The Smell of Regular Things

We don't know why some things smell the way they do. What do you mean we don't know what a walnut smells like? You heat it up, run it through a gas chromatograph, and look for the spikes. Right? Not so fast. For some things, like walnuts, we didn't know how to recreate its odor without an actual walnut. Cannabis too; we all know the most easily identifiable characteristic of cannabis is it's stinky skunky odor, and yet we don't know where it comes from, down to the single molecule. 

The problem is that some odors that we identify as distinctive, indivisible, or unique are actually more than one molecule; the secret is in the ratio. In other words, the secret ingredient in the secret sauce is the recipe itself, not the ingredient:

Researchers isolate key compounds in the aroma of walnuts

Jun 2023, phys.org

https://phys.org/news/2023-06-isolate-key-compounds-aroma-walnuts.html

As the team shows for the first time, the typical walnut aroma is created by the combination of two odorants that are present in the nuts in roughly a one-to-one ratio. The first substance is sotolon, which smells like Maggi Seasoning sauce and which, as a single component, characterizes the aroma of lovage, for example. The second compound is called (2E,4E,6Z)-nona-2,4,6-trienal. It is known from oat flakes and is responsible for the typical odor there.

British scientists had already olfactorily characterized numerous volatiles from walnuts about 50 years ago. However, none of the compounds they found had a specific walnut note. Thus, the researchers concluded that the characteristic walnut aroma is based on a combination of odorants. Despite this finding and further experiments, however, it had still not been clarified which odor-active compounds are decisive for the aroma of walnuts.

Not the components but the ratios of components -- "In our sensory tests, the walnut note intensified even further when we increased the natural concentrations of both odorants up to tenfold," reports Christine Stübner, a doctoral student who worked on the study. "However, it was important to maintain the one-to-one ratio," she continues.

(By the way, what's the purpose of all this -- based on these findings, new breeding strategies can now be developed to improve walnut aroma.) 

Finally, Instant Walnuts: Put a tablespoon of oatmeal in a glass, add a few drops of the well-known Maggi Seasoning seasoning sauce, shake it a bit and smell the mixture. (Maggi Seasoning smells like sotolon, fenugreek, hot transmission fluid.)

via Leibniz-Institut für Lebensmittel-Systembiologie (Inst for Food Systems Biology) -- Christine A. Stübner et al, Sotolon and (2E,4E,6Z)-Nona-2,4,6-trienal Are the Key Compounds in the Aroma of Walnuts, Journal of Agricultural and Food Chemistry (2023). DOI: 10.1021/acs.jafc.3c01002

https://dx.doi.org/10.1021/acs.jafc.3c01002

A closer look at the compounds and molecules involved in giving cannabis its unique scent

Nov 2023, phys.org

https://phys.org/news/2023-11-closer-compounds-molecules-involved-cannabis.html

(I was looking at the authors for Avery Gilbert, but no. I think some rec ognition is in order; he was the first to conduct smell research on cannabis.)

Using mass spectrometry, gas chromatography and flame ionization detection, researchers found that a molecule called 3-methyl-2-butene-1-thiol (321MBT), along with other volatile sulfur compounds (VSCs), appeared to play a prominent role in odor production. 321MBT is the same molecule that gives warm beer and skunk spray their distinctive smells. 

via terpene distributor Abstrax Tech: Iain W. H. Oswald et al, Minor, Nonterpenoid Volatile Compounds Drive the Aroma Differences of Exotic Cannabis, ACS Omega (2023). DOI: 10.1021/acsomega.3c04496

Research team identifies human odorant receptor for 'horse stable' odor, with implications for food testing

Aug 2023, phys.org

https://phys.org/news/2023-08-team-human-odorant-receptor-horse.html

Para-cresol (4-methylphenol) is an aromatic compound with a strong horse stable-like odor, it is formed during the microbial degradation of certain amino acids, but also during thermal degradation processes, it's also a characteristic odorant in whiskey and tobacco.

