The National Advisory Council on Alcohol Abuse and Alcoholism convened for its ninety-ninth meeting at 7 p.m., on February 6, at the Pook's Hill Marriott Hotel, Bethesda, Maryland, and at 8:35 a.m., on February 7, at the Natcher Conference Center, National Institutes of Health (NIH), Bethesda, Maryland. Dr. Mary Dufour, Deputy Director of NIAAA, presided during the closed session on February 6. Dr. Raynard S. Kington, Acting Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), presided during the open session on February 7.

In accordance with the provisions of Sections 552b(c)(6), Title 5, U.S.C. and 10(d) of Public Law 92-463, the meeting was closed to the public from 7 to 8:30 p.m., on February 6, for the review, discussion, and evaluation of individual applications for Federal grant-in-aid funds. The meeting was open to the public from 8:35 a.m. to 3:00 p.m. on February 7, for the discussion of program and policy issues.

Marilyn Aguirre-Molina, Ed.D. (open session only)
Sandra A. Brown, Ph.D.
Raul Caetano, M.D., Ph.D.
Richard A. Deitrich, Ph.D.
Reuben A. Gonzales, Ph.D.
Harold D. Holder, Ph.D.
Sheryl Ramstad Hvass, J.D.
Linda Kaplan, CAE
George F. Koob, Ph.D.
Matthew K. McGue, Ph.D.
Steven M. Mirin, M.D.

Alpha E. Brown, Ph.D., J.D., DMin
Anna Mae Diehl, Ph.D.
Barbara J. Mason, Ph.D.
Mr. Paul Samuels, J.D.

Mr. Roger Hartman, Ex-officio member of the Department of Defense (DOD)

In addition to Council members and outside speakers there were approximately 100 observers present during the open meeting including NIAAA staff, liaison organization representatives, and other observers.

Dr. Mary Dufour, Deputy Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), called to order the closed session of the ninety-ninth meeting of the National Advisory Council on Alcohol Abuse and Alcoholism at 7 p.m., February 6, for the consideration of grant applications.

Dr. Kenneth R. Warren, Director, Office of Scientific Affairs, reviewed the procedures for the conduct of grant application review, and reminded the Council members of the regulations pertaining to conflict of interest and confidentiality.

Members absented themselves from the discussion and evaluation of applications from their own institutions, or in situations in which a potential conflict of interest, real or apparent, might occur.

Council members concurred with all initial review committee recommendations for all grant applications available to them. Council members also concurred with the MERIT extension applications. Council did not review applications that were "Not Scored" or with a percentile score of 40 or higher.

Dr. Raynard S. Kington, Acting Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), called to order the open session of the ninety-ninth meeting of the National Advisory Council on Alcohol Abuse and Alcoholism, at 8:35 a.m., February 7, 2002.

Four council members, Dr. Kington noted, were unable to attend the Council meeting: Dr. Alpha E. Brown, Dr. Anna Mae Diehl, Dr. Barbara J. Mason, and Mr. Paul Samuels. Dr. Kington asked that Council members, and all other persons in attendance, to please introduce themselves.

Three Council members agreed to extend their terms 180 days beyond October 2001, and were presented with certificates of appreciation by Dr. Kington. The members are: Dr. Marilyn Aguirre-Molina, Dr. Harold Holder, and Dr. Matthew McGue.

Highlights from the Director’s Report were presented by Dr. Kington. Key topics included the following:

Selection of the new NIAAA Director is important to the Institute, and a 14-member search committee, created by Dr. Kirschstein has already met. Applications are due by May 1.

Dr. Kington noted that the selection committees for the National Institute of Mental Health, the National Institute on Drug Abuse and NIAAA are moving in parallel. All selection committees are receiving a great deal of input and enthusiasm from the scientific community.

Dr. Kington commented on the speculation of a potential merger of institutes at NIH and the two issues involved with that speculation. One is that the 2001 Labor/HHS appropriations bill called for a National Academy of Sciences study to assess, "whether the current structure of NIH is optimally configured for the scientific needs of the 21st century." Their report is expected one year after the start date of the new Director of NIH.

