- We have to understand that we are being outraged, outpaced by the biodiversity loss today.

- There is zero chance that de-extinction will become something that replaces the fight against extinction.

The goal is to place these animals back into an ecosystem so that some component of the role that the extinct species played can be refilled.

- Hey, smart people.

Joe, here, up until a few weeks ago, you'd probably never thought much about this animal, a dire wolf, me either, because they've been extinct for roughly 10,000 years.

But that was until a company called Colossal Biosciences announced that they'd brought dire wolves back from the dead.

- The comeback, some 13,000 years in the making.

- A stunning scientific breakthrough, the return of the dire wolf.

- Scientists say, "They've now brought them back."

- Something that sounds like it came straight out of science fiction.

- With three dire wolfs again, walking the Earth.

- This triggered a wave of responses from scientists and creators about what Colossal actually did or didn't do.

- That claim does not, in my opinion, hold up to scrutiny.

- There is drama in the world of evolutionary biology.

- It's not quite that simple.

- And they are purposefully marketing their stunt wrongly, to get more attention.

- The puppies are in no way dire wolves.

- This has captured global attention the way that few science stories have in recent years.

Like you, I was left with some important unanswered questions, and the best way to get those answers is to speak directly to the people doing this work, so that's what I did.

This is a deep-dive conversation with some of the scientists from Colossal.

It's a different style of video than you might be used to seeing on this channel, but it's a conversation that we think is really important, and that the world needs to have.

Reconstructing ancient genomes, editing genes, cloning, these technologies are here, and they're advancing.

If we have the power to create new species or bring back extinct ones in some strange way, what does that really mean?

And should we be doing this at all?

(upbeat rhythmic music) Welcome, to "Be Smart."

- (giggles) Thanks for having me.

I'm excited to be here.

- In the past several weeks, I have heard dire wolf, more than I ever have in my entire life, all added together.

- Hard same, yes.

(laughs) - Headlines, of course, reporting that Colossal has in some form or fashion brought the dire wolf back from extinction.

Did you do that?

(both laugh) - Well, you know, the arguments that we've heard are about whether we should actually call it a dire wolf or not.

- Before we get into the details, let's state this clearly, Colossal didn't resurrect the extinct dire wolf, not really.

What they made is not the same animal as the one that roamed North America during the Pleistocene, instead, they created something completely new, inspired by something very old.

Using ancient DNA samples, they reconstructed the extinct dire wolf genome.

They analyzed that rebuild genome to figure out how dire wolves were different from their close living relatives, gray wolves.

They used precision DNA editing technology to make 20 changes to 14 genes in the gray wolf genome.

They made embryos from these edited cells, implanted them into surrogate gray wolf mothers, and in late 2024 and early 2025, three pups were born, Romulus, Remus, and Khaleesi, they are larger than gray wolves, they have different-colored coats, the DNA of these new wolves is not identical to the extinct species, these are copies, Partially in form, but more importantly, in function, at least, that's Colossal's hope.

- We're never going to bring something back identical to something that used to be alive, and that's not the goal either.

But even if there were, I mean, animals and plants are more than the sequence of the A's, and C's, and G's, and T's that make up our DNA, we're a combination of that, and the environment in which we live.

The goal of these technologies is to create proxies of these extinct species, and functional de-extinction might be a better way to talk about it.

The idea, the goal is to place these animals back into an ecosystem so that some component of the role that the extinct species played can be refilled.

This is a de-extinct dire wolf, which is different from a dire wolf that lived in the Late Pleistocene.

- When we talk about de-extinction, creating these proxy species is really what we mean, creating an animal that in some ways, lives like, looks like, and does what that extinct species did.

But that requires knowing a huge amount about how these extinct species lived, and oftentimes, modern humans have never actually witnessed or lived alongside these animals.

How did you identify those specific genetic targets, and what made you think that those would be the things that pushed this living species closer to something that existed thousands of years ago?

- In 2021, I was part of a big international collaboration where we tried to sequence every dire wolf sample that was out there, so that we could better understand its evolution.

