Statement by Enoch Gordis, M.D., Director
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
Department of Health and Human Services

March 2, 1999


Mr. Chairman and Members of the Committee:

The FY 2000 budget request for NIAAA is $248.9 million, excluding AIDS, an increase of $5.8 million or 2.4 percent over the current FY 1999 amount. Including the estimated allocation for AIDS, total support proposed for NIAAA is $265.5 million, an increase of $6.2 million over the FY 1999 appropriation. Funds for NIAAA AIDS research are included in the Office of AIDS research budget request. The total NIAAA budget request includes support for the following NIH Areas of Special Emphasis: biology of the brain, new preventive strategies against disease, development of therapeutics, and genetics of medicine.

The mission of the NIAAA is to improve, through its research, prevention and treatment of alcohol disorders and their enormous consequences. Among the nearly 14 million adult Americans who suffer from alcohol disorders, 100,000 die of alcohol-related causes each year, according to NIAAA epidemiology research and American Psychiatric Association diagnostic criteria, and to independent researchers published in Scientific American, respectively. The NIAAA' s epidemiology research reveals that more than four times that many, 442,000, spend time in acute-care hospitals. Of the estimated $166 billion that alcohol disorders cost society annually, more than $22 billion is attributable to health care and more than $119 billion to lost productivity, according to a study conducted by NIDA and NIAAA.

GENETICS

Since the risk of developing alcoholism is influenced about equally by genes and environmental factors, one of NIAAA' s tasks is to identify the genes that are involved. The search has been a productive one. Investigators from the NIAAA-funded Collaborative Studies on the Genetics of Alcoholism, or COGA, have identified four chromosomal regions likely to contain genes that influence alcohol-related behavior. NIAAA' s intramural researchers independently identified one of the same regions and identified a fifth site. The task ahead is to identify the genes themselves, so that scientists may exploit the potential of this knowledge for more effective medication design and more targeted preventive interventions. Discovery of these chromosomal regions provides a crucial starting point for the search. In October, NIAAA will make COGA' s powerful data set available to as wide a scientific audience as possible, to expedite the search for specific genes implicated in alcoholism.

Using tools of molecular biology, NIAAA-supported investigators demonstrated an association between a gene mutation in fruit flies and an alcohol-induced behavior. This research is a striking demonstration of how the study of lower organisms can help us understand human biology, and has garnered a Presidential Early Career Award for Scientists and Engineers for one of its investigators. Fruit flies have in common with humans chemical pathways essential to survival. In tracking one of these chemicals -- cAMP -- researchers found that flies with a genetic mutation that makes them more sensitive to alcohol also produce less cAMP than do genetically intact flies. As seen here, flies with this mutation lost their coordination on exposure to alcohol fumes more rapidly than did other flies. Giving these mutated flies substances that increased cAMP levels made them less sensitive to alcohol. These findings suggest a link between this gene mutation, production of cAMP, and an alcohol-related behavior. In the future, findings such as this will provide guidance in the search for new sites for interventions.

NEUROSCIENCE AND MEDICATION DEVELOPMENT

Because genes, proteins, molecular biology, and neuroscience are closely related, studies in any one of these areas serve to inform the others, and all of them are highly relevant to drinking behavior. For example, genes encode proteins that play crucial roles in chemical pathways that influence behavior. For some time, scientists have known that alcohol affects several neuroreceptors in the central nervous system. How alcohol affects these receptors remains an important research question. In an ingenious series of experiments, NIAAA-supported researchers substituted protein sections of these neuroreceptors with genetically engineered sections, one at a time. Through this process of elimination, they found the part of the receptor molecule that was indispensable to alcohol' s action on the nerve cell. This type of research, in which investigators are beginning to examine intimate details of the structure of receptors, will serve as a guide to designing medications that counteract alcohol' s effects, in the future.

