Advisory Council Minutes, January 29-30, 1998

The National Advisory General Medical Sciences (NAGMS) Council was convened in closed session for its one-hundred and seventh meeting at 8:30 a.m. on Thursday, January 29, 1998, 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 29 from 11:05 a.m. to 3:15 p.m., followed by the closed session for consideration of grant applications.

Members Present:

David A. Clayton, Ph.D.
Sarah C.R. Elgin, Ph.D.
Lila M. Gierasch, Ph.D.
Carlos G. Gutierrez, Ph.D.
Wayne A. Hendrickson, Ph.D.
Susan A. Henry, Ph.D.
Freeman A. Hrabowski, III, Ph.D.
Angeline A. Lazarus, M.D.
Neil S. Mandel, Ph.D.
Eva J. Neer, M.D.
Steven M. Paul, M.D.
Christopher T. Walsh, Ph.D.

Members Absent:

Slayton A. Evans, Jr., Ph.D.
Daniel J. Kevles, Ph.D.

Special Consultants Present:

Franklyn Prendergast, M.D., Ph.D.
Department of Pharmacology
Mayo Foundation
Rochester, MN 55905-3008

Richard L. Simmons, M.D.
Professor and Chair
Department of Surgery
University of Pittsburgh
Pittsburgh, PA 15261-0001

Bruce S. Weir, Ph.D.
Reynolds Professor
Statistics and Genetics
North Carolina State University
Raleigh, NC 27695-8203

Discussant via Teleconference Call:

Thomas D. Pollard, M.D.
The Salk Institute for Biological Studies
La Jolla, CA 92037-1099

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. Pamela Moore, Capitol Publications
Dr. Georgia Persinos, Washington Insight
Dr. Muriel Prouty, Biophysical Society

Federal Employees Present:

National Institute of General Medical Sciences Employees:

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

Other Federal Employees:

Dr. Philip Harriman, National Science Foundation
Mr. Ed Overcash, National Science Foundation
Dr. Kamal Shukla, National Science Foundation


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. Eva Neer, Cardiovascular Division, Brigham and Women's Hospital; Dr. Lila Gierasch, Department of Chemistry, University of Massachusetts; and the new ex officio Council member from the Department of Defense, Dr. Angeline Lazarus, National Naval Medical Center. Dr. Cassman also introduced the guests present and the three ad hoc members of Council: Dr. Bruce Weir, Department of Statistics, North Carolina State University; Dr. Richard L. Simmons, Department of Surgery, University of Pittsburgh; and Dr. Franklyn Prendergast, Department of Pharmacology, Mayo Foundation.

Dr. Cassman announced that Dr. Slayton Evans is seriously ill and unable to attend this Council meeting.

Dr. Cassman announced several awards and recognitions that Council members have recently received. He congratulated Dr. Wayne Hendrickson for receiving the NAS Alexander Hollaender Award for outstanding contributions in biophysics; Dr. Eva Neer, who will be receiving the FASEB Excellence in Science Award in May; and Dr. Steven Paul, who has been elected to the Institute of Medicine.

Dr. Hinda Zlotnik, former director of the Office of Sponsored Research and a former professor in the Department of Microbiology and Medical Zoology at the University of Puerto Rico School of Medicine in San Juan, has been appointed a health scientist administrator in the Minority Access to Research Careers Program Branch, NIGMS.

Dr. Zach Hall, director of the National Institute of Neurological Disorders and Stroke, has left to take the position of associate dean for research at the University of California, San Francisco, School of Medicine.

Dr. Lin Hymel, in the NIGMS Office of Scientific Review, is leaving to follow a career in the law.

Ms. Pat Disque, head of NIGMS' Grants Records Management and Council Preparation Unit, retired in December 1997. Ms. Doris Brody, of NIGMS' Public Information Office, also retired in December.

Dr. Cassman noted that the fourth new member of Council, Dr. Daniel J. Kevles, a professor of humanities and social sciences at the California Institute of Technology, would start attending Council meetings in September 1998.

