Unexplainable - How to resurrect a mammoth

Episode Date: April 26, 2023

Scientists are hard at work trying to bring back woolly mammoths (and dodos). But should they? And what would they actually be bringing back? For more, go to http://vox.com/unexplainable It’s a great place to view show transcripts and read more about the topics on our show. Also, email us! [e-mail] We read every email. Support Unexplainable by making a financial contribution to Vox! bit.ly/givepodcasts Learn more about your ad choices. Visit podcastchoices.com/adchoices

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please contact connects Ontario at 1-866-531-2,600 to speak to an advisor, free of charge. BetMGM operates pursuant to an operating agreement with Eye Gaming Ontario. It's been thousands of years since Willie Mamma. roamed the earth, but the chance of seeing one walking around again may not be too far away. You hear that Yelp in the background? That's kind of how I felt when I first heard this. It sounds like a scene from Jurassic Park, but it's true. Scientists at a company called Colossil are trying to use genetic engineering to bring

woolly mammoths back. Using CRISPR genome editing technology, a team of scientists aimed to genetically resurrect a Woolly Mammoth by 2027. And all this is getting people pretty excited. Can I tell you I posted this question on my Facebook page? Yeah. Oh, boy. You got to check that out.

It is taking off. I checked it out. I'm new here, but at 76 years old, I say go for it. I'd rather see a Wully Rhino. Wasn't that your nickname in high school? They need to go back and watch Jurassic Park. Bring back Jesus. Colossal isn't bringing back Jesus yet, but to be honest, they're not really bringing back mammoths either.

I think to the average person, when they hear the word de-extinction, they imagine bringing back an identical copy in every way of a species that used to be alive. But the reality is that this is just not possible. Beth Shapiro is the lead paleontologist at colossal. What de-extinction really means is using modern biotechnologies to resurrect exhumated. distinct traits in species that are still here. Living species like elephants. The goal is to create an elephant that contains some mammoth-like traits. Colossil says mammothy elephants would be more cold-resistant and resilient,

and that if enough of them come back to their old Arctic habitats, they could help restore the ecosystem. Bring back grasslands, pack down snow. A lot of the permafrost is melting, and they're saying that these hybrid woolly elephants, mammoth thingies could take care of that. So far, Colossals raised over $200 million, because on top of biodiversity, they say this technology could have impacts from agriculture to biofuels to vaccine development. Who doesn't want to make potentially billions of dollars in returns on technologies that can be used for human health care? But despite all of these big claims, there's still a pretty important question.

Your scientists were so preoccupied with whether or not they could that they didn't stop to think if they should. That question was asked in Jurassic. Park. Go debate that on my Facebook page. Beth understands this debate as well as anyone. She's been writing about it since before colossal was even founded. I wrote a book called How to Clone a mammoth that was basically a long-form answer to why it's not possible to bring a mammoth back to life and all of the challenges, technical, ethical and ecological that would be associated with such a trend. That's why I wanted to talk to Beth in particular. She's voiced skepticism of de-extinction plans in the past.

And now she works with Colossil. It's a shift that's given her a unique perspective. De-extinction is not a solution to the extinction crisis that's underway today. But developing the technologies is absolutely critical to help species that are alive today adapt to their rapidly changing habitats. I'm Noah Massenfeld. And this week on Unexplainable, I talk with Beth Shapiro about colossal's de-extinction plans. exactly how possible is it to bring an animal or even just qualities of an animal back from extinction?

And what might happen if we do? So let's just start with who you are and what you do outside of working with Colossil. My name is Beth Shapiro. I am a professor of ecology and evolutionary biology at the University of California Santa Cruz, where I work on ancient DNA. And what kind of things do you work on usually? So my research is really aimed at trying to recover information from the past that can help us to make more informed decisions about protecting species and ecosystems that are around today, but perhaps, you know, in danger because of rapid changes to the climate and to the environment, using the past as a kind of completed evolutionary experiment. So you're basically studying, like, ancient environmental impacts. How do you end up getting into de-extinction? Everyone who works in my field, ancient DNA, has become accustomed to being asked what all of our research means to bringing mammoths back to life.