The whole ancient DNA community had been working on this, so a bunch of different labs had gone out and collected samples and were trying to generate data, and not having very much luck.

These animals lived in warmer climates than, you know, is good for long-term DNA preservation, and so we decided as a group to come together, throw all of the data that we've been collecting into a single paper, and we were able to get DNA from about five samples, tiny amounts of DNA, we tried many dozens of samples, but five had tiny amounts of DNA, and in the end, concluded that part of the data was showing that it was closely related to the clay that contains gray wolves and coyotes, and another part of the data was showing that it was closely related to jackals.

We went back to the two of the best-preserved of these five samples, and collected a lot more using slightly updated approaches to extracting and recovering ancient DNA, and were able to get decent-quality whole genomes for these two animals.

We decided on a gray wolf, because when you actually count the exact number of differences that are close to it, you get closer to a gray wolf and a red wolf than to other wolves.

More than that, because of the morphological similarity and because of the, you know, decades of research that we have that we can leverage, on surrogacy in gray wolves or domestic dogs, veterinary protocols, understanding about the genomics, that made it easier for us to be able to then choose the fewest number of edits that we could make to get to a predictable result as possible.

The challenge here is that, you know, these are still early days in gene editing, and animal welfare is paramount, we know that every edit we make carries a risk that it doesn't interact the way that we predict that it would interact in the genetic background of a different species.

And because we cannot make every single change, and we want to make as few changes as possible, the more information we have about that surrogate species, the better we're going to do at making sure that the outcome is predictable.

So, you know, when we were picking the mutations, doing selection scans, thinking about genetic pathways that we understand, focusing on these traits, size and musculature, there were a few things that we chose that had to do with the head shape, the placement of the ears, and then the coat color.

We studied each of these, and asked, "In these genes, is there any sign in the literature that there would be a negative health consequence or negative outcome of doing this?"

- One of the criticisms I've seen of, you know, in response to the headlines in response to certainly what's been out there in public, is that in creating a proxy species through limited information that we can pull from ancient DNA, and kind of aligning that to what we still have left today, but it's something like saying, you're gonna bring back Napoleon by just finding a short French guy and giving him Napoleon's hat.

What is your response to criticism like that?

- You know, it's an interesting question, we're not gonna be able to clone grandma or clone Napoleon because there's more to an animal than that.

I think that these tools have incredible potential to augment the suite of tools that we have at our disposal to help species to adapt to changing habitats.

I mean, habitats around the planet, are changing faster than evolution can keep up with, and so we need the ability to be able to help it along the way, to be able to take Hawaiian honey creepers and change their DNA so that they're resistant to avian malaria, or do the work like we've done in Australia with our collaborators, where we modify the genome of a Northern quoll to make it resistant to cane toad toxins, so that these animals don't become extinct, we'll get there, right?

But we have to start somewhere, and if people are just objecting to the idea that we haven't been perfect initially, well, cool, we haven't.

- There's a big debate here about the definition of a species, and that might seem like an easy one to answer.

What most people think of when they think about a species, is two organisms that can successfully reproduce, it's why a pug and a poodle can make a pugapoo, but they're still dogs.

On the other hand, a lion and a tiger can make a liger, but ligers are sterile, so they're not the same species, but even this definition gets messy.

Take the grolar bear, it's a hybrid of two species, but it can reproduce to make other grolar bears.

So scientists have other ways of defining species too, like morphology or how it's different from other animals.

Some species definitions are based on the unique niche a group of animals occupies in nature.

These species concepts are all valid in certain situations, and these are just a few of many.

- I think the challenge that we're having right now is, nobody's really had to figure out what species concept to use when we talk about something that has been brought back.

- When we get into sort of the species classification debate, you know, the counter question to, "Is it a dire wolf?"

Is, "Could you tell me what a dire wolf actually is?"

We have a good idea genomically, what a dire wolf is, phenotypically, we have some idea from the fossil record, we know what the skeleton looked like, we can make some inferences about morphology based on size and robustness of the skeleton, that indicates, you know, significant musculature in certain areas.

Obviously, we can't make inferences about social ecology or ecological impact, those are things that, you know, unfortunately, without a time machine, we can't go back and study.

