Radiolab - Baby Blue Blood Drive

Episode Date: July 8, 2022

This is an episode that first aired in 2018 and then again in the thick of the pandemic in 2020. Why? Because though Horseshoe crabs are not much to look at, beneath their unassuming catcher’s-mitt shell, they harbor a half-billion-year-old secret: a superpower that helped them outlive the dinosaurs, survive all the Earth’s mass extinctions, and was essential in the development of the COVID vaccines.  And what is that secret superpower? Their blood. Their baby blue blood.  And it’s so miraculous that for decades, it hasn’t just been saving their butts, it’s been saving ours too. But that all might be about to change.   Follow us as we follow these ancient critters - from a raunchy beach orgy to a marine blood drive to the most secluded waterslide - and learn a thing or two from them about how much we depend on nature and how much it depends on us. Radiolab is supported by listeners like you. Support Radiolab by becoming a member of The Lab (https://members.radiolab.org/) today. Our newsletter comes out every Wednesday. It includes short essays, recommendations, and details about special events. Sign up (https://radiolab.org/newsletter)! Follow our show on Instagram, Twitter and Facebook @radiolab, and share your thoughts with us by emailing [e-mail]. And, by the way, Radiolab is looking for a remote intern! If you happen to be a creative, science-obsessed nerd who is interested in learning how to make longform radio… Apply! We would LOVE to work with you.  You can find more info at wnyc.org/careers. Citations: Alexis Madrigal, "The Blood Harvest" in The Atlantic, and Sarah Zhang's recent follow up in The Atlantic, "The Last Days of the Blue Blood Harvest"  Deborah Cramer, The Narrow Edge Deborah Cramer, "Inside the Biomedical Revolution to Save Horseshoe Crabs" in Audubon Magazine  Richard Fortey, Horseshoe Crabs and Velvet Worms Ian Frazier, "Blue Bloods"  in The New Yorker  Lulu Miller's short story, "Me and Jane"  in Catapult Magazine Jerry Gault, "The Most Noble Fishing There Is"  in Charles River's Eureka Magazine or check out Glenn Gauvry's horseshoe crab research database

Oh, wait, you're listening. Okay. All right. Okay. All right. You're listening to radio lab. Radio lab. From WNYC.

Hello, I'm Lulu. This is Radio Lab. If I could give a time person of the year award to somebody, it would be the COVID-19 vaccine. And I know the vaccine isn't a person, but when I'm deciding the person of the year, it can be a vaccine. And I would award it and I would put it on the cover of all the mess in the world. I think it is pretty clear that the vaccine has done unthinkable good. And by now, you probably know a little bit about the story of how it was developed, but what

you might not know is the role that an ordinary crustacean, the American horseshoe crab, played in its development, and also in modern medicine as a whole. So today, we are going to bring you a story that we first aired four years ago and then updated in the summer of 2020. It's about the unexpected influence horseshoe crabs have on science and society as well as what their future looks like. It is also the first story that Latif and I ever reported together. And it's beachy. We head to the beach. So we hope you enjoy. Here it is. Hey, I'm Chad Abumrod. I'm Robert Klobich. Oh, I'm a bit any beachy. No, I'm not going to pick rod I'm Robert Kloich

Yeah, you're down 13 you're gonna see this you're gonna see the store on the right hand So you see liquor store on right hand side you can make it you're gonna make it less that's barbers actually It's barberspeaks in this oh it's called Bower's bitch is reporter lots of now, okay? Okay, okay, you don't want to go to you don't want to go for it, okay? So Three years ago. That's only two to the pier. That's only four years down here. Three or four years ago, I'd taken the bus down to Delaware and I stayed in this crappy hotel and then woke up super early, like 5 a.m. still dark out to hop in this cap.

You're going to see the horse in the car. Oh, you have gotten me really excited. Let me tell you. I just started working at Radio Lab. This is like my first time I'd been sent out to just go out and get tape. You're talking to anybody, or they'll take anybody lives on that beach to be glad to talk to you.

Awesome. Awesome. And the whole reason why I was headed down to this beach was to record myself, commuting with a horseshoe crab. Have you ever held one like this again? I've never held one in my hand. I would love to hold one in my hand. Robert, you sound very far away.

I know, it's a turn. Is it my caravan? Okay, just to explain, we sent lots of down to that beach. I never knew I could be like this. Because a few weeks earlier, all right, everybody say something. Hello, hello, hello. Robert and I had sort of fallen into this rabbit hole.

Hello. We'd spoken with a guy named Alexis Madrigal, who is a staff writer at The Atlantic. How did you get on the horseshoe grubs? Where did that start from? It was late at night and I was reading through this site where all these crazy press releases are published called urecaalert.com.

