Fruit flies sniff out heavy hydrogen

Here’s my latest news article for Nature. It’s worth checking out the comments on the Nature site.

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

Fruit flies can smell the difference between ordinary and heavy hydrogen, according to new research published today.

Efthimios Skoulakis of the Alexander Fleming Biomedical Sciences Research Centre in Vari, Greece, and his colleagues say that fruit flies show a preference for an odorant molecule containing ordinary hydrogen over the same molecule with the hydrogen replaced by heavy hydrogen (deuterium), when presented with both odorants in the two branches of a T-shaped maze.

The flies can also be conditioned to display a selective aversion to either of the forms of the odorant by electric-shock treatment, showing that they can clearly distinguish between them. The researchers report their findings in the Proceedings of the National Academy of Sciences USA [1].

Skoulakis and colleagues say that the results offer strong support to a controversial theory of how olfaction works, which has been proposed previously by Luca Turin of the Massachusetts Institute of Technology, who is also an author of the paper. According to Turin, odorants are identified by the olfactory apparatus not according to their molecular shape but their 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 in 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.”

Deuterium is an isotope of hydrogen: unlike ordinary hydrogen, its atoms contain a neutron in the nucleus 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. 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 theory [2], but there is no direct evidence for it in practice.

If Turin is right, deuterium-substituted odorants should smell different to those with ordinary hydrogen because they have different vibration frequencies.

There is not yet any good evidence that deuterated compounds smell different to humans [3], but subtle biases are hard to eliminate from such tests. That’s why Turin teamed up with Skoulakis to test fruit flies, which are less susceptible to biases and are known to have a good sense of smell.

When presented with the attractive (to flies) odorant acetophenone, the fruit flies showed an increasing aversion to it as more of its hydrogens were substituted for deuterium. The researchers could train the flies to associate either the deuterated or normal odorant with punishing electric shocks applied to their feet via 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 display a similar aversion to compounds called nitriles, since the vibration of the nitrile chemical group has a very similar frequency to that of the bonds between deuterium and carbon. They found this was so.

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 (2:1) difference in mass. After all, heavy water is toxic, and even in these odorants the substitution of deuterium changes properties such as melting and boiling points.

“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 [shape-based] sensing”, he says.

Vosshall is also sceptical. “Insects use odorant receptors that are structurally and functionally distinct from these human receptors, yet this group claims that the same vibration mechanism operates in these very distinct proteins”, she says. “This idea is difficult to reconcile with the current knowledge of how these completely divergent protein types detect odors.”

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 one case at least 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 exactly in the same way for humans”, he acknowledges. But he is convinced that something analogous applies.

References 

1. Franco, M. I., Turin, L., Mershin, A. & Skoulakis, E. M. C. Proc. Natl Acad. Sci. USA details to come.

2. Brookes, J. C., Hartoutsiou, F., Horsfield, A. P. & Stoneham, A. M. Phys. Rev. Lett. 98, 038101 (2007).

3. Keller, A. & Vosshall, L. B. Nat. Neurosci. 7, 337-338 (2004).