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Dire Wolves and the Audacity of Bringing Back The Extinct

Are we sure we know what we’re doing?
Are we sure we know what we’re doing?
dire wolves and the audacity of bringing back the extinct
Two of the three revived dire wolf pups named Romulus, Remus and Khaleesi. Photo: YouTube/Colossal Biosciences.
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An American biotech company announced this week that they had revived the dire wolf species with three new pups.

For Game of Thrones fans, this would have brought to mind the giant, highly intelligent wolf companions to the Stark siblings in the popular television series. The dire wolf, however, is not merely a fictional creature in a fantasy novel, but a real species of wolf that roamed the Americas millennia ago and faded into extinction 12 and a half thousand years ago.

Until now.

Fittingly named, the two male pups are Romulus and Remus (after the mythical wolf-fostered founders of ancient Rome), and the female is called Khaleesi (after a major character in Game of Thrones, albeit one generally more associated with dragons). The company, Colossal Biosciences, has a stated goal of “de-extinction”, the revival of extinct species like the woolly mammoth, and it appears that this is their first big accomplishment: the first species brought back from true extinction.

Let’s back up a little bit though, and break down the science and the caveats.

Colossal Biosciences is researching the genomes – the total of all genetic material in an organism, containing all the information required to grow and function – of endangered and extinct species. This is not exactly new. Arguably, genetic editing is something we’ve been doing since the dawn of agriculture. Crossing plants or animals to maximize their desirable traits, like size in tomatoes or hunting ability in dogs, is a form of genetic editing, just done slowly over generations. More recently, we discovered artificial cloning, the process of growing a new organism genetically identical to a “parent” organism. In the 90s, scientists made headlines with Dolly the sheep, the first cloned mammal. These days, the advent of CRISPR technology – a sort of “molecular scissors” that won its inventors a Nobel Prize – has let us become much more precise and targeted with gene editing. A scalpel instead of a cleaver. With this, we’ve become surgeons of the genome, and can do impossible-sounding things, like bringing back a long-dead species.

Technically, these new wolf pups are a hybrid species: they were created by carefully selective editing of the dire wolf’s closest living relative, the gray wolf. If you laid out the genomes of these new pups against the genome of a gray wolf and the genome of a dire wolf, they would much more closely resemble the living species than the dead. However, the regions of difference are critical: they code for phenotypic characteristics, or outward displayed traits, that are distinctly dire wolf. Things like a white coat of fur, a larger body, a different shape of skull, that do not match that of any living species on earth. Dire wolf 2.0, if you will.

One of the three revived dire wolf pups named Romulus, Remus and Khaleesi. Photo: YouTube/Colossal Biosciences.

In fact, this is how Colossal Biosciences did it. Using DNA extracted from fossils, their scientists assembled a picture of the dire wolf genome. By comparing against the genomes of living canine species like other wolves, and even foxes and jackals, they identified certain genetic traits that were specific to dire wolves. Using that knowledge, they edited those key genes in gray wolf cells, removing the gray wolf trait and replacing it with the dire wolf equivalent, then transferring the cells to embryos. Carried by surrogate dogs, the embryos eventually developed into three wolf pups of a brand-new hybrid species, now running around a private research site.

If this all sounds a little bit Jurassic Park, that’s because it sort of is. Admittedly, a few things are different and better. Rather than splicing together genomes of living and extinct, Colossal’s team simply rewrote sections of the gray wolf genome to match the reference they had built for the dire wolf. The wolf pups are, according to TIME magazine, being raised in an “undisclosed location” on a 2000-acre site, carefully monitored by experts and systems hopefully much stronger than those of Isla Nublar, to protect, study, and care for them.

While this is a huge technological achievement, it raises plenty of thorny questions. 

For one, what is the point of all of this? In some ways, these young wolves are a proof of concept. This kind of technology can be an enormous boon in saving critically endangered species. Endangered species often suffer from a limited gene pool, which happens when the living members of the species are too closely related and there is consequently little diversity in the genetic variations across the whole species. This leaves them vulnerable to extinction; for example, if a disease comes along that kills much of the population, few if any individuals may have a genetic variant that allows them to survive and continue the species. With the kind of “rewriting” technology used to create Remus, Romulus, and Khaleesi, genetic diversity can be reintroduced to a species without disturbing the wild population. 

Actually, Colossal is already working on it. Along with the dire wolf news, they also announced the birth of red wolf pups. The red wolf is an endangered species with extremely low numbers in the wild – and Colossal is part of a project to study and potentially introduce new wolves to the population. Such projects are a frontier in conservation efforts and may well represent a vital hope for biodiversity on our planet.

What about the idea of “de-extinction”? 

The dire wolves will live their lives in captivity to be studied. Genes are not one-to-one; a single mutation may have multiple, sometimes unexpected, effects. The pups will have to be monitored to see if the changes made to their genomes have consequences scientists didn’t predict. More importantly, when a species goes extinct, the ecosystem it lived in must shift to fill the role they once occupied. 

The dire wolf has been extinct for over 10,000 years. The prey it used to eat – mastodons, giant sloths, ancient bison – died out with it. We have no idea what effects it may have if reintroduced to the wild. Humans, in fact, are notoriously bad at judging this – just look up a list of invasive species online to see the havoc we’ve been causing by taking species to new habitats. 

Colossal’s website has utopian-sounding language about wanting to “jumpstart nature’s ancestral heartbeat”. But nature has evolved, and we humans ourselves have been an invasive species. Trying to restore what we still have is one thing; bringing back something long gone is another. Is it fair to bring a woolly mammoth from an Ice Age to a warming world? Are there health effects on the new hybrid species? What do we do if the genes that have been rewritten do things we don’t expect? Are there health effects on the surrogate animals that carry these embryos?

Perhaps we will use this technology wisely, perhaps we can use it as a powerful tool to stabilise the environment, conserve biodiversity, and help nature get back on its feet. Or perhaps we are headed towards a real-life Jurassic Park reboot even Spielberg didn’t see coming. Are we sure we know what we’re doing?

Kaivallya Dasu works as a bioinformatics analyst in the field of cancer diagnostics. She strives to use her story-telling skills to bring science to a wider audience. She has a degree in genetics and creative writing from the University of California, Berkeley.

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