Published online 14 February 2011 | Nature | doi:10.1038/news.2011.39

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Insects' ability to discriminate isotopes reignites debate over a controversial theory of olfaction.

Researchers have shown that flies can smell the difference between normal hydrogen and deuterium. iStockphoto

Fruitflies can smell the difference between ordinary hydrogen and its heavier counterpart, according to research published today.

Efthimios Skoulakis at the Alexander Fleming Biomedical Sciences Research Center in Vari, Greece, and his colleagues report that when presented with different versions of a fragrant molecule in the two branches of a T-shaped maze, fruitflies (Drosophila melanogaster) show a preference for the one containing ordinary hydrogen over that in which hydrogen is replaced by heavy hydrogen (deuterium).

The flies can also be conditioned by electric-shock treatment to exhibit a selective aversion to either form of the molecule, showing that they can clearly distinguish between them. The authors report their findings in the Proceedings of the National Academy of Sciences1.

Skoulakis and his colleagues say that the results offer strong support to a controversial theory of how olfaction works; a theory proposed previously by one of the report's co-authors, Luca Turin at the Massachusetts Institute of Technology in Cambridge. According to Turin, odorants are identified not according to their molecular shape, but their atomic vibrations.

"This is an important paper, and offers very strong evidence in favour of the vibrational theory of olfaction," says materials physicist Andrew Horsfield of Imperial College London.

But others are not convinced. Leslie Vosshall, a neuroscientist specializing in olfaction at the Rockefeller University in New York, considers it interesting that flies show such discrimination, but adds that "these findings by themselves do not provide strong support for any of the prevailing models of smell".

Different vibes

Deuterium is an isotope of hydrogen: unlike ordinary hydrogen, its atomic nucleus contains a neutron as well as a proton. This makes the atoms roughly twice as heavy. The chemical properties of deuterium are much the same as those of ordinary hydrogen, but its greater mass means that when the atoms are bonded to others in a molecule, they vibrate more slowly.

In the predominant theory of olfaction, odorant molecules dock into cavities in receptor proteins lodged in the olfactory membranes, like a key into a lock. This docking depends on a match between the shape of the odorant and that of the cavity; if they fit together, this triggers a neural signal to the brain.

But Turin thinks that, instead, the receptor proteins 'sense' the vibrations of the odorant, an effect made possible by the quantum-mechanical behaviour of electrons in the molecules. Horsfield and others have shown that this process could work in theory2, but there is no direct evidence for it.

If Turin is right, deuterium-substituted odorants should smell different from those containing ordinary hydrogen because they have different vibrational frequencies.

Sniffer model

So far, there is no strong evidence that humans can smell the difference between deuterated compounds and those containing ordinary hydrogen3, but subtle biases are hard to eliminate from such tests. Fruitflies are less susceptible to such biases and are known to have a good sense of smell.

When presented with the odorant acetophenone, which is attractive to fruitflies, the insects showed an increasing aversion to it as more of its hydrogens were substituted for deuterium. The researchers were also able to train the flies to associate either the deuterated or the normal odorant with punishing electric shocks applied to their feet through the floor of the maze, and to avoid them accordingly.

If the vibrational mechanism of smell is correct, the researchers reasoned that flies trained to avoid deuterated odorants should show a similar aversion to compounds called nitriles, because the vibration of the nitrile chemical group has a similar frequency to that of the bonds between deuterium and carbon. The flies responded as expected.

But Bill Hansson, a specialist in insect olfaction at the Max Planck Institute for Chemical Ecology in Jena, Germany, isn't persuaded. He points out that, although most isotopes are chemically identical, this is not always the case with hydrogen and deuterium, given their large difference in mass. After all, heavy water is toxic, and in the odorants used in the present experiments the substitution of deuterium changes properties such as melting and boiling points.

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"If hydrogen bonds between the odorant and corresponding receptor play a major role, insects may well be able to discriminate between deuterated and non-deuterated compounds using conformational sensing," he says.

Regardless of the mechanism, might humans discriminate isotopes by smell too? "Extrapolation to humans has to be treated with care," Horsfield warns. Turin has, however, received unpublished reports of isotopic smell-discrimination in dogs. "In at least one case the dogs are said to completely ignore the deuterated version of an odorant that they are trained to detect in the undeuterated version," he says.

"Things are unlikely to work in exactly the same way for humans," he acknowledges. But he is convinced that something analogous applies.