[RADIOLAB INTRO]

LATIF NASSER: 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.

LULU MILLER: Okay. Okay.

LATIF: Oh, okay. All right. Okay, then we—I don't need to tell the story if you've got it.

LULU: Well, no. No, I just am, like, I'm ready. Okay, we're following—was that a food chain?

LATIF: No.

LULU: Sorry, that's got ...

LATIF: I'll—I'll do it again.

LULU: Okay.

LATIF: Okay. So yeah, it starts with a sheep.

LULU: Mm-hmm.

LATIF: The sheep provokes a goose.

LULU: Okay.

LATIF: And the goose has gone to rats and bees, but especially most recently has gone to a snail that eats fish.

LULU: [laughs] I need it one more time. I need one more time.

LATIF: [laughs]

LULU: All right. I am Lulu Miller.

LATIF: I'm Latif Nasser.

LULU: This is Radiolab.

LATIF: And today, I'm gonna walk you, Lulu ...

LULU: Mm-hmm.

LATIF: ... 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.

LULU: Ooh!

LATIF: And how you feel. Literally.

LULU: Okay, so start with the sheep.

LATIF: Okay! But to actually get to the sheep, we gotta start with a guy.

[ARCHIVE CLIP, announcer: Members and guests, the honorable William Proxmire, Senator from Wisconsin.]

LATIF: William Proxmire.

[applause]

LATIF: Democrat from Wisconsin. Served over 30 years—1957 to 1989. He was tall, athletic. People knew him in the Senate as a maverick, as—as a champion of the people, as a quote, "friend of the little guy."

[ARCHIVE CLIP, William Proxmire: Thank you, Andy Mollison. I very much appreciate that—that gracious introduction. Wasn't long enough, but it was—it was a great one.]

LATIF: And Proxmire earned this reputation for a lot of different reasons. For one ...

[ARCHIVE CLIP, interviewer: For a while, you had not missed a vote. Are you still ...]

[ARCHIVE CLIP, William Proxmire: I haven't missed a vote since 1966.]

LATIF: ... he always voted.

[ARCHIVE CLIP, William Proxmire: And that's 22 years.]

LATIF: Actually, he still holds the Senate record for number of consecutive votes not missed.

[ARCHIVE CLIP, William Proxmire: I just think you are elected to be here and to vote and to do your job.]

LATIF: He also couldn't stand money in campaigns.

[ARCHIVE CLIP, William Proxmire: That's not the way it oughta be.]

LATIF: How people could just buy elections.

[ARCHIVE CLIP, William Proxmire: It's wrong.]

[NEWS CLIP: During his last two campaigns, he refused campaign contributions and spent less than $200 out of his own pocket.]

LATIF: But the thing that Proxmire was really known for was he hated the government wasting taxpayer money on unnecessary stuff.

[ARCHIVE CLIP, William Proxmire: By far the biggest drain is the military.]

LATIF: He would go after ...

[ARCHIVE CLIP, William Proxmire: And it's disgraceful. We should be cutting that.]

LATIF: ... the military, the medical industry.

[ARCHIVE CLIP, William Proxmire: The tax dollars we spend in agriculture? Absurd!]

LATIF: But even stuff like ...

[ARCHIVE CLIP, William Proxmire: Air Force One was a $180-million plane.]

LATIF: ... how his colleagues traveled.

[ARCHIVE CLIP, William Proxmire: Ridiculous.]

LATIF: Often by private jet.

[ARCHIVE CLIP, William Proxmire: They should travel coach. Not first class, coach.]

LATIF: Even, like, his office ...

[ARCHIVE CLIP, interviewer: It's different than a lot of senators' rooms.]

LATIF: ... unlike his colleagues who would have the government pay for fancy furniture ...

[ARCHIVE CLIP, interviewer: There's a lot of standard government issue in this room.]

[ARCHIVE CLIP, William Proxmire: I don't pay much attention to a room I'm in. Maybe I should. The people are important, but the room doesn't and the decorations don't. I'd be a terrible interior decorator.]

LATIF: And during his career, Proxmire 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.

[ARCHIVE CLIP, William Proxmire: Gold and fleece had a lot of appeal because gold stands for the money ripoff, and fleece for the fact that it is a ripoff.]

LULU: Baaaa!

LATIF: Yeah. [laughs]

LULU: That's your sheep!

LATIF: Yeah.

[ARCHIVE CLIP, William Proxmire: Ever since 1975, March of '75, every month I've given an award, a Golden Fleece, to the most disgusting, revolting, repulsive waste of the taxpayers' money by the federal government.]

LULU: And is this just like a fax?

LATIF: It came out in a newsletter that he would send out to everybody, and including the press.

LULU: And this is just for any big project waste?

LATIF: Yeah. A lot of different government projects, but a lot of them were these ridiculous-sounding research projects.

[ARCHIVE CLIP, William Proxmire: The first Golden Fleece we gave to an agency that spent ...]

LATIF: The first one went to the National Science Foundation.

[ARCHIVE CLIP, William Proxmire: ... spent $83,000 to try to find out why people fall in love.]

LATIF: Which, like, makes him seem like such a grinch, right?

LULU: Yeah. Yeah.

LATIF: But to him he was like, "Look, you could spend $10-million on this, you'll never find out why people fall in love. And ..."

