National Advisory Council for Human Genome Research
Summary of Meeting

Bethesda, Md.

September 11-12, 2000

The National Advisory Council for Human Genome Research (NACHGR) was convened for its thirtieth meeting at 8:30 a.m. on September 11, 2000, at the Natcher Conference Center at the National Institutes of Health (NIH). 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 4:45 p.m. on September 11, 2000. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 4:45 p.m. on September 11 until adjournment on September 12 for the review, discussion and evaluation of grant applications. (1)

Council members present:

Allen Buchanan
Aravinda Chakravarti
Ronald Davis
H. Robert Horvitz
Raju Kucherlapati
Jeanne Lawrence
Richard Lifton
Joseph Nadeau
Maynard Olson
Janet Rowley
Colleen Scanlon
Robert Waterston
Alan Williamson

Ad Hoc Participants:

David Burgess
William Gelbart
Bronya Keats

Ex officio member:

Gerard Schellenberg

Council members absent 9/11:

Wylie Burke
Kim Nickerson

Staff from the National Human Genome Research Institute:

Jane Ades, OD
Joy Boyer, DER
Lisa Brooks, DER
Jean Cahill, DER
Monika Christman, DER
Francis Collins, OD
Yasmin Cypel, DER
Tanya Dougans, DER
Adam Felsenfeld, DER
Elise Feingold, DER
Barbara Fuller, OD
Bettie Graham, DER
Mary Glynn, OD
Alan Guttmacher, OD
Mark Guyer, DER
Linda Hall, DER
Karen Hajos, OD
Kathy Hudson, OD
Linda Jacobson, OD
Karin Jegalian, OD
Elke Jordan, OD
Ron King, DIR
Charles Leasure, OD
Emily Linde, DER
Jean McEwen, DER
Monique Mansoura, OD
Susan Mix, DER
Ken Nakamura, DER
Diane Patterson, DER
Rudy Pozzatti, DER
Jane Peterson, DER
Robin Prigal, OD
Jerry Roberts, DER
Jeff Schloss, DER
Erin Shannon, OD
Geoff Spencer, OD
Sandra Taubenkibel, OD
Elizabeth Thomson, DER
Kris Wetterstrand, DER
Elsa Weinstein, OD
Cathy Yarbrough, OD

Others present for all or a portion of the meeting:

Ronald Abeles, OBSSR
Robert Boyd, Knight Ridder
Janet Dudrick, CSR
Dianne Flescher, Epilepsy Foundation
Maggie Fox, Reuters
Rosalie Goldberg, National Society of Genetic Counselors
Lila Guterman, Chronicle of Higher Education
Lauren Haffier, The Blue Sheet
Philip Harrisman, NSF
Steve Mitchell, Reuters Health
Pam Moore, Capital Publishing
Bernice Morrow, American Society of Human Genetics
Grace O'Malley, Patton Boggs LU'
Ad Patrinos, DOE
Maria Persinos, Washington Insight
Clifton Poodry, NIGMS
Amy Pradhan, PhRMA
James Shreeve, Freelance
Margaret Snyder, NIH/OD
Meredith Wadman, Nature
Rick Wilson, Washington University

INTRODUCTION OF NEW COUNCIL MEMBERS

Dr. Jordan introduced David Burgess, Boston College; William Gelbart, Harvard University; and Bronya Keats, Louisiana State University Health Science Center as new members who had joined council.

INTRODUCTION OF LIAISONS AND NEW STAFF

Dr. Jordan welcomed liaisons to the council from the professional societies: Rosalie Goldberg representing the National Society of Genetic Counselors and Bernice Morrow representing the American Society for Human Genetics.

Dr. Jordan also extended a welcome to visitors and members of the press.

APPROVAL OF MINUTES

The minutes from the May 22, 2000, NACHGR meeting were approved as submitted.

FUTURE MEETING DATES

The following dates were proposed for future meetings: February 12-13, 2001; May 21-22, 2001; September 10-11, 2001; February 11-12,2002; May 20-21, 2002; September 9-10, 2002.

