January 12, 2004 Meeting Minutes


Executive Summary

The 87th meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on January 12, 2004. NIH Director Dr. Elias Zerhouni began by introducing new members of the committee as well as the liaison representative from the NIH Council of Public Representatives (COPR). He later mentioned several committee members who are leaving ACD but said that Mr. Phillip Williams was reappointed for another three years.

Dr. Zerhouni described several recent key events, including public announcement of the NIH Roadmap, the NIH being recognized for leadership in its diversity practices, the NIH having supported several of the 2003 Nobel recipients, NIH participating in a global health collaboration, and, locally, Dr. Zerhouni participating in a town hall meeting with employees of the NIH. He also introduced several new senior staff members to the ACD and mentioned several senior staff members who recently left the NIH.

Dr. Zerhouni summarized recent and forthcoming interactions with Congress, including a hearing in October 2003 to review how the NIH manages its grants program and a hearing scheduled for later in January to consider conflict-of-interest issues. He said that an internal review revealed that all consulting arrangements involving NIH staff members were handled with appropriate recusals but noted that an independent oversight panel would be asked to further review such matters, in part to address any questions about appearances of conflict of interest. Other evaluations of programs at the NIH are under way, including a review of forthcoming Intramural clinical research activities, basic behavior and social science research programs, and of policies affecting postdoctoral-level researchers. Dr. Zerhouni said that, because the fiscal year (FY) 2004 appropriation bill for the NIH is pending, current funding levels remain at FY 2003 levels.

NIH Deputy Director Dr. Raynard Kington described efforts that involve five working groups with specific assignments to improve decision-making procedures and to review NIH-wide policies. In addition, an administrative restructuring advisory committee recently presented a plan to Dr. Zerhouni and to the Secretary of Health and Human Services, and its recommendations are being implemented. Reflecting a general policy at the NIH to review performances of Institute and Center directors at five-year intervals, four such reviews are to be completed by June 2004.

Dr. Zerhouni introduced two recently appointed Institute directors, Dr. Story Landis, Director of the National Institute of Neurological Disorders and Stroke, and Dr. Jeremy Berg, Director of the National Institute of General Medical Sciences. They presented brief overviews of principal concerns, programs, and research highlights pertinent to their respective Institutes.

Dr. Edward Benz summarized recent activities of the NIH Director's Blue Ribbon Panel on the Future of Intramural Clinical Research, a panel that he co-chairs with Dr. Joseph Goldstein. The panel is recommending that a new research agenda be developed for the Intramural Clinical Center, its oversight structure be revised, new training and career path programs be developed, and the study of rare diseases and the development of novel therapeutics be emphasized. The panel also recommends several changes in oversight and administration of Intramural Clinical Center research programs, including appointment of a new NIH Deputy Director for Clinical Research.

Dr. Thomas Ansfield and Mr. Larry Sadwin described their recent interactions with the NIH COPR and summarized its recent deliberations and activities, including establishment of a steering group to focus on issues relevant to the NIH and public trust.

Dr. Zerhouni summarized major challenges, themes, and implementation steps embodied in the NIH Roadmap, including examples such as the NIH Director's Pioneer Award Program, investments in an integrated database covering clinical trials, and other efforts being undertaken by nine implementation groups. NIH Assistant Director for Roadmap Coordination, Dr. Dushanka Kleinman, further described efforts to manage implementation of the Roadmap, including additional working groups, coordination and communication efforts, and ongoing searches for new personnel, such as a senior advisor for NIH clinical research.

NIH Associate Director for Budget, Mr. Richard Turman, briefly summarized the status of the NIH budget, noting that because of a continuing resolution in lieu of an appropriation bill for FY 2004, the NIH is basing its current spending on one-third of FY 2003 levels. Meanwhile, the President's budget request for FY 2005 is to be announced on February 2.

NIH Senior Advisor to the Director Dr. Ruth Kirschstein summarized recent efforts to reassess NIH postdoctoral training practices and policies. A work group of the ACD that is focused on these issues convened in October. Its report asks the ACD to consider several initiatives, including establishing offices at research institutions for dealing with postdoctoral-related issues, developing guidelines for uniform benefits for postdoctoral fellows, establishing data-collecting mechanisms to survey postdoctoral experiences, and providing portable grants to support postdoctoral researchers.

Finally, Dr. Zerhouni described several noteworthy NIH-supported research advances, including continuing genome-related activities, stem-cell research advances, and efforts to develop a vaccine to protect against Ebola virus, identification of depression-associated genes, and improved treatments for breast cancer patients.

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Director's Report

The 87th meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on January 12, 2004. NIH Director Dr. Elias Zerhouni welcomed two new ACD members, Dr. Raghavendra Vijayanagar, a cardiovascular surgeon from Florida who performed the first heart transplant in Tampa in 1985, and Dr. Sandy Williams, Dean of the Duke University School of Medicine, who is a cardiologist doing research in molecular genetics and believes in physician scientists. Dr. Zerhouni also re-introduced Mr. Larry Sadwin, who serves as liaison to the NIH Council of Public Representatives (COPR). Dr. Zerhouni mentioned several ACD members who could not attend the meeting.

Dr. Zerhouni described several noteworthy events since the June 2003 ACD meeting. For example, as part of introducing the NIH Roadmap, Dr. Zerhouni and others met with 150 constituents at the NIH on September 29, and then held a press conference on the following day. He said that Dr. Dushanka Kleinman, who is Deputy Director of the National Institute of Dental and Craniofacial Research (NIDCR), is joining the Office of the Director temporarily to lead efforts to implement recommendations within the Roadmap.

On October 15, the NIH received a Diversity Best Practice Leadership award at the Diversity and Women Leadership Summit, and it was the only federal agency so honored at that meeting, according to Dr. Zerhouni. He said that the NIH Office of Equal Opportunity and Diversity Management, which is directed by Mr. Lawrence Self, deserves credit for this honor. He also said that the NIH continues to make diversity a priority, particularly in health research.

Dr. Zerhouni noted that the 2003 Nobel prizes went to several scientists with connections to the NIH, including the prize for physiology and medicine that recognized a physicist and chemist for their contributions to magnetic resonance imaging, and the prize in chemistry, which was awarded to two physician scientists, Dr. Peter Agre and Dr. Roderick MacKinnon, who were NIH trainees.

The NIH is continuing to work on Grand Challenges in Global Health through the Foundation for the NIH and with the Gates Foundation, which provided $200 million for research on underfunded global health challenges, according to Dr. Zerhouni. For instance, these efforts are supporting research on vaccines to protect against diseases that occur during childhood and also on methods for controlling insects that serve as vectors for several diseases. This initiative also will be trying to develop accurate means for measuring disease and health status in developing countries. Some of these efforts in priority setting are similar in theme, albeit not in scope, to those faced by the NIH on a national level.

