The National Advisory Council for Human Genome Research(NACHGR) was convened for its twenty-seventh meeting at 8:30 a.m. on September 13, 1999, at the Holiday Inn, 8777 Georgia Avenue, Silver Spring in the Lincoln Room. 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 12:15 p.m. on September 13. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 1:30 P.M. on September 13 until adjournment on September 14 for the review, discussion and evaluation of grant applications. (1)
H. Robert Horvitz
William Nelson, Ex officio member
* Via teleconferencing
Jane Ades, OD
Lisa Brooks, DER
Erin Burgess, OD
Jean Cahill, DER
Monika Christman, DER
Francis Collins, OD
Yasmin Cypel, DER
Adam Felsenfeld, DER
Elise Feingold, DER
Barbara Fuller, OD
Alan Guttmacher, OD
Mark Guyer, DER
Linda Hall, DER
Karen Hajos, OD
Craig Higgins, OD
Kathy Hudson, OD
Linda Jacobson, OD
Karin Jegalian, OD
Elke Jordan, OD
Charles Leasure, OD
Emily Linde, DER
Jean McEwen, DER
Monique Mansoura, OD
Ken Nakamura, DER
Diane Patterson, DER
Jerry Roberts, DER
Jeff Schloss, DER
Elizabeth Thomson, DER
Elsa Weinstein, OD
Kris Wetterstrand, DER
Cathy Yarbrough, OD
Robert Boyd, Knight Ridder
Cheryl Corsaro, CSR
Matthew Davis, Washington Fax
Machi Dilworth, National Science Foundation
Dan Drell, DOE
Rosalie Goldberg, National Society of Genetic Counselors
Richard Harris, National Public Radio
Kurt Hirschhorn, American College of Medical Genetics
Garric Hunter, NIH
Tom Hogan, Blue Sheet
Eliot Marshall, Science Magazine
Usha McFarling, Knight Ridder
Pam Moore, Capitol Publications
Rebekah Rasooly, NIDA
Grace Shen, NCI
James Shreeve (Freelance Science Writer)
Laurie Tompkins, NIGMS
Dr. Jordan introduced ad hoc council member Dr. Kim J. Nickerson, Program Officer with the Minority Fellowship Program of the American Psychological Association, and stated that Dr. William M. Gelbart, Professor, Department of Molecular and Cellular Biology at Harvard University who chaired the special emphasis panel that reviewed the mouse sequencing grants, would be in attendance during the closed session.
Dr. Jordan welcomed liaisons to the council from the professional societies: Ms. Rosalie Goldberg representing the National Society of Genetic Counselors and Dr. Kurt Hirschhorn representing the American College of Medical Genetics. The liaison from the American Society for Human Genetics, Dr. Ronald Worton of the Ottawa General Hospital Research Institute, was not in attendance.
Dr. Jordan also indicated that council member Dr. Jeanne Lawrence would participate by conference phone and that Dr. Colleen Scanlon was not in attendance.
Several new staff members were introduced to council. Ms. Cathy Yarbrough, Chief, Public Information and Communications Branch; Dr. Karin Jegalian, Science Writer within the Public Information and Communications Branch; and Dr. Jean McEwen, Program Director, Ethical Legal and Social Implication Team. Ms. Yasmin Cypel and Ms. Kris Wetterstrand were also introduced as two new program analysts in the Division of Extramural Research.
The minutes from the May 17-18, 1999, (NACHGR) meeting were approved as submitted.
The following dates were proposed for future meetings: February 28-29, 2000; May 22-23, 2000; September 11-12, 2000; February 12-13, 2001; May 21-22, 2001; and September 17-18, 2001.
Dr. Collins reiterated the introductions of Ms. Cathy Yarbrough and Dr. Karin Jegalian, who are joining the Public Information and Communications Branch within the Office of the Director. Cathy Yarbrough was formerly with the American Heart Association and will be involved in both extramural and intramural communication activities and Karin Jegalian was formerly with the Dallas Morning News and will be working as our new science writer.
Dr. Collins reported on four Trans-NIH Initiatives concerning genomics and genetics at the National Institutes of Health.
