Historiography and Immunology Warwick Anderson and Neeraja Sankaran Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Early Histories of Immunology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 The History of Immunology Enters Philosophical Maturity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 “Denaturalized” Histories of Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Abstract In this chapter, we provide an overview of attempts from different disciplines to treat immunology and immunity as objects in the history of science. Despite the science’s immense potential, there is a paucity of broad, synthetic historical scholarship, compared to writings about the philosophy and, indeed, historiography of immunology. Following a reprise of the origins of immunology as a field of investigation, we trace the pathways through which histories of immunology, and their entwined philosophies, have developed and matured over the past century. The recent output of expansive “denaturalized” histories, which has given rise to a variegated and relatively autonomous historical landscape, is surveyed. The chapter concludes with a call for fuller realization of histories of immunology and immunity, with scholarship that is more comparative, connected, and transnational, rather than internally focused on biography, institutional development, and the succession of ideas and techniques. W. Anderson University of Sydney, Sydney, NSW, Australia e-mail: warwick.anderson@sydney.edu.au N. Sankaran (*) Independent Scholar, Bangalore, Karnataka, India e-mail: sankanet@gmail.com © Springer Nature Switzerland AG 2019 M. Dietrich et al. (eds), Handbook of the Historiography of Biology, Historiography of Science 1, https://doi.org/10.1007/978-3-319-74456-8_20-1 1 2 W. Anderson and N. Sankaran Introduction For a field of inquiry that has generated so little actual historical analysis, immunology continues to excite disproportionate and often disheartening historiographic disputation. During the past 30 years, we have heard (and sometimes delivered) lectures on the “infancy” of the history of immunology, its subordination to disciplinary scheming or philosophical argument, and its tantalizing “internalism” or deplorable lack of “context” (see Judson and Mackay 1992; Söderqvist 1993; Anderson et al. 1994; Söderqvist and Stillwell 1999). Paucity of substantive historical writing is more readily explained than the peculiar hypertrophy of historiographic discussion. The scientific novelty of immunology, which has developed and proliferated mostly since World War II, partly excuses the hesitation, or allergic reaction, of historians who prefer to stretch out their analysis over a longer span. Technical and recondite aspects of immunological arguments have deterred many historians without training in biology or biomedicine. Also, the theoretic ambitions of the science, which claims to arbitrate matters of “self” and organismal individuality, often have proven philosophically diverting, leaving history as mere appendage to the lively contest of ideas. Consequently, rather than add to expostulation of the “how” and “why” of histories of immunology or amplify polemics over what the history of immunology is a history of, we are tempted simply to urge the field’s would-be historians to write some more history. Yet we remain intrigued by the potential – indeed, the “pluripotency” – of immunology and immunity as objects of the history of science (Cambrosio et al. 1994; Sankaran 2012). Moreover, we are fascinated by how a science of memory has managed until recently to resist its historicity. And so, exigently, we venture once more into the historiographic fray. Memoirs and biographies of leading scientists, many of them hoping to secure intellectual hegemony in the immunological field, have rubbed uneasily alongside normative philosophical disquisitions about where the field should be and what it ought to encompass (we will return to these below). In 1994, historians Warwick Anderson, Myles Jackson, and Barbara Gutman Rosenkrantz instead recommended an alternative approach that dismantled the naturalized walls erected around the science of immunology and opened up historical study of the dispersed cultures of “immunity.” They envisaged a narrative synthesis that might draw together immunological knowledge, broadly conceived, whether from the laboratory, the clinic, public health, philosophy, politics, literature, or ordinary experience. Avoiding the constraining categories of biography, institutional history, and narrow philosophical argument, this sort of history would entail registering concept work around immunity generally (see Anderson and Mackay 2014a). Evidently, the authors were reflecting on the postulates of historical epistemologist Georges Canguilhem, who thought that too often the history of science “is done as natural history, because science is identified with scientists and scientists with their civil and academic biographies, or even because science is identified with results and these results with their present pedagogical statement” (Canguilhem 2005 [1975], 203). In contrast, the proper history of a science, he continued, “is related not only to a group of Historiography and Immunology 3 sciences without intrinsic coherence but also to non-science, ideology, to political and social practice” (204). In this chapter, we want to chart the development of various forms of the natural history of immunology, before tracing the recent emergence of what Canguilhem might have called unnatural histories of immunity, observing along the way the many impediments to the broad tolerance that such