Have you ever had a vaccine? A shot of morphine? An antibiotic injection? Then you should thank the horseshoe crab for your health. Every FDA-certified parenteral drug (a drug injected into the bloodstream) must meet a battery of standards, one of which is its purity with respect to harmful bacterial endotoxins. For example, the sickness caused by eating undercooked or “bad” meat is due to the endotoxin compounds in the bacteria living on that meat. Even in small concentrations, these compounds can cause disastrous health problems when passing through the digestive tract—which is why you really don’t want bacterial endotoxins in any medications or vaccines that are injected directly into your bloodstream. Thankfully, horseshoe crabs produce a very unique compound that modern medicine uses to ensure that vaccines, antibiotics, and other injected drugs are safe—keeping you healthy.

By nature of its lifestyle, foraging around in sediment in search of small clams, worms, and other crustaceans to eat, the horseshoe crab is constantly exposed to very large concentrations of endotoxin-containing bacteria. A horseshoe crab’s carapace protects the delicate tissues beneath, which include large sinus cavities where the crab’s blood comes into direct contact with its various tissues. Because these invasive bacteria can access the crab’s tissues more directly than in our own bodies, and the crab’s exposure to such harmful bacteria is significantly greater due to foraging, the horseshoe crab has evolved a magnificent defense mechanism, known as Limulus amebocyte lysate (LAL). Horseshoe crabs produce this special compound in their blood, where LAL can quickly coagulate on any endotoxin-containing bacteria that invade the crab’s circulatory system. This coagulation process incapacitates the bacteria, protecting the horseshoe crab.

Mating draws horseshoe crabs to shallow water, where they can be readily captured (and are later released). (Credit: Breese Greg, U.S. Fish and Wildlife Service, Wikipedia)

In 1956, Fred Bang, a researcher at the Marine Biological Laboratories in Woods Hole, Massachusetts, discovered this compound and observed its protective property in the blood of horseshoe crabs. His discovery, spurred by basic natural history observations, led to an unexpected applied result: the LAL test that pharmaceutical companies the world-over now use to ensure that blood-injected drugs are safe for their recipients. To test solutions of drugs for purity, a small amount of LAL is added. If the solution coagulates, the drug contains bacterial contamination. This method is so robust that endotoxin contamination can be detected at extremely low concentrations.

The method calls for the harvesting of large quantities of horseshoe crab blood, which means large numbers of horseshoe crabs are captured annually. It’s a bit of a gruesome process, in which crabs are collected at the shore and then partially bled in a laboratory. On the positive side, this process is more like a blood donation—most of the crabs live and are returned to sea, to continue their bottom-dwelling, sediment-foraging activities.

by Liz Boatman



Read more about the use of horseshoe crab blood for drug safety testing here.