The Shark Inside You

Summary

Radiolab Episode Summary: The Shark Inside You

Podcast Information:

• Title: Radiolab
• Host/Author: WNYC Studios
• Episode: The Shark Inside You
• Release Date: June 18, 2025

Description: Radiolab delves into the fascinating world of sharks and their unique immune systems, exploring how these ancient creatures might hold the key to revolutionizing human medicine, particularly in the fight against cancer.

Introduction: Diving into the Depths of Shark Immunity

The episode begins with producer Becca Bressler introducing listeners to the world of sharks, not as fearsome predators, but as potential saviors in medical science. Hosted by Lulu Miller and Latif Nasser, the narrative sets the stage for an exploration of shark antibodies and their groundbreaking applications.

Journey to the Lab: Unveiling the Secret of Shark Antibodies

Becca takes the audience to Dr. Aaron Matthew LeBeau’s laboratory at the University of Wisconsin in Madison. Dr. LeBeau, initially a football enthusiast, transitioned to chemistry and eventually became a leading scientist in immunology. The lab houses a “state-of-the-art 7,000-gallon saltwater tank” containing nurse sharks—Becca Bressler describes them as “swimming fossils” from a lineage dating back 400 million years (03:04).

Becca Bressler [04:04]: "These sharks come from a line that dates back 400 million years ago."

The Mysteries of the Immune System: Understanding Antibodies

The core of the episode delves into the complexity of the human immune system, specifically focusing on antibodies. Caroline Burrell, a biotech company leader, explains how antibodies function as a personalized army combating various threats.

Caroline Burrell [05:27]: "It's like an army of billions and billions of antibodies that are specifically designed to target that virus."

Evolutionary Insights: Sharks as the Pioneers of Advanced Immunity

Helen Dooley and Martin Flanik from the University of Maryland and University of Miami respectively, discuss the evolutionary journey of the immune system. Their research traces the presence of antibodies back through evolutionary history, highlighting that sharks possess an immune system akin to humans, making them the oldest living creatures with such capabilities.

Helen Dooley [08:49]: "It's like DNA mixing and matching to create billions of different antibodies."

Breakthrough Discovery: Flexible Shark Antibodies

In the late 1980s, Martin Flanik discovered a unique type of antibody in sharks with highly flexible arms capable of moving from 0 to 180 degrees. This discovery was pivotal, as these antibodies could latch onto targets in ways human antibodies could not.

Martin Flanik [21:30]: "They move from 0 degrees to 180 degrees, like a cheerleader with her arms out."

Experimental Triumph: Shark Antibodies Targeting Cancer

Dr. LeBeau describes an experiment where shark antibodies were trained to target prostate cancer cells resistant to chemotherapy. Injected into mice, these antibodies homed in on tumors with unprecedented precision, leaving no trace elsewhere in the body. This selective binding showcased the potential of shark antibodies in delivering cancer-fighting agents directly to tumor sites.

Dr. Aaron Matthew LeBeau [26:19]: "Honestly. Yeah. I've never seen antibody work that well."

Overcoming Biological Barriers: Immune Response to Shark Antibodies

A surprising aspect of the research is that shark antibodies do not trigger an immune response in mice, a phenomenon Dr. LeBeau finds both astonishing and promising for future primate studies. This lack of rejection suggests that shark antibodies could be used in humans without adverse immune reactions, opening new avenues for medical treatments.

Dr. Aaron Matthew LeBeau [27:24]: "It's one of those things that you have to see to believe. And we've seen it many times."

Expanding Horizons: Beyond Cancer

The potential applications of shark antibodies extend beyond cancer treatment. Dr. LeBeau mentions ongoing projects where different sharks are being trained to develop antibodies against various human ailments, including pain receptors, fentanyl addiction, lung cancer, breast cancer, and Alzheimer's disease.

Dr. Aaron Matthew LeBeau [29:55]: "I like to think that the future is shark, personally."

Reflections: The Symbiotic Relationship Between Humans and Sharks

The episode concludes with a philosophical reflection on the interconnectedness of humans and sharks. Becca Bressler ponders how these often-feared creatures embody a profound molecular entanglement that could pave the way for significant medical breakthroughs.

Becca Bressler [28:31]: "These animals that we don't even want to share the water with because we're afraid that they'll harm us, could actually save us."

Conclusion: A Future Fueled by Shark Biology

The Shark Inside You encapsulates a narrative of curiosity-driven scientific exploration, revealing how ancient sharks hold the secrets to modern medical challenges. Through innovative research and unexpected discoveries, the episode highlights the transformative potential of harnessing shark antibodies to combat some of humanity's most pressing health issues.

