Managing the future: the Special Virus Leukemia Program and the acceleration of biomedical research.

Studies in History and Philosophy of Biological and Biomedical Sciences 48 (2014) 231e249

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Managing the future: The Special Virus Leukemia Program and the acceleration of biomedical research 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 24 October 2014

After the end of the Second World War, cancer virus research experienced a remarkable revival, culminating in the creation in 1964 of the United States National Cancer Institute’s Special Virus Leukemia Program (SVLP), an ambitious program of directed biomedical research to accelerate the development of a leukemia vaccine. Studies of cancer viruses soon became the second most highly funded area of research at the Institute, and by far the most generously funded area of biological research. Remarkably, this vast infrastructure for cancer vaccine production came into being before a human leukemia virus was shown to exist. The origins of the SVLP were rooted in as much as shifts in American society as laboratory science. The revival of cancer virus studies was a function of the success advocates and administrators achieved in associating cancer viruses with campaigns against childhood diseases such as polio and leukemia. To address the urgency borne of this new association, the SVLP’s architects sought to lessen the power of peer review in favor of centralized Cold War management methods, fashioning viruses as “administrative objects” in order to accelerate the tempo of biomedical research and discovery. Ó 2014 Elsevier Ltd. All rights reserved.

Keywords: Cancer Virus Management Biomedicine Vaccination State building

When citing this paper, please use the full journal title Studies in History and Philosophy of Biological and Biomedical Sciences

1. Introduction In the winter of 1961, a worried mother contacted the Illinois branch of the American Cancer Society to report a “cancer epidemic” in Niles, a town just north of Chicago. In the previous year, eight children associated with the St. John Brebeuf parish school had died from leukemia and another five had fallen ill; a combined rate five times higher than the national average. An epidemiologist dispatched by the United States Public Health Service attributed the cluster of deaths to “an unidentified infectious agent.” While urging calm, two years later the Niles Board of Trustees mandated the reporting of all leukemia cases within the town, a measure invoked only for infectious diseases (Black, 1963; Hearst, 1962a; McGrady & Morgan, 1964; “Niles Board Cites Disease ‘Reportable,’” 1963, “Niles Hears Panel’s Views on Leukemia,” 1963, * Tel.: þ1 617 576 5091. E-mail address: rscheffl[email protected]. http://dx.doi.org/10.1016/j.shpsc.2014.09.005 1369-8486/Ó 2014 Elsevier Ltd. All rights reserved.

“Open Forum on Leukemia Will be Held,” 1963, “Seek Leukemia Clew in Study of Niles Cases,” 1961). Writing for the Journal of the American Medical Association, a Chicago hematologist, Steven Schwartz, announced that he had identified new antibodies in blood drawn from relatives of the children and even from laboratory workers who had handled blood samples. Speaking in the restrained tones of scientific prose, Schwartz concluded that the Niles outbreak lent “further credence to the viral etiological theory” of human leukemia (Schwartz, Greenspan, & Brown, 1963). He was more direct with a reporter for the Saturday Evening Post, stating, “you can’t see patients for twenty years without being convinced that certain things are so.leukemia looks to me like an infectious diseaseda virus” (McGrady & Morgan, 1964, p. 21). Alarmingly, it appeared that the Niles “outbreak” was not an isolated incident but symptomatic of rising childhood leukemia rates: in the early 1960s similar leukemia outbreaks were reported in Buffalo, New York; Bergen County, New Jersey; Cheyenne, Wyoming; Louisville, Kentucky; Mt.

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Prospect, Illinois; Seattle, Washington; and Orange, Texas (Schwartz et al., 1963, p. 106; Wallace, 1961). Yet the ominous threat that leukemia was caused by a virus also contained a kernel of optimism. Polio, another feared viral childhood disease, had just been vanquished by the Salk vaccine after an energetic research effort. Leukemia might fall to a similar campaign. Vaccination held center stage when Life Magazine introduced its readers to the National Cancer Institute’s “all-out assault” against childhood leukemia. While describing radiological and chemotherapeutic advances in leukemia treatment Life saved its greatest excitement for the implications of the discovery that “viruslike [sic] particles have been identified in the blood of leukemic humans” (Bradbury, 1966, p. 87). In 1964, to capitalize on the potential discovery of a human leukemia virus, the administrators of the National Cancer Institute (NCI) had launched a ten million dollar “superplan,” the Special Virus Leukemia Program (SVLP), to develop a vaccine. Modeling their efforts on the Defense Department’s successful oversight of complex aerospace projects, the administrators of the SVLP proposed to break the process of leukemia virus discovery and vaccine production into discrete components for delegation to coordinated teams of personnel spread among hospitals, academic departments, government laboratories, and industry. Unlike most biomedical research plans, Life enthused, these administrators had a strategy “that would do more than give out research money and wait for results. It.would plan research and make results” (Rosenfeld, 1966, pp. 110e111). Funding for cancer virus research grew rapidly, but not without opposition. Just before President Nixon declared a “War on Cancer” in 1971, virus studies were the highest funded area of research at the NCI save chemotherapy.1 The SVLP’s emphasis on directing and accelerating therapeutic breakthroughs stood at odds with the emphasis on slow, gradual progress adopted by most of the cancer research community. A rising chorus of critics charged that the SVLP’s management strategies were founded on the unsubstantiated assumption that viruses were a major cause of human cancer. To these critics, the SVLP was a moonshot without a moon, an effort whose misguided attempts to manage science threatened scientific autonomy (Wade, 1971). Later in the 1970s, the SVLP’s centralized, hierarchical, and contract-directed framework provided a template for more ambitious efforts to diminish the power of peer review and manage biomedical research (Chubin & Studer, 1978). As a result of these controversies, most scientific commentators have discussed the history of the SVLP in light of the retrospective knowledge that it failed to identify a significant human cancer virus and that cancer virus research in the 1970s established the importance of genes (oncogenes) rather than viruses in the genesis of cancer (Klein, 1999; Weinberg, 1998, pp. 66e84). While links between viruses and some cancers, notably Human Papilloma Virus and cervical cancer, were revealed later in the century, the prevalence of these virally caused cancers never fulfilled the promises of the SVLP’s advocates (Aronowitz, 2010; Kiberstis & Marshall, 2011). Against these frustrations, cancer virus research played an important role in the discovery of oncogenes, and in the elucidation the molecular mechanisms of processes of cellular regulation and development. The successor to the SVLP, the Virus Cancer Program, also provided important resources for elucidating the nature of HIV/AIDS (DeVita, 2002; Gallo, 1991, pp. 138e145; Gaudillière, 1993, p. 164; Morange, 1997). The aim of this article is not to evaluate the legacy of cancer virus studies at the NCI but to explain the remarkable fact that such a large program of research could start before its central object, a human leukemia virus, was known to exist. The explanation of this

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National Cancer Institute 1972 Fact Book (Washington: DHEW, 1971), 17.

fact requires understanding how human leukemia viruses became visible as coherent, productive, and tractable entities to both scientists and bureaucrats. This process of visualization extended to politics and culture as well as the laboratory (Creager & Gaudillière, 2001, pp. 204e205; Daston, 2000; Wailoo, 2001, pp. 23e25). The SVLP’s principal innovation was in presenting leukemia viruses as administrative objects as well as laboratory objects. The management of the SVLP faced two ambiguous worlds: the biological world of virus studies and the social world of biomedical research. This new way of thinking about leukemia viruses allowed both viruses and virus research to become more legible for state intervention (Scott, 1998). While the process of seeking human leukemia viruses was never severed from questions of their existence, the emergence of viruses and virus research as entities for bureaucratic control as well as laboratory inquiry accorded this question a secondary position to concerns of organization and rapid actiondconcerns inspired by the association of leukemia viruses with childhood disease and reflected in the Cold War genealogy of the SVLP’s management methods. Even if the SVLP did not conclusively reveal the existence of a human leukemia virus, the administrative machinery organized around the process of searching for it gained the power to shape the kinds of knowledge produced by experimental cancer research. The existence of the SVLP also gives further reason to suspect that the historical relationship between science and management was often much less antagonistic than the rhetoric of scientists suggests (Shapin, 2008). The history of the SVLP bridges efforts to manage biomedical research in the twentieth century, beginning with the efforts of the Rockefeller Foundation in the 1920s and 1930s and continuing today in the biotechnology industry (Fortun, 1998; Kohler, 1976, 1991). Decades before more notable “big biology” efforts such as the Human Genome Project, the SVLP sought to develop management structures for the acceleration of biomedical research.2 In the biological materials that it banked and circulated or the animal and in vitro models of disease it supported, the activities of the SVLP provide a window into how the development of the managerial and experimental practices helped constitute biomedicine in the late twentieth century.3 The unique features of the SVLP’s approach to the management of biomedical research, moreover, took shape in the broader context of profound transformations in the role of government in American society. While biomedical research was the beneficiary of exponential increases in public support and scored numerous

2 Others have suggested that the SLVP was an early instance of “big biomedicine” (Gaudillière, 1998, p. 158). The development of “big science” been extensively discussed in the history of physics and is reviewed in Capshew & Rader (1992) and Galison & Hevly (1992). 3 The definition of “biomedicine” and the scope of its history have been the topics of considerable debate among both practicing scientists and historical researchers (Löwy, 2011). Experimental biologists, especially molecular biologists, have often been aggressive promoters of the wide-ranging applicability of ‘basic’ or ‘fundamental’ research to human disease, although the insistence of the primary place of laboratory biology in medicine extends back to the mid nineteenth century (Bernard, 1957; Crick, 1969; Dill, 1999; Flexner, 1910). Historical commentaries stress that its primary feature is the extension of laboratory, especially molecular biological techniques, into medicine, a trend which accelerated after the Second World War as a part of the broader “(bio)medicalization” of society (Clarke, Shim, Mamo, Fosket, & Fishman, 2003; Conrad, 2007; Gaudillière, 2002, pp. 360e372). While not discounting the importance of this trend, I follow the insight of other recent scholars who have identified the importance practices which created new connections between laboratory and clinical spaces, including the development of in vitro disease models, as more characteristic of biomedicine. Indeed, very often activities, knowledge, and practices in the clinic or other sites outside the laboratory shaped the production of experimental knowledge in the life sciences (Cambrosio & Keating, 2001; Keating & Cambrosio, 2004; Landecker, 2007, pp. 14e 16; Löwy, 1996; Strasser, 2011). It is precisely for this reason that further historical research on the broader historical settings of biomedical research is so engaging.


