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National Advisory Council for Human Genome Research
Summary of Meeting

Natcher Conference Center
Bethesda, Md.

May 19, 2003

The open session of the National Advisory Council for Human Genome Research was convened for its thirty-eighth meeting at 8:40 a.m.. on May 19, 2003 at the Natcher Conference Center, 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 8:40 a.m. until 1:00 p.m. on May 19, 2003. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 1:00 p.m. on May 19, 2003 until adjournment for the review, discussion and evaluation of grant applications.

Council members present:

David Burgess
Ronald Davis (by phone)
Beverly Gaines
William Gelbart
Mary Hendrix
Eric Juengst
Bronya Keats
Richard Myers
Kim Nickerson
Janet Rowley
Robert Tepper
George Weinstock

Council members absent:

Vicki Yates Brown
Richard Lifton
Tadataka Yamada

Ex Officio member absent:

Gerry Schellenberg

Staff from the National Human Genome Research Institute:

Jane Ades, OD
Chris Austin, OD
Vence Bonham, OD
Joy Boyer, DER
Lisa Brooks, DER
Jean Cahill, DER
Francis Collins, OD
Elise Feingold, DER
Adam Felsenfeld, DER
Peter Good, DER
Bettie Graham, DER
Eric Green, DIR
Alan Guttmacher, OD
Mark Guyer, DER
Linda Hall, DER
Rabiah Hendricks, DER
Lynette Jackson, DER
Linda Jacobson, DER
Jean Jenkins, OD
Sandra Kamholz, DER
Rebecca Kohlberg, OD
Tim Leshan, OD
Emily Linde, DER
Jean McEwen, DER
Ken Nakamura, DER
Ken Ow, OD
Diane Patterson, DER
Allison Peck, DER
Jane Peterson, DER
Jerry Roberts, DER
Laura Rodriguez, OD
Ellen Rolfes, OD
Jeff Schloss, DER
Erin Shannon, OD
Elizabeth Thomson, DER
Susan Vasquez, OD
Kris Wetterstrand, DER
Lynn Zacharia, DER

Others present for all or a portion of the meeting:

Wylie Burke (by phone), University of Washington
Jennifer Couzin, Science
Edward Kloza, National Society of Genetic Counselors
Natalie Ochs, The Blue Sheet
Sharon Olsen, International Society of Nurses in Genetics
Ari Patrinos, U.S. Department of Energy
Cara Schmitt, Epilepsy Foundation
Jane Silverthorne, National Science Foundation
Fred Walker, NHGRI Office of the Director
Michael Watson, American College of Medical Genetics

Introduction of Liaisons and New Employees

Mark Guyer introduced new council members: Mary Hendrix from the University of Iowa, Richard Myers from the Stanford University School of Medicine, Beverly Gaines from Beverly Gaines, M.D. & Associates, PSC and George Weinstock from the Baylor College of Medicine. Dr. Guyer welcomed liaisons from professional societies, Ed Kloza of the National Society of Genetic Counselors, Sharon Olsen of the International Society of Nurses in Genetics, and Michael Watson of the American College of Medical Genetics, as well as members of the press, Natalie Ochs of The Blue Sheet and Jennifer Couzin of Science.

Approval of Minutes

The minutes from the February 10-11, 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.

Director's Report

General Announcements

The National Academy of Sciences announced the election of 72 new members and eighteen foreign associates, on April 29, 2003. Among those elected who have had important interactions with NHGRI were David Lipman, Director of the National Center for Biotechnology Information (NCBI); Joseph Takahashi, Northwestern Univeristy, a member of the NHGRI Mouse Sequencing Liaison Group; and Janet Thornton, Director of the European Bioinformatics Institute (EBI).

Ira Herskowitz, a long-time friend of NHGRI and many Council members, passed away April 28, 2003 after a long battle with pancreatic cancer. His research interests included the control of gene expression in yeast, cell signaling, cell morphogenesis and growth control, and pharmacogenetics. Dr. Herskowitz was co-director of the program in human genetics in the School of Medicine at the University of California, San Francisco, where he was also a professor in the Department of Biochemistry and Biophysics.

The University of Washington received a $70 million gift from the Bill & Melinda Gates Foundation. $60 million of it will go toward construction of new research space for the School of Medicine and its Department of Genome Sciences, which is chaired by Robert Waterston, a former Council member.

