Discovery of the anthrax toxin: the beginning of studies of virulence determinants regulated in vivo.

Anthrax kills many animal species. It was used to prove Koch's Postulates in 1876. Soon after that the classical bacterial toxins were produced in vitro, but up to 1950, a lethal toxin had not been demonstrated in either anthrax bacilli or filtrates from laboratory cultures. The cause of death had been an enigma for seventy years. During the 1950's, a toxin was recognized by examining bacteria and their products obtained from guinea pigs dying of anthrax. The toxin was found in their plasma and shown to contain two components. It was then produced in vitro and a third component recognized. The work reawakened interest in bacterial toxins after a period of dormancy and showed that toxins could be multicomponent. It demonstrated that previously unknown determinants of bacterial pathogenicity could be revealed by examining organisms grown in vivo. It was the beginning of such studies, which took a long time to evolve, but have now expanded greatly with the development of many new methods for examining bacterial activities in vivo. This paper is a personal account of the early work.