We perceive odors from the quantum oscillations of their molecules

I can't describe to you how excited I was driving to the Alexander Fleming Research Institute in Vari about ten days ago. Not only was it a bright sunny day, but it was the day I would finally be part of an experiment! In recent years I have been writing about experiments that have been done by others and in the past I have done many experiments myself. But never until that day had I been part of an experiment or, if you prefer, had I been a lab animal!

I imagine I've confused you. As if I hear you asking: "Why would anyone be happy about being a lab animal?" First, let's clarify that it is not a given that all lab animals suffer. And, in my case, I had long been a candidate for this role and was delighted that my request had been accepted. You see, I wanted to be one of the first people on the planet to help unravel a great mystery: how we smell.

Think about it for a moment: man has conquered space, created computers with unimaginable capabilities, cured diseases that have plagued him for centuries, but he still does not know how one of his five senses works. And we humans may tend to underestimate the sense of smell, compared to vision or hearing, but we are making a huge mistake. Remember this the next time a cold deprives you of your sense of smell for a few days: see how much poorer your world becomes without smells. Not to mention how much more dangerous it becomes, since no one would be able to smell either the smoke of a fire or a toxic substance.

Those who closely follow scientific developments may remember that in 2004 two American researchers, Richard Axel and Linda B. Buck, were awarded the Nobel Prize in Medicine for the discovery of olfactory receptors and the elucidation of the organization of the olfactory system. As the two collaborators found, olfactory receptors are proteins located in specialized cells of our nasal epithelium. (The specialization of the olfactory epithelium cells comes from the fact that each of them carries only one type of olfactory receptor.) These cells therefore perceive odors and inform our brain of their presence by sending electrical impulses initially to the olfactory lobe and then to other areas of it.

But while the pathways of electrical impulses from the nasal epithelium to the brain seem to be clear, the same is not true for the first step in the function of smell, which has to do with the interaction of odors with olfactory receptors. The original hypothesis was that odors and their receptors function like a key with a lock: each odor could "unlock" its corresponding receptor by binding to it.

As appealing as this hypothesis may sound, it has a flaw: “Scientific hypotheses are correct when they have predictive power,” Luca Turin, now a researcher at the Fleming Institute, told BHMAScience. Indeed, if the hypothesis that odorants have a stereotype complementary to their receptor really explains the function of smell, one should be able to predict how a substance would smell if one knew its shape in space. Correspondingly, one would expect substances with similar shapes to have similar odors.

However, as those who study the function of smell know, the above is not true. A very typical example is the pair ethanol – ethanethiol, which are substances with very similar stereostructures and diametrically opposite odors. The first smells like vodka, while ethanethiol, which is nothing more than an ethanol in which one hydrogen molecule has been replaced by a sulfur molecule, smells like a rotten egg. The smell of rotten eggs is also shared by a series of boron and hydrogen compounds, the boranes, whose molecule bears no resemblance to ethanethiol.

All of this made Turin, a biophysicist, skeptical about the explanation for the interaction of odors with their receptors. Turin thought that British chemist Sir Malcolm Dyson, who in 1937 had hypothesized that we perceive odors thanks to their molecular vibrations, was probably right. Looking for ways to investigate this hypothesis experimentally, Turin approached neurobiologist Efthimios Skoulakis of the Fleming Institute. Dr. Skoulakis and his colleagues investigate the mechanism of memory and learning using the fruit fly (Drosophila melanogaster) as a laboratory animal and have developed techniques for training the flies with the help of olfactory signals.

Exactly two years ago, the Skoulakis-Turin duo had demonstrated that it is indeed the molecular vibrations of a molecule, and not its stereostructure, that are the way flies perceive odors. However, they did not know whether this could also be true in humans. “The olfactory cells of flies are very different from ours, and only repeating the experiment in humans could solve the mystery,” said Luca Turin.

The experiment is simple to conceive but somewhat more difficult to implement. A molecule whose hydrogens have been replaced by deuterium (an isotope of hydrogen) retains its stereochemistry, but its molecular vibrations are different because of the different oscillations of the heavier deuterium. If Turin's theory is indeed correct, the deuterated molecule should smell different from the original.

To conduct this experiment, the two collaborators enlisted the help of Vioryl, the only Greek perfume company with a large research department. “Dimitris Georganakis from Vioryl and Cleo Maniati, who works in our laboratory, created the high-purity deuterated mask molecules we needed to investigate the correctness of our theory,” said Luca Turin.

Masks are a group of molecules widely used in perfumery. Purification by gas chromatography of both the regular and deuterated mask molecules, to ensure that the volunteers would smell only the substance without any impurities, was crucial to the experimentation. As a good volunteer, I arrived that bright morning in Vari and, full of impatience, saw the small laboratory bottles with the two types of mask, the regular and the deuterated, arrive in a box.

The first bottle, which I don't know what it contains, opens. I bring it to my nose and smell something indefinable, something reminiscent of plastic. It's the plastic that wraps around its cap. I have no idea what the contents of the bottle smell like. The researchers look at each other and smile. They give me the next bottle, nothing. They bring more from the lab. Nothing.

My career as a laboratory animal is over before it even begins. I am told that I am one of the 5% of the population who cannot smell masks! Fortunately for the researchers, there is the other 95%. As they note in their article recently published in the journal PlosOne, other volunteers were able to distinguish the normal from the deuterated molecules of the mask.