The National Advisory Council for Human Genome Research (NACHGR) was convened for its fifteenth meeting at 8:30 a.m. on September 11, 1995, at the Embassy Suites Chevy Chase Pavilion, Washington, D.C. Dr. Francis Collins, director of the National Center for Human Genome Research (NCHGR), called the meeting to order.
The meeting was open to the public from 8:30 a.m. to 12:30 p.m. on September 11. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 1:30 p.m. on September 11 to adjournment on September 12 for the review, discussion and evaluation of grant applications.
Dr. Anita Allen
Dr. Lennette Benjamin
Dr. David Botstein
Dr. R. Daniel Camerini-Otero
Dr. Ellen Wright Clayton
Dr. Troy Duster
Dr. Leroy Hood
Dr. David Housman
Dr. Richard Myers*
Dr. Diane Smith
Dr. Lloyd Smith
Dr. M. Anne Spence
Dr. Shirley Tilghman
Dr. David Valle
Dr. James Weber*
*Ad Hoc Member
Jane Ades, Committee Management Officer
Dr. David Benton, Assistant to the Director for Scientific Data Management
Karina Boehm, Public Health Educator
Erin Burgess, Budget Officer
Dr. Francis Collins, Director
Dr. Carol Dahl, Assistant Director, Sequencing Technology Branch
Linda Engel, Chief, Office of Scientific Review
Dr. Elise Feingold, Health Scientist Administrator
Leslie Fink, Chief, Office of Communications
Mary Glynn, Personnel Officer
Dr. Bettie Graham, Chief, Mapping Technology Branch
Dr. Mark Guyer, Assistant Director for Program Coordination
Linda Hall, Grants Management Specialist
Dr. Kathy Hudson, Assistant Director for Policy Coordination
Dr. Elke Jordan, Deputy Director
Robert Kuska, Writer-Editor
Kimberly Malone, Secretary
Carol Martin, Computer Programmer Analyst
Jean McKay, Program Policy Analyst
Tara Mowery, Grants Technical Assistant
Dr. Kenji Nakamura, Scientific Review Administrator
Tira Oliver, Clerk-Typist
Diane Patterson, Grants Management Specialist
Jane Paull, Grants Technical Assistant
Dr. Jane Peterson, Chief, Mammalian Genomics Branch
Michael Royal, Budget Analyst
Anne Rufo, Program Analyst
Dr. Jeffery Schloss, Health Scientist Administrator
Helen Simon, Chief, Program Planning and Evaluation
Ommie Smith, Program Assistant
Dr. Robert Strausberg, Chief, Sequencing Technology Branch
Elizabeth Thomson, Acting Chief, Ethical, Legal, and Social Implications Branch
James Vennetti, Executive Officer
Sally York, Grants Management Specialist
Asli Yucel, Program Analyst
Peter Ballard, The Blue Sheet
Robert Boyd, Knight-Ridder
Sarah Carr, OD, NIH
Dr. Cheryl Corsaro, DRG
Machi Dilworth, NSF
Dr. Dan Drell, DOE
Dr. Michele Durand, French Consulate General
Dr. Beverly Emanuel, American Society of Human Genetics
Liza Fires, Mayatech Corporation
Ms. Rosalie Goldberg, National Society of Genetic Counselors
Dr. Kurt Hirschhorn, American College of Medical Genetics
Anita Linde, Presidential Management Intern
Betty Mansfield, Human Genome News
Eliot Marshall, Science
Linda Mulhauser, Catholic University/Children's Hospital
Georgia Persinos, Washington Insight
Sara Radcliffe, SmithKline Beecham
Dr. Jay Snoddy, DOE
Sylvia Spengler, DOE
Dr. Marvin Stodolsky, DOE
Susan Wallace, HUGO
Dr. Jordan introduced Drs. Troy Duster and Leroy Hood, new council members, as well as Drs. Richard Myers and James Weber, ad hoc members of the council. Dr. Jordan then introduced Dr. Kurt Hirschhorn, liaison to NACHGR from the American College of Medical Genetics, Dr. Beverly Emanuel, liaison to the NACHGR from the American Society of Human Genetics, and Rosalie Goldberg, liaison to the NACHGR from the National Society of Genetic Counselors. She also introduced and welcomed visitors to the council meeting.
