Recent discoveries have proven that scent receptors are not limited to the nose! Recently, Dr. Hans Hatt and his team have found almost all human tissues have some of the olfactory receptors in large quantities.[1]
There are huge implications from this finding. The sense of smell has long been ignored as a primary scent, but research in the field has been growing at an exponential rate. Scientists who paid attention to under researched olfactory receptors, won a Nobel Peace Prize for “Demystifying the Sense of Smell.” Now, there are important learnings as to what this sense is and how it works. Scent has long been acknowledged as being tied to memory; it now is being tied to self-healing. The first mention of the category, Scent-based Medicine was in the New York Times in an article titled Smell Turns Up in Unexpected Places[2]. It revealed that “scent has different healing properties than previously thought” and first reported that scent receptors were not limited to the nose.
Dr. Hanns Hatt and his team of biologists has found, “More than 15 of the olfactory receptors that exist in the nose are also found in human skin cells. I’ve been arguing for the importance of these receptors for years,” said Dr. Hatt, who calls himself the Ambassador of smell, “It was a hard fight.” 2 Dr. Hatt has been a professor at the Faculty of Biology and owner of the chair for cell physiology at the Ruhr-University Bochum, where the study was done. He was the first to recognize that olfactory receptors also play an important role in cells outside the nose. The whole concept of scent receptors outside the nose seems alien, almost like science fiction.
It is, however, scientific fact that our odor receptors are among the most ancient chemical sensors in the body. Scent is finally coming of age as a critically important sense. Research is quickening on the validation of scent and its impact on health. Many are calling it Scent-based Medicine as an alternative to traditional pharmacology.
“Over the last decade or so, scientists have discovered that odor receptors are not solely confined to the nose, but found throughout body,” said Dr. Hatt, “in the liver, the heart, the kidneys and even sperm, where they play a pivotal role in a host of physiological functions.2” These discoveries pave the way for exciting new developments in scent, especially in healthcare. Dr. Hatt found there was a physiological response to exposing these receptors (named OR2AT4) to an odor known as Sandalore, a base note with a Sandalwood amyris woody type. In a series of human tests, skin abrasions healed 30% faster after exposure to Sandalore. A powerful diffusive that imparts a rich, warm, natural sandalwood character apparently creates molecular signals to induce healing of injured tissue. Scientists think this could lead to new products for aging skin and recovery treatments after skin trauma.
“If you think of olfactory receptors as specialized chemical detectors, instead of as receptors in your nose that detect smell, then it makes a lot of sense for them to be in other places,” said professor of physiology at Johns Hopkins University, Jennifer Pluznick, who found that olfactory receptors help control metabolic function and regulate blood pressure in the kidneys of mice. [3]
Dr. Hatt and his team have identified olfactory receptors in several other organs, including the liver, heart, lungs, colon and brain. In fact, there’s genetic evidence suggesting that nearly every organ in the body contains olfactory receptors. This highly important sense can detect a multitude of compounds. The capacity of the olfactory system to distinguish among a huge universe of chemical compounds depends on the encoding in the mammalian genome.
The odor information gathered is funneled through a single common signaling pathway. Researchers wondered whether this signaling pathway might be exploited to detect and respond to changes in the chemical composition of the kidney’s “internal environment”. Olfactory receptors are known to play chemosensory roles outside of the olfactory epithelium, most notably in sperm[4], although research continues other bodily functions, like the kidneys.
The kidney is an an ideal organ in which the capabilities of the olfactory chemosensory machinery could be brought to bear. The possibility of scent lowering blood pressure, reducing kidney stones or improving kidney health in humans is astounding. The kidney must keep careful track of the chemical composition of the tubular fluid as it moves through the different segments of the nephron. For example, scent may be beneficial to the kidney to adjust its filtration, reabsorption, or secretion rates in response to changes in metabolite levels, as well as to promote clearance of substances or dicarboxylic acids, to avoid renal stone formation. In their study, they examined whether olfactory-like signaling plays a role in the kidney by assaying for the presence of proteins necessary for olfactory signaling in the kidney, and by assaying renal function in mice lacking a protein necessary for olfaction. That may play a critical role physiologically in regulating fundamental aspects of renal function. In conclusion, they have uncovered the presence of the olfactory signaling system in the kidney, demonstrated its specific localization and are researching how scent can positively affect its function.
