An Update on Vibrational Theories of Smell

I’ve written a few times over the years about the vibrational theory of olfaction (VTO), the hypothesis that (at least some) olfactory receptors work by sensing vibrational levels of various functional groups, rather than using traditional stereoelectronic interactions. At a deeper level, this could involve electron tunneling at the receptors themselves – a direct quantum mechanical sensor. This idea, which has popped up more than once over the years, has most recently been identified with the work of Luca Turin, and it is fair to describe it as controversial.

Some in the field are prepared to dismiss it more or less out of hand (out of nose?), but the proposal has gotten a hearing. The problem is, experimental proof has been very difficult. An obvious test would be whether olfactory receptors respond differently to deuterated compounds as opposed to the standard light-hydrogen ones (same size, same polarity, different vibrational frequencies) but running that experiment at the desired level of accuracy has been unexpectedly difficult. Here’s an excellent recent review that goes into the details – from what I can see, it’s quite thorough and evenhanded. It takes the experimental attempts in historical order, and it’s a tangled tale. The first problem is purity: olfactory receptors are notoriously sensitive to particular compounds and functional groups. If a sample has even very small amounts of an impurity with a distinctive scent of its own, the experiment is demolished.

This has been an objection (over and over) to the various results in this area, which have been generated with work involving humans, bees, and flies in various formats. Some of these have shown discrimination is possible between deuterated and nondeuterated compounds, but all of the experimental results, as you’d figure, can also be explained by the presence of trace contaminants. Indeed, some of them have later been shown to have been confounded by just that problem, so it’s not just a hypothetical objection. Getting reliable sensory readouts from human subjects is rather tricky as well, even under the best conditions; the bees and flies are probably more convincing overall.

The review goes on to ask whether there are in fact results that can’t be explained by the existing theories of olfaction – in other words, is there a need for a new theory at all? The arguing is vigorous around this question as well, but a good case can be made that olfaction can still be explained by molecular surface shape, electrostatics, etc. Not everyone is convinced, of course. But the review goes on to mention something that many people in the field don’t bring up: even if vibrational sensing of this type isn’t going on in natural olfactory receptors, that doesn’t mean that it can’t work in artificial systems instead. We could perhaps engineer sensors for various applications that take advantage of the inelastic electron tunneling effect, and they could well be very sensitive and specific. In the end, this whole idea might still turn out to be quite useful, and the question of whether it occurs in nature or not may be come to be seen as an unfortunate and confusing detour. The VTO is dead, but long live the VTO?