DIRECTOR'S REPORT

General Announcements

The National Institutes of Health (NIH) is seeking candidates for the position of director, Office of Bioengineering, Bioimaging and Bioinformatics (OBBB). This position offers the opportunity to create and direct the new OBBB and will report to the director, NIH.

Andy Baxevanis, associate director of NHGRI's Division of Intramural Research (DIR) was awarded the prestigious Bodossaki Foundation Academic Prize. This award is Greece's highest honor for young researchers of Greek heritage.

Dr. Collins announced with deep regret the death of Chris Overton, a bioinformatics researcher who had a training grant in bioinformatics, served as a member of the Genome Study Section, and served as an ad hoc reviewer for GRRC.

New Initiatives in Genomics

NHGRJ is initiating a program to establish new academic centers for advanced genome research. The Centers of Excellence for Genomic Science (CEGS) are designed to address important biological problems on a genomic scale. September 1, 2000 was the deadline to submit letters of intent. The first set of applications will arrive October 1, 2000, and will be presented to council in May.

NHGRI, in a joint effort with National Heart Lung and Blood Institute (NHLBI), issued an RFA for the Network for Large-Scale Sequencing of the Rat Genome to expand the current NHGRI program for sequencing the rat. Awards are expected to be made by January 2001. NHLBI estimates it will contribute $32 million the first year and $26 million the second year.

Recent Scientific Accomplishments
Extramural Program

The Human Genome Project's (HGP) international sequencing consortium and Celera Genomics jointly announced the completion of the assembly of the working draft of the human genome sequence on June 26, 2000. The event was held in the East Room of the White House with opening remarks by President Clinton, live video hook-up with British Prime Minister Tony Blair, and remarks by Francis Collins and Craig Venter. Dr. Collins was gratified about the amount of media attention and thought the event had a great deal of good press coverage.

Researchers are now attempting to generate a sequence path across the genome ("the Golden Path") using the working draft data to merge together overlapping fragments and to order non-overlapping fragments. Much of the effort is being done by researchers at the University of California, Santa Cruz with comparable attempts by scientists at the National Center for Biotechnology Information (NCBI) and the European Bioinformatics Institute (EBI).

A notification about the Web site, "Human Genome Central" was published in the journals Scienceand Natureto alert scientists about the availability of up-to-date information on the details of the genome. The Web site provides a link to the assembled sequence through NCBI, FBI, UC-Santa Cruz and other sites.

Eric Lander, director, Whitehead Institute Center for Genome Research and John Sulston at the Sanger Centre have established and led the "Hard Core Analysis" group. The group meets every week by conference call to discuss the assembly and analysis of the working draft for publication later this year.

One quarter of the genome is currently in finished form. An International Strategy Meeting on Human Genome Sequencing is scheduled for September 15, 2000 in France to include members of the G-16. The discussions will include talks about the finishing challenge.

NCBI has taken on the task of setting up a repository so that sequence and traces of whole genome shotgun data for all organisms will be made available. A Trace Repository Workshop, chaired by Rick Myers at Stanford University, was held July 25, 2000, to develop recommendations on the need for establishing a sequence trace repository. NCBI announced plans to establish a Trace Archive that could accept data this fall.

In May, 129,000 SNPs deposited in dbSN7P were reported to council. Currently there are over 800,000 SNPs deposited, nearly 300,000 of them from The SNP Consortium (TSC). In July 2000, NHGRI and TSC joined forces to underwrite the production of double-ended sequences from small insert clone libraries. These sequences can be used to increase the number of SNPs as well as improve the order and orientation of the working draft sequence.

On August 7, 2000, NHGRI published on the Web an announcement about its program to sequence genomes of model organisms. The announcement summarizes the current portfolio which NHGRI supports, and describes which sequencing centers are working on the mouse and rat genome sequencing programs. Council discussed the definition of "model" organisms and the process by which genomes to be sequenced were to be selected. Dr. Collins suggested that this topic be brought back to council in February as an agenda item for further discussion.

