Beer from The Bottle
The Association for Chemoreception Sciences, North America’s main conference for smell and taste researchers, meets every April in southern Florida. The location isn’t accidental—the whole point is to give researchers the opportunity to leaven their scientific geekery with at least a few hours of sun and sand. This lends the meeting a remarkably relaxed, nonacademic feel, with sun-deprived, middle-aged folks clad in shorts and Hawaiian shirts thronging the bar or basking poolside in the sun. But that stereotypical Florida hotel ambiance quickly turns surreal, as the conversations on the sundeck turn not to shopping or the kids, but to G-protein-coupled receptors, the psychophysics of odor perception, or the olfactory abilities of mosquitoes. For four days in April, the Hyatt Regency Coconut Point in Bonita Springs is not your average Florida resort.
When attendees are not by the pool or talking science in the bar, they can often be found in the exhibit hall, where they can peruse posters that describe current research, or browse new scientific gadgets that vendors are selling. That’s where I first met Richard Doty, who was looking relaxed and informal in a green and black-striped rugby shirt. Doty—a fit-looking seventy-year-old with short, gray-tinged hair and a cheerful manner—is one of the world’s leading experts on the senses of smell and taste. In fact, he literally wrote the book on the subject: His Handbook of Olfaction and Gustation is the classic in the field. But even if you didn’t know that, you could guess his stature by the steady stream of eminent scientists who stop by to chat. Right now, though, Doty is playing the role of pitchman. The company he founded is hawking a new machine for testing people’s sense of smell, and they’re inviting all comers to try it out. Clearly, that’s an opportunity I can’t pass up.
Specifically, Doty’s machine is designed to measure olfactory threshold, an indication of how sensitive your sense of smell is. By “olfactory threshold,” he means the most diluted trace of an odorant you’re able to detect; the lower your threshold, the more acute your nose. One of Doty’s assistants took me through the process. You sit in front of the machine and put your nose into this little mask, he explained. Then the machine will give you two puffs of air, one after the other, and the computer will ask you which of the two carried the scent of phenylethyl alcohol, a pleasant roselike odor. And then you repeat the test again and again, until the computer instructs you to stop.
What the assistant didn’t tell me—but Doty did later—was that the olfactometer could vary the concentration of the rose scent in the loaded puff. If I failed to answer correctly which puff had the scent, the computer assumed there was too little scent for me to detect, and it stepped up the dose for the next round; if I answered correctly, it assumed the concentration was above my detection threshold and reduced the dose. Over and over we went, wandering up and down like a hyperactive kid on a staircase, until we settled on the odor concentration that sat at the boundary between right and wrong answers—my olfactory threshold.
At this point, Doty strolled over and glanced idly at the printout of my result. His eyebrows went up. He stopped and peered more intently at the printout, and then turned to me with an expression of concern. “Do you have an impaired sense of smell?”
Uh-oh. When the world expert on olfactory dysfunction takes an interest in my test results, that can’t be a good sign. Especially for me, especially now: How can a guy with an impaired sense of smell credibly write a book about flavor? (You’ll recall from the jelly bean test that flavor is mostly about the sense of smell.) As Doty showed me the printout, the news looked pretty grim: according to his machine, the rose scent had to be present in more than one part per thousand before I could reliably detect it, making my threshold about a thousand times worse than average.
Doty must have seen the pained expression on my face, because he pulled an envelope from a nearby box and said, “Here, why don’t you take this test, too?” The envelope contained another of Doty’s many claims to fame, the University of Pennsylvania Smell Identification Test. This test, universally referred to as the UPSIT, is a forty-item multiple-choice test that uses scratch-and-sniff scents. (“This odor smells most like a. gasoline b. pizza c. peanuts d. lilac.” Pizza, I thought.) Picking one of four multiple-choice answers avoids the well-known difficulty people have in putting a name to a smell. Most of the time, the right answer seemed obvious, but maybe five or ten of the forty were tough. “Is this turpentine or Cheddar cheese? I’m not sure,” I found myself saying. Even distinctive smells can be hard to recognize sometimes.
A few hours later, I bumped into Doty on the exhibit floor again and gave him my UPSIT for scoring. To my relief, I got thirty-seven of the forty right—enough to put me in the seventy-third percentile for fifty-five-year-old men. “You did very well,” said Doty. “Three-quarters of your friends did worse.” Whew! My nose doesn’t disqualify me after all.
Most likely, Doty speculated, the problem with the threshold test was the environment we were in: A bustling exhibit hall isn’t the ideal place to concentrate on subtle, barely detectable odors. Plus, I’d raced through the test as quickly as I could so that the next person could try it; in a doctor’s office, the test is given much more slowly, with pauses that allow the scent from one trial to dissipate fully before the next trial starts. These minor differences in procedure can make a huge difference to the outcome—a complication that colors almost all research on the sense of smell.
That was my introduction to the messy world of olfaction research, where everything is harder—and more complicated—than it looks. While taste research is enjoying something of a golden age, smell researchers are, for the most part, still mired in the Dark Ages. Given an unknown molecule, even the best scientists have only recently been able to predict whether it has an odor at all, and can barely guess at what that odor might be. In fact, researchers can’t even agree on the details of how olfactory cells recognize odor molecules. All of which means that we’re a long way from understanding the most important mystery of the sense of smell, at least from the perspective of flavor: Do your perceptions differ from mine, and if so, what does that mean for our appreciation of flavor?
The reason olfaction has proven such a tough nut to crack is that it’s much, much more complex than taste. As we saw in the last chapter, these two flavor senses really serve two different purposes. Taste draws us toward nutritive foods and pushes us away from poisonous ones—a fairly simple yes/no decision. That makes taste the easy part of the flavor equation: Our tongues use at most thirty or forty receptors to keep track of a half-dozen or so basic tastes. It’s pretty straightforward to understand what we’re talking about, and how our sense of taste works. Smell, on the other hand, answers the question “What is it?” which is a much more open-ended question. There are, after all, a vast number of smelly things out there in the world, and our noses need to be able to cope with all of them.
Imagine taking a whiff of your morning coffee. The steam rising from your cup carries with it hundreds of different aromatic molecules, which enter your nose as you sniff. Way up at the top of your nasal cavity is a little patch of cells, less than one square inch in area, called the olfactory epithelium. The nerve cells within this patch—about six million of them—each carry one of about four hundred different odor receptors on their surface. (Actually, a few cells major in one receptor and minor in another, but we can ignore that detail here.) These olfactory sensory nerve cells send their signals straight in to the brain, giving them the distinction of being the only nerve cells in your body that connect the brain directly to the outside world.
Each receptor, in turn, recognizes particular features of specific odor molecules from the coffee. Surprisingly, scientists still don’t know for sure how this recognition happens. Most think that particular shapes on the odorant molecules fit into complementary shapes on the receptors, like the camera-in-foam-case analogy we used for bitter receptors. A vocal minority, however, thinks that instead, each odor molecule has a unique pattern of molecular vibrations, which receptors recognize using an arcane process called quantum tunneling. A lively debate is still raging between the “shapists” and the “vibrationists,” though of late it looks like the shapists are winning.
For most purposes, though, it doesn’t matter exactly how this recognition happens. What’s important is that each odor receptor recognizes several to many different odorants, and each odorant binds to several different receptors. That means that each odor molecule activates a different mix of receptors—a different chord, if you will, on the olfactory keyboard. And your coffee contains not just one odor molecule but hundreds, each sounding its own distinctive chord in your brain. Some of those chords probably sound so faintly that you can’t actually “hear” them as part of your flavor experience. (In technical terms, their concentration is below your detection threshold.) But that still leaves a whole orchestra’s worth of important chords, as each above-threshold odorant tickles its own particular mix of receptors. Out of that cacophony, your brain somehow extracts a harmony: the flavor you know as coffee.
