How One Philly Institute Is Demystifying the Serious Science of Smells

Arlene Love’s 1975 Face Fragment sculpture at the Monell Chemical Senses Center / Photograph by Nick Higham / Alamy Stock Photo

Flashback to 1968, and the dining room of our house in Glenside. I’m 12. It’s a Friday night, and my mom is Catholic, which means for dinner, she’s made fish — a whole big sea bass baked with a topping of chopped tomato and onion and parsley, plus rice and a side of brussels sprouts. Mom bears it to the table proudly while my dad and three siblings grin in eager anticipation, ready to dig in. 

I make a face.

Mom sees it and frowns. “Just one bite,” she tells me. Easy for her to say.

I hate fish. All fish. Yes, even crab. Yes, shrimp, too. (Actually, especially shrimp. Why do fish lovers always ask, “Even shrimp?”) Flounder. Salmon. I HATE FISH — get it? And I’m the only one. In all my big, happy family, only I don’t salivate at a platter of mussels. Only I don’t get excited about calamari. Only I don’t live for our annual two weeks in Wildwood, when we go deep-sea fishing and eat out at the Crab Trap and get big sacks of takeout clams and oysters and generally exist in a miasma of piscine salt air. 

“Trimethylamine,” Danielle Reed says knowingly. And just like that, what made growing up in my fish-loving family such misery for me has a name.

Reed would know. She’s the associate director of West Philly’s Monell Chemical Senses Center, where she studies how genetics contribute to differences in people’s perceptions of taste and smell. TMA, she tells me, is a chemical found in fish, crustaceans and mollusks. (It helps their innards function under water pressure.) When TMA is exposed to air, it emits an odor that’s perceived as, well …

“One of my tricks when I go on visits to classrooms,” Reed says, “is to give everybody a little bottle of TMA and tell them to smell it. Then I observe the sea of faces. Some don’t smell anything at all. Some don’t mind the smell. But some are horrified.” 

Lucky me. I’m among the latter. 

Reed was in graduate school at Yale when she was struck by the realization that some people can taste or smell a certain compound and some can’t — “By the fact,” as she explains it, “that at this very basic level, people are very different, and we don’t understand why.” That propelled her to a post-doc program in genetics, so she could try to figure out “how our DNA affects who we are as people.” 

We don’t think about it much — if we think about it at all — but genetics determine our senses of smell. “Some of us are color-blind, right?” Reed points out. “We’re all born with some olfactory receptors that don’t work very well. If you lack the ones that let you smell freesias” — a glorious flower in the iris family, said to have an enchanting odor that I happen not to be able to detect — “you can try to smell them all the time, but it will never work.” Then she mentions a “big name” in the world of smell who once threw a dinner party “where he only served things that some people can smell and some can’t — and he had the table surrounded by freesias.” To Reed and her Monell colleagues, this is the height of droll humor. 

You’ll have to forgive them. They’ve spent their careers steeped in what Monell’s emeritus director and president, Gary Beauchamp (he pronounces it “Beech-um”), calls “the realm of the forgotten senses.” 

It makes them a wee bit tetchy about their field. As Monell neuroscientist Joel Mainland points out, “In grade school, you learn about the primary colors. You have music class. There’s no smell class.” Clearly, he believes there should be. Mainland pushes back at what he considers a common misconception: “People think humans are bad at smelling. We’re not.” The difference between us and dogs when it comes to scent detection, he says, is pretty simple: “Our noses aren’t at ground level.” When, back across the ages, proto-humans stood upright, vision and hearing became more important to us than our sense of smell. Mainland’s PhD adviser once proved that people are perfectly capable of tracking a scent across a field: “It’s just that we get no practice at it,” Mainland says. “If you practice, you get better quickly.”

But you’re not likely to put in the time. Nowadays, we humans have a certain societal shyness about odors, at least publicly. We slather our armpits in deodorant, use antiperspirant soap, gargle with mouthwash, repress our burps and farts, Febreze our cars and houses, and generally don’t talk about you know, no no no. And yet … “Scent is one of the most arousing things,” Danielle Reed says stoutly. “The sexuality of odors is primal.” She mentions a security guard at a building where she once worked — “an older gentleman. We had nothing in common, but he wore this cologne I just found so sexy. I would stand next to him and just sniff.” She laughs. “I’m sure he thought I was strange.” 

Such behavior doesn’t seem peculiar to the folks at Monell. Gary Beauchamp mentions a set of manuscripts currently in his office: “It’s huge. It fills half a bookshelf. I’m editing one volume, about the chemical senses — taste and smell. The other seven volumes are about vision, hearing and touch.” He pauses. “If a dog had written them, it would be the other way around.” 