II. Consideration of Minutes

The minutes of the September 11-12, 1997, 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 14-15, 1998
September 10-11, 1998
January 28-29, 1999
May 13-14, 1999
September 23-24, 1999

Dr. Cassman reminded the members of their responsibility and commitment, and asked that they not schedule any other meetings, etc., for the dates 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 discussed the outcome of the FY 1998 budget, pointing out that the 7.1 percent increase in the NIGMS allocation resulted in a budget that, for the first time, was more than $1 billion. This would provide funding for approximately 940 competing awards and a success rate that, once again, would be in the mid-30s. However, Dr. Cassman also noted that too much weight has frequently been placed on success rates as a measure of the health of the system. He said that he felt that a steady rate of growth in the total number of grants supported is much more indicative of health. In that regard, the projected FY 1998 level of 3,590 research project grants supported is the highest in NIGMS history and a significant increase over FY 1997. The President's budget for FY 1999 had not yet been released at the time of the Council meeting (it was subsequently determined to be a 7.5 percent increase), but Dr. Cassman noted that all the discussions reported in the media focused on the relative size of the increase to be provided to NIH--a much more promising signal than in years past. Given the tenor of the debate concerning future NIH budgets, Dr. Cassman suggested that previous policies and mindsets, which were focused on responding to increased budgetary constraints, might now be inappropriate. He indicated that, during future meetings, Council would be considering how to respond to the new budgetary climate.

Dr. Cassman moved to the changes that have been proposed for the funding of new investigators. He reminded Council of the discussion at the previous Council meeting of the report of the NIH Committee on New Investigators, which was co-chaired by him and Dr. Ehrenfeld, director of the Center for Scientific Review. The Council had concurred with the recommendations of the report, the most prominent of which was to eliminate the R29 (FIRST) award while maintaining a commitment to support, at a minimum, the same number of new investigators. This recommendation was approved by Dr. Varmus and the Institute and Center (IC) directors. After the May deadline for receipt of applications, R29 applications will no longer be accepted. Dr. Cassman said he felt that investigators receiving R29 awards this year would be caught in the middle, and he asked that approval be given to increase the awards to this year's applicants from the normal level of $70,000 to $105,000. The Council approved this recommendation.

V. Council Operating Procedures

The Council approved the guidelines and operating procedures (available from NIGMS).

VI. K-Type Awards for Clinicians

Dr. Michael Rogers, director of NIGMS' Division of Pharmacology, Physiology, and Biological Chemistry, discussed K-type awards for clinicians. He noted that PPBC staff had held a number of meetings with clinicians in the areas of clinical pharmacology, anesthesiology, and trauma and burn injury. These discussions presented a convincing case that clinicians embarking on a career in academic medicine often have not received sufficient training to make them competitive for completely independent research awards. Furthermore, the pressure on young clinical faculty to perform increasing levels of clinical service to provide their salary support greatly limits the time they have available for research. The K08 (Mentored Clinical Scientist Development Award) addresses both of these problems by providing salary support to allow more research time and by involving a mentor in the development of the young scientist. Dr. Rogers discussed the features of this award and the goals of NIGMS awards. NIGMS proposes to offer this award in the fields of clinical pharmacology, anesthesiology, and trauma and burn injury. Council discussion expressed support for NIGMS to offer this award, but questioned whether the salary amount to be offered was realistic. In response to a question, Dr. Rogers stated that the K08 would be available to those doing laboratory or hypothesis-driven clinical research. The Council thought this was appropriate and expressed sentiment that scientific rigor remain a feature of these awards. Dr. Rogers also discussed staff efforts to initiate a new NRSA award in clinical pharmacology, which would be linked to the General Clinical Research Centers and intended to increase the number of investigators in this area.

VII. Concept Clearance for the Human Genetic Mutant Cell Repository

Dr. Judith Greenberg presented the Council with a summary of the Human Genetic Mutant Cell Repository and concept clearance to recompete the contract that supports it.

