Radiolab - Golden Goose

Episode Date: February 17, 2023

After years of being publicly shamed for “fleecing” the taxpayers with their frivolous and obscure studies, scientists decided to hit back with… an awards show?! This episode, we gate-crash the Grammys of government-funded research, A.K.A. the Golden Goose Awards. The twist of these awards is that they go to scientific research that at first sounds trivial or laughable but then turns out to change the world. We tell the story of one of the latest winners: a lonely Filipino boy who picked up an ice cream cone that was actually a covert vampire assassin. Decades later, that discovery leads to an even bigger one: an entire pharmacy's worth of new drugs hidden just below the surface of the ocean. EPISODE CREDITS: Reported by - Latif Nasser and Maria Paz Gutiérrezwith help from - Ekedi Fausther-KeeysProduced by - Maria Paz Gutiérrez and Matt Kieltywith help from Ekedi Fausther-KeeysOriginal music and sound design contributed by Matt Kieltywith mixing help from Arianne Wack. Fact-checking by Emily KriegerEditing by Soren Wheeler, who thought the whole episode should have been a little shorter.  Special thanks to Erin Heath, Haylie Swenson, Gwendolyn Bogard, Valeria Sabate and everyone else at AAAS who oversee the Golden Goose Awards. Also to Maggie Luddy, and former Congressman Jim Cooper, Terry Lee Merritt at University of Utah, Jim Tranquada, John McCormack, and the Cosman Shell Collection at Occidental College.  CITATIONS: Videos - Gorgeous slo mo video of cone snails hunting (https://zpr.io/uiWrS3J2BuZM). A recent segment from our down-the-hall neighbors at On The Media (https://zpr.io/VZHSLPdkdAxH) about breakthrough science featuring the late Senator William Proxmire. Check out dazzling documentary shorts on each of the Golden Goose Awards winners (https://zpr.io/Tpxxrzzuz6GS) on their website. Our newsletter comes out every Wednesday. It includes short essays, recommendations, and details about other ways to interact with the show. Sign up (https://radiolab.org/newsletter)! Radiolab is supported by listeners like you. Support Radiolab by becoming a member of The Lab (https://members.radiolab.org/) today. Follow our show on Instagram, Twitter and Facebook @radiolab, and share your thoughts with us by emailing [e-mail].   Leadership support for Radiolab’s science programming is provided by the Gordon and Betty Moore Foundation, Science Sandbox, a Simons Foundation Initiative, and the John Templeton Foundation. Foundational support for Radiolab was provided by the Alfred P. Sloan Foundation.

So in a nutshell, this story starts with a sheep that provokes a goose, which goes to rats and bees, but especially most recently to a snail that eats fish. Okay, okay. Okay, all right, I don't need to tell the story. You forgot what you got it. No, I just am like, I'm ready. Okay, we're following, was that a food chain?

No. Sorry, that guy. I'll do it again. Okay. So yeah do it again. Okay. Okay, so yeah, it starts with a sheep. The sheep provokes a goose. Okay.

And the goose has gone to rats and bees, but especially most recently has gone to a snail that eats fish. I need it one more time. I need one more time. Alright, I am Lulu Miller. I'm Lotha Fnazza. This is Radio Lab. And today, I'm going to walk you, Lulu, through that little riddle, animal by animal,

which is actually a journey through some science that sounds silly, but actually has the ability to completely change what you feel. Ooh. And how you feel, literally. Okay, so start with a sheep. Okay, but to actually get to the sheep, we gotta start with a guy.

Members and guests, the Honorable William Proxmire, Senator from Wisconsin. William Proxmeyer Senator from Wisconsin. William Proxmeyer. Democrat from Wisconsin served over 30 years, 1957 in 1989. He was tall, athletic, people knew him in the Senate as a maverick, as a champion of the people as a quote, friend of the little guy. Thank you, Andy Mullis. I very much appreciate that gracious introduction gracious introduction wasn't long enough,

but it was a great one. And Proxmire earned this reputation for a lot of different reasons. For one, For a while you had not missed a vote. Are you still in a vote? I haven't missed a vote since 1966. He always voted.

And that's 22 years. Actually, he still holds the Senate record for number of consecutive votes, not missed. I just think we're elected to be here and to vote and to do your job. He also couldn't stand money in campaigns. That's not the way it ought to be. How people could just buy elections? It's wrong.

