This week, The Naked Scientists' senses month comes to a close as we tackle touch: how we develop a sense of touch, getting tactile when shopping and the secret to the perfect hug. Plus, making greener concrete and why bird populations are dropping in the South of England...
In this episode
00:41 - DNA Day: Hacking Genomes and Storing Data
DNA Day: Hacking Genomes and Storing Data
with Dr Johnathan Pettitt, University of Aberdeen, Dr Jossy Sayir, Cambridge University and EMBL-EBI
65 years ago the journal Nature published Watson and Crick’s historic paper revealing the structure of DNA or, as James Watson himself puts it “the secret of life”. Since the time when he famously raced into the Eagle Pub in Cambridge in 1953 to announce what he and Crick had found, the science of molecular biology as it’s known has taken the world by storm: the NHS is busy reading the genetic codes of 100,000 patients, and scientists in America have announced an ambitious plan to sequence the DNA of all life on Earth. Katie Haylor's been taking a look at two other recent DNA developments...
Katie - The iconic double helix: it’s like an extravagant staircase with phosphate sugar railings and steps made from bases; either C paired with G or A paired with T. These bases code for amino acids, which make up proteins and these have whole range of functions in the body. 65 years on from publishing The Structure of DNA, scientists are now using this amazing molecule in a number of different ways. One way is to go in and disrupt, modify, or make additions to existing genetic material and, as well as coding for you and me, DNA could soon be coding for music
It’s not just humans that have DNA: plants, animals, even microorganisms have it too. And once inside cells, viruses can hack into the replication machinery of other organisms to make many copies of their own DNA, or DNA’s chemical cousin RNA. Now bacteria have evolved a clever defence mechanism against this invasion; they chop up the viral DNA that’s starting to invade. Known as CRISPR, this DNa manipulation technique has now been harnessed by scientists and is having an incredible impact across biology. Here’s Jonathan Pettit from the University of Aberdeen…
Jonathan - CRISPR gives us the power, for the first time, to make changes at will potentially to anywhere in an organism’s DNA. It means that we can remove genes, we can modify genes, we can add in genes wo we could, potentially, modify an organism and give it a gene that it’s never had before.
The key thing behind CRISPR is that an enzyme, which cuts DNA at a specific point. It uses a programmable sequence that we can engineer to target it to a specific piece of DNA and it works, essentially, like molecular scissors; it goes to the place we’ve targeted it to and it makes a cut in the DNA. It’s having an enormous impact in basic biological research because questions that we previously wouldn’t have been able to attempt are now open to us. And my own research, for instance, I work on nematode C. elegans, and it’s a brilliant model organism for doing genetics but we’ve long wanted to be able to remove lots and lots of genes at once. Previously, that’s not be technically possible and now we can do that, and the key issue with that is that we know, for lots of animals, they have backup copies of given genes. So if you have say 11 genes doing the same thing or doing overlapping things, you often don’t see the effect of those genes until you’ve removed all 11, and we can do that now with CRISPR.
One of the things I haven’t mentioned is that all enzymes are error prone and so we know that it will cut most effectively in the region we’re targeting it to, but there are also off-target effects. And obviously, if we’re going to use it in a human scenario in therapeutics, that would need to be solved.
Katie - CRISPR can, in theory, be used in any situation where you’d want to study how genes work, and this is having an enormous impact on, for instance, research into cancer caused by mutated genes. But what about the molecule of DNA itself: could it serve another function?
DNA is kind of like a biological suitcase; it’s a great natural storage device. After all, everything that’s needed to make you is in it. So if this molecule can store one type of data - genetic data - what about other types? The modern world produces data at an incredible rate, from your phone, your laptops, spreadsheets. You name it, it all has to be stored stored somewhere, and having the capacity to do so is becoming a problem as we operate increasingly data hungry lives.
So could DNA be the new harddisk? Well, this week the word’s out that scientists in Switzerland are working to store Massive Attack’s album, Mezzanine, in DNA. But it’s incredibly expensive so is DNA data storage a realistic option for the non-famous as well as the famous? I spoke to information theorist Jossy Sayir from Cambridge University and the European Molecular Biology Laboratory…
Jossy - The main advantage of DNA is that you’re storing data at the atomic level, so you’re storing data in a much denser fashion. You can potentially solve the world’s storage problem and replace huge data farms that occupy whole city blocks.
Katie - You first need to repair the data in a way that will allow you to retrieve it from DNA storage. Then you send off your request to a specialised company and they’ll synthesise the DNA you’ve asked for and send it to you. Then, when you need to retrieve the data, you first amplify the DNA, sequence it, and this is where the data is read. And, hey presto, you’ve got back your photo, or word document or, if you’re a world famous music group - album.
Jossy - It is a gimmick technology, and there’s nothing wrong with that, but there is potential in the future for this technology to become extremely important and competitive. For that, there should be significant drops in the costs of storing DNA and improvements in the speed of storing it and retrieving it. When that happens, there is potential for a huge industry to develop.