narrative synthesis requires. Early Histories of Immunology The earliest historical accounts of immunology may be found embedded in histories of bacteriology or microbiology, which is hardly surprising since the origins of the two fields were intricately entwined. Scottish hygienist William Bulloch, author of what is generally regarded as the first “authoritative standard work” (Foster 1970, ix) on the history of bacteriology, found the source of the discipline in the French – or Pasteurian, as derived from the school of Louis Pasteur – sector of bacteriology. Since Bulloch’s book, which grew out of a series of lectures delivered in 1936 at the University of London, ended as early as 1900, he left the nascent specialty clinging to the maternal discipline. The new specialization, according to Bullock, concentrated on the problems of the prevention of infective disease by artificial inoculation, and the processes involved in the recovery from infection [which in turn] led to the creation of that branch of science called Immunology, for although the latter now has implications far beyond the bacteriological sphere, it was in connexion with bacterial diseases that it first took its root. (Bulloch 1938, 255) The publication record bears out Bulloch’s claims. Surveying articles and journals in the two fields from the mid-nineteenth century to the 1990s, historian Pauline M.H. Mazumdar noted that whereas articles specializing in immunology began to appear as early as the 1880s and 1890s, they were published in journals that featured bacteriological investigations in higher proportions. Well into the 1930s, in fact, the vast majority of immunology papers continued to appear in such journals, despite the establishment by then of three specialist immunology journals. It was not until a full century later that the number of stand-alone immunology journals overtook those of microbiology (Mazumdar 1989, 2–4). Bulloch’s book together with William Ford’s volume on Bacteriology for the Clio Medica series (1939) remained the only available chronicles of immunology for over three decades. Then, another British pathologist, William Foster, noting that nothing new had appeared in the interim, proceeded to “bring these histories up to date” with a book that extended until 1938 (Foster 1970, x). The growing importance of immunology in relation to its parent discipline is clearly in evidence in Foster’s book – beginning with the appearance of its name in the title. Furthermore, in contrast to Bulloch’s book – where the single chapter devoted to the “history of doctrines of immunity” was the last of eleven – Foster allocated two entire chapters out of a total of eight to the subject, focusing first on its scientific basis (92–126) and then on its applications in medical practice (127–164). 4 W. Anderson and N. Sankaran Foster’s treatment of immunology, being longer, is naturally more developed than that of either Bulloch or Ford, but all authors were largely in agreement with one another, both about the overall pattern of development of the field and the individuals whom they identified as important contributors. All observed the splitting of what they called “immunity science,” very early in its history, in two directions: a practical line directly arising from Pasteur’s work on immunization and a theoretical vein attempting to explain the mechanisms of immunity. These theories, in turn, led to the development of two distinct branches of immunology. One tendency, originating in the ideas of the Russian zoologist-turned-pathologist Ilya (Elie) Metchnikoff, derived from his observations of the cell-mediated phenomenon of phagocytosis,1 stressed the importance of cells in mediating immunity (Bulloch 1938, 259–260; Foster 1970, 92–100; see also Tauber and Chernyak 1991). No author identified a single counterpart of Metchnikoff to represent the rival, the so-called “humoral” theories of immunity, which attributed the property of immunity to protective substances, antibodies against bacteria, viruses, and sundry foreign material, in the blood and other body fluids (Bulloch 1938, 255–256). Not for a lack of choices, however, is such a figure missing, but rather, there were too many contenders: Paul Ehrlich (Silverstein 2001), Emil von Behring (Linton 2005), Jules Bordet, and Richard Pfeiffer, among many others, all made vital contributions to the early understanding and clinical applications of humoral immunity. Three of these men – von Behring, Bordet, and Ehrlich – received Nobel Prizes in Physiology or Medicine, specifically for their contributions to their branch of immunology that for a time was labeled “immunochemistry.” From the 1960s, memoirs supplemented these textbook digests and internalist accounts of the history of immunology. Both F. Macfarlane Burnet and Peter Medawar, who shared the 1960 Nobel Prize for Physiology or Medicine for their discovery of the mechanisms inducing the immunological tolerance of “self,” wrote accomplished and revealing autobiographies. In Changing Patterns: An Atypical Autobiography (1968), Burnet, a shy and introverted man, offered a survey of the changes in scientific aspects of medicine occurring over the course of his own life, including not just immunology but also virology and microbial ecology (see also Sexton 1991; Sankaran 2010b). In contrast, Medawar’s Memoir of a Thinking Radish (1986) cleverly skirted around his pioneering studies of transplantation immunology, preferring to display instead his consummate erudition, wit, and vivacity. Among the more revealing recent examples of this genre, Baruj Benacerraf’s From Caracas to Stockholm (1998) has