Vaccine safeguard found in sea
Blood of the unusual horseshoe crab, among oldest species on Earth, helps ensure shots are clean, safe
Far from the medical labs and test tubes, a fisherman in old rubber boots walks across the docks of West Ocean City to inspect his catch.
He peers in a crate of spiny tails and grasping claws, hundreds of a common yet precious creature, among the oldest species on Earth: horseshoe crabs.
The scene on the docks is a glimpse into a strange and guarded Maryland fishery, one supporting a multimillion-dollar industry as surprising as the catch itself — a seemingly alien creature with 10 eyes, 12 legs and magical, milky blue blood.
It’s the blood that everyone’s after. About three tablespoons extracted from a live, wild horseshoe crab is refined and used to detect toxins in everyday medical products: saline drips, flu shots, heart stents. The crab blood has been the worldwide testing-standard for decades, saving countless lives from infection by screening everything from insulin shots to breast implants.
And now the coronavirus vaccine.
As the first doses reach Americans, pharmaceutical companies are relying on the blood of horseshoe crabs from the Maryland coast to ensure the shots are clean and safe.
News sites around the world are calling attention to this real-life science fiction. “Why are we ‘milking’ crabs for a coronavirus vaccine?” asks BBC News in London. Anti-vaccine activists seized on the crab blood to discourage vegans from the shots.
Even as pharmaceutical companies step toward a synthetic alternative, blue-blood mythology grows.
The internet is rife with claims of horseshoe crab blood as gold: one quart worth $15,000, a gallon worth as much as a Lexus. The actual costs are proprietary and confidential. Still, the speculation’s enough to inspire bootleg bleeders. A horseshoes crab conservation group in Delaware gets offers of bottled blood from an Indonesian fishermanwhowantspaymentthroughWhatsApp.
In Maryland, the few horseshoe crab fishermen have largely retreated from attention. State officials permit three fishing boats to catch the crabs for bleeding then release them back at sea. Crewsdockinthe harbor of West Ocean City, at Martin Fish Co.
The story of the horseshoe crab is a lesson in humility. For all of science andengineering, manstill depends onMotherNature. Andhis plan to beat the coronavirus relies onhistory’s trash fish.
They survived the ice age
Considered living fossils, horseshoe crabs trace back 445 million years, before the first animals crept onto land. Not a crab at all, but genetically closer to a spider, it’s a relic of the ocean insects that scuttled across prehistoric sea floors.
They survived the catastrophe that killed off the dinosaurs; they survived the ice age, and the coming of man. These creatures changedsolittle that anOhiochurchsetouta 68-foot fiberglass horseshoecrabastestament to divine creation over evolution.
The crabs live only on the east coasts of Asia and North America. The world’s largest population of American horseshoes winters off Maryland shores and spawns each spring in Delaware Bay. The latest trawl survey puts this population at morethan14millionmature crabs.
TheAmericanhorseshoeisthebiggest and the darkest, enough so to frighten children at the beach, but it’s literally toothless. Their spiny tails are nobarbeddefense, but apropto right themselves in the waves. The crabs are harmless, just swimmingArmyhelmetsreally.
Throughout history, they were practically worthless, too.
Researchers believe American Indians first plowed the horseshoe crabs into the soil for crops. Centuries later, farmers around Delaware Bay adopted the practice. Horseshoes were dried and ground, then spread over peach orchards or fed to hogs as mash. Historic photosshowblanketsofthemdrying in the sun, by the hundreds of thousands, obscuring the fields. Towns built factories to crushthemintofertilizer. Thesmellwasoverwhelming.
By the 1960s, horseshoe crab populations plunged. Then chemical fertilizers arrived, and the factories closed. The crabs became bait, in smaller numbers, for eels and conch.