Scent has impact on procreation as well. Long held as an aphrodisiac, now scent has a more practical implication. Dr. Hatt was one of the first scientists to study these functions in detail. In a study published in 2003, he and his colleagues reported that olfactory receptors found inside the testes function as a kind of chemical guidance system that enables sperm cells to find their way toward an unfertilized egg, giving new meaning to the notion of sexual chemistry[5]. They identified, cloned, and functionally expressed a previously undescribed human testicular. In human sperm, the receptor for synthetic lily of the valley was detected and shown its activation leads to a positive chemotactic reaction of the human sperm and accelerates its rate. Dr. Hatt has shown in his lab the important functions of other olfactory receptors in both the sperm of men and over 20 fragrances in vaginal secretions by women. Taken together, the results indicated that human sperm chemotaxis may be a critical component of the fertilization process. This can be an indicator for new research to deal with infertility.
Prostate cancer is among the leading killer of men and scent may have a solution. According to the U.S. Centers for Disease Control and Prevention (CDC) the leading causes of cancer death in men are lung cancer, prostate cancer and colorectal cancer. Dr. Hatt and his team also reported that exposing olfactory receptors in the human prostate to beta-ionone, a primary odor compound in violets and roses, appeared to inhibit the spread of prostate cancer cells by switching off errant genes[6].
While preventing prostate cancer may not be possible, early detection does save lives. For example, early detection can offer many cures including aromatherapy with a high potential for therapy in clinical application. The laboratory of Dr. Hatt also intensively studies the effect of essential oils and spices on the trigeminal nerve channels and other areas of the body. His laboratory demonstrated that aromatherapy and its molecular mechanisms of action can be explained by the modulation of brain receptors through the use of perfumes.
Athletic recovery and combating the aging process for muscles could also be impacted by scent. Grace Pavlath, biologist at Emory University, published a study on olfactory receptors in skeletal muscles. She found that bathing the receptors in Lyral, a synthetic fragrance of Lily of the Valley, promoted the regeneration of muscle tissue. Blocking these receptors by neutralizing the genes, was found to inhibit muscular regeneration. This suggested that odor receptors are a necessary component of the intricate biochemical signaling system that causes stem cells to morph into muscles cells and replace damaged tissue.2 No doubt, few scientists ever imagined that fragrance would possess any significant medical benefits.[1] “This was totally unexpected,” Dr. Pavlath said. “When we were doing this, the idea that olfactory receptors were involved in tissue repair was not out there.”
The history of scent and the $43 Billion industry it has become is more than just a pleasant accessory. Olfactory receptors are the largest subset of G-protein-coupled receptors (GPRCs), a family of proteins found on the surface of cells, that allow the cells to sense what is going on around them. These receptors are a common target for drugs, 40% of all prescription drugs reach cells via GPCRs, offering a huge opportunity for what might be called scent-based medicine.
Due to the slow rate of adaptation in the Medical Industry, resistance to any “disruption”, the aversion to new things that are not pharma based, the true unexplored complexity of the olfactory system and the politics around “self-healing”, this opportunity will require time. Despite the recent advances, scientists so far have matched few of these receptors to the specific chemical compounds they react to.
Today, we can expand our understanding and think of olfactory receptors as a “lock-and-key system”, with an odor molecule as the key to the receptor’s lock. Only certain molecules fit with certain receptors. When the right molecule comes along and alights on the matching receptor, it sets in motion an elaborate choreography of biochemical reactions. Inside the nose, this culminates in a nerve signal being sent to the brain, which we perceive as odor. Today we know that the same apparatus can fulfill other biological functions as well. Welcome to the world of Scent-based Medicine!
Keith Kelsen
CEO and Founder Inhalio – Contact
[1] H. Hatt, G. Gisselmann, etal: Expression profile of ectopic olfactory receptors determined by deep sequencing. In: PLOS ONE. 8(2), 2013, Art. Nr. e55368.
[2] Smell Turns Up in Unexpected Places, October 14, 2014, on Page D3 of the New York edition: Order Reprints
[3] vol. 106 no. 6 Jennifer L. Pluznick, etal 2059–2064, doi: 10.1073/pnas.0812859106 Functional expression of the olfactory signaling system in the kidney
[4] Spehr M, et al.(2003) Identification of a testicular odorant receptor mediating human sperm Abstract/FREE Full Text
[5] Identification of a testicular odorant receptor mediating human sperm chemotaxis: US National Library of Medicine National Institutes of Health Science: 2003 Mar 28 Hatt H., Spehr M1, Gisselmann G, Poplawski A, Riffell JA, Wetzel CH, Zimmer RK
[6] Activation of an olfactory receptor inhibits proliferation of prostate cancer cells. In:J Biol Chem. 2009 Jun 12. Epub 2009 Apr 23, Neuhaus EM , Hatt H., etal:.