In Intolerant Bodies, Warwick Anderson and Ian R. Mackay sketch the trajectory of an etiological conundrum in twentieth century medicine, the realization that one’s immune system could itself produce illness. In the wake of the germ theory of disease and during the age of antibiotics, the diagnosis of autoimmunity was a throwback to an earlier constitutionalism. The authors suggest that it was a successor to the nineteenth century category of “fever,” capacious enough to cope with various maladies arising from individuality and variability. For a time, “connective tissue” or “collagen” disease served as a placeholder for autoimmunity, as did the invocation of allergy, which focused attention on external triggers. But in the end, the true culprit was found within. Autoimmunity redefined the central enigma of immunology, not least for Frank Macfarlane Burnet. The question was not, how do our bodies detect pathogens, but rather, how do we tolerate ourselves? And at what level could such exquisite self-recognition (and self-protection) operate: organism? cell? protein? gene?
Autoimmunity challenged, even repudiated, the triumph of reductionism in biomedicine. At a time when immunology was going molecular, autoimmunity was a stubborn reminder of the importance of whole bodies and problematic cases. I would underline Anderson and Mackay’s argument by observing that even the successes of molecular immunology, notably solving the antibody diversity problem, called into question a ‘central dogma’ approach to the immune system. Since the genome is not large enough to encode the antibody specificities for the millions of possible antigens mammals might encounter, the genes for antibodies are generated during an animal’s development, through translocation of genetic segments, high frequency mutation, and variable splicing. The resulting antibody ‘genes’ are not inherited in any straightforward sense from one’s parents. In other words, molecular biologists explained antibody generation, but at the cost of the gene’s meaning. Anderson and Mackay focus attention on their protagonist Burnet’s clonal-selection theory, whose demonstration relied on whole-animal experiments, not just the virtuosity of bench biologists. Molecular and especially chemical approaches (and their practitioners, those interloping “trans” immunologists, as Niels Jerne dubbed them) had to contend with the irreducibility of the immune system.
In the end, Anderson and Mackay make the striking remark that the autoimmunity’s “etiological framework is study enough, but it is empty.” In part, this is because the causes of autoimmunity remain so poorly understood. But there is more to it than that. The theory offers no simplistic answers. Indeed, the immune system works by being self-referential and cognitive rather than rooted in concrete determinants. By the same token, breakdowns occur at this systemic level. At the book’s end, the authors point out that the deconstructionist Jacques Derrida latched onto autoimmunity as a theory by which to understand the indeterminacy of language. Running along a parallel track, immunologists such as Francisco Varela and António Coutinho have invoked post-structuralism as a way to ground their immune network theories. This striking convergence between literary criticism and biological interpretation illustrates both the cultural permeability of knowledge and the tremendous resonance of the science of selfhood. Not that the issues are solely theoretical. Patients with autoimmune conditions, some as notable as Joseph Heller and Flannery O’Connor, have given eloquent testimony to the suffering entailed by their involuntary self-betrayal. Intolerant Bodies vividly captures this quizzical and fascinating field, which in turn provides a marvelous self-portrait (so to speak) of immunology.
Angela N. H. Creager is Philip and Beulah Rollins Professor of History at Princeton University and is currently a visiting scholar at the Max Planck Institute for the History of Science. Her most recent book is Life Atomic: A History of Radioisotopes in Science and Medicine (Chicago, 2013).