On February 10, 2003, Raynard Kington was appointed Deputy Director of the NIH, the position formerly held by Ruth Kirschstein. Dr. Kington has served as Associate Director for Behavioral and Social Sciences Research, NIH and Director of the Office of Behavioral and Social Sciences Research, NIH since November 2000. He also serves as the chair of the NHGRI working group on race and genetics.

NIH director, Elias Zerhouni, has initiated the NIH "Roadmap," an effort to identify new and exciting areas of research of trans-NIH interest for support. Fourteen working groups were established as part of theRoadmap effort. Two co-chairs guide each working group; with the single exception of NHGRI's Jeff Schloss, all of the co-chairs are IC directors. Dr. Schloss is co-chairing the working group on Nanotechology (along with NEI Director Paul Seiving). Dr. Collins is co-chairing two other working groups, Building Blocks for Biology (along with NIA Director Richard Hodes) and Molecular Libraries" (along with NIMH Director Thomas Insel). Dr. Zerhouni and the IC Directors will discuss the working groups' recommendations at the NIH Budget Retreat on June 20.

Completion of the Human Genome Project

Many events took place to mark the completion of the Human Genome Project and the 50th anniversary of the publication of the structure of DNA, and, a number of statements and proclamations were issued on the occasion. President George Bush wrote a message to the International Human Genome Sequencing Consortium that expressed his strong commitment to medical research. A joint proclamation by the heads of state of six countries, the United States, the United Kingdom, Japan, France, Germany and China, celebrated the completion of sequencing the human genome. The U.S. Senate issued a resolution designating April 2003 as "Human Genome Month" and April 25, 2003 as "DNA Day". The House Energy and Commerce Committee passed H. Con. Res. 110 "Recognizing the sequencing of the human genome as one of the most significant scientific accomplishments of the past one hundred years and expressing support for the goals and ideals of Human Genome Month and DNA Day."

Another very successful component of the April activities involved science museums across the country. Thirty-one museums from twenty states received "DNA kits" developed by the Science Museum of Minnesota, the Association of Science and Technology Centers (ASTC) and the NHGRI. The kits were designed to be used in hands-on demonstrations and programming on the museum floor.

On Sunday, April 13, 2003 a reception took place at the Arts and Industries Museum at the Smithsonian. Guests previewed portions of the Pfizer exhibit, "Genome: The Secret of How Life Works," which will open to the public on June 7, 2003. Entertainment included singing, speeches and an interpretive dance about DNA.

A scientific symposium, "From Double Helix to Human Sequence - and Beyond," was held on April 14-15, 2003 at the NIH. The program of the two-day scientific symposium consisted of more than 35 presentations on the science and history of the Human Genome Project and the application of genomics to medicine. It also featured several videotaped interviews with notable figures in the history of molecular genetics and the HGP. All symposium attendees received a double DVD set containing the entirety of these interviews, developed in part by NHGRI's Larry Thompson, and a copy of the human sequence. The symposium was broadcast and webcast around the world. A press conference was held on Monday, April 14, 2003 at which the International Human Genome Sequencing Consortium announced the successful completion of the Human Genome Project. On Monday, April 14, 2003, a gala for 490 guests, sponsored by the Foundation for the NIH, was held at the Great Hall of the Library of Congress.

A public symposium, "Bringing the Genome to You," was held on April 15, 2003 at the Smithsonian's National Museum of Natural History. The half-day event, moderated by Robert Krulwich, featured presentations and dialogue on how genomics influences health and society. About 500 people attended and many more viewed the event via the web.

Also on April 15, a special program was videotaped for use on National DNA Day. The program featured James Watson and Francis Collins exploring the past, present, and future of DNA with a diverse group of high school students drawn from twelve schools in seven states and the District of Columbia. The video was entitled "DNA - The Next Generation."

In conjunction with the NHGRI-sponsored events, several other NIH institutes held several satellite symposia. The National Institute for Nursing Research held "Linking the Double Helix with Health: Genetics in Nursing" on April 13. The National Institute of Environmental Health Sciences sponsored "Genetic Variation and Gene X Environment Interactions in Human Health and Disease" on April 16. On the same day "Genes, Brain, Behavior: Before and Beyond Genomics," sponsored by the National Institute of Mental Health and others, took place.

