National Advisory Council for Human Genome Research
Summary of Meeting
September 15, 2003
The National Advisory Council for Human Genome Research was convened for its thirty-eighth meeting at 8:36 a.m. on September 15, 2003 at the Bethesda Hyatt, Bethesda, Md. Francis Collins, Director of the National Human Genome Research Institute, called the meeting to order.
The meeting was open to the public from 8:36 a.m. until 1:00 p.m. on September 15, 2003. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 1:00 p.m. on September 15, 2003 until adjournment for the review, discussion and evaluation of grant applications.
Council members present:
Council members absent:
Vicki Yates Brown
Ex Officio member absent:
Staff from the National Human Genome Research Institute:
Christopher Austin, OD
Maggie Bartlett, OD
Vence Bonham, OD
Joy Boyer, DER
Lisa Brooks, DER
Jean Cahill, DER
Francis Collins, OD
Tanya Dougans, DER
Elise Feingold, DER
Adam Felsenfeld, DER
Peter Good, DER
Bettie Graham, DER
Alan Guttmacher, OD
Mark Guyer, DER
Rabiah Hendricks, DER
Lynette Jackson, DER
Sandra Kamholz, DER
Rebecca Kolberg, OD
Jean McEwen, DER
Ken Nakamura, DER
Ken Ow, OD
Allison Peck, DER
Jane Peterson, DER
Rudy Pozzatti, DER
Jerry Roberts, DER
Laura Rodriguez, OD
Jeff Schloss, DER
Geoff Sisk, DER
Elizabeth Thomson, DER
Susan Vasquez, OD
Fred Walker, OD
Esther Warshauer-Baker, OD
Kris Wetterstrand, DER
Jonathan Witonsky, DER
Lynn Zacharia, DER
Others present for all or a portion of the meeting:
Reid Adler, J. Craig Venter Science Foundation
Joann Boughman, American Society of Human Genetics
David Haussler (portion of the meeting, by phone), University of California at Santa Cruz
Andrew Hawkins, FDC - Reports
Sharon Olsen, International Society of Nurses in Genetics
Asha Pathak, Office of the Secretary, DHHS
Margaret Snyder, Office of the Director, DER, NIH
Ansalon Stewart, Office of Technology Transfer, NIH
Lawrence Sung, University of Maryland School of Law
Karen Wolfe, NSQC
Kevin Wright, NCI, NIH
Introduction of Liaisons and New Employees
Mark Guyer welcomed members of the press and liaisons from professional societies: Joann Boughman of the American Society of Human Genetics, Karen Wolff of the National Society of Genetic Counselors, Sharon Olsen of the International Society of Nursing and Genetics, and Andrew Hawkins of FDC-Reports. Dr. Guyer introduced new staff members: Fred Walker, NHGRI's new executive officer, Jonathan Witonsky, a new program analyst working with the genetic variation and ELSI programs, and Geoff Sisk, a program analyst working with the sequencing team and the genome informatics program.
Approval of Minutes
The minutes from the May 19, 2003 Council meeting were approved as submitted.
Future Meeting Dates
The following dates were proposed for future meetings: September 15-16, 2003, February 9-10, 2004, May 10-11, 2004, September 13-14, 2004, February 7-8, 2005 and May 23-24, 2005, September 12-13, 2005.
Mary Hendrix has been appointed president and director of Children's Memorial Institute for Education and Research. The institute is affiliated with the Children's Memorial Medical Center and the Center for Pediatric Research at Northwestern University. Currently, Dr. Hendrix is the head of the Department of Anatomy and Cell Biology at the University of Iowa in Iowa City as well as the deputy director of the Holden Comprehensive Cancer Center in the university's Carver College of Medicine. She is planning to relocate to Chicago in January 2004.
Dorothy Nelkin, former Council member and member of the ELSI Working Group, passed away on May 28, 2003, from cancer. Ms. Nelkin was a professor of sociology at New York University. She received a B.A. in philosophy from Cornell in 1954.
Dorothy Wertz, former ELSI grantee and internationally recognized social scientist, passed away April 29, 2003. Dr. Wertz was a senior scientist in social science, ethics, and the law at Eunice Kennedy Shriver Center. She earned her degree in social relations from the Buffalo Seminary and Radcliffe College, and she studied social anthropology at the London School of Economics. She earned her master's in sociology of religion at Radcliffe.
