Keynote Lecture: Basic Science and the NIH: American Society for Cell Biology Meeting
December 11, 1993
Harold Varmus, Director, NIH
I must begin with a confession: I have rarely attended a national meeting of this Society and (I am ashamed to say) I have been a member of ASCB for only a couple of years. (This was not for lack of desire; Marc Kirschner was unconvinced I was serious about cell biology and hence unwilling to sign my membership application until I published an article in Molecular Biology of the Cell.) Still, this feels like a homecoming--and even like a victory celebration. Despite the strains of the job for which I have finally been confirmed, I feel a special affection for those of you who have helped against great odds to put me there.
Let me tell you briefly how it happened. Just a few years ago, my interests in the politics of science were barely noticeable. Like most of you, I was reasonably content, and often very happy, to be doing science in this remarkably exciting era in biology. Then, seemingly all at once, a number of things happened. Science in general--and biomedical research in particular--was besieged with problems: low success rates in grant applications, especially among young investigators; allegations of scientific misconduct and of misuse of indirect cost reimbursements; and calls for more applied than fundamental science as a means of justifying public expenditures.
As a newly decorated Nobel Laureate, I was recruited to the fray by two of my favorite UCSF colleagues--and two of this Society's cultural heros. First, Bruce Alberts persuaded me to deliver the opening talk at a National Academy of Sciences (NAS) workshop on the funding of young investigators, an event that led to much greater involvement in Academy affairs. Then Marc Kirschner asked me to become an ad hoc member of his newly organized Joint Steering Committee for Public Policy--a consortium of bench scientists from several societies, including this one, banded together to work for changes in the new political climate, with the paid assistance of Peter Kyros, a former Congressman. This led, in turn, to my role in organizing sessions for the Congressional Biomedical Caucus; to the reconstitution of the Delegation for Biomedical Research (about which I'll say more later); and to many other things. When Bruce, as newly elected President of the NAS, was asked to chair a search committee to find a new NIH Director, my fate was sealed.
Elizabeth Maricola, the nation's leading FAX machinist, has kept many of you intimately informed of the Byzantine events that followed. I am grateful to all of you who wrote impassioned letters on my behalf to the Department of Health and Human Services (HHS), to the White House, or to Congress during the exasperating period that has so recently ended. But ultimately, you and I seemed to have convinced those in power that a basic scientist with minimal administrative experience should be allowed, even encouraged, to run a complex Agency with a budget of almost $11 billion--a budget over four logs greater than any I had ever managed before.
There is a thrill and a sense of wonder to our success in getting to this point. A few weeks ago, Marc visited me in Washington. In the evening, I took him to the NIH Director's Office in Building One--where we had felt like the dispossessed only a year earlier--and I enjoyed watching him take his measure of the office, like an absentee landlord. As we entered, I was concerned that he might behave like the enthusiastic mob at President Andrew Jackson's inauguration, who caused Jackson to be, in the words of one eminent historian,"pressed back helplessly as men tracked mud across valuable rugs and clambered up on delicate chairs to catch a glimpse of him .... The White House shook with their shouts, glassware splintered, furniture was overturned, women fainted." But, I am pleased to report, Marc was very well behaved.
So now that the scientific rabble has politely taken over the NIH Director's office, what are we going to do? What are the battles worth waging? and How do we wage them? Has the lure of authority been a mirage? or Was it correct to believe that one of us in the Director's job could make a significant change in the conduct of our science?
My efforts to think through these questions brought me back to last December. Those of us who had worked for the Clinton-Gore ticket in the fall of 1992 were feeling triumphant. But we also recognized that most of the problems faced by basic science had not been explicitly addressed during the campaign, despite the considerable emphasis on technology, on investment strategies, and on new jobs--components of our culture to which biomedical research, in particular, contributes in important ways. So with Bruce hovering over us like a newly appointed deity, Mike Bishop, Marc, and I sat down to write a letter of advice to the new Administration.