On National DNA Day, April 25, 2003, scores of researchers and administrators returned to their hometown high schools as"DNA Day Ambassadors" to speak about the Human Genome Project; the NHGRI Division of Intramural Research sponsored the program. The NHGRI and the American Society for Human Genetics (ASHG) also encouraged the mentorship network, with over 800 volunteers, to participate in DNA Day. In its preliminary report, the ASHG noted that it had received 53 responses from mentors who participated in DNA Day in 26 different states.

Extraordinary efforts were made by many to organize these events, efforts that were led at the NHGRI by Alan Guttmacher, Deputy Director and Jane Peterson, Associate Director of Extramural Research.

The 50th Anniversary/HGP completion celebrations were not limited to the U.S. A major event took place in London and Cambridge, UK April 23-26, 2003. A symposium was also held in Japan, and HUGO held its 8th International meeting on the human genome on April 27-30, 2003 in Cancun, Mexico. Invited representatives from NHGRI attended each of those events.

Last, but by no means least, the celebrations of these past achievements were coupled with a forward look as NHGRI's new research plan, "A vision for the future of genomics research," was unveiled on April 24, when it was published in Nature (432 (6934): 835-857).

Recent Scientific Accomplishments and Issues

Sequencing Update

Sequencing has actively progressed for the human, mouse, rat, chicken, chimpanzee, Drosophila pseudoobscura, honey bee, Rhesus macaque, sea urchin, and several fungal genomes. An assembly of the initial draft of the chimpanzee genome sequence is currently being put together. At the September 2002 Council session, the bovine genome was designated high priority for sequencing. NHGRI has committed to fund half ($25 million) of the project contigent upon funds for the other half being found. The state of Texas is considering contributing up to $10 million. Australia and New Zealand hare committed to $1 million each. NHGRI is currently awaiting a response from USDA. The International Sequencing Consortium (ISC) will hold its second annual meeting on May 29th, during the Cold Spring Harbor Laboratory's "The Genome of Homo sapiens" meeting.

As discussed in the closed session of February 2003 Council, the sequencing of the pig (Sus scrofa) and the Rhesus macaque (Macaca mulatta) genomes were designated as high priority, and the amphioxus (Branchiostoma floridae), cat (Felis catus), and Trichoplax adhaerens (a lower metazoan) genomes were designated as moderate priority. In February 2003, NHGRI received four proposals for sequencing the genomes of five more organisms; the results of the GRASPP review of those proposals were discussed in closed session. Also received in February 2003 were four proposals for the construction of BAC libraries of the genomes of fifteen different organisms. In the BAC library construction program to date, 45 proposals for have been accorded either high or moderate priority. Twenty libraries have already been constructed and are now available. [On Wednesday, May 20, the day after the Council meeting, the priority rankings and the white paper proposals for the most recent submission were posted on the NHGRI web site. The following organisms were designated as high priority: Drosophila simulans, D. yakuba, Schmidtea mediterranea (a planarian worm); C. ramanei (a nematode worm) was designated as moderate priority).]

With the completion of the human sequence, NHGRI Staff believe that it is necessary to consider a resource (HumanBase) to link the human genome sequence to biology, in a way that such resources are provided by several of the model organism databases that NHGRI supports. To discuss this proposal, a workshop is being planned for the fall, 2003. Under the direction of Peter Good, NHGRI Program Director, participants in the workshop will be asked to discuss the need and requirements for this resource, including the important qualities of a model organism database; available sources of information about human sequence and biology; and the scope of such a proposed resource. It is anticipated that the output of the workshop will be used by NHGRI in developing a plan forward for establishing HumanBase.

Extramural Program

The ENCODE (Encyclopedia of DNA Elements) Project was launched on March 7, 2003, after the release of two RFAs on February 21, 2003. The first RFA calls for applications for the pilot project production effort and the second for applications for technology development projects. Approximately fifty applications have been received and will be reviewed this summer.

As of May 5, 2003, the Mammalian Gene Collection (MGC) contained a non-redundant set of 19,003 clones (11,179 human clones and 7,824 mouse clones). The collection continues to grow, although it is becoming increasingly difficult to find novel transcripts from the randomly generated cDNA library approach that has been followed to date. Therefore, the effort is switching to a directed strategy. Bob Strausberg, the former manager of MGC, recently left NIH; Elise Feingold, NHGRI Program Director, will provide interim leadership until a replacement project leader is named by the NCI.

