Senses Month: Scents and Scent Ability

Who nose what goes on in your olfactory systems?
24 April 2018
Presented by Georgia Mills, Chris Smith
Production by Georgia Mills.


This week, senses month continues as the Naked Scientists get right up your nose! We find out how smells work, explore if stenches could help people give up smoking and sniff out the scent of nightmares. Plus, the science of running a marathon, a secret use for spleens and we go bananas over some dodgy science.

In this episode

Bisphenol A, which is found in plastic packaging and bottles, will be one of the first chemicals examined by a new project to research the health effects of everyday chemicals.

00:51 - Bacteria dine out on plastic

Could plastic-eating bacteria be a pollution solution?

Bacteria dine out on plastic
with John McGeehan, University of Portsmouth

Plastics are choking our oceans and decimating marine ecosystems, and so people are desperately searching for solutions. Most plastics can't be broken down by naturally occuring substances, but some bacteria do carry enzymes, which are biological catalysts, that are capable of attacking them. And a couple of years ago scientists in Japan discovered bacteria carrying a mutated form of one of these enzymes that was enabling them to degrade PET, one of the commonest forms of man-made plastic. Now John McGeehan, at the University of Portsmouth, has assembled a 3D-model of this mutant plastic-eating enzyme to understand how it works, and to help him to discover how to make the enzyme work even better. Chris Smith heard about the scale of the issue.

John - Everyone’s very aware of the problem, thanks to things like David Attenborough and Blue Planet, really horrific images of plastic leaking into our oceans and residing there for a long time.

Chris - Why are plastics particularly resilient?

John - Without going into too much detail, we need to understand how plastic is made in the first place. It’s basically two building blocks that are pulled together to form a very strong bond; it’s called an ester bond. And if you look at the label on your jacket or your fleece you’ll see the word polyester, and all that means is a long chain full of all these bonds.

Now, these sorts of bonds exist in nature and plant leaves are covered in a material call Cutin that protects them from invading bacteria. That is also a natural polyester and enzymes have evolved over millions of years to eat that material.

Plastics’ are a bit wider because they contain an aromatic compound called terephthalate acid - that gives us PET, that’s where it comes from. Those things don’t fit into natural enzymes very easily.

Chris - But in this paper you’re describing one particular class of microorganism that does appear to be able, or at least taken some steps to begin to degrade these things?

John - It’s fascinating what’s happened. When we looked at the 3D structure of this enzyme, we were stunned to see how similar it was to a natural enzyme called a cutinase that’s the type of enzyme bacteria use to invade a leaf cell, for example. The only difference is that the active site, the bit that does the chemistry, is opened up to be wider in order to accommodate this man-made substance.

Chris - This was first described by the Japanese, this class of microorganisms, as Ideonella sakaiensis.

John - Yes.

Chris - Where did they get it?

John - They actually found it in the soil and waste water runoff of a plastic recycling plant in Japan.

Chris - And it was there why?

John - Because bacteria are incredible organisms. If there’s a community of bacteria and one bacterium makes a mutation to allow it to survive on a new substrate, a new food that no-one else is eating, it’ll grow exponentially very quickly and outgrow the other bacteria. So there’s a massive selection pressure within a recycling plant, for example, for anything that can eat that substrate, in this case PET.

Chris - So you decided to ask: well how have they endowed their biochemistry with this ability and you found that they have altered their enzymes subtly. Is the change that they’ve made as good as it’s going to get or do you models predict that with some further tweeks they could become a lot more efficient?

John - Once you get a 3D structure, the first thing you do is compare it to the ancestral - in this case cutinase enzyme - to see what’s changed; how has it evolved? What we’re doing now is to see if we can unpick what are the important parts of the enzyme and how to make it better, but the potential for doing that is now huge.

Chris - How are you going about trying to optimise the enzyme in that way?

John - We use the 3D structure as a kind of starting point and what we do is nowadays it’s very easy to make synthetic DNA. So we can go in and make very specific changes, which changes the shape of the enzyme, particularly around the parts of the enzyme that recognise and bind the plastic, so that’s what we’re currently engaged with.

Diver collecting data on a reef

05:26 - The tell-tale spleen

How big spleens can help divers stay submerged for longer

The tell-tale spleen
with Melissa Ilardo, University of Copenhagen

Most people can hold their breath for about 30-40 seconds, but a population of sea nomads, called the Bajau, who live a marine hunter-gatherer lifestyle over the seas of southeast Asia can routinely manage to remain submerged at considerable depths for minutes at a time on just one lungful of air. And it turns out that their larger than average spleen - the fist-sized immune organ that sits at the top left of your abdomen - is what enables them to do it, as Georgia Mills heard from Melissa Ilardo...

Melissa - What we found was that they’d in fact adapted in a number of ways, but one of those ways is through bigger spleen size. And you might wonder what that has to do with diving but it turns out that when you dive it activates this human dive response and this is present in a number of diving mammals.