---

Notable Quotes with Timestamps:

• Becca Bressler [04:04]: "These sharks come from a line that dates back 400 million years ago."
• Caroline Burrell [05:27]: "It's like an army of billions and billions of antibodies that are specifically designed to target that virus."
• Martin Flanik [21:30]: "They move from 0 degrees to 180 degrees, like a cheerleader with her arms out."
• Dr. Aaron Matthew LeBeau [26:19]: "Honestly. Yeah. I've never seen antibody work that well."
• Dr. Aaron Matthew LeBeau [27:24]: "It's one of those things that you have to see to believe. And we've seen it many times."
• Dr. Aaron Matthew LeBeau [29:55]: "I like to think that the future is shark, personally."
• Becca Bressler [28:31]: "These animals that we don't even want to share the water with because we're afraid that they'll harm us, could actually save us."

Supporting Voices:

• Caroline Burrell: Biotech leader specializing in antibodies.
• Helen Dooley: Researcher at the University of Maryland focusing on immune system evolution.
• Martin Flanik: Immunologist at the University of Miami pioneering shark antibody research.
• Dr. Aaron Matthew LeBeau: Scientist at the University of Wisconsin developing shark-based immunotherapies.

Acknowledgments:

Special thanks to the entire LeBeau lab at the University of Wisconsin, Madison, and all members of the Radiolab team for their contributions to this groundbreaking episode.

---

This episode sheds light on the potential symbiosis between humans and sharks, advocating for a reevaluation of how we perceive these majestic creatures—transforming fear into hope for future medical advancements.

Transcript

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[Becca Bressler]

Oh, wait, you're listening.

[Caroline Burrell]

Okay.

[Becca Bressler]

All right.

[Lulu Miller]

Okay.

[Becca Bressler]

All right. You're listening.

[Radiolab Ad]

I'm listening to Radiolab Radio Lab from wnyc.

[Aaron Matthew LeBeau]

Yep.

[Lulu Miller]

My. The one thing I have to apologize for is I'm still kind of stuffed up. So you're gonna hear noses being blown frequently. But I will do it off mic.

[Becca Bressler]

Oh, that's okay. I'm not particularly sensitive to nose blowing, so.

[Lulu Miller]

This is Radiolab. I'm Lulu Miller, and today is day three of our week of sharks. Do you feel good? You in a zone?

[Becca Bressler]

You feel I'm in a zone.

[Lulu Miller]

And today's story comes to us from producer Becca Bressler.

[Becca Bressler]

Yeah, well, I do think that this is maybe the most interesting story I've ever worked on. Ooh. And it's actually kind of weirdly fitting that you're sick right now.

[Helen Dooley]

Okay.

[Becca Bressler]

But. Okay, so first couple of episodes, we were swimming in the shark infested waters of Australia. Today I'm gonna take you somewhere different.

[Lulu Miller]

Great. Where are we going?

[Becca Bressler]

Buckle up.

[Lulu Miller]

Buckled.

[Becca Bressler]

We are going to Wisconsin.

[Helen Dooley]

Have a nice day.

[Lulu Miller]

Okay. Midwest. Landlocked. This is not where I'm thinking you're gonna encounter a shark.

[Becca Bressler]

No, as I wasn't expecting it either, but I was going to see this scientist. Hey, Aaron. His Name's Aaron. Matthew LeBeau. How's it going?

[Aaron Matthew LeBeau]

Good, how are you?

[Becca Bressler]

And he.

[Aaron Matthew LeBeau]

I'm the least sciencey person I know.

[Becca Bressler]

Has a kind of funny way into this.

[Aaron Matthew LeBeau]

I originally went to Arizona as an undergrad to play football, have fun and party.

[Becca Bressler]

Took a chemistry class.

[Aaron Matthew LeBeau]

Absolutely fell in love with chemistry. And then from there on I just became a scientist.

[Becca Bressler]

But did you party too? Important question.

[Aaron Matthew LeBeau]

I partied a whole lot. Yes, I consumed my body volume in tequila many times.

[Becca Bressler]

Anyway, he gets his PhD.

[Lulu Miller]

Dr. LeBeau.

[Becca Bressler]

Dr. LeBeau ends up at the University of Wisconsin in Madison where he has his own lab. So can you say where we're headed right now?

[Aaron Matthew LeBeau]

We're headed to my laboratory on the. Oh, I can't say that.

[Becca Bressler]

A secret lab. Ooh. Oh, we're gonna hop on the shuttle now?

[Aaron Matthew LeBeau]

Yes.

[Becca Bressler]

Okay, so we took a bus about five to ten minutes across campus.

