Smoking delivers nicotine to the smoker. Nicotine is pleasurable, which is why he smokes. However, smoking harms him, and annoys those around him. But nicotine is addictive, so he can't give up. This dismal reasoning underlies one of the fiercest public debates of our time. A new finding (M. L. Pianezza, E. M. Sellers & R. F. Tyndale Nature 393, 750; 1998) offers a way out. Nicotine is largely oxidized in the liver to cotinine. People whose livers perform this reaction badly are much less likely to become addicted to smoking. Daedalus has three possible explanations of this finding, each with a useful twist.

If nicotine cannot go to cotinine in the body, it will go instead to nicotine N-oxide. Being very similar to nicotine, the N-oxide may be its antagonist — sitting on and blocking its receptors but failing to trigger their pleasure. This should protect the smoker from addiction. If so, it could form the basis of a splendid new anti-smoking treatment.

Alternatively, it may be that nicotine is the pleasurable agent of smoking, but it is cotinine that is addictive. Blocking the reaction to cotinine (by a suitable enzyme inhibitor) would then convert smoking from a degrading addiction to a voluntary pleasure. It would also prolong that pleasure. Deprived of its fastest degradation route, nicotine would last longer in the body. The smoker would be satisfied with fewer cigarettes.

Or cotinine might turn out to give both the pleasure and the addiction of smoking. This is the most revolutionary possibility of all. For smoking is a clumsy, annoying, inefficient ingestion process. It survives because nicotine is unstable in air; it cannot easily be packaged as a drink (like caffeine or alcohol) or a pill (like amphetamine). It must be thermally liberated from a stable precursor, and breathed in at once, before it degrades.

But cotinine is stable in air. So nicotine could be extracted from tobacco, converted to cotinine, and sold as a pill or a beverage. Smokers by the million would happily abandon their smelly habit, and satisfy their craving by a product that could be drunk or chewed. Their risk of lung cancer (triggered by all that tarry smoke) would plummet. So might their risk of heart disease, which is blamed on nicotine itself. Cotinine, a product of the body's detoxification mechanisms, should be far less cardiotoxic. The commercial possibilities are limitless. If Joe Camel doesn't do it, DREADCO will.