The 85th meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on December 5, 2002. NIH Director Dr. Elias Zerhouni began by describing the impact of several continuing resolutions (CRs) on NIH spending programs. These successive CRs during the first months of fiscal year (FY) 2003 hold the NIH budget to the FY 2002 level of $23.6 billion, and the CRs are prorated to each portion of a year to which they correspond. These CRs are not expected to have a significant impact on the NIH through December 2002, according to Dr. Zerhouni. However, maintaining the NIH budget at FY 2002 levels beyond the beginning of calendar year 2003 will begin having a detrimental effect on several programs, including efforts to fund renewal grants, to pay for buildings and facilities, and to develop biodefense research programs. Congress is expected to pass the NIH appropriations bill in late January 2003 before President Bush delivers the State of the Union message.
Dr. Zerhouni said he participated in two recent Congressional hearings: one focused on human embryonic stem cell research before the Senate Committee on Appropriations Subcommittee on Labor, Health and Human Services, and Education; the other hearing, which was convened by the counterpart subcommittee in the House of Representatives, focused on how effectively the NIH is using its resources.
During the former hearing, when Dr. Zerhouni and other NIH officials were asked by Senator Arlen Specter (R-PA) about the availability of stem cell lines for research, they provided detailed information about early efforts to build the infrastructure needed for supplying those cells to investigators who plan to conduct such research. Several additional witnesses emphasized the importance of having ready access to those cell lines, about eight of which are now available. Because the NIH needs to be more proactive and to remove obstacles that might interfere with progress in this field, Dr. Zerhouni has formed a Stem Cell Task Force.
The Stem Cell Task Force will be led by Dr. James Battey, who has identified several areas where progress is needed, including training investigators to conduct stem cell research, providing wider access to resources, and characterizing more fully those stem cell lines that are approved for research use. Dr. Zerhouni said the NIH has issued 40 supplemental grants to investigators who wanted to begin using such stem cells in established research programs, several new grants for conducting such research, and also several infrastructure grants. So far, some 78 institutions, including many outside the United States, have received human embryonic stem cell lines and are using them in NIH-supported research.
During the latter hearing, convened by Representative Ralph Regula (R-OH), Chairman of the House Appropriations Committee on Labor and Health and Human Services, Dr. Zerhouni provided specific examples of how increased resources made available to the NIH have been and are being used and how the NIH plans to use its resources in the post-NIH budget-doubling era.
Dr. Zerhouni described several ways the nation's return on these investments by the NIH can be quantified, particularly in terms of reducing the burden of disease. He also pointed out that these investments by the NIH have generated additional investments by the private sector into biomedical research. In 1991, for the first time, the size of that investment surpassed the annual NIH investment. Another sign indicating the importance of these NIH investments is that medical schools are actively building research facilities and recruiting scientists, according to Dr. Zerhouni, who cited a report from the Association of American Medical Colleges. These activities mark a substantial increase in the U.S. capacity for conducting biomedical research. Dr. Zerhouni said he and other NIH officials participated in a memorial service in October honoring former NIH Director Donald Fredrickson, who died in June. Later in October, there was a groundbreaking ceremony for the Family Lodge. Construction is being supported by the NIH Foundation, which received several gifts for that purpose, including one from the Edmond Safra Philanthropic Foundation. Early that month, Dr. Zerhouni also participated in a town meeting for NIH employees to discuss recent concerns, including heightened security; plans to build a fence around the NIH campus; the A-76 procedure, which is part of a plan to identify tasks that could be done by the private sector; and whether increased biodefense research efforts will lead to new restrictions on publishing and have other effects on the NIH.
Also in October, the NIH convened a workshop to address recent findings from a large-scale clinical trial evaluating the use of hormone therapy among menopausal women. This meeting followed an announcement in June 2002 from the National Heart, Lung and Blood Institute that a portion of the Women's Health Initiative clinical trial involving the use of combined estrogen and progestin therapy was being halted when it was realized that this combination led to a greater risk of breast cancer, stroke, and cardiovascular disease, according to Dr. Zerhouni. These findings provoked a strong public reaction and led the NIH to work with the Food and Drug Administration to convene the October workshop, at which, experts representing many different constituencies developed new consensus recommendations about hormone therapy for menopausal women.
Several researchers whom the NIH supported were recognized during October with Lasker Awards and also with Nobel Prizes. The latter include Dr. John Fenn, who used mass spectrometry to determine macromolecular structures and was supported by the National Institute of General Medical Sciences (NIGMS), and also Dr. H. Robert Horvitz, who works on apoptosis and was supported by NIGMS, the National Cancer Institute, and the National Institute of Child Health and Development. In addition, Dr. Vernon L. Smith, who was awarded the Nobel Prize in economics for his work on the psychology of decision making, received support from the NIH.
