The open session of the National Advisory Council for Human Genome Research was convened for its thirty-ninth meeting at 8:39 a.m. on May 23, 2005 at the Fishers Lane Conference Center, Rockville, Md. Francis Collins, Director of the National Human Genome Research Institute, called the meeting to order.
The meeting was open to the public from 8:39 a.m. until 12:56 p.m. on May 23, 2005. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 12:56 p.m. on May 23, 2005 until adjournment for the review, discussion, and evaluation of grant applications.
Vicki Yates Brown
Alice Martin, ad hoc
Vence Bonham, OD
Joy Boyer, DER
Lisa Brooks, DER
Comfort Browne, DER
Cheryl Chick, DER
Monika Christman, DER
Francis Collins, OD
Karen DeLeon, OD
Tanya Dougans, DER
Elise Feingold, DER
Adam Felsenfeld, DER
Barbara Fuller, OD
Bettie Graham, DER
Alan Guttmacher, OD
Mark Guyer, DER
John Hodges Howell, DER
Rebecca Kolberg, OD
Laura Liefer, DER
Carson Loomis, DER
Jessica Melone, DER
Jean McEwen, DER
James McWilliams, DER
Patrick Nailer, DER
Ken Nakamura, DER
Vivian Ota Wang, DER
Brad Ozenberger, DER
Diane Patterson, DER
Allison Peck, DER
Rudy Pozzatti, DER
Eddie Rivera, OD
Jerry Roberts, DER
Jeff Schloss, DER
Pam Sellman, DER
Geoff Spencer, OD
Shundel Stephenson, DER
Gary Temple, DER
Larry Thompson, OD
Susan Vasquez, OD
Kris Wetterstrand, DER
Jonathan Witonsky, DER
Lynn Zacharia, DER
Diane Baker, Genetic Alliance
Joann Boughman, American Society of Human Genetics (liaison)
Linda Brady, NIMH, NIH
Andrew Feinberg, Institute of Genetic Medicine, Johns Hopkins University
Rodney Howell, American College of Medical Genetics (liaison)
Sharon Olsen, ISONG/Johns Hopkins University School of Nursing (liaison)
Ari Patrinos, Department of Energy
Susan Poland, Georgetown, Kennedy Institute of Ethics
Gene Russo, The Blue Sheet/Washington Fax
Sharon Terry, Genetic Alliance (liaison)
Wendy Uhlmann, National Society of Genetic Counselors (liaison)
Mark Guyer introduced Sharon Terry as the new liaison from the Genetic Alliance. Dr. Guyer also introduced new employees Carson Loomis, a DER Program Director, and Marina Amoroso, working in the Office of the Director. Dr. Guyer noted departing employees Michael Shi, a DER Program Director, and Shira Katseff and Jonathan Witonsky, two DER Program Analysts.
The minutes from the February 2005 Council meeting were approved as submitted.
The following dates were proposed for future meetings: September 12-13, 2005, February 13-14, 2005, May 22-23, 2006, September 11-12, 2006, and February 12-13, 2007.
Research!America recently announced that Mary Hendrix has been elected as a new member to their board.
Two researchers from the NHGRI Division of Intramural Research (DIR), Paul S. Meltzer, M.D., Ph.D. and Pu Paul Liu, M.D., Ph.D. were recently named as members of the Association of American Physicians (AAP) during the joint meeting of the Association of American Physicians and the American Society for Clinical Investigation.
The National Academy of Sciences announced newly elected members, several of whom are genome and genetics researchers and are, or have been, NHGRI grantees, advisors and/or reviewers. They are David C. Page, Mary-Claire King, Daniel L. Hartl, Steven Henikoff, Brigid L.M. Hogan, Christine E. Seidman, and Alec John Jeffreys.
UNC researchers Skip Bollenbacher, Caroline Seay, and Rich Beckman were announced as winners of the 2005 Pirelli INTERNETional Award for the group's Microarrays MediaBook. The animated MediaBook was picked as the best product of multimedia education.
The Center for Scientific Review (CSR), the division of NIH that carries out peer reviews, announced the appointment of Antonio Scarpa, M.D., Ph.D. as new director. Dr. Scarpa is currently professor and chair of the Department of Physiology and Biophysics at Case Western Reserve University.
