Advisory Council Minutes, May 13-14, 1999

The National Advisory General Medical Sciences (NAGMS) Council was convened in closed session for its one-hundred and eleventh meeting at 8:30 a.m. on Thursday, May 13, 1999, in Conference Rooms E1/E2, Natcher Conference Center, Building 45. Dr. Marvin Cassman, director of the National Institute of General Medical Sciences (NIGMS), presided as chairman. The meeting was open to the public on May 13 from 11:02 a.m. to 4:06 p.m. and was followed by the closed session for consideration of grant applications.

Members Present:

David A. Clayton, Ph.D.
Sarah C.R. Elgin, Ph.D.
Slayton A. Evans, Jr., Ph.D.
Lila M. Gierasch, Ph.D.
Wayne A. Hendrickson, Ph.D.
Daniel J. Kevles, Ph.D.
Angeline A. Lazarus, M.D.
Leslie A. Leinwand, Ph.D.
Neil S. Mandel, Ph.D.
Eva J. Neer, M.D.
Steven M. Paul, M.D.
Robert S. Pozos, Ph.D.
Christopher T. Walsh, Ph.D.

Members Absent:

Isiah M. Warner, Ph.D.

Special Consultants Present:

Naji N. Abumrad, M.D.
Chairman and Professor
Department of Surgery
North Shore University Hospital at Manhasset
Manhasset, NY 11030-3801

David R. Burgess, Ph.D.
Academic Vice President and Dean of Faculties
Boston College
Chestnut Hill, MA 02467

Stephen K. Burley, M.D., D. Phil.
Laboratory of Molecular Biophysics
The Rockefeller University
New York, NY 10021-0000

Marian B. Carlson, Ph.D.
Institute of Cancer Research
Columbia University
New York, NY 10032-0000

For the record, it is noted that to avoid a conflict of interest, Council members absent themselves from the meeting when the Council discusses applications from their respective institutions or in which a conflict of interest may occur. Members are asked to sign a statement to this effect. This does not apply to "en bloc" actions.

Council roster (available from NIGMS).

Members of the Public Present:

Ms. Julie Grisham, Chemical and Engineering News
Mr. Tom Hogan, The Blue Sheet
Dr. M. F. Lima, Meharry Medical College
Ms. Pamela Moore, Capitol Publications
Dr. Georgia Persinos, Washington Insight
Ms. Jessica Schoengold, American Chemical Society

Federal Employees Present:

Dr. Christopher Greer, National Science Foundation
Dr. Philip Harriman, National Science Foundation

National Institute of General Medical Sciences employees and other NIH employees:

Please see the sign-in sheet (available from NIGMS).


I. Call to Order and Opening Remarks

Dr. Cassman called the meeting to order and introduced and welcomed the guests and the four ad hoc members: Dr. Naji Abumrad, chairman, Department of Surgery, North Shore University Medical Hospital, and co-chairman, Department of Surgery, New York University Medical Center; Dr. David Burgess, academic vice president, dean of faculties, and professor, Department of Biology, Boston College; Dr. Stephen Burley, investigator, Howard Hughes Medical Institute, and Richard M. and Isabel P. Furland Professor and head of laboratory, The Rockefeller University; and Dr. Marian Carlson, professor, Department of Genetics and Development and Microbiology and Institute of Cancer, College of Physicians and Surgeons, Columbia University.

Dr. Cassman introduced Dr. Patricia Straat of the Center for Scientific Review, who is on a 3-month detail in the NIGMS Division of Extramural Activities as a special assistant to Dr. Sue Shafer, director of the Division. Dr. Straat is doing analysis and evaluation projects and is also handling a portfolio of grants in the NIGMS Division of Cell Biology and Biophysics.

Dr. Cassman announced the appointment of Dr. Gary Nabel--a graduate of the NIGMS Medical Scientist Training Program--to the position of director of the new NIH Vaccine Research Center. The Center's initial focus will be to develop candidate vaccines against HIV. Dr. Nabel came to NIH from the University of Michigan in Ann Arbor, where he was the Henry Sewall Professor of Internal Medicine and a professor of biological chemistry. He was also a Howard Hughes Medical Institute investigator.

