14 June 1998

Drunk Fruit Flies Reveal Alcohol Sensitivity Gene

Never have fruit flies had it so good. First they were given a new lease on life with an anti-ageing gene that increased life spans by 40 per cent. And now they have been allowed to celebrate by getting hopelessly drunk. In a study touted as groundbreaking in laying the foundation "for a genetic approach to dissecting the acute, and possibly the chronic, effects of alcohol", fruit flies were encouraged to quaff and tipple while sober scientists looked on.

The study, reported in the 12 June issue of Cell, sought to determine what molecular factors influence a fruit fly's sensitivity to alcohol, with an aim to addressing the question of why some people are more apt to become alcoholics than others. Researchers from the University of California, San Francisco, set about "knocking out" different genes from the insects and then giving them booze as a way of revealing the role the missing genes would normally play.

When the scientists knocked out the gene known aptly as amnesiac, the fruit flies got drunker than their amnesiac-intact drinking partners. More importantly, when the scientists then examined how the amnesiac gene functions within the fly's neural system, they discovered that it regulates the cyclic AMP (cAMP) pathway, a signal transduction cascade that researchers have long known is affected by alcohol through studies in human cells.

The scientists deduced that greater intoxication resulted from reduced cAMP production, and tested their hypothesis by treating the mutant amnesiac flies with agents that increased cAMP levels. Significantly, they were able to reverse the alcohol sensitivity. The finding represents a giant leap from an isolated gene in fruit flies to an entire molecular pathway previously observed in animal and cell cultures.

"Our next step is to identify more genes in fruit flies associated with alcohol behaviours and to see if we can find homologous, or similarly acting, genes in higher organisms, including mice and humans," says Ulrike Heberlein, assistant professor of neurology and leader of the study. Which means a good many fruit flies will be waking up with hangovers.