National Advisory Council for Human Genome Research - Summary of Meeting

National Advisory Council for Human Genome Research
Summary of Meeting

Bethesda, Md.

February 20-21, 1997

The National Advisory Council for Human Genome Research was convened for its nineteenth meeting at 8:30 A.M. on February 20, 1997, at the National Institutes of Health, Building 31, Conference Room 6. Dr. Francis Collins, Director of the National Human Genome Research Institute, called the meeting to order.

The meeting was open to the public from 8:30 A.M. to 4:30 P.M. on February 20. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 4:30 P.M. on February 20 to adjournment on February 21 for the review, discussion, and evaluation of grant applications.

Council members present:

Dr. Lennette J. Benjamin
Dr. R. Daniel Camerini-Otero
Dr. Ellen W. Clayton
Dr. David R. Cox
Dr. Troy Duster
Dr. Richard Mathies
Dr. Rodney Rothstein
Dr. Diane C. Smith
Dr. M. Anne Spence
Dr. David Valle
Dr. Barbara Wold

Council member absent:

Dr. Leroy Hood

Ad Hoc members:

Dr. Aravinda Chakravarti
Dr. Joseph Nadeau
Mr. Mark Rothstein

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
David Benton, DER
Joy Boyer, DER
Erin Burgess, OAM
Jean Cahill, DER
Francis Collins, OD
Allison Deluhery, DER
Elise Feingold, DER
Leslie Fink, OPC
Mary Glynn, OAM
Bettie Graham, DER
Mark Guyer, DER
Linda Hall, DER
Kathy Hudson, OPC
Linda Jacobson, OAM
Jean Jenkins, DIR
Elke Jordan, OD
Jean McKay, OPC
Eric Meslin, DER
Tara Mowery, DER
Kenji Nakamura, DER
Diane Patterson, OAM
Jane Peterson, DER
Rudy Pozzatti, DER
Stephanie Reeves-Walker
Jerry Roberts, DER
Ellen Rolfes, OAM
Arline Sanchez, OD
Susan Saylor, OD
Jeffery Schloss, DER
Megan Sexauer, OPC
Ann Smith, DIR
Elizabeth Thomson, DER
James Vennetti, OAM
Monika Yakovich, DER
Sally York, DER

Others present for all or a portion of the meeting:

Marianne Bentz, OPRR
Joel Breman, FIC
Anthony Carter, DRG
Jean Chin, NIGMS
Cheryl Corsaro, DRG
Mary Davidson, Alliance of Genetic Support Groups
Dan Drell, Department of Energy
Michele Durand, MENESR
Linda Engel, DRG
Mark Frankel, AAAS
Philip Harriman, NSF
Nelson Hobbs, "The Blue Sheet"
Elliot Marshall, Science
Peggy McArdle, NIH
Elizabeth McPherson, GMU
Kathy O'Donoghue, College of American Pathologists
Ari Patrinos, Department of Energy
Georgia Persinos, Washington Insight
Maria Persinos, Washington Insight
Chris Peterson, SRI International
Anne Phelps, NIH
Sara Radcliffe, SmithKline Beecham
Angela Sharpe, Consortium of Social Science Associations
Marvin Stodolsky, Department of Energy
Susan Vazakas, KEVRIC
Meredith Wadman, Nature
Joan Weiss, Alliance of Genetic Support Groups

Introduction of New Council Members, Ad Hoc Members, Liaisons, Visitors and New Staff

Dr. Jordan introduced the ad hoc council members: Mr. Mark Rothstein, University of Houston Law Center; Dr. Aravinda Chakravarti, Case Western Reserve University; and Dr. Joseph Nadeau, Case Western Reserve University. New staff introduced included: Dr. Jerry Roberts, executive secretary for the Center for Inherited Disease Research Access Committee; Ms. Stephanie Walker, grants technical assistant; Ms. Susan Saylor, secretary; and Ms. Ellen Brewster, personnel specialist.

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 September 16-17, 1996 NACHGR meeting were approved as submitted.

Future Meeting Dates

May 19-20, 1997, September 11-12, 1997, and January 25-26, 1998 were approved for future NACHGR meetings.

Director's Report

Institute Status.

On January 13, at midnight, the NCHGR became the National Human Genome Research Institute (NHGRI). This action was prompted by the tremendous advances in human genetics research resulting from the Human Genome Project (HGP), the establishment of the Division of Intramural Research, and the far-reaching implications of the HGP for the advancement of research in human genetic disease. The mission and goals remain unchanged.