In fact, I was doing some research for my most recent book, Life As We Made It, and I found the New York Times article describing the very first successful ancient DNA experiment. It was in 1984 when a team from Alan Wilson's lab extracted DNA from a extinct type of zebra. And he was describing how exciting it was to have proven that DNA. can persist in remains of things that used to be alive when he became the very first ancient DNA scientist ever to be asked by a journalist what this meant about how long it was before we were going to have mammoths back and roaming around the Arctic. That is like the first thing that happened. Like someone talks about ancient DNA and it immediately goes to let's bring mammoths back? Well, as soon as they learn that we can't have

dinosaurs, it does tend to swap to mammoths. Yeah. And it is true. It becomes the question every time we publish a paper, and my research has never been focused on bringing extinct species back to life. This is just where everybody always goes when we publish our research. And of course, you know, it's still not possible to bring an extinct species back to life, but there are technologies now that should, in a future world, make it possible to resurrect some extinct DNA, and along with that, perhaps some extinct traits. I asked Beth to walk me through what this might actually look like, how colossal might bring back traits of a mammoth, assuming this tech continues to develop.

So go out of the fields and you can collect frozen specimens of mammoths. And Beth's actually done this part of the process herself. We've just found, you can see is one, two, three, four pieces of mammoth home here. This is from a video Beth did for National Geographic. She's excavating mammoth vertebrae at a gold mine in the Yukon by essentially blasting water. against frozen mud. See, these pieces are actually still frozen in the permafrost. We can't get them out at all.

Which means they're going to be really well preserved. At one point, all that blasted water actually gets a little close for comfort. You just heard that big splash of water back there. That means the other hole is broken through. Here comes the water. We better get out of here. And this is just one spot in Canada. We know that there are thousands of these across the Arctic. But scientists can't just take it.

DNA from these bones and clone a mammoth. Beth says healthy DNA is like a bunch of party streamers, these long, winding strands. But ancient DNA is more like a ton of confetti. As soon as an animal dies, the DNA starts to get broken down into tinier and tinier fragments until eventually there's nothing left. Because of freezing and thawing, because of sunlight. Because of things like microbes, fungi, and bacteria that chew it up, transforming it into the next generation of stuff. So scientists have had to painstakingly line up these bits of confetti on a computer to create a mammoth genome.

But this DNA sequence, it's just letters on a screen. Scientists need actual live DNA. So they look to the mammoth's closest living relative, the Asian elephant, and they try to make it look more like the mammoth sequence they see on the screen. So we map these tiny little broken mammoth DNA fragments to the Asian elephant genome on a computer. You can line them all up and scan across these four billion letters, that's how big the elephant genome is, and ask where they're different from each other.

At this point, scientists can edit the actual DNA itself. So then you would take a living cell from an elephant, and you would use the gene editing tools like CRISPR to basically cut and paste your way from an Asian elephant to a mammoth DNA sequence. But CRISPR still can't edit an entire elephant genome. CRISPR breaks the genome in a little place in order to make the swap out of the DNA letters. And if you break the genome at lots of places at the same time, it just causes destabilization and it falls apart. So Colossal has to choose its battles, essentially. And for mammothy elephants, they're focusing on specific genes that help with adapting to the cold.

Things like longer hair or thicker layers of subcutaneous fat that would make this animal better able to survive in the Arctic. Finally, once scientists have crispered up the elephant, DNA to make it more mammothy, they still have to actually create this new hybrid animal, which they do by cloning. The same scientific process that brought us Dolly the Sheep, for example. They take a regular elephant cell with edited DNA, put it next to an elephant egg cell. They've emptied out. Zapp them with a bit of electricity that causes the nucleus, where the genome is, to dump into

or transfer into that empty egg cell. And after a little more zapping, that new elephant, elephant egg cell with the edited DNA can develop into an embryo, which scientists can transfer into a surrogate host. Go through, in the case of an elephant, a 22-month gestation, and then hopefully you would have an animal born that was a little bit more mammoth-like than his mother. Colossal says this could happen by 2027. But this isn't the first prediction that de-extinction scientists have made. Back in 2017, before Colossol was even around, the now head scientist of the mammoth project, said he could get to a hybrid embryo in a couple years. Six years later, he's still working on it.

So it's probably worth taking this guess with a grain of salt. But the bigger question here is why Colossal is even doing this to begin with. What's the purpose of de-extincting at all, if that's the word? It's terrible, right? It's absolutely no idea how to conjugate that word. It's completely ridiculous. You know, I think to me, the motivation is really to see these technologies develop. Imagine if you could resurrect extinct diversity and introduce that diversity

into a population that's still alive today, but perhaps in danger. An example is the Blackfooted Ferret Project. The entire captive breeding population is very closely related to each other. There's not that much genetic diversity in that population. But there are frozen specimens of blackfooted ferrets that are in the collection at the San Diego Frozen Zoo. And one can use the tools of extinction, to resurrect lineages that used to be alive, and then one can introduce those lineages into the living population, increasing diversity, perhaps giving them a fighting chance at surviving. Interesting.

