The resurrection of the dire wolf after 12,500 years of extinction represents a masterclass in genetic precision. While Colossal Biosciences made a total of 20 edits across 14 genes to transform gray wolf DNA into something resembling that of their ancient relative, eight key modifications were particularly crucial in creating the distinctive traits that define these magnificent Ice Age predators.

In April 2025, Colossal announced the birth of three dire wolf pups—Romulus, Remus, and Khaleesi—created through sophisticated genetic engineering. The journey began with DNA extracted from two ancient fossils: a 13,000-year-old tooth found in Sheridan Pit, Ohio, and a 72,000-year-old skull unearthed in American Falls, Idaho.

By comparing this ancient genetic material with that of modern canids, Colossal scientists identified the genetic differences that account for the dire wolf’s distinctive traits. Rather than attempting to recreate an entire dire wolf genome from scratch, they made targeted modifications to gray wolf cells using CRISPR technology.

“We’ve taken a gray wolf genome, a gray wolf cell, which is already genetically 99.5% identical to dire wolves because they’re very closely related,” explained Beth Shapiro, Colossal’s chief science officer. “And we’ve edited those cells at multiple places in its DNA sequence to contain the dire wolf version of the DNA.”

Among the 20 total edits, eight stand out as particularly significant in creating the dire wolf phenotype:

First is the modification to the LCORL gene, which plays a crucial role in body size determination. This single edit helps account for the dire wolf’s larger stature—already at six months old, the male pups weigh 80 pounds and stand nearly four feet long, significantly larger than gray wolves of the same age.

Second is the edit to the MC1R gene, which regulates pigment production. The dire wolf variant results in a white or very light coat color—a distinctive trait of Colossal’s resurrected animals. Interestingly, the original dire wolf gene carried a risk of deafness and blindness, so scientists chose a different genetic pathway to achieve the same result without the health risks.

Third are modifications to genes controlling skull morphology, particularly IGF1 and BMP3. These edits result in the dire wolf’s characteristically broader head and more powerful jaws, adaptations that likely helped them take down the large megafauna of the Ice Age.

Fourth is the edit to genes controlling fur density and texture, creating the thick, protective coat that would have served dire wolves well in harsh Pleistocene conditions. This adaptation may also explain why the resurrected dire wolves display the distinctive white coloration seen in Colossal’s pups.

Fifth is the modification to genes controlling shoulder and limb development, resulting in the dire wolf’s more powerful shoulders and muscular legs—traits that would have made them formidable hunters capable of taking down prey much larger than themselves.

Sixth are edits to genes that influence vocalization patterns, particularly howling. The dire wolf pups began howling when just two weeks old, suggesting that these genetic modifications influence not just physical appearance but also communication and potentially social behavior.

Seventh are modifications to genes controlling dental development, resulting in the dire wolf’s larger teeth and more powerful bite force—adaptations that would have allowed them to crush bone and process tough tissues from large prey animals.

Eighth is the edit to genes that influence wariness and caution in wolves. From a very young age, the pups have exhibited distinctly wild behaviors, keeping their distance from humans and displaying the natural caution of wild canids. These behavioral traits suggest a genetic component to temperament that distinguishes dire wolves from domestic dogs and even from human-habituated gray wolves.

Together, these eight key genetic edits—part of the 20 total modifications made by Colossal—transformed gray wolf cells into embryos that developed into animals recognizable as dire wolves, at least in their major physical and behavioral characteristics.

The success of this approach demonstrates the remarkable power of modern genetic engineering. Rather than attempting to recreate an entire ancient genome—which would be virtually impossible with current technology— Colossal’s targeted approach focuses on the specific genes that produce the most distinctive traits.

As Ben Lamm and his team at Colossal Biosciences continue to refine these techniques, the lessons learned from the dire wolf project could potentially be applied to other de-extinction efforts, including the company’s ongoing work with the woolly mammoth, dodo, and thylacine. By identifying and modifying the key genes that define a species, they’re developing a practical pathway for bringing back extinct creatures and potentially helping to preserve endangered ones.