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Academic Medicine:
doi: 10.1097/ACM.0b013e31820cdc7f
History of Academic Medicine

Academic–Industrial Relations Before the Blockbuster Drugs: Lessons From the Harvard Committee on Pharmacotherapy, 1939–1943

Podolsky, Scott H. MD; Greene, Jeremy A. MD, PhD

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Author Information

Dr. Podolsky is assistant professor of global health and social medicine, Harvard Medical School, and director, Center for the History of Medicine, Francis A. Countway Medical Library, Boston, Massachusetts.

Dr. Greene is assistant professor of the history of science, Harvard University, and instructor in medicine, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital Department of Medicine, Harvard Medical School, Boston, Massachusetts.

Correspondence should be addressed to Dr. Podolsky, Center for the History of Medicine, Francis A. Countway Medical Library, 10 Shattuck Street, Boston, MA 02115; e-mail: scott_podolsky@hms.harvard.edu.

First published online February 21, 2011

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Abstract

Increasing discussion has developed in recent years over the nature of the relationship between academic medicine and the pharmaceutical industry. This article narrates the history of a little-known attempt at Harvard Medical School between 1939 and 1943 to establish an interdisciplinary, academic–industrial Committee on Pharmacotherapy to enhance and rationalize the relationship between the field of academic research in pharmacotherapeutics and the pharmaceutical industry. Using original archival materials, the authors depict the functioning of the committee, which was headed by Soma Weiss and included such members as Fuller Albright, Henry Beecher, and Walter Cannon. The committee would be collectively funded by seven pharmaceutical companies and was to be predicated on collaboration, both across the entire university and between academia and industry. It was expected to transform the bench-to-bedside study and testing of therapeutic compounds, to redefine the teaching of pharmacotherapy, and to create a unified forum through which to discuss the overall academic–industrial relationship and more specific issues such as patents. Unfortunately, the program proved to be short-lived, the victim of such contingent factors as the untimely death of Soma Weiss and America's entry into World War II, as well as such more fundamental factors as the inadequate and temporary nature of the funding stream and unresolved tensions regarding the goals of the committee on the part of both the medical school and its industry supporters. Nevertheless, these early forays into collaborative bench-to-bedside translational research and the rationalization of academic–industrial relations remain instructive today.

Increasing professional, popular, and congressional concern has developed in recent years over the nature of the relationship between academic medicine and the pharmaceutical industry.1 On the one hand, many argue that a close relationship with industry is vital for academic research to translate into useful clinical interventions—particularly in areas of biomedical investigation that require the intersection and translation of multiple academic disciplines.2 On the other hand, critics claim that dependency on industry funding has introduced systematic bias into the production and circulation of medical knowledge,3 the priorities of medical research and public spending,4 and the training and continuing education of physicians.5

Both advocates and critics of close academic–industrial relations point to a prior, simpler era in which ties between academia and industry were less problematic. Yet, scratching the surface reveals that no such halcyon days existed, and that similar questions concerning the relationship between academia and industry had emerged long before the marketing of the first blockbuster drug. We narrate here the brief life of an important but little-known attempt at Harvard Medical School (HMS) in the 1930s and 1940s to establish an interdisciplinary, academic–industrial Committee on Pharmacotherapy to enhance and rationalize the relationship between the field of academic research in pharmacotherapeutics and a newly expansive pharmaceutical industry.

The committee's stated purposes were to elevate pharmacotherapeutics on par with surgery as a means to alleviating suffering, and to energize and reform the teaching of pharmacotherapeutics at HMS. The immediate backdrop to the emergence of the committee reflected a confluence of forces external and internal to the medical school and university. From a disciplinary perspective, pharmacology had only recently emerged as a serious subject in medical schools, with its own association and journals; yet many within academic medicine, and at HMS in particular, were concerned that the extended power of pharmacotherapeutics would not be realized without interdisciplinary support—ranging from bench to bedside.6–9

At the same time, the Committee on Pharmacotherapy intended to address the relationship between academic medicine and the expanding, research-based pharmaceutical industry. The committee's founders and members acknowledged that although the university needed some productive interface with the pharmaceutical industry, such involvement must not compromise academic integrity. Examination of the brief life of the committee (1939–1943) helps us to explore how the 21st-century challenges of stimulating translational research, educating physicians about novel therapeutics, and regulating relations between academic medicine and medical industry are rooted in important 20th-century antecedents.