So what happens is, first your heart rate slows down, then you have peripheral vaso-constrictions so your blood vessels actually get smaller to preserve the oxygenated blood for your internal organs, and then the last thing that happens is this contraction of the spleen. The spleen holds oxygenated red blood cells, and by contracting it gives you this oxygen boost. We believe that this larger spleen adaptation that we see in the Bajau, where a group of these sea nomads is allowing them to dive for longer.

Georgia - How did you find out these people had large spleens? It’s not exactly an external organ is it?

Melissa - No. I actually took a portable ultrasound machine down with me to Indonesia and I took images of these people’s spleens. It was a little bit of weird request  to meet someone and say hey, can I take a picture of your spleen?

Georgia - A bit awkward?

Melissa - Yeah, a little.

Georgia - Was there a way of finding out whether this was an adaptation that came within life, so just practicing diving makes your spleen grow, or is there something else going on?

Melissa - Yeah, that was actually a really important question that we wanted to address because it could be that simply the activity of diving, because it’s causing this spleen contraction, could be increasing spleen size.

What we did to ask that question was we measured the spleen sizes of Bajau people who were diving and also of those who aren’t diving. At one point in time all Bajau were diving; now it’s about 50/50 in the population at least that we visited. So we were able to get about 50% Bajau people who were diving and 50% who weren’t, and when we compared those spleen sizes they all had about the same sized spleen. So that pointed to the fact that it might be something genetic rather than something that’s happening during their lifetime.

Georgia - Did you find the genes responsible for this?

Melissa - We did, yeah. We performed a selection scan to look at what regions of the genome of the Bajau have been under selection and, in doing that, we found a variant in the region of this gene PDE10A. What PDE10A does, or one of the things that it does, is to affect thyroid hormone levels, and the variant that we see in the Bajau is associated with higher levels of the thyroid hormone T4.

In mice it’s been shown that, if they have extremely low levels of T4, they have a drastic reduction in spleen size; however that effect is actually shown to be reversible through a T4 injection. So it seems to be that the connection is that the Bajau have these higher thyroid hormone levels and that’s leading to an increased spleen size which is then leading to an advantage while they’re diving.

Georgia - What does this tell us then?

Melissa - Well, it tells us a number of things. It tells us that there are ways for the human body to adapt to conditions of acute hypoxia. Hypoxia, or low oxygen is a really important issue in a lot of medical contexts. It’s been studied in other humans before but mostly by looking at these high altitude populations that are adapting to living at chronic levels of low oxygen. This population is instead adapting to these very acute bouts of low oxygen so they’re just suddenly cutting off their oxygen supply and it turns out that the body has ways of avoiding the negative effects of that as well.

Georgia - Is there anything that we could take forward from this then and use medically?

Melissa - Yeah, we’re hoping that there could be. A lot of the insights that they got from looking at these high altitude populations have actually already started to translate into medical applications, so we’re hoping that we might be able to do the same with what we learned from the Bajau and maybe other diving populations. In a lot of critical care conditions when people stop breathing or when they enter these bouts of acute hypoxia, it seems like people react to this very differently. It’s not really clear why certain people react so poorly to these hypoxic conditions when others don’t. It could be that maybe something we learned from our study and others like it is that there’s some kind of genetic predisposition to be able to react in certain ways to these conditions.

Marathons: Blood, sweat and... poo?
with Christof Schweining, University of Cambridge

This week, many brave individuals have been taking part in the London Marathon, which was a little bit of a hot one. But is running a marathon possible for anyone, and what does training do to your body? Georgia Mills and Chris Smith were joined by one of those brave individuals, Christof Schwiening, who is a physiologist at Cambridge University and joined them straight after running the marathon himself.

Christof - I’m fine. It was a bit of struggle getting there; the coach didn’t turn up so we had a bit of a rush to get down there but wonderful day. A really lively atmosphere and great weather. The support was fantastic; it was really really positive.

Chris - You’re saying the journey was harder than the marathon?

Christof - Oh, yeah, yeah. Because you know a last minute change of plan and suddenly you’re shooting down the motorway in a car not sure where you’re going to park up, and whether you’re going to get there or not. And, of course, are you going to get to the toilet stop in time and that’s really, for most marathon runners, a major thing.

Chris - It didn’t bother Paula Radcliffe!

Christof - Well, yeah.

Chris - She popped behind a tree.

Christof - I know she did.

Chris - Not today obviously. She wasn’t running today.

Christof - It happens to an awful lot of runners. More runners lose time over a toilet stop than pretty much anything other than simply’ hitting the wall,’ I guess.

Chris - Is that because they’re taking a lot of water in because they’re worried about over-hydrating or is there a physiological reason? Is there a reason why you need a wee more if you run more?

Christof - It’s not so much the wee I’m afraid.

Chris - Oh right, number twos?