• The OR9Q2 receptor was the only one that responded to physiologically relevant concentrations of the substance.
• Conversely, 4-ethylphenol was the only one of 176 aromas able to significantly activate the receptor. (and that's called being highly selective).
• "The receptor fills a gap in the recognition spectrum of the phylogenetically older human odorant receptor OR2W1, which detects a wide range of structurally different odorants, but not para-cresol."

via Leibniz-Institut für Lebensmittel-Systembiologie aka Leibniz Institute of Food Systems Biology at the Technical University of Munich: Franziska Haag et al, The multi-faceted food odorant 4-methylphenol selectively activates evolutionary conserved receptor OR9Q2, Food Chemistry (2023). DOI: 10.1016/j.foodchem.2023.136492

https://dx.doi.org/10.1016/j.foodchem.2023.136492

https://dx.doi.org/10.1021/acsomega.3c04496

Image credit: AI Art - Super Rich Monkey - 2022

Electronic Hedonics

Electronic noses sniff out volatile organic compounds

May 2023, phys.org

https://phys.org/news/2023-05-electronic-noses-volatile-compounds.html

Many e-noses generate different signals toward VOCs of the same concentration when the sensor is located in different parts of the "nose" chamber:

"To counteract this problem, the fluidic behavior of the gas flow needs to be well controlled," said author Weiwei Wu. "This ensures a uniform fluidic field and concentration of VOCs in the chamber and avoids generating any fake sensing characteristics."

A vertical chamber that looks much like a showerhead promotes vertical flow so gas spreads through holes at the bottom of the device and around to evenly distributed sensors.

via Interdisciplinary Research Center of Smart Sensors, School of Advanced Materials and Nanotechnology, Xidian University; Intelligent Perception Research Institute, Zhejiang Lab, Hangzhou: Controlling fluidic behavior for ultrasensitive volatile sensing, Applied Physics Reviews (2023). DOI: 10.1063/5.0141840

https://dx.doi.org/10.1063/5.0141840

Note: This problem has come up in two other papers where they talk about how the two different nostrils cancel each other out because they can't rely on evenly distributed air; it messes up the statistics, so at least with two different nostrils, you can have some error correction. See "Domestic cat nose functions as a highly efficient coiled parallel gas chromatograph", We et al. PLoS Computational Biology (2023). DOI: 10.1371/journal.pcbi.1011 https://pubmed.ncbi.nlm.nih.gov/37384594/ and "Odor representations from the two nostrils are temporally segregated in human piriform cortex", Dikeçligil et al, Current Biology (2023). DOI: 10.1016/j.cub.2023.10.021 https://dx.doi.org/10.1016/j.cub.2023.10.021

Image credit: AI Art - A Person Getting Their Head Electrocuted as Interpreted by the Internet - 2023

Perceiving the smell of lemon, geranium or eucalyptus: A study on the electrical signals behind human olfaction

Jul 2023, phys.org

https://medicalxpress.com/news/2023-07-lemon-geranium-eucalyptus-electrical-human.html

Somewhat related to electronic noses, real-live odor receptors obtained from nasal biopsies:

"Until now, nobody had measured in intact human tissue the electrical activity of cells, neurons and epithelial cells that form the olfactory epithelium of our nose in which odorant molecules are captured."

via International School of Advanced Studies, Aldo Moro University of Bari, University of Trieste, and the Otorhinolaryngology Clinic of Azienda Sanitaria Universitaria Giuliano Isontina: Andres Hernandez-Clavijo et al, Shedding light on human olfaction: electrophysiological recordings from sensory neurons in acute slices of olfactory epithelium, iScience (2023). DOI: 10.1016/j.isci.2023.107186

https://dx.doi.org/10.1016/j.isci.2023.107186

'Electronic tongue' holds promise as possible first step to artificial emotional intelligence

Oct 2023, phys.org

https://techxplore.com/news/2023-10-electronic-tongue-artificial-emotional-intelligence.html

It sounds to me a bit of a stretch right now to call this emotional intelligence; it sounds like basic chemical detection to me, but with the addition of a memristor.

The memristor is the new part, and one day we will have gustatory chips, and olfactory chips, vision chips, etc.; chips for everything; everything will have its own chip. Christmas chips and new mother chips and traffic chips for cars and ambient energy harvesting chips for sneakers and even organic chemistry chips for med students so they don't have to study. Everything will have its own chip. There won't be categories of chips, instead every single thing will have its own chip. Just not today. 

