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Short answer: Culture and biology of human smell are likely inextricable. Biology of human smell has two essential components, the emitter and the recipient. The emitter’s contribution, body odor, is a combination of genetics, glands, microbiota and diet. Perceived smell depends on an individual’s phalanx of odorant receptors (OR). Unsurprisingly, both odor and its perception vary widely between individuals in essential aspects, namely, odor strength and quality, and odor detection threshold, intensity and quality.

Longer answer: The story of smell can be explored through not just a biological but also a cultural lens. For most of human history pervasive smells have been part of daily life. Now many smells have rapidly and thoroughly vaporized from daily life, at least for urban and suburban-dwelling multitudes in industrialized countries. Though it happened rather swiftly, it’s astonishing how such an extremely dramatic change passed us by unnoticed. Perhaps because smells can’t be memorialized and inter-generationally transmitted, unlike visual memory which reaches us from the past through cave paintings, portraits, dageurrotypes, photos, videos and now instagrams. The economist Robert J. Gordon writes,

“As already seen, urban life in 1870 was dominated by the omnipresent horse, and this, too, had a health aspect. The average horse produced twenty to fifty pounds of manure and a gallon of urine daily, applied without restraint to stables and streets. The daily amount of manure worked out to between five and ten tons per square mile” (1).

How pervasive was horse urine and poop smell in that not too far off world? Likely extremely, in fact likely eye-poppingly so.

‘“In the geographically compact city of Boston in 1870, 250,000 citizens shared the streets with 50,000 horses. The density of horses in Boston was roughly 700 per square mile” (1).

Modern ventilation, indoor plumbing, electricity have eliminated smells otherwise mainstays through human history. Easy to take these 20th century life staples for granted. Yet they’ve only been the norm for less than a century. Consequently our own body smells can now dominate to an extent not possible earlier. Interesting to consider then whether their swift stigmatization is a consequence of their new-found prominence or something more invidious, an impossible demand stemming from a pathological need to subjugate the biological to the mechano-chemical. Gaining primacy over our environs is one thing. Is that process now extending its mandate and creeping into the domain of individual biology, ably and amply helped by those whose economic interests are vested in making us acquiesce to such fetishization of odor? I often wonder as I see yet another ad on indoor odor eliminators.

Are some people smellier than others? Probing the question’s premise reveals smell’s biological basis is a two-sided story consisting of the smell’s emitter and recipient. Result depends on both. I learned this in no uncertain terms by a markedly smelly experience for me but not for others. A past lab had a colleague I couldn’t bear to be around not for anything they did to me but for how they smelled, to me a distinct smell of long-standing, unwashed sweat. To some of my other colleagues? No problem at all. How do emitter and recipient combine to produce such variations in smell perception?

Smell emitter. Body odor is largely a combination of genetics, glandular activity, microbiota and diet. Manifested as volatile organic compounds (VOC), sources are blood, breath, faeces, hair, skin, scalp, sweat, urine, vaginal secretions (2). Blood is a source because many metabolic VOCs secreted into blood make their way into the environment as breath and/or sweat.

