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Council Minutes - September 2007

The 102nd Meeting
September 25–26, 2007

CONTENTS

  1. REVIEW OF APPLICATIONS
  2. CALL TO ORDER
  3. REPORT: Task Force on Minority Aging Research
  4. REPORT: Working Group on Program
  5. COMMENTS FROM RETIRING MEMBERS
  6. PRESENTATION: Update on NIH Peer Review Project
  7. PROGRAM HIGHLIGHTS
  8. ADJOURNMENT
  9. CERTIFICATION

Attachment A: Roster of the National Advisory Council on Aging
Attachment B: Director's Status Report

The 102nd meeting of the National Advisory Council on Aging was convened on Tuesday, September 25, 2007, at 3 p.m. in Building 31, Conference Room 6, National Institutes of Health (NIH), Bethesda, MD. Dr. Richard J. Hodes, Director, National Institute on Aging (NIA), presided.

In accordance with the provisions of Public Law 92–463, the meeting was closed to the public on Tuesday, September 25, from 3:00 p.m. to 5:00 p.m. for the review, discussion, and evaluation of grant applications in accordance with the provisions set forth in Sections 552(b)(c)(4) and 552(b)(c)(6), Title 5, U.S. Code and Section 10(d) of Public Law 92–463.1 The meeting was open to the public on Wednesday, September 26, from 8:00 a.m. to 1:30 p.m.

Council Participants:
Dr. John T. Cacioppo
Dr. Carl Eisdorfer
Dr. Lawrence M. Friedman
Dr. Mary Ganguli
Dr. Alan M. Garber
Dr. Paul Greengard
Dr. S. Michal Jazwinski
Dr. Sundeep Khosla
Dr. Virginia M.-Y. Lee
Dr. Terry L. Mills
Dr. John C. Morris
Dr. Orien Reid
Dr. Gary B. Ruvkun
Dr. Gerald P. Schatten
Dr. Albert L. Siu
Dr. Mary E. Tinetti

Absent:
Dr. Kenneth V. Brummel-Smith
Dr. Peggye Dilworth-Anderson

Absent Ex-officio Participants:
Dr. James F. Burris, Department of Veterans Affairs
Dr. Kenneth Pugh, National Naval Medical Center
Mr. John Wren, Center for Planning and Policy Development, U.S. Administration on Aging, DHHS

The Council Roster, which gives titles, affiliations, and terms of appointment, is appended to these minutes as Attachment A.

In Addition to NIA Staff, Other Federal Employees Present:
Dr. Priscilla B. Chen, Center for Scientific Review, NIH
Dr. Carol Hamelink, Center for Scientific Review, NIH
Dr. Jonathan W. King, Center for Scientific Review, NIH
Ms. Denise Manouelian, National Institute of Diabetes and Digestive and Kidney Diseases
Mr. Patrick Shirdon, National Institute of Mental Health
Dr. Lawrence Tabak, National Institute of Dental and Craniofacial Research

Members of the Public Present:
Dr. Nicholas A. Christakis, Harvard Medical School
Ms. Christy Gilmour, American Academy of Orthopaedic Surgeons
Ms. Chris Herman, National Association of Social Workers
Ms. Lee Herring, American Sociological Association
Dr. Frances McFarland Horne, Rose Li and Associates, Inc.
Dr. Douglas P. Kiel, Harvard Medical School
Ms. Patricia Kobor, American Psychological Association
Dr. Rose Maria Li, Rose Li and Associates, Inc.
Ms. Pam Moore, LRP Publications

Dr. Sean Morrison, University of Michigan
Ms. Tina Powell, Social and Scientific Systems
Ms. Michelle Rodrigues, SRI

I. REVIEW OF APPLICATIONS

This portion of the meeting was closed to the public, in accordance with the determination that it concerned matters exempt from mandatory disclosure under Sections 552(b)(c)(4) and 552(b)(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix).2

A total of 980 applications requesting $1,031,356,252 for all years underwent initial review. The Council recommended 455 awards for a total of $687,166,734 for all years. The actual funding of the awards recommended is determined by the availability of funds, percentile ranks, priority scores, and program relevance.

II. CALL TO ORDER

Dr. Hodes welcomed members to the open session of the 102nd National Advisory Council on Aging meeting and called the meeting to order at 8:05 a.m. on Wednesday, September 26, 2007.

A. Director’s Status Report

Dr. Hodes anticipated that the NIA would be operating under a continuing resolution, most likely at 2007 levels beginning October 1. As a result, NIA would postpone consideration of funding line, long-term planning, and new programs. Dr. Hodes reminded the Council that the current budget trajectory for NIA parallels that for NIH overall, peaking at the end of the budget doubling in 2003 and increasing at a sub-inflationary rate since then. The increase of 4 percent in current dollars over this period translates to a 14-percent decrease in constant dollars (adjusted for biomedical inflation).

Dr. Hodes next described the Office of Portfolio Analysis and Strategic Initiatives (OPASI). This office, best known for its role in overseeing the NIH Roadmap, or the Common Fund, is organized into three arms: (1) Division of Strategic Coordination (DSC), (2) Division of Resource Development and Analysis (DRDA), and (3) Division of Evaluation and Systematic Assessments.

The DSC manages NIH Roadmap activities. In 2006, funding for Roadmap was about 1.2 percent of the overall NIH budget, or $332 million, and was expected to increase to $440 million in 2007 and $500 million in 2008. The 2008 funding is about 1.6 to 1.7 percent of the NIH budget, and funding will remain at that level until the NIH budget increases beyond the rate of inflation. In 2006, 328 research awards were made, about 40 percent categorized as basic research, 40 percent as translational research, and 20 percent as high-risk research.

The NIH Director’s Pioneer Awards, another Roadmap initiative, support highly innovative research.  Dr. Hodes described the two-step review process, with the strongest candidates interviewed by a committee. Of approximately 1,000 applications, 12 were awarded. The NIA shared in the support of one such application. The NIH Director’s New Innovator Award also focuses on creativity and innovation but is specifically targeted to new investigators. Forty-one new investigators have received 5-year grants as a part of this program, which is budgeted at about $105 million. Dr. Hodes pointed out that these award mechanisms represent a modest investment in a new style of peer review where top applicants are interviewed before award decisions are made (see Dr. Lawrence Tabak’s presentation below).

Many pilots in multidisciplinary research have been funded as part of the Roadmap 1.0 Interdisciplinary Research Consortia. Most recent was a $25 million grant to the Buck Institute to establish the new field of geroscience. In its current instantiation, Roadmap now serves as an incubator space for cross-cutting, transformative research initiatives that warrant concerted attention from NIH as a whole. The first cohort of initiatives will soon graduate from the incubator space, and initiatives starting in 2008–2009 are now under consideration. Dr. Hodes discussed four proposed initiatives, the first two of which will move forward in fiscal year (FY) 2008.

Epigenetics: The regulation of gene activity that is not dependent on gene sequence but defines heritable or stable long-term alterations. This initiative will focus on a global analysis of epigenetic changes in the genome; i.e., epigenomics. Activities within this initiative will be carried out through partnerships and with support of the Common Fund. The NIA will participate in this initiative. An example of the relevance of epigenetics to aging can be found in a recent study of DNA methylation patterns in identical twins (Fraga et al. PNAS. 2005;102:10604). This study showed that although epigenetic patterns are identical at early ages, they increasingly diverge as twins grow older. The initiative will begin in 2009 with a request for applications (RFA) to study epigenetic factors that might be a function of disease.