Continuing:

The artificial tastebuds comprise tiny, graphene-based electronic sensors called chemitransistors that can detect gas or chemical molecules. The other part of the circuit uses memtransistors, which is a transistor that remembers past signals, made with molybdenum disulfide. This allowed the researchers to design an "electronic gustatory cortex" that connect a physiology-drive "hunger neuron," psychology-driven "appetite neuron" and a "feeding circuit."

"When detecting salt the device senses sodium ions. This means the device can 'taste' salt."

"We are trying to make arrays of graphene devices to mimic the 10,000 or so taste receptors we have on our tongue."

via Penn State: Subir Ghosh et al, An all 2D bio-inspired gustatory circuit for mimicking physiology and psychology of feeding behavior, Nature Communications (2023). DOI: 10.1038/s41467-023-41046-7

https://dx.doi.org/10.1038/s41467-023-41046-7

Smells Throughout History

Proof that part of the Roman Empire smelled of patchouli

May 2023, phys.org

https://phys.org/news/2023-05-proof-roman-empire-patchouli.html

Two thousand years ago, in the Roman city of Carmo (today's Carmona), in the province of Seville, someone placed a vessel of ointment in a funerary urn. A small hyaline quartz rock crystal flask, carved in the shape of an amphora, contained the ointment.

The ointment was preserved because of the Dolomite used as a stopper, and the bitumen used to seal it.

Two components of the perfume have been identified: a base or binder, which allowed for the preservation of the aromas, and the essence itself; these findings according with descriptions by none other than Pliny the Elder. The base was a vegetable oil, possibly olive oil. The essence was of patchouli, widely used in modern perfumery, but whose use in Roman times was not known. 

via University of Córdoba: Daniel Cosano et al, Archaeometric Identification of a Perfume from Roman Times, Heritage (2023). DOI: 10.3390/heritage6060236

https://dx.doi.org/10.3390/heritage6060236

Unbottling the scent of the afterlife: New study of ancient Egyptian mummification balms

Aug 2023, phys.org

https://phys.org/news/2023-08-unbottling-scent-afterlife-ancient-egyptian.html

They used gas and liquid chromatography to reconstruct mummification substances, i.e., balm residues, found in two canopic jars from the mummification equipment used to embalm the noble lady Senetnay in the 18th dynasty, circa 1450 BCE.

The team found that the balms contained a blend of beeswax, plant oil, fats, bitumen, Pinaceae resins (most likely larch resin), a balsamic substance, and dammar or Pistacia tree resin.

Working closely with the French perfumer Carole Calvez and the sensory museologist Sofia Collette Ehrich, the team meticulously recreated the scent based on their analytical findings.

(Sensory museologist: exists)

via the Max Planck Institute of Geoanthropology and Moesgaard Museum in Denmark: Barbara Huber, Biomolecular characterization of 3500-year-old ancient Egyptian mummification balms from the Valley of the Kings, Scientific Reports (2023). DOI: 10.1038/s41598-023-39393-y.

https://dx.doi.org/10.1038/s41598-023-39393-y

Image credit: AI Art - Person Holding Magnifying Glass - 2023

 

Coding for Information Overflow and Statistical Irregularity

Part of the "odor code" our brain uses to smell is tasked with overcoming the statistical irregularity caused by massive changes in airflow direction, speed, humidity, etc. as we pull that air through our nostrils. The cross-cancelling variables required in this effort are mentally exhausting to consider, never mind to calculate. But that's what we do when we smell:

How insects track odors by navigating microscale winds

May 2023, phys.org

https://phys.org/news/2023-05-insects-track-odors-microscale.html

"This is important because insects are typically tracking odor plumes in lower wind speeds, which indicates they are somehow making sense of the high directional variability they encounter," said Houle. "Turbulence intensity is strongly correlated with standard deviations in wind direction, which might be useful for future wind tunnel experimental designs aimed at recreating more 'natural' winds."

