Sniffing Out the Science of Smelling

Last winter, Andreas Keller decided the time was right to branch out from his day job as a neuroscientist and launch a new art gallery. Not just any gallery, but the country’s first and only commercial space devoted entirely to smell-based art. He rented a defunct barbershop in New York City’s Chinatown and teamed up with an artist named M Dougherty for his inaugural show in February of 2021, drilling a hole in the exterior wall to pipe a piney perfume called “Forest Bath” to the street outside. The fresh evergreen mingled with steamed dumplings and ripe dumpsters and the smoldering papers that Keller’s Chinese neighbors sometimes burned as an offering to their ancestors.

“The gallery had always been a fantasy, but the pandemic brought it into focus,” says Keller, sitting in his AstroTurf-carpeted back office (which he soon plans to sprinkle with a molecule that smells like fresh-cut grass). Not only did lockdown allow contemplative hours away from his work, but one of early Covid-19’s telltale symptoms gave him the hunch that there might, at long last, be a market for his dream.

Olfaction has always been our underdog sense. It’s both primitive and complex, which makes it hard to study and harder still to transfer to our increasingly digital existence. Our scientific understanding of how smell works lags so far behind our grasp of hearing and (especially) vision, and smells cannot at this point be recorded or emailed or Instagrammed. In one 2011 survey, more than half of young adults admitted that they would rather forfeit their ability to smell than their smartphones.

But just when it seemed that the nose could not recover from its nose dive, along came the coronavirus. Afflicted people robbed of their sense of smell realized that they couldn’t register the smoke of fires actively burning down their houses, or the scent of their spouses (torpedoing marriages, by some accounts), or even the savor of a candy bar—since many of what we think of as tastes, like the flavor of chocolate, are actually smells. That stank. “You don’t know what you have until it’s gone,” Keller says.

Even for those who avoided loss of smell, living in a world muffled by masks, or reduced to deodorized Zoom calls, heightened the collective desire to breathe deep and experience the scented realm anew. This likely explains the current perfume and home fragrance boom—and perhaps why so many curious passersby step inside Olfactory Art Keller, as the gallery is called.

“When you are asked to smell art,” Keller says, “you realize how impoverished your perception of the world is when you limit yourself to the visual.”

For several weeks, the gallery’s windows were tin-foiled over to allow for full immersion in the aroma of “old banana” versus “young banana” (one artist’s wink at a classic Velvet Underground album cover). Or the visitor may get a whiff of a perfumer’s interpretation of what a beaver might smell like to a dog (marzipan, maybe?) or the orchid bee’s homemade cologne, or George Washington’s false teeth. During my visit, I’m instructed to massage a rainforest landscape that turns out to be a sort of giant scratch-and-sniff sticker, unleashing a sudden rush of microencapsulated citrus, like jungle breath.

“Some people get very confused,” Keller says. Normally game gallery-hoppers may back out onto the street. “Then there’s always somebody who can’t smell anything and thinks it’s a prank.” A few bananaphobes came out of the woodwork during the banana stunt, the fruity smell triggering some deep and unexplained revulsion. (“I am actually friends with one of these people,” Keller notes. “She moves to a different table if someone is eating a banana and she refused to come to that show.”) Those visitors willing and able to stay and ponder a scent by the name of “Sinner” often bicker about what they are smelling—is that hospital disinfectant? Church incense? No: tandoori chicken!

These diverse personal responses are exactly what Keller has devoted much of his academic life to studying: why various individuals seem to perceive the same odors differently, or interpret the same odors in different ways, or not notice some of them at all. Such questions are at the heart of the larger problem of how smells are coded by the brain. How, for example, do a bunch of snorted-up proteins and carbohydrates result in our tangy awareness of just-baked sourdough, that pandemic crowd-pleaser?

