Scientists in Texas have generated worms that can’t get drunk after ingesting alcohol. The study, published in The Journal of Neuroscience today, relates how the researchers were able to alter a common human alcohol target — a molecular channel that binds alcohol in the brain — in Caenorhabditis elegans worms by modifying the worm’s genetic makeup. This, the researcher say, is the first example of scientists modifying a human alchohol target to successfully prevent intoxication in an animal.
drunk worms crawl more slowly and don't wiggle as much
Normally, when worms are put in a petri dish that contains alcohol, they become drunk. For a worm, this mean not being able to wiggle from side to side as much. It also means crawling much more slowly. But with the modified channel, the worms acted just as they did without the alcohol. The researchers were able to do this by tweaking the human alcohol target just enough to prevent "a research model worm from getting drunk," said Jonathan Pierce-Shimomura, a neuroscientist at the University of Texas at Austin and a co-author of the study, in an email to The Verge.
Moreover, "the way we tweaked it did not perturb the normal function of the target, allowing it continue functioning normally in the worm's brain," Pierce-Shimomura said. This is important because the channel that the researchers modified — called the BK channel SLO-1 — also plays a role in regulating the activity of blood vessels, neurons, and the urinary tract. "It is remarkable that [a] mutation … could have such a dramatic specific effect on ethanol modulation while minimally affecting basal BK channel function," the researchers wrote in the study.
"We tried a brute force approach, testing hundreds of mutations."
To find this target, Pierce-Shimomura and his team proceeded largely by trial-and-error. "We tried a brute force approach, testing hundreds of mutations to empirically determine which one would allow the BK channel to function normally [while still] preventing alcohol from activating it." Eventually, they stumbled upon a genetic modification of the channel that stopped it from activating in the presence of ethanol.
This effect is very different from "Asian flush" or "alcohol flush reaction," a condition that causes certain people, mostly of Asian descent, to process alcohol inefficiently. "Asian flush is due to slow metabolism of alcohol which produces a by-product called acetyladehyde," Pierce-Shimomura explained. "This is a poison, so people with Asian flush are being poisoned when they drink alcohol."
The researchers now hope to develop drugs that would have the same effect in mice — and eventually humans. "We found a way that future drugs may target a single human brain protein, called the BK channel, to stop alcohol from activating it and causing intoxication," Pierce-Shimomura said. If the scientists could find a drug that has the same effect as the mutation, they might be able to help people overcome addiction and the effects of withdrawal.
Of course, any drug of this nature is a long way off from human trials. And even if they do find such a drug, it probably wouldn't get rid of all the symptoms of intoxication, because alcohol acts on multiple targets in the human brain. Still, Pierce-Shimomura said, alcoholism "is a huge problem in society that needs more effort and funding. Almost everyone knows someone touched by alcohol abuse," so this is a path worth investigating further.