Dr. Zerhouni said the Institute of Medicine (IOM) and National Academy of Sciences are conducting several studies on issues that affect the NIH. One such study will reevaluate the NIH organizational structure; this study committee is chaired by Dr. Harold Shapiro, of Princeton University; and its report is expected by June 2003. Another group is called the Clinical Research Roundtable, and its members are focusing on how such research is organized. Yet another group, the Committee on Scientific Research Manpower Needs, is mandated by Congress to assess training needs on a periodic basis; Dr. Christine Cassel, a member of ACD, is part of that committee.
Dr. Zerhouni summarized several changes that affect NIH management. For instance, in the NIH Office of Director, Mr. Charles Leasure was appointed Deputy Director for Management and Chief Financial Officer; Mr. John Burklow, Acting Associate Director for Communications and Public Liaison; Mr. Donald Poppke, Acting Associate Director for Budget; Mr. Thomas Gallagher, Director of the Office of Community Liaison; and Dr. Mark Rohrbaugh, Director of the Office of Technology Transfer. Dr. Wendy Baldwin, the NIH Deputy Director for Extramural Research, will be leaving to become Vice President for Research at the University of Kentucky, while Dr. Ruth Kirschstein, the NIH Deputy Director, will assume the role of senior advisor to the NIH Director. Dr. Stephen Katz, is leading a committee to identify a replacement deputy director.
Dr. Zerhouni said there are ongoing searches for directors for several NIH Institutes and several recent appointments, including Dr. Thomas Insel, Director, National Institute of Mental Health (NIMH); Dr. Ting-Kai Li, Director, National Institute on Alcohol Abuse and Alcoholism (NIAAA); and Dr. Roderic Pettigrew, Director, National Institute of Biomedical Imaging and Bioengineering.
In evaluating Dr. Insel as a candidate to become the director of the NIMH, Dr. Zerhouni visited Dr. Insel at Emory University, where he ran a center that was funded by the National Science Foundation. Dr. Insel said he had worked at the NIH as a high school student and later spent 15 years in the intramural program at NIMH, working with Dr. Steve Paul among others. He said those experiences made it easy for him to decide to return to the NIH.
Dr. Zerhouni invited Dr. Li, who served recently as a member of the ACD, to speak to the committee. Dr. Li said that research on alcoholism is necessarily multidisciplinary, that he plans to emphasize that approach in developing programs within the NIAAA, and that he looks forward to being a part of the NIH team.
Dr. Zerhouni described his new Road Map for the NIH, which includes a new approach for presenting facts about the NIH and its programs and accomplishments to Congress and the public. The Road Map also outlines where the NIH is going over the next three to five years, and it incorporates representative examples of the noteworthy health impacts of NIH investments in biomedical research.
Dr. Zerhouni said some of the detailed information for the Road Map was developed in collaboration with the NIH Institute and Center directors and also the NIH Office of Science Policy, which is directed by Dr. Lana Skirboll. One approach to this analysis involves asking what would be the health status of the U.S. population without the NIH investment in biomedical research. For example, because the NIH invested in research on human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), which led to the early introduction of drug therapies, demographic projections now indicate that deaths from HIV/AIDS were significantly reduced in 2000 from an anticipated 77,000 to only 15,000.
The same approach was used to estimate the reduction in mortality rates from cardiovascular disease and stroke, according to Dr. Zerhouni. Although some 1.3 million deaths from cardiovascular disease would have been expected per year, this rate decreased by almost two-thirds, which means 815,000 deaths were prevented in 2000, indicating a very high return on the biomedical research investment. Similarly, there were 166,000 deaths from stroke in 2000 rather than the projected 407,000 deaths.
Other health impacts can be traced directly to the NIH investment in biomedical research, according to Dr. Zerhouni. For instance, the NIH supported research that led directly to the development of new tests for detecting the hepatitis B and C viruses in blood, which in turn led to significant improvements in the safety of the blood supply and reduced the overall risk for those receiving blood transfusions or blood-derived products of becoming infected by either of those viruses. Moreover, wide use of the vaccine to protect children against Hemophilus influenzae type B infections has nearly eliminated such infections among U.S. children and has sharply reduced the number of cases of mental retardation attributable to such infections — from 11,000 in 1987 to 2,300 or fewer in the years since the vaccine was licensed.