Claude Lenfant, M.D. announced his retirement as NHLBI Director effective August 30. Dr. Lenfant, who had been the longest serving director of NHLBI, held his position since 1982, when he arrived at the NIH from the University of Washington. Dr. Barbara Alving, who joined the NHLBI in 1999 to lead the Division of Blood Diseases and Resources and was named NHLBI Deputy Director in 2001, will be the NHLBI Acting Director until a new director is appointed.
Kenneth Olden, Ph.D., announced that he will step down as the Director of the National Toxicology Program and as the Director, NIEHS. Dr. Olden has been the National Toxicology Program Director and NIEHS Director for 12 years. Dr. Olden will continue to serve in both positions until a successor is named.
Dr. Zerhouni announced the appointment of Story Landis, Ph.D. to serve as the Director of NINDS, effective September 1st. Dr. Landis had served as the Scientific Director of the NINDS intramural program since 1995.
Jeremy Berg, Ph.D. has been appointed as the new director of NIGMS. Dr. Berg is currently director of the Institute for Basic Biomedical Sciences and professor and director of the Department of Biophysics and Biophysical Chemistry at Johns Hopkins University. He is expected to begin his appointment in early November.
Ellie Ehrenfeld, Ph.D., announced that she will step down as Director of the Center for Scientific Review (CSR) at the end of September after seven years. She will continue in her position as Chief of the Picornavirus Replication Section in the Laboratory of Infectious Diseases at the NIAID.
On July 25, Dr. Zerhouni announced the formation of the NIH Steering Committee, which is being implemented to improve the efficiency of trans-NIH coordination in light of the expansion of the number of NIH components in recent years, will oversee and develop policies for the NIH. The Directors of NCI, NHLBI, and NIAID, the 3 largest ICs, will have permanent seats on the Committee. The other seven members will have 3-year staggered terms on a rotating basis. The initial membership includes the Directors of the following ICs: NCCAM, NHGRI, NIA, NIAMS, NIDA, NIDCR, and NLM. Dr. Zerhouni will chair the Committee and Dr. Kington will serve as an ex-officio member. The Committee has already met twice. The NIH institute directors will continue to meet on a regular basis in alternating weeks.
On July 29, The National Research Council/Institute of Medicine released the report entitled "Enhancing the Vitality of the National Institutes of Health: Organizational Change to Meet New Challenges." The report was written by the Committee on the Organizational Structure of the National Institutes of Health, which was chaired by Harold Shapiro; NACHGR member Tadataka Yamada was a member of the Committee. The report is wide-ranging in its content. The overall structure and workings of the NIH were examined, and more attention to cross-institute issues at the NIH was suggested. Dr. Zerhouni and Dr. Shapiro will testify at a Congressional hearing to discuss the report in the near future. The institute directors met to discuss this report shortly after its release. One of the recommendations included the possible merger of NHGRI with NIGMS. While these institutes do share some overlapping areas, there are also major organizational differences and considerable thought needs to be put into the evaluation of this recommendation. Dr. Zerhouni plans to obtain a good deal of outside input before considering any action.
Dr. Zerhouni discussed the NIH Roadmap effort at the meeting of the Advisory Committee to the Director on June 30. The Roadmap effort is focused around three themes: new pathways to discovery, research teams of the future, and re-engineering the clinical research enterprise. The FY 04 budget provides $45 million to the Director's Discretionary Fund, up from $25 million in FY 03, to pursue roadmap goals. Fifteen working groups were established as part of the NIH Roadmap effort; three of these were co-chaired by NHGRI representatives. Francis Collins co-chaired the working groups on Building Blocks for Biology and on Molecular Libraries, and Jeff Schloss co-chaired the working group on Nanomedicine. Each working group was asked to recommend three major initiatives. These were then discussed by the IC directors, prioritized, and assigned dollar amounts for FY04. Implementation groups were then organized to develop plans and budgets for the initiatives over the course of the next 5 years, with immediate attention focused on the next 1-2 years.