Christof - It’s number twos. It’s because the whole stress of running a marathon actually causes, if you’ve still got food in your digestive tract to head downwards. And once it hits that internal sphincter and bounces around you’re on a limited fuse.

Chris - So what do you do? As well as what you do if you end up in that position?

Christof - If you’re lucky you get to a loo in time.

Chris - But dietary, is there anything you can do ahead of the marathon to limit that?

Christof - Yes there is. Every individual is different, but I know my gut transit time. So I know if I stop eating at 4 o’clock in the afternoon the day before a marathon, I’m absolutely fine. If I were to indulge, as the rest of the family were, in chips in the evening, then it’s going to get messy out on the course.

Chris - And there was me thinking when you see these athletes looking at their watches, that they’re looking at their track time, actually they’re not, they’re looking how far it is to the next loo stop.

Christof - Entirely possible.

Georgia - Wow. That’s a side to the marathon I hadn’t even considered. What I was thinking about is the temperature. It’s been absolutely gorgeous today, but how did that affect the run and what does it do to your body?

Christof - It’s so multifactorial. Heat plays on just about every physiological system. The really big threat of the heat is that you increase the amount of sweat that you produce and so you’re effectively running along as if you’ve almost been shot. You’re losing it out this fluid from your blood, the blood plasma, it’s leaking away…

Chris - Because it’s being turned into sweat?

Christof - Because it’s being turned into sweat. And that turning into sweat isn’t just a simple process, it’s a highly trainable process. So if you’re somebody who’s trained to sweat a lot then you can lose the sweat that is really very diluted, it’s almost like pure water and you can actually osmotically pull water out of your intracellular fluid compartments.I didn’t drink in today’s marathon, I was mainly splashing water on myself and I got faster as I went along, so the second half of the marathon I finished it one minute faster than the first half.

This dehydration that you get as a result of sweating doesn’t need to be performance limiting for the elites. They’ll dump about four to five litres of water out of their body so by the time they’re finishing the marathon and hammering down the Mall, they’re actually lighter and so they need less energy to go faster. While the guys at the back who are drinking a lot, they’re heavier by the time they’re finishing and it’s getting progressively harder and harder.

Chris - You said, Christof, that it’s trainable to control sweating, so in what way is it trainable and to what extent can you constrain how much or how little you sweat then?

Christof - It’s trainable in many different ways. First at the level of the skin itself, these sweat glands and you’ve got millions of them across the surface of your skin. You can grow them and make bigger sweat glands, and the biggest sweat glands can not just push out more sweat, but they’ll also reabsorb more sodium, so you lose less sodium. But also the drive to them, this thing that we call the sympathetic nervous system. It’s part of your peripheral nervous system that you have little conscious control over, you can train that as well so you get a big adrenal gland. All of that supports this ability to sweat for prolonged periods of time and to not lose so much circulating blood volume.

Georgia - So that’s one way that training for a marathon changes, you get this sort of super-sweater, but what else happens to your body? How does your body change to be able to do this?

Christof - One of the other major changes that occurs is this increase in blood volume, which most people notice as a gradually fall in their heart rate as they do exercise. What’s actually happening is - there are multiple different theories, but the most likely is that as you exercise you’re actually pushing a protein called albumin out of the interstitial space, which is outside of the blood vessels all around your body…

Georgia - Not the same stuff as you get in eggs?

Christof - I’m afraid it is, yeah. You’ve got it floating around and it enters into the actual circulatory system and attracts water with it, and that builds a larger circulatory system. And that larger circulatory system means, of course, you can push more blood through your whole body to the skin to lose heat and also though other muscles, but you’ve got more fluid in the first place when you start off running. So that loss of two or three litres of fluid during the course of the marathon has less of an impact.

Chris - But muscles themselves also change don’t they? The composition, the biochemistry of your muscles as you train?

Christof - Absolutely! At that level, there are literally thousands of changes and this is what makes predicting the time you can actually do to finish a marathon so difficult. You change the energy that’s stored within the muscles, the capillarisation that is the ability to get the blood down to the mitochondria - you get mitochondrial biogenesis. You’re actually growing more of these powerhouses within the muscle and you get this gradual change in what looks like the fibre type.

Georgia - Right. Talking about training, running a marathon I’d rather get into a spiders’ pit I think; it fills me with fear! Can anyone learn to run a marathon and how do you go about getting ready for one?

Christof - Everybody already has what’s necessary to run a marathon. And Georgia, you could certainly run a marathon right now; it’s just a matter of how long it would take you to complete a marathon.

Could you run 1 kilometre every day? Yes you could.

Could you do it for the next 42 days? Yes you could?

You could run a marathon but it might take you 42 days to do it.

The question is how long does it take to train to get to be able to complete a marathon within the time limit that the marathon sets? The faster that you want to complete the marathon, the more training you have to do. And anybody can do it, you just simply have to do what gazelles do - they don’t go to running school. You rarely see them sitting around discussing running technique, they just run and really that’s all it is. It’s not rocket science, I’m afraid!

