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National Advisory Council for Human Genome Research
Summary of Meeting

Bethesda, Md.

September 14-15, 1998

The National Advisory Council for Human Genome Research (NACHGR)was convened for its twenty-fourth meeting at 8:30 a.m on September 14, 1998, at the National Institutes of Health (NIH) Natcher Conference Center, E1 and E2. 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. until 6:00 p.m. on September 14. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 8:30 a.m. until adjournment on September 15 for the review, discussion and evaluation of grant applications. (1)

Council members present:

Aravinda Chakravarti
Ellen W. Clayton
David R. Cox
Leroy Hood
H. Robert Horvitz
Jeanne Lawrence
Richard Mathies
Joseph Nadeau
Diane Smith
David Valle
Alan R. Williamson
Barbara Wold

Ex officio members:

Joel N. Buxbaum
William M. Nelson

Council members absent:

Troy Duster

Liaisons from Professional Societies:

Rosalie Goldberg, National Society of Genetic Counselors
Kurt Hirschhorn, American College of Medical Genetics
Jeffrey Murray, American Society of Human Genetics

Staff from the National Human Genome Research Institute:

Jane Ades, OPC
Carol Almeida, OAM
Karina Boehm, OPC
Meg Bouvier, OPC
Joy Boyer, DER
Lisa Brooks, DER
Erin Burgess, OAM
Jean Cahill, OAM
Carol Carnahan, OSR
Francis Collins, OD
Elise Feingold, DER
Leslie Fink, OPC
Mary Glynn, OAM
Bettie Graham, DER
Eric Green, DIR
Mark Guyer, DER
Linda Hall, OAM
Craig Higgins, OPC
Kathy Hudson, OPC
Linda Jacobson, OAM
Elke Jordan, OD
Charles E. Leasure, OD
Tara Mowery, OAM
Kenji Nakamura, OSR
Jane Peterson, DER
Rudy Pozzatti, OSR
Robin Prigal, OAM
Jerry Roberts, CIDR
Jeffery Schloss, DER
Sandra Taubenkibel, OAM
Elizabeth Thomson, DER
Elsa Weinstein, OAM
Monika Yakovich, OAM
Sally York, OAM

Others present for all or a portion of the meeting:

Finley Austin, Merck Genome Research Institute
David Bentley, Sanger Centre, U.K.
Doug Birch, The Baltimore Sun
Kristina Borror, OD
Cheryl Corsaro, CSR
Camilla Day, CSR
Mary Davidson, Alliance of Genetic Support Groups
Matthew Davis, The Washington Fax
Lyle Dennis, The Genome Action Coalition
Dan Drell, DOE
Marvin Frazier, DOE
Ellen Gadbois, Senator Kennedy's staff
Justin Gillis, The Washington Post
Laurie Goodman, Genome Research
Carol Greene, American Society of Human Genetics
Karen Hopkin, Freelance writer
Michael Knapp, Celera Genomics
Rachel Levinson, OD/OSTP
Eliot Marshall, Science Magazine
Dave Martz, Incyte
Mary McCormick, Howard Hughes Medical Institute
Usha Lee McFarling, Knight Ridder
Jean McKay, NCI
Pamela Moore, Capitol Publications
Nancy Moy, SRI International
Ari Patrinos, DOE
Maria Persinos, Washington Insight
Garrick Peters, Incyte
Lisa Putman, The Blue Sheet
Sara Radcliffe, SmithKline Beecham
Angela Sharpe, Consortium of Social Science Associations
Paul Smajlik, The Scientist
Rebecca Spieler, The Blue Sheet
Michael Strazzella, American Society of Clinical Pathologists
Tim Taylor, Howard Hughes Medical Institute
Meredith Wadman, Nature
Leroy Walters, Georgetown University

Discussion of Five-Year Plan

Dr. Collins opened the meeting by initiating discussion of New Goals for the U.S. Human Genome Project, 1998-2003. This draft document is scheduled to be published in the October 23, 1998, Genome Issue of the journal Science. Dr. Collins invited council to review the document and make suggestions or possible revisions.

Dr. Aravindra Chakravarti, Chairman of the Planning Subcommittee, reviewed the planning process that led to the new five-year plan. The subcommittee members began by evaluating what the genome project had accomplished and how data would be gathered. Beginning in March 1997, and running through September 1998, the subcommittee held a series of meetings and workshops on a variety of pertinent issues, including sequence variation, function, polymorphism resources, human DNA sequencing, the mouse genome, informatics, sequencing technology, and large-scale sequencing. Following the workshops, an initial draft of the five-year plan was publicly presented at a gathering of scientists and other interested parties at the Airlie Conference Center in Warrenton, Virginia on May 28-29, 1998.

