September 23, 2004
Attachment A - Roster of the National Advisory Council on AgingAttachment B - Director's Status Report
The 93rd meeting of the National Advisory Council on Aging (NACA) was convened on Thursday, September 23, 2004, at 8:18 a.m., in Building 31, Conference Room 6, National Institutes of Health (NIH), Bethesda, Maryland. 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 Wednesday, September 22, 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 Thursday, September 23.
Council Participants:Dr. Marie A. Bernard Dr. Elizabeth H. Blackburn Dr. John T. Cacioppo Dr. David V. Espino Dr. Linda P. FriedDr. Alan M. GarberDr. F. Michael Gloth, III Dr. Eugene M. Johnson, Jr. Dr. Lewis H. Kuller Dr. Ronald D. Lee Dr. Virginia M.-Y. Lee Dr. Spero Manson Dr. Stanley B. Prusiner Ms. Judith A. Riggs Dr. Leon J. Thal
Ex-officio Participants:Dr. James Burris (Department of Veterans Affairs) Dr. Kenneth G. Pugh (U.S. Navy) Mr. John Wren (U.S. Administration on Aging)
Absent: Dr. Melissa M. Brown Dr. Peter W. NauertDr. Gary Ruvkun
The Council Roster, which gives titles, affiliations, and terms of appointment, is appended to these minutes as Attachment A.
Members of the Public Present: Dr. John Haaga, Population Reference Bureau Ms. Mary Jo Hoeksema, Population Assoc of America & Association of Population Centers Ms. Pat Kobor, American Psychological Association Dr. Alan Kraut, American Psychological Society Dr. Rose Maria Li, Rose Li and Associates, Inc. Dr. Nancy Moy, SRI International Dr. Christopher Murray, Harvard University Dr. Marco Pahor, Wake Forest University Mr. Tim Perrin, American Association for Geriatric Psychology Dr. Thomas Rando, Stanford University Dr. Eileen Resnick, Society for Women’s Health Research Dr. Carol Schutz, Gerontological Society of America
In addition to NIA staff, other Federal employees attending were: Dr. Deborah Carper, National Eye Institute, NIH Arlene Chou, NIBIB Dr. Francis Collins, National Human Genome Research Institute, NIH Dr. Charles Hollingsworth, Center for Scientific Review, NIH Dr. Anthony Demsey, Office of Extramural Research, Office of the Director, NIH Ms. Denise Manouelian, National Institute of Diabetes and Digestive and Kidney Diseases, NIH Mr. Larry Morton, Office of Extramural Research, NIH Ms. Maria Stagnitto, National Heart, Lung & Blood Institute, NIH
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 552b(c)(4) and 552b(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 835 applications requesting $867,024,280 for all years underwent initial review. The Council recommended 481 awards for a total of $634,633,080 for all years. The actual funding of the awards recommended is determined by the availability of funds, percentile ranks, priority scores, and program relevance.
Dr. Miriam Kelty called the meeting to order at 8:18 a.m. on Thursday, September 23, 2004 and welcomed members. Dr. Richard Suzman, Associate Director for the Behavioral and Social Research (BSR) Program, announced the availability of a new National Academy of Sciences publication, Understanding Racial and Ethnic Differences in Health in Late Life: A Research Agenda.
Director’s Status ReportDr. Hodes began with remarks on the status of the fiscal year (FY) 2005 budget. As there is not yet a budget, Dr. Hodes reviewed two current funding scenarios. The FY2005 House mark and President’s budget are the same. They provide an average cost increase of 1.9 percent for noncompeting continuation awards and allow an average cost increase of 1 percent for competing research project grants (RPGs). The Senate mark provides for an average cost increase of 3 percent for noncompeting continuation awards (representing full-commitment level) and a 2-percent average cost increase for competing RPGs. The Senate language reflects concern about a policy which does not provide full maintenance of commitments.
Dr. Hodes reviewed NIA’s budget history in current and constant (normalized against inflation) dollars. NIA’s FY2004 budget is $1.025 billion. The President’s budget, which is also the House mark, for FY2005 is $1.056 billion. This 3 percent increase is the same as for the NIH as a whole. The Senate mark is $1.095 billion, about $40 million more than the President’s budget, reflecting a total increase of nearly $70 million from FY2004 or a 6.8-percent increase, which is well above the 4 percent average increase proposed for the NIH by the Senate. The above-average increase proposed for NIA is presumably the result of support for research that is centered on Alzheimer’s disease, as well as other aging-related initiatives.
The average cost of competing RPGs is based on an amount that is designed to generate a set number of awards. For FY2004, the average cost was about $398,900 per grant, a modest increase over the $389,000 average in FY2003. In FY2004, NIA was able to achieve a payline at approximately the 17th percentile by imposing an average cost reduction of 18 percent for RPGs. Under the President’s budget for FY2005, the average cost would be $403,600, a small increase above FY2004. The Senate’s mark would result in an average cost estimate of $407,000. The House and Senate cost constraints across NIH create a formulaic constraint on the minimum number of grant awards. Limiting average increases in competing and noncompeting grants has the effect of increasing the number of grants that will be awarded. These constraints factor into considerations about portfolio balance; decisions about whether to fund an expensive grant are influenced by what will be displaced. Dr. Hodes reported that some have speculated that the average cost constraints are a response to sensitivity over the impact of slowed budget growth on multiple parameters including the number of grants, which typically has received public and political attention.
In response to questions from Council members, Dr. Hodes stated that contracts are not subject to average cost calculations, but shifting RPG funds to the contract line to fund a large project would make it more difficult to fund the required number of grants. NIA also is considering how to allow multiple related applications to be submitted and reviewed in a coordinated fashion as a way to meet scientific goals.
The total funding available for competing grants is estimated at $167 million for FY2004 or about 418 new grant awards. By the President’s budget, funds available for new grants in FY2005 would decline to $165 million, and the number of RPG awards would decline to 410. In sharp contrast, the Senate mark is estimated at $195 million, nearly a $30 million or 18-percent increase that would be associated with 480 new grant awards.
The House and Senate must meet in conference to produce a budget that is acceptable to the President. It is likely that the NIH will be operating under a continuing resolution. A continuing resolution usually means operating at the previous-year level with constraints against initiating new projects or activities. Funding decisions early in FY2005 will be made in the context of uncertainty about final funding levels. Like other Institutes, NIA will strive to ensure that funding is not overly restrictive. There is a need to determine how to use imposed cost reductions and/or to balance expensive and less expensive research in order to meet formulaic targets. Dr. Hodes welcomed Council members’ input on how to address the challenges of the situation constructively.