The second is an amendment contained within a November 2001 Senate bill reauthorizing the U.S. Department of Justice for fiscal year 2002. This amendment mandates that an Institute of Medicine report be initiated to study the pros and cons of merging NIAAA and NIDA into a single National Institute on Addictions. However, at this point, there is not an official administration or NIH opinion about the merger.

Dr. Kington reported fiscal year 2002 appropriations and the fiscal year 2003 President's budget are in the last two years of the five-year doubling of the NIH budget. The budgets represent about a 13 percent increase for 2002 and an 8.5 percent increase over 2002 for NIAAA in 2003.

Dr. Kalant will be the April 11, 2002, speaker at the Mark Keller Honorary Lecture. Previous lectures were very well attended by a variety of scientific and non-scientific staff.

Dr. Kington reviewed the ongoing activities associated with the NIAAA College Drinking Initiative. The report on college drinking will be completed shortly. Also to be completed is a series of commissioned papers for submission to peer-reviewed journals, which will be extremely important contributions to evidence-based prevention activities at colleges and universities.

The Leadership to Keep Children Alcohol-Free Initiative conference, Dr. Kington reported, had a number of important outcomes that will benefit alcohol research and the research community. The Governors' spouses continue to make important contributions to this effort Dr. Kington noted.

Dr. Mary Dufour represented NIAAA at the National Human Genome Research Institute conference on the future of genomics. Dr. Kington noted that at the meeting a goal was to map out for the next 10-20 years research beyond completion of the human genome map. A document outlining a strategic plan is expected shortly.

The Office of Collaborative Research arranged two important meetings. Drs. Faye Calhoun and Tina Vanderveen organized a three-day meeting on research training that was held in conjunction with the Indiana University Alcohol Research Center. The ins and outs of administering an NIAAA-supported training program under the National Research Service Award Program were covered one day. Dr. Kington remarked on the great success of the two-day scientific conference, "Alcoholism: Toward an Integration of Basic and Clinical Research Training for the 21st Century." This conference gave junior scientists, who are researchers in alcohol, the opportunity to present their research to peers and faculty in a supportive and encouraging environment.

NIAAA co-sponsored the Surgeon General's Conference on Health Disparities and Mental Retardation. Dr. Kington recognized Drs. Faye Calhoun and Deidra Roach who represented the Institute. A report will be forthcoming.

NIAAA submitted a Health Disparities Plan to the National Center on Minority Health and Health Disparities Dr. Kington reported.

Dr. Kington remarked on the recently printed report on the Interagency Coordinating Committee on Fetal Alcohol Syndrome Progress and Five-Year Strategic Plan. It will be sent to Congress in the very near future. NIAAA chaired the committee.

An HIV/AIDs program announcement and two RFAs should, Dr. Kington pointed out, stimulate research on the role of alcohol in exposure to and development of HIV-related illnesses.

Dr. Kington thanked Mr. Roger Hartman, ex-officio member, for his help in coordinating training for the Department of Defense for the 2002 National Alcohol Screening Day, which was organized by Dr. Faye Calhoun.

Dr. Kington highlighted two NIAAA international activities. One activity, which Drs. Kenneth Warren and Faye Calhoun helped to organize, was an international collaborative research conference on FAS research. Ms. Peggy Murphy launched an activity to increase attention to identifying and treating alcohol disorders in primary care settings.

Dr. Kington pointed out that the Office of Policy and Public Liaison (OPPL) has developed a new Seasonal Outreach series of fact sheets on the alcohol-related risk associated with holiday drinking.

The NIAAA Advanced Research Program biosensor initiative released an announcement soliciting applications January 7, 2002, Dr. Kington noted.

Dr. Kington drew attention to the Division of Basic Research stem cell workshop headed by Dr. Sam Zakhari, and the Symposium on the Neurogenetics of Alcoholism, organized by Dr. Antonio Noronha and Dr. Robert Karp.

Dr. Kington mentioned that the Division of Biometry and Epidemiology has issued a program announcement, to encourage researchers to analyze existing data sets entitled "Secondary Analysis of Existing Alcohol Epidemiology Data Sets."

