National Advisory Council for Human Genome Research
Summary of Meeting

Bethesda, Md.

May 19-20, 1997

The National Advisory Council for Human Genome Research (NACHGR) was convened for its twentieth meeting at 8:30 a.m. on May 19, 1997, at the National Institutes of Health (NIH), Building 31, Conference Room 6. Dr. Francis Collins, director of the National Human Genome Research Institute (NHGRI), called the meeting to order.

The meeting was open to the public from 8:30 a.m. to 5:30 p.m. on May 19. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 8:30 a.m. on May 20 to adjournment May 20 for the review, discussion and evaluation of grant applications.

Council members present:

Dr. Lennette J. Benjamin
Dr. Aravinda Chakravarti*
Dr. Ellen W. Clayton
Dr. David R. Cox
Dr. Ruth Faden*
Dr. Leroy Hood
Dr. Jeanne Lawrence*
Dr. Richard Mathies
Dr. Joseph Nadeau*
Dr. Diane C. Smith
Dr. M. Anne Spence
Dr. David Valle
Dr. Barbara Wold

Council members absent:

Dr. Troy Duster
Dr. H. Robert Horvitz*
Dr. Alan Williamson*

*Appointment pending

Liaisons from Professional Societies:

Ms. Rosalie Goldberg, National Society of Genetic Counselors
Dr. Kurt Hirschhorn, American College of Medical Genetics

Staff from the National Human Genome Research Institute:

Jane Ades, OPC
Kate Berg, DIR
Joy Boyer, DER
Lisa Brooks, DER
Erin Burgess, OAM
Jean Cahill, OAM
Francis Collins, OD
Adam Felsenfeld, DER
Leslie Fink, OPC
Bettie Graham, DER
Mark Guyer, DER
Kathy Hudson, OPC
Linda Jacobson, OAM
Elke Jordan, OD
Carol Martin, OIS
Jean McKay, OPC
Eric Meslin, DER
Tara Mowery, OAM
Kenji Nakamura, DER
Diane Patterson, OAM
Jane Peterson, DER
Rudy Pozzatti, DER
Jerry Roberts, DER
Jeffery Schloss, DER
Megan Sexauer, OPC
Elizabeth Thomson, DER
James Vennetti, OAM
Stephanie Walker, OAM
Elsa Weinstein, OAM
Jeff Witherly, DIR
Monika Yakovich, OAM
Sally York, OAM

Others present for all or a portion of the meeting:

Kristina Borror, NIH
Cheryl Corsaro, DRG
Mary Davidson, Alliance of Genetic Support Groups
Dan Drell, Department of Energy
Irene Eckstrand, NIGMS
Lily Engstrom, OASPE/DHHS
John Ferguson, OMAR
Bill Fitzsimmons, NIMH
Judith Groenberg, NIGMS
Steve Groft, ORD
Jim Hanson, OS/DHHS
Philip Harriman, NSF
Neil Holtzman, Johns Hopkins University
Doug Hussey, NIH
Sunil Iyengar, "The Blue Sheet"
Julie Kaneshiro, OSP
Pam Moore, Capital Publications
Kathy O'Donoghue, College of American Pathologists
Ari Patrinos, Department of Energy
Nancy Pearson, DRG
Maria Persinos, Washington Insight
Richard Riseberg, OGC/DHHS
Christine Seward, Texas A&M
Louis Sibal, NIH
Mike Watson, Washington University
Joan Weiss, Alliance of Genetic Support Groups

INTRODUCTION OF NEW MEMBERS, LIAISONS, AND NEW STAFF

Dr. Jordan introduced the new Council members: Dr. Aravinda Chakravarti, Case Western Reserve University; Dr. Ruth Faden, The Johns Hopkins University; Dr. H. Robert Horvitz, Massachusetts Institute of Technology; Dr. Jeanne Lawrence, University of Massachusetts Medical School; Dr. Joseph Nadeau, Case Western Reserve University; and Dr. Alan Williamson, Merck Research Laboratories. Drs. Horvitz and Williamson were not present. New staff introduced included: Dr. Lisa Brooks and Dr. Adam Felsenfeld, who are responsible for portions of the informatics and technology development portfolios; and Ms. Marchell Dickerson, grants technical assistant. Dr. David Benton has resigned to begin a new job with SmithKline Beecham.

Dr. Jordan introduced the liaisons to the council from the professional societies: Dr. Kurt Hirschhorn, representing the American College of Medical Genetics; and Ms. Rosalie Goldberg, representing the National Society of Genetic Counselors. Dr. Beverly Emanuel, who represents the American Society of Human Genetics, was not present.

APPROVAL OF MINUTES

The minutes from the February 20-21, 1997 NACHGR meeting were approved as submitted.