In all the other forms of storage or communication I’ve worked on, when you send data in a certain order it’s retrieved in that same order. In DNA that’s not the case, you put the data in a certain order and then it’s all stuck into a soup and, when you retrieve it, it comes back in a random order so that’s the sort of challenges I face. How do I prepare data in a way that when I retrieve it in a random order, I will still be able to give you back your photo, for example, without the pixels being all shuffled into a random order.
Katie - So that’s one challenge. cost and time are others. But some people, Jossy says, think that DNa storage could, potentially, safeguard some of humanity’s most valuable data.
Jossy - It’s the technological apocalypse scenario where, essentially, mankind will somehow self-destroy or, at least, lose all technological ability. There'll be new middle ages where we’ll basically go back to basic technologies, maybe because of a war. And so maybe, in a thousand years, we’ll have a new technological civilisation, they’ll come up with new methods of storage but they won’t necessarily develop the same methods we had, so they’ll never be able to retrieve our magnetically stored, or optically stored information.
However, they will have an incentive to learn about DNA because that is present in nature; that’s not something we’ve come up with. And hence, if we store our data using processes that mimic what happens in nature, the thought is that if they want to archive something really important that might survive this apocalyptic scenarios, DNA storage is an option for this. Even though it’s costly and slow, it may be worth going through that for mankind’s really valuable data.
08:17 - Making greener concrete
Making greener concrete
with Dimitar Dimov, University of Exeter
The world’s worried about carbon emissions, and the manufacture of cement to make concrete is one of the largest single contributors - at between 5 and 10% - of the world’s total carbon dioxide output every year. So can this be cut down? Well, researchers from the University of Exeter think they’ve found a way to do it by adding graphene - the stuff that makes up graphite: the carbon in a pencil lead - to the mix. Georgia Mills heard more from discoverer Dimitar Dimov…
Dimitar - We need to reduce the carbon emissions, and we need to make the construction industry a more environmentally friendly one. One way to do it is to reduce the amount of concrete used per cubic metre: if you can reduce the amount of concrete you decrease the amount of materials used on site and, therefore, there's less need for cement. But how do we do that? We need to change something fundamentally in order to make concrete stronger and more durable to be able to withstand the current loading specifications around the world.
Georgia - How are you looking into this?
Dimitar - We are introducing the wonder nanomaterial graphene through cement and concrete, and this results in increased strength and, therefore, we can decrease the amount of material used per cubic metre.
Georgia - What is graphene and how does it have this effect?
Dimitar - Graphene comes from graphite.
Georgia - The stuff off pencils?
Dimitar - Yes, exactly. The graphite, or the pencil: it’s structure is composed of thousands of identical layers stuck to the top of each other; one of these layers is called graphene. You can stretch it, you can bend it and it will retain its original shape and size so it’s almost indestructible. And, therefore, I thought okay, so why don’t we combine the strongest nanomaterial ever discovered with concrete, wouldn’t that make it even stronger.
Georgia - What happens then when you add the graphene?
Dimitar - It increases the compressive strength by 140%, it increases the flexural strength by 80%, and probably the most fascinating property is that it increases the water impermeability by 400% so, basically, it makes that material less permeable to water. This is very important for two reasons: first around the world you have some areas subject to flooding and if you have material which is less water permeable that will increase it’s life, and also water is one of the main causes for concrete degradation. This means that internally the concrete degrades with time when it’s subject to rain basically. So if you have a material which is less permeable, that only increases its life cycle and it means less maintenance costs.
Georgia - I guess graphene: it’s a strong material so adding it to another material it increases the strength. That makes sense, but why on Earth should it affect how water resistant it is?
Dimitar - That’s a good question. When we add the graphene it bonds with the cement crystals. These crystals, they are various in terms of sizes and shapes and when they react with water they just grow together and form a matrix. What happens is the graphene comes in and it attaches to these crystals and leaves less air voids, leaves less cracks. The mechanical interlocking between these crystals is actually enhanced; it’s much better than before and this all happens on a nanoscale level; therefore, when you have a denser matrix it’s more difficult for the water to go through the material.
Georgia - Right. So when you have concrete you have all these different little lumps of it all about and this graphene and essentially, it’s like a tiny tiny nanospider went in and threaded a web through it all and this catches the larger water molecules before they can get in an do damage?
Dimitar - Yeah, exactly.
Georgia - So what’s the catch then? It sounds too good to be true.
Dimitar - There is always a catch. I just haven’t discovered it yet because I haven’t performed enough tests to find a catch but, from what I’ve seen, it’s very promising. More research has to be done on the this topic.
Georgia - How easy will this be to scale up and actually put into use around the world?
Dimitar - Well, all my samples are tested according to British Standards for constructions so it’s readily applicable on site. And the method that we use currently produces more than 100 litres per hour because you literally take the graphene in powder form, you put it in water, you blend it, and there you go you have your graphene solution. You have your graphene in water and you mix it with cement and sands to make concrete.
If you can imagine if you take this to a factory, this could be easily scaled up. The method is very straightforward and you don’t use any expensive chemicals, so it’s very close to commercialisation I think.