We may all smell things differently, but we smell them the same way. Asked for a brief rundown of what makes our hearts go pitter-patter when bacon is frying, Reed gladly obliges. “Bacon has molecules,” she says. “Some are heavy and can’t come out of the meat when you heat it. But some of the lighter ones do, and they travel through the air to your nose. They enter the nose and go up through a layer of protective mucus to your olfactory epithelium, located in the ‘roof’ of your nose, right between the eyes.” There, the molecules bind to the (genetically determined) olfactory receptors. Different scents activate different combinations of these receptors — like different letters forming different words — which convert them into signals that enter the neurons in the brain. (Speaking of fish, all animals have some way of detecting chemicals in their environment; fish, which don’t have noses, do so with neurons on the outsides of their bodies.) 

Despite the differences among our receptors, humans are pretty universal in deciding what smells good and what smells bad. (Worldwide, the favorite is vanillin, as in vanilla extract.) Joel Mainland worked on an about-to-be-published study that sussed this out. “Most scent research on cross-cultural preferences has been done on modern, Western, industrialized societies,” he explains. “For this one, we worked with linguists who go out to field sites of various cultures — agricultural, hunter-gatherers, everything. We had 10 odors, and we asked our test subjects to rank them according to their pleasantness. We included New York subjects, too. We found there was almost no cultural variation.” He pauses, thinks. “It could be the odors we chose.”

He doubts it, though. “You know about durian?” he asks. I do. It’s a big spiny fruit native to Indonesia, Malaysia, the Philippines and Thailand that’s renowned — or reviled — for its fragrance, which is so powerful and disgusting that the stuff’s been banned from public transportation. (Its species name is derived from the Latin name for the civet, a cat whose perineal-gland secretions have a pungent, funky scent that’s a hallmark of Chanel No. 5 perfume — which my mom wore and I still wear.) “Even in cultures that eat durian,” Mainland tells me, “not everybody eats it. And even the people who eat it say it smells terrible. It’s the same with fermented herring in Sweden. It smells awful. People eat it anyway.”

That’s because while our senses of smell and taste are genetic, our preferences can be cultural. One of the most interesting studies Gary Beauchamp ever saw, he says, was done a few decades ago among the Inuit, who live in Arctic and sub-Arctic Greenland, Canada and Alaska. “Their traditional food back then was dead fish and dead caribou,” he reports, “which they put into the permafrost and allowed to rot. The smell of it … it was just abominable. Awful. You couldn’t eat it.” But the study showed that Inuit adults who’d been fed the carrion as infants liked the taste; otherwise, they found it offensive. That accords with other studies by Beauchamp showing that early exposure to foods through amniotic fluid and breast milk induces lifelong preferences. 

And it’s not just preferences that can be acquired. Maybe, like a certain Monell researcher — no need to say who — you drank too many tequila sunrises one year on spring break and now are revolted by the odor of orange juice and grenadine. Reed recalls that once, when she was a child coming down with stomach flu, her mom was browning flour: “I still can’t stand the smell.” When I was pregnant years ago, my sense of smell went haywire. “We definitely get reports of that,” Joel Mainland says. “It hasn’t been studied much. It’s inconsistent, and women don’t want to take part in studies when they’re pregnant. Are all women more sensitive to odors then? Are they sensitive to some odors but not all? Is it related to hormonal cycles?” These are the kinds of questions that intrigue the scent sleuths at Monell. 

For much of his career, Mainland has been trying to devise a way to tell what something will smell like from its chemical structure. Theoretically, this should be possible. After all, in vision, the wavelength of light correlates with color; in hearing, frequency determines pitch. And yet, as his Monell homepage notes, “There is not a scientist or perfumer in the world who can view a novel molecular structure and predict how it will smell.” I should mention that Mainland started out studying vision but found that, as he puts it, “So much is known in vision that the problems seem small.”

He says he’s making progress: “We did a study where we built a model and presented it with 400 different molecules. They weren’t standard. In theory, they had never been smelled before. We asked the model to predict what they would smell like. Then we presented the odors to a panel of 15 people. The smells were different from anything they’d smelled before, but they could still describe them. It’s like with a color you haven’t ever seen before — you’d say, ‘Oh, it’s like the color of this or that.’” The model, Mainland says, outperformed the average panelist at describing what an odor smelled like, even though the panelist could actually smell the molecule and the model could only look at its molecular structure.

