Inspired by sophisticated perfume fragrances, Italian scientist Luca Turin came up with an idea he then proved empirically. It could be summed up in just three words: fragrances are vibrations.
It’s remarkable how little we still know about the workings of our sense of smell. With sight and hearing, scientists know that they are carried by waves and vibrations. Images are made of light waves, while sounds are vibrations of air. As for the nature of smells, scientists still cannot agree on one theory. Traditionalists believe that particles of smell enter the nose and are then found by the right receptors, just like a key in a lock. However, some researchers believe that our sense of smell, just like sight and hearing, is based on vibrations. But what could be vibrating inside the nose, exactly? And how are those vibrations captured? Luca Turin, enfant terrible of biophysics and the biggest advocate of this hypothesis, was undoubtedly the best person to ask.
The inferior sense
If we want to start from the very beginning, we must go back some four million years. That’s when Australopithecus, on his way to further humanization, began walking on two legs and, as could be suspected, largely lost his sense of smell, so useful to him back when his nose grazed shrubbery. Further out on the path of evolution, we lost the functionality of the vomeronasal organ, used by animals to recognize pheromones – signals of fear or sexual availability, among others. Life could have been so much simpler if not for evolution…
Nature philosophers in ancient Greece considered the sense of smell to be inferior to the rest of our abilities. Hearing, they said, allows us to experience harmony. Sight lets us enjoy light, as well as the sky, sun and stars, inviting us to enter the world of ideas. They perceived smell as something more animalistic and primal.
Modern science seemed to have inherited this dismissive attitude towards olfaction, cemented by the French surgeon and anatomist Paul Broca. In 1879, he presented the results of his research, suggesting that the human olfactory bulb – the part of the nervous system responsible for experiencing smells – is remarkably small in relation to the brain size. This discovery led Broca to believe that sense of smell is much less important for humans than it is for dogs, cats or mice.
Not long after, in 1894, the German scientist Emil Fischer presented his theory of experiencing smells, still prevalent today and referred to as the lock-and-key theory. According to Fischer’s proposal, an odour particle falls into a receptor of the corresponding shape, inducing an impulse and sending the information to the olfactory bulb that passes it on to the brain. Similarly, the complementarity of structures, also called the guest-host system, is now used to explain many other phenomena of the human body, such as the workings of antibodies and antigens. This analogy lends some plausibility to Fischer’s theory, although it fails to explain some very serious doubts.
Shapes or vibrations?
In light of this theory, it is hard to explain several things, such as why particles of very similar construction can give the impression of a completely different smell. This issue captured the attention of some scientists, such as Scottish chemist Malcolm Dyson. In the trenches of World War I, he realized first-hand how important it was to recognize the smell of mustard (an indication of an incoming sulphur mustard attack – commonly known as ‘mustard gas’), or a musty hay odour (characteristic of phosgene, another lethal war gas). Those experiences left a mark on his health, but also encouraged him to carry on with his research. Dyson discovered that odourants of similar smells (olfactory groups) could have drastically different shapes while being made of the same sets of atoms. And so the scientist observed that various compounds of musky odours consist of a group made of carbon and oxygen, connected by a double bond (C=O). This discovery led him to coin a theory that it is not the shape of a particle but the vibrations of its bonds that create an odour.
At roughly the same time (we’re still in the 1920s), the Indian physicist Chandrasekhara Venkata Raman visited Europe. Upon seeing the opalescent azure of the Mediterranean, he theorized that the inelastic reflections of photons scatter some of their energy and cause vibrations of particles that are responsible for water opalescence. Inspired by Raman’s discovery, Dyson proposed a hypothesis that the nose is a type of Raman spectroscopy instrument used to determine the chemical structure of a particle by measuring the length of a wave emitted by it when moved. It was a breakthrough hypothesis, but scientists didn’t really try sniffing around it, as it did not explain how a nose can actually read those vibrations.
