I QUITOS is a hard place to get to. Nestled deep in the Peruvian Amazon, the city can only be reached by air or water – no roads connect it to the rest of the world. But for , that remoteness is part of the appeal. An odour prospector for the French fragrance company Behave, Piquart went to Iquitos to search for new aromas. In particular, he was looking for a fragrant plant root that the local Shipibo people use in a love and friendship potion. The root, which the Shipibo call piri-piri, has a remarkable fruity-leathery scent that Piquart has now brought to perfumery.
Visiting isolated places in search of new smells shows just how keen perfumers are on striking olfactory gold. That is driven by the sheer might of the fragrance industry. Always big business, it is now huge, with for not just perfumes but everything from soap and shampoo to candles and air fresheners. That is a lot of money to spend on nice smells. But what makes us like the ones we do?
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Smell is the least understood of our major senses, making this surprisingly tricky to answer. Neuroscientists, psychologists and even AI researchers are beginning to unpick the mysteries of how we perceive scent, while at the same time, fragrance researchers are devising new ways to tickle our olfactory neurons.
The first clear lesson in what makes a good scent is that different cultures have different ideas about which smells are pleasant. “In Europe, people love anise,” says , a master perfumer based in New York and Berlin. “In America, I wouldn’t think of putting it in a fragrance.” Similarly, North Americans find the smell of the wintergreen plant highly pleasant, at least partly because it is a prominent ingredient in root beer. Europeans, in contrast, find it unpleasantly reminiscent of liniment, the stuff you might rub on aching limbs.
Personal experience plays a key role in judgements of odour pleasantness. Unlike the other major senses, the nerve impulses involved in smell connect directly to the limbic system, the primitive parts of the brain responsible for memory and emotion. As a result, we judge the pleasantness of odours by the emotional memories they evoke. “A simple example is the scent of clove,” says , a chemist now retired from Givaudan, the world’s largest fragrance company. “I love it, because when I was a child, my mother used to make apple pie and put cloves in. But clove oil is also used in dentistry, so someone who has had a traumatic dental experience when there was clove oil will not like clove.”
Learning disgust
In fact, Sell says categorically that all odour preferences – from our fondness for vanilla to our dislike of decay – are learned. As evidence, he points to the willingness of young children to investigate anything. “They will do things that would disgust an adult, like attempting to eat the contents of their nappies,” he says. “It’s the immediate aversive reaction from their parents that teaches them this is a bad smell.”
It is a view shared by many experts, though there is surprisingly little research to back it up. Some studies, however, show that the very same molecule can smell pleasant or unpleasant, depending on which associations are triggered. Many cheeses, for example, contain the same odorous molecule – isovaleric acid – as sweaty socks, says , an olfactory researcher and independent consultant based in New York. “ they’re smelling. Nobody likes it when they’re told it’s dirty socks,” he says. “The smell didn’t change, but the judgement did. Those judgements, obviously, are all learned.”
Case closed? Not exactly, because there is another layer to this argument – one that requires a deeper explanation of how the sense of smell works. Unlike vision or hearing, which perceive relatively well-defined aspects of the world – a narrow band of wavelengths of light and an even narrower band for sound waves, respectively – our sense of smell is tasked with recognising an essentially infinite number of different molecules
To do that, our noses contain roughly 400 different odour receptors. Scientists still don’t fully agree on how these receptors recognise odorant molecules: most think each molecule’s shape matches a complementary one on the surface of the receptor, but a few believe at least some receptors work by sensing the frequency of vibration in the molecule’s bonds. However it happens, though, each receptor recognises a different, often overlapping set of odorant molecules, and each odorant can trigger just one receptor or many different ones. What we recognise as a smell, then, is a particular pattern of odour receptor activation, like a chord played on a 400-keyed piano.
The picture gets even more complex because each of us has a different repertoire of odour receptors, so we each play on our own, unique keyboard. “Nobody smells things the same way,” says Sell. And small genetic differences between individuals can affect how well a receptor latches on to its odorants.