FUTURE MEETING DATES

September 11-12, 1997, January 25-26, 1998, and May 4-5, 1998 were approved dates for council meetings. The following dates were proposed for future meetings: September 14-15, 1998; February 22-23, 1999; May 17-18, 1999; September 13-14, 1999; February 28-29, 2000; May 22-23, 2000; and September 11-12, 2000.

DIRECTOR'S REPORT

James Watson Awarded National Medal of Science

President Clinton awarded the National Medal of Science to Dr. Watson, citing his leadership in molecular biology, including his co-discovery of the double-helix structure for DNA, his advocacy for the Human Genome Project (HGP), and as the founding director of the National Center for Human Genome Research. The National Medal of Science, established by Congress in 1959, is administered by the National Science Foundation (NSF) and honors scientists in the fields of physics, biology, chemistry, mathematics, engineering, and sociology and other behavioral sciences. Dr. Watson was among the nine recipients of this year's award.

Eric Lander Elected to the National Academy of Sciences

On April 29, Dr. Lander, Director of the Whitehead/Massachusetts Institute of Technology Center for Genome Research, was elected as a member of the National Academy of Sciences. Dr. Collins noted Dr. Lander's achievements in producing the genetic and physical maps for the mouse and human, his role in scaling-up the human sequencing efforts and his pioneering efforts in the mathematical analysis of complex diseases.

First John Wasmuth Fellowship in Genomic Analysis

Award Dr. Collins announced that Dr. Elizabeth A. Winzeler, a developmental biologist, is the recipient of the first John Wasmuth Fellowship in Genomic Analysis award. Dr. Winzeler, currently a postdoctoral fellow in Dr. Ronald Davis's laboratory, plans to study factors in the cell that stabilize RNA. It is anticipated that the results from this ambitious project will expand the understanding of gene expression. Dr. Collins sent a letter to Mrs. Wasmuth informing her of the award.

Recent Scientific Meetings

The second international strategy meeting on human genome sequencing, sponsored by the Wellcome Trust, was held from February 28-March 2. Dr. Collins reported that all major international sequencing groups were represented and that participants reaffirmed the principles set forth at last year's meeting for acceptable error rates and rapid data release. In addition, the group adopted the following: a "no gaps" goal; gaps that are left must be annotated; and sequencing laboratories should have quality control procedures in place. There were also productive discussions about ways to divide the work of sequencing of the human genome to avoid duplication and methods to calculate sequencing costs.

On May 14, NIH Director Dr. Harold Varmus held a meeting of Institute, Center, and Division (ICD) Directors to assess the state of the science of three model genome systems and to consider ways to provide funds to move these projects forward. These three model systems are the rat, mouse, and zebrafish. The National Heart, Lung and Blood Institute (NHLBI) has the lead for the rat genome project. Dr. Collins provided the ICD directors with an update on the mouse genome project and noted that the NHGRI plans to issue an RFA to map mouse ESTs. Dr. Richard Klausner, director of the National Cancer Institute (NCI), gave a brief update on the status of the NCI Working Group on Preclinical Models for Human Cancers. Dr. Leonard Zon, from Children's Hospital in Boston, made a presentation on zebrafish. Dr. Collins noted that, for many reasons, the zebrafish is an attractive model for genetic studies, but it is unlikely that the NHGRI, on its own, would have the resources to support a zebrafish project.

The tenth annual Cold Spring Harbor meeting on "Genome Mapping and Sequencing" was held May 14-18. The meeting was organized by Drs. David Bentley (Sanger Centre), Eric Green (NHGRI), and Phil Hieter (Johns Hopkins University). There was a wide range of topics presented and Dr. James Watson gave the keynote address. Data presented at the session on large-scale sequencing projects indicated that 54.2 megabases of the human sequence have been completed, which represents 1.8 percent of the human genome. Over the next twelve months, it is expected that a total of 164 megabases will be completed, equaling 7.2 percent of the human genome. Dr. Eric Meslin organized the ELSI session, which included discussions on informed consent, gene therapy, and the National Bioethics Advisory Commission and human cloning. The eleventh annual Cold Spring Harbor meeting will be organized by Drs. Richard Gibbs (Baylor), Steve Brown (United Kingdom), and Mark Boguski (NIH).

