In real life, Dire Wolves, resurrected from the dead

[kayakingpoodle]

Here is another article though, I do not believe this is what they are selling it as, it is for those excited about it.
Austin American Statesman

 

[Charlaquin]

No one is saying that in the articles.

That’s exactly what this Beth Shapiro person is saying.

If the DNA is the prehistoric Dire Wolf, then the genus of the puppies is Aenocyon , not Canis.

Not according to Shapiro herself. From the linked newscientist article:

It all comes down to how you define species, says Shapiro. “Species concepts are human classification systems, and everybody can disagree and everyone can be right,” she says. “You can use the phylogenetic [evolutionary relationships] species concept to determine what you’re going to call a species, which is what you are implying… We are using the morphological species concept and saying, if they look like this animal, then they are the animal.”

She literally says their claim that these are dire wolves is not based on the phylogenetic definition of species. She’s just saying they look like dire wolves, therefore they’re dire wolves. By that logic, these would all be the same species:

 

[Yaarel]

That’s exactly what this Beth Shapiro person is saying.

Not according to Shapiro herself. From the linked newscientist article:

It all comes down to how you define species, says Shapiro. “Species concepts are human classification systems, and everybody can disagree and everyone can be right,” she says. “You can use the phylogenetic [evolutionary relationships] species concept to determine what you’re going to call a species, which is what you are implying… We are using the morphological species concept and saying, if they look like this animal, then they are the animal.”

She literally says their claim that these are dire wolves is not based on the phylogenetic definition of species. She’s just saying they look like dire wolves, therefore they’re dire wolves. By that logic, these would all be the same species.

From the news articles, Time and New Scientist, the following seems to be case:

Dire Wolf (Aenocyon dirus) and Gray Wolf (Canis lupus) are already 99.5% identical.

The debate seems to be about whether the gene edits are sufficient to account for the remaining 0.5% that differs.

If yes, then the puppies are living Aenocyon dirus (which is what the Time Magazine reports). If not, then they are something else, perhaps a new species.

In principle, it is irrelevant if the Dire Wolf DNA came directly from a remnant prehistoric cell in entirety, or was reassembled according to it.

What matters is, these puppies have the full genome of a Dire Wolf.

 

[mcmillan]

Biochemist checking in here.

From the news articles, Time and New Scientist, the following seems to be case:

Dire Wolf (Aenocyon dirus) and Gray Wolf (Canis lupus) are already 99.5% identical.

The debate seems to be about whether the gene edits are sufficient to account for the remaining 0.5% that differs.

If yes, then the puppies are living Aenocyon dirus (which is what the Time Magazine reports). If not, then they are something else, perhaps a new species.

In principle, it is irrelevant if the Dire Wolf DNA came directly from a remnant prehistoric cell in entirety, or was reassembled according to it.

What matters is, these puppies have the full genome of a Dire Wolf.

We know from what the company has told us that these absolutely do not have anything close to the full genome of a dire wolf.

Shapiro could not tell New Scientist how many differences there are but said the two species share 99.5 per cent of their DNA. Since the grey wolf genome is around 2.4 billion base pairs long, that still leaves room for millions of base-pairs of differences.

They only mutated 20 positions out of ~12 million differences. Of those 20 changes, only 15 were even changes to something that matched the dire wolf genome. The other 5 were ones they know do not match, but think makes it "look like" a dire wolf. One screenshot I saw but haven't able to find which source it a came from (none of the one's linked here, or a third I've also seen) said that one of those differences was needed to give a white coat, but because the mutating it to the dire wolf sequence would make it like one that was known to make mammals more prone to blindness they mutated a completely different gene that would also result in a white coat. Were actual dire wolves prone to blindness? Who knows? Instead were there other mutations that compensated for the effects of that mutation? Who knows. Did the original mutation even actually result in the same color coat? Who knows? (The New Scientist article says Shapiro said they won't know for a year if it even has the effect they think it did, much less if it was like the actual dire wolf). All we know is that Collossal made wolves that they think look like dire wolves and are doing PR telling people it's actually a dire wolf.

As for:

"it is irrelevant if the Dire Wolf DNA came directly from a remnant prehistoric cell in entirety, or was reassembled according to it."

This isn't the case. We know there are chemical modifications made to DNA that affect how some genes are expressed. These modifications can be from environmental exposure, as well as the parent DNA is inherited from. Using wolf DNA with some modifications wouldn't be able to reproduce any of these effects. We also know there are some genes that are influenced by the molecules from the parent egg (and to a lesser extent from sperm). These wouldn't be reproduced to give the same outcome as an actual dire wolf. There are effects of the mother that carries the fetus to term, using a dog surrogate would not reproduce these effects. Are any of these differences significant for trying to restore extinct populations? Who knows. There could be ways to test that using living populations, and potentially more recently extinct populations of animals. But those would be less exciting and wouldn't get a cover story on Time magazine. This is why biologists are cranky about the way this story is being framed and are saying this is basically just a publicity stunt.