successes, there was a growing sense among many of these researchers that the efforts of individual investigators themselves would not be capable of addressing complex diseases such as cancer. The expansion of public support for biomedicine also imposed demands for a much higher degree of accountability. State officials and leaders of the biomedical research community were forced to reckon with the question of how support for biological research advanced human welfare (Brandt & Gardner, 2000; Sabin, 1967). That the SVLP offered a promising answer to this question was due to its position at the intersection of concurrent transformations in scientific knowledge, medical philanthropy, and managerial theory after the Second World War. Two crises, real or imagined, provided the central impetus for these transformations. The first was the emergence of health activism and fundraising centered on children. Advocates of polio and leukemia research painted a compelling portrait of children as a vulnerable population menaced by disease. The second crisis transpired within the leadership of the National Institutes of Health as result of the administrative challenges posed by the Institutes’ rapid expansion during the 1950s and early 1960s. These leaders feared that they were losing their status as custodians of the nation’s health almost as soon as they had gained it. In the midst of these crises, human leukemia viruses acquired their administrative value as organizing objects for a network of resources and research contracts designed to hasten the discovery and production of a leukemia vaccine. Before moving to the political and cultural roots of the SVLP in hope and crisis, the first part of this article considers the resolution of some of the major experimental challenges faced by cancer virus theories in the early twentieth century. The discovery of new viruses and the application of new instrumentation and techniques to virology in the 1950s created a terrain much more favorably disposed to theories of cancer viruses. As significant as these developments were for the visualization of viruses, they did not amount to sufficient conditions for aggressively pursuing a cancer vaccine. By contrast, the second part of this article shows the dramatic changes in the visibility and organization of childhood disease research during the 1950s. Polio vaccination and the chemotherapy of childhood leukemia adopted a relentless attitude of hope, raising the possibility of accelerated, goal-oriented biomedical research aiming at not only the understanding and control but also the elimination of feared diseases. Fundraising appeals fostered an environment of crisis and urgency that allowed the federal government to take a role in cancer research. The final part of this article provides a genealogy of the SVLP as an administrative enterprise. The rapid expansion of state support for biomedical research created its own crisis of management. The administrative tools of systems planning drawn from the world of Cold War defense policy were ideally suited to framing leukemia viruses as administrative objects. Future-oriented planning addressed the environment of hope and crisis which had come to encompass childhood leukemia and vaccination. However, this vision also heralded a substantial shift in power over determining what research should be pursued from scientists to the state. 2. Dawn of the “the virus age” and cancer research While scientific developments alone may not have provided sufficient grounds for the enthusiasm of Life magazine and other boosters of leukemia virus research, experimental studies of viral carcinogenesis still played a necessary role. In particular, during the late 1940s and early 1950s two kinds of developments helped resolve persistent challenges faced by viral carcinogenesis theories earlier in the twentieth century. Changes in experimental design

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permitted the discovery of mammalian leukemia viruses that bore a closer relationship to human cancers. The effort to develop a polio vaccine sponsored the introduction of new molecular technologies into virology such as tissue culture, the ultracentrifuge, and the electron microscope, which assisted the case of associating viral particles with instances of cancer. Nonetheless, these developments did not meet with unequivocal acceptance from the cancer research community. Even if they had been embraced, cancer viruses were not necessarily a more pressing threat than the other causes of cancer that were commonly discussed in the 1950s. 2.1. Early theories of viral carcinogenesis and their experimental challenges In the early twentieth century etiological theories of cancer, like those of many other diseases, were caught up in a surge of enthusiasm for germ theory. This enthusiasm was result of the power of bacterial culture to render the causal force of the microscopic world visible, as was demonstrated dramatically in the case of tuberculosis. Moreover, the identification of microbial disease agents seemed closely linked to the development of therapeutic or preventative measures (Anderson, 2006, pp. 104e129; Geison, 1995; Gradmann, 2009; Latour, 1988; Tomes, 1998, pp. 91e112). Microbiologists embraced Robert Koch’s postulates as set of criteria for demonstrating the causal power of microscopic disease agents. These postulates required first, the association of the agent with every case of the disease, second, the absence of the agent in other cases, third, the isolation and preparation of a “pure culture” of the agent, and fourth, the inoculation of a new host with the pure culture and subsequent recovery of the agent.4 While popular understanding of cancer seems to have remained open to the identification of cancer as an infectious disease, these postulates were difficult for microbiologists studying cancer to satisfy (van Helvoort, 2000, pp. 318e320; Patterson, 1987, pp. 22e 23). Future Nobelist Peyton Rous’ work on the transmissibility of chicken tumors suggests these challenges. Rous could show that his agent was “filterable”dfilters capable of catching bacteria and cells did not diminish the infectivity of tumor extractsdand that extracts caused tumors in healthy chickens. However, he could not isolate the tumor agent or find analogous agents in animals more closely resembling humans. Moreover, the proposal of disease agents smaller than bacteria (viruses) was still hotly disputed (Becsei-Kilborn, 2010, pp. 118e139; van Helvoort, 2004, pp. 192e 195; Summers, 1999, pp. 82e96). Since efforts to culture potential cancer viruses outside of their host organisms were unsuccessful, the association and pure culture postulates remained onerous for virologists to satisfy until the midtwentieth century. Not all viral infections showed clear symptomsda host’s immune system could suppress the infection or the infection itself might be asymptomatic. In frustration, prominent virologists suggested that Koch’s postulates should be modified for viral diseases (van Helvoort, 1994; Rivers, 1937). These difficulties were compounded by the greater interest of experimental cancer researchers on hereditary and chemical theories of carcinogenesis. (Proctor, 1995, pp. 28e48) Notably, in 1929 Clarence Cook Little established the Jackson Laboratory to produce purebred mice for research on cancer inheritance. However, one researcher at the Jackson laboratory, John Bittner, found in the course of fosternursing experiments that a “milk agent” could cause a higher

4 This is an anachronistic rendering of the postulates in line with their later discussion in the 1950s cancer virus community (Bryan, 1962, p. 1031). Koch’s original schema seems to have only had three steps (collapsing the 3rd and the 4th) as he discusses them in relation to cholera (Koch, 1893).

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incidence of mammary tumors in lines of mice predisposed not to develop cancer. Bittner demurred from interpreting these results in infectious terms, discussing the milk agent as one part of a tripartite model of causation along with hormone levels and hereditary predisposition (Bittner, 1936; Gaudillière, 1994, pp. 62e69; Rader, 2004, pp. 184e186). Bittner later claimed that he chose the term “agent” rather than “virus” because cancer viruses were “unrespectable” and proposing a tumor virus would have threatened his grant applications (Klein, 1990, p. 122). Despite this lack of respectability, scientists associated with Rous’ laboratory at the Rockefeller Institute for Medical Research continued to investigate viral tumorigenesis. While their discovery of a rabbit papilloma virus in the mid-1930s gave some hope, their opinions were not widely credited in the cancer research community. Other proponents of viral carcinogenesis also modified their theories, proposing that the absence of an easily identified agent was proof of “masked” or “latent” viruses within tumor cells. This position, of course, asked for more credulity from critics rather than satisfying their demands for further evidence (Creager & Gaudillière, 2001, pp. 207e209; Rous, 1943; Shope, 1966, pp. 262e268). In 1938, a report on promising areas of etiological research for the recently established National Cancer Institute by America’s leading cancer experts dismissed proposals of viral carcinogenesis with a sentence. If viral infection did play a role in carcinogenesis, the report suggested, it was only with an enabling chemical agent (Byne-Jones, Harrison, Little, Northrop, Murphy, 1938, pp. 2127e2128). 2.2. Revival of cancer virus theories in the 1950s: new viruses and new techniques During the 1950s viral carcinogenesis proponents made great strides towards resolving the challenges presented by Koch’s postulates and the difficulties of experimental virus studies in animals. In 1953 Ludwik Gross, a researcher working for the Veterans Administration in New York, announced that he was able to reliably demonstrate the transmission of leukemia by a filterable agent by inoculating infant mice (Morgan, 2014). The weak immune systems of infant animals, it appeared, reduced the challenge of host resistance encountered in the use of adults.5 Unlike Bittner, Gross had found a more sympathetic audience for his work. His results appeared in prominent journals for the cancer research community, and the New York Academy of Sciences invited him to speak at a conference on cancer viruses in 1952 (Gross, 1952). The Journal of the American Medical Association also published reports of his results (“Filterable Agent Causing Mouse Salivary Gland Carcinoma,” 1953; “Transmissible Leukemia in Mice,” 1952). Critically, several researchers sought to duplicate his results. A series of mouse leukemia viruses emerged out of the work of investigators using infant mice. The Friend, Schwartz, and Graffi mouse leukemia viruses were announced in 1957, followed by the Moloney virus in 1960 and the Rauscher virus in 1962 (Moloney, 1960; Rauscher, 1962). Cancer virus studies received further impetus in 1958 when two researchers at the National Cancer Institute seeking to replicate Gross’s results, Bernice Eddy and Sara Stewart, found a virus, dubbed polyoma, capable of producing solid tumors in a wide variety of adult rodent species (Eddy & Stewart, 1958a, 1958b, 1958c; Eddy, Stewart, Kirschstein, & Young, 1959; Stewart & Eddy, 1959). The profusion of other tumor viruses in rodents, frogs, and birds was so great that when Gross published

5 From Jacob Furth, a researcher at Cornell Medical School in New York, Gross obtained the “AK” strain, 90% of which developed “spontaneous” leukemia (Bessis, 1976, pp. 291e295; Gross, 1953, 1951).

Oncogenic Viruses (1960), it ran to 393 pages. The work became a standard in the field, and the second edition, published in 1970, ran to 991 pages (Gross, 1961, 1970). The multiplication of viruses was matched by the multiplication of professional interest. Between 1957 and 1966 major centers of cancer research, such as the NCI (1960 & 1963), American Cancer Society (1960), and the MD Anderson Center (1957 & 1963), all sponsored multiple conferences on cancer or leukemia viruses (Beard, 1960; Rich and Moloney, 1966; Viruses and Tumor Growth, 1957, Viruses, Nucleic Acids, and Cancer, 1963; Weaver, 1960). That viral carcinogenesis received a more sympathetic hearing in the late 1950s was indebted to the fact that virologists developed powerful techniques which promised to allow the identification and culture of viruses to satisfy the causal criteria of Koch’s postulates (Rheinberger, 1995, pp. 49e60). Additionally, research with these techniques suggested that individuals carried a substantial number of previously unknown viral infections which caused no observable pathological symptoms, creating the sense, as the science journalist Greer Williams wrote, that “the microbe age is past.today we live in the virus age” (Williams, 1959, p. 4). In particular, tissue culture, ultracentrifugation (an instrument which generated higher forces than a centrifuge), and electron microscopy helped increase the plausibility of viral carcinogenesis by providing better means of detecting and manipulating viruses. Under the patronage of the National Foundation for Infantile Paralysis, tissue culture techniques progressed rapidly in the late 1940s and early 1950s. These methods substantially increased the number of candidate viruses for human diseases from twenty in 1948 to seventy in 1958 (Huebner, 1959). The sheer number of previously unknown viruses substantially revised the question of causality faced by virologists; the challenge was not which virus went with what disease but which disease went with what virus. The New York Times reported that a single virologist working for the National Institute for Allergy and Infectious Disease had used tissue culture and antibody tests to isolate twenty-five unique viruses from just two types of human and monkey tissue (Engel, 1957; Huebner, 1957, p. 380). The ubiquity of viruses and their diverse modes of infection suggested that individuals were already carrying many latent viruses within themselves which might give rise to illness, either alone or in combination with some other chemical or hereditary cause. “Neither the recent viruses nor their diseases are actually new but only our recognition of them,” commented a set of authors in the Annual Review of Microbiology (Schaeffer, Robinson, & Fodor, 1959, p. 345). While tissue culture revealed that humans carried numerous unknown and possibly harmful viruses, advances in instrumentation promised to isolate and identify these viruses. During the Second World War many physicians and biologists had mobilized to work on vaccine production, especially against influenza. In the process of developing vaccines, they gained experience with the expensive and novel ultracentrifuge as a means of better purifying, assaying, and classifying different virus strains. The ultracentrifuge was powerful enough to separate viruses from the detritus of ruptured cells this power reframed the problem of transmission and detection from a qualitative question of if masked or latent virus forms to a quantitative question of virus concentration (Gaudillière, 2000). Host immune responses or unknown competing infections, advocates of the ultracentrifuge contended, made the study of cancer viruses in animals too variable. The challenge of cancer virus studies, as they defined it, resided in obtaining pure samples of virus from the low concentrations present in tumors (Beard, 1948, 1956; Creager & Gaudillière, 2001, pp. 214e219). Among the new methods for virus detection and isolation, the electron microscope promised the most direct means of hunting


