Chemical Reaction: Nose News

“Smell is a potent wizard that transports you across thousands of miles and all the years you have lived.”—Helen Keller

The exciting thing about the sense of smell is that its mysteries are still being unraveled. Of course, more is known than in the Dark Ages, before Linda B. Buck and Richard Axel discovered the odor receptor gene family in 1991. They revolutionized the study of olfaction by enabling the tools of genetic research to be applied to the odor receptors. They were rewarded with the 2004 Nobel Prize in Physiology or Medicine, but the quest for deeper understanding continues. Not only has genetics provided new insights, but the understanding of the brain has taken the exploration of scent into the inner depths of the human mind.

The classic simplistic text book description of odor reception refers to hair-like cilia in the top of the nasal cavity. A signal is sent from the cilia to the olfactory bulb and on to the brain. Correct as far as it goes, yet it explains nothing about the detailed mechanism required to decode an odor. The generally accepted structure/odor theories stress either the shape of the odorant molecule or alternatively emphasize molecular vibrations.1

An airborne odorant comes in contact with a receptor, a 7-transmembrane protein (7TM) in the cilia in the top of the nasal cavity. The odorant molecule must be volatile, rarely bigger than a molecular weight of 300 and slightly polar. A signal is triggered, either due to conformation change or molecular vibration. The signal activates a G-protein, the discovery of which was recognized by the 1992 Nobel Prize.

The G-protein is both an on/off switch and signal amplifier. The cascade it generates opens an ion channel that travels through an axon to a ball of nerves called the glumerili. The glumerili reside in the olfactory bulb. From here, an impulse travels to several areas in the limbic system of the brain. Since the limbic system is the emotive part of the brain, it becomes clear why odors can have such profound effects on memories and feelings.

There are two glumerili for each receptor family, one on each side of the nose. Thus each rose receptor (not a real type of receptor), expressed on thousands olfactory cilia, connect to one of two rose glumerili, and so on for each of the 347 different functioning genes. The mechanism is clearly combinatorial, since humans can smell far more than 347 different odors.

Chemoreception, the ways chemicals around you are sensed, consists of the olfactory system, the trigeminal nerve and the Volmeronasal Organ (VNO) or Jacobson’s Organ. The trigeminal nerve is a hazardous warning system spread around the face, which may have some odor perception capability. The VNO is the putative human pheromone receptor. The existence and importance of human pheromones has been a controversial area of chemoreception science.

Insect pheromones are well-known, in addition to some animal pheromones. Pheromones have a variety of purposes, such as marking territory or laying down a path to food. Androstenone is called a pig pheromone by its detractors, to shed a bad light on its human effects. The classic work establishing the existence of human pheromones is McClintock’s work on menstrual synchrony.2 Note that McClintock refers to pheromones defined as chemical signals, not sexual attractants.

Buck’s recent work3 discloses a new family of chemoreceptors. The new class, trace amine-associated receptors or TAARs, are present in humans, mice and fish. The work done on mice showed recognition of volatile amines found in three sources: urine, a compound linked to stress and a potential pheromone. The ligands identified are thus associated with social cues rather than odorants. Extension of this work into humans can potentially yield a previously unknown mechanism for pheromone response.

Biology students have a simple experiment to show the effects of genetics in taste perception. It involves individual differences in the ability to detect phenylthiocarbamide (PTC) and propylthiouracil (PROP), materials with a bitter taste. It is absolutely hereditary. Globally, 55% of all humans can taste it and 45% cannot. The gene has been precisely identified4 and involves a G-protein that responds to the N – C = S moiety.

This is an aspect of psychogenetics, relating behavior and preferences to human genes. The presence of the PTC receptor increases the preference for glucose, apparently since the heightened awareness of bitterness requires more sweetness to overcome. The same genetic difference influences the response to sulfur-containing raw vegetables. Individual genes also can promote obesity by removing the ability to feel full after eating.

The application of psychogenetics to taste obviously will transfer into individual fragrance use, since the taste and olfactory systems are so closely related. In the realm of perfume preference, the possibility that genetics will provide a tool for correlating likes and dislikes with genes is a marketing tool potentially as important as the application of fMRI to brand recognition in neuromarketing.5

The regulatory environment is getting harder on fragrance, particularly in Europe. Having just adjusted to the EU allergen regulations, REACH now is bearing down. With so many challenges to the existing fragrance palette, it is fortunate that discoveries involving genetics, the receptor families and brain function may open new worlds of fragrance applications. It is the old adage at work: Every time a door closes, another one opens.

On a final note, Luca Turin recently has written a wonderful little book6 on smell to serve as a pendant to Chandler Burr’s The Emperor of Scent.7 It should be an excellent addition to the bookshelf of the general reader and fragrance professional both. For those who wish a quick overview of all the senses, a recent special edition of Scientific American is highly recommended.8


  1. S Herman, Good Vibrations, GCI (Jun 2003)
  2. MK McClintock, Menstrual Synchrony and Suppression, Nature 29(22) 244–245 (1971)
  3. SD Liberles and LB Buck, A second class of chemosensory receptors in the olfactory epithelium, Nature, 442 10 (Aug 2006)
  4. B Bufe et al, The Molecular Basis of Individual Differences in Phenylthiocarbamide and Propylthiouracil Bitterness Perception,, 15 322–327 (Feb 22, 2005)
  5. S Herman, Selling to the Brain, GCI (May 2005)
  6. L Turin, The Secret of Smell, Ecco (2006)
  7. C Burr, The Emperor of Scent, Diane Pub Co: Darby, PA (2004)
  8. Scientific American Special Edition, Secrets of the Senses, 16(3) (2006)
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