99% Invisible - 457- Model Organism

Episode Date: September 8, 2021

Axolotls are nature’s great regenerators. They are able to grow back not just their tails, but also legs, arms, even parts of vital organs, including their hearts. This remarkable ability is one of several traits that turned the axolotl into a scientific superstar. The axolotl is one of the most abundant laboratory animals in biology. They can be found swimming in tanks at universities all around the world. But in the wild they’ve only ever been found in one place: Mexico City.Model Organism

This is 99% invisible. I'm Roman Mars. If I'm being honest, I'm not a big pet guy, but I've had a couple over the years. My favorite was a snake named Chubaka that I had in grad school while I was studying corn genetics. He was pretty cool. I am definitely a pet guy. Right now, I have a dog and a cat shout out to Donnie and Lewis, but my first pet was kind of an odd one. That's producer Emmett Fitzgerald.

At a party in college, my friend Will handed me this Tupperware filled with water. I took off the top and there was this little animal floating there. It looked like an adorable chubby tadpole, with legs, and this delicate feathery boa of gills wrapped around its neck. Its face was locked in a placid, almost enlightened smile, like it knew something I didn't about the secret of life. Will told me that I was holding a kind of salamander called an axoloddle, and that he was giving

this axoloddle to me. Oh yes, my favorite kind of gift, the kind you have to work really hard just to keep alive. I put the top back on the Tupperware and named her Lenny. It turned out that Will had taken about 20 axolotl embryos from a biology lab where they had been discarded. He was raising baby salamanders out of his bedroom and distributing them to friends across campus, along with detailed instructions on how to care for them. I got Lenny a big fish tank and put her right on my mantel piece.

Axeluddles are amphibians. They hatch from eggs laid in the water, but while most amphibians will eventually transform into an adult form that lives on land and walks on four legs, axeluddles are different. They never transform. They live their whole lives in the water, like teenagers that never grow up. And that's not even the coolest thing about them. It turns out that axolotls have a superpower.

People discovered it after observing axolotls, biting off each other's tails and legs. They realized that these animals would grow back, whatever was bit off or cut off of them. This is Jeremiah Smith, a biologist at the University of Kentucky who works with axel bottles. He says that they are nature's great regenerators. So they can regenerate their arms, they can regenerate their tail, the piece of their liver, on parts of their hearts. They can even regenerate pieces of their brain.

As long as they're still alive, axolotls will regrow basically anything. You can't chop their head off and have them regrow their whole head, but most other things can regenerate. Those remarkable superpowers have turned the axolotl into a scientific superstar. Biologists have devoted their careers to this salamander that never grows up and can regrow

its toes and tail. And the dream for many of these scientists is that we might one day figure out how exactly axolotls do what they do, and maybe even learn to harness that power for humans. And this scientific obsession has turned the Axeloddle into one of the most abundant laboratory animals in biology. Today, smiling stalemanders like Lenny can be found swimming in tanks in universities all around the world, which is a little strange because in the wild, they've only ever been found in one place. Okay, well, my name is Luis Ambrano. I work in the National University of Autonomous of Mexico as a researcher in the Biology Institute.

Luis Ambrano is a biologist based in Mexico City. One of my fields is the conservation of one of the most iconic species in Mexico, which is the Asholot. There are a few different aquatic salamanders in Mexico, but Luis studies the embassistoma Mexicano, also known in Spanish as the Ajo Lotte, and in the Nahuatl language as Asholot, and in English as Axolotl, which is the most iconic of these sort of bunch of species of salamanders that lives only only Mexico City. The Axolotl has only one natural habitat and it's not some protected wilderness area.

