In Our Time - The Nervous System

Episode Date: February 10, 2011

Melvyn Bragg and his guests discuss the nervous system.Most animals have a nervous system, a network of nerve tissues which allows parts of the body to communicate with each other. In humans the most significant parts of this network are the brain, spinal column and retinas, which together make up the central nervous system. But there is also a peripheral nervous system, which enables sensation, movement and the regulation of the major organs.Scholars first described the nerves of the human body over two thousand years ago. For 1400 years it was believed that they were animated by 'animal spirits', mysterious powers which caused sensation and movement. In the eighteenth century scientists discovered that nerve fibres transmitted electrical impulses; it was not until the twentieth century that chemical agents - neurotransmitters - were first identified.With:Colin Blakemore Professor of Neuroscience at the University of OxfordVivian Nutton Emeritus Professor of the History of Medicine at University College, LondonTilli Tansey Professor of the History of Modern Medical Sciences at Queen Mary, University of London.Producer: Thomas Morris.

This BBC podcast is supported by ads outside the UK. Thanks for downloading the In Our Time podcast. For more details about In Our Time and for our terms of use, please go to BBC.co.com.uk forward slash radio 4. I hope you enjoy the program. Hello, running through every part of our bodies is a network of fibres. This is the nervous system, an elaborate structure which carries information throughout the body. It allows the brain to control our muscles and internal organs

and also conveys sensations such as sight, hearing, smell, taste and touch in the opposite direction. Scholars first described the nerves of the human body over 2,000 years ago. The Roman surgeon Galen believed there were channels for what he called animal spirits, mysterious powers which caused sensation and movement. It wasn't until the 18th century that scientists began to understand how nerves worked. Today, thanks to modern neuroscience, we know much more about the complex network of cells which controls and coordinates our bodies. With me to discuss the history and science of nervous system

are Colin Blakemore, Professor of Neuroscience at the University of Oxford, Vivian Notton, Emeritus Professor of the History of Medicine at University College London, and Tilly Tansy, Professor of the History of Modern Medical Sciences at Queen Mary University of London. Vivian Notton, interest in nerves began in the ancient world. Can we just have a quick reference to the first scientist to take an interest in the subject? The early Greeks believed that sensation reached the brain through channels, through your nostrils and through your ears. But Aristotle, the great dissector, had no interest in the brain,

and it was really about 270 BC in the Greek city of Alexandria in Egypt that the first investigations into the brain and the nervous system were made by two scientists called Herophilus and Eurysticester. Herophilus, if you like, mapped out the brain, but aerosistratus carried out investigations of the nervous system in the brain, showing how the nerves entered the brain, he looked at the cerebellum, the ventricles of the brain, and carried out experiments.

But then, for the next 350 years, we have almost silence. Dissection seems to have disappeared. Can you talk a bit more about the brain? those dissectioners, Alexandra. What did they dissect with? Who did they dissect? And when you say they discovered, what were they seeing?

I mean, how did they, they had their naked eye, they didn't have microscope, so what were they seeing? The tradition is that they dissected living human beings. We know from the fragments of their writings. You mean they would cut the top, sort of peel back the top of their heads? Probably not, but they certainly cut into the living human body. But these people are criminals, and it's argued that in doing this, well, they're sort of subhuman. They certainly cut up corpses, and they certainly cut up animals, to see what happens when the brain, if you like, moves.

What they could see was merely the gross structures of the brain. They could see the folds of the brain, and they could trace the bigger nerves coming into the brain with the naked eye. But that's all. And how did they write about that? Did they use words, was it anywhere near nerve? Because often a lot of our words are coming, especially in the Greeks, what are they seeing? What do they differentiate?