[ARCHIVE CLIP, William Proxmire: Even if they could give you the answer, I wouldn't want to know because the great thing about love is its mystery. And once the scientists can weigh it and measure it, you can kiss it goodbye.]

LATIF: Love is mysterious and that's how it should be forevermore. And then he gave one to the Agriculture Department for a $46,000 study of how long it takes to cook breakfast.

[ARCHIVE CLIP, William Proxmire: And then I gave it to an agency that spent $103,000 to try to find out whether sunfish that drink tequila are more aggressive than sunfish that drink gin. Sunfish!]

LATIF: One to the Law Enforcement Assistance Administration for a $27,000 inquiry into why inmates want to escape from prison.

[ARCHIVE CLIP, William Proxmire: Then 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 a day on a treadmill, would it ease their tensions? Well, they found out after several months of that, that pregnant pigs wouldn't talk.]

LATIF: And it just sort of just goes on and on. He gave one to the Smithsonian for spending $89,000 to produce a dictionary of an obscure and unwritten Mayan language. One to the FAA for spending $57,000 to study body measurements of flight attendants. One to the Health Care Financing Administration which quote, "Clipped the taxpayer $45-million by allowing Medicare to foot the bill for cutting toenails."

[ARCHIVE CLIP, interviewer: How do these things happen?]

[ARCHIVE CLIP, William Proxmire: That's the question. They happen because people come in, and they'll spend $50-60,000 before coffee in the morning and then another $100,000. And 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.]

LATIF: I sort of think of him like our curmudgeonly watchdog.

LULU: Yeah.

LATIF: He's like the one paying attention to these studies that nobody else is paying attention to, and he's calling people out.

LULU: Totally.

LATIF: You know? It's vital to have someone on the inside who's doing that.

ALAN LESHNER: 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, it's actually very important.

LATIF: Okay, so this is Alan.

ALAN LESHNER: Alan Leshner, and I am currently unemployed.

LATIF: Alan is kidding. He is retired after an illustrious career.

ALAN LESHNER: I was the CEO of the American Association for the Advancement of Science.

LATIF: He was the publisher of the journal Science. He held several leadership roles at the National Science Foundation.

ALAN LESHNER: 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.

LATIF: Actually, before we go too far, like, did you ever actually interact with William Proxmire? And if so, what was he like? Was he kind of a grump?

ALAN LESHNER: 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 gonna give you a couple examples.

LATIF: Please do.

ALAN LESHNER: Okay.

LATIF: So for example, Alan said back in the 1970s at the NIH, one of the things they were looking at was ...

ALAN LESHNER: ... alcohol use on rats.

LATIF: Which, you know, back then ...

ALAN LESHNER: Did it look funny to be studying alcoholic rats?

LATIF: ... seemed a little weird.

ALAN LESHNER: Of course.

[ARCHIVE CLIP, William Proxmire: Oh, that's absurd!]

LATIF: And when Proxmire heard about it, he gave it a Golden Fleece and he said that it was, quote, "An attempt to turn rats into alcoholics."

ALAN LESHNER: But a lot of what we came to understand about alcoholism started with studies of rats.

LATIF: Or ...

[ARCHIVE CLIP, William Proxmire: Then we had one that I want to tell you about.]

LATIF: 1980, a Golden Fleece to the Federal Highway Administration.

[ARCHIVE CLIP, William Proxmire: A terribly wasteful operation.]

LATIF: For spending over $240,000 to produce a computerized system that gives local directions to people who can't or won't read maps.

[ARCHIVE CLIP, William Proxmire: Think about that. That doesn't take any explanation at all.]

LATIF: Right. Right. I mean, just look at your phone.

[ARCHIVE CLIP, William Proxmire: It's just absurd! It's ridiculous!]

LATIF: And Alan told me about one ...

ALAN LESHNER: So one of my favorites ...

LATIF: ... that actually predates the Golden Fleece Award, but was constantly ridiculed in Congress.

ALAN LESHNER: The Department of Agriculture had a grant studying the sex life of the screwworm.

LATIF: [laughs] Uh-huh.

ALAN LESHNER: Now frankly, that sounds rather silly, but ...

LATIF: ... this screwworm ...

ALAN LESHNER: ... it's like a plague for cattle.

LATIF: And through this grant, they were able to figure out how to sterilize it.

ALAN LESHNER: And probably has saved millions and millions.

LATIF: Of cows or dollars?

ALAN LESHNER: Millions and millions of cows.

LATIF: Which is billions and billions of dollars.

LULU: Hmm.

LATIF: But anytime Alan tried to make his case to Proxmire ...

ALAN LESHNER: He'd cut me right off and go to the next one.

LATIF: And Alan, he felt, for Proxmire ...

ALAN LESHNER: He was looking to make the headline.

LATIF: ... this is all just a publicity stunt.

ALAN LESHNER: 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 percent of what it said ...

LATIF: And then ...

[NEWS CLIP: Senator William Proxmire hands out Golden Fleece Awards ...]

LATIF: Proxmire would send out that newsletter with a new Golden Fleece Award winner every single month to every major news outlet.

[NEWS CLIP: ... and ridicules grants to scientists.]

ALAN LESHNER: Often they would make national newspapers.

[NEWS CLIP: Wasting government money by studying why rats and monkeys clench their teeth.]

