The birth of immunology. II. Metchnikoff and his critics

The presentation of the phagocytic theory of immunity, proposed by Metchnikoff in 1883, was immediately attacked by German pathologists and microbiologists. Led by Baumgarten and Ziegler, criticism was levied against the hypothesis in three general respects: 1) Can an analogy truly be established between leukocyte phagocytosis and feeding of monocellular organisms? 2) What is compelling about the phagocytic process as a universal defensive activity? 3) General philosophic objections were raised, centered upon the accusation of a teleologic formulation. Underlying the argument was the rejection of the notion that the response of phagocytic leukocytes was truly causal in the successful response to infection. We note that the humoral school of immunity was not established until 1888-1890, and the early debate between Metchnikoff and his detractors was not over an alternative theory of an active immune response. There was none. With the development of the humoralist position, in direct response to Metchnikoff's formulation, a true dialogue about immunity, in the modern context of active host response, was initiated. The debate at this point changed to issues of mechanism (cellular versus humoral effectors), and the relative importance of defining innate versus acquired immune processes. Our study traces the scientific and logical basis of the initial rejection of the phagocytosis theory. More broadly, the analysis of this debate elucidates the emergence of a new concept of immunity that rested upon the notion of an active host response. The humoralists erected their theory on Metchnikoff's original scaffold, and the ensuing debate of the nascent science relied on the successful establishment of his basic concept. With the studies of Bordet, Metchnikoff's protégé, the essential resolution of the acrimonious debate was offered. Metchnikoff continued his research by attempting to apply the phagocytosis theory to mechanisms of senility, while immunology oriented itself toward the biochemical definition of immune recognition.