Next, Dr. Leroy Walters discussed the role of the ELSI Research Planning and Evaluation Group (ERPEG) in the planning process. This group is charged with providing expert guidance to NHGRI and DOE on matters relating to the extramural ELSI research portfolio as well as long-range planning. ERPEG members are drawn from the social sciences, law, medicine, public health and education. The group met four times as a committee between September 1997 and April 1998, to develop ELSI goals to be addressed over the next five years. ERPEG members participated fully at the Airlie House meeting. Dr. Walters indicated that genetics research has reached the stage where, "everything we do from this point on will have ethical implications."

Dr. Collins thanked the subcommittee chairs for their service in developing this draft plan, along with Dr. Jordan for taking staff leadership on development of the document. He also introduced Dr. Ari Patrinos, DOE Director, and NHGRI's partner in the U.S. Human Genome Project.

Dr. Patrinos indicated that the DOE had participated in the planning process through its Biological and Environmental Research Advisory Committee and its standing Subcommittee on Genome Research, chaired by Dr. Ray Gesteland of the University of Utah. Dr. Patrinos praised the cooperative efforts of NHGRI and DOE during the planning process, and said that he was looking forward to the next five years with hope, excitement and humility.

Dr. Collins characterized the draft five-year plan as being ambitious and audacious. He emphasized that the Human Genome Project (HGP) has always been an international effort, and will continue to be. Significant contributions have been made by researchers in many countries, particularly the United Kingdom, France, Germany and Japan. The Sanger Centre in Cambridge, England has been a particularly important collaborator, and Dr. Collins noted that Dr. David Bentley was in attendance representing the centre.

Dr. Collins also commented that the increasing involvement of the private sector in mapping the human genome was both anticipated and welcome. He indicated that he looked forward to collaborations with the private sector, but restated that one of the keys to the success of the publicly-funded genome research efforts was continued, strict adherence to the policy that all data are rapidly made publicly available.

The goals from the current five-year plan were published in the October 1993 issue of Science. Those goals that can be quantified have all been met or exceeded - the specified genetic and physical maps have been completed; as of October 1998, 180 Mb of human DNA sequence and 111 Mb of DNA sequence from other organisms had been completed (the 1993-1998 DNA sequencing goal was to complete 80 Mb of DNA sequence from all organisms); and in the area of gene identification, 30,000 ESTs have been mapped (the current plan called for improved technology for gene identification and mapping).

Dr. Collins then gave a brief overview of the draft of the new plan. Completion of the human sequence continues to be the highest priority goal of the HGP. The quality standards for the sequence product will be high accuracy and continuity (base pair accuracy of 1 in 10,000 and no gaps), and the entire sequence will be rapidly accessible to the public. The draft calls for the human sequence to be completed by 2003, two years earlier than the goal of the previous plan; coincidentally, 2003 is the 50th anniversary of the discovery of the double helix structure of DNA by James Watson and Francis Crick. Current information in Genbank indicates that approximately 6 percent of total human sequence has been completed, so this is a very ambitious goal.

The draft plan also proposes that one-third of the human DNA sequence will be finished by the end of 2001, with emphasis on gene-rich areas. One approach to identifying gene-rich regions of particular interest will be a peer review process to evaluate investigator requests to determine priorities for regions of special biological interest. Finally, the plan will call for coverage of at least 90 percent of the genome in working draft-quality sequence based on mapped clones by the end of 2001. This is one area where there is great potential for collaboration with the private sector.

Goal 2 states the continued need to improve the efficiency of DNA sequencing technology . While the focus is on the human sequence, there is also great interest in comparative genomics. We need to sequence many organisms. Completion of the mouse sequence would be particularly important. Resources must be invested to improve current technologies and develop new ones.

Goal 3 represents a new emphasis on cataloging human sequence variation. There are 3 billion base pairs in the genome, with an estimated 10,000,000 common variants, perhaps 200,000 of which have functional significance. Identifying these variations and understanding their relationship to biological function will reveal a great deal about human illness and how genes determine individual differences. Therefore, the new plan calls for development of technologies for scoring SNPs and creation of a map of single nucleotide polymorphisms (SNPs) containing more than 100,000 markers. To do this, we will need a public resource of DNA samples that are from anonymous donors, but which encompasses as much of the diversity found in the United States as possible.

Yet another goal calls for the development of new technologies to study functional genomics. In addition, for functional analyses, identification and sequencing of a set of full-length cDNAs that represent all human genes is a high priority.

