The quantum mechanics of smell

Olfaction (smell) is the most mysterious of senses, and is wrongly regarded as insignificant by most people. The sense of taste, for example, consists in large part of smell – try holding your nose next time you eat – and the recent identification of putative pheromone receptors in humans suggests that olfaction affects behaviour in as yet unknown ways.

The human nose, while not as sensitive as, say, that of a dog, can still detect very low concentrations of odorant molecules as they diffuse through the air. The initial event in the process of olfaction is the recognition of an odorant molecule by the olfactory receptors, which are proteins found in the olfactory epithelium. Olfactory receptors are transducers – they convert the ‘information’ in odorant molecules into electrical signals that are sent to the brain. It is only when these signals are processed in the olfactory cortex that we experience the smell.

While the higher order processing of the signals generated by olfactory receptors is relatively well understood, very little is known about how the receptors transduce the information contained in odorants into electrical signals. It has always been assumed that olfactory receptors function in the same way as other receptors – via the ‘lock and key’ mechanism. According to this well established model for the interaction of a receptor with its ligand (the molecule which binds to it), the receptor recognizes the three-dimensional shape of the ligand, and can only be activated by that specific molecule. Thus, in most cases, signal transduction begins with a molecular recognition event.

In the case of olfaction, however, there is a problem. A finite number of olfactory receptors recognize a seemingly infinite number of odorant molecules. So, although the shape and size of odorants is known to be important, olfactory receptors must also be detecting some other property of the odorants.

In the mid-1990s, Luca Turin, a biophysicist who was then at University College London, proposed a novel mechanism for olfactory receptor transduction. Few people know more about how the nose knows the difference between one odorant and another than Turin. He is, to borrow the title of a recent book about him, “the emperor of scent”. It is because of his expertise in olfaction that the French perfume houses consulted Turin about their new fragrances.

At UCL, Turin’s office doubled up as a makeshift laboratory. He spent much of his time in the long, narrow room, its walls lined from floor to ceiling with bottles of perfume, tirelessly investigating the relationship between the structures of thousands of aromatic compounds and their odours. His hypothesis was published in the journal Chemical Senses:

…olfactory receptors respond not to the shape of the molecules but to their vibrations. [The theory provides] a detailed and plausible mechanism for biological transduction of molecular vibrations: inelastic electron tunnelling.

In a non-biological system, inelastic electron tunneling is “a non-optical form of vibrational spectroscopy [which] relies on the interaction between electrons tunneling across a narrow gap between metallic electrodes and a molecule in the gap”. In a biological system, such as the olfactory system, this would involve the tunneling of an electron between a suitable donor molecule and specific, electrically-charged amino acid residues within the olfactory receptor.

Turin’s hypothesis was not controversial – he says it was “ignored rather than criticized”. But now, in a paper to be published in Physical Review Letters, Marshall Stoneham and colleagues, of UCL’s Department of Physics and Astronomy, report that they have performed calculations which suggest that Turin’s hypothesis is feasible:

We test the viability of [Turin’s] mechanism using a simple but general model. Using values of key parameters in line with those of other biomolecular systems, we find the proposed mechanism is consistent both with the underlying physics and the observed features of smell, provided the receptor has certain qualities.

News of the paper has generated some interest in Turin’s hypothesis. And Turin himself, of course, has always been adamant that his theory is correct. Several years ago, he set up Flexitral, a company which designs odorant molecules for use by the perfume industry. At the company’s headquarters in Chantilly, Virgina, Turin and his colleagues have been using the theory to predict the smell of odorant molecules before synthesizing them. Turin’s hypothesis explains not only how a limited number of olfactory receptors can detect a far larger number of odorants, but also why odorants with very similar molecular structures can smell very different, and, conversely, why molecules with different structures can have similar odours.