Or we can look to traits that evolved in mammoths, a species that could live in temperate and Arctic areas, and ask what differentiates mammoths from tropically adapted Asian elephants, and then use the tools of gene editing to introduce those traits into Asian elephants. So you could use the tools of de-extinction to augment species that are alive today, to speed up the pace of evolution so that they can adapt to their rapidly changing habitats. And all this de-extinction talk is still just augmenting, right? We still can't change the entire elephant genome. Yeah. But here's an important point as well. Even if we were to be able to make all of the changes and have a genome sequence in an Asian elephant cell that looks exactly

like a mammoth. Organisms are more than the sequence of letters that make up our DNA, where a combination of our genomes and the environments in which we live. If we were just our genomes, identical twins would be completely identical and interchangeable, but they're not, right? So all of our experiences, including those that happen in utero during those earliest stages of development, shape the way our DNA is expressed. We really can't come up with something that is 100% identical to a species that used to be alive. We can't reconstruct behaviors without knowing what those behaviors are or having animals around to teach these other animals.

We can't reconstruct the gut microbiome. We don't have the same habitat or environment. These habitats and environments are also extinct. But I also would argue that it doesn't really matter because back to your point of what is the purpose of this, right? The purpose isn't to create an identical copy of a species that used to exist just for fun. The purpose really is to create something that's going to be able to be reintroduced or rewilded into a habitat, and the presence of that organism will somehow reinvigorate that habitat,

will restore some ecological interactions to that habitat that might have been missing since the extinction happened, hopefully to making that habitat more resilient in the face of rapid climate change. Assuming this technology continues to develop, the path is there to create extinct animal hybrids. The bigger question is whether we should. Beth has wrestled with this question herself. A few years back, she was skeptical of a lot of de-extinction plans, and now she's Colossal's lead paleontologist. So what changed? That's next.

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Learn more about their customizable plans at squareup.com. I'll need a drop of blood. John, that hurts. Relax, John. It's all part of the miracle of cloning. Colossal isn't just working on de-extincting the mammoth. They've got a project to bring back the Tasmanian tiger, which went extinct in the 30s. And earlier this year, they announced a project to bring back the icon of human-caused extinction.

The Dodo. Dead as Dodo, they say. But now the extinct bird could once again be hopping and jumping. The Dodo was a short, flightless. bird from Mauritius, this small, relatively isolated island, about 700 miles east of Madagascar. It was one of the first species that humans drove to extinction in the modern world, and it just happened so quickly. Less than 100 years after humans first got to Mauritius, there were no dodoes left.

Beth led the team that sequenced the first complete dodo genome last year, and after being skeptical of de-extinction projects for a while, she's looking forward to working on the dodo. I mean, the dodo is the very first animal that I ever worked on as a PhD student. I've got a dodo tattoo in my arm. To me, I like the dodo. From the perspective of this project, I think it's really nice because it only ever lived in one place in Mauritius. The people of Mauritius are super excited and engaged in the project. We have collaborators on the ground in Mauritius that span scientists to government people,

to people interested in ecotourism, and they're excited to help. And I like that aspect of it. I also really think that biotechnology for birds is necessary and behind everything else. You know, we can clone mammals, which means that once we gene edit cells, there is a scientific tool that we can use to get those edits into living, breathing animals. We just can't do that with birds. Beth says that the main technical issue with cloning birds is the egg itself. Because to clone an animal, scientists need access to an egg cell that's ready to be forced. fertilized. But we don't have access to egg cells at that particular developmental stage in birds,

so it's not possible to clone birds. But Colossal has a plan for a potential workaround. When a chicken egg is laid, you can stick a needle into the egg and without hurting the embryo, suck out some of the cells that are going to be either sperm or eggs, depending on the sex of the animal that's developing. These potential sperm or egg cells are called primordial germ cells. They will eventually be germ cells. They're not the cells that form the bird. They're the sperm or egg cells that a bird will use down the line to make chicks of its own. Then you can inject them into a dish where they can live, and you can edit them there.