  • Genetics. The ABCC11 gene encodes an ATP-driven pump. Individuals homozygous for a single nucleotide polymorphism (SNP) 538G>A in the ABCC11 gene have weaker axilla (arm-pit) sweat odors (3, 4, 5). Predominant in Far-East Asians who also produce dry and white earwax in contrast to the yellow and wet earwax dominant in the rest of the global human population (6; see figure below from 7), this SNP contributes to a loss of function of this transport protein. Though ABCC11 is not solely responsible for VOC variations in humans (8), a study on ~17000 individuals (9) showed that AA genotypes were 5-fold over-represented in the experimental group that almost never used deodorants. Human body odor is also profoundly influenced by polymorphisms in another gene, gamma-glutamyl-tranferase 1 (GGT1) (10). Mapping genetic variations in VOCs is still  in its very early days.
  • Glands. VOCs are mainly secreted by 3 types of glands: Eccrine, Sebaceous, Apocrine (11). They’re differentially distributed across the body which is why distinct odors are associated with different body parts (12). Eccrine and Sebaceous glands are widely distributed all over the body. Concentrated on the hands and feet, eccrine glands are most abundant and produce odorless sweat. Concentrated in arm-pits and genitalia, Apocrine glands secrete lipids, proteins and steroids. Most concentrated on the head, sebaceous glands secrete sebum and lipids. Thus, the different secretions by these glands create different niches supporting the growth of different skin-associated microbes (13).
  • Microbiota. Varying hugely between individuals (14, 15), skin microbiota strongly influences human body odors (16, 17, 18). Back in 1953, Shelley and Hurley speculated arm-pit-dwelling microbes contributed to distinct human sweat odors (19). Of course now numerous studies have connected specific axillary odor components with specific microbial fauna (20, 21, 22, 23). Body odor differences between individuals may thus well be the result of different skin-inhabiting microbes (24). For e.g., presence of specific microbes is linked to sweat attractive for mosquitoes (18). As well, malodorous VOCs from arm-pits are mainly due to lipophilic corynebacteria (25, 26, 27).
  • Diet influences human odor. For e.g., red meat induces more intense and unpleasant axillary sweat (28). A field study in Burkina Faso found beer, not water, increased human attractiveness to Anopheles gambiae, the main malaria vector in Africa (29). Body odors of volunteers who drank beer increased mosquito activation and proportion of mosquitoes who flew towards their odors. Again, early days in understanding how diet affects VOC production.

Malodor-Associated Diseases

Reported all the way through history from ancient Indian tales to William Shakespeare (30), patients with the Fish Malodor Syndrome or Trimethylaminuria (TMA) secrete higher than normal trimethylamine levels in their urine, breath and sweat, resulting in an obvious unpleasant body and oral odor (31). Inability to N-oxidize trimethylamine, this genetic disorder is present in ~1% of the population with a higher proportion in women (32, 33). The liver flavin monooxygenases, specifically FMO3 is the enzyme that oxidizes TMA. TMA patients have a difference between dietary TMA intake and the liver’s capacity to process it. As a result, TMA accumulates in urine, sweat and breath. Genetic predisposition ranges from primary to less severe forms where manifestation is based on a combination of the genetic dysfunction, diet and environmental factors. Degree of genetic dysfunction depends on degree to which mutations inactivate the FMO3 gene. Transient TMA is associated with menstruation (34), diet (35) or specific outgrowth of gut microbes (36).

Other diseases such as inherited metabolic disorders, cancers and infectious diseases can also cause malodors (see tables below from 2).

Such disease-specific odors are the basis for using giant rats and dogs to sniff out (diagnose) tuberculosis and cancer (37, 38, 39, 40).

Smell recipient. Art and literature justly memorialize our odor-associated memories as they are among our strongest (41). Just as in Ratatouille (film), Remy’s dish effortlessly transports Anton Ego, the food critic, to his rural childhood and his mother’s version of the same dish, so too does the smell of a madeleine biscuit soaked in tea send Marcel Proust back on a journey through time in In Search of Lost Time (42). Odors are so much more effective than other senses in triggering emotional memories that this is even called the Proust phenomenon (Involuntary memory) (41)

We can smell odors because our olfactory receptors (OR) on nasal olfactory sensory neurons (OSNs) detect them chemically. This starts a neural sequence extending to the brain. As with the rest of biology, smell perception varies greatly between individuals in terms of detection threshold, intensity and quality. Also heritable, this ranges from hyper-acute smell sensitivity to hyposmias (greatly reduced sensitivity to an odor) to anosmia (smell-blindness).

Sense of smell and taste are inextricably linked because ‘we smell breathing in‘ and ‘taste breathing out, through retronasal olfaction‘ (43). Profound loss in terms of joy with accompanying anger and isolation accompanies losing the sense of smell. Unlike blindness and deafness, this is woefully under-appreciated by society.

SNPs in just one OR gene can dramatically change both odor and flavor perception (44, 45).

