The Power of Our Fifth Sense

In the scientific field, the often neglected fifth sense, the sense of smell, contributes to broadening our understanding of various phenomena, particularly in the field of biomarkers.Here, we will guide you along our lines of thought on the importance of our olfactory sense, and how it contributes to scientific exploration and biomarker identification.

From Perfume Making to Disease Diagnosis

The world of perfumery, rooted in countries like France and Switzerland, unveils the artistry of noses and fragrances. It’s a reminder that scent, whether associated with health or art, carries a narrative of its own. Take the case of Joy Milne, a Scottish retired nurse with a unique ability to detect Parkinson’s disease (PD) through her sense of smell. She presents with hereditary hyperosmia, an uncommon condition that amplifies her sense of smell. This heightened olfactory ability became apparent when her late husband, began emitting a distinct aroma, a change she detected years before clinical signs of PD.

The scent, however, can have a dark side. Does Jean Baptiste Grenouille trigger any memory?… “The Perfume” by Patrick Süskind. From the real-world potential of scent-based Parkinson’s detection to the fictional exploration of the dark side of scent, these narratives invite us to reconsider the depths of our sensory experiences.

Grenouille’s character is consumed by an obsessive desire to capture and control the essence of human scent, leading him to dark and macabre deeds. In contrast, Joy Milne’s journey begins with a natural and unassuming ability to detect subtle changes in scent associated with PD. Her motivation stems from a genuine desire to help others rather than any sinister inclination. Grenouille’s pursuit is driven by a quest for the perfect scent of love, often at the expense of ethical and moral boundaries. Joy Milne’s ability, on the other hand, uncovers hidden truths in a compassionate and altruistic manner, working hand in hand with scientists to translate this olfactory biomarker into a molecular signature. Her olfactory talent inspires the development of tools for early detection of Parkinson’s, providing invaluable insights into the world of medical diagnosis.

An Olfactory Throwback

Venturing into history, we find that the use of odors for medical purposes is not a new concept. In ancient times, physicians relied on the smells of patients’ breath or urine. Fast forward to the 17th century, when “plague doctors” put on peculiar costumes with beaked hats filled with aromatic herbs, a belief rooted in the notion of purifying the air from harmful influences.

From Canine Detectives to Mosquito Mysteries and the Essence of Biomarkers

As Human beings, we are way behind our four-legged companions in terms of olfactory capabilities… Did you know that they can exhale and inhale all at the same time, making their sense of smell thousands of times more acute than that of humans? Dogs, with their remarkable sense of smell, play pivotal roles in security and healthcare. Trained to detect narcotics, illegal food, explosives, and firearms at airports, they enhance safety measures. Through extensive training, they demonstrate an astonishing ability to detect scents associated with infectious diseases, various types of cancers, and metabolic disorders. This unique skill positions them as potential aids in early disease detection, complementing traditional diagnostic methods and offering a non-invasive approach to identifying health issues [1, 2].

In the animal kingdom, dogs are not unique. Imagine a quiet summer evening with friends, enjoying a barbecue and sipping rosé wine (your fifth sense enhancing the experience), only to be interrupted by the persistent buzzing of mosquitoes. The age-old question arises: why do they seem to prefer one person over another? The answer lies in the intricate world of scent. Mosquitoes, equipped with highly sensitive antennae, are drawn to the diverse scents surrounding us. The mystery of why mosquitoes favor one person—perhaps biting you while sparing your friend—is attributed to the nuanced interplay of individual scents. Our olfactory signature, a combination of genetic factors, body chemistry, and even skincare product odors influence mosquito preference [3-4].

At the core of this lies the presence of distinct volatile organic compounds (VOCs) detectable by our sense of smell and quantifiable by sensitive Gas Chromatography coupled to tandem mass spectrometry (GC-MS/MS) instruments,

Back to the Beginning: The Scent of Parkinson’s and Biomarker Analysis

Coming back to our starting point, the scent of PD: prompted by Joy Milne’s observations, researchers at the University of Manchester investigated her olfactory discernment and its potential utility in identifying individuals with PD. Their findings reveal alterations of lipids of high molecular weight among those afflicted with Parkinson’s, presenting a promising avenue for diagnostic applications [5, 6].

