Frankenscience

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

https://cen.acs.org/biological-chemistry/biochemistry/Chemists-propose-unifying-theory-musk/100/web/2022/11

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

http://dx.doi.org/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, phys.org

https://phys.org/news/2023-03-molecular-images-olfaction-door.html

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

https://dx.doi.org/10.1038/s41586-023-05798-y

Image credit: AI Art - Iridescent Myxomycete - 2023

Full Cat Moon Revisited

It's that time of year again where the smell of feral cats marking their territory scents your local neighborhood. Only it's not actually the cats, it's the plants themselves. English boxwood to be specific. At the right time of year (which is now in New Jersey), these popular shrubs are announcing their presence via the sharp smell of a well-used litter box.

The offending molecule, called “cat ketone,” is also a main component in blackcurrant. Pour yourself a dram of blackcurrant desert wine, take a sip, and then smell the inside of the glass. And there you'll have it. Now take a walk around the block (anywhere from August to October), and pay attention. Once you tune in, you'll notice it every time you pass one of these bushes.

Sometimes we actually like bad smells. Rather, we learn to like them. Maybe it has something to do with our ability to control the biosphere so expertly. We have refined the practice of fermentation such that it has become an integral part of our diets. Bread, beer, cheese, kimchi, sauerkraut, chocolate; all these things are fermented. Fermentation is controlled rotting, and it's unnatural. (It's described way better in this book about fermentation that won the James Beard Award in 2013 for Reference and Scholarship.)

Uncontrolled rotting makes bad smells. Controlled rotting still makes bad smells, but less. And we learn how to ... re-evaluate those bad smells in light of their finer attributes. "Parmesan cheese" (isovaleric acid) comes up a lot in regards to this. If you put isovaleric acid in a hundred small bottles and give them to a hundred people, half will call it gross and the other half will love it. I call it quantum hedonics, but you can just call it an acquired taste.

image source - natgeo

Here’s  a picture of a boxwood shrub:

Taking this from an article by Smell-Linguist Asifa Majid:

The Chukchi and Yupik of the Beiring Straits eat fermented fish, reindeer blood, and walrus fat and have even been said to have a preference for partially decomposed food.* This is reflected in vocabulary too: for example, Chukchi veglyt’ul ‘old edible’ versus pegyt’ul ‘old, should not to be eaten’; ... .

*Yamin-Pasternak, S., Kliskey, A., Alessa, L., Pasternak, I., Schweitzer, P. (2014) The rotten renaissance in the Bering Strait: Loving, loathing, and washing the smell of foods with a (re)acquired taste. Current Anthropology 55: 619–646.

In the Soviet era, some indigenous people were no longer exposed to these foods and odors; thereafter when the Soviet Union collapsed, younger people who had to go back to the fermented foods (or starve) had difficulties ingesting these potent odors. This goes to illustrate the importance of early experienced environmental odors.*

*Beauchamp, G. K. (2014) Foul odors of rotted food: Lessons from olfactory physiology. Current Anthropology 55: 634–635.

That all being said, it's not a bad thing that your blackcurrant apertif smells like civet; it's enriching your experience, and that's a good thing, right? Or would you rather not know?

“cat ketone”

4-thio-4-methylpentan-2-one

And here's a similar molecule that you can get as part of the AROXA Beer Taint Kit:

“buchu mercaptan”

p-mentha-8-thiol-3-one

Catty, like blackcurrant juice or tom cat urine, tomato plant

Notice below how this substance is described on the Good Scents Company directory for blackcurrant. They are used by the flavor and fragrance industry, so they are less likely to use the words "cat piss." "Catty" will suffice!

black currant bud absolute

powerful

impactful

green

incense

spicy

woody

herbal

berry

fruity

blackcurrant

blackberry

jammy

currant bud

catty

narcissus

boxtree

sulfur

sulfered family

unusual fruity aroma

Notes

The Art of Fermentation: An in-Depth Exploration of Essential Concepts and Processes from Around the World

by Sandor Ellix Katz

Winner of the 2013 James Beard Foundation Book Award for Reference and Scholarship, and a New York Times bestseller, The Art of Fermentation is the most comprehensive guide to do-it-yourself home fermentation ever published. Sandor Katz presents the concepts and processes behind fermentation in ways that are simple enough to guide a reader through their first experience making sauerkraut...

-goodreads link

Post Script

Civet is a kind of animal musk taken from a kind of cat/mongoose. It’s used in perfumes because humans like the way it smells. Maybe it reminds us of the “quantum hedonic” natural body odors that we wash off every day. Civetone is the name given to the molecule that most represents the Civet smell.