And I happen to see this really tiny study, which had the unpromising name, sublethal behavior and physiological effects of the biomedical bleeding process on the American Horseshoe Crab, limulus polyphemus. And I thought, this is gonna be my big story this year. And then I went and I thought, this is going to be my big story this year. And then I went and I did that thing that we do now,

you know, horseshoe crab and then Google Images. And they're on the screen, according to Alexis, he saw these pictures of a bunch of horseshoe crabs kind of propped up on these metal racks and they were all kind of tied in place. They were on the row and they all had these thin little plastic tubes coming out of their shells, all of them. And underneath them are what look like kind of a two liter bottle

and there's blue blood in it. Blue? Like baby blue blood. And what was just so fascinating is the strange blood. It turns out to be the least interesting part of the story. Like at some level, like it's just the visual that draws you in. Because inside their strange blood, the horseshoe crabs have a kind of superpower. It's one that has helped them survive hundreds of millions of years as the Earth has changed, as other species have come and gone, and it hasn't just been saving their butts. It's been saving hours for decades. Nearly all of modern medicine

would not be possible without this special little thing in their blood. But you might all be about to change. Oh wow. Oh, and you can over there. Yeah, yeah, yeah. That's the love blood. One thing that it does that is really cool is it like has a a prom, a sex prom every spring. Oh, you know, we should do we should all go together. Isn't it like it's the first? It's the first? It's in June and it's on the first June of June. Alexis, you wanna go? I do wanna go.

Let's go. Which is where I come in? Test, test, test, test. Right, because it ended up being that Robert and Alexis and I actually couldn't go. And then it was like, okay, then send the new guy, you know? No, I mean, at the time, it was like, oh, okay, then send the new guy, you know? No, I mean, at the time it was like you were just milling around the office and you look like maybe you needed an adventure.

So we were like, hey, do you want to go see these crabs? Like, see the sex problems? Yeah. Yeah. Yeah, business in front, stubby in the back. So anyway, so I go and then when I got there, it was still pretty early, like maybe six, seven in the morning. It was a little bit rainy,

but when you walked down the beach, it was just littered in probably thousands of horseshoe crab. This is what a horseshoe crab sounds like. Yeah, there's kind of no way to hear it. We just so we get a visual, like what does a horseshoe crab look like? It's kind of like a semi-circle, and then there's kind of like this front shieldy part, and then there's the tail and a... I would call it a Scotland catchers' mate.

Yeah, yeah, that's not bad. So there were these hordes of Scotland catchers' m, you know, Scotland around and they actually move really slowly. A lot of people. Many of them were from a big pharmaceutical company, which will make sense in a second. But my guide for this morning on the beach was a guy named Glenn. Glenn Govry. Thin Guy, short hair hair wearing socks and sandals. And I'm the founder and director of the Ecological Research

and Development Group. And also, is it true I saw? I think I saw in your resume that you were in the Air Force? I was. I was an Air Traffic Controller. And the first time I saw horse you crashed was in 1969 when I was stationed at Dover Air Force Base, Which is right in your bot.

Being a young guy and coming down to the beach looking for something that might be going on. And I saw horseshoe crabs. Oh wow. It wasn't until many years later that I kind of looped around into this thing. But that was the first time I saw them. Sort of saw some horseshoe crabs and kind of weirdly fell in love with them. And became really there like champion. They're not all that attractive unless you've been around them a while.

I find them quite beautiful. But Glenn now leads these, you know, educational tours of Horseshoe crabs, especially at this time of the year. And he walked me up and down the beach, painstakingly explaining to me the rules of the, you know, of this ex-prom. Look at them, the larger ones are females. There's an male. At one point, he pointed out two crabs that were stuck together.

So that guy that's attached to that female, that's his gal now. They were like locked to one another, stuck upside down. Which makes it harder for them to write themselves. Like right now, the surface rough enough, where if they were separate, there's a good chance it would flip them over and they'd be okay. But because he's hanging in there, the likelihood of that happening becomes more remote.

But he'll die with her. This is like a blockbuster romance here. This is like, yeah, I mean, you know, you had to go back to remember Bert Lancaster on the beach, you know, I forget what movie that was. I never knew I could be like this. The ways they're crashing over and that was symbolic of the romance and they were both in bathing suits, you know, embracing one another.

Nobody ever kissed me the way you do. Nobody. So we've got to got an animal world version of that going on on the beach right now. And Glenn's romantic eye just painted this sex orgy as a beautiful flowering, like, mating season, like, spring in nature, kind of a beautiful thing. Oh my god, look at that. But I realized really quickly was like,

What is in it? Are those like maggots? Who knows? Oh, that's gross. The reality of it was kind of horrifying. Is that a threesome? There'd be like piles of crabs trying to have sex with each other. How?

That works. Yeah, it's exactly. Big trains of them all hooked together. And they would be like going in the wrong direction all the time. Like, what is going on here? You'd see like one crab in the middle, like a female, like a bigger one. Oh, so he's got his claws gripping. Right? And then three or four males, like a female, like a bigger one. And then three or four males, like all trying to mate with this one crab at the same time.

And then when you look even closer, it turned out the female crab was dead. Like this weird like necrophiliac for some of crabs. It was kind of raunchy actually. Oh my glasses are getting all, all, all, I'm gonna talk to my, but while I was standing watching all this, you know, hurly burly of crabs X,

I was struck by what I think is one of the central questions of this story, because it's almost impossible not to notice that a lot of these horseshoe crabs are really banged up. Like chunks of their shells are missing, their eyes are missing. Yeah, you wouldn't think if someone had a hole in their head that size. It'd be just be walking around with a big deal. Exactly. Yeah.