They use the word neuron, which in Greek can mean any chord. It can mean a ligament, it can mean a tendon. But from about 320, it's applied to the very, very thin cords, which we call nerves. neuron, of course, we get neurology. And then we move swiftly to a few hundred years on to Galen, as you implied in

what you said, the Roman surgeon who had such an enormous effect. What were his main conclusions in this area? Well, his main conclusions are really three. The first is the absolute importance of dissection in order to understand how the body

is working for nervous diseases as well as the understanding of the structures of the brain. Secondly, he believed that the body had three systems. One connected through the veins, one connected through the arteries, one connected through the nerves. And the nerves contained a mysterious substance produced in what he thought was a network at the base of the brain. and the substance he called psychic puna,

which became translated into Latin and then into modern languages as animal spirits, because it gives you the soul, the spirits of the soul. And that's what he believed. He also believed in three channels with these things flowing through them. Can I turn to Colin Blakemore now? There's a 14-year gap after Gail

and his work is so authoritative that people dare not or do not and dare not challenge it for 400. We're going to take a very, as much smaller gap, Colin Blake. Can you briefly just tell us all how the nervous system works? If I tap the table like that, do anybody hear it? Tap it. Whatever. Tapped it. What happens in the nervous system? What's going on? In your nervous system or ours? Mine.

Well, all of us are seeing you and hearing you tapping the table, so things are happening in our brains as well, of course. In your brain, the contact between your skin and the table activates the terminals of sensory fibres, causes impulses to run up those fibres into your spinal cord, and from there, into your brain. I presume that that's responsible for your sensation of the contact with the table. It's also responsible for any actions that you then take, like lifting your hand off the table. But in addition to that, of course, the same fibers are having effects within your own spinal cord, producing reflex actions, changes in the tension in your muscles

as a result of contacting the surface of the table. So it's setting off a chain of reactions in your brain and your spinal cord in response to contact with the table. What makes me tap the table in the first place? Surely that's the end of the programme. All right, we'll come to that at the end of the programme. Okay. So we have Galen's view very clearly set out.

We do go after the Renaissance. It is the fastest fast forward you've ever done in this programme. Why, how, when were his theories superseded and by whom and why? Well, it depends which of his theories you mean, but I think we'll stick to the nerves. The question of, we had lots of views about that too, but the question of how this animal spirit was produced and what its real function was, I think, began to be questioned, as you say in the Renaissance, really, the end of the 1500s. and personally I think that Leonardo, although not a great biological scientist, played a part

when he began to dissect late 15th century beginning the 16th century. And he dissected it, of course, principally to draw better pictures, to understand the musculature and the form of the body, but began to discover things as he went along. And he really put to rest, or began to, this galenic idea that there are three chambers in the brain, full of this fluid that then circulates through the nerves, animal spirit, and though that fluid is responsible for our sensations,

for our thoughts, for our estimation, for our understanding, for our memory and everything. What Leonardo saw was, and he questioned the classic theory, was that the major nerve bundles that he could see coming in from the eyes and so on were running towards the middle of the brain, not as they were supposed to, in the Gallinic view, towards the very first of the chambers containing fluid. So he moved the labelling very neatly,

putting the cell theory label of the common sense, the sense was communis, that was the property of the first chamber of fluid, onto the middle chamber of the brain. In other words, he was following what he saw, what he observed, rather than the dogma, which, as you'd say, had really dominated views for 1,400 years since Galen.

And Veselius was extremely important. Well, important, of course, for the quality of his observations and dissections, and for his comparative studies as well, comparing different brains. And that set up a tradition, really, of arguing from differences between animals to what the function of parts of the body might be. Can we say about this time, because we're moving on to René Descartes,

that this area of research, this area of knowledge, is beginning to be explored. And for five or six hundred years, people are exploring and building on each other's work and moving slowly towards it. And technology develops, their interests develop, and the body of knowledge accretes and forward we go. Well, that's really the story of science, isn't it? But what about Descartes?

