The National Advisory General Medical Sciences (NAGMS) Council was convened in closed session for its one-hundred and twelfth meeting at 8:30 a.m. on Thursday, September 23, 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 September 23 from 11:05 a.m. to 4:30 p.m. and was followed by the closed session for consideration of grant applications.
David A. Clayton, Ph.D.Sarah C.R. Elgin, Ph.D.Slayton A. Evans, Jr., Ph.D.Lila M. Gierasch, Ph.D.Wayne A. Hendrickson, Ph.D.Daniel J. Kevles, Ph.D.Angeline A. Lazarus, M.D.Steven M. Paul, M.D.Robert S. Pozos, Ph.D.Isiah M. Warner, Ph.D.
Leslie A. Leinwand, Ph.D.Neil S. Mandel, Ph.D.Eva J. Neer, M.D.
Lewis C. Cantley, Jr., Ph.D.ChiefDivision of Signal TransductionBeth Israel Deaconess Medical CenterDepartment of MedicineBoston, MA
Andrew Clark, Ph.D.Professor of BiologyDepartment of BiologyPennsylvania State UniversityUniversity Park, PA
Carl F. Nathan, M.D.ChairmanDepartment of Microbiology and ImmunologyWeill Medical College of Cornell UniversityNew York, NY
Thomas Silhavy, Ph.D.ProfessorDepartment of Molecular BiologyPrinceton UniversityPrinceton, NY
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).
Ms. Pamela Moore, Capitol PublicationsDr. Georgia Persinos, Washington InsightMs. Jessica Schoengold, American Chemical Society
Dr. Arthur Bienenstock, Office of Science and Technology Policy, Office of the PresidentDr. Richard Rodewald, National Science Foundation
National Institute of General Medical Sciences employees and other NIH employees:
Please see the sign-in sheet (available from NIGMS).
Dr. Cassman called the meeting to order and introduced and welcomed the guests and the four ad hoc members: Dr. Lewis Cantley, chief, Division of Signal Transduction, Beth Israel Deaconess Medical Center; Dr. Andrew Clark, professor, Department of Biology, Pennsylvania State University; Dr. Carl Nathan, professor, Department of Microbiology and Immunology, Weill Medical College of Cornell University; and Dr. Thomas Silhavy, professor, Department of Molecular Biology, Princeton University.
Dr. Cassman thanked three of the four NAGMS Council members who completed their terms of service with the September meeting: Dr. David Clayton, Dr. Sarah Elgin, and Dr. Steven Paul. Dr. Christopher Walsh, the fourth outgoing Council member, was not able to attend the meeting.
With regret, Dr. Cassman announced that Dr. Sue Shafer, NIGMS' deputy director and associate director for extramural activities, would be leaving NIH after 25 years to take the position of assistant vice chancellor for research administration at the University of California, San Francisco.
Several new NIGMS staff members were introduced: Dr. Charles Edmonds, a special expert in the Division of Cell Biology and Biophysics; Dr. Paula Flicker, a health scientist administrator in the Division of Cell Biology and Biophysics; Ilene Glassman, John Matala, and Jaime Montes, grants management specialists in the Division of Extramural Activities; Dr. Richard Ikeda, a health scientist administrator in the Division of Pharmacology, Physiology, and Biological Chemistry; Laurette Langlois, a visual information specialist in the Office of Communications and Public Liaison; and Dr. Norka Ruiz Bravo, the new deputy associate director of the Division of Extramural Activities.
Nelson "Chip" Groh of the Division of Extramural Activities has left NIGMS to take a position as a computer specialist with the NIH Office of Extramural Research.
Dr. Michael Martin, the former deputy associate director of the Division of Extramural Activities, has taken a position as director of the Division of Physiological Systems in the NIH Center for Scientific Review.
Judy Reeves, NIGMS' former Council and financial assistant, left the Government for a job in the private sector.
The minutes of the May 13-14, 1999 meeting were approved as submitted.
