The Elusive Immune Self: A Case of Category Errors

PERSPECTIVES IN BIOLOGY AND MEDICINE Volume 42 ¦ Number 4 ¦ Summer 1999 THE ELUSIVE IMMUNE SELF: A CASE OF CATEGORY ERRORS ALFRED I. TAUBER* Introduction Immunology during the first half of the 20th century was preoccupied with the chemical questions ofimmune specificity, and the biological questions concerning immune identity were set aside [1] . But after World War II, transplantation and autoimmunity became increasingly relevant both to basic immunologists and clinicians. It was at this juncture that Sir Frank Macfarlane Burnet introduced the "self" into the immunological lexicon, and upon that metaphor erected a theory of immunological tolerance that was to dominate the field to this date [2, 3]. Most immunologists today define the discipline as the science ofself/nonself discrimination, and Burnet 's clonal selection theory (CST) by which selfhood is understood, "has passed from the status of theory to that ofparadigm" with only slight modification [4, p.15]. For those uncomfortable with such sweeping notions as "paradigms," there is still a general consensus, as another textbook writes, that CST "is no longer a theory but a fact" [5, p. 335]. The Immune Self has indeed become dogma, and the "self" versus "other" axis has assumed the role of an operative thought style which organizes the entire discipline. I am most grateful to Moira Howes for initiating a philosophical discussion, perhaps a debate, with me over the nature of the immunological self [6]. This is a topic of great importance for current theoretical immunology— the science itself—as well as for various philosophical attempts at clarifying our understanding of personal identity. Let me offer a brief summary of the issues surrounding this topic byway ofresponding to Howes' characterization of my work. * Center for Philosophy and History of Science, Boston University, 745 Commonwealth Avenue , Boston, MA 02215.© 1999 by The University of Chicago. All rights reserved. 0031-4982/99/4204-1113101.00 Perspectives in Biology and Medicine, 42, 4 · Summer 1999 459 Today, the general view is that immunology, since its very beginnings during the last 25 years of the 19th century, was committed to discerning those mechanisms by which the "self" discriminates host elements from the foreign. In this view, the latter are destroyed by immune cells and their products, whereas the normal constituents of the animal are ignored. In other words, the identity of the host organism was given or assumed. But such neat divisions or boundaries were adopted, or at best were drawn with a certainty that remained problematic. Aside from competing theoretical formulations, there were early discrepancies accompanying the full embrace of a self/nonself discriminatory mode to explain immune function. Concomitant to demonstrating the beneficial effects of immunity, these same defensive functions were shown to be the cause of much of tissue damage. But inflammation only broadened the conceptual arena of immune mechanisms and was soon incorporated as the necessary untoward effects of the defense system. However, the immune system not only was found to inflict damage as the price of cleansing, it also was capable of apparently capricious assault on its host. So-called autoimmune reactions were described at the turn of the century and later determined as cause of autoimmune disease, but because the entire orientation of the science was to see immunity as a mediator of host defense, these findings were viewed as a pathological aberrancy. Arising from an unregulated killer system gone awry, autoimmunity, in this view, could hardly be regarded as part of an expected continuum of normal immune function. In each case, "ideal" immunity was the agent of the self, and although there might be inconsistencies in behavior regarding that mandate, the basic structure of immunology demanded articulation of a model of identification and the protection of organismal identity. In short, by the mid-20th century, a formal theory of self/nonself discrimination was articulated that would attempt to clearly demarcate the host organism and the foreign by an immune system that under normal conditions discerned the self and protected it. This basic formulation has served as the foundation of the contemporary science. We can trace this theme of immunology's history as a result of those discoveries leading to the elucidation of the bacterial etiology of infectious diseases. This orthodox...