Ambystomology (AXOLOTLS… AND LIMB REGROWTH?) with Jessica Whited 01:28:05

I know I usually save my secrets for the end of the episode, but I'm going to tell you my secret favorite candy. It's Reese's Peanut Butter Cup.

It's really Reese's anything. But Reese's peanut butter cups are the thing that I'm like, have I had a bad day? I get these. Have I had a good day? I get these. Chocolate, salty peanut butter, the textures. I love everything about them. Also that there's two. So I'm like, oh, I get this one for later, which is one second later. Anyway, Reese's peanut butter cups. I love you. That's all. If you're me, you can shop Reese's peanut butter cups now at a store near you. Found wherever candy is sold. And I am.

Oh, hey. Hey.

Hey, it's your seventh grade yearbook photo. Allie Ward. Things are about to get a bit squishy and fancy around here with axolotls. They're more than just a Scrabble payday, folks. These are aquatic salamanders with feather head gills. They're demigods to some. They're pop cultural icons to others. And they're potentially the key to your survival. No pressure.

So this is a topic I've personally wanted to explore since high school when I had these little amphibians in my biology classroom and in my sketchbooks. And we are lucky to be talking with a scientist who not only cares for these creatures and raises them, but also leads research as a

principal investigator into their odd cell biology and what it could mean for humanity and other animals at her lab at Harvard Medical School's Department of Stem Cell and Regenerative Biology. Kind of a big deal. So we hopped on a call from her lab to discuss all things axolotl. But first, just a quick thank you to everyone who submitted excellent axolotl questions for this episode, including a lot from your children. And we kept the

adult language to a minimum for this one. But yeah, there are a few swears here and there. If you want 100% kids safe episodes though, we have a whole show for that. We have a brand new show and a feed for Smologies. They are shorter classroom, all ages episodes. Yes, you can subscribe at the link in the show notes. There's a ton of them there. Please tell your friends with kids.

And for Ologies, you can submit questions for future episodes at patreon.com slash ologies, and you can join that for as little as a dollar a month. And thank you to everyone who is having a summer in Ologies merchandise, including swimwear and hats and totes, which you can get from ologiesmerch.com. Also, thank you to everyone who has ever left a review for the show, because I do read them all, and I pluck a blossom.

from the bush to read you, such as this recent one from J. Madden Mass, who called the show always on point and a reality check in maddening times, which I appreciate. Thank you, J. Madden Mass. Let's take you on a weird wild ride. It does get funky. So axolotls, they're in the genus Ambostoma, which was this word coined by a Swiss naturalist who

botched the spelling. So it was supposed to mean blunt mouth, but he accidentally wrote it as a hybrid of Greek and Latin. So it actually means to cram into your short mouth, which honestly, I like it. I think it's an improvement. Now, these are hugely important species ecologically, as well as in biomedical research.

And this episode will touch on both factors. All right, so prepare for that. We're going to talk about how widespread axolotls are in the wild, who their closest cousins are, why they look like babies, the ethics of keeping them as pets, color morphs, the sexiest pyramid scheme possible.

on the planet, how to spot a genetically modified axolotl, changes to their homeland, why scientists are rushing to bring back ancient forms of farming, how you can adopt a salamander without ever having to smell one or change tank water, and...

Shockingly, why geneticists all over the world have them in their labs. So grab a worm, sit on a rock, clap your tiny slimy hands for axolotl researcher, regenerative biologist, professor, and ambistomologist, Dr. Jessica Whited. Jessica Whited, she, her. And Dr. Jessica Whited, correct? Dr. Jessica Whited, yes. I looked around for...

some of the best axolotl researchers and scientists in the world, and you are one of them. How many axolotl researchers are out there? Are there a few of you? Are there like five of you? Or are there like 5,000 of you? Well, there's somewhere between five and 5,000, but probably closer to five, but five is an underestimate. You know, maybe like 50-ish labs, I would say, in the universe that we know of. And how did you enter into the salamander axolotl

pond cave. What's your axolotl origin story? I mean, I was one of those kids that was just like always outside mucking around, like always filthy, spent the whole day outside playing in a creek, playing in the woods. But I wasn't sitting around thinking, oh, I'm going to be a biologist when I grow up. It was just like, I was just always doing those things. And I was into other things too. So it is kind of hard to decide what to study in college. But in the end, I went with philosophy and biology. Oh, wow. Wow.

Wow.

Really? Even though he was a philosopher? Yes. And so I was really interested in Evo Devo at the time, which is a field where people sort of integrate developmental biology and evolutionary biology. I interviewed at MIT and I met the guy who became my PhD advisor. And it was just like instantaneously, I want to work on these topics and with this person. So I went there instead to study basically how the nervous system develops.

using a fruit fly model. And like I was really always into insects actually when I was a kid, I had a butterfly collection and my mom was sort of like an amateur butterfly collector. And so Drosophila melanogaster is technically it is an insect of course, but it's also like not the kind of insect you imagine working on when you're into collecting insects, right? You want those big, beautiful, glorious ones out in the field. But it's a really robust genetic model.

P.S. Feel free to name a D&D character that Drosphila melanogaster, as it is both regal and intimidating. But do know that that's a species of fruit fly, and it's commonly used in research, including genetics, a lot. And for more on flies, including species named after drag queens, please see our dipterology episode linked in the show notes. It's fantastic. And once I started thinking in that direction, I was like, isn't it

also important to understand how the animal is resilient and how the animal keeps everything in place even during homeostasis. And then that led me to think, well, what about if the animal suffers a really dramatic injury or a loss of a body part? You know, what happens? And so then I thought,

So which animals are really awesome regenerators. And a lot of other ones also come to mind like planarians and starfish, for example. And I think those are amazing models also. But there was something about the salamander that was just sort of charming me into going in that direction. And so at that point, I realized I wanted to do this in salamanders and in axolotls. And then I would

It's time to find out where could I do that research, right? I hope that her one-time philosophy professor knows that she is working on exactly what happens when an animal gives its left big toe for something. And we are going to have much, much more on the science of regenerating whole-ass body parts in a bit. We're going to cover a lot. But first, the basics.

You must have had to learn a lot of axolotl anatomy and life cycle. And these little critters are so charismatic and so darling. Free flies got nothing on them. I mean, let's be honest. But can you walk me through a little bit of what is an axolotl? It is a salamander that is aquatic, but it's got a frilly face, which I understand are gills. What is it? What's going on with it?

Yeah. So the salamander that most people think of when they think of a salamander is the one that you might encounter in the woods, like under a log, for example. And most, but not all of those salamanders have this kind of lifestyle where the parents go to a pond. Sometimes these are called vernal pools, which is like melted snow. And they go back to the one where they came from and they breed in there and they lay hundreds of eggs. And then they

eggs hatch into these little baby salamanders, which at that point have no arms and legs, and they grow bigger in there, big enough to actually walk out of there eventually, right? And it's part of that metamorphosis. Then what happens is that

The gills are lost and then they become, you know, semi-terrestrial. They live on land, but they need to be kept moist. And so that's kind of what most people have in mind when they think of a salamander. And that's sort of an old lifestyle, whereas the axolotl has deviated from this a little bit where it skips that last stage. So it never loses its gills and it never becomes terrestrial. So it's kind of permanently stuck in this life.

aquatic phase, but it's permanent. It can get bigger there and it can reproduce there. And so it just chills out all the time. I'm just chilling. And what's the benefit of that from an evolutionary standpoint? Like, why do they, why do that? Why stay cute, cute, cute babies? So I'm going to probably be hand-waving a little bit here because we don't have a time machine and we don't, we can't really know for sure like what the pressures were, but I've heard this argument, which is that

They have everything they need. They don't need to leave that particular ecosystem or that particular habitat. Whereas that example where a salamander, like a tiger salamander, goes into a vernal pool, lays its eggs, they develop for a certain amount of time, then they lose the gills and they come out on land. Well, those vernal pools often dry up, like towards the end of the summer.

And so those animals really do have to crawl out and go on the land. And so it's perhaps an adaptation whereby they can get away with not going and doing that last step. Do axolotls live just in water then? I understand that they're from outside of Mexico City, right?

Whereabouts do they live other than tanks in people's homes or labs? Yeah, so they live in this lake and canal system outside of Mexico City. Unfortunately, I haven't personally been there, but I would love to go. And from what I can tell, they live there, they stay there. In the old days, they were plentiful and they were sort of like in harmony with their natural environment because people are taking care of it and everything.

Axolotls were quite numerous, in fact, so numerous that people ate them. Oh, so just a quick aside. Axolotls are relatively new species, evolutionarily speaking, and they're related to the tiger salamander and one of their only natural habitats.

