The single splashiest bit of science news so far this year arrived earlier this week, when Colossal Biosciences announced that its scientists successfully brought back a version of the dire wolf (Aenocyon dirus).
In the company’s announcement, Colossal has claimed that its three “dire wolf” siblings, Romulus, Remus, and Khaleesi, are the world’s first examples of de-extinction. But not everyone is on board with that assertion.
The wolves were created by genetically editing the DNA of gray wolf cells to more closely resemble that of a dire wolf; this edited DNA then served as the basis for embryos implanted in surrogate dogs.
Colossal has argued that these edits—20 in total—were enough to produce wolves that are phenotypically (physically or visibly) similar to the dire wolves that once roamed the Americas tens of thousands of years ago—an approach the company calls “functional de-extinction.” But at least some outside researchers aren’t so sure, arguing that these edits are far too few to truly bridge the genetic gap between today’s wolves and the dire wolves of the past.
For this Giz Asks, we reached out to experts in paleobiology and other relevant fields to get their take on Colossal’s novel—if potentially controversial—feat of genetic engineering. We also solicited a comment from Colossal’s chief science officer, Beth Shapiro, who is herself an evolutionary biologist. The following responses may have been lightly edited and condensed for clarity.
Anders Bergström
A biologist specializing in canine evolution and a lecturer at the University of East Anglia’s School of Biological Sciences.
No, it has not. What Colossal Biosciences has done is to genetically modify gray wolves to perhaps give them a slightly more dire wolf-like appearance. It’s wrong to say they have brought the dire wolf species back from extinction, or that these animals are dire wolves in any sense. It’s a technically impressive experiment to genetically modify gray wolves, but the company is massively exaggerating what this is and what it means.
Colossal first sequenced the genomes of two dire wolves by extracting DNA from ancient bones. They then compared these with gray wolves and other canids, aiming to identify what changes would be needed to transform a gray wolf into a dire wolf. It’s important to have some sense for the scale of the genetic differences between the species. Their DNA is ~99.5% similar, which may sound very high, but across the whole genome this translates to about 10 million differences. If you could somehow make all those edits to a gray wolf genome, then you would certainly get a dire wolf.
Colossal made only 20 edits. That is nowhere near enough to approach actual dire wolf biology. It should be acknowledged that, out of the several million genetic differences that distinguish gray wolves from dire wolves, most probably have no biological effect—these are what we call neutral differences. Currently, no one really knows how to tell which differences are biologically meaningful, but my guess is that you would need at least tens of thousands, perhaps even hundreds of thousands, of edits to turn a gray wolf into something that would have realistic dire wolf biology. 20 edits, whatever they are, cannot even come close.
Furthermore, the 20 chosen edits mainly targeted genes influencing traits visible to the naked eye, such as coat color and body size. But clearly there is more to species differences than these superficial traits: there is behavior, metabolism, immunity, reproduction, and so on. Colossal did not even attempt to approximate dire wolf behavior, as no one would even know where to begin to achieve that. Even the choice to make the wolves white seems only loosely grounded in the genomic data, but it is the kind of trait that makes the animals more visually striking.
There is considerable criticism of Colossal’s aims more generally, including whether an unrealistic focus on de-extinction might distract from the conservation of species that still exist. I am perhaps a little less negative than some about the basic idea, and would argue that the money currently flowing to Colossal is not from sources that would otherwise have spent it on conservation. But with this “dire wolf” announcement, I fear Colossal might damage the public perception of what real de-extinction would actually entail, and promote a superficial and incorrect view of species’ biology as something that can be changed with just 20 genome edits.
Phil Seddon
A conservation biologist and professor of zoology at the University of Otago in New Zealand who’s written about the pros and cons of de-extinction.
The simple answer is no.
So what’s happened is that they genetically modified gray wolves, which are a close relative, albeit six million years ago—these animals had a common ancestor. And what they’ve done is they’ve looked at the genome of the dire wolf and they looked at the genome of the gray wolf and they’ve identified a relatively small number of genetic differences relating to coat color and head size and general body size. And they’ve engineered those traits into a gray wolf. So you end up with a genetically engineered gray wolf, which is kind of a hybrid. And what we’ve seen is that they have white color coats and they’ll end up being a bit bigger, perhaps, than the average wolf.
I think that the achievement we should be focused on are the techniques they’ve developed to do this. That is, to identify genetic sequences and to re-engineer them into the genome of an existing species. So you can imagine them using this technology to perhaps re-engineer lost genetic diversity into existing species and preventing extinction in the first place, rather than creating these kind of genetically modified lookalikes [the same day as the dire wolf announcement, the company reported using its technology to clone several red wolves, the world’s most endangered wolf species living today].
While I’m down on the terminology being used, like “de-extinction” and resurrecting things. I am an enthusiast of the potential of the technology that’s been developed by Colossal Biosciences.