[Aaron Matthew LeBeau]

Is there a stop right here.

[Becca Bressler]

Got off and walked over to a nondescript location.

[Aaron Matthew LeBeau]

I can't tell you where it is.

[Becca Bressler]

I won't ask again, I swear. Went into this building and down a flight of stairs into the basement. The room we're in right now looks kind of empty. It's into this big abandoned lab.

[Aaron Matthew LeBeau]

It was, I think last used about 15, 20 years ago.

[Becca Bressler]

Empty cabinets, dusty black counters.

[Aaron Matthew LeBeau]

It's been abandoned since.

[Becca Bressler]

And then we turned around a cor into this other room. Where? Oh, whoa. In the middle of it. Can you just describe to me what I'm looking at right now?

[Aaron Matthew LeBeau]

Yeah, you're looking at a state of the art 7,000 gallon saltwater tank. There is a huge, huge, huge fish tank, basically.

[Becca Bressler]

And above ground pool of.

[Lulu Miller]

Whoa.

[Becca Bressler]

Sharks. Oh, my God. So how many sharks are in here?

[Progressive Insurance Ad]

Five.

[Becca Bressler]

Five sharks.

[Lulu Miller]

So you're in like an unmarked bunker with a pool full of sharks?

[Becca Bressler]

Yes, specifically nurse sharks.

[Lulu Miller]

Nurse sharks.

[Becca Bressler]

So they are, they're the littler ones. So these ones were only about like 2ft long, but these guys are also.

[Aaron Matthew LeBeau]

Not full grown yet. In the wild you have nurse sharks that are, you know, 8, 9, 10ft long, big.

[Lulu Miller]

Okay.

[Becca Bressler]

And they look shark like, but maybe not exactly what you're thinking.

[Aaron Matthew LeBeau]

They don't have the large jaws like a great white do.

[Becca Bressler]

They've got these tiny little mouths that suck up food. That's the sound of the suction. They also have whiskers. So some people call them cat sharks.

[Lulu Miller]

Okay.

[Becca Bressler]

But maybe most importantly, these sharks, these.

[Aaron Matthew LeBeau]

Are like swimming fossils.

[Becca Bressler]

They're ancient.

[Lulu Miller]

Ooh.

[Becca Bressler]

They come from a line of sharks that date back 400 million years ago.

[Lulu Miller]

Ooh. Huh.

[Becca Bressler]

And hidden inside of them, scientists like Aaron believe there is this very ancient key. A key that could unlock our ability to fight off some of the deadliest threats we face on Earth. And that's really the story that I want to tell.

[Lulu Miller]

Yeah. Okay. Keep us going.

[Becca Bressler]

Okay, first, to get to Aaron's lab, we have to go from sharks.

[Caroline Burrell]

Sounds kind of strange when you've got.

[Becca Bressler]

The headphones on actually talking back to us.

[Caroline Burrell]

I can't hear her now.

[Becca Bressler]

Hello.

[Caroline Burrell]

Oh, there we go.

[Becca Bressler]

Hi. Hey, Caroline.

[Caroline Burrell]

Hi, Becca.

[Becca Bressler]

Cuz to find this key, scientists first had to figure out something very deep and mysterious about humans. So I guess to just start this off. Caroline, can you tell me a little bit about who you are and what you do?

[Caroline Burrell]

Yeah, sure, Becca.

[Becca Bressler]

So.

[Caroline Burrell]

Yes. So I'm Caroline Burrell. I've always been passionate about life sciences. Kind of set off my career at university studying biochemistry, then moved on to a PhD.

[Becca Bressler]

She runs a biotech company now.

[Caroline Burrell]

Yeah.

[Becca Bressler]

And she spent a ton of time researching and studying the immune system and in particular, antibodies.

[Caroline Burrell]

Oh, oh, they're formidable.

[Becca Bressler]

One of the most incredible parts of our immune system that are protecting us.

[Caroline Burrell]

Non stop 247 from the onslaught of what's going on in our daily lives.

[Becca Bressler]

So let's say you're out in the world, like at a park or something, and some guy coughs right in your face, and let's say a little bit of that cold virus he has goes into your body, and what happens is just wizardry. These immune cells show up and each one of them starts pumping out hundreds.

[Caroline Burrell]

Of thousands of these antibodies.

[Becca Bressler]

So that quickly your body is full of this army of billions and billions of antibodies that are specifically designed.

[Caroline Burrell]

Their target that virus and an antibody.

[Aaron Matthew LeBeau]

It looks like a big yellow.

[Becca Bressler]

So this army of Y's surround this.

[Aaron Matthew LeBeau]

Virus, and the two arms of that.