Some of them, they have holes that you could see their legs underneath. That is nice. And they're all just fine. They just have all these kind of crazy, what would seem to be fatal injuries, but they're all just kind of walking around like it's no big deal. Just consider it on the species level. So like, here's a creature that has lasted hundreds of millions of years. It outlasted the dinosaurs and the asteroid that killed them,

it outlasted, freezing oceans, it so far has survived the industrial age of humans, and you look at it and you're like, how? What's its secret? How? What's its secret? And it turns out that part of the answer to that has to do with that Baby blue blood. This is Alexis Madrigal again So our blood is red because hemoglobin is rich in iron, right? And their blood is blue because it's rich in copper So their molecule that carries oxygen for them is called hemoscianin But what's really interesting about this blood

is this chemical system of slowing down bacteria. So say you're a horse you crap. And in your blood, there's a little bit of bacteria. Maybe you got through in a crack in your shell. Anyway, in your blood are these cells called amoeba sites. These oval cells that are sort of on patrol in the blood are these cells called amoebocytes. These oval cells that are sort of on patrol in the bloodstream. And when they encounter a particular kind of bacteria,

the amoebocytes, these oval cells, excrete this substance called coagulogen, which does exactly what it sounds like. The area around where the intruders are, just like, exactly what it sounds like. The area around where the intruders are, just like, boop. Turn into this like jelly stuff.

That bacteria that snuck in. It traps them. Like a grape trapped in a bowl of gel love. Wow. And that crack in the shell, the amoeba sites, seal that off too. And what does it do with the gel then? Is it poop it out or something?

Then it can actually attack the cells once they've been slowed down. Oh, so it blobs the invader and then it mobilizes it and then some other defense defenders come in and they can take it out. Take it out. And this superpower fighting its tiny battles in the bodies of these rather plain looking creatures.

Have you touched one of these guys before? No, first time. First time? How did it feel? Is the reason why people from pharmaceutical companies were on the beach that day? It's one of those things you live your whole life and you have a new idea that you... How would you?

Because this thing that's been playing out for literally millions of years, one day humans started to catch on to this. One day, humans started to catch on to this. And one human in particular. Good morning. To explain. We're gonna leave the horseshoe crab. Just for a minute.

And talk a little bit about injectable drugs. That scientist and innovator James Cooper. Any relation to James Fenmer Cooper of the... Like the last of the Mohicans guy? Cooper. His name is James Phenomarkouper. He was named after James Phenomarkouper, and his son is also named James Phenomarkouper. Wow.

Wow. But anyway, this James Phenomarkouper told us that while it was a total miracle when injectable drugs like morphine came onto the scene, it was also a bit of a nightmare because they didn't know about bacteria. Occasionally, the fluids they were injecting would become contaminated. As soon as they had injected this material, the patients get infections and develop terrible fevers.

Or even die. They can be incredibly dangerous to us. And so to make sure these drugs were free of bacteria that caused fevers, they didn't just try it on a person and see if they died, they checked it on a rabbit. And they would have like, like, racks and racks of rabbits, like 24 rabbits in a rack. They are restrained by the neck. Rather loosely. I mean, like a pilgrim being punished in the town square? Exactly right. And then they take a little sample of the thing they wanted to inject into a person, and then they would inject that into the rabbit's ear. And then they take a little sample of the thing they wanted to inject into a person, and

then they would inject that into the rabbit's ear. And if there's certain kinds of bacteria present, the rabbits will get a fever. Their temperature will go up, and the way they measure their temperature was with these electric thermometers up their bombs. So if the rabbit's temperature goes up, we know we shouldn't put this drug inside a person. But if there's no temperature spike, this solution is safe to inject into man, or woman, or children, or really anyone.

So that's how crude it was. And it turns out this test wasn't really that reliable either, because rabbits are like pretty sensitive. So even if sometimes they'll like see a new person and they'll get scared and then they'll just have a fever because of that. they'll like see a new person and they'll get scared and then they'll just have a fever because of that. So it was really, it was not a great test, not great for us, especially not great for the rabbit. After they would go through a few tests, sometimes even after only one,

they just, they kill them. And to Rabbit Hall of Famer, James Fenemore Cooper. My joke is that I love to talk to rabbits because they're all ears. Anyway, back in the late 60s, Cooper was a grad student at Johns Hopkins University. And one day, one of his professors came up to him in the hall or wherever. And kind of jokingly, maybe somewhat seriously, as Cooper, if you want to get out of this institution with your degree, you're going to need to find a way to pest for pyrogens by something other than the rabbit. Basically, find a better way. That was sort of a joke, although I think he met some of it.

Lucky for Cooper, around the same time, this other professor at his university, Dr. Levin, had just come out with a paper on how horseshoe crab blood could theoretically be used to test for bacteria in people. And hearing Dr. Leaven present about it, Dr. Cooper sat back in his chair and was like, wait a second, what if we use the horseshoe crab blood to test our drugs? Would it be possible then to take this test and adapt it to test drug products? Then we wouldn't have to kill all of those rapids. So they got together, made the test work, and...