Shortly after the Clinton inauguration, our letter was published in Science magazine as a Policy Forum.1
Because it was written before anyone knew that there would be a change in the NIH Director's Office--and certainly before anyone (including I) would have thought that I might occupy the office--the article publicly records my last opinions as a free and innocent man, unrestricted by the courtesies of political office or by the knowledge of insider information.
One of the many very generous letters that I have received in recent weeks recalled this article with admiration, then went on to say that "it is therefore refreshing, and at the same time almost unbelievable, that now only a few months later this perspective, and the culture of basic science, is leading NIH."
Under these circumstances, I thought it would be useful--and perhaps even entertaining--to look back at the eleven recommendations1 we then made and to ask some questions about them: Do I still subscribe to them? Has any progress been made in the first year of the Clinton Administration? Should we expect progress in the future? and What can we do, individually or together, to get what we want?
These pronouncements were based upon a shared creed, one that I hardly need to belabor for this audience. At its heart is the conviction that science is good for society; that a persistent investment in fundamental research is essential for the technological improvements our society seeks; and that our Nation's health and economy benefit from developments in biology.
1. Develop an economic strategy for optimizing investment in biomedical research, which would take into account the new opportunities that have been made available by the recent revolution in biology, the potential for reducing health-care costs, and the benefits to agriculture and industry. Until a full evaluation has been completed, we recommend increasing the NIH budget by 15% per year, which would double the budget in current dollars by 1998.1 This increase would provide funds for approximately 30% of approved grants, thereby retaining healthy competition and exploiting the major areas of scientific opportunity.
Our first proposal was arresting--by some accounts self-serving and naive--because we elected to give a number, albeit tentative, to annual increases for the NIH budget. You don't have to live in Washington very long to learn that our proposal to double the budget by FY 98 is simply not realistic. The five-year caps on discretionary spending, the large obligations to entitlements, the national paranoia about tax increments, and the gaping hole of the National debt are more than enough to restrain growth of the entire research enterprise, including NIH. To overcome hurdles of this sort, we will need a cell biologist to run the U.S. Office of Management and Budget, not just the NIH. In the meantime, we will be fortunate to stay ahead of inflation in the next few years.
But the real point of our recommendation can be found in the cumbersome and less arresting first sentence: to have a stable long-range plan for Federal support of biology in this time of unprecedented promise. On this front, I do have something encouraging to report. Just a few weeks ago, on November 23, 1993, the President established the National Science and Technology Council (or NSTC). This is not just another amalgam of Federal agencies charged to write reports, like the so-called FCCSET (Federal Coordinating Council for Science, Engineering and Technology) that the new Council replaces. Instead, the NSTC will be a true science cabinet, chaired by the President and staffed by the heads of all the Departments and freestanding Agencies responsible for allocating and spending Federal monies on science and technology. For what may be the first time, the Nation's entire $76 billion portfolio in research and development--for the military, for transportation, for health, for the environment--will be spread out on a single table and critically examined. At this level of analysis, even quite small shifts of emphasis could have very substantial effects. This should inspire optimism in a field like ours, which provides daily intellectual excitement and the politically popular prospect of improved health.
But such charged situations are not always predictable. Furthermore, the NIH, as a part of a much larger Department, does not have its own seat--despite the fact that it pays for one-seventh of the Nation's R&D and most of the research in academia. On the other hand, the NIH will be heavily represented in the several subcommittees that will be reporting to the Council on health, basic science, education, international issues, and many other matters that concern us. And NIH should continue to be well-served by the impending renewal of PCAST, the President's Council of Advisors on Science and Technology, whose members are drawn from the private sector, especially from universities.
The new Council is an important sign that President Clinton is taking very seriously his own statement that "science and technology are essential tools for achieving this Administration's goals." In the weeks ahead, people in all fields of basic science will have an opportunity to explain the significance of what they do, and they will be listened to at the highest levels. We need to be ready to respond to this challenge, for the stakes are high.