Meanwhile, a Johns Hopkins researcher studying the immunesystemofthecrabs had made a surprising discovery. Dr. Frederik Bang found that an injection of seawater bacteria causedtheir strange bloodtocongeal. A blue jelly would encase and trap the bacteria. Thesecrabs, after all, spent their lives slogging through a bacterial soup on the sea floor.
In the summer of 1963, another Hopkins researcher, Dr. Jack Levin, traveled to Cape Cod to study horseshoe crabs with Bang. Levin’s research would solve a problem that hadconfoundeddoctorssincetheinventionof hypodermicneedles: howtoensureinjections are clean and safe.
Even trace amounts of certain bacterial toxins can prove deadly when delivered into the bloodstream. Knownasendotoxins, these contaminates caused the infamous “injection fever” of the 19th century; septicemic blood poisoning fromatainted shot canstill befatal.
Medicine had long relied on laboratory rabbits to screen for this danger: a sick rabbit meant a bad dose. But Levin devised a better method with crab blood. He could mix an extract of bloodcells into asolution andwatch. If nothing happens, the solution’s clean; if the extract gels, it’s dirty.
Horseshoe crab blood could be medicine’s warning bell.
How many die?
Amultimillion-dollar industry grewonthe Atlantic coast. Workers with syringes drew the blood of horseshoe crabs at laboratories in the Lowcountry of South Carolina, near the Jersey Shore, on Cape Cod and Virginia’s ChincoteagueIsland. ASwisscompanywould bleed them in a Salisbury business park and truck the crabs backtoOceanCityforrelease.
Bythelate1990s, the numberofhorseshoes bled and returned to sea reached 260,000 a year, according to federal regulators. By the mid-2000s, the numberclimbedpast300,000 crabs. Researchers estimated by then the industry made $60 million a year.
The labs drew blood from nearly 640,000 horseshoe crabs in 2019, according to the Atlantic States MarineFisheriesCommission. Forthefirsttimeinhistory, thehorseshoecrab was worth more alive than dead.
Inside the labs, workers slide a needle through a hinge of the shell. They draw the blood from the crab’s slow-beating, tubeshapedheart. Thentechniciansspintheblood in acentrifuge to separate the cells. Theproduct is refinedandsoldasendotoxintestkits to pharmaceutical companies. The companies test injections and medical implants. They may, for instance, bathe a dental implant in water and test the water.
Few outsiders are allowed into the blood labs. The photos online capture a futuristic scene: technicians in white lab coats, rows of horseshoe crabs strapped to stainless-steel counters, the creatures dripping a blue milk into glass bottles.
“These things are being produced in clean rooms that look like the stuff they make microchips in,” said Glenn Gauvry, who runs ahorseshoecrab conservation groupin Delaware. Hisconservation workreceivesfunding from the labs. Though some wildlife groups consider the money compromising, Gauvry says he can influence the industry more from the inside. Heseeshimselfanhonestbrokerto the question that shadows the industry. How many crabs die?
The Swiss company Lonza bleeds crabs in Salisbury and finds 5% of them die. Some academic researchers believe more crabs die undersea; they put the death rate as high as 30%. The Atlantic States Marine Fisheries Commission, which regulates the industry, settles in the middle.
“Theygowith15% becausetheydon’tknow whether it’s 30% or whether it’s 5%,” Gauvry said. “In terms of what dies out there, of what gets released, it’s difficult to measure.”
A5% death rate wouldmeannearly32,000 crabs died last year; 15% would mean 95,000 deadcrabs. Bothestimates fall well belowthe half-a-million crabs or morekilled annually to bait eel andwhelkpots. Thefisheriescommission finds the population of American horseshoe crabs holding steady.
Still, the Sci-Fi photos of the bloodletting provoke sharp criticism from U.S. wildlife groups. Horseshoe crabs in Delaware Bay feed a beloved little bird on its migration from South America to the Arctic. The Red Knots, anenvironmentallythreatenedspecies, land in Delaware each spring andgorge onan abundance of horseshoe crab eggs to sustain their 9,000-mile journey. Without the crabs, the birds wouldn’t make it.