As soon as we made that publication in 71, then the pharmaceutical industry jumped right on it. And so this particular chemical substance is coagulogen in the Horseshoe crab blood. It actually became a major part of the way that we test things that we're gonna inject into our bodies. In every hospital as you walk down the the corridor you're looking at room there's an IV bag hanging surgical instruments on a tray. Injectibles for pain, infections. Your dad's pacemaker.

Cancer chemothera. Your grandma's new hip. Your kid's epic. Whooo! Immunization shots. Whooo! Whooo! All of these things have been tested with this material,

this test that we're able to do, using this chemical that we extract from horseshoe crabs. This 450 million year old species. Wow. Yeah, but in order to do all of that, in order to actually, you know, keep our medicines safe, they actually have to go out every year and drain horseshoe crab blood.

Seriously, they have to keep doing this all every year. Yeah, they go out, they get the crabs every year, they drain their blood, and then they go put them back out into the ocean, it's like a horseshoe crab blood drive. And the whole, I mean, there are a bunch of companies that do this in the whole industry is worth, you know, like tens of millions of dollars. Woo!

And so I really, really wanted to see this all in action. Like I wanted to go to one of these bleeding facilities. After the break, Latif and a very special guest will do just that. They will infiltrate, so to speak. One of these bleeding facilities and witness the baby blue blood drive firsthand. That's coming up.

This is Radio Lab. We're back with a lot of Nasser reporting on horseshoe crabs and the scientists who love them or at least love their very valuable blood. Maybe them too, but mostly their blood. And they're in Lizer up. So they're basically like, I think four or five companies that go out and find horseshoe crabs and then extract their blood. And I wanted to see what does it look like. So I sent out a few emails, and then I was emailing these companies

for like three years, and nobody ever returned my emails. I don't know why maybe they didn't want bad press or I don't know maybe they wouldn't bleeding that year or whatever. And so I'd basically given up on the story, but then this year, these folks at one of the companies

called Charles River Laboratories, and were like, hey, why don't you just come down to Charleston, South Carolina, and watch what we do here. So I went, and along with me, I brought... Dust, dust, dust. Lulu. Hey, how's it going? Lulu Miller. You guys shine the horseshoe crab signal on the moon and I come running.

Lulu Miller is a former radio lab staffer. Actually, she is the first radio lab staff member besides myself and Robert and Ellen and she is a co-creator of NPR's Invisibility. How did you get in on this? I weirdly have had affection for these creatures my whole life. I grew up with them. There's some of my first memories. What do you remember seeing?

I remember seeing what I thought was a crab. I was probably three or four on the beach with my parents in Cape Cod where we've gone my whole life. And I just remember walking on the beach and seeing this massive crab, a third of the size of my body, basically. And I remember kind of jumping back and my dad saying, oh, take it up. Poe got it, you know, interact. And so I kind of turned it over and I saw all those claws and I got scared. And then he, you know, he showed me it wasn't alive, it was a molt. Oh.

And he explained what a molt was that there had been a crab in there and it slid out and now was this perfectly intact skin of what it used to be. And you're wonder like, well where is it now and what's it doing now and do I ever leave a self behind? I don't know, it's just little and I thought it was cool and we brought it back to our porch. I remember that I had sat on our porch for years and like the dog would sniff at it. Where are we going? There's just ever since then, it's just been a like mild poetic fascination. It says visitors report to building sea.

So I think that's... And Lulo, did you have a feeling about this business of any sort before you went and visited? Yeah, there's a part of me that wondered, like, oh, I totally love these creatures. This big, bad company just exploiting it for their blood. And, you know, I went with a little skepticism. And you tore it up, great.

Thanks. And, you know, an eyebrow down and scrunched. So the bleeding facility was just in this kind of understated, nondescript office park land. There's like people in Capri pants and sandals. Basically, from the outside, it looks like every other one story brick building. Woo!

But then when you go on the inside, something like your hit with this like, I can smell it. Wash of a smell of crabs. That's amazing. Hey, wow, that smell, how would you describe that smell? Kind of crab mist. Yeah.

It's a high ceiling brightly lit room with industrial sinks along one wall, these shiny metal operating trays on wheels. And no matter where we were standing, we just sort of managed to be like exactly in the way of all these busy people rushing around. They've learned lab coats, they're wearing air nuts, and they're pushing around these big,

gray bins on wheels. And inside each bin are the horseshoe crabs. Twisting and turning a little, waving their tails. All heaped on top of each other, about 20 per bin. Flex in their claws. So we have our crabs coming in from our supplier. That's Brad Parrish, our guide. He explained to us that there are two parts to the blood donation.

We start by washing the animals, scrub the shell, pop the barnacles off, they spray it, dunk it, buff it. And the it of which you speak are living animals? Yeah, like one at a time. These smooth shells are past person to person, rinsed and shining. It's like wonka land for crabs in here. It's like a whole world. Yeah. We're like skinned away. Yeah, we're in the way. Once they're washed. It's a rack of one, two, three, four, five.

It's time for the bleeding. 16 crabs, weildover, gonna go in. Crabbs are taken out of their bins, folded in half. So their tails are kind of underneath. Then they're put on these racks where they're strapped down with a bungee cord to hold them in place. And then they're wheeled into this tent,

which is like a clean room zone that's like, like got these sort of like plastic curtains all around. Oh, we go in. We go in. Oh, we can't go in. Oh, we can't go in. Okay, got it.