Dr. Zerhouni said that, in developing the Road Map, he also asked whether these investments in biomedical research through the NIH represent an efficient way to direct federal dollars rather than investing them in other fields. He said this analysis indicates that the answer is "yes," and he has testified to that before Congress. Although the NIH budget about doubled during the past five years, private sector investments by the pharmaceutical and biotechnology industries in biomedical research and development (R&D) are growing at a faster pace and in 1991 surpassed those at the NIH, according to Dr. Zerhouni. However, the NIH and private sector investments have been synergistic and the NIH activities have helped to drive some of that private sector investment, encouraging the sustained formation of about 1,400 biotechnology companies and the creation of 191,000 jobs in the private sector.
Dr. Zerhouni also asked the Association of American Medical Colleges to provide data on how the NIH investment is affecting universities and medical schools. The information indicates that, from 1990 to 1997, such institutions spent $3.2 billion on renovating or building research facilities at medical schools; from 1998 to 2002, they spent an additional $5.4 billion, and they are projected to spend another $9.5 billion during 2003-2007. During this period, medical school faculties grew from 13,000 to 27,000, with much of that growth in clinical science departments so that there is now about an equal distribution of Ph.D.s in basic and clinical science departments.
Considerable NIH resources go into funding R01 grants to support individual investigators and their small research groups, and the number of such new and competing grants will rise to 9,864 in FY 2003 (up from 7,500 in FY 1998), with a total of 38,000 grants. This figure represents a substantial increase from 27,000 total grants in FY 1998, but it is not an exact doubling because the cost of each grant also has increased, on average, by 40 percent. This increase in the size for an individual grant from an average of $250,000 in FY 1998 to $370,000 in FY 2002 reflects a "catch-up" to match inflation as well as the increased scientific scope of research activities supported under such grants. Recent funding increases for such R01 awards now correspond closely to historic trends.
During this period of rapid NIH budget growth, the numbers of applications for R01 and comparable grant support rose from 24,000 in FY 1998 to 31,000 to 33,000 per year, while the success rate has remained steady at about 30 percent. These figures represent an overall gain in total numbers of awards and indicate a substantial increase in overall U.S. biomedical research capacity to accompany additional increased R&D investments in the for-profit private sector and by universities.
Dr. Zerhouni said that 30 percent of the NIH grantees are first-time principal investigators. One distinctive change amid these trends is that new, or "first-time," investigators being supported by the NIH are older than they once were. Thus, the proportion of first-time grantees under the age of 35 has dropped from about 23 percent to about five percent.
Meanwhile, the sharply increased biomedical research capacity is providing tangible changes, particularly in genomic research capacity, according to Dr. Zerhouni. For instance, the speed and capacity of genomics research are greatly enhanced, with sequencing rates increasing perhaps 100-fold, while the cost of analyzing each base pair has dropped from about $5 to only a few cents. The genomic sequences of about 100 organisms have been determined. The rate of vaccine development is also accelerating, with some 50 under active development at the NIH, 15 of which are nearing clinical trials. For instance, the NIH began work on a vaccine to protect against West Nile virus soon after the first cases were reported in 1999; a candidate vaccine is already nearing clinical trials.
The near doubling of the NIH budget has led to an expansion in the numbers and varieties of disease-specific research centers. For instance, there were 10 comprehensive centers studying only three specific cancer types in 1998, whereas now there are 30 centers studying at least 13 different types of cancer. These changes indicate an acceleration in the development of vertically integrated disease research activities accompanied by an expansion of clinical research trials. The NIH has quadrupled its investment in clinical research career awards, and there is a greater effort to translate and diffuse knowledge into clinical practice. There is also an increased investment in minority health and health disparities research. Similarly, programs to address bioterrorist-related countermeasures are expanding rapidly, and these new missions account for at least $2 billion in the NIH budget.
There is recognition of other emerging public health concerns as well as the impending health needs of the aging population, according to Dr. Zerhouni. For instance, 31 percent of the population is considered to be overweight, which increases the risk of developing diabetes. Perhaps 12 to 17 million Americans have diabetes; with obesity rates continuing to increase, 35 million could have the disease by 2050. Because diabetes can cause blindness and life-threatening heart disease, these trends could lead to substantially reduced life expectancies and other health burdens. These and other demographic trends already are affecting the overall costs of health care, which are rising from 14.3 percent to 17 percent of the gross domestic product (GDP) and could go even higher, with huge potential impacts on federal and state budgets as well as on society. Such developments indicate that helping to meet the nation's health needs through research will continue to be a critical challenge for the NIH and the biomedical researchers it supports.
Because the pace of biomedical discovery is accelerating, more rapid means are needed for translating those discoveries into practical benefits, according to Dr. Zerhouni, who resumed his description of the Road Map after an interlude of discussion among ACD members (see below). In general, the health care system strategy is to try to cure patients rather than to prevent diseases, particularly chronic diseases. Dr. Zerhouni said this paradigm needs to change, and biomedical research will be a key driver behind that change. Granting procedures at the NIH need to be adapted to changes in science that makes this possible.
