Thursday, December 21, 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,

"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,

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

Each nostril has a unique sense of smell, intracranial electroencephalogram study finds
Nov 2023,

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

Thursday, December 14, 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,

"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.

Washing with different soaps could make you more or less attractive to mosquitoes
May 2023,

"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.

Perfume component helps lure male moth pests
Apr 2023,

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

Good smells, bad smells: It's all in the insect brain
Aug 2023,

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

A non-invasive way to turn a cockroach into a cyborg
Sep 2023,

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

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?)

Thursday, December 7, 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:

Study sheds light on the neural underpinning of subjective odor perceptions
Sep 2023,

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

Social vs. language role: Researchers question function of two brain areas
Sep 2023,

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.

Thursday, November 30, 2023

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.

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"


  • "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."

  • 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


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.

Preprint fulltext:

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.

The Good Scents Company

Tuesday, November 28, 2023

Hope for Long Covid Parosmia Sufferers

Not one but two:

New Treatment Restores Sense of Smell in Patients with Long COVID
Nov 2023, Radiological Society of North America

Parosmia, a condition where the sense of smell no longer works correctly, is a known symptom of COVID-19. Recent research has found that up to 60% of COVID-19 patients have been affected. While most patients do recover their sense of smell over time, some patients with long COVID continue to have these symptoms for months, or even years, after infection.

The research team used a stellate ganglion block, which includes injecting anesthetic directly into the stellate ganglion on one side of the neck to stimulate the regional autonomic nervous system. The minimally invasive procedure takes less than 10 minutes, and no sedation or intravenous analgesia is necessary. CT guidance was used to position a spinal needle at the base of the neck for injection into the stellate ganglion. The researchers added a small dose of corticosteroid to the anesthetic in the pharmacologic preparation, suspecting that the COVID virus may be causing nerve inflammation. 

Follow-up was obtained for 37 patients (65%), with 22 (59%) of the 37 reporting improved symptoms at one week post-injection. No complications or adverse events were reported…

via the Radiological Society of North America and Jefferson Health in Philadelphia: New Treatment Restores Sense of Smell in Patients with Long COVID (press release). Nov 20 2023.

New clinical-trial data suggest that an antiviral pill called ensitrelvir shortens the duration of two unpleasant symptoms of COVID-19: loss of smell and taste
Nov 2023, Nature

From Japan - The medication is among the first to alleviate these effects and, unlike other COVID-19 treatments, is not reserved only for people at high risk of severe illness. The antiviral drug molnupiravir speeds recovery of these senses, but generally only the most vulnerable people can take it.

That is not true for ensitrelvir. In Japan, where it received emergency approval last year, the drug is available to  individuals with mild to moderate symptoms, regardless of their risk  factors. Its developer, Shionogi in Osaka, Japan, is continuing to conduct clinical trials of the drug, which has not yet been approved outside Japan.

In one such trial, people with mild or moderate COVID-19 symptoms were given either 125 or 250 milligrams of ensitrelvir or a placebo. At the start of  the study, 20% of participants reported some level of smell or taste loss. After the third day of treatment, the proportion of participants reporting such symptoms in the ensitrelvir groups started dropping more sharply than 
did the proportion in the placebo group.

“Most people will eventually recover on their own, but we know that some people have had 
long-term issues with smell and taste” 

via Shionogi in Osaka, and Fujita Health University: Nature. New pill helps COVID smell and taste loss fade quickly. Oct 17 2023. doi: 

Partially unrelated image credit: AI Art - The Human Condition is a Paradox - 2023

Further Reading:
Smell for Life: The Campaign to Tackle Smell and Taste Disorders
Apr 2023, Monell Center for Advancing Discovery in Taste and Smell

Thursday, September 7, 2023

Science Fiction Can Smell Too

Hella is a science fiction book by David Gerold from 2020. If you like science fiction, it's a good book by a good writer. (posting the bookshop link here in an attempt to support local bookstores?).