for cancer viruses as physical objects. Developed by the Radio Corporation of America during the Second World War, the electron microscope created widespread enthusiasm for creating images of the sub-cellular world (Rasmussen, 1997, pp. 28e70 & 197e221). Leon Dmochowski, a pathologist at the MD Anderson Center in Texas, emerged as the most visible hunter of virus particles using the electron microscope.6 In early 1957 Dmochowski announced to newspapers that he had placed viruses at the “scene of the crime” for human leukemia (“Scientist Finds Viruses ‘at Scene’ of Cancer,” 1957). Later that year, he claimed to have identified virus particles in the blood of individuals with leukemia visiting the MD Anderson Center (Dmochowski & Grey, 1958; MacCormack, 1958). These developments instigated widespread excitement. At the Third National Cancer Conference in 1956 Wendell Stanley, a virologist whose physiochemical studies of tobacco mosaic virus had been recognized with a Nobel Prize, stated that “the experimental evidence is consistent with the idea that viruses are the etiological agents of most, if not all, cancer, including cancer in man” (Stanley, 1957a, p. 47). In the following years, Stanley went on to reiterate this claim for many other audiences despite the fact that his UC Berkeley laboratory was not actively engaged in cancer virus studies (Stanley, 1957b, 1958, 1960). 2.3. Equivocal rather than enthusiastic: cancer researchers and virology Yet focusing on the statements and publications of a few notable researchers, or even broader consensus among virologists, does not account for the enthusiasm leukemia virus research attracted. The set of communities which converged on cancer virusesdvirologists, geneticists, physicians, cell biologists, epidemiologists, and othersdall followed different standards of experimental proof and sought to answer different questions. Before the mid-1940s, for instance, leukemia had often been identified as a blood disorder rather than a cancer. Even as leukemia’s status as a cancer solidified during the 1950s, the classification of its forms continued to hinge on and often contentious process of morphological inspection (Keating & Cambrosio, 2002, pp. 316e317). Consequently, advocates of the viral transmission for leukemia also had to answer the charge that at best they had demonstrated viral carcinogenesis in rare cases (Andervont et al., 1959). Meanwhile technical innovations for the detection of viruses, far from closing debate, often generated more doubt. One prominent polio virologist critiqued Dmochowski’s findings by reminding his audience that “particles are unlabeled in the electron microscope and I am sure that Dr. Dmochowski referred to them as virus particles rather than virus-like particles [to save time].we should remember that.the telling evidence to show a correlation between the particles and the virus activity has not yet been made” (Melnick, 1957). Indeed, Dmochowski was still seeking to confirm his observations a decade later (Dmochowski et al., 1967). Even the newfound ubiquity of viruses revealed by tissue culture created challenges. An invited speaker at a tumor virus symposium worried that “the considerable number of nononcogenic viruses in man, which might be present by pure coincidence in some cancer cells, complicate[s] our task tremendously” (Bernhard, 1960, p. 723).

6 Working within a tradition of visual inspection in pathology, Dmochowski aimed to use the electron microscope to satisfy the demand that virus particles be clearly associated with tumorous tissue. He initially adopted ultra-thin sectioning techniques employed for studies of sub-cellular structures to the search of virus particles in both mammary tumor cells and milk (“Briton Says Virus May be Cancer Cause,” 1954, “Dr. Leon Dmochowski, Researcher in Virology,” 1981; Passey, Dmochowski, Astbury, Reed, & Eaves, 1947, 1951).

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This shifted the burden of proof back to experimental work with animals, where cancer itself could be diagnosed and caused with greater confidence. Animal models of cancer, however, still faced a tepid reception in many parts of the medical community. Physicians could recall the failure of earlier cancer treatments deemed promising in animals to aid human patients. Oncologists argued that they did not catch cancer from treating patients in cancer wards (van Helvoort, 2004, pp. 193e194). Experimental cancer researchers were also wary of the extrapolation of mouse leukemia virus discoveries to human leukemia (Harris, 1965). Contemporaneous controversies over the use of laboratory animal models to demonstrate hormonal or radiological carcinogenesis demonstrate the fragility of the homology asserted in murine leukemia studies between animal and human cancers (Langston, 2010, pp. 17e27; Proctor, 1995, p. 168; Rader, 2004, pp. 246e249). Albert Sabin, a respected polio virologist, argued that that the study of human cancer was very different from animal cancers precisely because medical ethics foreclosed the reinfection of human subjects, a critical step for satisfying the causal criteria of Koch’s postulates.7 In the late 1950s, the importance of leukemia viruses was far from settled. Reviewing the evidence in favor for different causes of leukemia for readers of the New England Journal of Medicine in 1958, the Nobel Prize winning immunologist McFarlane Burnet dismissed viral leukemia as “a laboratory curiosity”(Burnet, 1958). In the early 1960s epidemiologic of surveys of leukemia placed greater emphasis on its possible environmental or genetic causes (Burch, 1963; Syverton & Ross, 1960). Reviewing the field, a cancer virologist conceded that “out of a massive flow of words and ideas it is difficult to synthesize a coherent picture and to sift out the meaningful from the imaginary” (Rowe, 1965, p. 1277). While the prevention of leukemia and other cancers was a matter of great concern, it was also by no means certain that virus research would be singled out as an especially important cause. The American Cancer Society directed its greatest public education efforts during this decade towards publicizing the link between cigarettes and lung cancer (Brandt, 2007, pp. 131e207; Patterson, 1987, pp. 201e230; Proctor, 1995, pp. 105e108; Ross, 1987, pp. 47e63). William Hueper, the head of the National Cancer Institute’s Environmental Cancer Section from 1948 to 1964, participated in a series of high profile campaigns to limit synthetic dyes in food as possible chemical carcinogens (Proctor, 1995, pp. 36e48). The studies of the Atomic Bomb Casualty Commission highlighted the link between radiation and some cancers, especially leukemia. The discovery that radioactive Strontium-90 from surface nuclear weapons testing found its way into children’s bones through the grass consumed by dairy cows caused particular consternation (Lindee, 1994; Proctor, 1995, pp. 183e192; Winkler, 1993, pp. 84e 108). Even had consensus emerged regarding the preeminence of viral etiological theories, the cancer research community would not have been quick to mobilize on behalf of an organized effort to develop a vaccine. Medical research, and cancer research in particular, were presented as a gradual processes of inquiry rather than a subset of public works. At the foundation of the NCI in 1937, a group of cancer experts cautioned that “in any program of cancer

7 Subcomm. On Government Research, Research in the Service of Man: Biomedical Knowledge, Development, and Use, S. Doc. No.90-55, at 163 (1966) (Conference Rep.). Contrary to Sabin’s optimistic assumption, the continuing use of human subjects for carcinogenesis research during the 1950s and 1960s provided a more sinister manifestation of doubts concerning the relevance of animal experiments to human cancer (Kutcher, 2009, pp. 97e159; Löwy, 1994, pp. 423e424). This was equally true of medical research more broadly, where episodes of human experimentation, often on unwitting subjects, remained common both before and after the abuses of Nazi Germany (Goliszek, 2003; Lederer, 1995; Reverby, 2009).

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research, patience and the adoption of a long-time point of view are essential” (Byne-Jones et al., 1938, p. 2130). Even after the Second World War, the leadership of the expanding National Institutes of Health (NIH) maintained that research was a creative act that could not and should not be directed by administrators (Kidd, 1953). As late as 1957 the Director of the NCI affirmed in a message to Congress that “scientific research is largely a cumulative process.it is of upmost importance to continue to preserve the freedom of scientists to pursue freely and independently avenues of investigation which their studies indicate are most promising.”8 Any therapeutic benefit from experimental cancer research, it was left unsaid, would be the serendipitous results of curiosity rather than the deliberate results of planning. 3. Children and accelerating the tempo of biomedical research The emergence of the SVLP rested upon a new understanding of the relationship between the public, the state, and the biomedical research community as much as any particular set of developments in the laboratory. The broader political economy of biomedical research has only recently started to receive attention (Creager, 2013). Foregrounding questions of political economy helps bring into focus the immense importance of childhood disease for remaking these relationships. The history of scientific research in the United States after the Second World War has generally been told from the perspective of the physical sciences, which found generous sponsorship from the National Science Foundation, Department of Defense, and the Atomic Energy Commission (later the Department of Energy). From these sources, the story seems to be one of cooperation, and sometimes conflict, between scientists and their federal patrons as the scale of scientific research grew.9 When historians of medicine have addressed the political history of medicine at midcentury, they have conflated this history with that of the medical profession’s relationship with the federal government, one defined by the contest for authority and professional autonomy between the American Medical Association and the federal government over matters such as medical education or national health insurance (Gordon, 2003; Starr, 1982, pp. 17e29; Warner, 2004). Likewise, the frustrations of the NIH in establishing authoritative cooperative drug evaluation programs with industry in the late 1940s have been seen as a zero-sum regulatory contest (Marks, 1992). It is plausible, but incorrect, to assume that these struggles for autonomy and authority also defined the character of biomedical

8 Office of the NCI Director office to Senator Lister Hill, 12 June 1957, RG 443 UD0D6, Carton 93, RES 9e7 National Cancer Institute (NCI) 1937e1968. National Archives and Records Administration II (College Park, MD) [hereafter cited as NARA II]. 9 Academic scientists authored numerous passionate appeals for their autonomy, often buttressed by anticommunist rhetoric. The version of the National Science Foundation famously proposed by Vannevar Bush in Science: The Endless Frontier (1945) was intended to avert a more populist and expansive plan proposed by the liberal New Deal Senator Harley Kilgore. The controversy over the structure of the Foundation did not so much draw upon preexisting categories of fundamental and directed scientific research activities as it created these ideas. Scientific autonomy and the cause of basic research were potent rhetorical tools in the context of growing anticommunism. The Foundation’s creation in 1950 as an organization with only grant-making power to fund “best science” as opposed to a more sweeping mandate to direct scientific research thus marked a comparatively modest intervention by the state in scientific life (Appel, 2000, pp. 47e54; Hollinger, 1990; Kevles, 1977; Reingold, 1994; Wang, 1995). More recently the terms of this debate, including the easy separation of “applied” from “basic” science and the assumption that academic scientists occupied a privileged position versus their contemporaries in industry or engineering have been challenged (Bud, 2012; Clarke, 2010; Edgerton, 2004; Shapin, 2008, pp. 127e164).