The rapid pace of discoveries and unprecedented technical advances in the biomedical sciences come while there also seems to be an inflection point in the biological sciences, according to Dr. Zerhouni. One important consequence of such changes is that biomedical research needs to focus more on dealing effectively with chronic diseases; another consequence is that dealing with the complexity of such diseases will entail concerted effort to work across disciplines and, at the NIH, among its Institutes and Centers.
To identify obstacles to furthering such efforts, the NIH consulted with more than 100 scientists from the extramural community, and the NIH leadership held an informal meeting early in September, according to Dr. Zerhouni. He said these discussions to identify priorities led to the development of a matrix for categorizing research undertakings in a way that distinguishes them on the basis of their relative risk (in terms of payoff) and whether those undertakings are likely to be short or long term. These discussions also focused on identifying key roadblocks to success. Some of those roadblocks are scientific in nature. For instance, the complexity of biological systems appears to be beyond the reach of current methodologies.
Overcoming this and other difficulties may entail administrative changes that will reduce the current reliance on R01 grant mechanisms, which might not be so well suited for studying biologically complex problems, according to Dr. Zerhouni. For instance, researchers recognize a need to analyze the structures of membrane proteins, which account for about 30 percent of the proteins in cells, but methods are not available for doing so. Multidisciplinary approaches are needed to develop such methods; yet, there are obstacles to forming the teams needed to develop those approaches. Moreover, there are additional obstacles to overcome in applying basic biomedical findings, such as those being developed rapidly in genomics, to clinical medicine. The infrastructure for doing so is missing, and clinicians in different disciplines often lack a common vocabulary.
From such discussions, the NIH has identified three strategic priorities:
New pathways to discovery, which includes a comprehensive understanding of the building blocks of the body's cells and tissues and how complex biological systems operate, regenerative medicine, structural biology, molecular libraries, nanotechnology, computational biology and bioinformatics and molecular imaging;
Research teams of the future; and
Re-engineering the clinical research enterprise
Evaluating such questions and implementing solutions will depend on continuing consultations with the extramural community and with representatives of patients' groups and the public.
Mr. Arthur Ullian, who asked for copies of Dr. Zerhouni's presentation, praised him for the way he explained the impact of NIH programs to Congress and to the public. Mr. Ullian said that mentioning how NIH investments serve as an economic stimulus is also particularly valuable.
Dr. Linda Waite said considerable evidence indicates that members of the American public are very interested in and value health. Dr. Paul agreed and said that relating these trends and their effect on GDP is an important component of Dr. Zerhouni's presentation about the impact of the NIH investment. He also suggested the NIH identify specific examples of scientific developments, such as analyses of enzymes that are targets for the statin drugs and of the HIV protease that is a target for certain antiviral drugs, which led to reductions in death rates from heart disease and HIV/AIDS, respectively.
Dr. Brody said it would be helpful for university and medical school faculty to review the material Dr. Zerhouni presented. In response to Dr. Brody's question about the appropriate maintenance figure for the NIH on a grant-by-grant basis and how to explain these concepts to Congress, Dr. Zerhouni said the scope of grants has changed substantially. However, without taking the change in scope into account, the NIH uses 3.7 percent as a core rate to compute the impact of inflation on grants. He said the NIH is working to develop an improved way to explain this concept of expanded research scope.
Dr. Dzau said the NIH should include information about how its research has helped not only to improve health but also to extend the productive lives of Americans. In response, Dr. Zerhouni said that disabilities among aging Americans dropped from 26 percent to around 20 percent over about a decade. He also noted that Dr. Hodes has said delaying the onset of Alzheimer's disease by five years would have a big impact on costs and productivity. Dr. Hodes said that 2.4 million fewer aging Americans have disabilities than would have been expected if the age-specific rates in 1982 had continued unabated. Dr. Cassel said that determining how much of this decline in disability is due to improvements in specific treatments and how much is due to broadly healthier aging and a better understanding of the biology of aging is difficult to determine. Although it may be difficult to convince members of Congress of this phenomenon, Dr. Hodes agreed with Dr. Cassel that conveying how basic research brings health benefits and opportunities for identifying additional benefits is important.
In response to Dr. Dzau's question about how many biotechnology companies were created because of NIH-supported research, Dr. Zerhouni said that, although precise the number is not known, the NIH provides more than $1 billion to more than 2,100 for-profit organizations. He also noted that the Bayh-Dole Act, which enables universities that receive federal grant support to license technology to companies, is the key tool behind this economic stimulus. Dr. Baldwin said the NIH also provides research support to companies through its small business innovation research program, which accounts for 2.5 percent of the total research budget of the NIH. However, because small biotechnology and other companies often are bought out or undergo other changes, it is virtually impossible to track how the NIH affects them.
