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(upbeat music) - What do a salamander and a mouse have in common?

They can both regrow body parts.

Researchers are working really hard to figure out how they do it.

And if they can figure out how they do it, maybe they can figure out how humans could do it too.

Think about burn victims being able to grow new skin or someone with a spine injury not needing to be in a wheelchair.

This has been a journey that I started with Larry Wilson, a biology professor at Emory University.

So what are we looking for, Larry?

- We're looking for salamanders, is we're in an urban park here in Atlanta, just to show that any kind of habitat, they're gonna be there.

And there's, in this park in particular, there's about four species that we'll be looking for.

One is just kind of a drab brown one called spotted dusky.

- [Sharon] So what else might we find, I hope?

- [Larry] Well, we're looking for southern two-lined, which is a bright yellow guy.

- [Sharon] Larry is like a machine flipping over rocks, his net ready to snare a salamander.

I'm pretty worthless to the hunt.

He knows what kind of rock to look for and soon he's found larvae that will become a red salamander.

- They have what's called chromatophores that give them their colors.

And they don't get that until they become adults.

Even newly metamorphosed, some of them aren't very colorful till they get a little bit older.

- What do they eat?

- They're carnivorous.

- [Sharon] They're carnivorous?

- [Larry] Yeah, they're going to eat any small insects, worms, things like that.

- [Sharon] But they look like a worm.

Look at their little, little legs.

- [Larry] Are in a family called Plethodontidae and they're lung-less.

So as an adult, this isn't gonna have lungs.

And then as an adult, it's gonna just get its oxygen through its skin.

- [Sharon] Their little legs are so cute.

- [Larry] Aren't they cute?

- [Sharon] Salamanders are animals.

And in the southern Appalachians, by weight, there are more salamanders than there are mammals or birds.

Tiny little thing.

- So this is a dusky and it's actually a young adult.

They don't get too much bigger than this.

And one of the things that's real characteristic of this group of salamanders is they like to jump.

If you look really closely at his eye.

- [Sharon] Yeah, he's got big eyes.

- [Larry] There's a little tiny stripe to the back of his jaw.

And that's characteristic of this genus.

But this is the most common salamander.

This salamander, as long as you've got water, even if it's slightly polluted.

- [Sharon] Doesn't care.

- [Larry] They can take it.

- [Sharon] We spent the day like this.

Pick up rock, grab for salamander.

See one?

- [Larry] Yeah, this is the other one.

This is a different species.

Oh, don't go away from me.

This is the southern two-lined, the one that's yellowish.

- [Sharon] Oh, how, oh, he's pretty!

- [Larry] And you can see he's got two lateral lines.

The cold weather's not bothering him at all.

- [Sharon] No, but yeah, I see the two stripes.

It doesn't take long to find three species.

- Oh!

It's a red salamander, and it went down a hole.

And he's a big guy.

If we can figure out how to get to him.

Oh, this is a pretty one.

(water splashing) - [Sharon] Oh my goodness.

He is big.

He's pretty.

- [Larry] Isn't he pretty?

- [Sharon] Yes.

- [Larry] That's full grown.

So this is...

There's a couple subspecies.

This is northern red salamander.

Now, up in the mountains- - Get some of this muck out.

- [Larry] Yeah.

Up in the mountains, we get one called the blackchin salamander who doesn't fade out as he gets older, he stays bright red his whole life.

We'll keep looking.

We'll probably find a younger one that's more red, but... - [Sharon] We get these rocks out.

- This is obviously a very important animal as far as the breeding population of this stream.

- [Sharon] You get a better view in his hand.

The skin is moist and smooth to the touch.

- [Larry] He's posing for you.

- [Sharon] He is.

Aren't you pretty?

- Dug me up.

Well, we're gonna put him back in his little lair.

- [Sharon] You remember where you got him?

- I do.

- [Sharon] Back up the hill, Larry pulled out some animals he found earlier in other spots.

What is this one called?

- [Larry] It's called a marbled salamander.

- [Sharon] A marbled salamander.

