DRUNK FLIES SHED LIGHT ON ALCOHOLISM

Why some imbibing insects can't handle their booze.

Soused fruit flies in a lab at UC-San Francisco may have solved the
mystery of how your college roommate could drink everyone else under
the table.

A newly isolated gene, aptly named ``cheapdate,'' explains why some
inebriated fruit flies can still fly gracefully -- while their
brethren stagger, fall and pass out in a drunken stupor, according to
a report in today's issue of the journal Cell.

While the finding cannot yet be applied to humans, it adds to the
growing body of research that contends that some alcoholics are born,
not made. In nature's genetic shuffling, it appears, the nation's
estimated 18 million problem drinkers have been dealt a bad hand,
inheriting genes that set the stage for alcoholism.

There have been no proposals to engineer genes to accommodate that
sixth shot of tequila.

Rather, scientists hope that by identifying the biological markers of
alcoholism, they can one day be able to test young people, screening
for the chromosomal quirks that predispose or protect against
alcoholism, and warn those at risk for developing disease.

The biological basis of alcoholism is complex, not influenced by
solely one gene.

But the new finding ``lays the foundation for a genetic approach to
dissecting the acute effects of alcohol and should increase our
understanding of the molecular mechanisms causing drug abuse and
addiction in the near future,'' said Hugo J. Bellen of the Howard
Hughes Medical Institute in an accompanying review in the journal.

Physiological pathway

The new study -- carried out in the Ernest Gallo Clinic and Research
Center at San Francisco General Hospital -- sheds light on one
specific physiological pathway, the genetically programmed route that
influences the effect of alcohol on motor skills. It is relevant
because it is believed that people who have a lower response to
alcohol -- in other words, who feel less drunk when they imbibe -- are
predisposed to alcoholism.

The University of California at San Francisco study was conducted on
the tiny fruit fly Drosophila melanogaster, favored by geneticists for
its taste for sweets and sex. The fruit fly is common on putrid fruit
and has the uncommon ability to reproduce itself 25 times in one year,
giving researchers the chance to study many generations in a short
period of time.

By disabling a gene in a fly, then testing its tolerance to alcohol,
lead researcher Ulrike Heberlein could determine the function of that
gene.

She enclosed 100 flies in a 4.5-foot-tall glass cylinder called an
``inebriometer,'' then piped in a potent vaporized form of ethyl
alcohol. Inside the cylinder was a fly-sized staircase.

Ersatz bar stools

Sober, flies buzzed around the top of the cylinder. But as they became
steadily more intoxicated, they tumbled from the platforms that served
as ersatz bar stools and bounced to the bottom of the cylinder, where
they were collected. The most susceptible flies lasted only 15 minutes.

Most remarkable were those who hung on for 20 minutes, said Heberlein,
an assistant professor of neurology at UCSF. While their drinking
buddies were dropping like, well, flies, they were merely weak-kneed
and wobbly.

Heberlein's subsequent genetic study found that a mutation in the
``cheapdate'' gene -- more formally known as the ``amnesiac'' gene by
its original discoverers at the Massachusetts Institute of Technology
- -- caused flies to become more inebriated than their drinking buddies.
The gene controls sensitivity to alcohol, she concluded.

The gene is responsible for production of a key biochemical called
cyclic adenosine monophysphate (cAMP), which triggers a chain reaction

of many cellular processes, including motor control. Without it, the
body may be more vulnerable to the effects of alcohol on the ability
to walk, talk, and find its way home.

``Mutations in the gene taught us that when flies cannot increase cAMP
normally, those flies are more sensitive to intoxication,'' said Heberlein.

Manipulating DNA in fruit flies is the cheapest, safest and most
effective way to figure out how genes work. Moreover, because the
genes encoding the basic cellular functions of animal cells have been
conserved through millions of years of evolution, it is estimated that
90 percent of the genes in fruit flies have counterparts in humans.

Such research suggests that the tragic soul who drank out of despair
and spiritual emptiness, immortalized in the plays of Eugene O'Neill
and Tennessee Williams, may in fact have simply carried bad genes.

Scientists say that although the disease of alcoholism can be
triggered by environmental or psychological factors, people may be at
excess risk because of an underlying biological predisposition.

The search for alcoholism's biologic underpinnings began in earnest in
the 1970s. Since then, it has been found that a genetic influence is
identifiable in at least 35 to 40 percent of alcoholics.

In 1990, a form of a gene on human chromosome 11 was found to be
carried by most severe alcoholics and absent in most non-alcoholics.
The gene creates the receptor for a neurotransmitter called dopamine,
known to be associated with pleasure-seeking behavior.

Other studies suggest that alcoholics do not metabolize alcohol
properly. Research also has found that alcoholics, as well as their
young children not yet exposed to alcohol, exhibit brain waves and
memory deficits different from non-alcoholics.

This new research suggests that if people inherit an increased ability
to tolerate alcohol, they may be at risk of dependence because they
don't learn when to stop.

Scientists now believe that although the dizziness and nausea of
drunkenness may make people feel miserable, such symptoms also offer
lifesaving protection against regular heavy drinking.

Checked-by: (trikydik)