And they didn't let us go in there because as regular bacteria carrying humans, we were far too dirty to enter this super, super clean room. But we could peek right in. And when we did, we saw that right at that fold in the crab's body. Right at that hinge, there's like a little opening and the needle goes in there.

And it was from that needle that this blood, it's like brilliant, yeah, kind of sci-fi, sky blue blood. It was slowly dripping into these glass bottles. And the crabs are kind of like, their little claws are are going but they just kind of look like they're sitting there and they're draining them of about a third of their blood. What is your emotional sense of this scene? Like it was kind of this oh feeling some sort of like what we're doing here is weird and kind of Vampire I don't know. It was like we're sucking their blood. So it was a little it was a little creepy

Like when So a lot of like I feel like when we were in there, there's so many... We were in the factory. Dozens and dozens of boxes filled each with like 10 huge crabs. And we were in that, yeah, in that processing zone. And before we went and saw the blood, this maybe sound cheesy, but it was actually profound and I keep thinking about it. There was this moment.

Okay, so here we, okay, what are we looking at? Can I touch her? When one of the guys in the factory had pulled out from these bins this big female horseshoe crab. Okay, oh yeah, she's going in a knock. Yeah, I do. And he's just sort of holding her by the shell.

Hi, hi. The tail is really coming right at me here. We got so her little claws are going up and her tail is kind of waving around. Right, so there's a lot of, yeah, claw activity. Exactly, and so it'll take these claws. And he like turned her over so she's upside down and then he took his hand and just let her claws kind of grab his hand. And so there's sort of pinching my hands here, but it doesn't hurt. There's not much power to them. They're just using that to sort of grab his hand. And so there's sort of pinching my hands here, but it doesn't hurt.

There's not much power to them. They're just using that to sort of grab the food. Can I try? And bring it into their mouth. Can I get a little pinch? Yeah, just. And so I just kind of slowly stuck my hand out toward her claws.

And her claws engulfed my hand. Oh, they're very close. They're very, very, very claspy. It wasn't a scrabbley kind of foreign touch. They all the claws clasped in a unison. Really tight. It's actually kind of, it's kind of a massage, right? So I am being like, this horseshoe crab is holding my hand. Wow.

To me, and of course this is just silly projecting, so I'm saying that, but it felt like, I know it wasn't, but it felt like a communication. Like I'm in this bin and these people are doing weird things and I want to be back in the sea and I'm upside down and I'm about to go into like have a sink, you know, one of those like shower heads spray it all up in my undersides and then I'm going to be bungee corded and drained. Like it was almost, it wasn't like it was in pain, but I had this almost like primal creature to creature help me. Yeah, like, I mean, part of me felt that too, but I mean, on the other hand,

like they do get to go home afterwards. So the same fishermen that bring the crabs to us are then going to deliver them back to the ocean and release them. They're set free. Straight back to the water. And how many crabs do they do this two every year? About 500,000 horseshoe crabs every year, get blood?

Do the crabs that get blood and then release them, do they just swim away fine or do they? So some of them do die after the bleeding. There's a small percentage, like I think the conservative estimates are in like 10%, but that might be a high estimate, or there might be a low estimate. I think it's 15%. Okay, so let's say like 15%. So if you're talking about 500,000 crabs being blood every year, that means about 75,000 horseshoe crabs are dying because of bleeding

every year. You know, they actually, in that original paper that I looked at, again, Alexis Madrigal, they were actually able to see that a lot of the crabs don't have like, blood crabs and non-blood crabs like have slightly different movement patterns. And that's because you know because maybe one of them is missing 30% of its blood, but they needed to double check on that. And so they did see that the blood animals appear more lethargic, they move more slowly.

And imagine if you had to go harvest deer and then bleed them of 30% of their blood and then you'd leave them back out in the forest, there's something about that that seems so bizarre. It seems very medieval. Is there any hope of getting out of this whole vampire relationship we have with the horseshoe crabs? Well, perhaps. And let me tell you a brief story about a bird.

A smallish bird, cinnamon in color, with a long bill, it's called a red knot. Now, the incredible thing about red knots is of all the birds in the world, the red knot makes one of the longest migrations near 10,000 miles. They go from the very southern tip of South America, all the way up to northern, northern Canada, up into the Arctic Circle, where they lay their eggs. And the whole journey takes about 5 months. And what happens is, thousands of these red-not birds will take off from South America, they'll fly like 4,000 miles north up to Brazil, and they'll stop there for just like

a couple days, rest up, eat some food. And then, the thousands of them take this guy's again, and they fly up along the eastern coast of South America over the Atlantic Ocean. But before they get to their final mesting grounds, they make one more stop, one pivotal, crucial rest stop in the Delaware Bay. Now, when I was in Delaware, there weren't like a ton of birds there but basically these birds when they make this journey They rely on horseshoe crabs because They need to eat millions of horseshoe crab eggs to complete their migration And this is the thing, it's weirdly these birds

