Advisory Council Minutes, January 28-29, 1999

The National Advisory General Medical Sciences (NAGMS) Council was convened in closed session for its one-hundred and tenth meeting at 8:30 a.m. on Thursday, January 28, 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 January 28 from 11:10 a.m. to 4:45 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.
Angeline A. Lazarus, M.D.
Leslie A. Leinwand, Ph.D.
Eva J. Neer, M.D.
Steven M. Paul, M.D.
Robert S. Pozos, Ph.D.
Christopher T. Walsh, Ph.D.
Isiah M. Warner, Ph.D.

Members Absent:


Special Consultants Present:

John N. Abelson, Ph.D.
Division of Biology
California Institute of Technology
Pasadena, CA 91125

Renato J. Aguilera, Ph.D.
Department of Molecular, Cell, and Developmental Biology
University of California, Los Angeles
Los Angeles, CA 90095-1606

Dale L. Boger, Ph.D.
Department of Chemistry
The Scripps Research Institute
La Jolla, CA 92037-1000

Mitzi I. Kuroda, Ph.D.
Department of Cell Biology
Howard Hughes Medical Institute
Baylor College of Medicine
Houston, TX 77030-3498

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:

Dr. Nancy Moy, SRI International
Dr. Georgia Persinos, Washington Insight
Ms. Jessica Schoengold, American Chemical Society
Ms. Haimi Shiferaw, The Blue Sheet

Federal Employees Present:

Dr. Philip Harriman, National Science Foundation
Dr. Kamal Shukla, National Science Foundation
Dr. Richard Rodewald, National Science Foundation
Dr. Marcia Steinberg, National Science Foundation
Dr. Roy White, 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 three new members of Council: Dr. Leslie Leinwand, professor, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder; Dr. Robert Pozos, assistant dean, College of Science, San Diego State University; and Dr. Isiah Warner, professor, Department of Chemistry, Louisiana State University. Dr. Cassman also introduced the guests and the four ad hoc members: Dr. John Abelson, Division of Biology, California Institute of Technology; Dr. Renato Aguilera, Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles; Dr. Dale Boger, Department of Chemistry, The Scripps Research Institute; and Dr. Mitzi Kuroda, Department of Cell Biology, Howard Hughes Medical Institute, Baylor College of Medicine.

Several new NIGMS staff members were introduced: Dr. Rebecca Hackett, a scientific review administrator in the Office of Scientific Review; Dr. A. Krishna Kumaran, a health scientist administrator in the Division of Minority Opportunities in Research; Dr. Derrick Tabor, a special expert in the Division of Minority Opportunities in Research; and Dr. Laurie Tompkins, a health scientist administrator in the Division of Genetics and Developmental Biology.

Dr. Cassman announced the appointment of Dr. Gerald Keusch as director of the NIH Fogarty International Center (FIC) and associate director for international research at NIH. He replaced Dr. Philip Schambra, who retired after more than 30 years at NIH, the last 10 of which he spent as FIC director. Dr. Keusch was most recently professor of medicine and chief of the Division of Geographic Medicine and Infectious Diseases at Tufts University School of Medicine and the New England Medical Center.

Mr. Carlos Ugarte has joined NIH as coordinator of the new Hispanic communications initiative.

Dr. Eugene Vigil was recently appointed the scientific review administrator of the special study section in the Cell Development and Function Initial Review Group at the Center for Scientific Review. Previously, he was a health scientist administrator in the NIGMS Division of Minority Opportunities in Research.

Ms. Naomi Churchill Earp was recently appointed assistant director for management at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Previously, she served as director of the Office of Equal Employment Opportunity, NIH.

Dr. Phillip Gorden announced that he will resign as director of NIDDK and return to its intramural program when a successor is named.

Dr. Americo Rivera has retired after 36 years of government service, 24 of which he spent with NIGMS. Dr. Rivera was a program director in the Biophysics Branch of the Division of Cell Biology and Biophysics, and he managed the Bridges to the Future Program in the Division of Minority Opportunities in Research.

