Molecular complementariness and serological specificity.

The ~dea that the striking specificity of serological reactions results from the possession by antibody and antigen of mutually complementary combining regions was suggested in the period around 1930 by Brelnl and Haurowltz (1930). Alexander (1931) and Mudd (1932). There is some intimation of it m the early work of Ehrhch and Bordet. Refinement of th~s idea and detailed experimental verification of many of the features of the refined theory of molecular complementariness of antigen and antibody were carried out in a series of studies in the Cahfornla Institute of Technology during a period of about ten years, beginning in 1939 Dan H. Campbell played an important part in this work. I had become interested m biological problems when Thomas Hunt Morgan came to the Calffornm Institute of Technology in 1929, bringing with him a number of very able younger biologists I had been working on the structure of inorgamc and organic substances, usmg the techniques of X-ray diffraction by crystals, electron diffraction by gas molecules, and analysis of the magnetic properties of substances. In 1934 I became interested in the general problem of the structure of proteins, especially hemoglobin. Charles D Coryell and I discovered the remarkable changes in the magnetic moment of the iron atom in hemoglobin accompanying the adt we accordingly feel that complementarmess should be g~ven primary considerahon in the discussion of specific attraction between molecules and the enzymatic synthesis of molecules." We mentioned that "the case might occur in which the two complementary structures happened to be identical; however, in this case also the stability of the complex of two molecules would be due to their complementarmess rather than their identity." Eaght years later (Pauhng. 1948) I &scussed the matter of gene replication in more detad: "'I beheve that the genes serve as the templates on which are molded the enzymes that are responsible for the chemical characters of the orgamsms, and that they also serve as templates for the production of replicas of themselves, The detailed mechamsm by means of which a gene or a virus molecule produces replicas of itself Is not yet known In general the use of a gene or virus as a template would lead to the formation of a molecule not with identical structure but w~th complementary structure It might happen, of course, that a molecule could be at the same time identical with and complementary to the template on which it is molded However, this case seems to me to be too unlikely to be valid in general, except in the following way If the structure that serves as a template (the gene or wrus molecule) consists of, say, two parts, which are themselves complementary in structure, then each of these parts can serve as the mold for the production of a replica of the other parL and the complex of two complementary parts thus can serve as the mold for the production of duplicates of itself" Between 1940 and 1948 the idea of molecular complementarlness as the bas~s of the speclfiClt~ of serological reactions and of biological mteractlons in