Perhaps scientists will soon catch wind of the answers, as the pandemic has also brought a flood of new funding to this sometimes overlooked, or perhaps undersniffed, field. The future could be a heady place, characterized not only by redolent art galleries like Keller’s, but also by the potential resurrection of technologies like Smell-O-Vision and the (more recently) fizzled oPhone, by scent-based strategies to diagnose Parkinson’s disease and treat post-traumatic stress disorder, by the launch of perfumed dating apps and fragrant Instagram food pictures and virtual shopping services that can sniff out the ripest avocado from afar.

Most urgently, tens of millions of otherwise recovered Covid-19 patients are still suffering from lasting olfactory problems. Many of these people are understandably discontented with the conventional wisdom that once a sense of smell disappears for six months it’s probably gone for good, and are now demanding new and better clinical approaches. “The amount of research has just gone up exponentially,” says Richard Doty, director of the University of Pennsylvania’s Smell and Taste Center. “It’s a pretty big deal in terms of interest. But this is a complicated sensory system. Understanding it is pretty difficult. I don’t think overnight we are going to have all the answers.”

Progress in this field may depend on unusual creativity and collaborations, between perfumers and linguists, artists and engineers and even perhaps anthropologists and foraging communities that have never before encountered a whiff of vanilla or Camembert cheese. Keller recently completed a PhD in philosophy, which he says complements his genetics PhD. “Perception is a philosophical as well as a scientific problem,” he says. The truth about smell seems to ambush and retreat, materialize and dissipate, like lilacs on a ticklish June breeze, or the ghost of yesterday’s stir-fry.

Why don’t we know what the nose knows? The fundamentals of color vision were more or less established in the 19th century, when scientists discerned that all the varied hues from red to violet are produced by just three types of receptors in human retinas. Taste depends on a whole order of magnitude more receptor types on our tongues, but still a reasonable amount.

But the nose—or rather, the clump of sensory neurons high inside your nostrils—boasts about 400 receptor types. In 2004, Richard Axel and Linda Buck were awarded the Nobel Prize in Physiology or Medicine for discovering the genes that encode these receptors, which sit on the surfaces of specialized neurons, allowing them to shoot information down leggy axons much deeper into the brain, to one of the two olfactory bulbs where smells are processed. But we still can’t fathom which odors many of the individual receptors recognize, let alone how they work in concert.

If vision is the default sense for Homo sapiens, why do we need so many more olfactory receptors? (“It seems like too many, doesn’t it?” one smell researcher acknowledged.) Light is electromagnetic radiation, and the same three color vision receptors can combine to process a range of wavelengths, covering the entire rainbow of visible light. But smells are not wavelengths coasting along a smooth spectrum. They involve a complex mix of chemical particles, bobbing around in the air. Our bodies have built receptors that can recognize a number of oddball molecules volatile enough to waft up into our schnozzes, which means we need lots of options.

For instance, the dreaded banana smell is a conglomerate of something like 20 or so molecules, each destined for overlapping sets of receptors, activating some and perhaps inhibiting others, and striking all chords in the concerto that we somehow register as banana. In a 2014 paper for Science, Keller and colleagues at Rockefeller University estimated that humans can distinguish (give or take) at least a trillion distinct smells lurking here on planet Earth. Complicating matters further, our legions of odorant receptors have lots of variants, some of them less sensitive or fully nonfunctional in large chunks of the population.

To begin his smell studies, Keller created mutant fruit flies by turning their olfactory receptors on and off, before realizing that his fellow New Yorkers were a sort of naturally occurring population of mutants, and much more diverse since they hailed from all corners of the world. Recruiting subjects via Craigs­list and other methods, he administered a battery of smell tests to hundreds of people and collected spit samples for genetic sequencing. The idea was to link specific anosmias—as singular smell deficits are known—to corresponding receptors involved in their processing, to figure out which of the 400-ish receptors did what, and why people perceived or preferred certain smells. “Once you find people with a nonfunctioning variant,” Keller explains, “you can study what that gene does for humans.”