In response to a question from Dr. Masters about the pharmaceutical industry, Dr. Zerhouni said he cited R&D figures and excluded advertising and marketing costs when he compared the NIH and private-sector investments in biomedical research.
Mr. Ullian said that, when the news media discuss increases in health care costs, they and the NIH should also mention improvements in health quality.
Dr. Smarr said the impact of baby boom demographics on national health care costs might be even greater if the obesity epidemic is fully considered. Dr. Spiegel stressed the urgency of dealing with these issues to avert a growing health care crisis. He also said the results of a clinical trial, which were announced in August 2001, indicate that lifestyle and appropriate drug interventions can prevent type 2 diabetes. However, sustaining such interventions is not easy, and additional behavioral research is critical for implementing these interventions.
Dr. Burgess said that, although health has improved for the general population, it has not done so for minority populations, and the gap is widening. He also said that enrollment of minority students in medical schools and the numbers of minority investigators being supported under NIH R01 grants are declining. In response, Dr. Zerhouni said that efforts to reduce health disparities are an important part of the NIH program and a driver of performance. Dr. Kirschstein said the NIH has tried to obtain data about researchers from minority populations. However, because such information is provided on a voluntary basis as part of grant applications, it is incomplete. She also said that several NIH programs to support the careers of minority investigators have proved frustrating, and new ideas for doing so are welcome. Dr. Francis said cutbacks in programs at the Health Resources and Services Administration to support health professionals are making the problem worse. In addition, his discussions with members of the Association of Minority Health Professional Schools suggest to him that the new NIH National Center on Minority Health and Health Disparities could provide an important mechanism for addressing these problems.
After Dr. Zerhouni described key priorities that are part of the new Road Map, Dr. Masters commented on the R01 grant mechanism, noting that it promotes individuals to develop ideas and recommending that the NIH remain flexible as it encourages investigators to develop "enabling" research. In response, Dr. Zerhouni said that "glue" grants and development of specific disease consortia, such as the Alzheimer's Disease Network, are good examples of innovative approaches being taken by the NIH.
Dr. Smarr said that assembling multidisciplinary teams is not necessarily the equivalent of promoting "big science" and that smaller assemblages could do productive multidisciplinary research. Dr. Dzau said that reviewing initiatives at the various Institutes and Centers of the NIH could be instructive in determining which innovative, multidisciplinary approaches have proved particularly successful.
In response to a comment from Dr. Francis about criticism of the impact of doubling the NIH budget on health overall, Dr. Zerhouni said that recent experience points to the difficulties in obtaining compliance among populations and the need for research to understand behavioral drivers that could improve such compliance. Dr. Zerhouni also said that one needs to ask whether diverting resources from the NIH would resolve outstanding health problems. He said the NIH is not wasting money, and it is important for the NIH to continue to seek information that will address the many health questions that remain unresolved.
Dr. Carter said the matrix approach of the NIH for identifying priorities is valuable and is similar to the way industry approaches priority setting. He said the biggest payoffs come from progress with problems that are high risk and long term and noted that progress in a specific research area can shift as particular challenges fit within that matrix. Dr. Zerhouni agreed that progress with challenges in one quadrant of the matrix can lead to developments that address or solve challenges elsewhere within the matrix.
In prefatory remarks, Dr. Zerhouni introduced Dr. Alan Guttmacher to discuss publication on December 5 of a report describing the sequence of the mouse genome and its biological consequences. Dr. Guttmacher said several research groups were involved in the mouse genome-sequencing project and that this information will provide insights into efforts to understand the human genome.
Discussion of training and the scientific workforce
Dr. Zerhouni introduced the first of two issues to be considered for further study by the ACD — namely, postdoctoral training and the aging of this component of the scientific workforce. Compared with a decade or more ago, it takes an average of two additional years for a young scientist to complete a Ph.D., and many of them are spending many more years at the postdoctoral level, not undertaking independent research as principal investigators until they are nearly 40 years old. Several studies by the National Academy of Sciences (NAS) further document these trends, and recent experiences within the Intramural program of the NIH are consistent with this trend, according to Dr. Zerhouni. He said academic institutions now tend not to expand faculty positions but to encourage faculty to recruit more postdocs, who are less expensive to employ.
Dr. Zerhouni requested comments from ACD members about what the NIH might do about these issues. In response, Dr. Cassel, who serves on a NAS National Research Council (NRC) Committee on National Needs for Biomedical and Behavioral Scientists, said the committee has identified several important issues to address. One is to determine whether to encourage the continued use of NIH R01 funds by universities to support postdocs as part of their research staffs. This issue revolves around whether this system is beneficial to science in general and to postdocs in terms of furthering their careers.