 

[Zardnaar]

Me dumd dumb. I'll let the scientists figure it out

 

[Yaarel]

I appreciate the scientific approach to the scientific discussion.

They only mutated 20 positions out of ~12 million differences.

This part was unclear to me. Colossal made "20 edits", or as you are saying "15 edits". It is unclear how many "differences" each edit entailed. Even so, if the DNA for the lighter fur wasnt according to the Dire Wolf, that would be problematic toward the purpose of "deextincting" the Dire Wolf. It would complicate arguments about genetic variation within a species.

The part that gave me pause was, the Dire Wolf and the Gray Wolf being separated by "six million years". This is the distance of us from bonobo and chimpanzee. Of course, a species that relies on its niche tends to minimize genetic variation, so some species have more conservative than others. Probably the Dire Wolf did have a tight niche, which is why it went extinct, while wolves and others flourished. But still. Six million years.

 

[Deset Gled]

Dire Wolf (Aenocyon dirus) and Gray Wolf (Canis lupus) are already 99.5% identical.

The debate seems to be about whether the gene edits are sufficient to account for the remaining 0.5% that differs.

For reference, 83% of the C. elegans nematode DNA is shared with humans. But that's not because we're cousins, it's because only 11% of the C. elegans proteome contains nematode-specific genes. Link: Identification of Novel Human Genes Evolutionarily Conserved in Caenorhabditis elegans by Comparative Proteomics - PMC

In general, "percentage" of DNA is the kind of language you expect in movies. When someone talks like this in a magazine interview, it's a red flag that they're either dumbing things down for the reporter, or that they're selling something.

 

[mcmillan]

One screenshot I saw but haven't able to find which source it a came from

I managed to track down the source to a New Yorker article behind a paywall, though this link will give access without a subscription. It's actually a pretty nice article that I feel gives a reasonably balanced description of why they're taking the approach they are and other more reasonable, but less PR-friendly projects. It also made me come away with a better impression of Shapiro with more of her acknowledging the limitations of what they are doing than came in other articles I've read. On the other hand, it seemed to support my impression of Lamm (the main source of money) as focused more on how to publicize things with quotes like

They made a shortlist of animals that Colossal would try to revive. The company would focus on what are known as “charismatic megafauna”—animals cute or scary or striking enough that their absence has left a significant mark on human consciousness. Lamm wouldn’t have been interested in starting on some tiny lizard or unloved beetle.

and

In 2023, at a two-day conference with the team heads and Colossal’s advisory-board scientists, the attendees had whiteboarded what other animals might fit their guidelines for deëxtinction, and the dire wolf had generated a lot of enthusiasm ... Another reason—“and this is really important,” Lamm said—was that dire wolves are top-line talent in pop culture.

Even so, if the DNA for the lighter fur wasnt according to the Dire Wolf, that would be spurious toward the purpose of "deextincting" the Dire Wolf. It would complicate arguments about genetic variation within a species.

Yep, that's the whole point of us saying that it's not really accurate to say that these are dire wolves, they are grey wolves with some changes.

It is unclear how many "differences" each edit entailed

This is a good point that I've missed based on some of my biases. Generally if I'm thinking about a "difference" in a sequence I'm tending to think in terms of single nucleotides (letters of the genetic code), or at most small insertions and deletions since that's the kinds of changes I usually make in my work. The technology they're using for this (called CRISPR) is capable of making larger changes all at once, so if they're talking of 20 edits, each of those edits could involve blocks of several hundred letters in principle. But it can also be used to make the same kind of single nucleotide change I'm used to, but in a more reliable way, which is the case here is harder to say without the actual changes being described (which apparently is being considered a proprietary secret). And it does seem a technical success that they were able to make all those changes at once, but we're still a ways away of from fully replacing the genome with the dire wolf sequence. In the New Yorker article Lamm made a comparison of doing that to cold-fusion, which is probably more accurate than he realized, and not a point in his favor.

 

[Umbran]

The moment a company wants to say that basic scientific terms are now up for debate, your instinct shouldn't be to accept anything else that comes out of their mouth.

Except when those "basic scientific terms" aren't so simple.

"Species" is rather like "sex" - it is presented in a very simple way to laymen, but the actuality is not straightforward.

Not to argue that these folks are doing good science - just that this particular reason for distrust is faulty.

 

[Bohandas]

We know from what the company has told us that these absolutely do not have anything close to the full genome of a dire wolf.

I immediately thought of the line of Jurassic Park where they padded everything out with frog DNA