Based on their findings, Houle and van Breugel hypothesize an optimal range of wind speed and environmental surface complexity may exist to help insects locate an odor source.

via University of Nevada at Reno: Discovered near-surface wind direction is often highly variable over timescales of less than 10 minutes. They also found wind direction variability to be consistently higher in environments with greater surface complexity (urban areas) and lower at higher wind speeds.

Domestic cats' noses may function like highly efficient gas chromatographs

Jun 2023, phys.org

https://phys.org/news/2023-06-domestic-cats-noses-function-highly.html

Yet another example of how in olfaction nature is still ahead of technology:

Researchers created a 3D computer model of the cat nose and simulated how an inhalation of air containing common cat food odors would flow through the coiled structures. They found that the air separates into two flow streams, where one spreads slowly above the roof of the mouth on its way to the lungs, and a separate stream containing odorant moves rapidly through a central passage directly to the olfactory region toward the back of the nasal cavity.

In essence, the researchers suggest, the cat nose functions as a highly efficient and dual-purposed gas chromatograph.

via Ohio State University: Wu Z, Jiang J, Lischka FW, McGrane SJ, Porat-Mesenco Y, Zhao K. Domestic cat nose functions as a highly efficient coiled parallel gas chromatograph, PLoS Computational Biology (2023). DOI: 10.1371/journal.pcbi.1011

https://pubmed.ncbi.nlm.nih.gov/37384594/

Each nostril has a unique sense of smell, intracranial electroencephalogram study finds

Nov 2023, phys.org

https://medicalxpress.com/news/2023-11-nostril-unique-intracranial-electroencephalogram.html

10 subjects with intracranial depth electrodes were delivered an odor to the left, right, or both nostrils through an olfactometer device designed to deliver odors by computer control. Subjects had to identify the odor and indicate which nostril the odor came from. Subjects performed better in detecting and identifying odors in the bi-nostril condition compared to uni-nostril conditions.

Odor identity could be decoded from oscillations in the piriform cortex brain region via neural activity recorded from an intracranial electroencephalogram. The researchers observed that odor identity was encoded in two distinct, temporally segregated epochs in the bi-nostril condition, suggesting a separate smell interpretation occurs via each nostril, suggesting a possible computational advantage in processing odors in stereo. 

via University of Pennsylvania and the Barrow Neurological Institute of Phoenix: Gülce Nazlı Dikeçligil et al, Odor representations from the two nostrils are temporally segregated in human piriform cortex, Current Biology (2023). DOI: 10.1016/j.cub.2023.10.021

https://dx.doi.org/10.1016/j.cub.2023.10.021

Image credit: AI Art - Big Tunnel Full of Numbers - 2023

Insects for Olfactory Insight

Insects are such an important part of olfactory science because they smell with their antennae, which are outside their bodies, making it easier to study. Also, their brains are pretty simple, which makes it easier to study how the most complicated and least understood sense works.

Another reason insects are so important to olfactory science isn't really about olfaction, it's about malaria, and Zika, and West Nile, you name it. Mosquitoes are one of the main drivers of infectious disease around the world. And if we could only figure out how they use their sense of smell to find us, we could stop them from finding us and infecting us.

The first article shows you just how important this effort is --

Researchers build mosquito testing arena to discover how they find us over long distances

May 2023, phys.org

https://phys.org/news/2023-05-mosquito-arena-distances.html

"This is the largest system to assess olfactory preference for any mosquito in the world."

Using an ice-rink-sized (1,000 m3) outdoor testing arena in Choma District Zambia, researchers found that human body odor is critical for mosquito host-seeking behavior over long distances. They had six people sleep in single-person tents surrounding the arena over six consecutive nights, and they used repurposed air conditioner ducting to pipe air from each tent—containing the aromas of its sleeping occupant.

The testing arena contained a ring of evenly spaced landing pads that were heated to human skin temperature (35ºC). Each night, the researchers released 200 hungry mosquitoes into the testing arena and monitored their activity using infrared motion cameras.

