Advisory Council Minutes, September 11-12, 1997

The National Advisory General Medical Sciences (NAGMS) Council was convened in closed session for its one-hundred and sixth meeting at 8:30 a.m. on Thursday, Septembe?r 11, 1997, 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 September 11 from 11:00 a.m. to 4:30 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.
Slayton A. Evans, Ph.D.
Carlos G. Gutierrez, Ph.D.
Wayne A. Hendrickson, Ph.D.
Susan A. Henry, Ph.D.
Freeman A. Hrabowski, III, Ph.D.
Alvin Manalaysay, M.D., Ph.D.
Neil S. Mandel, Ph.D.
Thomas D. Pollard, M.D.
Franklyn Prendergast, M.D., Ph.D.
Christopher T. Walsh, Ph.D.
Mary Wiley, J.D.

Members Absent:

Steven M. Paul, M.D.

Special Consultants Present:

Thomas K. Hunt, M.D.
Professor and Vice Chair
Department of Surgery
University of California, San Francisco
San Francisco, CA 94143-0522

Stuart McLaughlin, Ph.D.
Department of Physiology and Biophysics
State University of New York
Stony Brook, NY 11794-8861

Elliott M. Ross, Ph.D.
Professor of Pharmacology
Medical Center Pharmacology
University of Texas
Dallas, TX 75235-9041

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. William Brinkley, FASEB
Dr. Christine Carrico, ASPET
Dr. Howard Garrison, FASEB
Mr. Steve Heinig, FASEB
Mr. Nielsen Hobbs, The Blue Sheet
Dr. Tracy Lawless, ASPET
Mr. Tim Leshan, ASCB
Dr. Georgia Persinos, Washington Insight

Federal Employees Present:

National Institute of General Medical Sciences Employees:

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

Other Federal Employees:

Dr. Richard Rodewald, National Science Foundation
Dr. Kamal Shukla, National Science Foundation
Dr. Zeke Zalcstein, National Science Foundation


I. Call to Order and Opening Remarks

Dr. Cassman called the meeting to order and introduced and welcomed the guests present and the three ad hoc members of Council: Dr. Thomas Hunt, Department of Surgery, University of California, San Francisco; Dr. Stuart McLaughlin, Department of Physiology and Biophysics, State University of New York, Stony Brook; and Dr. Elliott Ross, Department of Pharmacology, University of Texas, Dallas.

Four NAGMS Council members completed their terms of service with the September meeting: Dr. Thomas Pollard, Dr. Alvin Manalaysay, Dr. Franklyn Prendergast, and Ms. Mary Wiley.

Dr. Cassman announced that Dr. W. Sue Shafer has been appointed as Deputy Director of NIGMS. She will also continue to serve as Director of the NIGMS Division of Extramural Activities. He also announced that Dr. Catherine Lewis has been appointed as Chief of the Biophysics Branch in the NIGMS Division of Cell Biology and Biophysics.

Ms. Chris Wisdom, NIGMS' Deputy Executive Officer, has left the Institute to assume the position of Executive Officer of the Center for Scientific Review, formerly the Division of Research Grants.

Dr. Zach Hall has resigned as Director of the National Institute of Neurological Disorders and Stroke. He will be returning to the University of California, San Francisco in December 1997.

II. Consideration of Minutes

The minutes of May 15-16, 1997, incorrectly listed Dr. Alvin Manalaysay as being absent. He should have been listed among the members present. The minutes of the May 15-16, 1997, meeting of the National Advisory General Medical Sciences Council were approved with this modification.

III. Future Meeting Dates

The following dates for future Council meetings were confirmed:

January 29-30, 1998
May 14-15, 1998
September 10-11, 1998
January 28-29, 1999
May 13-14, 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 noted that although there was not yet a bill passed for the NIH budget in FY 1998, both the House and Senate Appropriation Committees had recommended significant increases. With either of the two levels, NIGMS would be over the $1 billion mark for the first time. Also, the proposed levels for funding would result in an increase of between 50 and 100 total research project grants being funded, compared to FY 1997. The success rate for competing grants would be somewhere in the mid-30 percent range, as it has been in recent years. Other parts of the budget show small increases. Of particular concern, however, is the Research Management and Support (RMS) component, which is used to run the Institute. This aspect of the budget has been either unchanged or even reduced in recent years, putting considerable strain on our ability to manage the Institute satisfactorily. It is not clear at this time what the RMS levels will be in the FY 1998 budget.