They take off their helmet on an alien planet for the first time. "Tell me what you smell." I sniffed. A little at first. Then a little more. "I'm not sure," I said. I inhaled again. "Something sweet. Is that grass? Something else too." I looked up at him. "Does blue have a smell?" "That's what air smells like when it doesn't come from a can." (p27)

The electronic supernose: The conical rebreather on the front of the helmet adds enough carbon dioxide to every breath so that the wearer doesn't accidentally go hyper-toxic from too much oxygen, but more important, it also sniffs the air for all kinds of particles -- it's an electronic supernose. Thehelmet integrates all this information and superimposes the augmented data onto the display. It even includes a visual presentation of all the various smells and odors and scents it can recognize. It shows us which way the scents are blowing and that helps us know from which direction any carnivores are most likely to approach. (p29-30)

About the Author - David Gerrold has been writing professionally for half a century. He created the tribbles for Star Trek and the Sleestaks for Land Of The Lost. His most famous novel is The Man Who Folded Himself. His semi-autobiographical tale of his son's adoption, The Martian Child won both the Hugo and the Nebula awards, and was the basis for the 2007 movie starring John Cusack and Amanda Peet.

Thursday, August 3, 2023

Odor Hunter Extraordinaire Cliff the Z Man Zlotnick

Cliff the Z Man Zlotnick on IAQ Radio

If you suspect a dead animal hiding in your walls (because you're house smells like a dead animal), here's what Cliff the Z Man Zlotnick does, as described back in 2007 on the IAQ Radio Show:

Put a handful of raw ground beef in a garbage bag in a wastebasket and leave it outside. Within minutes, flies will be attracted to the meat. That's when you close up the garbage bag, bring it inside, open it back up, and watch as the flies fly straight to the problem. The gases that emit from a dead animal pass through the wall itself, and the flies can smell that. 

Mandatory shout out to Avery Gilbert and his I Smell Dead People Column on his First Nerve blog (or his newer substack).

Friday, July 28, 2023

Smells Like a New Car

That new-car smell may be a sign of exposure to a host of hazardous chemicals
Apr 2023,

They tested chemicals released into the air by just one vehicle -- a brand-new, midsize, plug-in hybrid SUV in a local outdoor parking lot tested every day for 12 consecutive days using gas chromatography-mass spectroscopy.

  • Air temps ranged from 21°C to 63°C (75F - 145F)
  • 20 common volatile organic compounds tested
  • Emissions dependent on material surface temperature rather than air temp
  • Formaldehyde exceeded Chinese government safety standards at some points by up to 35%*
  • Acetaldehyde exceeded standards by 61%*
  • Benzene levels described as being unsafe for drivers breathing it for long drives
  • They suggest new car buyers ride with the windows open

via mechanical and civil engineers and occupational health scientists with several entities in China and School of Mechanical Engineering and College of Architecture and Civil Engineering at Beijing Institute of Technology, Beijing Vehicle Emissions Management Affairs Center, Beijing Products Quality Supervision and Inspection Institute, Department of Occupational and Environmental Health Sciences at the School of Public Health of Peking University, and Department of Environmental Health at Harvard T.H. Chan School of Public Health: Haimei Wang et al, Observation, prediction, and risk assessment of volatile organic compounds in a vehicle cabin environment, Cell Reports Physical Science (2023). DOI: 10.1016/j.xcrp.2023.101375

*GB/T 27630 - Guideline for Air Quality Assessment of Passenger Cars - Standardization Administration of China, Beijing - 2011

Further Reading on the Smell of the New and a sommelier describing a bunch of new cars’ smells for Car and Driver magazine back in 2003:
Baked Goods, Network Address, 2018

And for those who venture the New Jersey Turnpike:
What Exit? The Smells of the New JErsey Turnpike, Network Address, 2016

Thursday, July 13, 2023

Plume Tracking and Odor Mapping Algorithms

A deep reinforcement learning model that allows AI agents to track odor plumes
Feb 2023,

Insects track odor plumes to find mates. (And there was a similar study done recently here.)