Dr. Wayne B. Jonas, who served a 3½-year detail as director of the NIH Office of Alternative Medicine, left NIH on December 31, 1998, to resume his research and teaching career as a medical officer with the U.S. Army.

Dr. Arthur Levine, scientific director of the National Institute of Child Health and Human Development, left NIH to join the University of Pittsburgh School of Medicine on November 1, 1998, as senior vice chancellor and dean for the health sciences.

Dr. Frederick Stone, a former NIGMS director, died of heart ailments on October 19, 1998. He served as NIGMS' second director from 1964 until 1970.

The National Institute of Dental Research changed its name to the National Institute of Dental and Craniofacial Research.

II. Consideration of Minutes

The minutes of the September 10-11, 1998, meeting of the National Advisory General Medical Sciences Council were approved as submitted.

III. Future Meeting Dates

The following dates for future Council meetings were confirmed:

May 13-14, 1999
September 23-24, 1999
January 27-28, 2000
May 18-19, 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 reviewed the FY 1999 budget. He pointed out that the NIGMS budget is now just under $1.2 billion, which resulted from a 12.8 percent increase. He then reviewed the distribution of the approximately $136 million increase. About 66 percent of the new funds are being used to support research project grants. This results in an increase of about 200 total grants funded and a success rate that will again be in the high 30s. Furthermore, there will be an increase close to 15 percent in the average cost of a new grant. This should begin to compensate for the years of constraint on the budgets of new and competing grants, which limited their growth.

The training budget will take up about 17 percent of the increase. Most of these funds are being used to pay for the 25 percent increase in both predoctoral and postdoctoral stipends initiated by NIH director Dr. Harold Varmus. Additionally, some new positions will be added to NIGMS' training grants. Most of these will be in the Medical Scientist Training Program (MSTP), but some will also be for postdoctoral fellowships in clinical pharmacology and computational and quantitative sciences. A new joint teaching and research postdoctoral training grant will be initiated, which will bridge research-intensive and minority-serving institutions.

The contract line went up substantially, utilizing 7 percent of NIGMS' budget increase. All of this is due to the added resources being put into synchrotron facilities to support X-ray crystallography. Dr. Cassman provided some background information on the development of this effort.

Finally, Dr. Cassman pointed out that NIGMS' minority programs represent about 8 to 9 percent of the increase. Much of this comes from a new initiative to develop and upgrade communication infrastructure at Minority Access to Research Careers and Minority Biomedical Research Support institutions, with some funds going to the expansion of efforts to support programs targeted to minorities at majority institutions.

Dr. Cassman then noted that the President's budget for FY 2000 had not yet been released and deferred further comments to the next meeting.

A discussion then followed on the modular grant proposal that will be initiated with the June 1999 submission date. This approach will require investigators submitting research grants of $250,000 or less to apply in units of $25,000, with minimal budgetary information provided.

Finally, Dr. Cassman asked for Council action on several items:

  1. Council approved an increase in the maximum limits on program projects and centers to $4.5 million over 5 years. The number will be adjusted yearly to reflect inflationary increases indicated by the Biomedical Research and Development Price Index.
  2. Council approved a change in the Institute's operating procedures, giving special consideration in funding to new investigators. This simply reflected existing policy.
  3. Council approved a change in the restrictions placed on administrative increases to read, "We may approve increases in the direct cost budget provided the increase does not substantially impact the scope of the project."

V. Public Access to Research Data

Dr. Wendy Baldwin, NIH deputy director for extramural research, reported on the Omnibus 1999 Appropriations Bill that directed the Office of Management and Budget to amend Circular A-110 to extend the Freedom of Information Act (FOIA) to "require Federal awarding agencies to ensure that all data produced under an award will be made available to the public under the [FOIA] . . . If the agency obtaining the data does so solely at the request of a private party, the agency may authorize a reasonable user fee equaling the incremental cost of obtaining the data."

Dr. Baldwin discussed the following points:

  • This law could affect each scientific field differently.
  • We are now in the public comment period on a Notice of Proposed Rule Making; NIH will be preparing comments. Individual investigators should comment from their own scientific perspective.
  • What is meant by data and when do data have to be released?
  • Is privacy of individual subjects protected?
  • Who is going to pay for obtaining and screening data?
  • How far-reaching is this legislation? This raises concerns for researchers with some Federal support who have collaborative studies supported by private funds; it could be a serious disincentive to collaborative research.
  • How long does such access remain in force?
  • How is compliance assured for grantees who no longer have research support?