During his last two campaigns, he refused campaign contributions and spent less than $200 out of his own pocket. The thing that Proxmire was really known for was he hated the government wasting taxpayer money on unnecessary stuff. He would go after the military, the medical industry, but even stuff like, how is colleagues traveled, often by private jet? They should travel coach, not first class coach. Even like his office. Unlike his colleagues, who would have the government pay for fancy furniture, there's a lot of standard government issues in this room. I don't pay much attention to a room, I mean, maybe I should. The people are important, but the room doesn't, and the decorations don't, I'd be a terrible interior decorator. And during his career, Proxima really got so fed up with the spending he saw all around him

that to shame his civil servant colleagues who were doling out money, he created this award. The Golden Fleece Award. Golden Fleece had a lot of appeal because Golden stands for the money ripoff and fleets for the fact that it is a ripoff. Ma. Yeah. As you sheep.

Yeah. Ever since 1975, Marks of 75, every month I've given an award, a Golden Fleece, the most disgusting, rewarding, repulsive waste of the the taxpayers money by the federal government. And is this just like a facts? It came out in a newsletter that you would send out to everybody and including the press. And this is just for any big project waste. Yeah, a lot of different government projects, but a lot of them were these ridiculous sounding

research projects. The first golden fleece we gave to an agency that spent... The first one went to the National Science Foundation. Spent $83,000 and try to find out how white people fall in love. Which makes them seem like such a grinch, right? Yeah, yeah. But to him, you was like, look, you could spend $10 million on this. You'll never find out why people fall in love. And...

Even if they could give you the answer, I wouldn't want to know. Because the great thing about love is it's mystery and once the scientists can weigh it and measure it you can kiss it goodbye. Love is mysterious and that's how it should be forever more. And then then I gave it to him. He gave one to the agriculture department for a $46,000 study of how long it takes to cook breakfast. Then I gave it to an agency that spent $103,000 and tried to find out whether it's sunfish that drank tequila or more aggressive and son fish that drink gin, son fish. One to view a law enforcement assistance administration for a $27,000 inquiry into why inmates want to escape from prison.

And we gave it to the Department of Agriculture for spending thousands of dollars to find out if you took pregnant pigs when they were confined in their pregnancy and required those pigs to jog an hour and a half day in a treadmill. Would it ease their tensions? Well, they found out after several months of that, the pregnant pigs wouldn't talk. And it just sort of goes on and on. He gave one to the Smithsonian for spending $89,000 to produce a dictionary of an obscure and unwritten, my-in-language.

One to the FAA for spending $57,000 to study body measurements of flight attendance, one to the healthcare financing administration which, quote, clipped the taxpayer $45 million by allowing Medicare to flip the bill for cutting toenails. How do these things happen? That's the question. They happen because people come in and they'll spend $50,000, $60,000 before coffee in the morning and another $100,000 and they go, it goes on and on and on.

Day after day after day, and pretty soon money loses all significance. And one way to get on top of that is to point out how utterly ridiculous and shameful it is to waste the taxpayers' money in that way. I sort of think of him like our curmudgeonly watchdog. Yeah. He's like the one paying attention to these studies that nobody else is paying attention to, and he's calling people out. Totally. You know?

It's vital to have someone on the inside who's doing that. You're right. We do need watchdogs. We do need people to hold everybody accountable, but you know what? The research he made fun of of it's actually very important. Okay, so this is Alan Allen Leshner and I am currently unemployed. Alan is kidding. He is retired after an illustrious career.

It was the CEO of the American Association for the Advanced Women of Science. He was the publisher of the Journal Science. He held several leadership roles at the National Science Foundation. And then I ran two different institutes of the National Institutes of Health. And at the time I became most aware of the Golden Fleece, I by then was at a fairly high level at the National Science Foundation. Actually, before we go too far, like, did you ever actually interact with William Proxmeyer, and if so, what was he like? Was he kind of a grump?

Actually, he could be very charming. I didn't know him personally that well, although I did have opportunity to have to sit across what you might think of as a witness stand, as he interrogated me about why was the National Science Foundation supporting this weird stuff? And again, you know, the research he made fun of actually was terrific. I'm going to give you a couple examples. Please do. Okay. So, for example, Alan said back in the 1970s at the NIH, one of the things they were looking at was

alcohol use on rats, which you know, back then did it look funny to be studying alcoholic rats? Seemed a little weird. Of course. Oh, there's absurd. What do we need to tell you? And when Crox might have heard about it, he gave it a golden fleece and he said that it was, quote, an attempt to turn rats into alcoholics. But a lot of what we came to understand about alcoholism started with studies of rats. Or, 1980, a golden fleece to the Federal Highway Administration, for spending over $240,000 to produce a computerized system that gives local directions to people who can't or won't read maps.

