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The nose knows. A scanning electron micrograph of the head of a Drosophila, and a cartoon depicting how a vibration-sensing receptor might work (inset).

CSIRO; (inset) Luca Turin;

Do Vibrating Molecules Give Us Our Sense of Smell?

That tingling in your nose may not be allergies. In a provocative new paper, a team of scientists suggests that tiny molecular vibrations give us our sense of smell. Some experts are skeptical, but if the work holds up it could upturn over a century of physiological research.

Mainstream researchers have long attributed our sense of smell to a "lock and key" hypothesis. The idea is that every odor molecule that enters our nose has a specific shape that fits a specific receptor—like a key fits a lock—allowing us to detect, say, the acrid aroma of burnt coffee. But the hypothesis leaves some questions unanswered. For one, it doesn't explain, why we can detect tens of thousands of odors with only a few hundred smell receptors. It also doesn't explain why odor molecules with very similar shapes give us such different smells; the molecules that gives us the smell of vodka and rotten eggs are almost identical, for example.

Enter vibrations. Chemists have long known that atoms in a molecule vibrate at a particular frequency, depending on their overall molecular structure. Even molecules that differ by a single atom can vibrate quite differently. In the new study, neurobiologists Maribel Franco and Efthimios Skoulakis at the Alexander Fleming institute in Athens and biophysicist Luca Turin and colleagues at the Massachusetts Institute of Technology tested whether these vibrations could account for our wide range of smell.

The researchers focused on Drosophila, or fruit flies, which don't bring the same subjective odor experiences to the table that a human might. They placed the flies in a maze with two arms, into which they pumped nearly identical odor molecules. Odorants such as acetophenone and deuterated acetophenone, for example, have the same molecular structure; one is just built from a slightly heavier hydrogen atom, known as deuterium. Despite these miniscule variations, the flies showed a consistent preference for one arm of the maze over the other, the team reports online today in the Proceedings of the National Academy of Sciences, suggesting that the flies could tell the difference between the odorants.

The findings are inconsistent with a shape-only model for smell, says Turin. Because odorants like acetophenone and d-acetophenone mainly differ in their vibration patterns, the most plausible explanation, he says, is that flies can "smell molecular vibrations." Turin and his colleagues suggest that even though we have a limited number of smell receptors in our noses, a combination of vibration- and shape-sensing components could account for our expansive sense of smell.

Leslie Vosshall, a neuroscientist at the Rockefeller University in New York City, is skeptical. "I think this paper nicely demonstrates that flies can tell deuterated and non-deuterated odors apart," she says. But "I do not think that this result on its own either confirms or refutes the vibration theory." She points to a 2004 study, for example, in which she and colleagues found no evidence that humans could discriminate between acetophenone and deuterated acetophenone. To really test the vibration idea, she says, scientists will need to perform more detailed studies on mammalian odor receptors.

Stephen Trowell, however, is more positive about the findings. "This is an interesting study that touches on an area that has been controversial for decades," says Trowell, a biochemist who is developing analytical devices for the detection of odors at the Commonwealth Scientific and Industrial Research Organisation, Australia's national science agency, based in Canberra. Although the lock-and-key hypothesis may explain some of our sense of smell, he says, it "is not the whole story." Knowing more about how our noses really work, he says, will help researchers better develop electronic noses that can assess food quality and even sniff out explosives.