The truth about Colossal’s dire wolves

Last week humanity witnessed a scientific miracle: the return of three dire wolf pups to Earth after a 12,000 year-long period of extinction.

This announcement by Colossal Biosciences in the pages of TIME sparked a fierce debate between those who celebrated this event as a scientific miracle (including me) and those who claim otherwise.

I think Palmer Luckey summarized my thoughts precisely:

“All the people whining that @colossal didn’t create dire wolves because they actually just spliced 10,000 year old dire wolf DNA with gray wolves should spend their time arguing that Jurassic Park did not, in fact, depict any dinosaurs.”

– @PalmerLuckey

Colossal Biosciences, founded only four years ago (2021) by Dr. George Church and Ben Lamm, now employes 130 scientists, has raised an impressive $200M+ at a $10.2B valuation, and has set out a bold sequence of Moonshots: to “de-extinct” the woolly mammoth by early 2028, with Tasmanian tigers, Dodo birds, and many other species to follow.

There’s been a lot of unwarranted and scientifically inaccurate criticism about this scientific miracle. My goal is to help set the record straight.

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The Dire Wolf Returns

Nature gave the world the dire wolf 2.6 million years ago, and then, through the hard hand of extinction, took it away between 10,000 to 13,000 years ago when the last of the species vanished. These magnificent creatures once roamed an American range extending from Venezuela to Canada, leaving behind only fossilized remains—until now.

On April 8th, Colossal announced a breakthrough that sounds like science fiction: three living dire wolf pups named Romulus, Remus, and Khaleesi.

So, how exactly did they accomplish this? I spoke with Ben Lamm yesterday to get the details.

The process begins with ancient DNA—specifically from a 13,000-year-old tooth and a 72,000-year-old skull. Colossal’s scientists meticulously analyzed this genetic material and compared it to the genome of the gray wolf, the dire wolf’s closest living relative (they’re 99.5% genetically identical). Through this comparison, they identified 20 critical differences across 14 genes that account for the dire wolf’s distinctive characteristics—its greater size, white coat, wider head, larger teeth, more powerful shoulders, more-muscular legs, and characteristic vocalizations.

Rather than using invasive tissue sampling, Colossal pioneered a revolutionary approach. They harvested endothelial progenitor cells (EPCs) from the bloodstreams of living gray wolves—a simple blood draw instead of a tissue biopsy. They then edited the 14 genes in these cells to express the 20 dire wolf traits.

This editing process required extraordinary precision. For example, the dire wolf has three genes coding for its light coat, but these same genes in gray wolves can cause deafness and blindness. Colossal’s team ingeniously engineered two other genes to shut down black and red pigmentation, achieving the dire wolf’s characteristic light color without harmful side effects.

The edited cell nuclei were then extracted and inserted into denucleated gray wolf eggs, which developed into embryos. Of the 45 embryos transferred to two domestic dog surrogates, one embryo in each took hold. After 65 days of gestation, Romulus and Remus were born via scheduled C-section. Months later, the same procedure produced Khaleesi from a third surrogate.

Importantly, Ben pointed out that recent studies have completely upended our understanding of dire wolf evolution. While some critics claimed dire wolves were more closely related to jackals, new data—with 500x more genetic information than previously available—confirms dire wolves are actually closer relatives to gray wolves, diverging from the wolf lineage about 3.5 to 5 million years ago.

Is It Actually De-extinction?

Colossal has always been very clear calling their process “functional de-extinction,” which is defined as: the process of generating an organism that both resembles and is genetically similar to an extinct species by resurrecting its lost lineage of core genes; engineering natural resistances; and enhancing adaptability that will allow it to thrive in today’s environment of climate change, dwindling resources, disease, and human interference.

One techno-optimist said it best:

“For all the haters out there saying “that’s not a real dire wolf,” let me ask you something. What was Jurassic Park about? Dinosaurs, you say? Are you sure? They were just genetically modified birds with dinosaur and frog genes added in. But of course everyone knows they were dinosaurs. If it looks like a dinosaur, sounds and acts like a dinosaur, it’s a dinosaur. Ditto with the dire wolves.”

But So What?

Well, you might like to know that the tech used for the dire wolves was also used to clone red wolves (the most endangered wolf in world) – creating four red wolves using this new, less invasive way of doing cloning from a blood draw.

Traditionally, cloning has required invasive tissue sampling. Scientists would take a skin biopsy from a living animal, grow cells from that sample, and use them in a process called somatic cell nuclear transfer. The nucleus from these cells—containing the complete genome—would be transferred into an egg cell whose own nucleus had been removed.

Colossal’s breakthrough blood cloning technique changes everything. Instead of cutting tissue from an animal, they can use a standard blood draw—the kind any animal might get during a routine vet visit. Within that blood sample are endothelial progenitor cells that, unlike red blood cells, contain a nucleus with DNA, and unlike white blood cells, don’t carry problematic genomic rearrangements.

The process is elegantly simple: the blood sample is centrifuged to separate its components by density. In the middle is a thin white layer called the “buffy coat” where these valuable cells reside. These cells are cultured in specialized media, allowing them to grow and differentiate before being used for cloning or gene editing.

This technique has profound implications for conservation. As Colossal says, “An ounce of conservation is worth a pound of de-extinction.”

The same technologies developed to bring back the dire wolf are now being applied to save critically endangered species like the red wolf.

The red wolf story is particularly compelling. By applying their blood cloning technique and analyzing the genetic makeup of recently discovered hybrid animals, Colossal was able to create four healthy red wolf clones. This achievement offers a roadmap for addressing genetic bottlenecks in endangered species—where limited genetic diversity leads to inbreeding problems, birth defects, and reproductive issues.

Bottom line for those who’ve been critical: Quit whining and be amazed by the incredible world we’re living in, and the miraculous work that Ben Lamm, George Church, PhD and their team at Colossal have accomplished and where they’re going next.

Until next time,

Peter