13:56 - Down to Earth: the mini vacuum pump
Down to Earth: the mini vacuum pump
with Dr Stuart Higgins, Imperial College London
Stuart Higgins has been finding out how technology intended to look for life on Mars can help to flush out explosives at an airport…
Stuart - What happens when the science and technology of space comes Down to Earth?
Welcome to Down to Earth from the Naked Scientists. The mini series that explores spinoffs from space technology that are being used on Earth. I’m Dr. Stuart Higgins.
This episode: how developing instruments to search for life on Mars has led to a miniature pump that can be used in a handheld explosives detector.
Millions of kilometres away, currently driving around the surface of Mars is the Curiosity rover. Launched in 2011 and landing less than a year later on the red planet, Curiosity is looking for signs that life could have existed on Mars. One of those signs is the presence of organic compounds; carbon based molecules that could have been formed by biological processes. To determine whether those materials are present, the Curiosity rover is carrying its own miniature mass spectrometer.
A mass spectrometer is a machine that can determine the relative amount of different atoms and molecules in the material. It works by first ionising a sample: electrons are stripped from outside the atom leaving behind charged atoms known as ions. If you pass ions through a magnetic field, they experience a force which can cause them to change direction depending on their charge and mass. The larger the mass, the smaller the change in direction.
In a mass spectrometer, this effect is used to deflect ions into a detector producing and electrical current. By varying the strength of the magnetic field, ions with different masses strike the detector at different times so it’s possible to build up a map of different masses in a sample. One critical requirement, however, is that the mass spectrometer operates under a vacuum to avoid the ions colliding with air molecules. That’s fine on a fine down on Earth, where we have the room and power for big pumping systems but on Mars they needed a smaller option.
A US engineering firm working with NASA developed a miniature turbomolecular pump. This is a special pump which, from the outside, looks like a mini version of a jet engine you’d see on a plane. Most normal pumps work by creating a difference in pressure. However, at very low pressures, the number of gas molecules left become so small that this approach no longer works. Instead, as the jet-like blades on the pump spin round, gas molecules enter by chance and are quickly knocked by the blades down into the pump and out of the system. And the miniature version of this type of pump is now finding new life in other mass spectrometers back on Earth.
If you’ve been through airport security recently you may have seen staff taking swabs from people’s bags and placing them into a machine. That machine is a mass spectrometer and it’s looking for traces of dangerous chemicals. While these machines are still relatively big and bulky, researchers and companies are working to find ways of using the miniature vacuum pump, developed for the Curiosity rover, in handheld detectors. So that’s how a miniature vacuum pump built to help find life on Mars is now being used to develop handheld detectors for explosives.
16:59 - What's bothering birds in the South of England?
What's bothering birds in the South of England?
with Dr Malcolm Burgess, University of Exeter
At least 4000 species of birds are long-distance migrants: they spend the spring and summer in locations like the UK, where they mate and rear their chicks, and then they fly off somewhere warmer for the winter. But for this to work successfully, the birds have to time their arrival in the spring so it coincides with a big surge in the caterpillars they need for feeding their young, which happens when the trees first burst into leaf. With the climate changing, though, some species are increasingly getting it wrong and arriving too late. So is this to blame for the drop we’re seeing in bird populations in the south of England? Or is something else going on? Chris Smith spoke to Malcolm Burgess from the RSPB and the University of Exeter…
Malcolm - We were trying to find out whether the extent of mismatch, that’s the mismatch between when the chicks are hungriest and the timing of the peak availability of their favourite food, which is caterpillars. We were interested in whether the extent of this mismatch differed between the north and the south of the UK. Our paper shows that spring is later the further north you go.
Chris - How did you actually do the study? What were the questions you were asking and how did you gather the information to nail this?
Malcolm - We’re looking a three levels really: we’re looking at the emergence of the oak leaves, when the caterpillars emerge and when they’re most abundant, and then we were looking at timing of breeding and the breeding success of the birds. We used citizen science datasets for the oak leafing data, we used records that people submit to the UK phenology network.
Chris - What’s that; people going out and asking is that oak in leaf yet?
Malcolm - That’s right. They’re noting down when they first see the buds burst of the oak trees right across the UK.
Chris - And the caterpillars and the birds?
Malcolm - The caterpillars is a bit harder. But I linked up to somebody called Ken Smith who’s come up with a very simple idea of collecting caterpillar droppings in a simple seed tray which we put underneath oak trees in woods across the UK all through the spring. Caterpillar poo is cylindrical in shape, so it means that we can separate it from everything else that falls in the traps, dry it and weigh it, and from that we an see very clearly actually, when the peak in the availability of caterpillars is.
Chris - What about the arrival of the birds; how did you log that?
Malcolm - We looked at both resident birds, which is blue tits and great tits which are in our woodlands all year round, and the migratory pied flycatcher. We measure their time of year breeding by monitoring their nests and, as part of the British Trust for Ornithology’s nest record scheme, many thousands of these nests are monitored each year, mostly again by citizen scientists. And we’re able to use this information from across the UK to quantify timing of egg laying, when the chicks hatch. And when they’re ten days old is when they require the most food and that’s the moment that needs to coincide with the peak availability of caterpillars.