For axolotls, for the last 10,000 years or so, were a few lakes southeast of this sprawling Mexico City. And indigenous Mesoamerican civilizations consumed them as food, used them for medicine, and they were still used as a food source recently. And people have said they taste like frog.

which is to say somewhere betwixt a fish and a chicken. But also they have been revered as a god by some for their power to hide. But due to this drainage they did to prevent flooding and build the city dating back to the 17th century, what remains most notably of those lakes are a few canals that tourists can check out by these colorful boats that you can rent out. But

Given that these kind of carrot-sized, foot-long-ish creatures burrow in the mud in the daytime or they hide in grasses and they're now heartbreakingly rare in the wild, it's not likely that a visit to those canals will get you an eyeful of these baby-faced beauties. So you might, though, however—

see an island in the canal that's strewn with some creepy old dolls and said to be haunted by the ghost of a young drowned girl. Many of the dolls, which are nailed into trees and hanging from strings, have faded, chipped faces, bodies askew, missing limbs, which they can't grow back because they are not freaking axolotls. And so back then, there were really plentiful

But now they're critically endangered. In fact, you know, they're basically almost extinct in the wild. Oh, no. Yeah. And is that habitat loss or predation from humans?

It's not predation from humans per se, but it's modifications to the habitat. So there's a combination of things like pollution, but also introduction of these invasive species that can eat the axolotls, where in the past they were sort of the apex predators in that system. But now there are tilapia and carp and other kinds of things that can eat them. Oh, no. Yeah. And so as apex predators, what were they feasting on before? Yeah.

Yeah, so an axolotl will basically eat anything that moves that it can get inside its mouth. Yeah, me too. But some of its favorite things were like small crustaceans, insect larvae, small fish, things like this. Yeah, and actually I learned...

that when you dissect an axolotl's gut, you may also find remnants of plants inside there. And so even though they're typically thought of as carnivores, sometimes they might have a snack on a leafy green. Oh, just a little salad today. Exactly. But an interesting thing about axolotls and many other salamanders is they love to eat each other.

No. Yes. They look so cute and sweet and sweet and cute. Yeah. Do they eat each other like, oh, here's a group of babies. I'm going to snack on that. Or do they...

start eating a whole adult? Are adults eating adults? As adults, it doesn't happen as much unless they're underfed. Now I'm talking about in captivity that if you have a couple of adults and you're not feeding them, which obviously is terrible, then they might bite each other's legs off or part of the tail or something. And that can actually lead to one of the adults dying because it could get infected or whatever. That can happen. But if you keep juveniles, they're much more voracious eaters. So

I have two sons and they have over the years had axolotls as pets. And I remember this one time they were about four and one of them just started freaking out, screaming and crying, mommy, mommy. And I came in and one of the animals had the entire other animal inside its mouth with just its head poking out. Life lessons, right? Yeah.

When you said you had two sons, I thought you meant like, I have two sons and man, can they mow through the pantry? I thought that's what you meant because juveniles do eat a lot. I wish they would just clean up after themselves. Every day I go home and it's like, I thought I left this clean and there's fruity pebbles crushed all over the entire kitchen. Oh, juveniles. Yes, exactly right. Yeah. So the juveniles are kind of naughtier about that. And it's interesting because this is something that people

People have speculated about in the wild also with things like these other kinds of salamanders, the tiger salamanders. And we have a collaborator in Berlin, this woman, Nadia Frobish, and she and her student Vivian have provided us direct photographic evidence that in their wild naturalistic pond that they have for the tiger salamander, that if you just sample animals out of there, that often they'll be missing more than one body part, like simultaneously. And so I think that it's a legitimate...

possible selective pressure on these kinds of animals because they're laid in such high density at this one defined time in the year

at least for tiger salamanders and ones like that. And that basically if they get hungry, that's who's there to eat. And limb regeneration is probably very handy if your peers are eating your legs. Exactly. Especially if you need to then crawl out. Like if you wash the axolotls in a tank, they're kind of swimming more than they're crawling. Yeah.

So they have arms and legs and they can use them to grasp onto rocks and things like this. But if you're aquatic and you have this really strong tail, which they do, most of the movement you see them doing is more swimming. Whereas when you're looking at a salamander crawling out of a pond, of course, it's literally crawling. Yeah. And for more on this, feel free to thumb through the study, Tail Regeneration at Different Ontogenetic Stages of the Tiger Salamander, which notes right up top that axolotls are pedamorphic,

retaining larval features throughout adulthood, and they do not naturally undergo metamorphosis. So unlike other salamanders, axolotls simply refuse to grow up because the feathery gills and the strong tail and the tiny teeth all work just fine. For

what they're doing and where they're at. Now, this trait, when it behooves a species to stay childlike, is called neoteny. You know, for example, the domestic dog has been bred for neoteny. So compared to a wolf, an adult dog has like floppier ears, bigger eyes. It's more docile, more playful, more like a wolf puppy. And so neoteny may also help in the survival of artists or

or sweet, cute boyfriends who don't want to pay rent. Now in the axolotl, honestly, having this wide flat head and like a naturally upturned little smile and gills that look like a carnival headdress has indeed kept their species alive, albeit in captivity. So being cute,

It sadly can save your life. Let's talk about their frilly, frilly gills. Because I feel like that's one of the things that makes them so interesting and charismatic. What are those gills doing? Do they have to gulp air or can they just be submersed like a fish and they're just good to go?

So they actually typically are literally breathing through those gills. And if you look at them under the microscope, even the ones that we have here in the lab, you can see the individual red blood cells coursing through them. It's very cool. What? Yeah. Like through a microscope or by the naked eye? I bet you could see them high mag on your iPhone. Probably, maybe. But

Just even a low mag microscope, you can see them. So they really are doing a lot of gas exchange in those gills. They can also perform some of it through their skin underwater. And then they do come up and gulp. It's debatable what the actual function of this gulping is. If you prowl around the internet, you can find lots of

Lots of theories about that, but I don't want to say any more about what the gulping definitely is or is not. She's right. People do debate this online, as I found out. Some people saying it could indicate poor water quality, a bloom of bacteria. Others saying that a tank, for example, needs more oxygen via a bubbler or plants. Well, some folks insist that they just gulp for buoyancy.

And still others say that it's just normal axolotl behavior, just to take a sip of air from above the waterline. Because while they have very adorable feathery frilly gills, they do have lungs. Oh, so they have these cryptic lungs. Yeah, they have a pair of lungs and they kind of have the appearance of almost like cellophane. But of course, they have blood in them. And I have a colleague who studies

limb regeneration, but he also has found that they can regenerate a chunk of their lung if you take it off, which is quite cool. Do the scientists think that they're using their lungs also? I would say that probably not so much, but they may be vestigial. So, you know, when an animal changes its life cycle, there could come some of the parts that were part of the previous life cycle from an evolutionary standpoint. They could just persist if it

or they might be lost, right? So cave animals are a famous example. A lot of cave animals have lost pigmentation, but they've also lost eyes. So it's a moving target, I would say, about why do they still have these lungs? It's maybe if we could fast forward time like millions of years, they would be losing them. I don't know. Okay. Okay.

I'm done with this. Well, you mentioned colors and that was a huge question I have. I feel like I've seen axolotls that are mottled, mossy, brown and green. And I've also seen ones that look just pink, straight up frilly. And what is up with their colors? Yeah.

Right. The wild type ones, which is what geneticists call the example that you would typically see in the field, is kind of a mottled blackish brown, like you just said. It's pretty dark, although there are axolotl morphs that just look jet black. They don't even look mottled. And then there are

Tons of other axolotl morphs, but the most famous one is the one that you refer to as kind of pinkish looking. And that one is actually called the white mutant. Oh. It's a mutant in its pigmentation pattern. It can actually make the pigment, like it has the biochemistry intact to make

Yeah.

So it's not a true albino, right? A true albino really can't make the pigment. And those also exist in axolotls. So there are true albinos and golden albinos, which look like true albinos, but then they also have these really cool silvery splotches all over them. And there's a whole bunch of other morphs if you were to look in the pet trade, yes. I needed to know some names here. And axolotl people...

you didn't disappoint. Morphs are named Firefly axolotl, Iridophore, Lucy, Chimera, Xanthophore, or even Mosaic, which is kind of like a Cruella de Vil split down the middle axolotl look.

And there are these beautiful apricot colored ones and mossy green mottled types. They have spotty granite looking axolotls and shades of brown and pink ones that don't not resemble human appendages of the below belt variety. And so do you think that the ones that we're used to that are that like soft pink color are those ones that would exist a little bit in the wild, but they've been bred and bred and bred for like the...

domesticated or like pet trade or research trade, are those pretty rare in the wild? Or are those like, oh no, there's some caves that just have a bunch of those? Yeah. I guess I would say that in any wild population of animals, there are going to be mutants, right? Everyone's a mutant. We're all mutants, right? But

Sometimes there's a mutation that causes a visible difference in the animal, right? And this can be an awesome thing because it might also sort of give the animal some selective advantage like, oh, now this animal has, let's just for devil's advocates.

say, this animal's got an extra arm. And isn't that handy? Now it can do all these things that it couldn't do before, right? But those things can only persist and pass their genes on, assuming it was genetically encoded, right? If there's some kind of advantage to having them, otherwise they'll be lost. And something like a pigmentation difference where you go from mottled brown and easily camouflaged, they basically look like camouflage,

to something that's bright white probably comes, we would guess, with a disadvantage, right? Because now if there is a predator, it's easier for that predator to spot that animal. You ever see an albino deer or a white buffalo? I mean, they do sometimes happen, but if left in the wild population, they might be easier for predators to spot. Yeah. Yeah. So it is true that the white axolotls have been selectively bred, but

So that we can use them as scientists because they're easier to see through their skin. You want to like look inside and see like, you know, what's happening down there. And so that's why they're preferred over the quote wild type ones. What about breeding? What about breeding in captivity versus breeding out in the wild? How are they getting it on? How are they making babies? And is it hard to do in captivity? Yeah.