Second Annual James Watson Lecture and Awards Ceremony.

On January 14, The Genome Action Coalition (TGAC) sponsored the second annual James Watson Lecture and Awards Ceremony and reception at the National Academy of Sciences. The lecture was delivered by Dr. Francis Collins; Dr. James Watson attended as the special guest.

TGAC presented their Congressional Award to Senators Nancy Kassebaum and Edward Kennedy, for their outstanding work as sponsors of the Health Insurance Portability and Accountability Act of 1996. TGAC Community Service Awards were presented to Sam Donaldson and Barbara Walters, of ABC News; Larry King and Jeff Levine, of CNN; and Donald Graham and Rick Weiss, of The Washington Post.

Scientific Update

Science "Genome Issue". Dr. Collins noted the publication of the Science "genome issue," on October 25, 1996. This issue included a gene map of the human genome, and papers on assessing sequence data with high-density arrays and the perspectives of consumers on genetic discrimination.

Location of Parkinson's Disease Gene Found on Chromosome 4. Scientists in the NHGRI intramural research program and colleagues at the National Institute of Neurological Disorders and Stroke identified the location of a gene on chromosome 4 believed to be responsible for some cases of Parkinson's disease. This discovery provided strong evidence that a genetic alteration is capable of causing the disease. The next steps will be to identify the specific gene involved and determine its function, which may help researchers design treatments for all forms of Parkinson's disease, including those with no familial link.

Prostate Cancer Gene Location Found on Chromosome 1. Scientists in the NHGRI intramural research program and their colleagues at the Johns Hopkins University identified the location of the first major gene that predisposes men to prostate cancer. The HPC-1 gene is situated on the long arm of chromosome 1. The finding is the first proof that genes conferring hereditary predisposition to prostate cancer exist. Once the HPC-1 gene is identified, scientists anticipate being able to learn how and why prostate cancer develops, and suggest strategies for prevention and treatment. In the United States, men have a one-in-five chance of developing prostate cancer, and approximately 1 in every 500 men is believed to have an altered version of the gene. Researchers estimate that alterations in the HPC-1 gene are responsible for at least a third of familial prostate cancer.

E. coli DNA Sequence Completed. On January 25, the complete genomic sequence of E. coli was available in GenBank. Access to the sequence can be obtained via the Entrez system or through the E. coli home page at the University of Wisconsin (http://www.genome.wisc.edu/). The sequencing of E. coli was carried out in the laboratory of Dr. Fred Blattner, at the University of Wisconsin, with support from the NHGRI.

Recommendations from the Cancer Genetics Studies Consortium. Two papers from the NHGRI-supported Cancer Genetics Studies Consortium (CGSC) that describe recommendations for follow-up care for individuals with inherited susceptibility to hereditary non-polyposis colon cancer (HNPCC) or breast cancer (BRCA1 and 2) have been accepted for publication by the Journal of the American Medical Association.

At the May 1996 Council meeting, Dr. Wylie Burke reported on the efforts of the CGSC to develop recommendations for cancer surveillance and prevention for individuals who have mutations in their BRCA1, BRCA2, or HNPCC genes. As part of this project, the CGSC conducted an extensive review of published studies of cancer risk, surveillance, and prevention and assessed these studies using the criteria of the U.S. Preventive Services Task Force.

The CGSC concluded that, while progress in understanding the molecular basis of cancer has led to the possibility of genetic testing and identification of individuals at increased risk for cancer, the effectiveness of cancer surveillance in these individuals remains unknown. The group recommended that individuals considering genetic testing for cancer be thoroughly counseled regarding the uncertainty of the benefits of the available surveillance options and be actively involved in choosing their course of follow-up. Recommendations for surveillance may be revised as new evidence emerges.

Dr. Collins recognized the contributions of Ms. Elizabeth Thomson, of the NHGRI ELSI Research Program, to the ongoing success of the CGSC. The CGSC is also supported by the National Cancer Institute and the National Institute of Nursing Research.

Task Force on Genetic Testing. On January 30, the draft recommendations of the Task Force on Genetic Testing were published in the Federal Register. The Task Force will accept for consideration written comments from the public on these draft recommendations until March 10. The final meeting of the Task Force will be held on March 17-18, in Baltimore. A final report, including the principles and recommendations together with background information and comments, will be issued shortly after this meeting. It is anticipated that the council will consider the Task Force recommendations at the May meeting.