A peeled banana

Mythconception: We share half our DNA with bananas
with Lewis Thomson, University of Cambridge

This week Lewis Thomson has been going bananas over this slippery science…

Lewis - All life on Earth shares the same basic code: DNA. And because all living things on Earth share a common ancestor, the DNA code in different organisms is much more similar than you might expect. It’s often said that we share 50% of our DNA with bananas! 

But as similar as our DNA is, it’s not that similar. The only organisms you share 50% of your DNA with are your parents and your children. When you were conceived, half of your father’s DNA joined with half of your mother’s DNA to make your DNA.

So where does this banana statistic come from? Is it just complete nonsense? Well, no. We do in fact share about 50% of our genes with plants – including bananas.
So what’s the difference between sharing 50% of our DNA with something, and sharing 50% of our genes with something? Well, rather surprisingly, genes – the regions of DNA that code for proteins – only make up about 2% of your DNA. So sharing 50% of our genes with bananas means we only actually share 1% of our DNA with them – not 50. So what’s the rest of our DNA for if only 2% makes proteins? Well, about 8% of our DNA is made up of gene regulatory regions – these act like switches to control when and where the genes are turned on and off. But the remaining 90% of our DNA is thought to be mostly non-functional – it’s often called ‘junk DNA’.

Some of this junk DNA is what we call ‘dead genes’. These are regions of DNA which used to be functioning genes, but because of mutations in evolution they no longer make proteins. For example, humans – along with many other mammals - have a dead vitamin C gene. Whereas some animals can produce their own vitamin C, we have to get it from our diet by eating fruit! There are also regions called ‘jumping genes’. When a virus infects a cell, it injects its own DNA into that cell, and this DNA replicates itself as much as it can. When this happens in sperm cells or egg cells, the offspring will have that virus DNA integrated into its own. Because viruses are everywhere, this has happened a lot in evolution – and so about 50% of our DNA is made up of these jumping genes. It’s like we have millions of sleeping viruses inside us! They’re called jumping genes because they can replicate and jump around, inserting themselves into random places. Thankfully, we have lots of genes dedicated to stopping these sleeping viruses from waking up, so they don’t do this.

But let’s get back to bananas. Even though genes only make up 2% of our DNA, it’s still surprising that half of the genes we have are also found in bananas. But animals and plants share a common ancestor – a single-celled life form which probably lived about 1.6 billion years ago. The genes that we share with bananas would have been present in that ancestor, and have been passed down to all animals and plants alive today. And the reason that we’ve kept these genes, is that they’re involved in fundamental cell processes – like making energy and repairing damage. Just like that single-celled ancestor, and our banana relatives, we need these processes to survive – and so we share half of our genes, but not half of our DNA with bananas.

Row of batteries

22:16 - Super-fast charging batteries

Lithium-based battery technology could revolutionise electric vehicles

Super-fast charging batteries
with Jean de la Verpilliere, Cambridge University and Echion

Each year Forbes Magazine publishes the Forbes 30 Under 30, what they dub their “annual encyclopedia of creative disruption”. These are people sitting on ideas and aspirations with the potential to change the world. And on the list this year is a group of Cambridge university engineers who want to change the way batteries work and the way we use them. Katie Haylor went to find out how...

Katie - Italian physicist Alessandro Volta is credited with creating the first electric battery in the 1800s. Although this voltaic pile, as it’s known, doesn’t look much like your average AA, both this and the batteries around today us chemical reactions which produce chemical energy. This is converted to electrical energy and that’s how things are powered in a circuit. These days, lithium ions are where battery power is at but despite their prevalence in computers, phones, power tools, and more, they’re not perfect. Here’s Jean de la Verpilliere from Cambridge University’s Engineering Department and spin out company Echion.

Jean - I’m sure you’re familiar with how the battery of your phone dies out quickly, how it takes time to recharge or, perhaps, you would be happy to switch from a petrol car to an electric car if you could use it more easily or drive longer on a single charge and that’s all down to the performance of the lithium ion battery. Essentially, we’re saying there’s a lot of room for improvement.

Katie - One area, Jean says, is safety. Lithium batteries can be dangerous if used at extreme temperatures or if they get significantly damaged. Another issue is energy density: how much energy you can store in the battery itself before you need to charge it again. But one specific issue that Jean and his colleagues are working on is charging time…

Jean - So right now, it takes anywhere between 40 minutes and 6 hours to recharge a battery. What we’re doing at Echion is we’re developing new materials that enable batteries to charge seven times faster, so you’re talking a full battery charge for your car or your phone, for whatever in five minutes.

Katie - Sounds promising! No more hanging around at a plug socket waiting for my ailing smartphone to come back to life. But how do these super-speedy charging batteries work and what makes them different from other lithium batteries? To find out, we took a trip down to the lab...