On March 3, the NHGRI and the Centers for Disease Control and Prevention (CDC) co-sponsored a meeting entitled "Hereditary Hemochromatosis: Gene Discovery and Its Implications." The purpose of the meeting was to examine the existing policies and practices regarding screening, diagnosis, and management of hereditary hemochromatosis (HH), and the implications that the gene discovery may have on the possibility of wide-spread genetic testing for this disorder. The meeting participants generally agreed that it was premature to consider population-based genetic testing; however, the group agreed to consider biochemical evaluation (i.e., transferrin saturation) for screening, perhaps with genetic testing for confirmation. The issue of blood donation by patients with hereditary hemochromatosis was also discussed at the meeting. Currently, most blood banks have a policy that prevents blood donated as a result of a therapeutic phlebotomy from being used for transfusions, even if the donor would otherwise meet the criteria to be a volunteer donor. In addition, many blood banks charge patients for therapeutic phlebotomies, the costs of which may not be reimbursed by insurance companies. The meeting participants adopted a resolution that this issue should be reconsidered. Stigmatization and discrimination remain unresolved issues for people with hereditary hemochromatosis. Dr. Wylie Burke is preparing a summary of the meeting. Dr. Collins recognized the efforts of Ms. Elizabeth Thomson in the planning and organization of this important meeting.

New Findings in Cancer Genetics

The NHGRI-supported Cancer Genetics Studies Consortium has recently published three papers in the Journal of the American Medical Association. Two of these articles are on recommendations for follow-up care of individuals with mutations in BRCA1, BRCA2, and hereditary non-polyposis colon cancer genes (March 19, 1997, vol. 277, no. 11; March 26, 1997, vol. 277, no.12). The third article describes the process and content of informed consent for genetic testing for susceptibility to adult-onset cancer (May 14, 1997, vol. 277, no. 18).

Dr. Collins noted that there have been four papers published recently in the New England Journal of Medicine on BRCA1 and 2. One of these papers, "The Risk of Cancer Associated with Specific Mutations of BRCA1 and BRCA2 Among Ashkenazi Jews" (Jeffery Struewing, et al, May 15, 1997, vol. 336, no. 20), reported that the lifetime risk in high-risk families is lower than previous estimates. Dr. Collins expressed his view that data such as these will permit researchers to more accurately estimate the risks of cancer. Dr. Spence noted that the contribution of environmental factors needs to be considered in such risk assessments.

LEGISLATIVE UPDATE

Appropriations

Dr. Collins reported that the House appropriations subcommittee on Labor, HHS, and Education, chaired by Representative Porter, held hearings on February 27. Most subcommittee members were present and supportive of NHGRI. However, the primary focus was on "Dolly," the cloned sheep. Representative Porter expressed his interest in another hearing with the NHGRI, the NCI, and the National Institute of Allergy and Infectious Diseases (NIAID). This hearing, which was scheduled for May 7, was canceled due to Representative Porter's illness; the hearing has not been rescheduled. The Senate appropriations hearings have been postponed twice; the hearings have not been rescheduled. There have been calls for a 7.5 percent or better increase for the NIH FY98 budget, but mark-up of the bills has yet to occur.

Reauthorization

The Senate Labor and Human Resources Subcommittee on Public Health and Safety, chaired by Senator Frist, held a hearing May 1 to discuss setting priorities at the NIH. This was the first of two hearings by the Subcommittee in preparation for the NIH revitalization process. Witnesses included Dr. Varmus, Dr. Kenneth Shine (President of the Institute of Medicine), and representatives from the research community and the public. Dr. Collins noted that Dr. Varmus made a very persuasive argument for the current prioritization process employed by the NIH. The council received a copy of Dr. Varmus's prepared statement to the subcommittee on setting priorities at the NIH.

Other Hearings

On March 12, the Senate Labor and Human Resources Subcommittee on Public Health and Safety, chaired by Senator Frist, held a hearing on cloning. Witnesses included Dr. Wilmut (scientist responsible for cloning the sheep "Dolly"), Dr. Varmus, attorneys, physicians and pharmaceutical company representatives. The hearings focused on scientific discoveries, ethical implications and scientific opportunities related to research on cloning. Dr. Collins noted that in late February, the National Bioethics Advisory Commission (NBAC) was asked by President Clinton to "undertake a thorough review of the legal and ethical issues associated with the use of [cloning] technology, and report back to [President Clinton] within ninety days with recommendations on possible federal actions to prevent its abuse." Dr. Cox, also a member of NBAC, noted that the recommendations will be available in the near future.

On May 8, the House Government Reform and Oversight Subcommittee on Human Resources, chaired by Representative Shays, held a hearing on informed consent, including issues related to needle exchange, the mentally challenged, children and drug abuse. Witnesses included Dr. Varmus, representatives from the Food and Drug Administration (FDA) and the CDC, researchers, and bioethicists.

Health Insurance Discrimination, Employment Discrimination, and Privacy

Dr. Collins noted that there are several bills that will be introduced addressing these issues, and credited the ELSI component of the HGP with elevating these important issues to the highest levels of state and federal government. In a recent commencement address at Morgan State University, President Clinton stated: "... No insurer should be able to use genetic data to underwrite or discriminate against any American seeking health insurance. This should not just be a matter of principle, it should be a matter of law. And to that end, I urge Congress to pass bipartisan legislation to prohibit insurance companies from using genetic screening information to determine premium rates or eligibility for health insurance."