  • Low concentrations of androstenone, a testosterone derivative abundantly produced by male pigs, is estimated not smelled by ~50% of humans, and described as musky, sweaty, sweet, urinous or vanilla by those who can (46). By cloning and individually expressing >300 Ors, Keller et al identified a single one, OR7D4, with strong response to both androstenone and its structurally related derivative, androstadienone (47). Sequencing OR7D4 from 391 individuals, they identified 4 haplotypes of which two had almost completely impaired function.
  • 23andMe surveyed ~10000 people for ‘asparagus anosmia‘ (48). Most people excrete a sulfurous metabolite after eating asparagus but smelling it is very variable (49). Among 10 OR genes associated with this anosmia, they found 2 SNPs in or around ORM27 to be most closely associated.
  • 23andMe also mapped perception of cilantro as ‘soapy‘ to an OR cluster (50). Unfortunately they didn’t complete the scientific cycle by validating these ORs functionally to asparagus and cilantro anosmia, respectively, so specific ORs connected to these anosmias remain as yet unidentified.

Bibliography

1. Excerpt From: Robert J. Gordon. “The Rise and Fall of American Growth: The U.S. Standard of Living since the Civil War (The Princeton Economic History of the Western World)”. Original data reference: “Greene, Ann Norton. (2008). Horses at Work: Harnessing Power in Industrial America. Cambridge, MA: Harvard University Press”.

2. Shirasu, Mika, and Kazushige Touhara. “The scent of disease: volatile organic compounds of the human body related to disease and disorder.” Journal of biochemistry 150.3 (2011): 257-266. http://dogs4diabetics.com/wp-con…

3. Preti, George, and James J. Leyden. “Genetic influences on human body odor: from genes to the axillae.” Journal of Investigative Dermatology 130.2 (2010): 344-346. http://ac.els-cdn.com/S0022202X1…

4. Martin, Annette, et al. “A functional ABCC11 allele is essential in the biochemical formation of human axillary odor.” Journal of Investigative Dermatology 130.2 (2010): 529-540. http://ac.els-cdn.com/S0022202X1…

5. Kippenberger, Stefan, et al. “‘Nosing Around’ the human skin: What information is concealed in skin odour?.” Experimental dermatology 21.9 (2012): 655-659. http://onlinelibrary.wiley.com/d…

6. Toyoda, Yu, et al. “Earwax, osmidrosis, and breast cancer: why does one SNP (538G> A) in the human ABC transporter ABCC11 gene determine earwax type?.” The FASEB Journal 23.6 (2009): 2001-2013. why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type?

7. Natsch, Andreas. “What makes us smell: the biochemistry of body odour and the design of new deodorant ingredients.” CHIMIA International Journal for Chemistry 69.7 (2016): 414-420.

8. Prokop-Prigge, Katharine A., et al. “The Effect of Ethnicity on Human Axillary Odorant Production.” Journal of chemical ecology 42.1 (2016): 33-39. https://www.researchgate.net/pro…

9. Rodriguez, Santiago, et al. “Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene.” Journal of Investigative Dermatology 133.7 (2013): 1760-1767. http://ac.els-cdn.com/S0022202X1…

10. Baumann, Tim, et al. “Glutathione‐conjugated sulfanylalkanols are substrates for ABCC11 and γ‐glutamyl transferase 1: a potential new pathway for the formation of odorant precursors in the apocrine sweat gland.” Experimental dermatology 23.4 (2014): 247-252. http://onlinelibrary.wiley.com/d…

11. Noël, Fanchon, et al. “Sweaty skin, background and assessments.” International journal of dermatology 51.6 (2012): 647-655.

