Baby Blue Blood Drive
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Hello, I'm Lulu. This is Radiolab. 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 Jad Abumrad. I'm Robert Kowalich. And this... Oh, it's called Bower's Beach? ...is reporter Latif Nasser. Okay, okay, okay. Okay, so...

Three years ago? 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 cab.

You're going to see a horseshoe crab. Oh, you have got me really excited, let me tell you. I had just started working at Radiolab. This was like my first time I'd been sent out to just go out and get tape. You'll talk to anybody. Anybody that lives on that beach will be glad to talk to you. Awesome. Awesome. And the whole reason why I was headed down to this beach was to record myself communing with a horseshoe crab.

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. Is it this one again? Okay, just to explain, we sent Latif down to that beach. I never knew it could be like this. Because a few weeks earlier, alright, everybody say something. Hello, hello, hello. Robert and I had sort

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 onto Horseshoe Crabs? Where did that start for you? It was late at night, and I was reading through this site where all these crazy press releases are published called EurekaAlert.com.

And I happened 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 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 there 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 all in a 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. Yeah.

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 ours for decades. Nearly all of modern medicine would not be possible without this special little thing in their blood. But it might all be about to change. Oh, wow. Oh, and even over there. Yeah, yeah, yeah. That's the love puddle. One thing that it does that is really cool is it like has a...

A prom, a sex prom every spring. Oh, you know what we should do? We should all go together. Isn't it like in a few months? It's in June and it's on the first full moon of June. Alexis, you want to go? I do want to go. Let's go.

which is where I come in. Test, 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, 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 looked like maybe you needed an adventure. So we were like, hey, do you want to go see these crabs, like see the sex prom? 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. Just so we get a visual, what does a horseshoe crab look like? It's kind of like a semicircle, and then there's kind of like this front shieldy part, and then there's the tail and a... I would call it a scuttling catcher's mitt. Yeah, yeah, definitely. Not bad, not bad. So there were these hordes of scuttling catcher's mitts,

you know, scuttling around. And they actually move really slowly. A lot of them would be knocked upside down by the waves. And you could see their soft underbelly. They have these ten lobster-like legs. And then walking around, them were... It's cold. It's bloody freezing. ...a bunch of people. Somebody stepping on a horseshoe crab. Was that one dead? Many of them were from a big pharmaceutical company, which will make sense in a second. But...

I'm Glenn. My guide for this morning on the beach was a guy named Glenn. Oh, Glenn.

Glenn Govry, thin guy, short hair, wearing socks and sandals. Which is right nearby.

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 their, like, champion. Oh.

They're not all that attractive unless you've been around them a while. I find them quite beautiful. 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 the sex prom. Look at them. The larger ones are females. There's a 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 right themselves. Like right now, the surf is 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. Oh, wow.

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 Burt Lancaster on the beach, you know? I forget what movie that was. I never knew it could be like this. The waves are 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.

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. But I realized really quickly was like... 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. I don't know how that works. Yes, 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. So he's got his claws gripping. And then three or four males, like, all trying to mate with this one crab at the same time. Damn. And then when you look even closer... Is this guy alive? Yeah.

It turned out the female crab was dead. Like this weird, like, necrophiliac foursome of crabs. It was kind of raunchy, actually.

But while I was standing watching all this, you know, hurly-burly of crab sex, 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. Oh, yeah, it goes right through. 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 that they'd just be walking around, no big deal. Exactly. Some of them, they have holes that you could see their legs underneath. That is nuts. 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, 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's so far has survived the industrial age of humans. And you look at it and you're like, 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 hemocyanin. But what's really interesting about this blood is this chemical system of slowing down bacteria.

So, say you're a horseshoe crab, and in your blood there's a little bit of bacteria. Maybe it got through in a crack in your shell. Anyway, in your 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, turns into this like jelly stuff. That bacteria that snuck in, it traps them, like a grape trapped in a bowl of jello. Wow. And that crack in the shell, the amoebocytes seal that off too. And what does it do with the gel then? Does 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 mobilizes it and then some other defenders come in. And then they can take it out. Take it out. And this superpower fighting its tiny battles in the bodies of these rather plain-looking creatures. Had you touched one of these guys before? No, first time. First time? How does it feel? Is the reason why people from pharmaceutical companies were on the beach that day.