Ms. Francine Little was recently appointed the associate director for management at the National Institute of Environmental Health Sciences. Previously, she served as director of the NIH Office of Financial Management.

Dr. Alfred Gordon was recently named to head the new Office of Special Programs in Neuroscience in the National Institute of Neurological Disorders and Stroke (NINDS). This office will focus on efforts to recruit and train the next generation of minority neuroscience research professionals. Previously, Dr. Gordon served as the NINDS special initiatives and developmental programs officer.

Dr. Jim O'Donnell, who for the past 9 years was director of the Office of Extramural Programs in the Office of the Director, NIH, retired after a 31-year NIH career.

Dr. Robert Q. Marston, who was the director of NIH from 1968 to 1973, died of cancer on March 14, 1999, at the Hospice of North Central Florida in Gainesville.

II. Consideration of Minutes

The minutes of the January 28-29, 1999, meeting incorrectly stated Dr. Steven Paul as being present. He should have been listed among the members absent. Dr. Daniel Kevles was not listed as being present or absent. He too should have been listed as being absent. The minutes of the January 28-29, 1999, meeting of the National Advisory General Medical Sciences Council were approved with these corrections noted.

III. Future Meeting Dates

The following dates for future Council meetings were confirmed:

September 23-24, 1999
January 27-28, 2000
May 18-19, 2000
September 14-15, 2000

Dr. Cassman reminded the members of their responsibility and commitment and asked that they not schedule any other meetings, etc., for the dates that they had just confirmed, and that they inform their secretaries of these dates so that other commitments would not be made for them.

IV. Report From the Director, NIGMS: Status of Appropriations

Dr. Cassman noted that the uncertainties regarding the budget for FY 2000 made it difficult to talk about detailed projections for the various initiatives that the Institute had put in place for funding next year. He pointed out that plans had to be made well in advance, before any budget numbers were available, in order to allow investigators time to develop their applications. However, the issuance of an announcement soliciting applications conveys an implied commitment by the Institute. Consequently, NIGMS plans to provide support for all of the programs that it has announced, although the extent of the support will depend on the budget the Institute receives.

Dr. Cassman also raised the possibility of expedited review by the NAGMS Council. This is a process that is intended to help reduce the interval between submission and award of a grant application through early approval by the Council. This would apply primarily to R01 applications, and the benefits would accrue largely to new applications and amended applications.

Dr. Cassman asked for comments from Council members on their interest in attempting such a process. The response was almost uniformly favorable, although a few members were concerned that this approach might limit the view of Council to the full range of research submitted to the Institute if proposals were seen at different times. Dr. Cassman pointed out that three institutes were now piloting an expedited review process. He proposed to provide a more detailed plan for this review and an update on the outcomes from the pilots.

Dr. Cassman then introduced Dr. Rochelle Long of the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry and Dr. James Anderson of the NIGMS Division of Genetics and Developmental Biology. Dr. Long discussed various activities related to the pharmacogenetics initiative, in particular the request for applications (RFA) designed to support the establishment of a series of multidisciplinary, collaborative research groups composed of investigators interested in studying how genetic variation contributes to interindividual differences in drug responses. A database group will also be established and will become responsible for the design and implementation of the pharmacogenetic database. A public briefing session on the pharmacogenetics initiative was held on April 6, 1999, on the NIH campus. Approximately 38 potential applicants attended, representing 23 different institutions. Since that time, NIGMS has received 25 letters of intent to submit an application. These included groups focusing on drug-metabolizing enzymes, drug transport, cardiovascular diseases and asthma, neuropsychiatric disorders, and cancer. Additionally, there were nine letters of intent submitted for the database.

Dr. Long also described the formation of a diversity advisory group, composed largely of lay members, to discuss ethical, legal, and social issues associated with pharmacogenetic research. She announced that this meeting would be held on May 27, 1999, and that it would be chaired by Dr. Daniel Kevles, a member of the NAGMS Council.