12. Smallegange, Renate C., Niels O. Verhulst, and Willem Takken. “Sweaty skin: an invitation to bite?.” Trends in parasitology 27.4 (2011): 143-148. https://www.researchgate.net/pro…

13. Dormont, Laurent, Jean-Marie Bessière, and Anna Cohuet. “Human skin volatiles: a review.” Journal of chemical ecology 39.5 (2013): 569-578. https://www.researchgate.net/pro…

14. Fierer, Noah, et al. “The influence of sex, handedness, and washing on the diversity of hand surface bacteria.” Proceedings of the National Academy of Sciences 105.46 (2008): 17994-17999. http://www.pnas.org/content/105/…

15. Grice, Elizabeth A., et al. “Topographical and temporal diversity of the human skin microbiome.” science 324.5931 (2009): 1190-1192. http://www.uniroma2.it/didattica…

16. Verhulst, Niels O., et al. “Differential attraction of malaria mosquitoes to volatile blends produced by human skin bacteria.” PLoS One 5.12 (2010): e15829. Differential Attraction of Malaria Mosquitoes to Volatile Blends Produced by Human Skin Bacteria

17. Verhulst, Niels O., et al. “Human skin microbiota and their volatiles as odour baits for the malaria mosquito Anopheles gambiae ss.” Entomologia Experimentalis et Applicata 139.2 (2011): 170-179.

18. Verhulst, Niels O., et al. “Composition of human skin microbiota affects attractiveness to malaria mosquitoes.” PloS one 6.12 (2011): e28991. Composition of Human Skin Microbiota Affects Attractiveness to Malaria Mosquitoes).

19. Shelley, Walter B., and Harry J. Hurley. “The physiology of the human axillary apocrine sweat gland.” Journal of Investigative Dermatology 20.4 (1953): 285-297. http://ac.els-cdn.com/S0022202X1…

20. Taylor, D., et al. “Characterization of the microflora of the human axilla.” International journal of cosmetic science 25.3 (2003): 137-145.

21. James, A. G., et al. “Fatty acid metabolism by cutaneous bacteria and its role in axillary malodour.” World Journal of Microbiology and Biotechnology 20.8 (2004): 787-793. Fatty acid metabolism by cutaneous bacteria and its role in axillary malodour

22. James, A. G., D. Hyliands, and H. Johnston. “Generation of volatile fatty acids by axillary bacteria1.” International journal of cosmetic science 26.3 (2004): 149-156.

23. Natsch, Andreas, et al. “A broad diversity of volatile carboxylic acids, released by a bacterial aminoacylase from axilla secretions, as candidate molecules for the determination of human‐body odor type.” Chemistry & biodiversity 3.1 (2006): 1-20.

24. Penn, Dustin J., et al. “Individual and gender fingerprints in human body odour.” Journal of the Royal society interface 4.13 (2007): 331-340. http://evolution.anthro.univie.a…

25. Natsch, A., et al. “Isolation of a bacterial enzyme releasing axillary malodor and its use as a screening target for novel deodorant formulations1.” International journal of cosmetic science 27.2 (2005): 115-122.

26. Barzantny, Helena, Iris Brune, and Andreas Tauch. “Molecular basis of human body odour formation: insights deduced from corynebacterial genome sequences.” International journal of cosmetic science 34.1 (2012): 2-11. https://www.researchgate.net/pro…

27. Barzantny, Helena, et al. “The transcriptional regulatory network of Corynebacterium jeikeium K411 and its interaction with metabolic routes contributing to human body odor formation.” Journal of biotechnology 159.3 (2012): 235-248.

28. Havlicek, Jan, and Pavlina Lenochova. “The effect of meat consumption on body odor attractiveness.” Chemical senses 31.8 (2006): 747-752. The Effect of Meat Consumption on Body Odor Attractiveness

29. Lefèvre, Thierry, et al. “Beer consumption increases human attractiveness to malaria mosquitoes.” PloS one 5.3 (2010): e9546. Beer Consumption Increases Human Attractiveness to Malaria Mosquitoes

30. Mitchell, S. C., and R. L. Smith. “Trimethylaminuria: the fish malodor syndrome.” Drug Metabolism and Disposition 29.4 (2001): 517-521. The Fish Malodor Syndrome

31. Calenic, Bogdan, and Anton Amann. “Detection of volatile malodorous compounds in breath: current analytical techniques and implications in human disease.” Bioanalysis 6.3 (2014): 357-376. https://www.researchgate.net/pro…

32. Al-Waiz, Makram, et al. “A genetic polymorphism of the N-oxidation of trimethylamine in humans.” Clinical pharmacology and therapeutics 42.5 (1987): 588-594.

