Preface: in this discussion the term "dire wolf" has too many meanings, as such I will be referring to them as follows:

Thrones' wolves: for the huge, white, fantasy animals from Game Of Thrones GMO wolves: for Romulus, Remus and Khaleesi, Colossal's creations, Canis lupus Aenocyon: for Aenocyon dirus, the true, extinct dire wolf known from fossils across North America

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Part 1: That's not a dire wolf-

The first question everyone has been asking is "So, are dire wolves de extinct now?" The answer is an emphatic "NO!" from anyone with knowledge of genetics, palaeontology, or taxonomy.

Aenocyon dirus were actually not wolves, nor dogs, but a secret third thing.

They are canids, but last shared a common ancestor with grey wolves and their lineage some ~5.7 million years ago.

For context, this paper suggests a similar divergence time between genus Homo (humans, Neanderthals and co) and Pan (chimps and bonobos); animals that look and behave markedly differently from each other.

The genomes of Canis lupus and Aenocyon dirus being 99.5% similar may sound like a lot, but again, humans share 98.8% with chimps, and 99.7% with Neanderthals, and yet are very distinct from both.

Skeletally, behaviourally, in soft tissue, etc, you could tell any of the three apart; the same goes for Aenocyon and Canis members.

Additionally, Colossal made 20 changes in 14 genes.

The grey wolf genome has 2,447,000,000 base pairs. Does that maths seem a bit off to you?

That's not even enough to change a grey wolf into a domestic dog, let alone an ancient outgroup!

This would be akin to modifying a lion to have bigger teeth and saying you resurrected Smilodon fatalis.

Or editing a Asian Elephant genome so they retain their juvenile hair and calling it a Woolly Mammoth.

It's a bold-faced lie.

Beth Shapiro says "they look and act like dire wolves" but that, too,simply isn't true.

Visually, the GMO wolves simply aren't what Aenocyon would have looked like. It's what a Thrones' wolf looks like.

Hmmmmm, funny about that, seeing George R R Martin helped fund the 'dire wolf project'...

As with many fossil animals, we don't know much about Aenocyon's behaviour.

You can't say the GMO wolves (who are also still pups) act like Aenocyon, because that's based off nothing.

What we do know is Aenocyon were likely pack animals (from the sheer number found in La Brea Tarpits), and crunched more bones than modern wolves (from their many broken teeth).

Also, crucially, they had Wild Sex Lives (from the many, huge, broken and healed bacula... youch).

Colossal is also being colossally shady by: doubling down on their bs use of the outdated "morphological species definition", blatantly misleading the public with their use of the words 'cloning', 'dire wolves', and 'de extinction', and refusing to share their methods in a peer reviewed paper before going public with a clickbait headline.

Do not trust them with your Red wolves either. They're using coyote hybrids and considering what they deem 'close enough' for a dire wolf, I wouldn't put any money on the quality of their GMO red wolves either...

Also can I just say, whatever genes they modified to "make the skull larger" clearly didn't impact the lower jaw...

No, I'm not sorry for this image uvu-b (But for real look at that poor pup and his overbite jfc)

Part 2: -and if it was, that wouldn't be good either.

I fundamentally do not support de extinction.

No, not even for the Thylacine, not even for passenger pigeons, nor the dodo. Even my beloved Homotherium should be left in the past.

This might be an unexpected stance because I am, surprising no one, a big fan of extinct animals, megafauna and otherwise.

But the thing is, I'm an even bigger fan of actual, living animals.

The animal ethics of de extinction are dubious at best.

The surrogate dog mothers of the GMO wolves likely won't live good lives.

I wouldn't be surprised if they were destroyed after being used, because their bodies could contain feto microchimerisms and Colossal absolutely doesn't want their special wolf genome getting out.

I doubt the GMO wolves themselves will live a full life before they outgrow their hearts, like Ligers.

This would likely be the case for any modern animal genetically modified into megafauna; a body not adapted to deal with the increased size.