• mosquitoes were not attracted to heated landing pads unless they were baited with CO2 
• human body odor was a more attractive bait than CO2 alone
• some people were more attractive to mosquitoes than others
• one volunteer with a strikingly different odor composition from the others consistently attracted very few mosquitoes
• people who were more attractive to mosquitoes consistently emitted more carboxylic acids probably produced by skin microbes
• the person who was least attractive to mosquitoes emitted less carboxylic acids but triple the amount of eucalyptol, which may be related to the person's diet
• the team identified 40 chemicals that were emitted by all of the humans, though at different rates.
• "It's probably a ratio-specific blend that they're following" 

via Johns Hopkins Bloomberg School of Public Health, Johns Hopkins Malaria Research Institute, and Macha Research Trust: Conor J. McMeniman, Human scent guides mosquito thermotaxis and host selection under naturalistic conditions, Current Biology (2023). DOI: 10.1016/j.cub.2023.04.050.

https://dx.doi.org/10.1016/j.cub.2023.04.050

Washing with different soaps could make you more or less attractive to mosquitoes

May 2023, phys.org

https://phys.org/news/2023-05-soaps-mosquitoes.html

"It's remarkable that the same individual that is extremely attractive to mosquitoes when they are unwashed can be turned even more attractive to mosquitoes with one soap, and then become repellent or repulsive to mosquitoes with another soap," says senior author and neuroethologist Clément Vinauger.

"What really matters to the mosquito is not the most abundant chemical, but rather the specific associations and combinations of chemicals, not only from the soap, but also from our personal body odors," says Vinauger.

via Virginia Tech: Clement Vinauger, Soap application alters mosquito-host interactions, iScience (2023). DOI: 10.1016/j.isci.2023.106667.

https://dx.doi.org/10.1016/j.isci.2023.106667

Perfume component helps lure male moth pests

Apr 2023, phys.org

https://phys.org/news/2023-04-perfume-component-lure-male-moth.html

Smells are so complicated: "Nonenal is a universal attractant that, by itself, doesn't have much of an effect, but when a certain percentage is added to the multi-chemical attractant mixture discovered nearly 40 years ago, it has a highly stimulatory effect."

(The researchers started examining ways to attract and then trap armyworm moths as part of a "mating disruption" strategy.)

via North Carolina State University: Ahmed M. Saveer et al, Nonanal, a new fall armyworm sex pheromone component, significantly increases the efficacy of pheromone lures, Pest Management Science (2023). DOI: 10.1002/ps.7460

https://dx.doi.org/10.1002/ps.7460

Good smells, bad smells: It's all in the insect brain

Aug 2023, phys.org

https://phys.org/news/2023-08-good-bad-insect-brain.html

I don't think I've ever heard the sense of smell referred to in this way: "While it is more of an aesthetic sense in humans, for insects, including locusts, the olfactory system is used to find food and mates and to sense predators."

It certainly is different, because in insects, their "palp" mouth triggers automatically to eat food just from the presence of some specific odors. I think we would usually see this difference in the context of the pheromone-receptor parts of our olfactory system, which don't actually work anymore in humans. Lots of animals, insects too, and beyond of course, have their behavior very strongly (could you call it irresistibly?) controlled by smells. 

Back to the study:

Interestingly, some of the locusts showed no response to any of the odors presented. They found that locusts only associated appealing scents with a food reward. Delaying the reward, they found that locusts could be trained to delay their behavioral response.

"All information received by our sensory apparatus, and their relevance to us, has to be represented by electrical activity in the brain. It appears that sorting information in between positive and negative happens as soon as the sensory signals enter the brain."

via McKelvey School of Engineering at Washington University in St. Louis: Rishabh Chandak et al, Neural manifolds for odor-driven innate and acquired appetitive preferences, Nature Communications (2023). DOI: 10.1038/s41467-023-40443-2

https://dx.doi.org/10.1038/s41467-023-40443-2

A non-invasive way to turn a cockroach into a cyborg

Sep 2023, phys.org

https://techxplore.com/news/2023-09-non-invasive-cockroach-cyborg.html

First, we made remote control roaches by smashing an electric circuit through their head. But now, it's as simple as slipping over their antennae a sleeve made of gold and plastic, and fixed in place by a blast of ultraviolet light, like plastic shrink-wrap.