The minutes from the May NACHGR meeting were approved as submitted.
The dates of February 5-6, 1996, May 20-21, 1996, and September 16-17, 1996, were approved.
Dr. Collins began his report with the announcement of the death on August 30 of Verne Chapman, chairman of the Department of Molecular and Cellular Biology at Roswell Park Cancer Institute, and one of the nation's leading mammalian geneticists. Dr. Collins reviewed many of the scientific contributions of Dr. Chapman, including investigations leading to the development of genetic and physical maps of the chromosomes of the mouse genome. These tools are critical to identifying and analyzing the molecular defects which are often associated with cancer. Dr. Collins also expressed appreciation for Dr. Chapman's service as the chair of the National Institutes of Health (NIH)-Department of Energy (DOE) Mouse Working Group of the former Program Advisory Committee on the Human Genome and the significant leadership and expertise he provided to that group.
Dr. Collins continued his report to the council by sharing highlights from a number of significant events in the NCHGR. On July 11 the National Action Plan on Breast Cancer (NAPBC) and the NIH-DOE ELSI Working Group sponsored a meeting on genetic discrimination and health insurance. The meeting included presentations from individuals from families with hereditary breast cancer, researchers, representatives from the insurance industry, and government agencies. By the end of the day, all participants had a clearer picture of the reality and potential for genetic discrimination in insurance and an understanding of the state and federal laws and regulations. The final session of the meeting was a discussion of the key issues and the changes required to prevent genetic discrimination in insurance. Following the meeting, the ELSI Working Group and the Hereditary Susceptibility Working Group of the NAPBC developed a set of specific recommendations for state and federal policy makers. These recommendations have been endorsed by the full NAPBC and the ELSI Working Group and were sent to NACHGR members prior to this meeting for their review. Kathy Hudson, Karen Rothenberg, Lori Andrews and Francis Collins have written a paper to be published in the October 20 "Genome Issue" of Science explaining the origin and purpose of these recommendations. Dr. Collins noted that Dr. Hudson would be reviewing these recommendations later that morning and he encouraged council members to consider endorsing these recommendations. He suggested that it is time to address this difficult issue with a legislative solution.
The Genome Action Coalition (TGAC) has grown exponentially since the last meeting of the council. It is a voluntary non-government group comprised of representatives of patient advocacy groups, professional groups, the university research community, biotechnology companies, and pharmaceutical companies. The coalition is a key advocate for government and private investment in genome research and the development and ultimate success of the Human Genome Project (HGP). It is also an educational vehicle intended to expand the knowledge and understanding of genome research. Members of the coalition, as well as some organizations that have not yet joined, have written strong letters of support for the NCHGR to both the House and Senate Appropriations Committee members. Dr. Collins expressed his gratitude for their support for the NIH in general and the NCHGR in particular. He noted the effective role that Dr. Kay Jamison, a former member of NACHGR, plays as chair of the steering committee of the coalition.
The HGP is celebrating a milestone - the fifth anniversary of the project. A number of events have been scheduled throughout the fall to note this milestone. On November 15, TGAC has planned a celebration at the National Academy of Sciences (NAS). The event will begin with a keynote lecture to launch the James Watson Lecture series, followed by a reception where awards will be presented to key Congressional and other leaders who have supported the HGP. TGAC will be inviting members of NACHGR to attend this special celebration. In early December, the NCHGR is sponsoring a one-day scientific symposium at the NIH on the future of sequence-based biology. The goal of this event is to look beyond today to the significant impact the HGP will have on all areas of biomedical research. The speakers will not be solely genome researchers, but will also include people working in the field who can project how the HGP alters how biomedical research will be carried out. Other events to note the fifth snniversary include three publications: the September 28 issue of Nature that will include a Genome Directory, the October 20 "Genome" issue of Science, and the anniversary issue of the Human Genome News to be issued in mid-November. The Genome Science and Technology and Centers (GESTEC) are being encouraged to sponsor local events. Dr. Collins observed that this fall promises to be an exciting time for celebration of all the achievements in genome research.