Human microbiome: The large population of microbes that inhabit the human body. Many of these have not yet been identified. The initiative will involve sequencing techniques on several parts of the human body to deduce the full scope of the microbiome, and it can be applied to understanding normal and abnormal flora, which will in turn inform understanding of human disease. An example can be found in recent studies comparing flora in the gastrointestinal tract between genetically obese mice and normal ones. When flora from obese mice were transferred to normal mice, those mice became obese. The reverse was also true.

The two proposed initiatives that are being further developed for possible initiation in 2009 are focused on the human phenome, exploring phenotyping methods and their application to multiple clinical and human studies, and on the proteome, exploring protein capture tools to identify all proteins in cells for purposes of detection and studying biological systems and networks.

The DRDA seeks to identify and quantify the nature of public health challenges and burdens and to use this information to inform decisions about NIH portfolio management. In 1998 and 2003, the National Academies of Science issued reports calling for changes in how research is conducted. In 2004, efforts were initiated to create an electronic coding system (Research, Condition, and Disease Categorization [RCDC]) to assist the NIH in classifying projects and in reporting costs associated with research in approximately 360 categories, conditions, or diseases. The RCDC, subsequently required by the NIH Reform Act of 2006, offers the advantages of consistency, transparency, efficiency, and opportunities for further portfolio analysis. NIH Institutes and Centers (ICs) have provided input into this system, and paradigms and algorithms for disease categorization will be derived from text in research applications and intramural research summaries. The NIH will introduce RCDC to the public in summer 2008, and the system will be launched in February 2009. Dr. Hodes also predicted that the amount of funds appropriated to specific areas would change substantially. He cautioned that the public would have to be informed and educated about the RCDC and understand that these changes represent a change in disease categorization only.

Dr. Gerald Schatten noted that NIA should be a significant beneficiary from Roadmap funding, particularly in the epigenetics initiative. He asked about return on investment and the extent to which NIA would recoup some of the funds it has contributed to Roadmap. Dr. Hodes responded that Roadmap had been funded initially by contributions of a percentage from each IC’s budget but that Congress appropriated Common Fund monies separately in FY2007. Dr. Hodes observed that NIA has benefited broadly from Roadmap initiatives. For example, Dr. Gary Ruvkun’s research has benefited from the NIH Molecular Libraries Initiative, which involves high-throughput screens of hundreds of thousands of molecules. He added that aging research will benefit from the techniques and applications generated through this initiative, even though the initiative itself is not targeted to aging.

Dr. Ruvkun emphasized the importance of informing NIA grantees about this and other large resources. He noted that many R01 applications propose some type of screen and have their budgets cut in study sections, and he suggested that investigators be directed to resources where money is already budgeted for these activities. Dr. Hodes responded that NIA is attempting to educate grantees about these resources and could do more to promote awareness.

Dr. Sundeep Khosla noted that efforts such as the NIH Roadmap and Clinical and Translational Science Awards (CTSAs) are changing the way clinical research is done. He also pointed out that NIH Directors and Presidential Administrations change, and he questioned whether these awards would continue. Dr. Hodes responded that some, like the CTSAs, will become institutionalized and, barring any unexpected negative outcome, will remain in place for some time. He reminded Council members that the Common Fund is only an incubator space and that initiatives moving out of the incubator will be sustained only if ICs or other agencies want to maintain them. Even so, the principle of supporting potentially transformative research most likely will survive because it is now legislated both in authorization and appropriation language.

Dr. Albert Siu discussed RCDC and asked how aging would be categorized. Dr. Hodes addressed questions about whether NIA will have to code every project in its portfolio individually or whether anything NIA supports will be considered aging research. He pointed out that any of these categories could have a narrow definition but that the importance of a broader category of related research must be communicated. Dr. Hodes also acknowledged that the relevance of some applications to a particular category might be coded differently among ICs, which could present a problem in development of automated systems. Ms. Kathie Reed confirmed that aging is one of the 360 categories that were identified over time by Congress as areas of interest for reporting.

B. Announcements

Dr. Hodes announced that Dr. Robin Barr has been officially appointed as Director of the NIA Office of Extramural Activities and that Dr. Judith Salerno, NIA Deputy Director, will be leaving the NIA to take a position at the Institute of Medicine. Dr. Hodes thanked Dr. Salerno for her efforts on behalf of the NIA, particularly in developing and sustaining partnerships with NIH ICs, Federal agencies, and other organizations. Dr. Hodes also announced that Ms. Patricia Lynch in the Office of Communications and Public Liaison (OCPL) will retire in January. Ms. Lynch has headed the Alzheimer’s Disease (AD) Education and Referral Center for 16 years and built it into a leading national information center for AD.

Dr. Richard Suzman introduced Dr. Partha Bhattacharya and Dr. Jonathan King. Dr. Bhattacharya, a health economist who recently joined the NIA, is working with Dr. John Phillips on the Behavioral and Social Research Program’s (BSR’s) health economics portfolio, including Medicare issues. Dr. King, who came to the NIA on detail from Carnegie Mellon University and the Center for Scientific Review (CSR), will be supporting BSR’s cognitive portfolio.

Ms. Vicky Cahan announced that Ms. Peggy Vaughn has joined the OCPL.

In response to a question about dissemination of NIA publications to communities and doctors’ offices, NIA OCPL staff reported that there are about 20,000 people on their mailing list who regularly receive a variety of NIA materials by mail and through electronic alerts. The NIA also has two toll-free numbers, an online ordering service, and active distribution through intermediaries such as AD Center Directors in an effort to effect broad distribution through relevant networks.

C. Future Meeting Dates

January 29–30, 2008 (Tuesday and Wednesday)
May 20–21, 2008 (Tuesday and Wednesday)
September 24–25, 2008 (Wednesday and Thursday)
January 27–28, 2009 (Tuesday and Wednesday)
May 19–20, 2009 (Tuesday and Wednesday)
September 22–23, 2009 (Tuesday and Wednesday)

D. Consideration of the Minutes of the Last Meeting

The minutes of the May 2007 meeting were considered. A motion was made, seconded, and passed unanimously to approve the minutes.

III. REPORT: Task Force on Minority Aging Research

Dr. Terry Mills reported on the previous day’s meeting discussion, including Dr. Taylor Harden’s presentation on the new NIH Roadmap emphasis area for 2008–2009 in health disparities that is being co-chaired by Dr. John Ruffin, Director, National Center on Minority Health and Health Disparities, and Dr. Jeremy Berg, Director, National Institute of General Medical Sciences, and also behavioral and social science research advances in health disparities.

The health disparities initiatives would link to common NIH Roadmap themes of studies and outcomes from the bench to the bedside; the development of genetics initiatives, for example with respect to AD or gene-environment interactions; and recent discoveries for complex diseases associated with aging, such as cancer and diabetes. Dr. Mills also reported that the task force discussed challenges, barriers, and solutions. 