LATIF: And Proxmire would boast about how his Golden Fleece Awards would get funding cut from a lot of these projects.

[NEWS CLIP: Proxmire bestowed one of his Golden Fleece Awards on the scientists.]

LATIF: That some projects would just completely fall apart.

ALAN LESHNER: And many scientists thought it ruined their careers.

LATIF: 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.

[ARCHIVE CLIP, interviewer: 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?]

[ARCHIVE CLIP, William Proxmire: Well, I hope that we can continue the Golden Fleece Award in perpetuity. I'd love to have it continued, but I just don't know. I think it's achieved something, and heaven knows we need it.]

[applause]

LATIF: Even though Proxmire didn't end up choosing a successor, and there is no longer such thing as the Golden Fleece Award, Alan says ...

ALAN LESHNER: Over the course of the last 30 years ...

[ARCHIVE CLIP, Bob Smith: Mr. President ...]

[ARCHIVE CLIP: Senator from New Hampshire ...]

LATIF: ... it's continued to live on.

ALAN LESHNER: ... many policy makers, members of Congress ...

[ARCHIVE CLIP, Bob Smith: The amendment will prevent the waste of approximately $15.5-million ...]

ALAN LESHNER: ... have made the same kinds of mockery ...

[ARCHIVE CLIP, Bob Smith: ... on wasteful research involving sending Russian primates into space.]

ALAN LESHNER: ... of research projects that they don't understand.

[ARCHIVE CLIP, Bob Smith: Let me repeat that because one may wonder why we're spending money to send Russian primates into space. I wonder that myself.]

[ARCHIVE CLIP, Rand Paul: This is crazy! Your government spent half a million dollars to study Panamanian male frog calls. Really?]

LATIF: Proxmire 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—and if you—if you think back to that first one ...

[ARCHIVE CLIP, William Proxmire: Established that in March of 1975.]

LATIF: ... the very first Golden Fleece Award.

[ARCHIVE CLIP, William Proxmire: To try to find out why people fall in love.]

ALAN LESHNER: You know, it's easy to make fun of. Love. Do we like love?

LATIF: [laughs]

ALAN LESHNER: Love is a very important phenomenon in human life. People kill over love.

LATIF: People uproot their lives because of love. They start families because of love.

ALAN LESHNER: What are the mechanisms? What are the characteristics that make someone feel that they are in love, or that they love someone?

LATIF: And to Alan, these questions in and of themselves, they're worth asking.

ALAN LESHNER: 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.

LATIF: And so to Alan, Proxmire and his Golden Fleece Award fundamentally misunderstood how science works.

LULU: Mmm.

LATIF: Like, science, you don't know.

LULU: That's the whole thing.

LATIF: Yeah. As an outsider, like, you certainly don't know what is and isn't 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.

LULU: Yeah, totally. Yeah. I feel like I heard this from my dad growing up all the time. He was a scientist. Like, you sprinkle the funds to test all the things. It's accident—discoveries are often accidental and, like, that—that you have to, like, fund the whole endeavor. And a lot of them won't work out, but that's part of science.

LATIF: 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. Like, you're cutting off curiosity, and ultimately that's an injustice to—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 awards!"

[ARCHIVE CLIP, announcer: Thank you for joining us for the 11th annual Golden Goose Awards ceremony.]

LATIF: The Golden Goose Awards.

LULU: [gasps] Honk! That's the goose!

LATIF: So the awards, it's in its 11th year.

MARIA PAZ GUTIÉRREZ: Okay, there's a map ...

LATIF: And so for the most recent one, we sent our producer Maria Paz Gutiérrez to cover it.

MARIA: Is this event a big deal?

AUDIENCE MEMBER: It's the Emmys of science.

LATIF: It was held in Washington, DC.

MARIA: Hi.

LATIF: In this big fancy building near the Capitol.

MARIA: So I'm asking people what they're wearing. What are you wearing?

AUDIENCE MEMBER: 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.

MARIA: It's a statement.

AUDIENCE MEMBER: With this window pane? Hello?

LULU: Oh my God, so she's, like, Joan Rivers red-carpeting?

LATIF: She's Joan Rivers red-carpeting.

MARIA: What are you wearing?

AUDIENCE MEMBER 2: Oh, I am wearing a pinstriped suit.

MARIA: Far out.

AUDIENCE MEMBER 2: And a flowery t-shirt, which matches my personality.

LATIF: Yeah, a lot of outfits.

MARIA: What are you wearing?

AUDIENCE MEMBER 3: So glad you asked. I'm wearing tiger print paisley pants that are from J Crew and brown loafers.

MARIA: I'm gonna, like, steal this outfit.

AUDIENCE MEMBER 3: I'm going to steal your outfit.

LATIF: But away from the red carpet ...

[ARCHIVE CLIP, announcer: Good evening, everybody.]

LATIF: ... to the 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."

LULU: Seemingly-obscure is maybe ...

LATIF: The—yeah. So okay. So if I was writing that, it would be ...

LULU: Yeah. How would you write it?

LATIF: "An award for studies that the US government funded that sounded dumb or frivolous at first, but turned out to change the world."

LULU: Oh, okay! Nice!

LATIF: Yeah.

[ARCHIVE CLIP, announcer: The Golden Goose Award has 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.]