that might actually free the horseshoe crabs from us. Yeah, yeah. And to explain, I got in touch with this guy. My name is Jay Bolton, a biologist in the global quality laboratories that Eli Lilly and company. So Eli Lilly and company, it's this huge pharmaceutical company that makes, you know, cancer drugs

and anti-depressants, a lot of insulin and things like that and real quick People are at the core of our commitment to manufacturing. Here's a message from an executive and the driving force behind our innovation Radio lab is brought to you by anyway One of the things the company's been helping innovate is horseshoeorseshoe Crab Blood. A synthetic version of Horseshoe Crab Blood. Yeah, so... And, you know, Jay explained to me, if you kind of zoom out for a second and think about what it means to use Horseshoe Crab Blood

for this, you know, phytoal thing in medicine. The problem is, there needs to be a supply of Horseshoe Crab's. And, you know... Global warming, global warming, climate change is real. Rising sea levels, habitat loss. I could have some supply chain consequences which isn't good no And so it was actually all the way back in 1997 some researchers out of the University of Singapore

Cloned this the factor C protein the essential factor C protein in horseshoe crab blood that goes that goes, blue, blue, blue, blue, blue, blue, blue? Around the bad bacteria. And now we can make the protein of interests instead of getting that directly from horseshoe crabs. Huh, so why aren't we already using that? Yes, of the problem. Well, Jay explained that there's a whole bunch of different reasons, but one of the big ones

was that you already had an industry built on horseshoe crab blood, and so there was no real immediate incentive to change, which is actually how we get back to... They're coming, they're coming! Output friends, the birds. So it turns out people like these birds a lot, like actually way more than horseshoe crabs, but since the birds eat the horseshoe crab eggs, their fate is kind of entwined. So like if the horseshoe crab is not doing well, then the birds not going to do well.

And so, Jay figured, why don't I just go around to all the bird conservationists? They use some of their political power and contacts. And it's only now that we're starting to come upon a new dawn. A New Dawn. So good afternoon everyone and welcome here. This is a great place to be today. In May of 2018, Jay was standing on a stage along with some conservationists to announce that Eli Lilly would be one of the first companies to use synthetic horseshoe crop blood. The big headline news here is that the pharmaceutical industry can actually replace probably up to 90%

of the use of horseshoe crab blood without incurring any major regulatory change. Woohoo! Which means these horseshoe crabs can finally be freed of their servitude and bondage to mankind and get back to doing. Is that a threesome? What is going on here? What they love. It's a big orgy. It's a big orgy.

Well, but here's the weird thing. I think like, if the synthetic comes through and we get it perfect and it works and we never have to drain another horseshoe crab, then they just become these weird kind of sea spiders again. And that could be a really bad thing for them. Yeah, exactly. This is actually something that Alexis Madrigal

talks about too. Because most of the other things that these horseshoe crabs have ever been used for in the history of their encounter with humans has resulted in the death of like large numbers of them. Because before we ever valued them for their blood. We basically did two things with them. Thing one. We'd turn them into a fertilizer. We would catch them, boil them.

And grind them. And then just stick them in the soil as a way of promoting plant growth. Or... Thing two. and then just stick them in the soil as a way of promoting plant growth. Or think too. We'd catch them, cut them up, and use them as bait to catch more valuable species, like a particular kind of snails. Okay, so I have right here in front of me,

this comes from the Atlantic States Marine Fisheries Commission, which their numbers say that, you know, as of the late 90s, there were nearly three million horseshoe crabs being killed every year for commercial fishing. 3 million, wow. But more recently, we put restrictions on how many horseshoe crabs can be used for commercial fishing, for bait.

It's even like in a lot of states, it's a crime to go to a beach and just take a bunch of horseshoe crabs. Like in New Jersey, if you take a horseshoe crab, you could get fined $10,000. The thing that I've always wanted to keep in mind with this is like, if you're gonna have to be hooked up to some economic system, which most animals in our world are, you kind of want to be hooked up to one that's super high value and that doesn't kill you.

And so the fear is, like if the synthetic works and we no longer need horseshoe crabs for their precious blood, then we just go back to chopping them up, putting them in the ground and using them for bait. Because they live where we live. They live along our most populous shore and they're right there for the taking. You know, they're not prepared for our murderous impulse. Hi, I'm Lutthiff. Nice to meet you.

Nice to meet you. Thanks for having us here. Yeah, we're glad to. And there was this moment where everything just kind of flipped for me, where I realized that as cruel and kind of grizzly as the draining of the blood seems, that actually may be the best thing for these creatures. Like, our selfishness may be protecting them.

Well, you want to see some mohorshi crabs? Yes, yes. So this was our very last stop on our trip down to South Carolina, and we met this fisherman named Jerry Galt, who is employed to collect horses of crabs for the company. What a peaceful little spot. So we're in this forest. Yeah, I know. This feels like the most secluded place in the world.

With Jerry walking around this little pond. I wore the exactly wrong shoes. I know, I just wore the wrong thing. What's known as a holding pond, where they put the crabs before they go off to the facility. And while we were down there, Oh, what you got there? Jerry scooped some water out of the pond. That's just a bottle of water. But then he held the bottle up to our faces.