Dr. Baldwin encouraged everyone to comment in a constructive manner before April 5, 1999.

VI. The Careers and Professional Activities of Graduates of the NIGMS Medical Scientist Training Program

Dr. Irene Glowinski of the NIGMS Office of Scientific Review and Dr. James Onken of the NIGMS Office of Program Analysis and Evaluation reported on a recently completed study of the Medical Scientist Training Program. The study was designed to assess the success of MSTP graduates in establishing research careers, examine their employment patterns, and identify the types of journals in which they publish. Data on MSTP graduates and members of several comparison groups were gathered from existing databases of NIH applications and awards and from the curricula vitae of study participants. On several measures of research activity, including applications and awards of postdoctoral research support, applications and award of research support, and publication records, MSTP graduates compared favorably to members of the comparison groups. Their success was similar to, and sometimes surpassed, NIGMS-supported graduates of traditional Ph.D. training programs. The study also revealed a pattern of professional and research activity among MSTP graduates that differs from that of graduates of traditional research training programs. The settings in which MSTP graduates work and the avenues through which they communicate the results of their research suggest a closer integration of their research activities with the practice of medicine. MSTP graduates are more likely than Ph.D. graduates to be employed in academia, and they are more likely to be located in clinical departments or to have appointments in both a clinical and a basic science department. They also are more likely than other NIH-supported Ph.D.s to publish in clinical journals or in journals that publish both clinical and basic research articles.

V. Cryo-Electron Microscopy Meeting Report

Dr. James Deatherage of the NIGMS Division of Cell Biology and Biophysics described the joint NIGMS/National Center for Research Resources Workshop on High-Resolution Electron Microscopy held on November 2-3, 1998. Drs. Wah Chiu (Baylor) and Stephen Harrison (Harvard) chaired the workshop. The 19 participants were prominent investigators active in the fields of electron microscopy, protein X-ray crystallography, and molecular cell biology. Dr. Deatherage distributed a draft report and summarized the workshop proceedings.

The panel evaluated prospects for utilizing electron microscopy to (1) determine the atomic resolution structures of isolated macromolecular assemblies in solution and (2) determine 3-D macromolecular arrangements in cells. Sessions I and II assessed current capabilities and limitations of electron microscopy and complementary structural methods; Session III defined research needs and goals; Session IV identified and classified into five general categories the technical problems that must be solved; Session V assessed the technical problems, prospects for solutions, and the types of research effort and resources needed; and Session VI defined the types of support required.

Dr. Deatherage summarized the panel's recommendations. The participants recommended adapting proven electron microscopy technology for practical use. The panel concluded that routine atomic structure determination of isolated macromolecular assemblies should be achievable with the next generation of electron microscopes and supporting incremental advances in current technology. The long-term goal of defining macromolecular 3-D arrangements and interactions in frozen-hydrated cells was considered to be at least partly achievable, but much more challenging. All goals will require major research and development (R&D) efforts. The biggest challenges will be in automation, detector technology, algorithm development, and high-throughput computation. It will be necessary to recruit expertise from other scientific disciplines to accomplish these goals. There is an immediate need for acquisition of the next generation of electron microscopes, with provisions for supporting their operation, including long-term support for high-caliber, career-track personnel.

Council discussion: Dr. Abelson noted that high-resolution electron microscopy is widely recognized as an exciting emerging area for the future. The Agouron Foundation undertook a similar study and reached similar conclusions. A number of foundations are very interested in investing in electron microscopy, so there are opportunities for leveraging of NIH support. Dr. Abelson noted that many major institutions are recruiting in the area, but that the pool of qualified investigators is small. He noted that software development in the field is lagging 10 to15 years behind X-ray crystallography and that long-term, career-track support for people working in centers is needed.