5ELSI Program

The May issue of the American Journal of Medical Genetics is devoted to "Genetic Testing and the Family." This volume grew out of the January 2001 "A Decade of ELSI Research" conference. Eighteen manuscripts were received and ten of them were published.

Intramural Program

A press conference was held April 16, 2003 to announce that a team led by researchers in Dr. Collins' intramural laboratory, notably Dr. Maria Eriksson, has identified the mutation responsible for Hutchinson-Gilford progeria syndrome (HGPS), referred to as progeria. The research team also included scientists from the Progeria Research Foundation, the New York State Institute for Basic Research in Developmental Disabilities, the University of Michigan, and Brown University.

A team of researchers at NHGRI in Eric Green's lab and at NINDS has identified the gene responsible for two related, inherited neurological disorders, Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy (dSMA) type V. The gene, GARS (glycyl-tRNA synthetase gene) is located on chromosome 7.

Dr. Colleen McBride will join the NHGRI intramural program as a Branch Chief on October 1, 2003. Dr. McBride is a behavioral epidemiologist at the Duke University Comprehensive Cancer Center. Her research has been focused primarily on developing and evaluating population-based interventions directed at smoking cessation and identifying teachable moments for behavior change interventions.

Minority Outreach Initiatives

NHGRI senior staff are actively working to develop relationships and partnerships with minority institutions, professional associations, and community organizations. Many have traveled, or will travel, to speak with a variety of groups, among which have been: Alpha Omega Alpha Visiting Professor Morehouse School visit in Atlanta, GA on February 12, 2003; National Hispanic Medical Association Annual Meeting in Washington, D.C. on March 22, 2003; Student National Medical Association in Washington, D.C. on April 18, 2003; and the Indian Health Services Research Conference in Scottsdale, AZ on May 13, 2003. Staff also plan to attend the National Council of La Raza Roundtable - Genomics and the Latino Community -- in Austin, Texas on July 15, 2003. In an effort to improve the dialogue with the American Indian community, NHGRI invited several members to the NIH in March 2003 to discuss the Haplotype Map Project and other subjects. This discussion led to Dr. Collins' attendance at the very useful Scottsdale gathering in which 400 people participated. Subsequently, the Navajo community invited Dr. Collins to meet with their Internal Review Board this summer.

NHGRI has formed a new working group, the "Race and Genetics Working Group," to explore the relationship of race and genetics. The working group will also seek input from other NIH researchers and from the broader academic community. The working group, chaired by Raynard Kington, NIH Deputy Director, and co-chaired by Vence Bonham, NHGRI's Senior Consultant to the Director on Health Disparities, meets monthly. In a related event, a scientific meeting was held last week, organized by Howard University's Genome Center, to discuss race and genetics.

The NHGRI Minority Action Plan, which requires our large grants to have a training component that reaches out to members of underrepresented groups, is moving forward. The first meeting of the Plan's Research Training Advisory Committee will be held Friday, July 25, 2003. The members of the committee are: Bronya Keats, Kim Nickerson, Walter Bollenbacher, Shirley McBay, Richard Morimoto, Gayle Slaughter, and Merna Villarejo. The purpose of the meeting will be to review the training plans of grantees and to provide feedback to the institute on the early phase of the Action Plan. A second meeting of the committee is scheduled for October 21, 2003.

NHGRI will host a two and a half day meeting November 19-21, 2003, on new opportunities for research in sickle cell disease. Sir David Weatherall will chair the meeting. The meeting will discuss how researchers can use the tools of genomics to move treatment for sickle cell disease forward.

On March 24, 2003, NHGRI launched a Spanish version of the "Talking Glossary of Genetics" on the NHGRI website. The glossary is also available on CD-ROM.


Since the last Council meeting, Congress passed the FY2003 Appropriations bill for the Departments of Labor and Health and Human Services. The bill included $27.2 billion in NIH funding, $3.8 billion more than last year; this represented the largest program increase in the Labor-HHS Appropriations bill. With that increase, the five-year doubling of the NIH is essentially complete. For FY04, the President has proposed an overall NIH budget of $27.7 billion, including $478 million for the NHGRI. Accounting for changes in facilities funding, this would amount to a 4.4% increase in research support. Dr. Collins participated in the Senate and House Labor-HHS Appropriations Subcommittee NIH hearing, at which there was clear interest in the completion of the human genome sequence and the next steps for the NHGRI.