Dr. Mills also discussed the Health Disparities Resource Persons Network, which is intended to provide technical and capacity-building assistance to the NIA and its research constituency to support efforts to improve minority health and reduce or eliminate health disparities and inequities. Dr. Mills reminded Council members of discussions at past meetings about the importance of establishing a network of investigators with previous experience in minority health research as well as of supporting minority scholars. At the Council’s recommendation, Dr. Harden constructed a file of individuals committed to engaging with the NIA and the task force. Approximately 100 individuals have been identified and can bring their expertise not only to review panels but also as resources in initiative development.

The task force also discussed behavioral and social science research advances in health disparities. Among these was a study, published in Stroke by Glymour, Avendano, and Berkman (2007;38:2415), examining whether the “stroke belt,” which is the South and Southeast, is “worn” from childhood. Although Glymour et al. concluded that the excess stroke risk for people who lived in the Stroke Belt during childhood implicates early life exposure, none of the correlations between incidence of stroke and period of residence in the Stroke Belt (i.e., early childhood, adulthood, or both) were statistically significant, generating discussion on the meaning and generalizability of the study findings. Another study, published in Circulation by Skinner, Chandra, Staiger, Lee, and McClellan (2005;112:2634-2641), found significantly higher risk-adjusted mortality after acute myocardial infarction (AMI) or heart attack in hospitals that disproportionately treat elderly Black patients with AMI. One striking finding from this study is that 69 percent of elderly Black patients are treated at 21 percent of the hospitals and that the majority of hospitals treating them are teaching or government (county) hospitals.

The task force also discussed Resource Centers for Minority Aging Research (RCMARs), which were established to

  • Advance scientific knowledge to decrease health disparities;
  • Mentor researchers for careers in research on the health of minority elders;
  • Enhance cultural diversity in the professional workforce;
  • Deploy strategies for minority group members in aging research;
  • Recruit established investigators to minority health and health disparities research;
  • Improve research methods and tools for use with diverse populations; and
  • Disseminate research results addressing resolution of health disparities.
RCMARs have been established in California, Colorado, Michigan, and Pennsylvania. One of the two in southern California serves as the RCMAR Coordinating Center. The most recent RCMAR has been established at the University of Alabama at Birmingham.

IV. REPORT: Working Group on Program

Dr. John Morris reported on several topics discussed during the previous day’s closed session.

In a presentation at the Working Group meeting, Dr. Marilyn Miller of the Neuroscience and Neuropsychology of Aging Program (NNA), pointed out that genes important for increasing susceptibility to or causing Alzheimer’s disease (AD) remain to be identified. Dr. Miller described the rapid development of an initiative applying new technologies for the study of AD that make it cost effective to study large numbers of individuals for genome-wide associations. Major discoveries have been made as a result of these studies in complex diseases such as diabetes and cancer. Development of the AD initiative began in June 2007, a meeting was held in August, and a consortium has been formed to move these efforts forward. The initiative is investigator driven, and a principal investigator has been identified. The ultimate goal is to enroll 10,000 patients with AD and 10,000 control individuals.

Dr. Neil Buckholtz of NNA presented an RFA concept clearance request to capitalize on the data and samples collected for the Biomarkers for Older Controls at Risk for Dementia (BIOCARD) study. The BIOCARD study began at the National Institute of Mental Health (NIMH) in 1995 and enrolled cognitively normal, first-degree relatives of patients with AD. These participants underwent annual evaluations of their cognitive function, donated plasma and cerebrospinal fluid samples, and underwent magnetic resonance imaging (MRI) every 2 to 4 years. The average age of this participant cohort was 55 years. The study was suspended in 2005. Of the 350 participants that remain in this cohort, 212 have agreed to continue their participation if the BIOCARD study is renewed. NIMH is in the process of identifying case report forms for participants, reviewing the electronic database, and examining inventories of frozen samples. Dr. Buckholtz requested clearance for an RFA to extend the BIOCARD study on the clinical and cognitive assessments for remaining participants—not to fund further MRI or cerebrospinal fluid or plasma collection—and make available to other NIH grantees the data that already have been collected. The Working Group on Program unanimously approved this RFA concept. In the full Council meeting, a motion was made, seconded, and passed unanimously to approve the proposed RFA to extend the BIOCARD study.

The Geriatrics and Clinical Gerontology Program (GCG) proposed the establishment of a Clinical Trials Advisory Panel that would serve as a Council task force to advise the program on large-scale clinical trials requiring at least $2 million per year in direct costs. Because these trials require substantial resources, there is a need for a systematic evaluation of needs and opportunities for potential and proposed trial initiatives. The advisory panel would help GCG prioritize initiatives, and recommendations by this group would come through the Council. However, because of this new mechanism, GCG would no longer accept investigator-initiated applications for large-scale trials. Some members of the working group expressed concern about this caveat and about operational issues related to articulation of its mission, constitution of the panel, and how the advisory panel would interact with staff and the Council. Dr. Evan Hadley, Program Director for GCG, noted that if the concept were approved, he would report to the Council once the panel and its working process were established. The working group approved this concept, with one abstention. In the full Council meeting, a motion was made and seconded to clear the establishment of a Clinical Trials Advisory Panel, and the Council passed the motion with one abstention.

Dr. Morris also reported that a group has been formed to review the Intramural Scientific Director of NIA. The group will focus not so much on scientific success and direction but on the director’s leadership. The group will report to Council once its review is completed.

Dr. Barr noted that the Council has received copies of the Extramural Program Data Statistical Package, which shows the number of applications received for this round distributed across the four extramural programs and across the grant mechanisms offered. The report also shows the performance of NIA-assigned applications in peer review. Dr. Barr pointed out that although the number of applications remains high, NIA is starting to see a decline in the number of new applications. This decline has been masked by increasing numbers of amended applications. Dr. Barr remarked that this trend is not unique to NIA. He also mentioned that approximately 100 fellowship applications have been received for this round and that this surge resulted from NIA joining two of the M.D./Ph.D. and dissertation-level predoctoral fellowship programs.

Dr. Siu asked whether the decline of new applications reflects a decline in the number of applications or in the number of applications per applicant. Dr. Barr responded that NIA is exploring the reasons for the decline.

V. COMMENTS FROM RETIRING MEMBERS

Dr. Hodes recognized and presented certificates to outgoing Council members. He noted how well Council has worked together and how collegial it is, and he pointed to the importance of outgoing members as ambassadors between the NIA and the research community.

Dr. Hodes acknowledged Dr. John Cacioppo’s work as a model for cutting-edge, transdisciplinary, translational research and his invaluable assistance to the Council. Dr. Cacioppo will continue his service to the NIA by co-chairing the review of the BSR Program. Dr. Cacioppo indicated that it was an honor and a privilege to serve on Council. He also noted that his term began when the NIH budget was still at its height and that in the face of increasing budgetary challenges, NIA staff have handled their increasing workload with grace, integrity, and commitment. He thanked the staff on behalf of all NIA-funded investigators.

Dr. Hodes thanked Dr. Alan Garber for his service and acknowledged that he provided an important perspective with respect to how NIA science translates to policy decisions. Like Dr. Cacioppo, Dr. Garber will continue serving NIA by co-chairing the review of BSR. Dr. Garber stated that he considered it an honor and a privilege to serve on Council. He recalled that when he began his Council term, the review of BSR was underway, and there were concerns about the grant review process, the NIA budget, and the Medicare budget. Dr. Garber indicated that he is impressed with his fellow Council members, particularly with the low amount of territoriality and the high degree of constructive spirit in efforts to understand the broad portfolio of NIA. He also is impressed by the dedication of NIA staff and leadership, as well as by its extraordinary stewardship.