Jean - That’s a material production lab where we make large quantities of nanomaterials, so hundreds of times smaller than the diameter of your hair. We use this material to make electrodes and batteries. That’s a piece of kit that enables us to make kilogrammes of quantities of nanomaterials that are then used into the battery to store the lithium ions. The kit that you see here starts from a precursor to our material, which is basically rust.

Katie - As in the stuff that I have to scrape off my bike?

Jean - Yes. So that’s the idea. Essentially a very very finely divided rust and because it’s nano we can use it into a battery, it works with lithium ions.

Katie - How is the rust involved in the battery?

Jean - This rust is going to go onto the negative electrode of your battery, so that’s the component of the battery that stores the lithium ions, the electricity, when you charge the battery.

Katie - Coating the negative electrode of the battery with very very small particles of rust gives a much bigger surface area for the reaction with the lithium ions, which means more opportunity for interaction and faster charging. Also, Jean points out, bigger sized particles of rust don’t actually interact very well with lithium ions. But why use rust in the first place?

Jean - If you take the current standard for the negative electrode of lithium ion batteries, it’s a material called graphite, essentially what you have on your pencils. This graphite material cannot accept fast charge. Fast charging your battery means bombarding your negative electrode with a high rate of lithium ions. If you try and do this with a graphite battery, the lithium ions will not nicely intercollate and be stored into the graphite. Instead they will be plated on top of the electrode and you will grow what’s called metal dendrites, which are little towers of lithium metal that will short circuit your whole battery and that will lead to a fire and an explosion.

Using this nanoscale rust, fundamentally, we can’t have this dendrite growth and, therefore, we can bombard the material with as many lithium ions as you want, very fast and it will still be safe, and will charge the battery very fast.

Katie - So nanoscale rust on the negative electrode can safely capture lots of lithium ions at a fast rate. The team are also adding carbon nanotubes to the rust, which act as a sort of ‘electron highway’ conducting the heat and electricity out of the electrode. So what kind of impact could this technology have? Back in his office, Jean told me that whilst there’s still work to do to bring the size of these batteries up to what’s needed, charging a car battery in minutes rather than hours could help make electric cars a more practical option for many people.

Jean - Being able to charge in five minutes basically means that charging becomes painless. Five minutes is about the time it takes for you to refill your car at the petrol station. What we’re saying is that if you can charge easily your can recharge more frequently and, therefore, you don’t need to carry a huge battery with you. And that’s important because the cost of the battery in an electric car right now is more than 50% of the cost of the vehicle and that’s because we need huge batteries because they charge so slowly. Let’s reduce the size of the battery by a factor of four, that will save a lot on cost, also on weight of the electric car, or if you’re powering a bus, the weight of the battery will be reduced and so you’ll be able to carry more passengers for instance.

An array of spices

29:07 - Who nose how smell works?

How does smell work, and how did our ancestors smell?

Who nose how smell works?
with Matthew Cobb, University of Manchester

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 Check out their website: they’re got some great self-help groups. There are some solutions.



Can smells help you give up smoking?
with Anat Arzi, University of Cambridge

Now, smell is a mysterious sense in many ways, but one thing that struck researchers is most odours don’t wake you up. There are exceptions: researchers in Japan are developing a wasabi scented fire alarm for deaf people, but most odours can really reek, and you’ll still sleep. So this gave scientists an opportunity to look at a hot topic - whether or not we can learn in our sleep. Audio books that supposedly teach you another language while you doze are still being sold, but there is no evidence that they actually work. But Anat Arzi, at the University of Cambridge, wanted to investigate whether smells might be different, and whether we can learn to associate odours in our sleep. This might, they think, provide a way to help people quit smoking! Georgia Mills spoke to Anat about how they did it...

Anat - We used a unique measure that we have in our FACTION and this is the ‘sniff response.’ I can tell if you like or dislike an odour only if I measure your respiration. For example, if you go by your favourite bakery and they’ve just baked fresh bread, you will take a deep inhale. However, if you go by a public toilet you might take a smaller inhale. And this change in nasal airflow in accordance with the properties of the odour is the sniff response. We are having a sniff response every day, on a daily basis automatically without being aware of it. What we discovered is that we also have it during sleep, so while you’re asleep you can perceive information from the environment and general an adequate behavioural response: a large sniff for a pleasant odour and a small sniff for an unpleasant odour.

Georgia - So when people are sleeping, if you shoved a croissant in front of their nose they might go “Mmm”, still not waking up but you know that means that they like the smell? And I suppose that makes sense because if there is a nasty smell it’s probably not a good idea for us to inhale a whole load of it?

Anal - Exactly. The sniff is a smart mechanism for us. And then, after discovering that we have this super cool implicit measure for processing in sleep we said okay, let’s see if we can test with this if we can learn during sleep.