The Trans-NIH Mouse Genomics and Genetics Resources Coordinating Committee is responsible for developing NIH priorities for mouse genomics and genetics resources. Dr. Jordan and Dr. James Battey, director, National Institute on Deafness and Other Communication Disorders (NIDCD) are the co-chairs of the committee and have been very successful in coordinating this effort. The mouse initiative is supported by other institutes at NIH and is going extremely well. As part of the mouse initiative, an RFA has been issued to start mouse genome sequencing. The applications responding to this RFA were reviewed in the closed session of council. In addition, two RFAs for mutagenesis and phenotyping centers and four other more specific RFAs have been announced. More information can be found on the Web at www.nih.gov/science/models/mouse
The Trans-NIH Coordinating Committee for Non-mammalian Models is responsible for developing NIH priorities for genomic analysis of non-mammalian model organisms. This committee is co-chaired by Dr. Jordan and Dr. Marvin Cassman, director, National Institute of General Medical Sciences. This committee started meeting on a monthly basis in June 1999. The group is currently gathering information about funded projects across the world and developing plans for how to respond to recommendations. More information can be found on the Web at www.nih.gov/science/models/nmm and www.nih.gov/welcome/director/CCNMM.htm [no longer an active link]. Special thanks were given to Dr. Bettie Graham for coordinating the efforts to have both the mouse and non-mammalian organisms Web sites added to the NIH Director's Homepage.
The Full-length cDNA Initiative was established to develop a catalog of human and mouse full-length cDNAs and is under the leadership of Dr. Richard Klausner, director of the National Cancer Institute (NCI)and Dr. Francis Collins, director of NHGRI. An implementation working group, with membership of both intramural and extramural scientists, meets every Friday at 3:00 pm. The sequencing of full-length cDNAs will be conducted under a contract. A contract solicitation is to be released within the next few months. Financial contributions from 13 Institutes and Centers (IC) totaled $10M in FY 1999. An RFA on technology development has also been issued. Finally, an External Scientific Advisory Committee has been established and will be co-chaired by departing council member Dr. Barbara Wold.
The Biomedical Information Science and Technology Initiative (BISTI) is a trans-NIH effort formed at the request of Dr. Harold Varmus in response to the report prepared by the Advisory Committee to the Director, NIH Working Group on Biomedical Computing, co-chaired by Dr. David Botstein and Dr. Larry Smarr. This report contained a series of four major recommendations designed to boost the area of computational biology. The most visible recommendation was the first, which proposed that the NIH set up Centers of Excellence. As a follow-up to the report, Dr. Varmus appointed Drs. Collins, Klausner and Cassman to co-chair an NIH-wide implementation committee.
Dr. Maynard Olson expressed his concern about the overwhelming need for training. Dr. Jordan indicated that the NHGRI training grants focus on this area and that the National Institute of General Medical Sciences (NIGMS) has launched a pre-doctoral program.
Dr. Joel Buxbaum asked about the pace of implementation of the program. Dr. Collins responded that the number of senior leaders in computational genomics is small and there is not much funding in FY 2000. However, as the FY 2001 budget is developed, this area will be heavily featured; this will be the case for the National Science Foundation (NSF) as well.
Dr. Collins added that NHGRI staff is taking this matter very seriously. One approach is in-depth discussions with experts in the field. The staff had the first of these brainstorming session with Dr. Mark Boguski of the National Center for Biotechnology Information (NCBI). Dr. Williamson suggested that maybe one or two people from industry could come and speak to council on their view of this report.
Dr. Collins attended the NIH IC Director's Leadership Forum on September 7-8, 1999. The meeting focused on a number of issues, but particularly featured trans-NIH projects and how to fund and coordinate them.
Fifth International Sequencing Meeting, September 1-3, 1999
The most recent of the series of meetings to discuss and coordinate the international human genome sequencing effort took place September 1 at the Sanger Centre. Fifteen centers participated. In addition to the five largest sequencing centers, groups from France (1), Japan (2), Germany (3), and the United States (four additional centers) also participated. The meeting, which was co-sponsored by the NHGRI, the Wellcome Trust and the Department of Energy (DOE), went very well. Fourteen action items came out of the meeting, with the most important being a set of standards to be met in order to declare a chromosome finished. The next International meeting is scheduled for January 13, 2000, and will be hosted by the Joint Genome Institute in Walnut Creek, CA.