Analyzing the intricate mixtures of metabolites present in lipid-rich biofluids, such as sebum, necessitates a sensitive and robust analytical platform. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) or High-Resolution mass spectrometry (LC-HRMS) emerges as a pivotal tool, enabling both qualitative and quantitative exploration of the diverse molecular species within complex mixtures like sebum. LC-MS/MS & LC-HRMS have proven invaluable to building our knowledge on complex diseases such as PD by studying various biofluids, extending its reach to blood, plasma, serum, urine, saliva, and cerebrospinal fluid (CSF). The analysis encompasses a broad spectrum, including alterations in metabolite expression. Within the blood and CSF metabolome, comprehensive studies have been conducted on elements such as catecholamines, dopamine metabolites, amino acids, urate, alongside investigations into fatty acid, energy, and kynurenine metabolism [7. The utilization of sebum as a specimen for early diagnosis of PD introduces an exciting perspective. It offers the potential for developing a non-invasive and cost-effective test capable of detecting the onset of the disease.

In conclusion, our exploration of scent takes us on a multidimensional journey – from medical diagnostics to historical curiosities, crime narratives, and the exceptional olfactory prowess of our canine companions. Our fifth sense emerges as a valuable tool in scientific inquiry, especially in the exploration of biomarkers.

At KCAS Bio, our bioanalytical services in biomarker analysis contribute to this journey at both preclinical and clinical levels, enhancing the understanding and application of biomarkers through various analytical capabilities: LC-MS/MS, LBA, PCR and Flow cytometry.

1. Buszewski B, Ligor T, Jezierski T, Wenda-Piesik A, Walczak M, Rudnicka J. Identification of volatile lung cancer markers by gas chromatography-mass spectrometry: comparison with discrimination by canines. Anal Bioanal Chem. 2012 Jul;404(1):141-6. doi: 10.1007/s00216-012-6102-8. Epub 2012 Jun 3. PMID: 22660158; PMCID: PMC3389235.
2. Fischer-Tenhagen C, Johnen D, Nehls I, Becker R. A Proof of Concept: Are Detection Dogs a Useful Tool to Verify Potential Biomarkers for Lung Cancer? Front Vet Sci. 2018 Mar 14;5:52. doi: 10.3389/fvets.2018.00052. PMID: 29594162; PMCID: PMC5861141.
3. Coutinho-Abreu IV, Jamshidi O, Raban R, Atabakhsh K, Merriman JA, Akbari OS. Identification of human skin microbiome odorants that manipulate mosquito landing behavior. Sci Rep. 2024 Jan 18;14(1):1631. doi: 10.1038/s41598-023-50182-5. PMID: 38238397; PMCID: PMC10796395.
4. Rankin-Turner, S.; Giraldo, D.; McMeniman, C. Exploring Mosquito Olfactory Preferences with Whole Body Volatilomics. Presented at the 71st American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics, Houston, Texas, June 7, 2023.
5. Trivedi DK, Sinclair E, Xu Y, Sarkar D, Walton-Doyle C, Liscio C, Banks P, Milne J, Silverdale M, Kunath T, Goodacre R, Barran P. Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum. ACS Cent Sci. 2019 Apr 24;5(4):599-606. doi: 10.1021/acscentsci.8b00879. Epub 2019 Mar 20. PMID: 31041379; PMCID: PMC6487537.
6. Sarkar D, Sinclair E, Lim SH, Walton-Doyle C, Jafri K, Milne J, Vissers JPC, Richardson K, Trivedi DK, Silverdale M, Barran P. Paper Spray Ionization Ion Mobility Mass Spectrometry of Sebum Classifies Biomarker Classes for the Diagnosis of Parkinson’s Disease. JACS Au. 2022 Sep 7;2(9):2013-2022. doi: 10.1021/jacsau.2c00300. PMID: 36186554; PMCID: PMC9516698.
7. Sinclair E, Trivedi DK, Sarkar D, Walton-Doyle C, Milne J, Kunath T, Rijs AM, de Bie RMA, Goodacre R, Silverdale M, Barran P. Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease. Nat Commun. 2021 Mar 11;12(1):1592. doi: 10.1038/s41467-021-21669-4. PMID: 33707447; PMCID: PMC7952564.