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National Advisory Council for Human Genome Research
Summary of Meeting
February 7, 2005
The open session of the National Advisory Council for Human Genome Research
was convened for its forty-third meeting at 8:35 a.m.. on February 7, 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 8:35 a.m. until 3:32 p.m. on February
7, 2005. In accordance with the provisions of Public Law 92-463, the meeting
was closed to the public from 3:32 p.m. on February 7, 2005 until adjournment
for the review, discussion, and evaluation of grant applications.
Council members present:
Marilyn Coors
Geoff Duyk, by phone
Sean Eddy
Beverly Gaines
William Gelbart
Eric Juengst
Bronya Keats
Jeffrey Murray
Richard Myers
Robert Tepper, by phone
George Weinstock
Tadataka Yamada
Council members absent:
David Burgess
Vicki Yates Brown
Mary Hendrix
Ex Officio member absent:
Gerry Schellenberg
Staff from the National Human Genome Research Institute:
Chris Austin, OD
Vence Bonham, OD
Joy Boyer, DER
Lisa Brooks, DER
Comfort Browne, DER
Brian Campbell, DER
Cheryl Chick, DER
Monika Christman, DER
Francis Collins, OD
Tanya Dougans, DER
Elise Feingold, DER
Adam Felsenfeld, DER
Peter Good, DER
Bettie Graham, DER
Alan Guttmacher, OD
Mark Guyer, DER
Linda Hall, DER
John Hodges Howell, DER
Jean Jenkins, OD
Shira Katseff, DER
Tim Leshan, OD
Laura Liefer, DER
Jean McEwen, DER
James McWilliams, DER
Jessica Melone, DER
Mark Moore, DER
Patrick Nailer, DER
Ken Nakamura, DER
Taiwo Oladapo, DEAS
Vivan Ota Wang, DER
Brad Ozenberger, DER
Allison Peck, DER
Jane Peterson, DER
David Rees, OD
Eddie Rivera, OD
Jerry Roberts, DER
Laura Rodriguez, OD
Jeff Schloss, DER
Michael Shi, DER
Shundel Stephenson, DEAS
Gary Temple, DER
Larry Thompson, OD
Elizabeth Thomson, DER
Susan Vasquez, OD
Fred Walker, OD
Kris Wetterstrand, DER
Diane Williams-Bey, DEAS
Jonathan Witonsky, DER
Lynn Zacharia, DER
Others present for all or a portion of the meeting:
Andrea Beckel-Mitchener, NIMH
Joann Boughman, American Society of Human Genetics
Ping Fan, CSR
Molly Laas, The Blue Sheet
Jose Ruiz, Office of the Director, NIH
Sharon Terry, Genetic Alliance
Wendy Uhlmann, National Society of Genetic Counselors
Introduction of Liaisons and New Employees
Mark Guyer introduced Sharon Terry from the Genetic Alliance, Joann Boughman
from the American Society of Human Genetics and Wendy Uhlmann from the National
Society of Genetic Counselors. Dr. Guyer also introduced Mark Moore, a contractor
working on a new project in DER, and Jose Ruiz from the NIH Director's office.
Approval of Minutes
The minutes from the September 2004 Council meeting were approved as submitted.
Future Meeting Dates
The following dates were proposed for future meetings: February 7-8, 2005,
May 23-24, 2005, September 12-13, 2005, February 12-14, 2005, May 22-23, 2006
and September 11-12, 2006, and February 12-13, 2007.
Director's Report
General Announcements
On January 26th, 2005, Mike Leavitt was confirmed as Secretary of Health and
Human Services, replacing former secretary Tommy Thompson. Mr. Leavitt has previously
served in the Federal Government as the Administrator of the Environmental Protection
Agency. Previously, he was the governor of Utah.
Maurice Wilkins passed away on October 5th, 2004 at the age of 88. Dr. Wilkins
shared the Nobel Prize with Jim Watson and Francis Crick in 1962. Maclyn McCarty
passed away on January 2nd, 2005 at the age of 93. Dr. McCarty worked with Oswald
Avery and Colin MacLeod in the 1940s on "the transforming principle,"
revolutionary research that proved that genes are made of DNA. Although their
research was never nominated for a Nobel Prize, without it, Watson and Crick
would likely not have divined the structure of the double helix. Another distinguished
figure in the field of evolutionary biology, Ernst Mayr, died at the age of
100.
On Monday October 24th, NIH announced the appointment of David A. Schwartz
as the new director of the National Institute of Environmental Health Sciences
(NIEHS) and the National Toxicology Program (NTP). Dr. Schwartz was previously
the director of the Pulmonary, Allergy, and Critical Care Division and Vice
Chair of Research in the Department of Medicine at Duke University, where he
played a principal role in developing three interdisciplinary Centers, in Environmental
Health Sciences, Environmental Genomics, and Environmental Asthma. Dr. Schwartz
replaces Kenneth Olden, Ph.D., who led NIEHS since 1991; Dr. Olden will remain
as a researcher in the NIEHS intramural program. Dr. Schwartz will join NIH
on April 4, 2005.
On February 1st, 2005, NIH announced the appointment of Elizabeth G. Nabel,
M.D as the new director of the National Heart, Lung, and Blood Institute (NHLBI).
Dr. Nabel, who most recently served as the Scientific Director of Clinical Research
in the NHLBI intramural program, began her appointment as director on February
1, 2005. She previously worked at the University of Michigan. Dr. Nabel's intramural
lab, which focuses on the development of novel genetic and cellular therapies
for cardiovascular disease, will be located in the Genome Technology Branch
of NHGRI.