described his life and times, placing his work in the genetics of the immune response in transnational contexts. A Venezuelan banker turned Nobel prize-winning immunologist, Benacerraf had a lot of material with which to work. Peter C. Doherty, who shared the 1996 Nobel Prize in Physiology or Medicine for his discovery of how the immune system recognizes 1 Metchnikoff has been variously described as a zoologist, embryologist, immunologist, or medical scientist by different writers. His own self portrait was that of a zoologist who “suddenly became a pathologist” (as quoted in Foster 1970, 92–93). Historiography and Immunology 5 foreign antigens in association with the body’s own tissue, or histocompatibility, antigens, told a similarly audacious story in A Beginner’s Guide to Winning the Nobel Prize (2006), which was heavy on scientific adventure and accomplishment, if light on personal detail. Understandably, most of these memoirs and tributes were designed to cement the place of the protagonists in the history of immunological thought and to entrench the boundaries of the discipline around them. Predicting the end of the history of immunology, the completion of inquiries, became a common trope. Burnet, for example, forecast in 1965 that immunology would soon run out of problems to solve. In retirement, he concluded that “most of the discoveries have been made and those that can be made are already discernable” (as quoted in Sexton 1991, 135). In 1967, Niels K. Jerne, who would receive the 1980 Nobel Prize in Physiology or Medicine for his cognitive model of the immune system, observed that “immunology will be completely solved within fifty years from now” (Jerne 1969, 347). Having labored hard in the immunological vineyard, Burnet and Jerne felt they could now “sit back, waiting for the End” (Jerne 1967, 601). In claiming their work as definitive and conclusive, Burnet and Jerne were not only securing their place in history, they were demarcating and validating what counted as immunology, or even as proper scientific research, and foreclosing on other, alternative styles of investigation. Thus, as historian Simon Schaffer (1991, 152) pointed out in his study of discourses on the “end” of physics, the strategic deployment of history can become part of the “theoretical technology of modern science.” Subsequent biographies of immunologists have proven more critical, sometimes even displacing them from their assumed central positions in the field. Thomas Söderqvist’s bold sally into the life of Jerne has proven particularly influential and controversial. In Science as Autobiography: The Troubled Life of Niels Jerne (2003), the Scandinavian historian of biology delved deep into the Danish immunologist’s psychological conflicts and disturbed personality as he attempted to show how existential strife might shape scientific research. Söderqvist believed that Jerne’s immunological research represented a flight from the guilt he experienced in his private life. But as historian Ilana Löwy (2004, 330) observed: “It is not clear how Jerne’s psychological profile explains his specific achievements as an immunologist or, alternatively, how his personality sheds new light on his work on antibodies or his talents as a scientific entrepreneur.” Söderqvist has remained a forceful advocate of biography as a means of understanding scientific creativity and as a way of making the history of technical matters more accessible, but few historians of immunology so far have followed his example.2 2 See the Journal of the History of Biology 44 (2011) for a special issue on scientific biography in general. 6 W. Anderson and N. Sankaran The History of Immunology Enters Philosophical Maturity Even when the science of immunology was somewhat inchoate, several of its active practitioners were thinking historically, in an analytically detached mode, about their newfangled enterprise. The Polish serologist turned philosopher of medicine Ludwik Fleck, for example, in the 1930s pondered the mysteries of the Wassermann reaction, a novel immunological test for the spirochete of syphilis. Genesis and Development of a Scientific Fact (1979 [1935]) traced the history of the Denkstil, the stylized or conditioned perception, which had rendered what was basically an allergic phenomenon, an indicator of host reactivity, into a test for an invasive microbe. Lost to obscurity until rediscovered and translated into English in the 1970s, Fleck’s treatise, in effect, presented the genealogy of a particular thought style in the emerging discipline, one that emphasized biological individuality and reactivity, rather than chemical specificity (Anderson and Mackay 2014a, 45–46; see also Löwy 1986; Moulin 1986). But as in many subsequent accounts of immunology’s development, the historical narrative was subordinated to philosophical argument, which in this case was advancing the sociology of knowledge, emphasizing the immunological thought collective’s “readiness for directed perception” when discovering and affirming scientific facts (Fleck 1979 [1935], 110). Like Fleck, most later historians of immunology have trained in the field: some quickly swerved into further education in the history of biology and medicine, whereas others waited to the end of their scientific careers before inclining toward historical reflection. A clinician tardily turned historian, Arthur M. Silverstein collected various essays on the history of immunological ideas in the synoptic A History of Immunology (1989), which covered mostly the exhilarating period of discovery between 1880 and 1930. Following Foster, he was particularly committed to