Dr. Zerhouni said that the NIH recently convened another town hall meeting of employees, a follow-up to an earlier one at which A-76 competitive sourcing for administrative activities was the primary focus. Although that earlier meeting provoked some anxiety, so far the NIH has won two competitions for services, one involving grants management and the other scientific facilities management. Since then, concerns over these out-sourcing issues have subsided, and discussions over parking dominated the more recent town meeting. Dr. Zerhouni said that similar meetings between employees and senior staff would be held on a regular basis to improve communications within the NIH.

Dr. Zerhouni and other officials from the NIH attended a joint House-Senate hearing on October 2, 2003 to consider a report from the Institute of Medicine (IOM) that recommends several administrative and other changes to enhance the vitality of the NIH. During the hearing, questions were raised over NIH grants supporting several specific projects in sexuality research, leading to a review of this field for its public health relevance. Dr. Zerhouni said that this recent review supports the peer review decisions that led to issuance of those grants. For instance, one such project being conducted by an American Indian is studying "two-spirited Indians" and represents a first-ever attempt to understand members of this stigmatized community within the context of tribal culture.

Officials from the NIH were scheduled to participate in a Senate hearing on January 22, 2004, following allegations that consulting being done by researchers at the NIH represents a conflict of interest. Dr. Zerhouni called the matter one of urgency because it reflects on the integrity of the NIH.

Dr. Zerhouni's immediate response to those allegations was to conduct a thorough review and to deal with these issues transparently. He said that a preliminary review reveals no evidence that any patient was harmed in any clinical trial, that all consulting agreements were disclosed appropriately and had been reviewed for ethical considerations, and that there has been no inappropriate influence on decision making at the NIH. He also said that collaborations between researchers at the NIH and those in the private sector are valuable, particularly for translating basic scientific findings into tangible products and practices that benefit patients.

However, because of continuing concerns that such practices might give an appearance of conflict of interest and with some other unsettled questions about setting limits on consulting relationships, a thorough review by an outside panel is warranted, according to Dr. Zerhouni. Members of the review panel will be asked to consider several questions, including whether general federal guidelines are sufficient for the NIH and whether current practices are adequate or need changing. This independent review panel will draw its members from outside the NIH but will be connected to the ACD for administrative purposes.

Meanwhile, a trans-NIH committee will begin immediately to review policy and develop a guidance document for consulting relationships. These efforts will go beyond a review that was already under way and being directed by Dr. Michael Gottesman that is considering ethical requirements relevant to human subjects research within the Intramural Program.

Dr. Zerhouni next reported on recent successes recruiting individuals to the NIH, including Dr. Story C. Landis to become the Director of the National Institute of Neurological Disorders and Stroke (NINDS), Dr. Jeremy M. Berg to be Director of the National Institute of General Medical Sciences (NIGMS), Mr. Richard Turman as the Associate Director for Budget, and Dr. Norka Ruiz Bravo as the Deputy Director for Extramural Research. He noted that Dr. Landis had served as the scientific director of the NINDS intramural program, Dr. Berg had been a fellow colleague while Dr. Zerhouni was at the Johns Hopkins University School of Medicine, Mr. Turman's extensive experiences at the Office of Management and Budget and in staff positions for members of Congress are an important asset, and that Dr. Bravo, who is helping to re-organize the grants management system, helped the NIH staff to win a competition to continue managing these programs internally. Dr. Zerhouni also thanked Dr. Belinda Seto who served as the Acting Deputy Director for Extramural Research before becoming Deputy Director of the National Institute for Biomedical Imaging and Bioengineering.

Other appointments to senior positions are pending, according to Dr. Zerhouni. A search is under way to replace Dr. Claude Lenfant, who retired on August 30, 2003, after serving as the Director of the National Heart, Lung, and Blood Institute (NHLBI) for more than 20 years. The search committee co-chairs are Dr. Francis Collins, who is the Director of the National Human Genome Research Institute, and Dr. T.-K. Li, Director of the National Institute on Alcohol Abuse and Alcoholism. Dr. Barbara Alving is the Acting Director for the NHLBI.

Dr. Zerhouni said that Dr. Kenneth Olden, the Director of the National Institute of Environmental Health Sciences and of the National Toxicology Program, announced plans to retire on July 29. On September 4, Dr. Elie Ehrenfeld announced plans to step down as Director of the Center for Scientific Review (CSR), where Dr. Brent Stansfield will serve as Acting Director. In addition, Dr. Gerry Keusch, the Director of the Fogarty International Center announced in November that he would step down, and Dr. Sharon Rinko, who was the Deputy Director, will serve as Acting Director.

Dr. Zerhouni referred to several panels that are evaluating programs at the NIH, including the NIH Director's Blue Ribbon Panel on the Future of Intramural Clinical Research that is co-chaired by Dr. Edward Benz and Dr. Joseph Goldstein; a Basic Behavioral and Social Sciences Research Working Group that is chaired by Dr. Linda Waite; and a Work Group of the ACD examining training and career opportunities at the postdoctoral level that is co-chaired by Dr. Ruth Kirschstein and Dr. David Burgess.

Dr. Zerhouni said that because the NIH appropriation for fiscal year (FY) 2004 is not yet set, the NIH is operating under a series of continuing resolutions. This situation could become problematic, particularly if it continues beyond January.

Dr. Zerhouni acknowledged and thanked those members of the ACD whose terms are expiring, including Dr. Christine Cassel, Dr. Thomas Cech, and Dr. Donald Wilson. He also said that Mr. Phillip Williams, whose current term is expiring, would serve for an additional three years.

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Deputy Director's Report

Dr. Zerhouni introduced Deputy Director Dr. Raynard Kington. Dr. Kington reported on three activities: a steering committee, the Administrative Restructuring Advisory Committee (ARAC), and reviews of Institute and Center directors.

At Dr. Zerhouni's request, Institute and Center directors early in 2003 began considering means for improving corporate — that is, agency-wide — decision making at the NIH, according to Dr. Kington. They also endorsed a shared governments model with a 10-member steering committee that is developing recommendations for governance issues at the NIH. The steering committee, which includes 5 working groups, will not consider scientific priority-setting issues, which remain the responsibility of the Institutes and Centers, according to Dr. Kington. The working groups are: management and budget, chaired by Dr. Stephen Katz and co-chaired by Mr. Charles Leasure; intramural activities, chaired by Dr. Francis Collins and co-chaired by Dr. Michael Gottesman; extramural activities, chaired by Dr. Stephen Straus and co-chaired by Dr. Ruiz Bravo; information technology, chaired by Dr. Lawrence Tabak and co-chaired by Dr. Gilman Grave; and facilities, chaired by Dr. Richard Hodes and co-chaired by Dr. Leonard Taylor. A human resources subcommittee of the management and budget workgroup is chaired by Dr. Barbara Alving and co-chaired by Dr. Robert Hosenfeld. The steering committee began meeting in September 2003, considering issues such as allocation of personnel across the NIH and a loan repayment program.

ARAC was formed in April 2003 and has reviewed several NIH functions, including acquisitions, budget, equal employment opportunities, finance, facilities, and grants management, while seeking means to improve efficiencies and to develop performance metrics, according to Dr. Kington. ARAC presented its recommendations in a report to Dr. Zerhouni that was also sent to Health and Human Services Secretary Tommy Thompson. After that report was approved, the NIH began to implement its recommendations and also arranged with the National Academy of Public Administration to consult on such matters.