Because this thing that's been playing out for literally millions of years, one day... Humans started to catch on to this. And one human in particular. Good morning.

To explain. We're going to 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 Fenimore Cooper of the. Like the last of the Mohicans guy? His name is James Fenimore Cooper. He was named after James Fenimore Cooper and his son is also named James Fenimore Cooper. Wow. Wow.

But anyway, this James Fenimore Cooper 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'd inject those materials, 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, you know, try it on a person and see if they died. They checked it on a rabbit.

And they would have like racks and racks of rabbits, like 24 rabbits in a rack. They are restrained by the neck. Rather loosely. You mean like a pilgrim being punished in the town square? Exactly right. And then they'd 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 bums.

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 pretty sensitive. So even if sometimes they'll 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.

Enter Rabbit Hall of Famer, James Fenimore 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, says, Cooper, if you want to get out of this institution with your degree, you're going to need to find a way to test for pyrogens by something other than the rabbit.

Basically, find a better way. That was sort of a joke, although I think he meant 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. Levin 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 rabbits.

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 category

chemical substance. This coagulogen in the horseshoe crab blood. It actually became a major part of the way that we test things that we're going to inject into our bodies. In every hospital, as you walk down the corridor, you look in a room, there's an IV bag hanging. Surgical instruments on a tray. Injectables for pain, infections. Your dad's pacemaker. Cancer chemotherapy. Your grandma's new hip. Your kid's EpiPen. Ah!

Immunization shots. 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 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, and the whole industry is worth, you know, like tens of millions of dollars. Woo! Scooby-Doo! Scooby-Doo!

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 Radiolab. We're back with Latif 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 therein lies the rub. So they're basically like, I think, four or five companies that go out, find horseshoe crabs, and then extract their blood. And I wanted to see, like, 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. And I was like,

I don't know why. Maybe they didn't want bad press or I don't know, maybe they weren'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 were like, hey, why don't you just come down to Charleston, South Carolina and watch what we do here?

So I went. You're just rolling. I'm rolling. Well, let me double check. 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 Radiolab staffer. Actually, she is the first Radiolab staff member, besides myself and Robert.

And Ellen. And she is a co-creator of NPR's Invisibilia. How did you get in on this? I weirdly have had affection for these creatures my whole life. I grew up with them. They're 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

And I just remember walking on the beach and seeing this like massive crab, you know, a third of the size of my body, basically. And I remember kind of jumping back and my dad saying, oh, pick it up, poke at it, you know, interact. And so I kind of turned it over and I saw 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 creature.

of what it used to be. And you 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 was just little, and I thought it was cool, and we brought it back to our porch. I remember that. It sat on our porch for years, and, like, the dog would sniff at it. So where are we going? Ever since then, there's just been a, like, mild poetic fascination. This is Visitor's Report to Building C. So I think that's...

And Lulu, 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. Is this big bad company just exploiting it for their blood? And, you know, I went with a little skepticism. Great.

Thanks. 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... Suddenly you're hit with this like... I can smell it. Wash of a smell of crabs. Yes, indeed. 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... Do you mind if I... Like exactly... Oh, you need to...

In the way of all these busy people rushing around. People are in lab coats, they're wearing hairnets. Got gloves on. 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. Flexing their claws.

So, uh, 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 passed person to person, rinsed and shining. It's like Wonka land for crabs in here. It's like a whole world. Yeah. Yeah.

Once they're washed, it's time for the bleeding. Crabs 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 got these sort of like plastic curtains all around. Can we go in? We cannot 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... This like brilliant, yeah, kind of sci-fi sky blue blood. Was slowly dripping into these glass bottles. And the crabs are kind of like, their little claws 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-y. I don't know. It was like we're sucking their blood. So it was a little creepy. Like when, so Latif, like I feel like when we were in there, there's like so many. We were in the factory. Dozens and dozens of boxes filled each with like.

Ten huge crabs. And we are in that processing zone. And before we went and saw the blood, this may 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. You want to knock? Yeah, I do. And he's just sort of holding her by the shell.

