Reviving The Woolly Mammoth ... With Mice

You've heard of the woolly mammoth. But have you heard of woolly mice? These critters were genetically modified by the Dallas-based biotech company Colossal Biosciences https://colossal.com/ to have the same "woolly" and fat appearance as the ancient mammoths. The mice are a key step in the longer journey to de-extinct the woolly mammoth. NPR's Rob Stein https://www.npr.org/people/146944972/rob-stein takes us to the lab where it all happened. Interested in more biotech stories? Let us know by dropping a line to [email protected] mailto:[email protected]. Listen to every episode of Short Wave sponsor-free and support our work at NPR by signing up for Short Wave+ at plus.npr.org/shortwave http://plus.npr.org/shortwave. See pcm.adswizz.com https://pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences. NPR Privacy Policy https://www.npr.org/about-npr/179878450/privacy-policy

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  This message comes from Doppel. Social engineering attacks come in disguise, but Doppel sees through them. The Agentic platform shuts down threats, turns employees into first line defenders, and more. Learn more at D-O-P-P-E-L dot com.

• 0:16Regina Barber?

  You're listening to Short Wave from NPR. Hey there, Shortwavers. Regina Barber here, and today I'm joined by NPR's Rob Stein. Hey, Rob.

• 0:26Speaker 02

  Hey, Gina.

• 0:27Regina Barber?

  Rob, you're usually here to talk about stuff related to health, like COVID or CRISPR or organ transplants, but word on the street is today is a little different.

• 0:36Speaker 02

  Yep, I'm here this time to talk about little fuzzy squeaky animals.

• 0:41Regina Barber?

  OK, let me guess, do they like cheese?

• 0:44Speaker 02

  How did you know? Yes, indeed. I'm talking about mice, and these aren't just any mice.

• 0:50Regina Barber?

  OK.

• 0:50Speaker 02

  These are, wait for it, woolly mice.

• 0:55Regina Barber?

  OK, woolly mice? Rob, what makes them woolly?

• 0:58Speaker 02

  Well, Gina, you've heard of the woolly mammoth, right?

• 1:01Regina Barber?

  Of course. I love those hairy elephants. They used to roam the tundra. They were actually still around when the pyramids were built.

• 1:08Speaker 02

  Exactly, before they went extinct thousands of years ago, maybe because of climate change and hunting.

• 1:14Regina Barber?

  OK, so these mice, they're like miniature versions of woolly mammoths?

• 1:18Speaker 02

  Bingo.

• 1:19Regina Barber?

  Cool. OK, but why are you bringing them up now?

• 1:22Speaker 02

  Well, because someday, some scientists want to bring a mammoth-like creature itself back from extinction.

• 1:29Regina Barber?

  Wow, so they have like Jurassic Park-like intentions?

• 1:33Speaker 02

  Yes, exactly. These scientists, they work at a Dallas biotech company called Colossal Biosciences, and they say these little woolly mice are a key step towards that audacious, and I have to say, quite controversial, call.

• 1:48Regina Barber?

  Wow, OK. So today on the show, woolly mice and what they mean for the elusive goal known as de-extinction. You're listening to Short Wave, the science podcast from NPR.

• 2:05Speaker 00

  Stay tuned for the following announcements and messages from our sponsors. This message comes from ProLon. Want to look and feel your best this fall? ProLon's five-day fasting-mimicking diet is a clinically-developed nutrition program with the goal of promoting fat loss while protecting lean body mass. Developed at USC's Longevity Institute, it aims to assist the body in entering a fasting-like state that helps reset metabolism, target visceral fat, and support healthy metabolic markers. Get 15% off plus a bonus gift when you subscribe at prolonlife.com/NPR. This message comes from Avalara Aviator. Aviator is the agent hub for tax and compliance. If you've listened to enough podcasts,

• 2:47Speaker 00

  you know a confident answer isn't necessarily a correct one. Sources matter. The same goes for AI, tax, and compliance. Aviator is grounded in 20-plus years of Avalara tax intelligence and delivers source-backed audit-defensible outcomes with human oversight built in. Because the AI said so, won't pass an audit. Visit avalara.com/aviator. In the much-talked-about new movie, Wicker, Olivia Colman plays a woman who commissions a husband literally made of wicker. Yes, wicker.

• 3:19Regina Barber?

  We'll tell you why the silly and bawdy new movie is also a nice cozy fall watch. Listen to Pop Culture Happy Hour via the NPR app or wherever you get your podcasts.

• 3:31Regina Barber?

  OK, Rob, we're going to go from mice to mammoths.

• 3:34Speaker 02

  Yeah.

• 3:35Regina Barber?

  Let's start with these woolly mice. Like, how are they different from normal mice? And how were they created exactly?