It's one of the largest cities in the world. Axolotl City is located in a Highland Valley and hundreds of years ago, the valley was filled with five lakes. Over centuries, various indigenous groups lived around these lakes, including the Aztecs. The Aztecs farmed on top of artificial islands called Chinampus, and it was in and around these floating farms that the Axolotl thrived. The Aztecs were fascinated by these trained salamanders. They ate them, and they used them

to make medicines, and they considered the axolotl, a sacred animal. The name axolotl comes from the god Shalatl, who was a sort of shape-shifting trickster figure. According to Aztec mythology, when our son was created it was stuck in one place all the time. And so the gods decided to sacrifice themselves, to try and get the sun to move across the sky. But when his turn was up, Shaladol decided he didn't want to go through with it. He turned himself into an ear of corn and a Nagave plant. And finally, he transformed himself into ash-yeluku. These aquatic salamanders have been important symbols in Mexican culture and art. You can find them in the murals of Diego Rivera and in the poems of Octavio Paz.

So it was really really attached to the Mexican culture for many many years more than 2000 years basically since we as a Mexican star here in Diwali. And for all those years, the Axelato remained confined to that valley. You basically couldn't find them anywhere else in the world. Until a French expedition to Mexico in 1863, during the trip, French officials collected a bunch of plants and animals to bring back with them to Europe, including a group of axolotls. So what we do know from historical records is that 34 animals were collected and taken to the museum in Paris. This is amphibian expert Richard Griffiths. He is a professor at the Dural Institute of Conservation and Ecology at the University of Kent. Richard says that in Paris, scientists started breeding some of those 34 salamanders that were taken from Mexico City.

And that proved very successful, and those descendants of those animals from the Paris Museum have been spread around the world. From the very beginning, European scientists were fascinated by the axolotl's strange appearance and its perpetual tadpole life cycle. And they started using them as model organisms for laboratory research. And axolotls were suited for the job. They survived well in captivity and were easy to breed.

Their cells were also large and simple to study, and later on their genes proved to be easy to manipulate. This means that you can use them as a good model for carrying out laboratory experiments on things such as the development of embryos, our hormonal systems, such as the control of metamorphosis. Axolotls were important collaborators in a lot of 20th century science. They helped us understand how organs developed in vertebrates and the causes of diseases like spinal bifida. And scientists had always been interested

in the salamanders' regenerative talents, but it's only in the last few decades as we've come to better understand axolotl genetics that we've really started to unlock the secrets of their superpower. Their genealogy is like utterly fascinating. Jeremiah Smith has spent years of his professional life pouring over the axolotls' massive genome.

In part, to try and figure out how they got so good at regeneration. Presumably, somewhere amongst all of that DNA, all of that information, is the information of how a salamander grows back a limb. One theory has to do with scarring. When humans have a large cut or some other kind of wound, the tissue that grows back is scar tissue. But axolotls don't scar. Part of what's thought to be responsible for their ability to regenerate is that they

resolve the initial wound in a way that doesn't involve scarring, or that it involves much less scarring. Jeremiah and his colleague Dr. Randall Voss recently finished building this comprehensive map of the axolotl genome. And as scientists learn more about axolotl genetics, there is a growing optimism that humans might actually one day learn how to imitate them. And so I had to ask Jeremiah the question that I imagine he's been asked dozens of times by annoying science journalists like me from your perspective, like how possible is it that humans are ever going to be able to grow back in arm? Yeah, I mean, it's a hard question to answer with any certainty. I mean, one person that interviewed me a couple of years ago, I said, you know, I mean, it's a hard question to answer with any certainty.

I mean, one person that interviewed me a couple of years ago, I said, you know, I'll be dead before I would have a chance to grow an arm back. I don't know if that's the right perspective anymore. We're probably not going to be regrowing entire arms anytime soon, but Jeremiah thinks that with the help of new genetic techniques, like CRISPR, the lessons that were learning from axolotels could help humans heal more minor wounds. I would say in the next 10 years, we might be effectively mimicking what salimanders can do.