In his legislative update, Dr. Collins reported that this was a busy time and a time of high anxiety. On August 4, the House passed the FY 1996 Labor, HHS, and Education Appropriations bill by a vote of 219 yeas to 208 nays. Despite the funding levels recommended in the FY 1996 Budget Resolution, the NIH received a 5.7 percent increase over FY 1996, representing broad and substantial support for the NIH. The NCHGR was proposed to receive $170,041 million, which is an 11.2 percent increase over FY 1995 and includes funds for high throughput sequencing. The Senate Appropriations bill is expected to be taken up the week of September 11. It has been noted by many that the intense lobbying effort by the biomedical research community saved the NIH in an otherwise bleak picture.
In the area of health care legislation, Senator Nancy Kassebaum has introduced the "Health Insurance Reform Act of 1995," a bi-partisan bill aimed at moderate health care reform. The proposal attempts to guarantee the availability of health care by prohibiting insurers from denying coverage based on health status, medical condition, claims experience, receipt of health care, medical history, evidence of insurability or disability of a participant. The bill contains pre-existing condition exclusionary clauses, but these are time limited. Senator Tom Harkin has offered an amendment in committee to include "genetic information" in the list of items on which insurers cannot base availability of coverage. The committee did not agree to the amendment; rather, they voted to place the inclusion of genetic information in the committee's report language accompanying the bill. There is still the possibility the Senator will offer the amendment again if the bill reaches the Senate floor. On September 29, Senators Connie Mack and Dianne Feinstein, co-chairs of the Senate Cancer Coalition, are holding a hearing on issues surrounding genetic testing and cancer. Witnesses will include Dr. Collins and Dr. Richard Klausner, NCI Director. The hearing will explore the issues of the status of genetics research and gene discoveries, recommendations on large-scale genetic testing, genetic testing and counseling issues, and genetic discrimination and health insurance. Dr. Collins concluded his legislative report by noting that on August 14, he had the pleasure of meeting with Senator Mark Hatfield and presenting the Hatfield lecture to the Oregon Health Sciences University faculty. Dr. Collins was pleased that he had the opportunity to discuss biomedical research in general and the HGP in particular.
Dr. Collins reported that he was happy to be included in a meeting of the Joint Executive Committees of the American Society for Human Genetics (ASHG) and the American College of Medical Genetics on July 12, in Chicago. It was a very productive meeting where information and views on the respective organizations were shared. Topics of discussion included the Task Force on Genetic Testing; the apoE statement endorsed by the ELSI Working Group; ELSI Branch's identification of education of primary care providers as a high priority area; the ELSI Working Group-NAPBC workshop on genetic information and health insurance; the statement on informed consent for archived tissue samples; and how to ensure that the organizations stay current with each other's activities. Dr. Collins congratulated Dr. Hirschhorn on being the Allan Award Lecturer of the ASHG. He also stressed the importance of keeping channels of communication open among these groups and expressed gratitude to Drs. Hirschhorn and Emanuel, and Ms. Goldberg for their roles as liaisons to NACHGR.
On Saturday, August 5, President Clinton visited the NIH. He stopped at the Children's Inn where he met families and staff and broadcast his weekly radio program on the benefits of the Family and Medical Leave Act on its second anniversary. Later the President went to the Clinical Center where he spent about two hours hearing about exciting areas of science and visiting some patients. Dr. Collins noted that genome science was one of the areas of science shared with President Clinton and the dialogue and questions were very good. Subsequently, President Clinton expressed how impressed he was by his time at the NIH.
