I like the way you move

Could smell come from the vibrations of individual molecules?
26 November 2013

Interview with 

Luca Turin, Alexander Fleming Centre, Athens


Now when we smell something, it's because small molecules have travelled up our nose, and have been detected by sensors. But how exactly this detection Water moleculesworks has been a subject of some controversy. Luca Turin was one of the first to suggest that it's not the shape of a molecule, but how it moves, that affects the signals sent to our brain, and the odour we smell. Kate Lamble caught up with him to find out how the current 'shape theory' works.

Luca -   The prevailing theory was, and to some extent still is, that the smell of a given molecule is written into its shape. Different receptors in the nose would each feel some part of the molecule and then report to the brain so to speak. That was the prevailing view and as I said, I'm pretty sure most people would still think that way and I proposed a different theory.

Kate -   What made you think that there might be something more to this idea of a lock in a key and these molecules just fitting together?

Luca -   For a start, a theory is a labour saving device in a sense that if one has theory of how smell is written into a molecule and you happen to be making, let's say, smelling molecules for fragrances or flavours, you would know how to make one. You would know exactly what to put in a molecule in order for it to smell of rose or bananas, or whatever. And this is absolutely not the case. In fact, the people who make molecules make thousands and can never predict the smell. The other major problem is the fact that we can smell chemical groups. Let's take an example with SH -- the SH famously gives virtually any molecule it's in the smell of rotten eggs. How does it probe the fact that there's an SH in all of those molecules and not, for example, an OH, which would not smell of sulphur and would be of a very similar shape. So, that was the thing that really got me interested and that could not be explained by a shape theory.

Kate -   So, if molecules which are so similarly shaped can smell so different, how does your theory differ from that?

Luca -   Well, for a start, it's not really my theory. It was proposed originally in the 1930s by Malcolm Dyson and it was basically a very simple - how does a chemist, how did a chemist in those days identify an unknown molecule? And the answer was, we put it through an infrared spectroscope and you measure its vibrations. The vibrations were very, very distinctive and they tell you about functional groups. They tell you what's in there and they also - each molecule, because the atoms are connected differently will have a different fingerprint (so-called) part of the spectrum. So, Malcolm Dyson and others were struck by the fact that a spectroscope pretty much behaved like the nose in a sense that it gave you the same information. In those days, it was politely received and in fact, it carried on being politely received for a long time. But as we knew more about receptors and about biology in general, there seem to be this insurmountable problem that there's no way of measuring the vibrations with a receptor. What I brought to this whole thing in '96 was a straightforward biological mechanism which in fact can deliver a biological spectroscope.

Kate -   And so, how do different molecules vibrate differently?

Luca -   A molecule composed of, let's say, 10 atoms, has - in the case of 10 atoms, it has 24 different vibrations. If you arrange the same 10 atoms differently, you will find that the vibrations are being changed. A simple analogy of this is, if you have two metal balls of different shapes or different size and you hit them with a wooden spoon, they will make a different sound. The molecule, because of the springs connecting the atoms will have a unique vibration spectrum and if you change the connections, the spectrum changes.

Kate -   We previously didn't think that the nose and these receptors could pick up these vibrations. Is it just that our understanding of how biology works has proceeded and you now think that the nose can pick up these vibrations?

Luca -   Well, yes. There's been a considerable amount of interest in a sort of subfield of biophysics called quantum biology, which is the realisation that in some parts of biology, you just don't understand what's going on unless you bring in quantum mechanics. Now, the mechanism that I proposed, it's a nanoscale mechanism that involves electrons jumping from one place to another, in such a way that when they jump, they bump into the smelly molecule and make it vibrate. Then you can have a protein based system that is capable of detecting the vibrations of a molecule and that is bound to it.

Kate -   And what evidence do we have for this? It's very nice to say these electrons are jumping from place to place,  presumably we can't just look down a microscope and see that. So, how do you do an experiment to work out how we're perceiving smell?

Luca -   You're absolutely correct -- that, in so far as we haven't been able to measure the electron movements inside smell receptors yet, much more modestly, what we were trying to do, in fact, we succeeded in doing in the last couple of years, is to show that fruit flies can distinguish from each other molecules that are identical in shape and only differ in their vibrations. The way you do that is actually very simple. You take a known molecule that has a smell -- whatever it is, X -- and you replace the hydrogens in the molecule with heavy hydrogen. Now, heavy hydrogen, also called deuterium, is exactly the same size and of course, shapes, because it's hydrogen, but it has an extra neutron in the tiny nucleus in the middle of the atom and so it's heavier. So, all the vibrations of the molecule that involve movements of the hydrogens are slowed down because the hydrogens are heavier. So, the big question is: do those two molecules smell different? And so, we found that yes, indeed, fruit flies could smell the presence of deuterium, and more recently we've done the same thing with humans using musks and we find that humans can tell them apart very easily.

Kate -   You mentioned when this theory was first brought up in the 1930s, you put it that it was received politely and your first experiments were met with a lot of criticism. There was one repeat of one of your experiments that found that humans couldn't tell the difference in smell between this hydrogen and deuterium. How have you reacted to that criticism?

Luca -   Well, first of all, that paper was absolutely correct it turns out. It appears that, if the molecule is small, it has -- let's say, in the case of the molecule that we're talking about, which is called acetophenone -- it has only 8 hydrogens, and it's pretty clear that if there is a difference, it's too small for humans to really detect it properly. Our results confirm that study that said that you couldn't smell the difference in that particular molecule. But we decided to simply go to a molecule that has more hydrogens, on the grounds that the effect would be larger and that's what happened. With musks that have 28 hydrogens, you find that people can smell the difference.

Kate -   What future experiments do you need to do for this theory in your mind to become fully accepted?

Luca -   I have absolutely no idea. Max Planck said that people don't change their mind. They just die.


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