- Hey, smart people!

Joe here.

Animals are great.

So smart, so weird.

I love 'em.

I mean, I am one.

But some of them have some explaining to do.

Like scorpions.

They just look like they're built to fight.

Angry in the front, angry in the back.

So aggressive!

Seems a little over the top if you ask me.

But maybe they're just misunderstood.

I am willing to change my mind.

So let's go to California and meet a scorpion biologist.

(record scratching) Yes, there are people who hang out with them voluntarily.

Maybe instead of scaring us to death, scorpions might actually be able to save our lives?

(playful mysterious music) (quiet playful music) - [Lauren] I'm Lauren Esposito and I'm the curator of arachnology, which means that I study spiders and scorpions.

- I'm friends with one of those things.

Maybe I'll be friends with both of 'em by the time we walk out of here.

My first question is, can they in fact rock you like a hurricane?

("Rock You Like A Hurricane") ♪ Rock you like a hurricane ♪ - Yeah, I mean, most definitely.

At least in the case of scorpions, they can definitely rock you like a hurricane, because they can sting and it really hurts.

- [Joe] They are not subtle at all.

Like, they're delivering a very aggressive energy with their entire body.

Every time you look at them it's just pokey, kind of angry.

- I mean, is it, though?

I feel like you're looking at it through the wrong lens.

- You need to help me view this through a different lens.

I'm not sure I am.

These guys have been wreaking havoc since prehistoric times.

They've been around for 450 million years.

I mean, that's longer than trees.

And 450 million years ago, there weren't even animals on land yet.

You know what scorpions were doing?

They were terrorizing anything edible living in the water.

- [Lauren] Most things were living in the ocean in, like, sort of early eras of life on Earth, and scorpions were no different.

Their ancestors were these things called eurypterids, or sea scorpions, and they were huge.

- [Joe] How big are we talking?

- I mean, in the case of the marine ancestors, we're talking like five meters, like really big, big animals, like massive.

- Did they have to be that big?

That's a little too big.

- Did they?

I mean, I don't know.

I feel like that was unnecessary, but I guess, like, evolution did some really crazy things back then, and there was all kinds of weird experiments.

- [Joe] Just trying all kinds of weird stuff.

- Yeah, like crazy experiments.

So they left the ocean, became amphibious.

So they were both using the ocean for part of their life, but also coming up on the land for part of their life.

And some of the earliest evidence we have for that is there's these trackways, so scorpion footprints alongside ancient riverbeds.

So they left their tracks in the mud of these rivers, and they were coming up on land to hunt spawning fish.

So they were sort of like the version of grizzlies today eating the ancestors of salmon back then, so kind of doing what grizzlies do.

- Thankfully, evolution took scorpions down a notch.

450 million years later, most scorpions can now fit in the palm of your hand.

Not that I recommend necessarily doing that.

(cat screeching) (glass smashing) (cheerful jazzy music) Which I definitely prefer over a scorpion half the length of a school bus.

(school kids screaming) But the crazy thing is that scorpions' basic body plan really hasn't changed.

They still look like bizarro lobsters with claws up front, stinger in the back.

They even still breathe the same way they did back when they lived in water.

They use these organs called book lungs that are essentially gills, they've just moved inside the body.

And it turns out this is a pretty solid body plan, because scorpions just keep existing.

443 million years ago, they survived a mass extinction that wiped out around 85% of life on Earth.

Then they rode out multiple ice ages, new predators, and that asteroid that killed the dinosaurs.

Nothing phases them.

And now there are nearly 3,000 scorpion species on Earth and counting.

And not just in the desert.

They live in tropical rainforests, savannas, the Himalayas, basically every part of Earth that's not frozen for most of the year.

- So they've been really, really successful both in terms of, like, long-scale, deep evolutionary time, but also in terms of where they live on the world, because they live basically everywhere.

And so if you wanna know about ecology and evolution, scorpions are a pretty good place to start.

(trees rustling) And so, like, what we do as scorpion scientists is we go out at night, usually on a moonless night, because that's when scorpion activity is the highest.

Their activity is reversely correlated with the moon.