Hi. Oh, whoa. The tail is really coming right at me here. Yeah, so her little, her claws are going up and her tail's kind of waving around. Right. There's a lot of, yeah, claw activity. Exactly. And so he'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 they're 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 and bring it into their mouth. Can I get a little pinch? And so I just kind of slowly stuck my hand out toward her claws. And her claws, like, engulfed my hand. Oh, they're very claspy. It wasn't a scrabbly kind of, like, foreign...

a touch, they all the claws clasped in 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 like, 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 sprayed 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 to every year? About 500,000 horseshoe crabs every year get bled. Do the crabs that get bled and then released, I mean, do they just swim away fine? So some of them do die after the bleeding. There's a small percentage, like I think...

The conservative estimate is around like 10%, but that might be a high estimate or it might be a low estimate. I have no idea. I think it's 15%. Okay, so let's say like 15%. So if you're talking about 500,000 crabs being bled 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? —

were actually able to see that a lot of the crabs don't have, like, bled crabs and non-bled crabs, like, have slightly different movement patterns. And that's because, you know, 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 bled animals appear more lethargic. They move, you know, more

more slowly. And, like, imagine if you had to go, like, harvest deer and then bleed them with 30% of their blood and then you'd, like, leave them back out in the forest. Like, 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 rednought.

Now, the incredible thing about red knots is of all the birds in the world, the red knot makes one of the longest migrations, nearly 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 five months.

And what happens is thousands of these red knot 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 the skies again. And they fly up along the eastern coast of South America over the Atlantic Ocean. But before they get to their final nesting grounds, they make one more stop. One pivotal, crucial rest stop in the Delaware Bay.

It looks like it's very fresh. Yeah. And not dried up. Yeah.

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, I don't know if you've been noticing all the eggs. They need to eat millions of horseshoe crab eggs to complete their migration. Oh, this is an egg cluster right there. Oh, wow. Oh, wow. Oh, I'm going to be really careful where I step now. And this is the thing. It's weirdly these birds that might actually free the horseshoe crabs.

from us. Yeah, yep. And to explain, I got in touch with this guy. My name is Jay Bolden. A biologist. In the global quality laboratories at Eli Lilly and Company. So Eli Lilly and Company, it's this huge pharmaceutical company that makes, you know, cancer drugs and antidepressants. 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.

Radiolab is brought to you by... Anyway, um...

One of the things the company's been helping innovate is... Horseshoe crab blood. A synthetic version of horseshoe crab blood. Yeah, so... And, you know, Jay explained to me, if you kind of like zoom out for a second and think about what it means to use horseshoe crab blood for this, you know, vital thing in medicine... The problem is there needs to be a supply of horseshoe crabs. 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. 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 bloop, bloop, bloop, bloop, bloop, bloop, bloop.

around the bad bacteria. And now we can make the protein of interest instead of getting that directly from horseshoe crabs. Huh, so why aren't we already using that? Well, Jay explained that there's, you know, 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!

Our good 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 bird's 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. Glory and freedom forever.

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 crab 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.

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? A little orgy. 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? We'd catch them, cut them up, and use them to, like, as bait to catch more valuable species, like particular kinds 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 3 million horseshoe crabs being killed every year for commercial fishing. 3 million, wow.

Wow. But more recently, we've 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, you know, 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 going to 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 Latif. Nice to meet you. Nice to meet you, too. Thanks for having us here. Yeah, more than glad to. This is so cool.

And there was this moment where everything just kind of flipped for me. You know, like where I realized that as cruel and kind of grisly 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 more horseshoe crabs? 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 horseshoe crabs for the company. What a peaceful little spot. So we were 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, me too. 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... What have you got there? Jerry, like, 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. Oh yeah, they do 100,000 eggs a day.

Wow. Yeah, they're like the size of a really round grain of rice. They're kind of like pearled couscous. Pearled couscous is right. Were they laying the eggs here, or did you get the eggs from where you were? They lay their eggs along the shore. Oh, on this bit of shore here? Yeah. Oh, literally right here. Oh, wow. That's so cool.

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 with ADD.

But Jerry told us the gist of it is back when his dad was doing seafood fishing. You know, I was just a tyke. 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, you know, he'd make a deal for me. He would buy them. Buy them for more money. So Jerry's dad said, sure. We've been doing it ever since.

But I've 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 I can't say that about soft-shell crabs or grouper, you know. Yeah, you touch every one and then you touch it again and return it. Well, 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 divine design, the horseshoe 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're important to human society. And it just draws me back to the idea that it was a divine design. They've been around for 400 million years. It took us this long to figure it out, I guess.