Chris - Bringing all of this information together, what trends emerge; what did you find?
Malcolm - We found that spring was later in the north but, importantly, the extent of mismatch in any one year didn’t vary across the UK, so a population in the north of the UK is just as mismatched as the population in the south. That’s really important because declines of many insectivorous birds and many migratory birds isn’t uniform across the UK. The declines are greater in southern England and it’s been very often linked to this mismatch theory, but importantly we show that that isn’t actually the case, there are other things driving these declines.
Chris - Obviously, the south is experiencing quite considerable development. So do you think that it’s a population/development/agricultural impact, all these things working together and they’re affecting the environment and that’s what’s impacting the birds?
Malcolm - Those things will certainly all affect the birds, yes. Particularly thinking again about insectivorous birds, all those things are detrimental to availability of insects. I’m sure that many of us can remember when we were younger the amount of insects that would hit our car windscreens which really doesn’t happen anymore. So yes, any development and agricultural intensifications have been well shown to affect insectivorous and seed-eating farmland birds for example.
What is touch?
with Professor Francis McGlone, Liverpool John Moores University
What exactly is the sensation we call touch? How do we feel things? Katie Haylor spoke to neuroscientist Francis McGlone from Liverpool John Moores University, asking him firstly to explain how the human body percieves an action like touching a table...
Francis - I think the easiest place to look at that is the skin has lots of little microphones in it, and those little microphones are basically encoding a mechanical stimulus that’s happened on the skin surface. They’re transducing that into an electrical signal which then passes up that nerve fibre. Now these nerve fibres are myelinated so the touch that most people know about is transmitted through myelinated nerve fibres. So that information is travelling faster than a Formula 1 racing car into your brain and the second you touch something or something touches you, you feel it immediately, and these are low threshold mechanoreceptors.
Katie - What is this myelination?
Francis - Myelination is an evolutionary trick, if you like. If you need to do something quickly then you need a myelinated nerve that basically allows that signal to get to the brain very quickly. Motor nerves are the densest myelinated nerves because if you wanted to move, then you move instantaneously. If you didn’t have myelin then there’d be a delay between your intention to move and moving. So we see the consequence of that, of course, with diseases where there’s demyelination such as multiple sclerosis.
Katie - I see. So what about these different inputs then? How about temperature, there’s pain, or even itch for example?
Francis - The somatosensory system, the skin senses are, in fact, multisensory. Most of us feel touch as just a mechanical sense, but there’s about 20 different types of receptors in the skin that respond to temperature, that respond to itch, and that respond to pain. So there’s an array of information coming in from the body that basically tells you the quality of something on your skin. Then, in muscles and joints we have more mechanoreceptors that basically tell your brain that a muscle’s moved or that a limb has moved.
So pain and itch are transduced by a different class of nerve fibre called C fibres. Now, C fibres are unmyelinated so they basically send information to the nervous system very slowly. So one has to ask well, why would these systems have any functions if they are transmitting information so slowly. Well, they’re moving that information into emotional systems to govern behaviours that have more of an affective quality to them. In fact, we have two pain system by the way: we have a fast one which gets you out of there quickly so if you put your finger on a hot plate you immediately pull back. That’s the first pain system protecting you to get away from that tissue threatening stimulus. But if you’ve ever done that, you know that a couple of seconds later that emotional throbbing, burning pain comes in - now that’s C fibres.
Katie - Talking of pain: what about nerve damage? How does damaging this particular system of affect our sense of touch? In the wider sense, I guess, touch I mean somata senses in general.
Francis - The classic loss of C fibres we see with diabetic neuropathy, so patients that have diabetes. These long nerve fibres, particularly the ones that innovate the feet are the first ones to get damaged, and diabetic patients can lose their sense of touch and, in fact, they lose their nociceptors sense of pain as well. So these nerve fibres can be damaged by conditions such as diabetes.
Katie - Okay. So inputs like temperature, pain, itch, they’re all coming through a similar system but it’s different fibres that are responding in order for these signals to get up the nervous system, if you like, into the brain?
Francis - Yes. Again, we go back to that point that C fibres play a fundamental role in protecting us and that protection is mediated by the behavioural state, so that’s accompanied by that affected state so it’s either rewarding or it’s punishing.
26:11 - Developing our sense of touch
Developing our sense of touch
with Dr Stephanie Koch, University College London
How do we end up with a somatosensory system in the first place? Georgia Mills spoke to Marie Curie Research Fellow Stephanie Koch from UCL, who studies how the somatosensory system develops in babies. First, Georgia asked, when are babies first capable of sensing touch?
Stephanie - We’re starting to get an idea of this. But to put this into context, it’s really important to remember that infants, unlike adults, can’t tell us when they’re experiencing touch or pain, so researchers and scientists really have to rely on behavioural cues and how they respond. And those are all spinal circuits, essentially looking at spinal circuitry, and when we look at that we can see that as soon as an infant is born, they start to respond to touch and pain and what changes over development is their sensitivity to touch and their sensitivity to pain. So infants are very sensitive to touch and to pain and we gradually become less so with age.