"Instead of running a traditional laboratory wind-tunnel experiment, we used a complementary 'in-silico' approach using artificial neural networks," Singh explained. "This helped us develop an integrative understanding of plume tracking across multiple levels, including emergent behavior, neural representation and neural dynamics."

To train their plume-tracking agents using DRL, the researchers first simulated an odor emanating from a source located within a windy arena with a total area of approximately 120 m2. When their agents identified where the source of the odor was located, they received a reward. In contrast, if they lost track of the odor plume and left the arena, they were "punished."

"The behavior that emerges in our trained artificial agents bears a striking resemblance to the behavior modules biologists have previously observed in flying insects performing plume tracking," Singh said.

via University of Washington and University of Nevada: Satpreet H. Singh et al, Emergent behaviour and neural dynamics in artificial agents tracking odour plumes, Nature Machine Intelligence (2023). DOI: 10.1038/s42256-022-00599-w

Thursday, July 6, 2023

E Noses Never

Read this to learn how basically e-noses are relegated to science fiction for the next 20 years at least:

How to make electronic noses smell better
Apr 2023,

via Xi'an China Northwestern Polytechnical University: Taoping Liu et al, Review on Algorithm Design in Electronic Noses: Challenges, Status, and Trends, Intelligent Computing (2023). DOI: 10.34133/icomputing.0012

'Electronic nose' built with sustainably sourced microbial nanowires could revolutionize health monitoring
Feb 2023,

Grown by bacteria. Great, but each nanowire needs to be programmed for each molecule, so a typical top-down approach.

via University of Massachusetts Amherst: Yassir Lekbach et al, Microbial nanowires with genetically modified peptide ligands to sustainably fabricate electronic sensing devices, Biosensors and Bioelectronics (2023). DOI: 10.1016/j.bios.2023.115147

A robot able to 'smell' using a biological sensor
Jan 2023,

10,000 times higher than the usual electric-based sensors, these are now biological sensors (not sure the difference). And then they program a "library of smells", so keep in mind that, like all other smell sensors out there, these don't just smell anything that happens to be in the environment -- they can only smell things that have been pre-selected and trained-on. 

via Tel Aviv University's Sagol School of Neuroscience and School of Zoology: Shvil Neta et al, The Locust antenna as an odor discriminator, Biosensors and Bioelectronics (2022). DOI: 10.1016/j.bios.2022.114919

New devices for conveying olfactory stimuli in virtual reality
May 2023,

Aerosols and atomizers add bulk to VR gear and entail bottle filling and cleaning. This new approach uses paraffin imbued with scents, released by a temperature-sensing resistor that controls a heating element - the more heat the more scent. But wait -- magnetic induction coils pull heat away from the face to cool the wax quickly when the scent is no longer needed. 

The removal of scent is actually the harder problem to solve than the introduction of scent in these kinds of systems.

via City University of Hong Kong, Beihang University and Shandong University: Yuhang Li, Soft, miniaturized, wireless olfactory interface for virtual reality, Nature Communications (2023). DOI: 10.1038/s41467-023-37678-4

Tuesday, June 27, 2023

Inhibition Is So Hot Right Now

First, whoever says scientists don't have a sense of humor don't have a sense of humor.

Image credit: This imaginary perfume bottle illustrates the role pheromones play in Drosophila courtship decisions by featuring the silhouettes of a male chasing a courted female. Naming this fictional eau de pheromone “Dew Lover” was inspired by the etymological origin of the genus Drosophila, which is based on the modern scientific Latin adaptation of the Greek words drósos (“dew”) and phílos (“loving”). Vernier et al.  show that the coupling of the perception and production of some mating pheromones is regulated by the action of a pleiotropic pheromone receptor. Credit: Digital art by Yehuda Ben-Shahar, Washington University in St. Louis

Now for the main point -- up until recently, much of our understanding of olfactory perception came from looking at receptor activity. You expose a receptor to an odor and see if it lights up, and with that you make a kind of odor map coordinating odorant molecules and receptor proteins. 