Dr. Hodes recognized Dr. Virginia Lee for her extraordinary service as a very active member of Council who provided guidance at and between meetings. Dr. Lee remarked on the privilege of serving on Council and on how much she has learned with respect to other aspects of aging. Her tenure on Council has helped her to appreciate better the many layers of complexity to aging research. She noted that in a time of tight budgets, NIA has made difficult decisions fairly, and she recognized NIA leadership and staff for their outstanding efforts. Dr. Lee acknowledged the late Dr. Leon Thal and his guidance when she first joined Council. She also expressed her desire to continue working with NIA and NACA.

Dr. Hodes noted that NIA was fortunate to recruit Dr. Gary Ruvkun to aging research. Because of researchers like Dr. Ruvkun, aging research has become cutting edge, and study sections no longer immediately reject applications focused on aging. Dr. Ruvkun commented that he has always felt well supported by NIA; the Biology of Aging Program (BAP) discovered him early in his career and supported his research in a proactive way unlike any other experience he has had with NIH, for which Dr. Ruvkun feels indebted. He views his time on Council not only as service but also as a way to educate himself, and he expressed his appreciation for the opportunity to serve.

VI. PRESENTATION: Update on NIH Peer Review Project

Dr. Lawrence Tabak, Director, National Institute of Dental and Craniofacial Research, provided an overview of NIH’s peer review approach, which includes seeking input from investigators, scientific societies, grantee institutions, and voluntary health organizations as well as from NIH staff. It is apparent that the NIH peer review system must adapt to emerging and rapidly changing fields of science, as well as to new and growing public health challenges, and adapt in a way that is efficient and effective for applicants and reviewers alike. Dr. Elias Zerhouni, NIH Director, has issued a broad mandate to assess how science is supported. Because peer review is a key component of scientific support, NIH, in partnership with the scientific community, has undertaken a self-study to strengthen its peer review process.

Two groups have been established for this purpose. The external Advisory Committee to the Director (ACD) Working Group on Peer Review includes representatives from academic institutions, scientific societies, and the NIH Director’s Council of Public Representatives, as well as ex-officio members Dr. Norka Ruiz Bravo, Director, Office of Extramural Research, and Dr. Toni Scarpa, Director, CSR. The internal Steering Committee Working Group on Peer Review includes directors from several NIH ICs as well as ex-officio members from the Office of Budget and the Office of General Counsel. These two working groups are coordinating with CSR to ensure an alignment of effort, as CSR also is engaged in initiatives addressing the mechanics of peer review, including review cycles, study section alignment, application length, and electronic reviews.

Phase I of the NIH self-study is diagnostic, beginning with a request for information (RFI) soliciting feedback about unique challenges in NIH research support and peer review as well as proposed solutions. The RFI further asked about core values of the peer review process, the scoring system, and the appropriateness of the peer review process for investigators at all career stages. Although the RFI closed on September 7, 2007, Dr. Tabak stated that feedback sent to PeerReviewRFI@mail.nih.gov was still welcome and would be considered. In addition to the RFI, two teleconferences and regional town meetings have been held. The first regional town meeting took place in July 2007 in Washington, DC, and involved professional organizations. Another town meeting was held in Chicago in the first week of September; three more are scheduled for New York City, San Francisco, and Washington, DC (patient advocacy groups).

The ACD Working Group has selected a series of science liaisons to further enhance outreach to stakeholders, and the Steering Committee Working Group has held three meetings and posted a Web-based survey to gather comments from ICs relative to their own missions. The Steering Committee Working Group is analyzing the literature related to peer review and considering approaches undertaken by other agencies, such as the National Science Foundation, the Department of Energy, the Department of Defense, and the Howard Hughes Medical Institute. A psychometric analysis of study section models also is underway. Dr. Tabak and Dr. Jeremy Berg, who chair the Steering Committee Working Group, are meeting with all NIH advisory councils during the fall, and they will receive the relevant transcripts from discussions occurring during the Council meetings.

Dr. Tabak pointed out that this study is on a fast track. Reports to the ACD and Steering Committee Working Groups will be completed by early December, and NIH leadership will consider all input in determining next steps by February 2008, with any pilot initiatives and their evaluations designed and implemented by March 2008. The results of these pilots and analyses will be used to develop a long-range implementation plan, with briefings for NIH staff, scientific societies, NIH councils, advocacy organizations, the trade press, and legislative bodies. These efforts will ultimately result in the expansion of successful pilots and the development of new NIH peer review policy. Dr. Tabak emphasized that pilots will be based on the best ideas, not necessarily the most popular ones, and that all ideas are under consideration.

To stimulate discussion, Dr. Tabak presented some ideas culled from the responses analyzed to date and emphasized that the ideas were not in any order of priority and are not necessarily to be implemented. Many comments applied to review criteria and focus, application structure, and whether funding decisions should be made based on the project or based on the applicant. Some respondents observed that the intramural process is a retrospective one whereas extramural reviews tend to be prospective. There also were calls for separate application tracks and review criteria for projects that lack preliminary data versus those that are extensions of current work. This track for new projects would eliminate the preliminary data section so that more attention would be paid to significance rather than feasibility.

Review mechanisms formed another emerging theme. Suggestions included the following:

  • Conduct a two-stage review process where the first stage would involve technical subject matter and content review and the second stage would involve an editorial board model that considers applications based on reviewers’ comments.
  • Conduct electronic review.
  • Allow virtual dialogue between applicant and reviewer to allow applicants to answer questions or address any reviewer errors that might affect the outcome of the review.
  • Use a different review processes for different types of science. For example, less than 10 percent of new applications are funded, and most clinical trial applications are submitted as new applications.
  • Ensure that the right reviewers are assigned to Small Business Innovation Research or Small Business Technology Transfer applications.
  • Have investigators designate one application as their primary application, then use different criteria to review and fund non–primary applications.
  • Provide useful core feedback for applications from new investigators, including clearer ranking for unscored applications or the elimination of triage.
  • Rethink design of original applications to avoid congestion in the queue. A redesign could include shorter preapplications to provide rapid identification and separation of competitive applications from noncompetitive applications as well as meaningful advice to new applicants.

Comments also focused on reviewer quality and reviewer culture, including how much information reviewers would need to have an appropriate context for an application. Publication of reviewer identities was a matter of debate. Suggestions for maximizing reviewer quality included the following:

  • Added incentives for reviewers.
  • Mandatory service by grantees.
  • More flexible service opportunities.
  • Increased support for reviewers.
  • Rating of reviewers and scientific review administrators.

Comments about scoring centered on issues such as binning and triaging, with several people requesting more information to help an applicant decide whether to bother with a resubmission. Dr. Tabak noted a common scenario where a grant applicant revises and resubmits an application only to receive a similar score. This can happen because reviewers change or because reviewers are loath to discourage an applicant the first time around. A two-score system was suggested as a way to combat this problem by providing the applicant with a score based on the application’s potential (e.g., if the idea is a sound one but the application itself needs some work) in addition to the usual score of technical merit.