Another important goal addresses the ELSI issues. The ELSI program is an integral component of the HGP, not an add-on. The HGP will have profound effects on society; for example, it will affect our conceptions of race and ethnicity. We do not want potentially beneficial science to be rejected by the public. Therefore, we need great intellects working on these issues.

Dr. Collins concluded his overview by indicating that the five-year plan was a well thought-out document. Input into this document came from many sources, and Dr. Collins cited his letter to representatives of biotech and pharmaceutical companies as an example of the many sources that were tapped. He indicated that these were ambitious, imaginative goals that should inspire the research community to stretch themselves. The council was then invited to comment on the draft plan on a goal by goal basis.

Goal 1 - The Human DNA Sequence
The council noted several points:

We need to develop a sustained capacity for genomic DNA sequencing in order to meet the ambitious sequencing goals identified in the draft plan. There should be an explicit target goal of 500 Mb finished sequence per year, and this should be amplified in the preamble.

While it will be extremely useful, it must be remembered that the working draft is not the final goal; finished sequence is.

It should be emphasized that the reason we are using public money for this project is that it is in the public interest to obtain and use genomic information to improve human well being. For this reason, it continues to be essential that the data produced by the publicly funded effort are completely and rapidly released.

The definition of "complete genome sequence" needs to be clarified, since at this time we don't know how much of the sequence will be possible to obtain. Specifically, a statement is needed that makes clear that not all of the DNA from the human genome can currently be cloned and manipulated. For example, centromeres are proving to be very difficult to analyze.

Continued coordination of international efforts is important, both for avoiding overlaps in regions being sequenced and in prioritizing regions of interest for finishing. This coordination is best done at the level of the agencies responsible for providing funding. It will be important to maintain and improve the electronic database system for identifying regions targeted for sequencing.

Goal 2 - Sequencing Technology
Council comments included the following:

Advances in sequencing technology provide tools not only for biological research, but also for medical research. There should be greater emphasis on the medical benefits to be derived from the HGP. Medical research should also be mentioned in the draft preamble.

It should be clearly understood that a very significant amount of funding will be needed for new sequencing technology.

Goal 3 - Human Genome Sequence Variation
Several comments were made by the council:

The utility of the rough draft sequence for the study of sequence variation and consequently the value to the health care community need to be emphasized more strongly.

The need to make information publicly available needs to stated more aggressively. There was discussion as to whether SNPs maps should be released to the public in the same time frame as sequence data. This is not as clear cut as in the case of DNA sequence data because there is a legitimate question as to when the "clock should start," i.e. when you first "discover" a SNP or when it is verified?

It was noted that a number of private entities are also creating SNP maps. However, this does not replace the need for a publicly available map. Access to such a map is critical for future progress in human genetics. To make the best use of the emerging SNP information, it was also emphasized that individual researchers need better tools to decode and analyze data.

Goal 4 - Technology for Functional Genomics
The council also made a number of points about this section:

The second sentence of the preamble for this goal should state that there are medical as well as biological benefits to be derived from functional genomics.

It is essential to remember that not all important biological information is in coding sequences; we should not be "protein chauvinists." There are many important non-coding functional sequences that are currently more difficult to identify than coding sequences. New coding regions for RNAs will be discovered. This should be added to the preamble. Functional RNAs are not found in cDNA libraries. This project is an experiment where we don't really know what the outcomes will be. While our current emphasis is on genes and sequence, we will undoubtedly discover there are other important issues.

The order of sections (b) and (c) should be reversed to give the big picture first.

There is no recognition of the fact that genes act in an environment. The draft preamble should discuss the function of genes in both internal and external environments. Part (d) should mention gene-based and phenotype-based models, and make the distinction between in vivo and in vitro studies.

Goal 5 - Comparative Genomics

Council members agreed that this goal was extremely important, and the role of comparative genomics should be elaborated upon in the preamble. Studies of closely-related model organisms will enable us to better understand how organisms close to the human can be used in comparative studies. However, we need to cut our teeth on simple cases first.

The goal of completing the mouse genome by 2008 was questioned. There was concern about committing ourselves to a date beyond the five-year plan timetable. Dr. Collins explained that this date was decided upon at the April meeting on the mouse convened by Dr. Varmus. Dr. Jordan is serving on an internal NIH committee that is looking into how to implement the recommendations from the mouse meeting.

It is possible that the target date for completing the mouse sequence will change. The approach to sequencing the mouse will depend upon what happens with the human sequence. By 2001 we will know a great deal more about the timetable for the human sequence. It was suggested that the goal for sequencing the mouse genome should be expressed in terms of a certain interval of time after the human sequence is completed. New strategies are being tested that may allow initiation of the mouse sequence effort sooner than originally expected. Council agreed with the need to make a commitment to sequence the mouse as soon as capacity now committed to human sequencing is made available. It was suggested that the goal be expressed in terms of completing the sequence of the mouse genome by 2008 or sooner, depending upon what we learn about human sequence.