LATIF: Okay, so quick recap: we started with a sheep—Golden Fleece—which provoked a goose—Golden Goose—which has gone to bees and rats.

LULU: Mm-hmm.

LATIF: Which is to say bee studies and rat studies.

LULU: Mm-hmm.

LATIF: And which brings us to ...

[ARCHIVE CLIP, announcer: So our very first award this year goes to the story that ...]

LATIF: ... the latest batch of award winners. The first went to these two researchers.

[ARCHIVE CLIP, announcer: Applying their principles of frugal science, they developed a paper microscope as you saw, called the foldscope.]

LULU: Foldoscope?

[ARCHIVE CLIP, announcer: Incredible, right?]

LATIF: Yeah, it's a little microscope made out of paper, and this tiny little lens. It almost looks like a little bead. And it all gets origamied together ...

LULU: Hmm.

LATIF: ... into a microscope. And—and microscopes this powerful usually cost, you know, thousands of dollars, but they made one for less than one.

LULU: Oh!

LATIF: Less than a dollar.

LULU: That's phenomenal.

[ARCHIVE CLIP, announcer: The foldscope has been used to diagnose infectious diseases ...]

LULU: Hmm.

[ARCHIVE CLIP, announcer: ... diagnose new species ...]

LULU: Hmm!

[ARCHIVE CLIP, announcer: ... identify fake drugs ...]

LULU: What?

[ARCHIVE CLIP, announcer: ... among many other applications. So would you welcome Dr. Prakash and Dr. Cybulski to the stage.]

LATIF: And then this one is just ...

[ARCHIVE CLIP, announcer: Our second awardees ...]

LATIF: ... wow!

[ARCHIVE CLIP, announcer: After a graduate student at the University of Michigan ...]

LATIF: 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, I'm probably gonna go blind." So he goes to see an ophthalmologist, and the doctor's like, "No, you're fine. Didn't do anything wrong. Eye's totally fine." And then the two of them team up, bring on a bunch of their colleagues ...

[ARCHIVE CLIP, announcer: A research collaboration—a remarkable collaboration!—resulted in the development of a bladeless approach to corrective eye surgery, also known as Bladeless LASIK.]

LULU: What? That's the story?

LATIF: Yeah.

LULU: Of how LASIK was invented?

LATIF: Yeah. Bladeless LASIK came from an accident.

LULU: Wow!

LATIF: And since then over 20 million people have had this surgery.

LULU: Wow.

LATIF: Okay, so ...

[ARCHIVE CLIP, announcer: Our final recipients here this evening ...]

LATIF: ... 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.

LATIF: Latif.

LULU: Lulu.

LATIF: Okay, so a sheep that provokes a goose that goes to bees and rats, but most recently to a snail that eats fish.

LATIF: Does it work for you, professor?

BALDOMERO OLIVERA: Sure, sure.

LATIF: Okay. Great.

LATIF: So—okay, so the story starts with this guy Baldomero Olivera.

LATIF: How should I refer to you, are you professor Olivera, or ...?

BALDOMERO OLIVERA: I think, just—just call me Toto.

LATIF: But he goes by the name Toto.

BALDOMERO OLIVERA: Baldomero is a long name.

LULU: Okay. Toto.

LATIF: Toto. How did you get that nickname, by the way?

BALDOMERO OLIVERA: I grew up in the Philippines. And the Filipino term for "little boys" is "totoy" with a "y." But my cousin couldn't pronounce it. She would call me Toto, and the nickname stuck.

LATIF: So Toto grows up an only child in the Philippines.

BALDOMERO OLIVERA: My parents encouraged me to have hobbies, so—because I spent ...

LATIF: So that you weren't bugging them, right?

BALDOMERO OLIVERA: Right. Because I spent a lot of time alone.

LATIF: 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.

BALDOMERO OLIVERA: And so I'd meet him to hitch a ride home.

LATIF: And because he was an only child and he didn't have anyone to play with, he would just sort of sit by the side of the tennis court.

BALDOMERO OLIVERA: It was sort of a clay court. And in those days ...

LATIF: 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.

BALDOMERO OLIVERA: And crush the shells, and then put the crushed shells over the court.

LULU: Hmm.

LATIF: So that was like the surface of the court.

LULU: Okay.

LATIF: And so next to the tennis court there'd be these huge piles of seashells.

BALDOMERO OLIVERA: So while I was waiting for my dad, I'd go through the pile and pick up interesting pretty shells.

LATIF: Take them home.

BALDOMERO OLIVERA: And keep the shells in cigar boxes.

LATIF: And over time, it becomes this hobby where he'd go pick out these shells.

BALDOMERO OLIVERA: I kind of felt like I was saving them from being crushed. [laughs]

LATIF: His parents got him a microscope.

BALDOMERO OLIVERA: So I could look at them more.

LATIF: Books.

BALDOMERO OLIVERA: For beginning shell collectors.

LATIF: And the cigar boxes in his room start to pile up, he's tucking them under his bed. But then one day at the tennis court, his dad's playing, little Toto is digging through this pile of shells when he sees this one particular shell.

BALDOMERO OLIVERA: Kind of like a tulip.

LATIF: Basically, it 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 ...

BALDOMERO OLIVERA: Is deadly.

LATIF: It's a killer.

LULU: Wait, what?