Note to self -- insects don't get "injured," they get "damaged" -- "damaging cockroaches during attempts to control them results in a very short life expectancy, which then results in very little payoff for a lot of work".

via Nanyang Technological University in Singapore: Qifeng Lin et al, Resilient conductive membrane synthesized by in-situ polymerisation for wearable non-invasive electronics on moving appendages of cyborg insect, npj Flexible Electronics (2023). DOI: 10.1038/s41528-023-00274-z

https://dx.doi.org/10.1038/s41528-023-00274-z

Post Script: For a cockroach, and for all insects, their antenna is their nose, and so this is how we'll do it for humans too. (Except laser pulses through the retina are a likely candidate as well. Why not both?)

Image credit: AI Art - Old Man Standing next to Giant Hairy Ant Monster - 2023

Subjective Olfactory Perception

Two reasons why we aren't good at talking about smells -- 1. we don't share a common percept, and 2.  

we don't share a common language for smells. 

We're genetically coded to perceive smells differently from one another, with a round number at 30% difference across a population. As far as smelling goes, you could say that many of us are mutants. Or you could say there is no "normal" and therefore no mutant. It's just part of the process of evolution. Because of this difference in smell receptors caused by changes in the genes, there are holes in our perception of smells, holes from a societal level, and so the statistics makes it so that the quality of the data, each individual's perception of an odor combined to that of a group of people, is not so good. 

Next, we don't share a common language for smells. Some of this comes from the above problem, but some of it comes from that fact that lots of smells are "social smells" and so the way we talk about them is first and foremost determined by social context, not by some objective characteristic of the smell itself. An example, sort of related, is that we don't talk about the smell of shit in public, it's just not good manners. Or another person's body odor, or the smell of semen, which is almost never ever ever written, not even the word, in general popular literature (in English; maybe this isn't the case in other languages but I don't know).

These two studies below bring some interesting additions to this idea, that the part of our brain that perceives odors is mediated by a pleasure-reward part of our brain, and that language itself comes in two kinds, social and non-social:

Image credit: Ryan Muldoon at University of Buffalo miscommunicating by Douglas Levere - 2023

Study sheds light on the neural underpinning of subjective odor perceptions

Sep 2023, phys.org

https://medicalxpress.com/news/2023-09-neural-underpinning-subjective-odor-perceptions.html

Participants rated 160 odors on 18 perceptual descriptors while under fMRI analysis -- the  orbitofrontal cortex is where the most detailed and subjective percepts reside, and not as much with the amygdala and piriform cortex, regions typically associated with odor processing. 

via Northwestern University, Rhodes College, University of Pennsylvania and NIH National Institute on Drug Abuse: Vivek Sagar et al, High-precision mapping reveals the structure of odor coding in the human brain, Nature Neuroscience (2023). DOI: 10.1038/s41593-023-01414-4

https://dx.doi.org/10.1038/s41593-023-01414-4

Social vs. language role: Researchers question function of two brain areas

Sep 2023, phys.org

https://medicalxpress.com/news/2023-09-social-language-role-function-brain.html

Language just got way more complicated:

"A research team led by Prof. Lin Nan from the Institute of Psychology of the Chinese Academy of Sciences found that during sentence processing, the neural activity of two canonical language areas—the left ventral temporoparietal junction (vTPJ) and the lateral anterior temporal lobe (lATL)—is associated with social-semantic working memory rather than language processing per se."

These regions were sensitive to sentences only if the sentences conveyed social meaning. 

These findings are likely to force a major reconsideration of the functional organization of the cortical language network.

via Institute of Psychology of the Chinese Academy of Sciences: Zhang, G. et al, A social-semantic working-memory account for two canonical language areas, Nature Human Behaviour (2023). DOI: 10.1038/s41562-023-01704-8.

https://dx.doi.org/10.1038/s41562-023-01704-8

The Olfactory Singularity Has Arrived

AKA Alpha Nose

Submitted to biorxiv's preprint server in September/December 2022, and published in Science September 2023, it's the first model to out-smell regular humans. If you think your sentient sovereignty is threated by a computer than can draw a picture, then it's probably time for you to get some benzodiazepines. 

You give this thing a molecule and it will tell you what it msells like. More specifically, if you type into a computer the name of a chemical, it will give you words that describe the way that chemical smells, and it will be better at doing it than a human. 

