Book Review

The Immune Self: Theory or metaphor?

N Engl J Med 1995; 332:1176-1177April 27, 1995

Article

The Immune Self: Theory or metaphor?
(Cambridge Studies in Philosophy and Biology.) By Alfred I. Tauber. 354 pp. New York, Cambridge University Press, 1994. $59.95. ISBN: 0-521-46188-X

With the publication of this book, Alfred I. Tauber, a physician and clinical investigator, joins company with today's leading scholars of the history and philosophy of science. His earlier work with Leon Chernyak on Elie Metchnikoff (Metchnikoff and the Origins of Immunology: From Metaphor to Theory. New York: Oxford University Press, 1991) was a superb analysis of Metchnikoff's thoughts about science and about how Darwin, who preceded Metchnikoff by almost a generation, influenced Metchnikoff. That book recounted how Metchnikoff broke away from the rigidity of 19th-century science despite the risk to his career, just as he was establishing himself as a productive and original investigator in embryology. Tauber and Chernyak pointed out that by creating the modern idea of immunity, Metchnikoff became the first immunologist. It is strange, then, that Metchnikoff so vigorously opposed the upheaval in immunology that began in the final decades of the 19th century — a revolution fueled by the discoveries of complement and antibodies. Metchnikoff dismissed these humoral components of the immune system as special cases of mere “ferments.” Ironically, Metchnikoff, who believed that phagocytes are the exclusive agents of immunity, had to share the Nobel prize in 1908 with Paul Ehrlich, the champion of antibodies. Tauber's account in The Immune Self of the Nobel committee's 1902 Secret Report, which recommended against Metchnikoff, is a fascinating reminder of the arbitrariness of prize committees.

The Immune Self follows the pattern laid down in the earlier book. The scholarship is excellent, the erudition impressive. Tauber's citations range from John Locke, the 17th-century philosopher, to John Grover, the 20th-century AIDS activist. But Tauber is not only an erudite scholar. He is also a physician who has worked for many years in the clinic and laboratory. He can thus legitimately argue that for reductionists — those who hold the belief that DNA is all — the patient is just a set of laboratory values and images, and he does so with feeling and authority. Tauber's powerful and eloquent argument against reductionism in The Immune Self comes at a crucial time in the history of science, and even of humankind. He joins the distinguished naturalist Jared Diamond in denouncing “the grim determination with which the molecular biologists have sought to extirpate non-molecular research in biology” (J. Diamond, “Portrait of the Biologist as a Young Man.” New York Review of Books January 15, 1995:16-9).

The Immune Self can be read as two books. The first is a superb account of the 100 years of immunology from 1880 to 1980. A tour de force of scholarship and engaging prose, it should be required reading for all graduate and postdoctoral students in immunology. Indeed, well-established immunologists will profit the most from reading this part of The Immune Self. In my experience, what practitioners of science (or medicine, for that matter), and even the leaders in the field, know about the history of their profession is at best primitive. Tauber gives a beautiful account of how McFarland Burnet arrived at his ideas about immune selection through his work on bacteriophages. Burnet introduced the “self” metaphor — the concept that the immune system learns to distinguish the body's own antigens from foreign antigens — and fathered the theory of clonal selection. Amazingly, Niels Jerne, whose ideas about immune selection antedated Burnet's, also came to the idea of clonal selection through the bacteriophage. Tauber's genealogy of ideas about immune tolerance, one of the leading topics in modern immunology, is clear, instructive, and marked by original insights.

The other “book” in The Immune Self is a detailed argument about the nature of the self (or selfhood). It uses philosophy, linguistics, psychology, psychohistory, and cultural history to find the scientific value of metaphors like that of self. “Metaphors in science, especially immunology, create reality for use,” he writes. “The inexorable demands of understanding the self metaphor have directed [me] to a deeper inquiry of immunology's governing agenda. . . . Metaphors and theory share an underlying structure, and thus their meanings are reciprocal and intimately linked.” And “more than a case study of academic semiotics, the self metaphor offers a lesson in the work of public language and of politics in the broadest sense.” For readers who savor scholarship, take an interest in the history of ideas, and can respond to the originality of Tauber's arguments, this part of The Immune Self will have great appeal.

My own view is that the time has come to abandon the self metaphor. I suspect that Tauber would agree that it no longer serves a useful scientific purpose and may actually be hindering progress. (For readers who believe that the end of immunology has come anyway, Tauber reminds us of Paul Cannon, the former president of the American Association of Immunologists and distinguished member of the National Academy of Sciences who, in the early 1940s, advised a young doctor, “No young man with aspirations for becoming a scientist should stake his future in immunology; all of the important questions have been answered.”) The value of the self metaphor plunged when it became clear that all T cells and B cells are both anti-self and anti-foreign. Their antigen receptors bind to particular autologous antigens and also to all structurally similar antigens, regardless of their origin in the self, or in microbial, allogeneic, or xenogeneic sources. The immune system, in short, does not operate by anthropomorphic principles such as “learn,” “self,” and “foreign,” nor is there a sharp line between “self” and “foreign.” A hepatitis virus surface protein is “foreign” to ordinary mice but becomes “self” in transgenic mice that bear in their germ line the gene for the viral protein. To a T cell, what counts is the affinity of its receptor for the three-dimensional structure of a peptide trapped in the groove of a major-histocompatibility-complex glycoprotein. Immunologists must, I believe, abandon the self–nonself question and focus on the rapid advances that are revolutionizing cell biology. The self metaphor has had its chance. It did not solve the transplantation problem, or those of tumor immunology, or even those of autoimmune diseases. It is time to adopt a new metaphor or move on to cell biology. Personally, I would choose the latter.

The Immune Self, I am sure, will prove influential among philosophers and historians of science. Physicians with a taste for history, for beautifully articulated arguments, and for an original point of view will also like this book. Perhaps readers who only want relief from the daily grind of bureaucratic edicts and restrictions on their professional work will find solace, escape, and even instruction in The Immune Self.

Robert S. Schwartz, M.D.