back, especially given their rapid and relatively recent extinction — far more recent than the dire wolf. It aims for the first hatched passenger pigeons in over a century in the 2030s.

“It comes down to the moral argument that we caused the damage, so we have an obligation to fix it,” Novak said. 

He also added that there are limitations on what this sort of work can do — even in the case of passenger pigeons. Few species can truly be de-extinct in the same way as black-footed ferrets — only ones that have died within the last 75 years or so who have cells frozen.

“We cannot recreate an extinct species genome unless we have living cells in a freezer, like what we have had to clone black-footed ferrets with. So even if all black-footed ferrets were to die today, the species would not technically be extinct because we would be able to go into a freezer, pick up some of their cells, and revive them,” Novak said. “We don’t have that for anything in the world prior to the 1950s because cryopreservation technology did not exist — and for most species, nobody has even bothered to freeze anything.”

Essentially, any de-extinction efforts for most species that have gone extinct will look similar to dire wolves: taking a close, living relative today and modifying their genome based on the information that can be gathered from bones and other fossils.

“When you sequence it, the whole genome is there, but it’s fragmented into pieces that, because of the way it’s fragmented, you can never actually fill the whole gap,” Novak said. “You can get close — 75 percent, 80 percent, maybe even over 90 to 95 percent of those little gaps filled, but there’s just a lot of information to put back together.”

This further underlines just how special the case of the black-footed ferret was — and how species prior to cryogenic freezing can almost never “truly” be de-extinct. 

So, are these true dire wolves? 

One of the Colossal Biosciences de-extinct dire wolves. Photo credits: Colossal Biosciences.)

“I would say from a scientific standpoint, from how we have defined de-extinction — which is not resurrection — that it is a maybe,” Novak said, saying we have to wait and see how the pups progress. “We don’t know what the traits are going to look like yet when they’re fully grown, so we have to wait for the data… and the scientific community so far has been given no data on which genes were edited and how the traits are forming… the scientific jury is still out.”

Regardless of where it falls on the true de-extinction debate, the potential these new technologies can play in balancing ecosystems is unparalleled. Questions of how to reintroduce an extinct species, as well as how to sufficiently diversify those populations, remain unanswered. For Novak, the research is justified if the goal is truly helping the de-extinct animals find their way back home to mother nature.

“The goal is to put something in the wild that will help the ecosystem fill an ecological role that’s no longer there,” Novak said. “There are species that went extinct 10,000 years ago that still have those vacant roles today.”

Woolly mammoths, passenger pigeons, perhaps northern white rhinos in the not too distant future — with all the buzz around de-extinction during Earth month, the question of whether this is a tool to right some of the wrongs humans have done to the planet or if this is just a money-grab, is up for debate.

What isn’t debatable, however, is the reality that there are species close to extinction on the planet right now — and whether or not de-extinction becomes a viable tool in conservation efforts, our goal should be to save them today, not try and resurrect them tomorrow.

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