BALDOMERO OLIVERA: Yeah, you don't expect that from a snail.

LATIF: So he was holding onto the shell of a cone snail, which is this venomous snail.

BALDOMERO OLIVERA: That according to these books were capable of killing people.

LULU: No!

LATIF: And in fact, there's one kind of cone snail which is the—the kind of most intense, it's called the geography cone snail, colloquially known, or it's been called the cigarette snail.

LULU: Hmm.

LATIF: Because if you, a person, gets stung by it, you have enough time to smoke one cigarette before you are dead.

LULU: [gasps] Before you're dead?

LATIF: Yeah.

BALDOMERO OLIVERA: That's not true, no.

LATIF: That's not true?

BALDOMERO OLIVERA: That's an old wives' tale, right? So it takes several hours typically before ...

LATIF: [laughs] That's not much more comforting.

BALDOMERO OLIVERA: No, it's no joke.

LULU: I've never heard of, like, a killer snail.

LATIF: Yeah, I know.

LULU: Ever.

LATIF: I know.

JOSEPH SCHULTZ: Yeah, it's amazing!

LATIF: Now just for a minute I want to step away from Toto, introduce you to somebody else.

LULU: Okay.

LATIF: Joseph.

JOSEPH SCHULTZ: Joseph Schultz. We are at the Cosman Shell Collection at Occidental College in Los Angeles, California.

LATIF: 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 ...

LATIF: Holy cow! What the heck is this thing?

LATIF: ... we had a little shell fashion show.

LATIF: Wow!

LATIF: He's got this huge wall ...

LATIF: Wow! I'm here for the shells, and you already have not disappointed.

JOSEPH SCHULTZ: Let's see here.

LATIF: … of all sorts of shells. There were ...

JOSEPH SCHULTZ: Fantastic.

LATIF: ... big shells ...

LATIF: It's like my whole arm.

LATIF: ... tiny shells ...

JOSEPH SCHULTZ: Yep. Like grains of sand.

LATIF: ... colorful shells ...

JOSEPH SCHULTZ: Opalescent.

LATIF: Corally colored. Shells you could wear.

JOSEPH SCHULTZ: And it goes on your head there.

LATIF: Oooh!

LATIF: There were also scary shells.

LATIF: It's like—like, hairy.

LATIF: Hairy shells.

JOSEPH SCHULTZ: Like it has an aesthetic, like it knows what it's doing.

LATIF: Fab shells, drab shells.

JOSEPH SCHULTZ: Some snails do it better than others.

LATIF: And wait, wait. And what is this little ice cream sundae over here?

LATIF: Oh, right. Ice cream cone.

JOSEPH SCHULTZ: Conus geographus. That is the deadliest cone snail.

LATIF: This one is the deadliest?

JOSEPH SCHULTZ: Mm-hmm.

LATIF: 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.

LULU: And is that—that's weird for a snail?

LATIF: Yeah. Just think of a fish and think of a snail!

LULU: I know ...

LATIF: You are a snail trying to catch a fish.

LULU: Okay, okay, okay. Okay, I see you. I see you. Fish are like, foom! Darting fast.

LATIF: Darting fast. Snails are notoriously extraordinarily slow.

LULU: Slow. Okay. It's like a turtle hunting a cheetah.

LATIF: Yeah, like—like, how would that—how could that possibly work?

LULU: How could it? Yeah.

JOSEPH SCHULTZ: I'm gonna help you through this. It's gonna be okay.

LULU: Okay, great.

LATIF: So Joseph walked me into his lab. It's a room with a bunch of small aquariums all around.

JOSEPH SCHULTZ: We can move around the animals.

LATIF: And in one of the tanks ...

JOSEPH SCHULTZ: Humans have been stung by ...

LATIF: Oh yeah. Let's see.

LATIF: Were four tiny, hangry cone snails.

LATIF: It's like my thumb. It's like a thumb size.

JOSEPH SCHULTZ: A little guy.

LATIF: They were just sitting there.

JOSEPH SCHULTZ: Could I give you a little background on it?

LATIF: Sure. Cone snail background. Basic biology. Give it to me.

LATIF: So the way Joseph explained it to me is that these cone snails are basically vampires. When the sun is out ...

JOSEPH SCHULTZ: They're hiding away, hiding under the rocks 'cause 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.

LATIF: In the darkness.

JOSEPH SCHULTZ: Searching for their prey.

LATIF: And just like vampires ...

JOSEPH SCHULTZ: Cone snails want nothing to do with old fish.

LATIF: They prefer to feed on the fresh blood of their victims.

JOSEPH SCHULTZ: They want to know they are alive to feed on them.

LATIF: And so ...

JOSEPH SCHULTZ: I didn't know if you wanted to see it feed. I could try to feed ...

LATIF: Yeah! Are you kidding?

JOSEPH SCHULTZ: Okay. [laughs]

LATIF: Joseph pulls out from another tank a tiny little fish, a little guppy.

LATIF: Oh, it's jumping. It's jumping.

LATIF: And then he grabs a razor and he basically slits ...

LATIF: Oh, okay, yeah.

LATIF: ... the guppy's throat.

LATIF: You just killed it there.

LATIF: By severing the spinal cord.

JOSEPH SCHULTZ: And then I'm gonna use my tongs.