Purely conjecture, but I also wouldn't be surprised if Romulus, Remus and Khaleesi have vision/hearing issues from their white coats.

White coats in wolves are associated with hearing impairments, so the gene used for these animals was from domestic dogs. Meaning Colossal has created a very expensive wolfdog.

Again, what kind of life are these wolfdogs supposed to live? As awful pets for the rich? In a zoo? Released to pollute wild wolf genomes? (assuming they're fertile; I hope not)

Regardless, it's not looking good if they ever planned to have them be 'wild animals'

Even true clones (which the GMO wolves are not) tend to have health issues.

Celia the Pyrenean Ibex (bucardo) was cloned, but the clone died after 9 minutes from a deformed lung.

So in 2003, this made the bucardo the first species to go extinct twice, yippee?

There's also the problem of genetic diversity.

How many intact genomes do you have on hand?

For dire wolves the answer is Zero!

To my knowledge, we don't have the full genome coded from one individual, just Frankenstein-ed from many. Which is fine for sequencing the canine family tree's relatedness, but not for cloning.

The absolute minimum individuals to survive a genetic bottleneck is said to be 50 in larger species. Called the 50/500 rule, it states that 50 is enough to survive, but 500 is required to prevent genetic drift.

To which I say, good luck!

Even with well preserved permafrost species (such as woolly mammoths), you'll have a hard time finding 500 individuals with prefect genomes.

And then, where will you put them?

If you were to, somehow, make a breeding population, where are they going? A national park? A zoo? Is their old habitat still available to them?

In Aenocyon, the answer is simply "they don't have a niche anymore".

Unlike the Thylacine or Dodo, humans did not directly cause the extinction of Aenocyon dirus. And even if they had, it was 10,000 years ago!

Would making room for a de extinct species impact the habitat/niche of another species?

Regular grey wolves fill Aenocyon's role as a canine mesopredator, with Puma as the apex (alongside bears as an apex omnivore).

With the loss of megafauna to prey on, a de extinct predator would just compete with other, also endangered species.

Animals also change the environment they life in.

Mammoths will clear trees like modern elephants. This would recreate the Mammoth Steppe, but those trees making up the taiga and boreal forests are themselves crucial habitat.

Other species have moved in since the mammoths' extinction. Siberian tigers, lynx, muskoxen, brown bears, elk, moose, and so many others; many endangered.

Trees also prevent erosion, which is already happening at unprecedented rates due to agriculture and deforestation.

Crucially: What's to stop an extinct animal going the same way it went out last time?

Ask yourself this:

Would the average American appreciate "flocks of Passenger pigeons big enough to darken the sky and whiten ground with their guano"?

Would people suddenly be okay with lions in Europe eating their livestock, when they are champing the bit to shoot Iberian wolves again?

Would Tasmanians suddenly feel the same about the Thylacine, when farmers in Australia still happily kill dingoes and eagles for lamb predation? [citation, I am an enviro technician and have had farmers tell me they shoot Wedge-tails, knowing I'm a toothless lion to stop them.]

I doubt it

At what cost?

Are we going to find 50 thylacine genomes?

If so (doubtful), how much will cloning and/or modifying a relative into a thylacine cost? Now that x50?

Wouldn't that money be better spent on quoll reintroduction?

What about finding 50 gestational carriers for mammoths?

Are you going to use their closest relative; the already critically endangered Asian Elephant?

Wouldn't that time and effort on those elephant mothers be better used making more elephants?

And the social cost:

If extinction isn't forever, what's to incentivize lawmakers to fund conservation?

Really, it comes down to this:

Why bring back the dire wolf when we could put this money into protecting the Iberian and Red wolves?

Why bring back the thylacine when their cousin is dying of a transmissible cancer?

We've already seen the impacts of "extinction isn't forever anymore", with those in power already trying to cut funding to conservation, because you can "just bring them back".

But as we've seen time and time again: there is no Planet B. There is no De-Extinction, not really.