Dr. Anderson then reported on a meeting on new research directions in metabolism to be held September 13-14, 1999, on the NIH campus. This meeting, to be co-sponsored by NIGMS and the National Institute of Diabetes and Digestive and Kidney Diseases, emerged from a small planning group meeting in December 1998 that concluded that research in metabolism is poised for rapid advance. The focus of the September meeting will be on ways to promote the understanding of how metabolic pathways are integrated and the development of technology for measuring metabolically significant molecules and reactions in vivo.

Finally, Dr. Cassman asked for approval to build an inflation factor of 3 percent into the maximum direct costs permitted for program project and center grants in coming years. A motion was made for approval and passed.

V. Structural Genomics

Dr. John Norvell of the NIGMS Division of Cell Biology and Biophysics summarized the progress of the NIGMS Protein Structure Initiative (Structural Genomics). This initiative's goal is the determination of a large number of protein structures in a high-throughput mode for the study of protein structural families and protein structural folds. During the past year, the Institute has held three workshops on this research initiative. The reports of all three meetings can be found on the NIGMS Web site at The latest, in February 1999, focused on protein family classifications, selection of appropriate targets for structure determinations, and international cooperation in structural genomics research. Dr. Chris Sander, Millennium Predictive Medicine, Inc., and Dr. John Moult, Center for Advanced Research in Biotechnology, chaired this workshop. The 34 participants were from the United States, Europe, and Asia, and included representatives from the six research groups that are engaged in these computational tasks and the eight research groups that have begun pilot projects in this field. Also attending, as observers, were numerous scientists in the field and representatives of Federal funding agencies. The co-chairs developed a Web site to assist the participants in comparing the results of the various family classification schemes and to aid in target selections. The workshop participants discussed the methodology and results of these protein family classifications, as well as the status of the current and planned structural genomics support programs and pilot projects. The need for coordination and cooperation received considerable attention, and this topic will be pursued at a subsequent structural genomics meeting in Europe early next year. NIGMS is preparing three announcements for support programs in this emerging research field: two program announcements (PAs) for methodology and technological development (one for individual research grants and program project grants and one for small business innovation research grants) and an RFA for research centers to serve as pilot projects for the subsequent large-scale production phase of structural genomics.

VI. Non-Mammalian Models Meeting Report

Dr. Judith Greenberg of the NIGMS Division of Genetics and Developmental Biology reported on a two-day workshop held in February 1999 at which NIH director Dr. Harold Varmus requested that NIGMS, along with several other institutes, make recommendations about the genomic resources that are needed to facilitate research on non-mammalian models. The workshop was chaired by Dr. Raju Kucherlapati of the Albert Einstein College of Medicine and Dr. David Valle of The Johns Hopkins University. The 80 scientists who attended included 8-10 investigators who work on each of the five major models--yeast, Drosophila, C. elegans, zebrafish, and Xenopus--as well as investigators who work on other non-mammalian models and researchers who represent the human and mouse genomics communities. During the first half day, the participants heard presentations about the state of the art for DNA sequencing and functional genomics, about the advantages and disadvantages of each of the major models, and about what genomic and genetic resources already exist for them. The afternoon was devoted to breakout sessions in which the groups were charged with coming up with recommendations and priorities for genomic needs for each of the five major models. The breakout groups' recommendations were presented and discussed by the entire workshop the following day. Finally, researchers representing nine other non-mammalian models gave presentations about the characteristics of their organisms and outlined their genomic needs.

As follow-up to the workshop, Dr. Varmus asked Dr. Cassman and Dr. Elke Jordan, the deputy director of the National Human Genome Research Institute, to coordinate efforts to implement the recommendations. One staff person at NIH will be designated as the primary contact for the research community associated with each model organism. A Trans-NIH Non-Mammalian Models Coordinating Committee with representatives from all the institutes and centers (ICs) is also being formed. This group will initially gather data about the genomic resources that are already being supported for each organism and will identify what the initial needs are for each community. This trans-NIH committee will assure that activities are coordinated among the ICs. A non-mammalian models Web site is being established that will contain information about the workshop's recommendations and the primary contact people at NIH. It eventually will contain PAs and RFAs related to genomic resources for these models.