- Because the moon's just a sun mirror, so they're just like- - It's a sun mirror, and they, like, don't want to be seen, 'cause they want to be, like, secretive and hunting like stealthy predators, and also mostly not getting eaten is the main thing.

So they come out on moonless nights and they're usually just out in their habitat doing their scorpion things, like looking for mates, looking for food, hanging out, drinking water, you know, whatever.

- It's actually easier than it sounds to look for scorpions on a moonless night because they have these fluorescent compounds in their exoskeletons and they glow under UV light.

No one's quite sure why.

It might be because seeing their own glow tells them when they're out exposed and they can get into hiding.

- Run!

- But scientists still really haven't figured this out.

Either way, it's how scientists like Lauren can easily find them.

- And yeah, you just kinda, like, stumble around looking with the blacklight.

And when you spot a scorpion, it's usually from pretty far away because they fluoresce really bright and it looks like toxic sludge green.

- [Joe] It's just like a totally unnatural color in the environment.

- Yeah, totally unnatural.

- It's like, bingo!

So after Lauren catches a scorpion, she sticks it in a container and takes it back to the lab.

Now, chances are if you know one thing about scorpions it's that they have a giant tail full of venom.

But the vast majority of scorpions are not gonna kill a human.

Like, what would they even do with you, like eat you?

Come on.

But they will hurt you.

- Does a super good job, yeah.

It feels like, you know, getting stung by scorpion, it's like the tiniest of pricks in your finger, like getting pricked with a thumbtack.

And yet it makes your brain think that, like, you just got smashed with a sledgehammer or, like, electrocuted or some really terrible thing happened to you.

- [Joe] Your brain's not just being dramatic here.

Scorpion venom is perfectly evolved to make nervous systems go haywire.

It has these protein segments called peptides that mess with the way that your nerves signal your brain.

They're a kind of neurotoxin.

They basically set off all these signals so that your brain starts screaming at you even if there's no actual emergency.

Wait, what kind of volume of liquid is being put in?

- We're talking about a drop, one drop of liquid.

- The thing is, in that drop, scorpions don't just deliver one type of venom.

Something like a black widow spider just has a handful of chemicals in its venom.

But scorpions deliver a whole cocktail of venom chemistry.

They have something like 250 unique components in their venom, perfectly concocted to mess you up no matter what kind of creature you are.

Some neurotoxins in that cocktail have evolved for defense.

They target the nervous systems of mammals.

which are scorpions' main predators.

But scorpions also have neurotoxins that affect insects' bodies, because they're a scorpion's primary prey.

These compounds basically paralyze insects instantly so the scorpion can eat them in peace.

They also have enzymes in their venom that help them start digesting their food outside their body.

Gross, but convenient.

So no matter where you reside on the tree of life, you probably don't want to be on the wrong side of a scorpion's stinger.

Scorpions have been refining this venom recipe for hundreds of millions of years, and the reason their venom is so complex might be because of this weird genetic quirk.

At some point over 400 million years ago, the common ancestor of all scorpions made a second copy of every gene in their body.

- And now all the descendants of that ancestor, so all modern scorpions and spiders, have two separate copies of the whole genome.

And what that means is they have two separate copies of all their genes.

- So you have, like, redundancy then.

- You do, you have built-in redundancy, which means, like, you have built-in chances for evolution to get to work and start to modify things through neutral mutations, but some of them work.

- So if you only have one copy of your genome, it's kind of dangerous for when mutations come along because you could break something.

But if you've got this extra copy, you get to get creative in the Lego lab and just see what you can build.

- I mean, I guess that that's a pretty accurate way of putting it.

Like the way that mutations occur is completely neutral, right?

So, like, mutations just occur randomly, and sometimes those mutations do nothing, like they're completely neutral.

Other times those mutations are, like, super negative, so it makes the thing that is supposed to happen not happen anymore, like the protein not get built or like your digestive enzymes no longer function to digest, or your ability to absorb oxygen no longer function.

But when you have two copies, all of those negative ones don't matter so much as long as you maintain one functional one.

And so those negative ones can continue to accrue and maybe at some point they flip switches and those things suddenly become positive and start to do something that's really powerful, like produce a venom that can effectively keep you from being eaten by your predators.

