北里柴三郎
Clinical descriptions of tetanus associated with wounds are found at least as far back as the 4th century BCE, in Hippocrates' "Aphorisms". The first clear connection to the soil was in 1884, when Arthur Nicolaier showed that animals injected with soil samples would develop tetanus. In 1889, "C. tetani" was isolated from a human victim by Kitasato Shibasaburō, who later showed that the organism could produce disease when injected into animals, and that the toxin could be neutralized by specific antibodies. In 1897, Edmond Nocard showed that tetanus antitoxin induced passive immunity in humans, and could be used for prophylaxis and treatment. In World War I, injection of tetanus antiserum from horses was widely used as a prophylaxis against tetanus in wounded soldiers, leading to a dramatic decrease in tetanus cases over the course of the war. The modern method of inactivating tetanus toxin with formaldehyde was developed by Gaston Ramon in the 1920s; this led to the development of the tetanus toxoid vaccine by P. Descombey in 1924, which was widely used to prevent tetanus induced by battle wounds during World War II.