LATIF: So he grabs the little guppy ...

JOSEPH SCHULTZ: By the tail.

LATIF: Okay, you're dipping it in there.

LATIF: Lowers it into the tank, and then ...

JOSEPH SCHULTZ: Here we go. I'm gonna be the fish.

LATIF: ... he starts wiggling it.

LULU: So it seems alive?

LATIF: Yeah.

LATIF: You're wiggling wiggling wiggling.

LATIF: And what happens is this snail near the fish, a little tube ...

JOSEPH SCHULTZ: Like a little worm.

LATIF: ... starts to emerge from the bottom of its shell.

JOSEPH SCHULTZ: Just starting to come out. See it?

LATIF: I see it, I see it, I see it.

LATIF: 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 ...

JOSEPH SCHULTZ: Oh!

LATIF: The snail shoots this little bony harpoon that it has concealed in this tube. Like, it's—it's, like, spring loaded.

LULU: What?

LATIF: It shoots it right into the fish.

LULU: What?

LATIF: And if you just imagine, like, the harpoon that they—you know, the old time-y whalers would use or something, like, it's literally that.

LULU: Wow!

LATIF: So it fires this harpoon, which accelerates at 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 ...

JOSEPH SCHULTZ: And then injected, then pulled back.

LATIF: Obviously, our fish was already dead to prevent excess cruelty to the fish. But Joseph says in the wild ...

JOSEPH SCHULTZ: You can see breathing movements.

LATIF: As the snail slowly pulls the fish in. And then what happens is ...

LATIF: Whoa!

LATIF: ... the snail's mouth-y/stomach-y part emerges from the shell.

JOSEPH SCHULTZ: He's swallowing it.

LATIF: Oh, that's—he's actually swallowing it. Yeah.

LATIF: And it quickly just—gulp!—engulfs the fish.

LULU: Oh!

LATIF: And then after it eats it, it basically burps out the bones and the scales and the harpoon.

LULU: Oh, wow!

BALDOMERO OLIVERA: You don't expect that from a snail.

LATIF: Okay, so back to Toto.

BALDOMERO OLIVERA: It's a—kind of a long story.

LATIF: Little Toto finds this terrifying ...

BALDOMERO OLIVERA: Beautiful cone shell.

LATIF: Adds it to his collection. And then when he gets to high school, he actually has this chemistry teacher ...

BALDOMERO OLIVERA: She gave me all these books to read and encouraged me to try to classify the different shells.

LATIF: And sets him on this path to really studying science. So 1961, he finishes undergrad, goes to the US to get his PhD.

BALDOMERO OLIVERA: I worked on DNA.

LATIF: Including with a Nobel Prize winner.

BALDOMERO OLIVERA: 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, right?

LATIF: So Toto starts splitting his time ...

BALDOMERO OLIVERA: Going back and forth ...

LATIF: ... between the Philippines and the US. But the problem was, the Philippines was ...

BALDOMERO OLIVERA: Frustrating.

LATIF: He couldn't import the equipment he needed to research DNA.

BALDOMERO OLIVERA: It was hard.

LATIF: So he was like, "Okay, what can I actually study here?" And then he thought, "Oh, yeah!"

BALDOMERO OLIVERA: Cone snails.

LATIF: He remembers these shells from his childhood.

BALDOMERO OLIVERA: They're all over the Philippines, so quite readily available.

LATIF: By this point, he had teamed up with a colleague down the hall.

BALDOMERO OLIVERA: Lourdes Cruz.

LATIF: She goes by Luli.

BALDOMERO OLIVERA: We decided we'd do research together.

LATIF: Toto was like, "Look, the thing that I love about cone snails, the thing I always found so fascinating was their ..."

BALDOMERO OLIVERA: Venom.

LATIF: This powerful venom that could not only kill a fish, but also could kill people.

LULU: Oh, right!

LATIF: Because the venom essentially 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?"

BALDOMERO OLIVERA: Nobody knew.

LATIF: So Toto and Luli go around buying up all these cone snails.

BALDOMERO OLIVERA: From fishermen. As many as we could.

LATIF: They would bring them to the lab, crack open the snail.

BALDOMERO OLIVERA: And then we would push out the venom from the venom gland.

LATIF: And through some fancy chemistry, they would break that venom down.

BALDOMERO OLIVERA: To the individual components.

LATIF: And once they did, they were like, "Wait a second."

BALDOMERO OLIVERA: Astonished that there was this complexity.

LATIF: This venom had, like, 200 different parts to it. And they figured, because they'd read about snakes ...

BALDOMERO OLIVERA: When you get bitten by a cobra, there's one very major component in the venom that causes paralysis.

LATIF: So they're like, "One of these 200 in the snail venom has to be the thing that's doing it."

LULU: And the rest is just ...

LATIF: I don't know. Filler?

BALDOMERO OLIVERA: Right.

LATIF: So to find it, they did something kind of funny. They took these lab mice and put them ...

BALDOMERO OLIVERA: Upside down on a wire grid.

LATIF: So they'd grab the grid with their toes.

BALDOMERO OLIVERA: And the mice would hang on for as long as you wish. You know, hours.

LULU: [laughs]

LATIF: And then they would take one part of the venom ...

BALDOMERO OLIVERA: Inject it into a mouse.

LATIF: Into its abdomen.

