Horseshoe Crab Blood

Every year, in late spring, America’s Atlantic coastline hosts one of the animal kingdom’s wildest orgies. The sandy shores are taken over by thousands of horseshoe crabs, who mate and lay clusters of eggs. This feverish lovemaking might be a part of why the species is so resilient.

Horseshoe crabs have been around for around 450 million years. They were here before the dinosaurs, and survived a mass extinction that wiped out 90 percent of life on Earth. But lately, a new species has joined the party: humans — humans who are, quite literally, out for the horseshoe crabs’ blood.

MARON: They have this somewhat magical blood. It’s used to do a lot of our pharmaceutical testing, everything from Covid vaccines to insulin to any injectable medications that we use on a day-to-day basis.

Horseshoe crab blood has been called the “medical equivalent of gold.” By one estimate, it’s worth around $60,000 dollars a gallon. And the growing market for it is at the center of an ethical debate between environmentalists and biomedical firms.

For the Freakonomics Radio Network, this is The Economics of Everyday Things. I’m Zachary Crockett. Today: horseshoe crab blood.

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To better understand how horseshoe crab blood became such a valuable commodity, I turned to an expert.

MARON: I’m Dina Fine Maron. I’m the senior reporter that covers wildlife crime at National Geographic.

Maron has investigated rhino horn trafficking, dinosaur fossil heists… even leech smuggling.

MARON: Yeah, it’s a pretty wild beat.

Her interest in horseshoe crabs began after she spotted one on a beach in Delaware.

MARON: They’re really weird looking creatures. They actually are not crabs. They’re more, like, closely related to scorpions and spiders. They have these lobster-like legs. There are ten of them. They have armored backs and a spear-like tail. And I was wondering, “Gosh, what are these things?” Then when I started digging in, I was really surprised to learn that they are such an integral part of our daily life.

The commercial market for horseshoe crabs began in the 19th century, when they were ground up and used as fertilizer and chicken feed. Fishermen eventually realized they could make more money selling them as bait to catch eels. But in the 1960s, an infectious disease expert named Frederik Bang discovered that horseshoe crabs could be used for a greater purpose.

MARON: From an evolutionary perspective for the crab, what’s pretty neat is, let’s say they crack their shell and some bacteria got in. There are components in their blood that are hyper sensitized to bacteria or specific kinds of bacteria called endotoxins. They’ll clot and they’ll sort of form this semi-solid gel wall all around the bacteria, keeping the animals safe.

That sensitivity is what makes the blood useful to humans. Even trace amounts of endotoxins introduced to our system can kill us. So, anything that comes into contact with our blood has to be tested before it’s approved for use.

Before Bang’s discovery, the only way for pharmaceutical companies to conduct these tests was to inject rabbits and see if they got sick. In horseshoe crab blood, Bang saw an easier and cheaper alternative. With his colleague, Jack Levin, he developed a new test called L.A.L.

MARON: L.A.L. is actually the acronym that’s referring to the product that is particularly in demand in the blood. It stands for limulus amebocyte lysate. What you do is you take the horseshoe crab blood and they mix it at a specified ratio with whatever you’re trying to test in the laboratory. And then they’re looking for a semi-solid blob that would form around something that’s a problem. And so if you don’t see that clotting taking place, you’re good to go.

The L.A.L. test was approved for use in 1977. Today, more than 80 million of them are used every year. The odds are extremely high that you’ve personally benefited from horseshoe crab blood. Pharmaceutical companies use it to make sure things like implantable medical devices, insulin, flu shots, and vaccines are free of toxins before they go into your body.

MARON: When people were developing Covid vaccines and they were preparing them to be used in humans, they needed to make sure that there was no bacteria that would, you know, then be injected into people. They needed to know that the solution holding the vaccine was safe. And so they would be testing that in the lab using, yes, an L.A.L. test. So we have horseshoe crabs to thank for the vaccines that we’ve continued to utilize.

So, how exactly is all of this horseshoe crab blood collected? And what happens to an ancient species when humanity finds a use for its blood?

MARON: We don’t really know the full impact of this demand for their blood on the animals and their long-term survival.

That’s coming up.

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There are four species of horseshoe crabs on Earth. Three of them live in waters around Asia. But the horseshoe crabs that are used to make L.A.L. tests for the U.S. market are only found on the Atlantic coast, from Maine down to Mexico. Every spring, they head to shore. Dina Fine Maron says it’s a wonder to behold.

MARON: Females are unsurprisingly in demand, so some males try to clasp onto the females in the water while they’re being turned over and over and over by the waves. So sometimes they’ll arrive beached, upside down, and they’re trying to fight to turn themselves over. A female will be surrounded by males who are all trying to win, if you will. Then the female lays her eggs in the sand and then they all hopefully return to sea.

It’s during this cycle that the biomedical firms swoop in. Only five companies in the United States are licensed to harvest horseshoe crabs for medical purposes.