research. At mid-century, a vast array of organizations supported biomedical research (American Foundation, 1955, pp. 107e121). Unlike physics, the political economy of biomedical research was a tripartite system comprised of the federal government (NIH and Atomic Energy Commission), private actors (philanthropy and pharmaceuticals), and academic scientists. Far from having a zeroe sum relationship, during the 1950s the pool of resources and scope of action for all of these groups expanded (Creager, 2008). To a widening group of administrators, scientists, and philanthropists the resolution of health challenges such as cancer appeared for to require more than the efforts of single investigators pursuing their curiosity. For the sake of efficiency and speed, new systems for the management of medical research would need to be developed. In many cases the impetus for planning and directing biomedical research was transferred by private actors to government agencies. Biomedical research had already hosted a number of private planning efforts. In the 1930s, the Rockefeller Foundation established itself as the single patron of biomedical research. Its research director, Warren Weaver, successfully sought to direct this research, establishing a coordinated program in “molecular biology” among its grantees (Kay, 1993, pp. 22e57; Kohler, 1976, 1978). During the Second World War many scientists and doctors served on largescale projects, such as the development of penicillin, blood plasma banking, or vaccine production, for the Office of Scientific Research and Development. This group ended the War with a heightened esteem for the capacities of industry and government to plan and organize results-oriented research (Creager, 1999; Gaudillière, 2000; Kay, 1993, pp. 164e193; Lenoir & Hays, 2000; Neushul, 1993; Rasmussen, 2002). This background, not the dualistic opposition of scientific autonomy and state planning, formed the political economy out of which the SVLP later emerged. 3.1. Polio vaccination When it came to the combination of infectious disease and research management, no disease was more prominent than polio. The announcement of the successful trial of Jonas Salk’s polio vaccine in 1955 stands as “biggest-of-the-big medical breakthroughs” in the iconography of laboratory medicine and public health. With the release of the Salk vaccine its patron, the National Foundation for Infantile Paralysis (NFIP) demonstrated that medical organizations could aspire to reach beyond treatment and education towards the eradication of feared diseases (Hansen, 2009, pp. 251e252). President Franklin Roosevelt, the most prominent modern casualty of polio, founded the NFIP in 1938 to support polio research and treatment after his previous fundraising efforts floundered on their association with the partisan controversies surrounding his presidency, especially the notorious “Court Packing” fight (Paul, 1971, pp. 148e160; Rogers, 1992, pp. 30e71). Basil O’Connor, Roosevelt’s law partner, envisioned the NFIP as part of a new strategy of medical philanthropy. Unlike other disease charities such as the National Tuberculosis Association or Roosevelt’s previous foundation in Warm Springs, GA, one of the NFIP’s primary aims would be to coordinate research into the nature of polio in addition to more conventional philanthropic activities such as providing therapy, social services, or public information (Shryock, 1957; Zunz, 2012, pp. 46e49). Polio was already thought to be a viral disease. Accordingly the NFIP’s Committee on Scientific Research, drawing upon the counsel of eminent virologists and polio experts, distributed generous multi-year grants in support of a broad range virology studies. In 1956 the NFIP was responsible for training a third of all virologists under the age of forty-five in the United States. These included investigators working on tissue culture techniques (John Enders and the Tissue Culture Association), the physical and biological


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aspects of virus structure (Wendell Stanley), protein and nucleic acid structure (Linus Pauling), and viral reproduction (Max Delbrück). Notably, James Watson carried out his first study of DNA at Cambridge while supported by an NFIP postdoctoral fellowship (Creager, 2002, pp. 147e148 & 171e175; Kevles, 1993, pp. 420e421; Landecker, 2007, pp. 129e137; Paul, 1971, pp. 316e319 & 373e381). Meanwhile, virologists working under Max Delbrück, such as Renato Dulbecco, used culture techniques to develop systems for the observation of viruses in vitro outside of their living animal hosts, allowing the incorporation into animal virology of the quantitative techniques developed by the phage school. This system was later adapted to the study of cancerous cellular transformation by Harry Rubin and Howard Temin, leading to the proposal that like “prophage” a cancer “provirus” integrated into the cellular genome (Creager & Gaudillière, 2001, pp. 226e229; Kevles, 2008, pp. 250e253; Rubin, 1966; Sankaran, 2014; Temin & Rubin, 1958). Supporting such a broad range of research so generously required an intense fundraising effort. However, in absolute terms polio incidence remained low compared to other childhood ailments. The NFIP’s fundraising arm, the March of Dimes, heightened the visibility of polio through an innovative medical fundraising campaign employing the crisis rhetoric and sentimental images of afflicted children that we now commonly associate with childhood disease philanthropy. The aim was to mobilize small donations from great number of donors rather than seeking large donations from a few (Oshinsky, 2005, p. 5 & 81; Rogers, 1992, 2006, p. 172). In the words of one chronicler, the March of Dimes raised the effort to cure polio to the level of “a holy quest.” Buoyed by these novel fundraising methods, the NFIP raised an average of $25 million annually from 1938 to 1962 (Oshinsky, 2005, pp. 81e83; Paul, 1971, pp. 308e316; Rogers, 1992, p. 172). These donors would not be satisfied merely by the accumulation of deeper knowledge about polio. To sustain its pace of fundraising the March of Dimes needed to be able to both promise and deliver upon the demand for therapeutic advances sparked by its fundraising campaign. Fundraisers were nervously aware of the need to strike a balance between hype, which could create disappointment and disillusionment if unmet, and restraint, which dulled enthusiasm for giving. A memo to members of its Speaker’s Bureau cautioned that “the word ‘soon’ can be variously interpreted; it could mean tomorrow or next year. In fact, we do not believe it will be either tomorrow or next year, but probably will entail at least several years.we must not mislead the public into thinking that all of these problems can be licked overnight even when a vaccine that seems.safe in experimental animals.”10 However, a pamphlet published within the same year as this admonition foretold that “the conquest of polio is now in sight” (Oshinsky, 2005, p. 129). O’Connor was frustrated by the tension between the hopes of his donors and the curiosity of his grantees, writing in 1944: “NodNodlet’s have a new philosophy of doing things in medicine.let [us] see how quickly we can do it.and not get lost on how we can study it.we get money to spenddand from the people.” (Quoted in Creager, 2002, p. 153) As an early account of the Foundation noted, the NFIP “could not appear sluggish or over-cautious. It was trapped within its own image of dynamic optimism” (Wilson, 1963, p. 81). Further complicating matters was the lack of urgency felt by the researchers supported by the NFIP. One grantee recalled that “most

of us were motivated mainly by curiosity and by the challenges of the many unsolved problems concerning the interaction of virus and host, rather than by the hope of a practical solution in our lifetime” (Quoted in Oshinsky, 2005, p. 95). In 1946, O’Connor decided that the slow rate of progress demanded drastic reorganization. He appointed a Wayne State anatomy professor named Harry Weaver to the newly created post of Director of Research. In a quasi-facetious memo Weaver later recounted the beginning of his efforts, dramatizing the conflict between seeking knowledge and seeking results. Soon after his arrival, Weaver wrote, he “became convinced that prevention.was the only promising avenue of approach.” However, at a research roundtable in 1947 he found with dismay that “an appalling few of the NFIP’s grantees were really trying to solve the problem of poliomyelitis in man.” By 1948 he concluded that the NFIP should start sponsoring “more research specifically directed at solving the many problems obviously pertinent to poliomyelitis.” While the failure of several efforts in the 1930s had dampened the enthusiasm of many polio experts for vaccination, Weaver committed the NFIP to the development of a vaccine.11 Developing a vaccine, Weaver concluded, required “group planning and the pooling of ideas and resources.a master plan which would permit a cheaper and quicker solution than is possible by the individual approach” (Quoted in Paul, 1971, p. 412). Consequently, many of Weaver’s first changes were organizational. Weaver reasoned that the scientist-directed Immunization Committee “was not able to function with the necessary dispatch,” so he replaced it with the public-health directed Vaccine Advisory Committee (Quoted in Carter, 1966, p. 176). Where he faced resistance from experienced grantees to the projects he deemed important, Weaver recruited less established investigators. Famously, Weaver appointed a young virologist named Jonas Salk to oversee an expensive program using rhesus monkeys to establish the number of polio virus strains. For Weaver, this effort stood as an exemplar of the large scale effort required for successful biomedical research into a disease. The major challenge was less intellectual than logistical, “few individuals.could obtain financial support in large amounts.investigators.committed what committed what we would describe as an unpardonable sin.[carrying] out with one or two monkeys, experiments that should have never been attempted without using scores of these animals” (Weaver, 1953a, 1953b, p. 7). Salk’s Pittsburgh laboratory alone, for example, went through 175 monkeys a month.12 However, an equal challenge was presented by the intellectual content of the work required, or lack thereof. Weaver wrote that “no single problem in all of medical science.was more uninteresting to solve.the solution necessitated the monotonous repetition of exactly the same technical procedures on virus after virus.for 3 solid years” (Weaver, 1953a, 1953b, pp. 12e13). Yet determining that the poliovirus came in three strains was of critical importance for the success of any vaccine. No investigator working unsupported could have so quickly produced a similar result. In a final flourish, the field trials of the Salk vaccine, involving almost two million children, offered a monumental testament to the power of coordinated and generously funded biomedical research (Creager, 2002, pp. 171e175; Smith, 1990, pp. 248e249). While many would continue to insist on the distinction between funding the best “basic” research and expecting therapeutic payoffs, the NFIP’s success elided such neat divisions. Although not “possessing the individual brilliance and scientific skills of [supported] investigators,” one early

10 Dr. Hart Edgar van Riper to “NFIP Personnel Making Speeches for MOD [March of Dimes], 7 December 1950, Medical Program Records, Series 14: Poliomyelitis Carton 15, Folder: Speeches and Speaker’s Bureau. March of Dimes Archives (White Plains, NY).

11 Harry Weaver to Basil O’Connor 27 June 1955, NFIP PR I, Subject Files, Carton A, Folder 11 (ACS). March of Dimes Archives (White Plains, NY). 12 Jonas Salk to Harry Weaver 16 August 1949, Unprocessed Grant Files Carton 1 Folder CRBS APR 11(1947). March of Dimes Archives, White Plains, NY.

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chronicler reflected, the NFIP staff “made an important contribution to maintaining the.tempo of polio research.by their cogent analysis of the validity of the myriad research projects within the scientific community” (Benison, 1972, p. 334). 3.2. Bringing the state into cancer research: children and chemotherapy To a modern reader it is especially striking that, at the height of national concern, the NFIP spent fifteen times more than the NIH on polio research (Smith, 1990, p. 249). This was by design. Fearing that federal action would impinge on its fundraising, the NFIP lobbied vociferously against government intervention (Smith, 1990, pp. 248e249). Indeed, it was notable that the NFIP needed to oppose intervention at all. Even as programs such as Social Security were instituted during the Great Depression, the presumption was that health was the province of either personal responsibility or voluntary organizations. The government had no beneficial role to play in medical research, a position reiterated often by the American Medical Association (Klein, 2003, pp. 158e206). Early twentieth century reformers, however, had established children as a unique subpopulation whose welfare in areas ranging from labor to public health required a greater level of state involvement (Lindenmeyer, 1997; Meckel, 1990; Skocpol, 1992). Since the vast majority of cancer cases afflicted adults, limited federal involvement in anticancer efforts should not be surprising. After its foundation in 1937, the NCI focused its efforts on intramural research rather than funding research in universities. The American Medical Association, for example, worried that government intervention in cancer research would diminish voluntary initiatives (Erdey, 1995, pp. 103e134; Shaughnessy, 1957, pp. 221e 264). With the exception of the distribution of radium for cancer therapy, this also characterized the stance of the NCI towards cancer treatment (Cantor, 2008). The most prominent anticancer research effort immediately after the Second World War was the endowment of the SloanKettering Institute in 1945 by General Motors engineer and executive Alfred Sloan. This institute rapidly grew into the nation’s largest private cancer research institute. Under a former chemical warfare officer, Cornelius Rhodes, Sloan-Kettering established one of the first large scale screening programs for anticancer chemotherapy agents, a program modeled on the divisional structure of automobile factories and large scale antibiotic compound screening by pharmaceutical companies (Bud, 1978, pp. 439e442). The first chemotherapeutic compound for cancerdnitrogen mustarddhad itself been discovered during the Second World War in the course of chemical warfare research (Chabner & Roberts, 2005, pp. 65e66; DeVita & Chu, 2008, pp. 8644e8645). Even widespread public enthusiasm failed to shift this stance. In the late 1940s, polls indicated that sixty percent of Americans feared cancer more than any other disease and nearly as many were willing to pay higher taxes to support a “Manhattan Project” to cure cancer (Gallup, 1946, 1947; Gross, 1946). In 1946 a bill was introduced to Congress calling for one hundred million dollars, an amount two hundred times larger than the annual NCI budget, for a “Mobilization of the World’s Cancer Experts.” However, both the NIH and the American Cancer Society (ACS) affirmed that patience was the watchword of cancer research. Opposing the bill, the Surgeon General testified that too few qualified cancer researchers were available.13 Meanwhile, the ACS feared the consequences of unmet public expectations for its fundraising (“Report on American

13 H.R.4502: Hearings on H.R. 4502, Day 1, Before the Committee on Foreign Affairs, 79th Cong. 3e9 (statement of Thomas Parran, Surgeon General).