A celebration of the first ten years of the ELSI program is being held January 16-18, 2001, at the NIH Natcher Conference Center. The conference is sponsored by NHGRJ and the Department of Energy (DOE), and will focus on the past, present and future of ELSI research. It will be organized around a series of plenary and concurrent presentations and a poster session highlighting a wide range of ELSI issues. A call for abstracts has gone out to the ELSI research community.

The first meeting of the ELSI Human Genetic Variation Consortium is scheduled to be held October 24-25, 2000, to include five variation grantees and others conducting related research.

Intramural Program

Four research papers from NHGRI's intramural program are of particular note. They include: (1) Molecular classification of cutaneous malignant melanoma by gene expression profiling, published in Naturewith lead author NHGRI scientist Dr. Michael Bittner; (2) Somatic deletions in hereditary breast cancer implicate 13q21 as a possible novel breast cancer susceptibility locus, published in PNAS co-authored by NHGRI senior scientist Dr. Olli Kallioniemi; (3) Mutations in TGIF cause Holoprosencephaly and link NODAL signaling to human neural axis determination, published in Nature Geneticsco-authored by NHGRI's Medical Genetics Branch Chief, Dr. Maximilian Muenke; and (4) Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome, published in Nature Genetics, with senior author NHGRI scientist Dr. Leslie Besecker.

Policy

The House and Senate appropriations committees passed the Labor, HHS, and Education appropriations bills as one of the first bills of Fiscal Year (FY) 2001, but a Presidential veto is expected. Serious negotiations between Congress and the White House are still needed before the bill can become final. The House and Senate have in general agreed to a 15 percent increase for NIH, with a commitment to double the NIH budget within five years. Distribution by institute has not been made available.

The June 26's announcement of completion of the working draft of the human genome spurred activity regarding genetic non-discrimination. Two days after the announcement, Senator Daschle's bill, S. 1322 was offered as an amendment to the Labor, HHS and Education and Related Agencies Appropriation bill (HR. 4577) for FY 2001. The Republicans countered by offering a limited amendment, the Jeffords-Frist-Snowe language from the Senate passed Patient's Bill of Rights legislation. The amendments inspired floor debate, however the Daschle amendment was defeated and the Jeffords amendment passed. Chairman Jeffords held a hearing on genetic discrimination in the workplace on July 20, 2000, in which Dr. Collins was a witness. The hearing emphasized the importance of attending to the issue of genetic discrimination, and NHGRI staff have been busy meeting with Congressional staff to understand the issues and craft legislative language.

The fifth and sixth meetings of the Secretary's Advisory Committee on Genetic Testing (SACGT) were held in June and August 2000. SACGT concluded that some tests, particularly predictive tests, require additional oversight to assure clinical validity. The Committee also recommends the Food and Drug Administration (FDA) utilize their legal authority to review all new genetic tests and correlate the level of review applied to each test with the level of scrutiny warranted. Criteria were developed for assessing the risks and benefits of genetic tests that could serve as the basis for a classification scheme. A flowchart was developed for determining the level of review of genetic tests. SACGT's recommendations on the oversight of genetic testing have been forwarded to the Secretary and are awaiting response.

Education and Outreach

Consumer Day 2000 is scheduled to be held November 9, 2000, at the NIH Natcher Conference Center. The second annual conference will open doors to those interested in the Human Genome Project (HGP). The conference will focus around concurrent sessions about how scientists are using information in this genomic era to understand, diagnose and treat disease. Dr. Harold Freeman will be the plenary speaker on the topic of genetic variation and how it relates to race and culture.