Finally, Dr. Tabak acknowledged suggestions to limit the percent effort that can be recovered on grants for principal investigators or to increase the percent effort to be a principal investigator to 50 percent.

Dr. Greengard acknowledged the problem of low-priority applications clogging the queue. He observed that the possibility of consulting research organizations in western Europe that focus primarily on track record was not discussed. Dr. Tabak noted that NIH is looking at agencies both in the United States and abroad, and he recognizes that many European organizations conduct review processes similar to the Intramural review process. Dr. Greengard then asked at what level, by whom, and by what criteria decisions about research fund allocations are made. Dr. Tabak replied that the method of decision-making varies across ICs. Dr. Hodes added that neither NIA nor other ICs have setasides; for example, for basic versus applied research. However, NIA does set aside funds for specific initiatives, and peer reviewers make recommendations for applications to be paid. Dr. Hodes acknowledged that the composition of review groups therefore could skew allocations but also described how Institute-level, program-level, and Council-level reviews historically have helped ensure that a disproportionate focus in one particular area does not occur.

Dr. Tabak added that NIH had been prompted to explore the locus of decision-making and noted a spectrum of suggestions. At one end of the spectrum, people are loath to compromise the integrity of peer review and would expect the Institute or Council to make decisions about portfolio balance. Those at the other end might argue that the number of applications in an area suggests an important health problem, and this consideration should be embedded somehow in the review process.

Dr. Khosla discussed shortened applications and suggested that reviewers shift their focus away from details to the investigator and “the big picture.” This would represent a substantive change in the culture of study sections, particularly among younger reviewers, who tend to focus more on details. Dr. Tabak acknowledged the need to determine the extent to which the review should help investigators improve their applications. The NIH community should decide what domains and parameters to include in evaluations, then scale its applications accordingly.

Dr. Lee asked Dr. Tabak to elaborate on the idea of training reviewers, particularly the expectations for more general reviewers. Dr. Tabak responded that the NIH has not yet considered implementation but that the acculturation process needed to produce savvy reviewers would have to be mimicked in a time-efficient way. He noted that observation works well but that senior reviewers also would need time to guide and help newer reviewers.

Dr. Mary Ganguli pointed out that as a once-junior reviewer looking for every flaw she has benefited over the years from good role models as well as guidance from program staff. She commented that it is now a confusing time for applicants and reviewers who must learn new electronic processes, particularly given the greater focus on the mechanics of submitting applications and the proliferation of different grant mechanisms. Applicants read announcements carefully and prepare their applications accordingly, but in some cases reviewers are told not to read these announcements. Dr. Ganguli also noted the counterintuitive instructions to reviewers to review the science and not the budget, when in fact reviewers are influenced by the budget when assigning priority scores even though the budget is not discussed in the written comments. She added that verbal comments made during the study section usually are not reflected in the written critiques, even though they would help investigators write more competitive applications. She further commented that with greater emphasis on translational research, study sections will have to be interdisciplinary and the appeal of a particular application must be persuasive to a more diverse audience.

VII. PROGRAM HIGHLIGHTS

A. Behavioral and Social Research: The Spread of Health Behaviors in Social Networks

Dr. Nicholas Christakis (Harvard Medical School) presented on the spread of obesity in a large social network over 32 years (Christakis and Fowler. The New England Journal of Medicine. 2007;357:370-379). Dr. Christakis and colleagues hypothesized that if people are influenced by those around them and if individuals in one’s social circle exhibit behaviors contributing to weight gain or weight loss, that person might reset his or her expectations about behaviors and acceptable body sizes, an idea that could help to explain the obesity epidemic in the United States.

Exploiting previously unused archival data, Dr. Christakis and colleagues developed a densely interconnected social network of 12,067 people assessed repeatedly from 1971 to 2003 as part of the Framingham Heart Study. Measured body mass index (BMI) and tobacco consumption were available for all subjects, and network analytic methods and longitudinal statistical models were used to examine whether weight gain or smoking cessation in one person (ego) was associated with similar behaviors in others (alter) such as friends, siblings, spouses, and neighbors. 

They coded nodes based on BMI and morbid obesity, looked at both genetic and nongenetic social ties, and found clusters of obese and nonobese individuals in the network at all time points. Using techniques developed by László Barabási to summarize the clusters, Dr. Christakis and colleagues found that the number of obese “alters” who are one degree removed from a person (an “ego”) exceeded that expected in a random scenario by 40 percent. That percentage excess decreased to 20 percent among alters two degrees removed from individuals and to 10 percent among alters three degrees removed. Only at the level of four degrees removed from an individual was no excess observed.

This type of clustering could be explained in one of three ways: (1) Homophily, or “birds of a feather flocking together”; (2) confounding, where two people are connected and both gain weight (for example, when a McDonald’s opens nearby); and (3) induction, in which behavior or weight gain in one individual directly contributes to or causes that in others. Clustering also could be explained by all three ways, in which case the reasons must be teased apart. When Dr. Christakis and colleagues examined the longitudinal information provided by the Framingham Heart Study, they found evidence for induction. Moreover, the use of regression models revealed that mutual friendships had the most influence on a person, followed by friendships identified by the person, followed by friendships identified by others. Further examination showed higher probabilities of influence among same-sex friends, same-sex siblings, and spouses but no effect among immediate neighbors. In addition, these effects held despite geographical distances between people within a network. Similar clustering was observed for smoking behaviors. Thus, as Dr. Christakis and colleagues had hypothesized, the appearance or behavioral changes of others within a person’s network influences that person’s behavior as well as his or her expectations or perceptions of norms. Friends with more education appeared to influence one another more than those with less education. Siblings and immediate neighbors did not exhibit these effects after accounting for their baseline smoking status. The spread of smoking cessation did not account for the interpersonal spread of obesity. 

Dr. Christakis’ findings have several implications. Network phenomena appear relevant to smoking cessation and obesity. Health, healthcare, and health behaviors might have specific, interpersonal, collateral effects. Dr. Christakis used the example of effects on property values in a neighborhood if one person renovates his or her house. Considering the effects of health behaviors not only on a person but also on the people around that person could generate a radical rethinking of policies and cost effectiveness.

Dr. Alan Garber commented on the endogeneity of the networks Dr. Christakis presented and asked how clusters changed over time or when someone became obese. Dr. Christakis imagined that the network could determine the outcome for the individual or the other way around. If baseline weight was controlled and ties fixed, one could examine how weight or behavior has changed. Dr. Christakis added that effects of obesity on social interactions (for example, divorce or breaking of friendship ties) also had been observed. In response to Dr. Ruvkun’s questions about whether influence is heightened at the extremes of obesity, Dr. Christakis pointed out that he and his colleagues had looked at that but were not sure how to interpret the observed effects. They used continuous measures of obesity and saw it at every point of the spectrum, and they dichotomized obesity to make associations easier to discern.

Dr. Khosla asked how applicable Dr. Christakis’ findings would be to schools and adolescent populations and what kind of insights the work might provide for intervention. Dr. Christakis reported that empirical data have been gathered on children as part of the National Longitudinal Study of Adolescent Health and are under analysis. One paper published in the Archives of Pediatrics & Adolescent Medicine (Strauss and Pollack, 2003;157:746-752) showed that obese adolescents were at the periphery of social networks. In terms of interventions, Dr. Christakis suggested identifying opinion leaders, or individuals particularly influential in a person’s network. He emphasized the potential for health policy if the notion of groups making choices together was considered and noted that externalities from interventions typically have been underestimated.