Think about that. That doesn't take any explanation at all. Right, right. I mean, just look at your phone. I mean, it's just absurd. It's ridiculous. And Alan told me about one. So one of my favorites.

That actually predates the Golden Fleece Award, but was constantly ridiculed in Congress. The Department of Agriculture had a grant studying the sex life of the screw worm. Now, frankly, that sounds rather silly, but... This screw worm? It's like a plague for cattle. And through this grant, they were able to figure out how to sterilize it. And probably has saved millions and millions.

Of cows or dollars? Mill millions and millions of cows or dollars millions and millions of cows Which is billions and billions of dollars, but anytime Alan tried to make his case to Proxmeyer He'd cut me right off and go to the next one and Alan he felt for Proxmeyer He was looking to make the headline. This is all just a publicity stunt. And his staff were very competent. They were very good at this. They could find these funny titles. And every grant has a public abstract. So they'd read the abstract.

They'd understand 10% of what it said. And then, Proxmeyer hands out Golden Fleece Awards. Proxmeyer would send out that newsletter with a new Golden Fleece Award winner every single month to every major news outlet. And Ridicule's grants to scientists often they would make national newspapers. Wasting government money by studying

why rats and monkeys clench their teeth. And Proxmeyer would boast about how his Golden Fleece Awards would get funding cut from a lot of these projects. Proxmeyer bestowed one of his Golden Fleece Awards would get funding cut from a lot of these projects. The Kloss Barb is told one of his Golden Fleece Awards on the side of the... That some projects would just completely fall apart. And many scientists thought it ruined their careers. Thank you very much.

He gave out these awards every month for over 150 months in a row. So from 1975 to 1987, and then he retired in 1989. And the final question is, do you plan to take the Golden Fleece Award with you as you leave the Senate or are you going to have a designated successor?

Well, I hope that we can continue the Golden Fleece Award in perpetuity. Dad, I'd love to have it continued, but I just don't know. I think it's achieved something and we haven't known as we need it. Thank you very much. Even though Proxmeyer didn't end up choosing a successor and there is no longer such thing as the Golden Police Award, Alan says... Over the course of the last 30 years, Mr. President,

Senator from New Hampshire, it's continued to live on. Many policy makers, members of Congress, the amendment will prevent the waste of approximately 15 and a half million dollars have made these same kinds of mockery on wasteful research involving sending Russian primates into space. Of research projects that they don't understand.

Me, you repeat that because one may wonder why we're spending money to send Russian primates into space. I wonder that myself. This is crazy. Your government spent half a million dollars to study Panamanian male frog calls. Really? Proxmeyer died in 2005. And I mean, he did a lot as a senator, but I also think about how one of his essential legacies is that he made this template

for going after basic science research. And if you think back to that first one, established that in March of 1975, the very first GoldenFleece award. Try to find out why people fall in love. You know, it's easy to make fun of love. Do we like love? Love is a very important phenomenon in human life. People kill over love.

People uproot their lives because of love. They start families because of love. What are the mechanisms? What are the characteristics that make someone feel that they are in love or that they love someone? And to Alan, these questions in and of themselves, they are worth asking. Even if you don't know what the benefits are going to be, because most or much of the time, you don't know what the ultimate benefit will be of basic research.

And so to Alan, Proxmeyer and his Golden Fleece Award, fundamentally misunderstood how science works. Like science, you don't know. That's the whole thing. Yeah, as an outsider, like you certainly don't know what is and is an important, but then even if you're on the inside of making a study, you don't know ahead of time what study

is gonna be a big breakthrough and what's not. Yeah, totally. Yeah, I feel like I heard this from my dad growing up all the time. He's a scientist. Like, you sprinkle the funds to test all the things. It's accidentally, discoveries are often accidental. And like that you have to like fund the whole endeavor

and a lot of them won't work out, but that's part of science. Right, exactly. If you just say we're not investigating that because that question is too silly, then you don't allow for some answer that'll lead to a new question, that will lead to a bigger question, that will lead to a bigger question. You're cutting off curiosity, and ultimately that's an injustice to science.

And so what happened is in 2012, this congressman, Jim Cooper, he brought together all of these people from science foundations, organizations, universities, publications, they got together and were like, you know what, we are sick of the legacy of the golden fleece, of politicians belittling our publicly funded research. And so you know what? You know what? Screw you, Golden Fleece! We are making our own own! Thank you for joining us for the 11th annual Golden Goose Award Ceremony. The Golden Goose Award. Oh, that's a goose!

