Who nose how smell works?

24 April 2018

Interview with

Matthew Cobb, University of Manchester

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Smell is a dramatically important sense, it affects our mood and how we taste our food. But what is smell and how does it work? Chris Smith was joined by Matthew Cobb from Manchester University, who researches this.

Matthew - There are molecules in the air which are of varying sizes and shapes, different chemical forms on them and, in ways we don’t fully understand, there are cells in the very top of our nasal cavity. In fact, they’re bits of your brain that are dangling down through the base of your skull at about the level of your eye into the very very top of your nasal cavity. As you inhale and breathe through your nose the molecules waft over those cells and are then captured; it’s a bit like a lock and a key; but they’re very weird locks and very weird keys. So if you imagine the smell as being like a key and it can bind, go into a particular kind of receptor, which is the lock, and then it activates; it makes it work in a particular way.

But the amazing thing is that each smell can activate more than one kind of cell, and each cell can be activated by more than one kind of smell. And even that activation isn’t simply binary so it’s not like you turning a switch and it’s either on or off. Cells will respond very very differently to different smells; they’ll give different signals in time to precisely identify the size of a molecule, its particular chemical group, and so on.

Chris - So what we’re calling a ‘smell’ actually, that’s a mixture of chemicals and it’s the way that the nerve cells at the top of our nose interpret that mixture and it’s the impression that makes on your nervous system that actually translates into the smell experience we have?

Matthew - Yes, pretty much. For example, in a rose, the smell of a rose, if you try and capture all the molecules that are produced by a rose you’ll find over 250 different types of molecule in the scent of the rose. Now that doesn’t mean to say that we detect each one of those, but most of the smells that we detect in the real world are very very complex. The smell of bread, or vanilla or whatever, they’ve got lots of complicated components in them and it’s the way that both the peripheral nervous system, which I’ve just been describing, but also the bits of the brain how they put that information together, that produces our perception of what a smell’s like.

Chris - These receptors, which are a bit like chemical docking stations, that are picking up these smell molecules, they’re encoded by our genes aren’t they?

Matthew - That’s right. You’ve got about 4 million smell cells, and they’re divided into about 4 hundred types, and each of those types is encoded by a single gene. So there’s a gene: we’ve got lots and lots of genes that produce these particular proteins that are the docks on the receptor that enable you to detect a particular range of smells.

Chris - If this is genetic then, that means that I’ve inherited my ability to smell from my ancestors so do we think that early human ancestors would have smelled smells the same way, or experienced smells the same way I and you do today?

Matthew - Yeah. We can go and understand that by going and looking to see in the genome of, for example, neanderthals and this mysterious people called the denisovans. We have their genome, so we have the genomes from our very close relatives and we can find the same genes that we have to produce these proteins.In one particular case that we’ve been studying we can actually identify the particular smell that that receptor encodes because, as I said, for most smells then they’re detected by more than one kind of receptor, and each responds to different kinds of smells.

There’s one exception to that in the human case and that’s something that’s called androstenone, which is often suggested to be a human pheromone. It isn’t, but what it is is something that varies substantially between different individuals so, for example, the response to that in different people is different. I think this smells quite sweet, many other people think it smells absolutely disgusting: like back allies, blokes have been peeing down there, a really fowl rank smell. Other people can’t smell it; other people again think it smells quite sexy. We can identify the basis of that physiological, that psychological response on the basis of single letter changes in the DNA that encodes the protein. If we have your DNA sequence, we can tell you, we can predict how you’re going to respond to this smell, and if you respond in a particular way, we can predict your DNA sequence.

Together with some colleagues in America, Karajova and Iramatsanami, what we did was to go and look at the genome of neanderthals and denisovans and say well, how would you have responded to this smell? And what we found was that the neanderthals would like most people’s from modern Sub-Saharan Africa will think that this smells absolutely disgusting, they would have hated it. The denisovans were very exciting because the denisovans had a variant that we have not seen in any human population.

Chris - And would that variant have made them like the smell?

Matthew - Well, that’s what we had to find out. We had to rebuild the nose - a denisovan nose - so this was a cell that hasn’t existed for 50/60 thousand years. We changed a normal human cell very very slightly, changed the genes so that it now had the same sequences as the denisovan version. And then we poured this androstenone over the cell, more or less, to try and see how it responded and it didn’t make any difference. This is kind of what we expected is that we know from the distribution of the “I really don’t like it” type in the modern world that mainly this is the ancestral form. It’s the form that came out of Africa so the neanderthals and the denisovans also had that form. So we’ve got, in a modern situation, some people like myself think it smells quite sweet.

And the interesting thing about this stuff is that is produced by pigs. It is, in fact, a pig pheromone and, if you are eating pigs, and you don’t castrate the boars then your meat will actually start tasting of this stuff, which some people find very unpleasant. One of the things we suspect is that the mutation to enable us to find this stuff not so unpleasant and actually quite nice for some people may have arisen in the same time and place, around 7,000 years ago in the Far East, where we started to domesticate pigs.

Chris - So we think that perhaps our agriculture has a genetic origin. Just to finish though, Matthew, very importantly what about people who don’t have any sense of smell - anosmia?

Matthew - Well, that’s incredibly significant in that, you smell with your brain but you taste with your nose. If you try eating something and you hold your nose it doesn’t taste of very much so smell is extremely important. Not only as you're going to be talking about for memory, but also for basic enjoyment of life - taste. And if you lose your sense of smell, in particular through an injury - a head injury, or even if you’ve never had a sense of smell through genetic factors, that can be very debilitating.

And if any of your listeners have recently lost their sense of smell, there’s a fantastic charity called fifthsense.org.uk. Check out their website: they’re got some great self-help groups. There are some solutions.

 

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