On September 5-6, the NIH held a Leadership Forum with institute directors and key staff of the Office of the Director to plan the course for moving forward together. The first session was on Fundamental Principles of Research Support and included discussions of the financial relationship with the grantee institutions and trade-offs in stability versus competitiveness. Two topics in this area included modular grants and the proposal to only allow one revised application. Dr. Collins noted that this latter proposal was particularly enthusiastically received by the Institutes and Centers (IC) directors. The second session was on presenting the NIH and included a discussion of the need to activate the grass roots. The third session was on streamlining and included a discussion of the Research Management and Support budget and the impending budget cuts in this area. This area is characterized by limited flexibility so there is a need to be very creative.
Dr. Collins concluded his report by announcing that Dr. Richard Klausner was selected as the director of the National Cancer Institute (NCI) and was sworn in on September 20 by Secretary Shalala. The NCI and the NCHGR are intensely involved in a number of productive collaborations, including the identification of the ataxia telangiectasia (A-T) gene and the Center for Complex Disease Research. Dr. Collins expressed enthusiasm for his continuing to work with Dr. Klausner in his new position.
Dr. Collins introduced Dr. Myers and commended him on the critical role he played in the development of the Stanford Human Genome Center. He invited Dr. Myers to update the council on the activities of the center. Dr. Myers began his presentation with a slide of the 28 members of the Stanford Human Genome Center who had contributed to the work.
The goals of the Stanford Human Genome Center include the production of a Yeast Artificial Chromosome (YAC)-based STS content and radiation hybrid map of the human chromosome 4; a 400kb resolution radiation hybrid map of the human genome by June 1996; a 100kb resolution radiation hybrid map of the human genome by November 1999; the sequence of 1.5 Mb of human genomic DNA by November 1997; and an education program.
The strategy for human chromosome 4 mapping is to make multiple maps, integrate them, and then identify the strengths and weaknesses of different approaches. For a 100kb average resolution human map, 30,000 markers and 10 to 20X clone libraries or 80 to 90 radiation hybrids are needed. To date, the Stanford Center has made 8,500 markers and is ahead of schedule.
Dr. Myers reviewed the informatics component of his center and underscored the usefulness of their relational database in verifying particular markers. He also discussed the pilot sequencing project at Stanford in the context of mapping, noting that a good quality, sequence-ready map is necessary and they use a bacterial clone map and transposon sequencing.
The Stanford Human Genome Center's genetic education program focuses on human genome curricula for high school students, genome center tours and student research internships for high school students.
Dr. Botstein reported to the council on this small meeting that included large scale physical mappers and large scale sequencers. The goal of the meeting was to address three issues: the status of the 100kb resolution map; resources invested to complete the map; and, is it still the right thing to do. The concept of what this map will look like has evolved considerably, but there was agreement that the goal is still appropriate. With regard to how many STSs are needed, it has been estimated that 50 to100,000 STSs will be generated by research already funded and, together with the next generation of radiation hybrids, YAC resources, and Bacterial Artificial Chromosomes (BAC), the result will be a map of the desired resolution. Thus, it was agreed that the number of STSs that will be produced by the grants already funded to date will be more than enough. It is expected that this map will be good enough so that any scientist interested in a particular region of the genome will be able to use it to place a new marker with regard to the ordered map in a small region with very high confidence. Dr. Botstein noted that the map is very democratic since it is publicly available. Sequencers are comfortable with the map and report that, when they have clones, they have no trouble ordering their regions. The data seem to be of high quality, the Massachusetts Institute of Technology (MIT) and Stanford Human Genome Centers have good concordance and are working well together. The centers that use the data are comfortable with the service.
The conclusions of the meeting were that the 100kb map will be a reality and no additional funds need to be committed. The only question is how the maps will be displayed - a database issue, not an issue for individual centers. In response to a comment from Dr. Tilghman that the standard of mapping adopted at Cold Spring Harbor has been generally adopted by other researchers, Dr. Botstein concurred that mappers seem to be comfortable with that standard and the only issue arises when discontinuities are identified and the size of the gap is unknown. Dr. Tilghman asked if, when researchers report progress in achieving 100kb resolution, they are using the standard nomenclature. Dr. Botstein responded that all have agreed on reporting sequences of primers, but there are nontrivial differences in the standards of reporting; however, these differences are more academic than substantive. Dr. Myers observed that the goal is to be sure there is consistency in how map data are reported. Dr. Myers also noted the lesson learned of the value of having two independent methods of approaching mapping.