On February 1st, Dr. Zerhouni announced a new supplemental ethics regulation
that will affect all NHGRI employees, which was drafted for NIH by the HHS Designated
Agency Ethics Official and the HHS Office of General Counsel. The new regulation
includes a moratorium on outside consulting with pharmaceutical and biotechnology
companies, restrictions on the receipt of awards, and restrictions and/or prohibitions
on the amount of stock individual employees may hold in pharmaceutical and biotechnology
companies. The new regulations are interim, with opportunity for reassessment
of their effects in one year. All intramural researchers have to terminate outside
positions within 30 days. All NIH staff must divest stocks to a $15,000 "de
minimus" level, and many holding senior positions must divest themselves
completely. This new policy could have a large effect on retaining and recruiting
intramural staff.
Rick Myers pointed out that most of the conflict of interest violations occurred
in clinical trial studies; however, NHGRI intramural scientists concentrate
mainly on basic science. There has been no distinction made between different
types of research for the new regulations. The Blue Ribbon Panel that was convened
to discuss the conflict of interest concerns concluded that many of the scientists'
relationships with industry were actually beneficial; however, there is much
concern in the Congress, the public, and the press about NIH scientists' behavior.
The regulations are stiff, but will likely not be changed soon.
On September 28th, NIH announced the first nine recipients of the NIH Director's
Pioneer Award, a central component of the NIH Roadmap for Medical Research.
The program is designed to support individual scientists and thinkers with highly
innovative ideas and approaches to contemporary challenges in biomedical research.
Each of the nine recipients will receive an award of $500,000 in direct costs
per year for five years. Among this year's recipients is Dr. Steven Quake, who
was supported by NHGRI with a FIRST (R29) award for new investigators in 1997
for his work in developing integrated nanofluidic chip systems and novel chemistry
for single molecule DNA sequencing. A result of that project is what appears
to be the first published report of single molecule DNA sequencing (Proceeds
of the National Academy of Sciences (PNAS) 2003. 100:3980).
The 2004 MacArthur Fellows program awardees included three genomic scientists:
Joseph DeRisi (Associate Professor of Biochemistry and Biophysics, UCSF), Vamsi
Mootha (Assistant Professor of Systems Biology, Harvard Medical School), and
Daphne Koller (Associate Professor of Computer Science, Stanford University).
Alan Guttmacher (Deputy Director, NHGRI) and Robert Nussbaum (Senior Investigator
and Chief Genetic Disease Research Branch, Inherited Disease Branch, NHGRI)
were elected to the Institute of Medicine this past October.
Dr. Collins attended the World Economic Forum annual meeting in Davos, Switzerland
January 26th to 30th, 2005. Dr. Collins is a member of the organizing committee
for scientific aspects of this meeting. This year, there was a strong focus
on the developed world assisting the undeveloped world. Global warming, biodefense,
AIDS, malaria, and TB were discussed in the scientific sessions. The representation
of scientists was not as strong as it might have been, given the elevated place
of science in the discussion.
Peter H. Byers is the new president of the American Society of Human Genetics.
Dr. Byers is Professor of Pathology and of Medicine and Adjunct Professor of
Genome Sciences at the University of Washington in Seattle, WA. Dr. Byers met
with senior NHGRI staff on January 11th, 2005. The cordial and productive working
relationship between ASHG and NHGRI will continue.
New NHGRI Initiatives
Several new NHGRI initiatives have been released. One of these, the K23 training
solicitation with Emphasis on Therapeutic Interventions Employing Genomic or
Proteomic Technologies, is a patient-oriented research career development award
to promote adequate mentoring with regards to clinical and basic science research.
Another new initiative, Molecular Screening Assay Development for Sickle Cell
Disease (RFA-HG-05-001), encourages the development of assays that will be appropriate
for screening by the NIH Roadmap Molecular Libraries Screening Centers Network
initiative. There was also an RFP released for mouse knockouts. This is an effort
by the NIH to procure mouse knockout strains that have been generated and phenotyped;
awards will be made by April or May.
Recent Scientific Accomplishments and Issues
NHGRI - Extramural Program
Sequencing. In October 2004, the International Human Genome Sequencing Consortium
published a paper describing the high quality finished human genome sequence
that was completed in April 2003. The finished sequence now covers more than
99 percent of the euchromatic (or gene-containing) portion of the human genome
and was sequenced to an accuracy of 99.999 percent. The number of human protein-coding
genes is now estimated at 20,000-25,000.
Two sets of new awards in the area of sequencing technology development were
funded since the last Council meeting. Under the "$100,000 genome"
program, ten awards were made that will support research to develop new technologies
to lower dramatically the cost of DNA sequencing. Some of the awards will be
directed at the development of full sequencing systems, while others will focus
on novel components or improvements for existing systems. Under the "$1,000
genome" program, four feasibility projects were funded to test new fabrication
and detection methods. In combination with similar grants awarded earlier in
the year, NHGRI made a total of twenty awards for sequencing technology development
in FY 2004, for a total of a $32 million investment in the $100,000 genome goal
and a $6.5 million investment in the $1,000 genome goal over the lifetime of
the grants. More applications submitted in response to these RFAs will be discussed
at the May council meeting.
The status of organisms in the NHGRI-funded pipeline was detailed in a handout.
A 3.3-fold coverage draft of the bovine genome was assembled in October 2004
and a first analysis of the chicken genome (6.6-fold draft) was published in
December 2004. The Mouse Genome Sequencing Consortium is on schedule to finish
the mouse genome sequence by the end of calendar 2005.