In 1972, NIGMS established the Human Genetic Mutant Cell Repository to facilitate research in genetics and related areas by providing high-quality, well-characterized, contaminant-free cell lines from patients with a wide variety of genetic disorders, as well as from individuals without genetic disorders. Over the years, the Repository has undergone an evolutionary process in the types of samples it acquires to meet--or anticipate--the needs of the research community. The collection currently includes cell lines that represent disorders that have been characterized at the molecular level. It also contains cell lines for which the cause of the defect is not at all understood. The Repository includes a large collection of cytogenetically abnormal cell lines. Cell lines also come from multigenerational normal families. About 10 years ago, the Repository began distributing a large collection of human-rodent somatic cell hybrid lines for use in gene mapping studies and DNA samples from most of the cell lines in the collection. In cooperation with the National Human Genome Research Institute, the Repository will soon embark on a new collection of samples that will allow researchers to study normal DNA sequence variation in the human population. This is expected to help identify genes involved in complex traits.

There are currently about 6,600 cell lines available from the Repository. In a typical year, researchers purchase about 3,000 cell cultures and an ever-increasing number of DNA samples, which last year numbered about 2,500. The cell cultures and DNA samples are used for a variety of purposes, including gene mapping and identification, studies on gene regulation and cell physiology, mutagenesis and carcinogenesis, DNA synthesis and repair, and cell biology. The cell lines are also commonly used as controls for clinical and diagnostic studies. Researchers pay a modest fee for the samples.

The Repository has a committee, the Working Group of the Human Genetic Mutant Cell Repository, that meets twice a year to provide advice on which samples to acquire and set general policy. Members of the Working Group review all submissions before the Repository makes them available to the scientific community. This is a very important part of the quality control for which the Repository is well known.

The Repository is supported by a contract, which is re-competed every 5 years to assure that the Repository maintains the highest scientific standards and operates in the most cost-effective way. Each time the contract is competed, any and all qualified organizations may apply. However, since the Repository began, the contract has been awarded to the Coriell Institute for Medical Research in Camden, NJ. The current contract, which ends December 31, 1998, costs about $2 million per year, and NIGMS estimates that the cost of the contract will be about the same over the next 5 years.

The Council unanimously approved a motion to compete the contract for another 5-year period.

VIII. Discussion of NIGMS Priority and Percentile Score Reporting Procedures

Dr. James Onken reported on this subject. Following up on a request made by Council at its September meeting, NIGMS provided data to the Council on the degree of unreliability that may exist in priority and percentile scores. The Council's request for these data was in response to concerns raised by a few investigators and study section members over procedures for rounding priority and percentile scores, which NIGMS implemented in October 1995. These procedures were implemented to express average priority and percentile scores at a level of precision that was believed to be more consistent with the degree of precision inherent in study section members' voted scores. In the discussion of these data, some members of Council recognized uncertainties in the assignment of percentile scores to applications, but most voted to re-establish previous procedures, which used priority scores rounded to a greater number of significant digits to establish percentile scores. It was felt that this change would dispel some perceptions that study section members' opinions were not being adequately represented under the rounding procedures. NIGMS staff agreed to make the required changes and report back to Council.

IX. Meeting Report: New Approaches to the Study of Complex Biological Processes

An NIGMS workshop on "New Approaches to the Study of Complex Biological Processes" was held on November 24-25, 1997, in Bethesda. A formal report of the workshop can be found online.

Dr. James Anderson provided background on the rationale and objectives for the workshop, and he introduced Council member Dr. Susan Henry, a workshop participant. Dr. Henry noted that the workshop panel included biologists working on model systems as well as clinical subjects, and that some of the participants had backgrounds in engineering, mathematics, physics, and other quantitative areas. She reported that the discussion was lively, with different participants having different views on what the word "biocomplexity" signified and what approaches were germane. Although no name for this emerging area was considered satisfactory, the participants agreed that biomedical science is entering a very exciting phase in which tools will be available to describe the functioning of biological systems at many levels of organization. Dr. Henry noted that the development of large databases and interdisciplinary approaches might change the nature of the type of research projects required. The participants also raised the question of how current and future generations of scientists would receive appropriate training. Council members commented that the trend identified by the workshop participants appeared to be a shift to a new emphasis on physiology, albeit with different methodologies. They agreed that interdisciplinary approaches, with the program project grant as a mechanism of support, would likely be required to move the science forward. Interest was also expressed in developing workshops and courses to acquaint researchers with the new methods. Dr. Cassman remarked that staff would work the recommendations into proposals before the next Council meeting. Dr. Henry concluded with a discussion of a statement adopted by the workshop participants urging Dr. Varmus to explore how access to commercial databases might be shared by the basic science community. The Council voted to approve the statement as a resolution, and Dr. Cassman agreed to bring it to Dr. Varmus' attention.

