Thursday, February 17, 2000

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

Mr. Chairman and Members of the Committee:

I am pleased to present the President's non-AIDS budget request for the NIAAA for FY 2001, a sum of $288,578,000, which reflects an increase of $14,587,000 over the comparable Fiscal Year 2000 appropriation. Including the estimated allocation for AIDS, total support requested for the NIAAA is $308,661,000, an increase of $15,427,000 over the Fiscal Year 2000 appropriation. Funds for the NIAAA's efforts in AIDS research are included within the Office of AIDS Research budget request.

Nearly 14 million American adults meet diagnostic criteria for alcohol addiction or abuse, and 100,000 Americans die of alcohol-related causes each year, according to NIAAA epidemiology data. While death is the ultimate consequence of alcohol-use disorders, their impact on the living, in sheer numbers, is even greater. The NIAAA's epidemiology research reveals that 442,000 people occupy hospital beds each year as a result of these disorders. The financial burden that alcohol misuse imposed on the Nation in 1998 was approximately $185 billion, in direct and indirect costs, according to the Lewin Group. The sequelae of alcohol-use disorders include damage to the liver, brain, and other organs; cancer; fetal alcohol syndrome and the lifetime disabilities it produces; accidental injury to self and others; property damage; crime; broken families; and loss of productivity that deprives the Nation of valuable resources.

Biological, behavioral, and social factors converge to produce alcohol-use disorders, making them particularly complex diseases. In terms of biology, alcohol is unique among addictive substances, in that it targets not just one but many neurotransmitter systems -- chemical messengers between nerve cells -- resulting in unusually pervasive effects on the entire nervous system and in unique challenges for scientists. Researchers have made striking advances in identifying the molecular structures where alcohol binds to these neurotransmitter systems and in learning how variations in genes determine alcohol's actions on them.

Neuroscience

Because alcohol's effects on the nervous system are so pervasive, neuroscience is a particularly active field of research at the NIAAA. One promising area involves neuropeptide Y (NPY), a substance in the brain that increases food consumption and relieves anxiety. Studies are underway to determine the role of NPY in controlling alcohol consumption. Preliminary studies suggest that NPY may, indeed, play a role in propensity for alcohol. Surprisingly, these studies revealed that mice in which the NPY gene was inactivated (knocked out) drank morealcohol than did their normal siblings and were less sedated by alcohol. If NPY is found to play a key role in human alcohol-use disorders, NPY and its receptors -- its "docking sites" on cells -- become potential targets for medications to control alcohol intake.

Physical problems from long-term alcohol use do not necessarily resolve once people stop drinking. Using new MRI techniques, researchers have found persistent damage in the cerebellum, the brain's locus of gait and balance, even in long-abstinent alcoholics. Previous anatomic measurements of cerebellar damage were difficult because of its convoluted structure, resulting in less accurate data. Scientists can use these new imaging techniques to clarify the potential for reversing cerebellar damage in recovered alcoholics and to explore a new topic: the role of cerebellar damage in cognitive impairment.

These and other findings from the NIAAA's comprehensive neuroscience portfolio reflect the ubiquitous nature of alcohol's effects on the nervous system. For example, research designed to identify the protein structures where alcohol binds to nerve cells may, one day, provide groundwork for development of better medications to treat alcoholism. In another protein-related finding, NIAAA-supported scientists have found that genes in the brains of deceased human alcoholics produced less of a crucial nervous-system protein, myelin, than did those in nonalcoholics. With this information, scientists can better define changes in gene activity that result in damage to specific areas of alcoholics' brains. Other investigators are identifying alcohol-related neurobiological risks that fluctuate during adolescence and that might be related to the higher risk of adult alcoholism predicted by earlier onset of drinking in the young.

Genetics

That genetics underlies much of the biology of alcohol-use disorders is unquestionable. Variations in genes result in variations in many components of the nervous system, and, thus, in how people's bodies handle alcohol. The way in which people's bodies handle alcohol affects, in turn, their behaviors toward alcohol and risk for alcoholism. Evidence suggesting that alcoholism is a polygenetic disease -- that many genes contribute to it -- greatly complicates the search for the genes involved.