Post Post Script

National Geographic attracting jaguars using Calvin Klein’s Obsession for Men 1986.

Why You Probably Don’t Know What Musk Really Smells Like

One of the big dogs of the perfume world is also a powerhouse of confusion. What the hell is musk? Do you know? Are you sure?

First, let’s disambiguate the basics. Musky and Musty are not the same thing. Musky is kind of like an animal smell – warm, sexy, intoxicating. Musty is related to moldy, it’s the smell of a dark hamper. Wet and dark, that’s musty. Thing is, body odor can be both musky AND musty, and this is one of the places where the two get intertwined. We can go on and on with this, because there’s this thing I call ‘river musk,’ which is absolutely intoxicating, to me at least, and is the by-product of stuff that lives in the river. Oceans have it too, but it tends to be mixed with dead fish. It’s a secondary metabolite, a kind of seaweed pheromone, which means it’s very similar to animal musk in that it’s a pheromone/chemosignal, but from plants. And yet, it’s related to wet things.

Parenthetically, body odor is actually not musty, for the most part. Usually it’s your dirty clothes that are musty, because they’ve been sitting in a pile on the floor, dark because they’re balled up, and damp because you just took them off, and your body is warm, and the air around you is less warm, so the water vapor in the air condenses on the clothes…either that or you were sweating just before you took them off. Either way, it’s your clothes that smell musty. That being said, we should also note that your armpits can get musty for the same reasons (it’s pretty dark in there). That isn’t what we call body odor, however.

Okay, so we got that out of the way. Sort of. Now for the anosmia part. Anosmia means you can’t smell something. Half the population is anosmic to something, and there are more people anosmic to musk than most other smells. Musk is a really big molecule, one of the biggest we can smell, and for some reason, bigger molecules tend to be invisible to us, but not in the way other anosmias work. It seems to go in-and-out.

Take the behemoth of the synthetic musks, Iso-E Super, which is so super that a perfume was made with only this as its only ingredient (and for non fragrance enthusiasts, that is totally unheard of). Lots of people can’t smell it. Saskia Wilson-Brown of the Institute for Art and Olfaction gave me a sample. I couldn’t smell it. Then I could. Then I couldn’t again. Anyway, because musk has this problem, or because we have this problem with musk, perfumers tend to use lots of musks in their formulas, to make sure that people will be able to smell at least one of the musks in there.

Next problem – the laundry detergent industry. Musks have this attribute where they do really well in fabrics and with detergents. They hold on for a long time (because they’re so big, as a molecule, among other reasons). They’re all over the world of laundry detergents; just about every laundry detergent smells like musk. But you probably don’t know that. You think that smell is the ‘smell of fresh laundry,’ not that of musk. When I tell people this, they don’t believe me, probably because they would rather not associate the smell of sweaty animal bodies with their freshly-laundered sheets. But alas, there it is: the smell of dirty is now the smell of clean.

What’s worse is that these sheets eventually end up in a dark hamper, and smell musty as well as musky. And so now you’re totally screwed. 

Why Do I Smell Cat Piss

AKA The Full Cat Piss Moon

I know this might sound crazy, but cat butts is a thing.

I wrote Hidden Scents because I have this thing where I smell what others can’t. This is not to say that my nose is any better than anyone else’s, only that I must pay attention more.

For example, I've been catching cat piss like crazy lately. Maybe you will too, now that I'm mentioning it.

The other day I'm at my friend’s house. “Come out back, check out my new weathervane.” I go outside, and BOOM, it hits me in the face. At first I thought they bombed their yard with mosquito repellent. Nah, that's definitely cat piss. You see, in a situation like this, I have learned not to say anything. Chances are they won't smell it, and I'll seem insulting. I wait a minute, just to make sure. After all, she is female, and I do smell “cat piss” on women sometimes (and once in awhile on men too) but I won't get into that...except to suggest that since civetone is such a big molecule, and lasts so long as a fragrance ingredient, that I might just be getting very old whiffs of that.

Anyway, finally I'm sure it's cat piss, so I go for it, “You have stray cats around here?”

“Yeah, why?“ “You don’t smell it?” No. They never do.

Yesterday it happened again. We are outside looking through the telescope – a crescent moon and Saturn – a beautiful night. And there it is. Listen – I actually don't mind the smell – it's fragrant! It's no coincidence that civet (which smells a lot like cat piss because it basically is cat piss) has been a primary ingredient in perfume for centuries.

Back to the backyard. The friends I’m with now are both male, so I don't hesitate, “You got stray cats up in here?”