Georgia - I’ve noticed, stinging nettles always used to hurt a lot more when I was little. Do we know how these systems do develop?
Stephanie - We were getting an idea of it. It’s really interesting that both touch and pain learn from experience, these somatosensory systems, like vision, like the auditory system. But, in a very unique way, they don’t learn from their own sensory modality so it seems like touch is actually learning from spontaneous movements like muscle twitches, for example, and pain is learning through the experience of touch. And that’s really interesting because biology has evolved to allow us to learn what pain is without having to have the infant go through all these potentially harmful experiences.
Georgia - Wow! That would seem quite counterintuitive. You’d expect that pain teaches more pain.
Stephanie - Right, exactly.
Georgia - So how do babies rely on touch to develop normally?
Stephanie - A lot of what we’ve seen in both clinical studies and in animal studies is that skin to skin contact is really crucial for the normal development of infants as well as animals, long term and short term. We know that these touch circuits are really critical for the normal maturation of pain in general, and that’s touch that’s passive through movements as well as touch that’s active in terms of interactions, for example. And that touch allows pain circuits to be formed both physiologically and biologically so that as adults we can recognise what a painful stimulus is and avoid it reflexively and protect ourselves.
Georgia - And that’s quite important so we don’t all end up burning our fingers off and things like that. Has anyone ever done the study to find out what happens if you’re deprived of touch completely?
Stephanie - We obviously can’t really do that with infants, with humans. So most of the studies that have been done looking at this is with animal studies, and if you deprive them entirely of touch then you stunt pain development. Even when the animals grow up they feel pain as if they were newborn, so their thresholds to pain are very low and their sensitivity to touch is very high, and that shows us how important touch is for the development of a pain circuit in itself.
Georgia - So that’s deprivation. What about if an infant did have a painful experience; for example premature babies might have to undergo surgeries or something like that, do we know what that does?
Stephanie - We’re starting to have more of an idea of that. We’ve really been talking about how experience is necessary for the building of a touch and a pain later experience in life and how we’re going to build our thresholds. So normally, whereas you and I will be able to have that key setting that will allow us to experience the world as we would otherwise. In some instances as your saying, like premature infants, they’re going to have repeated surgical interventions throughout their lives and that means that their somatosensory experience is altered. Studies that have followed these infants have shown that they have an altered pain threshold for the rest of their lives and, in some cases, these infants have higher pain thresholds and some instances they are lower pain thresholds. We don’t fully understand the implications of this but it’s an area of active research and it’s very important to look into.
Georgia - Right. What about birth itself because obviously we always talk about how painful birth is for mothers, what about the baby?
Stephanie - I think this is very interesting as a concept. We don’t fully know, and I’m not really sure how we’d look into it. But it’s clear that birth itself is a sensory experience for the child and I think what we’re looking at is how the infant is brought into the world and how that can perhaps prime them to be able to react with their surroundings later on.
31:31 - Hypersensitivity: when touch is too much
Hypersensitivity: when touch is too much
with Dr Paul Heppenstall, European Molecular Biology Laboratory, Rome
Physical touch is important for our development. But what feels like a gentle touch for some people can be very painful for others. Allodynia or hypersensitivity is debilitating - even individual hairs brushing against the skin can be enough to cause considerable pain. So what can be done about it? Well news is out of a potential light treatment that has shown promise in alleviating this hypersensitivity in mice. Georgia spoke to Paul Heppenstall from the European Molecular Biology Laboratory in Rome. Paul started off by explaining that hypersensitivity can come about as a symptom of what’s called neuropathic pain...
Paul - Neuropathic pain is a pain caused by injury to the nervous system that can come from a trauma, from an accident or from a metabolic disease such as diabetes or from chemotherapy, for example. This actually affects a large number of people; about 7-8% of people have some form of neuropathic pain. It has lots of different symptoms: an ongoing constant pain, hypersensitivity to touch, and also hypersensitivity to cold. These pains are chronic and they go on for a long time, often for a lifetime.
Georgia - Do we know why people are sensitive to touch? What were the theories?
Paul - There are two possibilities: one the pain sensing neurons become more sensitive so that they can then detect light touch; the other possibility is the gentle touch sensing neurons somehow change their connectivity in the brain or in the spinal cord and then these provoke pain instead of pleasure. This argument’s been going on for quite a while and this is what we tried to tackle.
Georgia - Is there anything we can currently do about this?
Paul - At the moment it’s very difficult to treat so most of the traditional ways of treating pain, for example opioids and morphine don’t really work with this type of pain. Antiepileptics are sometimes used for this; in these cases they are also not particularly effective. About one in three people report some improvement in their pain when they take one of these drugs and, of course, these have got quite horrible side effects as well.
Georgia - Right. So what have you been doing to investigate this?
Paul - We started off by identifying a type of neuron that is responsible for detecting the gentlest of touches. We’ve then gone on to show that this same type of neuron is responsible for this mechanical hypersensitivity in neuropathic pain. Further, we’ve devised a method where we can shut off this neuron in neuropathic pain, switch it off and stop the mechanical hypersensitivity in this condition.
