Advisory Council Minutes, September 12-13, 2002

The National Advisory General Medical Sciences (NAGMS) Council was convened in closed session for its one-hundred and twentieth meeting at 8:30 a.m. on Thursday, September 12, 2002.

Dr. Judith Greenberg, acting director of the National Institute of General Medical Sciences (NIGMS), presided as chair of the meeting. The meeting was closed to the public on September 12 from 8:30 a.m. to 10:30 a.m. The meeting was open to the public on September 12 from 10:35 a.m. to 3:40 p.m. and was followed by the closed session from 3:40 p.m. until adjournment for consideration of grant applications.

Council Members Present:

John N. Abelson, Ph.D. (participated via telephone conference)
Jay C. Dunlap, Ph.D.
Ira Herskowitz, Ph.D.
Corey Largman, Ph.D.
Eaton E. Lattman, Ph.D.
Douglas A. Lauffenburger, Ph.D.
Leslie A. Leinwand, Ph.D.
Robert S. Pozos, Ph.D.
Laura Roberts, M.D.
Debra A. Schwinn, M.D.
Susan S. Taylor, Ph.D.
D. Amy Trainor, Ph.D.
Isiah M. Warner, Ph.D.
Richard M. Weinshilboum, M.D.

Members Absent:

George C. Hill, Ph.D.

Special Consultants Present:

Barry M. Gumbiner, Ph.D.
Professor
Department of Cell Biology
University of Virginia
Charlottesville, VA

Richard B. Silverman, Ph.D.
Professor
Department of Chemistry
Northwestern University
Evanston, IL

Council roster (available from NIGMS).

Members of the Public Present:

Mr. Scott Jenkins, The Blue Sheet
Ms. Pamela Moore, Capitol Publications

Federal Employees Present:

Dr. Clare O'Connor, National Science Foundation
Dr. Sharman O'Neill, National Science Foundation

NIGMS employees and other NIH employees:

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

OPEN PORTION OF THE MEETING

I. Call to Order and Opening Remarks

Dr. Judith Greenberg called the meeting to order. She introduced and welcomed the guests and two ad hoc participants: Dr. Barry M. Gumbiner, professor, Department of Cell Biology, University of Virginia; and Dr. Richard B. Silverman, professor, Department of Chemistry, Northwestern University.

II. Consideration of Minutes

The minutes of the May 9-10, 2002 meeting were approved as submitted.

III. Future Meeting Dates

The following dates for future Council meetings were confirmed:

January 23-24, 2003       Thursday-Friday
May 15-16, 2003       Thursday-Friday
September 11-12, 2003       Thursday-Friday
January 22-23, 2004       Thursday-Friday

IV. Report from the Acting Director, NIGMS

Dr. Greenberg introduced Dr. Jerry Li and Dr. John Whitmarsh who recently joined the Division of Cell Biology and Biophysics as program directors, Donald Casavant who joined the Information Resources Management Branch as an information technology specialist, and Linda Joy who is a new technical writer in the Office of Communications and Public Liaison. Dr. Greenberg also reported on other recent appointments elsewhere at NIH. Ting-Kai Li, M.D., has been appointed director of the National Institute of Alcohol Abuse and Alcoholism, and Thomas R. Insel, M.D., has been named as director of the National Institute of Mental Health, Thomas Gallagher, Ph.D., has been named director of the NIH Office of Community Liaison, and, Jack Whitescarver, Ph.D., has been named director of the NIH Office of AIDS Research.

Dr. Greenberg announced that the Senate confirmed the appointment of Richard H. Carmona, M.D., M.P.H., as U.S. Surgeon General and that HHS Secretary Tommy G. Thompson named Julie Gerberding, M.D., M.P.H., director of the Centers for Disease Control and Prevention, and administrator for the Agency for Toxic Substances and Disease Registry.

Dr. Greenberg also announced that two long-time NIGMS grantees were this year's recipients of the Lasker Award for Basic Medical Research. They are Dr. James Rothman of Memorial Sloan-Kettering Cancer Center and Dr. Randy Schekman of the University of California, Berkeley.