differentiating the adherents to cellular (phagocytic) immunity, clustered around Pasteur and Metchnikoff in Paris, and the votaries of humoral (antibody-mediated) immunity, associated with Ehrlich and others in Berlin. Silverstein discerned three successive investigatory traditions or paradigms or thought styles: first, the early involvement with bacteriology, then the preoccupation with immunochemistry until the middle of the twentieth century, and later, the development of a biological mindset. As a clinician, Silverstein also proved attentive to pathogenic aspects of the immune response, especially autoimmunity – where the individual’s defense mechanisms are turned against normal body tissues – but also allergy and anaphylaxis. He described in meticulous detail the Berlin aversion to such dysteleological processes, contrasting this reaction to the peculiar conceptual terrain of early twentieth-century Vienna and Paris that was nurturing these, and other, disturbing notions. Silverstein’s fascination with Ehrlich was evident in his biography of the brilliant immunochemist (2002), which added immeasurably to our knowledge of the technical nitty gritty of research into antibodies and the convolutions of German institutional dynamics. In the second edition of A History of Immunology (2009), Silverstein expatiated on the period after World War II, examining the origins of the clonal selection theory of the humoral response, explanations for the generation of antibody diversity, Jerne’s network theories of the immune system, and so on – though steering clear of much recent molecular biology. Snippets of cultural and Historiography and Immunology 7 biographical context tantalized in the second section, which was misleadingly titled “social history,” for as philosopher of immunology Alfred I. Tauber (2010, 636) put it, “Silverstein’s reflections provide only glimpses of a highly competitive and highly rewarded discipline whose sociology has barely been scratched.” Anne-Marie Moulin embraced history of science not long after commencing her career in parasitology and immunology (see, for example, Moulin 1985, 1989). In the French tradition of historical epistemology, she was interested in how language framed scientific inquiry, particularly how metaphors and models such as the “immune system” shaped our understanding of embodiment and individuality. Le dernier langage de la médecine (1991) attempted a narrative synthesis of the history of immunological thought in the twentieth century, defining two distinct periods, the first focusing on the meaning of vaccination and the event of the antigen-antibody interaction, and the second concerning the concept of the immune system (see also Moulin 1989, 1993, 2000; Moulin and Cambrosio 2001). Moulin proposed that Metchnikoff’s idea of phagocytosis, dormant for much of the twentieth century due to the dominance of immunochemists, had prefigured the development of cellular immunology in the 1950s. From the 1940s onward, Burnet’s theories of antibody production and Peter Medawar’s research on tissue graft rejection increasingly implicated cellular processes in the immune response. According to Moulin, systemic thought in cell biology culminated in Jerne’s complex – and rather selfreferential – speculations on immunoregulation. Already Moulin (1986) had adroitly demonstrated the exchange of metaphor and model between the cognitive sciences and immunology during this period. But the binary logic of her book’s narrative was strained, and the argument for an epistemological cleavage in the 1950s proved difficult to maintain. Historian Peter Keating (1993, 611) admired Moulin’s historical ambition but regretted that the book “sometimes reads like an overwrought review article interlarded with potted biographies.” Nonetheless, Le dernier langage de la médecine remains the sentinel narrative history of immunology. The emergence of AIDS in the 1980s, seen as a devastating dysfunction or deficiency of the immune system, stimulated extensive historical and philosophical inquiry toward the end of the century into immunology and the defense of self – though rarely was the impetus explicitly acknowledged (but see Moulin 1991; Martin 1994). In Species and Specificity (1995), Pauline M.H. Mazumdar, previously a historian of human genetics, contrasted the ontological “specificity” of Berliners like Robert Koch and Ehrlich with “unitarian” biologists such as Carl von Nägeli, Max von Gruber, and the influential immunologist Karl Landsteiner, who emphasized physiological continuity and gradation (see also Mazumdar 1975). She saw this distinction as mapping onto the difference between structural chemistry and colloid chemistry. Mazumdar traced in particular the thinking of Landsteiner, following him from Vienna to the Rockefeller Institute in New York City, describing his interest in biological individuality and his efforts to redefine immunological specificity as the expression of graded quantitative 8 W. Anderson and N. Sankaran affinity, culminating in his major work, Die Spezifizität der Serologischen Reaktionen (1933).3 As Warwick Anderson (1997, 560) put it, Mazumdar chose “to illustrate the power of ideas in biology, their transmission through teacherstudent relationships, and their refinement in dialogue.” The clinical, institutional, and cultural contexts were drawn faintly, if at all. A few years earlier, Mazumdar (1989) had edited a collection of essays similarly exploring conceptual histories of immunology, many of them engaging with Burnet’s clonal selection theory of antibody formation. Until the end of the twentieth century then, the history of