Georgia - Right. How did you go about doing that then?
Paul - By trying to find molecular markers for these different populations of neurons in the skin. Then from these we made transgenic mice, which allowed us to manipulate these neurons, either by switching them on or by switching them off. Once we can do this, we can look at the behaviour of the mouse and see what happens to the behaviour when we turn on or turn off these neurons.
Georgia - Now we know which neurons are responsible for this is there anything we can do about it?
Paul - Yes. The next step is to be able to turn these neurons off by using pharmacological means rather than having to use transgenic animals to do this. This is what we’ve tried to do, we’ve developed methods whereby we can inject a chemical into the skin, shine light onto this chemical and then switch off these neurons and switch off the mechanical hypersensitivity.
Georgia - That sounds fantastic. But how does that actually work?
Paul - We found a naturally occurring molecule which binds only to these neurons when you put it into the skin. We’ve then taken this molecule - it’s a protein, and we’ve engineered it, and attached onto it a so-called photosensitizer. If you shine light onto a photosensitizer, it then releases free radicals and zaps everything within about ten nanometres of it. So we can load this onto the back of our protein, put it into the skin; it attaches to the neurons. We can then shine light onto the skin and it will clip off the ends of these neurons in the skin, cause them to retract and so that they no longer sense the forces which are acting upon the skin.
Georgia - Could you see a reduction of pain in the animal when you did this?
Paul - We saw a very strong reduction: the animals basically returned to normal and this lasted for about three weeks after a single treatment.
Georgia - Right. So by depriving a mouse of this kind of touch sensation, you’re equally removing this chronic and terrible pain that comes with it?
Paul - Exactly, yeah. I think that that is the trade off. The beauty of it is though is that you can target this to a very small area by shining the light only on the area where you have the pain. So you would still have your normal touch sensitivity elsewhere throughout the body but you would lose that pain in the area which is painful.
Georgia - Okay. So what has your work revealed to us about this then?
Paul - Firstly, it’s identified the neurons which were responsible for that. We’ve now got a handle on these neurons and we can try and find out how it is that they work. Secondly, this method of removing their endings by shining light onto them might be generalised for many other different types of sensory disorder, such as for controlling itch or for controlling other different types of pain.
Georgia - How feasible to you think this will be logistics wise, and price wise, and just scientifically to scale up to human use?
Paul - It’s very early stage. For us, the encouraging this is that it works and we’ve never seen anything work quite so well. We’ve now got to do a lot of safety tests on this approach. We need to know whether it causes inflammation in itself. Maybe it also causes pain in itself for a while. We need to be able to scale up and produce the chemical. It’s a protein that we’re producing and, of course, this is a challenge to make at reasonable levels. But with these results in mind, we think that it is worth it and that’s the way we’re progressing.
Georgia - Would you say then the debate has been put to bed by this research?
Paul - We’ve shown that if we remove the neurons, then mice don’t get neuropathic pain but also, if we activate the neurons, then they do get neuropathic pain. So I think these both is gain of function as we say, and loss of function experiments, so I think they really confirm that.
38:00 - Gentle touch - the science of the perfect hug
Gentle touch - the science of the perfect hug
with Professor Francis McGlone, Liverpool John Moores University
Touch stimulus is so important for developing babies, but it's importance doesn't stop there. Physical contact has a part to play throughout life, including into old age, and alongside the many advantages that our increasingly virtual world brings us, perhaps a consequential lack of physical touch could be a downside. Katie Haylor spoke to Francis McGlone, firstly asking if we are living in a less tactile world than previously...
Francis - In my experience… probably yes. And I think modern technology calls itself “social media” but it’s actually quite antisocial in terms of the fact that very little physical contact is mediated now between people, it’s done through a touchscreen. So, yeah possibly there is a less physical contact in terms of the way we socially mix.
Katie - Why is touch important for our health?
Francis - When I described touch earlier, I described the sense of touch that most people know about. Now that sense of touch is coded by what’s called fast myelinated nerve fibres, so when somebody touches you you feel it immediately. But, in the late 1980s early 1990s, another touch nerve was discovered in human skin, which is a C fibre. Now we’ve heard about C fibres earlier. C fibres are nociceptors; these are the nerve fibres that code for itch and for pain and they conduct information into the brain very slowly at sort of walking speed. So they can have no function in terms of altering you to something that’s going on in the world.
For 20 years now we’ve been characterising this C fibre that responds to gentle touch, and have built a whole litany of research understanding that this is the nerve fibre that basically activates when you’re cuddled or stroked or nurtured. It is probably, I would suggest, one of the most important nerve fibres we have developmentally and even across the lifespan because it basically drives the reward of physical touch between a mother and a baby, or two people.
Katie - It’s easy to understand why developing a response to pain is important. You have a stimulus that might be dangerous so stop touching that thing. From an evolutionary point of view, why is this idea of gentle touch important?
Francis - If we look at these C fibres, we know the C nociceptor is fundamental to survival. We know the the C pluriceptor is fundamental to survival and I think the C tactile afferent is equally fundamental to survival because this promotes the benefit of physical contact and social grouping.
