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In 1897, Paul Ehrlich published a selection theory of antibody formation that anticipated the theories of Jerne and Burnet by some 60 years. Ehrlich introduced into immunology the concept of the interaction of physiologically active substances with specific receptors, an idea that still dominates modern immunological thought. In this paper, we point out how Ehrlich's concept matured over 20 years, while it governed his studies in histological staining, in cell physiology, in hematology, and finally in his major contributions in experimental immunology., (Copyright 1999 Academic Press.)

In 1892-93, Paul Ehrlich published a series of experiments on the passive transfer of maternal antibody to fetus and newborn that deserve to be better known. He pointed out the importance of mother's milk to neonatal well-being. He was the first to define the difference between active and passive immunity. He was the first to demonstrate immune elimination of antigen and to explain the significance of each phase of the kinetics of the anamnestic antibody response. We point out how elegant were these early experiments and how far in advance of their times.

Immunology underwent a major change in direction during the 1950s and 1960s, from immunochemistry to immunobiology. A quantitative analysis of the participants at a large number of immunological meetings held during this critical period reveals much about the inner dynamics of the discipline. This new approach enables us to define the scientific leadership of the discipline and of its emerging subdisciplines, the interests of "mainstream" immunology, and when fields such as transplantation and allergy begin to join the mainstream. It is also suggested that some of these meetings, in addition to reflecting changes within the field, may have contributed substantially to these changes. Further, many of these meetings served to promote the institutionalization of the discipline and of its subdisciplines.

I have attempted here to define three distinct eras in the 110-year history of the discipline of immunology. The first, extending from 1880 to about the First World War, centered around the new bacteriology and infectious diseases, and had a distinctly medical orientation. Several of the components of the original research program in immunology failed to maintain their original momentum or to fulfill their initial high promise, and went into decline. These include the development of new vaccines, serotherapeutic approaches, the study of cellular immunity, and the study of diseases that might be mediated by cytotoxic antibodies. Two other subprograms followed a somewhat different course; the study of anaphylaxis and related diseases passed primarily into the hands of clinical allergists, while the development and adaptation of serodiagnostic techniques passed into the hands of the new discipline of serology, both fields out of the mainstream of post-World War I immunology. As interest in the components of the old program was falling away, there developed a new area of interest in immunology. Leadership in the field devolved upon a new group of individuals with a predominantly chemical orientation to the study of antigens and antibodies, who pursued a research program and developed a theoretical base that reflected this orientation well. It may be interesting to examine more closely the forces responsible for this shift in emphasis. When interest in the old areas waned, the medically oriented practitioners did not switch to more immunochemical lines, but went in other directions. Karl Landsteiner was the only prominent "old-timer" who contributed significantly to the newer immunology, and it was his work that set the tone and attracted the new generation of immunochemists who became the reigning Denkkollektiv. A science does not change its precepts and approaches spontaneously; it is moved to the new position by those who explore fertile new areas. This is not to say, however, that there was no longer interesting and important work to be done along the old lines--it was just that such work was no longer "fashionable", as the reception of the work of Dienes, of Rich, of Rivers, and of the early Medawar illustrates. Whereas the earlier immunological program had interacted extensively with many different fields of biology and medicine, the immunochemical era was characterized by a relative introversion, as compared with the broad influence exerted by the earlier immunological program (92). We can date this second era from about the First World War until the late 1950s and early 1960s.(ABSTRACT TRUNCATED AT 400 WORDS)