immunology would struggle to escape the confines of biography or the genealogy of big ideas, as revealed in the scientific journals. The metaphysical imperative was felt most strongly in the influential studies of Alfred I. Tauber, an immunologist turned philosopher of science. Even in 1991, with Leon Chernyak, Tauber was championing Metchnikoff as a theorist of organismic integration and individuality, and not simply a discoverer of cellular defense mechanisms. They claimed Metchnikoff argued that evolutionary struggle between different cell lineages dynamically negotiated the organism’s integrity or self-definition (Tauber and Chernyak 1991). Discussions of the immunological constructions of “self” also figured prominently in a collection of essays that Tauber (1991) edited that year. In the foreword, evolutionary biologist Richard C. Lewontin (1991, xvi) suggested that the crucial question is: “How does the cell know the difference between you and me?” Typically, he emphasized the importance of the “dialectic” between self and other. Similarly, Chernyak and Tauber in their contribution criticized Burnet’s clonal selection theory for reducing self to a blank in the immunological repertoire – to that which is tolerated or whatever does not induce a reaction. Rather, they insisted, “the Other as non-self, not as another example of self, not as essentially ‘the same,’ but rather as ‘otherness’ must be an essential constituent of Self” (Chernyak and Tauber 1991, 128). An intellectually probing immunologist, Tauber had been inspired by the philosophical ambitions of Alfred North Whitehead and Burnet. “If science is not to degenerate into a medley of ad-hoc hypotheses,” Whitehead (1925, 24) wrote, “it must become philosophical and must enter upon a thorough criticism of its own formations.” Whereas, Burnet (1965, 17), a close reader of Whitehead, had asserted that “immunology has always seemed to me more a problem in philosophy than a practical science.” Tauber was happy to take Burnet at his word. In The Immune Self (1994, 7, 82, 83), Tauber offered “a careful delineation of the scientist’s theoretical development,” showing how the Australian took “diverse conceptual threads from virology, ecology, genetics, developmental biology and, of course, immunology,” weaving them during the 1940s “into a fecund theory [of self-tolerance] that remains the crucial conceptual foundation of the discipline today.” “Analogous to the apperception of the transcendental ego,” Tauber wrote, “Burnet’s self is based upon a notion of unity—a coherent whole—to account for the inner, fundamentally integrated organism” (291). Tauber felt that Burnet’s innovative “concern for accounting for personal 3 Translated into English as The Specificity of Serological Reactions (1936). Historiography and Immunology 9 identity provides the link to Metchnikoff” (7), though he failed to adduce much evidence for the bond apart from the perceived homology of ideas. Indeed, he realized, “in tracing the linkage between Metchnikoff and Burnet, I may be accused of over-stretching my thesis” (97). Additionally, Tauber wondered if Burnet’s recourse to “self” might indicate the impact of Freudian psychology on the immunologist (Tauber 1994, 97; see also Tauber and Podolsky 1994). If he had visited the extensive Burnet archive in distant Melbourne, Australia, Tauber might have noticed the scientist’s indifference to Metchnikoff and distaste for psychology, as well as his contrasting enthusiasm for Julian Huxley, George Bernard Shaw, Henri Bergson, and Whitehead, among others (Anderson and Mackay 2014b). He would have learned about the local and yet cosmopolitan intellectual world that Burnet actually inhabited. Thus, while Tauber’s studies conveyed the impression of historical research, they did not derive from the conventional methods of the discipline. The Immune Self (1994, 295) concluded with a recommendation that “we abandon attempts to pinpoint and define the self, allowing its definition by expression in its phenomenological address: the subject becomes defined in the process of its encounter with the world.” Tauber worried that in absorbing Burnet’s term “self,” immunology had “borrowed a philosophical term to approximate a language that is inadequate to that task” (295). A few years later, medical historian Scott H. Podolsky joined Tauber in telling the story of Burnet’s resistance to instructional models of antibody formation and his advocacy of cellular processes for recognizing and responding the foreign or nonself (Podolsky and Tauber 1997). According to Burnet, tolerance of self mostly, or most efficiently, was imposed in vertebrates through contact with “self-antigens” during embryonic life, which effectively knocked out some antibody-producing cells. Podolsky and Tauber praised Burnet’s biological insight, his awareness that self-tolerance was more interesting biologically than defense, and his application of Darwinian mechanisms in his theory of how encounters with foreign antigens might select and stimulate preserved clones of antibody producing cells. They went on to examine exhaustively the rise of molecular approaches in immunological research, assessing their influence on theories of immune selfhood. Concerned that “self” was dwindling into a fixed genetic signature, Podolsky and Tauber sought process-oriented and functional, or contextualist, accounts of immunological responsiveness. The “newer view of immune function,” they concluded, “is fundamentally formulated as self-seeking, self-organizing activity, whose structure is decentered from any bounded self” (Podolsky and Tauber 1997, 375). They implied that Burnet was responsible for the cognitive encumbrance of this bounded self, overlooking his immersion in Whitehead’s process philosophy and his propounding of dynamic, ecological thinking in infectious diseases research.4 Thus, Burnet had become a useful straw man in philosophical 4 Tauber (1999, 459) later observed that Burnet “sought a firm definition of the immune self” (see also Tauber 2004, 2008, 2016). But see Anderson (2004) on Burnet’s ecological vision. In a recent synthesis, Tauber (2017, 228) has attempted to reconcile the two Burnets, concluding redundantly that “immunology deserves much greater attention by philosophers of science.” 