Paul Ehrlich's receptor immunology: the magnificent obsession

Although history of medicine is no longer devoted exclusively to great men and their research, they are still worth studying under certain circumstances, above all if they represent important scientific research strands and movements of their times. This is certainly true for the immunologist and bacteriologist Paul Ehrlich (1854-1915), whose work had an impact on several areas within twentieth-century biomedicine. Arthur Silverstein's book deals with one of the most important aspects of Ehrlich's work, namely his research in immunology, and describes and analyses the development of Ehrlich's "side-chain" or "receptor theory". Ehrlich promoted the application of chemistry in medicine and used tissue staining to analyse the chemical binding of substances to morphological structures, especially cells. He applied this work to the investigation of immunological problems. Antigens (or toxins) bind with specific "side-chains" of cells to unfold their effects. As many side-chains are bound by antigens, the cell "overcompensates" when releasing a large quantity of side-chains into the bloodstream. These side-chains function as antibodies able to bind antigens and to avoid further infection. In 1900, the sidechains were renamed "receptors". Ehrlich applied his theory to research on both cancer and chemotherapy, leading to his development of the famous substance Salvarsan for the treatment of syphilis in 1910. The strength of Silverstein's work lies in the medical detail of this important story. He offers interesting insights into the receptor theory's development and defence. For example, he explains Ehrlich's experiments in the field of paediatric immunology, and gives an interesting account of the debate between Ehrlich and Jules Bordet (1870-1961) of the Pasteur Institute in Paris. In discussing the views of Ehrlich's critics, Silverstein also analyses his explanation of the side-chain or receptor theory and looks at how immunologists received it. Although this is without doubt one of the book's merits, it also carries a basic methodological problem. Silverstein writes mainly from the perspective of the immunologist. He describes the path from staining to side-chains as a success story rooted in the genius of the "imaginative Paul Ehrlich" (p. 12). It is a history of ideas, describing the receptor concept as the logical outcome of Ehrlich's productive genius. Of course, logical sequence can be detected in Ehrlich's immunological investigations but it is important to consider that the realization of a new scientific concept depends not least on the specific circumstances of the scientist's social and academic life. Silverstein mentions the breaks and troubles in Ehrlich's life only randomly, although the end of Ehrlich's clinical career as well as his need as a Jew to get a safe position in the German university system were seemingly influential in changing his research interests and enabling him to make his intricate investigations on the side-chain and receptor theory. These shortcomings are surprising since Silverstein himself hints at such socio-historical perspectives, for example: "It was only the direct request of Behring ... that would allow Ehrlich to venture into an area to which his institute colleague had full priority claim" (immunological research on diphtheria, p. 42). Moreover, Silverstein's contribution is presentist. Even in the early stage of Ehrlich's career, he searches for "receptors" using the term when dealing with papers written before 1900. The book presents no new general interpretative approach to Ehrlich's immunology, and it does not reach beyond the splendid article on Ehrlich written by Claude Dolman in the Dictionary of