A spectrum of smells

Recent evidence suggests our sense of smell may work in quite a different manner than once thought…

Written by: Sam Cousins

Art by: Chalisa Iamsrithong

Olfaction – or sense of smell – has proved a puzzling sense to explain. Dependence on olfaction varies widely between species; Charles Darwin wrote that sense of smell was of ‘extremely slight service’ to the modern human, and yet, the genes for smell receptors alone comprise 1% of the entire human genome. Surely they must be of some importance?

Whilst the traditional view has been that humans have a poor sense of smell, recent research suggests that humans may have a sense of smell that rivals that of dogs and mice – organisms that were originally thought to be far superior in the olfactory department. Humans are even thought to be able to identify close blood-relatives by smell alone, as a mechanism of invest avoidance. Perhaps most intriguing is the concept of ‘smound’, a portmanteau that refers to the synesthetic (interaction between senses) phenomenon where a sound may  affect how a smell is perceived. But how exactly is a smell detected in the first place?

Perhaps the most widely accepted explanation for olfaction involves the shapes of molecules. In essence, an odorant (smell) molecule will bind to odorant receptors in the brain that have binding sites physically complementing the shape of the odorant. This binding then causes a cascade of signalling mechanisms that result in the brain identifying a smell. There are approximately 100,000 different smells the human nose can recognise, but we possess only 400 or so odorant receptor types; therefore, a ‘combinatorial code’ is in place. There is not one type of receptor for one type of odorant molecule; instead, one molecule can be recognised by multiple unique receptors, and a receptor can also recognise multiple unique molecules, vastly increasing the number of  possible combinations. Many things in molecular biology function based on shape, like enzymes, which lends credence to this theory. However, it can’t explain why some molecules may have very similar shapes yet produce different smells, or vice versa.

In 1938, British chemist Malcolm Dyson suggested a different explanation for olfaction – that receptors responded to the vibrations between the atoms of a molecule rather than their shapes. This would explain why isomers of a molecule (with almost identical structures), can produce different smells, such as vanillin and isovanillin, as they would vibrate differently. 

Dyson’s suggestion had no plausible mechanism until Luca Turin, working at UCL in 1996, suggested a quantum phenomenon known as ‘inelastic electron tunnelling’ was the answer. In this process, a particle can ‘tunnel’ through an energetic barrier that it would not normally be able to overcome, due to some fundamental principles of the quantum world. Once it tunnels through this barrier, some form of reaction can take place.

A simplified overview of Turin’s model dictates that the odorant molecule must first fit into the receptor binding site, as in the traditional model. In order to induce a response, an electron must would not be able to travel through the receptor to the electron acceptor site. However, under normal circumstances it would not be able to do this due to the energy required for the process. However, if a bound odorant molecule has a vibrational frequency that matches this difference, it essentially acts like a tunnel between the energy levels of the electron donor (start) site and electron acceptor (end) site, allowing the electron to move through the receptor molecule. The electron can then trigger a signalling cascade in the olfactory neuron leading to a response, allowing a smell to be identified.

If the vibrational frequency of an odorant does not match the energy difference in a receptor, then the transfer does not take place. Odour identities are classified by the activity of collections of receptors, in that a certain smell is the result of a number of receptors signalling  in tandem. This is what provides the unique ‘code’ for each smell. Similarly, the eye determines different colours from the collective activity of cones cells in the retina. This would therefore make smell a ‘spectral’ sense, like colour vision. It should be noted this model is semiclassical – it still relies on the size and shape of the molecule for initial binding.

In 2007, Brookes (also working at UCL), found that the principles of the model were compatible with the timescales of olfaction and ‘underlying physics’. Then in 2011, Turin showed how Drosophila melanogaster, the common fruit fly, could distinguish between smells of isotopes that were structurally identical, but had different vibrational frequencies. In this case, they used acetophenone and its deuterated analogue acetophenone-d8. The flies could be conditioned to ‘selectively avoid’ either molecule. Furthermore, the conditioned flies also avoided a structurally different molecule that had a vibrational mode in the same range as acetophenone-d8.

On the other hand, vibrational theory is still met with skepticism by many. For example, a study by Keller and Vosshall in 2004 found that humans cannot distinguish between acetophenone and the deuterated analogue like Drosophila could. On the other hand, a 2013 study at UCL (also involving Turin) found that humans could discriminate between the smells of large deuterated compounds and their protiated analogues. Larger hydrocarbons would have more C-H or C-D bonds, so the difference between the deuterated and protiated compounds would theoretically be more marked, potentially making it easier to detect and identify. Nonetheless, there are still questions to be answered.

The vibrational theory of olfaction is therefore still a topic of contention. Whilst the involvement of quantum mechanics in other areas of biology is more concrete (such as in photosynthesis), the field remains mostly an area of tentative speculation, with classical theories seeming adequate to explain most phenomena. Nonetheless, with the constant advancement of technology it becomes ever easier to explore the quantum world in the body, and the future may yet hold intriguing discoveries for the field.

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