The National Coalition for Health Professional Education in Genetics (NCHPEG), through a series of working groups, is working on getting educational items on the World Wide Web. Joe McInerney has been selected as the full-time Executive Director for NCHPEG and began work September 1, 2000. Alan Guttmacher, senior clinical advisor to the director of NHGRI and Lisa Lanier, the NHGRI education coordinator, will continue to assist on NCHPEG issues. The next NCHPEG Steering Committee will be held September 27, 2000, and the full NCHPEG membership will meet February 1-2, 2000.

REPORT FROM THE DEPARTMENT OF ENERGY

Ari Patrinos, Associate Director for Biological and Environmental Research, Office of Science at the Department of Energy reported to council on genome-related activities. DOE's Biological and Environmental Research Advisory Committee issued the report "Bringing the Genome to Life". This report summarizes plans for the future of energy-related biology in the new genomic era and can be found on the Web at http://www.science.doe.gov/ober/berac/genome-to-life-rpt.html.

The Office of Biological and Environmental Research (OBER) expects to move in three major directions:

  1. continued commitment to sequencing;
  2. structural genomics; and
  3. computational biology.

OBER is working with other agencies including NIH and the National Science Foundation on microbial genomics.

Dr. Patrinos discussed the future sequencing targets at the Joint Genome Institute. Two additional laboratories are now joining the JGI, the Oak Ridge National Laboratory and the Pacific Northwest National Laboratory. Finishing of human sequencing is going well under the leadership of Rick Myers at Stanford University. Some problems had developed at the production sequencing facility but did not affect human sequencing.

There is strong support for the budget of the genome program at OBER. That portion will be protected and may increase in FY 2001.

OVERVIEW OF TRAINING AND CAREER DEVELOPMENT PROGRAMS

Bettie Graham, program director, Genome Analysis and Training presented council with an overview of research training and career development programs at NHGRI. Dr. Graham thanked Yasmin Cypel for her efforts and help in preparation of the presentation.

Dr. Graham explained the history of NHGRI training programs between 1990 and 1995. Initially, the NCHGR funded four pre-doctoral grants and co-funded six with the National Institute of General Medical Sciences (NIGMS). The first Individual Postdoctoral Fellowship Program Announcement was published in 1991, and in 1992, the Special Emphasis Research Career Award was initiated and first awards were made. In 1995, seven new training grants were funded and co-funding of NIGMS grants stopped. In 1998, the Kl2 and K07 awards were implemented and the salary cap of K awards increased to the NIH limit for research grants of $l25,000. In 1999, NHGRI was able to remove the Institutional Allowance cap on T32 training grants and the Individual Postdoctoral Fellowship Program Announcement was reissued. In 2000, the first K22 awards were made and the first K01 was awarded in the ELSI program.

The objectives of NHGRI's training programs and the purpose of the various mechanisms were discussed. A bar chart showing the number of T32 training slots by academic year over the last five years was presented. The chart represents nine programs that have both predoctoral and postdoctoral training slots. Dr. Graham also presented data about the scientific disciplines of incoming trainees and their employment areas after training.

In summary, over 40 percent of the predoctoral students recruited under training grants have undergraduate degrees in non-biology sciences. Following completion of NRSA training, trainees are employed as follows: 65 percent in academia; 16 percent in biotechnology or pharmaceutical companies; 17 percent in government, hospitals or as entrepreneurs; and 12 percent are unaccounted for. Following completion of the career development program K01 awardees (about nine or ten), chose the following career paths: 33 percent in biotechnology or pharmaceutical companies; 22 percent as entrepreneurs, and 11 percent are unaccounted for. Two K01 awardees have received prestigious awards, the Presidential Early Career Award for Scientists and Engineers and the James S. McDonnel Centennial Fellowship.

NHGRI faces the following challenges for the future of training and career development: increasing the number of scientists trained in genomics; increasing the number of under-represented minority scientists trained in genomics; finding creative ways to recruit scientists from other fields into genomics; expanding the K01 award to recruit biologists who wish to specialize in bioinformatics or computational biology; and having the ELSI Research Advisory group address the training needs for the ELSI program.