The following dates for future Council meetings were confirmed:
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.
Dr. Cassman noted that the budget for NIH for FY 2000 had not yet been resolved. However, he was optimistic that NIH and NIGMS would emerge with a good budget. He pointed out that the Institute had come forward with a number of new initiatives in the expectation of appropriate funding to support them. These represent commitments to the research community and will be supported, if only at a reduced level, whatever the final budget outcome.
Dr. Cassman then discussed some of the progress with NIGMS' new initiatives. The pharmacogenetics announcement returned 25 applications, all of which will be reviewed December 9-10 and brought to the Council meeting in January.
The large "glue grant" applications will be reviewed in two parts. First, applicants will be considered for planning grants. Those who are successful can then apply for the full award, which is a maximum of $5 million per year for 5 years. Ten planning grant applications were received. Two were not responsive to the Request for Applications, although one of these is being considered by the National Institute of Neurological Disorders and Stroke. The remaining eight applications will be reviewed within the next few weeks. The successful applicants will then be invited to apply for the full award in late January.
The structural genomics pilot programs were reported to be at earlier stages, since letters of intent were not due until mid-October and applications were not due until early February. Plans are also under way to have an international structural genomics meeting in Europe in the spring of 2000. The purpose of the meeting would be to set guidelines for the release of data and to discuss issues of intellectual property and other matters that would need to be settled to allow effective international cooperation.
Dr. Cassman then discussed the issues raised at the Leadership Forum held this year by NIH Director Dr. Harold Varmus. A major focus of the forum was large, highly collaborative trans-NIH programs. Some representative questions included how one pays for a trans-NIH initiative, such as the Mouse Genome Sequencing Network, and how one sets priorities. The Biomedical Information Science and Technology Initiative--in which NIGMS already has a significant involvement--is another such example. Another important issue discussed at the forum was how to do peer review and manage conflict of interest concerns in programs that are so broad that many or most of the investigators in the specific research community are involved. Also discussed was how to deal with proprietary information and intellectual property rights when many collaborating individuals and institutions are involved in a project. The purpose of the forum was not necessarily to provide answers, but to frame the questions for later discussion. Working groups are now being established to address these and other questions.
Finally, Dr. Cassman reminded the group that NIGMS would be sponsoring a meeting on the development of databases of interacting systems on November 11-12, 1999, to be held at The Cloister on the NIH campus. Information on this meeting can be found on the NIGMS Web site at http://www.nigms.nih.gov/News/Meetings/pages/Databases.aspx
Dr. Robert Pozos and Dr. James Anderson of the NIGMS Division of Genetics and Developmental Biology reported on a workshop that took place on September 13-14, titled "Metabolic Research in the New Millennium," which was co-sponsored by NIGMS and the National Institute of Diabetes and Digestive and Kidney Diseases. The meeting comprised a wide range of investigators whose foci roughly divided between microbial systems, with emphasis on in vitro molecular and cellular approaches, and mammalian systems (humans in particular) that emphasize in vivo approaches. Additionally, experts in informatics, microchemical analytical systems, and computation provided their own views on the metabolic issues raised by both groups. Concerns were expressed about the difficulties of mounting clinical-basic science partnerships, keeping current on and obtaining access to emerging technologies, and attracting new people into metabolic research. Despite varying viewpoints, a number of common interests developed. Support was expressed for interdisciplinary research projects (particularly those with a computational focus), training in metabolism at the predoctoral, postdoctoral, and clinician levels, and funding technology/informatics development in metabolically relevant areas. Some of these suggestions and recommendations may have existing solutions, and others may be subsumed within broader initiatives, such as efforts to come to grips with the explosive growth of databases of all types. Yet others may require new activities, which staff will consider after further reflection and analysis. A report on the workshop will be produced and made available on the NIGMS Web site.