The Treatment Research Branch of the Division of Clinical and Prevention Research sponsored a recent workshop on measuring alcohol treatment efficacy. Dr. Kington noted that the FDA was involved with this workshop.

The variety of intramural research program activities would be outlined in detail by Dr. George Kunos' presentation Dr. Kington advised.

Dr. Kington acknowledged the lengthy list of new NIAAA members since June 2001. There were also a number of team appointees in the Division of Intramural Clinical and Biological Research, Visiting Fellows and a Senior Research Visiting Fellow.

President Bush signed a bill appropriating $23.5 billion for NIH on January 11, 2002 – an increase of almost 15 percent over FY 2001 levels. This appropriation includes $384 million for NIAAA, about a 13 percent increase over last year. This appropriation will enable funding of 192 new and competing research project grants, 15 research centers, 80 research career awards, and 247 full-time training positions. NIAAA’s projected success rate with this funding is 32 percent (about one of three grant applications received will be able to be funded), which is slightly less than that of other institutes.

President Bush is requesting $27.3 billion for NIH support in FY 2003, an increase of about $3.8 billion, or almost 16 percent over the FY 2002 appropriation. However, $1.4 billion of this increase is dedicated to bioterrorism research, and much of it is directed to the National Institute of Allergy and Infectious Disease (NIAID), whose budget would increase by about 60 percent. For NIAAA, the President’s request is $418.5 million, an increase of 8.5 percent over the FY 2002 appropriation – and comparable to the increases requested for most institutes. NIAAA’s projected success rate at this funding level is 30 percent. This request represents nearly a doubling of NIAAA’s budget for FY 2001, which was $227 million. FY 2003 is the last year of a five-year Congressional effort to double the NIH budget.

The Governors’ Spouses Initiative recently held a national conference attended by representatives of 49 states. The meeting highlighted several positive effects of the initiative, including:

• State budget funding of alcohol prevention efforts, such as public service announcements.

• Outreach to expand the influence of this coalition, including efforts to involve the spouses of American Medical Association members and U.S. Conference of Mayors’ spouses.

• Outreach to alcohol researchers, with several first ladies visiting alcohol research labs. This is an important opportunity for researchers to increase understanding of the importance of alcohol research and how it benefits the States.

• The Leadership launched a new website in October 2001, that is the only resource of its kind that provides research data, news and events, and prevention programs specific to pre- and early adolescent alcohol use, and highlights the activities of the Governors' spouses in underage drinking prevention within their States and nationally.

• A new video, funded by The Robert Wood Johnson Foundation, which depicts how young people, 9 to 15 years of age, are surrounded by alcohol images and messages, was developed for the Leadership initiative and is being made available as an educational tool for multiple groups and organizations.

Mr. Doug Hussey, of the National Center for Minority Health and Health Disparities (NCMHD), opened this discussion with an overview of his Center’s responsibilities and the NIH Health Disparities Plan.

The National Center was established by Congress in 2000 to conduct and support research, training, dissemination, and outreach to minority communities and other underserved groups, such as urban and rural poor. It funds research grants, endows centers of excellence at minority and other institutions, and loan repayment awards (see later discussion). The Center is responsible for leading and coordinating the NIH effort to reduce/eliminate health disparities and for creating a comprehensive strategic plan and budget for all NIH health disparities research activities.

This strategic plan, now under development, is designed to establish measurable objectives, detail how they will be achieved, and lay out a timeline for their completion. An important input to the plan is a trans-NIH strategic plan and reviewers comments developed before the Center was created. The Center has also asked each institute to submit a five-year strategic plan following a standard format. The format includes goals, objectives, and action plans in three broad areas: research, research infrastructure, and community outreach (including public education and information dissemination). The plan is nearing completion and will be posted on the NCMHD website when final; public comments will be welcome. NCMHD will report annually on NIH progress in implementing the plan.