• 3:41Speaker 02

  So to answer that, I have to start with the mammoths.

• 3:44Regina Barber?

  OK.

• 3:44Speaker 02

  Colossal Biosciences wants to bring the mammoth back by using the latest genetic engineering techniques to create modern-day elephants with key traits from the mammoth.

• 3:54Regina Barber?

  Cool.

• 3:54Speaker 02

  You know, traits like their signature thick coat and their fat metabolism that kept them warm in the Arctic.

• 4:00Regina Barber?

  And how do they go about doing that?

• 4:03Speaker 02

  So they started by comparing genomes from samples of ancient DNA recovered from mammoth remains with genomes from living African and Asian elephants, the mammoth's closest living relatives.

• 4:16Speaker 03

  We ask, where are all of the mammoths the same as each other, but different from an elephant? So this is narrowing down the focus on the genes that make mammoths mammoths instead of elephants.

• 4:28Speaker 02

  That's Beth Shapiro, the chief science officer at Colossal.

• 4:31Regina Barber?

  So in practice, I imagine they're like hunting for genes responsible for like iconic, you know, mammoth traits, like their distinctive coat.

• 4:39Speaker 02

  Yeah.

• 4:40Regina Barber?

  And their, maybe their fat?

• 4:41Speaker 02

  Exactly. And they narrowed down that list of candidate genes to 10 genes for the coat and the fat.

• 4:46Regina Barber?

  Okay.

• 4:47Speaker 02

  But they wanted to make sure that the genes they had identified were really responsible for the traits that they wanted. They couldn't just, you know, try to engineer Asian elephants with genes they thought might control those traits because it would be unethical, given the fact that Asian elephants are endangered.

• 5:03Speaker 03

  Here's a difference in a letter in a long string of As and Cs and Gs and Ts, a genome of a mammoth that we've gotten out of a bone that was preserved in the permafrost in Siberia. It's hard to test that in an elephant because an elephant is pregnant for 22 months and then it takes another decade to 14 years for that elephant to be able to have a baby.

• 5:23Regina Barber?

  Hmm. So it takes a lot of time to isolate those genes, insert them into like Asian elephant embryos, wait to see if that like pans out, then like go back to the drawing board with the next one?

• 5:34Speaker 02

  But a mouse is a different story.

• 5:35Speaker 03

  With a mouse model, we can really rapidly test these hypotheses and learn whether this change might be responsible for making the animal woolly. And now I can add that to the list of things that I want to change when I'm editing that elephant cell.

• 5:49Regina Barber?

  Yeah.

• 5:50Speaker 03

  So that I can have an elephant someday give birth to something that looks more like a mammoth.

• 5:55Regina Barber?

  Wow. Okay, so that's where the mice come in. Like they reproduce so quickly, there are so many generations, and like they get more data faster.

• 6:02Speaker 02

  Yeah, yeah, exactly. That's exactly how it works. The mice are great little critters for doing these kinds of experiments, seeing the effects of genetic changes, because they reproduce so fast and scientists, you know, they just know how to work with them.

• 6:15Speaker 03

  We look in the mouse for those same genes and instances where those genes have been involved with making a woolly coat, or longer hair, or changing the color of the hair.

• 6:24Regina Barber?

  And so they can see, like, did this gene that shows up in the woolly mammoth DNA have like the same effect in mice?

• 6:29Speaker 02

  Or giving the animals fat that protects them from the Arctic cold.

• 6:33Regina Barber?

  Okay.

• 6:33Speaker 02

  And once they did that, the researchers used different kinds of genetic manipulation to modify the genes in mouse eggs and mouse embryos, and then use those to breed mice they hoped would have those traits. And you know what, Gina? It appears to have worked.

• 6:49Regina Barber?

  Wow, that's so awesome.

• 6:51Speaker 02

  Yeah. One change gave the mice hair three times longer than usual. Another made their coats wavy. Another turned their coats this kind of golden blonde, you know, color like mammoths, et cetera, et cetera.

• 7:03Regina Barber?

  Wait, wait, so not dark brown, like children's books when I see the mammoths? Are those mammoths just like dirty?

• 7:08Speaker 02

  That's the idea. I mean, these, these little creatures, you know, they kind of look like what mammoths would look like if they had a good bath and a blowout.

• 7:16Speaker 03

  We ended up with some absolutely adorable mice that have longer woolly, golden colored coats.

• 7:23Speaker 02

  Gina, I'll send you some photos of them right now.

• 7:26Regina Barber?

  Okay, okay, I'm gonna look. Oh my gosh, they look like little craft, like, things that you could actually make, like little dolls.

• 7:34Speaker 02

  I know, don't you just want to cuddle up with them? They're so fuzzy looking.

• 7:37Regina Barber?