Things are different now, because instead of just looking at how receptors are stimulated by odors, we also look at how they are inhibited, because it turns out there is just as much to be learned from receptor inhibition as there is activation. And, the interplay of activate-inhibit sure sounds a lot like the ons and offs of computer processing, meaning that the nose-brain may be a lot more useful as a model for a primitive computer than we thought.

Examining the chemicals involved in insect mating
Jan 2023,

Researchers reported that a single protein called Gr8a is expressed in different organs in male and female flies and appears to play an inhibitory role in mating decision-making. The findings point to one of the ways that flies could put up behavioral barriers to protect against mating with the wrong kind of partner.

"A single pleiotropic protein can function as both a receptor for pheromones in sensory neurons, as well as contribute to their production in the pheromone-producing cells (oenocytes) of males, by way of a less-understood process."

The scientists still have not pinpointed exactly how the chemoreceptor affects the way the signal is produced, but they do know that it causes quantitative and qualitative differences in pheromones. And even small changes in pheromones could be enough to keep closely related flies from finding each other attractive—and change their mate choice behaviors.

"Based on what we have observed, mutations in a single gene could provide a molecular path for a pheromonal communication system to evolve while still maintaining the functional coupling between a pheromone and its receptor," Ben-Shahar said. "Our research uncovers a potential avenue for pheromonal systems to rapidly evolve when new species arise."

Or when a species decides to rapidly evolve itself; looking at you mass population control.

via Washington University St Louis: Cassondra L. Vernier et al, A pleiotropic chemoreceptor facilitates the production and perception of mating pheromones, iScience (2022). DOI: 10.1016/j.isci.2022.105882

Post Script - Pheromones Again
Pachyderm perfume: How African elephants use odor to communicate
Apr 2023,

We tested the DNA, glands, urine and manure of 113 African elephants in wildlife parks in Malawi to identify family groupings," and "We found a number of chemicals were common to group members, but others that were unique to each individual, and found that smell was used to distinguish characteristics including age, health, reproductive status and family relationships between elephants.

"We observed elephants greeting each other by squealing and flapping their ears," he said.

"We believe they're pushing their pheromones towards the other elephant as a sign of recognition.

"When elephants charge each other flapping their ears, rather than making themselves look bigger, we believe they're blowing their pheromones as a warning not to mess with them."

"Some of the animals in the study were bred in captivity, and one of the tricks they'd been taught was to take a tourist's hat and smell it," he said.

"When the tourist came back hours later the elephant would be able to immediately identify who the hat belonged to."

via University of Queensland: Katharina E. M. von Dürckheim et al, A pachyderm perfume: odour encodes identity and group membership in African elephants, Scientific Reports (2022). DOI: 10.1038/s41598-022-20920-2

Tuesday, June 20, 2023


This discovery provides a great example of how machine learning and optogenetics are blowing open our doors of perception.

In this case, scientists created an artificial olfactory receptor (this one derived from OR5A2). You can think of it like the ultimate musk receptor, because after matching it against 100 mammal-nose-brain gene sequences, it's the best-fit for all the animals at once.

But it doesn't really exist in any one animal; it's simply the most in-between of all of them. They call it a "consensus protein". I call it a frankenstein receptor. 

That was machine learning to the rescue, but then they called their friend optogenetics -- they further engineer this artificial protein to produce light when activated. This is a common technique these days that allows us to measure the receptor activity; it's like being able to ask an animal to tell you whether it smells something or not. Then they go back and find all the odorants that match this new frankenstein receptor -- if it lights up, it's a match.

They found no new musks actually, which suggests we know all of them already, but this could work for other odors:

Chemists propose unifying theory of musk - Engineered olfactory receptor may explain why structurally diverse molecules smell similar.
Chemical and Engineering News, Nov 2022

The three receptors known to recognize musk compounds only respond to a subset of musk-scented compounds.

