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From Crab to Lab

Fighting infections the natural way

More spider than crustacean, the horseshoe crab resembles a tarantula wearing an old army helmet. It’s a living fossil, its basic design unchanged in 440 million years. And the Atlantic horseshoe crab, Limulus polyphemus, can survive out of water for weeks, on beaches from Maine to the Yucatan. Moreover, royal bluebloods have nothing on the horseshoe crab. Its blood really is blue, enlisting copper, rather than iron, to transport oxygen. That blue blood—says John Dubczak, general manager of the endotoxin and microbial detection division of Charles River Laboratories, a US$1 billion-plus global contract research organization with headquarters in Wilmington, Massachusetts—is remarkable at detecting harmful impurities in pharmaceuticals and medical devices. 

Charles River has built its endotoxin and microbial detection business by harnessing the crab’s natural defense against infection: at the first sign of a toxin, the blood clots to block further spread. The company’s Limulus amebocyte lysate (LAL) test detects this clotting reaction and is “the most sensitive in the world for bacterial endotoxins,” says Dubczak, who is based in South Carolina, where he supervises the capture, blood collection and safe return of crabs to the sea.

Endotoxins or “pyrogens”—from the Greek for “fire” because they cause fever—reside in cell wall membranes of E. coli and other so-called gram-negative bacteria that can induce lethal bloodstream infections. These “dead bug parts,” as Dubczak calls them, in a concentration of 70 parts per billion, “will make a person sick.” Limulus blood clots when it encounters an endotoxin concentration of just 1 part per trillion. 

“You’ve seen an IV bag?” Dubczak asks. “The solution in that bag has to be tested for the absence of these pyrogens using our LAL reagent.” So do the tubes and needles connecting the bag to the patient.

Until Charles River pioneered the test in the 1970s, labs tested for pyrogens by exposing rabbits to the substance in question and then checking them for fever. The LAL is much less cumbersome, much more sensitive and is now the standard worldwide. What’s more, the horseshoe crab is a renewable resource. Technicians can remove up to a quarter of the crab’s blood without harming the animal, which is held for less than 24 hours. Dubczak meets annually with a state natural resources official, crab suppliers and handlers to discuss best practices for minimizing loss as crabs are shuttled between the ocean and lab and back. In the early 1990s, alarmed by dwindling crab populations, Charles River found itself in an unusual position for industry—lobbying for more regulation. South Carolina now limits times and places where crabs can be collected and bans their use as bait. Consequently, crab populations rebounded.

In recent years, Charles River invented a cartridge that requires 20 times less blood than its original assay. That’s good for business and horseshoe crabs.

Illustration by Nicolet Schenck

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