No wonder olfaction is so hard to understand. It has three separate sorts of complexity: diverse odor molecules, diverse receptors, and diverse “harmonies.” Let’s look at each one in turn, starting with the molecules. No one knows exactly how many different odor molecules there are in the world. For many decades, the standard answer to that question has been “about 10,000.” You’ll see that number bandied about everywhere from chefs’ blogs to scientific papers to neuroscience textbooks. Even Richard Axel and Linda Buck, who won the Nobel Prize for finding the receptors responsible for detecting odors, used it in their key paper. Bathed in Nobel glory, the notion of 10,000 different odors has come to take on the aura of received wisdom. And it adds to our general sense of incompetence when it comes to the human sense of smell. After all, psychologists estimate that we can recognize as many as 7.5 million different colors and 340,000 audible tones. Compared with that, recognizing 10,000 smells is pretty pathetic.
But a closer look shows that this 10,000-smells number, far from being hard science, is completely bogus. It comes from a seat-of-the-pants calculation dating way back to 1927. Two chemists, E. C. Crocker and L. F. Henderson, thought that smells, just like tastes, could be sorted according to four independent qualities. For taste, we have sweet, sour, salty, and bitter. (We can cut them some slack for missing umami, which few except the Japanese knew about back then.) For smell, they suggested fragrant, acid, burnt, and one more, which they first called putrid and later changed to caprylic, or goaty. And they further guesstimated that each of the four odor qualities could be assigned an intensity score between 0 (absent) and 8 (overwhelming). If so, there are 9 × 9 × 9 × 9 different ways to score a smell, a total of 6,561, which they generously rounded up to 10,000. Of such stuff is scientific orthodoxy made. If Crocker and Henderson had chosen to include a fifth quality—musky, say—and rate on a scale of 0—9, we would all have been talking about a universe of 100,000 smells instead.
So far, so bad. Joel Mainland, an olfaction researcher at Monell, thinks he can do better. Mainland is a compact, enthusiastic guy with a thin face, wire-framed glasses, and rapid speech. He started out in science thinking he would study vision, but realized early on that it would be hard to build a career there. “As I looked around the field, I realized that the big problems were solved,” he says. “And then you look at olfaction and the big problems are still not solved. To me, it was an easy switch to go to olfaction.” His hunch has paid off in spades: Mainland has become one of the brightest rising stars of olfaction research.
Recently, Mainland has tried to come up with a more educated guess at how many different odor compounds there are in the world. His reasoning goes like this: In order for us to smell a molecule, it has to be volatile—in other words, willing to launch itself into the air in gaseous form. Big molecules generally can’t do that, and in fact, chemists know of few smelly molecules that have more than twenty-one “heavy” atoms in them—that is, atoms other than hydrogen, the atomic featherweight. So let’s assume, he says, that only molecules with twenty-one or fewer heavy atoms could have odors. That gives us, by his estimate, about 2.7 trillion candidate molecules.
But not every one of those small molecules actually has a scent. Some have boiling points so high that they never become airborne at normal temperatures; others are so oily that they’re repelled by the watery mucus layer that lines the nose, so they can’t activate odor receptors. After some tinkering, Mainland and his colleagues came up with a way to use a molecule’s oiliness and boiling point to predict whether it would be smelly.
One morning in Mainland’s lab at Monell, I helped test some of his predictions. It turns out you can’t just give someone a sample and say, “Do you smell anything?”—the power of suggestion is so strong that they’ll often “notice” an odor that’s not really there, or pick up some stray odor in the room. Instead, the researchers use something called a “triangle test.” Mainland’s assistant sat me down at a table and blindfolded me, then waved three vials under my nose, one at a time, as a synthesized computer voice asked which one—A, B, or C—had the odor. After each set of three, they gave me a thirty-second “distraction break” to avoid nose fatigue: the computer played a short song clip and asked me whether the singer was male or female. (Mainland had intentionally picked ambiguous voices, so this was hard. Showing my age, I got Tiny Tim and a young Michael Jackson right, but was clueless on much of the contemporary stuff.)
Tests like these, performed on many different individuals, give Mainland the confidence to say that most people have a hard time telling male singers from female ones. More to the point, he also knows he’s about 72 percent correct in predicting whether an unknown molecule will have an odor. Applying his prediction method to the whole universe of 2.7 trillion candidates, he calculates that there must be a staggering 27 billion different smelly molecules in the world.
That’s not the same thing as saying there are twenty-seven billion different smells, though. After all, we know that several different molecules have an apparently identical sweet taste, and there might be hundreds of different molecules that give rise to a single bitter taste. If the odor universe is similarly full of “smell alikes,” then the number of unique odors could be much, much less than twenty-seven billion. But when I asked Mainland if he knew of any two molecules that smell exactly alike, he couldn’t think of any. “I was always told that no two molecules smell the same,” he said.
Now let’s switch over to the other side of the equation and look at the receptors that are responsible for detecting all those smelly molecules. Buck and Axel showed that the odor receptors are protein molecules embedded in the membranes of nerve cells in the olfactory epithelium. When geneticists first sequenced the human genome a few years after Buck and Axel’s discovery, they therefore knew an odor receptor gene when they saw it. To their astonishment, they found not just a few dozen olfactory receptor genes in the genome, but nearly a thousand! Stop and think about that for a moment: The human genome contains about twenty thousand genes in all, so out of all the genetic instructions needed to turn a fertilized egg into a functioning human being—hundreds of cell types organized into tissues and organ systems and a brain, all the molecular signals needed to keep everything running—one out of every twenty genes is for an odor receptor. That’s like walking into a library containing the world’s accumulated knowledge and finding that one in twenty books is about car repair. Who would have guessed that olfaction makes up such a large chunk of who we are?
On closer inspection, more than half of these odor receptor genes turned out to be what geneticists call “pseudogenes”—that is, the rusted-out hulks of genes that had broken sometime in our evolutionary past. Exactly how many odor receptor genes are still functional is a bit tricky to answer. The official human genome—largely that of the flamboyant genetic entrepreneur Craig Venter—has about 350 working odor receptors. But if the Human Genome Project’s gene sequencers had looked instead at your genome, they would have found that some of those 350 are broken in your genome, while others that were broken in the official version are working in yours. One team of researchers looked at a sample of one thousand human genomes and found 413 odor receptors that were functional in at least 5 percent of the population. If the researchers had looked at more people, they would no doubt have found a few more.
It’s one thing to count odor receptor genes, though, and quite another to understand which receptors recognize which odor molecules. The latter is much harder, largely because odor receptors normally live on the surface of nerve cells, which are challenging to grow in petri dishes in the lab. That makes experimentation difficult. As a result, the vast majority of receptors are what scientists, in a rare burst of colorful metaphor, call “orphan” receptors, meaning that we don’t yet know which odorant molecules they recognize.
Fortunately, molecular biologists have found a work-around by putting odor receptors onto the surface of kidney cells, which are much easier to grow in the lab. A few years ago, with a bit of hard work, Mainland and other researchers created a panel of kidney cell cultures expressing the whole range of human odor receptors, one per culture. With the panel in place, they looked forward to testing odorants, one after another, to see which receptors they triggered. Soon, they thought, they’d be able to “de-orphan” the lot. The olfactory code looked within reach at last.
No such luck. So far, Mainland and the other workers have only managed to find targets for about 50 human odor receptors. Try as they might, the other 350-odd receptors have remained stubbornly orphaned. “That means that about 85 percent of these receptors do not work in our assay system,” says Mainland. “That’s a lot.” It’s possible that the apparent failures detect uncommon odorants that Mainland simply hasn’t got around to testing yet—though the longer he looks, the less likely that possibility becomes. It’s also possible that some overlooked complication is preventing those receptors from working properly in the kidney cells.
