Paul Ehrlich and Ilya Metchnikov were awarded the Nobel Prize in 1908. Some have suggested that Ehrlich's work on antibodies and Metchnikov's work on phagocytosis laid the groundwork for the division of all things immunological into 'adaptive' and 'innate' processes. But their Nobel Prize lectures make two things apparent: Ehrlich and Metchnikov had distinct interests and any idea that either man would 'slice up' immunology into innate and adaptive processes is certainly an historical anachronism. For Metchnikov, biomedical questions were to be solved by studying comparative biology. Accordingly, his lecture begins with a discussion of the origin of digestive organs in the animal world and then proceeds to discussions of the “floating larvae of starfish” and infection of the water flea (daphniae) by a microbe that produces spores. Those early studies were central to Metchnikov's later work on phagocytosis and the complex processes involved in killing microbes, one of which was through 'digestion' of the microbe by a phagocyte.

For Ehrlich, the “problem of cell life” was to be answered by looking down an order of magnitude from organisms to “the most subtle chemism of cell life.” At the root of this endeavor was chemistry. The bulk of Ehrlich's lecture describes the many types of receptors or 'lateral chains'—for example, those beneficial for the organism were called 'nutriceptors'—that are “discharged from the cell in excess” and circulate as antitoxins (antibodies) with specificity for particular microbial toxins. Ehrlich's ideas, dubbed the 'side-chain' theory, were in part an extension of earlier work by Emil Fischer on the molecular 'lock-and-key' mode of chemical interaction.

In this issue of Nature Immunology, two reports pay homage to the achievements of Ehrlich and Metchnikov, who are often considered by others to be among the earliest true immunologists. Their individual achievements are discussed in an historical commentary by Stefan H.E. Kaufmann, and Carl Nathan presents an overview of the meeting “Metchnikov's Legacy in 2008” that recently took place at the Institut Pasteur. No doubt innate and adaptive aspects of immune responses owe their beginnings to Ehrich and Metchnikov, but their legacy would be more accurately seen as a seminal contribution to establishment of immunology as a distinct field of study.