What we can do is try to create these functionally extinct dire wolves, we try to bring back the dire wolf in a way that we could put them into settings, which is not what we're doing right now, but we could put them into settings where you could begin to try to understand, how does a larger, more robust wolf act around larger, more robust prey?

These three pups, give us a picture of sort of where they're living, and what they're living like today, because their habitat and their ecosystem doesn't exist anymore?

- So we went through great lengths in the sort of feasibility and analysis stage to really understand, what was a dire wolf's sort of everyday climactic condition and ecosystem composition picture, what did that look like?

And if you sort of look at the spatial and temporal distribution of dire wolves from the fossil record, you can identify in today's world where very similar climactic and fluoro-fauna composition exists.

And so, that was sort of the first step to understand where should the animals live?

We obviously sort of parsed out a significant piece of land, a 2,000 acre preserve, where we could have the dire wolves live their life in a very-semi wild, obviously acknowledging 2,000 acres isn't wild, but it is a very wild setting, especially as compared to my experience working with, in zoos and aquariums.

Obviously, when they were born, we were very hands-on, we had to be very hands-on, we had to raise them, we're starting to take that step back, as Romulus and Remus are now more than six months old, Khaleesi's only about three months old, we're beginning to sort of remove human intervention and encourage that more wild behavior.

- What's the next step as you and your team are out there in that wild space?

- For this case of the dire wolf specifically, there's no intention to replace this animal back in habitat, where it would compete with gray wolves, the niche that the dire wolf filled is filled right now by a gray wolf.

They probably ate larger things, because they were larger, we can learn these things by studying them in the fossil record, but the things that they ate are mostly extinct as well.

However, having something like the dire wolf as the first de-extinction, still has enormous benefits to developing tools like this for conservation, because it allows us to do this next phase of research.

Before you're going to put something back into a habitat, you have to study them and figure out the impacts of the edits, how they're interacting with each other and their landscape, whether they're healthy and safe, how many you need, how you would actually do this.

And I would argue that there are very few wild species that qualify for being able to give us the amount of scientific data that we will have from the dire wolf, and that's specifically because we know so much about gray wolves, because we know so much about domesticated gray wolves, which are domesticated dogs.

So we have tons of science that we can leverage from surrogacy to veterinary protocols, to understanding behavior and health, and the expectations for a normal life that we can then compare what we're seeing in our animals over the next, you know, 5 to 10 years.

- How confident can you be that what you're seeing in these animals reflects what you would've seen 10,000, 50,000 years ago?

- That's a great question, and I think the confidence level of what we can infer from observing these animals, one of the things we are learning that is really impactful to the de-extinction process is, what are the rearing conditions and what are the secondary and tertiary consequences of genetic editing for an animal?

And we can learn a lot and optimize from there.

So I'm really excited, because I think this is a fantastic first step for de-extinction that allows us to learn a lot and optimize our protocols, ensure optimal welfare for animals.

As we get into social ecology and hunting behaviors, and, you know, some of the anatomy/physiology, obviously, your confidence in being able to infer from an animal that existed 75,000 years ago to this exact specimen we're working with today, that starts to get a little blurry.

So we're not gonna make leaps in terms of what we can assume about dire wolves 75,000 years ago, 200,000 years ago.

However, we are working with an amazing group of scientific advisors, of academic researchers that have lots of questions, everything from the genetic and epigenetic effects of gene editing, to when these animals become adults?

We'll use advanced imaging like CT imaging to try to get 3D renderings of their skeletal morphology, and then we can begin to compare that to fossil record and try to understand where are they the same, where are they different?

- In terms of the technology that is at play here, Colossal, of course, markets and sell themselves quite a bit as a technology company, what is the scope of those technologies that are being innovated right now?

- The entire pipeline includes opportunities for innovation and technology, from, you know, going from sequences of genomes to predictable phenotypes, or genotype to phenotype.

We're not the only people trying to innovate in this space, thank goodness, because it is one of the hardest problems in biology and we need everybody who's thinking about it to also be thinking about how we can get better at it.