Current projections call for about 85 percent of the human sequence to be done by the five largest centers, the Joint Genome Institute, the Sanger Centre, the Whitehead Institute, Washington University and Baylor College of Medicine. The Principal Investigators (PI) of these centers meet every Friday by conference call and about every two months in a face-to-face meeting at one of the centers. The purpose of the frequent meetings is to forge these groups into an effective collaboration, and this seems to be coming along well, as the meetings discuss a wide variety of topics related to large-scale production sequencing. The working draft is expected by next spring. Dr. Collins noted that council member Dr. Waterston is a very involved participant in the collaboration.
As of September 3, 1999, GenBank reported the following numbers:
420,220 kb (13.1 percent) finished sequence.
328,281 kb (10.2 percent) working draft sequence.
748,501 kb (23.3 percent) total (including finished and working draft).
A meeting on SNPs was held June 7-8, 1999, in Bethesda. The meeting brought together PIs from the NIH grants funded under the SNP RFA with those supported by The SNP Consortium (TSC) to discuss coordination, SNP quality, resources and database. A summary of the meeting will be available on the Web within the next week or so.
Fifteen applications were received in response to the RFA on ELSI issues associated with studies of human variation. The applications will be reviewed in the fall and will be brought to the February council meeting.
The Center for Inherited Disease Research (CIDR) has been established for four years. Nine NIH institutes now support CIDR, with the recent addition of the National Institute on Aging. The Board of Governors recently agreed to a second five year contract period from FY 2002-FY 2006. A new funding structure will be implemented, with each of the participating institutes paying a small fixed annual fee based on its total budget and then being assessed a fee for each genotype completed for its grantees and intramural investigators.
Dr. Martha Krebs, Director of the Office of Science at the DOE visited the NIH. She discussed the progress of the Human Genome Project (HGP) with Drs. Varmus and Collins and was given a tour of the Division of Intramural Research (DIR) Program.
Dr. Collins announced the reorganization of the Office of the Clinical Director. Dr. Clair Francomano was appointed the new clinical director and Dr. Max Muenke took her place as the chief of the Medical Genetics Branch. NHGRI is currently interviewing candidates for the chief, Clinical Gene Therapy Branch and is searching to fill four tenure track positions.
The budget for FY 2000 is still under debate. Neither House nor Senate Committees have reported a Labor, Health and Human Services and Education Appropriations bill for FY 2000. Both subcommittees have been given allocations that are $10 to $14 billion less than last year. Resolution of appropriations for the next fiscal year will likely stretch into the fall.
On June 4, 1999, Secretary Shalala announced the appointment of the members of the Advisory Committee on Genetic Testing (SACGT). The committee is chaired by Edward McCabe, M.D., Ph.D. of the University of California in Los Angeles. This secretarial-level committee was created as a result of the Spence-Rothstein report and the report of the Task Force on Genetic Testing. Council member Dr. Wylie Burke plays a significant leadership role in this committee. The first meeting of the SACGT was held on June 30, 1999, at the NIH. U.S. Surgeon General Dr. David Satcher asked the SACGT to address four questions regarding the adequacy of governmental oversight of genetic tests and to gather public perspectives about the questions. A final report is due to Dr. Satcher on March 15, 2000. The next meeting of the SACGT is scheduled for October 25 and 26, 1999.
Privacy in Genetics Research
Seven medical record privacy bills have been introduced in Congress, three in the Senate and four in the House. At this time, none of these bills has been successful. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) called for the enactment of medical record privacy legislation by August 21, 1999. However, in the absence of such legislation, HIPAA called for the Secretary to promulgate regulations on the electronic transmission of medical records. Since Congress has not enacted medical record privacy legislation, the Secretary is currently working on these regulations. The Secretary's recommendations do not include specific recommendations for genetic information, but include genetic information under the term health information.
In September 1997, NHGRI co-sponsored a workshop with the National Action Plan on Breast Cancer regarding privacy in genetics research. Subsequently, Ms. Barbara Fuller and Dr. Kathy Hudson took the lead in writing an article with members of the workshop planning subcommittee. The article contains a series of recommendations to protect privacy in genetics research. This article, "Privacy in Genetics Research," was published in Science on August 27, 1999.