Dr. Collins noted that the recommendations on the use of genetic information in the workplace developed by the National Action Plan on Breast Cancer (NAPBC) and the ELSI Working Group were published in Science (March 21, 1997, vol. 275). The writing group was led by Ms. Karen Rothenberg. It is hoped that these recommendations will stimulate a comprehensive approach to the use of genetic information in the workplace. Several members of Congress have expressed interest in this issue.

The NHGRI and the NAPBC are co-sponsoring a workshop to address privacy and confidentiality of information in genetics research. This workshop will include an assessment of the current protections, an evaluation of key unresolved issues, and the development of a set of policy recommendations. A planning meeting will be held in June and the workshop is scheduled for September 16.

Tuskegee Apology

On May 16, President Clinton issued a formal apology to the participants in the Tuskegee experiment, their families, and the African-American community as a whole in a White House ceremony. In his speech, President Clinton stated that more needs to be done to ensure that research is sound and ethical, and that researchers work closely with the communities involved. He outlined a five-point plan for addressing these concerns:

  1. DHHS will award a planning grant to Tuskegee to establish a bioethics center in research and health care, along with a museum on the Tuskegee study.
  2. The DHHS Secretary will issue a report, in 180 days, detailing ways in which all communities, and minority communities in particular, can have more involvement in the development and implementation of research and health care.
  3. The DHHS Secretary will work with the higher education community to develop bioethics training materials for medical researchers. These materials will emphasize justice, respect for human subjects, the importance of informed consent and how these concepts can be used with diverse populations.
  4. DHHS will develop a postgraduate fellowship program in bioethics, particularly for minority researchers, that will accept its first class in September 1998.
  5. Extension of the NBAC charter to October 1999.
Health Professional Education
  • National Coalition for Health Professional Education in Genetics
    The first meeting of the full membership of the coalition was held March 10, at the NIH. Approximately 100 organizations representing health care professionals, consumer groups, industry, genetics professional organizations and government agencies participated in the meeting. The goals of the meeting were to persuade the leadership of key health professional organizations that genetics is becoming the central science of medicine, to build partnerships and encourage collaborations between participant organizations to address the issue of health professional education in genetics, and to obtain information from participants about ways in which the coalition can best meet their needs. Dr. Collins reported that the meeting was very successful and generated much enthusiasm among the participants. The coalition has identified the following issues as top priorities: a comprehensive, national genetics information center/clearinghouse (Web-based, initially); a core curriculum in genetics, which could be adapted by a variety of health care disciplines; the integration of genetics questions into licensure and certification exams; and reimbursement for genetics services. The efforts of the coalition have also been endorsed by the Task Force on Genetic Testing.

    In response to Dr. Benjamin, Dr. Collins stated that the National Medical Association was involved in the Coalition, and that there had been great efforts to reach out to minority organizations. However, he noted, there appeared to be an underrepresentation of the Hispanic community at the meeting.

  • American Medical Association
    In addition to its role in the Coalition, the American Medical Association (AMA) plans to hold a conference in 1998 on genetics education of primary care physicians. The NHGRI and the American Society of Human Genetics will assist the AMA in organizing this meeting. Dr. Collins noted that a Fall 1997 issue of the Journal of the American Medical Association will be devoted to genetics. Suggestions for topics can be sent to Dr. Collins, who will forward them to the journal's editors.

  • Macy Foundation
    The Josiah Macy, Jr. Foundation, headed by Dr. June Osborne, will hold a meeting from June 4 through June 6, in Williamsburg, Va. The purpose of the meeting is to discuss genetic services, the education of health care professionals in genetics, and the potential role of the Macy Foundation in meeting health professional education needs. The NHGRI provided assistance to the Macy Foundation in organizing the meeting.
Division of Intramural Research

Dr. Jeffrey Trent, NHGRI Scientific Director, will provide an update to the council on the activities of the Division of Intramural Research (DIR) at the September council meeting. Dr. Bert Vogelstein, from the Board of Scientific Counselors, will be asked to attend this meeting.

In the past four months, there have been several exciting scientific developments from NHGRI DIR researchers. Dr. Thomas Ried and colleagues tested spectral karyotyping against G-banding in fifteen patients with different forms of leukemia. Using spectral karyotyping, the researchers were able to detect aberrations in leukemia cells that were not detected using G-banding. Spectral karyotyping promises to significantly improve the diagnosis of certain types of cancer and possibly other diseases. These findings were published in the April 15, 1997 issue of Nature Genetics.