So the award is in its 11th year. Golden Goose Award. Oh, oh, that's a goose! So the award is in this 11th year. Okay, well, there's a map. And so for the most recent one, we sent our producer, Maria Paz Gutiérrez to cover it. Is this a big deal? It is the amuse of science. It was held in Washington DC in a big fancy building near the Capitol. So I'm asking people what they're wearing, what are you wearing?

That's a good question, I am wearing a suit, it's like mostly blue, but then there's this subtle light blue, it's pretty funky. It's a statement. With this window pane, hello. Oh my god, so she's like Joan Rivers red carpeting? She's Joan Rivers red carpeting. What are you wearing? Oh, I am wearing a pinstrip suit.

For out. And a flowery t-shirt, which matches my personality. Yeah, a lot of outfits. What are you wearing? So glad you asked. I'm wearing a tiger print paisley pants that are from J-Grew and brown loafers. I'm gonna like steal this outfit.

I'm gonna steal your outfit. But away from the red carpet. Good evening, everybody. To this ceremony. So on the website, they describe it in a very government like formal way, where it's like an award that would recognize the tremendous human and economic benefits of federally funded research

by highlighting examples of seemingly obscure studies that have led to major breakthroughs and resulted in significant societal impact. Seemingly obscure is maybe the... Yeah, so if I was writing that, it would be, yeah, how would you write it? An award for studies the US government funded that sounded dumber frivolous at first,

but turned out to change the world. Oh, okay, nice. Yeah. The Golden Goose Award is honored over 70 researchers who've discovered remarkable solutions and treatments for a variety of illnesses and autoimmune disorders led the foundational research which brought us COVID-19 vaccines

and transformed society as you've heard here tonight a little bit with so many new technologies. Okay, so quick recap, started with a sheep, golden fleece, which provoked a goose, golden goose, which has gone to bees and rats, which is to say bees, studies and rats, studies, and which brings us to... So our very first award this year goes to the story.

The latest batch of award winners. First went to these two researchers. Applying their principles of frugal science, they developed a paper microscope, as you saw, called the fold scope. Fold the scope? Incredible, right? Yeah, it's a little microscope made out saw called the fold scope. Fold the scope? Incredible, right?

Yeah, it's a little microscope made out of paper and this tiny little land almost looks like a little bead and it all gets origami together into a microscope. And microscopes this powerful usually cost you know thousands of dollars, but they made one for less than one, less than a dollar. That's phenomenal. The fold scope has been used to diagnose infectious diseases, diagnose new species, identify fake drugs, among many other applications.

So would you welcome Dr. Prakash and Dr. Sibowski for this day? And then this one is just. Our second award is, wow, after a graduate student at the University of Michigan, he was working in an optical, like a laser lab kind of thing and late one night, he has an accident and gets laser flashed in one of his eyes.

And he's like, oh my God, oh my God, like I'm probably gonna go blind. So he goes to see an ophthalmologist and the doctor's like, nah, you're fine. Didn't do anything wrong. I was totally fine. And then the two of them team up, bring on a bunch of their colleagues. Research collaboration, a remarkable collaboration resulted in the development of a

bladeless approach to corrective eye surgery, also known as bladeless lacic. What? That's the story of how Laysick was invented. Yeah, Blaysick came from an accident. Wow. And since then, over 20 million people have had this surgery. Wow. Okay, so our final recipients here this evening, it was this award winner where I was like,

oh yeah, come on, we have got to do a story about this. It is just too good. That story, the end of our little barnyard riddle, it's all coming up after the break. Stay with us. What the hell? Okay, so a sheep that provokes a goose that goes to bees and rats, but most recently to a snail that eats fish. Does it work for you? Sure, sure.

Okay, so the story starts with this guy, Baldomerro Olivera. How should I refer to you? Are you a professor Olivera? I think just call me Toto, but he goes by the name total But the mayor is a long name, okay total. How did you get that nickname by the way? I grew up in the Philippines and the Filipino term for little boys is taught toy with a Y

But my cousin couldn't pronounce it. She would call me Toto and the nickname stuck. So Toto grows up an only child in the Philippines. My parents encouraged me to have hobbies. So because I started to... So that you weren't bugging them, right? Right. Because I spent a lot of time alone. And one of the things that Toto did while he was alone

was when he was nine years old. His dad would play tennis near his school. And so I'd meet him to hitch right home. And because he was the only child he wouldn't have anyone to play with, he would just sort of sit by the side of the tennis court. It was sort of a clay court and in those days. In the Philippines because I guess there's so many beaches there. What they would do is they'd gather up all of these sea shells and then send them to tennis courts and Crush the shells and then put the crush shells over the court. So that was like the surface of the court Okay, and so next to the tennis court there'd be these huge piles of sea shells so while I was waiting for my dad I'd go through the pile and pick up interesting pretty shells

Take them home and give the shells and cigar boxes. And over time, it becomes this... hobby. Uh, where you go, pick out these shells. I kind of felt like I was saving them from being crushed. His parents got him a microscope, so I could look up them more. Book. For beginning shell collectors. And cigar boxes in his room start to pile up.

