Studies in History and Philosophy of Biological and Biomedical Sciences 48 (2014) 185e188
Contents lists available at ScienceDirect
Studies in History and Philosophy of Biological and Biomedical Sciences journal homepage: www.elsevier.com/locate/shpsc
Introduction
Following cancer viruses through the laboratory, clinic, and society Robin Wolfe Scheffler* American Academy of Arts and Sciences, 136 Irving Street, Cambridge, MA 02138, USA
a r t i c l e i n f o
a b s t r a c t
Article history: Available online 16 October 2014
These essays in this special issue follow cancer viruses as a means of better understanding the history of biomedicine. Spanning the worlds of chronic and infectious disease research, the history of cancer viruses touches upon an enormous diversity of settings and scientific disciplines. Cancer viruses appeared during the twentieth century as vaccine targets, vaccine contaminants, laboratory anomalies, and tools for molecular biology. Rather than picking one discipline or setting to privilege above others, this issue suggests what can be learned, not only about cancer viruses but also about the character of modern biomedicine, from following these viruses through their different historical trajectories. Ó 2014 Elsevier Ltd. All rights reserved.
When citing this paper, please use the full journal title Studies in History and Philosophy of Biological and Biomedical Sciences
There is a long history to the fear that cancer might be contagious. At the end of the 19th century, however, this fear was tempered by the new hope that discovering a cancer-causing infectious agent would enable the large scale prevention of cancer. This hope centered on the identification of cancer viruses. The six essays gathered in this issue provide a synoptic account of the pathways of cancer virus research and the research trajectories of cancer viruses ever since. These attempts to understand the relationship between viruses and cancer occupy a middle ground in the well-known transition from infectious to chronic diseases as the main focus of public health in industrial societies. Befitting this intermediate status, inquiries into the nature of cancer viruses incorporated practices from epidemiology, immunology, microbiology, virology, pathology, genetics, and molecular biology. By following viruses themselves from place to place and discipline to discipline, these essays individually and collectively shine new light on the critical roles that cancer viruses have played in the production of knowledge
* Tel.: þ1 617 576 5091. E-mail address: rscheffl[email protected]. http://dx.doi.org/10.1016/j.shpsc.2014.09.004 1369-8486/Ó 2014 Elsevier Ltd. All rights reserved.
in a wide range of biomedical fields. Starting at the beginning of the twentieth century, Neeraja Sankaran contrasts the biography of Rous Sarcoma Virus with bacteriophage, and shows the importance of analogies between the two for the development of virology and early molecular biology. Moving forward, Gregory Morgan examines the discovery of mouse leukemia viruses, a crucial event in the revival of cancer virus research in the middle of the twentieth century. Next, Brendan Clarke uses the history of Epstein Barr Virus to pose new questions about space and scale in cancer research; Laura Stark and Nancy Campbell follow the unexpected appearance of Simian Virus 40 as a possible oncogenic virus in human research settings; and Robin Scheffler raises the possibility that our understanding of the history of cancer viruses should also include viruses which are now thought not to exist, in this case a childhood leukemia virus. Finally, looking at the present, Alex Broadbent considers how the relationship between Human Papilloma Virus and cervical cancer forces us to clarify our understanding of what it means for a virus to “cause” cancer and the consequences this has for classifying illness. While cancer viruses have not lacked for chroniclers, the sinuous path of cancer viruses through the twentieth century fits uneasily into the history of cancer, medicine, or biology. The historiography of cancer tends to emphasize clinical treatment,
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authority, and culpability, arenas where cancer viruses do not usually appear.1 Likewise, cancer viruses have fallen into the divide between the clinic and the laboratory in the historiography of biology and medicine. Following the “social turn” historians of medicine sought to deemphasize the laboratory in their narratives while historians of biology focused on the creation of laboratorybased experimental systems far removed from the concerns of the clinic. Neither of these agendas captured the full set of activities associated with cancer viruses. Fortunately these divisions are eroding, and interest in the overlap of biology and medicinedbiomedicinedis on the rise (Huisman & Warner, 2004; Keating & Cambrosio, 2004; Löwy, 1996, 2011). As “tracers” for uniting the different sites and practices involved in writing a richer history of biomedicine, cancer viruses are exceptional precisely because of their multifaceted and unresolved history.2 Until the late twentieth century, the idea that cancer might be caused by an infectious agent offered the most therapeutically-relevant path of inquiry into the etiology of cancer. Demonstrating the genetic origins of cancer presented no hope for prevention or therapy, while exposure to environmental or chemical carcinogens could at best be ameliorated when such compounds were identified. By contrast, the identification of an infectious agent responsible for cancer promised widespread prevention through vaccination. Yet this promise did not immediately