Dr. Faye Calhoun, Associate Director for Collaborative Research, NIAAA, highlighted the ongoing collaboration between NIAAA and NCMHD (particularly in co-funding research projects), and she introduced NIAAA’s planning effort. Common features of each Division’s plan include:

• Addressing African Americans, Hispanic/Latino persons, American Indians, Alaska Natives, Asian Americans, Native Americans, and Pacific Islanders and subgroups within these populations.

• Presenting research-based goals that are realistic and achievable.

• Funding pilot studies, which will enable smooth progress from the initial, developmental stage of the plan.

• Using multi-disciplinary, multi-ethnic collaborative teams.

The following are some specifics from the plans NIAAA Divisions are developing.

Epidemiological research increases our understanding of the nature and scope of alcohol-related health disparities. NIAAA’s 1992 survey of the adult population of the U.S. found that risks differ for various alcohol-related consequences and by population group, but that no one ethnic or racial group consistently ranks high, low, or in the middle on all measures. For example, while similar proportions of persons of Hispanic origin and those of African-American (not Hispanic origin) consume an average of one or more ounces of ethanol daily, the proportion of Hispanics meeting the criteria for a diagnosis of alcohol dependence is higher – and a higher proportion of Hispanics die from cirrhosis.

Intriguing differences such as these raise important questions for future research. Why do patterns differ among populations? Are particular subgroups at higher risk? What are the risk and protective factors and do they vary by group?

To answer these and other questions, the Division’s proposed Action Plan focuses on two types of research.

• The National Epidemiologic Survey on Alcohol and Related Conditions, conducted by the Biometry Branch. During the first wave of the survey (2001-2002), 48,000 respondents will be surveyed, with an over sampling of African American and Hispanic individuals and young people. A second wave will interview the same respondents in 2004-2005 and permit estimating incidence rates for alcohol dependence and other alcohol-related consequences by racial and ethnic group.

• Grant-supported research (Epidemiology Branch). In addition to increasing the number of grants that focus on specific population groups, the plan includes: encouraging researchers on all relevant ongoing studies to analyze their data by race and ethnic group where possible; encouraging those designing new studies to over-sample by race; and inviting grant applications for secondary analysis of existing data by race and ethnicity.

ACTION ITEM:   Council members had a variety of questions about the National Epidemiologic Survey, including how information would be collected on smaller ethnic populations, such as Alaska Natives and Asian and Pacific Islanders, where it would be difficult to have an adequate sample size. An alternative strategy was suggested: encouraging grants that study smaller groups individually so a national sample isn’t required. NIAAA will follow up on these issues, and the next Advisory Council meeting will have further discussion of the National Epidemiologic Survey. Members will receive a package of information about the survey and the questionnaire prior to the meeting.

Biologic or genetic differences are a potential reason for the variations in risk seen among racial and ethnic groups. For example, research has found variations in the enzymes that metabolize alcohol in different ethnic/racial groups that affect risk. Included are variants of the enzyme aldehyde dehydrogenase (ALDH2*2) and alcohol dehydrogenase (ADH beta 2, ADH beta 3). One reason for studying basic mechanisms such as these is that it may enable the development of medications to reduce risks and health disparities.

The Division’s strategic plan is designed to elucidate basic mechanisms of risk and protection in racial and ethnic populations by answering questions such as the following, suggested by clues from previous research:

What are the mechanisms by which variation in alcohol-metabolizing enzymes or other factors contribute to tissue damage in different ethnic groups?

What are the candidate genes for alcoholism and their relation to phenotype markers in Native and African Americans?

Do sleep disturbances affect alcohol dependence in African Americans?

Are biological factors related to the increased prevalence of fetal alcohol syndrome (FAS) among African and Native Americans?

Does alcohol influence the vertical transmission of HIV in susceptible populations? Does it reverse the effects of the drug AZT in some populations?

The Division’s plan emphasizes funding workshops that crystallize these research questions, as well as encouraging grant applications on these topics.

ACTION ITEM:   Council members asked whether the May 1-3, NIAAA workshop on gene and environment interactions included a focus on racial and ethnic issues. This was subsequently confirmed to be the case.

