Corrections & Clarifications: A previous version of this story misidentified Jack Levin and Frederik Bang’s organization. It is the Marine Biological Laboratory.

EAST FALMOUTH, Mass. — For 450 million years, horseshoe crabs have scuttled along the ocean floor, coming ashore to lay eggs.

You need pretty strong defenses to survive mass extinctions and the oversized predators that evolved before man came on the scene. While its helmeted body certainly protected it, the horseshoe crab, living in a bacterial soup, had another defense — blood that quickly clotted to stop infection from cuts and loss of limbs.

Just as it is for this primordial animal, bacteria is all around us.

“It’s not dangerous until it crosses the blood wall,” said Brett Hoffmeister, limulous amebocyte lysate (LAL) production manager for Associates of Cape Cod in East Falmouth. “If it gets into the blood or spinal fluid, you have a problem.”

Because of its quick and detectable response to bacteria, horseshoe crab blood is used in testing anything that can be surgically implanted, injected or swallowed as medication. That includes hip replacements, heart stents, pharmaceuticals, intravenous solutions and vaccines such as the annual flu vaccine, and the coronavirus vaccines now in development with potentially worldwide distribution.

While other tests exist like synthetic LAL and a human blood test, LAL bacterial endotoxin testing is the gold standard, Hoffmeister said.

The LAL test was first developed in Falmouth by Jack Levin and Frederik Bang of Marine Biological Laboratory. Associates of Cape Cod, the first company licensed to manufacture it, was founded in 1974 by Stanley Watson, a Woods Hole Oceanographic Institution senior scientist who investigated the horseshoe crab extract as a way to measure bacterial biomass in seawater.

The company now has over 200 employees and offices worldwide, Hoffmeister said. There are only four manufacturers in the U.S.

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Hoffmeister said his company doesn’t anticipate a very big increase in demand for LAL to test and manufacture new vaccines. Very little is needed to test a sample of the vaccine, and it would take only a day of production to manufacture enough to assure the purity of even an estimated five billion doses, he said.

Back in the late 1990s and early 2000s, there was concern over the fate of the horseshoe crab. The crab’s numbers appeared to drop to the point where birders and national bird conservation organizations like the National Audubon Society expressed alarm over a lack of horseshoe crab eggs, a primary food for endangered shorebird species like red knot along their migratory route.

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Many were concerned about a big increase in harvests by a bait fishery in which the crabs were used to attract conch, eels and other species to traps. Others worried about the number of crabs dying from handling and bleeding in the biomedical industry.

Daily limits and bans on bait fishing in critical horseshoe crab areas like Delaware Bay and in Massachusetts and other spots along the eastern shore helped bring that fishery under control. The bait harvest peaked in 1999 at 2.6 million crabs and has remained under 1 million crabs since 2003, according to a 2019 stock assessment by the Atlantic States Marine Fisheries Commission.

In that 2019 assessment, the commission estimated a 15% mortality for the biomedical field. Most of the horseshoe crab blood is in the gills, and LAL technicians only use a small portion contained in sinus sack. The animal is returned to the water within 24 hours, Hoffmeister said. Total estimated mortality for the nearly 500,000 crabs used exclusively for the biomedical industry in 2017 was 72,674 animals. Over 990,000 were caught and killed in the bait fishery that year, according to commission data.

Derek Perry, an invertebrate fisheries biologist at the Massachusetts Division of Marine Fisheries, said that other fisheries dwarf the impact of the biomedical industry.

“In the (ASMFC) stock assessment, they say that discard mortality from the mobile gear fleet (fish trawlers and shellfish draggers) could be higher than the biomedical and bait fish combined,” he said.

Although they haven’t been able to determine what constitutes a healthy horseshoe crab population, or a sustainable amount to harvest, commission officials said that the majority of indices indicate these prehistoric survivors appear headed in the right direction.

Perry pointed out that trawl surveys along the East Coast, with the exception of the New York area, were all showing increased horseshoe crab abundance.

“Our trawl survey, with a 40 year history, had the highest data point in years this year, so our population seems to be increasing,” Perry said.

His agency sends guidelines to Associates of Cape Cod on how to safely handle crabs to reduce mortality, and they are in the East Falmouth facility once a month during the season to assess the health and handling of the crabs.

This article originally appeared on Cape Cod Times: COVID-19: Coronavirus vaccine tested with horseshoe crab blood

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