The chirality of smell

Limonene_struttura

Limonene

As I prepare the first half of my Science of Smell online class, I am having fun looking for various examples of all things biomolecular, biochemical, and genetic related to olfaction. If I were a taste and flavour chemist or a molecular gastronomist, I’d probably be interested in somehow exploiting the chirality of biomolecules in food and drinks!

Chirality refers to the non-symmetrical nature of some molecules. Non-symmetrical molecules are like our right and left hands: they appear the same in reverse but you cannot superimpose the image of one over the other in the mirror nor can a left-handed glove fit a right hand. In the pharmaceutical industry, chirality is very important because the enantiomer of a biomolecule that produces a positive outcome (like reducing morning sickness using thalidomide or hyperactivity using Ritalin) may cause a harmful effect (birth defects) or no effect. The handedness is determined by the stereocenter of a molecular. Those with ‘right’ handed stereocenters are ‘R’ or + enantiomers and those with ‘left’ handed stereocenters are ‘S’ or – enantiomers (the S comes from sinister, Latin for left).

Our olfactory receptors are clever things: they can tell the difference between the right and left hands! The two most common examples are of carvone and limonene.  The R-carvone/(-) carvone is recognized as mint and its enantiomer as carraway. R-limonene/(+) limonene smells ‘orange’ and its enantiomer is lemon (see image to the right). So next time you smell oranges and lemons at the same time, recognize the power of your nose to be ambidextrous by distinguishing between the two biomolecules!

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Is odorant diversity driving olfactory receptor genetic variation?

Olfactory receptor genes have more variation than most gene families in the human genome. The only family with greater diversity is the major histocompatibility complex (MHC). Both families also exhibit high heterozygosity. Due to its association with disease, the MHC is well-studied. The explanation for the maintenance of MHC diversity is pathogen-driven selection–either through heterozygote advantage or frequency-dependent selection (see here for a review); a small number of papers (here’s two: and 2) have also argued for divergent allele advantage. A diversity of  pathogens will result in a diversity of MHC genes over time; as a species develops resistance to a disease, an evolutionary respones occurs in the disease-causing agent. The common analogy is the evolutionary arms race, also called the Red Queen Hypothesis.

If we apply that same model to olfaction in light of a few recent findings. there might be something worth pursuing. We know we can smell millions of odors. Such a diversity of odorants in the environment that vary from region to region may result in incredible diversity in the human olfactory receptor subgenome–especially if we look at it from the perspective of divergent allele advantage.

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Stress and sex

A study from 2013 that documented sex differences in sleep needs (based on inflammatory markers) turned  my thoughts to stress susceptibility. I recently wrote about allostatic load, a measure of elevated cortisol (a stress hormone) in living human populations. While attempts to transfer the concept of allostatic load to the bioarchaeological record are lacking robusticity, there is a rich history of people writing about odonto-skeletal stress markers and variation within and among populations in the frequencies of these markers.

A commonly cited expectation is that male physiological vulnerability results in higher levels of stress markers unless otherwise culturally buffered by sex-biased investment in offspring. The assumption of sex-based differences in one stress marker (enamel hypoplasias) was reviewed and mostly dismissed by Guatelli-Steinberg and Lukacs (though read the paper to understand the weak effect sex may have in some cases, the data analyzed to make this conclusion, and other subtle findings). Instead, they find that the big effect in the development of sex differences is from culturally based sex-biased investment in children. The sex-bias is hard to show in the archaeological record: in other words, while the biological data may show a sex difference, determining if the differences are from sampling error (burials most often are small in sample size and non-representative) or cultural biases (interpretable often through the material culture record) is extremely challenging. 

According to a growing body of research (perhaps stemming from high rates of heart disease in modern females–number one killer), females have more inflammatory markers in their body and higher rates of inflammation. Inflammation is part of the native immune system and a basic sign of physiological stress. These findings, if they can be applied to past populations, suggest that females are not buffered biologically and archaeological data suggest that more often than not, females are also not buffered culturally.