2. Generate a comprehensive plan for the best use of federal funds for biomedical research. Development of new strategies, programs, and leading mechanisms should include the active participation of the scientific community and not originate solely from administrative directives.1
Our second proposal was an attempt to come to terms with one of the dominant themes of 1992--the planning of research strategies by our major institutions, including NIH. Strategic planning became a pejorative term in that year, because many of us were resistant to a process that seemed to be driven by forces unsympathetic to basic science. Yet those of us who participated in the discussions recognized that something significant and potentially useful was in motion. It seemed smart to be talking with our peers about whether we were doing the best things with the limited funds now available. The process itself had value. The product of the process--a turgid tome in a corporate style--was much less valuable--and has never been officially released by HHS Secretary Donna Shalala.
So how do we get more out of the process? and What kinds of things do we need to reflect upon? My first challenge as the NIH Director has been the intramural program in Bethesda and surrounding sites. Shortly before I arrived at NIH, Congress asked that the NIH re-examine the goals, mechanisms, and funding levels of the intramural program in each Institute. And just as I arrived, the impetus to respond was provoked by two long articles in Science magazine, criticizing many aspects of the intramural program. To cope with these developments, my colleagues at the NIH have assembled an unprecedented amount of factual information about the program--who is in it, how much is spent, what kind of work is done, how recruitment and tenure decisions are made, and how programs are planned. An external advisory committee of great distinction has been working feverishly for the past several weeks to digest this information and to give me advice about what should be encouraged and what should be changed on our campus.
While it would be wrong to prejudge their recommendations, I think it is safe to say that significant changes will occur. My own special passions about the intramural program center around two potentials: to bring the fruits of basic science into the medical practice efficiently at the Clinical Center and to provide newly trained investigators a marvelous chance to develop programs in a financially secure and intellectually rich environment. To exploit these features most fully, it will be important to fill all available positions with the best possible candidates. These will be largely, I suspect, recent graduates of our best post-doctoral programs in extramural institutions. You will doubtless be hearing more about such opportunities in the near future, and I hope those of you in this audience who love to do science will keep us in mind when you seek positions. The attractiveness of the intramural program is already being enhanced by the birth of the trans-Institute disciplinary groups recommended in the Klausner report2 last year. For example, a newly formed Cell Biology Group claims two hundred members from many different Institutes.
Despite the great attention being given at the moment to the intramural program, I am acutely aware that only 11% of the NIH budget is spent on it. So I am strongly disposed to worry about the extramural community as well: We spend most of our money on it and for twenty-three years I have belonged to it. But the extramural world is vast, complex, and continually in flux; and this job leaves me relatively little time to focus on its many problems. To help me understand it, I am currently trying to find a highly respected senior scientist who is willing to spend a year or two as an ombudsman for the community. This person will travel to the research centers where NIH has major investments; meet with trainees, junior and senior investigators, and administrators; hear about problems and solutions; and tell me about them. I can envision a variety of consequences: workshops that bring disciplines together for the first time; novel scientific initiatives; shifts of funding; or simply more efficient means of doing business.
3. Institute a mechanism for the periodic evaluation of peer-review procedures, utilizing scientists from inside and outside the government. Efforts should be made to ensure that the thematic alignments of review panels accurately reflect contemporary progress and opportunities in biomedical research.1
The mechanisms of peer review of grant applications are among the greatest sources of discontent I expect our ombudsman to confront. When we wrote our article, much of our attention was focused upon Bruce's favorite complaint--the outmoded alignment of some study sections. This is certainly an important problem, but far from being the only one, especially in times of low success rates, repeated submissions of applications, and a demoralized cadre of reviewers and study section administrators. I have been meeting with Jerry Green, the Director of the peer review system, to consider a number of suggestions that have been made to me in the past few months. The triaging of applications, for example, might give more time for consideration of the most competitive applications. Submission and review of applications on computer disks or by electronic networks could reduce the burden of paperwork. Efforts could be made to coordinate our application forms with those from other Agencies. Incentives might be created to encourage the best scientists to serve on study sections. And, of course, more broadly constituted study sections might remove unwarranted protection from dated disciplines. In the near future, we will test some of these ideas with experiments that allow us to know whether they help. In the next year, I expect to assemble a small workshop to think about other things we might try or to apply tested ideas more widely.