“All over…You smell it don't you??” He knows; he's the guy who helped me name my book so he's familiar with my nose-thing. I sniffed-out the mold in his house a few years ago. “It’s mating season, I hear ‘em at night going crazy.”

Later that night, and out of nowhere, he says, “Yeah, it's like a perfume, I can smell it now.” Finally. I'm not alone.

I urge anyone who knows more about this than I do to leave a comment, and I'll continue a bit about civet.

And is it really cat mating season?

*Let's get this out of the way real quick: there is an ingredient in perfume called blackcurrant bud that smells like cat piss, and it does grow around here, and it fruits in midsummer. My friends, however, do not have any blackcurrant bushes on their property. Thanks Perfume Shrine for this.

POST SCRIPT

Civet is a kind of animal musk. In this case, it is a fragrant substance taken from a certain kind of wild cat by the same name, and usually specified as the African Civet. For centuries, these cats (it’s technically more like a mongoose) were hunted and trapped for their potent, musky pheromones, which are repeatedly scraped from their anal glands while in captivity. At smaller dilutions it becomes very pleasant – just like grapefruit oil, which at the right concentration can make you vomit uncontrollably. Civetone is the name given to the molecule that most represents the Civet smell, and it is very similar to Musk/Muscone, and has in it traces of Skatole (faeces). I’m not certain of this, but I think any synthetic alternative to getting Civetone is kept a secret. You can buy it, but you can’t make it yourself (without hella experimentin’ chemists).

POST POST SCRIPT

In order to attract jaguars, National Geographic-type people are known to use Calvin Klein’s Obsession for Men 1986.

Why Do I Smell Cat Piss

 AKA The Full Cat Piss Moon

I know this might sound crazy, but cat butts is a thing.

I wrote Hidden Scents because I have this thing where I smell what others can’t. This is not to say that my nose is any better than anyone else’s, only that I must pay attention more.

For example, I've been catching cat piss like crazy lately. Maybe you will too, now that I'm mentioning it.

The other day I'm at my friend’s house. “Come out back, check out my new weathervane.” I go outside, and BOOM, it hits me in the face. At first I thought they bombed their yard with mosquito repellent. Nah, that's definitely cat piss. You see, in a situation like this, I have learned not to say anything. Chances are they won't smell it, and I'll seem insulting. I wait a minute, just to make sure. After all, she is female, and I do smell “cat piss” on women sometimes (and once in awhile on men too) but I won't get into that...except to suggest that since civetone is such a big molecule, and lasts so long as a fragrance ingredient, that I might just be getting very old whiffs of that.

Anyway, finally I'm sure it's cat piss, so I go for it, “You have stray cats around here?”

“Yeah, why?“ “You don’t smell it?” No. They never do.

Yesterday it happened again. We are outside looking through the telescope – a crescent moon and Saturn – a beautiful night. And there it is. Listen – I actually don't mind the smell – it's fragrant! It's no coincidence that civet (which smells a lot like cat piss because it basically is cat piss) has been a primary ingredient in perfume for centuries.

Back to the backyard. The friends I’m with now are both male, so I don't hesitate, “You got stray cats up in here?”

“All over…You smell it don't you??” He knows; he's the guy who helped me name my book so he's familiar with my nose-thing. I sniffed-out the mold in his house a few years ago. “It’s mating season, I hear ‘em at night going crazy.”

Later that night, and out of nowhere, he says, “Yeah, it's like a perfume, I can smell it now.” Finally. I'm not alone.

I urge anyone who knows more about this than I do to leave a comment, and I'll continue a bit about civet.

And is it really cat mating season?

POST SCRIPT
Thanks to Perfume Shrine for this one, such an indispensable source for odor disambiguation:
Blackcurrant buds smell like cat piss, which means I now have to figure out the overlap between blackcurrant bushes and the cat mating cycle.

And next: Civet. It's a kind of animal musk. In this case, it is a fragrant substance taken from a certain kind of wild cat by the same name, and usually specified as the African Civet. For centuries, these cats (it’s technically more like a mongoose) were hunted and trapped for their potent, musky pheromones, which are repeatedly scraped from their anal glands while in captivity. At smaller dilutions it becomes very pleasant – just like grapefruit oil, which at the right concentration can make you vomit uncontrollably. Civetone is the name given to the molecule that most represents the Civet smell, and it is very similar to Musk/Muscone, and has in it traces of Skatole (faeces). I’m not certain of this, but I think any synthetic alternative to getting Civetone is kept a secret. You can buy it, but you can’t make it yourself (without hella experimentin’ chemists).

POST POST SCRIPT

In order to attract jaguars, National Geographic-type people are known to use Calvin Klein’s Obsession for Men 1986.