JP2@CU.NIH.GOV (02/10/90)
Following is the executive summary for the NIH Human Genome Program Advisory Committee meeting held in early December. The five year plan mentioned in the report will be released in two weeks and may be requested from the Center [(301)496-0844]. We will post a summary of the plan when it is available. _________________________________________________________________ Third Meeting Program Advisory Committee on the Human Genome December 4, 1989 Wilson Hall National Institutes of Health Bethesda, MD EXECUTIVE SUMMARY Introduction The Program Advisory Committee on the Human Genome convened in Bethesda, MD, on December 4, 1989, to hear reports on the state of the genome project; reports of activities since the last meeting; a report from the ethics working group; a report on informatics activities; and a report on the future of sequence- tagged site (STS) maps and data dissemination policy; and to discuss the goals of the 5-year plan. The following Committee members attended: Norton D. Zinder, Ph.D., Chairman Elke Jordan, Ph.D., Executive Secretary Bruce M. Alberts, Ph.D. David Botstein, Ph.D. Jaime G. Carbonell, Ph.D. Joseph L. Goldstein, M.D. Leroy E. Hood, M.D., Ph.D. Victor A. McKusick, M.D. Maynard V. Olson, Ph.D. Mark L. Pearson, Ph.D. Cecil B. Pickett, Ph.D. Phillip A. Sharp, Ph.D. Nancy S. Wexler, Ph.D. The following liaison members also attended: Benjamin J. Barnhart, Sc.D. George F. Cahill, Jr., M.D. Mary E. Clutter, Ph.D. Ruth L. Kirschstein, M.D. Welcome and Administrative Remarks Dr. Zinder welcomed the members and participants. He noted that the year since the first meeting had been filled with startup activities and the formation of four working groups: training, centers, legal and ethical problems, and informatics. In addition, the Office of Human Genome Research at the National Institutes of Health (NIH) had grown to 20 people and is now a center. He added that the purpose of this meeting was to agree on a joint NIH/DOE 5-year plan that will be approved at various governmental levels and presented to the Congress in the spring. Approval of Minutes and Dates of Future Meetings Dr. Zinder called for a motion for approval of the minutes of the second Committee meeting held on June 19-20, 1989. The motion was made and seconded, and the minutes were unanimously approved. Dr. Jordan announced the dates of the next two meetings: June 18-19, 1990, and December 3-4, 1990. She also proposed that the third meeting be June 17-18, 1991, to which there was no objection. State of the Genome Project Dr. James Watson, Director of the National Center for Human Genome Research, reported that the planning meeting with the DOE in Cold Spring Harbor, NY, gave rise to the idea of redefining the centers as core centers and centers with focus. Letters of intent from groups that propose to establish these centers are beginning to arrive. The lack of money for construction is a major problem at many institutions. DNA sequencing, if performed in a cottage-industry fashion, will cost between $5 and $10 per base pair. Acceptable cost is on the order of $.50 per base pair. The first reviews of applications from groups proposing to explore large-scale DNA sequencing will occur in the next few months. A joint DOE/NIH informatics committee will devise a national plan for this area in the next year. Congress is interested in two issues: the ethical implications of the genome project and technology transfer as it relates to U.S. competitiveness. It is hoped that in 3 years the Human Genome Organization (HUGO) will be functioning effectively and that the major industrialized countries will participate in providing funding for HUGO activities. Applications Received Dr. Bettie Graham, Research Grants Branch, said that her office is receiving an increasing number of applications. Efforts are being made to increase the number of fellowship applications. Dr. Jane Peterson, Research Centers Branch, reported on a briefing in September attended by representatives from 17 institutions interested in submitting applications for center grants within the next year; applications are expected for both the P30 grants, the core mechanism for center support, and P50 grants, the mechanism for support for the specialized center. In the summer a briefing was held for intramural scientists to explain how they could participate in the genome project. Reviewers of intramural proposals will be those who have reviewed genome grants in the extramural program, providing continuity. Grants Funded and Workshops Planned Dr. Mark Guyer, Assistant Director for Program Coordination, outlined the existing portfolio of grants and noted that many applications overlap in subject areas. Dr. Jordan said that about 30 percent of approved applications were funded last year(the final percentage funded was 36% as compared to an average of 29% for all of NIH), but the percentage will be lower this year. Dr. Guyer reported on recent workshops: Human Gene Mapping Workshop 10 in June 1989; the second of the chromosome-specific physical mapping workshops for chromosome 16 last spring; the Wolf Trap Genome Sequencing Workshop; a meeting this fall of the CEPH [Centre d'Etude du Polymorphisme Humain] Consortium Map Group working on chromosome 1; and the mouse-mapping meeting. Two more workshops are planned for December in Houston, jointly supported by DOE. Several applications are pending for chromosome-specific physical mapping workshops on chromosomes 3, 5, 17, 21, and 22. Discussions have been held with communities of people interested in model organisms, with a view to getting organized on an organism basis. With respect to the prokaryotic world, a roundtable is planned for the ASM meeting to discuss bacterial genomes. Two applications are pending for meetings on the ethical, legal, and social aspects of the genome project. Reports of Meetings Joint NIH/DOE Planning Group. The planning meeting held in August 1989 at the Banbury Conference Center in Cold Spring Harbor resulted in the draft of the 5-year plan. Dr. Olson presented a report on the STS as a method of physical mapping and keeping