This Division’s plan addresses research on disparities in the delivery of prevention and treatment interventions as possible underlying causes of disparities in health outcomes. Several basic questions underlie the action plan:

Are there disparities among ethnic groups in access to health care, use of health care, quality of care, and outcomes? For example, research has shown that a primary reason for not seeking care among African Americans is difficulty in finding child care, while other groups more often fear being stigmatized or don’t accept that they have a problem.

How do expectancies, norms, and acculturation affect the development of alcohol problems across racial and ethnic groups?

How do ethnicity and culture influence help-seeking, treatment adherence, and relapse? For instance, some studies suggest that clients may be more likely to seek help when the clinician is from their ethnic/racial background.

How can prevention and treatment interventions be adapted for racial groups and subgroups, particularly HIV/AIDS, co-occurring disorders, and adolescents?

The goal of the Division’s Action Plan is to understand disparities in prevention in treatment and test interventions to address them.

The Plan:

• Provides continued support for existing grants and encourages competitive renewals. Projects already addressing disparities include replications and adaptations of community trials in minority communities; a prevention intervention specifically designed for American Indians in the Plains States; seven prevention trials on FAS in minority populations; and conducting a series of secondary analyses of Project MATCH data for Hispanic populations.

• Solicits new grant applications on the above questions.

• Encourages secondary analysis of existing data by race/ethnicity.

• Includes funding for workshops and literature reviews to update the state of knowledge.

• Asks researchers to look for opportunities within their current grants for special projects that could be carried out by promising minority researchers. For example, a current minority supplement is funding study of an extended case monitoring approach for improving access to health services.

ACTION ITEM:   Council members suggested that analysis similar to the very useful secondary analyses of Project MATCH data for Hispanic populations might also be conducted for African American populations. Staff will follow up on this suggestion and report their findings at the next Council meeting.

The Action Plan for this Office has three main thrusts:

• Coordinating a variety of NIAAA and trans-NIH activities to build the research infrastructure. Examples include:

• Supporting FAS research in minority communities through the collaboration on the Interagency Coordinating Committee on Fetal Alcohol Syndrome, which has Government-wide representation. A key challenge will be developing multi-site and multi-disciplinary studies on FAS that take advantage of information sharing and synergies among basic scientists and clinical practitioners.

• Identifying data from foreign studies on FAS in ethnic/racial populations of interest in the United States.

• Collaborating with the National Institute on Child Health and Human Development to determine whether there is a relationship between high alcohol consumption during pregnancy and incidence of still births and SIDS; some preliminary evidence suggests such a relationship.

• Increasing capacity to conduct alcohol research in minority-serving institutions. This is a long-time priority for the Office, which has used every granting mechanism available and has had particular success in encouraging R21 developmental research project grants. For example, eight trans-NIH developmental projects on high-alcohol malt beverages should soon move to a pilot phase.

• Increasing access to alcohol-related health messages among underserved communities. For consumer materials, the plan stresses working with minority health professionals and organizations to disseminate culturally appropriate, accurate materials. The plan also includes a focus on science education for minority communities, health professional education, and evaluating the impact of alcohol messages on behavior (e.g., the impact of the message in a Washington, D.C., media campaign, "Alcohol can affect your baby’s brain. Don’t drink while pregnant.").

Council members noted the relative lack of minority researchers and the need to improve ethnic/racial representation in the clinical work force and in public health/prevention. NIAAA is attempting to increase staff diversity and minority representation by broadening its outreach and developing new mechanisms to attract minority researchers, such as loan repayment programs (see later discussion on this issue) and the NIH undergraduate scholarship program. Collaboration between various Government agencies and health organizations will be needed to affect broader work force issues.

ACTION ITEM:   Members questioned how performance on diversity efforts would be evaluated. Some performance measures of diversity efforts already appear in the Action Plan described above. However, NIAAA staff will be revisiting this plan and may develop additional ideas.

NIAAA is working to develop a revolutionary new technology: a biosensor that can measure blood alcohol levels continuously in individuals and provide reliable, dynamic information on alcohol consumption in daily life. One of several projects generated by NIAAA's Advanced Research Program, the biosensor concept, received unanimous positive reaction from alcohol researchers asked to comment on its potential usefulness. The Institute approved the concept in April 2001.

