"Happily ever after" for cancer viruses?

Angela N.H. Creager

doi:10.1016/j.shpsc.2014.09.003

"Happily ever after" for cancer viruses?

Angela N.H. Creager

History

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Abstract

This essay discusses three common issues arising from the special collection "100 Years of Cancer and Viruses." The first is the tension between small-scale and big-scale approaches to cancer research; the second is the difference between how physicians and biologists regarded cancer, and how they assessed the value of investigating viruses as a causative agent; and the third is how the pace and temporality ofscience have varied over the century of research on cancer viruses. An unpublished piece written by C.H. Andrewes in 1935, "A Christmas Fairy-Story for Oncologists," provides the touchstone for the commentary.

Original language	English (US)
Pages (from-to)	260-262
Number of pages	3
Journal	Studies in History and Philosophy of Science Part C :Studies in History and Philosophy of Biological and Biomedical Sciences
Volume	48
Issue number	PB
DOIs	https://doi.org/10.1016/j.shpsc.2014.09.003
State	Published - Dec 1 2014

All Science Journal Classification (ASJC) codes

History
History and Philosophy of Science

Keywords

Big science
C. H. Andrewes
Cancer
Peyton Rous
Vaccine
Virus

Access to Document

10.1016/j.shpsc.2014.09.003

Cite this

@article{8c8efe7a23cc4d08917dbcb9ae322904,

title = "{"}Happily ever after{"} for cancer viruses?",

abstract = "This essay discusses three common issues arising from the special collection {"}100 Years of Cancer and Viruses.{"} The first is the tension between small-scale and big-scale approaches to cancer research; the second is the difference between how physicians and biologists regarded cancer, and how they assessed the value of investigating viruses as a causative agent; and the third is how the pace and temporality ofscience have varied over the century of research on cancer viruses. An unpublished piece written by C.H. Andrewes in 1935, {"}A Christmas Fairy-Story for Oncologists,{"} provides the touchstone for the commentary.",