In response to a request at the last Council meeting, data were provided about the number of women grantees who have received NIGMS MERIT Awards. The data show that the representation of women among MERIT awardees reflects the representation of women with grants of 15 or more years' duration - the pool from which most MERIT awardees are drawn. The data also show that the number of women in this pool has been increasing steadily since 1990.

Finally, Dr. Greenberg provided an update on NIH's loan repayment program for clinical researchers. Eleven applications were assigned to NIGMS, and nine awards were made. The program is being announced again for fiscal year 2003 and will be broadened to include clinical researchers who have support from NIH and from other sources.

V. Briefing on the Emoluments Clause

Dr. Norka Ruiz Bravo, associate director for extramural activities, briefed Council members on the Emoluments Clause of the U.S. Constitution that, in effect, requires that special government employees report their foreign activities. She indicated that the process for implementation of the requirement - although not the requirement itself - was new, and that she understood that it was cause for concern among some Council members. She asked for their patience as NIH works out the details of the process and mentioned that Ms. Gretchen Hirschauer, the NIH ethics counsel, is working on finding ways to minimize the impact of this requirement on Council members. In addition, she provided Council with a summary of the reporting requirement and Web sites for additional information.

VI. Updates on the Glue Grants

Dr. Pamela Marino of the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry reviewed the progress made to date by the Consortium for Functional Glycomics glue grant, which seeks to define the paradigms by which carbohydrate-binding proteins function in cellular communication. She provided a brief overview of the consortium; described progress made by each core laboratory on the first-year milestones; summarized the meetings held and advisory committee recommendations; and discussed second-year milestones, proposed changes, and supplements, including one related to bioinformatics. Additional information on the consortium's organization, goals, databases, members, progress, and reagents can be found at http://www.functionalglycomics.org Link to external Web site.

Dr. Scott Somers of the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry reported that the Inflammation and the Host Response to Injury glue grant http://www.gluegrant.org (no longer available) is nearing the end of its first funding year and is making satisfactory progress on all of its stated goals. Given that the effort involves 20 different institutions and many individuals, the logistics for establishing working relationships and communications were daunting, but consensus agreements have been established on all aspects of the project. A question was asked about whether the high profile nature of this project has led to any concerns or actual problems over the use of animals. Dr. Somers responded that the investigators are aware of the sensitive nature of the research, and are progressing with appropriate oversight and consideration of the welfare for the subjects. Finally, in response to a question, Dr. Somers stated that the bioinformatics group, expanded through hiring of qualified personnel, is working effectively, that a suitable senior advisory group is providing oversight, and the awarding of the recent bioinformatics supplement (providing extensive required hardware) all infused confidence in the bioinformatics component.

Dr. James Deatherage of the NIGMS Division of Cell Biology and Biophysics reported that in its first year, the Cell Migration Consortium (CMC) glue grant made significant progress on the specific aims of all its scientific components. Some important results are already in hand. Administratively, the CMC has organized itself into a cohesive unit, hired staff, set up internal and external Web sites (http://www.cellmigration.org Link to external Web site) and videoconferencing, held annual meetings of the participants and the advisory committee, established internal communications, developed new interactions, and developed scientific milestones for its second year of funding. Two new investigators are being added to the project.

Dr. Rochelle Long of the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry summarized progress during the second year of funding the Alliance for Cellular Signaling (AfCS) glue grant. The AfCS is a large-scale effort to build a quantitative model of cellular signaling in two primary cell types, murine cardiac myocytes and B lymphocytes. Dr. Long reviewed the accomplishments of the alliance for each of the seven core laboratories by project milestones and achievements. The web site http://afcs.lbl.gov/ Link to external Web site lists the proteins and molecules being studied, displays the data accrued to date, provides current literature reviews as "molecule pages," and links to a joint effort with the journal Nature called the Signaling Gateway. Dr. Long stated that the effort is well under way and that all data and the conditions under which they were collected are posted on the public Web site immediately after validation. These data are intended for use by the entire scientific community in follow-up experiments. The AfCS' External Advisory Committee commended it for accomplishments in developing the infrastructure needed to support this research endeavor. The Council asked whether students and post-docs are included as staff in the Alliance, which does not publish its results in a conventional, journal-based manner. The AfCS does not utilize young scientists in training, but instead employs non-faculty Ph.D. professionals as lab heads, so as to not disrupt the career development pathway for traditional scientists. The AfCS intends to chart a new course and views its own scientific organization as an experiment.

