The Race for a Coronavirus Vaccine Runs on Horseshoe Crab Blood

Pharmaceutical companies use the creature’s blue blood to test for contaminants

Horseshoe crab blood drain
Horseshoe crabs are bled to harvest a key ingredient in tests used to ensure injected medicines such as vaccines are free of contaminants. This photo was taken in 2014 at the Charles River Laboratory in Charleston, South Carolina. Photo by Timothy Fadek / Corbis via Getty Images

Humans owe a debt to the strange-looking, ancient horseshoe crab. Its blue blood is used in medicine to ensure that anything that gets injected or implanted into the human body is free of potential bacterial contamination. A special compound in the crab’s blood quickly clots in the presence of endotoxins, microbial byproducts that can be harmful, supplying a perfect natural test for purity. In the race to find a COVID-19 vaccine, horseshoe crab blood is very important.

But an estimated 50,000 crabs die during the annual blood harvest, and these ancient arthropods are also being threatened by pollution, overfishing (for use as eel bait) and habitat loss due to sea level rise, reported Sarah Zhang in the Atlantic in 2018. Moreover, humans aren’t the only ones depending on the crabs (which are actually more closely related to spiders than true crabs). Migratory birds such as the threatened red knot are sustained by the blue-gray bunches of eggs the shelled creatures deposit by the thousands on beaches along the east coast of the United States.

For these reasons, animal rights groups, conservationists and a handful of companies have been pushing for the development and approval of synthetic alternatives to the milky-blue crab blood, reports James Gorman for the New York Times.

Now, an influential United States group has abandoned plans to list a synthetic alternative, called recombinant Factor C (rFC), alongside the tried and true blue fluid, reports John Miller for Reuters. The move by medical standards group U.S. Pharmacopeia (USP) would have given rFC equal standing with crab blood, which has long been the industry standard for testing, per Reuters.

The gist of the USP’s rationale is that rFC requires more testing, and that the current crab-derived test has a 30-year track record of safe and effective use, reports the Times. Many expected the alternative test to be approved for widespread use as it was in Europe by the European Pharmacopeia, per the Times.

For drug makers in the U.S., using the synthetic alternative will require a kind of application designed to demonstrate that the non-standard test is up to snuff—a hurdle that makes companies less likely to abandon the animal-based test, reports Caroline Delbert for Popular Mechanics.

In 2018, the blood harvest drained a third of the vital fluids from nearly 500,000 crabs in the U.S., according to the Atlantic States Marine Fisheries Commission. After scores of steel needles suck their blood, each helmet-shaped crawler gets released back to where it was caught—but thousands of them die in the process. Exactly how many are lost is a matter of debate, but Miller, in another recent story for Reuters, reports that conservation groups estimate switching to rFC could save 100,000 crabs each year.

For their part, the companies that make Limulus amebocyte lysate (LAL), the component of crab blood isolated for use in drug purity testing, say the supply of horseshoe crabs is up to the task of approving the surge in vaccine testing amid the race for a cure to the novel coronavirus, reports the Times.

One company using rFC, which is created by inserting horseshoe crab genes into lab-grown microorganisms, is Eli Lilly, per the Times. Eli Lilly recently announced it had started testing a COVID-19 antibody in humans with nothing but rFC for purity testing, Jay Bolden, a biologist with the company, tells Reuters. Bolden tells the Times his company made the switch because of the synthetic product’s consistent quality, its reduced costs, lack of reliance on an animal population as well as the company’s desire to avoid harming animals where possible.

More than 40,000 samples tested by Eli Lilly using rFC suggested it was just as good as LAL, Bolden tells Reuters. “And that data is out there, and it’s either not being looked at or it’s being ignored… There’s no reason the USP should be asking for more data.”

Editor's note, June 23, 2020: This story has been updated to clarify that horseshoe crabs are overfished for use as bait and that bacterial contaminants are not life-theatening, as previously stated.

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