Dr. Kington said that Dr. Zerhouni recently reactivated a procedure whereby each Institute and Center director is reviewed every five years. This review procedure also was expanded to include directors in programmatic offices within the NIH Office of Director, including the Offices of Research on Women's Health, Disease Prevention, and Rare Diseases. Each panel will be chaired by someone from the extramural community, will include three or four additional members, and will take about six months to complete each review. Those being reviewed this year include Dr. Stephen Katz, Dr. Stephen Straus, Dr. James Battey, and Dr. Vivian Pinn.

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New Institute Director Presentations: NINDS

Dr. Zerhouni introduced Dr. Story C. Landis, who is Director of the National Institute of Neurological Disorders and Stroke (NINDS).

Dr. Landis said that the mission of NINDS is to reduce the burden of neurological diseases, of which there are more than 600 varieties, ranging from those with a relatively high prevalence, such as epilepsy, multiple sclerosis, stroke, and Parkinson's disease, to a very large number of rare diseases, many of which involve inherited metabolic abnormalities. Dr. Landis said that new treatments were recently developed for several of these diseases, including epilepsy, multiple sclerosis, and stroke. Moreover, recent findings indicate that deep-brain stimulation has a significant impact on the quality of life for patients with Parkinson's disease.

Other treatments can be expected soon, thanks to insights from ongoing research, according to Dr. Landis. For instance, because researchers now realize that the circuitry in the adult brain is not fixed, new strategies for rehabilitation are being pursued. In addition, the recognition that there are endogenous stem cells in the adult brain raises the possibility that they can be harnessed to restore lost functions. Alternatively or additionally, it may be possible to achieve repair with exogenous stem cells. Moreover, researchers are determining the three-dimensional structures for several membrane-resident proteins that serve as ion channels within the nervous system; in turn, this information will be used to develop drugs to treat diseases such as epilepsy in which ion channels are disrupted. Researchers are identifying genes that are associated with specific neurologic diseases, including Huntington's, Alzheimer's, and amyotrophic lateral sclerosis (ALS). For example, four specific genes are now associated with Parkinson's disease. Further, investigators are applying magnetic resonance imaging to view and analyze the anatomy and functions of the brain. All of these advances make us optimistic about the development of effective therapeutic strategies.

Because many therapies do not have obvious roots in other advances, NINDS researchers face a challenge in applying basic science findings from genetics, imaging, and other activities to the development of new therapies, according to Dr. Landis. Thus, several programs for this purpose are being developed, including one that provided supplemental support, enabling researchers to test more than 1,000 drugs that are already approved by the Food and Drug Administration (FDA) in a battery of cell culture-based tests that model neurodegenerative diseases. For instance, a cephalosporin-type compound identified on this basis and further tested in a preclinical model of ALS is headed to a clinical trial. Based on the success of this pilot program, NINDS has established a contract to conduct high-throughput screening of a larger battery of compounds.

Another grant program will enable investigators to develop promising leads from basic science and translate them into therapeutic strategies up to an application to the FDA for an investigational new drug application (IND), according to Dr. Landis. One of the seven funded new programs involves developing a gene delivery strategy for treating patients with Parkinson's disease. To increase the number of investigators who are interested in translational research, NINDS has created a program that involves mentoring Ph.D.s over five-year periods that want to conduct translational research in the neurosciences.

NINDS also is facing a question of how to attract and retain physician scientists, according to Dr. Landis. An informal survey several years ago indicated that recent numbers of applications from physician scientists for research support were dropping, whereas physician scientists who had trained more than a decade earlier were continuing to conduct research, based on higher numbers of them obtaining R01 grant support. Although these survey results are not statistically significant, they suggest that fewer physicians are being attracted into neurological research positions, and only some of those already in the field continue to pursue such research.

To remedy this situation, NINDS is instituting two programs, according to Dr. Landis. The first invites medical students who are doing research to visit the NIH and to meet with successful physician scientists who are conducting basic, translational or clinical neuroscience research and NINDS staff to encourage them to consider this as a career goal. The second is to increase the number of career-mentored trainees and to maintain contact with them during the early stages of their careers. She said that both these programs involve public-private partnerships, emphasizing the importance of the community in influencing these trainees. Another important point is that NINDS plans to increase the number of K23 awardees, to support those doing clinical research, and to add training programs that enable young investigators to come to the NIH or other sites for periods of several weeks to develop clinical protocols. Developing means to measure the effectiveness of these training programs will be another important component of these efforts, according to Dr. Landis.

Dr. Landis mentioned two other efforts that will benefit NINDS. One entails developing broader collaborations with several other Institutes engaged in neuroscience research. Earlier, for example, she developed a collaborative intramural program with her former counterpart at the National Institute of Mental Health (NIMH) that included a seminar series, a website based on research interests, and plans for using the new Porter Neuroscience Research Building that allocate space based on research discipline rather than on Institute affiliation. These efforts also led to development of multidisciplinary teams that cut across institutional boundaries.

Joint projects are in progress or being developed for the extramural programs of NINDS, according to Dr. Landis. For example, former NINDS Director Zach Hall led the several Institutes supporting research in neuroscience to pool resources and establish a single predoctoral training grant program. A more recent project brings together four Institutes to support a database for images documenting child brain development. Other collaborative projects are being catalogued, including funding of three microarray facilities and establishing joint core grants to support infrastructure needs in neuroscience research.

NINDS also is seeking to develop stronger interactions with health voluntary organizations, according to Dr. Landis. She said that, although such interactions sometimes were adversarial, she has met with representatives of more than 40 of 157 organizations so far, and expects relationships with many of them to become much more effective than in the past.

Dr. Landis said that NINDS will need to strike an appropriate balance among basic, translational, and clinical research efforts, as well as a balance between big and little science and also hypothesis-driven and discovery science. NINDS also needs to determine which research areas are being overlooked and to be creative in identifying and studying new areas, while remaining accountable for how resources are invested.


In response to a question from Dr. David Burgess about recent experiences of trainees in the neurosciences, Dr. Landis said that a previous director of NINDS changed the K awards from five- to three-year terms in an effort to accelerate the development of trainees into full-time investigators. However, this change was not successful. A further complication is that few medical students are choosing neurology as a field, meaning there are fewer candidates to pursue careers as physician scientists in the neurosciences. Dr. James Battey, Jr., Director of the National Institute on Deafness and Other Communication Disorders (NIDCD), and Dr. Nora Volkow, Director of the National Institute on Drug Abuse, said that similar problems are being seen in other neuroscience medical specialties as relatively few young physicians enter specialty practices and fewer of them choose to pursue careers in research. Dr. Paul Sieving, Director of the National Eye Institute (NEI), said that health care reimbursement issues are constraining efforts by academic departments to train physician scientists. NEI is offering a K24 award that will enable trainees to take research funds with them when they begin tenure-track positions.