The researchers compared the amino acid sequences for a given odorant receptor across 112 mammal species to determine the most common amino acid at each position and made a receptor with this so-called consensus sequence.

The engineered protein differs from human OR5A2 at 25 of its 324 amino acids ... .

Using the structures of compounds that do and do not activate the receptor, the researchers developed a machine learning model and used it to screen a database of odorant structures and human perceptions. The model, Mainland says, claims to identify known musk molecules much better than prior models trained only using the database. Although they do not report any new musky compounds in the study, the authors say that the Kao Corporation has filed patents related to the work.

via Duke University and Kao Corporation, Tokyo: Proc. Natl. Acad. Sci. U.S.A. 2019, DOI: 10.1073/pnas.1804106115

And this is a pretty big deal in smell science:
First molecular images of olfaction open door to creating novel smells
Mar 2023,

First molecular-level, 3D picture of how an odor molecule activates a human odorant receptor.

Odorant receptors are notoriously challenging, some say impossible, to make in the lab for such purposes. The Manglik and Matsunami teams looked for one that was abundant in both the body and the nose, thinking it might be easier to make artificially, and one that also could detect water-soluble odorants. They settled on a receptor called OR51E2, which is known to respond to propionate—a molecule that contributes to the pungent smell of Swiss cheese.

This molecular snapshot showed that propionate sticks tightly to OR51E2 thanks to a very specific fit between odorant and receptor. The finding jibes with one of the duties of the olfactory system as a sentinel for danger.

"This receptor is laser focused on trying to sense propionate and may have evolved to help detect when food has gone bad," said Manglik. Receptors for pleasing smells like menthol or caraway might instead interact more loosely with odorants, he speculated.

"We've dreamed of tackling this problem for years," he said. "We now have our first toehold, the first glimpse of how the molecules of smell bind to our odorant receptors. For us, this is just the beginning."

via University of California, San Francisco: Aashish Manglik, Structural basis of odorant recognition by a human odorant receptor, Nature (2023). DOI: 10.1038/s41586-023-05798-y

Tuesday, June 13, 2023

The Olfactory Determinants of Culture

First direct evidence that babies react to taste and smell in the womb
Oct 2022,

4D ultrasound -- Fetuses exposed to carrot showed more "laughter-face" responses while those exposed to kale showed more "cry-face" responses.

via Durham University: Flavour Sensing in Utero and Emerging Discriminative Behaviours in the Human Fetus, Psychological Science (2022). DOI: 10.1177/09567976221105460

Ancient humans had same sense of smell, but different sensitivities
Jan 2023,

"We had the odorant receptor genomes from Neanderthal and Denisovan individuals and we could compare them with today's humans and determine if they resulted in a different protein."

So then they tested the responses of 30 lab-grown olfactory receptors from each hominin against a battery of smells to measure how sensitive each kind of receptor was to a particular fragrance.

The laboratory tests showed the modern and ancient human receptors were essentially detecting the same odors, but their sensitivities differed.

Denisovans -- less sensitive to floral, better at sulfur, balsamic, and honey

Neanderthals -- less responsive to green, floral and spicy scents

via Duke University: Claire A. de March et al, Genetic and functional odorant receptor variation in the Homo lineage, iScience (2022). DOI: 10.1016/j.isci.2022.105908

Reminder that "mummy fever" was a thing back in the 1800's and it was a big deal to break out the mummy meat for your esteemed guests, because nothing identifies the top tier of society like eating small fragrant bits of ancient humans:
Teasing out the secret recipes for mummification in ancient Egypt
Feb 2023, Ars Technica

The results: “We could identify a large diversity of substances which were used by the embalmers,” co-author Maxime Rageot of the University of Tübingen told New Scientist. Those substances included oils or tars from juniper, cypress, or cedar; various resins, including some from Pistacia trees; and animal fats, beeswax, and plant oils. Most of those have been found before in mummies, but two resins—dammar and elemi—have not been previously identified anywhere in Egypt before. They also found bitumen from the Dead Sea. -via New Scientist

Tuesday, June 6, 2023

Stressed, Depressed, and Social Unrest

If you thought we had reached a new horizon of mass social behavior modification via electronic drugs  (ie social media and the consumer surveillance apparatus), then just wait until the smells show up. Smells have a direct line to the limbic system, which is called so because it controls your limbs; it literally makes you move, and it also controls your mood. 