NHGRI training programs are focused on recruiting individuals who do not have a biology background into biology. Such individuals can make major contributions to emerging fields such as genomics.

Dr. Jordan explained that at the start, the NCHGR training program had very ambitious goals but the applications were just not there. As a result, NCHGR co-funded with GM and held back on training. NHGRI has been pleased with the new training grants since 1995.

Dr. Lawrence suggested that someone with a master's degree in computer science might be a useful contributor as well as those who have a Ph.D.

Dr. Collins reaffirmed that the intention is to strongly support training, however, good candidates are needed. NHGRI is hopeful that the Centers of Excellence in Genomic Science (CEGS) program will attract good students and train some of the interdisciplinary scientists needed for the future.

Dr. Scanlon wondered whether it makes sense to have pre-doctoral ELSI training. Dr. Graham and Ms. Thomson answered that an ELSI researcher should have solid training in a particular area with ELSI added on top of the basic training, generally at the postdoctoral level.

NHGRI PLAN FOR REDUCING HEALTH DISPARITIES

Elke Jordan updated council on NHGRI's health disparities plan. Each institute was asked to develop a plan for reducing health disparities through a trans-NIH working group.

Health disparities is not a new concept to NHGRI. In 1998, a staff group considered the ELSI issues associated with launching a genetic variation research program. The staff group identified the need for ELSI research; for a better outreach program to minority groups; and for increased emphasis on education for diverse groups.

In 2000, NIH set up another staff working group to develop the current plan, which includes both ongoing and new initiatives. Clifton Poodry is on detail to NHGRI from the National Insitute of General Medical Sciences (NIGMS) to help expand these activities.

The plan identifies four goals: (1) genetic factors in diseases that affect minority populations disproportionally; (2) ELSI issues; (3) training of minority investigators; and (4) policy, education and outreach activities. The estimated budget for FY 2000 is $6.6 million.

Dr. Olson pointed out the importance of public education and encouraged NHGRI to use this as an opportunity for broader education. There is an urgent need for NHGRI to try to encourage discussion on health disparity issues in minority populations. He suggested getting involved at the K-12 level.

Dr. Burgess suggested NIH move a laboratory to a minority institution to help address strategies in reaching minority groups. He reports that minorities are not getting into graduate programs and that there are zero American Indian genetic counselors. There are also very few Hispanic counselors and some sub-groups of Asians are also under represented.

Dr. Collins noted that the ELSI program has played a significant role in health disparities issues and will continue to do so. The program will seek the input from communities at the First Community Consultation for the Responsible Collection and Use of Samples for Genetic Research meeting, organized by NIGMS and to be held September 25-26, 2000.

FINISHING OF HUMAN SEQUENCING

Richard Wilson, Genome Sequencing Center at Washington University School of Medicine and co-chair of the working group on finishing, updated council on the status of post-working draft efforts for finishing the human sequence.

Dr. Wilson discussed the following key topics: (1) what needs to be accomplished; (2) what is involved in finishing; (3) the role of the G-5 and G-16; and (4) the finishing working group.

In order to finish the human sequence, the following need to be accomplished: "top-up" of draft projects; finishing to uniform standards; direction and management of "turf" claims and monitoring progress; and adherence to standards.

Pre-finishing involves: checking for neighbor overlaps and contamination; adding new reads to provide order and orientation and to improve the consensus quality; identifying and tagging misassemblies, repeats and other problems; and rating the project with respect to the degree of difficulty.

Finishing involves: checking and editing; adding new reads to improve consensus quality; and resolving gaps, repeats and difficult regions. The Washington University Genome Sequencing Center has four finishing groups, each assigned to a particular chromosome. There is also a prefinishing group that directs production and a quality assurance group.

Dr. Wilson explained the role of the G-5 and G-16 and presented a chart showing the current assignments for finishing chromosomes for each center. The rule is that centers finish regions they have drafted. Where there are overlapping interests, an appropriate division is being negotiated by the parties.