Barbara Alving, M.D. will serve as Acting Director of the National Center for Research Resources (NCRR). Dr. Alving last served as the Deputy Director of the National Heart, Lung, and Blood Institute (NHLBI). Former NCRR director Judith Vaitukaitis, M.D. will serve as the Senior Advisor on Scientific Infrastructure and Resources to the NIH Director.
In response to conflicts of interest regarding NIH employees, the Interim Final Ethics Regulations in the Federal Register were made effective as of February 3, 2005. All outside activities with prohibited organizations, including pharmaceutical and biotechnology companies, grantee institutions, trade organizations, and consumer groups were to cease as of May 4, 2005. While it was critical to take steps to ensure that conflict of interest was not occurring, the new regulations are quite severe. All NIH employees would have to relinquish stock holdings above a de minimis amount in biotech or pharma, which could be a significant financial loss to those who would not be necessarily be viewed as in conflict. The regulations, in their current form, also prohibit intramural investigators from participating on a board or in a leadership position for not-for-profit organizations. It is expected, however, that revisions will come soon regarding divestiture and prohibition of NIH scientists from holding positions with non-profit organizations. In the meantime, there are high-level NIH scientists who have expressed discomfort with the new regulations and their impact on employees.
On April 29th, NIH issued the new "Policy on Enhancing Public Access to Archived Publications Resulting from NIH-Funded Research." The Policy requests and strongly encourages all NIH-funded investigators to make their peer-reviewed final manuscripts available to other researchers and the public at the NIH National Library of Medicine's PubMed Central immediately after the final date of journal publication. At the time of submission, authors are given the option to release their manuscripts at a later time, up to 12 months after the official date of final publication.
Applied Biosystems will deposit its sequence data from the human, mouse and rat genomes in GenBank, following the lead of the International Sequencing Consortium, which is a proponent of placing sequence information in the public domain according to the Bermuda Rules. The decision to release the information on July 1, 2005 will coincide with the expiration of subscriptions to Celera's database.
CNN has chosen the Human Genome Project as the number one medical story from the last 25 years.
As a component of a trans-NIH effort to apply the tools of genomics to the problem of sickle cell disease, RFA-HG-05-002, "Training in Genomics and Hemoglobinopathies," was issued to solicit applications to train experts in hemoglobinopathies in genomic science and methodologies. The application receipt date for this RFA is July 12, 2005.
Council member George Weinstock noted the opportunity for a connection between the ENCODE project and this initiative, as there are significant similarities between the two in terms of the kinds of technologies that will be needed for complete genomic analysis, the scale-up issues and the management demands. Sean Eddy mentioned the negative press coverage that this initiative has already received, including an article in the New York Times and one in Nature Biotechnology, neither of which accurately described the Hartwell-Lander report. Other Council members commented on the challenges associated with issues such as data transfer issues, information sharing, and reimbursement for diagnostic tests.
The next ENCODE Consortium meeting will be held in July. Immediately prior to the Consortium meeting, a "data fest" will be held, at which researchers from all of the groups participating in the ENCODE Project will jointly analyze the ENCODE datasets, interpret the results of the analyses, and identify gaps in the current strategies for determining the location of all functional elements in the human genome. For this purpose, an ENCODE Analysis Working Group has been formed, with five subgroups, each of which is focused on a different set of sequence elements. The five subgroups are Genes and Transcripts, Transcriptional Regulatory Elements, Chromatin and Chromosomes, Multi-species Sequence Analysis, and Sequence Variation. The results of the data fest will form the major agenda topic for the subsequent Consortium meeting, and will then comprise one of the major inputs into the NHGRI's assessment of the progress of the ENCODE pilot and to the Institute's decisions about whether the project is ready to scale to the entire human genome.
As of May 10, 2005, the MGC contained a non-redundant set of 12,424 human, 11,334 mouse, and 3,843 rat genes. The MGC infrastructure still supports the cloning and sequencing of Xenopus and zebrafish genes.
Mouse Transcriptome. Eleven NIH Institutes and Centers, led by NHGRI, funded a project to profile comprehensively the RNA content of 90 mouse tissues. The results have been deposited at the NCBI Gene Expression Omnibus (GEO) site (http://www.ncbi.nlm.nih.gov/projects/geo/info/mouse-trans.html), and on the Lynx/Solexa website (http://sgbpub.lynxgen.com). Analysis of the large amount of data generated is being performed by an international team.