The Collaborative Studies on the Genetics of Alcoholism (COGA), a major project supported by the NIAAA, has identified several chromosomal regions likely to contain genes that influence the risk for alcoholism. The NIAAA is pleased to announce that it is making available to the general scientific community the substantial data and DNA samples generated by COGA. Scientists who take advantage of these resources can analyze them further in their own research projects, expediting the search for genes that contribute to alcoholism. The data also can be used to evaluate new methods of statistically analyzing genetic data, not only for alcoholism, but also for other diseases.

Among the goals of the COGA project is to elucidate the genetics of alcoholism in African Americans. While COGA recruits both Caucasian and African-American subjects, the latter have not been present in numbers large enough to permit a reliable examination of whether the genetic basis of alcoholism is different in Black Americans than in White Americans. Through a NIAAA grant, Howard University Medical School will study this question and contribute its findings to the growing COGA database.

Neuropeptide Y, discussed earlier, is one of more than 20 substances that NIAAA scientists study as gene knockouts, to determine their influence on alcoholism. Some of these substances are found to increase alcohol consumption; others are found to reduce it. A recent study examined the effects of knocking out, in mice, the gene that produces protein kinase C epsilon (PKC Î), an enzyme involved in intracellular signaling. Absence of PKC Î resulted in significantly less alcohol consumption and abnormally high sensitivity to alcohol's sedating properties. Insensitivity to alcohol's sedating effects is among the factors that portend alcoholism at some point in life. Since much of the mouse genome resembles the human genome, these types of findings may lead to clues about human genetic defects related to alcoholism.

Toxicology

Alcohol is unique among abused drugs in the extent of the organ damage it causes. Animal studies by NIAAA intramural researchers have demonstrated that chronic alcohol use leads to a decrease in essential fatty acids (EFAs), nutrients that play a crucial role in brain health. The same investigators recently demonstrated that EFA-deficient rats lose nerve cells in an area of the brain involved in memory and learning, another common result of chronic alcohol use. The NIAAA continues to perform research to evaluate the potential of EFA supplementation to reduce organ damage among alcoholics.

Between 40 percent and 90 percent of U.S. deaths from cirrhosis are due to alcohol, according to NIAAA epidemiology data. These statistics underscore the importance of understanding the potential for reversing this currently irreversible disease. Scientists suspect that an immune-system protein, tumor necrosis factor- a (TNF a), plays a role in alcohol-induced liver damage. NIAAA-funded researchers recently found that alcohol-fed mice in which TNF a's molecular receptor had been genetically knocked out, eliminating TNF a's actions, suffered liver pathology seven times less severe than that of alcohol-fed mice with normal TNF a levels. This finding strongly supports the assertion that TNF a is involved in alcohol-induced liver damage and is lent even more significance by the recent development of pharmaceuticals that inhibit TNF a in the treatment of inflammatory diseases, such as arthritis.

Advances in Prevention and Treatment

Recent studies illustrate what the NIAAA's prevention research can contribute to decisions about alcohol legislation. Many states have taken the important step of lowering their legal definition of drunkenness from a blood-alcohol concentration (BAC) of 0.10 percent to 0.08 percent. However, studies of simulated merchant-ship piloting by maritime cadets revealed that even half of that concentration, a BAC of 0.04, resulted in significantly impaired performance. The cadets failed to sense their decreased judgment, underscoring the hazards of alcohol use in the context of heavy-machinery operation and the workplace. Many states still allow people to drive cars with a BAC more than twice that of the alcohol-impaired cadets.

