Horseshoe crabs are quiet stars of COVID vaccine-making efforts
When scientists come up with a vaccine for the global threat posed by COVID-19, they will have one of the planet’s oldest, strangest-looking and least understood — and decidedly blue-blooded — residents to thank.
The 450 million-year-old horseshoe crab, the closest living relative to the prehistoric trilobite — and a denizen of earth’s oceans since nearly 200 million years before dinosaurs showed up — is at the center of the race to make a safe and effective vaccine available to the planet’s 7.8 billion people.
Without horseshoe crabs’ deep blue blood, which is a crucial part of the biomedical research process to make sure new breakthroughs are safe, a whole bunch of medical miracles just wouldn’t happen.
“It’s actually important for the tests of anything that goes into the human body at all,” including vaccines and other injectible pharmaceuticals, heart valves and other breakthroughs, said Dave Hudson, a research scientist at the Maritime Aquarium at Norwalk.
One purpose of the Norwalk lab is to try to breed and grow horseshoe crabs to bolster their numbers in the Sound.
The Atlantic horseshoe crab, aka Limulus polyphemus, is found along the Atlantic and Gulf coasts of both the United States and Mexico, from Maine to the Yucatan.
The other three species all are found in Southeast Asia.
The Connecticut and New York populations are considered to be “vulnerable,” or “of concern,” which is one step better than being threatened, according to researchers and a 2019 report by the Atlantic States Marine Fisheries Commission.
In addition to being used for biomedical research, horseshoe crabs are heavily fished as bait for the whelk (scungilli) and American eel fisheries, which many researchers consider to be a greater threat than any increased demand from the biomedical industry.
The world’s human population currently is estimated at about 7.8 billion.
LAL produced by horseshoe crabs is used for the detection of bacterial endotoxins in medical applications.
Jennifer Mattei, professor of biology at Sacred Heart Universi
ty in Fairfield and the longtime leader of Project Limulus, a study and census of horseshoe crabs in Long Island Sound, said that while there are companies as near as Massachusetts that bleed horseshoe crabs to create LAL, Long Island Sound crabs “are not harvested or bled for that product.
Horseshoe crab populations have been in decline in Long Island Sound for at least 15 years.
Justin Davis, assistant director of the DEEP’s Marine Fisheries Division, said that while Connecticut horseshoe crabs currently are not used for biomedical purposes, “the available science suggests that their status ... is not great at this point.”
Davis, who is one of three Connecticut representatives on the Atlantic States Marine Fisheries Commission’s Horseshoe Crabs Advisory Commission, said the most recent stock assessment suggests that the Connecticut stock “is in kind of a depressed state.”
Over the last 18 years, the number of horseshoe crabs harvested in Connecticut has ranged from 12,175 in 2001 to a high of 32,535 in 2008. From 2013 through 2018 the number was about 20,000 per year.
The Connecticut Audubon Society in February urged state officials to ban the harvest of horseshoe crabs and increase law enforcement efforts to curtail illegal horseshoe crab harvesting.
The drop in the number of horseshoe crabs in Long Island Sound, as well as in Delaware Bay and other locations along the coast, is believed to have led to a decline in the population of Red Knots, which recently were listed as threatened under the federal Endangered Species Act.
One of the purposes of Mattei’s research is to try to understand the critters’ movement patterns in the Sound, including “whether or not we share the population with New York or whether we have a separate population in Connecticut.”
Over the years, they have tagged more than 90,000 crabs “and we have a huge database now” that shows “that they move all around,” Mattei said.
While each female horseshoe crab may produce up to 88,000 mature eggs, “only a fraction of the eggs laid make it to adulthood,” Mattei said.
Decades of research, harvests
Horseshoe crabs’ value for medical research was originally discovered in the late 1960s or early 1970s at Wood’s Hole Marine Biological Laboratory on Cape Cod, Mattei said. “They spilled some blood on a countertop and it immediately coagulated.”
Mattei said that the three Asian species of horseshoe, which are not protected the way Atlantic horseshoe crabs are, all are in decline, in part because of heavy fishing by China both for medical purpose and for food. In China, they eat the eggs,” she said.
Down in Delaware Bay, the shorebirds are eating the eggs.
That’s one reason why it’s not enough just for horseshoe crabs to not be threatened. “It’s one of the species that needs to be abundant,” Mattei said.
Protection
John Dubczak, executive director of reagent development and pilot program operations for Charles River Laboratories, one of the companies using horseshoe crab blood for the LAL test, said the biomedical industry’s need for horseshoe crabs and their blood does not constitute a threat.
In fact, it has “driven the development of laws to protect the animal,” Dubczak said “The animal’s best security is the biomedical industry’s continued reliance on horseshoe crab blood for LAL. Without the need for LAL, the legal protection for the horseshoe crab is not guaranteed, and they would again fall prey to overfishing and used as bait for eel and whelk.
“For this reason, it is critical that we serve as advocates for the humane treatment of these animals and strive to achieve balance between our need for this valuable material, and the livelihood of the animal that provides it,” he said.
Dubczak also said the additional demand because of the search for a COVID-19 vaccine poses no threat to the animals.
“If 5 billion doses of COVID-19 vaccine are needed, then that results in 50,000 batches of COVID-19 vaccine being produced to meet that need (the typical batch size is 100,000 doses),” he said in an email. “Three vials of the batch are tested for endotoxin (representing the beginning, middle, and end of the run) ... resulting in 150,000 samples that require testing. Each sample is tested in duplicate along with duplicate positive controls.
“A total of 600,000 tests will be performed” and “the amount of LAL needed for 600,000 tests amounts to less than a single, normal day’s production for the three LAL manufacturers in the United States,” Dubczak said. “This places no undue burden on the LAL supply chain or horseshoe crab populations.”
“It is critical that we serve as advocates for the humane treatment of these animals and strive to achieve balance between our need for this valuable material, and the livelihood of the animal that provides it.”
John Dubczak, executive director of reagent development and pilot program operations for Charles River Laboratories, a company that uses horseshoe crab blood