There’s another, more interesting possibility: Maybe some of our odor receptors aren’t there to detect odors at all. If you take a step back and look at the big picture, what odor receptors really do is to alert the body when they recognize particular small molecules in the environment. Some of those molecules are odors, but this sort of recognition plays lots of other roles, too. Our bodies need to recognize hormones and other signaling molecules that help the body keep organized during growth and development; they need to turn functions like digestion, reproduction, and immune defense on and off at the right times, and so on. Since evolution is the ultimate MacGyver, cobbling together solutions from whatever materials happen to be lying around, it would be surprising if at least a few odor receptors hadn’t been pressed into service for other functions now and then. Sure enough, when biologists have looked, they’ve found ORs all over the place: testis, prostate, breast, placenta, muscles, kidneys, brain, gut, and more. Some of these, no doubt, occur in the nose as well—but it’s at least possible that some do not.
But counting up odor receptors doesn’t tell the whole story of smell, because there’s another whole layer to the way we perceive odors that isn’t there for taste. Our sense of taste is what sensory scientists call analytic—that is, we easily break it down into its component parts. Sweet and sour pork is, well, sweet and sour. Soy sauce is salty and umami. Ketchup is sweet, sour, salty, and umami.
Our sense of smell doesn’t work that way. Instead, it’s a synthetic sense: Our brains assemble the component parts into a single, unified perception, and we can’t easily pick out the parts separately. That’s easiest to understand if you think about another synthetic sense: vision. When I gaze fondly at my wife, I don’t see lines, curves, and edges, even though that’s what my brain is actually detecting and processing. I just see her face, the synthetic object of my perception. Similarly, the individual odor molecules sensed by our nose can combine in our brain to create a new perception that’s entirely different from its components. If you combine ethyl isobutyrate (a fruity odor), ethyl maltol (caramel-like), and allyl alpha-ionone (violetlike) in the proper proportions, for example, what you smell is not caramel-coated fruit on a bed of violets, but pineapple. Similarly, one part geraniumy 1,5-octadien-3-one to one hundred parts baked-potatoey methional smells fishy—something neither ingredient shows the least hint of alone.
Neuroscientists like to refer to these new, higher-level perceptions as “odor objects.” Each one is, in effect, a unique pattern of activation involving a subset of the four hundred or so different kinds of odor receptors in your nose. In essence, these odor objects define reality in our olfactory worlds, just like my wife’s face is a visual object that seems more real to me than its component lines and curves.
And in the same way that you can create an essentially infinite number of faces out of a smallish set of lines and curves, our four hundred odor receptors can give rise to a dizzying number of different odor objects. A few years ago, researchers gave people mixtures of ten to thirty different odor molecules and asked whether they could tell them apart. Based on those results, they calculated that people ought to be able to distinguish at least a trillion different odor objects—a big step up from the fabled ten thousand smells of received wisdom. (By comparison, sensory scientists say our eyes can perceive a few million different colors and our ears maybe half a million pitches.) Since then, other researchers have pointed out that the “one trillion” number should be treated with caution, since it depends on several iffy assumptions. However, the general message—that the universe of smells is a huge one—still stands.
To understand how the brain processes these odor objects, I sought out Gordon Shepherd, one of the grand old men of olfaction research. Nearly everyone I spoke to at the Association for Chemoreception Sciences meeting in Florida, in fact, made a point of saying, “You should talk to Gordon Shepherd.” Some even suggested that he’s been so important to research on the neuroscience of smell that he deserved a share of the Nobel Prize for his work. He’s also written a terrific book, Neurogastronomy, about the biology of flavor perception.
When I caught up with Shepherd on the resort patio, I found a courtly, white-haired man in a red wool sweater, who was happy to spend the afternoon talking about olfaction. Odor objects have a physical equivalent in the brain, he told me. Each one of the nose’s four hundred odor receptors delivers its signal to a different part (or parts) of the brain’s olfactory bulb, the first relay station for odor information. If you imagine the olfactory bulb as a switchboard panel with lights corresponding to individual odor receptor types, then each odor object is represented by a distinct pattern of lights—its own olfactory image, in effect. But when your brain comes to process that pattern of lights, it doesn’t know whether they’re the result of a single odorant molecule or many: it just sees the pattern.
And we’re generally very bad at articulating complex patterns, says Shepherd. Just try to describe the face of someone familiar to you, or the art of Cy Twombly—you’ll probably struggle just as much as most people do in expressing the aroma of a beefsteak tomato or an artichoke. “It’s the same problem,” says Shepherd. “A highly complex image that’s almost impossible to describe in words.”
That certainly matches most people’s experience of talking about smells—and by extension, about flavor. Putting names to smells is something humans in general are “astonishingly bad at,” says Noam Sobel of the Weizmann Institute of Science in Israel, one of the most creative, and consistently provocative, smell researchers. To prove this incompetence to a skeptical family member, Sobel once asked her to close her eyes, then he pulled a jar of peanut butter out of the fridge, removed the lid, and waved it under her nose. Even though his relative ate peanut butter almost every day of her life, she couldn’t name that familiar smell. You can repeat the test yourself: Close your eyes and have a friend present you with some familiar household odors, and see how many you can identify. You’ll probably find, as Sobel and other researchers did, that you recognize all of them as familiar, but you can’t name even half of them successfully. (I once failed to identify the flavor of coffee, which at the time was my every-morning breakfast drink.) As one of Sobel’s colleagues is fond of pointing out, if you or I did that badly at naming colors or shapes, we’d go straight to a neurologist to see what’s wrong.
Another big reason we’re so bad at naming smells is that our brains process odor information—one of our most ancient senses—much differently than they handle newer senses like sight and hearing. Sights and sounds take an express route to the thalamus, the part of the brain that acts as the gatekeeper of consciousness. We’re wired to pay conscious attention to them. That direct line also means that sights and sounds have rapid access to the newer, more powerful brain regions that handle speech and language. In contrast, olfactory signals go first to the ancient, preconscious brain regions that control emotion and memory, the amygdala and hippocampus—which helps explain why smells are so powerfully evocative—and don’t pass through the gateway to consciousness and language until several stops later.
But there’s a second reason for our difficulty. In English—and most other Western languages—we pretty much lack a distinct vocabulary for describing odors. We describe smells, if we can describe them at all, by saying what they’re like: a New Zealand sauvignon blanc smells grassy, we say, or a furniture polish smells lemony, and that’s about the best we can do. Here’s an English-speaking American trying to put a name to the smell of cinnamon: ’’I don’t know how to say that, sweet, yeah; I have tasted that gum like Big Red or something tastes like, what do I want to say? I can’t get the word. Jesus, it’s like that gum smell like something like Big Red. Can I say that? Okay. Big Red. Big Red gum.” You’ve probably flailed about in a similar way trying to describe a smell—I certainly have. But we don’t do that for colors, for which we do have a specialized vocabulary. We don’t have to describe the colors of the Swedish flag, say, as lemonlike and skylike—we can call them yellow and blue.
And as it turns out, some cultures do that for smells, too. For a startling example of just how much better we could be at recognizing, identifying, and talking about smells, consider the Jahai, a small tribe of nomadic hunter-gatherers in the mountains of southern Thailand, near its border with Malaysia. The Jahai language has more than a dozen words to describe smells, none of which relate to the smell of any particular object. The Jahai might say, in their language, that something smells “edible” or “fragrant,” or, my favorite, “attractive to tigers.” Some of the actual concepts they’re expressing make no sense at all to an outsider—the word for “edible,” which sounds a bit like “knus,” is applied to gasoline, smoke, bat droppings, some millipedes, and the wood of wild mango trees, none of which strike me as particularly edible; “fragrant” includes several flowers and fruit, some other kinds of wood, and a species of civet cat.