translate to enthusiasm for cancer virus research. The separation of infection from other environmental or hereditary causes of disease was rarely so clear as advocates of bacteriology made it out to be (Löwy & Gaudillière, 2001). Even for bacteriologists, the techniques which worked well to reveal bacteria were incapable of visualizing viruses. For example, in 1911 the pathologist Peyton Rous determined that that agents smaller than bacteria were capable of transmitting tumors from one chicken to another. At an early point, Rous was tempted to identify this agent as a virus. However, he was unable to isolate it, and without a definite agent his laboratory findings seemed to fly in the face of clinical experience: doctors and nurses working in cancer wards did not catch cancer (BecseiKilborn, 2010; Helvoort, 2004). After several decades of muted activity, interest in cancer viruses began to revive in the 1940s with the discovery of mammalian papilloma viruses and the development of instruments, such as the electron microscope or ultracentrifuge, which allowed the treatment of viruses as physiochemical objects in the laboratory (Creager & Gaudillière, 2001; Kevles, 1995). As Morgan describes, this revival received further impetus from Ludwik Gross’s discovery of cancer causing viruses in mice during the 1950s, animals whose relevance to human disease was more widely accepted than chickens. The release of the polio vaccine inspired considerable optimism for vaccination as a public health measure, and during the 1960s, cancer viruses were the focus of an intense research campaign at the United States National Cancer Institute.
1 Writing a generation ago, David Cantor observed that the historiography of cancer was sharply split between social and experimental accounts.(Cantor, 1993) This has changed dramatically in the last decade. The most prominent concentrations of scholarship include those on the link between smoking and lung cancer(Brandt, 2007; Proctor, 2011), the contest between doctors and patients for authority over cancer, especially breast cancer, treatment (Aronowitz, 2007; Cantor, 2006a, 2006b; Gardner, 2006; Leopold, 1999; Lerner, 2001), breast cancer genetics(Cantor, 2006a, 2006b; Necochea, 2007; Palladino, 2002; Parthasarathy, 2007), and the hazards of environmental carcinogens(Brown et al., 2006; Langston, 2010; Proctor, 1995). Particularly relevant for historians of biomedicine and cancer viruses are a set of studies focusing on how knowledge of cancer is produced not only through laboratory studies but through practices such as clinical trials and diagnosis. (Keating & Cambrosio, 2012; Löwy, 2010; Timmermann, 2013). 2 This notion of a historical “tracer” is drawn from Angela Creager’s recent study of radioisotopes. (Creager, 2013).
Meanwhile, molecular biologists such as Renato Dulbecco developed tissue culture methods for the reproduction of animal viruses in vitro which were used to study a growing number of animal tumor viruses (Kevles, 1993). In the 1970s, cancer virus research resulted in the identification of cancer causing genes, or oncogenes, in both viruses and normal animal cells (Fujimura, 1996). Before the widespread adoption of PCR and restriction enzymes, cancer viruses provided one of the few means of manipulating individual genes in eukaryotic cells (Müller-Wille & Rheinberger, 2012, p. 162). In the 1980s and 1990s viruses were eclipsed by interest in the genetic basis of cancer. With work on the human genome, the discovery of oncogenes appeared to provide an ironic coda for cancer virus researchdthe search for an external cause of cancer had revealed a quintessentially internal cause (Helvoort, 1999; Klein, 1999; Weinberg, 1998). Recently, the development of the Human Papilloma Virus vaccine as a preventative for cervical, oral, and anal cancers promises to fulfill earlier hopes of vaccination, although not without controversy (Wailoo, Livingston, Epstein, & Aronowitz, 2010). Following cancer viruses grants insight into how biomedical research understands (or fails to understand) its objects of inquiry. While the history of science and medicine tends to focus on moments of understanding, the productivity of cancer viruses in biomedicine often emerged from their ambiguity. Sankaran’s parallel biographies of bacteriophage and Rous Sarcoma Virus illustrate this point neatly. The occurrence of cancer by viral infection seemed counterintuitive for the reason that viral infection typically killed cells. Unlike these infections, cancer viruses had the ability to “transform” cells, causing abnormal growth that appeared to be experimental precursor to cancer. She describes how the analogy drawn between transformation and bacterial lysogeny (the nonfatal infection of E. coli bacteria by bacteriophage virus) in the 1950s allowed the convergence of geneticists, bacteriologists, and virologists on cancer viruses, a mixing of scientific styles which helped shape the approach of molecular biology to eukaryotic animal cells. The very traits which made cancer viruses anomalous allowed a new understanding of viruses. Broadbent shows how the unique features of cancer viruses, especially the long period of asymptomatic latency between infection and the occurrence of cancer, provide an opportunity to reexamine the meaning of healthdis it equivalent to the absence of disease? Broadbent considers the case of Human Papilloma Virus and cervical cancer, particularly the complex chain of events between infection and tumorgenesis, to refine our understanding of why medicine should (or should not) classify diseases as a function of their causes. Efforts to resolve the ambiguity of cancer viruses have made explicit the considerable social and experimental work that goes into the constitution of “biomedical objects.”