Georgia - To test this, Anat and her team looked at one of the simplest forms of learning: conditioning, where you learn to associate two things together. So they took some people, while they asleep, and played them a note and then they played that note repeatedly with a bad smell, like rotten fish or eggs. This resulted in a small sniff response. And then they also gave some people a note and paired it with a nice smell, like shampoo, and this would have resulted in a larger sniff response. But then later that night, they looked at what happened when they played only the tones without the smell.

Anat - What we discovered is that when we presented the conditioning during sleep people then, during the same night of sleep, took a different sniff to the tone depending on which odour was presented. So if I presented a tone with no odour whatsoever during sleep, then the person took a smaller sniff if the tone was associated with an unpleasant odour. This means sleeping humans can learn a new association during sleep and implement them within the same night.

Then to test whether they can actual retrieve this information in the morning, we presented the same tones upon awake and we discovered that also, when they wake up they change their sniff to the tone even when there is no odour there. This means that they can learn a new association in sleep and retrieve them again upon awake.

Georgia - Did they have any awareness; were they aware of why they were doing this smell or were they like “oh, that’s odd”?

Anat - Excellent question. Absolutely not. We asked them if they smelt anything during the night or if they heard anything, and they said no, they had no clue.

Georgia - So does this kind of learning last for longer than the next morning? To find out more, Anat and her team, decided to look at smoking…

Anat - What we did, we invited to our lab people who are smokers who wanted to quit smoking and then, while they were sleeping, we presented a cigarette odour that was paired with a profoundly unpleasant odour. We made sure they really disliked this odour before they went to bed.

And then we asked them to fill in a smoking diary: they were filling in seven days before the experiment how many cigarettes they were smoking every day, and then seven days after the night in the lab. We presented conditioning either during non-REM sleep or during REM sleep - rapid eye movement sleep. What we discovered is that if we conditioned the cigarette odour with profoundly unpleasant odour during non-REM sleep, people reduced smoking about 30% in the week after the conditioning in the lab. If they were conditioned during REM sleep, they reduced smoking only in about 10%. What was fascinating was when the conditioning was presented during wake and they knew what is happening, they didn’t change their smoking habits so, only when the condition was implicit, it reduced smoking. It doesn’t mean that we found an alternative treatment for smoking - not at all. But it proves the concept that learning during sleep can moderate behaviour during wake.

Georgia - My question is then, were you a little bit worried doing this study that by pairing the nasty smell - a poopy smell - with the smell of cigarettes, were you a bit worried it might have gone the other way and they started to really get a bit addicted to the smell of poo?

Anat - I think the unpleasant odour are so unpleasant, and the cigarette odour even for a smoker is not that nice that it wasn’t a big concern.

Georgia - Now you’ve got this proof of concept that we can learn these basic things in our sleep, what’s really interesting is only seems to work when we’re asleep. What does this tell us about the brain and what next for the research?

Anat - There are several different lines of research we can continue from here and many open questions. One of them is to understand what is possible to learn during sleep; is it something that is unique to the sense of smell or can we learn different basic form of learning during sleep as well? And we still have a lot of  work to do in order to understand where is the line between what we can learn in sleep and what we cannot.

Child smelling a rose

Not to be sniffed at: Aromas and memory
with Andy Johnson, University of Bournemouth

Memory is very closely linked to smell. We’ve all experienced that feeling where you catch a whiff of something and it instantly transports you back to an occasion from long ago. So why is this, and why are smells so memorable? Chris Smith spoke to Andy Johnson from the University of Bournemouth, who looks into this...

Andy - This is a very common phenomenon that our participants will often report and one possible explanation is related to the structure of the brain. The limbic system contains the system within the brain that deals with smell, but it also within that system is the memory and the emotion systems. So, because of their close proximity, it is possible that this leads to these very strong associations between particularly emotional memories and smells.

Chris - So a smell elicits activity in a very similar bit of the brain to where you store memories, and so you’re saying there’s a strong overlap between the two?

Andy - Exactly right. Another account is that odours, at least at a perceptual level, are thought to be a single feature stimulus so it’s a lot easier for odours to associate with events compared to say for example of a visual stimulus, which is made of lots of different components.

Chris - Now, we were talking earlier to Matthew Cobb who was explaining that when I smell something, a whole constellation of different odorant chemicals goes up my nose and binds onto nerve endings at the top of my nose, activates those nerve endings, and these are then used to drive different parts of the brain and a sort of ‘smell fingerprint pattern’ is established in my brain. So how do I actually remember then what smell is what?

Andy - There is one account that uses this kind of configuration or pattern of receptors that are activated. It’s been suggested that within the olfactory cortex, you might process and then store this particular pattern of receptors that have been activated by a specific odour. And when we’re exposed to an odour we then kind of crosscheck or reference the current pattern or configuration with that which is stored within our memory.