A meeting of GROW was held on August 17, 1999, organized by the National Coalition for Health Professional Education in Genetics and co-funded with the American Medical Association (AMA) and the American Nurses Association (ANA). This meeting enabled 27 organizations to get together and look at overlaps and gaps of information available on the World Wide Web. Thanks were given to Dr. Alan Guttmacher for his efforts in coordinating this meeting. The meeting was very productive and another gathering is scheduled in March 2000 at NIH.
Microarray Technology, Applications and Analysis Meeting is scheduled for September 22, 1999, in Scottsdale, Arizona. The meeting is sponsored by Nature Genetics and co-sponsored by NHGRI. It is modeled on previous workshops hosted by Dr. Pat Brown at Stanford University and Dr. Jeffrey Trent, NHGRI.
On November 12, 1999, NHGRI will hold the First Annual NHGRI Consumer Day, which will focus on policy, research and medical issues.
Dr. Collins recognized and presented certificates to departing council members Drs. David Cox, Babara Wold, and Richard Mathies who were in attendance for their last meeting. He expressed deep appreciation for their service and contributions to the success of the genome project.
Dr. Daniel Drell, Life Sciences Division, Office of Science at the Department of Energy (DOE) updated the Council on genome-related activities at DOE. Dr. Ari Patrinos sent his regrets for not being able to attend. Dr. Drell reported that DOE's genome sequencing effort is doing well. Most of the resources remain dedicated to the Joint Genome Institute (JGI), which expects to complete the draft sequence of the chromosomes 5, 16 and 19 by the spring of 2000, about 310 Mb in total. The JGI has 50 capillary sequencers currently in production, and an additional 34 are being installed. To date, they have produced 85 Mb of sequence of which 32 Mb are finished. Rick Myers and staff at the Stanford Human Genome Center have joined in collaboration with the JGI.
The Eighth DOE Genome Grantee Contractor meeting is scheduled for February 27 through March 2, 2000, in Santa Fe, NM. It was noted that this meeting coincides with the next NACHGR meeting.
Microbial sequencing continues to go well. The Institute for Genomic Research (TIGR) is expected to submit a manuscript soon to Science with the entire 3 Mb sequence of Deinococcus radiodurans with a simultaneous paper from Michael Day's group at USUHS describing the genetic transformation of D. radiodurans to acquire toluene degradation and mercury transformation capacities. They expect an additional eight to ten completed microbial genomes from TIGR and the JGI to be put into the public domain by the end of FY 2000.
On September 20, 1999, ERPEG meets to begin finalizing its report on the Ethical, Legal and Social Implications (ELSI) programs. On September 30 through October 1, 1999, a small brainstorming workshop will meet to discuss the future directions of DOE's ELSI program. DOE is looking forward to some participation by NHGRI ELSI staff.
Dr. Drell noted that DOE is in the same state of uncertainty regarding its budget as NIH and mentioned the possibility of a continuing resolution.
Dr. Gerald Rubin of the University of California, Berkeley, updated the council on the status of the Drosophila Genome Project, the effort to decode the sequence of the fruit fly. The Berkeley Drosophila Genome Project (BDGP) is a consortium of the Drosophila Genome Center (funded by the National Human Genome Research Institute, National Cancer Institute, and the Department of Energy), and the Howard Hughes Medical Institute (which funds the Rubin and Spradling laboratories). Information can be found on the BDGP Web site [fruitfly.org]. The BDGP signed a Memorandum of Understanding with Celera Genomics in January 1999 to collaborate on the completion of the fly genome. The BDGP has already completed and released 28 Mb of finished sequence, and as part of the collaboration will be producing a Bacterial Artificial Chromosome (BAC)-based genome physical map, and a 1-1.5X coverage scaffold sequence of the genome. Celera Genomics will produce 10X whole genome shotgun data, and according to the agreement will release all the data to the public database no later than the end of 1999; Dr Rubin will receive no Celera data until it is publicly available. Together they will then produce the finished sequence, an initial annotation and a joint publication.
Dr. Rubin discussed how the BDGP is constructing the BAC map by using STS content mapping. They will then confirm and define the BAC map by polytene chromosome in situ hybridization, overlap between draft sequence of BACs, and fingerprinting of a three-deep clone path.