(Daston, 2000) Stark and Campbell draw attention to the importance, for both biomedical research and historical narrative, of the unexpected. They present the case of Simian Virus 40, a “stowaway” in the process of polio vaccine production. Initially a vaccine contaminant, the encounter of Simian Virus 40 with cancer virus researchers at the National Cancer Institute raised the frightening possibility that millions had been exposed to a cancer-causing virus. More than a threat to the safety of the polio vaccine, the unexpected appearance of Simian Virus 40 was a productive event. Critically, the appearance of stowaways carried important ethical and political stakes for biomedical research. In this instance, the appearance of Simian Virus 40 in a study of respiratory illness allowed researchers to convert this trial into one of the few that tested the carcinogenic potential of a virus directly in human subjects. Stark and Campbell raise the question of what ontological status objects like cancer viruses should possess in narratives of biomedicine. Should retrospective knowledge of current science
R.W. Scheffler / Studies in History and Philosophy of Biological and Biomedical Sciences 48 (2014) 185e188
frame these histories, or should the ideas and theories of historical actors take center stage? Following cancer viruses suggests that sometimes the most potent objects of biomedical research need not exist. In his examination of the emergence of leukemia vaccine research at the National Cancer Institute during the 1960s, Scheffler begins with a curious fact. The Institute built a large infrastructure for biomedical researchdlaboratories, tissue collection networks, and biohazard facilitiesdbefore any human leukemia virus was shown to exist. In this instance, leukemia viruses existed not as objects in the laboratory but as “administrative objects” for planning and management efforts that addressed the political culture of hope and crisis associated with childhood disease research. The Institute’s efforts might appear to be an instance of misguided optimism if not for the fact that the infrastructure inspired by leukemia viruses as administrative objects played an important role in later investigations of oncogenes and the Human Immunodeficiency Virus. Following cancer viruses also suggests new approaches to the question of scale in the biomedical sciences. The increasing scale of biomedical research with time appears inexorable. While following cancer viruses provide many instances which fit with this assumption, they also provide contrasting instances. Clarke explicitly tackles the question of his scale in his study of Epstein Barr Virus in the early 1960s. In the first historical analysis of its kind, he unpacks how the Scottish Surgeon Dennis Burkitt coupled creative geographic thinking with the repurposing of existing information and institutions dedicated to infectious disease research in East Africa to produce the most striking evidence until that time that a human cancer might have an infectious cause. Likewise, in his account of Ludwik Gross’s discovery of murine leukemia viruses in the 1950s, Morgan is at pains to emphasize that Gross’s exposure to the methods of the Pasteur Institute in Paris gave him a different approach to cancer research than his new American colleagues. Even from a marginal position in the American cancer research community, Gross was able to drive important developments cancer research from the trunk of his car. What both of these contributions suggest is the possibility that the practices and thought styles of “small science” in biomedicine may be studied with energy equal to that which has been devoted to the exploration of “big science.” Finally, the history of cancer viruses offers a set of cues as historians and philosophers working on medicine and biology begin to confront growing disillusionment with genomics as the ultimate explanation of disease (Evans, Meslin, Marteau, & Caulfield, 2011; Krimsky and Gruber, 2013). By some estimates, the Human Papilloma, Hepatitis, and Epstein Barr viruses are important causes of nearly 15% of all cancers globally (zur Hausen, 1991). With the exception of Human Papilloma Virus these viruses have received little scrutiny. Moreover, accounts of cancer viruses, along with most accounts of biomedicine, have been written with an emphasis on the industrialized world. However, where poverty and simultaneous infection with HIV weaken the immune system, infection by viruses may be responsible for 40% of all cancers (Livingston, 2012, p. 35). These statistics augur that as engaging as the essays in this issue may be, they stop well short of exhausting the insights that we stand to gain by following cancer viruses, which, as Angela Creager suggests in her final commentary, might be thought of as having successfully infected biomedicine itself! Acknowledgments This issue had its origins in a panel at the 2012 Three Societies Meeting in Philadelphia organized by Neeraja Sankaran. Many of the contributors had the opportunity to explore questions raised by that discussion in a subsequent panel at the 2013 International
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Society for the History, Philosophy, and Social Studies of Biology in Montpelier. The contributors extend their thanks to these audiences for their questions and comments, as well as particular thanks to Angela Creager and Ton van Helvoort for their comments and thoughts throughout the preparation of this issue. Gregory Radick provided helpful guidance in the preparation of this introduction.
