Highlights:
Issue 8 - August 2025
Issue 12 Article 3
Plumes from the Osmocosm
26/2/26
By:
Amitav Poduval
Edited:
Elijah Chew Ze Feng
Tag:
Anatomy and Pathology
When you see a colour you can name it, and when you hear a word you can write it down. If you feel an object you can guess at its shape, and if you put something into your mouth you can throw it into one or more of the five insipid categories that are the tastes. Yet the same cannot be done with a smell. One cannot tell when a smell begins or ends: it simply is, and it is all around us. We are totally enveloped in it, yet we cannot say where it came from. To name it requires more effort than we are willing to put in on a normal day. And so nameless it lurks, like thoughts in a dream in which we know something to be a fact but do not know how we know.
Fig. 1: The protagonist of Marcel Proust’s interminably long novel, In Search of Lost Time, experiences an involuntary memory upon the sensory stimulation of a cake dipped in tea.
This is not so much a matter of the limits of the human sense of smell but rather one of our lexicon literacy. Although the colours emerged in our vocabularies many millennia ago, in the matter of scents our dictionaries remain in their infancy. To describe a smell is to grasp at straws because we have no abstract idea to compare it to. We are forced to compare a real smell to the sum of a multitude of memories, creating a language which is, to the outsider, esoteric and even ridiculous. So a perfume may be said to contain “bergamot, cedar, and rose.” What is a bergamot? You would have to have smelt it before.
Basic facts to begin with
To begin to understand this sense, it is advisable, as it almost always is, to begin by exploring the genetic origins of smell. Humans have many genes coding for olfactory receptors. In fact, the superfamily of these genes is the largest group of genes coding for receptors in the human genome. These genes code for G-protein coupled receptors (GPCRs), which is the largest family of receptors in the human body. Among the 1282 GPCR genes in humans, 387 code for functional olfactory receptors. Apart from these, there are 495 olfactory receptor pseudogenes that are non-functional. It is now clear to see that the sense of smell is no small investment for a human, as is the case for many other mammals.
Despite the vastness of this sense, it is one of the most intimately connected to the world on a microscopic scale. Our sense of smell, with its vast array of sensory receptors, caters to the world of odorant molecules with microscopic specificity. We can even smell the difference between some molecules that are “mirror images” of each other (enantiomers) such as R-carvone, which smells of caraway, and S-carvone, which contributes to the smell of spearmint. The apparently decorative facial feature which goes ahead of us wherever we wander contains, deep inside, the only neurons in the body with exposed ends (dendrites). Contrary to popular belief, neurons can be regenerated, especially these olfactory neurons, which face a great deal of wear and tear, as can easily be imagined. They are located on the olfactory epithelium, a layer of skin very high up in the nose. Each olfactory neuron expresses only one type of receptor. However, a receptor may be bound to by a variety of molecules, and a single molecule may bind to a number of different receptors.
A closer look
I have no doubt that the vagueness of the previous sentence, with its frustrating impotent declaration of the lack of clarity in this science, is insufferably irritating to some readers. It is thus advisable to take a closer look at the proteinaceous receptors themselves. Modern chemical techniques have rendered us capable of visualising the taste receptor for sweetness as a 3-pointed figure symbolising 3 “functional groups” of the sweet molecule itself that are necessary to interact with the active site of the receptor. Similar attempts in the case of the sense of smell are far less numerous and less conclusive, and the simplicity of any models produced greatly belies the painstaking genetic and molecular procedures (not to mention the profusion of abnormal mice) required to produce them. Olfactory receptors, and other proteins like them (rhodopsin-like GCPRs), are made primarily of seven transmembrane alpha helices. A study on mice claims that the site that the smell molecule binds to (ligand-binding site) includes only three of the helices. The binding site tends to be a hydrophobic pocket. Usually, the amino acid residues interact with the odorant molecule through both hydrogen bonding and hydrophobic interactions.
It has recently been found that odorant molecules can not only activate olfactory receptors as agonists, but also act as antagonists, inhibiting them. Although olfactory receptors can accommodate a broad range of molecules, small changes to specific parts of the odorant molecule (and not others) can greatly affect the affinity of the receptor for it, or even change it from an agonist to an antagonist. For one of the mouse odorant receptors for eugenol, the main component that gives cloves their intense smell, it has been hypothesised that a phenylalanine residue’s benzene rings has pi-pi interactions with any variant of the odorant molecule that has an alkene group, preventing any conformational change in the receptor, so there is no reaction.
From the physical to the mental
All the neurons are covered by a layer of mucus, through which volatile molecules must pass if they are to be picked up by receptors. This leads to some interesting chemical effects. Hexanal changes into hexanol, which smells “green,” like cut leaves, when it passes through the mucus. Once volatile molecules are bound to the neuron’s receptors in sufficient numbers, a series of chemical and then electrical signals is passed from the olfactory neuron to some relay neurons at unfathomable speed. All neurons of the same kind have axon terminals (endings) in a single glomerulus. The glomerulus is the functional unit of the olfactory bulb where smells are processed. It is a ball-like bundle of neurons and there may be thousands in a vertebrate brain, organised in two groups.
From the glomeruli, information goes into the mysterious realm of perception – the way that our conscious minds experience things in the world, or “qualia.” However, the input from one glomerulus may be suppressed or intensified by the activation of neighbouring glomeruli, connected by relay neurons, changing the overall perception. When one sensory input is inhibited by a nearby one, it is called lateral inhibition. This happens for many other senses too, and it helps to increase the precision of the detection of the stimulus, giving us greater certainty that it is present. Even more interestingly, if glomeruli are activated in different combinations, different smells are registered. An interesting result follows: activating different combinations of glomeruli produces different sensations according to a neuronal “combinatorial code.” The colossal variety of possible combinations suggests that we can smell a diverse array of smells. Some of the input from the glomeruli also goes to the hippocampus, a region of the brain involved in the creation of memories. Small wonder, then, that smells can cause old memories to awaken so powerfully and involuntarily, as they did for the narrator of Marcel Proust’s In Search of Lost Time, upon smelling and tasting madeleines dipped in linden tea.
The changing osmocosm
It is the curse of modernisation that while we are plumbing the depths of the unfathomable with ingeniously designed tools, our native instruments concurrently fall into disrepair – near work dims sight, noise pollution dulls hearing. It is much the same with smell. Little imagination is required to imagine that pollution greatly reduces our olfactory capabilities. The harm is greatest for children. Weakness in the sense of smell lies at 2 percent in rural areas and at 10 percent in urban areas. In cities, people have a far higher risk of losing their sense of smell entirely. Far more insidious harms exist, however: nanoparticles from pollution can directly enter the brain and the bloodstream through olfactory neurons.
The sense of smell is a world in its own right, which is why the range of sensations produced by it is often termed “the osmocosm.” It is an integral dimension of the human Umwelt – the world of perception that we inhabit in our minds. Externally, however, it is only a tool, and like all tools, it degrades with disuse and abuse. Yet its regenerative abilities are found nowhere else in the nervous system. With consistent practice, in spite of the damage the olfactory system bears daily, one can observe great progress in scent discrimination and identification. The world of smell is wide; I choose to seek it, breathe it, live it.
References
Stephanie Heuet, Marcel Proust, In Search of Lost Time, Volume 1: Swann’s Way (Figure 1)
Smell: A Very Short Introduction, Matthew Cobb
Nose Dive, Harold McGee
https://www.bbc.com/future/article/20230220-is-air-pollution-causing-us-to-lose-our-sense-of-smell
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