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Bridging Boundaries

The role of pharmaceuticals—and pharmacology—in the rise of modern medicine was by no means self-evident to physicians in the 1930s. As Henry Christian,10 the Hersey Professor of the Theory and Practice of Physic at HMS and the first chief of medicine at the Peter Bent Brigham Hospital, related to the celebrated physiologist Walter Cannon in early 1936:

There is a well nigh universal feeling that in the United States Pharmacology is failing to be a significantly important department in Medical Schools. Very generally medical students speak of Pharmacology and its courses in terms of disparagement.… It would seem that, as at present organized and lead [sic], departments of Pharmacology are lagging behind the other departments of the preclinical sciences in leadership and influence in the Medical Schools of the United States.

Some at HMS would suggest abolishing the Department of Pharmacology.11 But Christian believed that pharmacology, by virtue of its interdisciplinary nature—among such fields as physiology, biochemistry, pathology, immunology, and bacteriology, and between basic science and clinical care—should be revitalized, rather than abandoned.10 He was supported in this effort by Cannon,12 who noted that the recent production of such innovative miracle drugs as insulin for diabetes and liver extract for pernicious anemia might signal the end of a “period of therapeutic nihilism” and the beginning of a new translational science of therapeutic discovery based on collaboration between bench pharmacologists and clinical researchers, between the medical school and the university as a whole, and between academia and industry.

To advance this vision, Cannon had initially proposed naming a university professor of therapeutics. But as the medical school reformulated its plans for the Department of Pharmacology (soon to be led by Otto Krayer, who would replace the retiring Reid Hunt), HMS Dean Sidney Burwell instead proposed a cross-university Committee on Pharmacotherapy, separate from the Department of Pharmacology itself, but “in which the departments of Pharmacology, preclinical and clinical sciences, and the Faculty of Arts and Sciences would be represented.”13 A potential leader for the envisioned committee emerged in the form of Henry Christian's proposed successor as Hersey Professor and chief of medicine at Peter Bent Brigham Hospital—the young clinician–researcher Soma Weiss, whose success at conveying therapeutic research principles from bench to bedside had earned him a reputation within both medical academia and the pharmaceutical industry. To fund the committee, Harvard University President James Conant and Dean Burwell spoke with friends in the pharmaceutical industry and ascertained that it would be plausible to fund five years of the project on a temporary basis while funds for an endowment could be pursued.14,15 The committee was appointed in April 1939, and its initial roster included Soma Weiss (chairman), Fuller Albright, Henry Beecher, Walter Cannon, William Castle, Louis Fieser, A. Baird Hastings, Frederick Lee Hisaw, Otto Krayer, Reginald Linstead, President Conant (ex officio), and Dean Burwell (ex officio)16 (Table 1). Seven pharmaceutical companies (Abbott Laboratories, Lederle Laboratories, Eli Lilly and Company, Mallinckrodt Chemical Works, Merck & Company, Inc., Parke, Davis & Company, and Sharpe and Dohme, Inc.) combined to fund the initiative at an annual rate of $27,000.17

Table 1
Table 1
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It is worth noting that Conant and Burwell saw opportunity, not conflict, in their appeal to the pharmaceutical industry to fund a program intended to bridge the boundaries among academic disciplines and between academia and industry. Although the American Society for Pharmacology and Experimental Therapeutics (ASPET) had infamously banned from membership any pharmacologist who received funding from industry, that practice was overturned in 1937 by a decision that encouraged ASPET members to act as paid consultants by industry.18 By the late 1930s, the prospect of individuals who could bring material from academia into industrial development—and, conversely, bring samples of promising new industrially developed compounds back into academic medicine for animal and clinical experimentation—had become increasingly desirable to both parties.19 If industry was to profit from this relationship, whether through increased access to experimental compounds or through the increased influx of highly trained manpower, it seemed reasonable to ask it to foot the bill.