However bizarre it seems to us, that specialized vocabulary makes it much easier for the Jahai to think and talk about smells. When researchers gave a standard smell-identification test to ten Jahai men, they found that the Jahai tended to be quick and consistent in describing the smells, even though most of the actual odors used in the test were unfamiliar to them. In fact, the Jahai proved to be just as comfortable describing odors as they were at describing colors. By comparison, ten English-speaking Texans were quick and precise at describing colors, but all over the map when it came to the smells. (One of those Texans was the source of the hopelessly inarticulate description of cinnamon quoted above.)
Fortunately, vocabulary is something we can learn with a little effort. Even we Westerners have specialized vocabularies for smells within certain domains. Just listen, for example, to a professional perfumer pick apart the olfactory spectrum of a fragrance, nimbly identifying the floral top notes, musky base notes, and the like. An experienced wine buff can do the same thing with what’s in her glass. In fact, tests show that wine experts’ noses are no better than yours or mine—they’ve just had more practice at noticing and putting into words what they’re smelling. Almost anyone can improve their nose for wine, no matter how hopeless they feel. As long as you can recognize that one wine is different from another, you’ve got the basic perceptual tools you need. All it takes is a little effort to nail down the vocabulary.
But there’s a limit to how well even the professionals can deconstruct the aromas of a glass of wine or a whiff of perfume. Way back in the 1980s, Australian psychologist David Laing presented volunteers with familiar odors like cloves, spearmint, orange, and almond singly or in combinations of up to five. He provided a list of seven possible odors and asked the volunteers to check off all the odors that were present. People did okay at single odors or mixtures of two, but their performance fell off dramatically at three or more. Not a single person correctly identified all the elements of a five-odor mixture. Later studies have confirmed this result—even professional flavorists and perfumers just don’t seem to be able to correctly identify more than three or four odors in a mixture, probably at least partly because the odors interfere with one another in our nose or brain. With this in mind, I’m inclined to look skeptically at wine tasting notes that claim to identify six or eight aromas.
Are there ways to help identify odors? That is, can we somehow sort odors into categories to make it easier to understand them? We do that for taste, after all: There’s sweet, sour, salty, bitter, umami, and maybe a few others. Color and sound are also simple to sort: It’s all about the wavelength of light or the frequency of a sound vibration. But odors are caused by thousands to billions of unique molecules, each with a different shape and each, apparently, activating a different set of odor receptors. How to make sense of all this?
Of course, people have tried, beginning long before they knew anything about molecules. Carl Linnaeus, most famous for his method of classifying all living beings, had a go at odors, too. All odors, he thought, fall into seven categories: fragrant, spicy, musky, garlicky, goaty, repulsive, and nauseating. A contemporary, Albrecht von Haller, had an even simpler system, sorting all odors somewhere on a spectrum between ambrosial and stench. And as we’ve seen, nearly two centuries later Crocker and Henderson—the ten-thousand-odors duo—thought there might be four dimensions: fragrant, acid, burnt, and goaty.
The list goes on and on, with many classification systems appearing bizarre when viewed from the outside. The Suya of Brazil regard odors as bland, strong, or pungent. Sounds sensible—but oddly, adult men smell bland, while women smell strong and the elderly smell pungent. The Serer-Ndut of Senegal have five categories: urinous, rotten, milky/fishy, acrid, and fragrant. Monkeys, cats, and Europeans have a urinous odor. Rotten-smelling things include cadavers (obviously), mushrooms (understandably), and ducks (um . . . ); acidic smells include those of tomatoes and spiritual beings. (Prizes for anyone who can explain what tomatoes and ghosts have in common.) The Serer-Ndut themselves have a fragrant odor, the most positive of the five categories—but then again, so do onions.
Any classification system that uses words (and their underlying concepts) is bound to suffer from cultural blinkers. You name what’s important to you—and that, overwhelmingly, is what’s in front of your nose from day to day. “We” always smell good, and “they” smell bad. You can’t understand goaty odors if you’ve never encountered a goat. As we’ll see, professional flavorists sort odors into categories like fruity, floral, and spicy: basically, the kinds of ingredients they deal with in their daily work.
Is there any way out of this cultural trap, any way to sort odors into dimensions without having to resort to language? Andreas Keller of Rockefeller University thinks so. A big bear of a man with a soft German accent, Keller works the boundary between sensory science and philosophy, making significant contributions to each. To test the dimensionality of smell from first principles, Keller sets out three vials with different odor molecules and asks people to group them by similarity. If everyone picks the same pair of odorants as most similar, he knows that those two sit together along some dimension—they’re both fruity, say. If no pair is put together more commonly than the others, on the other hand, then all three odorants must be equidistant from one another, like the points of an equilateral triangle. That means there must be at least two dimensions. Four equidistant odors require three dimensions, and so on. The concept is straightforward, even though the math gets more than a little bit hairy as the number of dimensions grows.
Keller’s hope is that sooner or later, adding more odors no longer requires new dimensions. The big question is whether that happens after just a few dimensions—in which case odors really do fall into meaningful categories—or many. The worst-case scenario would be that there’s a separate dimension for each of our four hundred or so odor receptors, which would effectively mean that there is no underlying structure, no effective way to group smells into perceptual categories. “I think everything up to about twenty or thirty dimensions would be interesting,” says Keller. His experiments are still ongoing as I write, but he’s less and less optimistic that he’ll end up with a manageable number of dimensions.
Our poor performance at naming and sorting smells is, no doubt, part of the reason why most people think humans are olfactory incompetents, with noses that are good for little more than keeping our glasses from falling off. But in fact, we’re too hard on ourselves. Our noses are a much more powerful tool than most of us realize—more sensitive, in many cases, than the most expensive piece of laboratory equipment.
Case in point: If you had happened to cross the University of California at Berkeley campus in the early 2000s, you might have noticed an undergraduate—blindfolded, earplugged, and wearing coveralls, knee pads, and heavy gloves—crawling across the lawn with nose to ground, zigzagging slightly back and forth. Was he rolling a peanut across the campus with his nose as punishment for some arbitrary offense during a fraternity initiation? Was he groveling before more senior fraternity brothers? No. He was following a scent trail laid down by a chocolate-soaked string—and doing it almost perfectly.
This rather odd spectacle was another of Noam Sobel’s slightly skewed brainchildren. (At the time, Sobel was a junior professor at Berkeley, though he’s now at Israel’s Weizmann Institute of Science.) For the chocolate-tracking experiment, Sobel and his students tested a total of thirty-two people and found that twenty-one of them could find and follow the chocolate track by nose alone, with all their other senses blocked. Better yet, when Sobel gave four of the volunteers a chance to practice repeatedly, every one of them got better at following the trail, moving faster and casting about less. When the trackers tried again while wearing a nose clip, every one of them failed to find the trail—clear proof that they weren’t navigating by some other cue that the experimenters had overlooked.
And it’s not just that we’re less worse than we thought: our noses actually compare favorably with those of other animals—even ones renowned for their sense of smell. Matthias Laska, a psychologist at Linköping University in Sweden, has been measuring the acuity of animals’ noses for decades, since long before Sobel’s chocolate study. The gold standard for this sort of thing is to measure the olfactory threshold, the lowest concentration of an odorant that can be detected—exactly what Doty’s machine tried to measure for my nose. Since you can’t just ask a monkey or an elephant whether it can smell something, Laska does the next best thing: He teaches the animal to associate the odor with a food reward—a yummy carrot for the elephant, for example, or a peanut for a squirrel monkey. Then he lets the animal choose one of two boxes: one unscented and empty, and the other bearing the tell-tale scent and containing the treat. If the animal picks the treat consistently, it must be able to smell the signal, and Laska repeats the test with a lower concentration of the odorant. When he gets to the point where the animal can’t tell which box has the treat, he knows the odorant signal has fallen below the olfactory threshold.
