FRUIT FLY CLUE TO ALCOHOLISM

Scientists hope 'cheapdate' gene defect can be found in humans too

Fruit flies that are literally falling-down drunk may provide the first
insight into why some humans are able to hold their liquor better than
others, San Francisco researchers report today.

The flies have a genetic defect, dubbed "cheapdate" by the scientists, that
causes them to display all the characteristics of human drunkenness -
hyperactivity, loss of coordination, disorientation and, ultimately,
unconsciousness.

Moreover, they become intoxicated on 30 percent less alcohol than is
required to produce the same effects in their healthier brethren,
geneticist Ulrike Heberlein and her colleagues at the University of
California at San Francisco report in the journal Cell.

The gene is the first that has been definitively linked to a propensity for
alcoholism , and, experts said, it is not unrealistic to think the
discovery could lead to new ways to reverse the effects of overimbibing.

"It's a very interesting and provocative result," said Bob Karp, director
of extramural genetic programs at the National Institute on Alcohol Abuse
and Alcoholism. "This is the beginning of the elucidation of a pathway for
sensitivity to alcohol."

Alcoholism is a pervasive public health problem, affecting an estimated 14
million Americans. Although it often strikes victims seemingly at random,
researchers have long suspected a strong genetic link.

People who have a sibling who is an alcoholic are three to eight times as
likely to develop alcoholism themselves as are those with no family history
of the disease.

No one has yet linked a single gene to alcoholism in humans, but the new
research gives them a good idea where to look for at least one of them.

Heberlein and her colleagues used a device called an inebriometer to screen
tens of thousands of laboratory-mutated flies to see how alcohol affects
them. The inebriometer is, in essence, a four-foot-tall glass dome with
funnel-shaped screens across it at regular intervals.

Fruit flies normally prefer to stay at the top of the dome, but as alcohol
fumes are pumped into the chamber, they become intoxicated and fall
progressively to lower levels. It takes normal flies about 20 minutes to
fail all the way to the bottom and out of the chamber. The cheapdate flies
fall through in less than 15 minutes.

Studying cheapdate's genes, Heberlein's team found that it has a mutated
copy of a previously known gene called "amnesiac," which produces memory
problems. The normal form of the gene stimulates production of a chemical
called cyclic AMP or cAMP. The cheapdate flies do not make as much cAMP in
their brains and that, Heberlein says makes them more sensitive to the
effects of alcohol.

But the team found that if they gave the flies drugs that increase
production of cAMP in the brain, the flies became more tolerant to alcohol
and could last as long as healthy flies in the inebriometer. Presumably,
similar drugs could help humans resist the effects of alcohol.

"Alcoholism ... is not due to a mutation a single gene," according to Dr.
Enoch Gordis, the alcoholism institute's director. "In all likelihood, it
is a handful of genes" that cause it.

The study provides "compelling evidence that cAMP metabolism plays an
important role ... in the acute response to ethanol in fruit flies," said
Dr. Hugo J. Bellen of the Baylor College of Medicine in Houston. "The fruit
fly may pave the way for an in-depth study of many of the genes involved in
the acute and chronic effects of ethanol" in flies and humans.

Scientists have been looking for alcoholism-related genes for more than a
decade, since Karp's institute began a massive project called the
Collaborative Study on the Genetics of Alcoholism.

Scientists have not yet found the amnesiac gene in humans, but that may be
just because they have not been looking. The human genetic blueprint
contains an estimated 100,000 genes, and researchers have so far identified
fewer than half of them.

Checked-by: (Joel W. Johnson)