May 10, 1997 in City

Tracking Of Genes May Yield Triggers Behind Alcoholism Susceptibility At Heart Of Study To Find Out How Disease Works

Ted Mcdonough Moscow-Pullman Daily News

Scientists probing human genes are unraveling the complex inheritance that points people toward alcoholism.

Researchers have known for decades that alcoholism runs in families. New developments are allowing scientists to determine some of the genes that make people susceptible and trace those genes to biological chemistry that can be manipulated with drug therapy, according to TinKai Li, who spoke this week at Washington State University.

A professor of medicine and biochemistry at the Indiana University School of Medicine, Li is a member of the National Institutes of Health advisory committee and serves on a National Academy of Sciences committee on raising the profile of substance abuse research. He spoke to students and professors on his work using animals to model human alcoholism.

Li said most of his genetic research is aimed not at eventual genetic manipulation to prevent or cure disease, but at understanding how diseases work on the body.

“The question is why do you want to identify genes,” he said. “You want to look at the genetics to understand disease. Once you find the gene, you can say this codes for this protein. What does this protein do?” Because alcohol isn’t addictive for most users, scientists studying alcoholism are concentrating on what makes some people susceptible, Li said. “Whether people drink or not is environmentally determined, but the amount and frequency is determined by genetics.”

In humans, scientists have discovered two genes that appear to greatly influence drinking behavior, Li said. Present in Asians, but not in Caucasians, the genes guard against heavy drinking. People who inherit the genetic material are five times less likely to become alcoholic than those without the genes.

Researchers have discovered other genes that appear to influence susceptibility to alcoholism, Li said. In rats, three to four biological systems have been identified that influence drinking behavior. Blocking one of those systems - the serotonin or dopamine system for example - can greatly influence drinking in rats.

Using the same approach, new drugs on the market in the United States and Europe appear to offer hope to alcoholics, Li said. Experiments are under way with drug combinations.

But even if drug combinations could be produced to block the workings of alcohol in the body of an alcoholic, science still wouldn’t have a cure, Li said. “Even in rats, we can’t cut (drinking) down to zero.”

The problem is that such approaches don’t deal with the alcoholic’s craving for alcohol, he said, noting that the medical profession has had access for years to drugs that make people ill if they drink. “The problem is compliance,” he said. Alcoholics craving alcohol simply stop taking the drug. “You have to treat the craving.”

Li and others are investigating what biological processes are at work in craving.

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