That is important, because an odour’s intensity has a lot to do with our perception of pleasantness. At low concentrations, an odour can be appealing, but as intensity goes up, people begin to find it less and less pleasant, says , an olfaction researcher at the Monell Chemical Senses Center in Philadelphia, Pennsylvania. , and thus perceived pleasantness. This might help explain, for instance, why people with one variant of the odour receptor OR6A2 are more likely to enjoy the smell of coriander than those with a different variant.
Odour receptors may not be the whole story, either. The mucus that lines the nasal cavity is loaded with enzymes that can alter odorant molecules before they even reach the receptors. No one knows yet how much difference these enzymes make to odour perception, but there are hints that they could be important. For example, some people describe a particular molecule as woody, whereas others describe it as raspberry. On closer study, it turns out that the two groups differ not in any odour receptor, but in an enzyme called CYP2A13, which converts the woody-smelling molecule to one with a raspberry odour.
“Many cheeses contain the same odorous molecule as sweaty socks”
These individual differences haven’t stopped olfactory scientists tackling the big question of what exactly makes an odour appealing. Given the molecular structure of an odorant, can we predict how pleasant people will find it? The first clue that this was possible came more than a decade ago. at the Weizmann Institute of Science in Israel and his colleagues asked 185 people to rate the pleasantness of 90 anonymous odorants. Then they turned to a database of physical characteristics of molecules – everything from number of atoms to various measures of shape, more than 1500 attributes in all – and used statistics to find out what combination of features best predicted pleasantness ratings.
They found that better smells tend to come from larger, more straggly molecules, while smaller and more compact ones tend to smell nastier. To provide an independent test of this conclusion, Sobel’s team predicted the pleasantness of 27 odours not used in the earlier experiments, before getting people to rate the smells. Sure enough, molecular size and compactness turned out to be a good – though not perfect – (Journal of Neuroscience, vol 27, p 10,015).
Since then, several other studies have yielded more or less the same result. “But why did the system evolve to extract that particular chemical aspect of the world? I don’t have a good explanation,” says Sobel. The answer, others speculate, might be to do with how our hunter-gatherer ancestors evaluated the freshness of potential foods. “The larger the molecule, the more intact the material you’re smelling is,” says Keller. “Decay bacteria eat the big compounds and break them down into smaller molecules. The smaller the molecules, the further away you are from life.”
Artificial intelligence can go even further in predicting odours. In 2017, Keller and his colleagues announced the results of their DREAM Olfaction Prediction Challenge, an international competition to see if there was a way to tell how a molecule smells just from its structure. Competitors were given data on more than 400 different molecules rated according to their pleasantness and other qualities such as fruitiness, spiciness and floralness, as well as physical descriptions of each molecule. The aim was to find out which machine-learning algorithm was best at predicting sensory attributes from molecular structure. Once entries were in, the researchers tested the accuracy of each program’s predictions on 69 other molecules.
, devised by Rick Gerkin at Arizona State University and his colleagues, was roughly 50 per cent accurate in predicting pleasantness ratings. That is better than it sounds, because a person’s rating of the same molecule varies somewhat from moment to moment. That variation sets an upper limit for accuracy – in this case, at about 65 per cent – for any algorithm. Gerkin’s algorithm had, in other words, predicted people’s pleasantness ratings almost as well as knowing how they had rated an odour on a previous encounter. It could also successfully predict descriptors such as “garlic”, “fish”, “burnt” and “sour”, raising the possibility of predicting the qualities of almost any molecule, and even of reverse engineering odorants by starting with a target smell and then making a molecule with that odour.
Whose nose
But these efforts have a big shortcoming: they focus on individual molecules. “There is no situation where you encounter just one type of odour molecule in nature, so all of us have been studying a stimulus that the brain didn’t evolve to decode,” says Sobel. “It would be a bit like saying you’ll try to understand how the brain processes language by studying pure tones. It just doesn’t work that way.” Sobel is now investigating how people perceive mixtures of odorants, though he won’t say much about his latest results because they are yet to be published.
