We've used it for hundreds of years, but we still don't know how anaesthesia works. Finding out could lead to safer drugs and unlock the mystery of consciousness

Out like a light? Francesco Bongiorni

COUNT slowly backwards from 10. Before you reach seven, you’ll be out like a light.

Without anaesthesia, surgery would be, and once was, excruciating. Yet, as anyone who has been put under will attest, general anaesthesia is a pretty drastic medical intervention itself: a sudden and total shutdown of consciousness. It’s not hard to see it as a little foretaste of death. General anaesthesia was first used for surgery in the 1840s. The shocking thing is that we still don’t really know how it works.

We do know that anaesthetic agents suppress signalling between neurons in the brain. We think we know which molecules the agents hit. But just how they do their silencing job is a mystery.

Fortunately, this lack of knowledge doesn’t stop anaesthetists wielding the drugs effectively. However, a clearer picture of what happens could not only help to avoid the rare but very real dangers of anaesthesia, but also help us develop more precisely targeted drugs and give us a better idea of consciousness itself, and what it means to toggle it on and off.

Recently, we have uncovered a few more clues as to how it all works, through research in biochemistry and more surprisingly in biophysics. But just how close are we to solving the mystery of how anaesthesia turns out the lights?

Many drugs work more or less in a “lock-and-key” fashion. They block biochemical processes because they precisely match the shape of specific molecules’ binding sites. And this seems to be how some classes of anaesthetics, including barbiturates, interrupt communication between our …