Short Wave - Medicine And The Horseshoe Crab

Episode Date: April 22, 2021

Horseshoe crabs have been around for 450 million years — nearly unchanged. And their blood has helped the medical world make some fascinating discoveries. Emily Kwong talks with Ariela Zebede about these living fossils and their role in making medicine safer. Get in touch! You can email Short Wave at [e-mail]. See pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. Well, hello there. Aurella Zabidi, once shortwave intern, forever Shortwave legend. Welcome back. Hi, Emily. I'm so happy to see you. Same. And I'm actually coming with some big news today.

I got vaccinated. Yay! Congratulations. Yeah, they opened it up to all adults in Florida a couple of weeks ago, so I got a lucky shot. Amazing. And you know that I've been waiting for this moment for months, but once I was actually in the room, the rest was easy. I got jabbed. I waited 15 minutes and I left. But sticking needles in our arms wasn't always such an easy thing. I talked to Alan Bergenson. He works for the biotech company, Lonza. And he told me, In the early days of injection, your doctor was literally taking your life into his hands. He had to decide whether the risk of injection was worth risking. your life? You know, was your disease that serious that you needed an injection? Why was an injection at that time so dangerous? Well, when people got injections at the turn

of the 20th century, sometimes they would get this thing called injection fever. And some people became really sick and they even died. And for a while, scientists didn't really know why this was happening. They finally found out that it was due to something called endotoxin, which is a ubiquitous substance in nature. It's on our skin. It's on environmental surfaces. I think I've heard of endotoxins. It's like this type of toxin found in some types of bacteria, right?

Like E. coli and salmonella. Yeah. And it's usually harmless. But if it gets into your bloodstream, it can be really dangerous. Nanogram amounts, that's one billionth of a gram, is enough to make you very sick. And a little bit more than that is enough to kill you. So that's why it's very important. that anything that's injected into the human body be checked for endotoxin.

Yeah, sounds very important. So how do scientists even check for endotoxins when figuring out whether it's safe to give someone a shot today? Well, Emily, we rely on the ancient survival wisdom of an unexpected critter, the horseshoe crab. Get out. What? Yes, and they've been quietly protecting all of us from infection for decades. Gates. I can't wait. So today on the show, we've got a story where these living fossils collide with dangerous toxins and medical injectables. We'll learn about horseshoe crabs and how they are essential

in bringing us tons of medical breakthroughs, including the COVID-19 vaccine. This is a shortwave, the Daily Science podcast from NPR. Okay, Arielizabidi, we are talking about horseshoe crabs and vaccines today. Two things I never thought would be brought together in a sentence, but here we are. Yeah. And I want to start off by talking about these animals because they are just incredible. And if you're on the U.S. Atlantic Coast, they're your neighbors. So before we dive in, I have to mention all of the biologists I talk to will kill me, these animals aren't really crabs at all. It's a misnomer. They're actually much more closely related to spiders or scorpions. Right, right. They've got that hard shell, that pointy tail.

And horseshoe crabs are ancient creatures, Emily. They've been around for at least 480 million years. I think that's my favorite thing about them. I mean, to put that into perspective for everyone, the oldest known homo sapiens, like our human species, are only a few thousand years old. So, you know, think about that. These are old, old, old creatures. Yeah, and I talked to Sam O'Con, a grad student. in paleontology who studies horseshoe crabs. They've been around for all five major mass extinctions. And I always like to joke that some groups got lucky and they've only had to go through one.

And even though that makes them survivors, horseshoe crabs are like the champions of surviving mass extinctions. Champions! And what's especially amazing about horseshoe crabs is that if you look at the oldest fossil records we have of them, and I'm talking 450 million years old, it looks just like the horseshoe crabs you'd see today

on the east coast of the U.S. That's why you sometimes hear them called living fossils. Don't fix it if it ain't broke. They're not going to change up their body plan if there are no real problems with it. Don't hate me because I'm perfect. That's what the horseshoe crabs would say. They're so cool. From above, they look kind of like military helmets, but they're flatter and really shiny.

Yeah, they give me strong military vibes. But I asked Sam, if you had to assign an emotion to these critters, what would you call them? probably unbothered. Unbothered. That is so good. They're actually really harmless. They're not venomous. They don't sting or bite. They're not exactly the type of animal you'd expect to have survive for so long. Yeah. How have they done that? Well, Sam says mass extinction survival is always a little bit of luck, but horseshoe crabs are also really resilient. It could be the fact that they're generalists. So they're not super picky about temperature or food, really. So, you know, if your environment's wildly fluctuating, it helps to not be picky because, you know, beggars can't

be choosers in an extinction. Yeah, so I guess their unbotheredness has kind of saved them. Yeah, exactly. But Sam told me there's something else going on to, something that might help explain their survival. And the key is in their blood. So their blood is blue because it has copy. in it as the major binding element to oxygen, whereas our blood's red because we have iron in our blood. So it's blue, which makes it really, really cool looking. And it has this really efficient way of fighting off bacterial infections. So say a horseshoe crab gets hurt and some bacteria gets into its bloodstream, while the blood immediately clots around the infection, basically sealing it off. Wow. And that stops more bacteria from coming in? Yeah, and it also stops the infection

from spreading to the rest of the body. In the mid-1900s, this guy, Fred Bang ran some experiments where he'd expose horseshoe crabs to bacteria. And he noticed this weird reaction where pretty much all of the blood in the entire horseshoe crab hardened and turned into this gel-like substance. What was causing that? Well, Fred and this guy, Jack Levin, partnered up, and they realized that endotoxins were responsible.