All this causes some hard feelings between communitiesofbird watchers andhorseshoe crab fishermen. Wildlife conservation groups haveurgedU.S. pharmaceutical companiesto quit testing with crab blood.
Meanwhile, researchers in Singapore cloned the blood of horseshoe crabs and developed a synthetic test for endotoxins. In Europe last summer, authorities announced they will accept the synthetic test as equal to crab blood.
Wildlife groups and pharmaceutical companies expected the same decision from the U.S. Pharmacopeia, which sets the national standards for medicine. Theapproval didn’t come, though the U.S. Pharmacopeia left open the door for companies that want to use the synthetic and are willing to demonstrate that it’s safe and effective.
Thedecisionfrustrated RyanPhelan, director of Revive & Restore, a California wildlife conservation group that lobbied for the synthetic. Phelan says the blood labs sowed doubt about the synthetic test.
“You’ve got a very large, biomedical bleeding industry with a vested interest in keeping those horseshoes crabs coming in and basically protecting this monopoly,” she said.
Still, signs show the industry coming around. Indianapolis drugmakerEliLilly and Company decided to test all its new medications with the synthetic. The Swiss company Lonza sells a synthetic test in addition to its crab-blood test. InDelaware, Gauvrybelieves the shift is inevitable.
For now, the industry says it has plenty of horseshoe crab blood to screen coronavirus vaccines. Pharmaceutical companies test a sample from a batch of vaccines, not every dose. And that sample size, say three vials, doesn’t change whether the batch contains 100,000 doses or 1 million, says Allen Burgenson of Lonza.
In fact, Burgenson says, the industry produces enough tests in one day to screen 5 billion doses of coronavirus vaccine.
Helping inoculate America
Back in West Ocean City, one of the few remaining work boats motors in past sundown. Thetrawlersits lowinthewater, its deckladenwithhundredsofhorseshoecrabs.
No one takes notice on this November evening. There’s noclue the catch might help inoculate America.
Once, the fishing harbor had dozens and dozensoftheseworkingboats. Theoldnames hangonthewallatMartinFishCo. like ghosts: L.D. Lynch, Gulf Rambler, Atlantic Girl. A faded red life ring reads “Suzanne.” Eachyear, it’s harder to make a living on the sea.
Three boats hold permits in Maryland to catch horseshoes for the labs. Two boats sell to Lonza, with its lab in Salisbury; one to a Japanese chemical company, with a lab on the Virginia Eastern Shore. A third company bleeds horseshoes in South Carolina and a fourth in Cape Cod — but that’s all.
Tothe handful of Maryland fishermen, the biomedical contract offerssteady work. Some summer nights, they fill their nets within an hour. Onetowmightdeliveramoundofcrabs chest-high; a crew may catch 1,200 horseshoes in a night. The work’s good enough to keep the boats running.
Their nightly catch is loaded on refrigerated trucks, temperature set to match seawater, and hauled to the Salisbury lab. By day, the crabs are washed and pricked; they bleed freely until they clot. Theshells are notchedso lab workers don’t bleed the same crab twice. Then drivers return the crabs to the docks.
By evening, the boats head out with the previous night’s catch. Crews don’t dump these crabs overboard, but slide them in the sea. As one fisherman likes to say, “We treat these crabs like babies.”
The coronavirus epidemic brings a flood of attention to their little fishery, and the men are waryof outsiders. But as the world strives against the virus, they are quietly proud of their contribution. “Blue bloods save lives,” one fisherman’s son told his school for the third-grade science fair.
On the docks now, a fisherman inspects the big crates: nearly 800live crabs. Like wet, black wood they glisten. They smell of brine. Their legs curl and uncurl reflexively.
Thefishermancradles a big oneonits back. With his fingertips, he brushes its spider mouth. The inky legs close around his hand.
More than ever, the futures of these crabs and of people are bound together.