Yeah. So one of the greatest days of my scientific life was after I first got axolotls. So I went to a lab. You have to do this thing called a postdoc, usually, not always, before you become a professor. And that's like your second massive research experience. And people like you to mix it up. So going from flies to salamanders, it was like, oh, perfect, right? And almost the night before I went, I almost didn't do it because...

Because I couldn't imagine like doing the surgeries to do the amputations. Right. And, and so it was a really hard transition, but when I got there, I was the only one working on X levels. So I had to import the X levels and like start the colony. Right. And I, after about a month there, I was like, well, time to breed them. And,

And so I literally just put a male and a female in the cage together. And I didn't really think anything would happen. And I went in like 20 minutes later and it was insane. But sadly, this is the best I'd ever seen it happening. And so I kind of like, oh, and I think I have a video from like an ancient phone, but I don't know what happened to it. But the girl was, I swear, following the male and sort of like,

He had his tail straight up in the air and it was bright red. Whoa. Yes. And she was sniffing it. This is what I remember, right? Yeah.

Usually when we make them in the lab, we don't really get all those visuals. And it usually happens when we're not around. They're kind of shy about it, you know? This is your first time. And it's actually a problem. Well, you got to keep track of how many times have they had sex, right? Because if you try to make them have sex too frequently, then they're like, no, we're not doing this. You won't get any babies, right? So we got to keep track and

No commentary on this, but you can mate the males more frequently than you can mate the females. With success, right? And so it's actually quite a cool process. It's so cool because...

What happens is that the fertilization is internal, but he doesn't go in there. What? Yeah. So they have a little mating ritual, which honestly I rarely see, but it exists. And for this kid's book, basically, we are illustrating that they cuddle because that has been seen. And the people who study their behavior, they kind of like nudge up against each other and they do this little ritual. And there are pheromones involved, actually. I'm very interested in those too, but that's like side note. And they share some chemical pheromones and

Anyway, so what he does is he lays this thing called a spermatophore, which I kid you not, it's like,

It's like, oh, I don't know, like three quarters of an inch tall. And it looks like a little pyramid, like a jelly pyramid. And it's kind of translucent. But at the peak of the jelly pyramid, it's opaque white. And it's just chucky jam full of sperm. And they have the coolest sperm. Like their sperm, if you put that in a petri dish and then you kind of like mix it around so you can break them all away from each other. The sperm tails on an axolotl sperm are just like super, super long and really coiled. They're beautiful. Wow.

Where can I see images of axolotl sperm? You're asking yourself, and I'm here to tell you in a 2021 paper titled Detailed Morphological Analysis of Axolotl Sperm, which has plenty of microscopy treats for you. And yes, these sperms, they look like a curved upholstery needle, like a curved needle with a long curly thread attached.

And according to the 2024 paper, Establishment of a Practical Sperm Cryopreservation Pathway for the Axolotl, a community-level approach to germplasm repository development. These spermies have different dances among them. Some will spiral, some will undulate, and some are wallflowers, tenderly described as static sperm.

And they're all in this little conical pouch, which he leaves as a gift for his potential baby mamas to make lifelong baby looking babies. So he lays a spermatophore and you got to give them a rock. They'll do it on a piece of plastic, like if you have a plastic bin, but it's not ideal. So we put rocks in there, like slate rocks, and then he lays a spermatophore. If you're looking for eggs and you see spermatophores, you're like kind of excited that

because it means you might get them. And then she goes and she...

literally like sticks her cloaca on top of the spermatophore and wiggles around and gets it up in there. So she kind of puts the sperm in there. Yeah. No way. She decides. Yeah. Well, that's kind of lovely. Yes, it's very lovely. And then she goes and lays the eggs if we're lucky. And then we collect the eggs and we do what we want to do with the eggs, which is usually inject them with constructs, which was like kinds of DNA that we've made in the lab to try to make transgenic axolotls or sometimes we'll knock a gene out.

So we'll use CRISPR on them. But it's really ideal to collect the eggs right after she lays them so that they're only one cell. And once they start dividing, you can still inject these ingredients and still get some effects. But eventually, though, it's like diminishing returns because there's just too many cells and et cetera. Right. So, yeah. So you want to get it when you've got 100 percent of the cells with the genetic code that you want.

Yeah. So the ideal situation is you got at least two people and somebody's helping you because you got to take them out of these jelly coats that they're laid in. So kind of like frogs, they're laid in a jelly coat and it's pretty big. It's like the size of like

you know, your fingertip. And there are several membranes inside there also. And you just have to get really good at using really fine forceps to pop the embryo out without destroying it. Because the minute you kind of poke it a little bit with your super fine forceps, it just explodes. Yeah. And the jelly coat is like, it's really cool because it's nature's way of protecting them from cooties, like bacteria, for example. So once they're out of the jelly coats, then you also have to cultivate them with antibiotics to

just to make sure that the embryos don't get infected. But yeah, you pop them out of the jelly coats and you line a whole bunch of them up. Like you line 50 of them up in this little gadget that we have that helps you line them up. And then you make your own needle. It's made out of glass and you fill it up with the DNA or whatever you're going to put in there. And then you have like a little tiny device that you can move all aspects of the needle and you line it up. But then in order to eject the DNA from it, you actually have to have a pressurized air system. So

You basically pump the DNA in there and then you get out as fast as you can because the longer you keep the needle in there, the more likely you're going to

Kill it, basically. Yep, I did not know this. Those teeny, teeny, tiny needles are made with a machine that heats glass and pulls it apart like taffy to make a hollow needle. And then these pulled needles, in some labs, they can get to be 1 20th the width of a human hair, depending on the application. Because, I mean, not everyone out there is making axolotls. And then how long does it take once something is an egg to hatch and then...

Do they molt or do they just get bigger and bigger? Yeah. So it takes about between like 10 days and two weeks, depending on the temperature, for them to hatch out of those eggs or for the ones that you've already gotten out of the eggs to fully develop into free living animals. About six or so days after fertilization, you can see them moving and you can start to see their little gills forming. They're absolutely adorable, like super cute.

So once they hatch out, then it's about a day or day and a half or so before they can start eating. So we have to monitor them and then they have to be fed something that is moving. So usually we use brine shrimp, which we have to hatch out here. We are now also transitioning some of the colony to rotifers for nutrition reasons. They seem to be more nutritious, but we're still piloting that. Just a side note, a rotifer is not a piece of drilling equipment.

It's a tiny, maybe half millimeter at most, spiraling, usually freshwater animal, a little teeny teeny, and it eats debris and it generally minds its own business. So you have to feed them live.

in the beginning. And then eventually you can wean them onto what we call pellets, which are like salmon feed. I remember feeding the axolotl in our science classroom tubaflex worms, just a little pinch of these wriggling red worms. And then they just eat them up like confetti, which was disgusting, but fun also. It's disgusting, but also you can't take your eyes off of it. Yeah. You're like, oh, so much wriggling. Can I ask you some questions from listeners?

Yes, let's do it. But before we do, let's take a quick break and donate some cash to a worthy cause. And this week, Jessica chose the Institute of Biology de la Universidad Nacional Autónoma de Mexico. And it's affiliated with this renowned Mexican axolotl ecologist, Dr. Luis Zambrano. And they have this program called Adopt an Axolotl, which raises money to help axolotl habitat rehabilitation and the conservation of local wildlife and protect

the strengthening of better agricultural practices, they say. So that donation was at the behest of Jessica and it was made possible by sponsors of the show.

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Okay, we are back with your questions. And let's start with one shared by patrons Gemma Mouse, Ilim Supreme Overlord, Zoe Litton, Sarah Williamson, and Sparky. Here's the deal. So I had so many questions from people with kids. Like we have Smologies, which is a separate show for kids. But I was like, why are so many people being like, my toddler has a question. And then I realized it was because of Minecraft. Are you, you have...

two kids are you familiar with the axolotls in Minecraft and how do you feel about the explosion of popularity of axolotls because of that yeah it's funny because I have two kids they're fraternal twins and they're boys they're both 15 and I don't think they would even be embarrassed for me to say that they have literally been addicted to Minecraft for at least a decade so my nieces and nephews yeah they

They still play it. We had like a whole era where every birthday cake, and I was crazy about that, had to be a Minecraft birthday cake and a Minecraft pinata. And like I even had Minecraft clothes. They had their Minecraft pajamas. Right. So Minecraft has contributed to this because they have these things called mobs in Minecraft. And they introduced the axolotl mobs a few years ago. Right.