Dr. Cassman introduced Dr. Arthur Bienenstock, the associate director for science at the White House Office of Science and Technology Policy (OSTP). Dr. Bienenstock began with an overview of the OSTP and a list of the topics in which its Division of Science is currently involved. He then presented detailed information on one of these issues--the problem of supporting large facilities, in particular, the synchrotron facilities, which are operated by the Department of Energy (DOE) and the National Science Foundation (NSF) and are of great importance to NIH because of their use in X-ray structure determination. He then noted the importance of the interagency committee on synchrotron facilities (chaired by Dr. Cassman) as a model for a collaborative approach to evaluating and supporting large national resources.
Dr. Bienenstock then pointed out the danger that arises from large increases in the NIH budget without at least reasonable increases in other agencies that support disciplines such as physics, computer science, and engineering. He noted that many of the recent advances in biomedical research depended on prior developments in other disciplines, and that future advances could be jeopardized if research support were significantly restricted for NSF, DOE, the Department of Defense (DOD), and the National Aeronautics and Space Administration (NASA), in particular.
Dr. Bienenstock then discussed the importance of the government-university partnership and the stresses that have been acting on it. He stated that a task force to review the issues was established in 1997, and a report was released in April 1999. After listing the principles that were developed, he singled out one as particularly important--the need to have transparent agency cost-sharing policies and practices. Although this seems straightforward, it turns out to have many complexities that have not yet been resolved. OSTP is holding a series of workshops to address these and other issues in the report.
Finally, Dr. Bienenstock discussed the OSTP concerns about the problems in developing a trained scientific workforce for the future. In particular, he was concerned that although African Americans and Hispanic Americans will rise to about 40 percent of the workforce in the next 50 years, they have not been a significant component of those receiving higher degrees in the sciences. The OSTP will be soon be issuing a report on this issue.
There were a number of questions from the Council on this issue of training. Dr. Bienenstock noted a number of Federal and state efforts that seem to be bearing fruit. There were additional questions about the role and stability of OSTP, Government priorities for science and science education, and the responsibility of the Government for oversight of genetically modified organisms.
Dr. Rochelle Long of the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry reported on the Pharmacogenetics Populations Advisory Group Meeting that took place on May 27, 1999. This group is a subcommittee of the National Advisory General Medical Sciences Council. There were nine consultants in attendance, including individuals with basic and clinical scientific expertise, historical knowledge, social policy perspective, genetic counseling experience, and outreach activity experience. There was also a representative of the patient community present. The group's goal was to consider the possible social and ethical ramifications of future research conducted in the area of pharmacogenetics. The NIGMS pharmacogenetics initiatives invite applications addressing the genetic basis for individual differences in responses to therapeutic medications. The initiatives are intended to stimulate research activities and to encourage the development of a repository of pharmacogenetic information. Because research will be conducted with human subjects, possibly as members of identified groups, NIGMS asked the group to provide advice regarding the views of--and potential areas of misunderstanding for--individuals and communities who might participate in these studies. The group compiled advice for the research community and made recommendations to NIGMS. The members of the group emphasized that they support pharmacogenetics research, that they will aid in the anticipation of issues that might arise, and that they will assist in implementing the recommendations. The full report of the meeting is posted at http://www.nigms.nih.gov/Research/SpecificAreas/PGRN, along with other information on the initiatives. The Council endorsed the group's recommendations and urged a continued dialogue in this area.
Dr. Judith Greenberg of the NIGMS Division of Genetics and Developmental Biology reported on a related meeting to the Pharmacogenetics Populations Advisory Group, the Workshop on Population-Based Samples for the NIGMS Human Genetic Cell Repository, that NIGMS held in July to obtain advice for the Human Genetic Cell Repository. This workshop addressed both the scientific and bioethical issues related to acquisition by the repository of samples from identified populations.
