Pasteur, Pastorians, and the dawn of immunology: the importance of specificity

Throughout his career, the problems that attracted Louis Pasteur almost invariably involved considerations of specificity of structure and/or of action. Thus, his work on asymmetric crystals showed that chemical form not only specifies crystalline structure, but affects the affinity of ferments as well. In his studies of diseases of silkworms, of beer, and of wine, he could unerringly distinguish with the microscope the specific agents of disease. From this emerged his concept of the specificity of species and against the nonspecificity of spontaneous generation, whence the germ theory of disease. It was in the new field of immunology, however, where the manifestations of an exquisite specificity were most clearly seen. Here, Pasteur's vaccines worked because he chose the specific pathogen in order to induce a specific immunity, and he succeeded each time. But the two most prominent Pastorian successors in immunology, Elie Metchnikoff and Jules Bordet, were not equally successful. Although each contributed significantly to the birth of immunology, each advanced a theory that neglected the principle of specificity and paid a price in consequence. Metchnikoff's phagocytic theory of immunity could not survive the demonstrable specificity of humoral antibodies, while Bordet's physical adsorptive concept of the antibody-cell interaction quickly fell to Paul Ehrlich's demonstration of the stereochemical determination of immunological specificity.