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Every spring, hundreds of thousands of horseshoe crabs walk the beaches of the East Coast of the United States to lay their eggs. For hungry birds, it is a feast, and for pharmaceutical companies it is a crucial resource for making human medicines safe.

This is because the milky blue blood of these animals provides the only known natural source of lysed amebocyte limulus (ALL), a substance that detects a contaminant called endotoxin.

Human health means their death

“All pharmaceutical companies around the world rely on these crabs. When you think about it, it’s pretty amazing how much we trust this primitive creature, ”says Barbara Brummer, director of state for The Nature Conservancy of New Jersey.

Every year, pharmaceutical companies collect half a million horseshoe crabs from the Atlantic, extract their blood and send them back to the ocean – a process in which many of them will die.

Extraction of blue blood from horseshoe crabs

This practice, together with the excessive harvesting of crabs for fishing bait, has caused a decline in species in the region in recent decades, according to National Geographic.

There are alternatives, but not everyone believes in them

Catching crabs and collecting their blood is time consuming, and the resulting lysate costs $ 60,000 per gallon (4.54 liters). In 2016, a synthetic alternative to crab lysate, recombinant factor C (rFC), was approved as an alternative in Europe and even a few US pharmaceutical companies started using it.

But on June 1, 2020, the American Pharmacopeia, which sets scientific standards for drugs and other US products, refused to place rFC on an equal footing with the crab lysate, claiming that its safety is still unproven.

Since July, Lonza, based in Switzerland, has begun manufacturing a Covid-19 vaccine for human clinical trials – and will have to use the lysate in the vaccine if it intends to sell it in the US.

Human health and safety, especially for something as high as the coronavirus vaccine, is paramount, says Brummer.

But she and other environmentalists fear that without rFCs or other available alternatives, the continuing burden on horseshoe crabs for COVID-19 and related therapeutic vaccines could endanger crabs and their dependent marine ecosystems.

Blue blood no longer presupposes privileges

Almost unchanged for hundreds of millions of years, horseshoe crabs have some unusual features. Despite their name, these creatures are more closely related to spiders and scorpions than to crabs. They have nine eyes – two compound eyes and seven simple eyes.

In 1956, medical researcher Fred Bang noticed another strange feature: when horseshoe crabs’ blood interacts with endotoxin, cells called amebocytes coagulate and form a solid mass.

Bang realized that these amebocytes – part of the crab’s old immune system – could detect deadly bacterial contaminants in the range of pharmaceuticals designed to enter human bloodstream.

Scientists eventually learned how to use amebocyte lysate to test drugs and vaccines, and in 1977, The US Food and Drug Administration has approved it horseshoe crab lysate for this use.

Since then, every May, crabs are brought en masse to specialized laboratories in the United States, where technicians extract blood from a vein near the heart before returning it to the ocean water. Their blue blood comes from the metallic copper in their oxygen-carrying proteins, called hemocyanin.

There are efforts to repair the damage

In the 1980s and into the early 1990s, the process seemed sustainable. The pharmaceutical industry claimed that only three percent of the crabs whose blood was drawn died. Population studies have shown that crabs are numerous and conservatives have not given much value to the species, says Larry Niles, a biologist at the Conserve Wildlife Foundation in New Jersey.

But in the early 2000s, the image began to change. The annual number of horseshoe crabs during the breeding season revealed a smaller number, and a 2010 study found that up to 30 percent of the crabs whose blood was drawn eventually died – 10 times more than it had been estimated for the first time.

“The fight we are fighting is not just a fight for horseshoe crabs. It’s about maintaining the productivity of ecosystems, ”says Niles, who has spent his career researching the environment and species in the Gulf of Delaware.

Lonza, the Swiss corporation, says it is “committed to protecting the welfare of the horseshoe crab”, for example, “actively supporting conservation efforts”.

According to the Lonza statement, Charles River Laboratories and another lysis manufacturer, Associates of Cape Cod Inc., grow horseshoe crabs in incubators and release them into the ocean. Lonza reports that in 2019, Cape Cod reintroduced 100,000 young crabs into the waters around Massachusetts and Rhode Island.

According to Lonza’s statement, the company would also prefer to use lysed alternatives and branded its own rFC, called PyroGene. But, as the American Pharmacopoeia’s decision illustrates, “regulatory barriers remain.”


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