NIGMS supports the largest amount of research on non-mammalian models of any of the ICs, and it will be involved in planning--although not providing all the funding for--a number of new initiatives beginning in FY 2001. It is expected that NIGMS will take the lead for coordinating the resources needed for Drosophila. The Council will be informed about these activities as they develop.

VII. Bioinformatics Training Meeting Report

Dr. James Cassatt of the NIGMS Division of Cell Biology and Biophysics presented plans for training in the area of bioinformatics and computational biology. These plans followed two meetings of outside advisors at NIGMS--one to review the Institute's training programs and a second follow-up meeting, organized by Dr. Cassatt, Dr. Marion Zatz of the NIGMS Division of Genetics and Developmental Biology, and Dr. Norvell, to provide specific guidance in the areas indicated above.

The first activity to be undertaken as a result of these meetings is an institutional predoctoral training program in the area of bioinformatics and computational biology. It is expected to be announced this summer. Like all NIGMS training programs, funded programs will be multidisciplinary and multidepartmental. They will attempt to bring together biologically oriented departments with departments of computer science, mathematics, and engineering--departments not covered by existing NIGMS training grant programs. In cases where a critical mass does not exist for a comprehensive training program in bioinformatics and computational biology, training in these areas can be combined with training in another area, such as structural biology or genetics, and a training grant proposal for a combined training program can be submitted.

One topic that was discussed at the training meetings and that is not covered by existing NRSA training programs is the professional master's degree. In areas of engineering and computer science, the professional master's degree is a legitimate terminal degree that equips the recipient for independent research. This is an area that NIGMS, together with the Sloan Foundation, is exploring. One idea NIGMS staff had was to support individual postdoctoral fellowships for newly graduated students with the Ph.D. degree in, for example, biology, to do research in the area of bioinformatics and computational biology, and to receive at the end of the fellowship a master's degree in computer science. The reverse could also work. A student with a Ph.D. degree in computer science or engineering could do a similar research project and receive a master's degree in biology.

NIGMS is also exploring the idea of a postdoctoral training program in bioinformatics and computational biology, but no conclusions have been reached regarding this activity.

VIII. Biotechnology Training Meeting Report

Dr. Warren Jones of the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry reported on the March 10, 1999, NIGMS meeting of those investigators/educators who serve as directors of the Institute-supported biotechnology research training programs. He noted at the outset that these university-based programs, which are interdisciplinary and interdepartmental, provide students with a broad understanding of the techniques and concepts widely employed in research and development by the biotechnology industry. Discussions between the program directors and NIGMS staff at the meeting included the following issues: funding patterns over the last 10 years for NIGMS biotechnology training; the recruitment practices used to attract graduate students into these programs; the nature and success of the didactic and laboratory courses that are required; the value of the industrial internships pursued by most trainees; the need for breadth in the training experience; and common features that peer reviewers expect in a well-developed biotechnology training program. Dr. Jones pointed out that the participants were particularly concerned about the decline in the number of NIGMS-supported biotechnology training programs in the last 5 years. Dr. Jones noted that the number of programs has fallen from 28 in 1994 to 18 in 1998 and that no new programs have been supported since 1994. The participants urged NIGMS staff to foster the creation of additional biotechnology training programs at appropriate institutions. They also asked that NIGMS continue to use a broad vision of what constitutes biotechnology training. Noting the strong representation of engineers among the training faculty and leadership of many biotechnology programs, the participants asked that peer reviewers and NIGMS staff be particularly mindful of the value that those trained as engineers can bring to biomedical research.

In the Council discussion following the report, it was suggested that the biotechnology training grant program might not be as useful in today's environment as it was when it began 10 years ago. However, it was pointed out that the NIGMS biotechnology training grant program is one of the few mechanisms employed by NIH to train engineering students in biomedical research.

