From “Publish or Perish” to “Patent and Prosper”

After spending more than 55 years doing research and 45 years teaching a graduate course in physical biochemistry with the last 5 years spent attempting to teach ethics in a required course on Responsible Conduct of Research, I had wondered about what to write in response to Herb Tabor's kind invitation and urging to submit an article on “Reflections.” Tempting as it is to write about my love affairs with the ultracentrifuge, tobacco mosaic virus, nucleic acids, ribosomes, and a host of proteins including aspartate transcarbamoylase in particular (1Schachman H.K. Still looking for the ivory tower.Annu. Rev. Biochem. 2000; 69: 1-29Crossref PubMed Scopus (4) Google Scholar), I decided instead to look back at the way science was done at the start of my career and how our research environment and academia, in particular, have changed in the past half-century. In doing so, I offer apologies at the outset. This account cannot be construed as “history.” Instead it offers personal recollections, biases, impressions, and evaluations, frequently without documentation. Indeed many of the papers and historical records that I would cite are not readily available. Regrettably from my point of view, Stanley Hall, my home on the Berkeley Campus for 50 years, was demolished several years ago to be replaced by a much larger laboratory, and this Reflections is being written in a temporary office. The following pages present my views on various topics such as how careers in science have changed, how federal funding of research in universities was initiated, and how politics interfered with the funding process. In addition, the peer review system is discussed along with the plight of dissatisfied applicants. Finally, I present my impression of the impact of federal funding on universities, the controversy over indirect costs, the burden of government regulations, the enduring struggle over fraud in science, and the major changes in the culture of academia and the commercialization of universities stemming from the Bayh-Dole Act. On many of these controversial issues I was personally involved both in advocating and opposing policies under consideration by government agencies. As President of the American Society of Biological Chemists (ASBC), now the American Society for Biochemistry and Molecular Biology (ASBMB), and later as President of the Federation of American Societies for Experimental Biology (FASEB) and Chair of the Public Affairs Committee of ASBMB, I traveled extensively to Bethesda and, in concert with other concerned biomedical researchers, helped to formulate positions that we hoped represented the working scientist's point of view. Moreover, I had the privilege of serving for 6 years as an advisor to the Director of the National Institutes of Health (NIH), Harold Varmus, and as its Ombudsman in the Basic Sciences. This part-time activity involved extensive visits to more than 45 universities and medical schools where I learned a great deal about the conduct of biomedical research and the problems encountered by investigators. To some extent, therefore, this Reflections, although not about my research, is indeed a personal memoir. Although a significant amount of material presented below is critical of government agencies and policies, university administrators, and actions of fellow scientists, I wish to emphasize that the triumphs of biochemistry in the past 60 years are almost impossible to encompass. Although biochemistry formerly was concentrated in medical schools and a few schools of agriculture, now university campuses throughout the country have thriving departments. Moreover biochemistry is “invading” chemistry and physics departments as well as engineering schools. Leadership in research is now in the hands of innumerable creative young people who have fallen in love with biochemistry and are largely responsible for the startling discoveries of the past half-century. The training of these scientists and the support of their research resulted from the magnificent contributions of those great institutions, NIH and the National Science Foundation (NSF). Conducting scientific research today is dramatically different from what I and others of my age experienced, and the pace of discovery is much more rapid. Superb commercial instruments for numerous techniques are now available. In addition, innumerable reagents biochemists formerly prepared in their laboratories can now be purchased, thereby freeing investigators to perform imaginative experiments. New journals, numbering in the thousands, are available for publication of the findings. Who could have imagined that the Journal of Biological Chemistry (JBC), which in 1945 had an Editorial Board of 12 members and published 365 articles comprising about 3600 pages, would 60 years later have 650 biochemists on the Editorial Board leading to the publication of about 5000 articles comprising 43,000 pages? And today's JBC pages are much larger than those in the 1950s. How did this come about? What factors led to such dramatic growth? How did little Biochemistry morph into Molecular Biology and Cell Biology, Big Science, and Big Business? How did academia change from “Publish or Perish” to “Patent and Prosper?” What may we expect for the next 60 years? As a newly minted Instructor in Biochemistry at Berkeley in 1948 just after receiving my Ph.D., I was acutely aware of the unpredictability and hazards of an academic career. My training as an undergraduate in chemical engineering at MIT followed by graduate school in physical chemistry at Princeton provided me with little knowledge of biochemistry, and there I was, by good luck, on the faculty of a biochemistry department. Accordingly, by auditing various courses, I slowly became familiar with metabolic pathways leading me to describe the auspicious position of Instructor as a “Hypothetical Unstable Intermediate.” Today, virtually no one is appointed as an Instructor. On the contrary, most individuals enter academia in science as Assistant Professors or even Associate Professors. Such appointments are made after they have spent several years, and often too many years, as postdoctoral fellows. It is now commonplace for young investigators to have two, or even three, different postdoctoral stints. As a consequence, researchers in the biomedical sciences do not become independent investigators until a significantly older age than was the case 40–60 years ago. Appointments to faculty positions at an older age coupled with the termination of mandatory retirement have resulted in numerous reports bemoaning the aging of the research community. I can recall joking 30 years ago that consideration of promotion of a biochemistry faculty member to tenure no longer involved reading their papers. The inability to comprehend the contents of the burgeoning literature resulted, according