Dr. Kelty noted that a written version of the Director’s Status Report contains additional budget information, further information about the NIH Roadmap initiatives, and a listing of congressional briefings and hearings involving NIA staff, as well as a list of relevant notices and initiatives published in the NIH Guide and information about staff changes. Dr. Kelty introduced four new NIA staff members: Dr. John Phillips, economist in the BSR Program; Dr. Lorraine Fitzsimmons, Director of the Office of Policy, Analysis, and Evaluation; and two grants management specialists, Mr. Joseph Ellis and Ms. Janice Peterson. Dr. Kelty also referred Council members to a summary of meetings and workshops, and stated that current Council members have an open invitation to attend any NIA-organized meeting at their own expense.
Future Meeting Dates
February 1–2, 2005 (Tuesday–Wednesday) May 24–25, 2005 (Tuesday–Wednesday) September 27–28, 2005 (Tuesday–Wednesday)
Consideration of Minutes of Last MeetingThe minutes of the May 2004 meeting were considered. A motion was made, seconded, and passed to approve the minutes.
Each retiring Council member was invited to make comments and was presented with a certificate of appreciation and letter signed by DHHS Secretary Tommy Thompson.
Dr. Hodes first recognized Dr. David Espino, acknowledging his dedicated efforts and contributions to NIA on planning and development activities, and his chairmanship of the Minority Task Force. Dr. Espino thanked his fellow Council members, especially Minority Task Force members, and NIA staff, for their support and assistance.
He particularly thanked NIA staff with whom he has worked closely during his tenure: Drs. Taylor Harden, Evan Hadley, Sid Stahl, Richard Suzman, Robin Barr, and Miriam Kelty. He also thanked Dr. Judy Salerno for her leadership on the Beeson Career Development Awards in Aging Research Program and Ms. Jeannette Wilson, NIA Council Manager, for her support and assistance. Dr. Hodes described Dr. Lewis Kuller as an active and vocal member whose perspective has come from a variety of disciplines and associations with a number of NIH Institutes. Dr. Kuller thanked everyone for what he described as having been a phenomenal learning experience. He recalled his early association with the NIA intramural program and reminisced about taking courses from Dr. Nathan Shock’s group. Besides the fact that he will no longer be protected from onerous NIH tasks as a result of his membership on Council, Dr. Kuller expressed only one disappointment—that the Council has not been more successful in publicizing the Institute’s work and bringing greater visibility to NIA-supported research, which could then translate into greater funding from Congress for important research. Based on his experience with many NIH Institutes, Dr. Kuller observed that NIA is the most enthusiastic, effective, and productive group he has ever worked with and reiterated his strong appreciation for NIA staff efforts.
Dr. Hodes thanked Dr. Stanley Prusiner for his astute review of specific applications and programs, and for his forward and innovative thinking that inspired some of the Institute’s initiatives. He observed that early on Dr. Prusiner asked the Institute to address the serious shortage of clinically trained individuals committed to research careers. Drs. Prusiner, Espino, and others worked with NIA staff to address this concern; the Beeson Program is the result.
Dr. Prusiner thanked his fellow Council members and NIA staff for a rich experience. He stated that he has been passionate for years about the training of physician-scientists and was delighted at the warm reception for this issue. He acknowledged the support of former Council member Dr. Dennis Ausiello, Dr. Espino, and others, particularly Dr. Salerno, for taking the effort to the finish. He added that Dr. Salerno successfully involved the Hartford Foundation to help support the Beeson Program. He termed the partnership an extraordinary example of innovation at the NIH led by NIA. Dr. Prusiner is proud to have been a part of this and is delighted with the outcome.
Finally, Dr. Hodes thanked Ms. Judy Riggs, who interacted with NIA in her capacity with the Alzheimer’s Association for many years prior to joining the Council. Ms. Riggs brought a public perspective to the Council in addition to representing a key constituency group. Ms. Riggs’ participation on the Council has given her greater insight into the process at NIA and Dr. Hodes praised her as a consistent and reliable attendee and contributor. Ms. Riggs thanked Dr. Hodes for the extraordinary privilege and learning experience. She said she has been struck by the dedication of the Council members to the entire research enterprise, and their extraordinary nurturing of that enterprise. She thanked NIA staff for their openness and responsiveness. She considered it an honor to be able to serve and appreciated Dr. Hodes’ and the Institute’s emphasis on trying to reinforce connections between the public and the scientific community. Ms. Riggs intends to continue work on improving the translation of science to policy and practice, and the behavior of those who are aging.
Dr. Espino reported on three main issues covered by the Task Force on Minority Aging Research at the September 22 meeting: (1) The National Research Council Report on Critical Perspectives on Racial and Ethnic Differences in Health in Late Life (NB Anderson, RA Bulatao, and B Cohen, Eds, Panel on Race, Ethnicity, and Health in Later Life, National Research Council, 2004) that contains ideas for new directions, particularly in tandem with NIA’s own strategic plan, including tracking minority recruitment; (2) a discussion about the perceived lack of prestige associated with a minority supplement. Some recipients choose not to list it on their CV; and (3) the difficulties often associated with addressing race and ethnic issues. The leadership of Dr. Taylor Harden navigating these difficult issues was acknowledged.
A. Biology of Aging: Aging, Stem Cells, and Tissue Regeneration Dr. Jill Carrington introduced Dr. Thomas A. Rando, Associate Professor of Neurology and Neurological Sciences at Stanford University, who was invited to present his work on tissue regeneration and stem cells. In addition to NIA support, Dr. Rando is funded by the Department of Veterans Affairs and the American Federation for Aging Research.
With age, there is a general loss of regenerative potential of most tissues. In addition to the gradual age-related decline in tissue structure, there is also an impaired ability of tissues to respond to an acute injury to regenerate and undergo repair. Both the gradual maintenance function and the acute regenerative response likely are mediated by the resident stem cells in the tissue. By most accounts, the number of stem cells in a tissue does not decline significantly with age. This raises a question as to why these stem cells do not function well in maintenance and repair in old tissues. At one end of the spectrum is the possibility that there are intrinsic, age-related changes in the cells themselves (“nature”). At the other end of the spectrum, stem cells retain all of their functional abilities with age, but the niche in which they reside undergoes age-related changes that preclude normal stem cell activation (“nurture”).