Cancer Society Directors’ Meeting,” 1947). Instead, at the NCI’s request legislators substituted a more modest measure to train researchers (Strickland, 1972, pp. 46e50). As the ACS and NIH worked to deflect government intervention, the seeds of cancer’s redefinition as a childhood disease were germinating. In the early twentieth century, the amorphous symptoms of common childhood cancers such as acute leukemia were easily masked by those of other childhood maladies. Acute leukemia appeared suddenly and killed quickly, so the taboo surrounding cancer was also multiplied by that surrounding fatal childhood illness. The decline of other childhood diseases in the 1930s promoted the recognition of pediatric cancers as a distinct disease category. The Memorial Hospital of New York City started to maintain a separate record of childhood cancers that formed the basis for the first textbook on pediatric cancers, Cancer in Childhood (1940) (Krueger, 2008, pp. 32e39). Childhood cancers received an even higher profile amidst fundraising for the Hospital’s expansion in the 1940s. In 1947, the Hospital partnered with the American Cancer Society to encourage parents to have their children examined regularly for signs of cancer. In addition to drawing funds and educating parents, these childhood images, appearing in Time and Newsweek, played a critical role in opening space for the discussion of cancer as childhood disease. Yet these emotionally arresting images were double-edged; the Hospital’s doctors could promise little by way of improved treatment, only screening and diagnosis (Krueger, 2008, pp. 52e54). Surgery and radiation, therapies tailored to attack solid tumors, offered little hope against leukemia, a cancer of the blood. The promise of effective therapy for children threatened by leukemia came from chemotherapy. Sidney Farber, a pathologist at the Children’s Hospital in Boston, tested the first class of effective chemotherapies for childhood leukemia in 1948. While the remissions Farber and other researchers attained were only measured in months, the fact of any remission at all inspired immense excitement. Encountering skepticism from his surgeryoriented colleagues, Farber forged an alliance with civic groups to establish the Children’s Cancer Research Foundation (CCRF). As with Memorial Hospital, Farber’s campaign simultaneously created medical and public knowledge about childhood cancer. This was particularly necessary for Farber (as it had been for polio fundraising) because acute leukemia accounted for a small proportion of cancers. For its inaugural event, the CCRF followed the example the NFIP in presenting a leukemic poster child. Unlike preceding childhood disease publicity campaigns, which typically introduced new children every year, the CCRF transformed its first “spokes child” into an icon of hope through the use of a pseudonym. “Jimmy,” unlike most children, had seen his leukemia go into complete remission following chemotherapy. An all-American name resonated with the consumer leisure venues, such as radio shows, movie theaters, and famously Red Sox baseball games, where the CCRF distributed its appeal. After only four years of fundraising, the CCRF was able to finance the construction of the Jimmy Fund Building at Children’s Hospital, a center dedicated to pediatric chemotherapy research which formed the nucleus of the modern Dana-Farber Cancer Center (Krueger, 2007, pp. 78e85). The CCRF’s campaign attracted wide notice because it suggested that cancer could be entirely cured. Activities in Boston energized other chemotherapy programs, such as those at Sloan-Kettering (Krueger, 2008, pp. 103e104). As the publicity drawn to childhood cancer increased the expected tempo of drug discovery, these private initiatives were soon overwhelmed by the volume of screening tests demanded (Löwy, 1996, p. 44). The yawning gap between expectation and organization in leukemia chemotherapy research became a unique site for forming new relationships among medical philanthropies, pharmaceutical


companies, and the federal government. In view of the need for large-scale chemotherapy screening and an equally extensive system of clinical trials to test the efficacy of promising compounds, the ACS decided to revise its posture towards the federal government. In its previous incarnation, the ACS had been the American Society for the Control of Cancer, a doctor’s organization focused on professional education and public outreach. This changed in 1944, when a group of lay activists led by Albert and Mary Lasker took control of the organization. Its new name reflected these activists’ greater ambitions and their dedication to the expansion of cancer research. A fervent supporter of national health insurance, Mary Lasker came to appreciate that the federal budget could constitute a greater source of funds for research than even the most dedicated of voluntary fundraising drives.14 While the NFIP and American Medical Association resisted federal involvement, Lasker followed the reasoning of voluntary social welfare agencies after the Second World War in envisioning the government not as a competitor for funds but as a supplier of basic services while the ACS focused its efforts on public education and the sponsorship of the most innovative research (Morris, 2009, pp. 35e78; Zunz, 2012, pp. 169e 200). Faced with the potential of chemotherapy and Lasker’s pressure, the ACS started to aggressively lobby Congress on behalf of the NCI. Deploying slogans such as “Every Three Minutes Someone Dies of Cancer,” ACS lobbyists and their allies within the NIH adroitly mastered the performative aspects of budget hearings (Patterson, 1987, p. 175). Administrators could submit low official budgets, while the ACS’s congressional allies could appear as paladins of American health by demanding in semi-staged exchanges if more resources were needed to defeat cancer after presenting the “official” budget. The answer was invariably yes, and the appropriation was increased (Strickland, 1972, pp. 75e108; Swain, 1962). Defying the fears of critics, the alliance of the NCI and the ACS resulted in increased funds flowing into both organizations (Creager, 2008, pp. 182e183). Spurred by the testimony of Farber and other researchers presented by the ACS, in 1955 Congress directed the NCI to establish the Cancer Chemotherapy National Service Center (CCNSC). A quasi-autonomous division of the NCI, the CCNSC relied on contracts rather than grants to coordinate the production and screening of tens of thousands of potential chemotherapy compounds by pharmaceutical companies. The CCNSC offered a new model of coordinating biomedical research practices between state, private, and academic institutions. The director of the CCNSC, Kenneth Endicott, explained that the “spectacular temporary remissions in acute leukemia” made chemotherapy work a promising area for the NCI to coordinate cooperative work: “with the impetus given this field by Congress, it has been possible to bring together the pharmaceutical industry, research organizations, private investigators, and the United States Government, each contributing their varied skills and resources to implement an effective cooperative national program” (Endicott, 1957, p. 275 & 293). Its efforts soon constituted the single largest budgetary item at the NCI, expanding to include extensive cooperative clinical trials spanning dozens of institutions under the supervision of NCI officers based in Bethesda (Gaudillière, 1994; Keating & Cambrosio, 2002, 2007, 2012; Krueger, 2008, pp. 95e99; Löwy, 1996, pp. 41e48).

14 Warren Shields to Wendell Stanley, 5 October 1959, Wendell Stanley Papers Carton 13 Folder “ACS Research Committee 1959e1965.” Bancroft Library (Berkeley, CA); Harry Weaver [Outgoing Research Director, ACS], “The Role of the American Cancer Society in Research,” p. 2, The Mary Lasker Papers, Carton 102, Folder “ACS Research 1960.” Columbia University Special Collections and Archives (New York, NY) [hereafter cited as Lasker Papers]. For published literature on this realignment see (DuShane, 1956; Patterson, 1987, pp. 180e184).

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The development of the CCNSC shifted the material locus of experimental cancer research at the NCI and beyond. For example, the CCNSC selected two mouse tumors and one strain of leukemia as the standard test for potential chemotherapy compounds, creating a demand for tens of thousands of purebred mice (Gaudillière, 1997; Rader, 2004, pp. 216e223). By contrast, Gross’ first experiments had employed a few dozen mice. The existence of a large chemotherapy screening effort dedicated to mouse cancer models considerably aided cancer virologists facing reservations regarding the applicability of murine leukemia findings to human cancer.15 In contrast to the doubts voiced by Sabin, Endicott confidently asserted that “in the mouse, leukemia is essentially a virus disease.It can be prevented by several techniques of vaccination.I, for one, do not believe that there is much difference between a man and a mouse” (Endicott, 1968). His statement was more than a personal opinion, by then Endicott was the director of the NCI. 4. Managing the future: systems planning and leukemia viruses In the absence of an identified viral agent, the organizational and cultural analogies drawn between polio vaccine development efforts or the CCNSC served as justification for the SVLP’s effort to accelerate the development of a leukemia vaccine. Planning for the SVLP addressed a crisis of managerial legitimacy within the NIH, which lacked the administrative capacity to keep up with the scale of research the public expected it to oversee. The development of the SVLP provided a robust alternative for the oversight of research. Ambitious NCI administrators transformed the as of yet undiscovered human leukemia virus into an object of administration through the application of systems planning theories drawn from a burgeoning community Cold War intellectuals and defense planners. The SVLP thus addressed both a crisis of safety surrounding childhood leukemia and a crisis of legitimacy surrounding the NIH’s organizational capacity. Both of these crises could be resolved by assuring the public that a human leukemia virus would be discovered under the direction of the SVLP and organizing the Program on that expectation. 4.1. Stopping a “slaughter of the innocents”: children and the urgency moral urgency of biomedical research By the late 1950s, advocates of leukemia vaccine research could draw on a climate of intense hope and fear surrounding childhood diseases. This climate created a unique moral space for cancer virus studies. Discussions of smoking or nutrition and cancer focused on the activities (and culpability) of adults while attacking fallout strayed into fraught politics of the nuclear arms race (Proctor, 1995, pp. 75e100 & 174e196). Leukemia vaccination, however, promised to save children. A novel, The Blood of the Lamb (1961), dramatizes this link. Its narrator-father, watching his daughter succumb to leukemia, condemned the cancer as a “slaughter of the innocents,” asking “who creates a perfect blossom to crush it?” (De Vries, 1961, p. 225). A concerned citizen wrote to Representative John Fogarty (D-RI), a leading advocate of the NIH, that “the scourge of cancer is America’s No.1 killer of our children,” and urged him to do even

15 Indeed recent scholarship on the use of animal models for biomedical research in suggests exactly this point: prewar intellectual controversies were no so much resolved as supplanted by the institutionalization of animals for basic biological testing and screening efforts (Kirk, 2008, 2010, 2012).