How did he build on what you described? Indeed. I mean, Descartes still adhered, this is now in the early 17th century, 1620s, still adhered very much to this classical view about the function of animal spirits, talked about fluids circulating as being the basis of thought and action, but began to see from his own dissections, and really also just from thinking out how it might work, that there had to be connections from these peripheral nerve fibres into the brain

which generated automatically perhaps even generated actions. There's a marvellous piece talking about touching the table where he describes the way in which putting your hand close to a fire might irritate the nerve fibres in your skin, setting up some sort of activity in those fibres which literally pulled on the brain and caused a redistribution of fluids. Like, as he said, pulling on a rope might cause a bell to ring in a bell. He didn't know what the nature of that transmission of information was,

but he realised it must be something going along the nerve fibres, and then setting off actions, still, as he thought, caused by the movement and the redistribution of fluids in the brain and into the nerve fibres. And he discovered or named reflex action? I think the actual name reflection was later in the next century, but certainly the concept that some automatic action produced by a sensory stimulation that was embedded in Descartes's idea, revolutionary really, at the time. I mean, he compares, for instance, the working of the human brain,

all of our thoughts, our emotions, our memories, our sensations, to the working of a clock. He says, you know, it's all automatic, like the working of a clock. Although he then got a bit hung up on why it is we can feel what's going on, presumably clocks don't feel things. And he solved that by cogito-e-e-e-go-sung. Well, it's a dualism of it. Yes, the notion that there are two sorts of processes going on, the brain, the automatic mechanical clock-like one, which is really how it works,

almost all of the time, but then some sort of interaction with the soul going on within the brain, through the pineal gland, he thought, which generates sensations and occasionally intervenes to produce voluntary actions and decisions. So we've got Descartes there.

We're setting out on a journey which is going to lead to what you three now, as it were. Where are we with Descartes' work? I mean, we're talking about fluid. There's a lot of the outlines that are familiar, as it were, but the instruments haven't been discovered yet to be more precise. We're talking about fluids.

So can you just tell us where we are with Decau? Well, Descartes really was almost in between. I mean, he was still carrying on the ideas of animal spirits and heralding new approaches, experimental approaches. He was a very, very keen deceptor. He believed in his own observations. For example, when he lived in Amsterdam, he lived near the butcher's quarters

so that he could knit next door into the Butcher. as watch them carving up animals and then he would scuttle back to his house with a carcass or a brain to start dissecting. What he could see, because of the technicalities of the time, we would now interpret what he could see, are very difficult. Because at that time, the brains were not fixed,

animals were not fixed in any way. So the nerves were not hardened for dissection. So the brain, for example, decomposes very quickly and becomes a very mushy substance. Descartes thought that he actually saw nerves He saw nerves coming out of the spinal cord and out of the brain And he cut them and he thought that he could see little tubes Which really was where the animal spirits would flow through

But he also said he saw little threads Which is what Colin has just talked about These rope pools that would activate a bit like a bell So he was halfway he was sort of thinking of animal spirits But I think he was sort of moving towards ideas Of this transmission along the nerves and very quickly after really they've begun to be overturned by others.

We're calling this program the nervous system, but there are constituent parts there. It is one system and at the same time it's divided. Can you just give us some idea of the geography of it? Yeah, yeah. Well, the basic division is between the central nervous system and the peripheral nervous system. The central nervous system is the brain, the spinal cord,

and most people also include the retina of the eye as part of the central nervous system. So those three things, are they conjoined? Yeah, yeah. None of these systems operate independently. And the word conjoint is a difficult word that we might discuss between connections of nerves and the nervous system. Those parts of the central nervous system are all encased in bone, in the skull and in the spinal column. And by definition, what is outside that is the peripheral nervous system. and we can divide the peripheral nervous system into two parts.