Dr. Baldwin said the NIH responded to an earlier NRC report that addressed these issues and noted that the NIH is not the only institution with an important part to play in shaping the scientific workforce. She said the slower growth rate of faculty positions leads inevitably to a larger number of scientists remaining in postdoc positions in academic settings. Also, foreign postdocs are not eligible to receive NIH National Research Service Awards (NRSA), which represent an important mechanism for supporting researchers during the early stage of their careers. However, as those researchers become older and remain in postdoc positions, their needs change and they seek to obtain more benefits. In approaching these issues, a systems approach is needed, and the NIH is only one of several players needed to resolve some of these questions, according to Dr. Baldwin. She agreed with Dr. Cassel that academic health centers need to be involved in these efforts. She also said recent reports suggest that newer scientists should consider alternative career tracks rather than simply aiming at obtaining tenure-track faculty positions.
Dr. Kirschstein said the NIH recognized 10 or 15 years ago that postdocs were taking longer to find permanent jobs and that they often were not being optimally mentored. In any case, they represent an important component of the scientific workforce and one that sometimes is exploited.
Dr. Pickett said that growing numbers of postdocs express an interest in careers in industry, but they seldom have opportunities for exposure to such careers during their training. He said universities need to do a better job of providing trainees with information about such opportunities. In response, Dr. Baldwin agreed that values and career structures need to be reconsidered. She also said that, although the NIH has collected little career development information from trainees, there are plans to begin collecting such information electronically and to compare the impacts of several training programs, including NRSA.
In response to a question from Dr. Masters about postdocs paying back money received under the NRSA program, Dr. Baldwin said that the second year on support under NRSA is counted as paying back for the first year of such support, which represents a dramatic change from earlier policies. Dr. Masters also asked about plans to increase salaries for postdocs, including those paid under R01 grants. In response, Dr. Baldwin said the NIH recommends but cannot determine appropriate stipend levels paid to postdocs at other institutions.
Dr. Burgess said that increases in budgets for the NIH led to increases in training of scientists, with a doubling since 1990 in the number of Ph.D.s in the natural sciences. Moreover, since 1985, larger numbers of non-U.S. citizens who received Ph.D.s in this country are choosing to remain here rather than return to their native countries. Although these increases in the numbers and in the quality of Ph.D.s benefit science, it is also risky, making training a very complex issue. Dr. Baldwin agreed, noting that different cultures, infrastructures, and other factors complicate efforts to analyze the impact of NIH training programs on global efforts in the sciences.
In response to a question from Mr. Ullian about the availability of Ph.D.s to work in industry, Dr. Pickett said it is difficult to generalize about such matters. However, supplies of Ph.D.s trained in organic chemistry and in working with in vivo systems are chronically short.
Dr. Zerhouni said ACD members need to focus on whether and to what extent the NIH should take charge of such training needs. Perhaps it is time to recognize that postdoctoral researchers are part of the scientific workforce, yet to what degree the NIH should attempt to shape the size and scope of this workforce component remains uncertain. One step the NIH can consider is to permit postdocs with sufficient experience to apply for their own R01 grant support, but this step would require the cooperation of academic institutions.
In response, Dr. Cassel, Dr. Dzau, and others said the NIH should delve into these training issues by seeking input from others who are involved in these matters, including postdoctoral researchers, faculty, and administrators from universities, organizations such as the Association of American Universities and the Association of American Medical Colleges, and representatives from pharmaceutical and biotechnology companies. Dr. Masters said postdocs should not be precluded from support under R01 grants but that limits might be set for how many years they can be supported in this way. She also said some postdoctoral researchers are being permitted to apply independently for R01 grants and are given appointments as research-assistant professors. Dr. Brody said he was wary of trying to micromanage this marketplace phenomenon.
In response to a question from Mr. Williams about the potential impact of aging postdocs on the quality of research being done, Dr. Zerhouni said there appears to be only anecdotal information to address such questions. Dr. Burgess said high-quality Ph.D.s will be discouraged from research career tracks if their best prospects are to remain in postdoc positions for extended periods. Dr. Zerhouni agreed, saying that individuals will choose alternative careers if the risk-reward of remaining in research is deemed too low.
Dr. Zerhouni and several members of the ACD agreed that training discussions should continue with the participation of university, industry, and representatives of other interested parties, including postdocs themselves, with the aim of better understanding the dynamics of this system. Although several members of the ACD said it would be helpful if the biotechnology and pharmaceutical industries could project manpower needs, other ACD members pointed to volatility in industry. In addition, Dr. Carter said that Ph.D.s need to adapt and be retrained for some of the tasks and challenges they encounter in industry settings.
