Development of the concept of immunologic specificity, I

Abstract

It was evident by the early 1930s that if Paul Ehrlich’s biologic theory of antibody formation was out of favor, his chemical concept of the basis for antibody specificity was very much in vogue (1). The very data that had made the antibody repertoire appear to be too large to be explicable in terms of naturally occurring antibodies almost demanded an immunologic specificity based upon a very precise stereochemical complementarity of configuration between antigen and the putative combining site of the antibody. Indeed, as we have seen, such chemical complementarity of structure was explicitly required by most instruction theories of antibody formation, each of which postulated the existence of some form of template upon which specific configuration might be molded (2). But the work of Landsteiner, on artificial haptens, and of Heidelberger and co-workers, on polysaccharide antigens, accomplished more than this; they signaled to a generation of immunologists that progress in understanding the functions of antibody and the nature of its specificity would only come from chemical approaches to the problem. Nor did biologically oriented immunologists have much to offer at this time in competition to the new trend. Their startling and attractive advances in antitoxic and antibacterial immunity, in novel techniques of serodiagnosis and serotaxonomy, and their important contributions to forensic medicine were mostly a generation in the past; while the discovery of immunologic tolerance and deficiency diseases, of transplantation immunobiology, and of the cellular functions in the immune response would only come with the new biology of a future generation. The occasional development of a new vaccine or the finding of a new blood group thus had little effect upon the growing influence of immunochemistry within the larger field of immunology between about 1920 and 1960 (3). The introduction of more chemical approaches to immunology-of quantitative methods and of approaches to the fine structure of antigens and antibodies-had profound implications for the science of immunology. Not only did it reorient the research goals of a generation of scientists, but it led to the production of impressive amounts of “hard” data that altered the nature of immunologic conceptualization. It is typical of the development of a science that, in its infancy, conceptual advances