IX. Clinical Advisory Workgroup Report

Dr. Michael Rogers of the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry reported on the April 12, 1999, meeting of the Clinical Advisory Subcommittee of the NAGMS Council. A copy of the executive summary of the meeting was distributed in the Council folders, and a complete report of the meeting will be distributed to Council at the September 1999 meeting. The discussion at the subcommittee meeting was focused on research opportunities and needs in the clinically relevant areas supported by NIGMS: anesthesiology, clinical pharmacology, and trauma and burn injury. Previous meetings have focused on training needs in these areas, and the Institute recently instituted the K08 award (Mentored Clinical Scientist Development Award) and a new F32 fellowship award in clinical pharmacology (Individual NRSA Postdoctoral Fellowships in Clinical Pharmacology) in response to these discussions. Despite this, a strong sentiment expressed at the meeting was the need to attract more talented M.D.s and Ph.D.s into these areas of research. Dr. Naji Abumrad, North Shore University Hospital, chaired the meeting. Council members Dr. Steven Paul and Dr. Robert Pozos participated in the meeting, along with 11 other scientists who work in anesthesiology, clinical pharmacology, and trauma and burn injury. Dr. Rogers pointed out that these three disciplines play a unique role at NIGMS because of their clinical focus and their translational nature. A wealth of basic science findings is now building that will need to be tested in the clinic. The subcommittee felt strongly that grant mechanisms, such as centers, need to be created or enhanced to encourage the interactions of M.D. and Ph.D. scientists in these areas. Bringing these groups together under one roof would provide important infrastructure for training new scientists in these fields. One common theme for all three areas is working with the altered physiology of the critically ill patient. There is much fundamental work needed in understanding cell changes and regulatory systems that control recovery ability. A common sentiment of the participants was that many of the recent initiatives announced by NIGMS, such as the pharmacogenetics and study of complex systems initiatives, were also important directions for the clinically related areas, and that more needs to be done to make these communities aware of NIGMS' interests. The ensuing Council discussion highlighted many of the difficulties now being faced by investigators in these areas caused by managed care and the greater debt burden of--and thus greater salary needs for--beginning M.D. researchers. One issue that received considerable discussion was the appropriate role of NIGMS in supporting the clinical activities of these communities. Also discussed were programs to provide Ph.D.s with exposure to clinical science and the potential for important scientific contributions to stem from the intensive care unit.

X. Synchrotron Update

Dr. Norvell presented an overview of recent NIH and NIGMS efforts to increase support for synchrotron facilities. The growth and importance of structural biology is well known, with rapid growth in the number of biological structures solved and $150 million of the NIH extramural budget spent in this field (NIGMS has 50 percent of this total). Synchrotron beamline stations are crucial to this research because an increasing fraction of these studies require the high-intensity and variable wavelengths produced by synchrotrons. Recently, five excellent national reports have demonstrated the difficulties and delays faced in obtaining synchrotron beamline access, as more and more scientists are using these resources. The latest of these reports, from the White House Office of Science and Technology Policy, recommended an interagency effort to provide additional support for these synchrotron facilities. Following the recommendations of these reports, Dr. Varmus has provided $18 million for upgrades to two of the five national synchrotron facilities that are performing biological structural studies. In addition, the NIGMS synchrotron initiative has provided support to enhance existing protein crystallographic beamlines at four of these U.S. synchrotrons. This support is intended to increase the capacity for crystallographic data collection by supporting additional staff and equipment upgrades. In addition, the Institute and the National Science Foundation are supporting the development of a new beamline at a sixth synchrotron facility, and NIGMS, in partnership with the National Cancer Institute (NCI), is planning the development and operation of two new beamlines at the Advanced Photon Source, the newest and most advanced U.S. synchrotron. This latter project will provide additional crystallography beamline time for NIH grantees and other users. A board of scientists with expertise in this field will advise NIGMS and NCI staff in the complex and detailed planning required by this initiative.

XI. Technology Transfer Issues

Dr. Maria Freire, director of the NIH Office of Technology Transfer, presented a report on issues and activities regarding intellectual property rights and technology transfer. Over the past 2 years, a group convened by Dr. Varmus has been looking into problems encountered in the use and dissemination of research tools. The fundamental recommendation was that NIH should be more proactive in ensuring that unique resources arising from NIH-supported research are made broadly available to the scientific community. As part of this effort, it was recommended that NIH issue guidelines to investigators and institutions on this issue. Dr. Friere announced that draft guidelines entitled "Principles for Recipients of NIH Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources" would be published in the Federal Register and made available for comment on May 25, 1999.

