The Immunological Self: A Centenary Perspective

THE IMMUNOLOGICAL SELF: A CENTENARY PERSPECTIVE ALFRED I. TAUBER* 1. Introduction The Tenth International Congress of Medicine opened in Berlin at 11:00 a.m. on August 4, 1890, in the Circus Renz, the only hall large enough to hold the 7,000 participants. Rudolph Virchow, who chaired the second day session, noted that there were 623 visitors from the United States, 421 from Russia, 352 from Great Britain, and 171 from France. Of these, we are most interested in the Russian expatriate, Elie Metchnikoff, who had joined Pasteur's newly formed institute 2 years earlier. Metchnikoff had presented a novel theory of immunity 7 years before, and controversy centered on his work [I]. He argued that immunity came from active defensive mechanisms of the host and that the principal mode of host resistance resided in the phagocyte. Reception of the so-called phagocytosis theory was mixed. His supporters included Virchow and Louis Pasteur, but his detractors were equally prestigious and were led, most notably, by Robert Koch. By 1890 the debate was polarized not so much over active defense as a principle of immunity, although that issue was still unresolved, but most clearly over the mechanism by which the host dealt with pathogens. The celebrated debate between the immunological cell advocates, led by Metchnikoff, and the German humor advocates, was in full sway at the meeting [2, 3]. The polemics were aggressive, and each side stubbornly defended its rigid position. The argument in this early period of immunology has given historians an interesting case study of the decline of a descriptive, teleological , even vitalistic vision of biology being replaced by the physicochemical reductionist program. The issues in 1890 were very complex and reflected fundamentally *Boston University School of Medicine, S Building-Room 301, 80 East Concord Street, Boston, Massachusetts 02118.© 1991 by The University of Chicago. All rights reserved. 003 1 -5982/92/350 1-0753$0 1 .00 74 Alfred I. Tauber ¦ The Immunological Self different visions of host defense and, more important, concepts of organismic integrity. They centered around Elie Metchnikoff's study of embryonic development in the lower phyla to establish the now-accepted function of amoeboid phagocytic cells. In the process, he formulated a new concept of immunity. For almost 20 years he worked on his embryological studies, to define the mesoderm in invertebrates, assign genealogical relationships, establish a model of the first metazoan, and contribute to the exciting debate initiated by Charles Darwin's Origin of Species; these may by considered as logically culminating in the phagocytosis theory [4, 5]. We have detailed that odyssey elsewhere [6], and here we hope to highlight the characteristic novelty of Metchnikoff's concept of the organism. His experience as an embryologist, his concern for relating developmental biology to the newly presented Darwinian theory , and the broad application of his research to seemingly unrelated issues of pathology and inflammation placed him in a unique position to contribute seminal insight into the nature of the immune reaction. Today we understand the phagocyte as a cell capable of engulfing particles and killing the ingesta. This insight has been attributed to the celebrated experiment of 1883, where Metchnikoff witnessed phagocytes attack rose thorns that he placed in transparent starfish larvae; this model is analogous to an inflammatory locus to which amoeboid phagocytes migrate. Certainly this class of cells is crucial for normal host defense against a variety of pathogens, but it is also the effector cell of chronic inflammatory diseases, where the host tissue becomes the pathological target of the phagocyte. Metchnikoff was the first to recognize the true significance of the phagocyte as an inflammatory cell, define its function in all its important particulars, and construct a modern concept of the immune process as a special case of inflammation. 2. Metchnikoff's Phagocytosis Theory Metchnikoff began his research career by first describing embryonic layers in primitive invertebrates and, in his study of the mesoderm, to define the function of the amoeboid phagocyte. He did so by seeking genealogical relations. In a phylogenetic synthesis, he discovered that, in organisms with a cavitary digestive apparatus, the phagocyte no longer had a nutritive function but continued to eat. The defense of the organism...