Dr. David Cox, a member of the Task Force, emphasized the importance of feedback from the public, noting that the Task Force had not yet come to closure on all of the issues under consideration.

NAPBC-ELSI Working Group Recommendations on Employment Discrimination. On October 4, 1996, the National Action Plan on Breast Cancer (NAPBC) and the ELSI Working Group held a workshop on genetic information and employment discrimination. It is anticipated that the recommendations from the workshop will provide meaningful information to policy makers as they discuss the need for additional legislative protections. The recommendations from the workshop will be published and widely disseminated to policy makers, consumer advocates, and other stakeholders. [Note: the recommendations were published in Science, March 21, 1997, vol. 275, pp. 1755-1757, "Genetic Information and the Workplace: Legislative Approaches and Policy Challenges."]

Legislative Update

Appropriations. Dr. Collins noted that the Human Genome Project was specifically cited by President Clinton in the State of the Union address. The President's FY 1998 budget includes an 8.6 percent increase for NHGRI. The House appropriations hearings for NHGRI are currently scheduled for February 27.

NIH Reauthorization. Both the House and the Senate have expressed an interest in taking up an NIH reauthorization bill this session. The House is expected to take up reauthorization first; the Senate has listed August 1997 as the anticipated date for reauthorization action.

ELSI Issues. Health Insurance Reform - Dr. Collins noted the passage of The Health Insurance Portability and Accountability Act of 1996 ("Kennedy/Kassebaum bill"), and referred the Council to an analysis of this Act developed by the Women's Legal Defense Fund.

Several bills have been introduced that specifically adopt the recommendations from the NAPBC/ELSI Working Group workshop on health insurance discrimination published in Science (October 20, 1995):

• H.R. 306 - The Genetic Information Nondiscrimination in Health Insurance Act of 1997 (Louise Slaughter)
• S. 89 - The Genetic Information Nondiscrimination in Health Insurance Act Of 1997 (Olympia Snowe)
• H.R. 328 - Genetic Information Health Insurance Discrimination Act of 1997 (Gerald Solomon)

Employment Discrimination - Several members of Congress have expressed interest in the use of genetic information in the employment setting and the NAPBC/ELSI Working Group recommendations from the October 1996 workshop.

Privacy/Medical Records Confidentiality - The Health Insurance Portability and Accountability Act of 1996 recognized the need to protect access and use of medical information, and directed the Secretary of Health and Human Services to promulgate regulations for medical records privacy protections by August 1997. These regulations will be enacted if Congress fails to act by 1999.

The Department of Health and Human Services has held the following hearings to discuss stakeholders' concerns about this issue:

• January 13 -14: Medical research, public health and health oversight.
• February 3 - 4: Insurers, employers, claims processors, pharmaceutical industry and social welfare agencies.
• February 18 -19: Law enforcement, health care providers and patient interest groups

Representative Gary Condit has reintroduced H.R. 52 - Fair Health Information Practices Act of 1997. Three other privacy bills introduced during the previous Congress are currently undergoing revisions and will be reintroduced this session: S. 1360 - The Medical Records Confidentiality Act of 1995 (Robert Bennett); H.R. 3482 - Medical Privacy in the Age of New Technologies Act (Jim McDermott); and the Genetic Confidentiality and Nondiscrimination Act of 1997 (Pete Domenici).

In a related area, Senator John Glenn introduced S. 193 - Human Research Subject Protections Act of 1997, which extends current federal human subjects protections (45CFR46) to all government agencies, including classified research, as well as the private sector.

Dr. Collins noted that incremental progress is being made to protect individuals from the misuse of genetic information.

Upcoming Meetings

February 27 - March 2: Second international strategy meeting on human genome sequencing
Purpose: to facilitate the coordination of research groups funded for large-scale human genome sequencing.

March 3: Hereditary Hemochromatosis: Gene Discovery and Its Implications
Purpose: to examine the existing policies and practices regarding screening, diagnosis, and management of hereditary hemochromatosis, and the implications that the gene discovery may have on the possibility of wide-spread genetic testing for this disorder.

The NHGRI is co-sponsoring this meeting with the CDC. It will be held in conjunction with the CDC's Second Annual Meeting on "Iron Overload, Public Health, and Genetics," scheduled for March 4-5.