X. Meeting Report: Genetic Architecture of Complex Traits

Dr. Irene Eckstrand and Dr. Bruce Weir reported on a workshop held December 10-11, 1997, entitled " The Genetic Architecture of Complex Traits." Genetic architecture refers to the spectrum of genetic and environmental factors--and their interactions--that underlie any given phenotypic trait. For such traits, the whole is not only greater than the sum of its parts, it is often different from the sum of its parts. The goals of the workshop were to identify barriers and opportunities to research, increase interest and stimulate collaboration among people studying various aspects of complex traits, and identify specific ways that NIGMS could facilitate development.

Dr. Weir noted that the architecture of complex traits is of considerable interest in many research communities. For example, pharmaceutical companies propose to develop drugs that work optimally in different individuals; thus, these companies have started research programs to study genetic variation and its implications for drug development. Dr. Weir also pointed out that genetic architecture is population-dependent and that a complete understanding depends on developing an evolutionary perspective. Addressing the needs in this area will require more data, more theory, more experimental designs, more model systems, and more analyses.

The Council expressed its support of the following three initiatives:

  1. A program announcement for population-based studies of genetic architecture, including human and model systems as well as mathematical approaches.
  2. A reannouncement of NIGMS' interest in training in mathematical approaches, including fellowships, training programs, and supplements.
  3. A program announcement for workshops to train scientists in the analytical tools that are available.

XI. MORE Division Institutional Postdoctoral Research and Teaching Career Development Award

Dr. Poodry reported that the MORE Division gathered a small group of advisors on December 12, 1997, in Bethesda to consider whether it should develop an initiative that would benefit both minority-serving institutions (MSIs) and developing scientists looking toward academic careers. The concept discussed was to provide a career development program that would combine research with teaching and other academic skills. The program would require a partnership between a research-intensive institution, which would serve as the main locus of the research experience, and an MSI, which would serve as the focus of the teaching experience. Council member Dr. Gutierrez reported that the concept was very well received by the group. He pointed to the many potential benefits identified by the participants. He added that the group urged that any announcement preserve flexibility in program design to encourage broad thinking among potential consortium partners. Various discussants urged the MORE Division to develop this initiative. Council was in agreement with the discussion and concurred.

XII. Undergraduate Research Opportunities

The Council continued the discussion of undergraduate research opportunities that was initiated at its previous meeting. Drs. Cassman and Norvell introduced the issue, giving the Council a background document that summarized existing support programs for undergraduate research. Dr. Cassman pointed out that support for undergraduates under the NRSA would require legislative authority. Dr. Elgin described these programs for the Council. The largest supporter of undergraduate research programs is the Howard Hughes Medical Institute, with about 5,000 students supported, mostly in the biological sciences. The National Science Foundation also supports a total of 5,500 through center programs and research grant supplements, with about 30 percent in biological areas. NIH AREA awards, NIH MARC awards, and a wide variety of other government, business, and university programs also support undergraduate students. Dr. Elgin suggested the need for a new undergraduate program at NIGMS, citing the advantages of a large, university-wide, and well-organized program, as opposed to programs that support individual students, such as with research grant supplements. Some Council members agreed that NIGMS/NIH should develop such a support program as a supplement to the predoctoral training grant programs, since they are well developed and would be a logical home for an organized program to direct an undergraduate research program. Other Council members were less convinced, arguing that there were many opportunities available and that an undergraduate supplemental program would unnecessarily burden the predoctoral programs. Dr. Cassman concluded the discussion, stating that he considered the program of supplements to predoctoral training grants to be unwise. He asked NIGMS staff to consider other mechanisms for support of undergraduate students.

XIII. Council-Initiated Discussion


XIV. Procedure for Conduct of Meeting

Dr. Cassman brought to the attention of the 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 which 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. Haney, 301-594-2172.


The meeting adjourned at 11:20 a.m. on Friday, January 30, 1998.


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