The mechanism for prioritizing specific regions of the mouse genome for sequencing should carry over from the human to the mouse.

Goal 6 - Ethical, Legal and Social Implications (ELSI)
The council had several comments on this section:

Additional introductory language is needed. There is too much emphasis on genes, although environment and free will also contribute to who we are.

There needs to be a phrase added concerning problems with the current health care system and how HMOs deal with genetic testing issues.

There was considerable discussion of the use of the word "appropriate" in part (b). Can we make these kinds of value judgments? We do not want to propose policies, but rather propose a process whereby policies can be made.

There was debate as to whether the HGP should be concerned about the impact of genome research on theology as discussed in part (d). There was concern that the intent of this section could be misinterpreted. Council members questioned who should be funding this kind of research and whether this was really part of the mandate of the HGP? Several council members were concerned about the title of part (d) which states that "... genetic knowledge challenges or affirms long-standing philosophical and theological traditions." It was suggested that the heading and first sentence of this section be rewritten to make it clear that we want to promote discourse, not develop positions in these areas. At the same time, a number of members felt that it was very important to promote dialogue with the religious community. It could be even more dangerous to avoid dealing with theological issues and we need to make science and religion the subject of calm, intelligent debate.

Part (e) should be rephrased. Genetics research will challenge our concepts of race and ethnicity, and this area needs to be treated with great sensitivity.

It was agreed that Goal 6 needed to be carefully thought out and reworded. Council members were invited to submit suggestions for changes to Joy Boyer. After further deliberations about this goal overnight, council agreed to a shortened version of the ELSI goals with reference to more detailed explanations on the NHGRI Web page. This approach avoids the difficulties of capturing complex issues in a brief statement.

Goal 7 - Bioinformatics and Computational Biology

There was concern that being listed seventh did not convey the importance of this goal. It would help to stress the importance of bioinformatics in the draft preamble. Dr. Collins stated that identifying bioinformatics and computation biology as a separate goal was intended to be an indication of their importance, as these fields are also an integral part of each of the other goals.

The need for annotation deserves more attention. It was decided to change the heading for part (b) to "Develop better tools for data generation, capture and annotation," and add a sentence to this section to indicate the value of annotation.

It was suggested that part (d) be edited to change the word "homology" where it appears in the heading and the text to "similarity."

Goal 8 - Training and Manpower

Although this goal is listed last, its importance should be highlighted in the document preamble.

Council members also reviewed the table and figures attached to the draft five-year plan and made some minor suggestions. Following this review, council voted unanimously to approve the five-year plan with the suggested changes.

Introduction of New Members, Liaisons and New Staff

Dr. Jordan introduced the liaisons to the council from the professional societies: Dr. Kurt Hirschhorn, representing the American College of Medical Genetics; Ms. Rosalie Goldberg, representing the National Society of Genetic Counselors; and Dr. Jeffrey Murray, representing the American Society of Human Genetics. Dr. Jordan also indicated that she had a new secretary, Karen Hajos. A new council slate has been approved by the Secretary, but the names cannot be publicly released until the individuals have accepted the appointments.

Approval of Minutes

The minutes from the May 4-5, 1998 NACHGR meeting were approved as submitted.

Future Meeting Dates

The following dates were proposed for future meetings: 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

General Announcements

Dr. Collins presented certificates to Ellen Clayton, Lee Hood, Diane Smith, and David Valle, who are rotating off council.

Dr. Gerald Fischbach, a distinguished neuroscientist, has been named the new cirector for the National Institute of Neurological Disorders and Stroke effective 7/15/98. Dr. Fischbach was formerly professor and chairman of the Department of Neurobiology at Harvard Medical School.

Recent and Upcoming NIH Meetings

Mouse Genomics and Genetics Resources Working Group

This working group, co-chaired by Dr. David Cox and Dr. William Dove, met March 19-21, 1998 in Bethesda, Md., to discuss what mouse genomic and genetic resources are needed in order to facilitate research in mammalian biology. Subsequently, Dr. Harold Varmus, NIH director, established a steering committee comprised of representatives from the various NIH Institutes and Centers (IC). The steering committee, co-chaired by Dr. Elke Jordan and Dr. James Battey, was charged with generating a plan to implement the recommendations made at the March meeting. Dr. Varmus is very interested in developing new research and training initiatives to make the mouse a more valuable and useful tool for understanding mammalian biology.

