Mutant Fruit Fly Gene Could Help Open Doors to Tailor-Made Anesthesia, Insights Into Anesthetic Action

Newswise — A single-gene mutation found in a tiny fruit fly could play an important role in helping to answer a question that continues to baffle anesthesiologists and researchers everywhere: Just how do volatile anesthetics work?

Volatile anesthetics are those that easily pass from the liquid to vapor phase and are readily inhaled. These inhaled anesthetics produce profound unconsciousness and are used for patients undergoing many different types of surgical procedures.

In a study published in the February 2009 issue of Anesthesiology, Berthold Bein, M.D., and his research group from Germany's University Hospital Schleswig-Holstein, Campus Kiel, found that a genetic mutation in the fruit fly Drosphila that causes it to need very little sleep also has a dramatic impact on its susceptibility to volatile anesthetics.

"Despite the widespread use of volatile anesthetics in medical practice, the specific mechanisms of action of inhalational anesthetic agents remain largely unknown," said Dr. Bein. "This hampers efforts to make general anesthesia more individually tailored, more effective and more convenient for the patient."

Individual anesthetic requirements differ markedly between subjects and are largely unpredictable. Dr. Bein said that, at present, anesthetic dosing recommendations are based on expert knowledge, which in turn depends on patient characteristics such as age and weight.

Specific understanding of genetic factors that affect anesthetic requirements in humans could dramatically change the way anesthesia is given.

Interestingly, the tiny Drosphila has more in common with humans than one might think, and studying it could offer important clues for eventual scientific breakthroughs in humans.

The fruit fly has a complex nervous system consisting of tens of thousands of nerves cells organized into circuits that control complex behavior, said Dr. Bein. "Moreover, like mammals, fruit flies exposed to volatile anesthetics proceed through a similar excitable state, followed by an uncoordinated state, to an unresponsive and immobile state."

The gene that Dr. Bein and his group isolated in Drosphila " the so-called "Shaker" gene " is responsible for regulating its extremely short-sleeping patterns. Dr. Bein wanted to know if the gene that affected the fly's sleeping pattern also would affect its anesthetic needs.

"We hypothesized that short-sleeping Drosphila mutants also would need increased concentrations of volatile anesthetics, thereby showing a common molecular target responsible for the similar, albeit different physiological states of 'sleep' and 'anesthesia.' This hypothesis was proven in our experiment."

Dr. Bein's study is perhaps the first to demonstrate a link between sleep and anesthesia on a molecular level and that a single-gene mutation can have a drastic impact on susceptibility to volatile anesthetics.

The study's applicability to humans may not be far off.

"For the first time, we have shown that sleep and anesthesia share a common molecular target. We and other researchers have previously demonstrated that this molecular target has been highly preserved during evolution and is nearly equally present in Drosphila and mammals, including humans," said Dr. Bein. "More important, these genetic insights may explain, at least in part, differing anesthetic requirements of patients throughout the world and may therefore help to enable individually tailored anesthetic delivery."

For more information visit Anesthesiology at www.anesthesiology.org.

Anesthesiologists: Physicians providing the lifeline of modern medicine. Founded in 1905, the American Society of Anesthesiologists is an educational, research and scientific association with 43,000 members organized to raise and maintain the standards of the medical practice of anesthesiology and improve the care of the patient.

For more information visit the ASA Web site at www.asahq.org.