10 W. Anderson and N. Sankaran disquisitions, but this meant that, while accruing some value in philosophy, Tauber’s representation of the immunologist lost credit as history (see also Cohen 2000). Ironically, Tauber has functioned as the expedient historian of immunology for most philosophers and anthropologists seeking insight into the “science of self.” When philosopher Thomas Pradeu (2012, 47), for example, asked, “Why does Burnet introduce the concepts of ‘self’ and ‘nonself’ to immunology, and what exact definition does he give them?”, he turned to Tauber for the answers. Pradeu thus attributed to Burnet the notion of a genetically determined self, which served to distinguish, misleadingly perhaps, his own “continuity” thesis (189). Similarly, anthropologist A. David Napier (2012, 130, 133) drew on an impoverished and distorted history of immunology when he claimed that Burnet’s clonal selection theory was based on a “culture-bound” assumption of an autonomous and static “self,” a “prior and persistent” identity. Instead, Napier imagined an immune system that engages with difference, rather than defends the body (Napier 2003). Such examples of metaphysical theories dependent on unreliable internalist histories of immunology could be multiplied indefinitely (see Anderson and Mackay 2014a, 144–51). “Denaturalized” Histories of Immunity Reflecting in 1992 on the recent Ischia conference on the history of immunology, science journalist Horace Freeland Judson and clinical immunologist Ian R. Mackay lamented that historians and scientists seemed prone to talking past one another (459–61). Evidently, there had been some friction on the island in the Bay of Naples, which occasionally flared into “open confrontation between ‘the scientists’ and ‘the historians’” (Cambrosio et al. 1994, 375). According to Judson and Mackay, historians frequently had missed the point of the science, and those scientists trying to take up historical inquiries often were resorting to tedious “hyper-review articles,” rather than attending to “intellectual context, social settings, scientific lineages, styles and influences, failures, missteps and conflicts, the stuff of what scientists do” (460; see also Gallagher et al. 1995). Soon Söderqvist (1993, 565) responded indignantly, complaining that the agenda of the history of immunology at Ischia and elsewhere was “still largely set by practising scientists.” He was disappointed that Silverstein and Moulin in their monographs had merely alternated “between analyses of leading ideas, concepts and experiments, descriptions of institutions and portraits of individual scientists” (565). Instead, he recommended two distinct approaches. A “structural” explanation would “focus on the overall cognitive structure of the disciplinary discourse as it exists independent of the historical actors and their social context” (566). In contrast, a biographical exposition, which he favored, would “take the subjective and idiosyncratic self-understanding of individual immunologists as the point of departure” (566). Later, Söderqvist would shift his ground, charging that “so far there have been no sustained attempts to place the development of immunological thought and practice in the context of twentieth-century science and medicine, not to mention the wider social and political context” (Söderqvist and Stillwell 1999, 215). Historiography and Immunology 11 In the wake of the stormy Ischia meeting, science studies scholar Alberto Cambrosio and colleagues assembled another conference on “Immunology as a Historical Object,” as part of the 1993 series of the Boston Colloquium for the Philosophy of Science (Cambrosio et al. 1994). As editors of the subsequent special issue of the Journal of the History of Biology, they discerned two themes in the contributions: the role of “experimental systems” and technique in immunological practice (Stillwell 1994; Löwy 1994; Silverstein 1994; Keating and Cambrosio 1994) and how foundational models and metaphors might guide or inhibit research (Söderqvist 1994; Tauber and Podolsky 1994). The first theme, at least, represented a deviation from scientists or philosophers setting the scene of historical investigation. In the concluding article, addressing historiographic lacunae, Anderson et al. (1994) issued their manifesto for the “unnatural history” of immunity, a plea for historians to inquire beyond conventional, or ostensibly “natural,” delimitations or even typologies of the field. They wanted a more ecumenical or multidimensional history of immunity, one that might encompass the laboratory, the clinic, experiences of immunological disorders, distinctive research schools, national styles of investigation, manufacture of biologics, literary descriptions, social theory, politics, and philosophy. Thus, they hoped for critical and independent historical inquiry into the enormous variety of immunological worlds (see Haraway 1991; Martin 1990, 1994). Arguing against simple filiative