See the babies? Oh, all of those? Wow, there's so many of them. How many? Yeah, they do 100,000 eggs a season. Wow. Yeah, they're like the size of a really round grain of rice. They're like pearled couscous.

Pearled couscous. Right. Were they laying the eggs here? Or did you get the eggs from the where you lay the eggs along the shore? Oh, I did a bit of shore here. So this spot, you've been in the air. Oh, literally right here.

Oh, wow. Oh, cool. So I feel like we heard a tiny bit about, but what's the story of how you went from or your family went from being kind of seafood fishermen to doing this kind of crazy different thing. Well, we're just a bunch of fishermen of ADD. But Jerry told us the gist of it is back when his dad was doing seafood fishing. You know, I was just a tank then I was in the 70s. His dad was catching a lot of horseshoe crabs selling them off for bait and then one day

this guy just showed up at his house, suit and tie. Told my dad that if he would quit selling them for bait, he'd make a deal for him, he would buy him. Buy him for more money. So Jerry's dad said, sure. We've been doing it ever since. But I got something I want you guys to know. As a fisherman, I'm proud to be part of it.

I find it to be, I want to say it's the most noble thing I do because I get to touch every one of you guys because it's used for making sure medication is safe for us and can't say that about soft-shell crabs or a grouper, you know. Yeah, you touch everyone and then you touch it again and return it. I touch you indirectly. Indirectly. I'm touching all of us here because we're all part of it.

So it's a pretty neat thing. If you had to describe your feelings for the crabs, for the horseshoe crabs, how do you feel about them? Well, I have a lot of respect for them. And I almost feel like it's a divine design. The worship crab is, you know, I've seen them fishing for them, you know, they're a nuisance then. And now I see them on this side where they the important to the human society. And I just draws me back to the idea that it was a divine design.

They've been around for 400 million years. It took them this, it took us this long to figure it out, I guess. At a curiosity, where did that leave the two of you? Well, for me, I mean, Jerry, the fisherman, he's totally right. We just figured this out. These crabs have been clark-kending us this whole time. They have this hard-won superpower that they've probably had since before like three branches on our evolutionary tree. And in evolutionary terms, like,

they're the winners. We're the, we're chumps. We're baby chumps. Yeah, and there's just like, there is something miraculous inside them. And in a certain way, it's easy to stand next to them and feel almost small. Like that we're not unlike an asteroid or just another thing they're probably gonna

endure like we are a blip to them and yet We're a dangerous blip and and in a weird way like People the people we met down here the people doing this work this blood harvesting work in a way came to represent the best way to treat the crabs. That's right, exactly. Treat them like eggs. There are these rules in place to make sure that the horseshoe crabs are only picked up by hand,

and you can't pick them up by the tail. Because you can injure the muscle and the tail. We keep them covered when we transport them. They're also on a time clock. We've got to get them back as quick as possible. They have to be back to the ocean within 24 hours when they get to the lab. We give it a manicure, pedicure.

Each one gets scrubbed clean by hand. And then they borrow some blood from it and bring it back and let it go. And he showed us how he returns them to the water and he like, he built this freaking water slide. It's slide to go down. To do it more gently. No, now we pick them up and set them into this slide and the water takes them down to the

river before we used to pick them up in Tossum. And we've got away from Tossum. It's amazing. I got a slide on my dock 200 feet long water slide where they rehydrate on their way to the river. See how fast they pull those away now? I don't want to get your finger cut in here. Wanna hold it? Yeah sure.

But I need to see this is the male. That's the male. Okay. And we just interrupted his embrace. His game. What? Is cuddling. He's cuddling.

So it's been around four years since we first reported that story about horseshoe crabs, you know, and the magical, super sensitive stuff that we take out of their blood, which I don't even know how we managed to do this. We didn't name the thing we take out of them, which is called LAL. Then, still early on in the pandemic, I called up Dr. James Fenemar Cooper, who is the guy who's been working on this basically since the 60s, just to find out,

given everything that was going on in the world, what was new? Tell me the story of LAL in the time of COVID, what, what, how is, how is it being used, what's going on? Well, that's a good question. Of course, the FDA will require the LAL reagent to be used to test all of the vaccine batches that are produced, that's required for every vaccine right now. So you're saying that no matter which one gets their first or, you know, however many get their first, they're all going to have to sort of as one of the final stages, they're all going to have to pass an LAL test, is that right? Yes. Huh. Yeah, but that doesn't even, that's not even the extent of it for the vaccine.

So even before they make the vaccine, Dr. Cooper says, they have to test all of their ingredients so the formulation, their waters, their salts, their buffers. Wow. And then not only that, it doesn't even end there. In some cases, they also test the packaging,

so like the glass vials. And according to Dr. Cooper, they're like, that's already happening. So like I imagine somewhere, there's, you know, just vials sitting that are just like horseshoe crab approved and they're just waiting for their big moment. Like they're just waiting to be filled up and you know, shipped out with that amazing.

Are there other ways that LAL has been used like for this epidemic in particular besides the vaccine? Well, it will have been used to test every medicine that is being injected and used to screen all the devices, needles and syringes, IV lines and things like that, it's used to test that. So imagine this, okay. So imagine you're walking into a hospital, you have symptoms, you test positive for COVID-19. What happens after that, right? So maybe doctor takes your blood. Syringe used to do that to run whatever blood test. The syringe used to take your blood. Serenj used to do that to run whatever blood test. The serenj used to take your blood.