Dr. Rando’s group has studied this question using skeletal muscle as a model system. Isolating muscle stem cells (“satellite cells”) makes it possible to study their behavior in vitro. Quantitative analyses show that there is a small decline in satellite cell number with age, but there is a much greater decline in the regenerative potential of aged muscle than can be accounted for by the small decline in stem cell number. Thus, Dr. Rando has studied young, adult, and aged satellite cells to understand what age-related changes in the cells or their niches may account for the impaired regenerative response.
The researchers’ previous work had demonstrated the critical role of the Notch signaling pathway in satellite cell activation and proliferation from young animals. These studies demonstrated that the first change that occurs after injury is the increase in expression of the Notch ligand, Delta. Following this, the Notch signaling pathway is triggered in activated satellite cells. This is essential for the proliferative expansion of these cells and their movement down the myogenic lineage pathway to generate myoblasts, which are cells that ultimately form new muscle. If the Notch signaling pathway is inhibited, satellite cells fail to activate and regeneration is blocked.
Interestingly, there is a failure of expression of the trigger, Delta, in older muscle in response to injury. Therefore, satellite cells that are present cannot respond and instead of generating myoblasts to form new muscle, they remain inactive. If this Notch signaling pathway is activated experimentally, then old satellite cells activate normally and muscle regeneration is excellent. Therefore, old muscle can be made to regenerate as well as young muscle, as long as resident stem cells receive the right signals. It appears to be more of a problem of the environment in which the cells reside (a “nurture” problem) than of the cells themselves.
This observation led researchers to ask what it is about young animals that provides the appropriate environment. They turned to the model of parabiosis in which two animals can be joined together surgically and develop a shared circulation. The tissues of one animal become exposed to the circulating factors of the other animal. Strikingly, when old mice were connected to young mice parabiotically for 6 to 8 weeks, their muscles were “reprogrammed” to be more like young muscles. In response to injury, the old muscle expressed the trigger, Delta, and activated Notch signaling in muscle stem cells. These cells then proliferated well and regenerated the injured tissue successfully. This effect of parabiosis to a young animal was not only seen in muscle but was evident in other tissues as well. By analyzing progenitor cell proliferation in liver and brain of the aged partners, researchers found that there was an enhancement of stem cells in those tissues as well. Therefore, it appears that there are factors present in the serum of young animals that have a “rejuvenating” effect on stem cells in aged tissues. If the mice are then separated, the effect is maintained for several weeks and then declines. The question of duration and continuity of exposure required for activation deserves further exploration.
Dr. Rando and his team are continuing several aspects of this research. First, they are working to understand the similarities and differences in the age-related changes in stem cells across different tissues. Second, they are interested in determining the nature of the systemic factors in young animals that have the capacity to enhance tissue-specific stem cell activity. Finally, they are investigating how such a signal may work to reprogram the aged stem cells or the environmental niche in which they reside. Ultimately, they hope to contribute to the emerging field of regenerative medicine in which a better understanding of the biology of aging will be translated into healthier aging.
In response to questions, Dr. Rando stated that his team has not examined whether satellite cells in caloric-restricted old animals function as well as the same cells in young animals, or whether young mice with defects in progenitor cell proliferation could still activate changes in an older mouse. Dr. Rando also remarked that stem cells are multipotential and satellite cells are known to produce muscle primarily, but there is now increasing evidence that they will produce adipocytes and fat, and evidence that they will produce bone. Most interesting in terms of aging is the ability of these cells to transdifferentiate or become fat. Clearly, old muscle has more fat but no one knows where that fat originates.
B. Geriatrics and Clinical Gerontology: Aging, ACE Inhibition, and Physical PerformanceDr. Hadley introduced Dr. Marco Pahor, Professor of Medicine at Wake Forest University, who has studied the basis for loss of muscle strength and frailty in older people. His work is notable for its diversity of strategies, ranging from epidemiology to clinical trials to animal models. Dr. Pahor is supported primarily through an NIA-funded Claude Pepper Older American Independence Center as well as through several other grants.
Addressing and preventing disabilities in older populations is one of the major goals of geriatric medicine. In the prevention of disability, strategies include averting potentially comorbid and disabling diseases and targeting factors that often are not associated with disease such as biological factors, behavioral factors, and genetic, socioeconomic, and environmental factors. Whatever the cause of impaired functioning, the disablement process often is accompanied by sarcopenia or muscle loss, which is associated with virtually all identified disability risk factors. Clinically, the association between body composition and physical performance has been documented by several studies. Since loss of strength is greater than loss of muscle mass with age, the quality of remaining muscle may be reduced. Although there are limited data explaining potential physiological mechanisms that contribute to muscle quality, sarcopenia frequently is associated with fat accumulation, and percentage of body fat increases with age even if weight does not. However, the relationship between fat and muscle function may not be linear, suggesting that there may be an optimal ratio of lean-to-fat mass for physical function.
There are no definitive pharmacological interventions to prevent a decline in physical function either by modulating body composition or other means. One exception may be angiotensin-converting enzyme inhibitors (ACEIs). ACE is an important component of the renin-angiotensin system (RAS), the central hormonal regulator of blood pressure. Recent evidence suggests that ACEIs may improve physical function by direct effects on body composition in older persons, rather than through blood pressure-lowering effects. Clinical and genetic studies in humans and experimental evidence in animals suggest that modulation of the RAS is associated with metabolic and biochemical changes in skeletal muscle and fat, which in turn are changes associated with declining physical function. ACEIs may modulate this process through a variety of molecular mechanisms including their influence on oxidative stress, and metabolic and inflammation pathways.
Dr. Pahor’s team has described potential biological mechanisms of ACE inhibition and its contribution to declines in physical performance and changing body composition. Promising pharmaco-epidemiological studies and experimental evidence in animals suggest that there are appropriate models in which to study this effect. Indeed, there is a growing body of literature attributing ACEIs with the prevention of disabling diseases such as stroke, heart failure, hypertension, diabetes, and renal disease. ACEIs have been found to have a direct effect on skeletal muscle; improving energy metabolism; remodeling; increasing vasodilation and blood flow; improving capillary density; and inhibiting lipogenesis, which has a direct effect on adipose tissue. Dr. Pahor also presented some evidence that polymorphisms of the ACE gene may modify physical function response to physical exercise, providing further evidence of a close link between the ACE system and muscle.