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more to help the NCI.16 Discoveries of numerous unidentified viruses associated with chronic respiratory diseases in children underlined the particular vulnerability of young immune systems to viral infection (Chanock, Parrott, Bell, Rowe, & Huebner, 1958). Moreover, the promise that a vaccine would eliminate a disease entirely, not just cure or control individual instances, made it especially appealing. The first stages of mobilization for leukemia virus research proceeded by analogy with polio. Harry Weaver moved from the NFIP to the ACS in 1955 to become its new director of research (“Profile: Research Team,” 1956). Like the NFIP, in its fundraising the ACS sought to balance urgency with restraint. After the Salk vaccine a writer in Cancer News cautioned that “the peak of enthusiasm was reached in the many assertions that ‘now polio has been beaten, cancer will be next.’.Some writers and their readers and the orators and their audiences have not made this distinction.no responsible authority at this point will predict the control of cancer in the near future” (McGrady, 1955, p. 23). However, a 1956 ACS ad asked, “The Next Medical MilestonedConquest of Cancer?.antibiotics, new wonder drugs.a vaccine for polio. We will see the conquest of cancer too if we want it badly enough” (“Advertisement,” 1956). In the early 1960s the ACS became more vocal in its appeal for research into a childhood leukemia vaccine. Reminding readers that leukemia claimed the lives of two thousand children annually and accounted for half of all cancer deaths among school children, a pamphlet drew links between laboratory research and the promise of a vaccine: Progress against leukemia encourages scientists to speculate that it may be one of the first forms of cancer in which there will be a major breakthrough. A virus has been isolated from leukemia mice and a vaccine has been developed which protects mice against the virus. Although this does not apply to man as yet, it offers a promising avenue of research.17 Public reaction to events such as the “outbreak” in Niles, Illinois, suggests that the fear of local outbreaks common for polio also transferred to leukemia. The lead researcher of the Niles events, Stuart Schwartz, even reported at an ACS-sponsored conference that he was working on a “crude” vaccine (“Medicine,” 1960). Primed by this dense web of associations, public sentiment favored federal efforts to develop a leukemia vaccine. In 1958 Congress voted to approve a special appropriation of one million dollars for leukemia virus research after being told by the director of the NCI that the “stage was set” for “major breakthroughs.”18 Advocates of virus studies could argue that vaccine development promised a more rational means of addressing the threat of leukemia than chemotherapy. Justified or not, chemotherapy suffered from a reputation as an empirical endeavor whose central activity, no matter how much it might be expanded, remained the more or less random screening of compounds (Keating & Cambrosio, 2002, pp. 317e318). Former NFIP grantee Wendell Stanley explained that unlike chemotherapy, “Viruses.provide [a] rational experimental approach to the human cancer problem, because they provide an experimental means of studying heredity and the whole evolutionary process and.because as examples of the simplest living

16 Joseph Writh to John E. Fogarty, 27 March 1958, John Fogarty Papers, SF-32, Folder 462. Providence College Manuscripts and Special Collections (Providence RI). 17 “Leukemia” Brochure, Lasker Papers, Box 102, Folder “ACS General 1960.” 18 Departments of Labor and Health, Education, and Welfare Appropriations for 1959: Hearings on Department of Health, Education, and Welfare, Day 5, Before the Subcomm. on Departments of Health, Education, Welfare, and Related Agencies Appropriations, 85th Cong. 390 (1958) (statement of John R. Heller, Director of the National Cancer Institute); (Annual Report of Program Activities, National Institutes of Health: National Cancer Institute, 1958, pp. 1e4).

agents they provide a unique probe for entering the living cell and studying life itself.”19 4.2. Organizing leukemia virus research at the National Cancer Institute As planning for leukemia virus research began, polio provided an important set of precedents for success. In early discussions of how to spend its special appropriation, NCI administrators also enlisted the advice and counsel of polio experts. The receptivity of these polio researchers was no doubt aided in part by an ironic consequence of their success. After the Salk vaccine lifted the immediate threat of polio in the public mind, the pace of NFIP fundraising efforts had collapsed (Oshinsky, 2005, pp. 255e257). Soon after the appropriation passed, the National Cancer Advisory Council invited a prominent polio researcher, Hilary Koprowski, to speak with them about the potential properties of a human cancer virus.20 A report drafted for the National Advisory Cancer Council by the Virology and Rickettsiology Study Section of the NIH indicated the excitement of these conversations, commenting that “in view of.recent discoveries, it is now fully evident that there are excellent opportunities for intensive investigations of virus tumors and tumor-viruses.in the areas of etiology.and of possible prevention by vaccines.”21 The scientific consultants invited to the newly established “Viruses and Cancer Panel” of the National Advisory Cancer Council also included several prominent polio virus researchers, including Koprowski, John Enders, Albert Sabin, and Jonas Salk.22 Early memoranda drawn up by the Viruses and Cancer Panel reflected the experience of these polio researchers, focusing on standardizing and distributing reagents, laboratory animals, virus strains, and cell lines that would be beyond the a capacity of any individual laboratory to develop.23 The panel recommended, in fact, that that the NCI buy up a half million dollars’ worth of leftover viral reagents from the NFIP (although the purchase price was eventually negotiated for half that amount) (Manlin, 2008, p. 81). Reflecting the importance of this logistical activity, in 1960 the NCI created both the Laboratory of Viral Oncology and the Virology Research Resources Branch. The latter was intended to “provide essential materials and services to all scientists working in the field” through “contracting with a commercial concern” so that in as short a time as possible the necessary cell cultures, animals, and virus strains would be available “in mass quantities” (NCI Office of Information and Publications, 1962, p. 9). As the NCI’s effort got underway, public expectations for a cancer vaccine breakthrough continued to rise. The NCI and NIH, however, struggled to find a form of management equal to public enthusiasm for biomedical research. The NIH had been slow to embrace research as a core mission, and by the late 1950s the strains of administering research threatened to tarnish its legitimacy as a protector and

19 Labor-Health, Education, and Welfare Appropriations Act for 1957: Hearings, Day 11, Before Comm. on Appropriations, 84th Cong. 1412 (1956) (statement of Wendell Stanley, Director of UC Berkeley Virus Laboratory); (Gaudillière, 1998, pp. 150e158). 20 Minutes of the National Advisory Cancer Council, March 2, 1959, RG 443 A1e27 Carton 15. NARA II. 21 Virology and Ricketssoiology Study Section, “The Role of Viruses in Relation to Malignancy,” 18 September 1958. Appendix A to the Minutes of the National Advisory Cancer Council, 3 November 1958, RG 443 A1e27, Carton 15. NARA II. 22 “Highlights of an Inter-Section Study Meeting on the Role of Viruses in Relation to Human Malignancies,” 16 September 1958, John Enders Papers (MS 1478), Series I, Box 12 Folder 246. Yale University Archives and Special Collections (New Haven, CT). [hereafter cited as Enders Papers]. 23 “Statement of the Current Areas of Interest, Virus and Cancer Panel,” 9 June 1960, Enders Papers, Series I, Box 12 Folder 247.


promoter of national health. In 1944, Surgeon General Thomas Parran outlined a far-reaching expansion plan for the Public Health Service which focused as much on public health activities as research activities. In 1946, the NIH’s extramural grant program expanded rapidly when it assimilated leftover wartime research contracts. In debates surrounding the scope of the National Science Foundation during the late 1940s, the NIH fought fiercely to retain control of these projects, asserting that they were not “basic” research but research for human health. However, this contention did not precipitate any attempt to direct or coordinate biological research for the sake of broader health goals in the early 1950s. The NIH presented its research grants chiefly as a means of developing an adequately trained scientific workforce (Reingold, 1995, pp. 319e 323; Strickland, 1972, pp. 15e31). This posture changed under the directorship of James Shannon. Shannon formed a lobbying alliance with Mary Lasker and her associates in Congress in order secure exponential increases in its research budgets. An increasing portion of these funds went for grants-in-aid to academic researchers rather than intramural research at the NIH. Its administrative capacity, however, failed to keep pace with the oversight demanded by these extramural grants. Indeed, the NIH explicitly abjured any attempts to direct research. NIH research grants terms stipulated that “the grantee is not required to follow the specific details of the project submitted for review, particularly if he finds promising leads that in his opinion are more likely to be more productive than the project proposal itself.”24 Starting with the 1958 Bayne-Jones Report, Congress placed the administration of research funds under increased scrutiny (Patel, 2012, pp. 105e112). Opponents of increased federal spending such as Representative Lawrence Fountain (DeNC) used these investigations to instigate a scandal over the administration of grant funds. During hearings in 1961e 1962, Fountain managed to maneuver the usually adroit Shannon into a series of statements appearing to dismiss the need for vigorous oversight of grants (Fox, 1987; Greenberg, 1968, pp. 276e 280; Strickland, 1972, pp. 169e177). More than individual lapses of oversight, these critics made it clear that the very essence of how the NIH supported research was in question. Fountain castigated Shannon in Congress: “we certainly ought to expect reasonable management procedures designed to ensure that the money is being spent prudently and for the purposes for which it was intended by Congress. This is all the more essential since you are spending many hundreds of millions of dollars to support research for which we cannot see and measure the results.”25 Press headlines, including “Overspending on U.S. Medical Research Cited,” “Stanford Denies Building Pool with U.S. Grant for Research,” and “Lack of Proper Policing Called Chief Fault in NIH Grant Plans,” were particularly embarrassing (Haseltine, 1961, 1962; Hearst, 1962b; Toth, 1962a, 1962b). Even a later report one of the NCI’s stalwart Congressional allies expressed disappointment in the “apparent lack of success of the Cancer Institute to date.in systematic development of this new knowledge with specific orientation to cancer.”26 Executives at the NIH and NCI conferred with great concern among each other as to how they could demonstrate the administrative capacity to spend taxpayer dollars not only

24 “Explanation of Statement of Grant Award,” July 1958, Charlotte Friend Papers, Alpha Series, Box 10, Folder NCI Grant. Mt Sinai Levy Memorial Hospital (New York, NY). 25 The Administration of Grants by the National Institutes of Health: Hearings, Day 1, Before Subcomm. of Committee on Government Operations, 87th Cong. 21 (1962) (comments of Lawrence Fountain, Chair). 26 Committee on Appropriations, Departments of Labor, and Health, Education and Welfare, and Related Agencies Appropriation Bill, 1965, H.R. Rep No. 88e69, at 23 (1964). 28. 88th Cong. 2nd session.

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responsibly, but also towards therapeutic benefits.27 An influential review of NIH administration conducted in 1964 concluded that “no matter how much the NIH may wish to leave the development of basic fields of science to be guided by the independent judgments of scientists in their private laboratories, a quite different set of policy questions is now forced on the NIH by the very magnitude of its program” (NIH Study Committee, 1965, p. 208).