Dr. Cassman then provided an update on several new initiatives that the Institute has begun. The Institute has received a significant response to the program announcement asking for high risk/high impact applications. In the first group considered, there were 91 applications that were broadly distributed among the Divisions in the Institute and the peer review groups. The reviews are now in progress and will be considered at the next Council meeting.

A second initiative that recently began was a proposal to accept supplements to support high-resolution structure determination in laboratories involved in biological studies. Fourteen applications have been received thus far, and NIGMS plans to fund seven of these. The time from receipt to award should be about 2 months, since these awards will be provided as administrative supplements, with in-house review. The Institute hopes to accelerate the process in the future.

V. Workshop on Genetic Architecture of Complex Traits

Dr. Irene Eckstrand reported to the Council on a planned NIGMS workshop examining issues related to the understanding of the genetics underlying complex traits. Complex traits are those with many interacting causes, including genes that affect many interacting biochemical pathways and structures, as well as external factors. Research on complex traits has emerged as critical to human health and disease; however, it has been difficult to identify the critical questions and encouraging approaches.

The workshop, entitled "Genetic Architecture of Complex Traits," will be held on December 10 and 11 in Bethesda. It will bring together many outstanding scientists from genetic epidemiology, human genetics, population genetics, and evolutionary biology to consider new ways to analyze complexity. The goals of the workshop are to identify barriers to understanding the factors that underlie complex traits, articulate research questions that must be addressed, and identify actions that NIGMS might take to facilitate research on complex traits. NIGMS also hopes that new collaborations will form, and that the workshop will stimulate novel thinking. The specific outcome of the workshop will be a formal report to the NAGMS Council.

VI. Workshop and Proposed Initiative on Systems Approaches to Complex Biological Processes

Dr. James Anderson reported on a forthcoming NIGMS-sponsored workshop, entitled "Systems Approaches to the Study of Complex Biological Processes," to be held November 24-25 in Bethesda. The purpose of the workshop is to provide NIGMS with a perspective on the emergence of new conceptual and experimental approaches to the study of genetic circuitry, metabolic regulation, macromolecular assembly, and other complex problems at all levels of biological organization. The workshop participants will focus on identifying obstacles that currently limit progress in understanding and representing the organization and dynamics of complex biological systems, discuss theoretical and technological approaches (current and hypothetical) that might address these problems, and make recommendations for actions that NIGMS could take to encourage and support this cross-disciplinary area. In discussion, Council members expressed interest in having the proceedings recorded and asked that any outcomes be reported back to them.

On a related topic, Dr. Anderson presented a paper proposing a new program to encourage the development of collaborations between NIGMS-funded investigators and experts in the quantitative disciplines such as engineering, physics, applied mathematics, and the like in order to address complex biological problems. The program would provide competitive supplements to existing NIGMS grants to provide salary, travel, and incidental expenses to support the collaboration. Because the collaborative project would expand the scope of the NIGMS grant, the applications for the supplement would be peer-reviewed. It was noted that the NSF and intramural NIH are also developing a program with similar objectives that would encourage collaborations between NIH intramural laboratories and NSF-supported physicists and engineers. Council members posed no objections to the proposal and agreed to consider a more detailed draft program announcement at their next meeting.

VII. New Investigator Report

Dr. Cassman reported on a recently completed study examining the support of new investigators within the NIH funding system, which looked at the success of the mechanisms developed by NIH to bring new investigators into the system. The study was requested by Dr. Varmus, Director, NIH, and was chaired by Dr. Cassman and Dr. Ehrenfeld, Director, Center for Scientific Review.

The study showed that the numbers of new applicants for individual investigator-initiated awards have remained roughly constant for about 15 years, although the average age of the applicant pool has increased. Although the success rate has been decreasing steadily, the rate of decrease has been the same for both new investigators and for their more experienced colleagues. There is no evidence that new investigators have been selectively disadvantaged as success rates have decreased. Similarly, although the probability of a funded applicant receiving an award without submitting an amended application has decreased sharply over the years, there is essentially no difference between new and experienced investigators in this respect either. Finally, new investigators with Ph.D.s and those with M.D.s show no difference in the probability of success.