Since that time, NIAAA has sought input from related medical societies and grantees doing sensor research and incorporated their comments into the planning process. It also sponsored a workshop for alcohol researchers, sensor experts, mathematicians, modelers, and "visionaries" to further elaborate how the product might be used and how it might work. In January 2002, the Institute issued a broad agency announcement to solicit proposals from potential contractors. Instead of the usual solicitation providing specifications a bidder must follow, this request outlines what the product needs to do - leaving the "how-to-build-it" decisions up to the contractor to outline. Proposals are due by April 5, 2002, and an award is expected in this fiscal year.

New scientific direction and recruitment, broader collaboration on scientific topics of cross-cutting interest, and a new off-campus facility are helping to expand NIAAA’s Intramural Research Program and integrate it into the wider NIH community.

The Intramural Research Program (IRP) is setting up an integrated neuroscience laboratory that combines the tools of electrophysiology and molecular biology with rodent behavioral science and mouse genetics. Newly recruited scientists will lead this program. Dr. David Lovinger who leads the integrative neuroscience program, and Dr. Steven Ikeda who leads a parallel program in molecular physiology that will focus on cellular signaling cascades as potential targets of ethanol. The search for the director of clinical research programs is temporarily on hold until a new NIAAA director is in place.

Many areas of scientific research have potential applicability to alcohol studies, and NIH is a natural setting to cross-pollinate ideas. For example, a collaborative effort between NIAAA’s neurogenetics lab and a schizophrenia researcher from NIMH identified the gene for an enzyme involved in metabolizing dopamine that is associated with schizophrenia. The project also identified a variant form of a gene that associates with certain forms of alcoholism. Another intramural project identified major components of the neurocircuitry that controls the appetite for food. This has important implications for both obesity and alcohol research, since many believe that alcoholism is an appetitive disorder.

Actively fostering collaboration is a cost-effective way of enhancing alcohol research and keeping NIH on the cutting edge of science. Some of the mechanisms the Intramural Research Program will use to accomplish broader collaboration include:

• Offering partial support, with other Institutes, for researchers in other fields who work on alcohol topics – for example, supporting post-doctoral studies.

• Developing individual scientific collaborations with a large number of scientists from NIH and other institutions.

• Working at the Institute-to-Institute level on topics of mutual interest, such as plans to cosponsor a conference on ingestive and appetitive behaviors with NIDDK.

NIAAA intramural researchers are currently scattered in a variety of off-campus buildings. In the near future, however, a large new facility in the Twinbrook section of Rockville, Maryland, will house all NIAAA intramural program researchers and administrators. The building is purposely larger than the intramural program needs. The vision is that scientists from related NIH intramural programs will also work there, enabling collaboration and a dynamic research environment. The building site, which is a large property, is also being considered for use as an NIH satellite campus with six research buildings.

NIH has offered congressionally established loan repayment programs since the 1990s. These programs, which have evolved as laws changed over time, are designed to help counter economic disincentives to biomedical research careers. They help researchers pay back educational loans in return for a commitment, such as agreeing to pursue specific areas of scientific inquiry for a stated time period. Another purpose of loan repayment programs has been to attract scientists from minority and disadvantaged backgrounds. Overall, NIH now offers five separate extramural loan repayment programs in the areas of clinical research, pediatrics, disadvantaged backgrounds, health disparities, and contraception/infertility.

For the first time, NIAAA is now offering loan repayments in the clinical research and pediatrics programs. Alcohol researchers may apply in the other three program areas, which other agencies administer. Important features of all five of these programs include:

• Repayment of up to $35,000 per year for two years is available towards outstanding education debt (the amount varies based on debt level). During the second year, recipients may apply for a third year of repayment.

• The recipient must commit to conducting qualifying research activities for at least two years (concurrent with the time of loan repayment, with large penalties for breaking the commitment).

• Eligibility requires debt of greater than 20 percent of an applicant’s salary and compensation on the date the contract is to be signed. Other requirements relate to citizenship and type of degree, and for some programs the applicant must hold an NIH grant or award.