- [Larry] And he's full grown.

Females guard the eggs and they move and sometimes you get hundreds of them in that area.

- [Sharon] They're just beautiful.

- [Larry] Ain't he gorgeous little guy?

- I just, I love their little feet.

He breeds in the water but spends most of his time back in the woods under logs.

In Georgia, we have just short of 70 species of salamanders.

They are the hidden jewels most of us never see.

Pretty big eyes too.

- Yep, pretty little guy.

- He is, I think they're beautiful.

- Yeah, when I saw him, I said, "I've gotta show this one to Sharon."

- [Sharon] (laughs) I'm so glad you brought him along.

The last salamander in the bucket was not what I was expecting.

- But we also have some of the biggest salamanders.

Okay, this guy's gonna be hard to hold.

I don't know if we can hold him or... - [Sharon] Yeah, maybe not.

- [Larry] This is, I'll hold him, but you need to be ready 'cause he's slippery.

Come on, buddy.

This is a greater siren.

- Siren?

- Siren.

At one time, they thought they made noises, and they do sometimes make a little bit of a clicking noise.

- Sirens can get almost three feet long and they are the only salamander that will occasionally bite.

But now I wanna show you why Larry is hooked on these little critters.

Weeks later, we met in a lab because Larry had gone hunting.

So Larry, that salamander is beautiful.

What is it?

- Common name's spring salamander.

Its scientific name's Gyrinophilus.

We always call 'em gyros.

- Gyros?

- Gyros.

But that's one of the prizes is it's a big salamander, it's colorful, it eats other salamanders primarily.

It likes cold weather, comes out even 40 degrees when it's raining.

- When you can see all the features of this big red salamander, it's amazing how common they are.

We just don't see them.

But you're about to see more bright beauties or, as Larry calls them, the gems of nature.

How much trouble did you go to to get that salamander?

- (laughs) I was out in pouring rain during a storm at between 10 and midnight, 12:30 or so is when I got home.

And we saw lots of, I saw lots of salamanders, lots of red salamanders, but that was the only spring salamander I got.

- Were you excited?

Did it make it worth it?

- I was, I kept thinking, "Sharon's gonna appreciate this."

- I do.

That's one of the prettiest ones I've seen so far.

Well, that was until this guy.

This beauty is a cave salamander.

Larry climbed inside a cave near Pigeon Mountain to find him.

- So he climbs up walls in caves and they live in what they call the twilight area of the cave where it gets a little tiny bit of light.

It's not the deep dark recesses.

And these guys can climb straight up walls.

So they're one of the few salamanders that has a prehensile tail and has really good ability to latch onto things.

- [Sharon] And then he decided to latch onto me.

- [Larry] Just fall off the edge there.

See all this five toes?

- [Sharon] I'm gonna keep my hand here just so you're not going try jumping off.

- [Larry] Gonna walk up on you.

- [Sharon] Hello.

Hello there.

He's looking at me with those big eyes.

Come to mama.

I'm honored that you chose to climb on me.

He's got more toes.

- Now, both of 'em have five toes in the back.

There's very few salamanders that have four toes.

- He likes this sweater.

It must feel like a cave.

Larry is the co-author of a book on salamanders.

He has a high regard for them in the world of ecology.

So much so that Larry will make that drive again and put all the salamanders he captured back where they came from.

It's like a snake, I just keep doing this.

- [Larry] Yep, that's exactly.

Notice they're all found their cover and that's where they're gonna hang out.

- [Sharon] He brought a handful of red salamanders.

There's a northern red and blackchinned reds.

The colors are amazing.

And he was able to find them because Larry went out on a rainy night.

That's like a green light for these guys to come out and play.

- [Larry] They're one of the ones when people find them, you know, it's really obvious.

First off, they get excited 'cause it's a bright colored thing.

- [Sharon] Yeah, they're pretty.

- [Larry] We always talk about the jewels of the mountains, the salamanders.

And now you can see why we call 'em the jewels of the mountains.

- [Sharon] Yeah, it is like a jewel.