The NHGRI Division of Extramural Research is examining the possibility of a
human "medical sequencing" program. The Institute organized a workshop
on January 5-6, 2005 to discuss a proposal for a pilot project to collect sequence
information from a large number of individuals, as the tool of large-scale sequencing
transitions from basic applications to clinical applications. Several protocols
for a pilot study were discussed, including targeted resequencing and whole
genome shotgun sequencing; collection of samples from unidentified individuals
(e.g., HapMap samples) or individuals with known (medical) phenotypes; and disease-related
phenotypes including common diseases, reproductive lethals, and rare recessives.
Many questions, in both scientific and ELSI areas, remain after the workshop.
NHGRI staff has formulated a plan, involving the organization of a Medical Sequencing
Working Group, to pursue these issues.
Dr. Myers asked about the technology discussion at the January meeting. New,
potentially disruptive technologies were discussed. There are several that are
currently under development, both in the academic sector with NHGRI funding
and in the private sector. None of them are available yet, but some people are
confident that they will soon be. A major question that the NHGRI is trying
to address as it plans the future direction of the sequencing program is how
can we design a future for the program that both generates important biological
data and drives the technology forward in an effective way. Staff noted that
another aspect of the Institute's planning activities for the sequencing program
was to obtain proposals from each of the large-scale sequencing centers for
how they would spend 10% of their budget on medical resequencing over the next
eighteen months. These proposals were reviewed during the administrative site
visits carried out last autumn, and the results will be discussed with Council
in the closed session.
International HapMap Project
A press release entitled "International HapMap Consortium Expands Mapping
Effort" was distributed to the Council. Phase 1 of the HapMap (analysis of
the samples from the Yoruba, Han Chinese, Japanese, and CEPH populations) will
be finished this month, in February 2005. Phase 2 will involve the low-cost (=
one cent per genotype) genotyping of an additional 3 million SNPs, thereby greatly
enriching the HapMap; the final HapMap will consist of 4.7M SNPs, or one SNP every
600 bases on average. The Phase II genotyping will be done by Perlegen with support
of an NHGRI grant. See below for a fuller description of the status of the HapMap
project.
ENCODE
NHGRI awarded six new grants for ENCODE technology development in September
2004. A project description paper about the ENCODE project was published on
October 22, 2004 in the "Genes in Action" issue of Science. The ENCODE
Consortium has established an Analysis Working group, to be led by Ewan Birney.
The third Consortium meeting was held on November 10th and 11th, 2004, in Cold
Spring Harbor, NY. The next Consortium meeting is scheduled for July 15th through
19th, 2005 in Rockville, MD. The July meeting will be preceded by a "data
fest" that will be organized by the Analysis Working group to carry out
the first detailed analysis of existing ENCODE data across the entire project.
At the meeting that follows, the results of this analysis will be the basis
of a discussion of the status of the project and the issues that need to be
addressed in order for the NHGRI to consider scaling up the ENCODE effort to
the entire human genome.
Mammalian Gene Collection
The human, mouse, and rat components of the Mammalian Gene Collection project,
as well as the associated xenopus and zebrafish projects continue to progress
according to schedule. A manuscript summarizing the status of the MGC was published
in Genome Research in October, 2004. See below for a fuller description of the
status of the MGC.
Mouse Transcriptome
In October 2003, 11 NIH Institutes and Centers, led by NHGRI, funded a comprehensive
mouse reference transcriptome project. The aim of this effort was to profile
the transcriptomes (all mRNAs) of 90 mouse tissues using the Massively Parallel
Signature Sequencing (MPSS) technology. The tissue collection is now complete,
and MPSS on 50 of the tissues have been completed so far. Results for these
tissues have been deposited at the NCBI Gene Expression Omnibus (GEO) site,
http://www.ncbi.nlm.nih.gov/projects/geo/info/mouse-trans.html. A temporary
project website also resides at NCBI (http://www.ncbi.nlm.nih.gov/genome/guide/mouse/MouseTranscriptome.html),
and a more comprehensive project website is under construction. A paper describing
the project and initial conclusions from the data will be submitted for publication
within the next month.
Centers of Excellence in ELSI Research (CEERs)
The first meeting of the Centers of Excellence in ELSI Research (CEERs) investigators
was held in Bethesda on February 3rd and 4th, 2005. The investigators had an
opportunity to learn about activities going on in each center and to discuss
how they might collaborate with each other. Other discussion topics included
how the investigators at the CEERs would interact with other ELSI research activities
and with other NHGRI program activities, including the CEGS program; evaluation
strategies; and the way in which CEERs could potentially help NHGRI to inform
policy decisions.
NHGRI - Intramural Program
On November 10th 2005, NHGRI announced that Dr. Elaine Ostrander had joined
NHGRI as the new chief of the Cancer Genetics Branch. Dr. Ostrander came to
NHGRI from the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, where
for more than a decade her laboratory has been a leader in mapping genes responsible
for cancer susceptibility in dogs and humans.
NHGRI is pleased to welcome Dr. Laura Elnitski to the DIR Genome Technology
Branch. Dr. Elnitski joins DIR from the Departments of Biology and Computer
Science at Penn State University. Dr. Elnitski is a molecular and computational
biologist who uses experimental and bioinformatic methods to discover non-coding
functional elements in the human genome. In the last 2 years, the intramural
program has hired seven tenured investigators, all of whom are women.
NHGRI Office of the Director
Family History Initiative
The U.S. Surgeon General's Family History Initiative was launched on November
8, 2004 to increase awareness about the importance of family history in health,
provide tools for communication and evaluation, and increase genomics and health
literacy for the American public and their health professionals. A web-based
and print tool entitled "My Family Health Portrait" was developed
in both English and Spanish to facilitate collection of family history data.