track of fragments of DNA. The report generated a great deal of enthusiasm and optimism that a sensible plan could be devised. Dr. Zinder suggested that a planning meeting be held every year at the end of August to review progress and revise the plan. This suggestion was accepted with enthusiasm. Sequencing Workshop. Dr. Pearson reported on the Wolf Trap meeting, whose focus was on technology and the development of methods for high throughput, high accuracy, and low-cost sequencing. A number of projects at the hundred kilobase sequencing level were discussed, a number of initiatives were described, and progress was reported in the development of a sequence for E. coli and a joint British/United States effort for C. elegans. There was discussion of the T-cell receptor locus, reports on X-chromosome sequencing, and reports on several "lurches" forward in front-end preparation of DNA samples prior to conventional sequencing, including application of robotics and the use of solid-phase methods allowing the fixing of DNA on various solid supports. A persistent theme of polymerase chain reaction technology as applied directly to sequencing pervaded the discussions, and progress in the development of vectors was reported. There is great activity in the development of new mapping tools. Discussions were held at a subsequent meeting at the National Library of Medicine on the development of tools for addressing the STS data-collection and map-generation problem and on chip development and large-scale integrated circuitry that would permit large-database searching to become more rapid and useful. With regard to policy, one issue was raised: data sharing and publication. Human Genome I. Dr. Charles Cantor, Columbia University, reported on the San Diego human genome meeting, the purpose of which was to describe the progress of the genome project to the scientific public. Sessions were held dealing with technology, progress in sequencing and mapping, studies on individual genes, and the political and organizational aspects of the project. The meeting will occur annually, and the next will be held October 22-24, 1990. Science intends to publish an annual report on the progress of the genome project. Santa Fe Meeting. Dr. Barnhart reported on the first DOE/contractor/grantee workshop held in the genome program. The area of physical mapping has made the most progress at three major centers: Los Alamos, Berkeley, and Livermore. Progress was also reported in the development of electronic notebooks. Capabilities for inputting data as generated and for storage and analysis using available hardware are being developed. Capabilities are also being developed for accommodating infor- mation at various levels of resolution. The meeting is expected to be held every 18 months. Budget Report Dr. Jordan provided an updated version of the budget and said that all figures are tentative. Department-wide reductions and reduction due to sequestration under the Gramm-Rudman-Hollings Act will be made. The final budget will be between $58 and $60 million. Dr. Jordan said that small shifts in funding can be accommodated but that any significant shift would probably go back to the Appropriations Subcommittees for approval. She said that there is a general sense that more flexibility is needed at the beginning of a project. Ethics Working Group Dr. Wexler reported that the group met on September 14-15, 1989, to draft a report focusing on goals and how to achieve them. The working group is planning its first interdisciplinary workshop early in 1990, with the intent of informally gathering groups from various areas, such as industry, the arts, and the media, to hear their points of view. Town meetings are planned for spring or summer. Internationally, a meeting was held in Europe on October 22 on the ethical, social, and legal aspects of the genome initiative. Dr. McKusick is the new chairman of the ethics committee of HUGO. Dr. Wexler said that because of public concerns, society should move slowly toward institutionalizing genetic testing. On the other hand, physicians need reassurance that they will not be liable if they do not provide testing. Report on Informatics Activities Dr. Pearson reported that genome informatics encompasses elements ranging from the acquisition of genome information (mapping and sequencing) to its ultimate analysis and biological interpretation. Genome informatics will generate a variety of maps as well as DNA and protein sequences. Meetings of members of the NIH and the DOE working groups and the GenBank Advisory Panel have produced a recommendation that a joint informatics task force be formed to deal with informatics issues. The task force would be responsible for genome informatics technology and would make policy recommendations to the parent committees on advancing the technology. Near-term goals include rapid acquisition and public dissemination of genetic maps and DNA and protein sequences; promotion of the development of software to support large-scale mapping and sequencing projects; and creation of database tools that allow ready comparison of the various types of data produced by the genome project. Long-term goals center on issues of connectivity and coordination. NIH/DOE 5-Year Plan- Next Steps Dr. Olson said that the concept of STS takes advantage of technical advances, in particular the polymerase chain reaction, to enable the use of a new class of landmarks as the common language of physical mapping. Resolution and continuity are affected by the spacing of these landmarks and the number of allowable gaps. During the course of the genome project, on the order of 100,000 of these landmarks should be defined, perhaps only a fraction of which would ever be mapped with sufficient certainty to be markers on the final map. Dr. Olson recommended the establishment of a working group to develop a detailed implementation plan. Policy on Data Dissemination Although there is consensus on the need to share information, it is difficult to define specific criteria and guidelines. It was suggested that this issue be on the agenda for the next informal retreat.