References Aronowitz, R. A. (2007). Unnatural history: Breast cancer and American society. Cambridge: Cambridge University Press. Becsei-Kilborn, E. (2010). Scientific discovery and scientific reputation: The reception of Peyton Rous’ discovery of the chicken sarcoma virus. Journal of the History of Biology, 43, 111e157. Brandt, A. M. (2007). The cigarette century: The rise, fall, and deadly persistence of the product that defined America. New York: Basic Books. Brown, P., McCormick, S., Mayer, B., Zavestoski, S., Morello-Frosch, R., Altman, R. G., et al. (2006). “A lab of our own”: Environmental causation of breast cancer and challenges to the dominant epidemiological paradigm. Science, Technology, and Human Values, 31, 499e536. Cantor, D. (1993). Cancer. In W. F. Bynum, & R. Porter (Eds.), Companion encyclopedia of the history of medicine (pp. 537e561). London and New York: Routledge. Cantor, D. (2006a). Cancer, quackery and the vernacular meanings of hope in 1950s America. Journal of the History of Medicine and Allied Sciences, 61, 324e368. Cantor, D. (2006b). The frustrations of families: Henry Lynch, heredity, and cancer control, 1962e1975. Medical History, 50, 279e302. Creager, A. N. H. (2013). Life atomic: A history of radioisotopes in science and medicine. Chicago: University of Chicago Press. Creager, A. N. H., & Gaudillière, J.-P. (2001). Experimental technologies and techniques of visualisation: Cancer as a viral epidemic, 1930e1960. In J.P. Gaudillière, & I. Löwy (Eds.), Heredity and infection: The history of disease transmission (pp. 203e260). New York and London: Routledge. Daston, L. (2000). The coming into being of scientific objects. In L. Daston (Ed.), Biographies of scientific objects (pp. 1e14). Chicago; London: University of Chicago Press. Evans, J. P., Meslin, E. M., Marteau, T. M., & Caulfield, T. (2011). Deflating the genomic bubble. Science, 331, 861e862. Fujimura, J. H. (1996). Crafting science: A sociohistory of the quest for the genetics of cancer. Cambridge, MA: Harvard University Press. Gardner, K. E. (2006). Early detection: Women, cancer, & awareness campaigns in the twentieth-century United States. Chapel Hill: The University of North Carolina Press. zur Hausen, H. (1991). Viruses in human cancers. Science, 254, 1167e1173. Helvoort, T. V. (1999). A century of research into the cause of cancer: Is the new oncogene paradigm revolutionary? History and Philosophy of the Life Sciences, 21, 293e330. Helvoort, T. van (2004). The start of a cancer research tradition: Peyton rous, James Ewing, and viruses as a cause of cancer. In D. H. Stapleton (Ed.), Creating a tradition of biomedical research: Contributions to the history of the Rockefeller University (pp. 191e210). New York: The Rockefeller University Press. Huisman, F., & Warner, J. H. (2004). Medical histories. In F. Huisman, & J. H. Warner (Eds.), Locating medical history: The stories and their meanings (pp. 1e30). Baltimore: Johns Hopkins University Press. Keating, P., & Cambrosio, A. (2004). Does biomedicine entail the successful reduction of pathology to biology? Perspectives in Biology and Medicine, 47, 357e371. Keating, P., & Cambrosio, A. (2012). Cancer on trial: Oncology as a new style of practice. Chicago; London: The University of Chicago Press. Kevles, D. J. (1993). Renato Dulbecco and the new animal virology: Medicine, methods, and molecules. Journal of the History of Biology, 26, 409e442. Kevles, D. J. (1995). Pursuing the unpopular: A history of courage, viruses, and cancer. In R. B. Silvers (Ed.), Hidden histories of science (pp. 69e114). New York Review of Books. Klein, G. (1999). The tale of the great cuckoo egg. Nature, 400, 515. Krimsky, S., & Gruber, J. (Eds.). (2013). Genetic explanations: Sense and nonsense. Cambridge: Harvard University Press. Langston, N. (2010). Toxic bodies: Hormone disruptors and the legacy of DES. New Haven: Yale University Press. Leopold, E. (1999). A darker ribbon: Breast cancer, women, and their doctors in the twentieth century. Boston: Beacon Press. Lerner, B. H. (2001). The breast cancer wars: Hope, fear, and the pursuit of a cure in twentieth-century America. New York: Oxford University Press. Livingston, J. (2012). Improvised medicine: An African oncology ward in an emerging cancer epidemic. Durham: Duke University Press. Löwy, I. (1996). Between bench and bedside: Science, healing, and interleukin-2 in a cancer ward. Cambridge, M.A: Harvard University Press. Löwy, I. (2010). Preventive strikes: Women, precancer, and prophylactic surgery. Baltimore: Johns Hopkins University Press. Löwy, I. (2011). Historiography of biomedicine: “Bio,” “medicine,” and in between. Isis, 102, 116e122.
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Löwy, I., & Gaudillière, J.-P. (2001). Horizontal and vertical transmission of diseases: The impossible separation? In J.-P. Gaudillière, & I. Löwy (Eds.), Heredity and infection: The history of disease transmission (pp. 1e18). New York, London. Müller-Wille, S., & Rheinberger, H.-J. (2012). A cultural history of heredity. Chicago: University of Chicago Press. Necochea, R. (2007). From cancer families to HNPCC: Henry Lynch and the transformations of hereditary cancer, 1975e1999. Bulletin of the History of Medicine, 81, 267e285. Palladino, P. (2002). Between knowledge and practice: On medical professionals, patients, and the making of the genetics of cancer. Social Studies of Science, 32, 137e165. Parthasarathy, S. (2007). Building genetic medicine: Breast cancer, technology, and the comparative politics of health care. Cambridge, Mass: MIT Press.
Proctor, R. (1995). Cancer wars: How politics shapes what we know and don’t know about cancer. New York: Basic Books. Proctor, R. (2011). Golden holocaust: Origins of the cigarette catastrophe and the case for abolition. Berkeley: University of California Press. Timmermann, C. (2013). A history of lung cancer: The recalcitrant disease. Basingstoke: Palgrave Macmillan. Wailoo, K., Livingston, J., Epstein, S., & Aronowitz, R. A. (Eds.). (2010). Three shots at prevention: The HPV vaccine and the politics of medicine’s simple solutions. Baltimore, MD: Johns Hopkins University Press. Weinberg, R. A. (1998). Racing to the beginning of the road: The search for the origin of cancer. New York: W. H. Freeman.
Contents lists available at ScienceDirect
Studies in History and Philosophy of Biological and Biomedical Sciences journal homepage: www.elsevier.com/locate/shpsc
Introduction
Following cancer viruses through the laboratory, clinic, and society Robin Wolfe Scheffler* American Academy of Arts and Sciences, 136 Irving Street, Cambridge, MA 02138, USA
a r t i c l e i n f o
a b s t r a c t
Article history: Available online 16 October 2014
These essays in this special issue follow cancer viruses as a means of better understanding the history of biomedicine. Spanning the worlds of chronic and infectious disease research, the history of cancer viruses touches upon an enormous diversity of settings and scientific disciplines. Cancer viruses appeared during the twentieth century as vaccine targets, vaccine contaminants, laboratory anomalies, and tools for molecular biology. Rather than picking one discipline or setting to privilege above others, this issue suggests what can be learned, not only about cancer viruses but also about the character of modern biomedicine, from following these viruses through their different historical trajectories. Ó 2014 Elsevier Ltd. All rights reserved.