keywords = "Big science, C. H. Andrewes, Cancer, Peyton Rous, Vaccine, Virus",

author = "Creager, {Angela N.H.}",

note = "Funding Information: Cancer Virus Big science Vaccine C. H. Andrewes Peyton Rous When citing this paper, please use the full journal title Studies in History and Philosophy of Biological and Biomedical Sciences On December 12, 1935 the British researcher C. H. Andrewes sent a whimsical tale entitled “A Christmas Fairy-Story for Oncologists” to fellow virologist Peyton Rous. It begins: Once upon a time there was a family of viruses, much like other viruses. Some of them liked mutton, others poultry. Some of them multiplied wantonly in the cells they inhabited and smashed up their homes; others, more restrained, practiced a magic which caused their homes to proliferate. But after a while most of the homes got broken up and the viruses had to seek new ones in new hosts. These new homes they penetrated by means of the powerful tusks in their upper jaws. The narrator proceeded to explain how, over time, these viruses lost their tusks. They began living in the hosts permanently as “feudal retainers,” allowed to enter into the inner sanctum (the germplasm) so long as they used birth control and left the furniture alone. But every now and again some damage to the house would given some of these viruses a chance to revolt against the master. By practicing their “ancestral proliferation magic,” these rebels would produce all manner of neoplasms in the host. As Andrewes concludes the story: “The hosts became alarmed at the increasing incidence of cancer and called upon the Goddess Evolution at a great religious revival. But, alas, the goddess had no interest in diseases which attack after they have successfully propagated themselves, and turned a deaf ear to their prayers.” 2 2 “A Christmas fairy-story for Oncologists” by C. H. Andrewes [1935]. Peyton Rous Papers, American Philosophical Society. Andrewes, Christopher H. Folder #1, 1929–1935. This charming fable rendered the complexities of tumor virology in terms that Andrewes felt even oncologists might be able to comprehend. And for good reason. During the 1930s, few biomedical researchers and even fewer physicians believed that viruses for human cancer existed, preferring explanations that focused on irritants (such as coal tars) or heredity ( Proctor, 1995 , esp. chaps. 2 and 10). Oncologists noted that clinical staff attending cancer patients did not catch their malignancies, which seemed to refute the role of an infectious agent such as viruses ( van Helvoort, 2004 ). Yet some evidence for transmissible cancer agents remained hard to dismiss, notably John Bittner's experiments documenting the transmissibility of mammary tumors in mice from nursing mothers to their offspring ( Fujimura, 1996 , chap. 2; Gaudilli{\`e}re, 1999 ). In the postwar period, private and public funding agencies (if not the majority of oncologists) started taking seriously the prospect of isolating viruses for human cancer—with the hopes of producing vaccines. This set of papers does a great deal to flesh out the complexities of these transitions in belief and practice, and to explore the reasons behind the shifts in the broader context of the development of biomedicine. I will focus on three tensions that emerge from the collection as a whole, tensions that I believe help account for why cancer viruses were neither completely disproven nor fully accepted during decades of intensive investigation. First, there is the question of how research aimed at controlling cancer should be organized ( Bud, 1978 ). Was the problem of cancer causation better suited to the individual researcher or to a large, coordinated team? To put in the terms of these papers, was this a task for “solitary virus hunters” or big science? For Gregory Morgan, Ludwik Gross illustrates the significance of the tenacious lone investigator, who kept his mice strains in his car when he lacked a proper laboratory. Gross's persistence paid off in the 1950s, when his tumor virus work was finally recognized. Along similar lines, Brendan Clarke uses the fieldwork on Burkitt's lymphoma in Southern Africa to demonstrate the continuing importance of “small science” to postwar virology. Identifying the role of Epstein–Barr virus in Burkitt's lymphoma in the developing world relied on relatively low-tech methods, such geographical mapping and the use of patient survey data collected for other diseases. Clarke uses this fascinating case to argue that low-tech, unplanned research on the relationship between viruses and cancer played an unacknowledged role in advancing scientific knowledge. Yet Morgan's and Clarke's examples do not controvert the importance of big science to this field. Robin Scheffler shows us compellingly how the US government drew on models of military organization and research management to pursue cancer viruses. World War II provided a crucial precedent for a multi-disciplinary, large-scale approach to medicine. This approach received a further boost from the successful development of polio vaccines. Proponents of large-scale, organized research in the US, however, had to contend with an ideology that valorized the solo, curiosity-driven scientist. To put it bluntly, Americans were wary of any scheme that smacked of socialism. Scheffler recounts how cancer research advocates and administrators overcame this antipathy to government involvement in research as they pushed for large-scale programs. Such programs, lavishly funded in the 1960s and 1970s, generated new critics. Many leading tumor virologists, reflecting their commitment to the tools and values of molecular biology, argued that funding should be awarded to the best, not the biggest, science. In part this reflected a competition for research funds between industry, which was often contracted for the large screening programs of the National Cancer Institute, and academic biologists, who preferred that cancer viruses be pursued through basic research grants to smaller university laboratories. 3 3 The valorization of basic, non-directed research has been subject to reevaluation, both historically and historiographically, e.g., Edgerton (2004) and Shapin (2008) . A second tension is that between cancer biologists and physicians over the relevance of laboratory research on cancer viruses. This conflict was not specific to virology. Biologists seeking to understand cell growth and cancer causation usually worked at a remove from the clinical setting, and oncologists understandably viewed the human disease as a more complex affair than was suggested by laboratory experiments. 