VII. Plans for Renewal of the Pharmacogenetics Research Network

Dr. Long presented the background, timing, and dollar amounts of support for the awards made in the Pharmacogenetics Research Network and Knowledge Base (see Pharmacogenetics Research Network). NIGMS plans to bridge some awards to bring them into synchrony, in order to issue a renewal of the original request for applications, RFA GM-99-004 (http://grants.nih.gov/grants/guide/rfa-files/RFA-GM-99-004.html) for funding in FY 2005. It is anticipated that the National Heart, Lung, and Blood Institute; the National Cancer Institute (NCI); National Human Genome Research Institute; the National Institute of Environmental Health Sciences; and the National Library of Medicine will continue their interest in this endeavor, and some other institutes have indicated potential interest as well. This network will be maintained as a broadly-based effort to understand the fundamental principles underlying pharmacogenetics, with an emphasis on common methodological approaches and specific research problems with broad applicability. NIGMS plans to continue to strategize how to best accomplish building a publicly accessible database (PharmGKB) intended for all researchers to deposit and share pharmacogenetics data relating phenotype to genotype. The Council recommended that new applications be allowed with the next RFA, which is consistent with NIGMS' views.

VIII. Update on Activities at Synchrotrons

Dr. Charles Edmonds of the NIGMS Division of Cell Biology and Biophysics reported on how NIGMS is committed to fostering efficient, state-of-the-art facilities at synchrotrons for the use of its grantees and the structural biology community as a whole. The Institute is partnering with the NCI to develop a sector consisting of one bending magnet and two undulator beamlines at the Advanced Photon Source, located at Argonne National Laboratory. In addition, NIGMS is providing supplemental support for equipment and personnel to five existing synchrotron facilities to enhance access for macromolecular crystallography. Dr. Edmonds gave an update on progress of both of these activities and discussed their present and likely future impact.

IX. Meeting Report: What IS Training in the Pharmacological Sciences?

Dr. Peter Preusch of the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry reported on a meeting held August 24-25, 2002, in which more than 150 scientists met to discuss the question, "What is training in the pharmacological sciences?" The meeting was organized to address a number of concerns regarding the NIGMS Pharmacological Sciences (PS) training grant program, including a recent decline in the number of programs and a decrease in the diversity of training opportunities available to students through the program. The meeting was attended by most of the 26 currently funded PS training grant program directors; representatives from more than 50 other potential applicant institutions; members of the NIGMS Biomedical Research Training initial review group; and representatives of relevant scientific societies, industry, and the government. Invited speakers and breakout discussion sessions addressed the following major topics:

  • What is core training in the pharmacological sciences that makes it a distinct NIGMS program? What is state-of-the-art training and how is it accomplished?
  • What is the proper balance between molecular/cellular and systems/integrative pharmacology? What can be done to restore balance?
  • What can be done to maintain scientific diversity in the portfolio of PS programs?
  • Would inclusion of a clinical experience in the PS graduate program be helpful?
  • Would inclusion of an industrial experience in the PS graduate program be helpful?
  • How have changes in medical education affected graduate education and vice versa?
  • How have changes in graduate recruitment affected PS training programs?
  • What is good training in the pharmacological sciences?
  • What have been the outcomes of training in the pharmacological sciences?

X. Meeting Report: Bioinformatics Aspects of Consortium Grants

Dr. Marino reported on a workshop held April 28-29, 2002, to bring together the principal investigators of NIGMS glue grants, their key bioinformatics personnel, and bioinformatics personnel from other NIGMS/NIH-supported large consortia to discuss cross-cutting issues of mutual interest in bioinformatics, provide NIGMS with information as to how these issues are being resolved, and identify future needs and opportunities in this area. Workshop participants identified a large number of core issues and potential barriers to progress. Dr. Marino summarized these and presented them as short- and long-term needs for large consortia. In response to this meeting, NIGMS agreed to provide supplements to consortium grantees who provide justification for expanded informatics needs.