B. Geriatrics and Clinical Gerontology: Efficacy of a Hip Protector To Prevent Hip Fracture in Nursing Home Residents—The HIP PRO Randomized Controlled Trial

Dr. Douglas Kiel (Harvard Medical School) presented the results of his recent clinical trial of hip protectors to prevent hip fracture, called the Hip Impact Protection Project, or HIPPRO (JAMA 2007; 298:413-422).Past studies of the efficacy of hip protectors to prevent hip fracture in nursing home residents have had conflicting results, possibly due to potential biases from clustered randomization designs and modest adherence to intervention. Therefore, Dr. Kiel’s team conducted a study to determine whether an energy-absorbing and energy-dispersing hip protector would reduce the risk of hip fracture when worn by nursing home residents.

Dr. Kiel, and his colleagues from the University of Maryland, Baltimore, Washington University, St. Louis, the University of North Carolina, and Maryland Medical Research Institute in Baltimore, conducted a randomized controlled clinical trial in which 37 nursing homes were randomly assigned to having residents wear a 1-sided hip protector on the left or right hip. Participants were nursing home residents who consented and adhered to the hip protector use during a 2-week run-in period. Mean duration of participation was 7.8 months. None were withdrawn because of adverse effects.

When residents were enrolled into the study, they were given undergarments with a 1-sided hip protector made of an outer layer of polyethylene backed by a hard high-density polyethylene shield that was backed by ethylene vinyl acetate foam. Each facility was visited 3 times per week to assess adherence and provide staff support. The main outcome of the study, hip fractures, were all adjudicated by an Endpoint Committee masked to whether the hip fracture had occurred on a padded or an unpadded hip.

After a 20-month follow-up (676 person-years of observation), the study was terminated due to a lack of efficacy. The incidence rate of hip fracture on protected vs unprotected hips did not differ. For the nursing home residents with greater than 80% adherence to hip protector use, the incidence rate of hip fracture on protected vs unprotected hips did not differ. Overall adherence was 73.8%.

Dr. Kiel and his colleagues concluded that they were unable to detect a protective effect on the risk of hip fracture, despite good adherence to protocol. These results add to the increasing body of evidence that hip protectors, as currently designed, are not effective for preventing hip fracture among nursing home residents. Dr. Kiel feels that potentially better hip protectors should be investigated in larger studies after rigorous laboratory testing of the energy absorbing capacity of a variety of products.  An international group of investigators in the field are currently meeting to identify future needs for research in the field.

Dr. Garber recalled being disappointed with these findings when they appeared in JAMA. He suggested that hip fractures might have a torsion component that would not be modified by the use of a hip protector and that people wearing hip protectors might feel more confident and try to move more. Dr. Kiel acknowledged that some falls are not purely lateral, and he added that fractures might also result from people tensing their muscles as they fall. In addition, NACA has discussed an add-on study to examine the possibility of increased confidence and mobility. However, reporting and the use of charts are fairly crude. Dr. Kiel suggested the use of accelerometers as a better way to measure activity.

Dr. Siu asked whether the underlying fracture rate was higher or lower in the study population than within the general nursing home population. Dr. Kiel and his colleagues also wondered whether they could examine trends before and after the intervention. However, the people participating in the HIPPRO study represented a small minority of the general population, the turnover rate was somewhat high, and information about pre-intervention fracture rates was not available because of the record keeping and the quality of care.

In response to questions from Dr. Greengard about bilateral protection, Dr. Kiel mentioned a consortium funded by the Canadian Institute for Health Research to further explore hip protection. Dr. Kiel and colleagues have developed a grant application as part of this consortium to determine the kind of testing to do next. Dr. Kiel pointed out that reductions in hip fracture were observed in studies done in Japan and Denmark and speculated that these observations had more to do with the study design than with any ethnic differences.

Dr. Khosla mentioned other types of protection; for example, a belt with a motion sensor attached to a device that would inflate when a person falls. Dr. Kiel acknowledged that such technology has been suggested previously but is expensive. He also mentioned a bed system that induces a floor transformation to an energy-absorbing surface if someone tries to get out of bed. This, too, would be expensive, but it might be beneficial for high-risk groups.

Dr. Hodes asked about engineering explanations for the failure of the HIPPRO study. Dr. Kiel discussed conversations with the engineers in the consortium and pointed out that basic drop experiments with hip protectors are flawed. More accurate measures of the energy required to break elderly hips, as well as more accurate thresholds, are needed. The consortium is working on developing the best testing system, threshold, and clinical trial.

C. Biology of Aging: Stem Cell Aging

Dr. Sean Morrison (University of Michigan) covered two subjects in his presentation: (1) Why old tissues have less regenerative capacity than young tissues and (2) whether stem cell chromosomes segregate asymmetrically.

Stem cells change properties with age, and the reduced potential for self-renewal is a fundamental aspect of the aging process. However, few mechanistic explanations for this phenomenon have been available. Even as progress has been made in model systems such as fruit flies and worms, studying stem cell renewal in mammalian tissue is more difficult because the aging knockout mouse is an expensive and risky endeavor.

Networks of proto-oncogenes and tumor suppressors regulate cancer cell proliferation, but they play similar roles in the self-renewal of normal mammalian stem cells. Dr. Morrison and his colleagues studied the network involving the proto-oncogene Bmi-1 and the tumor suppressor genes Ink4a/ARF (Ink4a). Bmi-1–deficient mice appear to represent a model of accelerated aging. They die by postnatal day 30 and have few to no stem cells in their brains, hematopoietic systems, testes, or other regions known to maintain stem cell populations throughout adult life. Dr. Morrison and his colleagues have learned that stem cells consistently need tumor suppressor–proto-oncogene mechanisms to maintain self-renewal and persist throughout adult life. In the absence of these mechanisms, senescence pathways turn on and shut down self-renewal.

To determine what happens in the context of normal aging, Dr. Morrison and colleagues studied a population of neural stem cells that persist throughout adult life in mice. These cells generate neurons that migrate into the olfactory bulb and regulate one’s ability to discriminate new smells. Dr. Morrison and his colleagues administered the thymidine analogue bromodeoxyuridine (BrdU) to label stem cells in young adult and older adult mice then cut coronal sections from the forebrain. These experiments revealed a three- to fourfold decline in stem cell proliferation in older mice compared with younger mice. Stem cell renewal and regeneration also appeared to decline. Similar results were observed in Bmi-1–deficient mice. Dr. Morrison and colleagues found that Ink4a expression, which is associated with cellular senescence, increased with age, suggesting that Ink4a expression causes the decline in stem cell activity and neurogenesis.