Instead, individuals from both academia and industry were far more concerned with the appearance of undue favoritism toward any one company or university than with the engagement between academia and industry in general. As George Clowes20 of the Lilly Research Lab wrote to Dean Burwell in 1939:

It is most important that this whole undertaking should appear from the beginning as an experimental enterprise carried out in the Harvard Medical School by means of the joint support of a group of corporations in the general interest of medical education and research in the United States. … If the matter is handled in this way the various corporations contributing to the fund are relieved of any embarrassment on the score of favoring Harvard University and Medical School as against other universities and medical schools [emphasis in the original].

Nonetheless, the prospect of who would pay for what remained an active question related to who would ultimately set the agenda for the program. Early planning meetings between George Merck, William Castle, and Soma Weiss featured almost comical contests over who would pay for lunch.21,22 Dean Burwell was cognizant of the fine line that Harvard was attempting to walk in accepting funding from industry for an academic–industrial collaboration. For example, during a planning phone call, George Merck asked Burwell, “What do we get out of this?” and Burwell23 noted:

In other words, says he, will the Harvard group be interested in the problems of industry? I told him that it seemed to me that the Harvard group should not be committed to anything; that naturally we would expect [the committee] to be cooperative and interested in general problems of industrial companies, but I was sure that they should not be subjected to the danger of getting involved in doing work which they didn't want to do, or of being accused of selling out to the pharmaceutical houses.… I think it is rather dangerous to get into a discussion of any problems; I think they ought to take it on trust for five years.

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Rationalizing Relations

The Boston Herald trumpeted the first meeting of the Committee on Pharmacotherapy in December 1939 with the headline, “Pharmacotherapy committee to co-ordinate Harvard Science,” and the effort received initial fanfare as an example of the new interdisciplinarity and translational emphasis of Conant's vision of the university.24 An unsigned editorial25 written by Weiss in the New England Journal of Medicine noted the new pharmacotherapeutics of the mid-20th century to be “a highly specialized field where physicians must use therapeutic agents which are often more effective and more dangerous than the scalpel,” and presciently concluded that “pharmacotherapy may be considered by medical historians of the future as one of the most significant developments in the history of medicine in the twentieth century.”

The committee officially convened 16 more times over the next four years, with important consequent research, educational, and policy accomplishments.26,27 From a research standpoint, Weiss began with a comprehensive “survey of pharmacotherapy work in progress within the University,” revealing nearly 210 such investigations spread across the campus. Demonstrating 51 hormone investigations, as well as 20 vitamin, 19 hematology, 16 cardiology, 16 sulfa drug, 10 neuromuscular, and 9 anesthetic investigations, the survey depicted the diversity of such interests across the university.28 At the same time, it served as a hoped-for precursor to efforts to coordinate investigations in the field of pharmacotherapy and therapeutics, as well as to give advice to those interested in problems relating to treatment of disease, both members of the university and outsiders.29 The committee hired Edwin Bennett Astwood to be an interdisciplinary junior professor of pharmacotherapy in 1940. Astwood's groundbreaking work under the auspices of the committee, demonstrating the utility of the treatment of hyperthyroidism with propylthiouracil, would represent the committee's most notable public achievement.30,31

From the standpoint of education, the committee was empowered to grant a cross-university, three-year PhD in pharmacotherapy. Formally announced on April 2, 1941,32 the program would be promulgated as an achievement by Weiss to a worldwide network of medical schools, foundations, and pharmaceutical executives, who declared their intentions not only to watch such developments closely but to offer opportunities for collaboration in the advancement of such a program.33