I don't think that's beyond the scope of reality. Largely because of all of this regeneration research, axolotls have proliferated in research institutions all around the world. But even as we continue to breed these animals in the name of scientific progress, we are driving the wild population in Mexico to the brink of extinction. In the last 50-60 years, the population of the Asholotles become very, very low. That's Luis Zambrano again. And he says that a client really traces all the way back to the 1500s and the Spanish

conquest of Mexico. In the centuries that followed, people drain the water out of the valley of Mexico and a megacity developed on top of the tri-leg bed. Today, the historic lake system is all but gone. There's really only a small marshy remnant left in the south part of Mexico City, an area known as Sochi Milco. So now we have a huge problem because we only have the 2% of the huge lake system. We only have 2% which is Sochi Milco. In this area is the only place that the has a little now can survive as a young biologist Luis wasn't all that interested in salamanders he was more of a fish guy used to be a fish man

I used to study and work with fish then in 1998 a colleague enlisted him to help with this big survey that they were doing of all of the axolotls in Sochi Milko. And it ended up being surprisingly difficult work. So at the beginning I didn't like it at all. So I said, okay, I will do this. I will never work with Ashilok Tuso Sochi Milko again. But then one of the most important axolotl scientists, Dr. Virginia Graue, tragically got cancer, which meant that she wasn't going

to be able to finish her research. And she went to Louise to say, okay, I got cancer, but we need to finish this research. And please finish it because I won't be able to do that. And I remember that Dr. Grawe has a very, very important piece of my life now. Yeah, she gave you a mission. Yeah, she gave me a mission, actually. The second way for projects, I fall in love with the actual hotel and with Huchimiko. It was like falling in love within a second date, basically. But as he was falling in love with Mexico's much loved salamander, he was also discovering

just how much trouble it was in. In Dr. Graway's last survey of Sachi Milco in 1998, she had found that there were about 6,000 salamanders per square kilometer. But when the Wies completed his follow-up in 2003, we only found 1,000 feet square kilometer. It was a huge decline. And from the data, Louise could see that lots of juvenile axolotls weren't surviving into adulthood. And so he had to figure out why not.

Why were all these baby salamanders dying? I mean, I can tell you this in less than 10 minutes, but it took us about 10 years to understand that. And science is like that. The arc of science is long, but it bends towards a truth that you can explain in 10 minutes if you're lucky. Luis and his colleagues eventually determined that there were a few different things contributing

to the collapse of the population, including invasive fish species like carp and tilapia, poor water quality, and illegal development. And we saw that the population is going, it would be going to the extinction really, really fast, if we don't do anything. The combination of human obsession and human neglect has turned the axolotl into this bizarre contradiction. It's so common in universities that someone just handed me one in college. And yet, at the same time, it's an endangered species. It's a paradox that you have this species that is probably the most widespread amphibian

in captivity in the world, and yet it is critically endangered in the wild. That's a Richard Griffiths again. I can't think of any other species, mammal, bird, fish, reptile, and amphibian, that has a parallel with that really. Given that dynamic, you can't help but wonder if they should just release fish-reptolaran fibio that has a parallel with that really. Given that dynamic, you can't help but wonder if they should just release a bunch of the laboratory axolotels into the wild. Yeah, I thought about that too. I mean, as much as I loved Lenny,

I would have happily donated her to the cause. You're a monster. Well, don't worry, it's not gonna happen because everybody that I talked to for this story said it was a pretty stupid idea. For one, the animals probably wouldn't survive anyway, and two, you run the risk of spreading diseases. But the more fundamental problem with that plan is that the wild axolotl and the laboratory

axolotl, they aren't really the same animal anymore. There's a very good argument to be made to say that the laboratory animals are not axolotls. That's Jeremiah Smith again. He says that over their long history and scientific institutions, the laboratory axolotl changed. At some point, scientists introduce the albino-tiger salamander into the population. So today, the salamanders and labs are more like axolotl-tiger salamander hybrids. And they've changed in other ways too. They're a little bit like cuter and cuddlier, less like a wild creature, I guess, than like

an axol from Zosha Milco. If they're cute, like, maybe you won't forget to feed them, and they'll live to make their own offspring, right? They're still great ever-generation, but at this point, the laboratory axolotl is more like a poodle than a wolf. For example, I walk into my laboratory and there's a whole bank of tanks

with axolotl's full of them. This is Dr. Randall Voss. He's a professor of biology at the University of Kentucky and the head of an axolotel research lab there. And I just walk around the facility and they just follow me, just to watch me because they know that humans feed them. They're like my dog following me around the apartment.