Over the years, Laska has used this method on everything from bats to mice to elephants to several species of monkey. Out of curiosity, he compared his results with what other researchers had reported for humans—and noticed that the animals weren’t necessarily any better smellers than we are. Intrigued, he started searching the literature for every study he could find that reported an olfactory threshold for a nonhuman animal, then looked to see if he could find a comparable threshold for humans.
The results showed that his initial comparisons weren’t a fluke. Human noses are more sensitive than those of rats for thirty-one of the forty-one chemicals that have been tested on both species, for example. Humans even outperform dogs in detecting five of fifteen scents. “The traditional textbook view that humans have a poorly developed sense of smell is not warranted,” says Laska. “We are not that hopeless.”
If so, why do customs agents use beagles instead of Bostonians to detect drug smugglers? Why don’t we track our dogs through the park as readily as they track us? Part of the difference may be that most of the time, we’re distracted by our senses of sight and sound. “Except for smell researchers such as me,” says Laska, “we are not constantly aware of the odor stimuli in our environment.” For one thing, it’s simply harder to pay attention to smells than to sights or sounds. If you’re looking for a friend’s face in a crowd, or scanning a bookshelf for a particular title, your vision is focused on a specific point in space. Similarly, when you’re trying to listen to one conversation amid a noisy cocktail party, you’ll turn to face the speaker and concentrate on that one spot. This tight spatial focus helps us notice what we see and hear.
By contrast, we don’t ordinarily focus our smelling in the same way. Sure, you can stick your nose into a wine glass, or take a sniff at the back of a toddler’s diaper—both instances where we really do pay attention to odors. But that’s not the way we usually use our noses. For most of the day, our noses aren’t focused on any one particular thing. Instead, we smell an undifferentiated mix of everything that’s going on around us, the olfactory equivalent of peripheral vision with nothing in the center of focus. Even when we’re trying to pay attention to a particular odor—what’s that herb in this sauce?—studies show we don’t get any better at detecting that target.
Subconsciously, we probably make a lot more use of smell than we think. For example, did you know that you tend to smell your hand shortly after shaking hands with someone? Well, you do. We all do. Sobel—him again—secretly filmed unsuspecting students who thought they were waiting idly to participate in a psychology experiment. The experimenter came in, introduced him- or herself—sometimes with a handshake, sometimes not—then left the room again. Within seconds, the students who had shaken hands would lift their hand to their nose and sniff it—especially if the experimenter was of the same sex as the student. “We would see people sniffing themselves just like rats,” Sobel told a reporter. Clearly, we’re taking in information of some sort, even though we’re not aware of it. (Knowing this may forever taint your experience of greeting people.)
Sight and sound also come to us in a continuous stream, while smell comes in discrete sniffs, separated by several seconds of “olfactory silence.” That may not seem like an important difference, but it is. Continuity makes it much easier to notice changing sights and sounds—and when there’s a break in continuity, we often become “change blind.” In one famous experiment, an actor carrying a map approached an unsuspecting pedestrian and asked for directions. Before the person finished giving the directions, an annoyingly oblivious pair of “workers”—actually accomplices in cahoots with the experimenters—barged between the two carrying a large door. While the view was blocked, a second actor took the first one’s place. After the workers left, half the people simply resumed giving directions and never even noticed that they were now talking to a different person. They were blind to the change that happened during the visual gap.
If change blindness affects even frontline senses like vision, it’s likely to be even more significant to our sense of smell, where the equivalent of a large door passes through after every breath. This change blindness makes the changing smellscape much harder to keep track of, and is another reason why we don’t notice smells the way we do sights and sounds, says Sobel.
But there’s an even simpler reason why we humans don’t often pay as much attention to smells as our dogs do. Dogs’ noses are down there near the ground where most of the smells are, while ours are way up in the air. Except in unusual circumstances, like Sobel’s human chocolate hounds, we simply aren’t aware of the rich olfactory world of scent trails that we could be monitoring.
Our noses may be poorly positioned for following scent trails on the ground, but there’s another class of odors that they’re perfectly positioned to appreciate: those that contribute to the flavors of food and drink. In fact, we humans might be the virtuosos of the flavor world. To understand why, we need to recognize that what we think of as “the sense of smell” is really two different senses that share the same equipment, like taxi drivers sharing a car on alternate shifts.
Until now, we’ve been talking mostly about smell as a process of sniffing air in through the nostrils to the olfactory epithelium. This kind of smelling tells you about what’s out there in the world: fragrant flowers, burning leaves, your nearby lover. Experts call it orthonasal olfaction, but it’s fine to think of it as just sniffing.
But there’s another route that odor molecules can take to get to the olfactory epithelium: through the backdoor. This retronasal olfaction only happens when we eat or drink something. As we exhale, some of the odor compounds from the food or drink rise up the back of the throat and into the nasal cavity from the rear. In fact, the shape of our throat helps push food odors into our nasal cavity as we exhale. To show this, Gordon Shepherd and his colleagues used CAT scans to determine the precise shape of the nose, mouth, and throat of a fifty-eight-year-old volunteer, then used a 3-D printer to build a full-scale model of her anatomy. When they measured airflow through this model, they found that air inhaled through the nose forms an air curtain in the throat that effectively walls off the mouth, so that food particles and odor molecules from a mouthful of food aren’t swept into the lungs. (That’s a good, practical reason for chewing with your mouth closed: airflow through an open mouth disrupts the air curtain.) The curtain also ensures that our orthonasal sniffing isn’t contaminated with food aromas from the mouth. But when we exhale, this air curtain shuts off, so that odor molecules from the mouth can eddy up into the nasal cavity and reach the olfactory epithelium. Retronasal olfaction, in other words, is all about flavor.
And according to Shepherd, retronasal olfaction is a skill that we humans are uniquely good at. Think about how the shape of a dog’s head compares with yours. The dog has a long snout and its head projects forward from the neck, so that its nasal cavity sits well forward of the back of the mouth. As a result, the retronasal path to the olfactory epithelium is a long journey down a narrow tube, and relatively few odor molecules are likely to make the trip. Dogs’ noses, in other words, are optimized for orthonasal smelling. In contrast, humans have relatively short noses. More importantly, our upright posture means that instead of projecting forward, our heads sit immediately above our necks, so that retronasal odor molecules just have to waft up a short way from the back of the mouth to the olfactory epithelium. It’s a much shorter, easier path, and it’s reasonable to think that our retronasal olfaction—and therefore, our appreciation of flavor—is correspondingly better. (We also have bigger brains to think about the flavors we taste, which further sharpens our appreciation. More on that in a later chapter.) The result is that when you sit back and appreciate the complex flavors of a soup or a glass of wine, you’re doing something that few other species—perhaps none—would be capable of. We should feel special!
The existence of these two ways of smelling might explain one of the peculiarities in our experience of flavor. Most of the time, sniffing a food tells us pretty much what flavor we’re going to get when we eat it—but not always. We can all think of foods—really stinky cheeses such as Limburger come to mind, and the notorious Asian fruit known as durian—that smell vile as you’re trying to work up the courage to eat them, yet “taste” divine once you actually put them in your mouth. Similarly, almost everyone loves the smell of freshly brewed coffee, but not everyone likes its flavor. Those differences—one professional flavorist told Mainland that they happen for about 15 percent of odors—would make sense if we respond differently to orthonasal smells than to retronasal ones.
