As senses go, smell is an incredibly interesting one. We really know very little about it. When you smell something tiny, tiny bits of it are floating off of it and wafting into your nose. There, the different molecules of which all things are made come into contact with some sort of receptor. Certain types of molecule activate certain types of receptor and these in turn send nerve impulses to the brain. That’s the basic picture.
But what is it about a molecule which makes it smell a certain way? Take a look at the three molecules below for example – two of them smell alike and one is the odd one out, but which one?
Well, despite the fact that the two compounds with rings in them look so similar in shape and size, it’s the small hydrogen cyanide (middle) and benzaldehyde (right) which smell the same (like almonds) – not that you would want to smell hydrogen cyanide of course! The other molecule (4-tertbutylbenzaldehyde) is the odd one out – it is responsible for the ‘lily of the valley’ fragrance. Lovely.
In most cases where small molecules fit into receptors (this is the subject of my PhD by the way) the internal cavity of the receptor must be complimentary to the guest. But here we have two molecules of very different shapes soliciting the same response from olfactory receptors. Strange.
Luca Turin is really the main man when it comes to theories of smell and he’s also a perfume critic as you may be able to elucidate from the picture below.
Turin is controversial, but in my opinion a brilliant thinker. He developed a theory of smell which says that the fit of a molecule to a smell receptor depends on its vibrational behaviour. The theory is a little complicated for our purposes, but it essentially means that actually it would be the type of functional group a molecule contains, rather than the overall shape, that would determine its smell. In fact it gets even more complicated after that because Turin suggests that the molecules act as a bridge for electron tunnelling from one side of the receptor cavity to the other; a weird quantum effect with a complicated physics explanation.
All this is by way of explaining the background to a new paper I spotted in Proceedings of the National Academy of Sciences (PNAS).
In the paper Turin teams up with Greek scientist Efthimious Skoulakis to conduct an experiment in an effort to demonstrate some evidence for his vibrational theory. They experimented with fruit flies, which are known to be able to recognise odours. They placed the flies in something a bit like a maze in which they could take two routes: one leading to a normal odour molecule (they used common smelly compounds like acetophenone), or a second leading to deuterated acetophenone (that is where the hydrogen atoms in the molecule have been replaced by their heavier isotope deuterium). The deuterium doesn’t change the overall shape of the molecule, but since it is heavier it alters the frequency at which the molecule vibrates. It’s an ingenious way to test the idea that smell receptors depend on vibrations rather than shape to recognise a smelly molecule.
Turin and Skoulakis found that the flies could distinguish between the deuterated and non deuterated acetophenone (they preferred the regular stuff). They also tried out some other common odourants like octanol and benzaldehyde and got the same results. They could also use electric shocks to train the flies to prefer the deuterated compound after a while.
This is great news for Turin’s theory, but it is not yet a proof. In theory, isotopes of two compounds differ subtly in more ways than just their vibrational behaviour. It’s worth mentioning too that when Turin previously performed similar experiments on humans, our own species couldn’t differentiate the isotopes. On the other hand dogs can. These discrepancies have led some scientists to speculate that whether we can tell two odourant isotopes apart is simply a matter of sensitivity.
We should admire Turin’s dedicated approach to testing his theory and we would do well not to dismiss it simply because it’s unusual – these results give us a good indication that molecular vibration is in some way implicated in olfaction even if it’s not the whole story.
M. I. Franco,L. Turin, A. Mershin and E. Skoulakis, PNAS, 2011,Early View.