No, absolutely, no, absolutely. And you have something that's really different, I think, than what we think of the axolotl from Mexico, the natural population. In my mind, it's already a different species. A species created by science and a species that probably shouldn't be released back into the wild. Like, just like we're not going to release poodles into the Yukon to hunt more.

But we have to do something, right? Don't we owe it to this animal that has given us so much? Luis Zambrano certainly thinks so. His devotion to the axolotl has only deepened over the years. It's less intense, but by far stronger. That is my feeling about the asholotus in some moments, well not in some moments, in most of the time I have them in my emotion and my heart basically that's okay. I have to do more things to save this very nice species. Luis knew that they needed to do everything they could to clean up the ecosystem at Sochi Milco, and deal with the various issues that were sending the Axeloddle to extinction. First, we have to reduce the population of Garbantilapia. Second, we have to improve the water quality,

and third, we have to stop the illegal organization in the Canal of Sochi Milco. But Luis also knew he didn't really have time to wait around for the government to implement some big top-down restoration program. So we decided to change the focus in terms of restoration and not to see the authorities as a solution, but the local people as the solution. In particular, they focused on the farmers or the Chinamperos, who still farm on islands in the water. Luis and his partners started working closely alongside them, and the idea

was to try and give farmers money and the tools that they needed to improve the habitat around their own piece of land. They designed simple low-tech filters that farmers can use to seal off individual canals. The filter helps to increase water quality and avoid the entrance of carpentelapia. They might not be able to fix sochi milko all at once, but they want to create pockets of clean, tilapia-free water, where the axolotl population can recover. It's hard to say how well these efforts are working. In his most recent surveys, Louise hasn't found a single axolotl, although he says that local farmers that he's working with have reported seeing them inside their canals. And so there's a lot at stake

in Louise's work, the fate of an ancient ecosystem, and it's iconic animal. And what happens in Mexico City could also have ramifications for all those scientists studying regeneration. In addition to being a professor at Kentucky Randall Voss is the head of the university's Ambas-Stomachinetic Stock Center. They breed axolotls and distribute them around the world. We provide axolotls to people for their research efforts. In fact, they're basically THE place to go if you want axolotls to do research with. And the amazing thing about these salamanders that are being bred at Kentucky today is that their descendants of the 34 animals which were taken from Sachi Milko

in that French expedition 150 years ago. They are the oldest population of laboratory animals in the world. Which means that Emmett's exalata-lennie probably was related to those 34 animals that were brought to Paris. Yeah, she almost certainly was. And while that lack of genetic diversity is great for doing experiments, it can also be a problem. It can lead to inbreeding. I mean, I think there are a lot of species that if you applied the same kind of management strategy over the time that axiots have been in captivity, they probably would be extinct. Randall says that there is no immediate cause for a alarm with his laboratory salamanders. But yeah, it's a concern. I mean, I do think it's important to consider that there may be other

sources of genetic variation out there in the world that could be used to invigorate our population. In an ideal world, they would introduce some more wild salamanders into the lab population. But those are pretty hard to come by these days. And if the wild axolotl were to go extinct at Sochi Milko, there would be no pool of genetic material left for scientists to pull from. Somewhere in the long story of the Mexican axolotl, the narrative diverged. It became two stories, one about science and biomedical innovation, and the other about habitat loss and an iconic but increasingly endangered animal. And these stories may very well continue on their separate paths, but it's also possible

to imagine a world where they loop back together again, where Luis's conservation efforts in Mexico are successful, and a healthy population of wild axolotls is able to provide Randall's laboratory salamanders with some much-needed genetic variation. Wow, that would be the ultimate, you know, happy ending. If that, it's what you just said could happen. That would be fantastic. But Randall and the other laboratory scientists that I spoke with were really clear that the

dream of re-growing a human arm is not the reason we should protect this endangered species. They just don't want to live in a world where magical creatures like the axolotl cease to exist. After all, it was the magic of the natural world that got them interested in science in the first place. Jeremiah Smith might spend his days in a lab now, but growing up he used to search for tiger salamanders in the fields of Wyoming. And even now, when he's not in the office, he's usually trampling around Kentucky with his kids, looking for amphibians. Not with the intent of collecting them or sampling them or doing any experiments or genetics, it's just sort of like to see them and appreciate them and then move on. Was there any, have you done it recently? Have you like seen a salamander in the wild recently?