Incorporating scents into a VR environment suitable for spacefarers
Jan 2023,

Building scents into a VR nature environment: A user could walk near a river in the VR environment and not only hear the sound of rushing water but also smell wet grass. This is accomplished by using hitboxes, which are invisible shapes in the VR environment that activate when the avatar collides with them.

When conducting their study, Abbott and Diaz Artiles measured users' anxiety levels before and after experiencing a stress-inducing event. The results showed that adding olfactory stimuli not only decreased users' anxiety levels after experiencing heightened stress but also reduced their stress and anxiety levels from their baseline.

via Texas A&M University College of Engineering: Renee (Woodruff) Abbott et al, The impact of digital scents on behavioral health in a restorative virtual reality environment, Acta Astronautica (2022). DOI: 10.1016/j.actaastro.2022.05.025

Dogs can smell when we're stressed, study suggests
Oct 2022,
93.75% accuracy detecting changes in breath and sweat, before and after a fast-paced arithmetic task, along with self-reported stress levels, heart rate and blood pressure.

via Animal Behaviour Centre at Queen’s University Belfast, and Newcastle University: Dogs can discriminate between human baseline and psychological stress condition odours, PLoS ONE (2022). DOI: 10.1371/journal.pone.0274143

Chances are we can smell stress too, we're just not tuned-in to it. If you want proof, you can look at post-handshake-hand-sniffing behavior and think about how we're subconsciously measuring the stress levels of the people we shake hands with as a way to assess how we should react to them.  

And now for some thoughts about depression, anosmia and long covid:
Potential found to counter depression by restoring key brain rhythm
May 2023,

Effective communication between brain regions requires groups of neurons to synchronize their activity patterns in repetitive periods (oscillations) of joint silence followed by joint activity.

One such rhythm, called "gamma," repeats about 30 times or more in a second, and is an important timing pattern for the encoding of complex information, potentially including emotions.

Although its causes remain poorly understood, depression is reflected in gamma oscillation changes, according to past studies, as an electrophysiological marker of the disease in brain regions that manage the sense of smell, which have also been tied to emotions. 

"Our experiments revealed a mechanistic link between deficient gamma activity and behavioral decline in mice and rat models of depression, with the signal changes in the olfactory and connected limbic systems similar to those seen in depressed patients,"

Feeding an amplified olfactory bulb signal back into the brains of depressed rats restored normal gamma function in the limbic system, and reduced the depressive behaviors by 40 percent (almost to normal).

via NYU Grossman School of Medicine and University of Szeged in Hungary: Antal Berényi, Reinstating olfactory bulb derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents, Neuron (2023). DOI: 10.1016/j.neuron.2023.04.013.

Partially unrelated post script:
In case you're ever wondering how do they actually measure depression in mice, they get dunked in a bucket of water to see how long it takes for them to stop swimming -- the sooner they give up, the more depressed they are. 

Tuesday, May 30, 2023

Olfactory Camouflage aka Artificial Animal Smells

Endangered birds can be protected from predators with chemical camouflage
Oct 2022, phys.or

"Predator control"

In the first treatment sites, the researchers spread waterfowl odor in wetland areas. With the chemical camouflage, a new method successfully tested in Australia and New Zealand, the researchers studied whether great amounts of prey odor in the area prevents predators from finding the artificial bird nests.

In other areas, the researchers used eggs containing an aversive agent causing nausea with the goal of conditioning the predators to believe that the bird eggs were inedible. The researchers also used control sites which they visited as frequently as the treatment sites for controlling a potential disturbance effect.

The study showed that especially the chemical camouflage decreased the predation of the artificial waterfowl nests by red foxes, but a similar effect was not observed with raccoon dogs, a harmful invasive species to Finland.