He's tucking them munderers bed. But then, one day at the tennis court, his dad's playing little totals digging through this pile of shells. When he sees this one particular shell, kind of like a two lip, basically looks like an ice cream cone, but less than an inch and covered in these delicate lines. And so, Toto carefully picks up the shell, because he knows from reading his books, that the snail that used to live inside it...

It's deadly. It's a killer. Wait, what? Yeah, you don't expect that from a snail. So he was holding onto the shell of a cone snail, which is this venomous snail. That according to these books, we're capable of killing people. No. And in fact, there's one kind of cone snail, which is the kind of most intense, it's called

the geography cone snail, colloquially known or it's been called the cigarette snail because if you a person gets stung by it, you have enough time to smoke one cigarette before you are dead. Oh, before you're dead? Yeah. That's not true, no. That's not true. That's an old wife's tale, right? So it takes several hours, typically, before.

It's not much more comfortable. No, it's not Joe. I've never heard of like a killer snail. Yeah, I know. I know. Yeah, it's amazing. Now, just for a minute, I want to step away from Toto and introduce you to somebody else.

Okay. Joseph. Joseph Schultz. We are at the Cosmonshell Collection at Occidental College in Los Angeles, California. Joseph is director and curator of the collection, and he teaches biology literally down the street from my house. I actually live closer to his lab than he does. And I gotta say, when we went into his office...

Oh my god! What the heck is this thing? We had a little shell fashion show. Wow! He's got this huge wall. Wow, I'm here for the shelves and you already have not disappointed. It's here of all sorts of shelves. Mm-hmm.

They're worth fantastic. Big shelves. It's like my whole arm. Tiny shelves. Yep, like grains of sand. Colorful shelves. Opulacent. Corally colored shelves.

You could wear. Gonna go on your head there. Ooh. There were also scary shelves. It's like, like, hairy shell. Like it has an aesthetic. Like it knows what it's doing. Fab shells, drab shells.

Some snails do it better than others. And what is this little ice cream Sunday over here? Oh, right. Ice cream cone. Honest geographies. That is the deadliest cone snail. This one is the deadliest? So Joseph, aside from overseeing a shell collection, not unlike Toto, he is one of the

world's foremost experts in cone snail biology. And he said one of the big reasons he got into it and was fascinated by cone snails is they are snails that hunt fish and eat fish. And is that, that's weird, first meal? Yeah. Just think of a fish and think of a snail. I know, like you were a snail, trying to catch a fish. Okay, okay, I see you. I see you, fish are like, boom, darn it fast.

Snails are notoriously, extraordinarily slow. Okay, it's like a turtle hunting a cheetah. Yeah, like how would that possibly work? How could it, yeah. I'm gonna help you through this, that's work? How could it? Yeah. I'm gonna help you through this. That's gonna be okay. Okay, great. I want it.

So, Joseph walked me into his lab. This room with a bunch of small aquariums all around. We can move around the animals. And in one of the tanks. Humans have been stung by... Oh, yeah, let's see. We're four tiny, hangry cones names. It's like my thumb. It's like a thumb side. Oh, yeah, let's see. We're four tiny, hangry cone snails. It's like my thumb. It's like a thumb side.

Oh, look, I... They were just sitting there. Could I... A little bit of a little background. Sure. Cone-snale background. Basic biology. Give it to me. So the way Joseph explained it to me is that these cone snails are basically vampires. When the sun is out... They're hiding away. They're hiding under the rocks, because they

don't want to be preyed upon, and at night, when the sun goes down, they come out, and they move among the sand. In the darkness, searching for their prey. And just like vampires, const nails want nothing to do with old fish. To prefer to feed on the fresh blood of their victims They want to know they are alive to feed on them and so I didn't know if you wanted to see it feed I could try to feed. Yeah. Are you kidding? Okay, Joseph pulls out from another tank Tiny little fish little guppy. Oh, it's jumping. It's jumping And then he grabs a razor and he basically slits. Oh, okay. Yeah, the guppies throw. You just killed it there by suffering the spinal cord. Then I'm gonna use my tongs. So he grabs little guppy Lovers it into the tank and then here we go. I'm gonna be the fish. He starts wiggling it. So it seems a lot

Yeah, you're wiggling wiggling wiggling and what happens is this snail near the fish. He starts wiggling it. So it seems a lot. Yeah, you're wiggling, wiggling, wiggling. And what happens is the snail near the fish, a little tube. Like a little worm starts to emerge from the bottom of its shell. Just startin' to come out. Oh, wait, oh, cool. I see it, I see it, I see it.