The goal was to have Family History Day commence on Thanksgiving, since families
traditionally gather together on this day. The event will continue annually
in the future. The Office of the Surgeon General, the National Institutes of
Health (NIH, NHGRI), the Centers for Disease Control and Prevention (CDC), the
Agency for Healthcare Research and Quality (AHRQ), and the Health Resources
and Services Administration (HRSA) contributed to the initiative.
DNA Day
National DNA Day commemorates the completion of the Human Genome Project and
the discovery of DNA's double helix in 1953. In its third year, the celebration
includes an Ambassador program, in which NHGRI investigators, pre- and post-doctoral
fellows and staff travel to high schools around the country to excite students
about the field of genomics. This year, there will be a focus on establishing
relationships with outreach schools. There will also be a webcast featuring
NHGRI intramural researchers lecturing to high school students, and a chatroom
with students. NHGRI will also hold a conference in March to provide a group
of teachers in the Washington D.C. area with DNA Day resources and information.
NHGRI partners with the American Society of Human Genetics in this effort.
NHGRI - Policy
The National Academy of Sciences Committee on Intellectual Property Rights
in Genomic and Protein-Related Inventions, a study funded by NHGRI, NIGMS, NCI,
NIDCR and the NIH OD held an international meeting in December in Bellagio,
Italy. The purpose of the meeting was to learn more about how European and Japanese
governments handle IP issues related to genetic and proteomic inventions. Tim
Leshan, Chief of the Policy and Program Analysis Branch, attended the meeting
as the NIH liaison. The meeting focused heavily on science, and the impact of
patenting on protein research and genomics was detailed.
The FY 2005 Labor Health & Human Services and Education Appropriations
bill, which includes NIH funding, was incorporated in an omnibus appropriations
bill that was finally passed in December. The conference agreement appropriates
$28.371 billion for NIH, an increase of $571 million (2.1%) over the FY 2004
level. The increase was offset in part by an across-the-board cut of 0.80 percent
in all non-defense and non-homeland security spending. The NHGRI received $492
million minus the 0.8% cut for a total of $488 million. The President will present
his FY 06 budget today. It is expected to be a flat budget for domestic discretionary
programs, and the Congress is expected to concur.
There are now two new Appropriations Committee Chairmen, Senator Thad Cochran
(R-MS) and Representative Jerald Lewis (R-CA). Both have said they want to pass
the appropriations bills as soon as possible after the passage of the budget
resolution. The Labor HHS Appropriations subcommittee chairmen, Senator Arlen
Specter (R-PA) and Representative Ralph Regula (R-OH), will remain in place.
The Genetic Information Nondiscrimination Act of 2003 (S. 1053), passed by
the Senate, was not taken up in the House last year. The Subcommittee on Employer
and Employee Relations of the Committee on Education and the Workforce held
a hearing on the subject, as well as the Secretary's Advisory Committee on Genetics
Health and Society (SACGHS). The SACGHS will follow-up with a report to Mike
Leavitt, the new Secretary of HHS, on the subject. This issue remains a priority
for NHGRI and we will continue to work on it with the new Congress. The new
Chairman of the Senate Committee on Health, Education, Labor and Pensions (HELP),
Michael Enzi (R-WY), has put S. 1053 back on the committee's agenda. He would
like to pass the same bill early in the session and it will be marked up in
committee this week. In the House, objections have been raised by the insurance
industry and the Chamber of Commerce.
The Secretary's Advisory Committee on Genetics, Health and Society (SACGHS)
held its fifth meeting October 18th-19th, 2005. Discussions included the importance
of family history in health, coverage and reimbursement, and a discussion of
plans for addressing large population studies and pharmacogenomics. The committee
also heard testimony about and discussed the issue of genetic discrimination.
Its next meeting is Feb. 28 - March 1, 2005. The possibility of a U.S.-based
large population study will be discussed at that next meeting. While a U.S.
study of this type has not yet received funding, there are ongoing analogous
efforts in the U.K. (BioBank), Japan, and Estonia.
Centers of Excellence in Genomic Sciences (CEGS)
The Centers of Excellence in Genomic Sciences (CEGS) program was formulated
in 2000 and 2001 to identify promote new areas of innovative genomics research.
This preceded the planning process for the 2003 Vision statement. CEGS grants
are intended to be for highly innovative efforts to develop new concepts, methods,
technologies, or ways to analyze data, and to advance the state of the art for
investigating genomic approaches to biological problems in a substantial way.
Tightly focused teams, synergy, and integration are key for this program, as
is training to increase the pool of professional genomics scientists and engineers,
and to ameliorate the shortage of genomics professionals from underrepresented
minority communities.
The CEGS program announcement (PA) was released in 2000. To date, forty-one
P50 (center) grant applications have been received and six P20 (planning grant)
applications have been received, but none have been funded. Nine CEGS awards
have been made, and information about the centers is available on the NHGRI
website. NIMH, which joined the original program announcement, has co-funded
two CEGS; one to Johns Hopkins University and one to Columbia University.
The CEGS PA has since expired. NHGRI has been conducting a variety of assessments
as part of its consideration of the program's future, including administrative
site visits to the first three CEGS that were funded (specifics of which will
be discussed in the Closed Session). The discussions have focused on CEGS program
quality, program consistency with the NHGRI Vision statement of 2003, program
objectives consistent with NHGRI objectives, and priority in the NHGRI portfolio.
Staff has concluded that CEGS have increased the visibility of genomics at institutions,
created genomic infrastructure and training opportunities, assembled good groups
of scientists, and approached problems that have been inaccessible through traditional
grant mechanisms. This is a mechanism to accomplish things that could not be
done with standard grants. The subject was put on the agenda of this meeting
to afford Council an opportunity to review Staff's findings and conclusions.