4.3. Managing the future: leukemia viruses as administrative objects While proposals after the Second World War for greater management of biomedical research had not gained traction at the NIH after the Second World War, the late 1950s provided a different set of intellectual resources for advocates of research planning. This included polio but vitally extended to innovations in the organization of military research and development. To address this dual crisis of childhood disease and institutional legitimacy, proponents of research planning at the NIH could now draw upon management methods developed by Cold War think tanks, especially those arising from the Air Force’s sponsorship of the RAND Corporation. In the 1950s RAND planners had applied the mathematical language of game theory and operations analysis first to questions of aerospace production and then to matters of defense planning and nuclear strategy. Reports produced by RAND stoked fears that the US was acutely vulnerable to attack by the Soviet Union, and notoriously provided the basis for the illusory “missile gap” debated in the 1960 presidential elections (Amadae, 2003, pp. 37e 57; Fortun & Schweber, 1993; Hounshell, 1997; Stockfish, 1987). Where RAND reports forecast crisis they also promised solutions. “Systems analysis,” devised by RAND defense intellectuals, provided the foundations for a new set of research and strategic management methods for defense research and development. His election in 1960, John Kennedy gave his Defense Secretary, former Ford executive Robert McNamara, a wide mandate to reform the Department of Defense. Reviews within the Department, such as “Project Hindsight,” had already initiated a debate over the utility of sponsoring freeform scientific inquiry for the sake of national security. Drawing from his prior experience as an automobile executive at Ford, McNamara formed a task force which combined accounting techniques with systems analysis to create a management method for defense projects known as the “Planning Program Budgeting System” (PPBS). While the intellectual merits of PPBS were fiercely contested during its application to procurement decisions, the econometric approach to “rational defense” policy succeeded in its broader aim of placing the different branches of the military establishment under tighter civilian control (Amadae, 2003, pp. 54e83; Anser, 2004; Novick, 1965; Palmer, 1978, pp. 39e77). McNamara subsequently incorporated these methods into a broader computer-based cybernetic vision of command and control war-fighting embraced by counterinsurgency and airdefense specialists (Beniger, 1986, pp. 390e425; Edwards, 1996, pp. 125e133). The promise of rational control and centralized planning offered by PPBS were highly attractive to other government agencies seeking to organize their operationsdit provided a template for applied research proceeding along a regular timetable amenable to

27 Memo: “The PHS and the Fountain Committee,” 15 March 1963, Carl Baker Papers, Virus and Cancer Programs Backup Memoranda 1963e1964, 1963. NIH Office of History (Bethesda, MD) [hereafter cited as Baker Papers]; “Draft List of ‘authorities on NIH machinery and procedures, for decision making,’” 4 September 1964, Baker Papers, Virus and Cancer Programs Backup Memoranda 1963e1964, 1964.

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Fig. 1. Carl Baker, the chief architect of the Special Virus Leukemia Program and later Director of the National Cancer Institute from 1970to 1972. Photo by Edwin Hubbard on behalf of the National Cancer Institute (NCI Visuals Online, public domain).

bureaucratic monitoring and management. Alarmed by criticism of its planning abilities, the NCI was in fact one of the first civilian agencies to adopt management methods derived from PPBS.28 Criticism provided an opportunity for Kenneth Endicott, the former head of the CCNSC head and new Director of the NCI (as of 1960), and his lieutenant Carl Baker to incorporate these management theories into planning for the development of a leukemia vaccine. Baker was one of the few members of the NCI with the experience to respond to the administrative challenges facing the NIH in kind. Trained as a doctor in Louisville, Baker served in the Navy during the Second World War and remained commissioned in the Public Health Service. After the War he obtained a master’s degree in biochemistry from UC Berkeley and moved to the NIH. Starting as a biochemist, Baker moved into grant administration. After his promotion to assistant director of the NCI in 1958 he played a critical role in overseeing and planning the work of the CCNSC (Baker, 1995, p. 2; Schudel, 2009) (Fig. 1). As he moved further up in the administration of the NIH, Baker’s interest in the management of research expanded. In 1957 he joined a discussion group at the NIH whose members sought to apply contemporary social scientific insights to the management of laboratory research. In the first meeting, Baker commented that “science in an organization.is a central problem for the NIH: How to encompass an essentially individual and autonomous problem within a purposive arrangement of forms and goals.”29 Baker continued to educate himself about management theory, including attendance at a 1961 Brookings Institute seminar on the

28 The National Aeronautics and Space Administration was another early adopter. Historians of RAND have assumed that 1963e1964 marked the “civilianization” of PPBS methods through their widespread use in programs initiated by Lyndon Johnson’s War on Poverty legislation (Jardini, 1996, pp. 334e343; Light, 2003, pp. 95e164). 29 Minutes, 23 January 1957, p. 5, Baker Papers, NIH 1950e1964, Group for Administration Discussion Meetings.

management of research featuring speakers largely from the Department of Defense and NASA.30 He also commissioned translations of articles on planning the construction of large infrastructure projects from the Revue Française de Recherche Opérationnelle.31 Leukemia viruses’ experimental promise and close associations with the millennial urgency of childhood disease cures were suggestive targets for a program of directed research. Although the NCI’s leukemia virus studies had commenced with a flourish in 1958, by 1961 Endicott was frustrated with the piecemeal structure of the various advisory boards and laboratories involved in leukemia virus research, writing that their fragmentation was of “deep concern for me, for I feel that we are on the verge of a major breakthrough in the cancer area, and I believe the Institute has within its own resources the capacity to make the break through with practical programs of cancer prevention and control.”32 As Director, Endicott placed Baker in charge of consolidating the various cancer virus boards and committees as part of his effort to strengthen his control over the activities of the NCI (Baker, n.d., p. 29 & 40). Baker argued to Endicott that the NCI needed “a mechanism to ensure not only support for, but forceful and rapid execution of research programs focused on specific problems of high priority and importance, urgently in need of solution.”33 Baker recruited Louis Carrese, an industrial psychologist and contract systems analyst for the Department of Defense, into the programs office of the NCI.34 Carrese’s experience with systems analysis buttressed Baker’s inception of a planning mechanism capable of rationally delivering rapid progress in cancer research, one readily supplied by Carrese and Baker’s shared experiences with RAND and systems analysis. In 1963, Endicott and Baker proposed a thirty million dollar program of leukemia virus research: the SVLP. They argued that the explosion of animal leukemia viruses and advances in tissue culture and electron microscopy made the time ripe for pushing forward to develop a vaccine.35 However, funds for the SVLP did not make it into the final NIH budget. Here the public culture of expectation surrounding leukemia viruses enabled Endicott to organize a special appropriation to get the SVLP started.36 Polio and defense research served as potent examples of the promise of research acceleration. Presenting leukemia virus research as primarily a logistical challenge of preparing standard reagents and organisms for virus research lent virus research to the budgetary and administrative strengths of systems planning. Endicott had previously testified that he viewed the NFIP’s greatest innovation as logistical and managerial: “with the availability of adequate funds and the attraction to the problem of large numbers of qualified investigators, the solutions to the problems could begin to come.” According to Endicott, the NFIP had possessed the resources to fund the extensive use of primates for

30 Brookings Institute Brochure, March 1961, Baker Papers, Virus and Cancer Programs Backup Memoranda 1950e1962, 1961. 31 “Graphs and Scheduling” translated from Revue Française de Recherche Opérationnelle v.6 #25 (1962), Baker Papers, Virus and Cancer Programs Backup Memoranda 1963e1964, 1963. 32 NCI Director to Chief of NCI Virology Research Resources Branch, 6 November 1961, Baker Papers, Virus and Cancer Programs Backup Memoranda 1950e1962, 1961. 33 Emphasis in original draft of memo for Kenneth Endicott by Carl Baker, 9 September 1962, as quoted in Baker (n.d.), pp. 51e52. 34 Louis Mario Carrese “Application For Federal Employment,” Baker Papers, Virus and Cancer Programs Backup Memoranda 1950e1962, 1962. 35 Minutes, NACC subcommittee on Carcinogenesis, 23 July 1964, p. 2, Randolph Lee Clark Papers, Series III, Carton 8, Folder 6. Texas Medical Center McGovern Library (Houston, TX) [hereafter cited as Lee Clark Papers]. 36 Director NCI to National Advisory Cancer Council, 10 September 1964, p. 1, Lee Clark Papers, Series III, Carton 8, Folder 6.


virus typing, and followed this typing project with the development of a tissue culture system for the virus that allowed rapid vaccine production. While no human cancer virus had yet been identified, Endicott argued that similar ambiguities had plagued polio research.37 Following their experience with the CCNSC and the example of PPBS, Baker and Endicott planned to administer the SVLP program through the extensive use of contracts, which allowed rapid expansion as well as centralized control and direction. Endicott explained that at the SVLP “we are trying to develop.a new sort of industry to do the types of technical jobs that need to be done here.” The Department of Defense, Endicott explained, “reached this scale a long while ago.a whole series of consulting laboratories.developed around the country.”38 He was more expansive regarding his ambitions in an interview: “We’ll build some industries. What the Hell! We’ll build them because we’ve got to have them.”39 Testifying in support of the SVLP, Endicott argued that the NCI was now poised to deploy a system of organization to meet the moral challenge of rapidly developing a leukemia vaccine once a leukemia virus was discovered: We believe that the developments in the research areas mentioned are so important and so opportune that we must do everything possible to push forward now.we have gradually acquired experience in working with industrial concerns and with directors of other cancer institutes.we cannot await full understanding of the nature of cancer.we have learned to work with mechanisms for a planned approach.we await with impatience developments in the human virus area which will demonstrate that a virus is a causative factor in at least one type of human cancer. Our organization is being made ready for such a development because we know that when this happens we must exploit this lead with all possible speed.40 In placing emphasis on the need for resources and organization to accelerate vaccine development Endicott neatly foreclosed debate regarding the viral etiology of human leukemia itselfdthe urgency of acting quickly to exploit a breakthrough reframed the question as not if leukemia had a viral cause but how to speed vaccine development. Headlines from the press, such as “Leukemia Cure Near?,” “Hope Raised for Cure of Leukemia,” “Virus Link Found: Huge Leukemia Project Pushed” indicate the success of Endicott’s narrative framing of the Program (“Leukemia Cure Near?,” 1964; Toth, 1964a, 1964b). An interview with Frank Rausher, a future head of the NCI and staff coordinator of the SVLP, appeared in the Baltimore Sun under the headline “Leukemia’s Cure Seen: Scientist Predicts Vaccine Within 5e7 Years.” (Fenton, 1965).

37 Departments of Labor and Health, Education, and Welfare Appropriations for 1964: Hearings on Part 3: National Institutes of Health, Day 3, Before Subcomm. On Departments of Labor and Health, Education, and Welfare and Related Agencies Appropriations, 88th Cong. 352e354 (1963) (statement of Kenneth Endicott, Director of the National Cancer Institute). 38 Departments of Labor and Health, Education and Welfare Appropriations for 1963: Hearings on Part 3: National Institutes of Health, Day 2, Before Subcomm. On Departments of Labor and Health, Education, and Welfare and Related Agencies Appropriations, 87th Cong. 1062 (1962) (statement of Kenneth Endicott, Director of National Cancer Institute). 39 Kenneth Endicott Interview Transcript, 30 October 1964, p. 50, Health Sciences Oral History Collection. Columbia University Rare Books and Manuscript Library (New York, NY). 40 Departments of Labor and Health, Education, and Welfare Appropriations for 1965: Hearings on Part 3: National Institutes of Health, Day 1, Before Subcomm. On Departments of Labor and Health, Education, and Welfare and Related Agencies Appropriations, 88th Cong. 192e193 (1964) (statement of Kenneth Endicott, Director of the National Cancer Institute).