There are lots of words for these, but for the moment I can use voluntary and involuntary. Collins already mentioned the voluntary part of the nervous system, and that comprises the nerves that link the central nervous system with the muscles and joints and skin, and messages are going backwards and forwards along those nerves. So that is a voluntary part of the peripheral nervous system. The involuntary part is often called the autonomic nervous system and that controls the routine functions of the body

so respiration, the cardiovascular system, excretion, the digestive system and that is conventionally divided now into two parts itself which act in a complementary way one effectively being an accelerating system and one really being a breaking system to actually control the functions of the viscerer. So the visceral. And that's an extraordinary setup, isn't it, really? It's incredibly complicated, but it's also very neat.

It's only one way of describing the nervous system or several ways of describing the nervous system, which have evolved over time. So we then move on Vivian Nutton to 17th century British scientists, including Newton and Harvey, but principally I think from what I've read. Anyway, Willis, taking the story on. What did they take on?

Harvey, in fact, is a dissector. He's not really interested in the brain, and he retains the standard view that the brain is the source of the nerves, and he compares it to a sort of tree with the nerves coming out of the brain. But he inspired Willis and others in Oxford to experiment on the brain and nervous system,

with also new techniques, including injecting the nerves with colouring, so that you could begin to see the nerves in a different way. But from then on, the question is, what is it that makes the nerves work? Can I just ask you all question? Dissection was a forbidden in the Christian world. So how are they finding, getting to their information here? They are using corpses. Dissection is perfectly permitted.

in an appropriate religious context. Right. But most of the... What's the appropriate religious context? Oh, you bury, you give a good burial to the corpse, and it's got to be a criminal and so on. But mostly, they're using all sorts of animals. Everything that you can use,

because you can see, more clearly, on a larger animal than you can, on a tidily human being. So they're working that way. Now, what is Willis, can you tell us a point? More about Willis. People might not have heard of him, and his contributions, as I understand, it was considerable. Thomas Willis was an Oxford professor who spent a lot of time investigating the brain and the nervous system, seeing where the nerves were, looking at how the blood supply to the brain functioned,

and in particular, just what it is that makes nerves carry messages so quickly. And he's the first of a whole series to give different explanations. he thought muscles operated as a result of a sort of gunpowder explosion when the animal spirits met Niter and caused an explosion that immediately meant that the muscles contracted. And don't forget, he's doing this at the time of the Civil War, so he got lots of experiences of gunpowder. Later on, Newton thinks in terms of pressure, air pressure.

Later on, a wonderful experimenter who was a vicarate Teddington called Stephen Hales thought of the fluid he saw was to nurture the nerves, but electricity was there in the coats of the nerves. All these are using, if you like, new scientific, physical, chemical ideas to explain what is going on in these channels.

Colin Blakemore, and in the 70-Nadges we have the We have Galvani, the Italian scientist, who made what turns out to be a crucial discovery. It's interesting, fascinating the way these people are moving, using whatever turns up, and shifting their points of, not as point of entry, to this subject, isn't it?

Galvani, as he said to have taken it on quite considerably. And moving from one area of science to another very freely. I mean, fortunately, they were able to do that those days, very difficult to do these days because it feels so specialized. But the story goes that, 1791, I think that Galvani was simultaneous as it were working on frog nerve

and muscle dissecting nerves and muscles and seeing what would make the muscle twitch and simultaneously had an interest in static electricity and was doing experiments on the generation of static electricity and the story is that his assistant handed him a scalpel that had become electrically charged

in the experiment on electricity and he used that to touch the muscle initially of a nerve muscle preparation from a frog and the muscle twitched. And a spark, he saw a spark go from the scalpel to the muscle. So he thought that the activation of the muscles must have something to do with electricity. My views about electricity were very primitive and just developing as well, of course, at the time.