(upbeat music) (upbeat music continues) (upbeat music continues) And the hits keep coming.

Next up is the northern slimy salamander.

- [Larry] And you find these under logs and stuff because that's one of the last places to dry out.

- [Sharon] Okay.

- [Larry] And then if those start drying out, then they go down to the ground.

So these are the same way as the other ones I was telling you about is they'll disappear once it starts getting hot.

During the summer, you won't see 'em.

- [Sharon] And as you can see, he leaves a trail of slime behind him.

Because of our camera, you are getting incredible images that most people could never see.

Next comes the Pigeon Mountain salamander, which is a protected species because Pigeon Mountain is the only place it is found.

Looks like he's got eyelids.

- [Larry] He does.

- [Sharon] Huh.

- [Larry] He can blink.

It's a southern two-lined.

- We found one of these when we were out in the field.

The bright yellow is stunning.

But again, you have to know where to look.

So Larry, you went out and took a whole day into the night to find all those salamanders for us.

- Yeah, if you didn't know what you're doing, you'd never find that many.

- No.

- But it was also perfect weather conditions.

- And you like to go out in the rain, that's when you find- - I do, I do.

I mean, it's not that I like to go out in the rain.

I like the results of what I can get when I'm out in the rain.

And with some of those salamanders, they're just not gonna be above ground moving unless it's just torrential downpour.

- And the prize.

- And as soon as it quits raining, they stop.

- The prize was the spring salamander.

- The spring salamander.

For me, I mean- - [Sharon] No, it was pretty.

And what I really respect about you is you're gonna put them all back where you found them.

- [Larry] Oh, absolutely.

In fact, if you were looking closely on all my Tupperware things is it tells me exactly where I got that particular one.

It's not I can just dump 'em up in North Georgia.

It's, they're gonna go back to their- - [Sharon] That's commitment.

- I figure I owe that to them.

If I'm gonna borrow them and they're, you know, is they should at least go back to their same place.

- [Sharon] That's because they have territories.

They would be lost, in a sense.

This female salamander would not be able to find her eggs.

Her rock would be missing.

Yeah, this one's a lot prettier.

- [Larry] Yep.

Ah, see that all that white?

- [Sharon] Yeah.

- [Larry] That's, that's... - [Sharon] Egg?

- [Larry] Eggs, yep.

This little female hasn't laid her eggs yet.

- [Sharon] We're not gonna take your eggs, baby.

- We'll put you back under your rock.

Oh, wait a minute.

I totally take this back.

She has laid her eggs.

There they are.

- Oh yeah?

Oh my gosh.

Look at that.

- So we'll put her back there and let her guard her eggs so she- - [Sharon] Oh my goodness.

- [Larry] So that's her eggs and she'll be keeping fungus off of them and turning them in the water.

- [Sharon] Oh, so you overturned that rock and the eggs were on the bottom.

- [Larry] I did, I did.

- [Sharon] Don't worry, mama.

- [Larry] Yeah, we're gonna put 'em right back.

Okay.

And then we need to get her back under there too.

There we go.

She immediately knew where she wanted to go.

- [Sharon] What a find.

- What a find.

And she was a pretty mom too, wasn't she?

- [Sharon] Yeah, she was very pretty.

To Larry, putting them back is important for a number of reasons.

- [Larry] And like I said when we were filming some of these is you notice that kept putting its nose down.

They're really pheromone dependent.

And these are chemicals that animals put out to communicate among their own species.

It's something humans don't really have.

We have evidence that we probably once had it, but some animals are really, like ants.

Ants are basically blind and everything they do is based on chemical cues and trails.

Well, same with the salamanders.

So mating and, you know, territory, all that.

- This is where I part ways with Larry because of this guy.

You can see the tip of his tail is a different color.

Something bit it off and the salamander just grew a new tail.

How do they do that?

My journey took me to the University of Kentucky where Ashley Seifert is one of many researchers across the world trying to figure out how regeneration works, especially in this funny looking fellow called an axolotl.

So what is so special about these salamanders that make them good for regeneration work?

