Secret Science Club North Post Lecture Recap: The Nose Knows, but Who Knows the Nose?

Last night, I headed down to the scintillating Symphony Space for the latest Secret Science Club North lecture, featuring Dr Leslie Vosshall of Rockefeller University's Laboratory of Neurogenetics and Behavior. Dr Vosshall is also a consultant for International Flavors and Fragrances Inc.

The topic of the talk being the sense of smell, there was a brief presentation before the lecture- six different fragrances, strips of paper infused with essential oils, were presented to attendees, who were tasked with identifying them. The first fragrance was spearmint, the second eucalyptus, the third lavender, the fourth rosemary, the fifth orange, and the sixth was cinnamon leaf
(reminiscent of cinnamon bark, but subtly different).

Dr Vosshall began her lecture by contrasting our knowledge of the sense of smell with our knowledge of color vision and of hearing. With color vision studies, we know the rules, there is a predictable relationship between the stimulus and the percept. Different wavelengths of light are associated with different colors- a honeybee would be able to perceive certain ultraviolet wavelengths and a rattlesnake would be able to perceive certain infrared ones:

Our perception of sound is also well understood, there is a predictable relationship between frequency and pitch. Musical notation can be likened to scientific notation, it's a diagram plotting pitch and time.

Smell is not well understood- different smells can be characterized as sexy, delicious, evocative, or disgusting, but there is a lot of subjectivity in this regard. In one case, there is a woman who claims to enjoy the smell of dirty diapers.

Dr Vosshall broke the subject down into a few subjects: Why does smell matter? What is the stimulus/percept problem involved? What is the role of genes in our perception of smell? What is the role of the brain in smell? Are pheromones fantasy?

Dr Vosshall then displayed a map of the world, with the countries ranked by incidence of smell disorders- the United States ranked high, with India also having a high degree of individuals with smell disorders. While blindness and deafness are considered to be tragic disabilities, an inability to smell is not generally considered to be that big a deal. To those suffering from anosmia, though, there is a decreased enjoyment of life- anosmia sufferers can inadvertently eat spoiled food, they can gain weight because of a diminished sense of taste which causes overeating, they have trouble gauging their hygiene and can compulsively wash themselves or be unaware of strong body odor, and they can fall victim to such dangers as gas leaks and chemical exposure. They can suffer mental health problems due to social isolation and a loss of links to past aromas.

Dr Vosshall displayed a couple of cartoons from an exhibition from artists James Auger and Jimmy Loizeau depicting doctors making diagnoses by smell and dogs sniffing out cancer cells, and posed the question, can dogs really sniff out cancer?

The topic then shifted to the stimulus/percept problem. Dr Vosshall showed us some diagrams of molecules which turned out to be beta-damascenone (a major component of a rose's bouquet) and 3-hexanol (a major component of grass' aroma). She noted that there is no disciplined way to predict how a particular substance will smell. A rose has over 260 odor molecules mixed in a certain combinatorial ratio. While different flowers have different aromas, there is a lot of overlap in their odor compounds. Dr Vosshall then displayed a diagram noting some odor compounds in common flowers:

Nature is the ultimate perfumier...

She then displayed a diagram displaying some odor compounds associated with human waste, such as skatole:

She then informed us that some of these 'waste' odor compounds are used in perfume making, wryly noting that perfumes contain a hint of 'stank', otherwise they'd smell flat.

As an aside, I have to note that these compound diagrams are fantastic.

Smells can be characterized by their intensity (strong vs weak) or valance (good vs bad), but there is no quantitative measure- a subjective element is at play. The culture in which one is raised has an effect on odor perception- one's perception of the smell of a durian, garlic, blue cheese, or cilantro is, to a large extent, culturally driven.

There is a difficulty in categorizing scents... we operate in a 'constrained space', having to describe aromas as 'floral' or 'citrus', or some other category. Even the descriptive terms are subjective... contrast that to a description of a musical note- Dr Vosshall joked about the difficulty in shopping for perfumes and quipped: "Nobody in a music store asks a customer, 'Do you like Middle C?'"

Dr Vosshall then displayed the body odor aroma wheel to kick off a discussion of the semantics of odor quality descriptors:

In the 1980's, researcher Andrew Dravnieks had subjects describe aromas using 146 different descriptors (PDF), though there are other breakdowns in the odor atlas. In a recent experiment, subjects were asked to describe 480 different odor molecules in their own words. At the low end, one subject merely used two words while another used 7,160 words to describe the different odors. Women typically used twice the number of words to describe aromas as men did. Certain compounds were easily described- R-(–)-carvone being described as having a minty aroma, D-camphor being overwhelmingly described as smelling like Vick's Vap-o-Rub. Other compounds were described using more varied terms, with vanillin being largely described as having a 'vanilla' smell, but also described as smelling 'sweet', or 'like chocolate'- Dr Vosshall joked that the descriptors for vanillin could be likened to the smell of Zabar's bakery section. On the other hand, methanethiol was described as smelling like feces, spoiled milk, rotten eggs, garbage trucks, and 'ass'. The descriptors are subjective, there's no scientific term to pin down an aroma.