Like many objects in the Minecraft video game universe, this axolotl is very blocky with a rectangle for a head that looks like a shoebox and then a longer rectangle for the body. And it has jagged lightning bolt-like gills and legs that look like upturned crucifix. They seem to make a lot of sounds best described, I think, as a sploot.

And I've even had people who are like professional video game players contact me to talk about axolotls. What are the differences between the Minecraft axolotls and the real life ones? And I'm like, well...

I know my kids are playing Minecraft, but I do not. So I had to like get in there and find out, you know, what, you know, what's, what's the deal. So yeah, that's kind of how I think the explosion in popularity for the axolotls is largely attributed to Minecraft. But even before that sort of, they're just so cute and there's these, you know, all kinds of stuffed animals with them and,

they have a lot of charisma. It is true. So yes, I get a lot of emails from little kids. And I also get a lot of paper letters, which are adorable, right? Handwritten letters about, yeah, about axolotls. And I know that most of them know that we're doing this for like scientific research, but it's a fine line that you have to toe when answering kids' questions because they want to know the real truth. And I don't believe in like

not telling that. But on the flip side, we're doing hardcore medical research here. And it's highly regulated as it should be and highly scrutinized and stuff. I've gotten better over the years at what to talk to kids about and what not to talk to kids about unless they go there. But I will go there with them. But I also think with kids, there's this added responsibility, which is all kids are starting to think about what they're going to do when they grow up, right? And so...

I try to respond as much as I can. Now, the last couple of years have been a little bit crazy, but in the past, what I would sometimes do would be like, oh...

Give me your teacher's email address and we'll talk or a lot of times the emails will come from the teacher and we could set up a Zoom call with like the whole class. So I used to do more of that than I do now, but I don't really have tons of time for it right now. And I used to write back like every email I would always write back. These days, I have to say like it's been harder to keep up with it. And so I want to get back to like that feeling of like always at least responding, but we'll get there. Yeah.

And should you ever need a scientist to Zoom or Skype in your classroom or a book club or scout meeting, hit up Skype a Scientist, which can match you with an expert for zero dollars. It's free. And that's run by Toothology episode, squid expert and Philadelphia based artist, Dr. Sarah McAnulty. And so if you think it's cool that they do that,

for free because they're a nonprofit, why not toss them five bucks or 10 bucks? You can go to skypeascientist.com to say, hey, it's cool that you do all that to help young science lovers get a leg up in the world, which was an embarrassment of a segue to a question asked by so many of you about

limb regeneration, patrons Patience Jensen, Samwise Kaikishimoto, Simone Francour's dad, Melissa Eller's son, Odin, Cecilia Morales, Courtney Horowitz's small egite Rory, Liz, Jeremy Glover, David Twin, A. Fromms, Les Johnson, and Bjorn Fredberg, who needed to know, in Bjorn's words, can they generate additional limbs? How many can they add on?

could you get an axolotl millipede? I think that's a no, buddy. But we do have a delightful episode on millipedes that we will link in the show notes, including why one expert recently named a new species after an up-and-coming artist named Taylor Swift. And getting to your work, I want to ask about that. So many people asked about it.

regenerative appendages, all of that stuff. Alex Glow wants to know, what can't they regenerate? Andrea wants to know, why does their regeneration ability not cause biological immortality? How does that work? What are you finding out? That's a big question. Yeah. So if we just back it up a little bit, people have known for

really long time, at least in the scientific literature, a couple of hundred years, that when you amputate the limb, then this bump forms. It's called a blastema, which means to bud in Greek. And this blastema contains basically all of the internal progenitor cells, so the building blocks that are going to be used to make the new limb. And so everybody really wants to know, well, how do you make a blastema? The other reason why you want to know that is because we don't actually make blastemas

following a limb amputation. But I would like to asterisk that because we also have to remember that if we were to suture the salamander limb closed after an amputation, it also doesn't grow a blastema and it fails to regenerate, right? So my secret hypothesis is that humans are probably doing a lot more than we give humans credit for as far as like the limb regeneration program, but they fail to actually go through it. And so because we don't see a blastema, we can't yet appreciate all the things that might be happening that are

positive towards the regenerative outcome, but the whole process sort of gets halted. So can the human body start to grow back an organ or a limb we've lost? Obviously not yet. Are there little nuggets in there trying their best? Dr. Wieden thinks it's possible, but for sure axolotls are doing it. She sees it with her own dang eyes. So after the blastema forms then,

It needs to keep growing. And then those new cells have to do something called differentiation. So the blastema cells all kind of look the same, even though secretly they're probably harboring memories from where they originated from. And then some of them go to become muscle. Some of them become cartilage. Some become bone, etc.,

And then eventually the new limb has to stop growing when it's the right size and the right amount has grown back. And then the nerves have to grow back in. The blood vessels have to grow back in. All these things have to happen. And those things are all really important and very cool. However, since humans don't grow blastemas, we have decided to focus mostly on what does it take to build a blastema? How are the cells computing that there's been this kind of injury, right? Because if you were to just give a salamander like a skin biopsy or a cut, it's going to

Typically, those don't just grow extra legs, right? Yeah, typically. How does the animal distinguish a cut from an actual amputation, right? And most people have been studying what the cells are doing right at the injury site, which is super important to know. That's also really important.

But what we found was that after an amputation, actually cells throughout the whole body get fired up as if they might regenerate something. Yeah, right. And so, you know, like the other leg, for instance, it's not just an inert bystander. We can't just say like, oh, it's doing nothing because what we found was that

cells start dividing over there too in response to an amputation somewhere else. And in fact, if you look inside the organs, if you give a limb amputation, then every place we've checked, cells start dividing. So the internal organs... Wow. Yeah, right. And so sometimes when you're working on something, you just have to go with your gut. Like,

In this instance, I just couldn't ignore that, even though I knew it was going to take us a really long time to figure out how this is happening and what the implications of it were. And so initially, we just had to publish that finding, basically, and a few things about it. And then it took us many years to figure out

how do these distant cells get sort of awakened by an amputation? And also, what does that mean to the animal that they've become awakened? And then thirdly, what can that tell us about this sort of logic, to go back to the philosophy part, the logic of how limbs regenerate? I think that this is a primary response to the amputation, and it's the beginning part of how progenitor cells might be selected to be used for regeneration. And it's

that they're broadly tapped by this information that a limb has been lost and only later do some of them go on to become blasphemy cells. And those are only the ones at the site of injury. And I think that's intrinsically interesting for understanding the logic of how limbs regenerate, but also the evolution of these processes. Because if you back it up and you think about like a planarian, which is a totally different kind of animal, it's like hundreds of millions of years removed from an axolotl and it's not a vertebrate.

When you amputate a planarian, you can cut that sucker in half and like the head grows a tail and the tail grows a head. Okay. And planaria, these marvels of the flatworm world, they're old. They're so old, half a billion years old. And for more on them, you can see our episode, Planariology, Very Cool Worms, I Promise, with one Dr. One Pagan, who truly and very deeply loves his worms.

which means, yes, he would love you if you were a worm, even a half worm growing the rest of your worm body. And when that happens, they first do this thing too, where they awaken all the stem cells throughout the whole body and they start dividing. And then only after a few days does it get refined to the site of injury. So I think that kind of like methodology that animals are using might turn out to be more generalizable.

So are the Blastemas just stem cells? Jessica says they don't really know yet, but there is a process called de-differentiation in some cells where they go from being a specialized, say, skin cell or a bone cell back into an embryonic form. That way they can shape-shift depending on what the body needs.

And for more on stem cells, we have a whole stem cell biology episode with Dr. Science Sam Yemien, who is wonderful. But no, Jessica says researchers still have to dive deeper into that process of de-differentiation. And so stem cells are kind of different because they never fully differentiate stem

They're kind of just set aside. So adults have, yeah, right. And so our work really highlights that, hey, actually stem cells are also getting activated and maybe we're not giving them enough credit in the field for what they're probably doing in the process of limb regeneration. So they could be serving as literal building blocks. So some of those blastema cells could have come from stem cells.

But also the ones that we've been analyzing, they tend to also be making a lot of signaling molecules. So like the kinds of molecules that cells use to talk to one another. And so those cells getting fired up, even if they don't go on to become a blastema cell themselves, they might be giving instructions to the other cells that do go become blastema cells, right? And so I think it's like pretty critical to think about it.

So they're like, yo, make me some bones. I'm asking you, please. But I asked Jessica if it ever feels like answering one question just makes you ask 50 more. And she said some grad students in her lab have started a list of her Midwestern Jessica-isms.

There will be phrases that I use, and one of them probably is can of worms. And I swear that we open up a new can of worms on a daily basis in the lab. And it's really hard to rein it in because the little kid in you just wants to keep going. But then in reality, in order to complete any scientific project, and these are really hard ones, right? You have to restrain yourself. But yeah, that whole activating the stem cells throughout the whole body, it turns out that

The way they're doing this is by using the peripheral nervous system. And so if you take away the nerves in these responding tissues, then those tissues can't activate the stem cells anymore. So that, I think, was one of our early clues that, hey, we should look at the nervous system in this process.