March 10-11: Meeting of the National Coalition for Health Professional Education in Genetics
Purpose: to heighten awareness among the member organizations of the need for genetics education for health professionals and to set the agenda for the coalition.

This will be the first meeting of the general prospective membership of the coalition, to include representatives from approximately 100 groups.

April 14-16: Consensus Development Conference - Genetic Testing for Cystic Fibrosis
Purpose: to bring together a panel of health care providers, researchers, ethicists, and consumers to consider: the current state of the science of genetic testing for cystic fibrosis; the ethical, legal, social, and other policy issues related to such testing; and whether such testing should be recommended.

Information Update

Presidential Early Career Award for Scientists and Engineers. Deirdre Meldrum, Ph.D. was one of ten NIH grantees selected by the White House Office of Science and Technology Policy to be among the 60 individuals to receive the Presidential Early Career Award for Scientists and Engineers. She was nominated by the NHGRI. Dr. Meldrum, an NHGRI grantee, was cited as "an outstanding young investigator who is employing a broad set of interdisciplinary approaches to make substantial contributions toward advancing state-of-the-art DNA sequencing technology and the important new field of genomic science." Dr. David Burke, another NHGRI grantee, also received this award; he was nominated by NSF.

These awards, created last year, recognize demonstrated excellence and promise of future success in scientific or engineering research, and the potential for leadership of the awardees in their respective fields. The candidates are nominated by agencies across the federal government.

NHGRI-ORMH-Howard University Initiatives on Genetic Diseases in Minorities. Dr. Collins described two projects that NHGRI intramural scientists, in conjunction with the NIH Office of Research on Minority Health (ORMH), plan to initiate in partnership with Howard University. The first project is a study of the West African origins of genetic susceptibility to non-insulin dependent diabetes mellitus in African Americans. Five proposals were selected from 24 responses to a Request for Proposals issued by Howard University and funded by the ORMH. The five principal investigators are from West Africa: two from Ghana and three from Nigeria. The study, using the affected sib pair approach, will collect fifteen sib pairs at each site, as a pilot project. If the pilot projects are successful, it is planned that several hundred sib pairs will be collected and analyzed over the course of the study. The NHGRI, largely through the Center for Inherited Disease Research, will perform the genotyping. The PIs met on February 11-13 for training on the pilot phase of affected sib pair collection.

The second project is a proposal to study the genetics and epidemiology of prostate cancer in African Americans. On January 27-28, a meeting was held to discuss the feasibility of the study. It was attended by 15-20 African American physician-scientists with access to large numbers of affected families. The outline of a cooperative multi-center study of hereditary prostate cancer in African Americans was developed. The ORMH is providing support for the planning phase of the study, and Howard University and NHGRI intramural scientists have begun to develop the scientific objectives for this project. A request for funding sufficient to allow the collection of 100 families has been made to the ORMH.

Dr. Collins will keep the council apprised of the progress of these two studies.

Center for Inherited Disease Research (CIDR)

Dr. Jerry Roberts provided the council with an update of the CIDR activities. The CIDR, supported by eight NIH Institutes and located at the Bayview Campus of the Johns Hopkins School of Medicine, will provide high-throughput genotyping for intramural and extramural scientists. Recruitment is underway for a director and staff; Dr. Valle is the acting director. Access to the CIDR is through the CIDR Access Committee (CAC). The CAC is a chartered committee of twelve extramural and intramural scientists; additional expertise will be provided by ad hoc reviewers. Extramural investigators can apply for CIDR access by incorporating the request into a research grant application. These applications will be reviewed by study sections in the usual manner; in addition, the project will be further evaluated for its suitability for the CIDR by the CAC. Intramural scientists can apply for CIDR access by preparing an R01-like application. The CAC will evaluate the suitability of the project for CIDR and the scientific merit of the project. Final scheduling of CIDR access will be made by the CIDR director in consultation with the CIDR Board of Governors. The Board of Governors is comprised of the eight Institute Directors, the CIDR Director, and one additional representative from the Johns Hopkins School of Medicine. Dr. Roberts has actively communicated the availability of the CIDR resources and expertise among the intramural and extramural communities in a variety of publications, meetings, and a Web page.

The council members were very interested in the type of technology that would be available through the CIDR and how new technology would be evaluated and implemented, as well as how much the CIDR plans to charge for genotyping and provision of other services. Some of these issues, particularly technology development and implementation, have yet to be fully addressed, pending the appointment of a director.