The topic of the talk then shifted to discrimination- how many odor molecules can humans perceive? One study by Dr Vosshall's team suggested that humans can distinguish a trillion smells. There are approximately 166,443,860,262 different odor molecules, out of which perfumiers use about five thousand. Dr Vosshall wryly noted that, if the publishing industry limited itself to five thousand words, books would be boring. Dr Vosshall admitted that the study stating that humans could discriminate one trillion olfactory stimuli was her 'most hated' paper, and then described the study itself. In the study, thirty olfactory compounds were mixed in various combinations, with a certain percentage of overlap. Three vials were presented to the test subjects- two relatively close, with one mixture significantly different... the test subjects were typically able to distinguish the 'odd vial out', the one with a significant percentage difference. Out of the various compounds, trillions of possible combinations were possible, and the scents produced were dissimilar from any familiar scents.

We are much better at smelling than we think. Smelling starts with sniffing- air containing odor molecules is inhaled through the nostrils and hits the olfactory bulb, where various olfactory neurons react to different odorants to different extents. Dr Vosshall played a short animation to illustrate the manner in which various odor molecules interact with different olfactory neurons:





Odor intensity is determined by how many neurons are activated by odor molecules- the more neurons stimulated, the more intense an aroma. The identity of odorants is deconstructed in the piriform cortex of the brain, though no patterns of brain activity regarding odor perception have been differentiated. Dr Vosshall noted that scientists are driven by ignorance- they thrive on such problems as the mystery of olfaction. She also noted that it is difficult to build sensors corresponding to all odors. That being said, she noted that the 2004 Nobel Prize in Physiology or Medicine was awarded to Richard Axel, Linda B. Buck for their research in olfaction- Dr Vosshall joked that this was the 'Smell Nobel'.

Humans have about 400 odor receptors, while rats have about 1,000 and dogs have about 2,000. Is smell unimportant to humans, or are 400 odor receptors sufficient? Every human has a unique nose and each of us is a bit 'smellblind'- everyone has different odor receptor functionality. To illustrate this, Dr Vosshall had three volunteers from the audience smell three vials of odor molecules- one of them (odor B) was androstenone, a sex steroid which drives female pigs in heat crazy (a similar compound, androstadienone, a product of the breakdown of testosterone in humans). The subjects were asked to describe the smell of the androstenone, and all three indicated that it did not have a strong smell, which elicited a joke from Dr Vosshall, about how she could tell them what their genomes were like. The gene OR7D4 responds to androstenone and androstadienone, and various individuals can perceive it as odorless, or sweet/floral, or urinous/sweaty. The OR7D4 receptor only responds to sex steroids, broken copies of OR7D4 cause individuals to perceive androstenone as less intense (for the record, when the vial of odor B was passed around, I perceived it as an acrid odor, almost painful to smell).

Dr Vosshall then brought up the topic of pheromones, nothing that the term originally applied to chemicals secreted by female insects to attract mates. She described one Israeli study, which she described as 'brilliant, convincing, and funny- a trifecta for scientists' that found that women's tears tended to turn men off. Tears are a chemosignal- in the study, women's tears were collected (the tears were induced by having the women watch sad movies, no onions were used in the experiment) and small patches were soaked in either saline solution or the tears of sad ladies, and these patches were placed under the noses of male subjects. There was no conscious odor difference between the tear-soaked patches and the saline-soaked ones. The male subjects were asked to rate the sexual appeal of different female faces, and the tears were found to reduce the sexual arousal of the men. Dr Vosshall noted that there is no real human equivalent to insect pheromones- any talk of human 'pheromones' involves a stretching of the term and some degree of confusion. She noted that the human pheromone literature is a 'toxic mess'.

After the lecture, there was a Q&A session. There were various questions about the evocative nature of aromas- Dr Vosshall indicated that smell tends to bypass semantic centers and hit emotional centers. Another questioner, noting that certain cooks are better at distinguishing ingredients than others, asked if one could improve one's sense of smell- Dr Vosshall noted that good smellers practice, they train themselves. Another questioner asked if any work was done to integrate odors in pedagogy, with, for example, pairing scents with chapters in a book- alas, this isn't typically done. There is a huge scent industry, though, and a lot of high-end hotels have scent designers 'imprinting' or 'training' customers with signature aromas, typically 'easy florals'. Some bastard in the audience, being a hard science junkie, asked Dr Vosshall about the differences in mammalian olfaction and insect olfaction (the last common ancestor almost definitely being an aquatic denizen of the Precambrian). Dr Vosshall stated that vertebrates and insects use completely different proteins to serve the same purpose- insects have fast-acting olfactory receptors, which probably co-evolved with flowering plants. Slower mammals evolved slower olfactory sensors.

Dr Vosshall opined that humans should be more like dogs, they should sniff around more, interact more with scents. I made a note of this advice before heading off to the subway...

Once again, the Secret Science Club has dished up a fantastic lecture in their Northern Outpost. Kudos to Margaret and Dorian and the staff of the Symphony Space. High fives all around. For those of you unable to attend, here is a video of a World Science Festival panel discussion featuring Dr Vosshall:





Crack open a beer and, if you're feeling adventurous, spray a little Odor B around the room, and inhale deeply through your nose... that's the smell of science!