That's been tested with LAL before it left a factory. Let's say you get hooked up to IV fluids. Those IV fluids would also be harsher crab approved, as would be the IV bag, the tubes, the catheter are going into your vein. Let's say worst case scenario, you need to go on a ventilator. The tube going down your throat, uh, that, at site of where it was manufactured,

that would have also had to be tested with the, with LAL with the blood of horseback. And it is true. I should say that there are some certain companies like Eli Lilly that are in the process of making the switch to the synthetic version, recombinant factor C, but LAL is still the standard. Holy moly. So it's like, it's everywhere. Wow. Super impressive.

But then there's another sort of little bell that's ringing in my head, which is like, oh no. Like that means we're gonna need a lot of extra horseshoe crab blood to do all this. Right. Like on the supply side, given that there are so many vaccines in development, given that won't it just

use up a ton of the LAL? Well, a number of months ago, the three major LAL producers got together and came up with a scenario that if they made five billion doses. Doses of vaccine, you mean? Yeah. Vaccine. Yeah.

How much LAL was that required? And their calculations show that it would require a couple of days production. And then I made a second calculation yesterday and I used 10 times as much LAL as they calculated and I found out it still wouldn't use one percent of their inventory. Whoa, that's reassuring. I know, I was about to say, it's like in a,

in a, in a, in a minefield of, of bad and terrible news, it's sort of a, it's like just a kind of, okay, this thing under control, got it covered. That's right. So I was like, I was like, what? I was like, this is not the, like even the toilet paper people when you talk to them, they're like, you know, this is a really hard time, but we're gonna make it work. Like the supply chain is really like toilet paper people, when you talk to them, they're like, you know, this is a really hard time,

but we're gonna make it work. Like the supply chain is really, like we got to, and these guys are like, no big deal. We got it. Are they bleeding more than they need to bleed? Like what is that seems? So they have said no. They have said no, like, and it's kind of the scale

that they're working on, because they do so much for so many things over such a big industry. The sort of the scale of it is such that it's already so big a scale and it's already so efficient a test that it's like a drop in the bucket. I see. Good. That's the claim.

I just am suddenly asking myself questions about the baseline scale at which they operate. I'm like, yeah, how is that possible? How is that possible? Like, do they have warehouses full of that blue blood just in case? Yeah. Well, it is a pretty important, like I don't know if that's the case I can find out. My guess would be because it's such a crucial thing, I would imagine that they're just anticipating any problems, and the fact that it's written into the regulations

that literally medicines need this thing. Interesting. You know, you need to have this much in a warehouse because it's so important. That'll be my guess, but I could look into that more. That's really interesting because it reminds me at the very beginning when you were hearing all these reports about how many masks the government had in its reservoir,

which was like, oh, I didn't realize that there was somebody who was putting masks in the mirror, but that seems so super smart. Now that you mentioned it, of course, there's horse shoe blood in the reservoir. Yeah, so, okay, so that's how how that's the company's sort of perspective. But then there's the question of like how are the horseshoe crabs doing actually? In the two years since we've run that story, like what's the status of the horseshoe crabs? So there has been, so we quoted in the story,

there's the thing the Atlantic States Marine Fisheries Commission. It's like basically a government survey. One came out last year, 2019. They found that across the whole eastern seaboard of the United States, the population of horseshoe crabs is remaining stable. And then basically in the south, it's actually doing, and I'm going to quote the technical term here, good. So, they, after we over-visioned them for basically a century, half, they're doing all right. And to me, there's something kind of profound about that.

Cause, like, right at this moment, where they're jumping in extra to save us, like it's nice to know that we are sort of saving them too. Thanks to Laquia Wimbish and everyone at Lanzas Global Endotoxin's testing summit, Mike Kendrick and Brad Floyd of the South Carolina Department of Natural Resources, also Tamara Anne Hull at Eli Lilly and of course Kate Contreras, John Dubcheck and the rest of the team at Charles River.

I'm Chad Abomran, I'm Robert Probech. Thanks for listening. Radio Lab was created by Chad Abomran and is edited by Soren Willer. Lutheum Miller and La Tifnasser are a co-hosts. Susie Lektemberg is our executive producer. Dylan Keith is our director of sound design our staff includes Simon Adler Jeremy Bloom Becca Brestler Rachel Qsick W Harry Fortuna David Gable Maria Paz Gutierrez

Sindu Nianosan Bandam Matt Kielty Annie McEwan Alex Niesen, Sara Kari, Anna Reskutpaz, Sarah Sandback, Aryan Wack, Pat Walters, and Molly Webster. With help from Bone Wong, our fact checkers are Diane Kelly and Emily Krieger. Hi, I'm Erica and Yonkers. Leadership Support for Radio Lab Science Programming is provided by the Gordon and Betty Moore Foundation, Science Sandbox, a Simon Foundation initiative, and the John Templeton Foundation. Foundation will support for Radio Lab was provided by the Alfred P. Sloan Foundation.