In response to a comment from Dr. Sanders Williams about a significant percentage of recipients of K awards never applying for R01 support, Dr. Landis said that such trends led NINDS to begin meeting intensively with trainee investigators to find concrete ways of encouraging them to apply for such grants and to pursue research careers.

Dr. Steven Paul praised Dr. Landis for her approach to supporting translational research, and he encouraged her to contact companies in the private sector to pursue collaborative efforts to develop new drugs. Dr. Landis said that such efforts are under way along with other efforts to identify drugs for treating rare diseases. Dr. Zerhouni pointed out that the national molecular libraries that are being developed as part of the Roadmap are not designed for direct drug-discovery purposes but to provide reliable tools for identifying inhibitors of particular proteins or metabolic functions. Dr. Paul noted that identifying molecular probes can be a very costly undertaking and often depends on luck.

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New Institute Director Presentations: NIGMS

Dr. Zerhouni introduced Dr. Jeremy M. Berg, Director of the National Institute of General Medical Sciences (NIGMS).

Dr. Berg said that the original mission statement for NIGMS, which specifies that it work on basic science with significance for two or more national research institutes, is very compatible with several principles embodied in the recent Roadmap for the NIH. Further, the four divisions within NIGMS each have two closely linked components, namely research and training, and the NIGMS program emphasizes investigator-initiated R01 grants. In FY 2003, NIGMS funded 3,700 such grants, representing 60 percent of its total budget and 85 percent of its research project grant budget. In its 42 years, 55 Nobel Laureates have received grant support from the NIGMS.

Dr. Berg said that some relatively recent programs at the NIGMS anticipated elements of the Roadmap. For example, glue grants that were started in 2000 enable investigators at several academic institutions to form research consortia to study particular biological questions. The first such consortium, called the Alliance for Cellular Signaling, is led by Dr. Al Gilman and supports investigators who are analyzing cellular signaling pathways in a particular cell type. There are now four additional glue grants supporting research consortia focusing on cell migration, inflammation and host responses, functional glycomics, and lipids. Although this program is relatively new, it appears to be effective, and one of its most important components is bioinformatics, according to Dr. Berg.

Another new program at NIGMS involves centers of excellence to study complex biological systems, according to Dr. Berg. Part of the goal of such centers is to develop computational tools with which to predict the behaviors of complex biological systems. Another program that NIGMS supports is development of molecular libraries in combinatorial chemistry and molecular imaging. In 2000, NIGMS began supporting the protein structure initiative, which extends the human genome program. However, this initiative is not attempting to determine and catalogue three-dimensional structures for every protein because the task is simply too huge. Rather, efforts are directed at developing sets of structures for representative proteins to which other proteins may be compared. This program also supports technology development, some of which is leading to development of instruments at the commercial level and also to improvement of synchrotron sources for structural analyses. Meanwhile, NIGMS continues to support individual investigators through R01 grants, some of whom are studying structures of membrane proteins.

Dr. Berg said that NIGMS also continues to support bioinformatics and computational biology. One recent program, called MIDAS, supports efforts to model the spread of infectious disease agents. Moreover, NIGMS is supporting interdisciplinary training programs, including in molecular biophysics, biotechnology, the chemistry-biology interface, and in computational biology. These programs not only train students, but also encourage institutions to work collaboratively. In addition, NIGMS is collaborating with the National Science Foundation on a mathematics and biology initiative.

Another area of interest for NIGMS involves the behavior of single molecules, such as expression of particular genes within cells, according to Dr. Berg. A related area is to understand the effects of slight variations in gene sequences between individuals. As an example of single molecule analysis, Dr. Berg cited the work of Dr. Sunney Xie of Harvard University who is using fluorescence microscopy to study such molecules, harnessing an enzyme that generates a fluorescent molecule but modifying that enzyme to make it unstable, meaning that the activity of only freshly synthesized enzyme molecules is being measured. This approach enables Dr. Xie and his collaborators to view expression of one or only a few such molecules in single bacterial cells, and could lead to analyses of interacting genes.

Dr. Berg referred to a recent statement by a drug company official who said that most drugs work in only 30 to 50 percent of individuals, suggesting that future drug development may require tailoring products to account for genetic differences among patients. The NIGMS began the Pharmacogenetics Research Network in 2000 to begin studying sequence variation in genes encoding drug transporter molecules and those that metabolize drugs. For instance, one bile-salt export pump molecule contains 41 single nucleotide polymorphisms among 247 individuals from whom its gene was extracted and analyzed. Several efforts are under way to interpret this finding and its implications for differences in drug efficacy from one individual to another.

While NIGMS is establishing such collaborative research enterprises involving researchers at several institutions, it also is trying to deal with challenges in establishing appropriate incentives and alternative means for assigning academic credit for those who participate in these programs, according to Dr. Berg. Academic institutions are comfortable rewarding faculty members who gain R01 support, but often these institutions do not know how to evaluate faculty members who receive these newer forms of research support. NIGMS is trying to establish criteria for evaluating the relative success of these programs and to determine which programs yield productive discoveries.


In response to a question from Dr. David Burgess about training initiatives, Dr. Berg said that NIGMS is evaluating training programs for their effectiveness and whether they comply with recent interpretations by the courts regarding support of minority groups. Dr. Berg reaffirmed that NIGMS is committed to working toward a racially and ethnically diverse biomedical workforce.

Dr. J. Michael Bishop agreed with Dr. Berg that crediting team research poses a problem for academic institutions, and he suggested that the NIH provide incentives for universities to reconsider these issues. Dr. Berg said that there are deep-seated structures that need to be reconsidered.

Dr. Zerhouni said that there is convergence between NIGMS and NINDS in the sense that these and other Institutes at the NIH are developing programs, particularly those that encourage science by teams, that have an important impact on the culture at universities. In response, Dr. Berg said that the NIH should identify ways to remove disincentives for supporting research with alternatives to R01 grants, which academic promotion committees recognize and often refer to when making tenure decisions. Those researchers who are supported by alternative programs thus may not gain the recognition and credit that they deserve. Beyond this level of analysis, the NIH needs to identify new incentives to encourage researchers to work in teams, a decision that often depends on identifying appropriate model systems on which to work.

In response to a question from Mr. Arthur Ullian about the impact of level funding on these new programs, Dr. Berg said that this issue looms as a huge challenge. Fortunately, some of these programs were begun during the period that the NIH budget was expanding rapidly. Dr. Landis said that, with modest budget increases, introducing new programs would require dropping older programs, forcing a critical evaluation of which programs are working. Dr. Zerhouni said that all 27 directors of the Institutes and Centers (IC) were asked to do five-year projections for their programs based on modest budget growth and to look for synergies and collaborations among the ICs. Dr. Zerhouni also said that such modest budgets would especially affect clinical trials, particularly in those cases where Institutes are supporting clinical trial infrastructure centers, as those programs come up for renewal. He said that the Roadmap would help to frame discussions when setting priorities. Mr. Ullian also suggested that the NIH include in its budget proposal a description of clinical infrastructure needs and other priorities.