Confirming this scientifically is easier said than done, because it’s not easy to study retronasal olfaction. You can’t just squirt a dose of coffee in someone’s mouth, since that also delivers taste and touch signals that aren’t there when you wave a cup of the stuff under their nose. Instead, scientists have to go all techno and thread two plastic tubes into the nose so that one opens just inside the nostrils and the other at the top of the throat. Then they can use a computer to deliver precise doses of odorant to either the orthonasal or the retronasal tube, while flowing unscented air through the other tube to avoid any telltale puff-touch signals.
These studies show that retronasal odors are indeed handled differently from orthonasal ones. For one thing, olfactory thresholds tend to be lower for smells that arrive orthonasally. That makes sense: Orthonasal delivers early warnings of changes in the environment, which would need the most sensitive detector available; retronasal, on the other hand, perceives the flavor of foods that are already in the mouth—there’s plenty of stimulus there, and it only needs to pick out the distinctive features so you can identify what you’re eating. And in keeping with that division of labor, retronasal odors turn out to be more effective at stimulating the brain regions responsible for processing flavor.
There’s likely to be a physical reason, too, why the same food might yield a different experience orthonasally and retronasally, and that has to do with the direction of airflow. Researchers haven’t worked out the details yet, but it’s becoming clear that our four hundred or so odor receptors aren’t scattered randomly across the olfactory epithelium, but instead are sorted into several zones with a different mix of receptors in each. In particular, our most ancient odor receptors—inherited from our fish ancestors, and tuned to water-soluble odorants, the only kind that fish could experience—are clustered right at the front of the olfactory epithelium. That means they get first crack at orthonasal odors, but are last in line for retronasal ones. By the time retronasal airflow reaches these fishlike receptors, many of the water-soluble odorants may have already dropped out, mired fruitlessly in the watery nasal passages farther back. Sure enough, Sobel (again!) has found evidence that the nose is actually sorting odors from front to back in the nose. The world smells different to each nostril, he finds, with the higher-airflow nostril more attuned to non-water-soluble odors, which the orthonasal air current carries farther back to the relevant receptors. For the same reason, odorants should sort differently when inhaling orthonasal smells than when exhaling retronasal ones. The real clincher would be if someone could show that the wonderful aromas of fresh coffee, and the obnoxious aromas of ripe cheeses and durian, tended to be water soluble so that they’re more accessible orthonasally than retronasally. Unfortunately, no one has done that yet, as far as I know.
The same day that I’d talked with Shepherd in Florida about retronasal olfaction, I unexpectedly put my newfound knowledge to use. I ate dinner that night in a cheap-but-excellent Mexican restaurant not too far from my cheap-but-adequate motel. I ordered a Negra Modelo, my favorite Mexican beer, and the waiter set the bottle on the table. I was about to ask for a glass—I’ve always been a bit of a snob about drinking my beer out of a glass “to appreciate the flavor better”—when I recalled something Shepherd had told me that afternoon. We forget what we know about retronasal smell, he said, as soon as we sit down to eat. “Think about it. Most of the flavor is when you’re breathing out.” Aha, I thought. The glass won’t do anything for the flavor of the beer—it will only enrich my orthonasal experience, which is different. I drank my beer from the bottle—and sure enough, the flavor was all there.
But what flavor was it? Let’s pause that scene—me with beer bottle to mouth, enjoying the chocolate and caramel flavors of the Negra Modelo—and ask whether someone else would have the same flavor experience. We already know that people differ in their taste receptors, so that your experience of the beer’s hoppy bitterness could be different from mine. And we already know that even people who taste a lot of bitter—like me—sometimes learn to love it in their beer. But since the lion’s share of flavor comes through retronasal olfaction (remember the jelly bean test!), it’s also worth looking at how people differ in their sense of smell.
We’ve already seen that people have about four hundred odor receptors, more or less. Here’s where things get interesting. Of those four hundred, about half work in everyone, so all of us can smell the molecules they target. The other half work in some people and not others, which means there’s a huge range of stuff that some of us can smell and others can’t. To further complicate things, even the working receptors often have small genetic differences from person to person, so that you might be more sensitive to certain odors than I am, and vice versa. In fact, the sample of one thousand genomes showed that you and I are likely to have meaningful differences—that is, differences that affect odor detection—in about 30 percent of our odor receptors. That means your flavor world is different from mine, and from your best friend’s, and even from your parents’. Chances are that no two people (except, perhaps, identical twins) share exactly the same sense of smell. Every one of us lives in their own unique flavor world.
Not only does each person have their own distinctive set of working and broken odor receptors, but every person’s nose probably mixes its receptors in different proportions. The evidence for this comes from Darren Logan, a virtuoso molecular geneticist at the Sanger Institute in Cambridge, England. Logan is a slender, compact bundle of energy with trendy glasses, dark hair cut in a short buzz, and a fascination with olfactory receptors. In particular, he’s used gene-sequencing technologies to measure the abundance of each of the hundreds of olfactory receptors in the nose. There’s a catch, though: To properly census an individual’s complete repertoire of receptors, he needs to study entire noses—or, more precisely, entire olfactory epithelia. It’s hard to convince a living person to sacrifice their sense of smell for science, and tissue from cadavers, even fresh ones, hasn’t been good enough. So Logan works on mice instead.
Mice use all 1,099 of their working odor receptors in their nose—but not in equal proportion, Logan finds. Instead, a few of the receptors are very common, a slightly larger number are moderately common, and most are rare. And that pattern seems to be dictated by genes. One of the advantages of working with mice is that you can pull out a catalog from a mouse-supply company and buy as many genetically identical animals as you want, from any of several very different strains. Sure enough, when Logan compares two genetically identical mice, they have exactly the same pattern of odor receptor frequencies. In other words, when it comes to the mix of odor receptors in a nose, genes rule. Pick a different mouse strain, and the pattern is much different. Take a mouse from a different subspecies, and the differences are bigger still, with half the receptors differing in abundance by as much as a hundredfold. “That means one strain is, in theory, a hundredfold more sensitive to whatever that receptor is detecting,” says Logan.
We have to be cautious about extrapolating from mice to people—plenty of researchers have ended up with egg on their face from doing that too glibly—but if people are like mice in this respect, then not only do you and I have slightly different sets of working odor receptors but we’re probably genetically programmed to mix them in different proportions. If so, then the olfactory chord that coffee sounds in your brain might be richer in the horns, while mine is richer in the strings. That would help to make your flavor world even more different from mine. As I write this, Logan is trying hard to secure fresher, better human olfactory epithelia so that he can test this idea directly. He’s got nine so far, donated by living people who were about to lose them anyway as a result of treatment for a rare cancer, but he needs a lot more. Stay tuned.
All this talk of genetics makes it easy to assume that where the sense of smell is concerned, you’re stuck with the hand nature dealt you. To some extent that’s true, of course; if you only have broken copies of a particular odor receptor gene, you’re never going to be able to make use of that receptor. But the reality is a bit more complex than that. Just ask Charles Wysocki.
Wysocki has been at Monell since the 1970s, making him one of the center’s longest-serving researchers, and right from the beginning he’s been fascinated by individual differences in the sense of smell. (For what it’s worth, early in his career, he also published a paper on how to tell male newborn mice from females.) It was Wysocki, together with Gary Beauchamp, who showed more than thirty years ago that a person’s genes help determine whether they can smell androstenone, a musky, urinous-smelling compound that male boars use to signal their virility and is also a key flavor component in truffles. Their study was one of the first clear proofs that genes affect the sense of smell. But along the way, they learned something else, too.