[Becca Bressler]

Y reach out and latch onto the virus.

[Aaron Matthew LeBeau]

Just kind of hold onto it really.

[Becca Bressler]

Tightly until other cells can come in and kill it.

[Caroline Burrell]

It's just. It blows your mind. It really does.

[Becca Bressler]

Because Caroline points out, it's not just that your immune cells are doing this for a virus. It can be something like a fungus, like a bacteria, maybe a parasite, a toxin.

[Caroline Burrell]

You know, you may get a small cut, you may get dust in your eyes, you may get something going on, whatever it is.

[Helen Dooley]

You can make antibodies against almost anything that's out there.

[Becca Bressler]

Tailor made, bespoke antibodies for anything.

[Helen Dooley]

Anything. Even if it's never existed in our environment before.

[Lulu Miller]

Wait, what?

[Becca Bressler]

Yes. Even for things that don't exist, your immune cells can make antibodies for it.

[Lulu Miller]

That is so cool.

[Martin Flanik]

It's amazing, actually. Sorry, it almost sounds religious. The Pope just died and I don't.

[Becca Bressler]

So these two new voices you hear Ye.

[Helen Dooley]

I'm Helen Dooley.

[Becca Bressler]

One is Helen Dooley. The other, Martin Flanik. Martin Flanik.

[Helen Dooley]

I work for the medical school here at University of Maryland, Baltimore.

[Becca Bressler]

So does Martin.

[Martin Flanik]

Almost 30 years at Maryland, and the.

[Becca Bressler]

Two of them, they study the evolution of immune systems to try and understand.

[Helen Dooley]

How the immune system that we have evolved.

[Becca Bressler]

So this is where the story really picks up, okay, Because Helena Martin explained when we first discovered antibodies, there was this real puzzle as to how they could even exist, how an immune cell can even do what it does, how.

[Martin Flanik]

It can generate billions of different antibodies.

[Becca Bressler]

Like that's something a cell shouldn't be able to do.

[Helen Dooley]

It didn't make sense because if you.

[Becca Bressler]

Think about, say, a hair cell, it has DNA in it that tells it how to make hair.

[Helen Dooley]

And we thought that was the same with antibodies. But then it turns out if you can make antibodies against all these different things, you would need so much DNA in your cells that the whole system just wouldn't work.

[Becca Bressler]

Literally can't contain that much information.

[Helen Dooley]

Yeah. So then in the 1970s, a group was looking at antibody genes, the genes that encode antibodies or part of antibodies.

[Becca Bressler]

And while they were looking at the genes in this immune cell, what they realized was that in it, there was something really special. There seemed to be a gene in there that was going around and snipping up DNA and then shuffling those bits and then snippets, stitching them back together.

[Helen Dooley]

And what that meant was the cell could mix and match different pieces of.

[Martin Flanik]

DNA, and by virtue of that, the.

[Becca Bressler]

Immune cell could create billions of different combinations in order to create billions of different antibodies.

[Caroline Burrell]

It just is incredible. It's incredibly complicated, but it's just amazing.

[Becca Bressler]

It's a sort of magic.

[Caroline Burrell]

That bit is genetically just wizardry that.

[Becca Bressler]

No other cell in our body can do, just our immune cells.

[Caroline Burrell]

But when they saw that, they thought, okay, that's interesting. And, of course, the beauty of academia is that they will then dive down and they will start asking more questions, trying to answer more questions, researching it. And that really was the start of the whole thing.

[Becca Bressler]

Because what scientists wanted to know now was, when did this happen? Like, when did this one cell, the immune cell, suddenly get? So, for years, what you had were groups of scientists like this team down.

[Helen Dooley]

In Miami, basically looking at the animals that were there in the waters off Florida and taking blood samples, looking for.

[Becca Bressler]

Antibodies, evidence of this superpower. And when it first showed up, so.

[Helen Dooley]

They were basically going back to other creatures to see if these antibodies were present or not at that point in time.

[Becca Bressler]

So the idea being they would take blood samples from these animals, comb through whatever it is they find in there.

[Helen Dooley]

And see if any of them kind of had the same weight or characteristics as a human antibody.

[Becca Bressler]

Classic Y, Right. The Y shape. So, first up, birds. Birds split off on the evolutionary tree about 300 million years ago.

[Lulu Miller]

Okay.

[Becca Bressler]

Turns out researchers already knew this, but birds have the little Y antibody. Yes. And so next step, they went back to reptiles. 320 million years ago, they have antibodies.

[Martin Flanik]

So back further.