In order to gain some understanding of Turin’s hypothesis, we first need to look at the structure of olfactory receptors. Olfactory receptors were first cloned by Buck and Axel in 1991. In mammals, olfactory receptors are G-protein-coupled receptors (GPCRs). The GPCRs constitute the largest known protein superfamily. Mice have approximately 900 odorant receptor genes encoding 1,200 receptors, and humans have about 350 receptor genes. GPCRs are embedded in the membrane of olfactory cells, and have a distinctive structural motif: the string of amino acids of which they are composed winds back and forth within the membrane, spanning it seven times.

GPCRs are named because they recruit intracellular proteins called G-proteins to transduce sensory signals. The exact mechanism of action of GPCRs is unknown, but very basically, it occurs as follows. When the receptor is inactive, it has an inactive G-protein bound to its intracellular surface. The binding of a ligand to the receptor’s extracellular surface causes a conformational change in the receptor, which results in the G-protein being activated. The activated G-protein is released from the olfactory receptor, and then binds to, and activates, other protein molecules within the cell, initiating a chain of biochemical reactions.

According to Turin’s hypothesis, olfactory receptors act like biological spectroscopes, with the transduction of olfactory stimuli depending on the detection of activity on the subatomic scale. Turin proposes that the binding of an odorant mediates inelastic electron tunneling, whereby an electron is transferred from a donor molecule to the receptor. Tunneling of electrons across the odorant’s binding site activates the receptor and causes the odorant to vibrate. It is these patterns of vibrations which are specific to the odorant, and which are detected by the olfactory receptors. Even the slightest difference in molecular structure therefore produces a different vibrational spectrogram. Together, the series of receptors in the olfactory epithelium cover the vibrational spectrum, and therefore can detect all possible odorants.

So what evidence is there that electron tunnelling takes place in olfactory receptors? As mentioned earlier, Turin is successfully using his model to predict the odor of chemicals before they are synthesized. Turin’s also theory makes a number of predictions about the functional properties of olfactory receptors. Firstly, because most odorants cannot undergo reduction-oxidation (or electron exchanging) reactions, the receptors must obtain the electrons used for tunnelling from another source, perhaps a soluble electron carrier or an enzyme. And, because many enzymes which transfer electrons require binding of metal ions, olfactory receptors may also be expected to have metal binding sites.

Analysis of DNA sequences of olfactory receptors shows that these predictions are correct. The olfactory receptors which have been sequenced are now known to contain a binding site for a molecule called nicotanamide adenine dinucleotide phosphate (NAD(P)H), a cofactor molecule which binds to enzymes and exchanges electrons with them. Sequence analysis also shows that olfactory receptors have sequences that are closely related to, and that function as, zinc binding sites. Zinc is known to be involved in olfacation, as a deficiency of the metal results in temporary, reversible anosmia (the inability to smell), but its exact role is unclear. Turin suggests that the zinc binding sites in the olfactory receptors are involved in binding G-proteins, and that the zinc ions themselves contribute to a molecular ‘bridge’ through which electrons tunnel during the transduction process.

References:

Turin, L. (1996). A spectroscopic mechanism for primary olfactory reception. Chem. Senses 21: 773-791.

Brookes, C. et al. (2006). Could humans detect odors by phonon assisted tunneling? Phys. Rev. Lett. (in press)

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15 thoughts on “The quantum mechanics of smell

  1. Interesting! Can Turin’s model and the swipe card idea be generalized to other types of quantum interactions which may be essential to consciousness? General anesthetic gas molecules act in hydrophobic regions of dendritic brain proteins by quantum London forces to selectively erase consciousness (evoked potentials, sub-gamma EEG, autonomic drives etc continue). See http://www.quantumconsciousness.org/documents/twined_000.pdf
    In the latter case, anesthetics disrupt normally occurring electron dipole oscillations (quantum London forces) which may be analogous to tunneling (i.e. tunneling within the hydrophobic region, coupled to protein conformation/phonons.