XI. Meeting Report: Evolution of Infectious Diseases

Dr. Irene Eckstrand of the NIGMS Division of Genetics and Developmental Biology reported on an August 29-30, 2002, meeting sponsored by NIGMS and the Ellison Medical Foundation on the evolution of infectious diseases. NIH grantees in this field, as well as their collaborators and students, discussed their current work and the next big questions facing the field. Several themes emerged from the meeting.

  • Many parasites that cause diseases such as anthrax, plague, malaria, and tuberculosis are monomorphic; that is, there are very few genetic or protein variants in these pathogens. However, the few specific genes that do show variation are likely the targets of intense selection.
  • By contrast, commensal microbes, such as Escherichia coli, Helicobacter pylori, and Streptococcus, tend to be highly polymorphic. Genetic variants compete with one another for niches and are held in check by competition. If a common strain is eliminated by antibiotic therapy, for example, a rare strain may be released from its competitive disadvantage and become common.
  • Population models have been developed with Drosophila or E. coli in mind. A challenge for population and evolutionary biology is to develop new mathematical models to explain the dynamics of infectious disease systems.

XII. Concept Clearance: Modeling of Intentional Release and Emergency of Infectious Agents

Dr. Eckstrand proposed a new initiative on modeling of intentional release and emergence of infectious agents, part of the overall NIH biodefense program. On August 5, 2002, a working group of experts met to discuss the scientific challenges and scope of such an initiative and recommended that it be based on the following principles:

  • Bioterrorism is a variant of the general problem of emerging infectious diseases. 
  • Modeling of infectious diseases must take a broad systems approach.
  • It is important to look beyond current human pathogens at the larger systems from which future pathogens will come.

The scientific scope of the initiative would address models of the microbe, models of within-host dynamics, models of evolution and ecology, response models, and improved statistics and models.

As the initiative develops, NIGMS will continue to work closely and collaboratively with the Fogarty International Center and the National Institute of Allergy and Infectious Diseases. The Council voted to endorse the proposed initiative.

XIII. Remarks from the Director, NIH

NIH Director Dr. Elias Zerhouni introduced himself to the Council and gave his views on how he sees NIH evolving as an agency during an era of scientific convergence. He commented that many of the emerging areas are already topics of importance to NIGMS, such as structural biology, complex systems, genomics, proteomics, and training. He praised the NIGMS "glue grant" program as an innovative mechanism to begin to grapple with complex biomedical problems. Dr. Zerhouni stated that the American public deserves to understand what NIH is doing with the increased funds that resulted from the 5-year budget doubling, invoking accountability and transparency in describing how current investments will pay off for improving health in future years. He called upon the Council to help identify and communicate NIGMS' achievements, and to interact with other advisory Councils on core issues of trans-NIH relevance.

Dr. Zerhouni spoke about adopting systems approaches to confronting tough problems in biomedical research, such as re-engineering the clinical research enterprise. Responding to questions, Dr. Zerhouni stated that his role in leading NIH is to be an advocate for obtaining and sustaining adequate budgetary resources, but he noted the importance of being cognizant of conflicting demands in the current national and international environments. Dr. Zerhouni affirmed the importance of building a diverse scientific work force, and he also mentioned coordination efforts between sister agencies, such as the Centers for Disease Control and Prevention, the Department of Energy, and the National Science Foundation, under the new Department of Homeland Security designation.

XIV. Report of the NIGMS Workshop on the Basic Biology of Mammalian Stem Cells

Dr. Marion Zatz of the NIGMS Division of Genetics and Developmental Biology reported to the Council on the NIGMS Workshop on the Basic Biology of Mammalian Stem Cells, held in June 2002 (Meeting Report). She summarized the events leading up to the workshop, noting that investigators for the first time can obtain federal support for research on approved human embryonic stem cell (HESC) lines. The workshop, organized by Dr. Judith Greenberg and co-chaired by Dr. James Thomson of the University of Wisconsin and Dr. Kenneth Zaret of the Fox Chase Cancer Research Center was designed to bring together basic biologists and stem cell investigators with the goal of better understanding the opportunities that HESC offer for addressing fundamental research questions, the unique characteristics of HESC, and the challenges of working with HESC. The conclusions from the workshop were that:

  • Stem cells will be a valuable model system for addressing fundamental research questions.
  • Stem cells may provide a unique primary cell system for drug discovery.
  • Much must be learned about HESC basic characteristics.
  • Interdisciplinary teams of scientists will be needed to advance stem cell research, and research centers will be needed to provide the infrastructure to enable scientists to exploit the research potential of HESC and to train scientists to work with HESC.