Non-mammalian Models for Human Cancers Working Group

Originally set-up by Dr. Richard Klausner, Director of the National Cancer Institute (NCI), as the Preclinical Models for Human Cancers Working Group, the group split up into three subgroups: 1) Mouse Genomics and Genetics; 2) Mouse Models of Human Cancers; and 3) Non-mammalian Models of Human Cancers. The recommendations from the group on non-mammalian models of human cancer were presented to the NIH Directors by Dr. Robert Horvitz and Dr. Mark Kirschner. The report made broad recommendations for genomic and genetic resources for yeast, C. elegans, Drosophila, zebrafish, and Xenopus, and recognized the need to have broader evaluation of genomic resource development, including consideration of additional model organisms. A workshop is planned for this January, jointly sponsored by NCI and NHGRI. Dr. Elise Feingold (NHGRI) and Dr. Robert Strausberg (NCI) will be involved in the organization of this workshop.

Full-length Human cDNAs

On June 10, 1998, NCI hosted a workshop to discuss strategies for obtaining the complete coding sequence and a representative full-length cDNA clone for every human gene. To follow up, Dr. Collins held a meeting on August 20, 1998 with those IC directors with an interest in cDNAs to discuss a trans-NIH initiative on mammalian full-length cDNA clones. This effort is related to but separate from CGAP, and should be treated as a new initiative separate from gene discovery efforts.

Brain Molecular Anatomy Project (BMAP)

This is a trans-NIH initiative that is being led by the NIMH and the NINDS. The focus is on gene discovery and comprehensive gene expression analysis relevant to the nervous system. This is a high priority effort that will require increased funding. An internal NIH steering committee will be established along with an external advisory committee.

Program Items of Interest

Human Genome Sequencing Projects Receive Third Year of Funding

The NHGRI will award $60.5 million over the next year to seven research projects begun two years ago to pilot test new sequencing strategies for completing the DNA sequence of the human. At the last council, it was reported that government funding had resulted in 120 Mb finished sequence.

In May 1998, the Perkin-Elmer Corporation, Dr. J. Craig Venter, and The Institute for Genomic Research (TIGR) announced their own plans for sequencing the human genome separately from the public effort. On June 17, 1998, the Energy and Environment Subcommittee of the House Committee on Science held a hearing on how private sector developments will affect the government program. Witnesses included Dr. Ari Patrinos, Dr. Craig Venter, Dr. David Galas, Dr. Maynard Olson, and Dr. Francis Collins. All witnesses agreed that it will be some time before data to evaluate the private sector initiative would be available, but that private and public efforts could and should be synergistic.

NIH Polymorphism Discovery Resource

This project is progressing well. The Coriell Institute for Medical Research is growing cell lines and making DNA. A diverse set of samples has been collected from donors in the United States whose ancestors came from Europe, Asia, Africa and the United States. Before the collection is distributed, all identifiers will have been removed and the samples will be completely anonymous. Efforts to deduce ethnicity of samples will be prohibited. There have been discussions with the Native American community to respond to their concerns about the possibility of identifying samples and using them for research beyond that approved in the informed consent. NHGRI recognizes the need to be sensitive to these kinds of issues.

Division of Intramural Research 5th Anniversary

On August 14, 1998 the NHGRI Division of Intramural Research (DIR) celebrated its 5th anniversary. A highlight of the festivities was the keynote address by Dr. Bert Vogelstein, Clayton Professor of Oncology at the Johns Hopkins Oncology Center. The brochure printed by the DIR on the occasion of the anniversary celebration describes "Five Amazing Years of Research." The success of this program stands as a great credit to its leadership.

Article in Nature Genetics on mouse mutation.

An article in the August issue of Nature Genetics by NHGRI investigator Dr. Anthony Wynshaw-Boris and colleagues describes a study of a mouse with aberrant activity of the Lis1 homolog. Mice lacking one copy of this gene exhibited defects in neuronal migration and in formation of layers. A second mouse mutant with even lower gene activity suggests the gene not only aids neuronal migration, but neural development as well.

Article in Nature Medicine on new "tissue chip"

DIR scientists led by Olli-P. Kallioniemi in collaboration with researchers at the University of Tampere in Finland and the University of Basel in Switzerland are developing a new research tool, which they call the "tissue chip." Using this array-based high-throughput technique, as many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue array, and parallel in situ detection of DNA, RNA and protein targets in each specimen on the array is possible. It is hoped that this new chip technology will illuminate the process of cancer development, which can be used to identify critical molecules for development of cancer therapies. Eventually, clinicians could use the technology to learn how to distinguish among subgroups of cancer patients and predict which ones will respond to specific therapies.