models and linear narratives, they demanded dispersive studies that would account, in particular, for the social and material conditions of knowledge production and transmission. In response to Canguilhem’s (2005 [1975], 198) question, “Of what is the history of science a history?,” they were imagining – despite using the term “unnatural” – richly “ecological histories of immunity” (587). They yearned for a diverse “ecology” of immunological knowledge and practice (Rosenberg 1979). Some two decades later, Sankaran (2012) would return to this nagging issue, advocating similarly “pluripotent” histories of immunology. “The history of immunology,” she wrote (2012, 49), “seems akin to . . . pluripotent stem cells; while not yet committed to any single path of development, it is prolific nonetheless, brimming with the potential to grow in diverse directions.” Late in the twentieth century, a few historians of science had begun to chart such materialist and encompassing histories of immunity. Ilana Löwy, who trained in cellular immunology, was connecting the developing science with literature (1988), the clinic (1992, 2008), and the contemporary theories of biological individuality (2003), exploring boundary concepts and federative experimental strategies. Combining historical and ethnographic approaches, her monograph, Between Bench and Bedside (1997), was a pioneering study of the links between the immunology laboratory and clinical research in a French cancer ward. Peter Keating and Alberto Cambrosio specialized in tracking monoclonal antibodies between laboratory and clinic, especially in Biomedical Platforms (2003) which documented in impressive detail the use of this technique in the classification of leukemias and lymphomas, showing the influence of processes of standardization and regulation (see also Cambrosio and Keating 1995; Marks 2015). Having immersed herself in the archives, Sankaran (2008, 2010a, b, 2013) set about placing Burnet and his immunological research in a broader bacteriological and biological context, as well 12 W. Anderson and N. Sankaran as a plausible institutional and national setting (see also Park 2009). Meanwhile, other historians surveyed the sensitive and reactive borderlands of immunological discourse, focusing on histories of “allergy,” an expansive field with an ambiguous relationship to the scientific discipline. Thus, Mark Jackson (2007) described the various scientific and clinical understandings of allergy since Clemens von Pirquet first coined the term in Vienna in 1906 to signify immunological hyperreactivity. A medical historian, Jackson, used the spectrum of beliefs about allergy – that new disease of civilization – to illuminate anxieties and insecurities about modern life (see also Jackson 2003, 2009; Jamieson 2010). As an environmental historian, Gregg Mitman (2007) preferred to regard allergy and asthma as sampling devices that might reveal American social inequality, habitat degradation, and political marginalization. Refreshingly, his attention to the clinical and civic dimensions of allergy and asthma included stories of the experiences of sufferers, not only analysis of the research conducted on them. The boundaries of what counted as immunological history were shifting. In A Body Worth Defending (2009), cultural historian Ed Cohen vividly depicted the passages of metaphor and model between the legal or political domain and the emerging immunological sciences, which shaped – or constituted perhaps – the meaning of modern personal identity. And so, at the beginning of the twenty-first century, we were gaining a clearer view of the historical heterogeneity of concepts of immunity. In Intolerant Bodies (2014a), Anderson and Mackay delineated the conceptual history of autoimmunity, or auto-allergy as it was once called, the excessive reactivity of the immune system against the body’s own constituents (see also Parnes 2003). It was, in a sense, the biography of a mode of pathogenesis, a historical inquiry into the longevity of notions of idiosyncrasy, diathesis, and individual variation in twentieth-century biomedicine. In trying to understand “how autoimmunity became thinkable” (4), they attempted to bridge the research laboratory and the hospital clinic, at the same time as they attended to the experiences of those suffering autoimmune disease, often articulated in literary forms, sometimes embedded in case histories. Additionally, they sought to adduce references to autoimmunity, usually figured as deconstruction of the self, in social theory and metaphysics, but their goal was to historicize philosophical speculation, not to use history to illustrate it. The book, they claimed, was “an attempt to describe the interpretation of disease—whether by scientists, physicians, philosophers or patients—as intellectual practice” (5). Importantly, they endeavored to situate, or contextualize, knowledge production about the reactivity and sensitivity of the modern self, focusing serially on the cultural settings and institutional matrices of Paris, Vienna, London, New York, and Melbourne. Once into the 1980s, however, the narrative became more schematic and less contingent, sometimes resembling one of those scientific review articles that Mackay had warned against. Tauber (2015, 385) generously regarded Intolerant Bodies as “perhaps the best overview of immunity (normal and pathological) available for the general reader,” but he chided the authors for their preoccupation with Burnet and his legacy, reproving them for brushing off Metchnikoff and limiting their philosophic ambition. Despite the book’s flaws, Anderson and Mackay hoped it