In fact, Galvani was responsible for a theory that electricity is an intrinsic property of living matter and essentially could only be generated by living matter. and it was a colleague and competitor of Galvani Volta who first showed that you could generate electric current from metals placed together without any contact with any living tissue so that it had an intrinsic physical property of its own but the view that electricity was responsible for activation of muscles and in turn of nerves

and that electricity might flow along nerves that was Garvani's idea into muscles and caused them to contract then became the dominant theme Electricity was a hugely dominating idea, wasn't it then? It was exciting, it was circus, it was science, it was horror stories. And of course permeating popular culture too. It was Galvani's book, which was on the reading list for Mary Shelley's group in, what, 1815 or something, that led to the Frankenstein theory, the Ankenstein story.

Tilly Townsley, we then have technology, other technology to bring into a kind of much more advanced microscopes enabling people to observe these nerve cells properly, as more fully for it were the first time. What were they seeing? What did they see, and how did that affect the way they studied it? Well, certainly really in the 19th century, better microscopes and also dyes to actually pick out the structure of individual nerve cells,

because if you could get a dye that stained, say, the entire brain, that was no use because everything was stained that colour. But if you could get a dye that just stained, one or two cells. How did you get that sort of dying? Well, the person who really invented one of the best was an Italian Camillo Golgi. And he had, it was a silver stain. And it was a very difficult stain. It just permeated a few cells of, say, the nervous system, the central nervous system. There's a very interesting story about Golgi and a Spanish histologist Kahal using these stains. But the first

people really started finding nerve cells and describing nerve cells were about the 1830s Deter. Pokinia. Yeah, Pokinia. Looking at very large cells and the cell in the same. It's interesting how this swirls around Europe, isn't it?

There's this whole pursuit. Anyway, that's just an... Well, it'sologics, and that's because of the education system. This is where the medical schools are. This is where people are being trained in medicine and actually starting to do experiments. And travel as well. And travel.

So much easier around Europe and from Europe. Europe to say the United States. I took you off your main point, which is describing the nerve cells, as it began to be seen properly, as it were, for the first time. And nerve cells in different parts of the nervous system have specialized structures. I mean, Colin has just mentioned the Pekingi cell, which is a specialized cell in the cerebellum. But all the nerve cells have a common purpose,

and that is communication and the passing of information. And so a basic kind of, of typical nerve cell has not only the nerve cell body, but it has processes to get information in and a process to get information out. Now, the processes, if you look at a nerve cell, it has lots of small extensions, the branch and branch like a tree.

And these are called the dendrites. And these are basically the antennae of the nerve cell. These are taking the messages in from other nerve cells. And then a nerve cell has just one very long extension, and this is called the axon. And this is where the message has taken out of the nerve cell. This is a conduction out of the nerve cell of the accumulated message to the next nerve cell.

And the axon will pass on the message to another nerve cell through the next nerve cell's dendrize, for example. So this is how connections and networks of nerve cells are seen to be built up. So we're talking... What's up to the idea of animal spirits, Vivian Hutton? William Nutton, sorry. Well, we go back about 100 years to the middle of the 18th century,

where a German professor called Albert von Hala develops the idea that, in fact, it's not something in the channels that becomes important, but a property of the actual muscle, the fibers. And he says that the fibers are now what matters in nerves, and he distinguishes two types, one of which is distinguished by irritability, and that is what causes your muscles to contract. And the other one he calls sensitivity, and that is what causes sensation.

So he makes this big distinction between irritability and sensibility, which then eliminates the need for these mysterious substances. and he sees them as properties of fibres, nothing to do with channels. And with fibers, you can then begin to investigate the structures of the nerves in a new way. Now, his arguments were not immediately accepted. It takes another 40 or 50 years. But he shifts the debate from something which is immaterial, these animal spirits, to something that you can now look at under the microscope.