And from there it became, well, what is it about the nervous system? And our recent research has really highlighted that adrenaline is one of the things that they use. No. Yeah. Really? Yes. No. I mean, it makes a lot of intuitive sense. This is the kind of thing that I could talk to you like a grade schooler about, right? Like,

Like if you're in the woods, you see a bear and then you can run faster than you ever ran before. Then you can think you're, you know, adrenergic system or your adrenaline, right? Because it can make you like do things you didn't think you could do. A man or a bear, a strange man you don't know or a bear. And, and,

It turns out that after an amputation, which is kind of not surprising, adrenaline in their bloodstream increases. And we're still trying to figure out because there's more than one possible source of that. And we haven't really figured all of that out yet. But...

adrenaline can be a way to communicate information to distant tissues. And those distant cells, they express these receptors for adrenaline. And basically, if you pharmacologically inhibit those signaling pathways, then you can inhibit this body-wide activation response from happening. And then if you inhibit one of them, you can actually inhibit limbs from regenerating.

So if you were to stop that flow of adrenaline in an emergency, you'd essentially cut the phone lines to parts of the body that need the message to get started on regrowing a limb. So no adrenaline, no regeneration, which is some staggering molecular communication to discover on this path toward self-healing in salamanders, at least.

And so I think like that's pretty cool, right? That they're using it that way. Yeah, that that might be that catalyst for like, all right, mobilize time to regenerate some stuff. We're freaked out. We just got bitten. Yeah, exactly. The other thing that's really cool about this is when the animal gets into this activated state. So we call this systemic activation when it gets into the state where the stem cells all over the body are fired up.

Then if I asked you, let's say, what if the animal is like got a second amputation somewhere else in the body? Do you think it's going to grow back faster or slower?

I would think maybe faster because it's already in that gear, but I don't know. That is what happens. Yeah. But we would not have necessarily predicted that because this is an area of research where people, there aren't a lot of wonderful experiments about the cost benefits or like what we call the trade-offs to regeneration. Because I get this question all the time from kids and adults alike. It's like, why don't we regenerate? It seems so useful. And it's like, well, in thinking about how

you know, animal change and evolution works, like a lot of times we have to think about what is the cost to the animal to do this amazing thing, right? And so those have been harder questions to get at, right? But in this particular instance,

When we saw that the legs regenerate faster, it wasn't necessarily given it was going to happen because you might also imagine that resource allocation needs to be dedicated to the limb that was already injured and that it's going to deprioritize these other things or it's going to cost some metabolic costs that would make the other one grow back slower, right? But we saw that they grew back faster. And I think this actually relates to the fact that in the wild, a lot of salamanders are really

really under this selective pressure to regenerate more than one limb at one time in this really short timeframe, right? And so it is likely to have some selective advantage that if you fire the stem cells up everywhere and then you have another injury, which is actually quite likely, then you have a jumpstart, like you said, a jumpstart to the regeneration process. So we've been working on lately is basically this sort of firing up and how that

helps the animals regenerate. No pressure, but when can I use it on my own failing body? I'm not the only one who's curious. Patron Will Clark asked, are researchers looking for particular scientific lessons or potential medical treatments from these creatures? Which was also on the minds of Don W. Robin C. Pike, future immunology researcher Renee Kay, and Paul McQueen, biologist. And yes, me.

And ultimately, this research in the future, if you had a time machine, like, do you see it going toward just limb regeneration or organ regeneration or nerve regeneration for diseases like MS or things like that? What parts of the healthcare industry are, like, raring to go with this? So I like to think of it as there's two parts.

applications when we bend them. One is the very long-term application and one of the more immediate applications. And I'm here for the very long-term applications, even if I don't live to see them, which I hope I do, which is that I think this is nature's instruction manual for how to regenerate a limb.

that looks like ours, that has basically all the same parts as ours, as far as we can tell. If we understood how they were doing this, we'll be in a much better position as scientists to figure out how to stimulate human limb regeneration in the future, which is obviously like a holy grail question in regenerative medicine, just because

It has such impacts on people's lives. No matter how fancy prostheses get, it wouldn't be the same as growing back the limb that you lost. So that's the long haul thing. But in the meantime, a lot of the lessons that we're learning could be applied more quickly, I think, to some of these other

So, for example, when they regenerate a limb, they don't scar. Wait, wait, what? Yeah. And you can't even tell which limb was lost given enough time. Super cool, right? And meanwhile, we always scar except for in like the inside of our mouth or for fetuses, like halfway through gestation, we start scarring.

but axolotls just don't ever scar, right? And so something like antagonizing scarring, which scientists like to call this fibrosis. So antifibrotic therapies, not just for skin scars, but inside your body when fibrosis sets in into organs, and a lot of deaths, maybe even 45% of deaths are attributable to some amount of fibrosis, like after a heart attack or pulmonary fibrosis, et cetera. Just

Just a side note, my dad had cancer in his intestines and they cut it out and then they stitched them back together, kind of like a garden hose. And then from that, scar tissue formed that ended up blocking his guts hose, if you will. But before we found out that's what happened, he was having these gut issues and I was consumed with guilt because I had made him some Brussels sprouts and I thought they were clogging up the tubes because he did not like them. And I think he swallowed them whole, to be polite. Anyway, it was scar tissue.

it can be quite unpleasant internally. A lot of the molecular biology, like the cell biology of those processes is...

fairly similar. And so if we find antifibrotic molecules in the process of studying limb regeneration, then somebody else can take those maybe and apply them towards these other applications in the shorter term rather than just, you know, regenerating legs. So that's one possibility. You mentioned nerve regeneration, but the central nervous system is a big area. So

Spinal cord injury is a huge problem. You know, people's lives are forever changed and there's really not any therapy that results in restoration of walking, for example, after a spinal cord injury. Whereas salamanders, if you do that to them, they will just completely regenerate and they can, it's like, you know, complete. I don't know if that'll happen, if that kind of application will happen sooner than limb regeneration, but I would guess it might. So maybe some of the insights from that will be...

more quickly turn into therapeutic outcomes maybe. And so it has the potential to improve and save so many lives, I imagine, across a lot of different species. Freddie B. wanted to know, like, what are the ethics around studying limb regenerations? Other people wanted to know, if you amputate, is there, do they have a painkiller? Like, is there anything taken to...

help the little guys. Patron Kelly Gaudert asked, "Is this research helping or harming these little guys in the long run?" And Jacqueline Church wanted to know, "What is being done to ensure they're not exploited into oblivion to feed the gaping maw of big pharma?" Now, this whole episode, I'm honestly, I'm grappling with it as I'm making it because it's inspiring, but also really uncomfortable to consider in terms of animal research.

Although the reality that we should all know is that most of us owe our lives to research animals in some part. It's just a huge factor in medicine. And yeah, it's hard to even think about. So this is a toughie because I guess I will say in full disclosure that

When you do a surgery on a mouse, you're required to give them painkillers for X amount of time, depending on the surgery. When you do a surgery to an axolotl, that doesn't happen. That same kind of painkiller doesn't happen. However, they're completely asleep when you do the surgery. The anesthesia that's used to put them to sleep also has some analgesic effect, which is basically like some kind of painkiller effect. And so,

I can't say with certainty, don't feel. We're very interested in their changes in their brain activity. We have a new collaboration going with a guy who developed these sensors that you literally implant into an animal's brain. And they're used to basically peer into the brain and see which nerves are firing, which, et cetera. And so we do have a new collaboration to look at that. And we also have collaborators who work in pain biology as well.

in rodents and in humans. And so these are things that we want to know the answer to also because we care about the animals, A, and B, also because sensation may be one of the primary inputs into the limb regeneration program. So when we think about firing those cells up all over the body,

It requires the peripheral nervous system, not just in these distant sites that are going to be responding. But we also found that if you remove the peripheral nervous system from the limb that's amputated, then that doesn't happen. And previously, people had shown like hundreds of years ago that that doesn't happen anymore on the amputated limb. You need the nerves on the amputated limb. And so I think this is one of the reasons why historically it hasn't been demanded of the field that

Right.

So yeah, doing animal research is highly regulated. Everybody has to be trained. Every single thing that you do to the animal has to be vetted by a committee. And on the committee are tons of scientists, but also medical doctors and also, quote, lay people, which just basically means anybody who's not a scientist so that they can be reality, like sanity checked. So I think personally, I have decided that

I take it very seriously. I still think about it all the time, but I feel like the long-term possible benefit to humanity is enough that I can justify doing this kind of work. Speaking of ethics, who asked about loving and keeping and staring at them for pleasure? Jeremy Alas and Kylie Smolenberg, first-time questioners, both asked in Jeremy's words, they're so adorable. Is it ethical to have one as a pet?