New NHGRI Initiatives
The ELSI program released an RFA soliciting applications for the development of Centers of Excellence in ELSI Research (CEER). These centers are intended to bring investigators from multiple disciplines together to address new ELSI issues arising from the advances in genetics and genomics in ways that cannot be effectively supported by current R01 and other grant mechanisms currently used by the ELSI program. Initial responses have indicated that the community is very interested in this new program. NHGRI estimates that it will commit approximately $3M in FY04 to fund 2-3 Specialized Centers for up to 5 years each, and 2-3 Exploratory Centers for up to 3 years each. The receipt date is November 24th.
Recent Scientific Accomplishments and Issues
Approximately one-third of the mouse genome sequence is now in finished form. The rat genome is in an advanced draft assembly, with N50 contigs of 18.5 million base pairs. The chicken sequencing effort has already reached approximately 2X coverage, the chimp sequence is at about 4X coverage, and the dog sequence already has 2X coverage. The Drosophila pseudoobscura, honeybee, and several fungi projects have been completed.
George Weinstock commented that analysis of the rat sequence is currently being completed, and many papers are being written. The plan is to publish a paper in Nature on the overall rat sequence, plus a large number of more detailed papers in a coordinated special issue of Genome Research.
An effort is also underway by the International Human Genome Sequencing Consortium to publish a paper on the final human genome sequence. At the same time, individual human chromosomes are being carefully annotated by the sequencing groups. A very interesting analysis of the Y chromosome sequence was recently published. The research team, which was led by David Page, Rick Wilson, and Bob Waterston, discovered that much of the Y chromosome is arranged in palindromes that contain, among other things, functioning genes important for male fertility. The team found that most of the palindromic sequences are greater than 99.97% identical. The extensive use of gene conversion appears to play a role in the ability of the Y chromosome to edit out genetic mistakes and maintain the integrity of the relatively few genes it carries in spite of not having a paired chromosome with which to recombine.
A multi-institution team, led by the Washington University School of Medicine, reported that it had sequenced 99.4% of the gene-containing region of chromosome 7 to an accuracy of greater than 99.99%. The team also described its analysis of this highly accurate reference sequence. Eric Green's laboratory at NHGRI was a significant contributor to this work.
NHGRI currently supports five CEGS grants and two additional awards will soon be made. The current and new CEGS grantees will meet for the first time in October 2003 in Seattle, and a report on the CEGS program will be presented at the February Council meeting. A new round of CEGS applications were received in June and will be reviewed at the February Council meeting.
The applications received in response to the two ENCODE RFAs will be reviewed later during this September Council meeting. The grants are expected to be awarded by the end of September 2003.
As of September 2, 2003, the Mammalian Gene Collection (MGC) contained a non-redundant set of approximately 20,000 clones (ca. 11,000 human clones and 9,000 mouse clones). Approximately 26,000 full-ORF sequences have been submitted to GenBank (approximately 15,000 human and 11,000 mouse sequences). There are several thousand additional candidate clones in the pipeline. Then there are about 5,000 (2,500 human and 2,500 mouse) additional known genes in the RefSeq resource that are not yet present in MGC collection; these could potentially be obtained with directed strategies that the MGC effort has not yet employed. The Baylor College of Medicine group has taken a significant leadership role in piloting directed efforts to find difficult genes using PCR capture. Three additional years of funding for MGC has been secured from the participating ICs, who have agreed that the primary goal should be the completion of the human and mouse collections. The generation of a collection of roughly 6,250 rat cDNAs has been added, thanks to a significant contribution from NHLBI, and the collaborations with the ongoing Xenopus (9,200 clones, spearheaded by NICHD) and zebrafish (10,000 clones, led by NIDDK) projects have been expanded. Elise Feingold continues to provide the acting leadership until a replacement at NCI can be found; in the meantime, Daniela Gerhard of NCI continues to provide considerable support for this initiative. The Request for Proposals to support the continuation for the MGC has been released.
The NHGRI Research Training Advisory Committee, which is responsible for providing advice and oversight of the Institute's Minority Action Plan and the research training programs of the NHGRI, met for the first time on July 25 in Bethesda. The purpose of the meeting was for the advisors to review the research training activities and to provide feedback to the grantees and to NHGRI. Council members Bronya Keats and Kim Nickerson were present at the meeting. Dr. Keats commented that the meeting went extremely well; Dr. Nickerson mentioned that there was a range of expertise with many different approaches for meeting the training goals. Bettie Graham has developed this program from its inception. The Advisors will have a satellite meeting with the grantees and training coordinators after the first annual CEGS grantee meeting in October 2003 in Seattle.