and also he divides this irritability and sensibility in such a way that people now think, ah, this is the cause of all illnesses. So if you've got your nerves, your nerves cause anything. Colin Blakemore, a century later, we've come to Charles Scott Sherrington and we're really approaching the modern age here. Can we rumble, ruminate about what he contributed and where we are at this stage? Yes, Sherrington, an enormously influential and important physiologist

and one of the founders really of modern neuroscience. Working in St. Thomas's and then Liverpool and eventually in Oxford, studied reflexes, the way in which reflex reactions like the jerk of a limb when you tap on the patella tendon, for instance, the knee jerk, or the way in which an animal or a human being will withdraw their limb if it's pinched or perhaps gets too close to a fire, as Descartes said. These are reflex and automatic actions. And Sherrington, using very simple, very beautiful techniques,

try to discover what... Is it possible to explain these very simple, but very beautiful techniques? He wasn't able to record electrical activity from inside nerve fibres and nerve cells as we can nowadays. He had to just watch the reactions. So he would elicitor reaction from an animal preparation, a decerebrate preparation usually in which the spinal cord had been separated from the brain.

But the reflex actions of the spinal cord were still working, so he could produce reliable, regular, repetitive actions. He'd stimulate, say, some part of the pore of the skin, of the paw of the paw of an animal, and look at the reflex withdrawal of the limb. And he showed, for instance, that if you reduced the strength of the stimulus, eventually that reflex would stop,

he'd find a threshold below which the reflex wouldn't happen. But if he applied two stimuli close together on the same, skin, each not capable of producing a reaction, the two of them together could. So his argument was that there must be something happening in the pathway, which is summing together two sub-threshold inputs. The impulses must be arriving, but something else must be filtering them and adding them together. He gradually accumulated with these simple observations, the concept of integration, spatial and temporal summation of activity onto individual nerve cells in the spinal cord from all of the incoming nerve fibres.

and from that he concluded that there must be something special about the contact between the incoming nerve fibres and the cell body. This notion of the synapse, and it was Sherrington who invented the word synapse for a connection between a nerve fibre and a nerve cell. Over the last few minutes, the spinal cord has come more into the discussion, hasn't it? Can you elaborate on why that is there? Well, it's what it might be called the headless chicken argument, which is why can the chicken run around when it's head. has been cut off. And this was a famous experiment that was done by Harvey and many others. But it's only in the late 18th century that people like Robert Witt and then Ungo in Germany

began to say, well, if the brain is removed and the spinal cord is still there, there must be something in the spinal cord, which corresponds to what we have in the brain. And so they begin focusing on the spinal cord. and the consequence then is that embryologists come in and by 1840 everybody was seeing the brain as an outgrowth of the spine which is the complete reverse of a hundred years before and people are now seeing with embryology the development of the fetus the development of the new tube and with new larger microscopes

they're beginning to focus not just on large, structures, but going down to the intimate structures of the cells, the axons and so on, with the new, if you like, scientific instruments that are there from the 1850s. Teddy Tanzi, we heard about how electricity is thought to make the nerves work. And then there was a switch from that. It moved onward, I suppose we might say. Perhaps two of the two Cambridge scientists were closely involved in this. Could you tell us who they were and what they did?

Well, the two people would be Walter Gaskell and John Langley. And what they did, they both individually and working together, they explored this involuntary nervous system, the autonomic nervous system. They looked at its anatomy, its physiology, its pharmacology, and this evolution. And they really mapped out very precisely the entire anatomical pathways and physiological functioning of the autonomic nervous system. And these two component parts that I talked about earlier, the speeding up part, which was called the sympathetic nervous system,

and the slowing down part, which Langley called the parasympathetic nervous system. Langley really went on, he got particularly fascinated in the physiology and pharmacology, and Gaskell got involved very much in evolution. But they had laid the framework of an experimental technique, of experimental techniques and a system to study a different way of neurotransmission, of chemical on your transmission. And this really came about very much from Langley's personal work. He was very interested in the effects of poisons on nervous system

because seeing what the effects were, whether it stopped the part of the nervous system, whether it's stimulated parts of the nervous system. And he did some very fine experiments using a paintbrush just to dab little bits of poison, specific parts of the nervous, particular part of the nervous system, look at what was happening. And he began increasingly to think, and this was in the 1890s,