We will make these technologies available to conservation partners, free, obviously, and a lot of things we're publishing, and so it's going to be easier, easy for the world to see, and have access to the types of technologies that we're working on.

I do see this as an opportunity to develop technologies that will be used more broadly, so Colossal does not plan to own all of the technologies that we're developing for conservation.

Oh, there's also the artificial womb.

(laughs) - Oh yes, we shouldn't not forget about artificial womb.

In some ways, what they've done with creating this proxy dire wolf is the easy mode of de-extinction.

We understand a lot about the biology of mammals, like Canids and how they grow and develop, and they have numerous living relatives that can be used to carry these embryos, but that's not true for other potential de-extinction species.

Elephants, who could be the surrogates for mammoths, they carry their babies for 18 to 22 months, that's a long time to have very little control over what's happening inside a surrogate mother's body.

And they also have super-complex social structures, and we have no way of knowing how those differ from what a mammoth herd would've been like, all those details of how they lived and learned.

When it comes to birds like the dodo, as of now, we have no idea how to clone a bird in literal eggs with shells, in a way that produces adults that possess gene edits that they will pass on to their young in the next batch of eggs.

Colossal's co-founder initially wanted to bring back a Steller's sea cow, which is basically a manatee the size of a short bus.

The closest relative we have for that animal is a manatee cousin, the dugong, huge technological leaps will be required to create what this company hopes to create.

- If you consider the same mother-to-calf ratio at birth, and the dugong was to be the surrogate of our Steller's sea cow, the newborn baby would be around the same size as, or slightly larger than its mom, which would probably not work out.

So, you know, obviously from an ethics perspective, that's a terrible idea, but also from a technicals perspective, like, we're not going to be able to do this until we had an artificial womb that would actually work, and maybe then, we would have to take a step back and consider whether the planet really needs Steller's sea cows.

- We love to pair each of our de-extinction projects with an extent species that's currently imperiled, by creating all the science for the dire wolf, we also created pathways that allow us to create a synthetic solution to genetically rescuing the world's most endangered wolf today.

When we work with woolly mammoths, we're studying Asian elephants, we created a vaccine that helps protect Asian elephants against one of the leading causes of death, EEHV in Asian elephants.

When we work with dodos, now, we're creating a genetic rescue platform for the Mauritian pink pigeon.

We're working with thylacine, we're creating genetic engineering solutions to help overcome toxicity of invasive species.

Why are we bringing these animals back right now into a world that perhaps, might not be ready for them?

My hope is that this acts as a beacon of hope that can help drive and inspire, by bringing the dodo back, can we go to Mauritius and we begin to carve out more and more nature preserves that will be ready to receive dodos?

That is fundamentally changing to the species that exist on Mauritius today as well.

- We know a lot more about things that lived at the same time as people.

So we know a lot more about a thylacine, for example, than we do about a mammoth, or about a dire wolf, and so when we're studying these animals and trying to figure out when is the right time to bring something back, does it make sense to bring it back?

Do we need it in this ecosystem?

Is it going to actually play a really important role, like it did before?

Have we solved the problems that caused it to become extinct in the first place, in the case of something like a dodo or a thylacine?

And the answer for both of those is no, we haven't actually solved those problems, but we have a path to solving those problems, and we can engage people in solving those problems in a way that has cascading benefits to species that still live in those habitats.

The dodo went extinct, because it is a flightless bird that laid a single egg in a nest on the ground, and it went extinct, not because people clubbed them to death or people ate them, in fact, there were some people who wrote down that they didn't taste particularly good, right?

But because when people arrived in Mauritius, they brought rats and cats and pigs, and these animals ate that egg, that single egg in a nest on the ground.

So if we are going to have dodos back in this ecosystem, we have to solve that problem, right?

We have to create opportunities for species that were introduced by people, that are also being pretty destructive to other endemic Mauritian native fauna.

So we have a community group, we're working with Mauritian Wildlife Foundation and Durrell Conservation Society, as well as government groups, and community members in Mauritius, and asking what to do?

And there's been renewed investment in trying to find places where we could introduce these dodos, because they want to see this animal come back.