MARON: They’re all scattered along the East Coast. There’s Associates of Cape Cod in Massachusetts, Limuli Labs in New Jersey, Lonza in Maryland, FujiFilm Waco Chemicals in Virginia. And then Charles River Laboratories in South Carolina and in Massachusetts.

None of these companies agreed to an interview. And that’s par for the course: the industry is extremely secretive. What we do know is that biomedical firms generally contract fishermen, who scoop up hundreds of crabs — either from the shore, or with trawl nets. They pry barnacles off their shells, then transport them by the truckload to a lab. In the lab, the live crabs are strapped to a long steel rack, and their blood is harvested.

MARON: Folks who are wearing lab coats and hairnets insert a needle and then blood drip, drip, drips down. It is this baby blue color and, like, milky consistency. It’s really striking. It doesn’t look like something you would find in nature because it’s just this distinctive color.

A single horseshoe crab can yield anywhere from 50 to 400 milliliters of blood. Once the blood is collected, tiny cells called amebocytes are extracted from the plasma and broken down in water to create the L.A.L. This solution is packaged and sold to labs across the country — sometimes, at a price of around $100 a test. A gallon of horseshoe crab blood has a market value of around $60,000.

That’s great for the companies that sell it — but not so hot for the crabs.

MARON: About a third of their blood is bled out and then they’re put back into the wild. But obviously some of these animals don’t make it, and an unknown amount of them may have sublethal problems as well.

In 2021, 718,000 crabs were harvested for blood. Around 15 percent of them died in the lab. And that figure doesn’t include the crabs that die after being released. There are also concerns about how the practice affects breeding.

MARON: Scientists in recent years have found that it looks like, unsurprisingly, once you take a third of an animal’s blood, they appear to be more lethargic, they’re less likely to come to the beach, which means there’s less likely to spawn, which raises questions about those animals’ future.

There have been efforts to mitigate these deaths.

MARON: One researcher I spoke to, he was trying to do the equivalent of just like after a human might donate blood and you might get cookies and juice after, he was wondering, “Well, what if we keep the horseshoe crabs ashore for a while longer, make sure we give them a good amount of food and rest before they’re released?” And he said that he was seeing really good outcomes. 

But researchers are up against a bigger problem. In addition to being harvested for blood, horseshoe crabs are still caught and sold as bait to catch eels. Some watchdog groups say that the dual threats of the biomedical and fishing industries could reduce horseshoe crab populations by 30 percent over the next four decades. The International Union for Conservation of Nature now lists American horseshoe crabs as a vulnerable species. Things are worse for the three species of Asian horseshoe crabs.

MARON: Norms are different there as far as the species are not returned to the water. Their horseshoe crabs are bled to death and then typically sold for food. And consequently, there’s concern that there could be more demand for the Atlantic horseshoe crab because of dwindling numbers of these Asian horseshoe crabs, some of whom are endangered.

These declines have conservationists worried. Because fewer crabs means fewer crab eggs. And that has potentially devastating effects on other species that depend on them as a source of food.

MARON: There is a shorebird called the Red Knot. A huge staple of its diet when it makes its fall migration is, in fact, the eggs of the Atlantic horseshoe crab.

Red Knots are also on the decline, largely thanks to the overharvesting of horseshoe crabs. Coastal states have placed quotas, moratoriums, and bans on the use of horseshoe crabs as bait. But the biomedical industry has historically faced little regulation. It can generally harvest crabs without limitation. These companies are well aware of potential supply issues. Their revenue depends on a sustainable harvest.

MARON: Lonza, which is one of the five biomedical companies that collects them, issued a report recently and said that they were really concerned about future supply. They felt that demand for gene therapies and personalized medicine were putting increased stress upon the species.

Currently, there is no widely available alternative to horseshoe crab blood. If it runs dry, the testing industry could face a crisis. Researchers have been looking into the possibility of a synthetic alternative.

MARON: The argument in the past was, “Hey, nothing’s as good as horseshoe crab blood, so we need these horseshoe crabs.” But in the last decade or so, there’s been a lot of work to develop synthetic alternatives, which do seem really promising. And actually, pharmaceutical giant Eli Lilly started to shift all its products that require endotoxin testing to the synthetic alternative back in 2016. Now 80 percent of Eli Lilly’s tests rely on the synthetic alternative, not a horseshoe crab blood.

But synthetics come with added costs that most companies aren’t willing to swallow. So, at least for the foreseeable future, horseshoe crabs will continue to see their mating ritual interrupted. This spring, just as they’ve done for 450 million years, they’ll crawl up onto the sandy shores in search of love.

MARON: Horseshoe crabs are creatures of habit, much like many of us who may return to the same areas. And if you return and there aren’t enough mates to be had, that’s going to be a problem longer term.

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For The Economics of Everyday Things, I’m Zachary Crockett. This episode was produced by Sarah Lilley and mixed by Jeremy Johnston. We had help from Lyric Bowditch, and Daniel Moritz-Rabson.

CROCKETT: Limulus amebocyte ly — that’s a hard word.

MARON: It’s quite a mouthful.