Basically, edit the DNA of those primordial germ cells to be more dodo-y. And then you can inject those edited primordial germ cells back into an embryo. The regular old bird embryo. And that bird, when it is born, will be totally normal. but some of its germ cells will be edited. So when that bird eventually has its own kids... The offspring will contain the edits. So all in all, while scientists can clone a mammal directly,

they need to go through an extra step for birds. An extra generation to make it work. They need to edit a bird's primordial germ cells, wait for it to develop and have children, and then those second-generation birds will end up changed. That's why I say that with different species, There's different technical challenges. You know, with mammoths, clearly having a uterus and an animal growing up inside a mom

is a really big technical challenge that we don't have in birds. But you can clone mammals and you cannot clone birds. Still, Beth says that developing this gene editing technology could be useful for bird conservation. And she thinks it's particularly worth it to do this research on the dodo. I love the idea that we could transform the dodo from this icon of human-cost extinction to an icon of hope of a future where we can use biotechnology to save species and ecosystems and to stop the destruction that's currently happening. But if the real goal here is conservation, why not just follow, you know, these normal

conservation methods for species that are currently at risk? Like you could do that without this almost sci-fi de-extinction thing. Yeah, absolutely. We should be working on those things. What this is is an injection of new money. And that's one of the exciting things. Recently, the company, Colossil, and I'm a scientific advisor for Colossil, they announced that they'd raised about $225 million to this de-extinction effort. And people have often asked, well, is that fair?

I mean, if you say you're developing tools for conservation, wouldn't it be better spent actually saving things using the traditional tools of conservation? Right. And I would argue that it's this draw, this idea of de-extinction. It's actually bringing in new money to conservation. These are not investors that would have given to traditional conservation approaches. And so what's happening now is new money is being brought in to develop new tools that will have application to present-day conservation projects. I think it is an incredibly beneficial thing to conservation to have people excited about this idea of de-extinction.

Okay, so then let's talk about some potential downsides because, like, we don't know how the Dota or the mammoth would behave. You know, we don't know the types of impacts of things in the microbiome or the mother's behavior or any of those types of impacts. Is it possible that, you know, we could be reintroducing a species that could become invasive in an ecosystem? I think we have a long track record of introducing species that become invasive in ecosystems. And obviously, there's always a potential that something could go wrong. But this is, we're not talking about today we're going to clone a mammoth and tomorrow we're going to have thousands of mammoths running around in, the Siberian permafrost. This is a long-term project, very slow-moving, engaging stakeholders. Colossil went to Alaska and had initial meetings with stakeholders from political groups,

Bureau Land Management and Indigenous People's Groups last year, which is decades probably before there might be any animal that's out there. But if there is a project in the background that's saying, well, we're working toward this goal, it's a long way off, but we're working toward the goal, it kind of lights a fire under everyone and says, let's get together and figure out what it is that we're going to do to think about regulation and ownership and governance. And these animals won't be just released into the wild. They would live in captive environments and then slightly wilder but still captive environments.

And we would have lots of opportunities to observe how they interact with other species. So, you know, I'm really curious about how you think about your work on the Dodo Project with how you used to think about colossal and de-extinction. Like I heard the CEO of Colossal Ben Lamb. He was talking about you in an interview recently, and he said, Beth Shapiro is now talking to the world today about the Dodo. She was actually one of our biggest voices of opposition when we started.

Now, you're working with them, and I'm wondering, like, did something in the tech change? Did how you see the project change? I think my opposition really comes to this general perception that it is possible to bring something that is extinct back to life. And I haven't changed my mind to this end. Once something is extinct, it's gone. I think, you know, people are excited about the idea of de-extinction. And I think most people who work with Colossil are careful to say it is not possible to bring a mammoth back to life. If you look on their website, it says they're creating an Arctic adapted elephant.

But there's this real push to keep saying they're creating a mammoth. It's simpler. It's obviously easier to get that sort of message across, but it's also not true. And I think it gives false hope and also maybe a little bit too much because we don't want people to start imagining that de-extinction is a solution to the biodiversity crisis. It's not. We need to stop species from becoming extinct, but that's precisely why we need these tools. These tools will help us to stop species from becoming extinct. I mean, Colossil says they're creating an elephant mammoth hybrid, but their site also says that they want to see the woolly mammoth

thunder upon the tundra once again, which sounds a lot like bringing back full mammoths. Yeah, it's certainly a semantic tension. And I think, you know, when I wrote the book in 2015, I was already saying that these technologies would be useful for conservation. And the technologies are coming along slowly and surely. I think it was just, you know, at some point you have to decide that you're going to embrace the semantic confusion, right? And so my, if my, if my objection is as a scientist, I don't think that it's possible to bring something back to life and therefore I disagree with the idea of de-extinction. But I'm also saying, oh, scientists, chill out, you know?

Just because we say de-extinction doesn't mean we don't understand that underlying this is the truth that we cannot bring something back that is identical to something that used to be there. Maybe it's my job to actually embrace this confusion, try to clarify what we mean, but it's a semantic thing. And I think we just all need to get over ourselves a little bit. Beth isn't the only scientist who's made this move of going from de-extinction skeptic to working with colossal.

