A handful of scientists based in a nondescript West Ashley lab have played an integral role in making sure millions of COVID-19 vaccines are safe and bacteria-free.
Tucked off Wappoo Road sits Charles River Labs (CRL), a four-building complex with an unassuming appearance that houses a global leader in medical technology, and with one step inside, it’s easy to see what it does — horseshoe crab posters line the walls and stuffed animals cover cubicles.
“When we started, the crabs were sold for bait — nobody cared about them,” said CRL senior vice president Foster Jordan. “They were chopped up in pieces and sold for 50 cents apiece because they were a nuisance.”
Now, South Carolina is the only state where horseshoe crabs are protected by federal regulations, limiting their use solely to biomedical sectors, thanks to the arthropods’ unique blue-colored blood.
Horseshoe crabs, ancient animals that have survived for 450 million years, have incredibly simple biology, Jordan explained. But since they live in high exposure to bacteria, their immune systems are also incredibly effective. That makes their blood an easily manipulated, efficient substance.
Between 1945 and 1987, the standard method of testing an injectable medication for contamination was known as the “rabbit test,” and it’s exactly what it sounds like. A rabbit would be injected with the medication and monitored, watching for anything abnormal that could signal a contaminated medicine.
But in 1971, the first-ever published test using horseshoe crab blood was published, though the research wouldn’t be picked back up and approved by the federal Food and Drug Administration (FDA) until 1987.
“It was the first-ever and still is the only FDA-approved alternative to an animal test,” Jordan said. “We’re still the only one because you can imagine how complex it is to replace an animal model. That’s why we’re still regulated by the FDA too, they’d never done this before.”
Using horseshoe crab blood, tests could measure bacterial contamination — a more effective process known as the limulus amebocyte lysate test, or LAL.
“Suddenly, you could start testing vials, stoppers, water, buffers — everything that went into contact with the final product,” Jordan said. “Since the LAL has been adopted, there’s never been, globally, an instance of a bacterial contamination in an injectable drug ever.”
The tests have taken various forms over the years, but these days, a clear liquid is used that turns yellow to indicate the presence of contaminants.
All this innovation positioned the Boston-based international pharmaceutical company perfectly for the onset of the pandemic, when the rapid and safe creation of a new, injectable COVID-19 vaccine became essential. CRL already worked on 85% of all drugs approved by the FDA in 2019, but Jordan estimates the number to be closer to 95% in 2020.
“It’s been a challenge for me and my team, and I thank them every day because without them coming to work every day and going into those suites, the drugs and the COVID vaccines sit on the shelf,” Jordan said. “They had to do the weekend work, the
shift work, the nights, the holidays, because without us, the drugs don’t get out.”
But that increased workload has also meant an increased reliance on wild-caught horseshoe crabs that must be harvested to have blood extracted before being released.
“Harvesting horseshoe crabs has impacts on the entire ecosystem of the Lowcountry,” said Emily Cedzo, Coastal Conservation League’s land, water and wildlife senior program director.
Part of the complication comes not from the actual harvesting of the crabs, but from how they are kept ready for harvest, in long-term holding ponds, Cedzo said.
“CRL contracts harvesters who stay in touch with the actual labs, and when there isn’t capacity for additional crabs, they put them in manmade ponds, since they already took them from the water,” she said. “They’re left there for indefinite amounts of time — could be weeks, could be months.”
Jordan said he and the team are aware of concerns, but said he thinks most of it stems from misinformation.
“We work with the state to actually protect the horseshoe crab,” he said. “This is the only state in the world where it can only be used for medical purposes, and as a result, we have the most stable population in the world.”
That claim stems from a 2019 report by the Atlantic States Marine Fisheries Commission, which noted the population of horseshoe crabs in the Southeast is stable and in good standing. But specific data on horseshoe crabs in South Carolina is hard to come by, Cedzo said.
“We need to know what the actual health of the overall population of the crabs are in the area, and it’s really difficult to tell. There’s no straightforward transparent data on the population in the state alone, and lacking that, it’s difficult to have a firm understanding of what’s happening in these ecosystems.”
In an October op-ed in The Post and Courier, Christian Hunt of the nonprofit conservation outfit Defenders of Wildlife contended that declines in crab sampling are to blame for not having a full picture of crab population health.
“By relying on combined data from Georgia, Charles River has created a false narrative about the health of South Carolina’s population and the clear impacts of overharvesting,” Hunt told the City Paper. “The company’s refusal to release localized harvest numbers tells you all you need to know.”
CRL officials said harvest numbers are kept secret for “competitive business reasons.”
Other environmental advocates are calling for approval and use of a synthetic replacement for the horseshoe crab blood, eliminating the need for harvesting, but Jordan says the science just isn’t there yet.