Chemists Tom Varley and Rose Gray of University College London joined us at the Secret Garden Party for Drugs Day to explore the mysteries of olfaction with a range of intoxicating chemicals, including ether and chloroform. They tell us what it was like shoving  a bottle of ammonia into somebody’s face at a festival – and why the science of smell is just so intriguing… 

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It’s amazing what people will try if you’re wearing a lab coat! After all, asking complete strangers at a festival to sniff a bottle of chloroform is either going to result in further curiosity, or a call to the police. Thankfully, whether it was down to our lab coats, haziness from the night before, or just the atmosphere of the Secret Garden Party, the crowd was keen to sample our olfactory offerings.

Armed with a suitcase packed with weird and wonderful chemicals (and some molecular models too), we were let loose on the Friday morning crowd. Some of our samples sparked reactions of delight (such as vanillin, the dominant smell molecule in vanilla); some were met with fascination (mostly chloroform and ether, both previously used as general anaesthetics); others made people run away, coughing and spluttering (two major culprits were ammonia and the vile, sulphurous mercaptans – we didn’t even fully open the bottles!).

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Besides wanting to see people’s reaction after they take a hefty hit of ether, we did have other reasons for wanting to talk about olfaction. Our brains have a staggering capacity for interpreting odours: as we saw at SGP, our reactions to smell can be extremely powerful: they can bring back vivid memories and deep emotions, or make us gag and recoil in horror. Various theories have been developed to try and explain why certain molecules smell certain ways, but none have ever really succeeded – it is still a mystery.

Many theories have focused on the shape of the molecules: that either the entire molecule, or parts of it, bind to receptors in the nose and trigger a signal. The signals are processed in the brain and interpreted as an odour. Though convenient, this model falls short in a lot of cases, as shape and scent don’t always correlate. Another theory is that odours depend on the vibrations of the atoms in the molecules. Understandably, trying to explain how the nose can act as a spectroscope is quite difficult, and this idea still doesn’t explain everything. For example, this theory would predict that mirror image molecules (enantiomers) should smell identical, but in reality they often smell completely different.

Bringing it back to SGP… we decided to carry out our own little experiments to test these theories. Along with chloroform (CHCl3), we also had its deuterated analogue chloroform (CDCl3) – here the hydrogen atom is replaced with its heavier isotope, deuterium, which barely affects the shape but does affect the vibrational frequency. We found that the vast majority of people could tell the difference. Though results have been conflicting, some studies have found that humans can distinguish isotopes, and flies can be trained to avoid deuterated odorants – support for the theory that vibration does play some role.

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So, this puts us in a bit of a pickle: we know from smelling enantiomers that molecular shape must be slightly important, but using shape alone can’t account for the differing smell of isotopically labelled molecules. However, a new (and slightly controversial) idea involves a bit of both, along with a bit of quantum mechanics, proposing a sort of “swipe card” mechanism: an odorant molecule must have approximately the right shape to fit into the slot, and the right vibrational frequency to trigger a signal from the receptor. Though complicated (inelastic electron tunnelling plays a crucial part), this idea is fascinating.

At SGP we displayed a variety of smells, from the exquisite to the atrocious. We saw a huge range of reactions, but a common theme was curiosity: to smell unusual things, but also to discover how it works. The same can be said for the scientific community. We don’t know how or when the mystery of olfaction will be solved, but there is definitely some exciting research going on – watch this space…

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