The Olfactory Determinants of Culture

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

Oct 2022, phys.org

https://medicalxpress.com/news/2022-09-evidence-babies-react-womb.html

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

https://dx.doi.org/10.1177/09567976221105460

Ancient humans had same sense of smell, but different sensitivities

Jan 2023, phys.org

https://phys.org/news/2023-01-ancient-humans-sensitivities.html

"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

https://dx.doi.org/10.1016/j.isci.2022.105908

Image credit: AI Art - Photograph of a Neanderthal Nikon 85mm DSLR - 2023.jpeg

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

https://arstechnica.com/science/2023/02/teasing-out-the-secret-recipes-for-mummification-in-ancient-egypt/

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

What Have We Become

It appears that we could be evolving to better tolerate each other's body odor by having our noses become less sensitive to that smell over time. And the guy in the picture above has been "evolved" to withstand a car crash.

Humans and other primates have evolved less sensitive noses

Feb 2022, phys.org

https://phys.org/news/2022-02-humans-primates-evolved-sensitive-noses.html

*Update Oct 20 2022: Didn't realize this study was prompted by Unilever trying to break into the Asian market; they thought maybe there's a problem with the genetics; turns out that's not it; but the Asian population does have less odor-producing glands in their armpits, which, presumably, is what leads to less sales in fragrance products like deodorant; or cultural expectations makes some people less likely to want to stand out. -Abigail Tucker for the Smithsonian, Oct 2022 

The purpose of this study was to see if the genetics for smell remain constant across people from different backgrounds other than the Caucasians typically studied. 

The results showed that yes, they do, but also something unexpected.

"People with the ancestral versions of the scent receptors tend to rate the corresponding odor as more intense." And in opposition, the "newer" versions of those receptors lead to people having less intense odor detection capacity. And this suggests that we are evolving to be less sensitive to odors. 

In order to test their hypothesis, they used odors that were already known to be variable in the ways people perceive them. For example, some smells are very intense to some people but barely perceptible to others. Some of this is because of genetic variations in the way the receptor works. 

An interesting aside in the discussion -- "OR51B2 variation drives differences in the perception of human body odor component 3-methyl-2-hexenoic acid (3M2H) ... which could be a target for future studies interested in malodor blocking, or discovering the mechanisms underlying social communication from body odor."

Back to the big part of this study, which is the unexpected part (always the favorite part of any scientific endeavor). They measured the "age" of these genes, and found that the "newer" genes were less sensitive to intensity, and refer to this as "Degeneration of olfactory receptor gene repertoires in primates."

Image credit: Graham is designed to survive a car crash, Victoria’s Transport Accident Commission, 2016. Designed by Melbourne sculptor Patricia Piccinini, Royal Melbourne hospital trauma surgeon Christian Kenfield, and crash investigator at Monash University’s accident research centre David Logan.

https://www.theguardian.com/world/2016/jul/21/road-safety-confronting-sculpture-shows-human-vulnerability-to-crashes

Bonus:

Large genetic databases can be used to understand OR function, a proxy for general protein function.

In the discovery study, we may have the benefit of measuring olfactory phenotypes in a large, homogenous cohort (Fig 1) where genome-wide genotyping had already been conducted, giving us the statistical power of a large population without the time or expense. In this study, the novel signals do not have much population differences in MAF or effect size (Table 1 and Figs 3 and 4), suggesting that the large sample size rather than its genetic similarity might be the more important reason behind the findings. Given the increasing number of open databases of sequencing data, this method is becoming a more reasonable possibility for easily testing genotype/phenotype associations.

Olfaction is an excellent use of this new resource because of the ease of understanding the functional output of genetic variation in the protein. 