Budget Issues
Fiscal Year 1999 Appropriations

While the NHGRI received a healthy increase under the FY 1999 President's Budget, the House has proposed a 13 percent increase and the Senate has proposed a 15 percent increase for FY 1999. The House proposal contains a one-time only allocation of $25 million to other NIH Institutes for sequencing projects. However, the House bill eliminated income for summer youth jobs and energy funds to assist low-income individuals, which may not be acceptable to the President. A compromise has to be reached between the House and Senate, before a bill can be submitted to the President for signature. A continuing resolution at the beginning of the fiscal year is very possible. However, things look optimistic for the long run.

Legislative and Policy Update
Health Insurance Discrimination

The Health Insurance Portability and Accountability Act (HIPAA), enacted in 1996, provided some protection against genetic discrimination in health insurance, but there are some loopholes that need to be addressed. While there is impressive support for further legislation in this area, discussions are continuing and no new legislation has been enacted. At a hearing held on May 21, 1998 before the Senate Labor and Human Resources Committee, industry witnesses supported limiting the definition of genetic information to the results of a genetic test. However, consumer groups are arguing to include both the results of genetic tests and family medical history in the definition of genetic information.

On July 17, 1998, S.2330, known as the Patients Bill of Rights, was introduced in the Senate. Title III of S. 2330 includes genetic non-discrimination legislation that is consistent with the Administration's draft bill relating to the use of "predicative genetic information." Democrats are working on an amendment to S.2330 that would address disclosure issues and workplace discrimination. However, sharp differences between the Administration and Congressional Republicans on various provisions related to patient protection, coupled with the limited time remaining in this session of Congress, make enactment of genetic non-discrimination legislation unlikely this year.

Supreme Court Decision on Bragdon vs. Abbott

This case involved an HIV positive woman whose dentist refused to fill a cavity in one of her teeth in his office. The patient filed suit, citing protection from discrimination under the Americans with Disabilities Act (ADA). In a 5 to 4 decision, the Supreme Court held that asymptomatic HIV infection is a disability under the ADA, since the immune system is damaged from the moment of infection. In a dissenting opinion, Chief Justice Rehnquist argued that this decision "would render every individual with a genetic marker for some debilitating disease 'disabled' here and now because of some possible future effects." This decision could have dramatic implications for genetics policy and pending employment and health insurance legislation. This interpretation is not in keeping with the intention of Congress when it passed the ADA.

Institute of Medicine (IOM) Report on NIH

The IOM Report, released on July 8, 1998, looked at how NIH sets research priorities and recommended that the NIH place greater emphasis on burdens and costs of disease in setting priorities. The report also recommended that Dr. Varmus should increase the involvement of the Advisory Committee to the Director (ACD) in the priority-setting process. Recommendations to increase communication and input from the public are being taken seriously, and Dr. Varmus is holding a meeting on September 23, 1998 on enhancing public participation in NIH activities.

Secretary's Advisory Committee on Genetic Testing

On August 7, 1998, HHS Secretary Donna Shalala announced that HHS was creating an Advisory Committee on Genetic Testing to help the department formulate policies on the development, validation, and regulation of genetic tests. This committee was established in response to the recommendations of two NHGRI advisory groups: the Task Force on Genetic Testing and the Joint NIH/DOE Committee to Evaluate the ELSI Program, a subcommittee of NACHGR. The Secretary hopes to appoint committee members by the end of the year. NIH will provide staff support for this committee and nominations are currently being submitted to NHGRI staff or to Lana Skirboll in the NIH Office of the Director.

Other Items of Interest
The National Coalition for Health Professional Education in Genetics (NCHPEG)

NCHPEG will hold its second full-membership meeting on October 12-13, 1998 in Bethesda. A public-private partnership, the NCHPEG is currently comprised of representatives from approximately 120 diverse health professional organizations, consumer and voluntary groups, private industry, managed care organizations, government agencies and genetics professional societies. The American Medical Association and the American Nurses Association have been very involved in establishing and supporting the Coalition. Recently, the National Foundation for Biomedical Research has recently agreed to serve as NCHPEG's fiscal manager. NCHPEG was set up to combat genetic illiteracy, and the upcoming meeting will provide updates on advances in genetic technology and implications for health care.

American Society of Human Genetics (ASHG)

Dr. Collins has been invited to present the new five-year plan in the "Highlights of the Year" session at the ASHG meeting to be held in Denver, Colorado on October 27-31, 1998.

In the discussion following the director's report, Dr. Jeanne Lawrence indicated that she was interested in learning more about how ELSI research leads to the development of policy at NIH. Dr. Collins said he would address this question at a future council meeting.