A meeting of the working group is scheduled for September 14, 2000, along with a meeting of the G-l6 that is scheduled for September 14-15, 2000, to be held in France. The working group will revisit all of the issues at this meeting.

Questions were raised about the rates of "topping-up" versus finishing. By next summer the group hopes to complete full shotgun of the entire human sequence.

Dr. Lawrence asked about the centromeres and other heterochromatic regions. An RFA has been issued to deal with theses and other difficult regions.

Dr. Chakravarti was concerned about how the finishing data will be released. Dr. Wilson explained that a proposal is being developed by the finishing group and will be discussed at the September 14th meeting.

DEMO OF MULTIMEDIA EDUCATION KIT

Kathy Hudson, director, Office of Policy and Public Affairs was asked to produce a multimedia educational kit on genomics and genetics directed to high school students and teachers to accompany the publication of the human sequence. The kit includes: a multimedia interactive CD-ROM, a 15 minute video documentary, an informational brochure and a commemorative wall poster. The educational kit is being produced by NHGRI with co-sponsorship by DOE, Howard Hughes Medical Institute, Pharmaceutical Research and Manufactures of America, and Nature and Science magazines.

Dr. Hudson played the 15-minute video documentary for council and demonstrated the functions of the CD-ROM. The multimedia interactive CD-ROM consists of a running timeline of about 90 major events in the history of genetics, a Web link to the NHGRI talking glossary of genetic terms, 3-D animations of cells and molecules, and various classroom activities on genome sequencing, genetic variation,and ELSI issues.

There was overall enthusiasm from the council members.

Dr. Williamson asked if there were plans for the kit to be put into other languages to be distributed worldwide. Dr. Hudson's hope is to do that but not in the first round of distribution. There are plans to set up a Web address with an order form that goes directly to the distributor, and a chat room and place for evaluation and feedback. The kit will be made available along with the publication of the working draft of the human genome. There will be subsequent Web-based modifications based on informal evaluations from biology teachers.

Several council members thought this would be a good tool for non-major and community colleges as well as high school students.

ANNOUNCEMENTS AND ITEMS OF INTEREST

Dr. Jordan noted the items of interest in the council folders, and referred council to the material under Tab "U."

COUNCIL-INITIATED DISCUSSION

Dr. Collins proposed having Dr. Eric Lander give a presentation at the next council meeting on the first pass of the annotation. The presentation would be held at the Masur auditorium and will be open to the NIH scientific community.

Council proposed a discussion on the process for prioritizing the sequencing of additional organisms. Dr. Mark Guyer will take the lead on this issue and present a proposal in February.

Dr. Collins suggested a presentation on research and activities in the NHGRI Intramural Research program. Dr. Collins suggested inviting one or two Howard University investigators to hold a discussion on health disparities and reaching out to the minority populations.

Dr. Jordan alerted the council that they would have a brief presentation to introduce the members to the electronic council book at the next meeting.

Several council members suggested having a presentation on the future portfolio of the human genome project. They would like to see a long-term perspective of where the genome project is going beyond sequencing. Dr. Collins suggested we focus on different topics for the next few council sessions, for example: technology for sequencing, genotyping or expression analysis.

BUDGET TABLE

Dr. Jordan referred to the budget table found under Tab "X."

REVIEW OF APPLICATIONS

In closed session, the council reviewed 115 applications, totaling $28,398,764. The applications included 27 regular research grants, four pilot projects, 33 ELSI grants, one center grant, three conference grants, one training grant, one continuing education training program, 22 SBIR Phase I, nine SBIR Phase II, three fellowship grants, two S.T.T.R. - Phase I, one program announcement, and eight others. A total of 56 applications requesting $15,168,173 were recommended.

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

11/14/00


Date Elke Jordan, Ph.D.
Executive Secretary
National Advisory Council for Human Genome Research
11/13/00


Date Francis S. Collins, M.D., Ph.D.
Chairman
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."

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Last Reviewed: May 2006