The human olfactory system has both robust assays to test the behavioral output of these proteins (psychophysics/rating odors) [5,6,10] and an established method for directly testing protein function in cells (heterologous cell-based assay) [42,43]. Genetic variation provides a strong tool for exploring olfactory coding and sheds light on how complex systems integrate information from variable sensors.

via Chinese Academy of Sciences Key Laboratory of Computational Biology at Shanghai Institute of Nutrition and Health, Monell Chemical Senses Center, Department of Neuroscience at University of Pennsylvania, and Sanghani Center for Artificial Intelligence and Data Analytics at Virginia Tech:  Li B, Kamarck ML, Peng Q, Lim F-L, Keller A, Smeets MAM, et al. (2022) From musk to body odor: Decoding olfaction through genetic variation. PLoS Genet 18(1): e1009564. doi.org/10.1371/journal.pgen.1009564

https://doi.org/10.1371/journal.pgen.1009564

Some interesting facts about the variation of olfactory perception among populations, most of which was already known, but now confirmed for a more diverse population that includes Han Chinese:

• Galaxide, a Musk molecule: Individuals can have specific anosmias to one or some, but not all musks, suggesting that there is not a single common coding mechanism.
• Trans-3-methyl-2-hexenoic acid (3M2H), a Body Odor molecule: Almost 25% of the population has a specific anosmia to 3M2H [23–26], but this anosmia has not been connected to any olfactory receptor.
• Aldehydes: Self-reported Asian populations rate aldehydes as more intense than Caucasian populations, but no specific genetic variants or receptors have been implicated. 

These are the receptors studied and their effects:

• OR4D6 M263T and S151T ^ Galaxolide intensity
• OR51B2 L134F ^ 3M2H intensity
• OR5A1 D183N ^ β-ionone pleasantness (for the validation cohort and the meta-analysis, but not the discovery cohort)
• OR7D4 R88W and T133M ^ Androstenone intensity and pleasantness (in the discovery cohort, for the validation cohort, only pleasantness)
• OR2J3 T113A ^ Cis-3-hexen-1-ol intensity
• OR1A1 =/= Caproic acid (although rs17762735 was associated with intensity in the validation study, the effect was in the opposite direction from the literature; there were no associations for 
• pleasantness)
• Aldehyde - There were no associations with aldehyde intensity or pleasantness 

On Body Odor:

3-methyl-2-hexenoic acid (3M2H) is also referred to as caproic acid, and as having a "hircine" odor, both of which refer to goats, because it smells like goats. Which means you smell like goats when you're hot and nervous and not wearing deodorant (although less likely if you're of Asian descent for whom one gene changes the production of body odor). Body odor in general is often characterized by thiolalcohols, which have sulfur molecules in them, although this one in particular doesn't have any sulfur in it. 

Related Post:

Social Deodorization

http://www.limbicsignal.com/2022/02/social-deodorization.html

Scientists Make Discovery

Olfactory neurons adapt to the surrounding environment

May 2022, phys.org

https://medicalxpress.com/news/2022-05-olfactory-neurons-environment.html

This title could have had way more clickbait. The news is that we have no idea what's going on with olfactory neurons. 

Not like it's ever been claimed; they just never seem to obey any sensical laws, and they're always doing things we can't understand, but now it seems that even basic assumptions about how they work are way off.

The scientists discovered an unsuspected variability in gene expression profiles depending on the expressed olfactory receptor and previous exposure to odors. 

And in a previous study, these scientists found that after stimulation of a receptor by an odorant molecule for less than an hour, the expression of the gene coding for this receptor decreased in the neuron, indicating a very rapid adaptation mechanism.

"While it was thought that the binding of an odorant molecule would only lead to the activation of the corresponding receptor, we discover that olfactory neurons drastically change their identity by modulating the expression of hundreds of genes after activation. And this new identity is again dependent on the expressed receptor. We are facing an unexpected, massive, rapid and reversible adaptation mechanism," explains Ivan Rodriguez, co-corresponding author of the study.