In response to questions from Senator Connie Mack about shifts in support from investigator-initiated to more targeted research, Dr. Zerhouni said that many past investigator-initiated projects could also be described as being targeted, but he agreed that there is tension between the two categories. He said that 57 percent of the NIH budget comes within the investigator-initiated, non-targeted category, about 33 percent is clinical research that ordinarily is targeted, and 10 percent is for training. He said that many constituencies are urging the NIH to increase research on particular diseases. Often in setting research priorities, the NIH assembles sets of diseases into groups, such as neurodegenerative diseases, assuming that they will have similar causes and other patterns. Nonetheless, the NIH cannot dictate the types of research to be done but instead sets broader challenges and targets, typically allowing investigators to assemble themselves into effective teams. The challenge is to focus on particular areas of medical need without undermining creativity.

In response to another question from Senator Mack about moving too far toward doing targeted research, Dr. Zerhouni said that opinions are divided among scientists on this issue. Dr. Sanders Williams said that the Roadmap leaves room for maverick researchers with creative ideas while establishing greater structure and also encouraging the development of valuable new tools for doing research. Dr. Zerhouni said that large-scale projects require more targeted approaches, and managing the balance between those approaches and traditional investigator-initiated research looms as a challenge.

Mr. Phillip Williams said that this discussion raises some questions about semantics, and he asked how much of the R01-supported research is basic. He said that it would be helpful to communicate these issues with greater clarity.

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Work Group Update - NIH Director's Blue Ribbon Panel on the Future of Intramural Clinical Research

Dr. Zerhouni described recent developments affecting the NIH role in clinical research, including an internal review among directors at the NIH, the report from the Institute of Medicine (IOM) that deals with clinical research within the Intramural program, and the fact that the new Clinical Research Center (CRC) will soon be opening on the NIH campus. He pointed out that circumstances for clinical research have changed dramatically since the first such research center opened at the NIH in 1953, when there were few if any clinical research centers associated with universities and medical schools, whereas now such centers are plentiful.

Nonetheless, the role of the NIH Clinical Center may take on renewed importance during the next decade because changes in the health care system and economic pressures are leading academic health centers away from clinical research activities, according to Dr. Zerhouni. He then introduced Dr. Edward J. Benz, Jr., President of the Dana-Farber Cancer Center in Boston, who with Dr. Joseph Goldstein co-chaired the blue-ribbon panel that reviewed prospects for the Intramural Clinical Research Program at the NIH.

Dr. Benz described Dr. Zerhouni's mandate to the panel, namely to advise the NIH on how the Intramural Clinical Research Program might develop its portfolio to produce paradigm-shifting research and how it can best complement clinical research being done elsewhere. The panel, which met three times with additional experts, included clinical investigators with different specialties from across the country. The panel agreed with Dr. Zerhouni that there are many outstanding medical centers around the country conducting robust clinical research, meaning the Intramural Clinical Research Program no longer plays the unique role it did several decades ago.

Dr. Benz said that, because the Intramural Clinical Research Program at the NIH cannot be considered unique, it needs to find a niche that complements extramural clinical research activities and that takes advantage of the NIH being somewhat insulated from health care reimbursement issues, which are in flux. Another important factor is that the Intramural Clinical Research Program does not support so broad an array of clinical training programs as can be found at medical centers in several major urban areas throughout the country.

Based on such considerations, the panel recommended changing the Intramural Clinical Research Program in several ways, including revising its oversight structure; developing new training and career pathways; shifting its focus to rare diseases, to studying basic pathophysiology, and to developing novel therapeutics; moving to create translational and multidisciplinary collaborative teams; focusing on excellence and distinction; and reducing regulatory impediments while improving infrastructure, according to Dr. Benz.

One particular strength of the Intramural Clinical Research Program is in dealing with rare or orphan diseases because the NIH can bring patients into the center for extended periods and also because of accessibility to experts in genomics and proteomics as well as other infrastructure strengths at the NIH, according to Dr. Benz. Some of this continuing focus within the Intramural Clinical Research Program on relatively rare diseases, including metabolic disorders involving lipid metabolism, could also prove important for emerging epidemics, such as obesity, that affect very large population groups. The panel also called for changes in oversight of the Intramural Clinical Research Program, recommending that these changes lead to a new emphasis within the NIH Office of Director to forging more extensive and more formal collaborative links with other clinical research programs.

The panel also recommended that the Intramural Clinical Research Program emphasize excellence and distinctiveness in choosing research problems on which to focus, according to Dr. Benz. Moreover, the Intramural Clinical Research Program should streamline its operations and consider, for example, whether relying on a single, or only a few, rather than many institutional review boards (IRB) would be beneficial.

Dr. Benz said that other consolidations should be considered. For example, there should be a single, high-level oversight committee for the Intramural Clinical Research Program, with representatives from the Institutes and Centers as well as from the board of governors for the Clinical Research Center, and it should report directly to the NIH Director, particularly in setting research priorities. Moreover, the NIH Director should establish an external advisory committee for the Intramural Clinical Research Program.

The panel also recommended that there should be a new position at the NIH, namely Deputy Director for Clinical Research, to emphasize the importance of these activities, according to Dr. Benz. He said that this recommendation poses a dilemma because the panel does not want to demote the current director of the Clinical Research Center and said that arranging these administrative responsibilities much as they are at many academic medical centers could accommodate this dilemma.

One measure of the success of new training programs within the Intramural Clinical Research Program would be in whether clinical investigators receive tenure for their clinical research contributions to the program, according to Dr. Benz. The NIH also should develop a centralized postdoctoral fellowship program within the Intramural Clinical Research Program for conducting translational research, for which the director of the Clinical Research Center would have responsibility. In addition, the program could sponsor an advanced research-training program for extramural faculty members, who would stay for one-year or 18-month periods. Meanwhile, the Intramural Clinical Research Program should emphasize research on rare diseases, while putting less emphasis on conducting clinical trials.


In response to a request from Dr. Sanders Williams for prototype examples of research partnerships that the Intramural Clinical Research Program could develop with academic medical centers, Dr. Benz referred to the rare disease Franconi's anemia for which cases are widely scattered geographically that could be studied within the Intramural Clinical Research Program in collaboration with other centers specializing in research on this disease. Other examples would be inherited obesity disorders or unusual potassium channel defects, for which patients would be seen mainly at outlying medical facilities, but studies could be coordinated through the Intramural Clinical Research Program.

Dr. Judith Vaitukaitis said that the NIH Office of Rare Diseases is establishing seven consortia among the academic General Clinical Research Centers (GCRCs) for the purpose of studying rare diseases grouped according to common themes, such as being blood-based or affecting a particular organ such as the liver. She said that the Intramural Clinical Research Program could also participate in this program. She also described a new network to provide resources for use in clinical research that also could prove useful for Intramural Clinical Research Program efforts. She noted that the NIH pays for the full costs of the GCRCs.