As mentioned at the May 2003 Council meeting, NHGRI convened a meeting on March 13-14, 2003 with several people familiar with the American Indian health research community and small number of staff from NHGRI and IHS. The topics of discussion included the attitudes of American Indian/Alaska Native communities toward possible participation in the HapMap Project, and in related research on genotype variation. The conclusion of the meeting, which was not intended to reach a consensus but was an opportunity for NHGRI to hear the individual opinions of people familiar with both biomedical research and the attitudes of American Indians, was that NHGRI should continue communicating with American Indian communities about participation in research of this type.
The ELSI Research Advisors (ERA) will meet on Tuesday evening, September 16, 2003. The ELSI Program Announcements (R01 and R03) are being revised and will be released this fall. The NIH Center for Scientific Review (CSR) has established a standing ELSI study section, which will be co-managed, on an alternating basis, by Rudy Pozzatti (NHGRI) and Cheryl Corsaro (CSR).
NHGRI's intramural program will be celebrating its tenth anniversary this year with a symposium in December 2003. At the symposium NACHGR member (and former member of the DIR Board of Scientific Counselors) Janet Rowley will give the first annual Jeff Trent lecture.
A team of researchers in DIR has demonstrated for the first time that the genetically engineered mouse virus used in gene therapy trials tends to insert itself at the beginning of genes in the target cell, potentially disrupting the affected gene's normal function. This study may lead to safer gene therapy techniques.
A research team, led by Eric Green, has compared the sequence of a large genomic region from 13 vertebrate species. The organisms included human, chimpanzee, baboon, cat, dog, cow, pig, rat, mouse, chicken, zebrafish and two species of pufferfish. This analysis provides convincing evidence that sequencing the genomes of a wide range of organisms can help to illuminate the human genome sequence.
NHGRI Office of the Director
NHGRI has established a new branch, known as the Education and Community Involvement Branch within the Office of Policy, Communications, and Education (OPCE). The Branch Chief is Vence Bonham, J.D., who also serves as Senior Advisor to the Director (NHGRI) for Societal Implications of Genomics. The branch will lead the Institute's outreach and public education programs and will work to enhance NHGRI's relationship with underrepresented and minority communities.
As mentioned at the May 2003 councilmeeting, NHGRI will host a two-day meeting November 19-21, 2003, on "New Directions for Sickle Cell Therapy in the Genome Era". The meeting, which will be jointly sponsored by NHLBI, NIDDK, FIC, ORD, along with NHGRI, will be co-chaired by Sir David Weatherall and Francis Collins. The purpose of the meeting is to discuss the tools of genomics can be used to move forward the effort to develop effective treatments for sickle cell disease.
The NHGRI communications office, led by Larry Thompson, has updated and reissued the DVD set that was distributed at the scientific and public symposia last April. The revised DVD set includes the final, finished sequence from April and additional interviews that address the impact of the Human Genome Project and the future of genomics.
The New England Journal of Medicine's series on genomic medicine, edited by Alan Guttmacher and Francis Collins, was completed with its September 4 issue. NHGRI is working with the NEJM on publishing the 11 articles and two accompanying editorials of the series as a softbound book, with an anticipated publication date of January 2004.
On July 10, the House passed the $138 billion Labor, Health and Human Services and Education Appropriations bill. Under this bill, the NIH would receive $27.7 billion in FY2004, an increase of $681 million (2.5%) over FY2003. On September 10, the Senate passed its version of the bill, which provided $27.982 billion for NIH, an increase of $1 billion (3.7%). Although the final funding level has not yet been decided, the Senate figure is likely to be the ceiling.
On May 21, 2003, the U.S. Senate Health, Education, Labor and Pensions (HELP) Committee passed the Genetic Information Nondiscrimination Act (S. 1053) by voice vote. The bill would prevent health insurers and employers from using genetic information to determine eligibility, set premiums, or hire and fire people. It is now hoped that the full Senate will take up the bill, which will be followed by consideration by the House. The White House is supportive of the bill.
