Intramural research at NIAAA - National Institute on Alcohol Abuse and Alcoholism, Perspectives on Current Research

Alcohol Health & Research World,  Fall, 1989  by Boris Tabakoff

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Intramural Research at NIAAA

Understanding how alcohol produces intoxication, addiction, and damage to the body, and how these destructive effects can be prevented and treated, is the research goal of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Scientific studies on alcoholism are supported in many different hospitals and institutions, including NIAAA's intramural research program, which is an integral part of our national research effort.

The intramural program permits the Institute to respond flexibly to new research opportunities and to highlight areas where work is needed. The over 80 scientists involved in this activity and the 30 support staff who assist them work in three separate laboratories.

The Laboratory of Clinical Studies, directed by Dr. Markku Linnoila, is the largest of these, and includes approximately one-half of the intramural program's research staff. The two other major components are the Laboratory of Physiologic and Pharmacologic Studies, headed by Dr. George Kunos, and the Laboratory of Metabolism and Molecular Biology, under the leadership of Dr. Richard Veech.

Although moving to a shared location that would offer the advantages of daily contact among our scientific staff is an important long-range objective, space shortages have forced us to locate the three laboratories in two suburban Maryland locations--on the campus of the National Institutes of Health (NIH) and in a building several miles away. This situation gradually is improving. The intramural research program now has, in addition to space in the NIH Clinical Center, a laboratory in the Nuclear Magnetic Resonance (NMR) Center, a recently built multi-institute facility on the NIH campus that is devoted to advanced neuroimaging techniques. Our involvement in this collaborative facility is important because some of the most advanced work being conducted on alcohol's mechanisms of action involves NMR.

Staff scientists will soon have space in another building that is now under construction on the NIH campus, the Child Health/Neuroscience Facility. This new location will permit scientists in the basic science laboratories to collaborate more closely with clinicians and clinical researchers working directly with patients in the NIH Clinical Center.

CURRENT RESEARCH

The intramural research program has been highly productive over the last several years. Last year, for example, we published 160 reports on various aspects of research, and several scientists received awards for their research excellence.

Two of the most exciting areas of research, from the standpoint of their potential long-range impact, are basic and clinical investigations in the neurosciences. For example, studying alcohol's effects on specific brain receptors and the possible role of various drugs in modifying alcohol's effects can enhance markedly our understanding of the mechanisms of alcohol intoxication as well as our understanding of the development of tolerance, dependence, and neural damage related to chronic alcohol use. The significance of these findings, and of evidence that disturbed neurotransmission may be involved in symptoms of withdrawal, is not confined to esoteric studies in the laboratory. These findings can already be applied to improving clinical management of alcohol-dependent persons, to improving pharmacologic treatment of alcohol withdrawal symptoms, and to reducing rates of relapse.

Intramural research endeavors have practical implications with wide-ranging significance. For example, in molecular genetics the ability to clone enzymes--that is, to produce the DNA that provides the code for the enzyme molecule--has specific implications. Many of these enzymes are believed to be important in moderating the harmful effects of alcohol; one of the best ways to understand the role of these enzymes is to elucidate their exact structure through cloning. In this regard, Class 3 alcohol dehydrogenase and P450IIe, a component of the microsomal ethanol metabolizing system, have been cloned by Dr. David Goldman (see sidebar) and Dr. B.J. Song and their colleagues, respectively. Cloned DNA also serves as probes in genetic linkage studies designed to determine whether a given enzyme system is associated with a genetic predisposition to alcoholism.

Another aspect of the molecular genetics research that is full of intriguing long-range possibilities is the finding by Dr. Goldman's group of a genetic linkage in mice with a locus that determines the mouse's alcohol preference. These genetic linkage studies now being performed with animals are, of course, applicable to humans. They may provide new insight into genetic factors that play a role in individual susceptibility to alcohol and its effects.

The clinical group led by Dr. Linnoila has undertaken a large-scale diagnostic classification of alcoholic patients using standardized structured clinical interviews, such as the Schedule for Affective Disorders and Schizophrenia (SADS-L), and other tools. Careful diagnostic determinations can provide a clearer understanding of the relationship, or comorbidity, between alcoholism and other psychiatric disorders. This work also may allow for the classification of patients or clients into categories, such as those proposed by Dr. Robert Cloninger, that could have far-reaching genetic and etiologic implications. Improved classification is directly related to prevention and treatment. The ability to categorize alcoholics into more homogeneous subgroups could result in better tailoring of treatment, interventions and prevention measures.