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.