On May 22, 2003, the Health Subcommittee of the House Energy and Commerce Committee will hold a hearing on the future of genomics at the NIH. Dr. Collins will be the lead witness, along with Ari Patrinos of the DOE, Muin Khoury of the CDC, and Craig Venter of the Institute for Biological Alternatives. The subcommittee is conducting this hearing in order to gain insight into how the NIH as a whole is planning to coordinate its research portfolio in the field of genomics now that the human sequence is complete.

The Senate HELP committee is attempting to work out the differences between the genetic discrimination bill that Senator Tom Daschle introduced and the one introduced by Senator Olympia Snowe. On May 14, 2003, HELP Committee Chairman Judd Gregg brought the Snowe bill up before the committee and offered substitute language to the bill that reflected the compromises between the parties to date. The Committee expects to mark up the bill on May 21, 2003, after which it will be brought to the Senate floor. We hope the committee will be able to create a bipartisan bill. In the mean time, Rep. Louise Slaughter has reintroduced a version of Senator Daschle's bill in the House, where it was referred to the Energy and Commerce Committee. If the Congress were able to pass a bill this year, the President is on record as being supportive of such legislation.

Report from the Department of Energy (DOE)

Ari Patrinos reported on recent activities at the U.S. Department of Energy (DOE). He expressed his excitement regarding the April celebrations and reaffirmed his gratitude for the camaraderie with NHGRI during these events and over the years. Dr. Patrinos and Eddy Rubin, Director of the DOE's Joint Genome Institute (JGI), are moving aggressively forward in transforming the production genome center into a "scientific user facility". They have also issued their own call for "white papers", (which was published in the Federal Register) to propose organisms for the JGI to sequence and to help fill the JGI's sequencing pipeline until more permanent processes are in place.

The JGI is currently averaging 2 billion Q20 bases per month. The poplar (Populus) tree sequence will reach six-fold sequence coverage by July. This project is currently at two-fold sequence coverage. The Chlamydomonas reinhardtii, a single-celled chlorophyte, and Thalassiosira pseudonana, an ocean diatom, genome sequencing projects are currently at nine-fold sequence coverage respectively. The Xenopus tropicalis (frog) sequencing project is currently at two-fold sequence coverage and will reach six-fold sequence coverage by the end of the year. A description of the finished sequence of human chromosome 19 will be published by the end of July. Likewise, papers on the sequences of human chromosomes 5 and 16 will be published by the end of 2003.

Dr. Patrinos is also involved in the DOE's response to the country's high-end computing initiative. He is convinced that many biological applications will require this type of informatics capability before too long. He encouraged members of the life science community to become involved in this initiative and to make their needs known.

NHGRI Policy on Pre-Publication Data Release

In January 2003, the Wellcome Trust hosted a meeting in Fort Lauderdale to discuss issues surrounding pre-publication release of large-scale sequence data and whole genome assemblies. Participants in the meeting concurred with the policy of immediate release of sequence data and recommended extending the principles initially established at the 1996 Bermuda meeting to include assemblies. To address some of the complexities of a policy involving no restrictions on the use of pre-publication data, the Fort Lauderdale meeting introduced the concept of tripartite responsibility, in which data producers, funding agencies and users each have a responsibility to ensure the continued functioning of the system of rapid release of data coupled with appropriate recognition of the data producers' contributions. An update of the NHGRI institute policy on data release reflecting the outcomes of the meeting was discussed at the February Council meeting. The updated policy addresses only those large projects declared at the time of initiation by the Institute as community resources. As per the Council discussion, after the February meeting, the draft policy was posted on the NHGRI Web site for comment from the community. Dr. Guyer reported that very few comments were received. Two of the four responses were from the authors of a letter sent to Nature addressing this issue.