Bradley Shaffer
A distinguished professor at UCLA in the Department of Ecology and Evolutionary Biology and the Institute of Environment and Sustainability, as well as director of the California Conservation Genomics Project.
It’s a complicated answer to a simple question. So if I took that absolutely at face value and said: Has the dire wolf, whatever we exactly mean by that, been reconstructed by Colossal in their efforts? I would say no.
Why not? Because, A, I’m not even sure what it means to reconstruct a species, and the dire wolf is a species. And B, I have looked into some of the technology that they’ve used. This is complicated technology having to do with ancient DNA reconstructions, and similar to the complicated technology that we use with human reconstructions of extinct Neanderthals, or other human ancestors, or human members of human lineage. And it’s very tricky. It’s very degraded DNA.
You have to map that DNA back to a target species. There are biases when you do that. Colossal has done a lot to try to eliminate those biases; whether they have completely or not, it’s unclear. Here, they have chosen not every difference between the gray wolf and their fragmented dire wolf genome, but some of the differences that they think are important. And they’ve used gene editing techniques to make those changes to reconstruct canid individuals that have some of those dire wolf features.
So is that a dire wolf? Probably not. We’ll never know for sure. Is it more like a dire wolf than a gray wolf? Almost certainly. And is it a major accomplishment in using gene editing to construct a target species or a target organism that has certain characteristics and is sort of a breakthrough in that sense? I think it is. And I think they should be very proud of it. I think it’s a very interesting set of accomplishments that they’ve made doing that many simultaneous gene edits and having organisms that can then grow up and not only survive but thrive, at least as puppies.
That’s a big accomplishment that may have repercussions for certain aspects of conservation biology, and maybe for certain aspects of human biology. Is it the dire wolf? Probably not. Does it have all the same ecological features as a dire wolf? Probably not. Does it have some of them? Yeah. And my guess is that’s as much as they hoped to accomplish and they’ve probably accomplished their goals.
Has the dire wolf been “de-extincted or whatever the correct terminology is for that? I don’t think that Colossal or at least Beth Shapiro would say it has, unless you define de-extinction in a certain way. And I don’t think that was their goal to create a perfect stock. And my guess is, honestly, that the press has taken this in directions that are probably premature, given that the scientific peer reviewed papers haven’t been published yet [According to Colossal, the very first paper on their dire wolves will be available as a preprint later this week]. The experts can’t really evaluate all the nuances of the ancient DNA techniques and the multiple iterative mapping techniques that they’ve used and everything else.
And so it’s probably a bit premature to just declare a huge success or exactly what that success comprises.
Beth Shapiro
Chief science officer at Colossal Biosciences, and an evolutionary molecular biologist specializing in the genetics of ice age animals and plants.
In a world where headlines too often herald disaster, my colleagues at Colossal Biosciences have given us something extraordinary to celebrate: the return of the dire wolf. But as with any scientific breakthrough, skeptics have emerged, questioning whether these striking creatures, with their light-colored coats and impressive stature, are truly dire wolves or merely modified gray wolves.
This debate misses the point.
The science: We and our academic partners collected DNA fragments from a 13,000-year-old tooth and a 72,000-year-old skull. Colossal’s scientists then used this dire wolf DNA to identify and reintroduce key dire wolf DNA variants linked to many of the dire wolf’s unique traits from the light coloration of their coats to their imposing stature. These key genetic variants haven’t been expressed for thousands of years. These animals aren’t mere approximations; they embody many of the critical traits that made dire wolves unique ecological actors.
Remember what de-extinction is actually about. It’s not about creating perfect genetic copies of individual animals. It’s not about populating de-extinction amusement parks. It’s about restoring lost ecological functions and enhancing biodiversity. It’s about developing technology capable of adding robustness and resilience to our ecosystems. It’s about doing something powerful and precise in the face of our current extinction crisis.
The implications for conservation are profound. The same technologies that brought back the dire wolf have already yielded dividends for endangered species conservation. To much less fanfare, Colossal also announced the successful birth of four red wolves—the only endemic American wolf and one of the most endangered wolf species alive—using cells isolated directly from a simple blood draw. With fewer than 20 red wolves remaining in the wild, this breakthrough could help save a species from extinction.
Beyond the technical achievement, there’s something more profound happening here. In an era dominated by climate anxiety and biodiversity loss, our dire wolves and our red wolves are symbols of optimism. It is within the realm of human endeavor to reverse species decline. For young people considering careers in science and conservation, what could be more inspiring than watching the impossible become possible?
Has the dire wolf been resurrected? Dire wolf DNA is specifying uniquely dire wolf phenotypes in living canids for the first time in 12,000 years. Functional de-extinction, partial genetic resurrection, call it what you will. I call it hope.
