Last week I wrote about the de-extinction of the dire wolf by a company, Colossal Biosciences. What they did was pretty amazing – sequence ancient dire wolf DNA and use that as a template to make 20 changes to 14 genes in the gray wolf genome via CRISPR. They focused on the genetic changes they thought would have the biggest morphological effect, so that the resulting pups would look as much as possible like the dire wolves of old.

This achievement, however, is somewhat tainted by overhyping what was actually achieved, by the company and many media outlets. Although the pushback began immediately, and there is plenty of reporting about the fact that these are not exactly dire wolves (as I pointed out myself). I do think we should not fall into the pattern of focusing on the controversy and the negative and missing the fact that this is a genuinely amazing scientific accomplishment. It is easy to become blase about such things. Sometimes it’s hard to know in reporting what the optimal balance is between the positive and the negative, and as skeptics we definitely can tend toward the negative.

I feel the same way, for example, about artificial intelligence. Some of my skeptical colleagues have taken the approach that AI is mostly hype, and focusing on what the recent crop of AI apps are not (they are not sentient, they are not AGI), rather than what they are. In both cases I think it’s important to remember that science and pseudoscience are a continuum, and just because something is being overhyped does not mean it gets tossed in the pseudoscience bucket. That is just another form of bias. Sometimes that amounts to substituting cynicism for more nuanced skepticism.

Getting back to the “dire wolves”, how should we skeptically view the claims being made by Colossal Biosciences. First let me step back a bit and talk about de-extinction – bringing back species that have gone extinct from surviving DNA remnants. There are basically three approaches to achieve this. They all start with sequencing DNA from the extinct species. This is easier for recently extinct species, like the carrier pigeon, where we still have preserved biological samples. The more ancient the DNA, the harder it is to recover and sequence. Some research has estimated that the half life of DNA (in good preserving conditions) is 521 years. This leads to an estimate that all base pairs will be gone by 6.8 million years. This means – no non-avian dinosaur DNA. But there are controversial claims of recovered dino DNA. That’s a separate discussion, but for now lets focus on the non-controversial DNA, of thousands to at most a few million years old.

Species on the short list for de-extinction include the dire wolf (13,000 years ago), woolly mammoth (10,000 years ago), dodo (360 years), and the thylacine (90 years). The best way (not the most feasible way) to fully de-extinct a species is to completely sequence their DNA and then use that to make a full clone. No one would argue that a cloned woolly mammoth is not a woolly mammoth. There has been discussion of cloning the woolly mammoth and other species for decades, but the technology is very tricky. We would need a complete woolly mammoth genome – which we have. However, the DNA is degraded making cloning not possible with current technology. But this is one potential pathway. It is more feasible for the dodo and thylacine.

A second way is to make a hybrid – take the woolly mammoth genome and use it to fertilize the egg from a modern elephant. The result would be half woolly mammoth and half Asian or African elephant. You could theoretically repeat this procedure with the offspring, breeding back with woolly mammoth DNA, until you have a creature that is mostly woolly mammoth. This method requires an extant relative that is close enough to produce fertile young. This is also tricky technology, and we are not quite there yet.

The third way is the “dino-chicken” (or chickenosaurus) method, promoted initially (as far as I can tell, but I’m probably wrong) by Jack Horner. With this method you start with an extant species and then make specific changes to its genome to “reverse engineer” an ancestor or close relative species. There are actually various approaches under this umbrella, but all involve starting with an extant species and making genetic changes. There is the Jurassic Park approach, which takes large chunks of “dino DNA” and plugs them into an intact genome from a modern species (why they used frog DNA instead of bird DNA is not clear). There is also the dino-chicken approach, which simply tries to figure out the genetic changes that happened over evolutionary time to result in the morphological changes that turned, for example, a theropod dinosaur into a chicken. Then, reverse those changes. This is more like reverse engineering a dinosaur by understanding how genes result in morphology.

Then we have the dire wolf approach – use ancient DNA as a template to guide specific CRISPR changes to an extant genome. This is very close to the dino-chicken approach, but uses actual ancient DNA as a template. All of these approaches (perhaps the best way to collectively describe these methods is the genetic engineering approach) do not result in a clone of the extinct species. They result in a genetically engineered approximation of the extinct species. Once you get passed the hype, everyone acknowledges this is a fact.

The discussion that flows from the genetic engineering method is – how do we refer to the resulting organisms? We need some catchy shorthand that is scientifically accurate. The three wolves produced by Colossal Biosciences are not dire wolves. But they are not just gray wolves – they are wolves with dire wolf DNA resulting in dire wolf morphological features. They are engineered dire wolf “sims”, “synths”, “analogs”, “echos”, “isomorphs”? Hmmm… A genetically engineered dire wolf isomorph. I like it.

Also, my understanding is that the goal of using the genetic engineering method of de-extinction is not to make a few changes and then stop, but to keep going. By my quick calculation the dire wolf and the gray wolf differ by about 800-900 genes out of 19,000 total. Our best estimate is that dire wolves had 78 chromosomes, like all modern canids, including the gray wolf, so that helps. So far 14 of those genes have been altered from gray wolf to dire wolf (at least enough to function like a dire wolf). There is no reason why they can’t keep going, making more and more changes based upon dire wolf DNA. At some point the result will be more like a dire wolf than a gray wolf. It will still be a genetic isomorph (it’s growing on me) but getting closer and closer to the target species. Is there any point at which we can say – OK, this is basically a dire wolf?

It’s also important to recognize that species are not discrete things. They are temporary dynamic and shifting islands of interbreeding genetic clusters. We should also not confuse taxonomy for reality – it is a naming convention that is ultimately arbitrary. Cladistics is an attempt to have a fully objective naming system, based entirely on evolutionary branching points. However, using that method is a subjective choice, and even within cladistics the break between species is not always clear.

I find this all pretty exciting. I also think the technology can be very important. Its best uses, in my opinion, are to de-extinct (as close as possible) recently extinct species due to human activity, ones where there is still something close to their natural ecosystem still in existence (such as the dodo and thylacine). Also it can be used to increase the genetic diversity of endangered species and reduce the risk of extinction.

Using it to bring back extinct ancient species, like the mammoth and dire wolf (or non-avian dinosaurs, for that matter), I see as a research project. And sure, I would love to see living examples that look like ancient extinct species, but that is mostly a side benefit. This can be an extremely useful research project, advancing our understanding of genetics, cloning and genetic engineering technology, and improving our understanding of ancient species.

This recent controversy is an excellent opportunity to teach the public about this technology and its implications. It’s also an opportunity to learn about categorization, terminology, and evolution. Let’s not waste it by overreacting to the hype and being dismissive.