NIH Division of Research Grants (DRG)

Dr. Elvera Ehrenfeld, the new director of the NIH Division of Research Grants, described initiatives that are underway to address issues that have been raised regarding the DRG. Recurring themes include: the most interesting, innovative science is being reviewed by a small subset of the study sections; the breadth of study sections is being sacrificed in order to provide depth to reviews (which is also needed); some science areas are not being well-served by the current review system. In response to these concerns, Dr. Ehrenfeld has established a multifaceted set of changes that can be characterized by two initiatives. The first addresses the review processes (e.g., how to shorten time between review and award, amendment procedures, etc.), changes in which were occurring as part of government reinvention activities. The second initiative is to ensure that the science that is funded is fundamentally and programmatically important and not determined by the structure of the study sections. Dr. Ehrenfeld also stressed the development of stronger partnerships between the DRG and the Institutes and Centers.

In response to many comments from council members, Dr. Ehrenfeld acknowledged that there are segments of the community that are not well-served by the current review process. These areas include behavioral science and technology development. There are plans to bring a social scientist and a clinical researcher to the DRG to work for a limited period of time as liaisons to these areas and to implement solutions to these problems. Other issues raised by council members included the difficulties in obtaining expertise on study sections, citing the significant workload that being a reviewer entails, need for flexible appointment terms, and a triage mechanism. Dr. Ehrenfeld agreed, recognizing the need for the system to be flexible in order to obtain expert reviewers. Dr. Ehrenfeld may be contacting council members to acquire additional information about these and other issues.

Report on the ELSI Evaluation Committee

Dr. Spence and Mr. Rothstein presented the report of the ELSI Evaluation Committee, which they co-chaired. The report was transmitted to Dr. Collins and Dr. Patrinos on December 12, 1996. On December 19, 1996, the report was released to the public. However, no action had been taken by the NHGRI, pending the outcome of the Council's discussion and recommendations.

Dr. Duster, who is the chair of the ELSI Working Group, provided the group with a document developed by the Executive Committee of the ELSI Working Group, which supports the recommendations of the ELSI Evaluation Committee. Dr. Duster emphasized three key points: the issues triggered by the Human Genome Project transcend a single Institute; the three layers of committees recommended by the ELSI Evaluation Committee need to have a measure of vertical integration; and these committees needed to be started from scratch and, to this end, the ELSI Working Group members were prepared to submit their resignations.

Dr. Hirschhorn reported that the American Society of Human Genetics and the American College of Medical Genetics supported the recommendations of the ELSI Evaluation Committee. Dr. Hirschhorn noted that the draft recommendations of the Task Force on Genetic Testing also included the formation of a Secretary-level advisory committee.

Many council members expressed concern about how the recommendations would be implemented, and Dr. Collins noted that there had been considerable discussion within the NHGRI regarding possible approaches. Dr. Collins proposed that the NHGRI develop a response to the recommendation for the formation of an advisory committee on the NHGRI and DOE ELSI research grant programs.

Dr. Clayton made a motion that the NHGRI commend the efforts of the ELSI Evaluation Committee, that the council endorse the idea of the opportunity for public input described in the recommendation for a Secretary-level advisory committee on genetics and public policy, that the council endorse the recommendation for an NIH-level committee on ELSI issues, and that NHGRI staff be directed to develop a proposal for the an ELSI Research Evaluation Committee for consideration at May council. The staff should think in broad terms about the organization and operation of the proposed committee and should state clearly how input from the public would be sought and used by the committee to obtain the best possible understanding of the ELSI program. Dr. Duster seconded the motion. The motion was approved unanimously.

Recommendation #1: The existing Working Group should be restructured and designated the ELSI Research Evaluation Committee, housed within NCHGR [NHGRI] as an advisory committee to the director and the council and within the DOE as advisory to the Health and Environmental Research Advisory Committee and the DOE Genome Project.

Council Action: The council endorsed this recommendation and directed NHGRI staff to prepare an implementation plan to be considered and acted upon at May council.

Recommendation #2: The Director of NIH should consider establishing an ongoing process to coordinate the exchange of information on the ethical, legal, and social implications of genetic research among the NIH Institutes.

Council Action: The council endorsed this recommendation. While recognizing the leadership role that the NHGRI has played in developing the ELSI program, the council noted that ELSI issues arise in other NIH Institutes, Centers, and Divisions.