And this little tube keeps growing and growing and growing. Like it's almost feeling its way through the water until it gets right up next to the fish. And then, all of a sudden, the snail shoots this little bony harpoon that it has concealed in this tube. Like, it's like spring loaded. It shoots it right into the fish.

What? And if you just imagine like the harpoon that the you know old timey whalers would use or something like it's literally that. So it fires this harpoon which accelerates to basically the rate of a bullet coming out of a gun. Now the harpoon isn't the thing. The harpoon is just the delivery device. So the harpoon pierces the fish and then behind the harpoon is this venom. So the

venom comes rushing down this tube, instantly knocks out this fish, paralyzes the fish, and then injected, then pulled back. Obviously our fish was already dead to prevent excess cruelty to the fish, but Joseph says in the wild, you can see breathing movements. As the snail slowly pulls the fish in, and then what happens is, Whoa! The snail's mouthy stomachy part emerges from the shell. He's swallowing it.

Oh, that's, he's actually swallowing it, yeah. And it quickly just, whoop, engulfs the fish. Oh. And then after it eats it, whoop, engulfs the fish. Oh. And then, after Dietzet, it basically burps out the bones and the scales and the harpoon. Oh, wow. You don't expect that from a snail.

So, okay, so back to Toto. It's kind of a long story, but... Little Toto finds this terrifying, beautiful conch shell. As it to his collection. And then when he gets to high school, he actually has this chemistry teacher. She gave me all these books to read, encouraged me to try to classify the different shells. And sets him on this path to really studying science. So 1961, he finishes undergrad, goes to the US to get his PhD.

I worked on DNA, including with a Nobel Prize winner. But I also wanted to return to the Philippines. That's what I always had planned, and my parents have no other children, and so they expected me to return. So, Toto starts splitting his time. Going back and forth between the Philippines and the US. But problem was, the Philippines and the US, but problem was the Philippines was Frustrating he couldn't import the equipment he needed to research DNA. Give us hard. So he was like okay

What can I actually study here? And then he thought oh yeah Constance you remember these shells from his childhood? They're all over the Philippines, so quite readily available. By this point, he had teamed up with a colleague down the hall. Lurdis Cruz. She goes by Lulee. We decided we'd do research together. Total was like, look, the thing that I love about Constance,

the thing I always found so fascinating was there. Vanum. This powerful... Venom that could not only kill a fish, but could also kill people. Oh right. Because the venom is actually paralyzes your diaphragm, so you suffocate.

And Toto was like, well, clearly there is something incredible. And powerful inside of this venom, but what? What's the thing that can paralyze a person in here? Nobody knew. So, Toto and Lulee go around buying up all these cone snails. From fishermen as many as we could.

They would bring them to the lab, crack open the snail. And then we would push out the venom from the venom gland. And through some fancy chemistry, they would break that venom down to the individual components and was they did they were like Wait a second astonished that there was this complexity This venom had like two hundred different parts to it and they figured because they'd read about snakes, when you get bitten by a cobra, there's one very major component in the venom that causes paralysis. So they're like one of these 200 in the snail venom has to be the thing that's doing it. And the rest is

just filler. Right. So to find it, they did something kind of fun. They took these lab mice and put them upside down on a wire grid. So they grabbed the grid with their toes. And the mice would hang on for as long as you wish, you know, hours. And then they would take one part of the venom injected into a mouse into its abdomen. And see whether... The mouth fell. Paralysis.

But they would do tiny, tiny, tiny miniscule doses. So it wouldn't kill them, wouldn't paralyze their diaphragm, but it would paralyze their paws. Okay. So they're basically just going down this list, injecting one after the other. Exactly. Right. So they're looking for the one part that causes paralysis.

Okay. Got it. Okay. So they're going down the list part that causes paralysis. Okay, got it got it. Okay. So they're going down the list and they're like, nope, not that one, not that one. That one doesn't seem to do anything, not that one. And one day in the lab at the University of Utah where Toadho was working this undergrad he had hired. Name Craig Clark. He came in the lab, took a look around and was like, named Craig Clark. He came in the lab, took a look around and was like, this whole thing hanging the mouse upside down. It's very nice, but I have a better idea. We should inject the venom components directly

into the brain of a mouse. Why? Seems weird, right? I thought, what? You're just going to kill them. So I wasn't convinced. And that does seem like a bad idea, like putting venom right in the brain. Right, it seems to me. What are you going to learn, what? You're just going to kill them. So I wasn't convinced. And that does seem like a bad idea, like putting venom right in the brain.