Ray Kurzweil smirks. (Because it's not 2030 yet.)

The language of smell has been a tricky thing for a long time. It became pretty obvious just how tricky when we all woke up one day to realize that you can't google smells. And then, by extension, we realized that the Internet doesn't smell, and something must be wrong, because if it's not on the internet, then it doesn't exist. 

Attempts were made to correct this. The DREAM dataset, sometimes referred to as Keller 2017, sometimes as the Rockefeller study, was the first to use the power of machine learning to crunch chemoinformatics and natural language into a prediction machine for speaking in smells. But even they had some problems, and were not able to score better than humans. Only five years later, and it's done (with the help of the Google Brain, of course).

Today, the Internet can smell.

Image credit: Omid Mousakhani 3D Artist - Zbrush VDM Human Nose Brushes, Alpha, FBX, OB - 2023

Introductory Remarks:

• “In olfaction, no reliable instrumental method of measuring odor perception exists, and trained human sensory panels are the gold standard for odor characterization.” (17)
• “The model is as reliable as a human in describing odor quality: on a prospective validation set of 400 novel odorants, the model-generated odor profile more closely matched the trained panel mean than did the median panelist.”
• The model "performs roughly on par with the median human panelist, beating a chemoinformatic baseline."
• "The model is as reliable as a human in describing odor quality"

Methods:

• "To generate odor-relevant representations of molecules, we constructed a Message Passing Neural Network, a specific type of graph neural network, to map chemical structures to odor percepts. Each molecule is represented as a graph, with each atom described by its valence, degree, hydrogen count, hybridization, formal charge, and atomic number. Each bond is described by its degree, aromaticity, and whether it is in a ring. Unlike traditional fingerprinting techniques, which assign equal weight to all molecular fragments within a set bond radius, a GNN can optimize fragment weights for odor-specific applications."
• "To train the model, we curated a reference dataset of approximately 5000 molecules, each described by multiple odor labels (e.g. creamy, grassy), by combining the Goodscents and Leffingwell flavor and fragrance databases."
• Also, for novel odors, "We trained a cohort of subjects to describe their perception of odorants using the Rate-All-Tat-Apply method (RATA) and a 55-word odor lexicon."

Results:

• called a Principal Odor Map (POM)
• faithfully represents known perceptual hierarchies and distances
• extends to novel odorants
• is robust to discontinuities in structure-odor distances
• generalizes to other olfactory tasks.

Notes of Interest:

• The term "Odor Islands" is used when referring to certain globs of similar odors in odor space; just a cool term that was never able to exist before this model was created. 

• Another term, "ground-truth" used while describing the model's ability to match novel odorants, "establish the ground-truth odor character for novel odorants." It's funny because the term "baseline" is corrupt in that it can sometimes refer to the previous chemoinformatics baselines, which are now inferior.

• On Musk: "When we disaggregate performance by odor label, the model is within the distribution of human raters for al labels except musk" (which they later explain as it having 5 structural classes, as opposed to garlic or fishy which have clear structural determinants like sulfur or amines; but also the "well-documented phenomenon" of genetic variability of perception to musk.

• On Familiarity: "[W]e see strong panelist-panel agreement for labels describing common food smells and weak agreements for labels like musk and hay."

• On Flavor and Fragrance vs Everyday Smells: The model is better for things that have lots of training data like fruity sweet floral, less so for the less so ("ozone, sharp, fermented").

• On Sulfur: Disaggregated by chemical class, sulfur-containing molecules showing strongest performance.

• On Why the Language of Smell is Hard for Humans: People guess the odor wrong (aka correlation to panel mean is low) because 

1. genetic diversity for musk* (problems with the humans)

2. structural diversity like musk (problems with the chemoinformatics data)

3. unfamiliar like ozone (again problems with the humans**) 

*I thought genetic diversity was also strong for anything with a specific anosmia like putrescene or trimethylamine, then again, they didn't test "bad" smells or what I call everyday smells; the traditional Dravnieks dataset is ultimately a legacy of the flavor and fragrance industry, so it weighs heavier on good smells vs bad.