[Becca Bressler]

Amphibians about 360 million years ago, antibodies even further. Back to fish 430 million years ago, antibodies again 450 million years ago. Sharks, they have them, too. And then it stopped.

[Lulu Miller]

Hmm.

[Martin Flanik]

So animals without backbones. Everybody would know the sea urchin, which.

[Becca Bressler]

Is about 500 million years old, when.

[Martin Flanik]

You look at those creatures, there are no antibodies.

[Becca Bressler]

What they have are much simpler immune cells that can defend against far fewer things.

[Martin Flanik]

That's right.

[Becca Bressler]

And so sharks are really.

[Lulu Miller]

Wait, hold on.

[Becca Bressler]

Literally.

[Lulu Miller]

Sorry, I have to stop talking. I have to blow my nose because I can't hear you.

[Becca Bressler]

Oh, yeah, sure. Okay.

[Lulu Miller]

Like, are there antibodies in that snot?

[Becca Bressler]

I, I think so. I, I mean, that's not really.

[Lulu Miller]

Okay, keep going.

[Becca Bressler]

Okay. Anyways, so sharks are the oldest living things on earth that have an immune system like ours. It's like pretty much where our immune system began.

[Lulu Miller]

Does anyone know why? Like, why were sharks the place where this immune system first showed up?

[Helen Dooley]

Yeah. So around that time, there were some.

[Martin Flanik]

Interesting things that happened. 450 to 500 million years ago.

[Becca Bressler]

Through the randomness of evolution. The branch that had sea urchins suddenly split. And now you started to have animals with a backbone, a tail, fins, a.

[Helen Dooley]

Head, a jaw and teeth, a large brain, complex, neuronal circuits.

[Becca Bressler]

You get fish that lead to bigger fish and eventually the shark, a predator that the world has never seen before. And once you have a predator, pretty much everything else becomes prey.

[Martin Flanik]

And there is going to be a ratio that you have to maintain.

[Becca Bressler]

Like there has to be some sort of balance. Yes.

[Martin Flanik]

You can't have too many predators with prey.

[Becca Bressler]

If you did, all the predators would eat all the prey. There would be nothing left to eat. And so what you see Martin says.

[Martin Flanik]

Often in nature is predators in general don't have very many offspring.

[Becca Bressler]

They have fewer babies. So it maintains this balance.

[Martin Flanik]

Now this is heavy speculation. Okay, okay.

[Becca Bressler]

But Martin's theory is if you have fewer offspring, then those offspring will need every defense they can get. Such as little Y shaped molecules with two arms antibodies. And what scientists piece together is that right here around that split, when you have jawed predators with teeth, that simple immune cell in sea urchins.

[Martin Flanik]

The idea is it was this lucky.

[Becca Bressler]

Event where this little rogue piece of DNA that you can find in all animals just so happened to make its way into that simple immune cell and tweak one of its genes and give.

[Helen Dooley]

It this property where now it can mix and match different pieces of DNA.

[Martin Flanik]

The ability to generate billions of different antibodies.

[Becca Bressler]

It's almost like mj. Let's go. The way that I think about it is the spider that bit Peter Parker like bit this immune cell, this like proto antibody, and suddenly you have this superhero immune cell that can defend against.

[Martin Flanik]

Anything that has come in from the outside.

[Becca Bressler]

That's one theory. On the phone you said there are others. And you very funnily suggested they're all wrong. But do you know what they are? Are there any other. Any Other big theories out there?

[Martin Flanik]

I. I can tell you one. I can tell you one. Okay, so this one's called the Jaws hypothesis.

[Becca Bressler]

Jaws. So once jaws emerge, you have these species that can eat things with bones. They can munch on their bones, and.

[Martin Flanik]

The bones during digestion could cause scarring of the digestive tract and therefore, you know, cause potential infections.

[Becca Bressler]

So some people think it evolved because you are now exposed to so many more things and you need to fight off those different infections that could arise.

[Lulu Miller]

Okay, right, that makes sense. Like the more opportunities there are to be exposed to things that kill you, therefore defeating things that kill you must be better, Right?

[Becca Bressler]

Exactly. But the funny thing is that once scientists started to really put this whole puzzle together of how we got this immune system, when they found it in sharks, they were just like, meh. Okay.

[Helen Dooley]

The prevailing thought was that sharks had a very simplistic version of our immune system, almost like the, you know, the Model T Ford of our Ferrari immune system.

[Becca Bressler]

Like, we can make antibodies in three to four days.

[Helen Dooley]

Sharks, we're looking at three to four months.

[Becca Bressler]

They thought it's not that efficient.

[Helen Dooley]

Its immune responses are very slow.