A team of scientists from the NHGRI, the NIDDK, the NCI, and the National Center for Biotechnology Information (NCBI) has identified a gene that can cause multiple benign tumors of the parathyroid and pituitary glands, as well as islet cell tumors leading to pancreatic cancer. Their discovery of the gene for multiple endocrine neoplasia, type 1 (MEN1) is reported in the April 18, 1997 issue of Science.

The NHGRI and Howard University plan to establish a center for collaborative research on genomic analysis of diseases that disproportionately affect African Americans. The center will build on the programs supported initially by the NIH Office of Research on Minority Health. These programs include the non-insulin dependent diabetes mellitus (NIDDM) study (now in its pilot phase) and a study of hereditary prostate cancer in African Americans. The center will lay the foundation for training African-American graduate students and postdoctoral fellows in human genome research. Dr. Charles Rotimi, from Loyola University in Chicago, will oversee the project, and has visited the sites in West Africa where the NIDDM study will be conducted.

NHGRI Administrative Review

Citing the change to institute status and the rapid growth of the NHGRI, Dr. Collins has initiated a review of the administrative structure of the institute. This review will assess the current structure and make recommendations to Dr. Collins regarding its responsiveness and appropriateness to the institute's functions. An administrative review committee, co-chaired by Mr. Tony Itteilag, the NIH Deputy Director for Management, and Mr. Bill Fitzsimmons, the Executive Officer of the National Institute of Mental Health (NIMH), has been established. The members of the committee are: Ms. Laura Rosenthal, Executive Officer of the National Institute on Drug Abuse (NIDA); Mr. Charles Leasure, Executive Officer of the National Institute of Environmental Health Sciences (NIEHS); and Mr. Donald Poppke, the Executive Officer of the National Library of Medicine (NLM). The committee's report is expected by mid-August.

TASK FORCE ON GENETIC TESTING

Dr. Neil Holtzman and Dr. Michael Watson, chair and vice chair, respectively, of the Task Force on Genetic Testing, presented the final recommendations of the Task Force to the council for their consideration. Dr. Holtzman gave a brief history of the Task Force, its organization and composition, and the process by which the final recommendations were developed. It is envisioned that the final document will contain, in addition to the principles and recommendations, chapters and appendices that will provide a history of genetic testing and background material.

The major recommendations were in five areas:

  1. Development of new genetic tests.
  2. External review of new genetic tests.
  3. Laboratory practices.
  4. Understanding [of genetic tests] by providers ordering tests.
  5. Provision of tests for and information about rare genetic diseases.

Dr. Holtzman noted that the Task Force found it difficult to determine an appropriate definition of "genetic test." The definition used by the Task Force emphasized the purposes for which genetic tests are used, particularly those used as predictive tests; however, the definition is not limited to predictive uses.

A major concern of the Task Force was that new tests would reach the market without adequate data to assess their analytic validity and clinical utility. Therefore, the Task Force recommended that sponsors of these genetic tests must have institutional review board (IRB)-reviewed protocols in place to collect these data. IRBs would be required to review these protocols for adequate human subjects protections, scientific merit, appropriate study population, measures of sensitivity and predictive validity, and the rate of false positives. Recognizing that the IRBs would quickly become overwhelmed if required to review all protocols in this manner, a strategy was developed to prioritize tests for which such stringent scrutiny would be necessary. The Task Force recommended that an advisory committee be established by the Secretary of Health and Human Services (HHS) to examine genetic tests and specify which of these would require stringent scrutiny. The advisory committee would also provide guidance to the IRBs reviewing protocols for evaluating these tests.

For those genetic tests that are already in the process of being assessed, the Task Force did not want to inhibit their continued evaluation. Therefore, options ranging from voluntary compliance to a regulatory requirement for approval were discussed by the Task Force. Each of these options required a review of the data at the "local" level (e.g., hospital laboratory review committee) and at the national level (e.g., professional societies, consensus conferences, technology assessments). The Task Force did not recommend specific criteria that a test had to satisfy before it was deemed ready for general use; the Task Force recommended instead that sufficient data should be available so that providers and consumers could judge the appropriateness of a genetic test for themselves.

The Task Force recommended a mechanism for ensuring the quality of genetic tests performed in clinical laboratories. Building on the Clinical Laboratory Improvement Amendments (CLIA) of 1988, the Task Force recommended that a genetics subcommittee be established as part of the CLIA Advisory Committee. The Task Force also recommended that a genetics subspecialty be established as part of the CLIA laboratory certification program. The Task Force encouraged participation in the College of American Pathologists-American College of Medical Genetics quality control program. CLIA is administered jointly by the Health Care Financing Administration and the CDC.