Dr. Duster asked if any institution was charged with administering and coordinating this activity. Dr. Botstein replied that was the council's responsibility, to be sure that funds used for this purpose were used effectively. This is why the NCHGR sponsored this workshop and the news was good. Dr. Botstein noted that although there are still researchers who do not believe they need them, the maps will be very useful for sequencers. Dr. Lloyd Smith stated that the difference between the STS map and the sequence-ready map is not trivial and the problems involved must continue to be addressed. Dr. Botstein concurred that an STS map is different from a sequence-ready map. Dr. Collins concluded this discussion by noting that the council would be reviewing applications at its next meeting to get the maps ready, applications submitted in response to an NCHGR Request For Applications (RFA).
Dr. Hudson described a July workshop co-sponsored by the ELSI Working Group and the National Action Plan on Breast Cancer (NAPBC). This workshop used breast cancer as a case study to address genetic discrimination in health insurance. Key issues discussed at the workshop were: evidence that discrimination is taking place and the results from an NCHGR ELSI Program funded survey showing that 22 percent of families with genetic diseases had been denied health insurance; the impact on research of discrimination or fear of discrimination; the absence of federal laws in this area; and, the existence of some state laws and their limitations. Following the workshop, the NAPBC and the ELSI Working Group developed four recommendations that were presented by Dr. Hudson:
Definitions: "Genetic Information" is information about genes, gene products or inherited characteristics that may derive from the individual or family members. "Insurance provider" means an insurance company, employer or any other entity providing a plan of health insurance or health benefits including group and individual health plans whether fully insured or self-funded.
The goal is to use these recommendations in four ways: to share them broadly with federal policy makers, to share them with key Congressional Committees, to stimulate preliminary discussions of co-sponsoring regional seminars in this area, and to publish an article in Science that lays out the issues.
Dr. Hirschhorn asked for clarification of recommendation III and the prohibition from requesting or requiring collection or disclosure of genetic information. He asked if this would create a practical problem as an insurance company may receive information that includes genetic information and it may be very difficult to enact this prohibition. Dr. Allen noted that there is an interplay between recommendations I and III that addresses this issue and that even if insurance companies have genetic information they can not use it. Dr. Hudson stated that the spectrum of how Americans pay for health insurance may be too broad to cover all types.
Dr. Botstein expressed concern about recommendation III and asserted that recommendation I is an important point. The prohibition on requesting information made him uncomfortable, but the prohibition against companies using the information is the key. Dr. Collins responded that use of genetic information should be decided by the patient.
Dr. Lloyd Smith stated that the distinction between insurance providers and physicians is confusing and that this is a statement of principle. He asked if a disclaimer should be added that recognizes the critical need of physicians and other health care providers to have genetic information.
Dr. Clayton stated the critical importance of these recommendations, noting that genetic predispositions must be addressed relative to health insurance. As a clinician, she asserted that it is difficult to distinguish what is genetic. Much family history is environmental, while other aspects are genetic.
Dr. Collins noted that it would be difficult to amend these recommendations at this juncture as they had already been endorsed by the NAPBC and the ELSI Working Group. He stated that the document could have clarifications of particular points, however.
Dr. Weber addressed recommendation III, the second paragraph and stated that "other holders of genetic information" could be a problematic prohibition as information from relatives should be able to be used anonymously to improve health care. Dr. Collins stated that the Institute of Medicine Panel concluded that individual privacy and confidentiality supersedes the right of the family. Dr. Spence observed that genetics has always leaned toward the right of individual privacy, but the standard will ultimately be decided in courts of law. Dr. Lloyd Smith requested that explicit wording of clarification be developed and reviewed by the council at a later time.
