Drunken flies that carry a genetic mutation named "cheapdate" are helping scientists unravel one of life's mysteries: why some people can hold their liquor better than others.
The research found that fruit flies - and perhaps people, too - are especially apt to get inebriated if they naturally produce low levels of a chemical called cyclic AMP.These are, of course, just flies, but scientists have long known that the basic processes of life in such simple creatures often turn out to be virtually identical to the ones involved in more complicated animals, like people.
Indeed, given too much alcohol, speck-size fruit flies act remarkably like humans on a bender. They become hyperactive and uncoordinated, buzzing about erratically. After a few minutes, they fall into a dazed stupor and then pass out.
A team led by Dr. Ulrike Heberlein of the Gallo Center (named for the California wine family) at the University of California at San Francisco created thousands of fruit flies with genes randomly knocked out. One of the flies, it turned out, couldn't hold its alcohol. They dubbed its genetic flaw "cheapdate."
The researchers put flies inside a 4-foot glass dome - called an inebriometer - and pumped in alcohol vapor. The dome is crisscrossed with mesh landings. Ordinarily, the flies like to stay near the top. But as they got drunk, they fell from level to level.
Ordinary fruit flies take 20 minutes to hit bottom. But the cheapdate mutants tumbled down in 15 minutes.
Further research found that the easy drunks were missing a gene called "amnesiac," so-called because its deletion causes bugs to have very poor memories. Flies missing this gene are believed to have lower than usual production of cyclic AMP, a chemical messenger known to be involved in many critical processes, including memory and hormonal responses.
The study, published in Thursday's issue of the journal Cell, is the first clear evidence in a living creature of a link between cyclic AMP and reaction to alcohol. The scientists blocked other steps in the production of this chemical and found these, too, made the flies more prone to drunkenness.
"If you're a fly and your cyclic AMP levels are low, then you are sensitive to alcohol," Heberlein said. "In people, it's been studied, but it's not so clear."
In a laboratory dish, alcohol stimulates human cells to make more cyclic AMP. However, long-term exposure has the opposite effect, making cells gradually produce less of the chemical. No one knows for sure if the same thing happens inside the body.
However, the fruit fly experiment suggests it does, said Dr. Hugo J. Bellen of the Howard Hughes Medical Institute at Baylor College of Medicine in Houston.
People who can hold their liquor, especially at a young age, are more likely to become alcoholics than are those who get drunk easily. This tendency is inherited.
Bellen said the accumulating evidence raises the possibility that individual variations in production of cyclic AMP might contribute to the way people handle alcohol.
For instance, those whose normal production is low might get a big boost of cyclic AMP when they drink, while those with naturally high production get less of a kick.
However, these high producers could over time be more susceptible to alcoholism, because chronic exposure to the higher levels of booze they can tolerate suppresses their cyclic AMP production. So they drink to bring their cyclic AMP back up to normal.
Certainly, the body's response to alcohol is more complex than this, and the theory is still speculative. But Bellen said the fruit fly study "opens the door to understanding the chronic response to and need for a drug, in this case alcohol."