to folklore, in the practice of “weighing” the papers and, at a later time, of “counting” them. Finally, a rebellion occurred over the “quickies,” and academic departments began considering content again. However in the past 10 years, it appears that more consideration is focused on where an article was published rather than on what was published. Fortunately, leading academics responsible for this “need” to publish in Cell, Nature, Science, or the Proceedings of the National Academy of Sciences (PNAS) are now realizing that they have become captives of their own creation; papers in those journals are essential for winning prizes and for promotion of younger faculty members to tenure. Although there is still considerable “hype” by Editors of these prestigious journals in order to attract papers, resentment is now growing in the academic community about this emphasis on where to publish. Whether this change in the culture of academia will have an impact on young investigators and their decisions as to where to send their “hot” papers remains to be seen. In that regard, it is relevant to ask whether the almost limitless proliferation of journals will ever end. Professional societies justify publishing new specialized journals based on the growth of science, and private companies have found science reporting a profitable venture. From the perspective of today it is difficult for those whose careers began in the 1940s to recall how research was done before federal funds became commonplace. The birth of the NSF in 1950 was the outcome of the remarkable report (2Bush V. Science—the endless frontier.A Report to the President on a Program for Postwar Scientific Research. U. S. Government Printing Office, Washington, D. C.1945Crossref Google Scholar) by Vannevar Bush to the President of the United States on July 5, 1945. That insightful and visionary report, entitled “Science—The Endless Frontier,” should be required reading today for Members of the United States House of Representatives and the Senate as they are perilously close to reducing the budget of NIH for next year. The report of only 40 pages, plus the more detailed appendices by various subcommittees, has only 6 parts (or chapters). Individual sections are devoted to research aimed at understanding and eliminating disease, the benefits to public welfare from scientific research, the need for training future generations of scientists, the importance of openness in science and the “freedom of inquiry,” and finally the establishment of a government agency to foster and fund scientific research in universities. Basic scientific research and training in this country today stem directly from the Bush report, an outgrowth of his experience as head of the Office of Scientific Research and Development (OSRD) in supervising civilian scientific activities during World War II. The recognition of the invaluable contributions to the war effort made by the scientific community led to extensive deliberation of the potential role of government in the support of science in peacetime. Not only is the NSF the direct beneficiary as spelled out magnificently in the section termed “The Means to the End” but also, to a substantial extent, that “great invention,” NIH, from which most biochemists receive research support, owes its largesse to the spirit of the Bush Report in the part entitled “The War Against Disease.” However it should be noted that 5 years elapsed between the submission of the Bush Report and the establishment of the NSF. During that interval of debate and political bickering over the governance of the proposed agency (3Lomask M. A Minor Miracle: an Informal History of the National Science Foundation. National Science Foundation, Washington, D. C.1975Google Scholar), the medical community, many of whose members were not enthusiastic about biomedical research being centered in the new foundation, devoted efforts to steer more government funds to the Public Health Service and thereby to NIH. That activity led to the astonishing increase in NIH funding for extramural research from less than 1 million dollars in 1946 to about 4 million in 1947 (4Allen E.M. Early years of research grants.NIH Alumni Association Newsletter. 1980; 2: 6-8Google Scholar). Ever since, NIH has become the sponsor of most biomedical research and training. The role of NSF in supporting basic biological research is meager by comparison. Whereas there was substantial support for doubling the NIH budget recently, a similar effort to double the NSF budget has not been successful. Indeed Congress and the public have been extremely enthusiastic about increasing funding for research aimed at improving the health of the citizenry. Almost invariably over the past 60 years, the annual increases in NIH funding approved by Congress exceeded those proposed by the President. Some have attributed that to the personal interests of members of Congress in their own health. Whatever the motivation, funding of NIH has increased phenomenally, reaching the present staggering level of about $29 billion. But it should not come as a surprise that the “doubling” policy of funding from 1999 to 2003 was bound to end. The scientific community was hoping for “a soft landing” with increases of 7–9% annually as contrasted to the 15% increase during the doubling period. That soft landing has not materialized, and complaints are now widespread about the inadequacy of annual increases that do not even account for inflation. As can be readily gleaned from this brief history of federal funding, scientists of my generation did not spend much time writing grant applications as they launched their careers. In my first few years as a faculty member, I received funds kindly provided by Wendell Stanley who, as a Nobel Laureate, had grants from various private foundations. The first graduate student in my laboratory was supported by university funds. Several years after initiating my research in Berkeley, I received my first grant. Actually it was a contract, of about $7,000, from the Office of Naval Research (ONR) for research on tobacco mosaic virus and the ultracentrifuge. Administrators at ONR were enthusiastic about basic science and provided enormous freedom to investigators. After a few years, many of the staff at ONR moved to NSF, and I began receiving funding from NSF. That support for many years, years later in an annual budget of about In the of federal support, I had the that my laboratory was not doing biomedical research, and I to NIH even larger grants were readily available. My NSF grant was for many in the were supported as teaching or research by grants to faculty members or funds. A laboratory would have one or graduate a and one a from the research of Although most scientists were about the Bush report and the of federal funding of research at universities, some there was considerable about the of