Dr. Steven Paul praised the recommendations in the blue ribbon panel report, drawing attention to its emphasis on conducting pathophysiology and translational research. He added that obtaining access to candidate drugs to evaluate had been a problem for researchers in the Intramural Clinical Research Program when he was associated with it. Dr. Zerhouni asked Dr. John Gallin, Director, NIH Clinical Center to respond, who said that the National Cancer Institute is developing a facility that will overcome such access problems by producing compounds suitable for testing on patients within the Intramural Clinical Research Program.

In response to a question from Dr. Gallin about the top-level administrative changes for the Intramural Clinical Research Program recommended in the panel report, Dr. Benz said that the new position of Deputy Director for Clinical Research would be equivalent in rank to the current Deputy Director for Intramural Research.

Dr. Gallin noted that there are 17 Institutes with programs at the NIH CRC. In response to a question from Dr. Zerhouni, he said that several of the institutes manage accredited fellowship programs. Dr. Gallin further said that it is feasible for the center to consolidate separate fellowships into a single program. Dr. Benz said that the panel envisioned this program leading to a new form of certification that would be nationally recognized at academic medical centers and GCRCs.

In response to a question from Dr. Paul about cooperation within the CRC, Dr. Gallin said that the Institutes are far more prone to share such resources than they once were, and thus space in the new hospital will be shared among partner teams instead of being assigned to particular Institutes. He further said that the external review committee that is recommended in the new report would help to make Intramural Clinical Research Program research programs innovative. It remains the responsibility of the Institutes to maintain strong clinical research programs within their particular areas of expertise.

Dr. Michael Gottesman said that not all clinical research being done by scientists in the NIH Intramural Program is being done at the NIH CRC. A substantial amount of such research is being done at other sites, such as in Arizona, North Carolina, Baltimore, and at nearby Suburban Hospital in Bethesda, Maryland. An oversight committee could help to coordinate these activities with those going on within the CRC itself.

In response to a question from Dr. Zerhouni about low regard for clinical research, Dr. Benz said that research excitement is being stirred by progress in laboratories, whereas it remains difficult to recognize excellence in purely clinically based research activities. Further, clinical research requires large teams, making it more difficult to recognize individual excellence and also leading to longer times to publish fewer papers. These issues are by no means confined to the Intramural Clinical Research Program but affect clinical research everywhere.

In response to a question from Senator Connie Mack about controversy among the recommendations, Dr. Zerhouni said that it could prove challenging to reconcile some of the administrative recommendations within the panel report with others that appeared in the recent IOM report. He said that members of the OD staff would be meeting later in January to evaluate these proposals and try to resolve these issues.

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ACD Liaison Report

Dr. Thomas Ansfield, who serves as liaison from ACD to the NIH Council of Public Representatives (COPR), said that Dr. Zerhouni asked the members of COPR to consider which diseases particularly challenge the American people. This assignment asks COPR members to look beyond their own interests in particular diseases and to identify areas where cross-disciplinary strengths can lead to successful research strategies.

COPR members are organizing their efforts by forming several specific work groups, according to Dr. Ansfield. One such work group is focusing on the Public Trust to work with the NIH to improve the responsiveness of the NIH to better meet the health needs of the American people.

Mr. Larry Sadwin, who serves as the liaison to the ACD from COPR, said that COPR members have formed working groups that provide structure while still permitting them flexibility to respond to issues that arise. The mission statement of one of those groups, the Public Input and Participation Work Group, emphasizes the importance of public access to NIH decision-making processes and of making those processes more transparent. To meet those goals, the work group members plan to identify the practices at various Institutes and Centers that best engage the public in helping to set priorities at the NIH. In addition, the work group is seeking ways to enhance the transparency of those processes.

As part of this effort, work group members are conducting interviews and developing a catalogue of best practices, according to Mr. Sadwin. Some of these best practices include NIH staff leaving the campus to meet the public in various forums, partnering with local communities and grassroots organizations, outreach efforts such as posting strategic plans on Institute websites, establishing more partnerships among Institutes and Centers, improved communications with community members, and reinforcing the belief that public opinions need to be taken into account by decision makers at the NIH.

The COPR Agenda Issues Working Group is guiding the council's response to the IOM report, according to Mr. Sadwin. As part of this effort, Dr. Ansfield provided guidance that helped COPR members to develop its consensus position.

Mr. Sadwin said that perhaps the most important development at the COPR October 2003 meeting was formation of the group now planning a National Workshop on Public Trust. The outcome anticipated from this workshop is a series of recommendations in a report that is to be presented to Dr. Zerhouni. He recently requested COPR input on several issues raised in the news media, and COPR is developing a response.


In response to a question from Dr. Zerhouni about priority setting, Mr. Sadwin said that Dr. Zerhouni and Dr. Kington have helped COPR to gain focus and develop a structure for its activities. Dr. Zerhouni pointed out how COPR quickly supported specific recommendations in the IOM report that relate to priority setting and public participation.

In response to a question from Senator Connie Mack about how COPR members are selected, Dr. Zerhouni and staff members described the public nomination process.

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Introduction of Roadmap Presentations

Dr. Elias Zerhouni reviewed key components of the NIH Roadmap and the main reasons for producing it. He said that major challenges include a shift from acute to chronic diseases in the United States necessitating a shift in research priorities; aging of the U.S. population accompanied by diseases that emerge only toward the end of life; an increased emphasis on health disparities; and emerging and reemerging diseases, including infectious diseases, lifestyle diseases such as obesity, and biodefense-related diseases. Dr. Zerhouni said that the trend toward more of the population being older affects health care costs, as do other factors, leading those costs, which are growing by more than 10 percent per year, now to account for more than 14 percent of the gross domestic product. According to a recent study by the Centers for Disease Control and Prevention, each American spends an average of $5,400 per year on health care.

These challenges make it imperative for the NIH to accelerate the pace of discoveries at all levels and to find and develop new means to meet health care needs, according to Dr. Zerhouni. Hence, the NIH developed a Roadmap for achieving these goals, and it describes a three-part plan, including developing new pathways to discovery, building research teams of the future, and improving clinical investigations. Meeting these goals will entail providing appropriate incentives. One such example is the new Director's Pioneer Award through which the NIH will invest in creative scientists who are doing novel research.

Another new program is the National Electronic Clinical Trial and Research System (NECTAR), an information network that will help in determining what clinical interventions are effective by providing comprehensive data on cumulative knowledge coming from clinical trials at all levels across the country, according to Dr. Zerhouni. Another new idea is to form a NIH Clinical Research Associate Corps that will consist of community-based physicians whose activities and findings are linked through NECTAR with research being done at academic institutions and also the NIH. Broad-based efforts to deal with some 30,000 patients with cystic fibrosis (CF) through nearly 200 local community-based practices and 14 academic centers, coordinated through the University of Washington in Seattle, represent an example of how such networks function. Dr. Zerhouni noted that these efforts have lengthened the average life expectancy of CF patients from 10 to nearly 40 years.

The Roadmap initiatives are starting with a modest investment, with money contributed from the budgets of each of the Institutes and the Office of the Director, according to Dr. Zerhouni. Plans call for a commitment of such funds over several years and then to evaluate the effectiveness of the Roadmap initiatives. Although these funds represent less than one percent of the overall budget for the NIH, they can stimulate changes in the way each of the Institutes and Centers set general priorities for spending the bulk of their budgets. The earlier presentations of Dr. Landis and Dr. Berg provided examples of how some of these changes are being implemented.