Dr. Allen reported to the council on the July 10 meeting of the ELSI Working Group and invited council members to review the agenda and minutes of that meeting included in their folders. She also referenced the NAPBC/ELSI Working Group meeting discussed by Dr. Hudson previously. Dr. Allen noted that the July meeting had been the first meeting that included Lori Andrews as the new chair as well as new members. She observed that the first day of the meeting had been focused on introducing the new members and orienting them to the ELSI program and issues.
Ms. Thomson requested council approval of the ELSI Program Announcement that had been sent to Council members as approved by the ELSI Working Group. She reviewed the history of the ELSI program by noting that the original ELSI Program Announcement was issued in 1990 and cast a broad net, including clinical issues, privacy and fair use of genetic information, and education, and these issues were very broadly defined. Now, five years later, there is a need to crystallize high priority research areas to encourage research proposals within these areas. Ms. Thomson reported that 10 percent of the ELSI program budget was spent on genetics research issues, with four active grants; half of the budget is devoted to clinical issues, including testing and counseling; 20 percent of the ELSI budget is spent on issues surrounding the use and interpretation of genetic information, conceptual issues, philosophical issues, and privacy and fair use; and 20 percent of the ELSI budget is spent on education. No guidance was provided in the original Program Announcement for education. Subsequent to the meeting sponsored by the NCHGR in April and reviewed at the May NACHGR meeting, high priority areas were identified in the field of ELSI education.
Dr. Duster pointed out that the Program Announcement (PA) stated that television documentaries were a lower priority, i.e., they are expensive and it is difficult to assess educational benefits. Dr. Spence endorsed the proposal that the PA have a single receipt date for education applications. In response to a question from Dr. Valle on the size of the ELSI portfolio, Ms. Thomson stated that 50 ELSI grants are active and between five and 10 new grants are funded each year.
The council endorsed the PA as presented.
Ms. Jane Paull asked for council discussion of the electronic transfer of summary statements to council members. Reactions were quite diverse, from some members who had not used the electronic version at all to others who found it quite useful. When put to a vote, only four council members were in favor of continuing to use electronic versions of summary statements. However, it was agreed that electronic transfer would be given another trial at the next council meeting.
Dr. Dan Drell gave the report from DOE and stated that the main item he wanted to present was the DOE human genome budget. He noted that the process was not completed yet, but all indications were that the budget would be $70 million in FY 96 as in FY 95. The DOE is realigning and restructuring so a flat budget is actually a triumph and reflects the priority given to genome in the DOE and Congress. Dr. Drell also informed the Council that the September 28 issue of Nature included the genome directory and the highly detailed chromosome 16 map from the Los Alamos laboratory. It is anticipated that, by the end of the year, the Genome Data Base version 6 will be released. In addition, the DOE genome project has pilot sequencing efforts underway and is struggling, as the NCHGR, is with choosing a strategy to support as improved technologies are anticipated. Finally, Dr. Drell reported that the DOE ELSI program had a panel meeting and that education grants had been rated rather well. The DOE endorses the NCHGR effort to improve specificity in this area in its research solicitations.
Dr. Jordan then called the attention of the council to items that were available in their table folders, including:
It was agreed by the council members that Dr. Gerry Rubin would be invited to present to the council at its February 1996 meeting and that an ELSI speaker would be invited to the May council meeting to brief members on the cancer studies consortium.
Dr. Jordan read the Conflict of Interest statement and reminded the council members that all review materials furnished to council members are privileged information. Conflicts involving institutional affiliations already had been identified. Members were asked to absent themselves also during discussions of any applications in which there was a personal or professional conflict not identified by staff.
Council reviewed 228 applications requesting $64,541,826. The applications included 26 regular research grants, 11 pilot projects, 73 program projects, 10 ethics grants, three research center grants, four conference grants, 13 training grants, 13 small business innovative research grants, one continuing education grant and 25 other grants. A total of 156 applications requesting $45,802,914 were recommended for approval.
The meeting adjourned at 3:00 p.m. on Tuesday, September 12, 1995.
|Top of page|
Last Reviewed: March 2006