Out of curiosity, where did that leave the two of you? Well, for me, I mean, Jerry, the fisherman, he's totally right. Like, we just figured this out. These crabs have been Clark Kenting us this whole time. They have this hard-won superpower that they've probably had since, you know, before, like, three branches on our evolutionary tree. And...

And in evolutionary terms, like, they're the winners. We're chumps. We're baby chumps. 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, we're not unlike an asteroid or just another thing they're probably going to endure. Like, we are a blip to them. And yet...

We're a dangerous blip, 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 in 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 I 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? Slide to go down. To do it more gently. Now we pick them up, set them into this slide, and the water takes them down to the river. Before, we used to pick them up and toss them. And we've gotten away from tossing them. It's amazing. I've got a slide on my dock, 200-foot-long water slide, where they rehydrate on their way to the river. See how fast they pull those their way down? You don't want to get your finger caught in there. Do you want to hold it? Yeah, sure.

So this is the male. That's the male. And we just interrupted his embrace. His game. His 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 L.A.L.,

Then, still early on in the pandemic, I called up Dr. James Fenimore 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,

you know, what was new. Tell me the story of LAL in the time of COVID. 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

That's required for every vaccine right now. So you're saying that no matter which one gets there first or, you know, however many get there 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 L.A.L. 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 vaccines, Dr. Cooper says they have to test all of their ingredients of 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. That's 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. OK, 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, that's been tested with LAL before it left the factory. Let's say you get hooked up to IV fluids. Those IV fluids would also be horseshoe crab approved, as would be the IV bag, the tubes, the catheter going into your vein. Let's say worst case scenario, you need to go on a ventilator.

Wow.

But, uh, but LAL is still the standard. Holy moly. So it's like, it's like, it's everywhere. Wow. Super impressive. Um,

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 going to 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 of the L.A.L.?

Well, a number of months ago, the three major LAL producers got together and came up with a scenario that if they made 5 billion doses. Doses of vaccine, you mean? Yeah. Vaccines, yeah.

how much LAL would that require? 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 1% of their inventory. Whoa, that's...

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 going to make it work. Like the supply chain is really like where we got it. And these guys are like, nah, no big deal. Uh,

Are they bleeding more than they need to bleed? So they have said no. They have said no. 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 scale of it is such that

Like 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. Got it. That's the claim. I just am suddenly asking myself questions about the baseline scale at which they operate. I'm like, what are they –

How is that possible? How is that possible? Do they have warehouses full of that blue blood? Yeah. Just in case like... Yeah. Well, it is a pretty important... 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 like...

just anticipating any problems and the fact that it's like written into the regulations that literally medicines need this thing. Oh, interesting. You know, like it's like you need to have this much in a warehouse because it's so important. That's interesting. That would be my guess, but I could look into that more. That's really interesting because, I mean, it reminds me of 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 road. But that seems so super smart. Now that you mention it, of course, there's horseshoe blood in the reservoir. Yeah.

So, okay, so that's 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 this 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, after we overfish them for basically a century and a half, they're doing, they're doing all right. And, 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, we are sort of saving them too. Yeah.

Thanks to Lakia Wimbish and everyone at Lonza's Global Endotoxins Testing Summit, Mike Kendrick and Brad Floyd of the South Carolina Department of Natural Resources. Also, Tamara Ann Hull at Eli Lilly. And of course, Kate Contreras, John Dubcheck, and the rest of the team at Charles River. I'm Jad Abumrad. I'm Robert Krowich. Thanks for listening.

Radio Lab was created by Jad Abumrad and is edited by Soren Willer. Lulu Miller and Latif Nasser are our co-hosts. Susie Lechtenberg is our executive producer. Dylan Keefe is our director of sound design. Our staff includes Simon Adler, Jeremy Bloom, Becca Bressler, Rachel Cusick, W. Harry Fortuna, David Gable, Maria Paz Gutierrez, Sindhu Nyanasambandham, Matt Kilty, Annie McEwen, Alex Neeson, Sara Kharey,

Anna Raskwit-Paz, Sarah Sandbach, Arianne Wack, Pat Walters, and Molly Webster, with help from Bowen Wong. Our fact checkers are Diane Kelly and Emily Krieger.

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