The development of antitoxin in the bodies of animals injected with diphtheria toxin is one of the best established of facts. Since von Behring and Roux announced the results of their investigations, large numbers of horses have been injected with toxin and have developed abundant antitoxin.
Unaltered diphtheria toxin has been used also as a stimulating injection in man, but it has to be used in very small and repeated doses; otherwise it would produce annoying local reactions and possibly even paralysis. It was early realized that if we ever attempted actively to immunize children, the advantage would be great if we could replace pure toxin with an altered toxin which would be equally effective and without danger.
USE OF TOXIN MODIFIED BY ANTITOXIN FOR ACTIVE IMMUNIZATION IN ANIMALS
The earliest knowledge that injections of toxin almost neutralized by antitoxin are capable of stimulating in animals the production of antitoxin
WILLIAM H. PARK. TOXIN-ANTITOXIN IMMUNIZATION AGAINST DIPHTHERIA. JAMA. 1922;79(19):1584–1591. doi:10.1001/jama.1922.02640190022009