The Secretary's Advisory Committee on Genetics, Health and Society (SACGHS) held its inaugural meeting on June 11-12, 2003. Presentations were made on genetic technologies in bioterrorism, forensics, intellectual property, ethical, legal, and social implications, and the integration of genetic technologies into health care and health practice. The Committee has identified genetics education and training of professionals and the adequacy of the genetics workforce as areas of interest and priority.
Council member Mary Hendrix inquired about governmental efforts for inter-agency collaboration. Francis Collins mentioned that he and Ari Patrinos (DOE) received the gold award from Secretary of Energy Spencer Abraham last week. This award is the highest given by the Secretary. DOE and NHGRI have partnered in the past on sequencing efforts.
Research on Intellectual Property
Jean McEwen discussed an RFA on intellectual property research that will soon be released by NHGRI. Lawrence Sung of the University of Maryland has advised NHGRI on the writing of the RFA. The purpose of this initiative is to stimulate research in the field of intellectual property as it applies to genomics and genetics (as distinguished from all areas of biotechnology and contextual IP issues in different cultural and belief systems). The RFA will deal with patent application issues, ownership of intellectual property rights and the Bayh-Dole law, licensing and associated mechanisms, enforcement, international issues, and impact on research, commercialization, health care, science and the general public. Multidisciplinary teams will be encouraged for these areas of research, and U.S. policy-related applications will be accepted from foreign investigators. The RFA will likely be funded out of FY04 funds, and will use the R01 and R03 mechanisms with an approximate commitment of $2 million.
Council member Mary Hendrix asked about the involvement of attorneys, and she was told that many of these applications would likely involve this type of researcher. Council member Eric Juengst commented on the amount of staff effort that will be required to maintain this initiative. The National Academy of Sciences may be formulating a study on biotechnology intellectual property issues; this study might encompass other agencies. Council member Tadataka Yamada suggested that this initiative might be amenable to contract work.
Lisa Brooks presented a summary of recent activities of the Intenational HapMap Project. Currently, a project description manuscript is being written and an official website is being developed for the HapMap project. An initial success has been to meet the need for the additional SNPs needed to complete the project. The number of SNPs in dbSNP has increased from 2.8 million to 5.6 million due both to resequencing efforts and improved analytical techniques. At least 1.3 million of these are so-called "double-hit SNPs" (those in which both alleles have been independently observed at least twice), which are more likely to be valid and common.
As part of an effort requested by the Analysis Group to develop a resource in which the haplotype structure of the human genome is completely known, an effort to resequence 5 Mb of human genomic DNA (comprising 10 of the ENCODE regions) in 48 HapMap samples has gotten underway. All of the SNPs generated from resequencing and all SNPs in these regions from dbSNP will be genotyped in all of the HapMap samples. SNPs with potential functional significance will be given priority. Council suggested a directed approach to discovering SNPs of this type.
The CEPH samples have been reconsented, Japanese sample collection has been completed, and Yoruba and Han Chinese samples are in the process of being collected.
Council voiced interest in hearing about the science behind community consultation. An independent site evaluator recently visited the Yoruba community to evaluate those sample collection processes. An oversight group for community engagement exists, and there is also a council oversight group involving members with expertise in bioethics. A third oversight group consists of international representatives from several countries involved in the project.
David Haussler of UCSC, a computational biologist, joined the meeting via teleconference for this discussion, which was led by Peter Good.
NHGRI currently funds a number of model organism genome databases, including MGI, FlyBase, SGD, WormBase, ZFIN, as well as the Gene Ontology Consortium. In FY 2003, NHGRI's commitment to these efforts was approximately $21,000,000. NHGRI is considering the need for an analogous genome database for human data. Such a resource could provide integration of large-scale genomic information from many different projects, e.g: ENCODE and MGC. There are already many resources for human genome data, including chromosome annotation projects, NCBI, OMIM, Ensembl, and the UCSC Genome Browser; the question is whether the research community's needs are met by the existing resources or whether some sort of enhancement is needed. One proposal would be to develop a "HumanBase" with the essential functions of a Model Organism Database, into which existing resources could be incorporated or linked to. What this proposed database would add to what is already done by the existing efforts is curation of information by Ph.D.-level curators, and integration of information to simplify knowledge acquisition by research and clinical scientists. This question will be addressed at a workshop, co-sponsored by NHGRI and the Wellcome Trust, entitled "Informatics Resources for the Human Genome." At the workshop, several proposed goals for a human genomic information database will be laid out. Participants will include scientists who currently run model organism databases, people who provide human genomic resources such as Ensembl and NCBI, bioinfomaticians who use large datasets, and members of the user community slanted towards human genetics. The chairs of the workshop are Sean Eddy, Tim Aitman, and David Valle.