Right, it seems to me. What are you going to learn, right? Did he want to do it just because he thought it would be more efficient? No, no. He's a very creative guy, and it's a little hard to explain, you know, why people get their ideas. Don't you get it, Lulu? He's just creative. Okay.

And I was kind of dragging my feet, but he persisted. And eventually, Toto was like, okay, sure. We can try. So they take some of these components of the venom and one by one, they inject a tiny, tiny bit

into the brains of these mice. To their surprise, their results were spectacular. What they find is that each one of these parts of the venom that previously had done nothing, now each one of them was causing mice to behave in a totally different way. Huh. So, one of the components makes mice start scratching themselves. One makes mice run around.

In circles. Another makes them stand on their back legs. Another cost mice to shake. Another one cost mice to become really hyperactive. Another one cost mice to slow down. Another one cost mice to just go to sleep. And so, that's when everything changed. Because now everything became interesting.

It's sort of like they went looking for a hammer and they found a hardware store full of tools. Right, that's exactly right. Which meant for Toto, why does it put mice to sleep? Now each part of the venom... Why does it make my scratch? Ask some interesting question about, like, how the brain works, or how the brain in the body communicate.

It opened up all kinds of possibilities. And it's like, forget the paralysis thing. Let's take one of these, one of these new tools, and figure out what it's actually doing. That's exactly. That was our hope, yeah. So, Toto applied to the US government for funding twice, got denied twice.

I'm a persistent guy. And on an appeal, he got it. From the National Institute of General Medical Sciences. So they decided to focus on the part of the venom that was causing mice to shake, which they called the shaker peptide. The shaker peptide. It's clearly potent. Incredibly potent. So it's a good one to study. Very, very small amounts would cause mice to shake.

Like as if they were having a seizure or something? It was like a tremor, an uncontrollable tremor. And eventually, they were able to figure out that this tiny little shaker peptide, what it was doing is it was jamming up this one little thing in the mouse's brain. Called a calcium channel. So, in your brain, in a mouse's brain, whatever, you basically have... electrical signals kind of moving all around all the time, right? Uh-huh.

Also in the brain, you have these calcium channels that are sort of like a switch. They have to be open for the signal to pass through, to get to where they need to go. Right, and so there were, people were calcium channels along known thing, did people know that that was? They were known but not well understood. And that discovery led to other groups

making other discoveries about other calcium channels, you know, in the rest of the body. One group injected the shaker peptide into a mouse's spinal cord. And what they found when they looked at the spinal cord was that the peptide bound to a very, very specific place. It only bound to the region where pain fibers come in. Oh, okay. So, for example, like, let's say you get hurt somewhere on your arm or something. There's

this like very specific spot where your nerves like basically take that pain to your spinal cord. And just as it enters the spinal cord to go to your brain, it has to go through these calcium channels. And so this little peptide was blocking those calcium channels, therefore blocking paint. Yeah, if you block those calcium channels, the pain signal never reaches the brain. Meaning you don't perceive pain at all. Right. At all? Right.

So biomedical company made a drug based off this little shaker peptide, and they did human trials. And it worked like gangbusters. It totally blocked the perception of pain. In 2004, nearly 40 years after Toto started studying this nail venom, the FDA approved this drug for use in the US. A year later, in 2005, the FDA approved this drug for use in the US a year later in 2005 the European Union also approved it. It is a thousand times more powerful than morphine, but very safe for several reasons. One is that you don't build up a tolerance for it over time.

It just keeps working the same amount, unlike opioids. Also unlike opioids, if you get off it, there's no withdrawal. It's like a whole other kind of painkiller. Why isn't this what we're all getting every time we get a headache or get into a car crash? So there are a few downsides. Well, first of all, it's of course more expensive

than opioids, which are dirt cheap. And then thing two is that you need to administer it basically inside the spinal cord. So you need like a special implant pump that will like pump the medicine in for you. And so they'll use this as sort of a last resort for people who are, you know, extreme desperate cases, people with MS or AIDS or cancer and it is making a really big difference for them. And what's interesting is usually most drugs you tweak them a bit and change their chemistry a bit.

