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

Department of Health and Human Services


I am pleased to present the President's budget request for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) for Fiscal Year 2002, a sum of $381,966,000, which reflects an increase of $41,288,000 over the comparable Fiscal Year 2001 appropriation.

Alcohol-use disorders impose an enormous toll on society. They cost the Nation $185 billion each year, one-and-one-half times as much as all illegal drugs combined, 1and 100,000 people die of alcohol-related causes annually. 2These figures reflect only the toll imposed by the 14 million adult Americans who are physically dependent on alcohol or who abuse it to the point that it disrupts their lives, but who aren't dependent on it. 3Still others add to the burden when they occasionally drink to excess and, temporarily impaired, injure or kill themselves or others, or damage property.

ALCOHOL IS UNIQUE

Among substances of abuse, alcohol is unique in a number of ways. It is a toxin that can cause damage to any tissue in the body. The resulting diseases range from certain kinds of cancer to liver and heart disease. Alcohol also is unique in the pervasiveness of its actions in the nervous system, the body 's command center, through which alcohol exerts its behavioral effects. Rather than affecting only one or a few neurotransmitter systems - that is, the crucial chemical systems through which components of the nervous system communicate with each other and with the outside world - alcohol affects every neurotransmitter system that we have studied to date.

Alcohol also affects parts of the membrane that surrounds nerve cells, the "point of entry" for substances of abuse, that illegal drugs do not appear to affect. These factors greatly complicate the search for alcohol's sites of action in the nervous system.

Policy and legal issues -- as well as social ones -- also confer unique status on alcohol. For example, alcohol raises the need for laws on minimum drinking age, maximum allowable blood levels for driving, and zoning and licensing. Alcohol raises the issue of revenue, since it is associated with a tax-paying industry, an industry that promotes alcohol's use through advertising. Alcohol also raises the issue of warning labels on beverage containers.

Another of the ways in which alcohol is unique among substances of abuse is that it is a food, since it has caloric value. The brain regulates appetite for food through neuropeptides, pieces of protein. Evidence suggests that, to some extent, craving for alcohol might be driven by the same or similar biochemical pathways that drive appetite for food.

NEUROSCIENCE HOLDS THE KEY TO BEHAVIORS OF ALCOHOLISM

Some people can drink lightly and occasionally and never develop problems with alcohol, while at the opposite end of the spectrum of alcohol use, it takes over people's lives and they become physically dependent on it. Between these two scenarios lie varying degrees of use and misuse. What accounts for these differences in how people respond to alcohol, differences that may decide whether or not it destroys their lives?

Environmental factors -- family and peers, for example -- play a role, but variations in our nervous systems constitute the largest part of the differences in our behaviors toward alcohol. It is here that alcohol affects a multitude of biologic events that determine our propensity for drinking and our vulnerability to the biologic process of becoming dependent on alcohol. Before we have taken our first drink, the genetic and molecular make-up of our brains influences, largely, how we will respond to alcohol once we are exposed to it.

Substances ultimately stimulate the same major reward pathways of the brain. However, various substances first stimulate other, different biochemical pathways before they "light up" these major reward pathways. Thus, substances differ in the mechanisms, and in the complexity of those mechanisms, that lead to reward. The routes of alcohol's actions appear to be particularly pervasive.

Alcohol's effects on the nervous system vary throughout the life-span, from the uniquely devastating damage it causes in the fetus, to disruptions in development of the adolescent brain, to the patterns of biologic risk and damage we see in adults. Among substances of abuse, alcohol is, by far, the greatest inducer of neurologic and other birth defects.

THE ANSWERS WE SEEK

Alcohol research seeks to answer these questions: What are the genetic and molecular factors in the brain that determine these differences in how we respond to alcohol? How does alcohol change "hardwired" functions of the brain to cause physical dependence? What role do environmental factors play in alcohol dependence? Can we design interventions that disrupt these biologic and environmental pathways, to prevent alcohol's harmful effects? In each of these areas and others, we are making advances.

ADVANCES IN ALCOHOL RESEARCH

Our neuroscience research is aimed at understanding how a multitude of biologic factors combine to form neural circuits -- networks of nerve cells and the thousands of biochemical activities associated with them -- that mediate alcohol 's actions. Our research links these biologic events with alcohol-related behaviors and the impact that environmental influences have on them.

