Discovery and Early Development of the Limulus Test

Abstract

This is a first-hand description of the discovery by the author that the blood coagulation mechanism of Limulus polyphemus, the horseshoe crab, was exquisitely sensitive to bacterial endotoxins. The author recognized the potential usefulness of this observation and utilized his data to provide the basis for the invention of the Limulus amebocyte lysate (LAL) test for the detection of bacterial endotoxin. The great superiority, both in sensitivity and ease of use, of the Limulus amebocyte lysate test to the then utilized rabbit pyrogen test (RPT) eventually resulted in its official approval. Subsequently, the LAL test became and remains the international standard for the detection of bacterial endotoxins in parenteral drugs, intravenous fluids, and implanted biomedical devices.