In the meantime, we are left with expert hunches about what makes a pleasing mix of odours. “My best guess, which is really not very good, is that we love complexity,” says Luca Turin, a biophysicist at the Alexander Fleming Biological Sciences Research Centre in Vari, Greece. “We like an orchestral sound in smell space, so to speak.” The hundreds of chemicals in roasted, toasted compounds such as coffee or bread give a richness to their aromas that simpler mixtures can’t match.
“Surprisingly, it matters very little whether individual ingredients smell pleasant”
Master perfumers have a few tricks of their own when it comes to creating that richness in their own concoctions. A typical fragrance – whether intended for soap or a fine perfume – will usually have several dozen ingredients, and the perfumer must get the dose right for each one so that no single smell dominates. Perfumers also layer ingredients that evaporate at different rates, so that the fragrance evolves over time from evanescent top notes towards more lingering base notes.
Surprisingly, it matters very little whether individual ingredients smell pleasant. To add complexity to their formulas, perfumers often include small amounts of unpleasant sounding “animalic” ingredients, such as faecal-smelling skatole or the anal secretions of the civet, a small mammal from Asia and Africa (see “Scents from strange places”).
The desire to spice up scents is driving the hunt for new molecules for fragrance companies to add to their formulas. That is what leads Piquart to the Peruvian Amazon and many other remote parts of the world. There is no shortage of new ingredients to discover, he says. “There are many, many things that smell, many possibilities when I go to a country,” he says. “We have discovered only 20 per cent, maybe.”
Many companies, though, prefer to have their chemists synthesise the key odorants in the lab (see “Secrets of a fragrance laboratory”). With this approach, who knows what exotic molecules we will be smelling in the future.
Where does all this leave us in the hunt for what exactly makes a good smell? The perception of smells is a complex, subjective and counter-intuitive business, where even seemingly disgusting odours can be attractive. There is no simple formula. But that isn’t something to turn your nose up at.
Secrets of a fragrance laboratory
Not all new aromas are prospected out of the rainforest. Some are right under our noses, so to speak. “One of our biggest achievements was to extract apple. The fruits are full of water, and in perfumery we hate water,” says Hervé Fretay.
He directs the natural products division of Givaudan, a fragrance company that, along with three other large multinationals, controls more than half the global fragrance market.
Givaudan has also succeeded in extracting fragrance from ceps, the prized wild mushroom. “It doesn’t seem exotic, but for perfumery it was something really unique,” he says.
Once chemists find an interesting molecule, they play with it, making slight changes to see how they affect the odour. Givaudan chemists, for instance, took an extract of patchouli oil and fermented it, using enzymes to add peppery notes to its earthy and woody character. The result, an ingredient called akigalawood, is one of the hottest new perfume components.
Finding odour molecules isn’t the biggest challenge, though. “The problem nowadays isn’t getting molecules that smell like such-and-such,” says Charles Sell, a retired fragrance chemist. “The problem is getting a molecule that smells that way and doesn’t go off, doesn’t interfere with other ingredients or biodegrade quickly, and is totally safe on the skin.” Many citrus-scented molecules are unsuitable for use in candles, for example, because they flare and smoke, or form nasty, petrol-smelling compounds when burning.
Scents from strange places
When it comes to prized perfume ingredients – now made synthetically, you’ll be pleased to hear – our tastes are far from vanilla.
Ambergris
This rare aroma from intestinal secretions of sperm whales, found washed up on beaches, is one of the most expensive natural substances. It has been used in perfumes, medicines and aphrodisiacs for centuries.
Skatole
Named after skato, the ancient Greek word for excrement, this compound is found in faeces, but also in some flowers. Foul-smelling at high doses, it has a flowery aroma at lower levels.
Castoreum
Produced as a scent marker, this compound from glands near a beaver’s anus has musky, fruity notes.
Civetone
This strong, musky secretion from the anal glands of civets, smells pleasant at low concentrations.