The Human Genetic Cell Repository, supported by NIGMS since 1972, supplies the research community with well characterized cell lines and DNA samples derived from people with a wide variety of genetic disorders. The repository also contains samples from individuals that are included because of their association with an identified population. These population-based samples have no phenotypic information connected with them. Nevertheless, by virtue of being grouped into distinct populations, these samples are of value for a variety of genetic studies. For example, they are used to help identify genes involved in both rare and complex traits; to identify polymorphisms, including single nucleotide polymorphisms; to determine allele frequencies; to distinguish between a disease-causing mutation and a normal polymorphism; and to answer fundamental questions related to population structure, including questions on evolution and migration.
These samples are extremely popular, and the scientific community has requested that the repository acquire samples from more such populations. However, acquiring and studying samples from identified populations raises human subjects concerns stemming from potential group harm, such as stereotyping and stigmatization by others or by the population itself, discrimination in access to social benefits, conflict with the population's cultural beliefs, and community disruption. Therefore, before deciding whether to expand the collection, NIGMS sought advice about whether the scientific benefits of making these samples available would outweigh the risks to populations, and if so, what could be done to reduce the risks.
Expanding the collection also raises scientific questions. These relate to the number and characteristics of the populations that should be represented, the appropriate number of samples that should be collected from each population, and how best to identify a person as a member of a population.
The workshop participants, who included population geneticists, physical and cultural anthropologists, bioethicists, physicians, and lay people whose backgrounds were in psychology and patient advocacy, produced a series of recommendations that were later refined and elaborated on by means of a e-mail group discussion. Most importantly, the workshop participants endorsed the further collection of samples from anonymous, unrelated individuals from identifiable populations, without phenotypic information. They provided guidelines on how to define a population. They articulated the scientific benefits of studying both homogeneous and admixed populations. They addressed the number of samples that should be collected from each population. They also listed the kinds of scientific documentation needed for these samples.
The participants recommended that the repository acquire samples from identifiable populations only if their collection meets a set of standards in addition to those currently required by the regulations for the protection of human subjects, which include review by an Institutional Review Board (IRB) and obtaining informed consent. A key set of recommendations describes the establishment of special oversight groups that would be distinct from, but would complement the activities of, the IRB. The oversight group would assure that the samples are acquired consistent with a set of protections for the population. In particular, the special oversight group would assure that appropriate consultation and communication with members of the population occurs at all stages--in advance; during the collection, acquisition, and distribution of samples; and following the generation of research results. The special oversight group would also assure that the population is informed about the planned use of the samples, the potential benefits promised, and the potential harms, and that the population is informed of what will be done to minimize those harms. It would also make sure that the informed consent document that each individual signs addresses these issues. Submitters of samples would be required to provide documentation addressing all of these points, and scientists purchasing the samples would have to agree to abide by any provisions or restrictions stipulated by the oversight group.
The special oversight groups would be convened by the repository, with input from NIGMS, and would be composed of individuals with expertise in scientific and bioethical issues, as well as members of the population under consideration or others who are sensitive to their interests.
The concept of special oversight groups to address issues related to the protection of populations--as opposed to IRBs whose focus is on the protection of individuals--is a novel one. The workshop participants recognized that the special oversight groups could never guarantee that populations will be safe from any potential group harm, but they believed that the oversight groups would afford an increased level of protection.
NIGMS plans to solicit feedback from members of various populations and from the scientific and bioethics communities. It is hoped that by disseminating these recommendations, other groups dealing with genetic research on identified populations will consider adopting similar approaches. The report on the Workshop on Population-Based Samples for the NIGMS Human Genetic Cell Repository can be found on the NIGMS Web site at http://www.nigms.nih.gov/News/Meetings/pages/CellRepos.aspx.
Dr. Andrew Clark, who participated in the workshop, elaborated on the scientific utility of stratifying humans by ethnicity. Dr. Robert Pozos cautioned that even with the added protections recommended by the workshop, it is possible that data from identified populations would be misused.
