On the Nature of Diphtheria Toxin

The chemical nature and the formation of bacterial toxins has been widely discussed. Diphtheria toxin may be regarded as a classical subject. Most of the earlier authors regarded it as a protein or a product derived therefrom. Recently some American authors, Warden, Connell, and Holly, have emphatically declared the toxin to be a "colloidal" mixture of fats and protein. As to the formation of the toxin, it has commonly been regarded as a secretion of the living bacilli, but some authors claim it to be an autolytic postmortem product. One author, S. Martin, has advanced the theory that the toxin is not secreted from the bacilli directly, but is formed from the proteins of the infected tissue, by means of some agent produced by the microorganism. Several authors, Ehrlich, Morgenroth, and others have assumed the existence of "protoxins" and "toxoids," which in some way or other can be activated into toxins. The reaction of the medium has been found to play a great r61e in the toxin production. I t has been found that toxin is formed when the reaction of the broth is alkaline, but if it is acid, toxin does not appear. Recently Bunker has studied this question with modem methods and declared that the toxin should be harvested when the broth has reached a reaction of pH about 8. A higher alkalinity destroys the toxin. His views have, however, been criticised by Davis, Abt and Loiseaux, and others, who do not believe the pH stands in any constant relation to toxin production at all. Hartley has also studied the influence of pH upon the toxin production and obtained results similar to those of Bunker. In a series of papers I have studied the production of diphtheria toxin and I shall give a short review of the most important facts recorded. 1. The changes in pH in broth cultures depend upon whether the