Discussion of multidisciplinary research teams
Dr. Zerhouni suggested that several factors could be impeding the development of multidisciplinary research teams, including the fact that academic institutions do not reward such teamwork and that NIH training programs do not foster the development of quantitative and computer skills. One possibility is that market forces will bring about the development of such multidisciplinary teams.
Dr. Smarr said recent projections about needs in bioinformatics have vastly underestimated the growth in this sector. In an earlier study, the President's Information Technology Advisory Committee concluded that the National Science Foundation (NSF) was not providing appropriate incentives to foster computer science research and that universities needed to encourage teamwork as well as efforts by individual investigators. These recommendations led the NSF to form the Information Technology Research program, which issues large, medium, and small grants. This program stimulated academic computer science researchers to form teams. Separately, the panel members who developed the NIH Biomedical Information Science and Technology Initiative report recommended more modest approaches for encouraging the development of multidisciplinary teams with strong bioinformatics components. One critical need was to establish centers where such teams could form and the necessary cross-training could occur. For that effort to succeed, it also will be necessary for the NIH to change how reviews of such proposals are conducted.
Dr. Paul asked whether there are lessons to draw from successful, NIH-supported teamwork efforts in genomics.
Dr. Cassel said researchers at academic institutions are forming local and regional multidisciplinary teams to respond to the NIH biodefense initiative. However, those researchers are learning that the NIH requires each such team to identify a single principal investigator, a stipulation that causes problems among many universities from which those team members typically are drawn. Dr. Masters said members of the research community need to deal with universities sometimes establishing sub-par multidisciplinary programs.
Dr. Dzau said universities typically promote faculty members on the basis of their individual achievements, and this practice is a major deterrent to the development of multidisciplinary research teams. Dr. Paul agreed, saying that interdisciplinary research is very common in industrial settings but can be a challenge to accomplish in academic settings.
In response, Dr. Zerhouni said the NIH prepared a briefing paper on these issues, and it contains several potential means for overcoming these obstacles, including establishing a prestigious multidisciplinary research award and also developing infrastructure in academic medical centers. To what degree should the NIH force these issues rather than allow market forces to drive the changes? Dr. Brody suggested the NIH review how particle physicists, who often work in large teams, have dealt with such issues. Dr. Burgess urged that the NIH continue to sponsor investigator-initiated research, noted that much of the genome project was done by technicians rather than graduate students and postdocs, and said that the NSF sponsors proportionately more multi-institutional research teams. He also said that, if the NIH wants to encourage researchers to form such teams, it needs to sponsor more large-center grants.
Dr. Smarr said that multidisciplinary teams need not be large. Instead, they may consist of a few members drawn from different disciplines who choose to work on problems that are too complex to solve single-handedly. These teams could still be investigator initiated. He also said the NSF has implemented such programs in several areas, including fostering the development of science and technology centers, engineering research centers, and computer sciences research centers. Dr. Burgess said these NSF centers are required to include educational components that prepare graduate students and postdocs for nonacademic careers.
In response to a question from Dr. Zerhouni about whether the NIH has any specific impediments to developing similar programs, Dr. Baldwin said the NIH programs are flexible, particularly in the area of bioengineering. Thus, although the Bioengineering Research Partnership is built on familiar mechanisms of the NIH, it conveys explicitly to academic institutions and members of the research community that the NIH is seeking to encourage the development of multidisciplinary teams. Dr. Francis said the NIH has additional experiences in developing specialized centers that can be reviewed as it seeks to improve and broaden this concept.
Dr. Zerhouni asked ACD members to comment on whether the NIH or universities need to change policies to foster the development of such multidisciplinary research teams.
Dr. Dzau said the NIH could identify areas on specific diseases or technologies to which multidisciplinary research should be directed. Other issues, such as who receives credit, how funds are allocated, and who is designated as the principal investigator, could be addressed separately. When it comes to evaluating proposals for multidisciplinary projects, evaluations also need to be multidisciplinary in character.
Dr. Zerhouni questioned what might be lost if multidisciplinary research teams were not formed. He said part of the problem is a shortage of qualified people to form such teams. In response, Dr. Pickett said that perhaps there are no NIH initiatives that require such teams. Dr. Carter said putting multidisciplinary teams together can lead to a creativity that otherwise would not have occurred. Dr. Zerhouni agreed with Dr. Pickett and others that it makes more sense to start with specific scientific challenges before forcing the development of multidisciplinary teams on an abstract basis.
Dr. Smarr said the NIH Biomedical Informatics Research Network is working well as it builds a national software network and data repository through a multi-institutional faculty network.
