Horseshoe crab blood is key to making a COVID-19 vaccine—but the ecosystem may suffer.

Conservationists worry the animals, which are vital food sources for many species along the U.S. East Coast, will decline in number.

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An Atlantic horseshoe crab lies on the beach in Stone Harbor, New Jersey, not far from Delaware Bay.

Each spring, guided by the full moon, hundreds of thousands of horseshoe crabs clamber onto beaches across the U.S. mid-Atlantic to lay their eggs. For hungry birds, it’s a cornucopia. For drug companies, it’s a crucial resource for making human medicines safe.

That’s because these animals’ milky-blue blood provides the only known natural source of limulus amebocyte lysate, a substance that detects a contaminant called endotoxin. If even tiny amounts of endotoxin—a type of bacterial toxin—make their way into vaccines, injectable drugs, or other sterile pharmaceuticals such as artificial knees and hips, the results can be deadly.

“All pharmaceutical companies around the world rely on these crabs. When you think about it, your mind is boggled by the reliance that we have on this primitive creature,” says Barbara Brummer, state director for The Nature Conservancy in New Jersey.

Every year, pharmaceutical companies round up half a million Atlantic horseshoe crabs, bleed them, and return them to the ocean— after which many will die. This practice, combined with overharvesting of the crabs for fishing bait, has caused a decline in the...

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