This work reveals that olfactory neurons are not to be considered as sensors simply passing from a resting state to a stimulated state, but that their identity is in permanent evolution, not only according to the expressed receptor but also according to past experiences. This discovery adds another level to the complexity and flexibility of the olfactory system. 

via Faculty of Science and the Faculty of Medicine of the University of Geneva: Luis Flores Horgue et al, Transcriptional adaptation of olfactory sensory neurons to GPCR identity and activity, Nature Communications (2022). DOI: 10.1038/s41467-022-30511-4

https://dx.doi.org/10.1038/s41467-022-30511-4

Image credit: Unexpected Outcome, by shironosov and Getty, 2022 - Three shocked scientists looking at the obtained substance expressing intense emotions [link]

Post Script:

Consider that the olfactory family of genes is evolving within us in real time. It's a huge group of genes, being the largest family there is, at 2% of the genome, and it's highly variable in the population, with a 30% variation from person to person. 

Do you remember that item we learned back when the Human Genome project came out, that we share over 90% of our genome with monkeys, and almost as much with bananas? Now consider that our individual olfactory apparatus is 30% different from that of other humans. There's a lot of action here in the olfactory system.

Just wait until we figure out that it's running our immune system, because that's when things will get really crazy. 

Categorgonzola

A perennial topic on this weblog is the categorization of smells. Today I'm looking at a study from 2011 that looks at common features that group smells together. One of the common denominators is hedonics, or pleasantness vs non-pleasantness.

It always makes me pause to think about this, because it seems that people can never really agree on what makes a smell good or bad, and yet the hedonic dimension is the only one that keeps coming back as the primary distinction between odors. I guess that's just the law of large numbers at work, a law which is against natural human cognition.

If you include enough people in your study, the differences between us cancel out and you're left with a fuzzy but recognizable picture of a smell map, which is seen above.

The other common denominator (it’s not a denominator if there’s two, right?) is a dimension the researchers call natural/chemical.

This map is organized as follows: Whereas the pleasantness of an odor can be predicted on the number of carbon atoms per molecule (related to how fast it evaporates), the natural/chemical dimension is predicted by the polarity of the molecules, or how attracted they are to water.

Why? Not so sure. Mention is made to the difference in the olfactory receptors themselves - some are from when we were fish and some are from when we became land animals, so the two may have a different relationship with water (polarity).

For example, odorants are dispersed more slowly in the water. Also, smellable molecules to fish don’t have to be volatile organic compounds, because for a fish, the air itself is already a liquid. So fish detect water soluble molecules whereas humans detect airborne molecules.

Actually, now that I look at the ‘natural’ part of the map, I realize that none of those things exist underwater, right? Burnt? Nope. Moldy? Although mold is always associated with moisture, it doesn’t grow underwater. And Earthy? Kind of the opposite of water.

Natural - Burnt, Smoky, Nutty, Woody, Resinous, Musty, Earthy, Moldy, Almond, Popcorn, Peanut Butter, Oily, Fatty, Warm, Dry, Powdery

Chemical - Etherish, Anaesthetic, Chemical, Medicinal, Disinfectant, Carbolic, Sharp, Pungent, Acid, Gasoline, Solvent, Cook, Cooling, Cleaning Fluid, Paint, Camphor

Good - Fragrant, Sweet, Perfumery, Floral, Light, Aromatic, Cool, Cooling, Fruity, Citrus, Rose

Bad - Sharp, Pungent, Acid, Heavy, Musty, Earthy, Moldy, Burnt, Smoky, Oily, Fatty, Sour, Vinegar

-image source: link

Notes:

In search of the structure of human olfactory space. A. A. Koulakov, B. E. Kolterman, A. G. Enikolopov, D. Rinberg. Front. Syst. Neurosci. 5, 65 (2011).

doi: 10.3389/fnsys.2011.00065

Roses Are Made

This year, if you get a picture of a rose instead of an actual rose, keep the following in mind: Roses that make a good picture don't smell like much, so you're not missing anything!