Yeah, last weekend. And probably going out this weekend again to see some other ones. Even as old as I am, I still really get a check out of it. My Lenny was not a wild salamander. I didn't find her flipping over rocks in some pristine forest stream, but I got a kick out of her too. She was a sunny presence on my mantelpiece for over a year. And then without warning, she died in the night. I still don't know exactly what happened, although after talking to Randall and Jeremiah, I'm a little worried that it was probably my fault.

Like most of her kind, Lenny lived her whole life in tanks, and so we decided to give her a send off befitting a water god, a proper Viking funeral. We built a raft out of clementine crates, and later a top a pire of shredded cereal boxes. I think there were at least seven people in attendance. I said a few words, my friend will read a slightly too long Keats poem, then we lit the makeshift boat on fire and pushed her out into the Narragansett Bay. For a second it looked like the wind was going to blow the boat back to shore, and it was smolder there awkwardly against the rocks.

But then it changed directions, and took Lenny out to sea. Coming up, Emmett and I are talking about the possibility of resurrecting extinct species after this. Okay, we're back with Emmett Fitzgerald. Hey, Emmett. Hello. And so you have another aspect of the story that you wanted to share? Yeah, so towards the end of my conversation with Jeremiah Smith, he brought up a kind

of wild idea that I hadn't considered before. Basically, he told me that if the wild acts a lot, we're to go extinct in Mexico City. He thinks he could bring it back. Yeah. I mean, I guess there's this deeper question of like de-extinction, right? So are you familiar with this concept de-extinction, Roman? I mean, I think I was made most familiar with it in the movie in the book, Jurassic Park. That's basically what you're talking about, right? Yeah, that's basically the gist of it. I mean, the idea is that with modern gene editing

techniques, we could recreate something that no longer exists in the wild or something very similar. And, you know, as Jurassic Park, the idea was like to profit off of that into film theme park, but you know, when conservationists and conservation biologists are thinking about this, the idea would be that you would reintroduce that animal into the ecosystem where it quote, unquote, belongs. And so there's been, and there's, you know, real conversations are happening in the world of conservation

biology around this. People have talked about trying to resurrect the woolly mimith in the passenger pigeon and, you know, real conversations are happening in the world of conservation biology around this. People have talked about trying to resurrect the woolly mimith in the passenger pigeon and, you know, this relative of the zebra called the quaga. And is the notion that this is like a stunt as it was in Jurassic Park or is something actually valuable to, you know, ecology? Yeah, I mean, there's a whole debate about this.

Some people think it's like our duty to bring back species to ecology. Yeah, I mean, there's a whole debate about this. Some people think it's like our duty to bring back species that we made extinct and others think it's an extravagant waste of resources. I don't want to get into the debate, but the axolotl, you know, is sort of an interesting case study. It's not extinct yet. That's important to say, but if it were to happen, in a way, it would be a better candidate to bring back than something that's been extinct for centuries

because you have that population of laboratory axolotls. And Jeremiah thinks that if they could figure out exactly on a genetic level, like what are the differences between the lab axolotls and the wild ones, then they could basically back engineer a salamander from the lab population that was more like the wild ones and then release it into such a milk. We could probably generate an extra act of the information to sort of like make a more axolotally axolarable from the colony. What do you think about that?