- Well, one of the nice things is that, as adults, they maintain an aquatic lifestyle.

So it makes 'em much more conducive to keeping 'em in captivity.

Easier to feed, easier to care for.

And then most importantly, we can breed them in captivity.

And that means we can get eggs and it means we can modify those with transgenic technology.

So if we wanna label cells and we wanna follow those cells, look at the identity of those cells and try to understand how they work during regeneration.

- They almost look like fish.

- Well, you can see on the outside of their heads, these red feathery, those are gills, external gills.

So they utilize those to both acquire oxygen and offload CO2.

- So how much do they regenerate?

Like if you, I'm not into animal cruelty or anything, but if you chopped off a leg, would it grow back?

- It would, 100%, so- - Get outta here.

- So, you know, these axolotls are considered to be like sort of the champions of vertebrate regeneration.

They can regenerate their tails, their limbs, their digits, their external gills.

Their spinal cord, if you sever it, they're able to regrow that, and they can even regenerate whole compartments of their brain if it's excised.

- And to think these salamanders, which hold so much promise, are critically endangered in the wild.

They are from Mexico and the two lakes they live in are polluted and partially drained.

Luckily the species is a favorite of scientists and pet owners.

It's that little smile.

I found them for sale on several websites and there are humorous memes that feature that somewhat silly looking round face.

But here in the lab, things get serious.

Speak to a first grader and explain molecular structure and how... - Sure, so the cells that are there following an amputation, say for something like a limb, they need to communicate to one another, right?

So they obviously have their DNA packed within the cell that has all the instructions for how they develop the limb.

So now they need to reactivate some of those specific signals, communicate to one another, and start to rebuild the limb slowly over time.

And so that's what I mean by molecular circuitry.

We know a lot about those signals, how the genome works during regeneration, and how those cells are responding specifically to injury so they can replace the right amount.

We don't want them growing a limb that's too long or too short, with too many or too few digits.

- That's amazing.

And it has to be frustrating to know how they do it, but not be able to figure out how we could do it.

- Exactly.

I mean, that is one of the big mysteries, right?

I mean, I look at my hand, if you look at your hand, you look at your digit and when you look at the size of some of these salamanders in here, you can see that its limb is, you know, not much bigger than, say, my digit right here.

And so they have all the same components, right?

A skeleton, muscle, nerves, skin.

And so when we can watch them sort of rebuild the structure over time, it is kind of frustrating because we've been working on this for a long time.

I mean, when I say we, generally the scientific community.

And you know, we just haven't been able to figure out what's missing in terms of those signals or how our immune system responds or if we're deficient in a cell population.

But yes, frustrating indeed.

We'd like to be able to figure out how to do that.

- [Sharon] It's a matter of getting a set of instructions which tell the cells how to talk to each other, how to rebuild.

For example, when a mammal is injured, the cells don't rebuild.

They patch the injury over with scar tissue.

Salamanders don't patch things over but actually rebuild cells at the injury site.

We need to figure out how those cells communicate.

I met Ashley again in the mouse house.

- [Ashley] Those were born probably yesterday.

- [Sharon] Oh my goodness.

- [Ashley] And then these other ones right here that are like a little more shelt, they're probably four or five weeks old.

And then the ones that are brownish, like that buffy red, those are- - [Sharon] And he's got skin missing, right?

- [Ashley] Yeah.

'Cause when their hair actually grows back, it grows back pigmented.

- [Sharon] And that's why we're here.

These are spiny mice, found in Africa.

And spiny mice can regenerate skin.

- From our work and in the work of others, they're capable of regenerating their skin.

So that was some of my original study back in the 2000s.

And then we've turned to using their ear pinna as a model of complex tissue regeneration because it has cartilage, muscle, skin, nerves.

- So the ear will grow back.

- So the model we use is we make fairly large, circular through and through punches through the ear completely.

And what they do is completely replace that tissue in a sort of proximal head out to the tip.

- [Sharon] If the ear is cut off completely, it will start to regrow but aborts.