BALDOMERO OLIVERA: And see whether ...

LATIF: The mouse fell.

BALDOMERO OLIVERA: Paralysis.

LULU: Oh!

LATIF: But they would do tiny, tiny, tiny miniscule doses.

BALDOMERO OLIVERA: So it wouldn't kill them, wouldn't paralyze their diaphragm. But it would paralyze their paws.

LULU: [laughs] Okay. So they're basically just going down this list, injecting one after the other.

LATIF: Exactly. Right. So they're—they're looking for the one part that causes paralysis.

LULU: Okay. Got it. Got it. Okay.

LATIF: 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."

BALDOMERO OLIVERA: And ...

LATIF: One day in the lab at the University of Utah where Toto was working, this undergrad he had hired ...

BALDOMERO OLIVERA: Named Craig Clark.

LATIF: Came in the lab, took a look around and was like, "This whole thing, hanging the mouse upside down ..."

BALDOMERO OLIVERA: It's very nice, but I have a better idea. We should inject the venom components directly into the brain of a mouse.

LULU: Why?

LATIF: [laughs] Seems—seems weird, right?

BALDOMERO OLIVERA: I thought, "What? You're just going to kill them." So I wasn't convinced.

LATIF: That does seem like a bad idea. Like, putting venom right in a brain.

BALDOMERO OLIVERA: Right. What are you going to learn, right?

LULU: Did he want to do it just because he thought it'd be more efficient?

LATIF: No. No.

BALDOMERO OLIVERA: He's a very creative guy. And it's a little hard to explain, you know, why people get their ideas.

LATIF: Don't you get it, Lulu? He's just creative.

LULU: [laughs] Okay.

BALDOMERO OLIVERA: And I was kind of dragging my feet. But he persisted.

LATIF: 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.

BALDOMERO OLIVERA: And ...

LATIF: To their surprise ...

BALDOMERO OLIVERA: ... the results were spectacular.

LATIF: 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.

LULU: Huh!

LATIF: So one of the components makes mice start scratching themselves.

BALDOMERO OLIVERA: One makes mice run around.

LATIF: In circles.

BALDOMERO OLIVERA: Another makes them stand on their back legs. Another caused mice to shake.

LATIF: Another one caused mice to become really hyperactive, another one caused mice to slow down. Another one caused mice to just go to sleep.

BALDOMERO OLIVERA: And so that's when everything changed because now everything became interesting.

LATIF: It's sort of like they went looking for a hammer and they found a hardware store full of tools.

BALDOMERO OLIVERA: Right. That's exactly right.

LATIF: Which meant for Toto ...

BALDOMERO OLIVERA: Why does it put mice to sleep?

LATIF: Now each part of the venom ...

BALDOMERO OLIVERA: Why does it make mice scratch?

LATIF: ... asks some interesting question about, like, how the brain works or how the brain and the body communicate.

BALDOMERO OLIVERA: It opened up all kinds of possibilities.

LATIF: 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.

BALDOMERO OLIVERA: That's exactly—that was our—our hope, yeah.

LATIF: So Toto applied to the US government for funding. Twice.

BALDOMERO OLIVERA: Yes.

LATIF: Got denied twice.

BALDOMERO OLIVERA: I'm—I'm a persistent guy. [laughs]

LATIF: And on an appeal he got it.

BALDOMERO OLIVERA: From the National Institute of General Medical Sciences.

LATIF: So they decide to focus on the part of the venom that was causing mice to shake, which they called ...

BALDOMERO OLIVERA: The shaker peptide.

LATIF: The shaker peptide. It's clearly potent.

BALDOMERO OLIVERA: Incredibly potent.

LATIF: So it's a good one to study.

BALDOMERO OLIVERA: Very, very small amounts would cause mice to shake.

LATIF: Like as if they were having a seizure or something?

BALDOMERO OLIVERA: They're—it was like a tremor, an uncontrollable tremor.

LATIF: 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 ...

BALDOMERO OLIVERA: Called a calcium channel.

LATIF: So in your brain, in a mouse's brain, whatever, you basically have electrical signals kind of moving all around all the time, right?

LULU: Uh-huh. Right.

LATIF: Also in the brain you have these calcium channels that are sort of like ...

BALDOMERO OLIVERA: Sort of like a switch.

LATIF: They have to be open for the signal ...

BALDOMERO OLIVERA: To pass through.

LATIF: ... to get to where they need to go.

BALDOMERO OLIVERA: Right. And so there were ...

LATIF: And did people—were calcium channels a long-known thing? Did people know that that existed?

BALDOMERO OLIVERA: They were known but not well understood.

LATIF: 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.

BALDOMERO OLIVERA: And what they found when they looked at the spinal cord was that the peptides bond to a very, very specific place. It only bonds to the region where pain fibers come in.

LULU: [gasps] Okay.

LATIF: So—so for example, like, let's say you—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.

LULU: Hmm.

LATIF: And so this little peptide was blocking those calcium channels, therefore blocking pain.

BALDOMERO OLIVERA: Yeah. If you block those calcium channels, the pain signal never reaches the brain.

LULU: Meaning you don't receive pain at all?

LATIF: Right.

LULU: At all?

LATIF: Right. So a biomedical company made a drug based off this little shaker peptide. And they did human trials.