The public also benefits from prevention findings that the NIAAA provides to alcohol-treatment practitioners. Thirty percent of Americans are subjected to domestic violence at some point in their lives, according to studies published in the New England Journal of Medicine and funded by the National Institute of Mental Health, the Emergency Medical Foundation, and the UCLA Southern California Injury Prevention Research Center. NIAAA-funded investigators recently concluded, in the Journal of Studies on Alcohol, that a combination of behavioral marital therapy and standard treatment for alcoholism resulted in a six-fold reduction in domestic violence. Of significance here is not only the magnitude of reduction in violence, but also that the reduction is sustained, as investigators determined in a 2-year follow-up study.

In the treatment arena, NIAAA-supported studies reveal that the new medication nalmefene is at least as successful in preventing relapse among recovering alcoholics as is naltrexone, the recently FDA-approved drug of choice. Nalmefene may have advantages over naltrexone, including less risk of liver toxicity, providing another option for recovering alcoholics whose livers have been damaged by alcohol. A Finnish company plans to seek FDA approval for this new medication.

Adolescent Alcohol Use

During last year's hearings, the NIAAA reported that initiation of drinking earlier rather than later in youth is associated with a dramatically higher risk of alcoholism at some point in life. For this and many other reasons, the NIAAA continues to make drinking among adolescents a research priority. The "hard-wiring" of the brain is vulnerable to change during adolescence, including change caused by toxic substances. Investigators supported by the NIAAA have found that adolescent animals are less sensitive than adult animals to the motor-incapacitating and sedating effects of alcohol. This suggests that adolescents have higher drinking capacities, perhaps putting them at higher risk for alcohol-related problems. Other researchers have found that human youths who engaged in heavy, protracted drinking during early and middle adolescence, when compared with nonabusing adolescents of similar demographics, score significantly more poorly on neuropsychological tests, and that these dificient scores may persist. For example, young people who have withdrawn from alcohol recently have poor visuospatial functioning, and those who have withdrawn in the past show poor retrieval of verbal and nonverbal information.

The Washington Post and CNN recently reported another NIAAA finding: An estimated one in four U.S. children is exposed to alcoholism in the family. The stressful and unpredictable environment in such families can lead to a variety of problems in these children.

Outreach

In addition to conducting research on adolescent alcohol abuse, the NIAAA has taken a leadership role in the Surgeon General's campaign to prevent alcohol use among youth and engages in numerous outreach activities. Recently, the NIAAA issued a pamphlet that educates parents about alcohol use among youth, and this pamphlet now is being written in Spanish. The NIAAA also is collaborating with the Robert Wood Johnson Foundation to recruit governors' spouses in a National Leadership Initiative to Keep Children Alcohol-Free. In January, the NIAAA and Mothers Against Drunk Driving held two press briefings, one for editors of teen magazines and the other for editors of women's magazines. The NIAAA and the Substance Abuse and Mental Health Services Administration (SAMHSA) are preparing to award a grant for public-service announcements aimed at preventing underage drinking. In addition, prominent scientists and 10 college presidents have formed a subcommittee of the NIAAA Advisory Council, to identify ways of reducing binge-drinking among college students.

Other NIAAA outreach activities include Alcohol Screening Day, the first of which was held last year. Almost 500 college campuses were among the 1,700 sites that participated. Approximately 52,000 people attended, and 29,000 of them asked to be screened. This successful event will be held again on April 6, 2000.

To ensure that its research findings reach the people to whom they matter most -- people who suffer from alcohol disorders -- the NIAAA, in collaboration with State agencies and SAMHSA, cosponsors a Research-to-Practice initiative. Senior clinical investigators spend several days at alcohol-treatment facilities, giving staff hands-on help in incorporating innovations from basic and clinical research into their treatment regimens.

The NIH budget request includes the performance information required by the Government Performance and Results Act (GPRA) of 1993. Prominent in the performance data is NIH's first performance report, which compares our FY 1999 results to the goals in our FY 1999 performance plan. As our performance measures mature and performance trends emerge, the GPRA data will serve as indicators to support the identification of strategies and objectives to continuously improve programs across the NIH and the Department.

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

Updated:February 17, 2000