But in this case, the commercial product is identical to what the snails make. It's absolutely... What does that tell you? Well, I think it says that the snails are able to be pretty good at making drugs. And remember, this drug just came from one of the venom components. There were all these other ones. Remember the one that made them sleep, the ones that made them scratch. So are they continuing to look at other ones? Oh, yeah, no, no. We have two that are already reached you

on clinical trials. One for epilepsy. One is a totally different kind of pain killer. Other news, there is fascinating research are being done right now on snails. They have one that hasn't yet reached clinical trials, but look super promising. That venom includes insulin.

Insulin that could possibly be way faster acting than the one we use now. Wow. Really fascinating stuff. Yeah, I mean, you would never even think of that. It's kind of mind-boggling to be honest with you. And the thing that I just marvel at is,

like, this all began with Toto and his team looking at this one component from this one snail's Venom, that turned out to be very, very useful. looking at this one component from this one snail's venom. That turned out to be very, very useful. But the thing is, that was just one of 200 components. From one of as many as 1,000 species of cone snail, which in turn is just one group in a way bigger, super family of thousands more snails, many of which are venomous.

Like, it's like all of a sudden you're like, woof. This is an enormous, enormous kind of universe. You know, if you tell people you're studying the balance of snails, they look at you a little funny. Because it sounds like trivial or because it sounds obscure? I don't know. I think, you know, my dad never understood why I was studying these nails. And, you know, after 20 years or so towards the end of his life, he'd say to me,

aren't you done with that project? How do you, I mean, is it finished yet? How do you persuade people to give you money to keep on studying those snails, you know? So it's just kind of, I think, intrinsically not a very easy thing to explain, right? But we knew why we wanted to do it. Fascinating, right? And a group of these highly venomous simolecs, the team would go on to discover the raw material

for this non-opioic pain reliever, powerful new tool for studying the central nervous system. So we welcome the awardees to the stage, Older Miro Olivera, Lorde's Cruz, Michael McIntosh, and the family of Craig Clark to accept his award, please come on up. This episode was reported by Lutthiff Nasser and Maria Paz Gutierrez with reporting help from Akete Foster Keys. It was produced by Maria Paz Gutierrez and Matt Kilti with help again from Akete Foster

Keys. Original music and sound design contributed by Matt Kilti with mixing help from Arian Wack, fact checking by Emily Krieger. Editing by Sorn Wheeler, who thought the whole episode should have been five minutes shorter, big special thanks to Aaron Heath as well as Haley Swenson, Gwendolyn Bogard, Valeria Sabate, and everyone else at Triple A-S who oversee the Golden Goose Awards, can I... pretty please host them next year. He really wants to thanks to former Congressman Jim Cooper, who is to the Golden Goose, what

Proxmeyer was, to the Golden Fleece, thanks to Terry Lee Merritt at University of Utah, Jim Tranquata, John McCormick, and the Cosmon Shell Collection at Occidental College. And a final thank you to Toto's high school chemistry teacher, Dolores Dolly Hernandez, to recognize her Toto actually named a new species of cone snail that he discovered after a coneous Dolly A. So to all the chemistry teachers out there, keep doing what you're doing. Maybe one day you will have a murderous,

malice named after you. And finally, I wanted to let folks know about a really great episode of On the Media, which has a surprise appearance in a way by Proxmeyer himself. So they recently did a segment that's called a scientific devolution. But I thought you might like to listen to it as a complimentary piece. I certainly did. The OTM team is always amazing. So just check them out.

A scientific devolution. That's all from us. Catch you next time. Keep it, keep it, Shelley. Keep it, keep it, snip, snip. I'll pop out, I'll pop out, snail you later. Snail you later. Snail you later.

Snail you later. What the shell? Okay, bye. Okay, bye, thanks. Thanks for listening. Catch you next time. Radio Lab was created by Jad Abberrod and is edited by Soren Wheeler. Lulu Miller and Latif Nasir are our co-hosts. Dylan Keef is our director of Sound Design.

Our staff includes Simon Abber, Jeremy Bloom, Becca Bressler, Rachel Blue, Beckab Russell, Weichel Kusset, Akari Foster Keys, W. Harry Fortuna, David Gable, Maria Pasco, T.R.S, Sindhu Nanasambamdown, Matt Kewti, Anime Q.N, Alex Nisen, Sarekari,

Anna Hrasquett-Pas, Sarah Sandbach, Arianne Wack, Pat Walters, and Molly Webster, with help from Andrew Vinyales. Our fact-checkers are Diane Kelly, Emily Krieger,

and Natalie Metalton. Hi, I'm Ram from India. Leadership support for Radio Lab. Science programming is provided by the Gordon and Biti Mode Foundation. Science Sandbox is Simon Foundation initiative and the John Tempukan Foundation. Foundation support for Radio Lab was provided by the Alfred P. Sloan Foundation.