"Red foxes might rely more on their sense of smell to find bird nests, while the raccoon dog might find the nests by happenstance when they move in the area," says Senior Researcher Vesa Selonen from the University of Turku, Finland.

via University of Turku: V. Selonen et al, Protecting prey by deceiving predators: A field experiment testing chemical camouflage and conditioned food aversion, Biological Conservation (2022). DOI: 10.1016/j.biocon.2022.109749

Thursday, April 6, 2023

Non-Invasive Behavior Modification

Can someone say "mind-control deodorant"?

Once we learn to activate olfactory receptors through the eyes with lasers, you'll be "tuned" before you enter large gathering spaces to be more socially compatible with the other occupants.
Researchers identify neurons that 'learn' to smell a threat
Jan 2023,

Researchers found that "inhibitory" neurons (nerve cells that act by silencing their synaptic partners) in an area of the brain responsible for interpreting social smells become highly active and change their function when males repeatedly meet and increase their territorial aggression. By disrupting the neurons associated with neuroplasticity—learning—in the accessory olfactory bulb, researchers revealed that territorial aggression decreased, linking changes to cellular function in the pheromone-sensing circuity of the brain to changes in behavioral responses to social threats.

"It abolished the ramping aggression that is typically exhibited," said Zuk. "It indicates that this early sensory inhibitory neuron population plays a critical role in regulating the behavioral response to social smells."

via University of Rochester Medical Center: Kelsey E. Zuk et al, Arc-Expressing Accessory Olfactory Bulb Interneurons Support Chemosensory Social Behavioral Plasticity, The Journal of Neuroscience (2023). DOI: 10.1523/JNEUROSCI.0847-22.2022

Totally unrelated image credit: I'm endlessly fascinated with psychoanalyzing the artificial mind, in this case, one which cannot understand what fingers are: AI Art - A Person Who Conceals Their Face with their Hands AKA Damn Fingers - 2023

Scientists show that odors from other people's sweat can help treat social anxiety
Mar 2023,

Social anxiety was reduced when patients underwent mindfulness therapy while exposed to human 'chemo-signals', or what we commonly refer to as body odor, obtained from underarm sweat from volunteers.

Combining these chemo-signals with mindfulness therapy seem to produce better results in treating social anxiety than can be achieved by mindfulness therapy alone".

via the Karolinska Institute and The European Congress of Psychiatry taking place 25-28 March 2023, in Paris.

*This work is part of the EU-funded Horizon2020 project POTION ("Promoting Social Interaction through Emotional Body Odors") 4. 

Promoting social interaction through emotional body odours
The way chemistry influences human communication is one of the most intriguing and debated topics. More specifically, the nature of chemosignals and their sphere of influence on social interaction is a very important key to understanding human behaviour. POTION proposes a novel technological paradigm to delve deeper into understanding meaningful social interaction, combining new knowledge about the chemical composition of human social chemosignals together with a novel olfactory-based technology designed to drive social behaviour. A first challenging analysis on human chemosignals to delineate the chemical underpinnings of the emotions of happiness and fear will be carried out since they are the representative emotions that drive approach and avoidance behaviour, i.e. the fundamental building blocks of social interaction between individuals of the same species. Results of this analysis will be used to artificially synthetize the chemosignals of these two emotions, which will provide the basis of an innovative computer-controlled odour delivery system able to drive the approach-avoidance social strategy. This breakthrough device will be controlled in a closed loop by the social-emotional state of the subjects evaluated through a novel computational neural model. The POTION system will be applied and tested in both social and clinical scenarios. In the social scenarios, we venture to reveal how olfaction clues work in managing the feelings of trust, presence and inclusion, in both virtual, real, and social media contexts. In the clinical scenario, POTION will propose a new human chemosignal-based diagnosis and treatment for social anxiety, phobias and depression, which are known to all share impaired social functioning. POTION will provide further insight to the fundamental underpinnings of human behaviour with the goal to help establish healthy social relationships through trust, leading to an overall improvement in wellbeing.