In a lively discussion, Council members made a number of points about the
CEGS program and the CEGS grants:
- The CEGS program echoes the goals of the Roadmap by creating interdisciplinary
research; it may take several years to gauge the success of the centers, as
they take a long time to get going.
- The CEGS are productive, innovative projects that take us in new directions
that would have been difficult without the mechanism.
- CEGS drive technology, with the emphasis on leveraging technology to create
new abilities and bringing projects together to achieve greater things than
normal grants can achieve.
- CEGS have stimulated the use of genomic information by people that would
normally not be working in the area, e.g. engineers have been brought into
biology.
- It can be a challenge for the CEGS to keep up with their success, and it
is difficult to gauge progress in the CEGS program.
- A high level of innovation must be maintained for researchers to join the
CEGS program. This criterion will ensure that the funding level of the program
doesn't exceed $30 million.
- The CEGS can bring minorities into genomics research in new and important
ways.
- CEGS provide a critical investment in new technology. There is a high price
tag for the program because the CEGS are a long-term investment and long-term
follow-through with the individual grants is required.
- There is synergism between and among the CEGS, and they are talking and
learning from one another. The grantee meetings aid in collaborations between
the CEGS.
- The second grantee meeting showed considerable progress when compared to
the first meeting.
Council members also noted a number of issues for Staff to consider in developing
the CEGS program further:
- The site visits have been focusing upon where the centers are in their
development and whether or not they are still on the cutting edge of the research,
recognizing that the CEGS program was designed to support centers for up to
10 years.
- Some CEGS might lose their innovative position or innovation might come
in smaller steps; these CEGS might need to be eliminated if they cannot keep
up.
- Technology distribution is also important.
- There are surely new technologies and new efforts that can benefit from
the CEGS approach; the portfolio might need to be balanced further.
- It is not sufficient for a CEGS merely to stay on the track that was laid
out at the beginning of the award. Something that was very innovative when
a grant was written may not be innovative today.
- Some of the centers might eventually switch to a focus on data collection,
but in doing so would become something other than a CEGS.
- NHGRI should continue to explore the development of new mechanisms to support
specific Institute objectives other than the R01.
In summary, the general consensus of the council was that the CEGS program
should be continued. At the May and September Council meetings, there will be
broader discussion of funding the CEGS program in the context of other NHGRI
initiatives.
Minority Action Plan (MAP)
The main goal of the NHGRI's Minority Action Plan (MAP) is to increase the
number of underrepresented minority investigators in scientific and ELSI research.
The MAP opportunities have been incorporated into all of NHGRI programs, including
those in the DER, DIR, and OD, and must be available at all career levels. Programs
must be anchored in institutions involved in genomics and ELSI research, have
achievable goals, and undergo review. There are several components, including
research training, research collaborations, education, outreach, communications,
and partnerships with other institutes.
The MAP was begun in 2001, when Council approved the plan. With respect to
the DER component, the first supplement requests were received in March 2002,
and the first awards were made in September of that year.
MAP program requirements have been tailored for different types of grants.
Training grants are required to have 10% of trainees from Underrepresented Minorities
(URM) within the next 3 years. CEGS are also required to have 10% URM. The data
production centers and databases are encouraged to recruit, foster, and guide
employees to enhance their research careers, starting at the technician level.
In the overall DER MAP, supported activities range from K-12 to faculty-level
programs. Many of the activities are focused on undergraduates. The total investment
is currently $4.7 million. There are currently 11 active T32 NHGRI training
grants. The numbers of URM are increasing, and we are working with those T32
grants that are not faring as well. According to a recent review by the MAP
Advisors, 50% of programs have been successfully implemented, 20% are doing
fine but need monitoring, and 20% need to be closely monitored.
A number of lessons have already been learned, as described at a MAP grantees
meeting last fall and summarized by the MAP Advisors:
- Grantees should recruit within their own institutions.
- Students should be taught to network and encouraged to recruit friends.
To facilitate networking, an MAP web site should be constructed.
- A coordinating center could also help to facilitate networking, tracking,
and program evaluation.
- The number of undergraduate students, graduate students, and postdoctoral
fellows should be increased.
- NHGRI should better articulate the expected goals and outcomes to grantees.
Evaluation is an important component of the MAP. Evaluation plans for individual
programs and the overall MAP program should be developed and implemented.
- The level of MAP participation appropriate for non-academic institutions
should be reconsidered. Many non-academic institutions lack the infrastructure
necessary for these efforts.
In the ensuing discussion, the Council members made a number of points:
- The Council is pleased with the progress of the Minority Action Plan to
date.
- There was some concern about the relative distribution of the current investment
in the K-12 arena. On one hand, the earlier we begin to expose people to genomics
in the MAP program, the greater the likelihood of keeping a portion of them
in the pipeline as they get older. On the other hand, there are problems when
centers only have a K-12 effort.
- More emphasis should be placed on undergraduates and the transitions between
undergraduate and graduate school and between graduate school and postdoctoral
training.
- NHGRI should not go overboard in either direction. The MAP should have both
K-12 efforts and later efforts. NHGRI needs to be smarter about the way in
which the K-12 programs are operated, rather than eliminating them. We should
build on existing programs in math and science.
- The coordinating center is important, but it is expensive to engage in this
effort correctly.
- The NHGRI's goal of doubling the number of minority investigators in the
next five years will be difficult to achieve but important. Each of the centers
is currently dealing with small numbers and there was some concern about a
quota-driven approach to these programs, rather than a best career-based approach.
- An overriding vision is critical for following through with the program
the plan to incorporate the CEERs into the MAP will be very helpful, and will
increase the numbers of URM considerably. ELSI is a critical part of genomics,
and even though these researchers are not going into the laboratory for basic
science work, they are still an important to the field.
