Nature of Formalin Inactivation of Bacteriophage

Abstract

Immunologists and students of the filtrable viruses are familiar with the fact that formalin possesses the unique property of converting toxins to toxoids and viruses to what may be called “virusoids” and of doing this without greatly impairing the antigenicity of these agents. While various physical and chemical agents readily inactivate toxins and viruses, such inactivation is generally associated with complete loss of antibody stimulating powers. The unique property which formalin possesses has interested us for some time. Schultz, Quigley and Bullock, 1 in discussing the antigenicity of formalin inactivated bacteriophage suspensions stated that “it is by no means clear that formalin actually kills or effaces the identity of the virus.” We have felt for some time that the preservation of the antigenicity of formalin inactivated toxins, bacteriophage and of animal viruses might possibly rest on some common mode of action—one in which the toxin or virus is not permanently altered, but is held in an inactive state only so long as the formalin is combined with the antigen, and that the antigenicity of formalin inactivated toxins or viruses might be explained on the basis of a “dissociation” which is later effected within the body. It seems possible that the inactivation itself may be of the nature of an ordinary “formol reaction” in which formaldehyde combines with the amino group to form a methylene derivative and that after injection into the body the formalin radical in the new complex may be removed by some chemical process, probably oxidative in character, which restores the toxin or virus to its native state. The difficulty in testing such an hypothesis consists, of course, in finding a method which will release or destroy the linked formaldehyde without at the same time destroying the toxin or virus.