From Bacterial Poisons to Toxins: The Early Works of Pasteurians

We review some of the precursor works of the Pasteurians in the field of bacterial toxins. The word "toxin" was coined in 1888 by Ludwig Brieger to qualify different types of poison released by bacteria. Pasteur had identified the bacteria as the cause of putrefaction but never used the word toxin. In 1888, Émile Roux and Alexandre Yersin were the first to demonstrate that the bacteria causing diphtheria was releasing a deadly toxin. In 1923, Gaston Ramon treated that toxin with formalin and heat, resulting in the concept of "anatoxin" as a mean of vaccination. A similar approach was performed to obtain the tetanus anatoxin by Pierre Descombey, Christian Zoeller and G. Ramon. On his side, Elie Metchnikoff also studied the tetanus toxin and investigated the cholera toxin. His colleague from Odessa, Nikolaï GamaleÏa who was expected to join Institut Pasteur, wrote the first book on bacterial poisons while other Pasteurians such as Etienne Burnet, Maurice Nicolle, Emile Césari, and Constant Jouan wrote books on toxins. Concerning the endotoxins, Alexandre Besredka obtained the first immune antiserum against lipopolysaccharide, and André Boivin characterized the biochemical nature of the endotoxins in a work initiated with Lydia Mesrobeanu in Bucharest.