33. Zhang, A. Q., S. C. Mitchell, and R. L. Smith. “Discontinuous distribution of N-oxidation of dietary-derived trimethylamine in a British population.” Xenobiotica 26.9 (1996): 957-961.

34. Mitchell, S. C., and R. L. Smith. “A physiological role for flavin-containing monooxygenase (FMO3) in humans?.” Xenobiotica 40.5 (2010): 301-305; Shimizu, Makiko, John R. Cashman, and Hiroshi Yamazaki. “Transient trimethylaminuria related to menstruation.” BMC medical genetics 8.1 (2007): 2. BMC Medical Genetics

35. Etienne, P., et al. “Clinical effects of choline in Alzheimer’s disease.” The Lancet 311.8062 (1978): 508-509.

36. Wills, MICHAEL R., and J. O. H. N. Savory. “Biochemistry of renal failure.” Annals of Clinical & Laboratory Science 11.4 (1981): 292-299. http://www.annclinlabsci.org/con…

37. Williams, Hywel, and Andres Pembroke. “Sniffer dogs in the melanoma clinic?.” The Lancet 333.8640 (1989): 734.

38. Church, John, and Hywel Williams. “Another sniffer dog for the clinic?.” The Lancet 358.9285 (2001): 930.

39. Emma Young, Mosaic, Feb 16, 2016. The animals that sniff out TB, cancer and landmines

40. Kizito Makoye, LiveMint, March 29, 2016. Giant rats to sniff out tuberculosis in Tanzania, Mozambique prisons

41. Toffolo, Marieke BJ, Monique AM Smeets, and Marcel A. Van Den Hout. “Proust revisited: Odours as triggers of aversive memories.” Cognition & emotion 26.1 (2012): 83-92. https://psy.psych.colostate.edu/…

42. Proust, M. (1913). A la Re´cherche du Temps perdu. Paris, France: Bernard Grasset.

43. Bee Wilson, The Guardian, March 26, 2016. ‘I’ve been told bacon smells lovely’ – life without a sense of smell

44. Menashe, Idan, et al. “Genetic elucidation of human hyperosmia to isovaleric acid.” PLoS Biol 5.11 (2007): e284. Genetic Elucidation of Human Hyperosmia to Isovaleric Acid

45. Lunde, Kathrine, et al. “Genetic variation of an odorant receptor OR7D4 and sensory perception of cooked meat containing androstenone.” PLoS One 7.5 (2012): e35259. Genetic Variation of an Odorant Receptor OR7D4 and Sensory Perception of Cooked Meat Containing Androstenone

46. Wysocki, Charles J., Kathleen M. Dorries, and Gary K. Beauchamp. “Ability to perceive androstenone can be acquired by ostensibly anosmic people.” Proceedings of the National Academy of Sciences 86.20 (1989): 7976-7978. http://www.pnas.org/content/86/2…

47. Keller, Andreas, et al. “Genetic variation in a human odorant receptor alters odour perception.” Nature 449.7161 (2007): 468-472. http://vosshall.rockefeller.edu/…

48. Eriksson, Nicholas, et al. “Web-based, participant-driven studies yield novel genetic associations for common traits.” PLoS Genet 6.6 (2010): e1000993. Web-Based, Participant-Driven Studies Yield Novel Genetic Associations for Common Traits

49. Lison, M., S. H. Blondheim, and R. N. Melmed. “A polymorphism of the ability to smell urinary metabolites of asparagus.” Br Med J 281.6256 (1980): 1676-1678. http://bioserv.fiu.edu/~biolab/l…

50. Eriksson, Nicholas, et al. “A genetic variant near olfactory receptor genes influences cilantro preference.” Flavour 1.1 (2012): 22.

https://www.quora.com/Why-are-some-people-smellier-than-others/answer/Tirumalai-Kamala

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