The Task Force recommended that health care professionals be educated in genetics and supported the mission of the National Coalition for Health Care Professionals. Concerned that the tests for many rare diseases were developed in research laboratories that may not continue to support the test or that particular area of research, the Task Force recommended that a mechanism be developed to ensure continued access to genetic tests for rare diseases.

Council Discussion of Recommendations

Dr. Clayton supported the principle put forth by the Task Force on maintaining confidentiality of test results, noting that this principle did not agree with a statement being developed by the American Society of Human Genetics. Dr. Clayton also noted that a definition of clinical utility would be very helpful, particularly in justifying state-mandated screening programs. Several members expressed their concern about the ability of IRBs, as they are currently constructed, to be able to implement the review of protocols for evaluating genetic tests in the manner recommended by the Task Force. Dr. Holtzman recognized these concerns and called for the proposed DHHS advisory committee and the Office for Protection from Research Risks to simplify IRB review of collaborative studies. Dr. Wold suggested that an appeal mechanism be built into the IRB review process; Dr. Holtzman responded that this suggestion could be included as part of the narrative.

Clarification of the role of the proposed DHHS advisory committee was requested. Dr. Watson and Dr. Holtzman explained that the committee was envisioned as a public/private partnership that would provide advice and guidance to the DHHS Secretary to ensure that adequate processes and policies were in place to ensure the safety and efficacy of new genetic tests. Dr. Holtzman agreed that it would be desirable to more clearly outline the role of the proposed advisory committee. Dr. Cox noted that there was a lack of consensus among the Task Force on the role of this committee, and that it was unlikely one would be achieved at this time.

Dr. Clayton made a motion that the Council transmit the report to the Secretary of DHHS, and recognize the very valuable accomplishment of the Task Force. Dr. Mathies seconded the motion, which passed unanimously.

ELSI RESEARCH PLANNING AND EVALUATION GROUP DRAFT IMPLEMENTATION PLAN

Dr. Eric Meslin presented the draft implementation plan for the proposed ELSI Research Planning and Evaluation Group (ERPEG). The proposed mission of the ERPEG is "to provide the NHGRI and the OHER/DOE with expert guidance on matters relating to their extramural ELSI research portfolios. This mission is understood to include long range planning and evaluation activities." It is anticipated that the ERPEG will be established as a working group of the council and the DOE Health and Environmental Research Advisory Committee (HERAC); comprised of nine members, including an individual from the general public and two individuals from the council; meet two or three times a year; and staffed by the NHGRI ELSI Research Program. In addition, it was proposed that the ERPEG be evaluated in 2000. The NIH and DOE will share the costs of operating the ERPEG. Dr. Meslin recognized the contributions of Ms. Elizabeth Thomson, Ms. Joy Boyer (NHGRI), and Dr. Dan Drell (DOE) to the development of the implementation plan.

Dr. Spence commented that, from the perspective of the ELSI Evaluation Committee, the evaluation component and the number of members is consistent with the spirit of the Committee's recommendation. However, she noted that the involvement of the public and the evaluation of the research portfolio may need further clarification to reassure potential critics that public input is important and that the ERPEG will be able evaluate the research portfolio in a meaningful way. Dr. Clayton expressed concern about the identification of a member from the general public, and recommended that the council provide advice for the selection of this member. In response to a question about HERAC membership on the ERPEG, Dr. Drell noted that representation from HERAC is implicit. Dr. Mathies requested clarification about the status of the ERPEG Chair at the council meetings. Dr. Jordan noted that the chair would be expected to be a participant in all council meetings in a specified capacity. Dr. Cox proposed that one option was for the Chair to be a member of the council in order to ensure that roles and relationships with respect to the council and the NHGRI are very clear.

Dr. Hood raised the issue of linking the ERPEG activities to the Human Genome Project. Dr. Jordan stated that the ERPEG would have at least one genome scientist as a member and would be closely linked with the development of the next five-year plan. One of the first activities of the ERPEG would be developing the five-year plan for ELSI research. Dr. Benjamin stated her concern about planning before evaluating. Dr. Meslin noted that the proposed ERPEG activities were not compartmentalized and would be closely coordinated. A workshop is planned for early 1998 to seek public input on the past, present, and future ELSI research areas, and will involve the ERPEG, and current and former ELSI grantees.

The role of the ERPEG with respect to other NHGRI ELSI activities (i.e., the Office of Policy Coordination and the DIR Office of Genome Ethics), particularly as these activities relate to policy formulation, was discussed. Some members observed that the ERPEG is not a policy committee and others suggested that members could have expertise in both science and policy.