Dr. Rubin gave a summary of clone-based genomic sequencing. The effort is split between the BDGP (Lawrence Berkeley National Laboratory and Baylor College of Medicine), and the European Drosophila Genome Project. The estimated size of the genomic sequence is 143 Mb. 29 Mb are at phase 3, and 76 Mb are at phase 1. 536 BACs have been sequenced, and 309 remain. In the next grant year the BDGP will finish assembly, undertake gap closure, resolve low quality regions, and produce an initial annotation.
Dr. Rubin described a table (located on the BDGP Web site) that lists the sequence similarities between human disease genes and Drosophila genes. Out of 104 human disease genes, 80 percent have Drosophila homologues.
In the past year, the BDGP invited the community to participate in an experiment to assess the "state of the art" of sequence annotation for long genomic sequences. The workshop was entitled: "The Challenge of Annotating a Complete Eukaryotic Genome: A Case Study in Drosophila melanogaster." Seventeen different groups participated.
Dr. Kucherlapati was interested in how the Drosophila community is taking advantage of the data produced. Dr. Rubin responded that the community is very quick to work on the genes and realize the power of having the genome sequenced. Dr. Cox applauded the rigor and vision of the BDGP to get the most reliable scientific answers.
Dr. Rubin also spoke briefly about the advantages of comparative sequencing for gene identification, annotation, and understanding regulatory sequences, citing studies on the apterous gene of Drosophila melangaster and Drosophila virilis as an example. Dr. Olson expressed the need for additional experimentation to address the degree of quality required from a comparative sequence to extract the optimum biological information.
Dr. Charkravarti asked Dr. Rubin to explain how the BDGP will use Celera's shotgun data. Drs. Horvitz and Olson were interested in the extent to which Celera was likely to use the already completed 29 Mb of public data in their own assembly, both in regard to the information available to Celera's customers and the information released to the public before the end of the year. Dr. Rubin indicated that 29 Mb is in GenBank, and that Celera will need to use it at least to decide which data to use in collaboration with the BDGP; Dr. Rubin also pointed out that the BDGP data are publicly available for anyone to use.
Dr. Burke asked if Celera was patenting genes and if that would restrict research. Dr. Rubin answered that 300 to 400 Drosophila genes are likely to be patented and he doesn't think that will affect academic research. Dr. Williamson added that it is hard to determine if this will affect industrial research.
Dr. Buxbaum asked if Dr. Rubin would work with another commercial entity again. Dr. Rubin replied that he would, as long as the data are available to the public. Dr. Rubin currently has a long-term relationship with Motorola, which has supplied some of the staff at his center. Dr Rubin added that companies have a lot of infrastructure that could be of use to the public effort, and we should take advantage of it.
Dr. Collins asked Dr. Rubin to summarize the repeat structure of Drosophila sequence, in relation to the question of the appropriate level of effort to devote to completely sequencing repeat regions. Dr. Rubin discussed the variation within some middle repetitive sequences, and the cost and benefits of careful annotation of repeat regions versus completely sequencing these regions.
At the close of the presentation, Dr. Rubin stated that, even with all the changes and uncertainties presented by events in the last year, the BDGP remains committed to attaining the goals as stated in the grant.
Dr. Collins thanked Dr. Rubin for his presentation to the Council.
Dr. Jordan noted the items of interest in the council folders, and referred council to material in Tabs "L through R."
Council members thought it might be useful to have a presentation on computational biology and a follow-up to the Botstein-Smarr recommendations. Dr. Olson recommended a discussion on NHGRI training efforts in computational biology and across the board. Council members would like to know what we are currently funding. Dr. Collins was open to suggestions as to who can present. Dr. Collins suggested Dr. Boguski or Drs. Botstein and Smarr would be good candidates to invite to present to council.
In closed session, the Council reviewed 85 applications, totaling $91,324,578. The applications included 23 regular research grants, four pilot projects, 23 ELSI grants, 16 in response to requests for application, two conference grants, four research career development awards, and 13 small business program grants, phase I. A total of 58 applications requesting $86,589,781 were recommended.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
 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: March 2006