- There are often geographical areas that are difficult to reach.
- Basic and clinical sciences need more mutual understanding. The connection
to the medical profession is useful for enticing interest in genomics.
- Outreach to distant minority communities could be accomplished through DNA
day activities, whether they are through ambassadors or grantee institutions
(see above). Other NIH institutes have responsibilities in the area of minority
involvement as well.
ELSI Research Advisors (ERA) Report
Eric Juengst presented a report on the recent ELSI Research Advisors (ERA)
meeting. ERA is a subcommittee of Council; there is an ERA evaluation and report
every five years.
The ELSI program has revised its Program Announcements to incorporate issues
relevant to the Vision statement of 2003. Much of ELSI funding is now going
into the "Genomes to Health" arena that looks at medical issues. There
are perennial ELSI challenges, including expansion of ELSI disciplines and researchers,
integration between ELSI research and genomic laboratory research, and more
effective translation of ELSI research findings to products that can inform
policy deliberations.
The Centers of Excellence in ELSI Research (CEER) program has been developed
to address a number of ELSI program goals, and there are CEERs that are addressing
research issues in each floor of the Vision. CEERs can build communities, increase
efforts in training and outreach, and translate research into policy. All of
the CEERs have minority outreach training programs. However, CEERs cannot replace
the investigator-initiated grant portfolio, or accomplish their own goals without
additional grants for collaborative research, trainee research opportunities,
and collective evidence-based policy initiatives.
The issue of the difference between the scope of ELSI research and the funds
available in NHGRI to support that area of research was discussed by ERA. Members
noted that the research programs of many other NIH institutes can benefit from
genomic approaches and ELSI research, and ideally NHGRI would not be the only,
or even primary source, of funds. In reality, however, while many other institutes
have signed onto the ELSI Program Announcement, the relative amounts of NHGRI
and non-NHGRI funding are not proportionate. In ERA's opinion, there is an NIH-wide
need for ELSI programs, but there are currently not resources to develop these
programs in other institutes. ERA discussed several ways to encourage this at
the NIH.
Council concurred with the importance of incorporating ELSI research and bioethics
research into science across the NIH. Unfortunately, members noted that the
fact that R01 funding rates are dropping precipitously in this tight funding
climate does not encourage such a new investment. Council asked whether the
NIH Roadmap could be a vehicle for a specific trans-NIH ELSI initiative. One
interesting theme could be the ELSI issues surrounding the development of a
predictive and preventive medicine. IRB consistency is another important topic.
Investment in this area could make translational research much smoother. Dr.
Collins noted that harmonizing translational research protocols was originally
suggested as a Roadmap Initiative in 2003.
Budget
The budget tables for FY 2004, 2005, and 2006 were distributed. The proposed
FY 2006 budget has an increase of 0.5%, which is the smallest in many years.
Any budgetary increase from year to year must encompass the traditional 3% increase
per year in an award's budget. Previously funded grants need to be funded at
full levels as well. The House and the Senate will now take up the proposed
President's budget. Over the next few years, the NIH will likely have budget
figures that do not keep up with inflation.
NIH Roadmap Status Report
The NIH Roadmap is a cross-institute effort to fund broad initiatives that
do not fit within the purview of a specific institute. Accelerating research
and eliminating roadblocks are important to the Roadmap. New Pathways to Discovery,
Research Teams of the Future, and Re-engineering the Clinical Research Enterprise
are the three themes of the Roadmap. NHGRI is mainly involved in the New Pathways
to Discovery theme, and is particularly involved in the Molecular Libraries
and Imaging, Nanomedicine, Computational Biology, and Building Blocks, Biological
Pathways and Networks Initiatives.
Within the Molecular Libraries and Imaging Initiative (MLII), the NIH Chemical
Genomics Center (NCGC) has been implemented within the NHGRI's Division of Intramural
Research. The larger high-throughput screening program will comprise the Molecular
Libraries Screening Centers Network (MLSCN), in which the NCGC will participate.
The extramural components of the MLSCN will consist of pilot screening centers,
which be funded later in FY2005, after review by the NIMH Council. The MLSCN
program will be co-managed by NHGRI and NIMH. Other components of the Network
will include a new database at NCBI, called PubChem, where the screening centers
will deposit their data and which will also contain the chemical structure of
small organic molecules and information on their biological activities, and
a compound repository. Two other grant programs in the Molecular Libraries Initiative
are being managed by NHGRI and will require second-level review by the Council
in August. Specifics on the early concurrence process will be provided at the
May Council meeting.
In other Roadmap initiatives of interest to NHGRI, four National Centers for
Biomedical Computing have been funded. The Nanomedicine Initiative has funded
concept development for centers, and center awards will be made at the end of
FY 2005. NHGRI is also involved in the Building Blocks, Pathways, and Networks
Initiative and the Pioneer Awards. Re-engineering the Clinical Research Enterprise
is another major Roadmap activity and is designed to support the NIH's aims
to improve the process of taking science from bench to bedside to practice.
Overall, Roadmap efforts have brought staff together from many different institutes
to work closely to plan and manage these initiatives. The initial set of Roadmap
initiatives will be reviewed by the Institute and Center (IC) Directors at an
upcoming retreat, and the possibility of developing a set of new initiatives
will be discussed. However, as the NIH is experiencing such a budget crunch,
institutes may not feel comfortable with expanding their contribution to Roadmap
funds. The Roadmap Initiative, averaged over six years, is about 0.9% of the
total NIH budget. More information on the NIH Roadmap can be found at http://nihroadmap.nih.gov.