These three C fibres that evolved before the fast ones by the way. The first systems to go down that basically protect, and once you have those systems in place you can get off your rock and start exploring. So the C tactile one is the one that basically drives the benefit of social contact.
Katie - It’s not just with children that touch is important is it? It’s important to mention other stages of life and in the elderly population as well.
Francis - Oh absolutely, across the lifespan. There’s the scientific evidence that elderly people, who are just touched on the shoulder in an old people’s home, eat more more food - it’s called the Midas Touch. So, yes, across the lifespan these C tactile afferents are playing a fundamental role in engaging social interactions between humans. And the less we do this, I think there’ll be a cost.
Katie - If I get a hug from my friend because I’ve had a horrible day, emotionally that makes me feel better. But why is that; why does touch have such a strong psychological impact?
Francis - Well that’s basically because the nerve fibres that are optimally responding to that gentle touch are C fibres. We spoke earlier about the fast touch nerves that tell you that something’s touched your body, but the C fibres basically project into areas of the brain that process emotion. The classic C fibre in the nociceptor, so the reason that pain is so distressing is the C fibres project into brain areas that are basically produce an affective state. And the C tactile afferent, this gentle touch nerve, also plug into brain networks that are processing emotion, so they’re encoding that affiliative affective state that we get when we’re cuddled, stroked, or hugged.
Katie - Is there a certain frequency of gentle touch? What makes a touch gentle?
Francis - There is indeed. Well we record from these nerve fibres. We’ve got the only lab in the country that’s using this technique of microneurography. We put a small electrode into a nerve bundle and then we can record from a C tactile afferent. And when we do finally get one, if you stroke across its receptive field, it’s tuned for a particular velocity, basically roundabout 3 to 5 centimetres per second stroking velocity that nerve fibre is firing optimally. If you go faster or slower, the nerve fibre basically responds less.
Now if you ask people at a psychophysical experiment, and you produce different velocities of stroking over the skin again, they will say that roughly 3 to 5 centimetres per second is far more pleasant than say one at 30 or one a less than 1.
Katie - Me and Georgia are here in the studio practicing…
Francis - Stroking each other.
Katie - Wow, that’s amazing.
Francis - This is a beautiful system. The first neuron responds optimally to exactly the stroking velocity that you would stroke your baby or your partner.
Katie - So it’s basically the formula for the perfect hug?
Francis - Absolutely! I mean these nerve fibres respond optimally to a gentle stroking, but they will also respond to a gentle static touch. But the optimally prefer something which is moving across the skin in a stroking movement rather than just a physical contact.
Georgia - Francis, I have a quick question: why is it some people sort of like the sensation, other people if you run a finger down their arm they will lose their mind and curl up into a ball because it tickles them so much? Do we know why some people just cannot deal with it?
Francis - Well, I’m probably a victim of that being brought up by my parents in the 50s, where hugging was not a particularly common thing to do. There’s some developmental influences in terms of physical contact between parents and kids. Some people don’t like being stoked or touched and other people can’t get enough of it, but I think to a large extent it may be experience. That’s one of our sort of theories that neglect is so devastating to the developing social brain.
43:35 - Tactility in the shops
Tactility in the shops
with Dr Cathrine Jansson-Boyd, Anglia Ruskin University
Sensory stimuli such as vision and smell can be powerful marketing tools, so can the same be said for touch? Katie Haylor went for a browse in a department store with consumer psychologist Cathrine Jansson-Boyd from Anglia Ruskin University to find out why, for shops, touch is big business...
Cathrine - What people try to achieve in terms of marketing techniques is that they want people to touch products and goods in general within a store environment. What happens is that it changes people’s perception. To start off with it feels like something belongs to you, you take ownership of the item that you’re actually touching and that effectively means it increases the likelihood of purchase.
But then, it’s also about trying to enhance the fact that something feels in a certain way - luxurious perhaps so that you’re a little bit more prepared to part with your money. But, equally, it could be that you’re just trying to get people drawn to a particular item so that they’re more likely to buy this over the competitors. So if you make something look quite touchable effectively, then people are more likely to go up and touch that particular item.
Katie - I think we should escape the wind and go inside this department store and see what we can browse…
Cathrine - Okay.
Katie - I’ve got to be honest, whenever I come into a shop like this I just go round touching everything!
Cathrine - That’s quite common. You’re not on your own.
Katie - I’m not on my own?
Cathrine - No. A lot of people have a genuine need for touch which is what you’re describing. And those consumers, in particular, will go around and touch virtually anything that they think maybe they will want to have a closer look at.
Katie - It’s quite easy to see how you would want to understand the touch of clothes because you’re wearing them on your skin. Where it becomes perhaps less obvious is in things like packaging or displays. Why is touch important there?
Cathrine - For the similar kinds of reasons. To start off with it’s purely about attracting someone to go up to touch it so that they actually want to buy it, but then it’s about reinforcing something. So if you have a perfume box that has a certain kind of texture on it, that might send you signals that if feels luxurious, maybe it feels cheaper, and often the boxes are a reflection of the actual price and the image that perhaps the perfumery is trying to portray.