Dr. Williamson brought to council's attention a bill before Congress on patenting electronic databases. Dr. Clayton mentioned that a colleague at Vanderbilt University was working to ensure that scientific databases could not be patented and that the AAAS was becoming involved. Dr. Patrinos indicated that DOE staff had looked into this issue and were advised that the bill applied to the music industry, and that we shouldn't call attention to scientific databases. However, Dr. Nadeau indicated that he knew of a colleague who had applied for a patent on a relational database, and that this is an issue on which council might want to take a stand.

Report from the Department of Energy (DOE)

Dr. Ari Patrinos brought the Council up to date on developments at the Joint Genome Institute (JGI). The JGI has been organized to consolidate and coordinate the genomic research efforts of the three National Laboratory-based DOE genome centers at the Lawrence Berkeley, Lawrence Livermore and Los Alamos National Laboratories, and thereby enable the DOE to support its share of the sequencing efforts of the HGP. As of last month, the JGI had met its goal for this fiscal year of 20 megabases of finished sequence, and will surpass that goal before the year is over. Dr. Patrinos is optimistic about the future and the ability of the JGI to meet sequencing goals.

The new "factory," the Production Sequencing Facility (PSF) in Walnut Creek, California, will be fully operational by the beginning of the year, and there will be a ribbon cutting on January 12, 1999. Coupled with this celebration will be the DOE-Genome contractors' meeting.

The BAC end sequencing program, involving work done by the TIGR and Lee Hood groups, is progressing well.

Contacts have been made with Dr. Craig Venter and Celera to keep the channels of communication open and explore possible types of collaboration.

The House and Senate have met DOE budget requests, but differences must still be resolved in conference before the bill can be sent to the President for signature.

The draft five-year plan will be presented to the DOE statutory Biological and Environmental Advisory Committee at its meeting, November 4-5, 1998.

Dr. Patrinos expressed excitement about a new initiative, whereby teraFLOP computing, developed for military use, will be made available to the scientific community. This project is being spearheaded by DOE and the NSF, with support and approval of NIH.

Genome Scholar Development and Faculty Transition Award

Dr. Bettie Graham gave a presentation on a proposed K22 award that would enable promising new genome researchers to establish an independent interdisciplinary research program in genomic research and analysis and to secure a tenure-track appointment in an academic institution in the United States. Currently, seven other NIH Institutes have K22 programs.

The proposed Genome Scholar Development and Faculty Transition Award would be available to researchers with a doctoral degree (or its equivalent) who are engaged in technology development or applied research as it relates to genomics, and who have had no more than five years of postdoctoral experience at the time of application. Examples of research areas that could benefit from this program include large-scale DNA sequencing, human genome sequence variation, functional genomics and bioinformatics and computational biology.

The award will have two phases: 1) a Genome Scholar Development Phase and 2) a Faculty Transition Phase. Applicants may apply for both phases or for the Faculty Transition Phase alone. The total number of years of support cannot exceed five for the two phases. Awardees may elect to perform the scholar development phase in either an extramural laboratory or in an NIH intramural laboratory. NHGRI will support all extramural scholars; however, scholars who work in NIH laboratories will be supported by the NIH component where the research is conducted. All awardees will be supported by NHGRI during the Faculty Transition Phase of the award.

The budget for the scholar development phase is limited to $150,000 per year. The budget for the faculty transition phase may not exceed $250,00 per year in direct costs, and the salary is limited by the NIH salary cap,which is currently $125,000. All Genome Scholar Development and Faculty Transition Award applications will be reviewed by the Genome Research Review Committee. It is anticipated that NHGRI will make up to four new awards per year depending upon the availability of funds and the quality of the applications.

This program was influenced by the success of the Lucille P. Markey Scholar Awards in Biomedical Sciences and the Burroughs Wellcome Fund's Career Awards, and will hopefully provide an opportunity for promising genome scientists to find tenured positions outside the NIH. Scholars will have up to two years to establish a research program and to secure a tenure track or equivalent faculty appointment.

Council members wanted clarification that awardees can be principal investigators on R01 grants once they obtain a tenured position, although they cannot have an R01 grant when they first apply for the for K22 award.

Discussion also centered on the fact that genome researchers may have difficulty getting tenured positions because they are working in areas that "fall between departments," such as bioinformatics and technology development. Genome research requires a global approach, and the language in the award announcement should not be too restrictive.

Under the terms of the award, awardees will be encouraged to change institution when they move from the scholar development phase to the faculty transition phase. This is to ensure that the individual will become established as an independent researcher. However, council members agreed that candidates could petition the NHGRI to remain at an institution when there was reasonable justification.