Dr. Morrison and colleagues generated mice deficient in Ink4a. Although this deficiency had no effect on the frequency of cells that form stem cell colonies in young adult mice, the frequency was increased in older mice. Moreover, self-renewal potential and, to a small degree, overall proliferation increased in older mice deficient in Ink4a. The earliest progenitors in the subventricular zone were most sensitive to these effects. BrdU experiments revealed substantially more newly born stem cells in Ink4a-deficient mice as well as a higher rate of neurogenesis. Thus, the need to suppress cancer and the need for rapid cell division are balanced throughout life, and the balance shifts with age. Tumor suppressor mechanisms are turned off or less active in fetal development, where cells must divide rapidly to create tissues. Tumor suppression and cell proliferation become more balanced as an individual moves into early adulthood, where stem cells are mostly quiescent unless they need to divide to repair tissue. In old age, where the risk for cancer increases, tumor suppressors such as Ink4a are ramped up.

Two other papers were published at the same time as that by Dr. Morrison’s group. Dr. David Scadden’s group published similar results observed in the hematopoietic system, and Dr. Ned Sharpless’ group published similar results in the pancreas. Since then, several groups have conducted single nucleotide polymorphism analyses to examine genes associated with various aging-related diseases, including type 2 diabetes, coronary heart disease, and myocardial infarction. The Ink4a locus was identified in all these analyses, suggesting that Ink4a is important not only in regulating stem cell aging but also in pathways underlying aging-related diseases.

Dr. Morrison then discussed protective mechanisms used by stem cells. It has long been hypothesized that because stem cells are mitotically active throughout adult life, there is a risk for accumulating mutations. Stem cells might protect themselves by segregating chromosomes asymmetrically when they divide, retaining the old or immortal strands and segregating the new strands into daughter cells that will differentiate. The immortal strand model would predict that BrdU incorporated under steady-state conditions would be lost at the first division. Conversely, the model would predict that BrdU administered when stem cells are expanding under symmetrically dividing conditions would be incorporated by older strands and that once these cells resume asymmetrical division, BrdU-labeled strands would be retained indefinitely. On the basis of the rates of BrdU incorporation, one would predict that stem cells will lose BrdU at their first division once BrdU is removed from the environment and that less than 1 percent of the hematopoietic stem cells would retain BrdU after 70 days, if the cells indeed follow the immortal strand model. If chromosomes are segregated randomly, however, one would predict a slower loss of BrdU once this analog is removed from the environment.

Dr. Morrison and colleagues used BrdU-labeling experiments to assess this hypothesis in the hematopoietic system, based on the kinetics of BrdU incorporation. In so doing, they found some evidence that stem cells segregate chromosomes randomly. However, they also found that BrdU retention was a poor marker of hematopoietic stem cells (HSCs) because it offered poor sensitivity and specificity and because BrdU retention was not a general feature of adult HSCs. To test the immortal strand model directly, Dr. Morrison and colleagues administered chloro-BrdU (ClBrdU) to mice for 10 days, then iodo-BrdU (IBrdU) for another 10 days. They found that the frequency of cells positive for ClBrdU and IBrdU was similar to the frequency of cells positive for ClBrdU alone multiplied by the frequency of IBrdU-positive cells, consistent with what is predicted for random segregation. Dr. Morrison’s group conducted another experiment in which stem cells were labeled in vivo then sorted into different wells of a 96-well plate. In examining all the daughter cells after one or two rounds of cell division, there were no circumstances under which BrdU was preferentially inherited by some daughter cells and not others.

On the basis of these observations, Dr. Morrison and colleagues concluded that HSCs do not follow the immortal strand model. Although some evidence of asymmetric segregation has been observed in studies of muscle satellite cells, asymmetric segregation is not a general feature of stem cells. Thus, aging stem cells, particularly HSCs, must use other mechanisms to avoid the accumulation of mutations.

Dr. Schatten asked whether aging-related changes in Ink4a in embryonic stem cells differ in vitro from those occurring in vivo. Dr. Morrison responded that there were differences but that the process for Ink4a is somewhat complicated. Ink4a is regulated differently in vitro versus in vivo. Because it is meant to be a surveillance mechanism for the cell, it is tightly regulated in vivo, and its expression is difficult to see in the adult mouse. In cultured cells, however, the stress of cell culture induces Ink4a expression. Dr. Morrison cautioned that in vitro experiments can be misleading and that embryonic stem cells might not be a good model. He further noted differences between mouse cells and human cells, and he added that when cells are selected that can grow indefinitely in culture, the ability of those cells to induce Ink4a is selected against.

Dr. Hodes asked whether there are multiple occasions when non-telomere–based senescence can be reversed by modulating Ink4a expression. Dr. Morrison responded that it was difficult to identify senescent cells in mice because these cells were defined in vitro, and available markers are not very good. In Ink4a knockouts, however, his lab has observed increased proliferation and neurogenesis. Likewise, Dr. Sharpless’ laboratory saw similar results among pancreatic beta cells, which are known to become depleted with age. In addition, Dr. Scadden’s laboratory was able to extend serial transplantation of HSCs by using Ink4a-deficient cells. Dr. Morrison concluded that, at least in these contexts, progenitor activity in tissues increases in the absence of Ink4a.

Dr. Khosla asked whether changes in Ink4a were intrinsic or resulted from the microenvironment. Dr. Morrison speculated that Ink4a changes were autonomous in the cell.

D. Neuroscience and Neuropsychology of Aging: How Individual Are Neurons? Necessity to Identify Similarities and Differences Among Brain Neurons

Progress in understanding many neuropsychological and neurodegenerative diseases has been hampered by the complex nature of the brain. An estimated 100 billion to 400 billion nerve cells exist in the brain, in addition to glia, which appear to play an important role in nerve cell function. Nerve cells differ widely and appear to fall into several subtypes. Yet neuroscientists have tried to study the biochemistry of nerve cells without any idea of the similarities and differences among them.

Dr. Paul Greengard’s laboratory has collaborated with Dr. Nathaniel Heintz’s laboratory to approach the problem of nerve cell heterogeneity using a technique called “BACarray transcriptional profiling.” They initially studied the striatum, a relatively large area of the brain that seems to be almost unparalleled in its simplicity. About 95 percent of all nerve cells in the striatum are of a single morphological type known as the medium spiny neuron, which exist in two subtypes based on the way they transmit dopamine signals. In the direct pathway, dopamine activates D1 receptors in the medium spiny neurons, which stimulates these cells to inhibit output nuclei in the substantia nigra. In the indirect pathway, dopamine acts on D2 receptors in the medium spiny neurons and inhibits their function in the globus pallidus, resulting in less excitatory output of the subthalamic nuclei. Dopamine thus causes a synergistic action involving increased inhibition in one area and decreased excitation in another.

Because the two types of medium spiny neurons are morphologically indistinguishable and anatomically intermixed, further studying their composition has been almost impossible. Moreover, many techniques to study these cells involve postmortem analysis, which can introduce artifacts. Dr. Greengard and colleagues fused a cell type–specific promoter to a ribosomal protein tagged with green fluorescent protein (GFP), or myc, such that mice carrying this transgene would have tagged protein only in those cells which contain the specific cell type promoter. They removed sections of the striatum, purified polysomes, performed immunoprecipitation based on the tagged protein, and extracted the actively translated RNA messages for BACarray analysis. In so doing, they identified several hundred new transcripts specific to medium spiny neurons in the direct or indirect pathway.