Roses are popular, and they have been cultivated over centuries to have all kinds of different features. Some are chosen to smell good, and some to look good. That usually means the roses that look good do not smell good. (Some varieties are simply more durable; when you're shipping those flowers all over the world, durability is a desired trait.)

And wouldn't you know it; people tend to like the kind that look good more than the latter. This means most of our roses these days have lost their multisensory seduction.

This is great example of natural selection at its most sophisticated –in the domain of the anthroposphere. It is true that humans are selecting the flowers they want to propagate, and that doesn't sound like nature at the wheel.

But these humans impose their artificial selection pressures only in response to market forces, or customer demand, or fashion, or whatever you want to call it. And as any fashion designer will tell you, there is not much reasoning behind the preferences of populations. Individuals perhaps, but populations not so much.

In a game of complexity theory, every individual makes decisions that are a result of every other individual. The resulting decisions then determine the kinds of flowers selected. Channeling Dawkins' Memetics, the scentless rose is an extended phenotype of our collective selection process. Is that natural or artificial?

Notes:

New genetic details may help roses come up smelling like, well, roses

Susan Milius for Science News, 2018

O. Raymond et al. The Rosa genome provides new insights into the domestication of modern roses. Nature Genetics. Published online April 30, 2018. doi:10.1038/s41588-018-0110-3.

Scientists Figure Out Why Roses Don't Smell as Good as They Used To

Mental Floss, 2018

The Extended Phenotype

Richard Dawkins, 1982

Post Script:

Favorite "Rose" perfume:

Mon Nom est Rouge by Majda Bekkali (for women and men)

The Evolving Artificial Organism

A taste of things to come, researchers are finally firing-up an artificial organism to record how it evolves from primitive unicellular origins to hyper-plexed associative memory network.

The artificial organism unfolds in a virtual world at over ten-thousand generations per hour (kind of hard to do in real life). We can then see how higher beings develop the ability to create associations, and eventually use this knowledge to build more intelligent robots.

Good thing olfaction is the prototypical primordial sensory system, because that’s why this new research is being posted right here. But think about this for a moment – there is no artificial nose. We already have the seeing retina, the hearing cochlea, and even a hand that feels. The nose however, has not been reverse-engineered.

There is a true challenge in replicating the sense of smell, and that is because our sense of smell is programmed by our autobiography. Smells don't mean much to us outside of our subjective experience with them. You just can't upload a dictionary of smells into an electronic nose and expect it to recognize random odors in its environment.

The only way you could do that is if you had a robot that grew up, just like a little kid, with multimodal experiences, social integration, and existential episodes, all associated together and built together into the tangled ball of nerve fibers that we call Self.

Your robot would then have its own limbic system, programmed by a childhood of interaction with the world. It would have to develop a life of its own, an autobiography. This self-identity would then be the substrate upon which the odor network is built. It could then recognize odors, as they would stimulate physiological and emotional responses and associative episodic memories.

Because smell is so tied to our limbic system, it requires a body in order to work. A cerebral organoid isn't a body per se. And neither is an artificially intelligent neural network. And neither is a robot that “comes to life” as a fully-formed adult, all booted-up and ready to go. Humans don’t do it like that. You can’t have a self without a history. (See Patient HM for more on that, however.)

What this new research now reminds us, is that not only does an artificial intelligentity need a body in order to smell, it also needs a lifetime of learning as well.

Notes:

Evolution of learning is key to better artificial intelligence

Sep 2019, phys.org

Anselmo Pontes et al. The Evolutionary Origin of Associative Learning, The American Naturalist (2019). DOI: 10.1086/706252

Post Script:

Finally seeing someone recognize the utility of studying olfaction in the context of machine learning artificial intelligence:

"Srinivasan says he will focus on how noise or variability in odor coding determines the balance between discrimination and learning, explaining that the variability the duo is finding in their work might be a mechanism for distinguishing odors, which could be applied to making better machine learning or AI systems."

How mammals' brains evolved to distinguish odors is nothing to sniff at

July 2019, phys.org