When citing this paper, please use the full journal title Studies in History and Philosophy of Biological and Biomedical Sciences
There is a long history to the fear that cancer might be contagious. At the end of the 19th century, however, this fear was tempered by the new hope that discovering a cancer-causing infectious agent would enable the large scale prevention of cancer. This hope centered on the identification of cancer viruses. The six essays gathered in this issue provide a synoptic account of the pathways of cancer virus research and the research trajectories of cancer viruses ever since. These attempts to understand the relationship between viruses and cancer occupy a middle ground in the well-known transition from infectious to chronic diseases as the main focus of public health in industrial societies. Befitting this intermediate status, inquiries into the nature of cancer viruses incorporated practices from epidemiology, immunology, microbiology, virology, pathology, genetics, and molecular biology. By following viruses themselves from place to place and discipline to discipline, these essays individually and collectively shine new light on the critical roles that cancer viruses have played in the production of knowledge
* Tel.: þ1 617 576 5091. E-mail address: rscheffl[email protected]. http://dx.doi.org/10.1016/j.shpsc.2014.09.004 1369-8486/Ó 2014 Elsevier Ltd. All rights reserved.
in a wide range of biomedical fields. Starting at the beginning of the twentieth century, Neeraja Sankaran contrasts the biography of Rous Sarcoma Virus with bacteriophage, and shows the importance of analogies between the two for the development of virology and early molecular biology. Moving forward, Gregory Morgan examines the discovery of mouse leukemia viruses, a crucial event in the revival of cancer virus research in the middle of the twentieth century. Next, Brendan Clarke uses the history of Epstein Barr Virus to pose new questions about space and scale in cancer research; Laura Stark and Nancy Campbell follow the unexpected appearance of Simian Virus 40 as a possible oncogenic virus in human research settings; and Robin Scheffler raises the possibility that our understanding of the history of cancer viruses should also include viruses which are now thought not to exist, in this case a childhood leukemia virus. Finally, looking at the present, Alex Broadbent considers how the relationship between Human Papilloma Virus and cervical cancer forces us to clarify our understanding of what it means for a virus to “cause” cancer and the consequences this has for classifying illness. While cancer viruses have not lacked for chroniclers, the sinuous path of cancer viruses through the twentieth century fits uneasily into the history of cancer, medicine, or biology. The historiography of cancer tends to emphasize clinical treatment,
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R.W. Scheffler / Studies in History and Philosophy of Biological and Biomedical Sciences 48 (2014) 185e188
authority, and culpability, arenas where cancer viruses do not usually appear.1 Likewise, cancer viruses have fallen into the divide between the clinic and the laboratory in the historiography of biology and medicine. Following the “social turn” historians of medicine sought to deemphasize the laboratory in their narratives while historians of biology focused on the creation of laboratorybased experimental systems far removed from the concerns of the clinic. Neither of these agendas captured the full set of activities associated with cancer viruses. Fortunately these divisions are eroding, and interest in the overlap of biology and medicinedbiomedicinedis on the rise (Huisman & Warner, 2004; Keating & Cambrosio, 2004; Löwy, 1996, 2011). As “tracers” for uniting the different sites and practices involved in writing a richer history of biomedicine, cancer viruses are exceptional precisely because of their multifaceted and unresolved history.2 Until the late twentieth century, the idea that cancer might be caused by an infectious agent offered the most therapeutically-relevant path of inquiry into the etiology of cancer. Demonstrating the genetic origins of cancer presented no hope for prevention or therapy, while exposure to environmental or chemical carcinogens could at best be ameliorated when such compounds were identified. By contrast, the identification of an infectious agent responsible for cancer promised widespread prevention through vaccination. Yet this promise did not immediately translate to enthusiasm for cancer virus research. The separation of infection from other environmental or hereditary causes of disease was rarely so clear as advocates of bacteriology made it out to be (Löwy & Gaudillière, 2001). Even for bacteriologists, the techniques which worked well to reveal bacteria were incapable of visualizing viruses. For example, in 1911 the pathologist Peyton Rous determined that that agents smaller than bacteria were capable of transmitting tumors from one chicken to another. At an early point, Rous was tempted to identify this agent as a virus. However, he was unable to isolate it, and without a definite agent his laboratory findings seemed to fly in the face of clinical experience: doctors and nurses working in cancer wards did not catch cancer (BecseiKilborn, 2010; Helvoort, 2004). After several decades of muted activity, interest in cancer viruses began to revive in the 1940s with the discovery of mammalian papilloma viruses and the development of instruments, such as the electron microscope or ultracentrifuge, which allowed the treatment of viruses as physiochemical objects in the laboratory (Creager & Gaudillière, 2001; Kevles, 1995). As Morgan describes, this revival received further impetus from Ludwik Gross’s discovery of cancer causing viruses in mice during the 1950s, animals whose relevance to human disease was more widely accepted than chickens. The release of the polio vaccine inspired considerable optimism for vaccination as a public health measure, and during the 1960s, cancer viruses were the focus of an intense research campaign at the United States National Cancer Institute.
