Blue Bloods

Each year, roughly 600,000 horseshoe crabs are plucked from local beaches and transported to biomedical laboratories, where researchers extract some 30-40 percent of their unique blue blood before returning them to the ocean. Horseshoe crab blood is the only known source of Limulus amebocyte lysate (LAL), a distinctive substance used to test all FDA-certified medical implants and pharmaceutical drugs and vaccines — including those being developed for COVID-19 — for dangerous endotoxins.

Now, as pharmaceutical companies race to manufacture millions of doses of the new COVID-19 vaccines, they are looking to LAL to make sure the injections are safe. The question is: Will this put added pressure on the horseshoe crab population?

The impact of blood harvesting on horseshoe crabs has been studied for decades by Win Watson, UNH professor emeritus of zoology. Most recently, in 2019, Watson, Meghan Owings ’17G and Chris Chabot from Plymouth State University published research that found the crabs spawn less often immediately after being returned to the water and remain in deeper water months after being bled instead of moving into shallow water to spawn.

As it is, approximately 10 to 25 percent of the crabs that are bled do not survive. But Watson’s spawning data suggests that harvesting the crabs’ blood has farther-reaching and longer-term impacts on the crab population than had been previously known.

It is tough to get a definitive answer from the pharmaceutical industry about whether or not the global demand for COVID-19 vaccines will mean an increase in the number of horseshoe crabs harvested for blue blood, but one fact about how LAL is used to test vaccines indicates that vaccine-related harvest increases, if they occur, might be minimal. Vaccines are tested in batches, not by doses, which means very little LAL is needed to test the safety of hundreds of thousands of vaccines at a time.

Even so, that’s not necessarily good news for these special arthropods.

Professor Win Watson and Meghan Owings collect horseshoe crabs in the Great Bay Estuary as part of their study on the impacts of the biomedical bleeding process.

Credit: Steve De Neef

“Even without the vaccine, LAL demand is increasing. We see this across the industry as biologics become more prevalent,” says Dave Peterson ’14, a scientist at Lonza — one of the manufacturers of the COVID-19 vaccine — and a Navy veteran, as well as a former student of Watson’s. “LAL remains the industry standard across the globe for bacterial endotoxin detection.”

To date, efforts to gain FDA approval for a synthetic alternative that would replace LAL has been unsuccessful. So, at least for the time being, the U.S. biomedical industry is reliant on horseshoe crabs’ precious blue blood.

But Watson says that even without reducing the number of crabs bled each year, changes could be made to improve their chances for survival and reproduction. In a 2020 paper, he, Owings and Chabot reported that other aspects of the bleeding process — including removing the crabs from water for as long as 72 hours and keeping them in warmerthan-normal conditions — were more deleterious than the actual loss of blood.Professor Win Watson (left) and Meghan Owings collect horseshoe crabs in the Great Bay Estuary as part of their study on the impacts of the biomedical bleeding process on horseshoe crabs.

Watson says that the crabs should be kept cool and moist and that the entire bleeding cycle should be completed as quickly as possible. He also recommends feeding them before and/ or after they are bled to help replenish their hemocyanin — copper-containing proteins that, like our hemoglobin, are used to transport oxygen in the crustaceans’ blood.

Not too much to ask to protect an ancient species so essential to modern human health.