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In an article for Management Science entitled “The Convergence Technique: A Method for the Planning and Programming of Research Efforts,” Carrese and Baker explained that biomedical research could be approached as a set of “integrated, closely coordinated research programs directed toward the expeditious solution of specific disease problems.” The overall plan for the development of a vaccine regarded scientific experiments or projects as “tactical elements” in a series of concurrent lines, or “flows,” of experiments, resources, and information arranged within a matrix of possible outcomes: the linear array. At “monitoring” and “decision” points administrators assessed research flows to decide if they warranted further effort: this was a model of not only rapid but also rational research that “optimized” performance within the linear array (Baker, Carrese, & Rauscher, 1966; Carrese & Baker, 1967; Rauscher, Carrese, & Baker, 1966). The combination of crisis rhetoric and systems planning produced human leukemia viruses as distinctly administrative objects. This vision of planning as Baker and Carrese described neatly matches similar efforts by military planners to create “closed worlds” in the 1960s: bounded spaces described in the language of engineering with the aim of allowing no event to fall outside of the defined space. Like the military, the vision of the SVLP was one in which every action could be be directed back towards the central effort of developing a vaccine (Edwards, 1996, pp. 7e15). Treating human leukemia viruses as administrative objects provided the lynchpin of the convergence technique’s effort to enclose all possible outcomes of leukemia virus research. The creation of this new kind of object was inseparable from the moral urgency of leukemia research. Explaining the rationale for this new form of management to a symposium of biomedical researchers, Baker explained that during the two days of the symposium, 160 people had died “of leukemia and lymphomas.those of you who must deal with leukemia patients and their problems.must feel a strong sense of urgency associated with solving problems associated with leukemia.” Baker elaborated that organization was as critical a “methodological” concern for biomedical researchers as any of the experimental topics discussed at the symposium (Baker, 1965, pp. 215e216). The assumption that “at least one virus is an indispensable element.of at least one kind of human leukemia,” animated the SVLP’s operations. For the SVLP, the urgency of uncovering a human leukemia virus provided the central axis for enfolding leukemia virus research in the convergence technique. Management methods were geared towards time as much as efficiency in biomedical research. This kind of thinking was encapsulated in the planning documents produced by its staff. The 1967 annual report included a chart comparing the effort to develop a human leukemia vaccine to other efforts in virologydespecially polio, measles, and a range of other animal tumor viruses. The most interesting rhetorical work was performed along the sides of the chart. The stages along which progress was plotteddAcquisition of Materials, Detection, Isolation, Replication, Identification, Characterization, Industrial Replication, and Controldwere presented as true of all viruses, even those which had only just been isolated, much like the stages of economic development posited by modernization theory. Moreover, the progress vector for each virus was labeled with the number of years the viruses had been studied. Most beguiling, however, were the “dotted” lines included with the human leukemia viruses: evidence of discoveries that were anticipated and amenable to acceleration (Fig. 2). In 1967 the SVLP’s activities encompassed four major areas: Human Leukemia Etiology and Prevention, Special Animal Leukemia Etiology Studies, Biohazards Control and Containment, and Human Leukemia Therapy. The majority of the program’s activities focused on the pure culture of different virus strains, the cultivation of human cancer cells in vitro, the creation of immunological

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Fig. 2. Planning Chart, Special Virus Leukemia Program Progress Report #4 (1967), p. 7. Courtesy of the Office of History, National Institutes of Health.

diagnostic tools, the maintenance of germ-free animal colonies, and the collection of potential oncogenic viruses “from nature.” These projects were pursued through a mix of grants and contracts awarded to universities, government laboratories, and private companies. Particular projects included those for germ-free animal facilities (Germfree Life and Oncogenesis), development of tumor tests systems (Pfizer), filter evaluation (US Army), biohazards containment (Dow Chemical), mammalian cell culture facilities (UC Berkeley), and the collection of plasma from acute leukemia cases (Hospital for Sick Children). The Program was also moving to aggressively investigate the link between a “herpes-like virus” and Burkitt’s lymphoma, a cancer found chiefly in Africa.41 In 1966, the NCI broke ground on a whole building equipped with special equipment to work with human cancer viruses once they were discovered (“Ground Broken for New NCI Facility,” 1966, pp. 1e2). To stress a critical distinction: while the chemotherapy screening program at the NCI sought to scale up methods drawn from industry, the ambitious management methods used by the SVLP were more directly inspired by military systems planning and project development.42 In this effort, the SVLP promised to confront a clear crisis in both administration and public health rather than simply to conduct research more efficiently. Endicott argued that the planning efforts of the NCI, and especially the SVLP, provided a “prototype” effort for the rest of the NIH as the institution embraced it role in the management of biomedical research.43 In

41

Special Leukemia Virus Program Progress Report #4 (FY 1967), p. 17, 22, 24 & 39. A recent book on chemotherapy has stressed the same distinction (Keating & Cambrosio, 2012, pp. 168e175). 43 “Minutes on Planning Conference,” 8 July 1965, p. 2, Baker Papers, Virus and Cancer Programs Backup Memoranda 1965e1966, 1965. 42

1966, for example, the SVLP provided a template for a far-ranging reorganization of the CCNSC (Zubrod et al., 1966). The result of a confrontation in 1965 between Endicott and the leadership of ACS over the use of contracts for the pursuit of accelerated research demonstrates the traction that this new model of management had gained. Unlike the model proposed by the SVLP, grants were awarded under the supervision of the National Advisory Cancer Council, a body controlled by an alliance of scientists and the ACS. The assessment of grant applications was conducted by decentralized peer review panels. The use of contracts to administer the CCNSC and SVLP centralized these decisions at the expense of the Council’s power. The ACS protested, seeking legislation that would require the Council’s approval for contracts as well as grants. NCI administrators contested this requirement, and the dispute prompted the formation of a committee to report on the NIH’s contracting authority. The committee, chaired by the President of the Institute for Defense Analysis, sided with the leadership of the NCI, bemoaning that the arrangement of priorities at the NIH was such that “many of the staff members who have the technical competence for program management are motivated, by the attitudes of their professional community, to apply this competence in individual research rather than to ‘waste’ it in management affairs.” Singling out the NCI as a notable success, the review committee urged that the rest of the NIH emulate the example it set by seeking administrative personnel with “top flight managerial talent” for the direction of research programs (Report of the Secretary’s Advisory Committee,” 1966, p. 16 & 30). 5. Conclusion The rhetoric of hope and crisis which emerged from childhood disease philanthropy, when coupled with the new management


methods advanced by the Cold War, produced a powerful new way of thinking about biomedical research. In framing the future of scientific innovations as a space for management, the SVLP’s use of administrative objects moved beyond industrial organization precedents in structuring its mission and effort around the existence of as of yet undiscovered viruses. Its innovation was in fashioning management structures equal to the temporality of the crisis invoked by advocates of childhood cancer research. Like other Cold War planning efforts, the future could be managed and shaped through the appropriate blend of laboratory science and managerial technology (McCray, 2013, pp.14e16). For a time, it appeared as if this mode of thinking would be applied to biomedical research writ large, especially during the expansion of cancer research efforts during the War on Cancer of the 1970s e the most ambitious intervention of the federal government in biological research ever attempted (Chubin & Studer, 1980; Rettig, 1977, pp. 298e304). The managerial systems developed by the SVLP did not ultimately succeed in developing a leukemia vaccine. However, these cultural expressions of hope or paper promises of managerial efficiency should not be understood merely as discursive events epiphenomenal to laboratory findings. Since possible human cancer viruses often existed at the limit point of the epistemological criteria used by virus researchers, the performance of scientific and managerial acumen became an integral part of setting the terms of intervention by the NCI in biomedical research (Gordin, Tilley, & Parakash, 2010; Martin, 2013). Moreover, once these kinds of political imagination start to direct the construction of buildings, the funding of scientists, or the collection of materials, they create a social and material infrastructure that embodies a particular political moment long after the moment fades. Mundane acts of infrastructure provide a critical base for knowledge production in the modern biomedical sciences, one often neglected by a focus on the activities of individual investigators (Creager & Landecker, 2009; Edwards, 2003, p. 189; Pickstone, 2007). When the NCI’s cancer virus efforts became unstable under the weight of their own promises and frustrations in the late 1970s it did not collapse outright. Rather, the resources it had mustered found new directions and new uses (Belich, 2009, pp. 548e560; Kaiser, 2012). The creation of connections among academic, state, and industrial laboratories by the SVLP’s successor programs, for example, have been identified an important factor in the development of biotechnology, the discovery of oncogenes, and the identification of HIV (DeVita, 2002; Fujimura, 1996, p. 162; Gallo, 1991, pp.138e144; Gaudillière, 1993). The themes at play in the formation of the SVLP remain endemic in the contemporary anticipatory politics of biomedical research (Adams, Murphy, & Clarke, 2009). The SVLP suggests that this rhythm of hope and hype associated with biotechnology and patient activism today was also present during an earlier era of state patronage and mass consumer philanthropy (Brown, 2003; Mirowski & Horn, 2005; Rajan, 2006; Rose, 2001; Rose & Novas, 2005). For the SVLP, it was not only an activist but an administrative vision that animated such a vast research endeavor, one which in turn had profound consequences not only for cancer virus studies but also the development of biomedicine. As historians of the biomedical sciences we must consider how our narratives can step back from the bench-top to ask how politics and culture themselves shape the frameworks and flows that enable biomedical research and the possibilities and constraints that these events impose on our knowledge of health and disease. Acknowledgments Research for this article was supported by fellowships from Yale University and the National Science Foundation, as well as grants

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from the Yale Club of Philadelphia, the American Philosophical Society, and the Rockefeller Archives Center. David Cantor, Sejal Patel, and Barbara Harkins were wonderful hosts at the National Institutes of Health Office of History. David Rose at the March of Dimes Archives helped me locate papers relevant to the relationship between the National Foundation for Infantile Paralysis and the American Cancer Society, and the March of Dimes has generously given permission to quote these papers in this article. Thanks to audiences at the Harvard History of Medicine Working Group, the Yale Holmes Workshop, the Stevens Institute of Technology, and the 2012 Three Societies Meeting for their comments on early versions of this paper. Particular thanks are in order to Neerja Sankaran who organized the original panel which gave rise to this special issue, and to Angela Creager, Daniel Fox, Ton van Helvoort, and two anonymous reviewers for their thoughts and comments on drafts of this article. 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Future directions for biomedical engineering research: Recommendations of an evaluation workshop for the NIGMS physiology and biomedical engineering program.

The present and future role of microfluidics in biomedical research.

The sympathy of policy-makers towards animal-rights activists, and the future of biomedical research.

Foreword to the Virus Research special issue on "hantaviruses".

Microarrays-Current and Future Applications in Biomedical Research.

Rebuttal to the commentary regarding: The sympathy of policy-makers towards animal rights activists, and the future of biomedical research.

Future directions: managing the cost-quality paradigm.

The role of biomedical scientists in research.

Enhancing diversity in the public health research workforce: the research and mentorship program for future HIV vaccine scientists.

Aging research: the past and the future.

Biomedical materials research in the USSR.

The crisis in biomedical research funding.

The Future of Research Communication.

Unbridle biomedical research from the laboratory cage.

Biomedical research gone to the dogs.

[WHO Special Program of Research, Development and Research Training in Human Reproduction (HRP). A summary].

Enhancing the Careers of Under-Represented Junior Faculty in Biomedical Research: The Summer Institute Program to Increase Diversity (SIPID).

The future of stress and health research.

The past and future of nursing research.

Research and the future of health education.

The misuse and abuse of statistics in biomedical research.

The evolution of biomedical science: past, present, future perspectives.

Reproducible Research Practices and Transparency across the Biomedical Literature.

Research and the National Cancer Program.