Now semiretired, Wysocki is a small man with a slight stoop, thick gray hair, and an extravagant organ-grinder’s mustache. “I started working with the compound in 1978,” he recalls. “I could not smell it at all—was totally oblivious to it. I just had to trust the scales, the balances, that I was making the right stuff.” After a few months of working with the compound daily, he started noticing a new odor around the lab. To his surprise, the culprit turned out to be androstenone. Somehow, he had acquired the ability to smell it. And he wasn’t the only one—some of his technicians reported the same thing. Intrigued, he tested a larger sample of people. Sure enough, half of the nonsmellers became much more sensitive after a few weeks’ exposure to the compound. “These people went from a nonsmeller to a pretty sensitive smeller,” he says—though they never got to be as good as the best natural smellers, who can detect androstenone at just a few parts per trillion.
The picture gets even more complicated. Wysocki has tried the same experiment with other odorants, such as the sweaty-smelling 3-methyl-2-hexenoic acid, and found no change in detection ability. His colleague, Pam Dalton, showed that repeated exposures to Maraschino-cherry-smelling benzaldehyde do lead to improvement—but only in women of reproductive age, not in men, young girls, or postmenopausal women. Even now, nearly three decades later, Wysocki’s not sure why some people get better at detecting some odors after being exposed to them, while other people do not.
Some of the answer, no doubt, has to do with the odor receptors themselves, and the way they interact with the odorants. But some, too, must depend on the way your brain processes odor information. People who measure olfactory thresholds quickly learn that they don’t stay put. Your detection threshold for a particular odor can vary many thousandfold from one test to the next—and it doesn’t matter whether the tests are separated by thirty minutes or more than a year. That’s probably at least partly because our noses don’t always claim the same share of our conscious attention.
That’s not to say we can’t get better at recognizing and identifying odors. Practice clearly helps. You can prove this yourself by pulling a bunch of spices off your kitchen shelves and trying to identify them with your eyes closed. After a few rounds of trial and error, you’ll get better. The most vivid demonstration of the power of practice, though, comes from wine experts, who are much better than the rest of us at putting names to the aromas rising from their tasting glasses. But whenever scientists have tested such experts (which doesn’t happen often—what wine pundit would run the risk that their nose might be shown up as below average?) they’ve found that their olfactory ability is nothing special. What gives their ordinary noses the ability to perform extraordinary feats of perception is simply experience. That’s encouraging news for anyone who wants to sharpen their flavor senses.
If you’ve booked a table at the best restaurant in town, or plan to open a treasured bottle of wine, there may be other ways to amp up your sense of smell to wring more flavor out of the experience, though you may look a bit odd in the process. Nasal sprays containing sodium citrate or a compound called EDTA bind calcium ions in the mucus layer coating the olfactory epithelium, and this makes olfactory cells more sensitive for a few minutes before things return to normal.
If the thought of spritzing your schnozz every fifteen minutes at the French Laundry restaurant in California is a bit off-putting, here’s another option: Use one of those nasal dilator strips that professional athletes wear across the bridge of the nose to hold their nostrils open. Athletes use them to help inhale more air faster, but as a side effect the dilators also improve airflow to the olfactory epithelium. Tests have shown that this makes it easier to detect and recognize odors.
But even if experience can alter our odor perceptions somewhat, it’s clear that our genetic makeup of odor receptors is driving the flavor-perception bus. It’s not just a question of odor receptors, though. More than a thousand other genes affect what happens in the sensory pathway after an odor binds to its receptor. Differences in these genes undoubtedly mean that some people have a more acute sense of smell overall than others do, just as some people see or hear better than others. Not many researchers have measured how big these differences in general olfactory sensitivity are, alas, so the subject remains a big question mark.
We’re just starting to understand how these differences in genetic makeup affect our experience of flavor. For example, many people—but not all—notice a distinctive asparagus-type odor to their urine shortly after eating that vegetable. Proust noted that asparagus “transforms my chamber pot into a flask of perfume.” For many years, scientists assumed that the smelly pee folks digested asparagus in a way that produced an odorous molecule called methanethiol, while the others—can we call them sweet pees?—did not. But in 1980, researchers fed a pound of canned asparagus to a sweet-pee volunteer, collected his urine afterward, and offered a whiff to unsuspecting volunteers. To the researchers’ surprise, they found that anyone who could smell asparagus in their own urine could also detect it in the supposedly sweet pee of the donor. In other words, the difference between sweet and smelly is not in the digestion of the eater, but in the nose of the smeller. We now know that a particular odor receptor, OR2M7, may be responsible. (Actually, it turns out that there are a few people who really do produce odorless urine, for unknown reasons.)
It’s likely that differences in odor perception help explain why people like different foods. Take cilantro, for example. Most people love its bold, grassy flavor, but a substantial minority detests the stuff, describing its flavor as soapy or “buglike.” (How do they know that, I wonder?) Scientists at the personal-genomics company 23andMe recently linked this preference to differences in or near the OR6A2 gene.
But on closer examination, there’s a cautionary story here for anyone who’d like to believe that genes are destiny. If every person with one variant of OR6A2—let’s call it variant X—loved cilantro and every person with variant Y hated it, then we’d say that OR6A2 explained 100 percent of the difference in perception. If OR6A2 had no effect at all, of course, it would explain 0 percent of the difference. The closer to 100 percent you get, the stronger the effect. For cilantro preference, OR6A2 turned out to explain less than 9 percent of the difference in perception. In practical terms, OR6A2 isn’t telling us much about cilantro preference at all.
A lot of olfactory genetics turns out to be like that, as I learned when I asked Joel Mainland to profile my own olfactory genes. Since scientists know only a handful of olfactory receptor genes so far that affect perception, this involved identifying my variants of just a few OR genes, rather than doing my whole genome sequence. A few weeks later, I visited his lab and sat through a battery of olfactory tests where I rated the intensity and pleasantness of the odors targeted by those genes.
The results could only be described as disappointing. Take OR11A1, for example. This OR detects an earthy-smelling molecule called 2-ethylfenchol that sometimes appears as an off flavor in beer and soft drinks. Three variants, or alleles, of this OR are common in the human population, one that is good at detecting 2-ethylfenchol and two that are relatively poor at the job. Mainland’s peek at my genome showed that I have two copies of the sensitive allele, which should make me an especially sensitive smeller of 2-EF. And, since people tend to find stronger odors less pleasant, Mainland predicted that I’d rate 2-EF more unpleasant than the average person.
In fact, though, both predictions turned out wrong. On a scale from 0 (undetectable) to 7 (overpoweringly intense), I rated the intensity of 2-EF as 3.4, much less than the 4.8 that Mainland predicted. I gave it a 5.0 for pleasantness (evidently I like the smell of dirt), while Mainland predicted I’d rate it just 3.2, or mildly unpleasant. Other pairs of receptor and odor, such as OR10G4 and smoky-smelling guaiacol, OR11H7 and cheesy/sweaty-smelling isovaleric acid, and OR5A1 and floral-smelling beta-ionone gave similarly confusing results. Occasionally things worked out more clearly. I’ve got one functional and one broken copy of OR7D4, the receptor that detects androstenone, the boar-urine-and-truffle odor that Wysocki studied. That should leave me as a moderate smeller and an enthusiast for truffles—which, in fact, I am. But it doesn’t always turn out that way, says Mainland. “We have a lot of people who have two functional copies and don’t smell it, and we have some people who have two nonfunctional copies and still smell it.”
It’s not surprising that single genes do such a poor job of predicting flavor perceptions, says Mainland. Since most odorants trigger more than one receptor, my response to any given odor probably depends on my genetic makeup at several genes. That muddies the waters a lot. “I’m dividing you based on one receptor, but you also have 399 other receptors, and that’s a lot of noise to push through,” he says. For example, he and his colleagues have found that OR10G4 can detect both guaiacol and vanillin, the key molecule in the aroma of vanilla, but it’s much more sensitive at detecting the former. When they look more closely, they find that people with a damaged copy of OR10G4 tend to report that guaiacol smells less intense, but report no difference in vanillin—which, presumably, depends largely on another receptor instead. Clearly, linking genetics to flavor perception still has a long, long way to go.