The upshot is that you can expect about 30 percent of your receptor arsenal to function differently than your neighbor’s, which explains why conversations starting with “Do you smell that?” so frequently devolve into farce. A substance like androsterone—a musk found in human sweat, truffles and elsewhere—can smell like sandalwood or urine or nothing at all, depending on the nature of the smeller. For a long time researchers believed that “asparagus pee” wasn’t universal, because only certain people reported a malodorous bouquet after consuming the spiky veggie. In fact, only some unlucky noses can detect it, but for those who can, the odor is universal—a fact those subjects realized “only when they smelled each others’ urine,” Keller says. Even professional perfumers sometimes need a helping nose when it’s time to dose the cinnamon, for instance.

In addition to all these wonky odorant receptors, a bunch of which work in some people but not others, there are some 600 additional smell “pseudogenes” that, at least as far as scientists can tell, don’t code for working receptors in anybody alive today. Some researchers take this chunk of dormant DNA as evidence of the nose’s terminal decline. Perhaps our sense of smell started eroding when we changed the way we select our mates, prioritizing other factors above scent. Such atrophy is not unheard of: Bottlenose dolphins and other toothed whales apparently relinquished olfaction long ago, possibly to free up head space for echolocation.

But other explanations circulate, too. With so many smells in play, a single-receptor deficit is rarely a death sentence, relaxing selection pressure on these genes. (Although try telling that to the 20 percent of the population that is oblivious to the bitter-almond scent of cyanide.)

There is marked variability in the other senses, to be sure. Some gifted people can discern subtler differences in color than the rest of us, while about 5 percent of the population is partially colorblind. But it’s striking that pretty much everybody is noseblind to something or another, and usually to multiple things, be it freesia or wet basement or cilantro. Often, our commonplace specific anosmias are starker than the gaps in our other senses. While a colorblind person might insist that grass is red instead of green, a noseblind person essentially perceives no grass at all. (Here’s where that philosophy degree might come in handy.)

Or to return to the technical, someone with a less-sensitive version of odorant receptor OR2J3, related to the ability to smell low concentrations of cis-3-Hexen-1-ol, the grassy-smelling molecule, might be oblivious when Keller finally gets around to perfuming his AstroTurf.

To learn more about my own sense of smell, I swung by Philadelphia’s Monell Chemical Senses Center, home base of Joel Mainland, a star in this field and Keller’s frequent collaborator, at least before the downtown art scene tempted him away. While Mainland has not yet opened his own avant-garde gallery, in his lab I detected a by-now familiar blurring of art and science. He described one graduate school experiment that sounded more like experimental theater, in which he was blindfolded and headphoned and instructed to follow a scent through the grass of a public park. It was part of a test to see if humans could track, canine-style, by scent alone. They could, but not nearly as well as dogs. (When the scenario was repeated with a duck corpse, two actual dogs in the park intervened, charging past the slower-moving human smellers to prove their superiority.)

At present the tools of Mainland’s trade include sleep apnea masks and a fake plastic proboscis that looks as if it’s been ripped off a Groucho Marx mask, although really it’s repurposed from a commercial contraption called the Nasal Ranger, designed to help humans track offensive and potentially dangerous odors. Mainland modifies these gizmos to deliver odors in reliable quantities to human subjects, a tricky task indeed. Vision scientists can grab a standard color monitor off the shelf at Best Buy to display the colors and images they want, which can then be easily shared with subjects and colleagues worldwide. “But there is just not a great way for you and me to communicate about smells without being in the same room,” Mainland said—and even then, it’s touch and go.

Odors cannot so far be stored electronically, and of course they constantly drift off and degrade in a most demoralizing manner. Capturing and keeping them is an art form in and of itself. To evoke a “smoky” essence, lab members use an infuser to warm cotton balls, then store the cotton balls in a tightly sealed container to use as a training tool for experiment volunteers. A jar marked “Animal” holds harvested horse sweat. While Mainland is not tasked with catching lightning in a bottle, he does somehow need to entrap “Ozone,” that fresh, elusive post-electrical storm smell. I pointedly did not ask about the contents of the jar marked “Fecal,” though I know it could be worse: Other labs stock a man-made compound called “U.S. Government Standard Bathroom Malodor,” based on real-life military latrines and colloquially known as “Stench Soup.”