  Totally. I mean, they, they must be so excited about this.

• 7:40Speaker 02

  Yeah, and that's exactly what Beth told me when I talked to her about this.

• 7:43Speaker 03

  For us, it's an incredibly big deal. I mean, this is really validation that what we have in mind for our longer term de-extinction projects is really going to work.

• 7:52Speaker 02

  And that will enable them to create mammoth-like Asian elephants by genetically engineering Asian elephant embryos with the traits that made the mammoths mammoths, and planting those edited embryos into female Asian elephants, you know, surrogates, to hopefully breed these mammoth-like creatures with the ultimate goal of releasing herds of these creatures back into the Arctic someday.

• 8:16Regina Barber?

  Which on one hand, like, is a huge deal, right? But like, on the other hand, is pretty controversial. So do you have a sense of like, what other scientists think about all this?

• 8:25Speaker 02

  Well, you know, some other scientists think it's pretty cool, at least on one level, like, you know, Vincent Lynch, he's a professor of biology at the University of Buffalo.

• 8:34Speaker 04

  You know, I'm pretty skeptical about this, but that mouse is pretty adorable. And for people like me who want to understand the genetic basis of traits, this is particularly impressive.

• 8:43Speaker 02

  But Vincent and others caution, a mouse is not an elephant, so who knows if they could do the same thing with that species?

• 8:50Regina Barber?

  Right, right.

• 8:51Speaker 02

  And even if they could, Vincent is among those who don't think bringing back the mammoth is such a great idea.

• 8:58Regina Barber?

  Oh, okay, why is that?

• 8:59Speaker 02

  Well, they think, first of all, that the money would be much better spent saving species that are still alive but are on the brink of extinction.

• 9:07Regina Barber?

  Wow.

• 9:08Speaker 02

  And also, who knows what unintended consequences could result? I talked about this with Carl Flessa, he's a professor of geosciences at the University of Arizona.

• 9:18Speaker 05

  They sort of want to mess around on a pretty large scale. I don't know what the downside of having a bunch of hairy Asian elephants stomping around in the tundra might be. I don't know what would happen. They don't know what would happen. They can't really assure me that, oh, everything will be just fine, everything will be just like it was back in the Pleistocene. I'm not ready to play God like that.

• 9:35Regina Barber?

  Wow, I hadn't thought of that. So what do some folks at La Colosseal say about all these, like, concerns?

• 9:41Speaker 02

  Well, Beth and her colleagues, they defend their project. They say reintroducing mammoth-like creatures could actually repair the environment by, you know, helping restore the ecosystems where the mammoth once lived.

• 9:53Speaker 03

  Our intention is to recreate these extinct species that played really important roles in ecosystems that are missing because they've become extinct. And that is our goal with our de-extinction projects.

• 10:05Speaker 02

  And Ben Lam, Colossal's founder and CEO, says the tools the company's creating in this project could help prevent more species from going extinct.

• 10:14Speaker 06

  Current conservation models work. They just don't work at the speed at which we are changing the planet and eradicating species. So we need new tools and technologies so that we can engineer life in a better way that's more adaptable to be co-existent with humans.

• 10:29Speaker 02

  The researchers say they hope to produce their first mammoth-like Asian elephant embryos next year.

• 10:35Regina Barber?

  What?

• 10:36Speaker 02

  Yeah.

• 10:36Regina Barber?

  That's so soon.

• 10:37Speaker 02

  Yeah, and then they'll implant them into female Asian elephants, which will hopefully give birth to the first mammoth-like Asian elephant calves by 2028.

• 10:47Regina Barber?

  Wow, I'm going to mark my calendar.

• 10:49Speaker 02

  Yeah.

• 10:49Regina Barber?

  Sorry, sorry. I'll let you keep doing it.

• 10:50Speaker 02

  And, you know, Gina, they're also working on bringing back other extinct creatures, like the dodo bird and the Tasmanian tiger.

• 10:57Regina Barber?

  Wow. OK, well, Rob, you've given me a lot to think about. Thank you so much for bringing this story to Short Wave.

• 11:05Speaker 02

  Oh, anytime, Gina. It's been fun.

• 11:12Regina Barber?

  For all you listening, if you liked this episode, make sure you never miss a new one by following us on whatever podcasting platform you're listening from. And if you have a science question you'd like us to investigate, send us an email at [email protected]. This episode was produced and edited by our showrunner, Rebecca Ramirez. Tyler Jones checked the facts. Robert Rodriguez was the audio engineer. Beth Donovan is our senior director, and Colin Campbell is our senior vice president of podcasting strategy. I'm Regina Barber. Thank you for listening to Short Wave from NPR.

• 11:55Regina Barber?

  Stay tuned for the following announcements and messages from our sponsors.