Of course, not everybody is an average panelist. Just for kicks, they threw a professional perfumer into the mix. “His descriptions were much better,” Mainland says, a little enviously. “He said that one smelled like a campfire after it had been put out. For another, he said, ‘It smells like a hot tub is nearby.’”

If you’re at all familiar with University City, you’ve seen the huge gilded nose and mouth of Arlene Love’s Face Fragment sculpture outside the Monell Center building at 35th and Market, in the University City Science Center. The Monell Center is an outgrowth of the Monell Foundation, begun in 1956 by Maude Monell Vetlesen in honor of her first husband, Ambrose Monell, who died quite young. Gary Beauchamp explains that Ambrose invented Monel metal alloys, which withstand corrosion and water damage — they’re still used in stuff like submarines and fishing lures. “A few years after I moved to Philly,” Beauchamp reports, “my water heater failed. When the workmen were removing it, I saw it had “Monel” stamped on it. What a coincidence!” He pried the plate off and kept it as a souvenir. 

Maude’s initial gift establishing the Monell Foundation was modest, Beauchamp says — less than a million dollars. Headquartered in New York City, the Monell Foundation funds various cultural and scientific endeavors — the ballet, the American Museum of Natural History, medical research. “One of the directors was a larger-than-life guy named Hank Walter,” Beauchamp explains. “He was an attorney, but he was really interested in science. He was the president and CEO of International Flavors and Fragrances — a big, powerful company.” IFF still exists; its website says it supplies “the food and beverage, fragrance, home and personal care, and health and wellness end markets with innovative solutions that allow them to create the products consumers know and love.” It’s obvious why IFF would have an interest in taste and smell. 

“Walter had an ulterior motive,” Beauchamp acknowledges. “But he and my predecessor, Morley Kare, thought it was strange that there were institutes that focused on vision and hearing — senses that people worry about losing. But there was none in the world of taste and smell.” Together, Walter and Kare pitched the Monell Foundation on their idea to create a novel institution to study these neglected senses. Eventually, the foundation did. (Incidentally, if you saw the Showtime series Masters of Sex, the Dan Logan character was based on Hank Walter; William Masters and Virginia Johnson were trying to develop pheromonal perfumes that would arouse sexual desire.) 

Walter and Kare shopped the concept of the research center to different universities, and Monell became an institute at Penn. The foundation tossed in $1 million — its biggest gift ever. Half of that paid for Monell’s labs and offices — “The second building in the University City Science Center complex,” says Beauchamp. “It was completed in 1971, which is when I came. The area was a wasteland at the time. It had been a very dynamic African American community, but the city tore everything down and created the Science Center. Ever since, it’s been growing and expanding.” In the late ’70s, Penn relinquished its affiliation, and Monell became an independent organization. The two institutions maintain a relationship, though, seeing as they’re neighbors. 

When Beauchamp first came to Monell in 1971, he did so in a rental truck from Chicago. “My wife drove our car,” he recalls. “She had ferrets and guinea pigs I was experimenting with in the car, and I had six donated kittens from a pet food company in the truck. I was interested in cats in particular. They’re odd animals from a taste point of view — they only eat meat. You can’t find a vegetarian cat.”

At the time, Beauchamp was studying the human preference for sweet things. “It’s found in newborns and even in premature infants,” he tells me. “It might be the most potent chemical force in the world.” That’s because it signals the presence of extra calories in a plant, cueing creatures to gnaw on that option to survive. “But what,” Beauchamp asks, “if an animal doesn’t eat plants?”

It turns out that cats don’t give a damn about sugar — “They can’t even taste it,” says Beauchamp. “In the 2000s, we, with others, identified the receptor for sweetness and were able to show that in cats and many other animals that only eat meat, long ago in their evolution, those receptors mutated and lost their ability to detect sugar’s sweetness.” That could have been the end of cats — without the energy that sugar provides, they wouldn’t have survived to reproduce. But by happenstance, Beauchamp says, other receptors also mutated, and cats developed a liking for amino acids, which are found in … meat. “One of my favorite experiments ever was when we went up the road to the Philadelphia Zoo and did work with lions and tigers and leopards,” Beauchamp recalls fondly. “None of them have any taste for sugar.” Yet they rose to the top of the food chain. Who says science is dull? 

And I haven’t even gotten to Smell-O-Vision yet. 