Even so, here is a mammal that compared to others has a very advanced regenerative ability.

- So there was a study that came out in the spring earlier this year, which was fascinating work done by a group in Portugal where they completely severed the spinal cord and the animals were sort of paralyzed from the waist down.

But after, I believe it was five to six weeks, they already showed rapid signs of recovery and then months later were walking around and that was- - After severing the spinal cord.

- Yeah, so this has been a pretty kind of shocking study.

We've actually done work here at UK as well using a crush injury.

And there we see the same type of protection.

So it's unclear mechanistically whether they're regrowing a lot of spinal cord or neural tissue.

What it looks like is they're sort of protecting themselves from that secondary injury, which a lot of times will cause a lot more of the damage which leads to paralysis.

- So they're pretty amazing little creatures.

- Yep.

Other organs in their bodies, we've done some studies, our group and another group over at the Hubrecht Institute, looking at how their heart responds to a myocardial infarct.

And there again we see that they incur the same amount of damage compared to, you know, another laboratory type mouse.

But then they're able to recover to a larger degree and then resist sort of the lethality.

- This is pretty amazing.

All of these are spiny mice.

- In this room here, all of these animals are spiny mice.

They're the same species.

- And you have more mice in there.

- We have, you know, one of the largest, if not the largest active breeding colony in the world.

And so we use these animals for our experiments in the lab, but other laboratories, we help send those animals to them so they can start their own colonies or for other researchers who want to use them, we're able to supply them.

- [Sharon] He discovered the reality of the ability these mice had in Kenya.

He heard that they would jump out of their skin to evade a predator.

- Once I heard that, I was kind of entranced with the idea that a mammal would've evolved a mechanism to release portions of its skin easily.

Doesn't sound like the kind of adaptation, right, that makes one super or helps you avoid predation, right?

It makes you actually pretty susceptible to your skin drying out, right?

To infection, things like that.

So I went over to try to trap some of these in the field and see if that was true.

From the very first animal that I actually trapped, it had tried to escape from me, it tore off a huge, you know, portion of its back.

And that sort of started my fascination with trying to look at the repair process in their skin.

And... - [Sharon] If they can repair their skin, grow a new skin, I keep wanting to jump to humans and I know that it's way, way off.

But think of burn victims.

- Well, burn victims are a great example.

There's a situation where we know the inflammatory response is one of the problems, right?

You've probably burned yourself before, like we all have at one time or another, and you know how hot that area is on your skin.

Like how irritated it is, how red and inflamed, and it persists for many, many, many days beyond when a normal scrape or cut would be.

And so there's actually been a study conducted on these animals with second degree thermal burns and they've found that they're capable of repairing those very rapidly.

And again, that's likely due to a bit of the dampened inflammatory response that they sort of mobilize following an injury.

- [Sharon] Regeneration, growing back an injured part of your body, has captured the minds of scientists across the world.

Just down the hall from Ashley's lab, the focus is on zebra fish.

They can regenerate retinas, a potential game changer in the blinding world of eye disease.

There's a lot going on.

- "Science Magazine," I think it was in 2006, basically had a big issue where they said, "What are the 25 most pressing questions in all of science?"

And regeneration, the topic of regeneration made that list amongst all scientists, right?

So fundamentally we have this desire, as we often do, to anthropomorphize things and wanna figure out what's wrong with us.

We look at these other animals that can do it.

What are we missing, right?

Why are we deficient?

So I think there is a lot of interest, but it's also overshadowed by a lot of big human health problems.

Cancer, aging, diabetes, right?

All big concerns which we should be focusing a lot of our efforts on.

But at the same time, this sort of question that lingers out there, right?

Could I be the person who could help to contribute information to regenerate a limb one day or a digit?

It attracts a lot of of interest and there's many prominent scientists who even later in their careers sort of circle back, right?

To sort of take a chance because it is kind of hanging out there and it's been a question that's persisted for quite some time.

- It might not be in my lifetime, but these tiny little critters could someday lead to major advancements in the world of medicine.

I'm Sharon Collins.

We'll see you next time.

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