National DNA Day. On April 25, 2005, "National DNA Day," teachers and students across the nation participated in the annual celebration of the genome, using educational tools provided by NHGRI. As part of the festivities, NHGRI hosted an on-line webcast/chatroom in which students were able to ask NHGRI researchers many questions of interest to them. DNA Day has been sponsored by NHGRI, ASHG, The Genetic Alliance, the National Society of Genetic Counselors (NSGC) and the Genetics Society of America (GSA). This year two new partnerships, with the National Science Teacher's Association and the National Association for Biology Teachers, were added. Another component of DNA Day was The Ambassador Program, in which 55 NHGRI Investigators visited 60 high schools throughout the month of April. 75% of schools visited this year were identified as 'outreach' schools. Another program, Teach the Teachers, involved 11 high school science teachers invited to the NIH to review DNA Day materials and provide feedback.
Family History Initiative. The agencies involved in the U.S. Surgeon General's Family History Initiative are making plans for National Family History Day on Thanksgiving Day, 2005. NHGRI is working with the Foundation for NIH to look at the possibility of raising funds for future family history activities.
Community Genetics Forum. Seattle, Washington was chosen as the first site outside of Bethesda to hold a Community Genetics Forum because of the very strong genomic presence and established outreach activities in that community. The event was very successful, with 340 people attending the Forum in April. A long list of follow-up activities is now being pursued.
NAS Committee on intellectual property. The National Academy of Sciences Committee on Intellectual Property Rights in Genomic and Protein-Related Inventions has been conducting a study funded by the NHGRI, NIGMS, NCI, NIDCR, and the NIH OD. The committee held its final meeting in April and is now attempting to finalize a report. There is apparently general agreement on a set of recommendations for the report and June review is anticipated. The review is scheduled to last six weeks, after which the report will be released to the NIH.
FY06 Appropriation. At the end of April, Congress passed its budget blueprint for FY06. This includes the Administration's FY06 request for NIH of $28.7 billion, which is an increase of less than one percent. The Senate Budget Committee had passed an amendment to its version of the budget that would have provided an additional $1.5 billion for the NIH, but that was not incorporated into the final budget resolution. This summer, the House and Senate Labor-HHS Appropriations Subcommittees will attempt to move the appropriations bill for the NIH. It is anticipated that the NIH will not receive funds beyond the President's budget.
NIH Reauthorization. The House Committee on Energy and Commerce has been drafting an NIH reauthorization bill over the past several months. The NIH has not been formally authorized by Congress since 1993, but since we are authorized to exist under the Public Health Service Act, yearly authorization is not required. Following a March 17th committee hearing at which Dr. Zerhouni testified, the committee staff identified three major areas to be considered for the legislation: 1) increasing the NIH Director's authority, 2) streamlining NIH reporting requirements, and 3) the development of a concept known as "budget clusters." The details on these items are not yet clear, but it has been suggested that NHGRI would be a part of a budget cluster with other "science-enabling institutes," such as NIGMS and NIBIB. The schedule for consideration of the reauthorization legislation is also unclear, and the level of interest in the Senate is unclear. The NIH is taking this effort seriously and responding to requests from committee staff. It is important to realize that, even if reauthorization legislation is not enacted, many of the issues raised in the process could be addressed in other ways. There are a few specific items that NHGRI would like to see covered in any NIH reauthorization bill, including updating of Title 42 and legislative authorization of the Institute.
Genetic Information Nondiscrimination Act. The U.S. Senate unanimously passed S. 306, the Genetic Information Nondiscrimination Act in February. While there is hope that this bill will pass in the House this year, no action is scheduled yet. The Coalition for Genetic Fairness, headed by Sharon Terry, has been working closely with the offices of Reps. Biggert, Ney, Slaughter and Eshoo (who introduced the bill) and they expect action this year. If the House were able to pass the bill, it is expected that the President would sign it. The Secretary's Advisory Committee on Genetics, Health and Society (SACGHS) has also been working to bring the new Secretary up to speed on this matter, in the hope of getting his support for the legislation.
PubChem. In 2004, as part of the NIH Roadmap Initiative to speed new medical treatments and improved health care to all Americans, the NIH launched a database called PubChem. PubChem is intended to be a new and comprehensive database of chemical structures and their biological activities, and will house both compound information from the scientific literature as well as screening and probe data from the NIH Roadmap's Molecular Libraries Initiative (MLI). The MLI is designed to bring chemistry into biomedical research on a large scale for the first time, with a focus on the identification of small molecules as new probes for biological investigations. PubChem is designed to provide access to basic information about a wide range of chemicals, and to seamlessly integrate this information with other databases and the biomedical literature. Hosted by the National Center for Biotechnology Information (NCBI), PubChem will link basic chemical information and the data generated by the MLI with the biomedical information about DNA sequence, genes, proteins, protein structures, and cellular pathways that is in other NCBI databases, such as GenBank, PubMed, GEO, OMIM, and others.
