05/11/2025
Horseshoe Crab Blood Has Long Helped Us Make Safe Medicines.
Now, Alternatives That Spare the Ancient Creatures Might Be Breaking Through
An enzyme in the blue blood has been key to testing vaccines since the 1980s, raising concerns for the crabsâ population. But regulatory approval and new data are signaling the tide may be turning
Each May, hundreds of thousands of horseshoe crabs climb onto beaches along the eastern coast of the United States. An invertebrateâs âLove Island,â males compete to procreate with the largest females. The hum of scampering claws and tapping shells fills miles of beach.
The American horseshoe crab is not the most glamorous or endearing animal. With its long, spiky tail, helmet-shaped shell and ten eyes, the 445-million-year-old species did not get this far relying on its good looks. But in this annual event, called a mass spawning, the crabs leave behind tens of thousands of eggs, which contribute to a wider ecosystem along the Eastern Seaboard and allow the ancient species to continue thriving.
Itâs âthe most magical natural phenomenon,â says Will Harlan, who acts as the Southeast director at the Center for Biological Diversity. He took his kids to witness a horseshoe crab mass spawning in Delaware last spring. Usually, his children are glued to their screens, says Harlan, but that night, they couldnât look away from the sea of crabs scuttling ashore under a full moon.
Fun fact: Horseshoe crabs arenât really crabs
Despite their name, horseshoe crabs are not crabs or crustaceansâtheyâre chelicerates, more closely related to spiders and scorpions.
Since the 1980s, humans have prized horseshoe crabs for another reason: The invertebratesâ light blue blood has likely benefitted anyone who has ever received a vaccine or flu shot. Equipped with a system that detects toxins as soon as they enter the crabsâ bloodstream, the blood is a key ingredient in a product that can detect contaminants in medicines. Pharmaceutical companies use the mechanism to ensure their drugs are safe. But amid concerns for the horseshoe crab population, conservationists, biotechnology experts and drug manufacturers alike have spent decades pushing for the adoption of synthetic alternatives that donât harm the animal.
This spring, that effort reached a new milestone. For the first time, the industryâs primary regulatory body, the U.S. Pharmacopeia, officially recognized the alternatives as an option for companies to test vaccines. Now, 11 major pharmaceutical companies have reported an initial shift or intent to shift to these alternatives in a survey conducted by conservation groups. And the biggest producer of the blood-derived product publicly backed the crabless alternatives this summer.
Harlan says his organization, which worked on the survey of the pharmaceutical companies, hopes to see all 50 of the largest companies by profit shift to these alternatives. But it might not be a rapid transition, as making that change involves navigating an intricate network of corporations and regulatory bodies.
Around the time Harlan took his kids to Delaware Bay, Allen Burgenson took the day off work to visit another beach and flip horseshoe crabs that had gotten stuck on their backs during the spawningâa tradition heâs had since he was 3 years old. This small act can save the invertebrates from an immobile death sentence on the shores of the bay, he says. Burgenson has spent his career in biotechnology researching, advising and working on the horseshoe crab blood tests and alternatives.
Jay Bolden, too, traveled to Delaware Bay last spring as part of a meeting of leaders in the pharmaceutical industry. Bolden spearheaded the first widespread shift to the crabless alternatives in the U.S. at Eli Lilly, where he works as a senior director and biologist. He and his peers at other companies spent several days learning about these alternatives, discussing the possibilities for their respective companies and seeing the crabs in action. His beach day, he says, was âgratifying.â
âA lot of the time, people donât think beyond the four walls of the lab,â he says. âBut to make that connection, to see it and hear it and smell it, is really cool.â
Harlan, Burgenson and Bolden share a deep love for the species and its natural ecosystem. Although they approach the issue from different worldsâconservation, biotechnology and pharmaceuticalsâthey all say the new, crabless alternatives are the future. But that future has long faced regulatory roadblocks, conflicting research and an extremely cautious pharmaceutical industry.
Horseshoe crabs predate dinosaurs. Can they survive us?
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https://www.smithsonianmag.com/science-nature/horseshoe-crab-blood-has-long-helped-us-make-safe-medicines-now-alternatives-that-spare-the-ancient-creatures-might-be-breaking-through-180987553/?utm_source=smithsoniandaily&utm_medium=email&utm_campaign=editorial&lctg=91983098