BACarray analysis can be used to examine genetic, pharmacologic, and environmental changes in transcription. For example, Dr. Greengard and colleagues have studied the effects of cocaine on medium spiny neuron signaling. Cocaine induces a large increase in the frequency of firing among direct cells but not among indirect cells. The use of BACarray analysis to study molecular differences among closely related cell types also can be applied to studies of neurodegenerative diseases such as AD and Parkinson’s disease. For example, direct pathway cells are vulnerable in Parkinson’s disease whereas indirect pathway cells are not. BACarray analysis can aid in the identification of proteins that confer vulnerability in one cell type and resistance in the other.

Thus, various neurons in the brain, even those that appear to be closely related, differ dramatically in mRNA and protein composition. Characterizing the molecular profile for each of these cell types will provide an unprecedented database of information on the individuality of neurons. This information should then permit a vastly increased understanding of distinct physiological characterizations of each cell type, an understanding of the etiology of various neurological and psychiatric disorders, and development of therapeutics specific to nerve cell type.

Dr. Hodes asked about Dr. Greengard’s assessment of the facility or resource in which to deposit the data he and his colleagues generate. Dr. Greengard responded that the group intends to publish their database and that their paper contains a full list of proteins in each pathway. They will do the same when they identify proteins involved in cells vulnerable and invulnerable to AD. They also are comparing their database with the Genset database and the Allen Brain Atlas. Dr. Greengard cautioned that the Allen database is full of errors, but he also pointed out that this group is redoing their study and would most likely have more reliable data in the future.

Dr. Hodes also asked whether, at this early stage, differences in vulnerability were related to the differential transduction of signals or to downstream events. Dr. Greengard responded that in the case of dopamine and Parkinson’s disease, differences in vulnerability most likely were related to inherent protein differences. The types of differences are not known for AD. It is not clear in this disease whether neurons die because of proteins they express or because of differences in the neurotransmitters that activate them. Dr. Greengard expressed the hope that by comparing different cell types, he and his colleagues would be able to identify proteins that confer vulnerability or resistance.

VIII. ADJOURNMENT

The 102nd meeting of the National Advisory Council on Aging was adjourned at 1:04 p.m. on September 26, 2007. The next meeting is scheduled for January 29–30, 2008.

IX. CERTIFICATION

I hereby certify that, to the best of my knowledge, the foregoing minutes and attachments are accurate and complete.3

Richard J. Hodes, M.D.
Chairman, National Advisory Council on Aging
Director, National Institute on Aging

Prepared by Robin Barr, D.Phil.
With assistance by Rose Li and Associates, Inc.

 

  1. For the record, it is noted that members absented themselves from the meeting when the Council discussed applications (a) from their respective institutions or (b) in which a conflict of interest may have occurred. This procedure only applied to applications that were discussed individually, not to “en bloc” actions. (Back to text.)

  2. For the record, it is noted that members absented themselves from the meeting when the Council discussed applications (a) from their respective institutions or (b) in which a conflict of interest may have occurred. This procedure only applied to applications that were discussed individually, not to “en bloc” actions. (Back to text.)

  3. These minutes will be approved formally by the Council at the next meeting on January 29–30, 2008, and corrections or notations will be stated in the minutes of that meeting. (Back to text.)

Attachment A: Roster of the National Advisory Council on Aging

MEMBERSHIP ROSTER
NATIONAL ADVISORY COUNCIL ON AGING
NATIONAL INSTITUTE ON AGING

(Terms end December 31) (*WGoP Member)

Chairperson
Richard J. Hodes, M.D.
Director, National Institute on Aging
National Institutes of Health
Bethesda, MD

Kenneth V. Brummel-Smith, M.D. (2009)
Professor and Chair
Department of Geriatrics
Florida State University College of Medicine
Tallahassee, FL

*John T. Cacioppo, Ph.D. (2007)
Blake Distinguished Service Professor
Department of Psychology
Director, Center for Cognitive and Social Neuroscience
University of Chicago
Chicago, IL

Peggye Dilworth-Anderson, Ph.D. (2010)
Professor, Health Policy & Administration
Associate Director, Aging and Diversity/ Institute on Aging
University of North Carolina, Chapel Hill
Chapel Hill, NC

Carl Eisdorfer, Ph.D., M.D. (2009)
Knight Professor and Director
Center on Aging
University of Miami
Miami, FL

Lawrence M. Friedman, M.D. (2009)
Independent Consultant
11712 Farmland Drive
Rockville, MD

Mary Ganguli, M.D., M.P.H. (2009)
Professor of Psychiatry, Neurology, and Epidemiology
Department of Psychiatry
University of Pittsburgh
Pittsburgh, PA

Alan M. Garber, M.D., Ph.D. (2007)
Director
Center for Primary Care and Outcomes Research
Center for Health Policy
Stanford University
Stanford, CA

Paul Greengard, Ph.D. (2008)
Vincent Astor Professor
Laboratory of Molecular & Cellular Neuroscience
The Rockefeller University
New York, NY

S. Michal Jazwinski, Ph.D., (2010)
Professor
Department of Medicine
Tulane University Health Sciences Center
New Orleans, LA

Sundeep Khosla, M.D. (2010)
Professor, Endocrine Research Unit
Division of Endocrinology, Metabolism, & Nutrition
Mayo Clinic College of Medicine
Rochester, MN

*Virginia M.-Y. Lee, Ph.D. (2007)
Professor
Dept of Pathology & Laboratory Medicine
Univ of Pennsylvania School of Medicine
Philadelphia, PA

Mills, Terry L., Ph.D. (2008)
Dean, Division of Humanities & Social Sciences
Morehouse College
Atlanta, GA

*John C. Morris, M.D. (2009)
Professor
Washington University School of Medicine
St. Louis, MO

Orien Reid (2010)
Chairman, Alzheimer's Disease International
President, Consumer Connection
Laverock, PA

Gary B. Ruvkun, Ph.D. (2007)
Professor, Molecular Biology
Massachusetts General Hospital
Boston, MA

*Gerald P. Schatten, Ph.D. (2009)
Professor, Pittsburgh Development Center
Magee-Womens Research Institute
University of Pittsburgh
Pittsburgh, PA

Albert L. Siu, M.D., M.S.P.H. (2008)
Ellen and Howard C. Katz Professor
Chairman, Brookdale Department of Geriatrics and Adult Development
Mount Sinai School of Medicine
The Mount Sinai Medical Center
(and Director, Geriatric Research, Education, and Clinical Center, Bronx Veterans Administration)
New York, NY

*Mary E. Tinetti, M.D. (2008)
Gladys Phillips Crofoot Professor
Department of Internal Medicine, Epidemiology, and Public Health
Director, Program on Aging
Yale University School of Medicine
New Haven, CT

EX OFFICIO MEMBERS

Michael O. Leavitt
Secretary
Department of Health and Human Services
Hubert H. Humphrey Building
Washington, D.C.

Elias Zerhouni, M.D.
Director
National Institutes of Health
Public Health Service
Bethesda, Maryland

James F. Burris, M.D.
Chief Consultant
Geriatrics & Extended Care Strategic Healthcare Group
Department of Veterans Affairs
Washington, D.C.

Kenneth G. Pugh, M.D.
Commander, MC, U.S. Navy
Department of Medicine
National Naval Medical Center
Bethesda, MD

John Wren
Director, Center for Planning & Policy Development
U.S. Administration on Aging, DHHS
Washington, D.C.


Page last updated Sep 26, 2008