The De-Extinction of the Dire Wolf
From fantasy to reality
nce, they roamed the icy forests of the Pleistocene. Mythic in size and legend, dire wolves (Canis dirus) went extinct over 10,000 years ago. Now, Dallas-based Colossal Biosciences has done the fantastical: three pups, Romulus, Remus, and Khaleesi, have been born, marking the world’s first successful de-extinction of a lost predator. For the first time in millennia, the howl of the dire wolf may echo again.
The Biotech company Colossal may already sound familiar from the article “From Woolly Mouse to Mammoth.” Now, the same company has turned its attention to the dire wolf, announcing the birth of the pups this past April 8th. Some of you may recognize dire wolves from the iconic book and TV series Game of Thrones. In a moment of poetic symbolism, the pups were photographed atop the Iron Throne, and separately alongside author George R. R. Martin himself.
In a moment of poetic symbolism, the pups were photographed atop the Iron Throne, and separately alongside author George R. R. Martin himself.
Beyond fantasy, dire wolves were legendary in their own right. They grew up to 1,8 metres in length and weighed up to 70 kg. Compared to modern wolves, dire wolves were larger, more muscular, and had a stronger bite. Fossil evidence of dire wolves was discovered in North America, though they are believed to have roamed from Venezuela to Canada. While commonly associated with the Canis genus, genetic research suggests their closest living relative is the gray wolf (Canis lupus), even though they diverged more than five million years ago.
But how does the de-extinction of such a predator work?
“De-extinction is the process of restoring ecosystems and biodiversity by resurrecting lost species through bioengineering techniques. The production of new versions of extinct organisms can contribute to efforts to restore ecological roles and enhance biodiversity,” explains Dr. Bridgett vonHoldt, Professor of Ecology and Evolutionary Biology at Princeton University and core collaborator and scientific advisor at Colossal Biosciences.
The Colossal Biosciences team analyzed the genome of the dire wolf using DNA from a 13,000-year-old tooth and a 72,000-year-old skull. They compared it to the genome of a modern gray wolf and identified 20 key differences across 14 genes that account for the dire wolf’s distinguishing characteristics. Next, they harvested endothelial progenitor cells (EPCs), which form the lining of blood vessels, from the bloodstreams of living gray wolves. The 14 genes in the nuclei of these cells were then edited to express the 20 specific dire wolf traits.
“The most challenging part was genome alignment and making sure we didn’t cause harm,” says Dr. Chris Mason, Professor of Genomics, Physiology, and Biophysics at Weill Cornell Medicine and Co-Founder of Biotia.
The edited nuclei were then extracted and inserted into denucleated gray wolf ova, which were transferred into the wombs of two domestic hound mixes. Romulus and Remus were born from one of the surrogate mothers, and Khaleesi followed a few months later from the other. The dire wolves now live in a 2,000-acre preserve surrounded by a 10-foot fence, under constant monitoring and care.
Lastly, while the revival of an extinct predator may sound like something out of Jurassic Park, there’s little reason to worry, wolves tend to fear humans more than we fear them.
One of the most intriguing questions is how much the three pups actually resemble the extinct dire wolf now that they’ve been born. “Those combinations of DNA are indeed revived. The genetic modifications made to the gray wolf genome were selected to make a large phenotypic impact and to be safe for the animal,” explains Dr. vonHoldt. Dr. Mason adds, “So far, they match the extinct species very closely, but we won’t know the full extent until they’re fully grown.”
Beyond the “wow” factor, Colossal Biosciences´ technologies also support ecosystem restoration. Their Ghost Wolf Genetic Rescue Initiative aims to rebuild the lost genetic diversity of the ancestral red wolf. “The cloned red ‘ghost’ wolves are a direct example of conservation,” explains Dr. vonHoldt. “They allow genetic rescue without removing animals from the wild and give us new options for restoring red wolf diversity and health.”
Lastly, while the revival of an extinct predator may sound like something out of Jurassic Park, there’s little reason to worry, wolves tend to fear humans more than we fear them. Still, bringing back a lost species raises ethical questions. Are we playing God, or is this a natural step in our evolution? “We are on the edge of that line, but this is an essential part of the stewardship of life, and unavoidable,” reflects Dr. Mason. In the end, only time will tell how the pups will develop. You can follow their journey on Colossal Biosciences website:
Original publication:
Gedman, Gregory L., et al.
On the Ancestry and Evolution of the Extinct Dire Wolf.
bioRxiv, 9 Apr. 2025, Preprint.
DOI: doi.org/10.1101/2025.04.09.647074
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