political and of Indeed over the years, there have been such as the NIH grants to individuals were of their political In was the of began on as of and in the and the of grants to and other were both NIH and in the extramural community. Some leading at NIH were about the policy by the that they to some of the investigators that they a as the in which case the grant would still be to the 4 years elapsed before the policy of under the policy by was During that who the section on Molecular Biology at NSF and was one of the at both ONR and NSF, me an for a review of an from for funding his research supported by NIH. to my I was a detailed review of the along with a that the proposed research was and would have a great impact on our understanding of In addition, my “The is a in the of science and is and to perform the research that is That was for the The response was much more personal I well and on his It I to a research grant from in physical chemistry and its to biological was Not only did NSF, fund grant but others who were by NIH received funds from NSF. have been other of political in the of the with the most during the in for the training grant at NIH was from the the of review was funds were and to the National from NIH were Finally, Director of NIH for 5 years, was in for to with the Office of and in basic research that time the peer review was in less on the grant at NSF and NIH with appointments to level such as the Director of the NSF or at NIH. Some grant applications have been a political that government should not support the of research in the who in agencies over grants whose by publishing his of complaints were often with peer review in of or political controversy such as science, or However by and agencies have to political with the of the response to in the during of in the 1940s that funding of research by government would be or by politics have not Although actions in the past few years have about political the peer review and with the freedom of the agencies have The of the grant not that for grants were not On the contrary, over the past 40 years there have been many the scientific community has been in about the of funds. investigators of today almost will that my of experience on sections of NSF and NIH in the and is As members of an NSF we were to of the applications being at a even some of were our of The at in for the in Washington, required several of receiving in the of were of the applications did not receive to funding, and a significant were as a young Assistant it was a reading applications and with older members who were my in I can recall being to that members on the were in their review of the as well as and in their After about 4 years my and I was appointed to an NIH where I a culture we were about to our on a one of the more members next to me how I was to My response was, it is the will not and the research is not To which NIH we ever grant that time NIH was growing with increasing and was to young investigators. NIH staff for funds on the that many approved applications were of funds. the in culture and funding between NSF and NIH, I that I would the that the research would not be But my at the me that applications with a of would be many of those with a of were In that one I learned how much it was to receive support from NIH than from NSF. That is still but now to NIH are major and even first receiving of or are not being about are and young on the even about my scientists have a of the members on the or to and funds for research on During my tenure in the as NIH Ombudsman in the Basic I had the of in at many of different those scientists whose applications did not to funding, I can cite in the is much too much by members of the such as is too the on the is not with the still to they been for some years and are now replaced by in to be kind in their frequently offer thereby an impression about the of the often are not with the As a submit a that a there are too many often have too many Some of by the to the research of to great to their by the are too are thereby the of these I the of the most and often complaints is that members support according to the are with the on my experience as an at as I have no that members and that their about the of the they to such But this of the peer review system is not 50 years ago in a on a at the on I the of the of a grant the of the grant it still has some of the complaints about the peer review system are but it is astonishing to scientists, whose grant applications were not NIH or NSF the decisions were largely by of My to the is that the are to the of the members on the review and is have the peer review The of Research a of from 1946 to National Institutes of Scholar), and their invariably have led to in the The of Research in many over the years in response to from the extramural community, and an change occurred that was in to the for Scientific A major of is now being Although scientists have about which will review their this was in biomedical science over the past 50 years have resulted in changes in the way research is Whether this new will the of that of scientific research between the remains to be seen. will on the conduct of and by NIH staff to in to It should not be a for that a comprising many and would to these However in the scientists other found and the of their were In my this of has occurred in the of chemistry and in other of scientific This is to be as a of the complaints about peer review will and even increase the for more from the growing scientific community the available of funds. That government has to the scientific community the to and the peer review system is a remarkable and is During the and the of graduate in biochemistry and increased appointments to the faculty and new departments were in many Berkeley in the we had both a biochemistry and a that was later into a of Molecular for faculty graduate and university funds. was in by the increased federal funding for biomedical My own laboratory including from both Biochemistry and Molecular Biology, had to about 5 graduate several and the increase in the of postdoctoral and the establishment of NIH there was a need for funding to faculty in I to NIH for funds and received my and still NIH grant entitled of Biological which was significantly larger than the NSF grant. faculty members similar and not problems became New became the in of departments at Berkeley about years ago there was a major The Biochemistry and Molecular Biology of about faculty members was as 1 of 5 in the of Molecular and Cell Biology comprising about This has been in faculty and graduate and the on coupled with the of has led to for even more and not a of Whether this growth has resulted in a of community and is for others to Moreover, it will be of to the of the in the Stanley there be extensive leading to Big Science, or will there be just more scientists in the not to one