[Becca Bressler]

It's like 400 million years old. Of course, it's not as good as ours. Yeah, but that idea would.

[Lulu Miller]

Sorry.

[Becca Bressler]

It's okay. That idea would be proven to be very, very wrong. Dead wrong. We'll be right back.

[Lulu Miller]

Stick with us, partner.

[Progressive Insurance Ad]

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[Becca Bressler]

Thanks.

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[Lulu Miller]

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[Becca Bressler]

Immune systems are just insane. I mean, just the fact that we can create antibodies against things that don't even exist in nature. What?

[Lulu Miller]

That's so cool.

[Becca Bressler]

Yeah.

[Lulu Miller]

Okay, wait, so let's zoom way out. Okay, so just a recap.

[Becca Bressler]

Go ahead.

[Lulu Miller]

We meet a guy named Aaron. He takes you to a bunker. He's curious in immune responses. We're learning about, like, you know, probably there was this Big Bang around 500 million years ago that goes hand in hand with complexity. And now. Yes. Where are we going next?

[Becca Bressler]

Yeah. So where we left off, scientists had discovered sharks have an immune system, but thought it was pretty simple compared to ours.

[Lulu Miller]

Right.

[Becca Bressler]

You know, the Ford to our Ferrari, as Helen put it. But that all started to change in the late 80s when Martin showed up.

[Martin Flanik]

Got my first job in 1987 at.

[Becca Bressler]

The University of Miami in an immunology lab.

[Martin Flanik]

And there they worked on sharks, obviously.

[Becca Bressler]

Looking at their immune cells that make their antibodies.

[Martin Flanik]

We wanted to isolate the cells from the shark and then study their functions.

[Becca Bressler]

So when they started playing around with these cells, they saw, of course, they made shark antibodies, Right? Obviously, that's right. But then he also saw this other.

[Martin Flanik]

Thing that the shark was making that.

[Becca Bressler]

Sort of looked like an antibody, but a little different. It had the same Y shape, the two arms, but it was smaller.

[Martin Flanik]

And that was weird.

[Becca Bressler]

Hadn't seen that before.

[Martin Flanik]

No.

[Becca Bressler]

So he grabs some of these itty bitty Y's, puts them under a microscope.

[Martin Flanik]

It's called electron microscopy.

[Becca Bressler]

And what he sees is that the arms on these things were highly mobile, like really flexible.

[Martin Flanik]

They move from 0 degrees to 180 degrees, like a, you know, a cheerleader with her arms out.

[Becca Bressler]

Hmm. And this was something completely new. We've never seen it before in a shark, in us, in any immune system.

[Martin Flanik]

Yeah. It just smelled to me like this was something interesting.

[Helen Dooley]

I think that's kind of where. I think that's kind of where I came in.

[Becca Bressler]

So over the next few years, Helen and Martin, they would do these experiments where they would take something that didn't belong in a shark, put it inside of it, and watch these little Y's surround this thing in the shark. And with their flexible arms, they would get into it and they would hold it super, super tightly.

[Martin Flanik]

Just amazed by it.

[Becca Bressler]

And the two of them were like, it's amazing. Oh, these are antibodies. These are Like a whole new type of antibody.

[Martin Flanik]

That was fantastic.

[Becca Bressler]

So when you discovered this, did you understand the implications of it?

[Martin Flanik]

No, I probably should have. I probably should have, but, you know.

[Becca Bressler]

So Martin, he's just seeing something new, basic science.

[Lulu Miller]

He just saw a thing.

[Becca Bressler]

He just saw a thing. However, because these antibodies are so tiny and so flexible and so sticky, scientists today actually think that they might be the key to. To. What's the word I'm looking for? Not solving, but, like, the. The key to curing cancer in humans. In humans?

[Listener]

What?

[Becca Bressler]

Yes.

[Lulu Miller]

Wait, what?

[Becca Bressler]

How? Okay, stick with me. So can I take photos or is that a no? No, absolutely. Okay. This is actually where I want to take us back to Aaron's lab in.

[Lulu Miller]

A basement in Madison.

[Becca Bressler]

In a basement in Madison.

[Aaron Matthew LeBeau]

The big boy there is Mr. Stamper.

[Becca Bressler]

Because Aaron is one of the few people who is developing these antibodies to try to cure cancer. So we've got nets out, and you're.

[Aaron Matthew LeBeau]

Using the nets to corral these sharks into place so we can catch them with a big net here.

[Becca Bressler]

And so how this works is they catch a shark. So we got a shark. Oh, should I move? I should move. They dump them in this bucket full of anesthesia to put them to sleep. If you weren't putting pressure on the top, would it, like, fly out of the bin?