However, once we’ve made that kind of familiarity judgement, once we’ve gone okay, I think there’s a match and this odour is familiar, we’re actually very bad and then going on to identify what that odour is. One of the possible reasons for that is an evolutionary one in that we didn’t really need to be able to identify odours because it was a close or near sense where we were essentially making a good/bad judgement typically about food; whether we spit or whether we swallow and, therefore, being able to identify the odour wasn’t really necessary.

Chris - What are the studies that you’re doing to try and understand how smell and memory are linked?

Andy - Our main focus is to look at the extent to which smell memory, or short term memory for odours works in a similar way to other types of stimuli, so we’re examining evidence that smell memory is in some way different. Looking at odour memory is fraught with quite a few challenges. The first thing is when you’re looking at smell memory, what you really want to be measuring is ‘smell memory,’ which might sound kind of obvious but the default strategy that people use in memory tasks is to try and verbalise. They’ll always try and assign a verbal label to those odours to make it easier so we initially have to try and make that harder by our selection of odours, and also by giving them secondary tasks to do that might use up their verbal systems. We have to try and change some of the existing memory tasks which are kind of weighted heavily towards verbal memory so that they can be applied to odours.

Chris - What have you found so far?

Andy - Invariably the answer is “it depends”, and that’s the same with our works. On some studies we find that odour memory works in a very similar way to say visual and verbal memory. In other times it seems to be a bit different so we have these mixed findings. One of the possible explanations for that is we see, across the literature generally, a lack of control over the odours that people are using in this research. And there is some evidence to suggest that we process nameable and hard-to-name odours differently. There’s an imaging study showing that different parts of the brain are activated for odours that are easy to name compared to odours that are hard to name.

Chris - And why does this matter; why is this important, Andy, that you’re able to put a finger on this?

Andy - Personally, I think it’s interesting because we don’t know much about smell memory relative to other senses, but I appreciate everyone is not as exciting as me. The other kind of big exciting element of our memory is that it’s been shown, to some extent, to be predictive of Alzheimer’s onset. There is a study that examines people with a very rare gene that looks at early onset Alzheimer’s, and people who have that gene have been shown to be poorer at odour recognition even though they don’t show any other clinical signs. There’s other studies also looking at people with mild cognitive impairment, so not an uncommon feature of getting older and those people with poor odour identification were at higher risk of developing Alzheimer’s later down the line.

Chris - So you could potentially use this as maybe a screening test to see who might be at risk of things like dementia?

Andy - To some extent, but it’s important will all the kind of predictive studies, the biggest predictor of dementia is old age so that kind of accounts for the vast amount of the variants.

Dog nose

48:25 - Sniffer dogs and the smell of nightmares

Can dogs really smell if you're having a nightmare?

Sniffer dogs and the smell of nightmares
with Rob Hewings, UK College of Scent Detection

Dogs have incredible olfactory capabilities: compared with the 4 million smell receptors in the average human nose, a dog has 300 million; and the brain region devoted to decoding smells is roughly 40 times bigger than our own. As a result, the things they can smell continue to amaze us, from bacterial infections to cancer. And now, the UK College of Scent Detection has even trained dogs to recognise the smell of nightmares. But why? Georgia Mills spoke to Rob Hewings, Head Manager at the UK College of Scent Detection to find out how they go about training a dog to learn a new smell for example a competition favourite, gun oil!

Rob - The first thing we’ll do is we’ll pair the gun oil, we’ll classically condition that scent so that the dogs knows every time I sniff gun oil something great’s going to happen. Whether it’s “I sniff gun oil, I get my toy; wow, this is like the best thing ever”. “I sniff gun oil, I get a fantastic treat; this is the best thing ever”.

We can set it up so I can put a couple of drips of gun oil in an appropriate container, get the dog to sniff it, drop a treat in, and “I sniff and I eat my treat. I sniff, I eat my treat; I sniff, I eat my treat”, and then we store that scent of gun oil in their scent library as soon as they get that association classically conditioned. And we can go all the way back to Pavlov’s bell where dogs were classically conditioned to expect food, these dogs are classically conditioned to realise that the scent of gun oil, for example, gets something great for them. It’s all on force-free friendly training - it’s all fun.

Georgia - Okay. Then basically, if they smell that any time they’ll be like: oh boy, here comes a treat?

Rob - Yeah, exactly right. Then we teach them what to do when they find gun oil; we’re just teaching them and indication because they need to know “when I sniff this scent, I need to do something for you. I need to tell my daft fat dad that I’ve found something” so we ask them to either do a freeze on all four feet on the ground staring at the contact scent, or they might sit. Or worse case scenario, or best case scenario if they find something like explosive, they need to step back a little way and stare right at the area where they’ve found it so that the handler can deal with that problem.

The first thing we do is classically condition the scent. Next of all teach them what to do when they find it: the indication which takes us a long long time time. And after the indication then we can introduce the super sexy search stuff.

Georgia - And how does the super sexy search stuff work?