1 Writing a generation ago, David Cantor observed that the historiography of cancer was sharply split between social and experimental accounts.(Cantor, 1993) This has changed dramatically in the last decade. The most prominent concentrations of scholarship include those on the link between smoking and lung cancer(Brandt, 2007; Proctor, 2011), the contest between doctors and patients for authority over cancer, especially breast cancer, treatment (Aronowitz, 2007; Cantor, 2006a, 2006b; Gardner, 2006; Leopold, 1999; Lerner, 2001), breast cancer genetics(Cantor, 2006a, 2006b; Necochea, 2007; Palladino, 2002; Parthasarathy, 2007), and the hazards of environmental carcinogens(Brown et al., 2006; Langston, 2010; Proctor, 1995). Particularly relevant for historians of biomedicine and cancer viruses are a set of studies focusing on how knowledge of cancer is produced not only through laboratory studies but through practices such as clinical trials and diagnosis. (Keating & Cambrosio, 2012; Löwy, 2010; Timmermann, 2013). 2 This notion of a historical “tracer” is drawn from Angela Creager’s recent study of radioisotopes. (Creager, 2013).
Meanwhile, molecular biologists such as Renato Dulbecco developed tissue culture methods for the reproduction of animal viruses in vitro which were used to study a growing number of animal tumor viruses (Kevles, 1993). In the 1970s, cancer virus research resulted in the identification of cancer causing genes, or oncogenes, in both viruses and normal animal cells (Fujimura, 1996). Before the widespread adoption of PCR and restriction enzymes, cancer viruses provided one of the few means of manipulating individual genes in eukaryotic cells (Müller-Wille & Rheinberger, 2012, p. 162). In the 1980s and 1990s viruses were eclipsed by interest in the genetic basis of cancer. With work on the human genome, the discovery of oncogenes appeared to provide an ironic coda for cancer virus researchdthe search for an external cause of cancer had revealed a quintessentially internal cause (Helvoort, 1999; Klein, 1999; Weinberg, 1998). Recently, the development of the Human Papilloma Virus vaccine as a preventative for cervical, oral, and anal cancers promises to fulfill earlier hopes of vaccination, although not without controversy (Wailoo, Livingston, Epstein, & Aronowitz, 2010). Following cancer viruses grants insight into how biomedical research understands (or fails to understand) its objects of inquiry. While the history of science and medicine tends to focus on moments of understanding, the productivity of cancer viruses in biomedicine often emerged from their ambiguity. Sankaran’s parallel biographies of bacteriophage and Rous Sarcoma Virus illustrate this point neatly. The occurrence of cancer by viral infection seemed counterintuitive for the reason that viral infection typically killed cells. Unlike these infections, cancer viruses had the ability to “transform” cells, causing abnormal growth that appeared to be experimental precursor to cancer. She describes how the analogy drawn between transformation and bacterial lysogeny (the nonfatal infection of E. coli bacteria by bacteriophage virus) in the 1950s allowed the convergence of geneticists, bacteriologists, and virologists on cancer viruses, a mixing of scientific styles which helped shape the approach of molecular biology to eukaryotic animal cells. The very traits which made cancer viruses anomalous allowed a new understanding of viruses. Broadbent shows how the unique features of cancer viruses, especially the long period of asymptomatic latency between infection and the occurrence of cancer, provide an opportunity to reexamine the meaning of healthdis it equivalent to the absence of disease? Broadbent considers the case of Human Papilloma Virus and cervical cancer, particularly the complex chain of events between infection and tumorgenesis, to refine our understanding of why medicine should (or should not) classify diseases as a function of their causes. Efforts to resolve the ambiguity of cancer viruses have made explicit the considerable social and experimental work that goes into the constitution of “biomedical objects.”(Daston, 2000) Stark and Campbell draw attention to the importance, for both biomedical research and historical narrative, of the unexpected. They present the case of Simian Virus 40, a “stowaway” in the process of polio vaccine production. Initially a vaccine contaminant, the encounter of Simian Virus 40 with cancer virus researchers at the National Cancer Institute raised the frightening possibility that millions had been exposed to a cancer-causing virus. More than a threat to the safety of the polio vaccine, the unexpected appearance of Simian Virus 40 was a productive event. Critically, the appearance of stowaways carried important ethical and political stakes for biomedical research. In this instance, the appearance of Simian Virus 40 in a study of respiratory illness allowed researchers to convert this trial into one of the few that tested the carcinogenic potential of a virus directly in human subjects. Stark and Campbell raise the question of what ontological status objects like cancer viruses should possess in narratives of biomedicine. Should retrospective knowledge of current science