- Basically this duplicate genome lets scorpions' venom evolution go on fast-forward.

Long story short, it doesn't matter if you're a human or a spider or any other animal, scorpion venom probably has something uniquely awful just for you.

But the fact that scorpion venom is so good at hijacking the nervous system of mammals might also be useful to us.

Like if we could understand how scorpion venom causes pain, maybe we could use the same biological pathways to relieve pain.

In fact, at least one animal is already a step ahead of us on that.

- [Narrator] Grasshopper mice frequently eat scorpions of the genus Hadrurus.

This scorpion is almost as big as a grasshopper mouse, and of course, its tail is equipped with a large poisonous stinger.

- Like this mouse has been in an arms race with scorpions where the mice love scorpions.

They're, like, a really delicious snack.

But in the case of these mice, what they actually have evolved over time is a resistance to the scorpion venom.

And so instead of causing pain, their nervous system now blocks pain signals when they're stung by scorpions.

And so instead of their pain pathway being activated, their pain pathway is deactivated and stings don't even hurt them.

- So they become, like, more invincible when they get stung.

They like, laugh the pain off.

- Yeah, they're like, "Yeah, this isn't doing anything."

- Imagine a drug that could just block the triggering of our pain switches.

If we could take just a few pointers from this mouse, maybe doctors could stop prescribing so many opioids, or offer people relief from chronic pain using scorpion venom as a key ingredient.

And that is not the only promising science happening with scorpion venom.

Some researchers are also working on using one toxin from scorpion venom to treat brain cancer.

Now, when a surgeon is trying to take out a tumor, it's not always obvious which cells are cancerous and which cells are healthy.

Sometimes they all look alike.

And no one really wants to take a scalpel to the brain without knowing exactly what to cut.

So researchers wanted to find a molecule that would attach to cancer cells in the brain and basically tag just the bad cells.

And they were in luck, 'cause a few years earlier a neuroscientist had discovered that one scorpion known as the deathstalker had a special ingredient in its venom called chlorotoxin.

Chlorotoxin is harmless to humans, but it binds to a type of cancerous brain cell and leaves regular cells alone.

- So this team of scientists was like, "Well, this sounds like a great idea, because suddenly maybe we could use this to treat brain cancer."

And the idea that they came up with was converting these molecules into kind of a micro paint, like molecular paint.

- But first they needed to get their hands on some chlorotoxin.

Turns out it's hilariously difficult to milk a deadly scorpion, so they decided to make a synthetic version.

Then they attached the fluorescent dye to it and sure enough, it lights brain tumors right up!

You could see the tumors.

- So you could see 'em, like it actually painted it with a UV dye.

So similar how scorpions fluoresce, just coincidentally.

- They made a tumor paint out of scorpion venom.

And now this deadly scorpion is kind of a lifesaver instead.

- And so by painting the cancer cells, you can go in with microsurgical equipment and pull out all the cancerous brain cells and leave the healthy ones.

And so like really reducing- - Minimizing.

Yeah, minimizing side effects.

- Minimizing side effects, minimizing the damage to the healthy brain, and hopefully helping both the mice and, well, now people, because it's moved on to human clinical trials that have been super successful, helping them minimize the damage to their brain following a brain cancer event.

- So after 450 million years on this planet, scorpions have come up with some pretty amazing venom.

They'll still be happy to stick you with it and make you suffer, but they might also help prevent a lot of suffering in the future.

Stay curious.

Mission accomplished.

I have a much healthier respect for scorpions.

I think they're buds now, okay.

Here I am, rock you like, oh, hey.

Didn't see you there.

Thank you so much for sticking around to the end of the video.

As always, I wanna send out a huge thank you to everyone who supports the show on Patreon.

We literally could not make the show without your help.

These episodes take a lot of work, a ton of research, and the support of our patrons literally makes it possible.

You can help our show stick around for as long as the scorpions have, though we are a less spicy.

Just click that link down in the description if you'd like to learn more and we will see you in the next episode.

Hey, smart people, I'm coming for you!

Dr. Joe's here to bring you some science!

Oh yeah!