Mutant worms withstand boozy bender
Single gene linked to alcohol tolerance.
12 December 2003
HELEN R. PILCHER

Mutant worms can soak up the equivalent of twenty times the human drink-drive limit.
© SPL

Some worms can really hold their drink. A genetic twist of fate renders them immune to alcohol, new research reveals.

The study may explain why a small sherry sends some people slurry but leaves others sober. It may also aid the development of therapies for alcoholism.

Give a normal nematode alcohol and it gets drunk, explains Steve McIntire from the University of California, San Francisco. Wasted worms wiggle less, move more slowly and lay fewer eggs. “Eventually they fall into a state of profound sedation,” says McIntire.

But some mutants can soak up the equivalent of the human drink drive limit and appear normal. These alcohol resistant animals have a fault in the gene slo-1, McIntire’s team has discovered. Some humans with a high toerance may share a similar makeup.

The study suggests that slo-1 may control our behavioural response to alcohol. If the gene is defective, alcohol may have no effect. Drugs that affect this system may alter the response to alcohol, McIntire suggsests.

Related therapies might also treat alcoholism. People who become drunk less easily are more prone to becoming alcohol dependent. “Genes like slo-1 may also affect ethanol sensitivity,” says worm researcher Mark Alkema from the Massachusetts Institute of Technology in Cambridge.

Any such treatment is a long way off, cautions Alkema. “For now, drink responsibly instead of relying on drugs after a pub crawl,” he advises.

Some people stay drunk for longer than others because they metabolize alcohol more slowly. Women, for example, have lower levels than men of alcohol dehydrogenase, the enzyme that breaks down alcohol. The gene slo-1 is not involved in this process, however.

Acting up

The gene encodes a pore-shaped protein, called a potassium channel, that regulates nerve firing. If these channels are under-active – as in the mutant worms – neurons fire normally despite the presence of alcohol, rendering a champagne cocktail as potent as a glass of milk.

The big question now is whether this channel is equally important
in humans
Nick Franks
Imperial College

Over-activity of these channels interferes with communication between cells in the brain, triggering shambolic behaviour. Worms with overactive SLO-1 channels act as if drunk even when they haven’t touched a drop, the team also found1.

“The big question now is to find out if this channel is equally important in humans,” says Nick Franks of Imperial College, London, who studies such ion channels. This is likely, claims McIntire – alcohol affects the same protein in cultured human cells, and worms and mammals succumb to equivalent doses of alcohol.

References
Davies, A. G. et al. A central role of the BK potassium channel in behavioural responses to ethanol in C. elegans. Cell, 115, 655 – 666, (2003). |Homepage|

© Nature News Service / Macmillan Magazines Ltd 2003