Dr. Pahor called for more mechanistic studies in humans and animals; metabolic, body composition, and physical function outcome studies; investigations of the potential effect of angiotensin receptor blockers, enhanced epidemiological studies and behavioral or pharmacogenetic studies; and, ultimately, definitive randomized clinical trials (RCT) to support modifications in clinical practice. He pointed to the Trial of ACE Inhibition and Novel Cardiovascular Risk Factors and the Lifestyle Interventions and Independence for Elders Study as two examples of ongoing trials, the first a double-blind trial of fosinopril 40 mg for persons at high cardiovascular risk, and the second a pilot RCT of exercise to prevent disability. These initial studies will provide the foundation for more definitive studies.
C. Behavioral and Social Research: Understanding the Evolution of the Global Burden of DiseaseDr. Suzman introduced Dr. Christopher Murray, the Saltonstall Professor of Public Policy at Harvard University and Director of the Harvard University Initiative for Global Health.
Dr. Murray highlighted one of the key debates underlying different visions about the future of health. The mainstream view is that traditional societies, if one survives childhood, have low levels of the classic risk factors for noncommunicable diseases. Most well-known risks are income elastic so that epidemics of noncommunicable diseases would be seen as due to aging of the population and also to rises in age-specific death rates and incidence. On the other end of the spectrum is a growing body of literature that argues that exposure to both infection in childhood or nutrient or micronutrient deficiencies from fetal stage to about age 5 as represented, for example, by Barker and his colleagues, lead to sustained levels of increased noncommunicable disease risk (Barker DJ, The developmental origins of well-being. Philos Trans R Soc Lond B Biol Sci 359(1449):1359-66, Sep 29, 2004). If the nutrient deficiency theories and infection theories are correct at the macroscale, one may expect that adult noncommunicable disease death rates will be declining in parallel to what has happened historically for children, but with a 30- to 70-year time lag. Future development of population health including disability rates in middle- and high-income countries depends on the balance of these two competing views of the epidemiological transition. Dr. Murray presented data from the NIA-supported human mortality database that contains the longest time sequence of vital registration data available, going back to 1750 for Sweden. Dr. Murray focused on the declining probability of death between ages 15 and 60 (45q15), which he considered to be a robust measure over time and across place because age misreporting is less of an issue for this age group. Randomly selecting from countries with reasonably complete vital registration systems, Dr. Murray showed generally sustained declines in adult mortality. There is a growing variance in the trend of adult mortality in the last two decades but little evidence of rises associated with an “evils of westernization” model. However, he highlighted three exceptions: (1) The mortality pattern in the Russian Federation associated with alcohol restriction policies; (2) a subgroup of populations in the U.S. with no improvement in mortality; and (3) those parts of sub-Saharan Africa with HIV epidemics above 5 percent seroprevalence where adult mortality for males and females is rising dramatically.
Dr. Murray pointed to evidence of steady declines in age-specific death rates overall from noncommunicable diseases. This is more in keeping with the Barker infection hypotheses than with the expected impact of income-elastic risks. Although the interpretation of mortality declines is debatable because of differences in cause attribution, Dr. Murray concluded that after taking into account causes of death assigned to poorly defined codes, noncommunicable disease age-specific mortality rates have been declining for most countries. The risk of dying from noncommunicable diseases appears to be higher in low- and middle-income regions than it is in Japan, Australia, New Zealand, Western Europe, or North America. This is consistent with the idea that overall risk of noncommunicable disease death declines with improvements in life expectancy and development.
The declines in age-specific noncommunicable disease death rates could be associated with rises or declines in functional health status/disability. Self-reported health status items provide a method for measuring individual or population health in multiple domains. The main challenge is to make self-reported information from individuals comparable. Anchoring vignettes provide one cost-effective method to enhance the comparability of self-reported survey items. Respondents answer the same item for a series of descriptions of a fixed level on a domain. The World Health Survey 2003 included anchoring vignettes in 71 country population surveys. Dr. Murray noted that people’s use of response scales may vary or change over time, so that over decades the stability of response scales may be called into question. It also was noted during the discussion that a growing propensity to declare race and ethnicity and a mismatch between race/ethnicity data in census reports and on death certificates have complicated comparisons by race/ethnicity in the U.S. This issue has defied solutions to date and is particularly problematic for Hispanic subgroups.
In a series of papers, Dr. Murray and his colleagues presented two sets of risks: there are the risks of the very poor in poor countries—underweight, unsafe sexual practices, unsafe water, indoor air pollution, iron deficiency, zinc deficiency, vitamin A deficiency, unsafe injections, and lack of contraception; there are seven major risks that drive noncommunicable diseases across middle, low, and high-income countries—blood pressure, tobacco, alcohol, high cholesterol, obesity, low fruit and vegetable intake, and physical inactivity. These seven factors seem to be where focus should be placed to understand trends in noncommunicable diseases worldwide. (Ezzati M, et al., Selected major risk factors and global and regional burden of disease, Lancet 360(9343): 1347-1360, 2002; Ezzati M, et al., Estimates of global and regional potential health gains from reducing multiple major risk factors, Lancet 362(9380): 271-280, 2003; Rodgers A, et al. Distributions of major global health risks: Findings from the global burden of disease project, PLoS Medicine 1(1): e27, 2004)
Available data suggest that obesity rises dramatically at very low incomes. The highest observed levels of obesity are in the Middle East; Jordan shows rates higher than in the U.S. Cholesterol rises somewhat later in terms of economic development than obesity. The U.S. National Health and Nutrition Examination Survey data suggest that at any given level of household income, obesity is increasing. There is, therefore, a global rise in obesity, including areas in the U.S., which is affecting subgroups differentially.
To understand world trends, particularly in middle-income and low-income countries in their early phases of the obesity expansion, Dr. Murray believes it is important to understand trends in the seven key risk factors. Obesity is one of the few risks that is increasing, unlike cholesterol levels. Tobacco use is declining in high-income countries but is on the upswing in middle-income countries. The research team is working on indirect estimation techniques to correct vital registration data, employing exploratory strategies such as sibling survival questions with some correction in household surveys. Additional work is needed to clarify ambiguity about cause-of-death coding. It is important to validate the anchoring vignette strategy through comparison with performance tests. Another possibility is direct measurement of energy expenditure as a proxy for exercise and diet to understand obesity changes.