Dr. Collins summarized the action items: Dr. Spence will provide language to clarify the role of the ERPEG in the evaluation of the ELSI research portfolio; the Council members will provide suggestions for ERPEG members to Drs. Meslin, Jordan, or Collins; and the NHGRI will provide a revised implementation plan and slate to the council at their next meeting.

UPDATE ON FIVE-YEAR PLAN ACTIVITIES

Dr. Chakravarti described the five broad areas that would form the foundation of the next five-year plan: 1) finishing the human sequence; 2) developing sequencing technology for the future; 3) sequence variation; 4) functional studies; and 5) integration of the ELSI five-year plan. A subcommittee has been established to determine how to develop each part of the five-year plan to accomplish 1-5. The subcommittee, which includes members of the council and the NHGRI, and experts in genomics and genetics, as well as representatives of several NIH Institutes, will meet May 20-21.

Dr. Chakravarti provided an update to the council on the March 31-April 1 "Workshop on Human DNA Sequence Variation." The outcomes of the workshop were: 1) identification of a critical and immediate need for NIH to stimulate and support pilot projects investigating a number of important questions in population genetics; 2) a resource of cell lines and/or DNA appropriate for studying a variety of questions pertaining to human sequence variation, which would be available to the scientific community; and 3) further research into efficient methods of detecting DNA sequence variation and genotyping, particularly research aimed at increasing sample throughput and decreasing the cost of analysis. Dr. Jordan reminded the council that, at each council meeting, they would be provided with progress reports on the development of the next five-year plan.

UPDATE ON DEVELOPING SEQUENCING STANDARDS

Dr. Peterson described NHGRI efforts to develop and implement sequencing standards for the NHGRI sequencing grantees. At the international sequencing meeting, held earlier this year, it was agreed that it was possible to achieve 99.99 percent accuracy, and that the sequencing community should strive to reach this goal. However, the difficulty in achieving such a goal was recognized.

Dr. Peterson described the process by which the NHGRI pilot sequencing projects are attempting to assess the quality of the sequence. In April, eight grantees, in round robin fashion, received two clones and raw data files from which they reassembled the original sequence using whatever tools were available to them. They were not to resolve discrepancies by any resequencing experiments. The results from the initial round demonstrated the feasibility and value of this approach, as well as some of the difficulties in exchanging data. Dr. Peterson noted that, when comparing the same clones, there was agreement among the participants on what was "bad sequence" and "good sequence." During the next phase, grantees will be asked to resolve any discrepancies by sequencing or by obtaining biological information needed to resolve discrepancies. Dr. Peterson estimated that it would take five months to complete this process.

Dr. Hood noted that when the sequence was originally produced by a grantee was an important consideration in determining the quality. Sequences done several years ago may not be as "finished" as those done more recently. Dr. Cox stated that this may be a way to determine which bases are the most problematic, and provides an opportunity to fix mistakes or remove them from GenBank. Dr. Collins noted that the time frame for this particular process was from the beginning of the pilot sequencing projects, which were funded a year ago.

A meeting of the participants in the quality assessment process was held recently and the results were discussed. The participants were receptive to the process and wanted to continue to participate. Dr. Peterson stated that the grantees will be asked, during their third year of funding, to propose a quality control plan, from which the NHGRI will develop a quality control center to provide this service. Dr. Cox recognized the efforts of Drs. Peterson and Schloss in organizing this process. Dr. Collins will keep the council informed about progress in this area.

FOLLOW UP ON R21 MECHANISM

At their meeting in February, the Council made three recommendations to enhance the effectiveness of the R21 program: 1) develop a process for third year funding for exceptional situations; 2) transition from R21 to R01 type 1, rather than type 2; and 3) continue to educate study sections regarding appropriate evaluation of these types of projects. Dr. Guyer provided an update on the status of these three recommendations. The education of study sections is ongoing. As a result of Dr. Guyer's discussions of recommendation 2 with the NIH-wide Extramural Program Management Committee and with the Chief of the Division of Research Grants Referral and Review Branch, R01s that are submitted as continuations of R21s will be coded as new grants. The recommendation about third-year funding has not yet been addressed.

CONSENSUS DEVELOPMENT CONFERENCE ON GENETIC TESTING FOR CYSTIC FIBROSIS

Ms. Thomson presented the outcome of the consensus conference on genetic testing for cystic fibrosis (CF). The meeting, held April 14-16, brought together a panel of health care providers, researchers, ethicists, and consumers to consider: the current state of the science of genetic testing for CF; the ethical, legal, social and other policy issues related to such testing; and whether such testing should be recommended. Dr. Ferguson, from the NIH Office of Medical Applications Research, explained the process of the consensus development conference; Ms. Thomson offered to provide those interested with the conference materials.