Dr. Clifton Poodry, director of the NIGMS Division of Minority Opportunities in Research (MORE), discussed the evolution of the division's programs over the past several years. He indicated that the division's mission remains to substantially increase the numbers of underrepresented minorities who are engaged in biomedical research. There is evidence that, despite some promising statistics, increases in the number of Ph.Ds in the biomedical sciences, outside of psychology, have not been significant. In order to stimulate change that will result in increases in these numbers, the MORE programs have been revised to conform to two basic tenets. First, the activities supported by the division must be developmental, with significant improvement as an outcome, including measurable objectives and anticipated milestones. Second, all programs must include evaluations by the applicants with respect to their own goals and measurable objectives. The division feels that this will allow it to engage new minds and new partners in its efforts. Additionally, the division is providing technical assistance to the institutions involved in areas such as grant writing, evaluation development, and computer communication infrastructure.
Dr. Ernest Marquez of the NIGMS Division of Minority Opportunities in Research, Minority Biomedical Research Support (MBRS) Branch, described the replacement of the original MBRS awards with programs for research development (Support of Continuous Research Excellence (SCORE) Program) and student development (Research Initiative for Scientific Enhancement (RISE) Program) at minority institutions. The associate investigator effort was replaced by a new program supporting student development at research institutions (Initiative for Minority Student Development (IMSD) Program). The IMSD Program supports students at institutions that have fully developed research capabilities. The institutions were asked to come up with new approaches to support underrepresented minority students and stimulate their progression to a Ph.D. The SCORE Program is primarily an investigator-initiated research program, while RISE is for student, faculty, and institutional development. The RISE Program is available to smaller institutions without significant research capability, as well as to larger schools. Another recent change is that the monetary caps were removed in the newly restructured SCORE program, with the result that the individual investigator budgets increased significantly to a level that was realistic to allow for progress. An early indication of results was also presented.
Dr. Adolphus Toliver of the NIGMS Division of Minority Opportunities in Research, Minority Access to Research Careers (MARC) Branch, described the replacement of the MARC Honors Undergraduate Research Training (HURT) Program with the MARC Undergraduate Student Training in Academic Research (U*STAR) Awards Program. As with other components of the MORE Division, the intent is to allow institutions with different capabilities to match their needs to their opportunities. For example, schools with limited research capabilities can send their students off campus for the mandatory summer research experience. Although the program is limited to junior and senior students, there are opportunities for pre-MARC student development programs. The change in the program has resulted in an increase in the number of schools and students participating.
Dr. Irene Eckstrand of the NIGMS Division of Minority Opportunities in Research presented information on the Bridges to the Future Program, which was established about 7 years ago. The program is cooperatively funded by NIGMS and the Office of Research on Minority Health, Office of the Director, NIH. The program focuses on two transitions: the Bridges to the Baccalaureate Degree component promotes the transition from 2-year to 4-year schools, and the Bridges to the Doctoral Degree component promotes the transition from the master's degree to the Ph.D. The purpose of the program is to partner institutions on each side of a transition so as to cooperate in developing programs that will help students who wish to move to a higher level of academic accomplishment. A secure online database tracks the progress of students in the Bridges Program. Early results suggest significant benefits from the program. For example, after 5 years, 70 percent of community college students in the Bridges to the Baccalaureate Degree Program have made the transition to a four-year college. This compares to 39 percent of those who are not in the program. Similarly, there is an attrition rate of only 10 percent of students in the program compared to 26 percent of those who are not in the program. It was noted that an advisory group was to meet the week after the Council meeting to discuss desirable goals and measurable objectives for the Bridges to the Future Program.
The presentation was followed by extensive discussion from the Council, as well as a presentation by Dr. Michael Martin of the NIH Center for Scientific Review on the outcome of an August meeting on research training needs and the development of research capabilities in American Indian populations. The meeting was sponsored by NIGMS and the Indian Health Service. This was an occasion to build collaborations and provide new opportunities for the American Indian community. A report will be issued and future developments will be reported to Council.
