The history of the development of the Limulus amebocyte lysate test

The Limulus Test for bacterial endotoxins was developed as the result of investigations of the effects of Gram-negative bacteria on blood coagulation in the horseshoe crab Limulus polyphemus. Analysis of the factors required for blood coagulation (all of which are contained within Limulus amebocytes) has revealed marked similarities between blood coagulation in the horseshoe crab and mammals. The Limulus Test (LT) is the most sensitive test for bacterial endotoxins now available and correlates with a wide variety of other assays. An increasing number of applications of the LT have been described, including detection of endotoxins in pharmaceutical preparations, food, radioisotopes, water supplies, and medical devices, as well as in various body fluids such as blood, cerebrospinal fluid, and urine. The "basic research" that unexpectedly led to the discovery and subsequent development of the Limulus Test provides an example of the value of biomedical investigations directed at understanding pathophysiologic phenomena and demonstrates the importance of studies of comparative physiology.