Recently, the American Chemical Society (ACS) expressed concern that PubChem is in direct competition with the ACS's Chemical Abstracts Service (CAS). While in NIH's view, the two databases are, in fact, complementary, ACS has called for significant limitations on PubChem. Discussions are on-going with the ACS and other relevant participants to find a resolution that would allow the scientific community to benefit from both data sources.
Secretary's Advisory Committee on Genetics, Health and Society (SACHGS). The SACGHS held its sixth meeting February 28th through March 1st. Topics included genetic discrimination, coverage and reimbursement, and a lengthy discussion of large population studies. While there was much discussion of large population studies to date, the committee did not yet agree on any recommendations in this area. The next meeting of the committee is June 15-16, 2005.
Dr. Ari Patrinos, the Associate Director of the Office of Biological and Environmental Research in the Office of Science at the Department of Energy, updated the Council on the DOE's genomics research program. The Community Sequencing Program received proposals for sequencing the genomes of 135 organisms; after peer review, the program is proceeding with the sequencing of the genomes of sorghum (related to biomass issues), monkeyflower (related to bioremediation) and a number of smaller genomes including those of some extremophiles and environmental communities.
Another area of competition was for the Genomes to Life (GTL) program, and announcements of awards are expected soon. There is a great deal of enthusiasm for the GTL program's emphasis on development of new facilities. A new announcement of a competition for a protein production facility will be issued shortly. DOE's interest is in the high-throughput production of microbial proteins, but the facility could be used for production of proteins from other sources as well.
Dr. Patrinos also noted that some concerns have been expressed about their synthetic biology biology program and stated that the DOE's ELSI will be expanding to include efforts addressing this area, as well as nanotechnology.
Finally, Dr. Patrinos mentioned the uncertainty about the future of the nuclear medicine program and the possibility of a joint DOE-NIH proposal to the National Academy of Science for a report on the future of this field.
As a result of a request from the Council for information about epigenetics and epigenomics, Dr. Andrew Feinberg from the Johns Hopkins University Center for Epigenetics of Common Human Disease, one of the Centers of Excellence in Genomic Science (CEGS), was invited for a presentation to review the field.
Epigenetics refers to the fact that DNA sequence alone does not define a cell and its function; additional, "epigenetic" information is also inherited during mitosis and possibly meiosis. Our understanding of epigenetics has dramatically changed over the last 20 years.
For example, it is now know that histone proteins interact with genomic DNA in organized structures known as nucleosomes, and that the acetylation, methylation, phosphorylation, and ubiquination of histones affect gene expression. Histone modification has been revealed as central to the regulation of transcription. In another epigenetics advance, genomic imprinting is now known to be linked to human disease. Loss of imprinting (LOI) of certain genes can be associated with increased risk of cancer. The common occurrence of LOI suggests that stringency of maintenance of epigenetic markers may be genetically determined.
The overall lessons of modern epigenetics are the specificity of chromatin biochemistry, the intimate link between epigenetic programming and the machinery of transcription, and the possibility that the epigenome may be a frequent environmental target in common disease. The integration of epigenetics and genome science is important. Tools for epigenotyping focus on DNA methylation, allele-specific expression, and histone modification. Alterations in epigenetic modification can be due to individual variation, tissue-specific variants, age-dependent variation, or heritable markers in a family. Quantitative epigenetics is used to test for epigenetic transmission in families or epigenotype-phenotype associations.
In summary, Dr. Feinberg argued that epigenomic biology and technology are not as arcane as was once thought. Understanding the epigenome has the potential for simplifying genetic analysis and understanding gene-environment interactions.
In the discussion, Council member Mary Hendrix asked about the prospect of pharmaco-epigenomics. Dr. Feinberg discussed a few possible applications in this area, for example looking at the epigenetic effects of a pharmacological agent.
Dr. Collins thanked Dr. Feinberg for an interesting and provocative presentation.