We have made major advances. For example, we are closing in on specific regions of the nerve-cell membrane where alcohol initiates its effects. This kind of information raises possibilities for design of medications that block such sites. Among our priorities is to develop medications that will be effective in a wider range of people with alcoholism than are current medications. For example, our research on a nervous-system protein (protein kinase C e) has resulted in a treatment-development project by a pharmaceutical company.

Animal and clinical neuroscience findings are guiding our efforts to develop medications for alcoholism that target optimal molecular sites in the nervous system. For example, naltrexone, approved for alcoholism treatment by the FDA in recent years, targets a specific neurotransmitter system -- the opioid system -- and is among the more promising pharmaceuticals currently in use.

In the genetics arena, we have found several chromosomal regions likely to contain genes that influence our susceptibility to alcoholism. Our challenge is to pinpoint their exact locations. Because alcoholism is a genetically complex disease -- that is, multiple genes influence it -- the search for these genes is complex. Our Collaborative Study on the Genetics of Alcoholism addresses this issue and has generated data used by other disciplines with an interest in addiction and by the scientific community.

We are conducting studies in rodents in which we either " knock out" or enhance the activities of genes, to see how this affects behaviors toward alcohol. These studies are providing us with information about biologic mechanisms that contribute to the risk of becoming alcoholic. Another genetics technology (microarray technology) is telling us which genes appear to be active under various scenarios of alcohol use. This technology enables us to scan much of the human genome for changes in gene activity that occur with physiologic states associated with alcohol; for example, alcohol dependence.

Our research is revealing mechanisms that mediate alcohol's damage to the fetus and evidence that adolescent brains are vulnerable to alcohol-induced damage. New NIAAA research also links stress-induced hormonal changes in infancy with risk of alcohol problems later in life.

Ultimately, these kinds of studies can guide us to points for pharmaceutical intervention in the biochemical pathways through which alcohol exerts its effects. We are capturing the potential of neuroscience through collaboration. Alcohol research covers the spectrum from genetics to behavior and all of the intricate molecular biology that lies between. However, so many areas of expertise now exist in neuroscience that integrating research and results relevant to alcohol investigations is difficult. To ensure that we do not miss opportunities, our Integrative Neuroscience Initiative on Alcoholism is encouraging investigators from different fields to integrate their work and their findings. We expect this major initiative to speed the translation of new findings into clinically useful data.

BEYOND BASIC SCIENCE

Our research on social and policy issues extend far beyond questions of legislation. For example, drinking among college students is a complex problem entrenched in campuses and communities. Evidence suggests that intentional and unintentional injury, including death, associated with this problem is much greater than previously suspected. Our investigators are pursuing estimates of alcohol-related death rates among this vulnerable age group, and avenues for prevention. Minority groups provide another example. Certain minority groups appear to respond differently to alcohol, physically and behaviorally, than does the general population. Our epidemiology research identifies these kinds of public-health issues, and these findings lead to basic and behavioral research that investigates root causes and potential interventions.

We bring our research findings to the public in a variety of ways. Our Research to Practice Initiative is an excellent example. In collaboration with the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment, we arrange with States to meet with treatment providers and administrators. After exchanging information about our current research findings and the practitioners' obstacles to providing treatment, we place experts in temporary residencies in treatment programs that have identified specific areas of need.

We bring our findings to the public via Alcohol Screening Day, a nationwide event that enables people to receive free screening for alcohol problems and, if needed, referrals. Last year, almost 1,500 sites across the country participated, more than 370 of them college campuses. We also are dealing with the difficult issue of college drinking through our Advisory Council's Subcommittee on College Drinking. The Subcommittee, a collaboration between researchers and college presidents, has been meeting since 1998 and has commissioned major papers and panel reports to guide efforts to prevent drinking by students.

Drinking by youth is not limited to college students, and we are reaching children and adolescents through our Governors' Spouses Initiative. Spouses of governors in 28 states have joined this project to reduce drinking by young people; a crucial effort, given our findings that early initiation of drinking portends dramatically higher risk of alcoholism later in life. These efforts will be accompanied by public service announcements on underage drinking.

GOVERNMENT PERFORMANCE AND RESULTS ACT

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 second annual performance report, which compares our FY 2000 results to the goals in our FY 2000 performance plan. As performance trends on research outcomes emerge, the GPRA data will help NIH to identify strategies and objectives to continuously improve its programs.

Footnotes :
1 Updated figures from Lewin Group, 1998.
2,3 NIAAA epidemiology data

 


Posted: May 22, 2001