And I was curious to hear from someone who was asked to work with colossal, but declined. So I called up Tori Herridge. She's a paleobiologist at the Museum of Natural History in London. I'm not inherently averse to de-extinction or even discussing it. In fact, I find it absolutely fascinating. What I find difficult to swallow is the kind of certainty that this is going to change the world,

and I don't think it's going to change the world. Tori agrees with Beth that bringing back extinct genetics is exciting, that it's worth pursuing, but she's skeptical about the way Colossal presents the potential impact here. She's not sold on how much mammothy elephants would actually transform the Arctic, and she's worried that not all of this funding is just new money, that it might take away space from other less speculative conservation work. It's a private company that is there to make money, And a business will always have different agendas to publicly funded science.

And finally, Tori worries about what framing this as, quote, de-extinction says to the public. They are kind of riding on the coattails of a public perception that DNA has the answer. And if we can get something's DNA, we can make it. It's a sort of tabloid-esque version of science. I found this last criticism especially interesting. Because it's something Beth is clearly aware of. She even mentioned it in our conversation. Organisms are more than the sequence of letters that make up our DNA.

We're a combination of our genomes and the environments in which we live. So I wanted to know how Beth felt about this kind of criticism, whether it says something about us that a lot of people might not get excited about conservation unless it's framed as this exciting neon lights de-extinction project. I don't know. You know, I think that one of the main strategies for getting people to invest in conservation is to tell people how terrible things are, how species are about to become extinct, how habitats are being destroyed, how everything is really just going to hell in a handbasket.

Like the world is falling to pieces. I think people are just tired of hearing that. Everybody wants a positive story, so why can't we tell them one? And this is an exciting thing that biotechnology might bring us that has the potential to help species not become extinct. You know, we need this sort of investment into biodiversity conservation. We need to be able to talk in ways that engage people rather than put them off. And I think this is, is this an example of how hard that is?

It still isn't clear whether this will ultimately amount to anything. Whether colossal can actually make a mammothy elephant anytime soon or figure out how to make some kind of hybrid dodo bopping around Mauritius. But I get the hope of it all, trying to bring back species that we've killed, or even just trying to bring back a few traits they've developed over millions of years of evolution, and then wanting to call this kind of moonshot de-extinction. Whether that's a misleading description or a practically worthwhile metaphor, it's hard to say. It could honestly be both. But the bigness and the weightiness of this word, de-extinction,

it speaks to the enormous scale of the crisis facing us. D-extinction is never going to be a solution to the extinction crisis. But hopefully, just discussing it might serve as something like a wake-up call. Of just how much harm we've done and how much work we still have to do. This episode was produced by me, Noam Hassenfeld. We had editing from Brian Resnick and Catherine Wells, mixing and sound design from Christian Ayala, music for me, fact-checking from Zoe Mullock and Mandi Nguyen, and Meredith Hadnott is our headshot.

chef. Bird Pinkerton nervously walked toward a strange color-shifting blob in the middle of the room. I've been waiting for you, said the octopus. Hand me your king. Special thanks this episode to Amanda Luellen, Sionap Etros, Hadi-Mawagdi, Shining Zhang, and Matt Colette for their voice talents. And just a quick note, in our conversation, Beth was talking about how colossal describes the mammoth as a modified elephant. She said the website says Arctic adapted elephant, but the exact language it uses is a cold resistant or cold tolerant elephant. If you have thoughts about this episode or ideas for the show, please email us. We're at Unexplanable at Vox.com. We'd also love it if you left us a review or rating. Unexplainable is part of the Vox Media Podcast Network, and we'll be back next week.

One last thing before we go. Beth mentioned that it's still not possible to clone a dinosaur. But just in case you were wondering why Jurassic Park isn't a real possibility, here's what you told me. In order for us to be able to resurrect an extinct trait, we have to know the DNA sequence for that extinct trait. So I have a really well-preserved dodo that we've been able to get from the Danish Museum of Natural History, and we have sequenced its whole genome. The same is true for mammoths. But the oldest DNA that has been recovered from a bone is only a million or so years old, and even that is rare. most of the DNA that we recover dates to within the last several tens of thousands of years.

And dinosaurs, as we know, non-avian dinosaurs anyway, have been extinct for more than 65 million years. There is no DNA remaining in any dinosaur fossils. These are all rocks, right? So Jurassic Park is not possible. We can't clone a dinosaur because we'll never know what a dinosaur's DNA sequence looked like. And we can't, therefore, use that as a template to gene edit any living birds to look like an extinct. bird. And just in case you're still wondering, hey, what about the mosquito in the amber thing? Beth tried that too. Didn't work. Sorry, Jurassic Park, true believers.