BALDOMERO OLIVERA: And it worked like gangbusters. It totally blocked the perception of pain.

LATIF: In 2004, nearly 40 years after Toto started studying this snail venom, 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.

LULU: What?

LATIF: 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.

LULU: Why isn't this what we're all getting every time we get a headache or get into a car crash, or ...

LATIF: Right. So there are a few downsides.

BALDOMERO OLIVERA: Well, first of all, it's of course more expensive than opioids, which are dirt cheap.

LATIF: 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—and it is making a really big difference for them.

BALDOMERO OLIVERA: And what's interesting is usually most drugs, you tweak them a bit and change, you know, their chemistry a bit, but in this case, the commercial product is identical to what the snails make. You know, it's absolutely ...

LATIF: Wow! What does that tell you?

BALDOMERO OLIVERA: [laughs] Well, I think it says that snails are able to be pretty good at making drugs.

LATIF: 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.

LULU: So have they—are they continuing to look at other ones?

BALDOMERO OLIVERA: Oh yeah. No, no. We—we have two that are already reached human clinical trials.

LATIF: One for epilepsy, one is a totally different kind of painkiller.

[NEWS CLIP: In other news, there is fascinating research being done right now on snails ...]

LATIF: They have one that hasn't yet reached clinical trials, but looks super promising.

[NEWS CLIP: That venom includes insulin.]

LATIF: Insulin that could possibly be way faster acting than the one we use now.

LULU: Wow!

[NEWS CLIP: Really fascinating. Yeah, I mean, that—you wouldn't ever even think of that. It's kind of mind-boggling, to be honest with you.]

LATIF: And the thing that I—like, 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. But the thing is that was just one of 200 components from one of as many as a thousand 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—whoosh!—this is an enormous, enormous kind of universe.

BALDOMERO OLIVERA: You know, if you tell people you're studying the venoms of snails, they—they look at you a little funny. [laughs]

LATIF: Because it sounds, like, trivial? Or because it sounds obscure?

BALDOMERO OLIVERA: I don't know. I think—you know, my dad never understood why I was studying these snails. 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?"

LATIF: [laughs]

BALDOMERO OLIVERA: "How do you—I mean, isn't it finished yet? How do you persuade people to give you money to—to keep on studying those snails?" You know? So—so it's just kind of, I think, intrinsically not a very easy thing to explain, right? But we knew I wanted to do it.

[ARCHIVE CLIP, announcer: ... and a group of these highly-venomous sea mollusks. The team would go on to discover the raw material for this non-opioid pain reliever, a powerful new tool for studying the central nervous system. So we welcome the awardees to the stage: Baldomero Olivera, Lourdes Cruz, Michael McIntosh and the family of Craig Clark to accept his award. Please come on up.]

[applause]

LATIF: This episode was reported by Latif Nasser and Maria Paz Gutiérrez, with reporting help from Ekedi Fausther-Keeys. It was produced by Maria Paz Gutiérrez and Matt Kielty, with help again from Ekedi Fausther-Keeys.

LULU: Original music and sound design contributed by Matt Kielty, with mixing help from Arianne Wack. Fact-checking by Emily Krieger.

LATIF: Editing by Soren Wheeler, who thought the whole episode should have been five minutes shorter. Big special thanks to Erin Heath, as well as Haylie Swenson, Gwendolyn Bogard, Valeria Sabate and everyone else at AAAS who oversee the Golden Goose Awards. Can I pretty please host them next year?

LULU: He really wants to! Thanks to former Congressman Jim Cooper, who is to the Golden Goose what Proxmire was to the Golden Fleece. Thanks to Terry Lee Merritt at University of Utah, Jim Tranquada, John McCormack, and the Cosman Shell Collection at Occidental College.

LATIF: 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 her—conus dalli. So to all the chemistry teachers out there, keep doing what you're doing. Maybe one day you will have a murderous mollusk named after you.

LULU: [laughs] 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 Proxmire 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 complementary piece. I certainly did. The OTM team is always amazing, so just check them out—"A Scientific Devolution."

LATIF: That's all from us. Catch you next time.

LULU: Keep it—keep it shell-y. Keep it ...

LATIF: [laughs] Uh ...

LULU: Snail ...

LATIF: Okay, how about "Snail you later?"

LULU: Snail you later!

LATIF: [laughs]

LULU: Snail you later.

LATIF: What the shell.

LULU: Okay, bye!

LATIF: Okay, bye. Thanks. Thanks for listening. Catch you next time.

[LISTENER: Radiolab was created by Jad Abumrad and is edited by Soren Wheeler. Lulu Miller and Latif Nasser are our co hosts. Dylan Keefe is our director of sound design. Our staff includes Simon Adler, Jeremy Bloom, Becca Bressler, Rachael Cusick, Ekedi Fausther-Keeys, W. Harry Fortuna, David Gebel, Maria Paz Gutiérrez, Sindhu Gnanasambandan, Matt Kielty, Annie McEwen, Alex Neeson, Sarah Qari, Anna Rascouët-Paz, Sarah Sandbach, Arianne Wack, Pat Walters and Molly Webster. With help from Andrew Viñales. Our fact checkers are Diane Kelly, Emily Kreiger and Natalie Middleton.]

[LISTENER: Hi, I'm Ram from India. 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.]

 

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