But perhaps the most instructive and thorny efforts of the Committee on Pharmacotherapy regarded its attempts to articulate a formal relationship between academic medicine and the pharmaceutical industry. As head of the committee, Soma Weiss served as a conduit for communication with pharmaceutical companies and used the committee's relationship with the pharmaceutical industry to leverage a broader discussion of the applied future of the interdisciplinary field. Representative of such efforts was a 1941 conference at which Committee on Pharmacotherapy-funded faculty presented their work for visiting representatives from funding firms; it seems to have been part dog-and-pony show, part forum for discussions regarding the ambitions of the field.34,35

The committee would have less success in confronting the question of patents. After making public the patent for liver extract for the treatment of pernicious anemia in 1928 (the result of research conducted with support from Eli Lilly & Co.),36 the medical school had established a policy that

[n]o patents primarily concerned with therapeutics or public health may be taken out by any member of the University, except with the consent of the President and Fellows; nor will such patents be taken out by the University itself except for dedication to the public.37

In contrast, the University of Wisconsin had during the previous decade famously patented vitamin D—permitting its profits to be applied to research funded by the Wisconsin Alumni Research Fund—in an attempt both to protect the remedy from unscrupulous manufacturers and to fund further scientific research.38 From its earliest meetings in December 1939, the Committee on Pharmacotherapy highlighted the problem of patenting as a paramount concern for academic–industrial relations, noting that

the possibility was pointed out that if the University were to enter actively into the field of patents, criticism might result to the effect that the University had ceased to do disinterested research and this criticism might in turn influence the decisions of private donors.28

A subcommittee consisting of William Castle, Louis Fieser, and A. Baird Hastings was convened. On the one hand, as a broad framework, it was clear to them that “the University should not undertake to administer patents or derive profit directly from patents … nor should individual members of the Faculty profit either personally or by direct support of research from the proceeds of patents,” and that “no agreement should be entered into between an individual and a commercial company which would give the company control of the results of the research.”39 On the other hand, in the setting of remedies deemed “to have commercial value and to be of concern for the Public Health,” such possibilities as issuing licenses to “qualified manufacturing companies” or assigning the patent to a “foundation organized to transact business for the advancement of science to which its profits are applied” were entertained and weighed.39 No resolution was achieved, however, and divisions on this issue within the Committee on Pharmacotherapy would soon be overshadowed by other threats to the committee's mission and mandate.

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In fact, the committee's goals swiftly exceeded the limits of its infrastructure, and local contingencies rendered these early schisms between expectation and reality all the more visible. From the start, the goals of the committee were quite ambitious, especially in the context of the limited budget allotted it by the very industry whose financial relations with academia the committee was intended to examine critically. In this context, while it was reasoned that it would take time to conduct the novel bench-to-bedside research initially envisioned, Dean Burwell had voiced frustrations regarding the committee's traditional forms of research by 1941.40 Such concerns were paralleled by increased disenchantment by the sponsoring firms, who had perhaps expected that the committee would focus more on producing a streamlined academic process for developing or testing innovative patented compounds. As the minutes of a meeting in 1942 recorded,

some of the Sponsors were disappointed that the Committee had not developed into [sic] a testing ground for their products; others thought that the chief purpose of the Committee was to be the training of students [for jobs in industry].41

With such tensions in place, the Committee on Pharmacotherapy was unable to withstand two nearly simultaneous blows. The first was the sudden death of Soma Weiss from a subarachnoid hemorrhage in January 1942. Weiss had clearly represented the force around which the project and its supporters gravitated. The second was the advent of U.S. involvement in World War II, which focused university resources and faculty efforts elsewhere and precipitated a crisis of identity over “the purpose of the Committee and … what should constitute legitimate Committee activities in war work.”42,43 Lofty concerns regarding the elevation of pharmacotherapy and the relation of academia to industry were subordinated to pragmatic contributions to the war effort—for which the Office of Sponsored Research and Development (OSRD) now offered a new, nationalistic model of collaborative research by academia, industry, and government against a common enemy. When, by late 1942, research proposals submitted by committee members to the OSRD were rejected, the committee's end was already in sight.44