• Loan repayment funds are taxable, and 39 percent of the total loan is credited directly to the recipient’s IRS account.

NIAAA has $726,000 available to fund loan repayments in FY 2002, which can fund at least eight awards. To learn more about the programs, visit www.lrp.nih.gov.

In rodent studies, dependent rats in withdrawal, and even rats with a past history of dependence, self-administer much higher levels of alcohol than non-dependent animals. The concept of allostasis (the ability to achieve stability following change) helps explain these findings. A concept from physics, allostasis suggests that following a major physical change, such as prolonged ingestion of high levels of alcohol, the body does not return to normal when the change ends (alcohol is withdrawn). Instead, it returns to an abnormal set-point (excessive alcohol intake following withdrawal) that persists over time. Brain and neurotransmitter changes demonstrated in rodent studies help elucidate this pattern, which may offer insights into how dependence develops.

Various studies have identified neurotransmitters in the extended amygdala involved in creating the acute reinforcing effects of alcohol, which can occur at any stage of the continuum from preoccupation/anticipation to withdrawal. Those driving the allostatic response to alcohol withdrawal in dependent rodents appear to be related to the negative reinforcement caused by withdrawal. The neurotransmitters GABA and corticotropin-releasing factor (CRF) appear to play an important role in the development of alcohol dependence.

• GABA. A variety of studies suggest that a deficit in the GABA mechanism is associated with alcohol dependence. In one study, administration of a GABA-A agonist had no effect on drinking in animals that were not dependent. Another study found that the more GABA-A dependent rats receive, the less alcohol they take.

• CRF. This peptide, located in the basal forebrain, is involved in the body’s response to stress. During alcohol withdrawal, rats are hypersensitive to stress. Knocking out the CRF-1 receptor blocks withdrawal-induced anxiety. Studies also show that administering a CRF antagonist blocks excessive self-administration of alcohol in dependent rats during withdrawal and even after protracted abstinence; it has no effect in non-dependent animals.

The Advisory Council’s Subcommittee on College Drinking has completed its report (release date, April 9, 2002), which summarizes the state of the science and identifies critical research gaps in the epidemiology/natural history of college drinking and in prevention interventions. An NIAAA RFA scheduled for award on October 1, 2002 or before, seeks grant proposals that address research gaps identified in the report for both topics. About $4 million is budgeted, ideally to be split between the two.

Although much is known about the epidemiology and natural history of drinking among college students, much remains to be learned. In particular, we have insufficient knowledge about the relationship of alcohol consumption during college and academic progress and attainment, social and emotional development, physical and psychological health, and eventual personal and financial independence. We also need enhanced understanding of alcohol consumption, risk and protective factors for use, and consequences of consumption among different race/ethnic groups of students, and among populations specific to college, such as members of Greek organizations and student athletes. More complete information about the roles of antecedent factors, such as drinking in high school, family history and personality factors, and environmental factors; such as, college location, size, and alcohol policies in the surrounding community, in college student alcohol consumption is needed. New work should also strive to improve upon the methodologies used in past studies, which in some cases, have limited generalizability and have often relied on student's reports about their drinking and its effects. Although longitudinal studies are needed to answer many important questions, cross-sectional studies will also continue to be useful.

Very little research has been conducted on environmental interventions, which are the sole topic of this element of the RFA. Environmental approaches have three targets:

• Social norms, which may support or hinder high-risk college drinking. Some research suggests that changing social norms may be effective in reducing college drinking problems, but more research is needed on how to accomplish the change in different student groups and campus-wide.

• The campus environment, which includes policies designed to prevent college drinking. Currently, little is known about how to influence the campus environment positively. Research is needed on policies such as disciplinary practices for alcohol offenses, banning alcohol on campus, and banning alcohol advertising on campus.

• The community around a campus both affects and is affected by college drinking. However, more studies are needed that clarify how community policies (e.g., enforcement of minimum legal driving age or driving under the influence laws) and different types of campus-community relationships affect college drinking behaviors. A particular area of interest for the RFA is joint campus-community interventions to reduce high-risk drinking.