What we’d really like, of course, is to understand olfaction well enough so we can reproduce smell sensations artificially, as we do for sights and sounds. When Luke Skywalker’s X-wing Starfighter destroys Darth Vader’s Death Star, we see Luke in the cockpit, even though what’s really before us is just pixels on a screen. That’s because we know how to make a video image that mixes those pixels in a way that our eyes and brain interpret just the same as if it were really happening. We hear the explosion, even though none really occurred (and no sound waves would travel through the vacuum of space, but that’s a different issue), because we know how to re-create sounds from a string of zeros and ones in a digital file.
We’re nowhere near being able to do that for flavor. Sure, you can find a few oddball episodes in cinematic history where people have re-created—or, more precisely, imported—specific odors that fit the scenes of a movie. Take Smell-O-Vision, for example. In 1960, film producer Mike Todd Jr. (Elizabeth Taylor’s stepson) employed a system for mechanically releasing odors into a movie theater during the movie Scent of Mystery. Audiences were supposed to get a whiff of pipe smoke, for example, when one particular character appeared onscreen. The system cost tens of thousands of dollars per theater—a lot of money in 1960—and didn’t work very well. In 2000, readers of Time magazine voted Smell-O-Vision one of the “Top 100 Worst Ideas of All Time.” Still, that hasn’t kept novelty-seeking filmmakers from trying again now and then, albeit usually using scratch-and-sniff cards instead of a forced-air system.
But all of these novelties merely used odors prepared ahead of time. In that sense, they’re the equivalent of showing someone a photocopied picture. The real goal of digital olfaction—being able to make up any smell (and hence, any flavor) you want, to order, by combining elements from a small set of “primary odors”—was nowhere in sight.
Today, several decades later, that goal might just be visible. At the very least, we can estimate the scale of the problem. Every smell on Earth must be encoded by some combination of our four hundred-odd odor receptors. In theory, then, an arsenal of about four hundred primary odorants, each of which tickled a different odor receptor, should allow you to mix and match to recreate any smell. In practice, the task ought to be somewhat simpler than that, because it’s likely that some of our odor receptors are redundant copies. For anyone interested in digitizing only flavor-related odors, the field gets a little narrower yet, since we can ignore all the receptors that are never activated by food odorants. In fact, Mainland thinks it should be possible to get at least a rough sketch of the odors—and therefore the flavors—of the vast majority of foods with many fewer primaries than that. He’s been working with a flavorist at Coca-Cola who claims that with just forty primaries, you can get a recognizable facsimile of 85 percent of all foods.
When I visited Mainland’s lab, he screwed the top off a vial and gave me a whiff of the concoction. “Do you recognize this?” he asked. It certainly smelled familiar, but—as so often happens when we try to identify smells cold, without any prompting—I found myself tongue-tied and unable to put a name to it. Once he told me—strawberry—it all snapped into place: Of course, strawberry! It was indeed a recognizable, though not perfect, imitation. A real strawberry contains hundreds of scented molecules. But with just four of these—cis-3-hexenol (cut grass), gamma-decalactone (waxy), ethyl butyrate (generic fruitiness), and furaneol (caramelized sugar)—Mainland can build a mix that smells recognizably like strawberry. It’s not perfect, he admits—more like a pixelated image than a high-resolution version. However, he says, “We’re okay with eight-bit graphics that gives you a sketch of what’s going on. If we’re making a poor strawberry, but it’s still strawberry and not cherry or banana, we’re happy with that.”
Even if he could match the real thing perfectly, people might not realize it. “The problem we have is that everybody tells us it’s a terrible strawberry,” Mainland says of his facsimile. “But if you smash up a strawberry and put it in an olfactometer, people will also tell us it’s a terrible strawberry.” In our day-to-day lives, it turns out, we don’t generally notice all the components of a familiar odor, so we often don’t have a very good mental image of what the real thing smells like—especially when we lack the visual context. People don’t usually notice the green, vegetative note in strawberry, for example, so its presence in a crushed-up real strawberry can strike them as false, somehow.
So far, all of Mainland’s efforts to mimic strawberry or blueberry or orange aromas use odor components that are naturally found in the target aroma. Ideally, he’d like to go one better someday. “What we would really like to do is make strawberry without anything that’s in a real strawberry,” he says. To that end, he’s intrigued by a molecule known to chemists as ethyl methylphenylglycidate, a mouthful unpronounceable without sounding like Sylvester the cat spluttering at Tweety Bird. To flavorists, the chemical is known as “strawberry aldehyde.” As you might guess from the name, it has a strawberrylike aroma and is often used as an artificial strawberry flavor, even though it doesn’t occur in a real strawberry. (You can’t always trust a name, though—despite its moniker, strawberry aldehyde isn’t actually an aldehyde.) Mainland would love to know whether strawberry aldehyde activates the same odor receptors as the components of real strawberry odor, to see whether that accounts for its mimicry.
But what if you wanted not just eight-bit graphics but a high-resolution image that reproduces the real flavor precisely? So far, the closest approach to this ultimate goal comes from a recent German study led by Thomas Hofmann at the Technical University of Munich. In what can only be described as a heroic assault on the university library, Hofmann and his colleagues (including the delightfully named Dietmar Krautwurst, who was clearly destined for a career in food science) read through more than sixty-five hundred scientific books and papers that analyzed the flavor molecules present in particular foods. They winnowed these down, selecting only the best and most detailed studies, until they ended up with more than two hundred food items—everything from mushrooms to taco shells, Scotch whisky to donuts—for which the key odorant molecules had been identified. Most of the papers even took things one step further by showing that a mix of those key odorants smelled indistinguishable from the real item.
The surprising thing is that the aromas, and hence the flavors, of all these diverse foods could be re-created using a palette of just 226 key odorants. That’s remarkably encouraging, given the thousands of smelly molecules present in that range of foods. Some of these key odorants are what they call “generalists” that turn up over and over again. The cooked-potato-smelling methional, for example, figures in the odor of more than half the foods, while green-grassy hexanal and fruity-fresh acetaldehyde play a role in 40 percent and 29 percent, respectively. Many other odorants contributed a distinctive note to just a few food items, such as garlic’s diallyl disulfide and grapefruit’s 1-p-menthene-8-thiol.
Sometimes, they found, it takes only a handful of key odorants to replicate a food’s flavor. Cultured butter, for example, needs only three: the buttery-smelling generalist butan-2,3-dione, coconutlike delta-decalactone, and sweaty-smelling butanoic acid. Other foods, like beer and cognac, required eighteen and thirty-six key odorants, respectively, to mimic their bouquet precisely—a lot, but still just 10—15 percent of the total set of primaries.
Of course, trying to build a digital-flavor unit with 226 primaries is still a huge technical challenge. But if you could do it—even if it took trained technicians and an expensive, well-stocked lab—then the sense of smell (and, by extension, much of flavor itself) would finally free itself from subjectivity and be on a truly objective footing. We could take an olfactory “snapshot” of a ripe Georgia peach or a tomato fresh from the garden in the heat of August and reproduce it exactly. We could save a famous chef’s signature dish and archive it in a museum. And we could collect flavor memories of our travels and revisit them at home, just as we now do with photographs.
There’s a lot of work still to be done before those fantasies can become realities. And not just on the olfactory front, either. As it turns out, there’s more to flavor than just taste and retronasal smell. The physical sensations of touch—texture, temperature, and the like—also play a huge role in it.