de-extinction

De-extinction company announces that the dire wolf is back

Biology, colossal, de-extinction, dire wolf, Science, wolves / Kelly Newman / April 8, 2025

On Monday, biotech company Colossal announced what it views as its first successful de-extinction: the dire wolf. These large predators were lost during the Late Pleistocene extinctions that eliminated many large land mammals from the Americas near the end of the most recent glaciation. Now, in a coordinated PR blitz, the company is claiming that clones of gray wolves with lightly edited genomes have essentially brought the dire wolf back. (Both Time and The New Yorker were given exclusive access to the animals ahead of the announcement.)

The dire wolf is a relative of the now-common gray wolf, with clear differences apparent between the two species’ skeletons. Based on the sequence of two new dire wolf genomes, the researchers at Colossal conclude that dire wolves formed a distinct branch within the canids over 2.5 million years ago. For context, that’s over twice as long as brown and polar bears are estimated to have been distinct species. Dire wolves are also large, typically the size of the largest gray wolf populations. Comparisons between the new genomes and those of other canids show that the dire wolf also had a light-colored coat.

That large of an evolutionary separation means there are likely a lot of genetic differences between the gray and dire wolves. Colossal’s internal and unpublished analysis suggested that key differences could be made by editing 14 different areas of the genome, with 20 total edits required. The new animals are reported to have had 15 variants engineered in. It’s unclear what accounts for the difference, and a Colossal spokesperson told Ars: “We are not revealing all of the edits that we made at this point.”

Nevertheless, the information that the company has released indicates that it was focused on recapitulating the appearance of a dire wolf, with an emphasis on large size and a white coat. For example, the researchers edited in a gene variant that’s found in gray wolf populations that are physically large, rather than the variant found in the dire wolf genome. A similar thing was done to achieve the light coat color. This is a cautious approach, as these changes are already known to be compatible with the rest of the gray wolf’s genome.

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“Wooly mice” a test run for mammoth gene editing

Biology, de-extinction, fur, gene editing, Genetics, mammoths, Mice, Science / Kelly Newman / March 5, 2025

On Tuesday, the team behind the plan to bring mammoth-like animals back to the tundra announced the creation of what it is calling wooly mice, which have long fur reminiscent of the woolly mammoth. The long fur was created through the simultaneous editing of as many as seven genes, all with a known connection to hair growth, color, and/or texture.

But don’t think that this is a sort of mouse-mammoth hybrid. Most of the genetic changes were first identified in mice, not mammoths. So, the focus is on the fact that the team could do simultaneous editing of multiple genes—something that they’ll need to be able to do to get a considerable number of mammoth-like changes into the elephant genome.

Of mice and mammoths

The team at Colossal Biosciences has started a number of de-extinction projects, including the dodo and thylacine, but its flagship project is the mammoth. In all of these cases, the plan is to take stem cells from a closely related species that has not gone extinct, and edit a series of changes based on the corresponding genomes of the deceased species. In the case of the mammoth, that means the elephant.

But the elephant poses a large number of challenges, as the draft paper that describes the new mice acknowledges. “The 22-month gestation period of elephants and their extended reproductive timeline make rapid experimental assessment impractical,” the researchers acknowledge. “Further, ethical considerations regarding the experimental manipulation of elephants, an endangered species with complex social structures and high cognitive capabilities, necessitate alternative approaches for functional testing.”

So, they turned to a species that has been used for genetic experiments for over a century: the mouse. We can do all sorts of genetic manipulations in mice, and have ways of using embryonic stem cells to get those manipulations passed on to a new generation of mice.

For testing purposes, the mouse also has a very significant advantage: mutations that change its fur are easy to spot. Over the century-plus that we’ve been using mice for research, people have noticed and observed a huge variety of mutations that affect their fur, altering color, texture, and length. In many of these cases, the changes in the DNA that cause these changes have been identified.

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De-extinction company manages to generate first elephant stem cells

Biology, colossal, de-extinction, elephants, mammoths, Science, stem cells / Mike M. / March 6, 2024

Large collection of cells with a red outline and white nucleus.

A company called Colossal plans on pioneering the de-extinction business, taking species that have died within the past few thousand years and restoring them through the use of DNA editing and stem cells. It’s grabbed headlines recently by announcing some compelling targets: the tylacine, an extinct marsupial predator, and an icon of human carelessness, the dodo. But the company was formed to tackle an even more audacious target: the mammoth, which hasn’t roamed the northern hemisphere for thousands of years.

Obviously, there are a host of ethical and conservation issues that would need to be worked out before Colossal’s plans go forward. But there are some major practical hurdles as well, most of them the product of the distinct and extremely slow reproductive biology of the mammoth’s closest living relatives, the elephants. At least one of those has now been cleared, as the company is announcing the production of the first elephant stem cells. The process turned out to be extremely difficult, suggesting that the company still has a long road ahead of it.

Lots of hurdles

Colossal’s basic road map for de-extinction is pretty straightforward. We have already obtained the genomes of a number of species that have gone extinct recently, as well as those of their closest living relatives. By comparing the two, we can identify key genetic differences that make the extinct species distinct. We can then edit those differences into stem cells obtained from the living species and use that species as a surrogate for embryos produced from these stem cells. This will have to be done using stem cells from a number of individuals to ensure that the resulting population has sufficient genetic diversity to be stable.

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