Rob - We gradually, gradually build search. I use a lot of equipment; for example pots and pipes and I’ll put them in long linear lines and I’ll move the contact scent from one pipe to another, move it around, and he’ll sniff along the lines and he knows what to do when he sniffs. He knows what to do so he’ll stand with his nose in the pot and freeze.

Then we’ll add two rows, and then three rows, and then I might move the pots and pipes to different levels, different surfaces. And then, eventually, make the gun oil smaller, and smaller, and smaller so it’s just on the tip of a cotton bud - a tiny tiny amount. And you can imagine with that little bit of cotton bud, we could hide that anywhere in a room and the dog could come in and start to search in that room, and get some fantastic results.

There are facts that are out saying a dog can find one trillionth of a gram of TNT whilst he’s searching and that’s an unbelievable measurement.

Georgia - What are the various different reasons people train dogs to smell?

Roy - It can be a vast vast amount of reasons. We’ve got the enrichment, we’ve got the fact that when a dog is searching and he’s sniffing it releases dopamine in the brain, so they love it; that’s just great. So that’s your family pet dog enjoying life as much as he can enjoy it.

But lets deal with it on how dogs can help humanity. I trained an epilepsy alert dog that can give the handler 20 minutes notice upon an epileptic attack. We all know about diabetes alert but, more interestingly than that, I’m working with an excellent charity at the moment, Bravehound, which are a Scottish veterans charity and they deal with our veterans that have given so much in their lives back to us. So they’ve gone to Afghanistan, Iraq, Northern Ireland; they have given their all, and now they’re back and some of them of them suffer from PTSD (Post Traumatic Stress Disorder).

These guys have nightmares and daytime anxiety attacks and, together with Bravehound, the UK college of Scent Detection are working on a research project that involves training the dogs to recognise the scent of nightmares. And when that scent of a nightmare sparks of thought processes in the dog, so the scent of the nightmare becomes the antecedent - something that makes that dog do something - the behaviour. The dog gently gets up onto the client’s chest and every so gently licks his neck or does whatever we have trained the dog to do to appease that client. Then the consequences are the client is woken up, the nightmare stops, he’s got his best buddy alongside him, and then the dog goes back to sleep. The clients can go back to sleep with the confidence to know that if this nightmare happens again, he’ll be woken up. Some clients won’t go to sleep because of this nightmare fear and to put yourself through sleep deprivation is torture.

Georgia - Right. For these nightmares: do we have any idea what the smell of a nightmare actually is?

Rob - I would love to just put my cards on the table and say it must be some kind of mixture with cortisol for the stress hormones or adrenaline, but I think that mixture is unique to the person so the dog has to be trained on that person. What we do is we take sweat samples and the person tells us I had a dreadful nightmare last night, these are my sweat samples, and we work off those sweat samples.

Georgia - So you have an individual nightmare profile for someone. And then has this been shown then that this does work that the dog can sense the difference between a nightmare and just a normal sleep and be a nice dream?

Rob - Yeah, absolutely. Our clients in the past have shown it does work. Yes, it is successful. It’s happening in America; I’ve been across to Oregon in the USA. I’ve a charity working for me in Oregon doing exactly the same thing. And eventually, what I hope to do is share the knowledge. The UK College of Scent Detection: we’re sitting around and I think one of us, one of the brave guys in the college has got to put pen to paper and write a paper on this. We’ve got to share it.


Polar bear

Super Smellers: Polar Bears
with Andrew Derocher, University of Alberta

Andrew Derocher from the University of Alberta presents the case for polar bears...

If there are champions among mammals with excellent senses of smell, polar bears are on the podium.  The bears rely on their sense of smell as they hunt across huge areas of snow covered ice.  The short hunting season is a compelling force: what happens during the spring hunt may determine life or death, reproducing or not.

The main prey of polar bears are ringed seals which are hugely abundant and less than keen to be eaten.  At their most vulnerable to predation in the spring when giving birth to pups and mating, ringed seals make dens under the snow that piles up on top of jagged ice.  These dens have an underwater escape route through the ice.

The key to being a successful polar bear is locating these seal dens.  To do so, the bears rely on their sense of smell – all seals have fishy smell and during the breeding season, males have an odour reminiscent of sport socks and petrol.  Such a stink might be easy to find out in the open but once under a meter of snow, polar bears have to pinpoint the precise location of the seal.

How far away can a polar bear smell a seal?  Lacking controlled experiments, we don’t have great insights but given that there can be hundreds or thousands of seals within a day’s walk, the bears really need their sense of smell to provide their seal’s exact location. 

Tracking bears over the sea ice, it’s clear the bears use wind to their advantage: walking crosswind provides a smorgasbord of seal smells but some are obviously more enticing and provoke a sudden upwind stalk. Walking on sea ice is like walking on a drum: one false crunch in the snow and your dinner will escape.  The bears use their sense of smell to get close and then use snow structure (possibly even sounds made by the seals) to make their final pounce.  If the bear has done its job, it’s a seal dinner.


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