When scientists come up with a vaccine for the global threat posed by COVID-19, they will have one 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.
You might know tank-like horseshoe crabs primarily as the heavily armored, exceedingly leggy creatures you sometimes find on Connecticut beaches in Old Saybrook, Guilford, West Haven, Milford, Stratford, Fairfield, Norwalk and Greenwich, among other places.
Perhaps you even once flipped one rightside-up to help it survive after its long, pointed tail failed to do the job.
But 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 The Maritime Aquarium at Norwalk, which recently opened its new “Horseshoe Crab Culture Lab,” with a window that lets the public watch as staff work and young horseshoe crabs molt their exoskeletons to grow.
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. More closely related to spiders and scorpions than actual crabs, the misunderstood critters are one of four species of horseshoe crab in the world.
The other three species all are found in Southeast Asia: Tachypleus tridentatus, T. gigas, and Carcinoscorpius rotundicauda, which occupy coastal waters of Asia from India to Japan, including waters around the Dutch East Indies and the Philippine Islands.
Horseshoe crabs, which also are important sources of food for migratory birds, do better in some places than others — Delaware Bay seems to be the center of horseshoe crab life here in the United States.
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.
Biomedical companies “bleed” horseshoe crabs and then return them to the ocean, although about 15 percent of the horseshoe crabs taken to be bled don’t survive the process, researchers say.
“I have a contacts highly placed within the industry, who I respect,” who “basically said they’re talking about a couple of days production” for all of the Limulus amebocyte lysate, or LAL, that would be needed for production of enough vaccines to inoculate the world’s population, said Mark Botton, professor of biology and co-director of the Environmental Sciences Program at Fordham University.
The world’s human population currently is estimated at about 7.8 billion.
“I would think that this is not going to push (horseshoe crabs) over the edge,” said Botton, co-chairman of the International Union for Conservation of Nature Horseshoe Crab Specialist Group and has been doing research on horseshoe crabs for many years. “Even if they required double the number of crabs, it’s still a relatively small number compared to the amount of horseshoe crabs that are taken for the bait-fishing industry.”
LAL produced by horseshoe crabs is used for the detection of bacterial endotoxins in medical applications. Immune proteins in horseshoe crab blood clot when exposed to bacteria, Botton said.
There currently are six companies along the Atlantic coast that extract horseshoe crab blood to produce LAL. They are located in Massachusetts, New Jersey, Maryland and Virginia, according to the state Department of Energy and Environmental Protection.
Jennifer Mattei, professor of biology at Sacred Heart University 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.
“But on the other hand, our population is in decline” and the Atlantic States Marine Fisheries Commission’s Horseshoe Crabs Advisory Commission “cited New York and Connecticut as having a poor management plan right now because the population is in decline.
“They’re supposed to change the management rules and the harvest rules this year,” said Mattei, who has studied horseshoe crabs in Sound for 22 years. “So we’re waiting to see what they’re going to do.”
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, and also a member of the commissioner’s Horseshoe Crab Management Board, said the most recent stock assessment suggests that the Connecticut stock “is in kind of a depressed state.”
A 2019 ASMFC assessment found that the New York fishery, which includes New York, Connecticut and northern New Jersey, was the only one of four geographical horseshoe crab fisheries rated “poor.” The Northeast (Maine, Massachusetts and Rhode Island) fishery and the Delaware Bay fishery both were found to be “neutral” and the Southeast fishery was rated “Good.”
“Unfortunately, with this species we don’t have the good scientific models that we have for some of the other species,” said Davis. “It’s one of those species where we know that it’s threatened, but we don’t really know ... why it’s threatened.”
Since 2001, Connecticut’s annual fishing quota for horseshoe crabs has been set at 48,689 crabs, while the actual annual harvest has varied between 15,000 and 30,000. In 2018, more than 99 percent of Connecticut’s harvest was taken by just 12 license holders, according to DEEP figures.
Fishing generally takes place on land when the animals come up on beaches to spawn, Davis said. “Our annual quota is much smaller than New York’s and we don’t harvest the entire quota,” he said.
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.
“Crabs may be on our beach, and then two years later they’ll be on the North Shore of Long Island,” she said. Fifty to 60 percent of the horseshoe crabs appear to be “home bodies” that don’t travel much, but the rest appear to move mostly from east to west, and sometimes cross the Sound, Mattei said.
“So there’s one population, one genetic population, in the Sound,” she said.
It takes a horseshoe crab about 10-12 years to mature, which is when the females start laying eggs, and they live for probably another 10-12 years beyond that, Mattei said. “The oldest can be 20-25 years old.
“The problem is, particularly in the Sound, that not many make it to adulthood,” she 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.”
Prior to that, researchers used rabbits to assay the purity of new medical breakthroughs, she said. “This sped up the process. That’s why everybody’s talking about it ... they can do an immediate test with the horseshoe crabs.”
Horseshoe crab spawn during the late spring on coastal beaches along the Atlantic and Gulf of Mexico coasts. They lay their eggs in nests buried in the sand, generally in areas within bays and coves that are protected from the surf.
New Jersey has banned the harvesting of horseshoe crabs and in Delaware Bay, which is bordered by New Jersey on the north and Delaware on the south, only males may be taken, said Mattei.
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.
Botton said horseshoe crab eggs also are eaten as food in parts of Thailand, Vietnam and Cambodia, as well as Southern China.
Down in Delaware Bay, however, it’s the shorebirds that are eating the eggs.
That’s one reason why its’ not enough just for horseshoe crabs to not be threatened. “It’s one of the species that needs to be abundant,” Mattei said. “In Delaware Bay ... shorebirds eat the eggs ... It helps fuel their flight to the northern areas where they lay their eggs.”
“The population in the Sound is not big enough for that ... and that’s one of the reasons why there’s not a lot of shorebirds,” Mattei said. “It’s not going to go extinct, but they are not functioning well in Long Island Sound.”
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.
In South Carolina, for example, “we have driven the development of laws to protect the horseshoe crab against commercial bait fishing,” Dubczak said.
The bleeding process “involves draining up to 30 percent of the animals’ blood, where the LAL is extracted, and then returning the crab to its environment,” Dubczak said. “In South Carolina, the regulatory statutes require that horseshoe crabs be returned alive to coastal waters of comparable salinity.”
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.”
mark.zaretsky@hearstmediact.com
The Link LonkOctober 05, 2020 at 09:00PM
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Horseshoe crabs - yes shelled arthropods - are quiet stars of effort to find a coronavirus vaccine - CT Insider
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