**Although unfamiliarity is a reason for this type of identification-difficulty, it should be extended beyond the individual human to our society, or maybe a bit of the fragrance industry with a bit of academia. The semantic dataset, which I will call the RATAset for "rate-all-that-apply," which is like the opposite of a multiple choice, and great for naming smells, still only uses 55 terms taken from Goodscents and Leffingwell. I would be willing to bet that more people actually know what ozone smells like, for example, they just don't have the right language at hand for naming it.  

• On Odorant Sample Contamination: The entire section on quality control is fascinating, and news to me. "Chemical materials are impure -- a fact too often unaccounted for in olfactory research. (24: M. Paoli, D. Münch, A. Haase, E. Skoulakis, L. Turin, C. G. Galizia, Minute Impurities Contribute Significantly to Olfactory Receptor Ligand Studies: Tales from Testing the Vibration Theory. eneuro. 4, ENEURO.0070–17.2017 (2017).)"

• Contamination, continued: Not only were there cases where the descriptions given by panelists seemingly inaccurate and later proven by GC/MS QC to be contaminated (so the panelists were right; their guess didn't match the molecule as named by the lab that sent the sample, but it did match the GCMS), but in some cases even the model got it "wrong," which implies that much of the training data is wrong, which means many of the samples of that particular chemical are likely to be contaminated. They only tested 50 of the 400 with this GCMS, but of the 50, they removed 26!

• Contaminated Vials vs Non-Contaminated Datasets: The datasets do have words like burnt, fishy, animal, musty, sour; but these are all words that can be used to describe good parts of flavors and fragrances ("slightly burnt" or "slightly fishy"). People don't use the word semen, ever; and you will almost never see that word written in regular discourse about olfaction or the language of smell, or even when talking about linden blossoms (go right ahead, try it for yourself); it's like we're literally not allowed to talk about it. Same with the word fecal or shit or etc. There is no "dirty sock," "cigarette butt," or "cat pee" in either the Goodscents or the Leffingwell datasets. Which leads us to this --

• They recommend characterizing the perceptual quality of contaminants.

• "[I]t is not safe to assume that the odor percept of a purchased chemical is due to the nominal compound." (And they add that non-flavor-and-fragrance chemical commodities are not incentivized to minimize contaminants.)

• Beyond the Perimeter of Ignorance: They created a potential odor space of 500,000 odorants "unknown to science or industry". And then then compute for us that it would take "70 person-years of continuous smelling time" to collect. (that's a lot of smelling time)

• Limitations: The model's main limitation is that it can predict the odors of only single molecules; in the real world of perfumes and stinky trash bags, smells are almost always olfactory medleys. “Mixture perception is the next frontier,” Mayhew says. The vast number of possible combinations makes predicting mixtures exponentially more difficult, but “the first step is understanding what each molecule smells like,” Meyer Rojas says. -Scientific American Dec 2023 Machine Learning Creates a Massive Map of Smelly Molecules https://www.scientificamerican.com/article/machine-learning-creates-a-massive-map-of-smelly-molecules/

Notes:

via Michigan State University Department of Food Science and Human Nutrition, University of Reading Department of Food and Nutritional Sciences, Google, and Monell Chemical Senses Center: A principal odor map unifies diverse tasks in olfactory perception. Brian Lee, Emily Mayhew, Joel Mainland. Science. 2023 Sep;381(6661):999-1006. doi: 10.1126/science.ade4401.

https://pubmed.ncbi.nlm.nih.gov/37651511/

Preprint fulltext:

https://www.biorxiv.org/content/10.1101/2022.09.01.504602v4.full

Formal citation:

Lee BK, Mayhew EJ, Sanchez-Lengeling B, Wei JN, Qian WW, Little KA, Andres M, Nguyen BB, Moloy T, Yasonik J, Parker JK, Gerkin RC, Mainland JD, Wiltschko AB. A principal odor map unifies diverse tasks in olfactory perception. Science. 2023 Sep;381(6661):999-1006. doi: 10.1126/science.ade4401. Epub 2023 Aug 31. PMID: 37651511.

Leffingwell Flavor-Base http://www.leffingwell.com/flavbase.htm

The Good Scents Company http://www.thegoodscentscompany.com