Several of the conclusions and recommendations of the panel were discussed by the council:

  • The goal of genetic testing is to provide individuals with information that will permit them to make informed decisions.
  • Counseling services must be accurate and provide balanced information to afford individuals the opportunity to make autonomous decisions. Every attempt should be made to protect individual rights and to prevent discrimination and stigmatization.
  • Access to genetic testing in the prenatal setting enhances the ability of couples to make reproductive choices, as shown by their interest in and use of the information they gain. The cost is reasonable in relation to the benefits obtained.
  • The panel recommends offering CF genetic testing to adults with a positive family history of CF, to partners of people with CF, to couples currently planning a pregnancy, and to couples seeking prenatal testing.
  • The panel does not advocate offering CF genetic testing to the general population or to newborn infants.

Dr. Hirschhorn reported that the American College of Medical Genetics was concerned that there are not enough genetics professionals (e.g., genetic counselors) to implement the recommendations. Dr. Clayton expressed her concern that genetic testing for CF will not be completely voluntary: health care providers will offer the test to reduce their liability, and most patients will agree to have the test because it is offered by their health care provider. Dr. Spence noted that in California, some patients found out that they were screened for alpha-fetoprotein when they received a call that said the test was positive and to seek genetic counseling. Several other council members expressed similar concerns. Dr. Wold noted that these concerns may be perceived as "academically high-handed," and may imply that only highly motivated and educated individuals would understand the implications of being offered the test. Others noted that eventually these issues will have to be dealt with and that the first steps may be difficult to undertake.

Ms. Thomson outlined the next phase, which will involve interactions with those who will have to implement the recommendations. It is possible that there will be a meeting with members of the American College of Obstetrics and Gynecology and the American College of Medical Genetics, as well as with members of professional societies representing family practitioners, nurses, pediatricians, genetic counselors, and other health professionals. In addition, educational materials appropriate for each of the populations to whom the test is likely to be offered will be developed. Dr. Collins noted that he has asked the panel to include in their final report a statement to the effect that immediate implementation of these recommendations is not anticipated or desirable.

REPORT FROM THE DEPARTMENT OF ENERGY

Dr. Ari Patrinos reported that progress continues on establishing the Department of Energy (DOE) Joint Genome Institute and identifying a site in the San Francisco Bay area for the large-scale sequencing operation. Four bids have been received for the sequencing project and the DOE anticipates making a selection in July for funding in FY98.

The National Academy of Sciences sponsored a symposium in recognition of the DOE environmental science and research program, entitled the "Legacy and Promise of the Environmental Research Program." Other meetings and activities of interest included: continuation of the series of workshops for judges on genetics and the courts; cDNA meeting (May 19); review of the Genome Data Base (June 9); DOE interagency workshop "Genetics Research and Human Subjects: The Changing Landscape," organized by the DOE (Susan Rose) and the NIH (Elizabeth Thomson) (June 26-27); and a meeting on BAC end sequencing (late June).

IMPLEMENTATION OF NIH POLICY ON THE INCLUSION OF WOMEN AND MINORITIES AS SUBJECTS IN CLINICAL RESEARCH - NHGRI COMPLIANCE

Ms. Cahill described NHGRI compliance with and implementation of the NIH policy on the inclusion of women and minorities as subjects in clinical research. These activities include reviewing applications to ensure that, as appropriate, each one meets the standard for inclusion of women and minorities. Those that fail to meet this standard are given an unacceptable gender or minority code, which results in an administrative bar-to-funding. These applications are given a second-level review in the closed session of the Council meeting. If funding is likely, then the NHGRI staff works with the applicant to resolve compliance issues. In addition, NHGRI staff serve on an NIH-wide committee charged with oversight of this activity. Dr. Jordan agreed to bring data on NHGRI-funded research subjects to a future Council meeting.

The council unanimously concurred that the NHGRI was in compliance with the policy.

ANNOUNCEMENTS AND ITEMS OF INTEREST

Dr. Jordan noted the items of interest, which are listed on the agenda.

COUNCIL-INITIATED DISCUSSION

Agenda items for the September council meeting included: review of the genomic technologies RFA; report from the NHGRI Division of Intramural Research; and the impact of funding the sequencing projects on other areas of the research portfolio. Suggested agenda items for future meetings included a report from Dr. Klausner on the Cancer Genome Anatomy Project, and a discussion of the problems arising from the patenting of research tools, such as DNA chips.

REVIEW OF APPLICATIONS

The Council reviewed 58 applications, totaling $13,875,614. The applications included 18 regular research grants; five pilot projects; two program projects; 13 ethics grants; one in response to request for application; two center grants; three conference grants; one continuing education training program; 10 small business innovative research, phase I; one small business innovative research, phase II; and two fellowship grants. A total of 36 applications requesting $8,874,257 were recommended.

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Last Reviewed: April 2006