Dr. Patrinos reported that the DOE intends to harmonize its policy with that of the NHGRI. Consideration will need to be taken of the different circumstances that might apply to different organisms. Depending on genome size or other characteristics, some projects may be considered community resources, requiring immediate pre-publication data release, while others may not. For example, the DOE advisors recommended a policy that would allow up to a six-month delay in the release of sequence data for microbes below a certain size. The trans-agency microbe group is also considering this issue, but has yet to develop a policy. However, it is likely that certain projects, such as microbial sequencing projects, will need to be considered on a case-by-case basis. In addition, there will undoubtedly be unpredictable projects, such as Ciona savignyi, in which the high degree of polymorphism in the species makes assembly extremely difficult. While sequence traces have been available for some time from the C. savignyi project, the release of the assembly, which is of essentially two haplotypes and therefore difficult to complete, has been delayed.

After some discussion, Council members agreed to adopt the NHGRI policy as written.

Implementation of the New NHGRI Vision for Genomics

Mark Guyer provided a status report of the initial efforts at implementing the institute's new vision for the future of genomics research. He described how NHGRI is or could be involved in particular grand challenges and cross-cutting elements of the plan and will present to the Council, sometime in the future, a fiscal accounting of efforts in the different categories.

Floor 1 (Genomics to Biology: Elucidating the structure and function of genomes)
Grand Challenge I-1 (Comprehensively identify the structural and functional components encoded in the human genome). On-going or already initiated efforts include a comparative sequencing workshop in July, the renewal of the large-scale sequencing program, and the ENCODE RFAs for pilot projects and technology development. Potential new programs include model organisms parts lists, and extending the Mammalian Genome Collection (MGC) project to include alternatively spliced cDNAs and ORFs in expression vectors.

Grand Challenge I-2 (Elucidate the organization of genetic networks and protein pathways and establish how they contribute to cellular/organismal phenotypes). Projects under consideration are technology development and production efforts for gene expression, proteomics technology development, and pathways and networks research and technology development.

Grand Challenge I-3 (Develop a detailed understanding of the heritable variation in the human genome). The Haplotype Map project is well under way, while the "small-scale" variation projects in additional populations and technology development for comprehensive studies of sequence variation and genotype to phenotype correlation are under consideration.

Grand Challenge I-4 (Understand evolutionary variation across species and the mechanisms underlying it). The comparative sequencing program is particularly relevant to this area, and further technology development would be very useful.

Grand Challenge I-5 (Develop policy options that facilitate the widespread use of genome information in both research and clinical settings). New policies concerning release of different data types are being discussed, and the concept for an RFA to solicit research projects concerning intellectual property will be presented to the Council at its September meeting.

Floor 2 (Genomics to Health: Translating genome-based knowledge into health benefits)
This floor is probably the least well-developed component of the DER program at the moment. The NHGRI Division of Intramural Research (DIR) will undoubtedly play a large role in Floor 2. The development of an NIH effort in the area of chemical genomics was discussed separately on the Council agenda (see below).

Floor 3 (Genomics to Society: Promoting the use of genomics to maximize benefits and minimize harms)
Grand Challenge III-2 (Understand the relationships among genomics, race, and ethnicity, and the consequences of uncovering these relationships). As noted earlier, the NHGRI has organized a genetics and race working group. Similarly, many items mentioned previously in the Director's report are relevant to this grand challenge.

Grand Challenge III-3 (Understand the consequences of uncovering the genomic contributions to human traits and behaviors). This will be a major agenda item at the September meeting of the ELSI Research Advisors group (ERA).

Grand Challenge III-4 (Assess how to define the ethical boundaries for uses of genomics III-4). This topic is scheduled to be a major agenda item at the January ERA meeting.

Cross-cutting elements

  • Resources: genomic sequence production, cDNA generation, etc.
  • Technology development: numerous program announcements mentioned previously
  • Computational biology: development of HumanBase, new technologies and new ontologies
  • Training: minority action plan, new K23 program announcement
  • ELSI: ELSI centers of excellence
  • Education: ELSI education grants, NCHPEG

ERA Report

Wylie Burke reported on the April 15, 2003 of the ELSI Research Advisors (ERA). The committee discussed how the ELSI program needs to proceed in light of the outcome of the NHGRI planning process. ERA currently has ten members, including four new ones (Paul Miller, Scott Ramsey, Arti Rai and Sarah Tishkoff). The new membership reflects ERA's desire to represent new areas of research.