Lynn Zacharia presented a concept clearance for a cell repository RFP. An NHGRI-funded sample repository would make samples collected during NHGRI-sponsored projects, such as the HapMap and possibly medical sequencing efforts, available to the research community.
To date, samples obtained during the HapMap Project have been maintained at the Coriell Institute under the NIGMS Human Genetic Cell Repository contract; this was the NIGMS contribution to the HapMap Project. However, the HapMap Project's sample requirements have now exceeded the capacity of the NIGMS contract. Furthermore, support for the Community Advisory Groups that have been and will be established where HapMap samples were collected will require on-going, and perhaps expanded, interactions with the repository. There is also a need for more flexibility in administration of the samples. Thus, staff is proposing that NHGRI establish its own cell repository to meet the Institute's specific needs.
The cell repository would establish cell lines for new samples, maintain and distribute cell lines and DNA for all new and existing samples, maintain a database and an online catalog of samples, and establish and maintain community interactions with donor communities. HapMap samples stored in the cell repository would include the following collections, the Yoruba from Ibadan, Nigeria; Japanese from Tokyo, Japan; Han Chinese from Beijing, China; Luhya from Eldoret, Kenya; Metropolitan Chinese-Americans from Denver, CO; samples of Mexican origin from Los Angeles, CA; samples of African ancestry from the southwestern United States; Tuscans from Sesto, Italy; samples of Gujarati Indian ancestry from Houston, TX; and Maasai from Webuye, Kenya. The CEPH samples studied in the HapMap Project will remain under the NIGMS contract. In total, there will be 1,120 HapMap samples from 10 populations to start. One to four additional HapMap populations, as well as samples from 1,000 to 10,000 phenotyped individuals from sequencing studies, could also be included over the next five years.
The contract expenses will be the greatest during the first year due to costs associated with establishing the repository and sample collection. If the additional HapMap samples are collected, the cost will be $350,000 per population as these samples will have to be transformed into cell lines.
Council voted to approve the concept for the repository RFP.
Bradley Ozenberger presented an update on the status of the Molecular Libraries Initiative (MLI). One part of the initiative is designed to offer public sector biomedical researchers access to high-throughput screening of a large collection of small organic molecules based on investigator-submitted assays. The purpose of the program is to identify and develop compounds that can be used as experimental chemical probes to study the functions of genes, gene products, cellular pathways, and cells. It is hoped that his approach will provide researchers in the academic and public sectors with an approach to explore the functions of cells in human health and disease that is new to them, but currently available to many of their colleagues in the private sector. In addition to the screening component, the MLI includes a database (PubChem, see above) to collect and disseminate the information garnered in the Initiative, as well as technology development and cheminformatics programs in a number of relevant areas.
The MLI is overseen by the Molecular Libraries and Imaging Roadmap Implementation Group, which is co-chaired by three IC directors: Francis Collins of NHGRI, Tom Insel of NIMH, and Rod Pettigrew of NIBIB. Within the MLI, the Molecular Libraries Screening Centers Network (MLSCN), to be comprised of nine to ten centers, including the intramural NIH Chemical Genomics Center, will provide the high-throughput capacity for screening compounds and assays. Day-to-day management of the extramural centers will be provided by two program managers, Ingrid Li of NIMH and Carson Loomis of NHGRI, acting on behalf of the MLSCN Project Team which has membership from the large number of Institutes and Centers interested in the MLI.
NHGRI is the lead Institute for two of the technology development and cheminformatics programs within the MLI, Screening Instrumentation Technology Development and Exploratory Centers for Cheminformatics Research. Applications submitted in response to RFAs for these two programs are under review and will be reviewed by the Council at, or before, its September meeting.
There was no additional Council-initiated discussion.
Dr. Guyer read the Conflict of Interest policy to Council and asked the members to sign the forms provided.
In closed session, the Council reviewed 168 applications, requesting $54,810,517. The applications included 42 regular research grants, 10 pilot projects, 41 ELSI grants, 29 responses to RFAs, 1 center grant, 3 conference grants, 1 research career development award, 1 training grant, 1 continuing education training program, 19 SBIR Phase I grants, 6 SBIR Phase II grants, 4 fellowship grants, 3 STTR Phase I grants and 7 others. A total of 100 applications totaling $26,710,145 were recommended.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Date Mark Guyer, Ph.D.
National Advisory Council for Human Genome Research
Date Francis S. Collins, M.D., Ph.D.
National Advisory Council for Human Genome Research
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Last Reviewed: March 23, 2012