Smell-O-Vision could be considered a scent scientist’s holy grail. Its use with films dates back as far as 1906, when the operator of a theater in Forest City, Pennsylvania, in Susquehanna County, soaked a cloth in rose oil and stuck it in front of an electric fan while showing a film about the Rose Bowl. A couple decades later, the manager of a Boston theater poured floral scent into its ventilation system to accompany the film Lilac Time. Walt Disney hoped to produce Fantasia with accompanying scents but was deterred by the cost of the project. Smell-O-Vision makes — well, sense, if you think about it. Movies were already appealing to audiences’ vision and hearing; why not smell as well? Yet the idea never really caught on.

The problem, Joel Mainland explains, wasn’t presenting the scents; it was eliminating them: “It’s very difficult to control smell. When you disperse it, it’s not like clicking from one slide in a slideshow to the next. You have to get the odor to everyone at the same time — and then get rid of it in time for the next one. These are soluble problems, but not with current technology. People are working on it, though.” He mentions a virtual reality headset he owns that’s equipped with a smell device: “There’s definite interest.” In April, the Museo Nacional del Prado in Madrid mounted an exhibition pairing the early-17th-century painting The Sense of Smell, by Flemish artists Jan Brueghel the Elder and Peter Paul Rubens — it depicts Venus and Cupid lolling in a garden — with 10 scents delivered via diffuser, from orange blossoms to civet musk to ambergris.

Speaking of interest, you may have noticed an uptick in attention being paid to the sense of smell of late. The Monell scientists aren’t grateful to COVID for that upturn, exactly. “But it has been a boon to researchers,” Mainland admits. “Before COVID, we struggled to explain to people what it’s like to lose your sense of smell. They didn’t take it seriously. Now, more people are realizing how important it is. It’s not a throwaway sense.” 

Researchers at Thomas Jefferson University Hospital released a paper this year that helped explain what happens when COVID patients lose their senses of taste and/or smell. “It’s not the olfactory receptors in the nose that are affected,” Danielle Reed explains. “It’s the neighboring cells. Basically, they release chemicals that shut down the receptor’s ability to regulate the signals it sends.” So coffee may smell like feces — or may have no smell at all. “Not all variants have the same effect,” Reed adds. “It’s less with Omicron and Delta. The older variants were harder on the sense of smell. And some 10 to 15 percent of those affected with the worst variant don’t get it back.” 

If there’s a silver lining, she says, “It’s that we’re really going to be able to dig in and figure out how to fix it — and learn more about how smell fits into people’s lives.” One thing we know about that: Our senses of taste and smell fade as we age, just like hearing and eyesight. “That’s why here, we’re strong advocates of universal smell testing,” Reed says. She helped develop such a smell test at Monell. “It’s a guessing game,” she explains. “You have three patches, and only one of them has an odor. You have to pick that one, and then you rate the intensity of its smell. That’s the guts of the test: How strong is the smell? And then you guess what it is — say, caramel, or coffee?” She’d like such testing to become standard at doctors’ visits, especially since so many older people lose interest in food as their senses of taste and smell dim and become malnourished as a result. 

There’s one more aspect of this forgotten sense that COVID could help unravel, Gary Beauchamp notes: “If you think about the anatomy of the sense of smell, the olfactory receptors are way up in the nose, on neurons that synapse directly into the brain. By some definitions, they’re part of the brain. And that provides a path for something” — something like, say, a virus — “to directly enter the brain.” Those receptors are exposed to the brain and to the outside environment — “So they’re really open to all kinds of potential danger.” 

To mitigate that, these neurons are able to regenerate much more quickly and much more often than others in the body, Beauchamp says — “And there’s a very big interest in that. If we can figure out how they regenerate, that will tell us how other parts of the brain could regenerate.” And that could lead to treatment for everything from Alzheimer’s to strokes to Parkinson’s to epilepsy.  

We humans already rely on our sense of smell (whether we acknowledge it or not) in all kinds of ways: to choose whom to mate with, decide what’s safe to eat, avoid dangerous surroundings, locate enemies. Danielle Reed mentions that during World War I, when German forces were employing mustard gas against the Allies, the stuff would congregate in low-lying areas, because its molecules are heavier than air. “Soldiers who were good at smelling it would go over the hill first,” she explains, “then tell the others if it was safe. Those guys saved a lot of lives.” 

The thing is, they were good at smelling mustard gas because of their genes. Which means all those “just one bites” of fish Mom made me take were completely in vain. (Parents! Take note!) And I can guarantee you, if the other members of my family knew what trimethylamine really smells like, they’d never go near fish again. 

Published as “Crankcase: Does This Smell Fishy to You?” in the June 2022 issue of Philadelphia magazine.