4 4 For a more sophisticated analysis, see L{\"o}wy (1996) . As Morgan and Scheffler both observe, progress in isolating causes, or at least inciters, of cancer often relied on animal models. Yet the relevance of mice with mammary tumors or transformed tissue culture cells to cases of human cancer remained tenuous and contested. Strikingly, cancer virus work seems to have often been scientifically productive in the absence of leads for new therapy—or even identifiable viruses. In particular, there was a curious disjunct between etiology and therapy around leukemia viruses. Scheffler observes that Special Virus Leukemia Program was launched despite the lack of evidence for a virus causing human leukemia. Critics referred to it as a “moonshot without a moon.” Tumor virologists were equally critical of the successor Virus Cancer Program for its lack of intellectual rigor ( Wade, 1971; Yi, 2011 ). Yet the National Cancer Institute's funding of these efforts contributed to the establishment of a technical infrastructure for identifying and characterizing a host of retroviruses, ultimately including HIV ( Gallo, 1991 ). The lavish funding for cancer virus research benefited the research-based attack on AIDS, including the development of anti-retroviral drugs, even if did not produce the hoped-for vaccines or therapies for cancer. In other words, funding of laboratory approaches had unpredictable results for the clinic. Not to mention the consequences for biology: in the 1970s the National Cancer Institute was supporting half of the National Institutes of Health-sponsored research in molecular biology ( DeVita, 2002 ). Relatedly, the collection illustrates that the fate of cancer viruses remained intimately connected to other developments in biomedicine. Neeraja Sankaran offers an elegant comparison of the debates over bacterial viruses and Rous sarcoma virus, pointing out that while there were not explicit cross-references, both discussions hinged on similar conceptions of disease agents and causation. She draws on Ton van Helvoort's argument that two antithetical thought styles (after Ludwik Fleck) framed how researchers regarded bacteriophages, either as exogenous infective agents, essentially submicroscopic bacteria, versus endogenous physiological disturbances, causing the production of bacteriophage enzymes that pathologically attacked the cell itself ( van Helvoort, 1994 ). A similar dichotomy characterized the debate over Rous sarcoma virus, showing that cancer viruses were not conceptually insulated from other biological entities. I would add that these links were material and instrumental as well as conceptual. As Scheffler's paper recounts, the tools of biochemistry, biophysics, and molecular genetics—from electron microscopes to the “plaquing” of animal viruses—proved especially critical to the mid-century search for tumor viruses. Finally, the long dur{\'e}e of the debate over cancer viruses as documented in this set of papers invites reflection on the pace and temporality of research. The collection documents moments of acceleration (Scheffler) and stagnation (Morgan). Laura Stark and Nancy Campbell discuss illuminatingly how finding hitherto unknown viruses—in their case, SV40—not only changed the entities populating the scientific realm but also researchers' perceptions of what had existed, if invisibly, in the past. Their notion of scientific stowaways provides an elegant heuristic for considering how the science of a particular moment carries seeds of a different future, and with it, a recast past. Quite recently, new developments have reinvigorated cancer virology. Alex Broadbent's paper addresses the reemergence of the viral etiology of cancer in the late twentieth century, as evidenced by the development of Gardisil, a vaccine against human papilloma virus (HPV) that protects against cervical cancer ( Wailoo, Livingston, Epstein, and Aronowitz, 2010 ). He argues that there has been a historical transition from the predominance of monocausal explanations of disease, associated with the golden age of bacteriology, to a multifactorial mode of disease that fits better with the chronic disease burden of the late twentieth century. Both the monocausal and multifactorial models have shortcomings, which Broadbent's own contrastive model of disease is aimed at redressing. Irrespective, he suggests that the multifactorial disease model has facilitated acceptance that a sexually-transmitted virus is a cause of human cancer, allowing that cases of cervical cancer may exist in the absence of this virus. After a century of debate over whether virus research can contribute meaningful to cancer control, the case of HPV has provided decisive evidence in its favor. In reviewing the history of cancer viruses in the twentieth century, perhaps it is fair to say that these viruses were successful in infecting biomedicine itself. 5 5 Here I take inspiration from Henry Cowles's notion of “endogenous analysis” ( 2014 , p. 15), with which he describes my use of radioisotopes as historical tracers ( 2013 ). These papers, in turn, speak of the course of this infection over the decades. If its onset was Rous's isolation in 1912 of a virus for chicken sarcoma, the mid-twentieth century proved to be a period of latency for tumor virology, during which time few investigators and even fewer physicians sought to attribute cancer to viruses. 6 6 This despite the isolation of a papilloma virus in rabbit by Richard Shope ( Creager & Gaudilli{\`e}re, 2001; Kevles, 1995 ). By contrast, research on putative cancer viruses re-emerged and expanded in the 1950s, reflecting a culture of confidence that cancer could be vanquished, like polio, by virologists. Scheffler's emphasis on hope seems crucial to understanding why the investments in cancer virus research continued even when a virus for human leukemia, for instance, failed to materialize. 7 7 I cannot do justice to this theme, but for suggestive analysis, see Delvecchio Good (1991); Adams, Murphy, and Clarke (2009) . Tumor viruses as laboratory residents thrived in the scientific research establishment of the postwar decades, due to both their productivity in the hands of molecular biologists and the public's continuing faith that their study could lead to a cure for cancer ( Rettig, 1977 ). While current researchers would disavow the notion of a single cure for cancer, both the enduring infrastructure of tumor virology and the development of an effective cervical cancer vaccine suggest a happier ending to the tale of cancer viruses than either Andrewes or Rous dared dream. Publisher Copyright: {\textcopyright} 2014 Elsevier Ltd.",

year = "2014",

month = dec,

day = "1",

doi = "10.1016/j.shpsc.2014.09.003",

language = "English (US)",

volume = "48",

pages = "260--262",

journal = "Studies in History and Philosophy of Science Part C :Studies in History and Philosophy of Biological and Biomedical Sciences",

issn = "1369-8486",