HapMap Update
The first phase of the HapMap, which will be completed by the end of February,
has involved genotyping 1 million SNPs across the human genome, or on average,
one SNP every 5 kb across the genome. Genotyping in the CEPH samples is the
most complete at this time, since they were the first available, but the genotyping
of the three additional populations is rapidly being completed.
The second phase of the HapMap will involve 4.7 million attempted SNPs. The
HapMap pipeline will use SNPs discovered in the ENCODE regions, as well as SNPs
discovered in the MGC project. The Phase II genotypes will be done by July 2005,
and the second phase of the HapMap will be completed in October 2005. The total
of approximately 5 million SNPs expected to work across the genome will produce
a better HapMap and enable discovery of SNPs in linkage disequilibrium (LD)
with other SNPs, including SNPs involved in diseases. This will result in a
good selection of tag SNPs for use in research. Most common SNPs and many rare
SNPs will be in databases, which will enable research on numerous diseases.
The third phase of the HapMap will involve looking at samples from additional
populations beyond the initial four, in the HapMap ENCODE regions, to examine
how applicable the HapMap is to other populations.
Overall, Council was impressed by how well the HapMap has progressed, and its
user-friendly interface.
Mammalian Gene Collection (MGC) Update
The MGC is a multi-institute effort to produce high-quality cDNA sequences
with the full Open Reading Frame (ORF) for all human and mouse genes, and for
a set of 6,250 rat genes . The MGC pipeline is also used to develop Xenopus
and zebrafish collections. All MGC data and materials are publicly available.
The MGC is approximately 53% complete for human, with 12,237 non-redundant
full-ORFs, and 48% complete for mouse with 11,151 non-redundant full-ORFs. The
EST-based strategy for identifying MGC clones reached a point of decreasing
yield for both human and mouse last year. As a result, new strategies have been
initiated for the completion of the human and mouse clone collections. This
primary new strategy involves PCR-rescue of clones that have well-known RNA
structure and function, or known structure but no known function. PCR-rescue
of predicted genes has also been initiated. Contracts have been awarded to Baylor
College of Medicine and British Columbia Genome Sequencing Center to start PCR
rescue programs. 60% recovery of genes is expected during the first two contract
years. Current PCR rescue efforts are slightly behind schedule, but the centers
have ramped up so that they can meet the first-year goals by the end of the
initial contract year.
For the testing of prediction-based strategies, contracts have been awarded
to Washington University in St. Louis and the University of California Santa
Cruz (UCSC). Exoniphy, with EST support, and Twinscan, without EST support,
are the algorithms that are being used for this effort. Coordination with the
ENCODE program has been initiated. So far, the success rate is approximately
60-70% for predictions with EST support, and 15% for those without EST support.
Other possible strategies for obtaining currently missing genes include synthesis
of full-ORF genes, purchasing full-ORF genes from private collections, exchanging
full-ORF genes with other public collections, and advertising to the research
community for genes that they could provide to the collection.
Another potential future program being considered involves converting the human
MGC clones to an expression-ready format. This would allow the use of MGC clones
for large-scale proteomics, permit N- and C- terminal tags, and eliminate the
PCR step usually necessary for putting the clones into expression vectors. Issues
being addressed include the vector to used, how to build on existing expression-ready
collections, whether to include stop codons (the so-called closed format) or
not (the open format), the effect of an expression-ready format on cost and
timelines of PCR rescue, and funding considerations for this program.
Council members asked about:
- Overlap with the RIKEN clone collection, as MGC could save time and money
if those clones were available.
- Staff will investigate whether or not there are still intellectual property
concerns with their clones.
- Plans to extend the clones through the 5' UTR.
- There are no such plans at this time; the amount of money that is currently
allocated in R01 grants for converting clones into expression-ready formats.
Consolidation of these funds could be an efficient way to create an expression-ready
collection.
The Encyclopedia of DNA Elements (ENCODE) Project Update
The Encyclopedia of DNA Elements (ENCODE) project is being approached in a
phased approach. There is an ongoing pilot project that targets 1% (30 Mb) of
the human genome, as well as a technology development effort. The goals of the
pilot project are to test and compare existing experimental and computational
methods for analyzing of the human genome. The ENCODE website is www.genome.gov/ENCODE.
A project description paper was published in 2004.
DNAse hypersensitive sites, long-range regulatory elements, cis-regulatory
elements, and other targets are being examined using numerous techniques. To
inform the human ENCODE regions, the orthologous regions from numerous other
organisms are being sequenced to a comparative-grade finish. The ENCODE Consortium
holds regular meetings and teleconferences.
Data from the ENCODE project are stored in public databases. The sequence-based
data are displayed on the UCSC genome browser. The NHGRI intramural program
is developing a portal for accessing the non-sequence-based ENCODE data.
Overall, data release has gone smoothly. Data verification and data standards
are being implemented, although much of the data is in different formats. Dr.
Myers, who is a member of the ENCODE Consortium, commented that it has been
difficult for groups to adapt to the program's data release policy; some groups
have been concerned about data quality. He is confident, however, that any problems
that have been encountered can be solved and that data will be released expeditiously.
Dr. Eddy asked about the timeframe for expanding ENCODE to the rest of the
genome. Expansion could happen as soon as one year from now, but the plans for
doing so are under active discussion within the Consortium and with the program's
External Scientific Committee (ESC). The establishment of quality control and
finishing criteria will be prerequisites to scaling up.
Concept Clearance for an ENCODE Project for Model Organisms
Dr. Feingold presented a new initiative to undertake an ENCODE-like project
for one or more well-studied model organisms, in order to accomplish the following
aims: to coordinate research on genome function for these organisms; to complement
the current human ENCODE pilot project; and to help inform methods for scaling
ENCODE to the entire human genome.