[Aaron Matthew LeBeau]

It would fly out of the bin, yes.

[Becca Bressler]

And once it's out, he's out. Okay, we got a sleepy shark. They inject a little piece of the surface of a cancer cell into that shark.

[Lulu Miller]

Is this any kind of cancer? Is this a particular kind of cancer cell?

[Becca Bressler]

Prostate cancer.

[Aaron Matthew LeBeau]

This is prostate cancer that is resistant to all forms of current chemotherapy.

[Becca Bressler]

Okay, and where are you. Where are you putting this injection? Last time we did the left fin.

[Georgina]

So this time we're doing the right finger.

[Becca Bressler]

And once they have this little bit of a cancer cell in the shark.

[Aaron Matthew LeBeau]

You have a huge immune response.

[Becca Bressler]

The shark starts producing millions of antibodies, and then you deliver repeat booster shots of these. They do it again and again.

[Aaron Matthew LeBeau]

For a terrible analogy, getting these sharks.

[Becca Bressler]

To make these antibodies over and over.

[Aaron Matthew LeBeau]

It's kind of like playing basketball. So if you practice more, you're a better shot. Same with the immune system.

[Becca Bressler]

This is immunotherapy, training antibodies to be really good at latching onto to a target. Because once you've trained it to, say, latch onto a cancer cell, you can attach a little, like, radioactive bomb to the antibody.

[Aaron Matthew LeBeau]

You basically use the antibody as a delivery system to efficiently deliver this little.

[Becca Bressler]

Bomb to the cancer cell to kill it.

[Aaron Matthew LeBeau]

Yes, correct.

[Becca Bressler]

And this is also something we do with human antibodies even for, like, certain types of cancers. But sometimes human antibodies are not very good at sticking to cancer cells. But shark antibodies, with those small, flexible.

[Aaron Matthew LeBeau]

Wiggly arms, they can essentially do molecular yoga and adopt many different shapes. And by adopting many different shapes, they can get into nooks and crannies of targets that human antibodies can't access.

[Becca Bressler]

Like certain parts of cancer cells.

[Aaron Matthew LeBeau]

Yes.

[Becca Bressler]

So Aaron said that it takes about two months to train these antibodies, and that the first time they went to test one of these things, oh, this.

[Aaron Matthew LeBeau]

Is about two years ago, they took.

[Becca Bressler]

The shark antibody, injected it into a mouse with a tumor through the T vein of the mouse, did some fancy.

[Aaron Matthew LeBeau]

Imaging, and I thought, wow, I've never seen this before. Within a day, we saw the antibody homing to the tumor and just collecting there.

[Becca Bressler]

They were just latching onto these tumor cells and nowhere else. They didn't find it anywhere else in the body. It, like, laser focused right to the tumor.

[Lulu Miller]

It moved like we think sharks move, like, where they, like, detect, stealth, detect a drop of blood. And then what?

[Becca Bressler]

Were you surprised by this or were you expecting these results?

[Aaron Matthew LeBeau]

I've been doing mouse radiology for 20 years, and it knocked my socks off.

[Lulu Miller]

Really?

[Aaron Matthew LeBeau]

Honestly. Yeah. I've never seen anything. I've never seen antibody work that well.

[Becca Bressler]

And they would follow up that study with another where they attached a little bomb to the antibody and it worked.

[Lulu Miller]

Wow.

[Becca Bressler]

They eradicated the cancer.

[Lulu Miller]

Wow.

[Becca Bressler]

Do you see any immune response to the antibody? Because I guess I would just expect that a shark antibody for a mouse is like a foreign invader that the mouse would then, you know, produce antibodies against.

[Aaron Matthew LeBeau]

Yeah. So for some reason, we do not see an immune response, and we don't really know the concrete reason why. We've done studies in mice and other rodents, and there are a few other people working on shark antibodies in the world. And that's one thing that we all talk about is how we don't see an immune response against them.

[Becca Bressler]

I mean, I think that's so fascinating because, like, even for a human, if you're growing a fetus that's half genetically yours, your body will launch an immune response. Like, that's the, you know, the purpose of the placenta and the sort of struggle of pregnancy. I just can't even grasp that a shark antibody would not trigger an immune response.

[Aaron Matthew LeBeau]

Yeah, it's. It's one of those things that you have to see to believe. And we've seen it many times. And we're gonna do a primate Study. We're gonna do an imaging study to see where this antibody goes in the body of a non human pr. And then we're gonna also repeatedly dose the primate with the antibody to see if we do generate an immune response against it. And my hunch is we won't see any antibodies against our shark antibody.

[Listener]

Wow.