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Roadmap Update

Dr. Dushanka Kleinman said that she and other officials at the NIH are developing operating principles for guiding management of 28 Roadmap initiatives. According to these principles, this management should be a collaborative process and should permit flexibility, allowing science to drive the process. The Roadmap initiatives are meant to complement Institute initiatives and are considered value-added. She said that as experiences accumulate, officials would evaluate progress to determine whether particular components of the Roadmap will require adjustments.

These management efforts are being administered through the NIH Roadmap Implementation Coordination Committee whose members include co-chairs of the nine implementation working groups and senior leadership from the NIH Office of the Director, according to Dr. Kleinman. Each of the 28 Roadmap initiatives has a lead Institute or Center as well as staff working with the nine work groups to coordinate these linked activities and to serve as a liaison with the outside community. In addition, the NIH has an ongoing search for a senior advisor who will deal with the Roadmap's clinical research re-engineering segment.

Communication is another key component of implementing the Roadmap, and that communication is not only internal to the NIH but also with other agencies within the Department of Health and Human Services and to representatives of the extramural community, according to Dr. Kleinman. Some of these communication efforts may entail town meetings and videoconferences with academic health centers, professional organizations, and voluntary groups.

Another important component of these Roadmap activities is to evaluate progress in implementing its initiatives, according to Dr. Kleinman. By late 2003, 14 of the Roadmap initiatives had been made public, and applications in response to those initiatives are due in February and March. Plans call for funding successful applications within the current fiscal year and continuing to evaluate and adjust initiatives during the next five years.


In response to a question from Dr. Sanders Williams about the search for a senior advisor for re-engineering the clinical research enterprise, Dr. Kleinman said that several candidates are being interviewed. Dr. Zerhouni said that this appointment would be separate from other advisory positions affecting the Intramural Clinical Research Program, such as the positions called for in the IOM report and in the report from the blue ribbon panel.

Dr. Zerhouni said that representatives from several academic health centers have asked the NIH for advice on translational research and other matters that are addressed in the Roadmap initiatives. Dr. Kleinman said that implementing the Roadmap entails a dynamic, interactive process with such centers and the broader research community.

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NIH Budget Overview

Mr. Richard Turman, the new Associate Director for Budget, said that he planned to present details about the fiscal year (FY) 2005 budget proposal at the next ACD meeting in June and that the final appropriation for FY 2004 was still not available to the NIH. Instead, the NIH is spending at FY 2003 levels under a continuing resolution (CR) from the Congress. Spending at this level, which so far amounts to one-third of the FY 2003 appropriation, has not proved easy but remains manageable because outlays for many NIH grants are not made until later. Furthermore, a House-Senate conference agreement from November 2003, which provides guidelines and also specifies that there will be an increase of 2.8 percent for the NIH, is helpful to officials during this interim period.

Mr. Turman said that an appropriation bill could pass before the end of January. Moreover, by June, the FY 2005 budget proposal will be open for full discussion.


Dr. Zerhouni said that FY 2004 marks a strategic change from FY 2003 because the NIH faced a number of one-time expenditures in FY 2003 for construction, and these changes in the way spending is planned for FY 2004 make it more difficult than usual to work under a CR.

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Work Group Update - Postdoctoral Training

Dr. Ruth Kirschstein said that Dr. David Burgess served as the chair of an ACD Work Group on postdoctoral training. Work group members met with other participants on October 23–24, 2003, including representatives of the National Postdoctoral Association and Dr. Maxine Singer, president emeritus of the Carnegie Institution and chair of the IOM Committee on Science, Engineering, and Public Policy (COSEPUP).

Dr. Kirschstein cited several points from Dr. Singer's presentation during the October meeting, including the fact that the postdoctoral experience is a period of apprenticeship to gain skills, postdoctoral researchers should receive appropriate recognition, including being credited as senior authors on research publications, and they also should receive employee benefits.

Dr. Kirschstein cited additional points presented by Dr. Thomas Cech, saying that postdoctoral researchers should make joint decisions with their mentors; be provided with reasonable access to research facilities, equipment, and supplies; face no surprise responsibilities; and receive performance reviews as well as help and advice in finding subsequent positions. In addition, mentors should meet regularly with postdoctoral fellows, provide them feedback, discuss career opportunities as well as research findings, and provide opportunities to develop other professional skills. Postdoctoral researchers remain responsible for investigating positions before accepting them, learning from mentors what is expected, and ascertaining the experiences of other recent graduates from the group-in sum, for taking responsibility for their own careers. Funding agencies also have responsibilities for postdocs and should provide opportunities such as a laboratory management-training course and also should set limits on how long postdocs can be supported, with a maximum of five years considered reasonable. Beyond that, funding institutions should consider a new category for further support, such as a career-track research position with appropriate support and benefits.

Participants at the October meeting agreed that mentors should be encouraged to serve as role models and to submit effective mentoring plans as part of their research grant applications to the NIH, which would become a condition for receipt of federal funds, according to Dr. Kirschstein. One such participant, Dr. Trevor Penning of the University of Pennsylvania, directs an office for postdocs that serves as a resource for them and to advise faculty and staff about postdocs.

Dr. Kirschstein described several recommendations that were developed based on presentations and discussions during the October meeting. They include development of a request for application (RFA) to support one-time-only administrative costs associated with establishing postdoctoral support offices at research institutions. Such offices would benefit postdocs by providing career development information as well as advice to faculty members and administrative support for developing standards and policies. Another proposal is that the NIH mandate uniform benefits packages for postdocs to ensure equitable treatment. A third proposal is that the NIH work with research institutions to collect data to assess postdoctoral experiences. A fourth proposal is to provide portable, transition-type support that would enable postdocs to launch independent positions at academic institutions.

Participants also discussed alternative career tracks for postdocs, including moving into industry and teaching, according to Dr. Kirschstein. Further discussions are being planned, including participation in a meeting that the National Academy of Sciences is planning for the early summer of 2004.

Dr. Singer said that there is tension between what postdocs and principal investigators (PIs) see as the principal purpose of postdocs, a training opportunity versus a source of labor, respectively. She said that although the proposals from the ACD work group could prove helpful to postdocs, they do not address the important underlying challenge of attracting talented people into research careers, particularly if they perceive such extended apprenticeships at low annual salaries as a barrier to the realization of their personal career goals.


Dr. David Burgess said that members of underserved groups are particularly sensitive to the structural problems described by Dr. Singer. Moreover, there are few minority mentors at many of the institutions that they attend, which provides a perception that they will not be welcome, and also adds to pressures from family members who say the students should be looking for "real," meaning "permanent" positions, rather than temporary work as postdocs. Such students are also sensitive to complaints that they hear from faculty members, who frequently express insecurities about grant support, and from other graduate students, who sometimes spend many years before they complete their Ph.D.s. He called the system dysfunctional.