4. Facilitate the application of fundamental discoveries by encouraging technology research in the private sector, stimulating alliances between industry and academia, and clarifying the federal stance on conflict of interest.1
Our fourth recommendation sounds like apple pie, delivered to the team that was already enthused about technology. But the theme is a big and troubling one to all of us, because we have yet to establish comfortable rules to guide the relationships between industry, government, and academic institutions. We still don't know what we should patent, how we should set the terms for co-sponsorship of research, and when we are jeopardizing our integrity by deal-making. The question of whether it is possible to patent anonymous cDNA sequences has yet to be unequivocally settled--though a group is slated to advise me next week about whether to pursue the issue to its ultimate conclusion. Similarly, we have yet to tell Congressman Wyden's committee about the fair standards for industrial sponsorship of academic research--though again I hope to be learning from experienced advisors when we hold a workshop on this topic next month. These problems are among the most difficult ones facing us as a result of recent successes in biology, and we all need to give serious thought to them.
5. Ensure that new departures by the NIH and NSF [National Science Foundation] in education and technology do not diminish the support of basic research. If the Administration or Congress provides new mandates or new requirements for the NIH and NSF, it should also provide the necessary additional funds.1
We wrote this terse statement to convey our concerns about a simple but profoundly important issue: If we as scientists are told to do specific new things, however important, with a constant pot of money, we will inevitably do fewer of the things that we have done in the past. Since the investment in basic research has been hugely successful--I hardly need to convince this audience of that--and since we are not likely to see more money in the next few years, we must fight to defend the core of our enterprise.
This fight can take many forms--publicizing the importance of basic research, visiting your Congressional representatives to tell them how research is done, or explaining to advocates for targeted funding why the fundamentals are such a valuable investment.
6. Strengthen the position of the presidential adviser on science and technology. The adviser should have strong credentials as a scientist and as an administrator, be alert to contemporary developments in both the biological and physical sciences, be encouraged to consult the diverse representatives of the research community, and have regular access to the president and vice president.1
The new science advisor, Jack Gibbons, has been in government for many years and would be the first to acknowledge that he is no longer a working scientist. But he has now brought a dynamic, active investigator, M.R.C. Greenwood, a physiologist from UC Davis, into his office; he has remarkably cordial relations with the Vice President and President; and he has been the motive force behind the new Council on Science and Technology, which will bring science advising to a new level of power.
7. Establish the NIH as an independent federal agency and consolidate the authority of the director over the individual institutes.1
A few nights ago I had dinner with Mike Bishop in California and he accused me of retreating from my commitment to free agency status for NIH, because I have publicly declared my affection for Donna Shalala and Phil Lee, my superiors in the Department of HHS. There is no doubt about the benefits of the protection provided to NIH by a large department when we are on such good terms with its leaders. I am happy to have debates about scientific misconduct located outside NIH and I enjoy having strong allies in budget negotiations. But we all know that there are times when it seems that we might do better with greater visibility, so that NIH might be as well known as NASA (National Air and Space Administration) and so that we would be directly represented, like NSF, on the Science Council.
The second part of this recommendation--more power to the NIH Director--may seem parochial to some of you and, now, self-serving to others. But the investment of greater authority in my office will certainly help if we are to make significant changes in the intramural program, especially, and in the extramural programs as well. One way this can happen is through the delegation to me of authority that now rests in the Department, particularly authority to make appointments and to use more competitive pay scales. There is reason to hope these things will come to pass.
Another way this might happen is through a demonstrated ability to improve the way NIH conducts science. I am eager to persuade the Vice President that NIH is the optimal setting in which to reinvent government. After getting enthusiastic endorsement of this idea from Donna Shalala and Jack Gibbons in late October, we immediately wrote a letter of invitation to Mr. Gore. But, when I met him last week at a holiday party, he was bewildered by my inquiries about a visit. The next day I found that the letter of invitation had been slowly passing through Department channels and had yet to be sent. So my efforts to get him to visit us have only illustrated what is wrong with Government.