NIH Policy On Reimbursement of Tuition

In February 1996, new NIH policy guidelines were issued which put a cap on tuition reimbursements. These guidelines were developed to establish a uniform tuition policy across all institutes, and to avoid NIH having to cut back on training programs due to steadily rising tuition costs . At the time the policy went into effect, it was understood that it would not apply to training grants that had already been awarded, but would kick in at the time of renewal.

In 1995, NHGRI awarded seven training grants that are coming up for renewal in May 1999. The principal investigators (PI) of these grants are very concerned about the financial impact of this policy on their institutions, and may not be in a position to submit the competing renewals. They have expressed these concerns in a letter to Dr. Graham, which she presented to the council for discussion. The discussion centered on whether NHGRI should pursue an exception to the policy that would allow the Institute to fully fund trainees even if other institutes don't. We need to balance this with the fact that if we provide full tuition reimbursement, we will end up funding fewer students.

The general feeling was that PI's are performing a community service by establishing training programs. Although a recent National Research Council report indicates that we are training too many people in the life sciences, there is a lack of manpower in the field of genomics, both at academic institutions as well as in the commercial sector. NHGRI can make a strong argument for an exception based on the need for genomics researchers. The council expressed its support for full tuition reimbursement for NHGRI training grants.

Advanced Technology Development

Robust technology is needed to improve efficiency and cost effectiveness in the DNA sequencing production line. Technologies developed within individual laboratories need to be tested extensively and hardened, so promising technologies can be introduced into production labs. While this could be accomplished via commercial means, development of commercial products takes a long time and requires that there be a large number of end users for the products. However, some sequencing technologies might be very useful for a limited number of researchers who have special needs, and these technologies may not be appropriate for commercial development. The question of how to effectively introduce promising new technologies into DNA sequencing production was discussed at the May planning meeting at Airlie House. As a result, there was a specific recommendation that NHGRI initiate an Advanced Development program.

Dr. Jeffery Schloss presented to council a concept proposal for a Genomics Technologies Advanced Development Program. The proposal involves a multi-disciplinary approach in which there is a close collaboration between the developers of the technology and those who would use it in production. This concept also involves close monitoring by NHGRI staff to ensure that funds are spent effectively and that projects that do not progress according to schedule are either allowed to restrategize or are terminated. It is anticipated that a typical project will require $1 to $3 million/year for 3 to 5 years, and that, eventually, the development of 5 to10 new technologies could be supported each year. Thus, it is expected that commitments would total approximately $15 to $30 million by the third year of this program.

Council members agreed that this was the right program at the right time. They pointed out that the cost of developing new technologies tends to be evolutionary, and increases as the project progresses. They also mentioned that developing the interface between the developer and the user was incredibly important, and the program should remain flexible enough to encourage this kind of interaction. Dr. Cox noted that, realistically, this is an expensive proposition to do correctly. Accordingly, in order to ensure a return on our investment, continued funding for projects should be dependent upon achievement of specific benchmarks. Technologies should show real promise to justify the next step of development. Dr. Schloss assured council that this program was not designed to support the development of technology "concepts," but rather to support the engineering development and hardening of new, promising technologies. Council endorsed the program unanimously.

Announcements and Items of Interest

Dr. Finley Austin announced that the Merck Genome Research Institute had committed $300,000 for the development of SNP resources. Dr. Austin announced that she would be working with Dr. Lisa Brooks on this project.

Dr. Jordan noted the items of interest in the council folders, and referred council to the material in Tabs "S through X."

Council-Initiated Discussion

Several topics were suggested for presentations at future council meetings. These included a discussion of how we move from ELSI concerns to implementation of official policy and the long-range continuity problem in genomic DNA sequencing.

Review of Applications

In closed session, the council reviewed 107 applications, totaling $57,003,996. The applications included 16 regular research grants, three pilot projects, one program project, 19 ethics grants, 37 grants in response to requests for applications, one conference grant, one research career development award, 17 small business innovative research awards - phase I, two small business innovative research awards - phase II, seven fellowships, and one other. A total of 69 applications requesting $37,773,623 were recommended.

I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.(2)

Date Elke Jordan, Ph.D.
Executive Secretary
National Advisory Council for Human Genome Research

Date Francis S. Collins, M.D., Ph.D.
National Advisory Council for Human Genome Research

1. For the record, it is noted that to avoid a conflict of interest, council members absent themselves from the meeting when the council discusses applications from their respective institutions or in which a conflict of interest may occur. Members are asked to sign a statement to this effect. This does not apply to en bloc actions.

2. These minutes will be formally considered by the council at its next meeting, and any corrections ornotations will be incorporated in the minutes of that meeting.

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Last updated: March 01, 2006