Dr. Hendrickson asked about the state of the field in the United States compared to the rest of the world. Support for a strong and diverse community of principal investigators, especially new investigators, is strong in the United States, but with a few notable exceptions, long-term R&D lags. Drs. Warner and Elgin asked about NIGMS support for parallel developments in atomic force and light microscopy. This was discussed, and Dr. Cassman suggested that these might be examined in a future workshop or perhaps in a short session of the Council itself. Dr. Hendrickson noted the close relationship between electron microscopy and X-ray crystallography and the reservoir of talent there that could be motivated to enter electron microscopy. A number of Council members discussed issues of NIH support for instrument development in general. It was agreed that this should be made more visible and that it should be advertised. There was a general consensus that electron microscopy is an important area that needs to be developed. It was agreed that an infusion of funds targeted in the right way could give the field a significant stimulus. Dr. Cassman said that NIGMS staff would prepare program announcements before the May Council meeting.

VIII. Future Training of Biomedical Research Scientist Meeting Report

Dr. Marion Zatz of the NIGMS Division of Genetics and Developmental Biology initiated the discussion by summarizing for the Council the rationale for the November 12, 1998, meeting on the Future Training of Biomedical Research Scientists. Dr. Clayton, who participated in the workshop, summarized the discussion and recommendations that emerged from the meeting. The Council discussion centered on one of the recommendations, which was the need for training in the area of bioinformatics. The issue of whether there was a need for a new and separate training program, versus modification of existing programs, was debated. A secondary issue was whether or not there was a need for training of predoctoral and/or postdoctoral trainees, as well as training at the Master's level. Several Council members, including Drs. Gierasch, Elgin, Walsh, and Clayton, expressed a preference for a separate and distinct institutional predoctoral training program. The rationale was that a new program would give credibility and currency to the area, would have the greatest impact, and would be more likely to identify a unique pool of students with specific needs. It was felt that this is a legitimate new area, for which the initial demand may be small, but for which the volume would increase. The area should go beyond bioinformatics to include engineering and computer science--at a minimum.

Additional general issues related to training were briefly discussed, including whether undergraduate students with sufficient quantitative skills are being recruited into graduate biomedical training programs, whether anything needs to be done about the length of time to the Ph.D. degree, and whether more structured and mentored postdoctoral training should be encouraged at academic institutions. Several Council members agreed that quantitative training of students at the undergraduate level was a problem, but they felt that some university systems, including the California system, were beginning to address the problem.

The discussion concluded with a request from Council that NIGMS staff report back in May on what additional steps are planned for training in the area of bioinformatics.

IX. Discussion of the Planning and Priorities Document

Dr. Cassman described the development of the planning and priorities document that was distributed to Council. In part, this was an attempt to define for the scientific community, the public, and Congress what it is that the Institute does and how it arrives at the decisions about areas of research to be specially encouraged. It was emphasized that this was just a draft and that comments and recommendations for changes by Council were welcome. Another version will be presented to Council at the May meeting.

X. Structural Genomics

Dr. John Norvell of the NIGMS Division of Cell Biology and Biophysics summarized progress on the NIGMS structural genomics initiative, which involves the determination of a large number of protein structures in a high-throughput mode. This project will follow the completion of the sequence of the human genome, and it is aimed at the determination of the structure and function of all proteins. Data from the Human Genome Project has led to comparative protein sequence analyses and numerous efforts to develop methodologies for the identification of protein families and target selections. The NIGMS initiative will support the structural determination of representative proteins from each family, leading to the discovery of many unique structural folds and functions.

During the past year, several meetings and workshops have been held on this scientific topic, including one sponsored by NIGMS last April. As previously reported to the Council, this workshop concluded that the project was feasible, important, and should be undertaken. NIGMS staff have been exploring the initiation of this project and organized a subsequent meeting of advisors on November 24, 1998, for the purpose of planning an NIGMS support program. Dr. David Eisenberg of UCLA was asked to chair the meeting, and 11 scientists attended, including several with strong interests in structural genomics and several others with research focused on function-based structural biology. The participants discussed the experimental and computational components of this project, as well as the two approaches to structural determination: the sequence/computational approach and the more familiar function-based approach. There was also discussion about the possible impact of this project on grant funding, a possible change in the culture of research in this field, and the possible inappropriateness of these projects as research training experiences. The participants also discussed the staff proposal for a support program for structural genomics, focusing on the appropriate scale of pilots for a structural genomics program, and noted the role of pilots in the development of the Human Genome Project. The planning group concluded that: (1) knowledge from a structural genomics project will be important for the biological sciences, (2) much of the necessary technology has been developed, and (3) pilot projects should be supported as research centers to provide further development of the technology and knowledge for large-scale projects.