Oh, that's the toxins found in some of the bacteria we talked about earlier. Exactly. And they had this big aha moment where they realized they could use the horseshoe crab blood to detect endotoxins. So they created this new test called limelis amoebocyte or LAL for short. And I mean, this stuff is amazing, Emily. It can detect even tiny, tiny trace amounts of endotoxin. Well, one, great pronunciation there. Two, you know, when it comes to keeping vaccines and other injections safe, a test like that must have just revolution. It did. You know, before LAL, pharmaceutical companies had to keep these giant colonies of rabbits, and they'd basically inject them with whatever drug, and then they'd wait a few hours to see if the rabbits developed a fever. That had to be really tough for the rabbits. Yeah, and LAL was also cheaper and more efficient than the rabbit test, which meant pharmaceutical companies could test for endotoxin at various points throughout the process. Allen says that today everything used to make an injectable drug, from water to the vials it sits in, all the way to that final product are typically tested for endotoxin.

Every last lot of COVID vaccine or any other vaccine or any other injectable, every lot by law must be tested. So LAL has become really, really important. But the process used to make it can pose some real complications for horseshoe crabs. What kind of complications? Because I've been wondering how this impacts the horseshoe crabs. Yeah, well, first let's talk about how LAL is made. Okay. Every company does this a little bit differently, but basically they're extracting horseshoe blood.

And horseshoe crabs spend most of the year in deep waters. But in the late spring and early summer, when it's time to mate and lay their eggs, they come up to shore and they have this little party. I've actually witnessed this event many times throughout my childhood. It's like piles and piles of horseshoe crabs all over each other, and they cover the entire beach. Yeah, so once they come up to shore, that's when they're collected, and they're cleaned off and brought to a nearby facility where they use needles to extract the blue blood from the crabs into these clear bottles. And they're really interested in the stuff that hangs out inside the blood cells. So once they've collected the blood, they pop those cells open and isolate what's inside.

And what happens to the crabs after the bleeding? You can think of it as similar to when we get blood drawn. They take a portion of blood from each crab without depleting them entirely. So the bleeding process takes about a day and then the crabs are brought back to the water. So how does that impact the horseshoe crabs long term? Well, we know that the body can regenerate lost blood. And the majority of horseshoe crabs survive, but not all of them. An expert commission estimates that about 15% of the crabs die soon after bleeding,

but there's a wide range of mortality estimates. Okay, so the takeaway here is that some of the horseshoe crabs do die from this bleeding process. Yeah, and there's also evidence that getting bled leaves the horseshoe crabs weak, making it harder for the females to lay eggs. Yeah, so have we seen declines in Atlantic horseshoe crab populations because of our dependence on them for this? So there was definitely a decrease in the early 2000s, and there are a lot of potential reasons for this decline. I talked to Helen Cheng, she's a marine biologist.

In addition to the biomedical industry, they're also harvested as bait for other fisheries like eel and kank. The other thing is coastal development. So as more and more people decide to live on the coast or by the coast, it's essentially impeding on their prime habitat, which are coasts. and sandy beaches. Yeah. When you started this story, I just felt so appreciative of horseshoe crabs and this role they play. But it's really sad to think that these creatures who have survived every mass extinction our planet has seen could be so impacted by us. Yeah, and it's unclear how much the bleeding process specifically is contributing to this decline compared to all the other factors.

But ironically, the fact that the biomedical industry depends. on these animals has actually inspired some conservation efforts. Oh, yeah. I mean, it's like we selfishly need to keep these animals alive. Right. And in recent years, we've actually seen populations stabilize in some areas, but the population still isn't what it used to be. And other animals in the ecosystem that depend on horseshoe crabs or food have suffered for it. I mean, look, it is remarkable that a chemical from this ancient animal is so effective at detecting endotoxins. But, But it is strange to me that we haven't come up with an alternative, you know, so that we don't have to rely on horseshoe crabs anymore for this.

Well, scientists have actually engineered a synthetic version that could potentially replace the traditional LAL test. In Europe and China and Japan, the two tests are recognized as equivalent. But the U.S. hasn't jumped fully behind the new version just yet. And until then, we'll continue to rely on the LAL test and our new favorite invertebrates, because they've made amazing things possible. Well, I'm glad we're taking a moment to think about it because it sounds like we wouldn't be where we are right now with managing this pandemic, with modern medicine, without them.

Absolutely. And obviously, these critters have been essential and so much of modern medicine. But I'm hopeful that in the future, we can have safe injectables while also not relying so much on these animals that have already given us so much. Well, Aurella Zabidi, thank you so much for this reporting. Thanks for having me, Emily. This episode was produced by Thomas Liu, edited by Beatle and Griesel Grayson, and fact-checked by Burley McCoy.

The audio engineer for this episode was Josh Newell. Special thanks to Heidi Swanson at the Ecological Society of America and Charles Riverville Laboratories for the audio. You're listening to Shortwave, the Daily Science podcast from NPR. In stressful times, you want to spend your time checking out not just what's best, but what's best for you. We know you care about what you watch, what you read, and what you listen to. NPR's Pop Culture Happy Hour podcast is with you five days a week to make sure that time is well spent. Listen now to the Pop Culture Happy Hour podcast from NPR.