Methodology is also a major concern for environmental research applications. Gold standard experimental designs are difficult to do on college campuses. However, quasi-experimental designs and natural experiments can also provide useful information if they include careful process evaluation and multiple outcome measures.

Council members questioned how the Institute would ensure that only environmental intervention research applications would be funded, given that some individual-focused applications had been funded under a previous RFA on prevention of drinking problems among college students. Dr. Boyd explained that the current RFA specifies that non-environmental projects will be considered non-responsive.

Stem cell research has important applications in the alcohol field, both in expanding our understanding of basic biologic mechanisms and in overcoming the organ and tissue damage related to excessive alcohol use. It is important for NIAAA to get involved in this type of research, because no other Institute will address many of the key alcohol-related issues.

All stem cells are not alike, and political and scientific debate continues about which types should or should not be used in research. The three sources of stem cells for research use include:

Embryonic stem cells. These cells come from the inner layer of early stage fertilized eggs. They have the ability to grow other stem cells or make any type of tissue. To harvest these cells, the outer layer of the embryo must be destroyed. Political opposition to stem cell research centers on this process, because a complete fertilized egg has the potential to develop into a human being. Currently the United States government only supports research using existing stem cell lines (which came from "extras" created for in vitro fertilization clinics).

Adult stem cells. These cells reside in the tissues and organs of adults. They can regenerate to form more of themselves, or they can differentiate to form another type of cell, tissue, or organ. They are currently being used in research, but there are too few available to meet all the demand.

Parthenogenesis. This is a method for causing an egg to divide by applying an electric stimulus rather than fertilizing it with sperm. The products of this method contain stem cells that can develop into different tissues – but these eggs have no ability to grow into human beings.

Excessive alcohol use causes many kinds of damage and illness, including liver cirrhosis, pancreatitis, cardiomyopathy, immune and endocrine dysfunction, cancer, fetal alcohol syndrome, and behavioral/cognitive impairment. Stem cell research could help us address problems like these by increasing our understanding of human development and of alcohol’s effects on stem cells. Why does a stem cell differentiate into one type of tissue versus another? Are there genetic factors or errors that cause illness by affecting embryonic or adult stem cells? For example, is the impaired ability of the liver to regenerate itself in alcoholics the result of alcohol’s effects on adult stem cells in the bone marrow or the liver?

In addition, longer-term applications could potentially create personally tailored therapeutic delivery systems and organ/tissue transplants. For example, stem cell research could point the way to a method for overcoming rejection following organ transplantation, such as by growing tissue that is compatible with the recipient.

Mr. Paul Smedberg, Director of Governmental Affairs for the National Health Council on Budget and Legislative Issues, discussed the 121 agency-member Council primary goal. This goal is to generally improve the quality of health care for all people in American, particularly those with chronic disease and disability.

The National Health Council (NHC) is extremely active with a number of coalitions working on issues which may impact the National Institute on Alcohol Abuse and Alcoholism (NIAAA). NHC has been working with the Ad Hoc Group for Medical Research Funding and the Coalition for Health Funding to push for budget increases for NIH.

NHC is interested in the President's budget entries for NIH proposed for fiscal years 2004 and 2005.

Mr. Smedberg discussed the origination of the prevention group, Research to Prevention. The mission of this organization is to improve the Nation's health through prevention.

Mr. Hartman shared a couple of brief comments. First, he announced that the Department of Defense has a new Assistant Secretary of Defense for Health Affairs as of November 2001, Dr. William Winkenwerder. Dr. Winkenwerder comes to Defense from the Blue Cross and Blue Shield where he was a senior executive.

Dr. Faye Calhoun, Ms. Peggy Murray, and their colleagues at NIAAA, were thanked by Mr. Hartman for providing an excellent training session on January 8, 2002 on how to conduct Alcohol Screening Day. This "excellent training was very well received," and was provided to military personnel who will be involved with Alcohol Screening Day on April 11, 2002.

The Council adjourned at approximately 3:08 p.m.

CERTIFICATION

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