During Council discussion, Dr. Hendrickson, who was one of the members of the planning group, explained that the pilots need to be supported at the level of research centers so they will provide the appropriate model for the subsequent large operation phase of the project. Dr. Cassman noted that support for this project would not diminish NIGMS support for the many function-based projects that it currently supports. He pointed out that the Institute plans to support about six centers at $3 million each, and that the Institute is actively pursuing complementary support for the structural genomics project from other U.S. and international agencies and foundations. After discussion on the details and goals of the project, the Council voted to accept this plan.

XII. Glue Grant Initiatives

Dr. Michael Rogers of the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry presented a report on proposed new initiatives to support collaborations. The need for new approaches to support collaborative efforts was first evidenced during the Council subcommittee meetings of May 1998. NIGMS senior staff discussed possible responses to this expressed need during the summer and suggested a new approach whereby resources would be given to independently funded investigators to foster and support their collaborative efforts, but not their independent efforts. In essence, NIGMS would provide the "glue" to bring scientists together in collaborative efforts, and thus, the initiative was commonly referred to as "glue grants." The recommendation was made at the NIGMS Planning and Prioritization Meeting in November 1998 that the Institute pursue two new initiatives, one for an RFA to support large-scale collaborations, which staff titled "Large-Scale Consortium Awards," and one for a PA to support small- to moderate-scale collaborations, which staff titled "Consortium Grants for the Support of Interactive and Collaborative Approaches to Research." The large-scale awards would support comprehensive, highly integrated efforts on a biological problem of major scope and significance. These projects would require considerable infrastructure to accomplish and would have an upper limit of $5 million per year in direct costs. The smaller-scale projects would be for projects with more limited scope and needs, and would have an upper limit around $300,000 per year in direct costs. Participants would not be limited to NIGMS grantees. For both, a major decision factor in making awards will be the value added by using the consortium approach. Council discussion centered on why current mechanisms do not satisfy the need; the fact that these will be experiments in the organization of integrative science; the usefulness of consortia in collecting reference data and developing new technology that are difficult to justify on individual projects; the need to include international collaborations; and the need for rapid and open data sharing. Council voted concurrence with NIGMS plans to further develop and issue these initiatives.

XIII. Council-Initiated Discussion

Ms. Annette Hanopole, an NIGMS grants management specialist, presented background information and a concept paper on Summer Research Experiences for Undergraduates.

Recent discussions by the Council have involved the consideration of a program to support summer research experiences for undergraduates. NIGMS recognizes the increasing trend toward the use of interdisciplinary approaches to advance the nation's research endeavor, and in particular, the need for students with quantitative backgrounds to become involved in biomedical research. Thus, a concept paper was developed for this purpose.

The Summer Research Experiences for Undergraduates would provide a mentored, innovative, and realistic research experience during the summer months for a cohort of students. The emphasis would be on programs that recruit from quantitative and physical disciplines, such as engineering, mathematics, computer sciences, and physics. The mechanism to support this activity would be the Research Education Project (R25). Allowable costs would include salary and wages for students, supplies, and limited facilities and administration costs of 8 percent.

Council discussed the proposed RFA and recommended that NIGMS proceed with it.


XIV. 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.

XV. Review of Applications

A summary of applications reviewed by Council is available from NIGMS.

Appendix I: Research grant applications
Appendix II: SBIR applications
Appendix III: Institutional fellowship applications
Appendix IV: Minorities in biomedical research applications

These appendices are available upon request from Ms. Pam Haney (301-594-2172).


The meeting adjourned at 12:00 p.m. on Friday, January 29, 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