[1st Place] - Beyond our Flesh & Bones: An Insight into Human Olfaction

The human body is a complex entity divided into several hierarchical levels of organisation (cells, tissues, organs, and systems). These structures work synonymously to enable the expression of a diverse array of functions. Externally, these functions enable humans to engage and interact with their outer environment. However, the means in which humans process these interactions differ leading to individual differences in perception. From a sensorial viewpoint, perception stems mainly from the 5 senses: touch, taste, smell, sound, and sight. The sense of smell or olfaction is an interesting field of study as it is multifunctional and known to affect aspects such as mood, cognition, and behaviour. However, olfaction is probably the least discussed of the 5 human senses. This article will attempt to shed light on perception derived from scent and its roles.


Olfaction is a physiological process involving the detection of odorant molecules in the environment. Odorant molecules are volatile chemical compounds that can impart a fragrance. These are found in a variety of sources such as fruits, spices etc. The process of olfaction is complex, and research is still ongoing regarding its mechanism. Nonetheless, an overview of the known process will be provided. The process of olfaction occurs through what is known as the olfactory system. Olfaction begins when volatile odorant molecules enter the nasal cavity through direct inhalation of scents (orthonasal olfaction) or by indirect release of molecules into the mouth and throat via methods such as chewing food particles (retronasal olfaction). In the nasal cavity, the molecules are exposed to the olfactory epithelium which houses olfactory sensory neurons (OSNs) and their corresponding olfactory receptors (ORs). Components known as odorant binding proteins (OBPs) and xenobiotic metabolising enzymes (XMEs) are also present. However, these are currently poorly understood and proposed functions in areas such as odour transformation remain a speculation. Discrimination of scents occurs in a combinatorial pattern in which an OR responds to a range of odorants or odorants activate a range of ORs. Binding of the molecules to the ORs initiates a signal transduction pathway that transmits olfactory information to regions in the brain: from the olfactory bulb to the primary olfactory cortex (consisting of the piriform cortex, entorhinal cortex, amygdala) and to the orbitofrontal cortex for odour perception.

Odour perception amongst humans is non-uniform, complex and highly subjective. Between humans, sensitivity and perception towards various types of odorants differ. Odorants that smell pleasant to one individual may smell repulsive to another. Research suggests that odour perception is affected by factors such as genetic makeup, health, experience, and age. While not all the proposed factors can be studied empirically, links have been found relating genotype to phenotype for odour perception. Humans possess around 400 ORs. A study by Trimmer et al reported that individuals with a less functional OR11A1 receptor were found to smell 2-ethylfenchol (an earthy odour molecule found in beets) less intensely than those with a fully functional OR11A1 receptor indicating that a change in a single OR could affect odour perception. Based on these findings, it was further suggested that differences in OR11A1 may contribute to the dirt-like taste and smell some individuals attribute to beets. This was supported by a previous study by Mainland et al which reported that 86% of OR genes found in participants had polymorphisms which affected OR function. Despite such research being published however, the road to fully understanding the role of genetics towards human olfaction remains cumbersome due to the intricacies of the olfactory system and limited knowledge of odour processing and interpretation.


As mentioned previously, odour perception can be affected by health. The most recent example of this is anosmia or loss of smell which occurs during the early stages of a COVID-19 infection. The underlying mechanism of this is still being investigated by researchers, but a commonly proposed mode of action is viral infection of sustentacular (support) cells surrounding OSNs which lead to neuron disruption. Regardless of the process, anosmia is accepted as a hallmark symptom in COVID-19 patients. However, this statement is not all encompassing as patients that contracted the Omicron variant of the SARS-CoV-2 virus were noted to have lesser occurrences of exhibiting anosmia for reasons not yet understood. Most individuals regain sense of smell a few weeks after recovery. However, a review of 18 smell loss studies showed about 5% of recovered individuals still retained symptoms of anosmia. To add to the mix, certain patients that recovered from COVID-19 derived anosmia were reported to suffer from parosmia, a condition that transforms previously perceived pleasant odours into unpleasant odours. Favourite dishes began to smell like rotten food or garbage which affected enjoyment of taste and aroma leading to emotional distress. In such scenarios, it becomes apparent that anosmia and parosmia require some form of treatment so that patients may return to a better quality of life. The conventional method of treatment utilised is olfactory training. The process involves exposing individuals to 4 types of essential oils. The idea is to sniff each scent while concentrating on the memory of each corresponding scent, twice a day over several months. While other methods such as antibiotics, corticosteroids and acupuncture have been attempted, olfactory training remains prevalent due to its ease, inexpensive and risk-free nature. Retraining the olfactory system in scent discrimination is an arduous process for the patient but for sufferers of olfactory disfunction it is a means of reverting their olfactory system to its previously functional self thereby giving them hope for a sense of normalcy in terms of scent perception.

As such, it is evident that scent perception and olfaction within humans is complex but crucial. This fact was further highlighted with the recent COVID-19 pandemic that showcased the importance of studying the olfactory system. While it remains an arduous journey to fully understand human olfaction nevertheless its importance in shaping perception is not to be ignored, proving indeed that humans are more than just ‘flesh and bones’.



 

References

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Dolgin, E. (2022). The science behind COVID’s assault on smell. Nature, 606(7915), S5–S6. https://doi.org/10.1038/d41586-022-01627-w


Meunier, N., Briand, L., Jacquin-Piques, A., Brondel, L., & Pénicaud, L. (2021). COVID 19-Induced Smell and Taste Impairments: Putative Impact on Physiology. Frontiers in physiology, 11, 625110. https://doi.org/10.3389/fphys.2020.625110


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Ojha, P., & Dixit, A. (2022). Olfactory training for olfactory dysfunction in COVID-19: A promising mitigation amidst looming neurocognitive sequelae of the pandemic. Clinical and experimental pharmacology & physiology, 49(4), 462–473. https://doi.org/10.1111/1440-1681.13626


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Saniasiaya, J., & Narayanan, P. (2021). Parosmia post COVID-19: an unpleasant manifestation of long COVID syndrome. Postgraduate medical journal, postgradmedj-2021-139855. https://doi.org/10.1136/postgradmedj-2021-139855


Sell, C. S. (2014). The Mechanism of Olfaction. Chemistry and the Sense of Smell, 32–187. https://doi.org/10.1002/9781118522981.ch2


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This article which won 1st Place in our MBIOSymposium Article Writing Competition was prepared by Madri Amran

 

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