Mainland decanted some liquid samples for me. He did so with very careful hands, as he—like many in his field—has nightmarish tales about accidents that befoul laboratory air for days. (Mainland once fumbled a vial of vile grapefruit mercaptan, which smells like sulfur crossed with fruit snacks. For Keller, it was popcorn-like diacetyl.)

Right off the bat I picked up on a smoked sausage vibe: guaiacol, which some people find to be overpowering and repulsive, but just made me kind of hungry.

Then we moved onto the musks. One smelled powdery and sweet, a little like Necco Wafers, but mostly I drew blanks, performing about as well as a bottlenose dolphin.

“Try this guy,” Mainland said, uncorking another.

“I have no idea,” I stammered after a few deep, desperate breaths of what seems like nothing. “Plant water?” I guess. “Dog breath?”

He gave me a sharp look. “It’s conceivable that you can’t smell musks.”

Then again, it was possible that some of these samples had decayed past the point of potency. Short of sampling my genome, we may never know, as Mainland has previously established that he himself cannot detect some of these substances. It could be a classic case of the noseblind leading the noseblind.

Just a few weeks before my visit, Mainland’s lab, with Keller and other co-authors, published a paper on the genetics of musk sensitivity. The work was partially funded by the beauty and personal care company Unilever. The global fragrance industry has been intoxicated by the notion that the genetics of smell could help them to entice heretofore reluctant consumers. “A lot of companies came to us,” Mainland recalls, “and said, ‘We have a lot of trouble making fragrances for the Asian market. Can you tell us which fragrances are going to be most liked by them by looking at their olfactory receptors?’”

To that end, the researchers asked 1,000 Han Chinese to rate a handful of common odors. They compared the results with those from hundreds of ethnically diverse New Yorkers previously smell-tested and genotyped by Keller. Scientists recorded varied reactions to two substances. One is a molecule naturally present deep in the human armpit, a powerful and unpleasant component of body odor (which deodorant companies are eager to mask). The other was Galaxolide, a woody-smelling artificial musk that is a popular additive to soaps and kitty litter (although how it smells to cats themselves is anyone’s guess).

The divergent reactions to the two chemicals correlated with genetic differences among individuals for two odorant receptors, suggesting for the first time what role they play in the body.

Mainland showed me how the researchers were able to double-check these findings at his lab, in cell culture. First, they cloned the genes for the two suspect receptors and their more and less sensitive variants. They inserted those DNA snippets into host cells, which were then tricked into manufacturing a given receptor type on their surfaces.

Next Mainland’s team pipetted the liquid musk and sweat odor onto the freshly sprouted receptors, warming the pungent marinade of smells and cells in an incubator. After about four hours, the receptor types that recognized the odors produced light, courtesy of a reporting system inside the cells that uses bioluminescence from fireflies. The more active the receptor was when given its matching odor, the more the cell glowed—a handy little hint about the whole wondrous structure stuck up our noses.

But while the study revealed these genetic and sensory differences between people, the variations did not shake down along ethnic lines. Rather, all of the key receptor types were sprinkled throughout New York and China alike. This is probably because our odorant receptor variants are quite ancient, with the mutations predating the relatively recent divisions between Asian and European and African populations. But that insight isn’t terribly useful for commercial giants pining for genetically calibrated musk combos that will sell out in Shanghai.

“I think they had hoped that this would be a magic bullet for them,” Mainland said. “And it is not.”

Many variables beyond receptor type influence how and whether and what people smell and like to smell. Biological sex is one—females are more sensitive to smells and better attuned to stenches like body odors. Mental health is in the mix, with some conditions, like autism, linked to an enhanced sense of smell, and others, like Parkinson’s disease and depression, related to reduced sensitivity.

Perhaps the most mysterious driver of our differences is culture, and questions go well beyond why people in some swaths of the world turn their noses up at perfume. Why do Swedish people crave fermented herring? Why do Singaporeans covet durian, a mango-like fruit that reeks?