The NIAAA' s efforts include not only this important basic-science research, but also testing of existing new medications for their utility in treatment. Project COMBINE, a large NIAAA-funded clinical trial, is testing two medications, naltrexone and acamprosate, that represent a new generation of pharmaceuticals for the treatment of alcoholism. These medications act directly on pathways thought to be important components of addiction by blocking rewarding sensations associated with alcohol or blocking aversive effects of abstinence, respectively. Both medications are being tested alone and in combination with behavioral therapies refined from results of Project MATCH, a previous NIAAA-supported clinical trial that compared outcomes of various behavioral treatments. NIAAA neuroscience research provides the type of information that, after testing for safety and efficacy in the laboratory and in small-scale human trials, then large-scale clinical trials, may result in medications with clinical utility.

PREVENTION

Just as careful, controlled trials are needed for medication development, they are equally necessary for proving the effectiveness of prevention efforts. The NIAAA has an extensive prevention portfolio that addresses a variety of topics, such as drunk driving and underage drinking, that are in various stages of investigation. Alcohol use among youth is a major area of concern at the Institute. Preventing young people from developing alcohol disorders is, of course, preferable to treating them. The NIAAA and CSAP are cofunding research to determine effects of alcohol advertising on initiation and continuation of drinking among youth. Recently, the Surgeon General introduced an initiative aimed at preventing underage drinking. The NIAAA is the leading contributor to this new effort.

College-age drinking is a difficult and widely publicized problem, and one that receives special emphasis in NIAAA' s research. An example of a recent finding in this area is described in this poster, which summarizes data from one of the few randomized, controlled trials conducted in this population to date. Previously, we had informed the Committee that a brief, one-time session that corrected high-risk college students' expectations about how much their peers drank appeared to reduce these students' drinking and alcohol-related problems. The recently published results of this trial support that assertion. As this 2-year follow-up graph indicates, high-risk students who received the intervention declined in their rates of drinking and harmful consequences significantly more than did high-risk students who received no intervention. This excellent study is a rare example of interventions that have been evaluated in this manner. Research has yielded several promising remedies that await similar -- and necessary -- rigorous testing, and additional investigations are underway. The Institute' s National Advisory Council also has formed a subcommittee on college-age drinking, cochaired by the president of the University of Notre Dame and an eminent alcohol researcher. Ten college presidents and 12 leading researchers comprise this subcommittee. After assessing the entire college-drinking area, this subcommittee will advise the Institute about productive research avenues.

NIAAA epidemiology data dramatically revealed that earlier age of drinking onset is associated with increased likelihood of lifetime alcohol dependence. The reasons for this phenomenon are now subject to investigation. On one hand, it is possible that neurobiological changes in the adolescent brain are related to this increased risk; on the other hand, various psychosocial factors may be involved. Results from research in this key area will add to scientists' understanding of how alcoholism develops and will provide direction in the search for effective interventions.

FETAL ALCOHOL SYNDROME

Fetal alcohol syndrome (FAS) remains the leading cause of preventable birth defects in the United States, and the NIAAA is approaching this issue from a variety of angles. In animal studies, scientists are identifying biological changes that occur in embryos exposed to alcohol. Of particular interest is the neural crest, a group of embryonic cells that later develop into cells of the brain and spinal cord, among other structures. The timing of developmental events that occur in neural crest cells is critical, and the changes that alcohol causes in them are now being related to FAS. Researchers also have established that a class of molecules called free radicals, which are generated by alcohol and other substances, damage neural crest cells and that antioxidants mitigate that damage. Diagnosis of FAS at birth by physical characteristics is difficult; investigators therefore are searching for a surrogate chemical indicator, suitable for clinical diagnosis, of fetal damage induced by alcohol. NIAAA-supported scientists have identified a potential biomarker, an elevated level of a protein, that may lead to methods of prenatal diagnosis of FAS and, thus, early intervention.

One of the Institute' s tasks is to prevent FAS more efficiently, especially by reaching women who have not had access to the message that alcohol damages unborn children. The NIAAA currently is conducting large-scale research on how to prevent alcohol use among pregnant women and is stimulating further research on this topic.