In response to a question from Senator Connie Mack, Dr. Kirschstein said that postdocs are spending extended periods at this level not because they lack skills but because there are relatively few tenure-track positions available at universities. Dr. Singer said that many postdocs feel pressure to continue their particular projects in hopes of achieving major breakthroughs rather than agreeing sooner to move on to other projects. Dr. Burgess said that another problem is that many PIs who mentor postdocs provide advice only about academic careers, providing a narrow message and leading postdocs to limit their career searches.

Dr. Donald Wilson said that limits should be imposed on the duration of postdoctoral stints. He also said that the future of individual postdocs perhaps should not be left to only one mentor. He further said that educators should begin working with minority students very early, before college, to encourage them to pursue careers in medicine and research.

Dr. Cecil Pickett said that he has spent his entire career in industry. He said that when visiting with young researchers, they often tell him that they also want to pursue careers in industry in part to avoid having to apply for grant support and also to earn higher salaries than they can expect as postdocs at academic institutions.

Dr. Kirschstein, who said that participants at the October meeting heard very different views about career opportunities in industry, asked Dr. Pickett whether it is better for researchers with new Ph.D.s to go directly to industry or to spend additional time as postdocs at universities. In response, Dr. Pickett said that opinions vary, but he recommends that young researchers choose where to work based on their interest in the science being done. Dr. Burgess agreed that many postdocs would like to work in industry but often they are encouraged not to do so by PIs in academic settings.

In response to a question from Dr. Zerhouni about setting limits on postdoctoral stints, Dr. Kirschstein said any formal recommendations would also involve a cultural change that will require leadership on the part of the NIH. Additional cultural hurdles include requiring PIs to explain their mentoring plans as part of research grant applications and establishing new postdoc advisory offices when budgets are tight. Dr. Wilson expressed concerns with the NIH imposing such mandates on recipients of R01 grants because those new requirements could become intrusive. Dr. Singer said that freezing postdoc salaries after a specific number of years is one way to set limits on the length of postdoc stints. She further said that a postdoc who is particularly valued could be assigned to a research staff position after serving a five-year stint.

In response to a suggestion from Dr. Burgess that the Postdoctoral Training Work Group wait until the June ACD meeting to formalize its recommendations, Dr. Zerhouni said that delaying action was not right because so many postdocs-about 62,000-are being funded by the NIH. Dr. Singer also encouraged the NIH to move ahead, pointing to the forthcoming COSEPUP meeting at NAS as an impending deadline.

Dr. Zerhouni further said that the postdoc issue is important because efforts to encourage young and talented potential investigators to pursue research careers are essential for the future of biomedical research.

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Final Comments

Dr. Zerhouni described several noteworthy scientific advances during 2003. Besides completing a refined version of the human genome sequence, researchers very rapidly identified the viral agent responsible for severe acute respiratory syndrome (SARS). This effort moved so quickly in part because of advances in genomics and in using DNA arrays to analyze gene expression. In this case, such analysis was consistent with the signature of coronaviruses, which led investigators to identify the SARS virus.

Dr. Zerhouni said that there were significant advances studying adult and embryonic stem cells, including efforts to use such cells to restore heart functions. Also, baby teeth were identified as an alternative source of human stem cells. Other breakthroughs are coming in biodefense research, with promising development of a vaccine to protect against the Ebola virus. Elsewhere, letrozole appears promising as a treatment for breast cancer. Meanwhile, investigators are identifying several genes associated with depression, including abnormalities in a serotonin transporter gene that correlate with episodes of depression and numbers of suicide attempts. Other researchers from several institutes collaborated to study a family with a high incidence of Parkinson's disease and identified a gene that encodes the protein synuclein, which aggregates in individuals with this disease. Mutation analysis indicates surprisingly that the gene is duplicated in such patients, and this discovery could lead to novel treatments.

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Summary and Conclusions

The Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) convened on January 12, 2004, to review recent events affecting NIH, to learn of new plans under way at two Institutes, to hear about plans for enhancing Intramural Clinical Research programs and progress in implementing the Roadmap, and to consider proposals for postdoctoral training activities and programs.

The ACD acknowledged and commented on these programs and issues and encouraged the NIH to establish an outside panel to review conflict-of-interest issues and also develop plans to implement improvements in programs that support postdoctoral researchers.

I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.

Raynard S. Kington, M.D., Ph.D.
Executive Secretary, Advisory Committee to the Director,
Deputy Director, NIH

Elias A. Zerhouni, M D.
Chairman, Advisory Committee to the Director,
Director, NIH

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Table of Abbreviations

AAMC Association of American Medical Colleges
AAU Association of American Universities
ACD Advisory Committee to the Director
AIDS Acquired Immunodeficiency Syndrome
ALS Amyotrophic lateral sclerosis
ARAC Administrative Restructuring Advisory Committee
BISTI Biomedical Information Science and Technology Initiative
CDC Centers for Disease Control and Prevention
CF Cystic fibrosis
COSEPUP Committee on Science, Engineering, and Public Policy
CIDR Center for Inherited Disease Research
CR Continuing Resolution
CRC Clinical Research Center
COPR Council of Public Representatives
CSR Center for Scientific Review
DARPA Defense Advanced Research Projects Agency
DHHS U.S. Department of Health and Human Services
DOE Department of Energy
FDA Food and Drug Administration
FY Fiscal Year
GCRCs General Clinical Research Centers
GDP Gross domestic product
HHMI Howard Hughes Medical Institute
HIV Human Immunodeficiency Virus
ICRP Intramural Clinical Research Program
IND Investigational new drug application
IOM Institute of Medicine
IP Intramural Program
IRBs Institutional review boards
ITR Information Technology Research
MIRN Medical Informatics Research Network
MOU Memorandum of Understanding
NAS National Academy of Sciences
NCI National Cancer Institute
NCMHD National Center on Minority Health and Disparities
NCRR National Center for Research Resources
NECTAR National Electronic Clinical Trials and Research Network
NEI National Eye Institute
NHGRI National Human Genome Research Institute
NHLBI National Heart, Lung, and Blood Institute
NIAAA National Institute on Alcohol Abuse and Alcoholism
NIAID National Institute of Allergy and Infectious Diseases
NIAMS National Institute of Arthritis and Musculoskeletal and Skin Diseases
NIBIB National Institute of Biomedical Imaging and Bioengineering
NICHD National Institute of Child Health and Human Development
NIDA National Institute on Drug Abuse
NICHD National Institute of Child Health and Human Development
NIDCR National Institute of Dental and Craniofacial Research
NIDDK National Institute of Diabetes and Digestive and Kidney Diseases
NIGMS National Institute of General Medical Sciences
NIH National Institutes of Health
NIMH National Institute of Mental Health
NINDS National Institute of Neurological Disorders and Stroke
NRC National Research Council
NRSA National Research Service Awards
NSF National Science Foundation
OSE Office of Science Education
OSP Office of Science Policy
OTT Office of Technology Transfer
PI Principal investigator
RFA Request for application
SARS Severe acute respiratory syndrome
SBIR Small business innovation research

This page last reviewed on February 12, 2011