And John Yurek said that their spouse wants to know how easy they are to keep his pets. A ton of you had this question. Emma Fury, Kara Young, Connor Day-Them, Sarah Rayleigh King, Nahima Miles, Alex Alottel, Kathleen Sachs, Remy, Sarah Piette, Olivia Eliasson, Hannah Nolan, Megan Walker, Mish the Fish, Chrysalis Ashton, Maya, Kristen Fuller, Laura, Anastasia Doherty, Max Aroni, Audrey Hudak, Amanda Panda, Eating Dog Hair for a Living, and Jadalyn.

Some people had questions about ethics of keeping them as pets. A lot of folks who listen have pet axolotls. Zachary wanted to know. Hello, my name is Zachary and I live in Maine. For the majority of the ones that you find online or at pet stores, are they wild-caught or captive bred? If you want to become a parent of an axolotl. Oh, I see, I see. Yeah, if you want to become an axolotl parent, I would say I would not worry about that just because I'm...

Fairly certain all of them came from the original stocks that were taken out and moved to Paris in like the 1800s, mid-1800s.

I'm sorry, what? So yes, apparently a guy from France, a photojournalist, journeyed to Mexico City in the mid-1860s and somehow nabbed 34 axolotls as a souvenir and took them back to Paris to say, ooh la la. And these kidnapped amphibians were given a home in a French menagerie, a French zoo. So apparently France...

being a quite horny and romantic place, did some magic. And they soon reproduced and people were simply captivated. And this one biologist received six of that offspring and then began breeding them and just passing them out like batches of cookies to his science friends all over Europe. And now we have them in pet stores and labs everywhere.

but not in the rivers and the lakes that they're used to back in Mexico, as they are critically endangered in the wild. So scarce are our little friends that... So I don't think anybody's getting axolotls in the pet industry from wild sources these days. I think they've just been...

spilled over from scientific inquiry into the pet industry would be my guess. Actually, when my kids were small and there was a pet store by the house and I would go in there sometimes to get supplies for the aquatics room here and they had the axolotls in there. And I remember the day I went in and realized they had a whole bunch of GFP axolotls in the pet store. And it's like, well...

Those definitely probably somebody moved into the pet industry, pet trade from the lab, right? So personally, I don't think there's any ethical problem with having axolotls as pets right now because there's no indication that they're actually coming out of the wild. In fact, I think it's really hard to find a wild axolotl right now.

I did not want to interrupt to ask what GFP was, but apparently it stands for green fluorescent protein. And according to the 2006 paper, a germline GFP transgenic axolotl, and it's used to track cell fate, dual origin of the fin mycenacime during development and the fate of blood cells during regeneration. Scientists have been using this jellyfish fluorescent to track cell changes for decades. But I'm sorry, what are these? Are these like stoner blacklight posters, but also an underwater...

phallic dragon? What's happening? How could you tell that they are GFP? Well, that pet store had them labeled as such, but also you can see if you have like a really bright light that's got all the wavelengths coming out of it, they do actually have a hue. They look a little different from the white ones. So like if I took you in the basement here, we have a lot of GFP animals and you can tell which ones they are without us putting it under the microscope that gives them the blue light. Because normally if you put them on the microscope that gives them the blue light, they're going to look crazy.

crazy fluorescent green, but even in ambient fluorescent lighting, you can tell. Really? Wow. Yeah. So from a jellyfish, I mean, that jellyfish gene has been cloned into so many animals and plants, even like, you know, all kinds of plants and stuff. Yeah. Oh, that's exciting. Rachel Von Morgan wanted to know, they always look like they're straight chilling, but they've got to have personalities. Are there sassy ones?

emo ones, the ones that are chipper in the morning without coffee? Do they get the zoomies? Do they like scritches and tickles? This is a quality question. And axolotl personalities were also a subject of curiosity from patrons Neen, Haley, and Gustav Golden. Any thoughts on the personality of axolotls?

Yeah, well, I think some of them are assholes. When you put them together, there's always, you know, one of them is usually the aggressor, right? Yeah, you know, like they have personalities. I think they have personalities. Some of them like to be left alone more than others. We have to give them hides in the lab. So yeah.

In the lab, one of the things you have to do is provide environmental enrichment to laboratory animals so that you've actually like accounted for their sort of well-being. You don't want them to be bored. This is true, right? And so one of the things we give them are PVC pipes as a hideout. Yeah, they're really cute in there. And so some of them spend a lot of time in the PVC pipe with just their little head poking out. And some of them are like, I don't even care about the PVC pipe, right?

Yeah. So definitely there are personalities for, I think for sure there are personalities. Yeah. Amazing. I have a few more lightning rounds here. Eli said, I've heard that their skin is super sensitive and it burns if you touch them. Is this true? It burns them or it burns the human? I don't know. It burns them, I guess. Does touching them...

burn their skin at all or no? Yeah. So like all amphibians have a sensitive skin because they breathe partially through their skin. So it's not a great idea to pick your pet axolotl up with your bare hands just because they're coated in mucus and that's a protective layer. Yum. And it's probably helping them like ward off infection. And so if you handle them too much and you remove some of that mucus, it's not great, but you could wear a glove, which kind of mitigates it. I don't think picking them up every once in a while is the end of the world, right? But like

all amphibians are more sensitive in their skin than like, for instance, we are because the outside of our skin is actually secretly dead, right? It's like cornified dead layers, right? But that's not the case for them. And so you got to be careful. It's also one of the reasons why amphibians are, you know, declining worldwide just because of pollution, et cetera. And then there's this fungal infection that,

that amphibians can get and salamanders can also get that infection. So, you know, you want to take good care. It's tempting to want to pet it all the time, but maybe not the best for its health, but it's not going to hurt it if you do it once in a while, you know.

Yeah. So this frog fungal disease is called catidriomycosis, and it causes red, peeling skin and temperature regulation issues, muscle weakness, and even death. And there are about 200 species of frogs and salamanders impacted on every continent except Antarctica.

Antarctica, most notably in Central and South America. And yes, touching an axolotl can damage their very fashionable slime coat, or they can thrash about and get hurt, or a substance on your hands, even your finger oils, can disturb their very sensitive skin. Are they going to die on contact? Probably not, but it's

best to transport them by just nudging them into a little tub or being very, very gentle. So do not pet the small mucus monster. Just stare at them. Well, to discourage people from doing that, perhaps you can answer Olivia Lester's question who wants to know, what do they feel like? Eels? Do they feel like eels? Do they feel like slimy little guys? I don't think I've ever picked an eel up. Like a hagfish?

I love the way they feel. I love them. They're kind of, they're not so slimy that you're like grossed out, but they are so slimy that when you hold an adult, you need to use two hands or the first thing it's going to do is just scoot right on out onto the floor, which usually is, I mean, it's not great for the animal, but it doesn't kill them. So you want to use two hands and be firm and make sure that it doesn't slide out because your hands will make a tube. It is pretty slick, but it's not like disgusting slime. And you can feel like

Like you can kind of feel its internal structures while you're holding it because you do have to apply a little bit of pressure so that it doesn't wiggle out of your hand. I like the way they feel. They look like they feel soft and squishy and fun, but you shouldn't squish them. Yeah, exactly. Yeah. Charlotte Parkinson wants to know, is it true that their teeth never develop? And if so, how do they nom down on what they eat? That's a great question. So

When we've had pet axolotls, I do remember a family member getting, quote, bitten and then me going in and being like, give me a break. Were you really egregious by this fight? It doesn't really seem that bad. So they do have like these little rudimentary teethy things, but...

Truthfully, they don't hurt when they bite. I've never seen them ever draw blood when they bite. They're not trying to bite. They think your finger is a piece of food, probably. They're not so great at hunting out food. So in the lab, when we drop these pellets, you have to drop it right in front of its face and then it grabs it while it's coming down, while it's floating down. And if it doesn't grab it while it's floating down, it's game over. It just ignores the pellet sitting there, which is...

Oh, no. Annoying because then it goes and dissolves and mucks up the water. But, you know, we have all these like filtration units and all this kind of thing to mitigate that. But yeah, they do have these little rudimentary teeth and they're kind of cute the way that sometimes they do just try to like snap a little bit. But I think it's because they think you're food, not because they're being aggressive. Yeah.

That makes sense. Yeah. And Kelsey Lohr asked, are their reflexes that bad? And a few people, including Alex W., had questions about vision. Looking at you, Josh Waldman, Denny, Ashley Mars, who noted their kawaii cute wide eyes, and Andrea, who says, it always seems like there is nothing going on behind their eyes. How big are their brains and how good is their eyesight?

And also, side note from Alex, Alex says, I have a domestic axolotl named Julio Cortazar because I'm a little nerd. Apparently Julio Cortazar wrote a poem about an axolotl. People asked about that. Have you heard of that poem? Yes, yes, yes, yes, yes, I have. Yeah, I can't recite it or anything. But yes, I've heard of it. I've seen it. People have sent it to me. Yes, of course.

So patrons Elizabeth Potter, Carrie Overall, Bennett Vanderbosch, and Chandler Witherington, who wanted to know if she had read this story by this Argentinian writer about a fateful encounter and a descent into fascination and metamorphosis into the axolotl. And yes, she is familiar. And for the rest of you, now you are. And there's a short story for your reading list, your walks. But back to the original question from Alex. But Alex W. wants to know that

that he, well, he is the derpiest derp, but I swear he recognizes at least that food comes from people if not specific humans. But essentially, Alex W. wanted to know how bad is their eyesight actually?