might serve as a template for more elaborate and circumspect histories of immunity. Historiography and Immunology 13 During the past decade, a spate of histories of recent immunology has washed over the heads of the public. Mostly, these books manifest the desire of senior immunologists to instruct the common reader in the excitement and adventure of scientific discovery, but the density of detail contained in the texts, along with an emphatically teleological trajectory, has meant inevitably that their primary readership consists of medical doctors and neophyte investigators. Indeed, one author of such a work has declared his imagined readers are “research and clinical immunologists as well as students and teachers of immunology” (Nagy 2013, xv). Even when seeking to render esoteric knowledge exoteric and publicly accessible, as Fleck (1979 [1935]) would have said, these scientific authors have tended to revert, again, to extended reviews of immunological publications (Rees 2015; see also Brent 1997). The more appealing accounts of seminal events and major breakthroughs in recent immunological research function also as memoir, permitting the reader a sense of immediacy and human interest (Paul 2017). Too abstruse and Delphic to succeed as popular history, these chronologies of immunology will provide future historians of biology with ample material for less hermetic analysis. Conclusion Conflict and disputation have marked the historiography of immunology, whether between scientists or clinicians and intellectual or cultural historians or between those favoring conceptual history or historical epistemology and those seeking historical cases that neatly illustrate philosophical speculations. Some historians have turned to biography to find an overarching telos, while a few historically inclined scientists have resorted to thinly contextualized literature reviews. Too often, historical research has been harnessed to scientific or institutional or philosophical agenda. The reasons for the narrow and dependent character of so much of the history of immunology remain enigmatic, but no doubt the novelty and extremely technical nature of the science have contributed to conceptual restraint and subordination. When so much effort is invested in attaining competence in the science, historiographic ambitions can become subsidiary – even as the desire for philosophical probing abideth forever, so it seems. Such historical reticence or timidity might pertain to other fields of biological inquiry, such as the neurosciences, but seldom has it been as severe or constraining as in immunology. Until recently, there was reluctance to engage with the social and cultural histories of immunity or to look beyond the rigid boundaries of disciplinary expertise. In the past decade or so, however, we have discerned several attempts to write richly situated and deeply contextual histories of immunity, rendering possible the emergence of more encompassing and resourceful narratives. These studies have revealed the scattered and fragmented geography of immunological knowledge and practice, showing us multiple heterogeneous sites of scientific work and influence, or “biomedical platforms,” many of them located far from conventional North Atlantic hotspots. Thus Melbourne, Singapore, Tokyo, and many other places have joined Paris, Berlin, Vienna, London, and New York as locales for immunological knowledge production. Our histories are gradually becoming as cosmopolitan as the 14 W. Anderson and N. Sankaran science. Progress along this path so far has been tentative, and such densely situated and contextualized narrative histories of immunology or immunity remain rare. Nonetheless, there are, as we have suggested, some promising signs that the historiography of the investigatory and clinical enterprise is becoming less esoteric and less auxiliary to other modes of inquiry. One might say the history of immunology is moving away, slowly, from typological and subsidiary styles toward more entangled, situated, and connected – rather than derivative – ecological explanations. As the history of immunity belatedly gets lodged in particular cultures, institutions, and social structures, additional challenges arise. In emphasizing the multiplicity and dispersion of knowledges of immunity, we run the risk of writing a profusion of fragmented, isolated stories, which overstate the disunity of science. When scientists and philosophers dominated the history of immunology, this was never a problem: instead, they assumed the singularity of science and imagined the simple diffusion, or laminar flow, of scientific ideas around the globe. Now, we need more comparative and connected histories of immunity, critical studies that help us to understand how immunological knowledge and practice travel, how they are transacted, adapted, and contested at various sites, on different terrains (Anderson 2018). That is, we should be wondering what the transnational or postcolonial history of immunology might yet be. Acknowledgments Warwick Anderson is grateful for research support from the Australian Research Council (DP120100861). References Anderson W (1997) Review of Species and specificity: an interpretation of the history of immunology, by Pauline M.H. Mazumdar. Isis 88:560–560 Anderson W (2004) Natural histories of infectious disease: ecological vision in twentieth-century biomedical science. Osiris 19:39–61 Anderson W (2018) Remembering the spread of Western science. Hist Rec Aust Sci 29:73–81 Anderson W, Mackay IR (2014a) Intolerant bodies: a short history of autoimmunity. 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