The Committee on Pharmacotherapy would meet only one time more, in May 1943; with no endowment forthcoming it was formally dissolved in November 1943 by Conant,45 who announced that “after four years of experience, it appears that the broad plan as originally outlined has failed to succeed.” Nonetheless, Conant45 hoped,

it may have given some indication of the potential value of voluntary collaboration both within the University and with the pharmaceutical industry along the lines of the original plan.… Possibly after conditions have returned to normal, we may revive the idea. For the time being, we shall have to proceed along other lines.

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Revival

Although the scope of the Committee on Pharmacotherapy seems almost quaint by today's standards, its ambitions remain relevant today. As we now know, the committee's dissolution seems to have impeded comprehensive and strategic planning regarding therapeutics on the very eve of the wonder drug and molecular revolutions.46 The collapse of this conversation at Harvard mirrored in microcosm the broader failure of academic medicine to take seriously the logistical and ethical challenges posed by academic–industrial relations amidst the new enthusiasm for novel therapeutic products. The years following World War II saw an expansion of novel innovative therapeutic categories such as antipsychotics, antibiotics, antihypertensives, and many other branches of contemporary pharmacotherapy.47 But, at the same time, this period witnessed a tremendous expansion of wasteful “me-too drugs” that simply replicate existing therapies, frivolous and often harmful drug combinations, the gross expansion of brand-name pharmacotherapy, and the breakdown of the medical profession's ability to educate physicians regarding novel therapeutics without dependence on pharmaceutical advertising and marketing.48 One is left to wonder whether a stronger means of academic–industrial communication during this period might have helped play a stronger role in shaping rational therapeutics and physician education.

The past decade has witnessed a renewed effort in breaking down disciplinary boundaries in therapeutic research; the National Institutes of Health has awarded $500 million per year from 2006 to the present in a novel program of Clinical and Translational Science Awards (CTSAs) to encourage universities to think more concretely—and collaboratively—along trajectories from bench to bedside.49 At the same time, academic medicine has found itself at the center of a renewed discussion about its relationship with the pharmaceutical and device industries regarding both clinical research and medical education. Reeling from powerful external critiques by the lay press and prominent congressional hearings, academic medicine has recently begun to study in earnest the intricacies of clinical and academic conflicts of interest.50 Emblematically, HMS itself was 1 of 14 recipients of the first round of CTSAs in 2008, while at the same time recognizing the need to readdress its conflict-of-interest policy.51,52

Both of these recent trends in contemporary academic medicine pick up the vital conversation regarding the relationship between academic medicine and the pharmaceutical industry that the Committee on Pharmacotherapy began so earnestly in the late 1930s and early 1940s, on the eve of the first blockbuster drugs that would open up the powerful pipelines of the American pharmaceutical industry. Medical schools continue to struggle today to rationalize their involvements with the innovative pharmaceutical industry, caught between the demand for translational research that reaches from bench to bedside through industry and the problematic revelations of conflicts of interest of recent years. This narrative of a brief attempt by a small group of academic elites to take on the same issues at the dawn of the era of modern pharmacotherapeutics is instructive to help understand how we can map the roots of our present dilemma backward—and hope to chart a transparent path forward.

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Acknowledgments:

The authors would like to thank Jeffrey Flier for his support of this project since its inception. The authors also benefited greatly from Jerry Avorn's insightful comments on an earlier draft, from the comments of members of the American Osler Society, to whom a talk based on this article was presented at the Mayo Clinic in April of 2010, and from the archival input of Jack Eckert.

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Funding/Support:

None.

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Disclosures:

None.

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Ethical approval:

Not applicable.

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© 2011 Association of American Medical Colleges

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