Do they have really bad eyesight? I think most people are surprised when they come into the colony and they see how sedentary they are and how much they are just chilling out. They really are like kind of slow, you know? I don't know. I'm going to just be guessing, but they're nocturnal. And so if you look at some of the ecological studies, then they have tagged axolotls down there in the wild and observe them to be more

active in the night. And we have seen this here also. And so because they're nocturnal, I would have guessed that they probably have better eyesight than we give them credit for because they do like to feed on live things, but maybe they're mostly detecting the change in the motion in the water or like, you know, vibrations in the water or something. I can't really tell you for sure about this.

On that note, Natalie Jones asked about their blank stares and Alicia Clarkson wanted to know why are they so derpy? Or more directly, Gerhard Vanderwad asked, how smart are they? Same with Monica Olvera, Jamie, Dig, and Travis Justin. And bassist ex-Machina, Ryan Brubaker, and MB asked in MB's words about their wild ability to grow brains. Like new ones?

Some people asked about their brains. If they have big brains, little brains, if they're smart. Basis X Machina wants to know, can they really regrow parts of their brains? How big are their brains and can they grow them? Yes, these are great questions. So before we answer the questions about the size, I don't like to think about whether things are smart or not, because actually I think...

everything is just perfectly evolved for what it does. You know, I was just listening to this plant book recently called the light eaters. And it was like, the case is pretty well made that maybe plants have some kind of ability to, I wouldn't want to say think they wouldn't say think, but like make decisions and stuff. Right. So like,

I don't know if I would say that they don't seem smart. When you see them not going after the food, you're like, huh, maybe. But the interesting thing about their brain is it is tiny compared to their head. Because they have big heads. They have huge heads. And inside the brain is like, it's not even that much longer than my pinky fingernail. It's pretty small, considering especially the size of the head.

And it's different than our brain in some ways and similar in other ways. But one of the ways it's different is that it doesn't have this layering, the cortical layering and like those involutions that, you know, are characteristic of things like humans, for example. And so a lot of neuroscientists will say,

say that there's a correlation between how smart something is or they wouldn't use that term but you know basically that and then like the brain folding or or the cortical folding yeah this these animals don't look like that the lamination or like the layering of those um layers in the brain isn't really there but if you look at the gene expression that defines the different kinds of cells in there you can still see regionalization of of those genes so i would say i

jury's out on how quote smart they are and that kind of depends on how you define it but it is true they can regrow parts of their brain nuts yes nuts the fact that that can happen yes so you can like give them a partial lobotomy and then they grow part of the brain back i don't want to do that i mean absolutely bonkers and i can see why this field is like so exciting i mean did you see godzilla minus one i did by chance no godzilla is somewhat amphibious in it

And I don't want to spoil too much, but there is regeneration involved. I feel like maybe it would be exciting for you. I need to watch that. Yeah, you need to watch it. If you can deal with subtitles instead of the dubbed version, definitely watch Godzilla Minus One in Japanese and just read along. Tiny spoiler alert, but it's been out a few months, so don't blame me. Blame yourselves. I'm telling you, it's pretty bonkers. And I feel like it's maybe Godzilla's part axolotl. I don't know. But

A couple more questions. Alexander Von Fitsibitz and his mom, first-time question askers, want to know how long do axolotls tend to live? Oh, God.

Oh, if you scour all the sources, you will might come up with a number that says 25-ish years. However, I don't know if we really know how long an axolotl can live, but I do believe there are documented cases of 25 years. Could be longer. Could be longer. Yeah. I have some in the colony here that are like 12 years old. Yeah. And do they stay an adult size or do they get bigger and bigger and bigger and bigger? Yeah.

So this is also interesting. This kind of segues with this idea of something called indeterminate growth. So you probably are aware there are some fish that will just get as big as the tank will allow them to get. There's room for a little more. And axolotls, some people say axolotls are indeterminate growers. I think there is actually some evidence this may be the case, but the plateau is...

It's not that steep at the end. So if they are secretly growing a little bit bigger, it's a little bit. But I have met people who have axolotls that appear to be twice as massive as even the biggest ones that I have in my colony. What? Yes. I have seen them in person. Yes. Twice as big as her biggest ones. How big are we talking? Like an arm? Not like most people's arm, but like a child arm. Yeah. I would say, you know, like pretty big.

Of course, there are other salamanders in the world, like the Chinese giant salamander. I don't know if you've ever seen a photo of one of those. I've seen a picture and it looks photoshopped, but I understand that it's not. Yeah, you could lay both of your arms out and then put the salamander on there. There's a guy at this hospital around here, Brigham and Women's Hospital, who had a really cool paper a few years ago, back to the mucus question, where he and his colleagues, because some of them were in China, they milk salamanders.

the mucus, they scrape it off of the Chinese giant salamander and they actually showed that it can accelerate wound healing in a mouse model. The mucus alone, which I think is really cool because probably some of how they are such amazing super healers is probably due to their skin and the stuff their skin is making. So I think that's actually quite cool. I

And yes, Chinese salamanders are huge, with the London Zoo reporting them to be around the size of a fully grown man at 1.8 meters in length, or six feet for those of you in America. And also, if you're doing the math, 1.8 meters is actually 180 centimeters, is actually just 5'9". So if you're a short king getting discriminated against on American dating apps, put your height in centimeters. Let's

Let them figure it out. But back to mucus. In previous episodes, such as Hagfish and Rhinology, about noses, I have bleeped the word mucus.

to take a stand about how gross I find it. But I have matured and I bear with it now. Perhaps the best type of exposure and response prevention therapy I could undergo would be a mucinology episode. I'm going to do my best. No promises. And Jesse asked, is there a possibility in the future that Hollywood doctors would use axolotl science to keep celebrities looking even more freakishly youthful? On that note, we had a great question about this. Olivia Lester.

Given their regenerative abilities, are axolotl facials a thing yet in the Kim K household? Will these properties be used for very expensive facials? Honestly, I do think they will be, but I think that the day is going to come someday. But I would actually say that it's really important to distinguish between

if it's insights from these animals or actual stuff from them. And I would not be in support of actual stuff from them. I think that's horrifying with some exception. Actually, I do know of a, of a company that is making like a temporary skin covering out of decellularized axolotl skin. Wow. And I think, honestly, I feel like from an ethical standpoint, even though personally I wouldn't want to do that research, you know, I can get my head around it, but I think anything that you're going to do for cosmetic reasons, you,

is not going to be predicated on using the actual material harvested from the actual animal. However, the insights from the animal and then use those insights to synthesize those kinds of molecules in the lab, and I wouldn't be surprised

Yeah. Hey, does an axolotl want to hang out with you or anyone? Patrons Alex Nelson, Hannah Johnson, The Joyful Spitfire, Violet, Lux Vega, and Patrick Duffy asked in Patrick's words, do they have best friends? What's their family group like? And Earl of Grameelton noted that these neotenous creatures look innocent of all wrongdoing ever. And Natalie Wagner want to know, do they live solo or in pods?

They eat each other sometimes, but maybe just juveniles. Do they tend to just be like chilling in their own PVC pipe or they're under their own rock and just like, I'm good? Yeah. So if you have a whole bunch of them in one tank, it's kind of all bets are off. I mean, usually they're kind of just chilling by themselves. Although I would say, I think I remember reading that in these studies where they microchipped them and then figured out where they were hanging out at different times of the day, that there was evidence that they do get together occasionally, but that doesn't

I don't think we know that much about like what their social life is when they hang out in the same vicinity. That doesn't mean that they're like having a beer or something, you know? Yeah. Apparently tortoises have preferred associates. They'll go visit one tortoise's burrow more often than another. I think that's very cute. That is very cute. Yeah. They can tell from one another, I think, because like,

Tiger salamanders are super closely related to axolotls, and there's this really cool literature on tiger salamander cannibalism, whereby if you put a bunch of them together and then

they start to become cannibalistic, only one of them will turn into a, change its jaw shape and make it bigger so it can turn into this cannibalistic morph and then it inhibits the others from doing that. That's crazy. For an absolute pitcher of tea on this, please see the 1983 paper, Head, Shape, and Size in Cannibal and Non-Cannibal Larvae of the Tiger Salamander from West Texas.

Texas. Interesting. But another thing that they found was that they prefer to eat more distantly related, yes, animals rather than like their direct siblings. So they can... I would not be surprised if salamanders can kind of distinguish these relationships and how it happens. No one knows. But you can...

force a salamander or like an axolotl and a tiger salamander in the lab, you can make hybrids of them. And all of the axolotls that are now in the laboratory setting, at least in the US, maybe everywhere, they actually are secretly 6% of their genome is tiger salamander DNA because this was done in one of the stock centers a long time ago and it sort of got lost.

the lineage information. But yes, I have a colleague who has published this and he's the director of the Axolotl Stock Center. So there's an Axolotl Stock Center in Kentucky. He's a very cool dude. Yeah. That's so interesting. Angela Hawkins, first time question asker, asked what's up with that genome size? I get it's most likely from repetitive DNA, but damn, why, how? Do they have a ginormous genome? They have an enormous genome compared to humans. It's 10 times bigger than the human genome. What?