The current ELSI portfolio is strong in several areas, including support for a broad array of social science research, in-depth studies of certain topics, and studies in several other areas of high interest (patenting, insurance discrimination, use of race as a variable in research). However, there are also several areas of weaknesses: certain research areas are under- represented; there are few minority investigators; there is no "rapid-response" mechanism; and the impact of education projects has been limited.

ERA concluded that:

  • investigator-initiated research is key to maintaining quality and diversity of research projects,
  • RFAs are an effective mechanism for generating good research proposals and should be used more frequently,
  • in agreement with the conclusions of the planning process, in the area of education, the focus should be on support for education research projects, rather than educational programs and there should only be limited funding for maintenance of resources.

ERA also identified three areas for emphasis in the near term:

  • development of rapid response mechanisms,
  • use of existing resources to develop useful products,
  • development of more ELSI grant solicitations, specifically RFAs in specific topic areas and for an ELSI center grant program (see below).

Dr. Nickerson asked about the need for a standing review committee for ELSI applications. CSR and NHGRI staff are working to formally establish a committee in CSR. Such a group has been operating on an ad hoc basis. Council discussed the potential ramifications of the recent court activity regarding diversity criteria in university acceptance and the use of budget set-asides.

Concept Clearance - ELSI Centers

Elizabeth Thomson presented a concept for an initiative to create Centers of Excellence in ELSI Research (CEER). The purpose of the new program is to provide a mechanism to support researchers from a variety of disciplines to work together to address innovative ELSI topics. NHGRI plans to devote up to $3 million of its budget in FY2004. The RFA will be re-released as a program announcement about six months after the first grants are funded.

Dr. Nickerson suggested inviting people to think about how research is done by asking for projects addressing methodological challenges. Technology development should also be stressed. It needs to be made clear that the training component applies to both P20 and P50 mechanisms. NHGRI should consider adding language that encourages investigators to partner with minority institutions.

Dr. Juengst observed that centers could be foci for generating rapid responses to ELSI issues. Council agreed that groups addressing policy alone would not constitute a center, but that policy research could be a component of the center. Dr. Burgess encouraged NHGRI to make sure that there are sufficient funds in the P50 to create a pool of graduate students.

Council approved the concept with the aforementioned modifications.

Concept Clearance - Sequencing Technology Development

Jeff Schloss presented two concepts for basic sequencing technology development. It has not yet been decided if these announcements will be issued as PAs or RFAs. The grant mechanisms have also not been determined. Technologies covered by the initiatives include methods, technology, and hardware and software development.

The first concept paper was for a technology development effort for the '$1,000 genome', i.e. to reduce the cost of DNA sequencing by about five orders of magnitude. The objective is to achieve this milestone in about ten years. In order to achieve this goal, NHGRI needs to fund some risky projects. Two receipt dates are planned in the first year, and one in the following years. Applications from academia and the private sector are expected. Built into the management of the program are concrete milestones, grantee meetings, mechanisms for feasibility of phase-up and administrative site visits to assess progress. NHGRI will devote up to $6 million in the first year, with a maximum per year grant cost of about $2.5 million. NHGRI will be open to awarding grants for five years. The other second concept was to solicit applications for more near-term technology development to reduce sequencing costs by two to three orders of magnitude. This program will be managed more tightly. A number of research groups are already working on this problem.

Council cautioned that getting a good review of this potentially risky science might be difficult. Council recommended that NHGRI recruit reviewers from the user community, as well as the engineering community, and communicate the expectations of the program to the review committee. The approach to reviewing SBIR applications could be used as a model. Especially for the $1,000 genome initiative, exploratory approaches must be considered in order to advance the field. NHGRI should both instill confidence in potential applicants and educate reviewers on how to deal with the issue of risk. Five-year project periods will definitely be needed.

Council agreed that these programs are needed and approved the concepts.

Haplotype Map Project Update

Lisa Brooks presented an update of the Haplotype Map Project. A number of efforts are underway to obtain enough SNPs for the Project. In addition to utilizing the SNPs in dbSNP, additional whole genome shotgun re-sequencing reads are being generated at the Baylor College of Medicine Human Genome Sequencing Center and the Whitehead Institute/MIT Center for Genome Research. Those two groups, plus the Washington University Genome Sequencing Center will also be generating more sequence data using sorted chromosome libraries; this is being done to ensure that the same type of data are available for all human chromosomes as are now available for the chromosomes being genotyped by the Sanger Institute.