Ancient Computers

Cerebral cortexes are cool and all, but the "dumber" parts of the brain have a lot of good secrets in there too.

Lost fish find their way, thanks to their 'ancient brain'
Dec 2022,

They put tiny translucent zebrafish, barely half a centimeter in length, in a virtual reality environment that simulates water currents.

The researchers expected to see activation in the forebrain -- where the hippocampus, which contains a "cognitive map" of an animal's environment, is located. To their surprise, they saw activation in several regions of the medulla, where information about the animal's location was being transmitted from a newly identified circuit via a hindbrain structure called the inferior olive to the motor circuits in the cerebellum that enable the fish to move. When these pathways were blocked, the fish was unable to navigate back to its original location.

These findings suggest that areas of the brainstem remember a zebrafish's original location and generate an error signal based on its current and past locations. This information is relayed to the cerebellum, allowing the fish to swim back to its starting point. This research reveals a new function for the inferior olive and the cerebellum, which were known to be involved in actions like reaching and locomotion, but not this type of navigation.

via Howard Hughes Medical Institute: Misha B. Ahrens, A brainstem integrator for self-location memory and positional homeostasis in zebrafish, Cell (2022). DOI: 10.1016/j.cell.2022.11.022

Image credit: Homotopical Topology by Fomenko and Fuchs

Friday, February 10, 2023


Sounds like a big deal. Also sounds like a great explanation for the phantom "Iso E Super" anosmia that isn't a full anosmia.

Researchers reveal an added layer of nuance in our sense of smell
Jan 2023,

They've discovered something called a depolarization lock to add to the standard combinatorial coding model used for odor detection, and it turns off the receptors when presented with high concentrations of an odor. 

You might already be familiar with this phenomenon for odors like violet and hydrogen sulfide (H2S). In the case of H2S, this receptor-deactivating behavior can be life-threatening, which is why you're supposed to wear a supplemental gas monitor, in addition to your nose, when entering areas suspected to contain high concentrations of the gas. 

^This write-up does a good job of explaining the fruit fly experiment that led to this discovery, as well as possible reasons why this would be needed for olfaction. 

via UC Santa Barbara: David Tadres et al, Depolarization block in olfactory sensory neurons expands the dimensionality of odor encoding, Science Advances (2022). DOI: 10.1126/sciadv.ade7209

Post Script:
In addition to Iso E Super, Hedione is another perplexing odorant that's in almost every fragrance formulation from floor cleaners to face cream, and yet most people can't actually smell it. Well, you can smell when it's NOT there, but you can't smell when it is. (Old post mentioning Hedione)

And if I'm reading this correctly, it sounds like someone with a hypersensitive nose might be more likely to lose their sensitivity altogether. I seem to have some kind of hyperosmia myself, and yet when I go out to sample perfume, I often can't smell anything at all. Take the same perfume, put it on a strip of paper and leave it on a table in my house for the next 3 weeks, and I will smell the whole bouquet revealed one at a time as the mixture breaks down. The theory being that if you're hypersensitive to a specific odorant, or all odorants for that matter, your "depolarization lock" will kick in at low concentrations. 

Post Post Script:
Hella synonyms for the musky odorant referred to above, in fact so many that I just wanted to list them here: Iso E Super, Tetramethyl acetyloctahydronaphthalenes is a synthetic ketone fragrance also known as octahydrotetramethyl acetophenone (OTNE) and by other commercial trade names such as: Iso E Super, Iso Gamma Super, Anthamber, Amber Fleur, Boisvelone, Iso Ambois, Amberlan, Iso Velvetone, Orbitone, Amberonne. It is a synthetic woody odorant and is used as a fragrance ingredient in perfumes, laundry products and cosmetics.
-Hall, John B. & Sanders, James Milton, "Perfume composition and perfume articles containing one isomer of an octahydrotetramethyl acetonaphthone", issued 1975