Although mentored scientist awards and R03 awards to new investigators were considered in the report, the primary issue for this Council was the R29, or FIRST, award. The data demonstrated that although new applicants for an R29 were more likely to be successful than new applicants for an R01, they were less likely to be successful on competitive renewal. As a consequence, the report concluded that the preferential funding of R29 applicants was counterproductive to the goal of retaining new investigators into the research system. It recommended that the R29 be abolished and that new investigators be identified clearly on their R01 application, that the length of the award be 5 years, and that the amount of the award be allowed to be at whatever level review groups and the funding Institutes thought was appropriate. The report also recommended that the number of new investigators should, at a minimum, be set at the replacement level for individuals leaving the research system. This would amount to roughly the same numbers of new investigators currently being funded.

The NAGMS concurred with these recommendations and asked that their opinion be transmitted to the Director, NIH.

VIII. Evaluation of MERIT Award Program

Dr. Paul Coates, Deputy Director of the Division of Nutrition Research Coordination, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), presented highlights of an evaluation of the NIH MERIT (Method to Extend Research in Time) Award Program. The MERIT Award Program was intended to provide long-term, stable support to selected principal investigators with superior research competence, productivity, and long-term scientific achievement.

The MERIT award has two parts: an initial 5-year award, followed by expedited staff review of a competing continuation for an additional 5 years. However, in NIDDK and NCI, only a 3-year extension was given. Since the program was initiated in 1986, some 11 years ago, 1,640 such grants have been awarded throughout NIH. NIGMS has made 223 MERIT awards, making it one of the largest contributors to the pool of 1,640. In the first 4 years of the program, nearly half of all of the extant MERIT awards were made. Since 1991, the institutes and centers have reached a steady state.

Of the 223 NIGMS MERIT awards, almost all of them were unamended competing renewal applications with scores better than the 10th percentile. Eighty-three percent of the NIGMS applications came from individuals whose grants were of greater than 10 years' duration. Other institutes and centers had more variable selection criteria. Of the NIGMS MERIT awards, 172 have gone through the first 5-year period of this two-phase award and were eligible for consideration for the expedited staff review, council consideration, and extension for an additional period of time. About 90 percent of them were extended and almost all of them were extended for the full 5 years. Of those not extended, many were due to retirement or other employment-related issues.

So far, across NIH, 181 former MERIT awardee applications were not funded on the first competing submission. Of these, 102 have submitted amended applications and 51 percent have been successful. Overall, about two-thirds of former MERIT awardees across NIH are successful in achieving funding either with their first competing application or with the first amended application thereafter.

The mean percentile ranking of awarded applications has declined compared to the percentile on the original MERIT award application. In NIDDK, that was from the 4th percentile, on average, to the 20th percentile, on average; essentially, the same thing is true when data for former MERIT awardees across NIH is examined.

The performance of these former MERIT awardees was compared with a group of grantees whose unamended competing renewal applications were of greater than 10 years' duration. The success rate, simply defined as a percent of applications that were funded on the first submission, has gotten worse since 1987 for both groups. However, the gap between the two groups is consistently in favor of former MERIT awardees doing better on recompetition than other applicants.

Across NIH, fewer than 400 of the 1,640 original MERIT awards have gone through the complete process of award, extension, and recompetition. Dr. Coates concluded that a significant percentage of these will be reviewed in the next 2 years, at which time the program should be reevaluated.

Council members urged that as further analyses of this program were designed, issues such as the age distribution of MERIT awardees, whether long-term support leads investigators to take greater risks with their research programs, and the influence of other support (such as from the Howard Hughes Medical Institute) be considered.

IX. Council-Initiated Discussion

Dr. Elgin observed that the most effective way to recruit bright and enthusiastic students into a research career is to provide them with an opportunity for summer research. She suggested that the Institute consider allowing NIGMS predoctoral training grant applicants to include a component to support such research experience for undergraduates in their application. The Institute could take advantage of the existing infrastructure of such grants. Council members agreed that it is important to give undergraduates a research experience. Some expressed concerns that using our training grants would merely be shifting costs from existing sources of funding. It was agreed that a detailed discussion of this topic would be placed on the agenda for the next meeting. Issues such as the legality of using training grants in this way are among those that need to be explored.

There was a brief discussion on minority recruitment on training grants, following up on the extensive discussion at the NAGMS Council meeting last spring. Staff will keep the Council informed about actions taken to stimulate minority recruitment.

The Council-initiated discussion concluded with some observations by Council members on the value of the priority score and percentile rounding that NIGMS has recently employed. It was agreed that further analysis is required before a conclusion on the merits of the rounding approach can be reached. The issue will be examined again at the next meeting of the Council.


X. 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.

XI. 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 11:40 a.m. on Friday, September 12, 1997.


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