And so we see that just having these conversations initially, from a conservation perspective has really had benefits to other species that are there, even though, we are obviously, many years away from having a wild population of dodos anywhere, right?

- There is a worry that some people who create policy around conservation might point to a technology around de-extinction as an excuse to do less, and we've already seen a few hints of that perhaps coming out, what is your response to some of those early hints or people who might have that mindset?

- No one is arguing that this sort of technology should replace traditional approaches to conservation.

We need to continue to invest in habitat restoration, in stewardship, in traditional approaches to conservation, absolutely, this is not a silver bullet, right?

And extinction is forever, like we said, we have a de-extinct dire wolf that represents some aspects of the dire wolf, but certainly not all.

There is zero chance that de-extinction will become something that replaces the fight against extinction.

But I do think that having tools to modify genomes and to help species to adapt more quickly to changes to their habitat, could be something that helps us get more of a leg up in the war against extinctions.

This is one of many new bio technologies that should be coming online, that people should be working on, to be able to augment what we're doing.

We still need habitat protection, we still need endangered species protection.

- For the 15 years working in a nonprofit conservation space, I felt that there wasn't enough action to do what we should be doing, that there wasn't enough action to protect habitats, to protect species, but that was driven primarily by a lack of resources.

I am hoping, and what I'm seeing so far, is that Colossal is driving interest and funding into a space that typically lacked funding, and did not have the interest it deserved.

So I think this is not a either-or proposition, this is a complementary effort to conventional conservation.

I think our activity in the space will drive more interest, more money into conventional conservation.

We have to understand that we are being outraged, outpaced by the biodiversity loss today.

We continue to accelerate our impacts on nature, not reduce it, so we need to also begin to create solutions for tomorrow that can help slow and reverse that trend.

- What does success look like?

- I'm not sure that we'll ever achieve success, a hundred percent success, I think we will win battles along the way, but success won't really be here until we have stopped the bleeding, until we have stopped the biodiversity loss that is driven by human activity right now.

- The ethical debates around de-extinction are complicated, and there's a lot of risk involved in creating these proxy species.

John Muir once said, "When we try to pick out anything by itself, we find that it's bound fast by a thousand invisible cords to everything in the universe."

What that means is that ecosystems are these complex webs that push and pull on each other in ways that we're still understanding.

It's also true for genomes, the complex networks that genes interact with and regulate each other.

We find ourselves at a time when this is no longer hypothetical, it's possible, scientists all around the world are working on technologies like these in different ways.

So the big question is, should we be doing de-extinction at all?

- In some cases, it probably will be useful to reintroduce species to habitats, or maybe not.

But the argument that we just shouldn't do this, that it's too risky, that we can't possibly understand all of the complications that surround ecosystems, it assumes that the better thing to do is to do nothing.

I need to push back on that, because choosing not to do this because we think we're not smart enough to understand all of the risks and unintended consequences that potentially might arise, it ignores the fact that there are intentional consequences of what we're doing, and that the choice not to do it, is also a choice that has consequences.

We need to give ourselves the space and time to develop new tools and to evaluate them, rather than just to push back on them because they're scary in some kind of wiggly way that we can't really articulate.

- The fact is, this does feel scary or different, or some other complex feeling that's difficult to describe, because humans haven't faced a situation like this, where science has given us the power to create life that's never existed before, or recreate something like past life, simply if we choose to.

Powerful ideas deserve powerful criticism, and the concerns and cautions presented by many people are valid and worth hearing, because dire wolves will not be the last species that's brought back in this way.

It's likely that several species disappear from Earth every day, that doesn't make headlines, but obviously, this does.

Does getting more attention paid to biodiversity loss make this worth the potential trade-offs?

Or should we stop experimenting with life and ecosystems when we are the reason these species are extinct to begin with?

We don't know the answer yet, science is an ongoing process, and we have to consider the effects and impacts of ideas, and we hope we've done that here, stay curious.

Do you wanna give a shout-out to your T-shirt real quick?

It looks like, - Yeah.

(giggles) - [Joe] I just thought it deserved a little camera time, that is a good one.

- Team Dore Wolf.