Study of `hangover gene' in fruit flies may hold key to humans' capacity to develop tolerance for alcohol

DNA of drinking ability

December 31, 2005|By JULIE BELL AND NICOLE FULLER | JULIE BELL AND NICOLE FULLER,SUN REPORTERS

Ever wonder why some poor sots fall off their bar stools after one drink while others imbibe into the evening?

The answer, it turns out, may lie partly in the hangover gene.

Addictions expert Ulrike Heberlein and fellow researchers reported this year in the journal Nature that they had discovered it in drunken fruit flies. Now they're working with experts in human genetics to see whether people have it, too.

"Firstly we'd have to figure out whether ... people who have differences in their ability to develop tolerance have different versions of this gene," said Heberlein, whose University of California-San Francisco lab has studied loaded fruit flies for years.

In its normal configuration, the hangover gene - so named by its discoverers - appears to help fruit flies develop a tolerance to alcohol, given repeated exposure to it. But fruit flies with a mutant form of the hangover gene couldn't hold their liquor (actually, ethanol fumes) even after practicing.

The finding follows others that point to genetic bases for differences in innate alcohol sensitivity, alcoholism rates and the ability to develop tolerance.

But don't assume you can drink with impunity during New Year's Eve revelry if you're not a genetic mutant: Some previous science indicates that people with high tolerance are at greater risk for alcoholism. And, no matter what your makeup or experience, studies indicate that you should consider parking your car keys with a nondrinking friend.

That's because even those who quickly metabolize alcohol - burning it up so they can drink more before feeling drunk - tend to be impaired before realizing it.

"People underperceive how it affects their performance," said George Bigelow, a psychologist and Johns Hopkins University professor who has studied aspects of alcoholism. "You can see that in lab studies."

Drinkers interviewed this week in one Federal Hill tavern - an alcohol laboratory of sorts - seemed to think Heberlein's latest findings are just more evidence of the obvious.

Some people have the makeup and drinking experience to hang all New Year's Eve, popular thinking goes; others should recognize their genetic limits and call for a Diet Coke.

Phil Jacoby believes he's probably among the former. The 53-year-old financial consultant, who lives in Federal Hill, said his tolerance for alcohol is high, which he attributes to genetics and his healthy appetite for Bushmills Irish Whiskey.

Earlier this week, he and friend Karen Karash, 41, were among those visiting the Thirsty Dog Pub. They threw back some Black and Blonde Dog Ales and picked up pepperoni pizzas. By 8 p.m. Karash was on her eighth beer, Jacoby on his sixth. Neither felt wasted. Both surmised they must not have the mutant form of the gene.

Karash, who said she has been drinking recreationally since about age 14, called her tolerance level, "high, very high."

"My grandmom and my pop drink," Karash said. "There's nothing wrong with it."

Jacoby interjected: "As long as you don't drink and drive. That's why you live in Federal Hill. You can walk here."

Fellow drinker Mark Caputo, 39, who stands 6-foot-1 and weighs 230 pounds, said his burly frame gives him an advantage over slighter drinkers. And he built up his tolerance, he said, knocking back beers in college.

"Divorce and a couple of kids brings the tolerance level up," Caputo said jokingly. "It's from years of practice."

It's precisely the second part of Caputo's statement that UCSF scientist Heberlein set out to study. She wanted to know the basis of her fruit flies' ability to learn to "drink" more before falling down drunk.

To find the answer, researchers plied fruit flies with ethanol fumes inside a contraption called the "inebriometer." (Heberlein, an anatomy professor and fruit fly expert, also conducts experiments in a "booze-o-mat," but that's another matter.)

Each inebriometer stands 4 to 5 feet tall and features a descending series of platforms on which the critters stand as they inhale the ethanol fumes. As they get tipsy, they behave a lot like drunken people: slumping, falling down and finally passing out.

"As they breathe it in, they gradually lose their ability to stand on those baffles," Heberlein said, explaining that they tumble from platform to platform and eventually fall out the bottom, drunk. "What we measure is how long they're able [to stand] before they come out the bottom."

The flies took about 20 minutes to hit bottom the first time they went through the inebriometer. Four hours later, when the same ones were loaded in again, the normal ones had developed tolerance and took 28 minutes to topple drunkenly to the base.

But those the lab engineered to have the mutant hangover gene didn't gain much tolerance. They also seemed, in separate experiments, to have a defective response to environmental stressors such as heat.

Ultimately, Heberlein said, her experiments might help lead to a drug that could inhibit the tolerance-building function of the hangover gene, making it act like its mutant. That could make those with drinking problems have less tolerance for alcohol, something Heberlein surmises might cause them to drink less.

"People drink to a certain level of intoxication," she said. "If you had no tolerance, you would drink less."

That's not news to some at the Thirsty Dog, such as Caputo. He already avoids some drinks that he believes he doesn't tolerate well.

"Tequila," he said, noting one. "Very bad."

juliana.bell@baltsun.com nicole.fuller@baltsun.com

To see the drunken fruit flies, go to baltimoresun.com/fruitflies.

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