Dr. Murray also was asked to comment on prospects for population-level interventions that may be successful at a public health level. Attention has focuses on blood pressure, cholesterol, and tobacco because interventions for these are available. Advertising bans, taxation, decreasing access for different groups, and making smoking socially uncomfortable all seem to lower tobacco use.
D. Neuroscience and Neuropsychology of Aging: The Amyloid Cascade HypothesisDr. Marcelle Morrison-Bogorad introduced Dr. Virginia M.-Y. Lee, Professor of Pathology and Laboratory Medicine at the University of Pennsylvania School of Medicine, and a Council member. NIA has been funding Dr. Lee’s amyloid research for more than ten years.
Dr. Lee presented results from experiments conducted by a former graduate student, Mr. Eddie Lee, as part of his thesis. One of the characteristic pathologic lesions of Alzheimer’s disease (AD) is the senile plaque, composed predominantly of the amyloidogenic peptide Beta Amyloid (Aβ). Although the proteases that cut the amyloid precursor protein (APP) to produce Aβ have been identified, the mechanisms leading to senile plaque formation in vivo are still obscure.
Both the amount and type of Aß produced are important for AD pathogenesis. Thus, increased production of Aß or increased production of Aß1-42 relative to Aß1-40 can accelerate the production of senile plaques and the development of AD. In addition, subcellular sites where Aß is produced also may play a role in AD pathogenesis. APP and the enzymes that cleave it colocalize throughout the secretory pathway, and Aß can be produced at multiple intracellular sites. In neurons, previous studies have shown that APP undergoes fast anterograde transport to nerve terminals and is metabolized into Aß peptides that are released and deposited as amyloid plaques around nerve terminals. Thus, the axonal/synaptic fractions of APP appear particularly important in the generation of Aß species that are ultimately deposited in amyloid plaques.
To further explore the relationships between the quantitative, qualitative, and spatial factors that influence Aß production and deposition, researchers produced transgenic mice that expressed increased levels of the ß-site APP cleaving enzyme (BACE). BACE overexpression resulted in increased protease activity and increased levels of C99, the penultimate precursor to Aß; however, a surprising inverse relationship between BACE expression and Aß production/deposition was found. Efforts to understand this paradoxical result led researchers to discover that BACE overexpression shifted the sites of APP processing in such a way that APP proteolysis occurred predominantly in neuronal perikarya rather than in axons and axon terminals. This alteration of APP processing upon BACE overexpression, together with the reduction of Aß accumulation, indicates that Aß generated proximally in neuronal perikarya has a different fate than Aß that is generated at or near the synapse.
Several lines of experimental evidence indicate that APP is depleted prior to axonal transport. First, biochemical analysis of BACE transgenic mice demonstrated that N- and O-glycosylated forms of APP are diminished due to increased ß-cleavage, indicating that APP cleavage is occurring soon after carbohydrate processing in the Golgi apparatus. Second, phosphorylation of the cytoplasmic region of APP is almost undetectable upon BACE overexpression. Since APP phosphorylation is a posttranslational modification found selectively within neuronal growth cones and neurites, the lack of phospho-APP indicates that APP was proteolyzed in early compartments. Third, after radiolabeling retinal ganglion cells with [32P]-orthophosphate, no radiolabeled APP could be recovered in optic nerves of BACE transgenic mice, indicating that increased BACE activity diminished levels of phosphorylated APP species in axons. Fourth, BACE overexpression resulted in a marked reduction in APP accumulation upon ligation of sciatic nerves, again demonstrating the lack of APP transport in axons. Finally, radiolabeling of newly synthesized APP by [35S]-methionine injection into the spinal cord demonstrated that APP turnover is increased significantly upon BACE overexpression so that little radiolabeled APP is available for axonal transport. These results indicate that Aß peptides that deposit into senile plaques are derived from axonal and synaptic APP. Conversely, Aß peptides produced near neuronal perikarya are cleared efficiently by the central nervous system, perhaps due to the spatial localization of Aß degrading enzymes.
Although the reduction of Aß amyloid deposition upon BACE overexpression was unexpected, the finding that synaptic Aß is crucial to the development of amyloid plaques offers several new avenues of research that may improve our understanding of the pathogenesis of amyloid plaques. Thus, further progress toward understanding APP transport, Aß aggregation within axonal or synaptic vesicles, and the distribution of Aß-degrading enzymes may yield insights that may prove to be clinically relevant.
Dr. Hodes introduced Dr. Francis Collins, Director of the National Human Genome Research Institute (NHGRI). He noted that there is a productive collaboration between NIA and NHGRI staff on AD and the genetics of aging.
Dr. Collins focused on three initiatives and invited discussion about ways NHGRI could contribute to the field of aging research. All have the goal of using modern tools of genomics and genetics to trace the origins of common disease. He began with a brief summary of the Human Genome Project, which began about 14 years ago.
The Human Genome Project achieved its ambitious milestones ahead of schedule, culminating just over a year ago in the completion of the sequence of the human genome. More than 99 percent of the euchromatic portion—the gene-containing portion of the genome sequenced to an accuracy of no more errors than 1 out of every 100,000 base pairs—is available on the internet for use by the scientific community. Dr. Collins turned to the question of next steps for understanding the causes of disease and developing new approaches for prevention and treatment of disease: (1) HapMap Project; (2) American Gene-Environment Prospective Resource; and (3) the NIH Roadmap Molecular Library Initiative. (Additional information about these tools and others is available at www.genome.gov.)
The HapMap Project (www.hapmap.org) is an international effort to study human genetic variation across all human chromosomes. The NIH funds about a third of this project; other sponsors include the Wellcome Trust and funding agencies in China, Japan, and Canada. Although this effort is less visible than the Human Genome Project, its focus on the .1 percent of the genome where people differ is considered important for medical purposes. The HapMap Project will contribute to our ability to track down genetic susceptibility factors for common diseases like AD, osteoarthritis, obesity, diabetes, stroke, osteoporosis, heart disease, and cancer. For these conditions, there are probably a dozen or more genes involved, and it is a combination of the particular variants a person has inherited plus the environmental triggers that he or she may have experienced that leads to health or disease. The complexity of the analysis demands information about genetics and environmental exposure, and large numbers of subjects to attain sufficient power for statistical significance. The HapMap approach simplifies the problem of collecting relevant genetic information by using the fact that human genetic variations occur in correlated clusters (haplotypes). The search for multi-genetic origins to disease is reduced from a random search of perhaps 10 million variants to a task that decreases the amount of work by a factor of 40. However, at the current time, it is not possible to recognize computationally where the boundaries of these haplotypes are; the boundaries only can be determined by experiment.
