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Drinking Gene

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  • Drinking Gene

    Alcoholics may one day get help from drugs that turn off a switch that triggers drunkenness. As this ScienCentral News video reports, scientists studying worms have discovered a gene that controls intoxication.

    Drunk Worms

    Behind well-manicured suburban lawns, Susan Cheever learned to become an alcoholic. At six, she could mix a martini. Later, she could name the drinks dominating cocktail hour, sipping from adult glasses to feed a palate already growling for alcohol.

    With dependence on drink firmly anchored, Cheever grew to adulthood, slipping behind steering wheels with beer in hand, spinning in and out of marriages and penning memoirs thick with the haze of drinks past.

    To curtail the devastating impact of alcohol dependency on people like Cheever, now a sober, successful writer, researchers at the University of California at San Francisco (UCSF) have been studying the effects of alcohol exposure in worms. They've discovered a gene that seems to turn off the master switch that triggers drunkenness, a finding that may lead to a drug that would make alcohol less appealing to alcoholics.

    "Whether one looks at a fruit fly, a worm, a fish or a mammal, they all become intoxicated at essentially the same dose of alcohol," explains Steven McIntire, lead scientist of a UCSF study that was profiled in the March issue of Discover Magazine. "This has led people in the field to believe that there's likely to be a molecule or set of molecules in the brain that alcohol interacts with to cause intoxication."

    To test this theory, McIntire used DNA-altering chemicals to engineer two types of a microscopic worm called C. elegans, those with an over-active version of a gene called slo-1, and those with a mutant, under-active version of slo-1. Worms use slo-1 to fire brain signals to a protein called a potassium channel . The protein acts to widen or narrow the channel where brain signals pass.


    C. elegans, the worms used in the study

    Mutant worms, those with under-active slo-1, narrow potassium channels to block signals. With the signals stopped, "alcohol doesn't have a normal target to act on in the nervous system," so they don't get drunk when exposed to levels of alcohol that would leave normal worms comatose, McIntire explains.

    Conversely, worms with over-active slo-1 "allow more current to flow through," McIntire says. These animals are bombarded with signals that trigger symptoms of drunkenness like less wiggling, slower movement and laying fewer eggs. When McIntire removed over-active slo-1 these lightweights became almost completely resistant to alcohol.

    At work in people too, slo-1 controls our response to alcohol in much the same way that it does in worms, though other biology, like metabolism, contributes to human drunkenness. People who metabolize alcohol slowly stay drunk for a long time. That's because they have low levels of alcohol dehydrogenase, the enzyme that breaks down alcohol.

    McIntire would like to use this research to create a drug that will keep the potassium channel narrow in the human brain, blocking signals that trigger drunkenness. That would make alcohol less appealing, he believes.

    Cheever is wary of such an approach. She quit drinking in 1992 and considers Alcoholics Anonymous (AA) the best way to conquer alcoholism. In the last years of life, her father, the Pulitzer Prize-winning writer John Cheever, sobered up by attending AA meetings. "He went from being a very unpleasant drunk and sick, a sick, sick man to being an extraordinary father," she says.

    AA's long-standing success led Cheever to write a new book about the group's co-founder. Entitled My Name is Bill: Bill Wilson—His Life and the Creation of Alcoholics Anonymous, Cheever's book heralds Wilson as a man whose contributions to tackling alcoholism are unprecedented. "His ideas about alcoholism and how to treat it, which came out of his own personal experience, really led to a way to treat alcoholism which has gotten millions and millions of people sober," Cheever says.

    She'd like to see society do as much as Wilson did for alcoholics. Right now, Cheever looks around at an American culture that she believes glorifies drinking by advertising it on television and holding up heavy drinkers as idols. "It makes me sick," she says.

    McIntire's science might not offer a cure for alcoholism, but he believes that a drug that blocks the effects of alcohol would still benefit alcoholics. With 14 million Americans battling the disease to varying success, drugs that curb alcohol dependency could aid those who, unlike Cheever, are losing the sobriety struggle.

    This research was published in the December 19, 2003 issue of Nature and was funded by UCSF, the Department of the Army, the National Institute of Alcoholism and Alcohol Abuse, and the National Institutes of Health.
    \"No, I think Space is a dimension of Time. My theory is that Time is a field and that Space exists as an aspect of Time.\" Michael Moorcock

    \"All I know about anything is \"I wasn\'t. I am. I will not be.\" Michael Moorcock
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