Alas, human culture cannot be probed in cell culture, so Mainland and other researchers recently borrowed another artist’s tool: a felt-tipped marker, to be precise, except that instead of colors it contains odors.

“Super cool,” Mainland said, uncapping one of these so-called Sniffin’ Sticks in his office. “You put the odor in here and it wicks up. It maintains its scent for a long period of time. They are easy to ship because there is no actual liquid to spill out,” he adds, and there’s little chance of them raising a stink in the airport’s TSA line.

Mainland and his colleagues dispatched Sniffin’ Stick sets to researchers working with ten diverse populations, including the Seri, a small indigenous fishing community in northwest Mexico’s coastal desert; the Chachi, a plantain-farming people in tropical Ecuador; and Malaysia’s Semelai rice growers and rubber tappers. Some have little contact with the world of the WEIRD, as scientists call Western, Educated, Industrialized, Rich and Democratic nations.

What olfactory overtures have our finest scientists made to these populations? One of the Sniffin’ Sticks delivers a pleasing little blast of vanilla. Another, though, smacks of something ripe and rank: call it feet cheese, although isovaleric acid is the technical term. It’s a funk horribly familiar to anyone who’s ever delved the depths of an adolescent’s laundry basket, or tangled with certain Limburgers. After a long whiff, the malodorous molecule seemed to be stuck in my skull, no matter how intensely I willed my olfactory receptors to unbind.

Tasked with inhaling the isovaleric acid and other ambassador odors, the subjects were asked to place the Sniffin’ Sticks in a row, ranked from like to dislike. (One group, consisting of 55 hard-nosed New Yorkers, used a numerical ranking system to do the same.)

The results, published this spring in Current Biology, were nose-opening. As usual, some eccentrics liked the smelly feet cheese best, or the garlicky dimethyl disulfide. But a broader consensus also emerged: On average, people around the world enjoyed the sweet vanilla and shunned the rancid scent.

This jibed with an earlier finding by Asifa Majid, an Oxford University linguist and an author of the Sniffin’ Sticks study. In 2018 she’d exposed Dutch and Malaysian subjects to a variety of odors, from fruity and flowery to downright foul. While the groups described the smells quite differently, analysis of their facial expressions showed that their initial emotional responses to the odors were similar across the board.

Such findings are a breath of fresh air for the field, suggesting that—at least when it comes to what we like to smell, as opposed to what we are able to smell—there is a core hierarchy, and the headstrong human nose is beholden to some kind of universal principles, which scientists can presumably decipher if they put their noses to the grindstone.

Some of the divergence of our noses may be rooted in the tongue—that is, the tongue we grow up speaking. The Jahai of the Malay Peninsula, who spend their days navigating the light-starved rainforest, are extremely good at noticing and describing smells, but are their senses actually sharper than ours, or do they just spend more time thinking and talk about scents? Majid spent weeks with them foraging for wild ginger, and toddling across broad river stones as butterflies that looked as big as dragons swooped overhead. She learned that the Jahai language contains features linguists once thought did not exist: specific words with meanings like “to have a stinging smell” or “to smell of human urine.” The Jahai smell lexicon is understandably rich in tiger vocab, including a verb for “to have a bloody smell which attracts tigers.”

If English speakers stink at identifying smells, perhaps we’re tongue-tied, not noseblind, and just need a little practice. Or maybe our sense of smell has physically decayed due to our changing relationship with the natural world. Because smell neurons must mingle directly with molecules, they basically hang out of the front of our heads, growing through the bony plate that protects the brain. They are “the periphery, the sensing surface,” says Venkatesh Murthy, a professor of molecular and cellular biology at Harvard University. Exposure to the elements means that these neurons are especially prone to damage from environmental toxins—perhaps explaining why residents of the Cook Islands in the South Pacific, one of the world’s least polluted places, tend to ace smell tests.

But scientists have checked, and English seems to have been a relatively smell-averse language even before the Industrial Revolution. So the key transition may have happened much earlier, when people abandoned hunting and gathering, a lifestyle in which odors are a powerful orienteering tool. In tribes that have just recently switched to farming, smell words often vanish, and it’s an open question how that might affect perception a few centuries down the line. How would a rose smell if we had no name for sweet?