NIH is very interested in shortening the time from grant application submission to funding, especially for new investigators, who usually have to wait about 11 months, and for investigators with amended applications, who may wait 17 months or more. All investigators would benefit from knowing as soon as possible whether their grants will be renewed so they can plan earlier. Several other NIH institutes have piloted and adopted expedited en bloc council concurrence of their best applications, reducing the time from application receipt to funding from 11 to 12 months to about 7 months. Under the proposed system, Council would give its en bloc concurrence or approval for funding consideration prior to the actual Council meeting, enabling NIH staff to award approved grants earlier than usual. This streamlined procedure would expedite funding actions by the NIH institute, and the benefits to all investigators are clear.
Dr. Cassman presented this idea at the January 1999 NIGMS Advisory Council meeting, and members agreed to explore it further. Three council members, Drs. Clayton, Gierasch, and Pozos, were asked to participate in a small pilot for the May 1999 Council meeting. An NIGMS committee composed of Dr. Jean Chin of the Division of Cell Biology and Biophysics, Grace Tuanmu and Marcia Hahn of the Division of Extramural Activities, and Christina Zimmerman of the Office of Program Analysis and Evaluation explored the parameters, compared the processes in the other NIH institutes, and organized the small pilot. Only R01 applications that would normally go to Council were considered. Applications having animal or human subject concerns or those from foreign institutions were excluded from this pilot. A list of applications, which also served as a vote sheet, was e-mailed to the reviewers about 7 weeks before the Council meeting. Comments from the Council reviewers were received 2 weeks later. At the September 1999 Council meeting, Dr. Chin discussed and demonstrated the process, with Ms. Tuanmu's assistance, on the computer.
The Council members who participated in the small pilot were enthusiastic about expedited en bloc concurrence. They liked starting the process earlier and at their convenience, and they did not miss lugging their Council books around. They would have liked more guidance on what should and should not be expedited, but they felt that the expedited review process would be worthwhile if funding decisions could be made more quickly for the best proposals.
A few Council members felt that they could not start their review much earlier than they presently do. Starting 2 months earlier would require 2 months of Council-related efforts rather than 1 month. They felt that it would be more work, since they would have to review summary statements earlier and then re-review them to refresh their memory. Others liked working at the last minute. Another problem was the sometimes unpredictable access to the Web and the electronic council book.
Providing CD versions of the NIGMS summary statements could solve most of these problems. This way, notes could be made to remind Council members of concerns, and the CD would be accessible at any time and at any place. Until they are comfortable reading summary statements electronically, Council members would still receive hard copies of the applications assigned to them. Another solution would be to shorten the time between the expedited en bloc concurrence and the Council meeting. In the end, Council members agreed that expedited en bloc concurrence was good for investigators, especially those with new or revised applications.
Council approved a pilot for the January 2000 Council meeting in which R01 grant applications that are 10 percentile points within the previous fiscal year's payline would be eligible for expedited en bloc concurrence. Foreign proposals and those with animal or human subject concerns would not be eligible. Summary statements would be required for this approval and for funding. Applications about which any Council member has concerns would be excluded from consideration via expedited review.
In addition to discussing the expedited en bloc approval process, Dr. Chin and Ms. Tuanmu gave a brief demonstration of the NIGMS Electronic Council Information Book and its features: Council orientation, e-mail and Web links, agenda, reports, and staff organization. This information book was developed by Kay Cornwell of the NIGMS Information Resources Management Branch, Ina Barke of the NIGMS Division of Extramural Activities, Sally Lee of the NIGMS Office of the Director, and other Council Preparation Group members. Having this information accessible electronically will eliminate preparing and mailing out hard copies of Council agenda items to Council members and NIGMS staff.
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.
A summary of applications reviewed by Council is available from Pam Haney, 301-594-2172.
The meeting adjourned at 12:00 p.m. on Friday, September 24, 1999.
I hereby certify that the foregoing minutes are accurate and complete to my knowledge.