The report of the workshop highlighted potential problems in reviewing applications that, of necessity, may be descriptive rather than hypothesis-driven. In the Council discussion that followed, Dr. Leslie Leinwand noted the importance of obtaining initial data on all available HESC lines, in order to analyze their similarities and differences. She suggested that the NIH consider facilitating such an effort.

XV. Concept Clearance for NIGMS Human Embryonic Stem Cell Initiatives

Dr. Zatz described two initiatives to encourage and facilitate HESC research by investigators with little or no prior experience working with HESC. The first initiative is an RFA for P20 Exploratory Center Grants, to provide institutions with $500,000 in direct costs per year, for 3 years. The goals of these Centers would be to:

  • Establish an infrastructure for HESC research.
  • Develop molecular markers and tools for working with HESC.
  • Support pilot projects that explore the use of HESC as a model system to address fundamental research problems.

The centers would offer training opportunities to students, fellows, and investigators, and would sponsor interdisciplinary workshops to continue the dialog between basic biologists and stem cell researchers.

The second initiative is administrative supplements to existing NIGMS grants. These supplements would enable principal investigators to explore the use of HESC as a model system to further the specific aims of their funded grants. Each supplement would provide $75,000 per year in direct costs for the duration of the funded grant. Applications would be submitted for a single receipt date and would be reviewed administratively.

Council members asked whether these initiatives would include adult or non-human embryonic stem cells, whether investigators would have difficulty obtaining HESC, and whether other NIH Institutes would participate in these initiatives. Dr. Zatz and Dr. Greenberg responded that the focus was on HESC, but that comparative studies with other stem cell types could be included as part of the exploratory center activities. It was noted that the difficulty in obtaining HESC is likely to diminish as more providers scale up their production efforts. Other institutes of the NIH declined the opportunity to participate in this RFA.

The Council voted to endorse both initiatives, as proposed.

XVI. Concept Clearance: New Initiatives Proposed by the Division of Minority Opportunities in Research (MORE)

Dr. Clifton Poodry of the NIGMS Division of Minority Opportunities in Research described three new initiatives.

MARC U*STAR Supplemental Grants for Curricular Development in the Quantitative Sciences

The MARC Branch proposed a two-phase mechanism to introduce into pre-MARC and MARC undergraduate student science curricula quantitative analytical methods in the study of biological and biochemical processes. The first phase would support planning to develop pedagogical tools for the introduction of quantitative concepts, computational skills, and principles of mathematical modeling in the analysis of biological processes. The second phase would support implementation plans and would be a part of a competing MARC U*STAR application and/or a competing supplement to a MARC U*STAR grant. Only those applicants that receive Phase I support would be eligible for Phase II funds.

Additional MARC U*STAR Trainee Slots for the Participation of Students Majoring in the Quantitative Sciences

The MARC Branch proposed to provide a few additional trainee slots to successful MARC U*STAR programs to enable these programs to include students majoring in quantitative sciences such as physics and mathematics. The Branch asked for Council endorsement to provide MARC U*STAR programs, upon request, with up to six trainee slots above the number originally recommended by Council for a specific program.

Minority Medical Student (MMEDS) Award

The MARC Branch proposed a new Minority Medical Student (MMEDS) Award. This award would use a fellowship mechanism to support a 1-year mentored research experience for underrepresented minority medical students who are interested in research, are in good standing, and have completed their second year of basic medical training.

The Council endorsed all three proposed initiatives.

CLOSED PORTION OF THE MEETING

XVII. Review of Applications

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

ADJOURNMENT

The meeting adjourned at noon on Friday, September 13, 2002.

CERTIFICATION

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

 

_____________________
Judith H. Greenberg, Ph.D.
Acting Chair
National Advisory General
Medical Sciences Council
           _____________________
Norka Ruiz Bravo, Ph.D.
Executive Secretary
National Advisory General
Medical Sciences Council