Olfaction is also shaped by changes more recent than the Neolithic Revolution. Aged reindeer blood apparently gives fermented herring some competition for the Most Repulsive Smell in the World, but the native people of the Bering Strait once found it mouthwatering. When the Soviet Union took over its remote territory, some of these people lost access to traditional dishes, and within a few generations younger people were unable to stomach the smell. Researchers think that the pre-Soviet indigenous people had been habituated via mothers’ milk, an established influence on regional smell preferences, which explains why it shifted quickly once the food disappeared from nursing mothers’ diet.

Sometimes the key forces aren’t what scents people have learned to prefer, but what olfactory preferences their society permits them to express. In traditional Asian societies, and also under the austere rule of Chairman Mao, it would have been considered rude and anti-social to douse oneself in cologne. But now the increasingly individualistic Chinese are more willing to flaunt their favorite smells, and pay handsomely for them.

Keller’s art gallery recently hosted an exhibit called “Scents of Exile,” in which an artist interviewed immigrants from Ghana, Iran and elsewhere about the aromas of their home countries and interpreted them through a pandemic-appropriate medium: hand sanitizer. The lost world of 1980s Ethiopia, for instance, was conjured through notes of “hay,” “cattle” and “moist air.” German-born Keller told me how his own bespoke hand sanitizer would likely include elements of gingerbread and sunscreen: In his native Nuremberg, the baking of the region’s famous Lebkuchen holiday cookies commences in August, blending with burnt grass.

Olfaction is not only genetically modulated and culturally loaded but autobiographically specific to the extent that certain smells evoke a visceral reaction in you and you alone. This is frustrating to scientists looking to suss out the nose’s fundamental rules. Even fecal smells, supposedly the worst, can awaken a mother’s fondness for the days her child was in diapers or an immigrant’s homesickness for the manure of his ancestral dairy farm.

Smells have a privileged relationship with memory that scientists are still trying to understand. When Proust rhapsodized about his madeleine, his nose (masquerading as his taste buds) was likely his time machine. But was this a mere literary device, or real life? In one famous experiment, researchers asked people to reminisce when exposed to the sound of a campfire and then the sight of a campfire. While both prompts brought to mind vivid recollections, the subjects were suddenly able to access more emotional memories when they were exposed to the smell of a campfire. The smell of a crayon is likewise more evocative than a picture of a crayon, experiments suggest.

“Odor is the arbiter here,” says Steve Ramirez, a Boston University neuroscientist. “It opens up the door to more episodic memory.” He believes that smells suddenly trigger gripping flashbacks, both joyful and traumatic, because of how the brain’s storage system works.

The idea is that most memories dim because they are transferred over time from the hippocampus, where they are first formed, to the prefrontal cortex, but that smell can reawaken these memories. To test this theory, Ramirez exposed mice to a series of electrical shocks. Returned to the shock container the next day, the animals, likely accessing their fresh fear memories, showed activity in their hippocampus. For a separate group of mice returned to the container after three weeks, the hippocampus stayed quiet. But a group of animals exposed to the smell of almond extract during the initial electrical shocks continued to show hippocampal activity when they smelled the almond three weeks later, suggesting they preserved the memory differently. It’s unclear why. Maybe it has to do with the fact that olfactory processing takes place next door to the hippocampus, somehow allowing smells to shortcut a memory loop. Ramirez is interested in using these findings to treat PTSD, part of a larger project of intentionally editing human memory by replacing old triggers with new.

Because olfactory neurons must weather the elements, including viruses and bacteria in addition to pollutants, they seem remarkable among nerve cells for their ability to regenerate—and this is another reason why smell is arguably our most plastic and mysterious sense. The neurons don’t always grow back in the same numbers and combinations. Thus, identical twins who started life with identical olfactory receptor DNA can—depending on where they take up residence and which diseases they catch—end up with very different senses of smell. All of us can expect our sense of smell to wax and, mostly, to wane over the life course as our cells lose the ability to turn over. The decline starts in earnest around age 50, and by 80 three out of four of us have what could be clinically classified as a smell disorder.