Council has previously encouraged NHGRI initiate a parallel project to ENCODE
(modENCODE) to find all functional sequence elements in the entire genome of
one or more model organisms. The concept presented at this meeting proposed
to consider analysis only of very well-studied model organisms with strong functional
genomics communities, specifically S. cerevisiae, C. elegans and D. melanogaster.
NHGRI has encouraged each of the three communities to discuss the capabilities
and advantages of each model system for a potential modENCODE effort. As a result,
white papers will be submitted this spring. After reviewing these, staff will
evaluate whether there is a need for a small, focused workshop to help guide
the NHGRI's decisions about the goals of the modENCODE initiative. It is not
yet known whether NHGRI could afford to do a modENCODE project for all three
organisms, or just one. The scope of modENCODE would be somewhat broader than
that of the human ENCODE pilot phase. For example, modENCODE would address the
entire genome of the target organism(s).
Each group will develop, by this spring, a white paper outlining their conclusions.
The concept clearance proposed that mechanism of support would be the cooperative
agreement, although it remains to be decided whether a single, omnibus application
will be sought from each community or whether individual R01 or R21-scale applications
will be solicited and coordinated upon funding. Additional mechanisms may be
used to support other activities necessary to meet the needs of this project,
such as the development and distribution of common reagent sets and a centralized
database.
Dr. Myers mentioned that much work in this area has already been done on yeast.
This would potentially decrease the costs needed for a yeast modENCODE project.
Dr. Eddy noted his preference for smaller projects instead of an omnibus proposal,
to encourage more of the community to be involved. Dr. Gelbart said that there
might be an intermediate ground. The Council approved the concept as presented.
Memorandum of Understanding
The statement of understanding between NHGRI staff and the NACHGR was amended
based on previous Council discussion and re-presented to the Council. The Council
had been concerned that the staff administrative authorities originally proposed
might be too large for some large grants, such as sequencing centers. Therefore,
staff suggested that a cap of 1 million dollars be added to the 25% authority.
Expedited Council approval for administrative actions was also included in the
memorandum. A summary of expedited actions will be distributed to Council after
Council has approved the actions.
Council approved the revised Memorandum of Understanding.
2005 Biennial Advisory Council Report on Population Tracking
Every two years, the NIH requires a presentation to Council of how well NHGRI
has tracked women and minority participants in clinical research. Clinical research
includes patient-oriented research, epidemiological and behavior studies, outcomes
research, and health services research. NIH has developed a population tracking
database, and program directors must examine enrollment data for proposed studies
to see if it complies. The NACHGR must prepare a report on the inclusion of
women and minorities in clinical research. Most of the NHGRI-funded clinical
research is housed in the ELSI program, as NHGRI does not fund clinical trials.
Issues with the inclusion of women and minorities must be addressed and corrected
before a grant application can be reviewed and funded. Enrollment data for clinical
research is based on what is called for in the protocol.
Dr. Murray pointed out that aggregate data might not accurately reflect the
inclusion of woman and minorities in specific projects. Program Directors must
be aware of inclusion statistics on a case by case basis.
Dr. Gaines said that if all of the protocols do not have the same requirement
in terms of the groups enrolled, then we are potentially not inclusive or fair
overall. The review groups examine the applications to see if the groups enrolled
are scientifically warranted; if they are not, then the priority score must
be decreased to reflect this problem.
Some clinical projects in the NHGRI ELSI program exclusively include minorities,
but none would exclusively include Caucasians. NHGRI Program Directors make
sure that the investigators recruit the woman and minorities that have been
specified in the grant application. Overall, women are more likely to volunteer
to participate in genetic research. The NIH does not require tracking of participation
in non-clinical, biomedical research as of yet.
Council-Initiated Discussion
Last council, Mary Hendrix mentioned that she would like to hear a discussion
of epigenetics and NHGRI's involvement in this area. There is interest in inviting
Dr. Feinberg (JHU) to speak at the May Council meeting.
There will also be a discussion of the NHGRI budget at the May Council meeting.
Dr. Weinstock mentioned that since so many genomes are being sequenced, the
research community is asking if there will be a resource for having particular
tiling path clone sets available. There is currently a gap between where the
large clone sets lie and making tiling paths available to the public. Dr. Myers
said that there is potential interest in the biotechnology sector. Paying for
the tiling path and the freezers is a concern of industry, although there is
industrial interest in clone distribution. Dr. Patrinos has raised this issue
in regard to Joint Genome Institute projects. NHGRI staff will investigate this
topic. NHGRI can take leadership in this area, but since NHGRI has already paid
for development of the tiling path, there was concern expressed about committing
additional funds.
Announcements and Items of Interest
Dr. Guyer noted two items of interest in the Council folders, including a report
from the National Society of Genetic Counselors on their activities and a report
on a workshop held to discuss long-term maintenance of genome sequence assemblies.
The workshop discussed the importance of strict data deposition standards at
the trace repository, as well as strict data quality standards.
Conflict of Interest
Dr. Guyer read the Conflict of Interest policy to Council and asked them to
sign the forms provided.
Review of Applications
In closed session, the Council reviewed 117 applications, requesting $41,137,929.
The applications included 57 regular research grants, 12 pilot projects, one
program project, 13 ELSI grants, two area grants, three center grants, three
conference grants, one research career development award, two training grants,
11 SBIR Phase I grants, five SBIR Phase II grants, two fellowship grants, three
STTR Phase I grants and two others. A total of 70 applications totaling $31,897,135
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.
Chairman
National Advisory Council for Human Genome Research
Last Reviewed: May 27, 2008
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