Katie - Oh, okay. So fancy, luxurious box - fancy luxurious perfume?
Cathrine - Absolutely.
Katie - Can we take a look at a couple of displays? We’re going to head over to the clothes section now. This is really common, you see this in so many clothes shops: there’s clothes hanging up on the racks, but there’s also a table where you have, for example, jeans folded and you are allowed to go up and touch them.
Cathrine - Yes, we are. And now we’ve got a shop assistant who may look at us - we’ll find out what happens. But effectively, you unfold something, they’re folded up so you can’t see them fully.
Katie - You’ve just unfolded a pair of very nice looking white jeans.
Cathrine - Yes, I have. You might see the colours and you think oh, they’re attractive colours but actually to see what it looks like you need to go up and unfold them. Again, this increases the likelihood of you purchasing them because you have just taken ownership of them psychologically. You think oh, they look quite nice now let's try to find my size.
Katie - We’ve now wandered over to a childrens’ toy section, and there’s one particular item that’s caught our attention. It’s a sticker box designed for ages three and above and, despite having a lot of interesting pictures on it, it also feels quite interesting.
Cathrine - Yes, it does. And this is because children who are visually drawn to something would go up and touch it extensively. The tactile sense is the first sense to develop in the womb and when children come out, they explore things haptically. I’m sure you know, vision is impaired in the newborn and so forth so they really really experience things through their bodies. Of course, if you then look at when they start crawling and moving, they usually go up and they touch everything in sight. This is because they have a need to understand things through their tactile sense as that is their dominant sense.
Now what happens is, as children get older, somewhere between the ages 9 to 11, there’s a convergence in your brain between vision and touch whereby vision actually takes over and becomes more of a dominant sense. Having said that, what we don’t know from science before you say well, but you said earlier that some people are very touch driven is we don’t know whether this convergence takes place in everyone. So there’s neuroscience in small numbers of studies that demonstrate that this definitely happens. So this is why this particular box that you describe is so interesting because you are almost guaranteed that a child’s going to go up and feel the differences in texture and actually not let go of this box until they go “need this, need this, need this” a thousand times and the poor parent will leave buying this box guaranteed.
Katie - It seems like an increasingly common form of shopping is to go online and pick your items that way. So if tactility is so important when it comes to consumer behaviour, isn’t that a bit of a problem?
Cathrine - Yes and no. It also depends on how much of a need for touch you actually need. We know that people who have a high need for touch are more likely to send things back, but you can overcome this for consumers who have a high need for touch, you can describe things in more detail for them. Tell them what something actually feels like. Don’t say it feels course, explain why it feels course. What does it compare to? Is it like sandpaper? So that they can actually understand what it feels like. But, again, you wouldn’t online perhaps want to create unusual experiences for consumers when it arrives at home because, again, if they have expectations and you don’t meet them the likelihood of sending it back increases. So consistency rather than surprises is even more important in those particular scenarios.
Katie - Technologically speaking, are there any ways to genuinely communicate how a product feels even if it’s not right in front of you?
Cathrine - Not reliably for the moment. I know there is a bunch of French researchers that are looking into this and they’re trying to create some sort of tactile pad, a little board that you effectively touch and you can sort of feel what things feel like. I don’t think they’re anywhere near completing this yet. There was a university further down south in the UK who was also looking at having some kind of feedback in terms of what things felt like. So there are lots of people working on this.
50:09 - Super feelers: the mighty termite
Super feelers: the mighty termite
with Dr Beth Mortimer, Oxford University
In our last report on animal supersensors, Beth Mortimer from Oxford University puts forward her case for the fungus-growing termite...
Beth - Many animals whose sense of touch involves detecting vibrations along surfaces, but my vote for Super Sensor would go to a small invertebrate that does this particularly impressively - the attractively named fungus-growing termite (Macrotermes natalensis).
These termites live in galleries, elaborate structures with exquisite environmental control that can be up to nine metres tall. Their vibration sense comes into play when predators attack the colony. When attacked, soldiers drum their heads against the ground, creating vibrations that propagate along the gallery walls. Other termites are sensitive to these signals. Soldiers will respond by drum,ing themselves; this creates a kind of Mexican wave of vibrations that amplifies the signal so it reaches more termites.
What has granted them Super Sensors status is their ability to detect the direction the vibration is coming from. Worker termites move away from the source of vibration, whereas soldier termites move towards it. The ability to detect vibration relies on detecting differences between senses in different places; for example hearing something louder or earlier in one ear rather than the other.
Termites detect vibrations through their legs, but the distance between their legs is under 16mm. This raises the question: how do they overcome the limitations of their small size? Researchers from Ruhr University in Bochum, Germany designed a clever experiment to answer this.
Termites were placed on a split platform where vibrations into the legs on either side of their body could be independently controlled. They show that termites detect a time difference between their legs, so the side of their body that detects the vibration first points towards the source. The termites are remarkably sensitive, able to detect time differences as low as 0.2 milliseconds. The sensory systems of these termites have, therefore, compensated for their small dimensions illustrating that being small doesn’t stop you being a Super Sensor when it comes to touch.