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Resilience and adaptation/Canalization and stress

This is a very belated follow-up to a previous blog on the stress concept in biological anthropology. The utility of resilience in interpreting the archaeological record is under-rated as are the parallels of homeostasis and stress in human biology. I first became involved in studying resilience theory at UAF when I joined the RAP faculty. I presented some of this work in a seminar in Japan in 2009. After that and in a series of papers led by my archaeology colleague (Mark Hudson at NishiKyushu University Japan), we have explored resilience theory as a method of examining the archaeological record. We weren’t the first to think of this (here for a start). In the past two years, I have been looking at the parallels to concepts long used in biology, canalization and stress. The fundamental unit underlying these concepts is systemic integrity and external forces acting on that integrity. This concept appears across the academy with parallels in physics (surface tension), engineering, etc.

My interest is human biology from an evolutionary perspective (including the archaeological record). As biocultural beings, humans are shaped by biology and culture. When we look at evidence of physiological activity in the past, the context of those artifacts is key. Understanding when an organism is resistant to change (from external forces) while remaining internally coherent is, at the base of it, no different than understanding when a society is resistant to change while remaining internally coherent. Another way to understanding the competing forces of stability and change (in organisms or in society) is to look at how the system (biological or cultural) may adapt (or change, interpreted very loosely) in response to external forces. Adaptation is part of the resilience cycle. The difference between this and collapse is that the essential parts of the system (organismal or cultural) maintain integrity, as opposed to simply disappearing or being assimilated. More archaeological data are showing the persistence (in some capacity) of collapsed, dominated, or assimilated cultures (see here for some examples).

In modern societies, the system itself can be understood as well as the context; what cannot be understood is longitudinal change. Archaeological materials and their interpretation can provide the longitudinal data that measure system continuity (or lack thereof) after a period of prolonged or severe acute external stress; the challenge lies in reconstructing the system (and which components are essential). Combining these two datasets (contemporary and past) adds tremendous value to projections for the future–we get rich longitudinal data and rich system data, the combination of which provide a template for modelling future outcomes to responses to change.

Coming back to the biological parallel, we can use these sets of data to test resilience–was a population cultural resilient but biologically in decline or was a population experiencing improved biological conditions but cultural unstable. Since a key feature of modern resilience theory is both cultural and physiological well-being (again, defined broadly), a truly resilience system will show evidence of maintenance (or improvement) in both sectors. If we examine the data and find that a group shows cultural resilience but poor health or vice versa, were they truly resilient? Perhaps a better way to look at this is through the modified cycle of systems where resilience can be considered a reorganization. The moment (in archaeological time) when a system is experiencing external stress but maintaining culture and health is a precursor to the moment when the system is unsustainable and must reorganize. The maintenance of health and basic cultural values will persist even if the system appears to be dramatically changed. In some cases, the decline is too great and the system integrity is compromised and changes rather than adapts.

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Inhale for health

This research is a bit old (October 2013) but recently caught my eye:

Research out of Japan shows that walking in the woods also may play a role in fighting cancer. Plants emit a chemical called phytoncides that protects them from rotting and insects. When people breathe it in, there is an increase in the level of “natural killer” cells, which are part of a person’s immune response to cancer.

“When we walk in a forest or park, our levels of white blood cells increase and it also lowers our pulse rate, blood pressure and level of the stress hormone cortisol,” Michelfelder said.

There is rare evidence of cancer (osteocarcanoma) in prehistoric hunter-gatherer populations (see here for a nice public science summary) and mummies (another public science review is found here). This may be because we can’t detect it and accurately determine its frequency. Modern techniques like CT scanning make inroads into non-invasive paleopathology data gathering but skeletons have a limited capacity to reveal diseases of the past. This is partly because the lesions (like most pathologies) often don’t reach the bones, take too long to reach the bones before death, or are nonspecific.

The rarity of evidence for cancer may also be because it simply wasn’t there. Most cancers occur at the end of of or after reproductive years; the shorter human life span ‘in the wild’ would likely lead to fewer cases of cancer experienced by our prehistoric relatives and not impact net reproductive success (meaning any cancer-causing genes would persist in human populations). Persistent cancer-causing genes interact with the modern environment and longer life span to reach modern cancer frequencies. I wonder if lifestyles that take one into the woods for significant periods of time (e.g., prehistoric hunter-gatherers, modern populations leading ‘traditional’ lifestyles) reduce cancer incidence?