The goal of the HapMap Project is to present to investigators a standard set of SNPs that represent genome variation across all of the chromosomes in an efficient way. The HapMap is being used by researchers working on the genetics of common disease, who download these data and set up experiments to look for common haplotypes, allowing for a more systematic and global search of candidate genes. Dr. Collins noted several caveats: First, the strategy works if one is looking for a relatively common variant that undergirds the disease risk. ApoE4 is an excellent example. Association studies may fail if there are multiple, individually rare alleles underlying the disease. Second, although haplotypes provide a shortcut to identifying a segment that is involved in disease risk without having to type 10 million SNPs, because the haplotype appears on all of the SNPs, the SNPs will be inter-correlated so it will be difficult to discern the causative variant. Functional studies follow. In addition, it is unlikely that a single gene will have a very large effect in diseases like diabetes, AD, or osteoarthritis. Thus, a large number of well-phenotyped cases and controls will be needed to achieve statistical power. Dr. Collins reiterated that genetic susceptibilities are not deterministic but interact with environmental factors, which also must be assessed carefully. The HapMap itself collects no clinical information on the 270 DNA samples. However, in a large genetic study, it would be unfortunate not to collect information about environment. Despite these caveats, Dr. Collins believes that the haplotype map will advance the ability to uncover causes of common disease at the genetic level more rapidly than has been possible in the past.
A second and still hypothetical initiative is for a large, prospective, population-based cohort study, the American Gene-Environment Prospective Resource. Such a study would complement case-control studies and should represent minority groups, a broad range of ages, genetic backgrounds, and environmental exposures; collect clinical and laboratory data with regular follow-up; and include family-based recruitment for at least part of the cohort. The study also should collect technologically advanced dietary, lifestyle, and environmental exposure data; collect and store biological specimens; have a sophisticated data management system; permit access to materials and data by all researchers; and should not be “hypothesis limited” since the data are expected to lead to unanticipated discoveries. For the study to be successful and accepted in the community, comprehensive community consultation from the outset is needed as well as state-of-the-art consent to allow multiple uses of data and regular feedback to participants. Many countries are planning large population studies of genes, environment, and health, but these will not substitute for a major initiative that captures the U.S. environment and mix of ethnicities.
Dr. Collins pointed to the Framingham Study, a well-known prospective cohort study, as an example of how much can be learned. Given the projected NIH budget, it will be a challenge to undertake a study that enrolls half a million or more subjects and follows them over time. To initiate this type of project, Dr. Collins believes that other agency partners will be necessary and that the project will have to be a national priority.
Unlike the initiatives that focus on causal components, the third initiative presented by Dr. Collins addresses the drug development pipeline. Many believe that making small molecule technologies available to academic researchers will have a transformative effect on basic biomedical research, speeding the determination of genome function and development of new therapies. Many academic researchers have no access to that technology and little familiarity with it. Yet the Human Genome Project has made available many targets, most of which are not being investigated vigorously by the private sector because they are not clearly connected to a disease or may not seem to be promising avenues for drug development. An extensive library of small molecules is available at a reasonable cost from existing chemistry and compound libraries. Robotic technology makes it possible to screen hundreds of thousands of compounds for a particular assay. All these developments argue for a public sector screening and chemistry initiative now implemented as the NIH Roadmap Initiative on Molecular Libraries. The goal is to empower academic investigators to contribute more effectively to the front end of the drug development pipeline, beginning with target identification and proceeding through U.S. Food and Drug Administration approval.
The NIH Roadmap Initiative on Molecular Libraries includes six national screening centers for small molecules; one is operated in the intramural program and another five will be funded through extramural programs. A public database for “chemical genomics” exists where data about molecules and screens will be deposited. The NIH is funding technology advances in library diversity, assay format, robotics, and virtual screening. Dr. Collins noted the NIH Chemical Genomics Center which is capable of screening half a million compounds in about 30 hours. An investigator can design an assay and bring it to the center, allowing the identification of small molecules. Dr. Collins reported that many in the biotechnology and pharmaceutical industries see this as a valuable contribution of NIH research that does not compete with the pharmaceutical industry, which is more focused on later stages of drug development.
One Council member asked when the national screening centers for small molecules will be operational. Dr. Collins expected that the intramural center will begin chemical genome screening by spring. The extramural centers will be funded by April and some will be able to perform phenotypic screens in a year. Dr. Collins clarified that extramural researchers can apply to the intramural center for access, conditional on well-conceived assays and their feasibility in a high throughput format.
The prospective cohort study generated much discussion, beginning with a question about sample size. Dr. Collins stated that there is no absolute answer in setting the exact size of the study population; it depends on the disease incidence and genetic or environmental risks. Looking at gene-environment interactions will require double power to detect not only their individual effects but also interaction effects. It also was observed that a population-based cohort study would capture only a small number of twins. However, there is a large twin study in Europe, the EU Twin, which now is enrolling tens of thousands of monozygotic and dizygotic twins. An international network is needed to compare findings from different study designs, populations, and environments. There could be significant advantage in leveraging existing samples to modulate the need for an enormous and expensive new study, particularly given that people already have agreed to participate in the research, data exist about their phenotypes, and DNA has been collected in some cases. Dr. Collins reported that there are about 2 million people already enrolled in NIH-sponsored prospective cohort studies, some funded by NIA. However, existing studies will not suffice since many of the existing cohorts are focused on older age groups. One possible complement is the National Children’s Study (NCS), which was mandated by Congressional language in 2002. For the NCS researchers seek to study 100,000 individuals from the time of conception. It focuses on environmental exposures during pregnancy or early childhood through the first few decades of life and includes genetic data collection. It will not reveal much about adult onset diseases for a long time. Dr. Collins noted that a long-term prospective cohort study should spin off ancillary studies so that new ideas about environmental exposures or other biological hypotheses could be tested.
One Council member raised concerns about embarking on such a large prospective study. He questioned whether prospective studies like Framingham have provided new information. Rather, these studies have provided risk estimates. All of the risk factors that Framingham identified were identified previously by some other type of study design. It would be more useful to do case-control studies to inform a large prospective study. Where epidemiology really has paid off is when populations under study are very different, for example, atherosclerosis in the Japanese versus Americans and the correlation with omega-3 fatty acids. The Council member opined that advances in science have come largely from leads generated by animal experiments, natural experiments, or true experiments in humans with different dosages of a specific intervention.