A solution emerged in the 1980s with findings of Luca Turin, the perfume-loving enfant terrible of modern science.
“The fragrance was, and still is, a radical surprise. A perfume, like the timbre of a voice, can say something quite independent of the words actually spoken. What Nombre Noir said, was ‘flower.’ But the way it said it was an epiphany. The flower at the core of Nombre Noir was halfway between a rose and a violet, but without a trace of the sweetness of either, set instead against an austere, almost saintly background of cigar-box cedar notes. At the same time, it wasn't dry, and seemed to be glistening with a liquid freshness that made its deep colours glow like a stained glass window.” This was the fragrant revelation experienced by a young Luca Turing in the Galeries Lafayette in Paris at the premiere of the Nombre Noir perfume. That’s when he decided to do serious research on the nature of a fragrance.
Leaning in favour of the vibrations theory, Luca came across a description of an analysis technique called IETS (Inelastic Electron Tunnelling Spectroscopy). It uses the quantum phenomenon called tunnelling – an electron’s ability to ‘melt’ when it penetrates the energetic barrier and emerges on the other side. During the IETS test, two metal plates are placed very close to each other. When voltage is applied to the negatively-charged plate (called a donor), electrons gather on it and are then pulled in by the second plate, charged positively (the acceptor). In the world of classical physics, electrons don’t have enough energy to make a jump between the plates, but since they are quantum objects, they can tunnel from donor to acceptor. It’s an elastic tunnelling process, as electrons do not lose nor gain any energy from the leap. But it can happen that an electron with a lower energy level appears on the acceptor side; that’s what we call inelastic tunnelling. In that case, some other compound has to exist between the plates in order to absorb the difference in energy levels.
Turin believes that the same phenomenon takes place in the olfactory receptors. In place of the donor plate, there is an electron nestled in the receptor molecule. Once an acceptor approaches – in the form of an odourant with matching vibration – the electron tunnels, and the excess energy activates proteins that cause neurons to send information.
Turin confirmed his theory with a series of experiments where he modified olfactory particles without changing their shapes. The scientist achieved it by replacing hydrogen with its heavier isotope, deuterium, whose nucleus has not only a proton but also a neutron, making it heavier so that it oscillates in lower frequencies. This seemingly innocuous swap resulted in a change in perceived smell.
Turin also cross-checked his findings in the opposite direction. Here is how he did it: thiols, a –SH functional group (where S signifies sulphur, and H is for hydrogen), have a peculiar odour, hailed by the beloved Polish cartoon character Tytus de Zoo in a little poem: “Rotten egg poured inside whole, garlic, onion, smells galore.” Knowing that the bond of sulphur and hydrogen vibrates on a frequency similar to barium and hydrogen bond, Turin predicted that a compound known as decaborane would have a similar odour. And he was right. This experiment was the first case of someone guessing a molecule’s scent based on its structure. That’s a feat that the whole perfume industry had struggled with for years, blindly producing molecules only to examine their fragrances post-factum (well, decaborane did not smell too nice, but that’s not the point here).
Turin’s theory caused a wave of criticism across the scientific community. When I asked the author about the reason for such defiance, he explained that apart from the aversion to novelty that is common even among scientists, his ideas, balanced between physics and biology, cause a mix of confusion and hostility. It also couldn’t have helped that among the most devoted advocates of the classic lock-and-key theory were Richard Axel and Linda Buck. They were the most accomplished of all olfactory system researchers, responsible for discovering the genes coding the proteins of the olfactory receptors.
We should also note (Turin did not say it to me, but it is common knowledge) that since the very beginning of his career, the Italian researcher has exhibited exceptional talent for getting into conflicts with the scientific community.
Aged 27, he moved from London to Nice; in the early 1980s, France invested generously in science, and its institutions attracted many talented students. Another advantage of the city was its proximity to Grasse, a centre of the perfume industry. For this reason, Nice was full of old pharmacies where Turin could shop to his heart’s content and grow his collection of unique perfumes and forgotten fragrances.