OUTREACH

In addition to its ongoing efforts to disseminate information, the Institute is engaged in several special projects aimed at raising public awareness and improving clinicians' skills in dealing with patients who have alcohol disorders. One of these projects is a curriculum that enables medical schools to integrate information on alcohol disorders into their programs. This substantial curriculum, shown here, is entitled A Medical Education Model for the Prevention and Treatment of Alcohol Use Disorders. Too often, health practitioners have received little training in how to diagnose and treat their patients' alcohol problems, and increasingly busy health practitioners sometimes do not adequately address them. This omission has significant medical and social consequences. The curriculum shown here enables students and physicians to recognize alcohol-related problems and to intervene more efficiently and productively. Ultimately, patients are the beneficiaries of this valuable resource.

One of the Institute' s goals is to translate findings from alcohol research into applications that can be implemented in a variety of clinical settings. In response to requests from State officials and others, the Institute held its first Research-to-Practice Forum in New York, in partnership with the State and with other Federal and national organizations. During this NIAAA-led meeting, scientists, administrators, and providers discussed methods of incorporating current research findings on alcohol disorders into clinical practice. Another forum will be held in North Carolina in November, and the State of Hawaii has requested a similar event, to be held in March.

Although alcohol is a highly prevalent disorder in our society, only a fraction of the people who would benefit from treatment are getting the help they need. To increase the number of people who can improve their lives through treatment and avoid the disastrous consequences of drinking, the Institute is embarking on a new project: National Alcohol Screening Day. The first will take place in communities across the country on April 8. This event is being offered by the NIAAA in partnership with the National Mental Illness Screening Project and will offer free screening and referral services to anyone who asks for them. It will also educate the public about alcohol disorders. The Institute' s goal is to enlist 2,000 sites, 650 college campuses among them, that will offer these services. Several private organizations have joined the NIAAA, which is the major funder of the event, in supporting National Alcohol Screening Day. An additional 19 prominent national organizations have endorsed it.

A partnership between the NIAAA and the Kettering Foundation promises to raise the Nation' s awareness of alcohol disorders and their consequences. For the past 16 years, the Foundation has chosen a topic of public interest and has sponsored community discussions throughout the Nation. The topic for this year' s National Issues Forums is alcohol use and the public' s attitude toward alcoholism. The goal of the Forums is to help an informed public take an active role in policy decisions. At the National Press Club, Forum representatives will summarize, for the media, the outcome of the national discussions and will describe the direction the citizenry has taken on alcohol issues. A PBS presentation will be the final event in this valuable effort.

SUMMARY

Alcoholism is a complex disease, not only because it is influenced by several genes and by multiple biological interactions, but also because it is influenced by many other factors, such as family and social environment. The NIAAA maintains a research portfolio that balances these complex issues. We will continue to identify the biological mechanisms that predispose people to alcohol disorders and to develop methods of altering those mechanisms. At the same time, we recognize that behavioral interventions can prevent people from engaging in activities that trigger biological mechanisms involved in alcoholism, and our portfolio reflects that understanding, as well. All of this research is occurring in the context of collaborations with public and private partners and of outreach to the people to whom it matters most: those at risk of suffering from alcohol disorders or those at risk of suffering the consequences of someone else' s abuse of alcohol -- and that represents all of us. The activities of the NIAAA are covered within the NIH-wide Annual Performance Plan required under the Government Performance and Results Act (GPRA). The FY 2000 performance goals and measures for NIH are detailed in this performance plan and are linked to both the budget and the HHS GPRA Strategic Plan, which was transmitted to Congress on September 30, 1997. The NIH performance targets in the Plan are partially a function of resource levels requested in the President' s Budget and could change, based on final Congressional Appropriations action. NIH looks forward to Congress' feedback on the usefulness of its Performance Plan, as well as to working with Congress on achieving the NIH goals laid out in this Plan.

My colleagues and I will be happy to answer any questions you may have.

Updated: March 2, 1999