8. Apply appropriate criteria to the choice of science administrators. Appointments should be based on stature in the research community and administrative ability rather than on political and religious considerations.1
Our concerns about the criteria for selection of leaders of our scientific Agencies have faded with the advent of the Clinton-Gore Administration. Within days of his inauguration, the President lifted the ban on the use of fetal tissue for research, and we knew a new day had dawned. Apart from the changes at NIH, we enjoy an academic physicist, Neal Lane, at the head of the National Science Foundation and many other enlighted scientists throughout the Federal Government. Many of these gathered for dinner at Bruce's apartment in the Watergate last week, and the collegial atmosphere gave confidence that new possibilities have been created.
In this buoyant climate, it is advisable to consider ways to make political criteria less likely to be applied under any administration. In the case of NIH, a useful proposal--one that has been made many times before--is to establish a fixed six-year term on the Directorship. At the moment, six years seems like a pretty long time to me, but it is probably what is required to accomplish something ambitious. And a legislated asynchrony with the electoral process would be inherently healthy.
9. Implement a uniform and comprehensible policy for indirect costs that provides incentives to institutions for cost savings and ensures that the funds will be used only to support the infrastructure required for research.1
Our concerns about indirect cost reimbursements have also retreated measureably in the past year, with the revision of the Federal rules in Circular A-21 that govern reimbursement schedules. In this case, the wheels of progress were set in motion near the end of the previous Administration. But a novel political development, external to government, had a very significant role in the successful resolution of many contentious issues. Despite recent tussles over the disposition of scarce NIH funds, bench scientists and their academic administrators were able to recognize a common purpose in developing sensible, nonpunitive indirect cost rates. To achieve this goal, an antique organization, called the Delegation for Biomedical Research, was re-tooled to provide a forum at which button-downed university and medical school administrators and unruly basic scientists could resolve at least most of their differences to avoid a Draconian solution.
Recent attempts to reduce the deficit--for example, the bill proposed by Representatives Penny and Kasich--vividly illustrate that threats to reasonable reimbursement of indirect costs are not dead. For this reason, organizations like the Delegation--which is currently back in mothballs as far as I can tell--need to be kept in a state of preparedness.
10. Create a program for long-term investment in research laboratories and equipment based on peer review of merit and need rather than on political affiliations.1
The deterioration of buildings and equipment in many of our major institutions is one of the most flagrant consequences of constricted funding for research. I believe we have been wise to invest in people and their ideas, rather than in bricks and centrifuges, in times of constraint, but soon the piper will have to be paid. At the NIH campus in Bethesda, for example, the large building that houses all of our clinical research and nearly half of our laboratory research is over forty years old and has been certified for replacement or radical renovation, at a cost that currently seems difficult to finance.
But we must now begin to consider how we will do this, at NIH and elsewhere. It is crucial that the investments be made judiciously, by deliberate peer-review, not by arbitrary Congressional earmarking to satisfy constituents. Here, Congressman George Brown of California has been heroic in leading the charge against the willful annual spending of hundreds of millions. Now we need to find some way to divert funds that would otherwise have been earmarks to a peer-reviewed program for building facilities where they are most needed and best used.
11. Increase federal attention to science education. Measures could include the development and dissemination of new curricula and textbooks, enrichment programs for established teachers, improvements in the training of science teachers, and scholarships and other incentives for prospective science teachers.1
In our final recommendation--note that we were running out of imperative verbs--we suggested ways that the Federal Government could remedy a problem that has languished in the hands of most State and local governments: the teaching of science to our children. Scientists nationwide have responded to this challenge, and Bruce Alberts is making it the centerpiece of his new administration at the NAS. At the NIH we have a relatively small investment in K-12 science education compared to our better known investments in graduate and postdoctoral training. But many of our Institutes run special programs for teachers and students in local schools; middle and high school students spend weekends or summers in our laboratories and classrooms; and campus learning centers are often visited by local students. Still, our many programs lack coordination with each other and their effectiveness is difficult to evaluate. We all will need to watch closely as Bruce and his colleagues try to develop sensible standards for what should be taught as science and how we should teach it.