Dr. Zerhouni noted that former NIH Director Dr. Harold Varmus established the NIH Council of Public Representatives (COPR) in 1998, prompted in part by a report from the IOM recommending that this step be taken to facilitate interactions between the NIH and the general public. Dr. Zerhouni said he met with the COPR for the first time in October 2002 and decided that better linkages are needed between the ACD and the COPR. He then introduced three members of the COPR — Mr. Larry Sadwin, Ms. Debra Hall, and Mr. Bob Roehr — to describe recent COPR activities and priorities.
Mr. Sadwin said the purpose of the COPR is to provide advice to the NIH Director on matters related to research, NIH policies and programs, and public interest and participation in those activities. The COPR also serves as a sounding board for the NIH Director, who appoints the 21 members of the council. COPR membership is diverse and includes patients, family members, health care professionals, communicators, and representatives of science and health-related societies.
Ms. Hall said COPR members have established and served on several working groups addressing several subjects, including health disparities, human research protections, outreach to other public members serving on NIH advisory committees and councils, and advice to the IOM on revising the NIH organizational structure. COPR members also have participated in NIH budget discussions, served on review and evaluative panels, and participated in scientific meetings. They have helped to present information about the NIH to various groups on site visits in several states. During their October meeting, COPR members took several actions, including developing testimony to IOM, identifying priority-setting issues for the Agenda Work Group, and establishing improved communications with public members on other advisory bodies within the NIH.
Mr. Roehr said the COPR is seeking to encourage public input at every level of decision making within the NIH, particularly in setting research priorities and in obtaining patient perspectives in clinical trials. In meeting the extraordinary challenge of communicating information about the NIH to the American public, the COPR is seeking to network with other advisory councils throughout the NIH.
In response to a question from Dr. Dzau about how the COPR communicates to the public, Mr. Roehr said some COPR members make use of the organizations they represent, while he communicates to the public on NIH-related matters as a journalist. Mr. Sadwin said an important role of the COPR is to facilitate reciprocal communication between the NIH and the public.
In response to a question from Dr. Dzau about efforts by the COPR to communicate about the NIH with community groups, Mr. Roehr said a long-range goal for the COPR is to become a training program for members of the public who will serve on federal and local advisory boards, including institutional review boards. In response to a question from Dr. Francis about the composition of the COPR, Dr. Kirschstein said its members were chosen on the basis of widely advertised, open nominations. The initial list was evaluated by internal and external advisors to the NIH and pared down; then, former NIH Director Dr. Varmus appointed 21 individuals to serve initially for two years. A similar procedure is under way, and Dr. Zerhouni will soon be appointing 9 members to replace those COPR members whose terms are expiring. Dr. Kirschstein said that, although COPR members may be drawn from health-advocacy organizations, they are expected to set aside such interests to serve the needs of the general public.
Dr. Zerhouni pointed out that the ACD includes one-third public representatives as do other advisory councils within the NIH, which means the NIH has access to a great deal of input from advocacy groups and the public. Nevertheless, a recent survey indicates that only 6 percent of Americans identify the NIH as the institution that supports the most biomedical research in the United States, whereas another 22 percent cite other institutions as playing that role. Hence, the NIH needs to improve its communications with the public.
In response to a question from Dr. Zerhouni about improving NIH communications with the public, Ms. Hall said his earlier presentation of the impact of the NIH investment in health represents a good approach in terms of language and examples the public can appreciate. Mr. Roehr added that the COPR identified five important principles in its report to IOM, including empowering patients and the public as full partners in research, promoting transparency, treating the whole patient and not just a disease, strengthening the link between bench and bedside research, and enhancing communications as a way of integrating research. Mr. Sadwin said the Institutes within the NIH need to speak with a common voice.
Ms. Hall said the COPR and public members of other NIH advisory councils are planning to convene in a summit meeting. Dr. Zerhouni said the NIH staff and COPR members are also taking steps to coordinate public outreach efforts.
The ACD of the NIH convened on December 5, 2002, to meet new Institute Directors, to review recent events affecting the NIH, to learn about Dr. Zerhouni's new Road Map for the NIH and his new approach to presenting information about NIH accomplishments to Congress and the public, and to consider issues such as postdoctoral training, institutional barriers to forming multidisciplinary teams, and the role of the NIH Council of Public Representatives.
The ACD acknowledged and commented on these programs and issues and agreed to engage in broad-based discussions of training needs and to consider novel means for overcoming barriers to multidisciplinary research.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Ruth L. Kirschstein, M.D., Executive Secretary, Advisory Committee to the Director, Deputy Director, NIH
Elias A. Zerhouni, M.D., Chairman, Advisory Committee to the Director, Director, NIH