Sponsored by the U.S. Department of Energy Human Genome Program
Human Genome News Archive Edition
Human Genome News, May-June 1995; 7(1)
The National Advisory Council for Human Genome Research convened for its 13th meeting on January 30 in Washington, D.C. Francis Collins, Director of the NIH National Center for Human Genome Research (NCHGR), presided. Noting that 1994 was a banner year for scientific achievements in the Human Genome Project, Collins highlighted progress in physical and genetic mapping and in sequencing.
Lloyd Smith (University of Michigan) reported that the December 15, 1994, meeting of NCHGR directors of genome science and technology centers (GESTECs) focused on transition to large-scale sequencing. At the meeting, three concerns related to the scientific community's desire for transcription maps were cost, funding balance between production and technology development, and portfolio division among technologies.
Smith pointed out that the NCHGR budget proposed at the directors' meeting includes a sevenfold funding increase for sequencing in a few years, representing a reorientation of project goals. After Robert Waterston (Washington University) outlined for the directors a concrete plan for accomplishing human genome sequencing (see "Scenario" below), meeting attendees agreed on the need to determine how sequencing methods will scale, where substrate cosmids will originate, and how to assess accuracy. Smith also described a proposal by Leroy Hood (University of Washington, Seattle) to regroup genome project goals into high resolution (sequence) and low resolution (genetic and STS maps).
David Botstein (Stanford University School of Medicine) recommended that political considerations not deter the council from their sequencing emphasis and that mouse sequencing, while critical, be added only when completion of the human sequence is within sight. He asserted that mouse geneticists can readily study sequences conserved in human and mouse. Collins stated that the current 5-year plan includes limited mouse sequencing in parallel with human DNA sequencing.
Waterston reviewed the status of Caenorhabditis elegans sequencing for the council and described his ambitious scenario, devised with John Sulston (Sanger Centre), for human genome sequencing. Drawing upon their experience in coordinating the C. elegans project, Waterston proposed that a human genome map should be produced at sequence level by 2001 to locate all human genes from various sources in context. Sequencing would be done chromosome by chromosome, permitting methodological flexibility; and mouse and human data comparison could be included at some stage. Waterston's strategy is to carry out low-pass shotgun sequencing with fully automated data analysis. Results expected are 99% coverage with 0 to 2 gaps per cosmid, oriented contigs, estimated gap sites, and 99.9% accuracy at an estimated $.10 per base. For each center doing 200 Mb annually, the cost will be $20 million to $25 million each year.
Jane Peterson (Chief, NCHGR Mammalian Genomics Branch) presented for discussion a draft RFA, arising from the December GESTEC meeting, for pilot projects for large-scale sequencing of human DNA. After suggested revisions have been made, the draft will be brought to the council again.
A second RFA proposed for concept clearance involved sequencing the Escherichia coli genome. Discussion leader Robert Strausberg (Chief, NCHGR Sequencing Technology Branch) observed that cost-effectiveness must be demonstrated and time lines and milestones made clear. He suggested that applicants establish goals for accuracy and that peer reviews evaluate them. The goal is to complete these projects in 2 years at a cost of no more than $2 million, which the group agreed seemed realistic for research groups already doing sequencing. The council endorsed the RFA as presented.
Elizabeth Thomson (Acting Chief, NCHGR ELSI Branch) reviewed ELSI education grants for FY 1990-94 and reported that 122 applications were received for FY 1995, of which 22 were education applications. She added that the NCHGR ELSI program has funded about two to four education programs each year and that a group of advisors will be invited to discuss priorities for funding ELSI education grants.
Reporting on the DOE ELSI program, Daniel Drell stated that DOE concentrates on genetic privacy research and scientific and ELSI education. Applications have stabilized at 35 per year with one review cycle. The previous 2:1 ratio of research to education applications has reversed because the education applications competed more favorably in peer review.
Commenting on recent activities of the ELSI Working Group at which she represents the council, Anita Allen (Georgetown University Law Center) stated that the group collaborated with the NIH Office of Protection from Research Risks (OPRR) to issue informed-consent guidelines for which dissemination mechanisms are being explored. Joan Porter (OPRR) reported that participants at the first meeting of the NCHGR-National Cancer Institute cancer studies consortium had pointed out generic and genetics-specific problems with informed consent, some of which may be addressed in a limited way through institutional review boards [HGN 6(4), 15 (November 1994)].
Noting that the ELSI Working Group has never had a formal mission statement outlining goals and delegation of authority, Collins submitted a mission statement to the council for review.
In response to concerns expressed at a previous council meeting, Bettie Graham reported that she had analyzed the NCHGR portfolio to determine the funding status of young investigators. After comparing NCHGR's R01, R26, and GESTEC statistics historically with those of NIH, she concluded that statistics for the two groups are very similar.
Smith recommended that the council discuss software modularity and interchangeability at its next meeting. He urged that investigators reduce duplication of effort by cooperatively establishing standards and following guidelines. Jay Snoddy (DOE) stated that DOE is addressing these issues through informatics meetings, and David Benton (NCHGR Office of Scientific Data Management) reported that the NCHGR GESTECs planned two joint informatics meetings.
A report from the DOE genome program will be a regular feature of future council meetings.
The council reviewed 154 applications requesting $40,841,162, including 103 regular research, 5 pilot- project, 19 ethics, 6 center, 4 conference, 10 small business innovation research, 1 research career development, and 3 continuing-education training grants. A total of 128 applications requesting $29,781,878 were recommended for approval.
The council agreed to meet May 22-23 and September 11-12, 1995, and January 29-30, 1996.
The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v7n1).
The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.
Published from 1989 until 2002, this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research.