Recommendation #3: The Secretary of Health and Human Services should establish, in the Office of the Secretary, a chartered Advisory Committee on Genetics and Public Policy. This Committee will assume the role of identifying issues and formulating policy to ensure integration of new genetic knowledge into health care standards.

Council Action: The council endorsed this recommendation. However, the council noted the existence of the National Bioethics Advisory Commission, as well as a proposed recommendation by the Task Force on Genetic Testing for a similar Secretary level advisory committee. The council directed this recommendation to be transmitted to Secretary Shalala.

Strategies for a New Five-Year Plan

Dr. Chakravarti, a geneticist from Case Western Reserve University, is providing guidance to the NHGRI in the development of the next five-year plan for the Human Genome Project. Council members will be asked to take part in these planning activities as participants and advisors. Three broad scientific areas have been identified as components of the next five-year plan: DNA sequence and sequencing technology, human polymorphisms, and function maps. A series of workshops is planned to facilitate discussion of these topics and to serve as the foundation for the five-year plan. The first workshop on sequence variation will be held March 31-April 1. Other proposed workshop topics include sequencing technology (Fall 1997), gene function (Fall 1997), and finishing the human sequence (Winter 1998). It is anticipated that the council will receive regular updates about the outcomes of these workshops. In Spring 1998, a final workshop will be held to draft the five-year plan; the plan will published in October 1998. Dr. Chakravarti will provide an update to the council on the March 31-April 1 workshop at the May meeting.

Dr. Collins noted that there would be a separate planning process for ELSI, and that the ELSI research program evaluation group, if established, will have a major role in the development of the ELSI plan. The council will be provided regular updates on the progress of the development of the ELSI five-year plan.

Update on the ELSI Working Group

Dr. Duster reported that the ELSI Working Group has four areas of activity: the Task Force on Genetic Testing; employment discrimination; consumer issues; and developing its statement on informed consent and the use of stored tissue samples.

Report from the Department of Energy

Dr. Ari Patrinos reported that the genome program is the only DOE research program to receive an increase in FY 1998, demonstrating its prominence and importance. Some of these funds will be for the recently-established DOE Joint Genome Institute. The DOE plans to collaborate with academia and industry on a "major sequencing factory." Negotiations for this project are in the early stages; Dr. Patrinos will provide updates on these efforts at future council meetings. Other DOE initiatives include: the microbial sequencing RFA (issued on February 19, 1997), which focuses on the sequencing of non-pathogenic microbes, functional genomics, and bioinformatics; and the ELSI RFA, which will be issued in early Spring and will focus on complex conditions, informed consent, and education initiatives aimed at the general public and health professionals.

Dr. Patrinos described a meeting with the JASON Group, which includes physicists, chemists, and biologists who want to make a contribution to the genome effort, particularly in the areas of quality assurance and quality control for sequencing, and informatics. Tours of sequencing centers and an intensive two-week course are planned for the group. Dr. Collins, who has also spoken to this group, encouraged cross-disciplinary interactions, such as these.

Small Business Innovative Research (SBIR) Program

Dr. Bettie Graham reported on the NHGRI SBIR Program. The NHGRI has allocated approximately 2.5 percent of its budget for this program, and in FY 1997 will invest $3.5 million. The success rate of the applicants is 28 percent, which is comparable to other granting mechanisms (e.g., R01, P01, etc). Examples of successful projects are included in the mapping and sequencing portfolio. Dr. Graham noted that the most successful applicants are the ones who work closely with those doing work in genome sciences, or who are successful in other grant programs. While the NHGRI has found the SBIR program to be valuable and productive, this may not be the experience of all NIH Institutes and Centers. In addition, some investigators fear that the SBIR program will decrease the amount of funds available for other grant programs (e.g., R01). The unused funds for the SBIR program cannot be used for a different funding mechanism. Dr. Peggy McArdle, from the NIH Office of Extramural Research, explained that Institutes and Centers (IC) can and do fund good-scoring applicants from other IC in an effort to fully use the appropriated funds. The council recommended that efforts be made to ensure that the small business community is aware of this program.

R21 Pilot Project Analysis

Dr. David Benton summarized an evaluation of the NHGRI R21 program. The purpose of the evaluation was to determine how the program is used, if it is successful in soliciting high-risk, high-payoff pilot projects and feasibility studies, and if these research projects are successful. The evaluation was conducted in three parts: 1) evaluation of statistical information about applications and awards; 2) examination of final progress reports from R21 projects and peer review critiques of follow-on R01 grant applications; and 3) telephone interviews with selected R21 grantees. This evaluation showed that the R21 program has been successful in soliciting and funding applications for high-risk and pilot project research that may not have been supported under traditional research grant mechanisms, and has contributed to the research successes of the NHGRI.