The NIH and those of us who work with its funds face another educational mission: Telling the general public about what we do with its money and the importance of basic biology for improving health. One way I would like to do this is to organize a travelling NIH fair that stages in our major cities a weekend of scientific entertainments--talks, exhibitions of experiments, and panel discussions of issues that range from molecules to ethical questions our science raises.
In all of our talk about education, we need to place special emphasis on attracting female and minority students into science--and keeping them there--topics we failed to consider adequately last year. Science loses many from these categories because of stereotyped expectations and inadequate inner city schools. But in the work force of the next century, few will be white males. If we don't encourage the others to engage in science, our enterprise and our Nation will suffer greatly.
The conclusion from our Policy Forum in Science1
We look to our new president and vice president for leadership in fulfilling the promise of science for our nation. We hope that they will not fall prey to the view that the problems of our society might be solved by a shift in emphasis from basic science to applied research. Instead, the U.S. federal government should act decisively and soon to revitalize the support of fundamental as well as applied research. President Clinton and Vice President Gore have spoken clearly on health care, economic policy, and education. We ask them to do the same on the issues that confront science (3).
As indicated in our final plea, we "look to the President and Vice-President for leadership", for a sign that they support and encourage the role of basic science in our society. Despite this year's preoccupations with the budget, NAFTA (North American Free Trade Agreement), the Brady bill, and especially health-care reform, some very clear signs of the leadership we want have emerged. In a major message on technology issued last February, the President included a number of important clues to his convictions. For example, he wrote that "it is essential to recognize that technical advances depend upon basic research in science, mathematics, and engineering" and "we will not allow short-term fluctuations in funding levels to destroy critical research teams that have taken years to assemble" and "the long-term scientific and technological vitality of the U.S. depends upon adequate and sustained funding for university research grant programs at NSF, NIH, and other research agencies."
Now I do not expect a critical audience like this one to accept such statements at face value, when so many have been hurt by the current fiscal climate. But I was recently further encouraged by a more subtle and unpublicized event that I was privileged to attend. On December 3rd, the Swedish Prime Minister came to town, and the President took the occasion to invite this year's Nobel Prize winners to tea. To my pleasure and surprise, it was not a perfunctory greeting. Both the President and Mrs. Clinton had substantial conversations with many of their guests and the comments I heard them make about science policy were informed and enthusiastic. I predict we will hear more about the White House's commitment to science in the coming months.
Remember that our article was directed to the leader of the executive branch. But much of the action must be carried out by others--by the Congress, by the NIH, and by you, the rank and file of biological scientists. For the NIH to maintain the success of basic biomedical science, I will need the help of all of you to carry out many of the themes I have briefly touched on this evening.
Many of you have asked me how I feel about my new job. Here is one answer: I feel like the fly fisherman who has stepped down from the bank and waded into the stream in search of his prey. Now the fish are closer and easily seen. But I am also standing in a swift current of paper flow, political problems, and many irrelevancies. Those of you still standing on the bank must give me a hand. Maybe together we can bring some of our biggest fish to the net.
References and Footnotes
- J. Michael Bishop, Marc Kirschner, Harold Varmus. "Science and the New Administration." Science, 259, 444-445 (22 January 1993). The authors are on the faculty of the School of Medicine at the University of California, San Francisco, and are members of the Joint Steering Committee for Public Policy.
- "Report of the Task Force on the Intramural Research Program of the National Institutes of Health." April, 1992.
- This policy forum is based in part on a statement prepared in November 1992 by the Joint Steering Committee for Public Policy, representing the American Society for Cell Biology, the American Society for Biochemistry and Molecular Biology, the Biophysical Society, and the Genetics Society of America.