Testing for Bacterial Endotoxins

Testing for endotoxins (a toxin present in a bacteria cell that is released when the cell disintegrates) in injectable biologics was revolutionized in Building 29A by Drs. Edward Seligmann and H. Donald Hochstein. Endotoxins are part of the outer membrane of the cell wall of Gram-negative bacteria and had been discovered to be the cause of fevers in some patients receiving injections.

Pyrogens are endotoxins that cause fevers. Building on previous studies by scientists at Johns Hopkins University, Drs. Seligmann and Hochstein developed a new calibrated test, Limulus amebocyte lysate (LAL), for pyrogens using horseshoe crab blood instead of rabbits’ ears. For thirty years, the standard test had been to inject rabbits’ ears and measure the reaction. This new LAL test was more sensitive, rapid, and economical. The LAL became the standard worldwide test for bacterial endotoxins.

This testing was conducted in the Pyrogens Section of the National Institutes of Health (NIH) Division of Biologics Standards (DBS) Laboratory of Control Activities, which was located in Building 29, fourth floor from 1960 to 1967, then moved to Building 29A, first floor when the annex building opened in 1967.