Yes, but they have a similar number of what we would annotate as genes, but the genes are not all the same, but there's like a lot of overlap. But every time we do a regeneration study, there's like usual suspects, genes we've heard of in humans. And then there's always like a third or something of complete mystery genes. And I'm very interested in what those are doing. They're harder to work on. But I think it's really cool to think that, you know, maybe some of those mystery genes are part of the reason why they're such awesome regenerators, right? Yeah.

So as of 2019, the axolotl had the largest genome of any organism ever sequenced with 32 billion base pairs, as opposed to the human genome, which has about 3 billion base pairs of AT or GC. So axolotl, way to go. You win. Wait, no, you don't. Because since then, bigger genomes have been sequenced. And I know you're thinking like a whale or an octopus, but no, no.

The Japanese canopy plant has 149 billion base pairs of DNA, nearly 50 times that of you. You boring, simple ape.

And last listener question, Amy Lee, first time quest jostler, wanted to know what, if anything, we can help to protect them in the wild or if the future relies more on captive populations. But how can we help the axolotls of the world that are endangered? Yeah. So I want to give a plug for this really excellent New York Times article that came out right after Christmas this past year. And

And this article is titled, What It Takes to Save the Axolotl. And it was written by Jenny Aaron Smith. And it explains that the home region of the axolotl lies in what are now canals that make up a 1,000-year-old wetland farming system called chinampas. And the axolotl once thrived in these conditions. So Dr. Luis Zambrano, known for his work in axolotl conservation, we talked about him earlier, he's working with this team of scientists to study and bring back

these ancestral ways of farming as salamander sanctuaries. And side note, the very colorful party boats that celebrate the axolotl in these canals also contribute to the trash and pollution that's killing them. And many of the axolotls in fish tanks on display for tourists are

just from pet stores, and they bear little resemblance to the wild ones whose population has taken this steep decline. And so Dr. Zambrano and colleagues are releasing a really small number of axolotl from wild stock into canals that are designated as sanctuaries and are safe from invasive predators and are closely monitoring everything from pollution to oxygen levels and plant life and crustacean life. And so far,

Of the 12 in a recent pilot study, 11 have survived. And the article says that they're fat and happy. And our donation this week went to that program. So you are helping out just by listening.

And I would say that's the really amazing, very recent source for all of the conservation effort information. And some of the actual scientists in there, the ecologists working in the field, they have conservation programs that you can get the link right in that article. Great. And I know they're declining populations are a bummer, but in general, what about your job sucks the most? What's the most annoying thing?

the most tedious thing, the biggest bummer? What is one thing about your job that is not fun? So I don't know. I don't want to speak for all scientists, but most of us who get into this are sort of dorks and nerds and everything. And we're in it for the science and we like doing the science. But after you get to be the professor, you're not the one sitting there getting to do the fun part anymore. Instead, you're advising the people. And that's also kind of, of course, that's exciting, especially when stuff is working. But one of the things that a lot of us aren't

trained for that's super great at is sort of like managing. Yeah. I always say the same thing about creatives. I live in LA. I have so many friends who are creatives and artists and stuff. And if you're lucky enough to make a living out of it, then you have to run a business. And you're like, oh, the whole reason I got into this because I don't know how to run a business. So, so much of it is like these business skills. And I think some people are

learned it by osmosis and they have people in their family. But very few scientists are trained in both of the realms. And then suddenly you become the professor and you just have to do this whole set of other things. And most of us, for me, it was just trial and error, trial by fire, right? Which doesn't feel great, but yes. I get it. I get it. There are certain reasons why some people are like,

I don't think I'd be good working for a company. So I'm going to go out and muck around in boots and stuff or go out and paint murals or whatever. And then before you know it, you're like, oh, I got to figure out how to pay health insurance and how to order stuff and whatever. Exactly. Yeah. And of course,

Another bummer is finding funding. And she says that's because the axolotls need care for at least a year until they're breeding and that axolotl science is already inherently pretty risky because so many things don't work in a salamander that work in a mouse or a fly. And she adds that most of the times the people reviewing the grants are not salamander people. But I don't know, maybe all the Minecraft pop culture clout will yield some kind of pay dirt of grant gold.

What about your favorite thing about what you do? Oh, God. There's so many favorite things. But I mean, sometimes I'm just walking in here and I'm like, even if this shit is hitting the fan at home and it often is, I'm just like, pinch me. I am literally doing this thing that when I was five, if somebody had told me this was going to be my job, I would be like, hell yeah.

I can't wait, right? So most of the things I really do love. But the favorite thing is when somebody in the lab has a new result. And it's not just like, oh, I think this is happening. It's like they come in, they show me the pictures and the graph, and it's significant. And I'm like, oh, my God, we are the only people in the whole world

that know how this works, right? And it doesn't happen every single day, but when it happens, it's like this amazing feeling because humans are just trying to figure out how the natural world works with what we got, which is like our senses. And like, we're going in there just tinkering in a way and we don't really know. We don't know so much, right? And so the idea that for a hot minute, like the two of us know something that nobody else has ever appreciated, even if it's tiny, I love that.

Oh, that's so exciting. It's like mysteries, solving mysteries all the time, and then having more questions and more cans of worms. Yes, yes, yes. And I also really enjoy mentoring because it is something that I think you can't really want to be a professor unless that's like really important to you. It's like raising up the next generation of people who are going to go on and carry on this kind of work later, or maybe they're not. They're just going to use the skills that they got in graduate school to go and like conquer some other kind of

professional world, but they're still really important because, you know, graduate school teaches you supposedly how to think about problems, right? And so it's always really cool to see them go off and achieve their dreams, you know? I'm so glad that you have achieved this dream and we got to ask you so many questions about axolotls.

I feel like I know them better now. And also I'm in wonder of them. I wonder how many people are going to get axolotl pets after this. Honestly, do a lot of reading before you even consider one. And because they're now so rare in the wild, most of the pet trade actually descends from that Parisian population that was taken from Mexico. But many countries and states ban them or require them.

Thank you.

Joey's wig said from my mom, my niece's pet axolotl seems to lead a dull life. Is there any way to entertain her? What else? Any pet care tips? Ooh,

Oh, I would say, you know, you got to watch the water quality because that's the number one thing that can stress your axolotl out if it gets too hot. So like if you're going on vacation, don't turn the AC off because that's like the thing that they hate the most is they don't like an elevated temperature. It will stress their whole all their body systems out. So be careful about that would be like one of my number one tips, I would say. And I also think like they love to eat night crawlers. So if you just get one styrofoam container from the tackle, like the bait shop, you're

You can keep it in your fridge and it'll last like six months because they also breed in there. And then you just take a night crawler out and they're so happy. It's like candy to them. A literal can of worms. Those are my pet axolotl tips, I would say. That's amazing. Thank you so, so much for doing this. And yeah, this was a dream come true.

And when you asked me the question about do I get back to all the kids always, like it breaks my heart to say that now I can't, which for like, otherwise I wouldn't sleep. But doing things like this makes me feel like it's so much more efficient. And I feel like so lucky to sometimes get these kinds of opportunities. So thank you, Ellie. Oh, good.

So axolotl, smart people, a lot of not smart questions, because that's how they learned what they know. And now you know. And for more on Dr. Whitehead's lab and the work of Dr. Luis Zambrano and the Adopt an Axolotl program, you can find links in the show notes and also linked to our social media at ologies on Instagram and X. I'm Allie Ward with one L on both.

Thank you to Aaron Talbert, who admin's Theology's podcast Facebook group. Aveline Malick makes our professional transcripts. Kelly R. Dwyer does the website. Our scheduling producer is Noelle Dilworth. Managing director of so many things is Susan Hale. Jake Chafee is an outstanding editor, as is the marvel of lead editor, Mercedes Maitland of Maitland Audio. Nick Thorburn wrote the theme music. And if you stick around until the end of the episode, I'll tell you a secret. And when I was in Mexico City, I went with my friend who saw...

one of her best friend's husbands at a pool with his mistress. My friend looked like she was frozen in ice. She just went stiff all of a sudden. And then she had to text me from two feet away to tell me what was going on. And his wife already knew that he had stepped out with someone. They were in the process of separating, but wow, that was a spicy encounter.

I would have rather seen an axolotl, if I'm honest. Okay, bye-bye. Hackadermatology. Homeology. Cryptozoology. Litology. Meteorology. That beautiful creature right there. Cam found out that group chats between different phones aren't private. Or encrypted. Or encrypted, thank you. We only text in code. Yes, which I created. I created a code. Yes. Which can be a little annoying. Wait, what's...

Was that your attempt at the code? You already forgot the code, didn't you? I should have written it down. The place to safely send messages between different devices. WhatsApp. Message privately with everyone.

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