Council expressed interest in having HumanBase be a unique resource, including human sequence annotation, and not simply effect the integration of other resources. David Haussler suggested that working at the interface between the manual annotation and the automated methods is an important task. Council asked about the ability to pull in information about phenotypes, pathways and mechanisms that could enrich the understanding of gene families. This may begin slowly, but the resource should be robust enough that it could be eventually used for this purpose. Council also stressed the importance of establishing a common dictionary and integrating the user community into any planning steps. Council proposed that this new database incorporate a strong advisory group. Peter Good will distribute the list of workshop attendees to the Council members.
Report on the Workshop on Selecting New Sequencing Targets
Jane Peterson discussed a workshop that was held on July 21st and 22nd in Reston, Virginia to consider the current NHGRI process for choosing the next set of sequencing targets for NHGRI, and whether that process needs to be modified. Council member William Gelbart chaired the meeting. The meeting specifically addressed future goals for comparative genomic sequencing, and a re-evaluatation of the so-called "white paper process" presently used for the selection of organisms for sequencing.
Major recommendations by the workshop attendees included:
- Comparative analysis of the human genome sequence with to the genomes of several model organisms reveals significant information.
- The primary goal of NHGRI is to provide genomic resources to understand basic biology and human health.
- NHGRI should not express in advance how much money should go to any specific area.
The attendees also recommended modifying the organism selection process, basing it on expert working groups that would address different research applications for genomic sequence and comparative analysis, including understanding the human genome, understanding the genomes of major experimental organisms, understanding the genomes of model organisms, and identifying systems that would illuminate human biology in novel ways, and understanding evolutionary mechanisms. While the working groups were proposed to play the major role in identifying new sequencing targets, the workshop also concluded that the NHGRI should continue to provide an opportunity for investigators to submit white papers. A coordinating committee was proposed to coordinate the plans presented by each of the working groups and develop an overall prioritized proposal to the Council for new sequencing targets. The Council concurred with these recommendations, and the working groups will be recruited and established immediately. The coordinating committee will be also established; it will meet next April to develop the first set of proposed targets for consideration at the May 2005 Council meeting.
Announcements and Items of Interest
Joann Boughman from the American Society of Human Genetics provided an update on ASHG activities. The Genetic Discrimination Act is of interest to ASHG, which remains hopeful that the legislation will be adopted. Francis Collins and David Valle have planned a special symposium for the upcoming national ASHG meeting. The ASHG-NHGRI Mentorship Network now numbers 900. It was suggested that educational materials from the projects like the CEGS could be useful for students in the network.
Dr. Guyer noted the items of interest in the Council folders. These included a summary of the BECON Symposium on Catalyzing Team Science. This symposium incorporated case studies, one of which was a genome center.
In February, there will be a discussion of the CEGS program. ENCODE will also be underway. Bill Gelbart suggested a discussion of the maintenance phase of all whole genome shotgun sequencing projects. A mechanism for periodic competition and evaluation of these projects may be useful. Evaluating assemblers and assemblies of these genomes is important.
Conflict of Interest
Dr. Guyer read the Conflict of Interest policy to Council and asked the members to sign the forms provided.
Review of Applications
In closed session, the Council reviewed 196 applications, totaling $311,452,472. The applications included 45 regular research grants, 16 pilot projects, 2 program projects, 26 ELSI grants, 63 responses to an RFA, 5 center grants, 5 conference grants, 1 research career development award, 2 continuing education training program grants, 19 SBIR Phase I, 2 SBIR Phase II, 6 fellowship grants, 3 STTR Phase I and 1 other. A total of 119 applications requesting $290,006,850 were recommended.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Last Reviewed: December 6, 2012