R.W. Scheffler / Studies in History and Philosophy of Biological and Biomedical Sciences 48 (2014) 185e188
frame these histories, or should the ideas and theories of historical actors take center stage? Following cancer viruses suggests that sometimes the most potent objects of biomedical research need not exist. In his examination of the emergence of leukemia vaccine research at the National Cancer Institute during the 1960s, Scheffler begins with a curious fact. The Institute built a large infrastructure for biomedical researchdlaboratories, tissue collection networks, and biohazard facilitiesdbefore any human leukemia virus was shown to exist. In this instance, leukemia viruses existed not as objects in the laboratory but as “administrative objects” for planning and management efforts that addressed the political culture of hope and crisis associated with childhood disease research. The Institute’s efforts might appear to be an instance of misguided optimism if not for the fact that the infrastructure inspired by leukemia viruses as administrative objects played an important role in later investigations of oncogenes and the Human Immunodeficiency Virus. Following cancer viruses also suggests new approaches to the question of scale in the biomedical sciences. The increasing scale of biomedical research with time appears inexorable. While following cancer viruses provide many instances which fit with this assumption, they also provide contrasting instances. Clarke explicitly tackles the question of his scale in his study of Epstein Barr Virus in the early 1960s. In the first historical analysis of its kind, he unpacks how the Scottish Surgeon Dennis Burkitt coupled creative geographic thinking with the repurposing of existing information and institutions dedicated to infectious disease research in East Africa to produce the most striking evidence until that time that a human cancer might have an infectious cause. Likewise, in his account of Ludwik Gross’s discovery of murine leukemia viruses in the 1950s, Morgan is at pains to emphasize that Gross’s exposure to the methods of the Pasteur Institute in Paris gave him a different approach to cancer research than his new American colleagues. Even from a marginal position in the American cancer research community, Gross was able to drive important developments cancer research from the trunk of his car. What both of these contributions suggest is the possibility that the practices and thought styles of “small science” in biomedicine may be studied with energy equal to that which has been devoted to the exploration of “big science.” Finally, the history of cancer viruses offers a set of cues as historians and philosophers working on medicine and biology begin to confront growing disillusionment with genomics as the ultimate explanation of disease (Evans, Meslin, Marteau, & Caulfield, 2011; Krimsky and Gruber, 2013). By some estimates, the Human Papilloma, Hepatitis, and Epstein Barr viruses are important causes of nearly 15% of all cancers globally (zur Hausen, 1991). With the exception of Human Papilloma Virus these viruses have received little scrutiny. Moreover, accounts of cancer viruses, along with most accounts of biomedicine, have been written with an emphasis on the industrialized world. However, where poverty and simultaneous infection with HIV weaken the immune system, infection by viruses may be responsible for 40% of all cancers (Livingston, 2012, p. 35). These statistics augur that as engaging as the essays in this issue may be, they stop well short of exhausting the insights that we stand to gain by following cancer viruses, which, as Angela Creager suggests in her final commentary, might be thought of as having successfully infected biomedicine itself! Acknowledgments This issue had its origins in a panel at the 2012 Three Societies Meeting in Philadelphia organized by Neeraja Sankaran. Many of the contributors had the opportunity to explore questions raised by that discussion in a subsequent panel at the 2013 International
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Society for the History, Philosophy, and Social Studies of Biology in Montpelier. The contributors extend their thanks to these audiences for their questions and comments, as well as particular thanks to Angela Creager and Ton van Helvoort for their comments and thoughts throughout the preparation of this issue. Gregory Radick provided helpful guidance in the preparation of this introduction.
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