Horseshoe crabs carry haemocyanin rather than haemoglobin, giving the blood a blue colour when oxygenated. Their immune defence relies on amoebocytes that release a cascade of clotting factors when they encounter lipopolysaccharide from Gram-negative bacteria. Extracted and freeze-dried, that cell lysate becomes Limulus amoebocyte lysate, or LAL, which gels in the presence of vanishingly small quantities of endotoxin.
Since the 1970s LAL has been the workhorse assay for endotoxin in injectable drugs, vaccines and implanted devices, replacing an older rabbit fever test. Crabs are collected, bled of roughly a quarter to a third of their blood volume, and released. Mortality estimates for the bleeding process vary widely, and sublethal effects on movement and spawning have been reported in returned animals.
A synthetic alternative exists. Recombinant factor C reproduces the first step of the cascade without any crabs, and regulators and pharmacopoeias have progressively accepted it, though adoption has been slower than its advocates expected. Horseshoe crabs are also still harvested as bait, which is a separate and, in some areas, larger source of mortality.