Dr. Collins agreed that case-control studies must continue to be the engines for the discovery of candidate variants. Applying discoveries about genetic variants to public health will require knowledge about quantitative risk in the whole population. Thus, the prospective cohort studies could lead to investigation of biomarkers for disease. The issues of public acceptance, how to handle informed consent, and how to carry out meaningful consultation with communities were discussed. With American Indians, Alaskan Natives, and African Americans, it would be ideal to begin the consultation process early, to listen to concerns, and to try to adjust the research plan without compromising the integrity of the science. There is a wonderful opportunity to launch an education program to explain the benefits of such research.
In response to a question about whether the diversity of the American population would hamper the efficiency of the HapMap resource, Dr. Collins stated that the haplotypes in European, Asian, and African origin populations are actually quite similar. He further stated that the goal of the HapMap Project is to generate flexibility in the kind of tagged SNPs that an investigator may want to utilize.
A Council member asked whether whole genome amplification techniques are adequate for use with existing DNA banks. Dr. Collins commented that it is very exciting to see how good whole genome amplification seems to be for SNPs, that it may not be as good for microsatellites, but that the field is shifting to SNPs, and there are a number of papers now that have looked at thousands of loci. In general, the data look encouraging for studies that did not make cell lines where DNA is beginning to be a limiting factor. A related question was whether amplification can salvage studies that did not immortalize. Dr. Collins thought the case for immortalizing DNA is now less compelling because of genome amplification.
Dr. Hodes announced that Ms. Jane Shure, head of NIA’s Office of Communications and Public Liaison for more than 30 years, is leaving NIA to join the American Chemical Society. Her contribution to the history, impact, and development of the Institute has been immeasurable. Ms. Shure remarked that it has been an honor and a privilege to work at the NIH for as many years as she has for a series of extraordinary directors at NIA. She thanked Dr. Hodes and described him as an extraordinary person who is not only brilliant but kind, human, warm, very funny, and of moral fiber that is a credit to government.
Dr. Kelty announced the departure of Ms. Marta Campbell. Ms. Campbell has been with NIA for more than a decade and has led a number of efforts including managing NIA’s international program and coordinating NIA’s technical assistance workshop and women’s health issues trans-NIH.
Dr. Kuller reported on deliberations of the Working Group on Program (WGOP), which met on September 22. Dr. Hodes presented the WGOP with an update of NIH Roadmap activities. Much of the discussion related to infrastructure development and new technology, ways of discovering new molecules and constructing libraries of small molecules, interdisciplinary research, and infrastructure technology development. There was a discussion about how to do clinical research in areas where there is a growing need for larger sample sizes reflecting the greater diversity of the U.S. populations. Dr. Kuller remarked that Dr. Collins’ presentation echoes previous WGOP discussion in considering the efforts of other nations and the scientific competitiveness of the U.S., particularly since other countries have greater ability to recruit large populations at a lower cost. The WGOP also discussed the consolidation of grants management support at the NIH.
Dr. Kuller noted that the review of the BSR Program was discussed, and that Dr. Ronald Lee would present the report. Copies of the Review Committee’s report were available at the meeting.
Dr. Kuller then drew attention to the statistical data on extramural programs. He reported that Dr. Hodes led a discussion about the increasing number of applications submitted to NIA, and their impact on success rate, so that even if the number getting funded every year remained constant, the percentage funded would decline as the number of applications continues to rise. The data suggest that NIA is receiving an increasing number of applications that score well in review.
A. Advisory MeetingsTwo meetings were discussed on topics for which concept clearance was requested to issue Requests for Application (RFA).
B. RFA Concept Clearance Dr. Kuller presented a proposed RFA on the Biology of Perimenopause: Impact on Health and Aging, the topic of a recently held NIA workshop. The goal of this initiative is to solicit research on underlying biologic mechanisms associated with the increased risk (or decreased protection) for health problems and conditions associated with the menopausal process in middle-aged women. Dr. Kuller remarked on the continual interest and lack of understanding about the better life expectancy of women compared to men in most societies for persons above the very low-income range. Women throughout their life spans continue to have much lower rates of coronary heart disease, for example, than men. This RFA focuses on trying to better understand how hormones and lifestyle factors may interact to generate this difference in disease rates between men and women. A motion was made, seconded, and passed to approve the development of this RFA.
A second proposed RFA on Inflammation as a Common Pathway for Age-Related Comorbidities was the subject of a recent exploratory workshop. Researchers’ abilities to measure cytokines and chemokines in the blood or in other tissues and relate these to numerous outcomes has outpaced their understanding of subclinical inflammation as a possible common pathway for multiple morbidities. There is a need to bring multidisciplinary groups together to improve the understanding of the pathobiology of inflammatory markers. The Working Group considered it an excellent opportunity to move the field forward. A motion was made, seconded, and passed to approve the development of this RFA.
Dr. Ronald Lee began his report of the BSR Program Review by describing the review process. The BSR Program Review Committee, chaired by Dr. Lee, included five members from the Council (Drs. Ronald Lee, John Cacioppo, Linda Fried, Alan Garber, and Spero Manson), three previous Council members (Drs. James Jackson, Anderson Smith, and David Wise), and two outside experts (Drs. Daniel Kahneman and James Smith). Dr. Lee briefly described the review process—teleconferences and an in-person meeting of the Committee before the May Council, as well as the formation of 14 subgroups that consulted on specific topic areas: health and retirement economics, behavioral economics, cognitive aging, psychological development in integrative sciences, behavioral genetics, formal demography, biodemography, health disparities, health services research, behavioral and social interventions, translational research, analytic methods, training programs in psychology of aging, and macroeconomic and demographic aspects of population aging. Some of these topic areas were selected because they were considered promising; others selected issues that merited further investigation were identified. Dr. Lee mentioned the Committee’s deliberations about health services research. Led by Dr. Garber, the Committee proposed guidelines for the BSR Program to consider to better define its scope.
The Committee produced two documents: (1) A formal report distributed publicly and (2) subgroup reports, which represent the opinions of subgroup members, many of whom were not members of the Committee. The latter report is available upon request.