The samples to be genotyped for the large-scale component of the HapMap Project will come from four populations (Northern and Western European [taken from the CEPH collection], Japanese, Han Chinese and Yoruba). The CEPH samples are already available and community engagement and/or sample collection are under way for the other three.

There are several analysis groups collaborating on the development of the scientific strategy for the Project. The current plan is to genotype about 600,000 SNPs at five-kilobase spacing in each population. Additional SNPs will be added to fill out regions that do not coalesce int haplotype blocks after the first round of genotyping; ultimately, it is anticipated that about 500,000 "tag" SNPs will be identified that capture most of the common variation in the genome. There are eight genotyping groups, and among them they are using several different technologies. Each group will be assigned specific chromosomal regions and they will genotype all the samples in those regions.

Each population will have different levels of linkage disequilibrium, so the results of analysis of the inheritance pattern of the 500,000 SNPs will overlap, but be slightly different, between populations. The initial set of SNPs to be used will be double-hit SNPs (seen independently in two different samples) and need to have a minimum minor allele frequency of 5 percent

In addition to the large-scale genotyping efforts, small-scale projects are planned to be done with the following populations: Xhosa in South Africa; Luhya in Kenya; Gujarati in the United States, Italy, and Finland; African-American in Oklahoma; Mexican-American in California; Moroccan in Israel; Chinese in Colorado and others to be determined. The second strategy meeting for the International HapMap Project will be held next week at Cold Spring Harbor Laboratory.

Chemical Genomics

Chris Austin provided an overview of one way that NHGRI could play an important role in translational research, an important component of the recently developed research plan for the Institute and of the emerging NIH Roadmap. Based on discussions with both NIH and non-NIH scientists, he has developed a concept for how scientists might put together a tool box for assigning function to all the genes in the genome. It should demonstrate utility, be high throughput, flexible, beyond the reach of individual researchers, or be currently made or employed repetitively by multiple researchers. Some such tools are: the transcriptome reference set, knockout mice, cDNAs and small molecules/chemical genomics.

Dr. Austin outlined the pros and cons of small molecules as a research tool, and provided a list of small molecules and the functions they are known to play in gene function. A small molecule initiative is enabled by recent developments in biology and chemistry, such as the availability of targets, compounds and screening. NHGRI is not going to become a pharmaceutical producer, but NHGRI and public sector science can help accelerate the early phase of drug development by helping to develop a chemical genomics program. Needing to create a commercial product, as the pharmaceutical industry needs to do, would not restrict NHGRI's efforts.

Dr. Davis said that he would be strongly supportive of such an initiative. These compounds could be screened against a number assays and results stored in a common database. It would also be important to have access to these compounds and the compounds shold be well characterized and of high quality. Dr. Gelbart observed that the overall goal is the "functionation" of the genome. There are a number of ways to achieve this, such as approaches to target-specific tissues. Dr. Tepper suggested targeting some model pathways and model organism systems.

A chemical genomics effort relates to the NIH Roadmap groups that Dr. Collins is co-chairing. One possibility in the near term would be to set up a centralized screening facility, analogous to high throughput genotyping (CIDR) with support from multiple NIH institutes. NHGRI could also support a database of information about small molecules, standardize collections of compounds and support research into ways to improve combinatorial libraries. NHGRI expects to contribute to established programs, engage the enthusiasm of other NIH institutes in joint ventures and take a leadership role in targeting what approaches may be missing.

Announcements and Items of Interest

Dr. Guyer noted the items of interest in the Council folders.

Council-Initiated Discussion

The next session of Council, in September, will have a very full agenda. In light of this, no additional topics were suggested.

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 137 applications, totaling $50,753,580. The applications included 55 regular research grants, one response to a program announcement, nine pilot projects, one program project, 21 ELSI grants, three center grants, one conference grant, one research career development award, two training grants, one continuing education training program grant, 20 SBIR Phase I, five SBIR Phase II, five fellowship grants, four STTR Phase I and eight others. A total of 84 applications requesting $29,481,803 were recommended.

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

Date Mark Guyer, Ph.D.
Executive Secretary
National Advisory Council for Human Genome Research

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

Last updated: November 16, 2010