[Becca Bressler]

Yeah.

[Lulu Miller]

I mean, I don't know if we should do any meaning making here, but can I just like.

[Becca Bressler]

Yeah, go for it.

[Lulu Miller]

I mean, I think so much of what we learned in the first couple days of our week of shark is like that, a monster, it maintains its fear by being unknown, unseen sort of other. And there's something like if at the molecular level we can embrace these things as us, there is like profound molecular entanglement. Like they are so much closer than I ever thought.

[Becca Bressler]

Yeah, yeah. I mean, like it's. That entanglement is precisely why they can heal us. You know, like these animals that we don't even want to share the water with because we're afraid that they'll harm us, could actually save us. Oh, wow. So each shark you're using for different.

[Aaron Matthew LeBeau]

Each shark is fighting a different disease.

[Becca Bressler]

And not just from cancer.

[Aaron Matthew LeBeau]

The shark we have right here is being injected with proteins that are expressed when we sense pain.

[Becca Bressler]

So with one of those sharks, they're developing antibodies against pain receptors that you find in humans. So they can help us find where that pain is in the body.

[Listener]

Wow.

[Aaron Matthew LeBeau]

We had one shark that was pumped full of fentanyl to make anti fentanyl shark antibodies.

[Becca Bressler]

They're developing antibodies against lung cancer, breast cancer, Alzheimer's.

[Lulu Miller]

Okay, wow. So you're saying just like there's this burgeoning hope of potential for what these antibodies could heal or make clear?

[Becca Bressler]

Yeah, yeah, yeah. What do you think about that?

[Aaron Matthew LeBeau]

It's pretty cool. It's beautiful. Yeah.

[Becca Bressler]

Do you think that sharks like these antibodies could be the most powerful tools we have to fight these diseases?

[Aaron Matthew LeBeau]

Never say never. Potentially.

[Becca Bressler]

Potentially.

[Aaron Matthew LeBeau]

I like to think that the future is shark, personally.

[Becca Bressler]

The future is shark.

[Aaron Matthew LeBeau]

Yes.

[Becca Bressler]

I feel like that's a good place to end.

[Aaron Matthew LeBeau]

The future is shark.

[Lulu Miller]

This episode was reported by Becca Bressler. It was produced by Becca Bressler and Matt Kilty. Original music from Matt Kilty. Sound design contributed by Matt Kilty, Jeremy Bloom and Becca Fact checking by Diane Kelly and edited by Pat Walters. Special thanks to Gihan Gunrothnan, Jay West, Kendall Ott and the entire LeBeau lab at the University of Wisconsin, Madison. Go Sharks. Not actually their mascot, but maybe it should be. One more thing we want to give a big thanks to everyone out there who is a member of the Lab, our membership program. Your support makes big projects like this possible and we are so grateful. And if you aren't a member or you've been thinking about giving more, this is a great moment to take the plunge because if you join or re up right now, you'll receive a very cool gift, a limited edition Week of Sharks Hat designed by the awesome Maine based artist and surfer Ty Williams. It's so beautiful and fun and it gives you a chance to show the world you support public radio in the form of Radiolab, but also support seeing sharks in a new way. The Shark Hat is available to everyone who joins the Lab this month, even for as little as $7 a month. You can [e-mail] join existing members. Check your email for details and thank you so much. Swim on back over to us tomorrow morning where there will be yet another episode about sharks surfacing in the Radiolab feed.

[Listener]

Hi, I'm Georgina and I'm from China and here are the staff credits. Radiolab was created by Jad Abumrad and is edited by Soren Wheeler, Lulu Miller and Latif Nasser, our co hosts. Dylan Keith is our Director of Sound Design. Our staff includes Simon Adler, Jeremy Bloom, Becca Brassler, W. Harry Fortuna, David Gabel, Rebecca Lacks, Maria Paz, Gutierrez Sindhu, Nana Sambadhan, Nat Kilty, Annie McEwen, Alex Neeson, Sarah Curry, Sarah Sambach, Anissa Vitze, Ariane Wack, Pat Walters, Molly Webster, Jessica Young with help from Rebecca Rand. Our fact checkers are Diane Kelly, Emily Krieger, Anna Bijou Mazzini and Natalie Middleton. Hi, I'm Daniel from Madrid. Leadership support from Radiolab. Science programming is provided by the Simons foundation and the John Templeton Foundation. Foundational support from Radiolab was provided by the Alfred P. Sloan found.

[Georgina]

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[Becca Bressler]

For 140 years, MultiCare has been in Washington prioritizing long term solutions, partnering with local communities and expanding access to care. Together, we're building a healthier future. Learn [e-mail].