Dr. Freire gave an example of an agreement that had been worked out with DuPont regarding the use for research purposes of an important reagent that had previously had unacceptable restrictions on its use. She also described the difficulties of addressing the needs of scientists to obtain reagents required for their research, together with the needs of technology transfer offices to demonstrate that they are capturing the economic benefits that may derive from research within their institutions. In response to questions from the Council, Dr. Freire pointed out that the population of researchers is not uniform, and that there is a broad distribution of investigators, from those who are very active in promoting technology development through entrepreneurial start-ups to those who have no interest in technology development at all. Technology transfer offices must deal with all of these, but particularly with those who are not themselves interested in commercializing an invention but would like to see inventions arising from their research translated into potential benefits to the public.

A Council member also pointed out that the transfer of materials between research institutions, even when there is no apparent issue relating to commercial development, is as difficult as when one of the parties is a for-profit organization. Dr. Freire pointed out that some 200 universities have signed an agreement saying that all material transfer can be accomplished by a simple agreement called the "Uniform Biological Materials Transfer Agreement" (UBMTA). However, this has not been used as much as might be expected. One of the recommendations of the report noted above is to promote wider use of the UBMTA.

The session concluded with a discussion of the benefits and shortcomings of the increased development of intellectual property rights in biology and its relation to the core mission of the Institute.

XII. Update on Glue Grants

Dr. Zatz summarized for Council the status of two initiatives for interactive and collaborative research, nicknamed "glue grants." She reported that these initiatives evolved from a series of workshops and Council discussions that centered on how the Institute could promote collaborative research on complex biological problems. The two initiatives are in the form of a PA and an RFA that will be released shortly in the NIH Guide for Grants and Contracts. Both of these are intended to bring people and resources together to promote research on problems of central interest to NIGMS.

Dr. Zatz summarized the key features of the PA and the RFA. The PA is geared to a modest level of support (up to $300,000 per year in direct costs) involving two or more currently funded investigators and will utilize the R24 consortium grant mechanism. It will be an ongoing announcement with no set-aside of funds. The principal investigator must have at least 2 years of NIGMS grant support remaining at the time the consortium funding is awarded. Other participants must have research support from an externally peer-reviewed source for research in the area of the NIGMS research mission. Applications in response to the PA will be reviewed by the NIH Center for Scientific Review.

The RFA will be funded in two phases. Phase I will use the R24 planning grant mechanism and will be for up to $25,000 in direct costs. Phase II will utilize the U54 cooperative agreement mechanism and will provide up to $5 million per year in direct costs. The RFA will have a single deadline for submission, with the possibility of a subsequent reannouncement. Only Phase I awardees will be eligible for Phase II awards. The Institute plans to spend up to $20 million in FY 2000 to support up to five such awards. There will be a public briefing in the summer to provide additional guidance to applicants. An informational statement will also be posted on the NIGMS Web site.

The presentation was followed by discussion and questions from Council members. It was emphasized that these "glue grants" are not intended to provide central core resources, but rather to facilitate the integration of people and resources.


XIII. Procedure for Conduct of Meeting

Dr. Cassman brought to the attention of Council members the procedures for the conduct of the meeting. Council members were reminded that all of the review materials furnished are privileged information. Although most conflicts of interest involving institutional affiliation already had been identified, members were asked to absent themselves during discussion of any application in which there was a personal conflict that was not readily apparent.

XIV. Review of Applications

A summary of applications reviewed by Council is available from Ms. Pam Haney (301-594-2172).


The meeting adjourned at 12:00 p.m. on Friday, May 14, 1999.


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

Marvin Cassman, Ph.D.
National Advisory General
Medical Sciences Council
W. Sue Shafer, Ph.D.
Executive Secretary
National Advisory General
Medical Sciences Council