The Return of the Dire Wolf?

Monday, April 7th, 2025

Time magazine announces the return of the dire wolf:

The dire wolf once roamed an American range that extended as far south as Venezuela and as far north as Canada, but not a single one has been seen in over 10,000 years, when the species went extinct. Plenty of dire wolf remains have been discovered across the Americas, however, and that presented an opportunity for a company named Colossal Biosciences.

Relying on deft genetic engineering and ancient, preserved DNA, Colossal scientists deciphered the dire wolf genome, rewrote the genetic code of the common gray wolf to match it, and, using domestic dogs as surrogate mothers, brought Romulus, Remus, and their sister, 2-month-old Khaleesi, into the world during three separate births last fall and this winter—effectively for the first time de-extincting a line of beasts whose live gene pool long ago vanished. TIME met the males (Khaleesi was not present due to her young age) at a fenced field in a U.S. wildlife facility on March 24, on the condition that their location remain a secret to protect the animals from prying eyes.

The dire wolf isn’t the only animal that Colossal, which was founded in 2021 and currently employs 130 scientists, wants to bring back. Also on their de-extinction wish list is the woolly mammoth, the dodo, and the thylacine, or Tasmanian tiger. Already, in March, the company surprised the science community with the news that it had copied mammoth DNA to create a woolly mouse, a chimeric critter with the long, golden coat and the accelerated fat metabolism of the mammoth.

If all this seems to smack of a P.T. Barnum, the company has a reply. Colossal claims that the same techniques it uses to summon back species from the dead could prevent existing but endangered animals from slipping into extinction themselves.

[…]

It takes surprisingly few genetic changes to spell the difference between a living species and an extinct one. Like other canids, a wolf has about 19,000 genes. (Humans and mice have about 30,000.) Creating the dire wolves called for making just 20 edits in 14 genes in the common gray wolf, but those tweaks gave rise to a host of differences, including Romulus’ and Remus’ white coat, larger size, more powerful shoulders, wider head, larger teeth and jaws, more-muscular legs, and characteristic vocalizations, especially howling and whining.
The dire wolf genome analyzed to determine what those changes were was extracted from two ancient samples—one a 13,000-year-old tooth found in Sheridan Pit, Ohio, the other a 72,000-year-old ear bone unearthed in American Falls, Idaho.

[…]

Colossal’s dire wolf work took a less invasive approach, isolating cells not from a tissue sample of a donor gray wolf, but from its blood. The cells they selected are known as endothelial progenitor cells (EPCs), which form the lining of blood vessels. The scientists then rewrote the 14 key genes in the cell’s nucleus to match those of the dire wolf; no ancient dire wolf DNA was actually spliced into the gray wolf’s genome. The edited nucleus was then transferred into a denucleated ovum. The scientists produced 45 engineered ova, which were allowed to develop into embryos in the lab. Those embryos were inserted into the wombs of two surrogate hound mixes, chosen mostly for their overall health and, not insignificantly, their size, since they’d be giving birth to large pups. In each mother, one embryo took hold and proceeded to a full-term pregnancy. (No dogs experienced a miscarriage or stillbirth.) On Oct. 1, 2024, the surrogates birthed Romulus and Remus. A few months later, Colossal repeated the procedure with another clutch of embryos and another surrogate mother. On Jan. 30, 2025, that dog gave birth to Khaleesi.

[…]

“The idea that we could just take a vial of blood, isolate EPCs, culture them, and clone from them, and they have a pretty high cloning efficiency, we think it’s a game changer,” says George Church, Colossal co-founder, and professor of genetics at both Harvard University and the Massachusetts Institute of Technology. The less invasive cell-sampling process will make the procedure easier on animals, and the fact that Colossal’s methods worked on this early go-round boosts company confidence that they are on track for much broader de-extinction and rewilding.

Borrowing a name from Game of Thrones for a dire wolf makes perfect sense, but Khaleesi? The actual (fictional) dire wolves in the stories are:

Grey Wind, adopted by Robb Stark.
Lady, adopted by Sansa Stark.
Nymeria, adopted by Arya Stark.
Shaggydog, adopted by Rickon Stark.
Summer, adopted by Bran Stark.
Ghost, adopted by Jon Snow.

Scientific purists will note that the “dire wolves” created by Colossal are merely ordinary wolves with a few gene edits. Previous “dire wolves” have been dogs bred to look like wolves.

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