The idyll ended soon, when Turin, then a young scientist at the French National Centre for Scientific Research, accused his team leader of forging test results. And even though years later it was proven to be true, the Italian quickly became a persona non grata in all scientific circles over the Seine. Turin was unafraid to criticize big institutions, including the prestigious MIT, where he had worked for many years. In some interviews, he accused the management of predatory policies of grant distribution.
Despite his difficult character, the Italian managed to win himself some allies, such as Efthimios Skoulakis from the Alexander Fleming Biomedical Sciences Research Center in Greece. Skoulakis did a clever experiment on fruit flies. He locked the insects inside a labyrinth and sprayed acetophenone through one of the exits. The compound, known for its stifling sweet aroma of hawthorn or dried roses, attracted the flies every time. In the next stages of the experiment, the scientist left acetophenone in one part of the labyrinth but added a manipulated version of the same compound elsewhere. He gradually replaced hydrogen atoms with deuterium: first three, then five and eight atoms were swapped for the heavier isotope. When he replaced just three atoms with new ones, the flies got confused, as the olfactory difference proved to be minimal. But at five or eight atoms, flies picked up on the trickery and went straight for the original acetophenone instead, ignoring the manipulated version.
Turin also did some experiments on himself. He locked himself inside his laboratory with a deuterium-heavy version of acetophenone, took a few deep breaths, and decided, not without satisfaction, that just like he suspected, particles with altered vibrations give a different fragrance: “Less sweet, more solvent-like.”
But an experiment carried out on just one participant who, on top of that, was very interested in the results, is not enough in light of the scientific method. No wonder that Leslie Vosshall and Andreas Keller from the Rockefeller University replicated the experiment, inviting 24 volunteers to participate. The results, published in Nature Neuroscience, stated clearly that not a single participant noticed any difference between one fragrance and another.
It dealt a serious blow to Turin’s theory, but the rebellious Italian kept on going. In 2012, he conducted the same test once again at University College London, this time with a group of 11 volunteers. None of them recognized the altered acetophenone, which confirmed Vosshall and Keller’s findings. However, Turin had one more molecule ready for testing, in which he swapped not eight, but 28 hydrogen atoms for deuterium. This time, most of the subjects noticed that the odour had changed.
Where two worlds meet
The various applications of quantum mechanics in biology are summed up well in the fascinating book Life on the Edge: The Coming of Age of Quantum Biology by British physicists Jima Al-Khalili and Johnjoe McFadden. The authors prove that the main obstacle in accepting the quantum side of life is the very particular quality of quantum events. A regular rubber ball will not roll over to the other side of a hill unless it goes at a certain speed. Meanwhile, an electron is perfectly capable of doing so, through the previously described event called tunnelling. In the macroscopic world, such miracles never happen, as can be confirmed by anyone who has ever tried to tunnel their head through a wall.
And yet, the authors show us that there are cracks where those two realities meet, and that’s where quantum mechanics can affect our life processes. Such events belong to the field of quantum biology, a relatively young science that emerged in the late 1990s. That’s when the quantum compass was discovered – a mechanism used by birds to navigate their intercontinental travels.
In Luca Turin’s theory, electrons are used to enable understanding of the fleeting yet physical reality of fragrances. This concept was later synthesized with the lock-and-key theory. In the middle-ground version, the shape, or maybe rather the size, of an odourant is only responsible for the intensity of a scent. As for the dispute on the functioning of nose, it was taken to a different field completely, namely the philosophy of science. This shows the conservative character of the scientific community, which sometimes goes as far as to value tradition more than empirical proof. And when we take a good long look at the science that strives for new solutions while blindly trusting its former discoveries, we may notice that it reminds us of Nikolai Gogol’s Collegiate Assessor Kovalev, who chased his own nose.
Translated from the Polish by Aga Zano