The general view of the Committee was that the BSR Program is creative and dynamic, takes risks, aggressively pursues opportunities, moves into new areas, and is highly interdisciplinary. Dr. Lee noted the many important BSR Program achievements, including development of new datasets that have facilitated areas of research, leadership in scientific areas such as biodemography, participation in productive collaborations with other Federal agencies, and proactive efforts in recruiting outstanding researchers to the field. The Committee addressed seven broad topics that centered on promising new directions for BSR Program efforts and portfolio balance, and on larger strategic and organizational issues, such as staffing; relationships with other units in NIA, the NIH and elsewhere; the appropriateness of the allocation of funds across funding mechanisms; whether the program has been served well by the grant application review process; and the adequacy of BSR Program data collection efforts.
There are 16 full-time equivalent staff assigned to the BSR Program, with 5 current vacancies including the deputy associate director. The Committee believed replacing the latest vacancy was of paramount importance and that now has been accomplished with the recruitment of Dr. John Haaga. The Committee also considered it a priority to hire a branch chief for the Population and Social Processes Branch and was pleased to hear that searches are under way for two health scientist administrators. Dr. Lee noted the impressive staff accomplishments despite the staff shortage that has limited the ability of the BSR Program to take full advantage of available opportunities.
Dr. Lee noted the many successful collaborations between the BSR Program and other units within NIA and the NIH, as well as elsewhere in the Government. The Committee praised BSR interdisciplinarity, but acknowledged that the natural outgrowth of such inclinations is to increase the potential for boundary conflicts. NIA should embrace the opportunity to share expertise across programs and encourage the BSR Program to support a full range of research methods, which increasingly involve behavioral genetics and neuroimaging, to address cutting-edge research questions. Applications that address BSR topic areas should not be assigned on the basis of methods and techniques that are being used, but rather on the substantive issues that those projects address. It was clear to the Committee that there are gains from collaboration across programs, and it would be valuable for NIA leadership to actively foster these intersections.
The Committee recommended that another advisory group be appointed to consider the adequacy of the grant application review process as the topic was considered too complex to be addressed adequately in the time available. Dr. Lee clarified that the Committee believed that NIA internal review processes have been working well.
The Committee noted the $30 to $40 million annual investment in data collection efforts and observed that the BSR Program’s past achievements in meeting data needs serve as a model for other countries. It considered the timing appropriate for a dedicated group to review the BSR Program’s data collection portfolio to consider areas outside of health and economic behavior of the elderly that are ripe for greater investment.
Dr. Suzman thanked Dr. Ronald Lee for his considerable efforts in leading the BSR Program Review. Dr. Suzman also introduced Dr. Haaga, who recently accepted the position of Deputy Associate Director for the BSR Program.
The 93rd meeting of the NACA was adjourned at 1:48 p.m. on September 23, 2004. Dr. Hodes closed the Council session by thanking all of the speakers and Council members for their participation. The next meeting is scheduled for February 1–2, 2005.
Attachments:A. Roster of Council Members B. Director’s Status Report to the NACA
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 Miriam F. Kelty, Ph.D. With assistance by Rose Li and Associates, Inc.
MEMBERSHIP ROSTERNATIONAL ADVISORY COUNCIL ON AGINGNATIONAL INSTITUTE ON AGING (Terms end December 31)
ChairpersonRichard J. Hodes, M.D. Director, National Institute on Aging National Institutes of Health Bethesda, MD
Marie A. Bernard, M.D. (2005)Donald W. Reynolds ChairDepartment of Geriatric Medicine University of Oklahoma College of Medicine Oklahoma City, OK
Elizabeth H. Blackburn, Ph.D. (2006) Professor Dept of Biochemistry & Biophysics University of California San Francisco, CA
Melissa M. Brown, M.D. (2006) Director Center for Value-Based Medicine Flourtown, PA
John T. Cacioppo, Ph.D. (2007) Blake Distinguished Service Professor Department of Psychology University of Chicagoand Institute for Mind & BiologyChicago, IL
*David V. Espino, M.D. (2004) Professor and Vice Chair Dept. of Family & Community Medicine Division of Community Geriatrics University of Texas Health Science Center San Antonio, TX
Linda P. Fried, M.D., MPH (2006) Professor, Medicine, EpidemiologyHealth Policy DirectorDivision of Geriatric Medicine & Gerontology Director, Center on Aging and Health The Johns Hopkins Medical Institutions Baltimore, MD
Alan M. Garber, M.D., Ph.D. (2007) Director Center for Primary Care and Outcomes Research Center for Health Policy Stanford University Stanford, CA
F. Michael Gloth, III, M.D., (2005) President Victory Springs Senior Health Care Reisterstown, MD
*Eugene M. Johnson, Jr., Ph.D. (2005) Norman J. Stupp Professor, Department of Neurology Professor, Dept. of Molecular Biology & Pharmacology Co-Director, Alzheimer's Disease Research Center Washington University School of Medicine St. Louis, MO
*Lewis H. Kuller, M.D., DrPH, MPH (2004) University Professor of Public Health Professor of Epidemiology Department of Epidemiology University of Pittsburgh Graduate School of Public Health Pittsburgh, PA
Ronald D. Lee, Ph.D. (2005) Jordan Family Chair of Economics Professor, Demography and Economics Director, Center on Economics and Demography of Aging University of California Berkeley, CA
Virginia M.-Y. Lee, Ph.D. (2007)Professor Dept of Pathology & Laboratory Medicine Univ of Pennsylvania School of MedicinePhiladelphia, PA
Spero M. Manson, Ph.D. (2006) Professor of Psychiatry and Head American Indian & Alaska Native Programs University of Colorado Health Sciences Ctr Aurora, CO
Peter W. Nauert, J.D. (2005) Principal Insurance Capital Management Chicago, IL
Stanley B. Prusiner, M.D. (2004)Director and Professor Institute for Neurodegenerative Diseases School of Medicine University of California San Francisco, CA
*Judith A. Riggs, M.A. (2004) Washington, DC
Gary B. Ruvkun, Ph.D. (2007) Professor, Molecular Biology Massachusetts General Hospital Boston, MA
*Leon J. Thal, M.D. (2005) Professor and Chair Department of Neurosciences University of California San Diego School of Medicine(and Staff Physician, Neurology Service, San Diego Veterans Medical) La Jolla, CA
*WGoP Member
Ex-Officio Members
Tommy G. Thompson Secretary Department of Health and Human Services Hubert H. Humphrey Building Washington, D.C.
Elias Zerhouni, M.D. Director National Institutes of HealthPublic 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.
[1], [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.
[3] These minutes will be approved formally by the Council at the next meeting on February 1-2, 2005, and corrections or notations will be stated in the minutes of that meeting.
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