    Stuart Hameroff
    http://www.quantumconsciousness.org

  2. Umm…good question! Perhaps if Luca returns he can answer it for you. Penrose talks about quantum consciousness in “The Emperor’s New Mind” and “Shadows of the Mind”. I read both, over 10 years ago, and understood only one word – microtubules.

  3. Yes, I introduced Roger Penrose to microtubules, and we have developed the Orch OR model of consciousness.

    A related point: Gamma synchrony coherence is the best neural correlate of consciousness, yet the precise zero-phase-lag coherence seen in gamma synchrony cannot be accounted for by conventional neuronal explanations. Gap junctions are required but also introduce phase delay. Several authorities have suggested quantum correlations are required to account for gamma synchrony. Are you aware of explanations based on classical
    neuronal effects? (This question is fleshed out in my Anesthesiology paper cited above.)

    You quote Minsky: Mind is what the brain does. But how does the brain do it? Comparing the brain to classical computers does not work.

  4. I’ve been meaning to read some literature on theories of consciousness, but haven’t done so yet. I suppose your paper would be a good place to start.

    Comparing the brain to classical computers does not work. Superposition in quantum computers immediately sprang to mind. I’d venture to say that the brain might be compared to a quantum computer using superposition to simultaneously execute a near-infinite number of calculations. But I’m way out of my depth here, so I may be heading up the wrong path.

  5. Dr. Hameroff, I have followed your work for years and loudly cheered you and Penrose along.

    I have also been interested in anaesthesia for a long time, not least because anaesthetic gases are odorants. In fact, I used to say to my students, as Moheb will attest, that “The only thing we know for sure about consciousness is that it’s soluble in chloroform”.

    I have bet a case of claret with my eminent colleague Marshall Stoneham at UCL, who is building a room temperature quantum computer. The bet is this: magnets are getting stronger and stronger, and one of these days a human will wander into a magnetic field strong enough to disrupt spin pairing (>30 T?) and fall unconscious to the floor.

  6. Smell certainly isn’t regarded as insignificant in our family. One of my boys has such a heightened sense of smell that daily life can be literally nauseating for him. His behaviour is manageable at home where I am better able to control what smells assault him, but out in the world at large his hyper-reaction to smells that he finds obnoxious makes for an interesting life style. There again, if you gag at the odor of oatmeal, loose sugar and the newly acquired Christmas tree, (as well as the artificial one) you can have a glimpse of how exciting daily life can be. Cheers

  7. Mcewen, it is well known that pregnant women have an enhanced sense of smell. This is probably due to the effects of hormones on the olfactory system. When my girlfriend was pregnant with our son, she found the smell of certain foodstuffs overpowering and nauseating.

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  9. I enjoyed your article and have just ordered Turin’s book.

    You mention that “Turin’s theory explains not only how a limited number of olfactory receptors can detect a far larger number of odorants . . .”

    If our eyes can discern hundreds of different colours with just three different colour receptors (red, green and blue), then surely 350 or so different receptors will be sufficient to allow us to resolve tens if not hundreds of thousands of different chemicals. I don’t understand how Turin’s theory adds anything that isn’t also explained by most other theories of olfaction.

  10. [Dead link removed]

    Some remarks on an experiment suggesting quantum-like behavior of cognitive entities and formulation of an abstract quantum mechanical formalism to describe cognitive entity and its dynamics. Abstract:
    We have executed for the first time an experiment on mental observables concluding that there exists equivalence (that is to say, quantum-like behavior) between quantum and cognitive entities. Such result has enabled us to formulate an abstract quantum mechanical formalism that is able to describe cognitive entities and their time dynamics.

  11. Initially intrigued by Turn’s model, I’m now a little worried. Is the synopsis given here indeed correct? It would seem to imply that a given receptor can–by itself–discriminate odors. That would not be in keeping with studies that imply that it is the odorant receptor neuron, and not the receptor itself, that determines odor perception.

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