I am reminded of something I heard when I was a kid about the actor Dirk Benedict (from Battlestar Galactica–the original Starbuck!–and the A-Team) having had overcome prostate cancer by disappearing into the woods and the wilds of the country and eating a macrobiotic diet. I looked up his story to see if I remembered correctly. I had mostly:

When I learned I had a tumor—I refused to be tested for malignancy—I weighed 180 pounds. When I came out of the mountains of New Hampshire six weeks later, I weighed 155. I went to stay in a friend’s cabin because I didn’t want any distractions, any temptations, anybody calling up to say, “Let’s go have a bagel.” Well, all hell broke loose. Some days I felt on top of the world, and other days I couldn’t get out of bed. Sometimes I couldn’t walk up the stairs, and sometimes I’d ride, run and chop wood for 24 hours.

I never did go into a hospital. Instead, I packed up my duffel bag and became a vagabond, traveling to Montana, Maine, California, New York City, Wisconsin, hitchhiking across the country once and driving across twice.

Did the woods help? Maybe! The sense of smell–yet another benefit!

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The Scent of a Man

A new study (published here) suggest that scientists unable to replicate  behavioral studies in rats and mice may be due to the presence of male researchers.

The presence of male experimenters produced a stress response in mice and rats equivalent to that caused by restraining the rodents for 15 minutes in a tube or forcing them to swim for three minutes. This stress-induced reaction made mice and rats of both sexes less sensitive to pain.

The chemical signals emitted by males of any species are detectable by other species. Since males secrete these pheromones at higher concentrations than women, the effects tend to be limited to male researchers. Rats and mice acclimatize over time to the male researchers, suggesting an ‘easing’ in period prior to experimentation or perhaps, even better, even more effort to promote women in science!

Since there is growing evidence that humans respond to pheromones, I wonder if there is a similar effect caused by male researchers on human subjects; namely, is stress induced in males and females when experiments are conducted by men? Outside the lab, does the scent of a man induce stress and reduce pain response, but in a good way? I’ll end with ‘Boys‘ by Robots in Disguise.

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Smell up and taste the environment

I came across this piece on how a contrived multisensory environment influences perception, in this case of whisky. Three different multisensoriums were created for one whisky.

Each room had a unique visual appearance, soundscape, fragrance, and feel which was designed to emphasize a different attribute of the whisky; its grassiness, sweetness, or woodiness…The room that was designed to emphasise the ‘grassiness’ of the whisky had a turf floor and a soundscape recorded in a summer meadow (which included sheep ‘baa-ing’ in the background). This contrasted to the other rooms, such as the one that was designed to emphasis ‘woodiness’, which had a fragrance of cedarwood and tonka bean and a soundscape that included the sound of creaking timbers, log fires, and wood instruments.

The senses used to direct perception would resonate cross culturally–even if a particular stimulant (e.g., tonke bean odor, sheep) is unfamiliar, the others likely will evoke the desired response.

The Japanese have been playing with smell in the work environment for some time, creating temporal smellscapes that promote mental faculties and mitigate behaviors that might interfere with work (e.g., an odor to counteract sleepiness after lunch). Industrial designers work with clients to create brands that promote specific values (wealth,  modernity, humbleness, etc) that are meant to resonate with the target audience of the client (i.e., the clients clients).

Taken to an extreme (possible Portlandia spoof), a bar would have to have drink-specific seating. But, this study explores the idea that our perceptions (and the associations formed with them) are more than simply personal preference. In the wrong environment, a drink (or food, film, music etc) might not be perceived the same as previous experiences. If this happens enough times and the environmental influence is subtle, you might not know why you ‘went off’ something. It also adds a little depth to why certain drinks are preferred in certain environments (rail gin or PBR in a dive bar versus champagne at a penthouse rooftop cocktail party). The same could go for any sensual input–an art film at a Regal or Cinemark versus an old Roxy, punk rock in the Bowery versus Barneys.

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