I mean, you would hope you would never have to do it, right? It's like, I hope my house never burns down, but if it does burn down, well, then I'll probably rebuild it. It's, you know, you wouldn't want to do it, but if you had to do it, maybe you could. Yeah, I mean, he seems like appropriately imbiblet about it. Like being cautious and not just wanting to do it

because you can, obviously, the best way to do things is to conserve. Yeah, exactly. But it's the choices between not having wild ax levels and having wild ax levels, then I mean, I'm for it. I think it would be a good last ditch, important thing to do for them. I mean, in a way, it would be a way for the biomedical scientists to lend their knowledge and expertise, you know, to help bring back the animal in the wild, you know, like this is a way to reciprocate all the, that the actual auto has given us.

Yeah, I think that's right. And you know, one of the big critiques of this sort of thing over the years has been that humans are meddling too much in nature that it feels like we're playing God. Right. That was certainly the narrative with Jurassic Park that we deserve to be eaten by Tyrannosaurus Rex if we bring Tyrannosaurus Rex in the world. Right.

That's like the role, like the Jeff Gold Bloom character is playing in the movies. Like, you know, these arrogant humans think they can mess with nature sort of thing. Yeah. The lack of humility before nature, it's being displayed here on staggers. But you know, I do think like human impacts on the natural world are so obvious and omnipresent. Now that the concern, to my mind, the concern about playing God almost feels a little bit quaint. Like we're already playing God, you know, destroying the lake system that was this animal's habitat,

like that's playing God. Right, if we're gonna play God, why don't we be a benevolent God? Right, right. Like at least we can try to do our best to do that. Yeah, I mean, I guess one thing that, you know, concerned that I have personally with a concept like de-extinction and the axiotals of good example here is that like in situations like this,

if you know you have the possibility of bringing an animal back, you could really, I can see that people might begin to think, well, oh, well, we don't need to worry that much about that endangered animal, that axolotl or whatever endangered animal we're talking about, because we always can just use their DNA to bring them back later on. Oh, totally. It creates a moral hazard. If you know that there's this, you know, kind of safety valve to this topic, extinction

down the line, then it could, you know, encourage us to do bad things in the present. I totally agree with you. Yeah. And you know, when I was talking to Louise, like for him, it's as much about the health of the ecosystem at Sochi Milko as it is about the axolotl on its own. You know, like he wants to save that animal because he wants to save the ecosystem that that animal is a part of. Yeah.

And the interesting thing about, you know, this is is even if you brought back the axolotl 50 years from now, it would still need a place to live. All those concerns are still relevant. You still need to have a healthy ecosystem to release that animal into. Absolutely. You create thousands of de-extincted axolotls and introduce them into the valley, and they would just die all over again. I mean, it's not like those conditions have changed that make it poorer for axolotls. Yeah.

And to my mind, you know, like de-extinction is interesting, and I think it's like an interesting thing we should talk about, but it doesn't change the need to deal with the water quality and the invasive fish and the illegal development. If you want to have some place for a de-extincted salamander to go, you need to still work on those things. You need to make space in Mexico City for Mexico City's beloved salamander. Yeah. Yeah.

So it's a good thing to have in our back pocket, but we have to fix everything else in addition to it. So, you know, but that's still a really fascinating science and it's, you know, an interesting thing to keep in mind as we're deciding what to do as the world changes, as the baseline shifts even more and more. Cool. Well, thank you, Emmett. Appreciate it. Thank you. 99% Invisible Was Produced This Week By Emmett Fitzgerald, Mixed By Jim Briggs, Music By Our Director Of Sound, Sean Riel. Delaney Hall is the executive producer, Kirk Cole said, is the digital director. The rest of the team includes Vivian Lay, Joe Rosenberg, Chris Barube, Christopher Johnson, Lashemadon, Sophia Klatsker, and me Roman Mars. Special thanks to Will Trophy.

We are a part of the Stitcher & Serious XM Podcast family. Now headquartered six blocks north in the Pandora building. In beautiful, uptown, Oakland, California. You can find the show and join discussions about the show on Facebook. You can tweet me at Roman Mars and the show at 99PI org. We're on Instagram and read it too. You can find links to other Stitcher shows I love as well as every past episode of 99PI at 99PI.org.

What do you call a baby axolotl? An axolittle. Stitch our series exam.