Of course Covid accelerated that time line, especially for those of us infected with the original variant, currently recognized as the most caustic to the nose. The virus apparently attacks the neighboring cells that nourish our olfactory neurons, and also reduces the number of active olfactory receptors being built. The end result may be a kind of brain damage—a smell-related tissue deficit in our olfactory processing regions that scientists observe in neurological scans of otherwise recovered Covid patients.

I contracted the virus in the spring of 2020, so maybe this is the real reason why I couldn’t decipher the musks in Mainland’s musks lab test. While my nose is mostly back to normal, I have noticed a few odd and lingering tweaks. Sometimes—often at night—I smell smoke when there is no fire (although this “phantom smell” problem is admittedly far less dangerous than the reverse predicament that other patients report). My favorite perfume now falls flat for me, one spritz no longer kicking off a happy cascade of remembered wedding and date nights.

This raises a philosophical question: If we can’t smell as we once did, are we still who we were? Maybe not. “I would be willing to bet anything,” Ramirez says, “that any permanent modification of how we view the world today is going to retroactively shade how we recall the past.”

New smell therapies for Covid survivors are in the offing. Smell training might prompt the recovery of old signaling. Nasal steroid sprays, and jabs of platelet-rich blood plasma straight to the nose, could speed cellular healing.

Market researchers have noticed that the public has lately been gravitating toward unaccustomed smells. “We knew because of Covid, there were going to be shifts in terms of consumer behavior,” says Fabien Craignou, who studies finicky global perfume markets for the Swiss fragrance company Firmenich, including how adverse events like economic recessions shape our noses’ collective whims. Not only did Covid-era focus groups reveal an increased demand for scented products in general, but people seemed to crave previously unthinkable combinations of citrus, traditionally associated with hygiene, and coconut, a more cozy and comforting note. A trek down the shampoo aisle confirms that these traditionally appear in separate products. But now focus groups seem to want them packaged together, to feel highly sanitized and soothed in the same breath. “We call it ‘Sereni-Clean,’” he says.

Lately, Mainland has taken up a new approach that breaks with previous generations of smell research: one that snubs the nose entirely. Since research on humans hasn’t yet cleared our view up the nostrils, Mainland has begun studying the odorant molecules directly. His team recently found that simple criteria—like how small and hydrophobic the molecules are—can forecast which chemicals give off a smell in the first place. That study, published this spring in the journal Proceedings of the National Academy of Sciences, also concluded that there are billions of yet-to-be synthesized potential smells that nobody has smelled yet.

Mainland is hoping to identify what researchers call primary odors, a few dozen smells that combine to create most others. Such basic rules would be essential to future technologies that could capture and share smells, using a sensor to snag real odors, an algorithm to digitize them, and a device to reproduce them at the other end.

A more immediate goal is to anticipate precisely how a molecule will smell, without a person ever smelling it. What makes several different molecules all register as woody, for example? They must share characteristics in order to light up similar combinations of receptors inside of our skulls, causing us to experience that hard-to-articulate woodiness. Probing the molecules is not for the faint of heart, but maybe it beats getting led around by the nose.

“If you want to understand this stuff you have to get back into the body,” Mainland assured me. “But at this point we understand the chemistry much better than the biology.”

It’s worth noting that I’d been in my body the whole time. I couldn’t shake those molecules of isovaleric acid, smelling to high heavens. My snout, however Covid-compromised, sucked in the essence of sweaty pennies and wounded celery and the unique wave of who-knows-what billowing out of the bright yellow supply cabinets where Mainland’s industrial-grade stink bombs were housed, the collective effect reminiscent of a bonfire of rotten gummy bears.

So when one final foul cloud enveloped me just as I headed for the exit, I fled its cheesy and lightly fruity fetor before realizing that it was just microwaved lunch leftovers—lasagna, quite likely—and that to somebody somewhere, it smelled mighty good.