The council was supportive of the R21 mechanism and recommended that the NHGRI consider the following: 1) developing a process for third year funding for exceptional situations; 2) transitioning from R21 to R01 type 1, rather than type 2; and 3) continuing to educate study sections regarding appropriate evaluation of these types of projects.

Concept for an RFA for Sequencing Technology

Dr. Jeffery Schloss presented a concept for a request for applications (RFA) for "Low-Cost, High-Accuracy DNA Sequencing Technologies." The purpose of the RFA would be to stimulate research on next-generation technologies that have the potential to reduce the cost of high-accuracy genomic DNA sequencing. The goal of the research conducted under this RFA would be to decrease the total cost of obtaining accurate de novo sequence to well below $0.05 per base pair. Specific areas of interest included: the study of novel principles that are likely to be applicable to DNA sequencing; the study of the application of principles from other fields of science and/or engineering that have strong potential for application to sequencing; and the further development of technologies for which proof of principle for DNA sequencing may already have been demonstrated, but that require substantial additional work to achieve high throughput for genomic sequencing. In addition, the development of computational tools needed in support of systems or components eligible for funding under the RFA and research on all steps in the sequencing process are also eligible for support.

The council enthusiastically supported this concept. An October 15 receipt date was proposed and awards would be made in the Summer of 1998. It is likely that the RFA would be reissued next year. The amount of funding is approximately $5 million.

Concept for an RFA for a Mouse Transcript Map

Dr. Mark Guyer presented a concept for an RFA for "A Mouse Transcript Map." The purpose of the RFA would be to develop a mouse gene map, which would increase the usefulness of the mouse as a model system for studying human disease, health, and behavior. The proposed RFA would solicit applications for the mapping of up to 40,000 gene-based sequence tagged sites over a period of two years. The council supported this concept, and recommended that language about achieving optimal resolution by mapping on the most appropriate resources be added rather than assuming that an existing radiation hybrid panel would be used.

NHGRI Sequencing Standards

Dr. Jane Peterson presented the proposed standard for finished human DNA sequence. The standard had two criteria: 1) the sequence error rate should approach 1:10,000; and 2) the sequence should be determined either from both DNA strands or from one strand by two different chemistries. There was substantial discussion among the council about setting such a standard and what it would actually mean if sequencers did not meet the standard. Overall, the council was supportive of developing a standard, recognizing that there will be no ideal way to do this and that any standard will likely need to be modified as technologies change and improve. Dr. Collins suggested that the NHGRI form a small group following the outcome of discussions at the international strategy meeting on human genome sequencing (February 27-March 2). The council agreed with this suggestion, and will receive an update on this issue at the May meeting.

Report on the December 1996 Meeting of the Advisory Committee to the Director, NIH, and the Meeting of the National Advisory Council and Board

There was no report on this topic.

Statement of Understanding between the NHGRI Staff and the National Advisory Council for Human Genome Research

The statement of understanding addresses the review of applications by the council and guidelines for NHGRI staff to negotiate adjustments in grant amounts and terms. Dr. Jordan reviewed the two changes to this understanding, which resulted from the change to Institute status. The Statement of Understanding was approved by the council.

Announcements and Items of Interest

Dr. Jordan noted the folders prepared by the NIH Office of Extramural Research, which contained information to assist council members when they are asked about the role of NIH in biomedical research.

Council-Initiated Discussion

Council members expressed interest in following up on the budget projections discussion (September 1996 council meeting), particularly the impact that sequencing ramp up would have on other programs. Topics for discussion at the May meeting included sequencing standards and a report on the sequencing variation workshop.

Conflict of Interest

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.

Review of Applications

The council reviewed 80 applications, totaling $21,846,605. The applications included 22 regular research grants, 3 pilot projects, 2 program projects, 1 ethics grant, 31 grants in response to request for applications, 1 AREA grant, 2 conference grants, 2 research career development awards, 1 training grant, 9 small business innovative research awards - phase I, 1 small business innovative research awards - phase II, 4 fellowship grants, and 1 R41. A total of 61 applications requesting $20,261,612 were recommended.

Top of page

---