that the chemicals of the poisons were interacting with chemicals that must be in the nerves. This must be how they were having the effects. And at the same time, he believed, as Colin has just described with Sherrington, about the synapse, a gap between nerve cells. And he was increasingly beginning to think

that somehow chemicals were involved in the transmission across that gap, simply because chemicals stopped that transmission. And so that was very important. Langley himself was quite cautious, and how he expressed this, that he inspired a number of very important students who carried the work on further

and looked at the role of chemicals in the transmission of nervous effects. Colin Blatman, can you tell us about it's approaching where we are now? There was a huge debate about nerves broke out over the neuron doctrine involving Golgi and Kahal. Can you bring us in there? Yes, Tilly's already mentioned and Ramon Icahal, this Barcelona physician and anatomist,

who discovered this silver impregnation technique that Golgi had developed a few years earlier. In 1888, he read the paper, I think, and looked, and he wrote very well and gives this beautiful, poetic description of looking at slices of the nervous system, stained with this. And he said it was like a fresh drawing with ink

on Japanese transparent paper. He could see the individual, nerve cells with all of their processes, the dendrites and their axons, but only a few percent of them were stained, so he could map them out clearly in a way that you couldn't when every nerve cell was stained. That was really one of the problems the anatomist faced, that if they stained everything, it was such a jumble of stuff that couldn't follow anything, but the Golgi stain will add them to. And he got very close to realizing that if you could stain a nerve cell in its entirety with all of its processes, then all of the individual nerve cells must be

separate from each other. There must be barriers between them to stop the stain running from one to another. He didn't quite actually say it, actually. It was a German, Willem Waldaya, yes, in Berlin, who postulate and put forward this neuron hypothesis, the idea that all of the nerve cells of the brain were distinct and separate from each other. Because there had been, and Golgi himself, the discoverer of the stain, still supported the view that the nervous system was a continuous network of intimately protoplasmically connected cells all joined together, just running continuously.

Because if they were, the brain couldn't possibly work. I mean, how could it calculate information if everything was connected to everything? But it was really Cahill's work, Sherrington's work on reflexes, and Valdea's suggestion to the neuron doctrine which led to this revolutionary change of view, that the nervous system was a collection of enormous numbers

of separate. We're talking millions really? Billions altogether, yes, certainly hundreds. Terrifying anything what's happening inside there. Yeah, exactly. But all separate from each other, but communicating with each other. So then the question was, how did they communicate? What was the nature of this

synaps, as Sherrington had called it, between nerve fibres and nerve cells? Vivian Nuttons, so where were the connections thought to be? The brain is now part of the nervous system. In that sense it's joined, but how did they prove the connections that Colin Blakemore's been talking about?

Well, one of the things is they're using different animals. One of the great experiments involves the octopus and particularly the squid, because these are big animals that you can then use to look at in a different way from very small animals. And in particular, the squid turned out to be the most fascinating, creature because it has a single axon which stretches the whole length of its body. Indeed, it's so large it was thought to be a blood vessel.

And it was J.Z. Young, who did a wonderful experiment to show that, in fact, it was an axon, not a blood vessel. And from then on, people began cutting up this squid axon to examine the cells, to examine its workings, in this larger environment that they could see, they could dissect more easily they could observe, and which in fact help to clarify that bundle of cells that Colin has just been talking about.

It seems it's increasingly becoming to be like a detective story here. We're sort of getting to the final solution, but Tilly Tansi. There was Henry Dale made a surprising discovery which took the journey on. Can you discuss what he? Well, Henry Dale had been a student of J.N. Langley's in Cambridge. So he was very impressed and very taken with this idea that nerve cells communicated with chemicals.

In the beginning of the 20th century, he was actually in a unique position. He worked for a pharmaceutical company. He worked in the Welcome physiological labs of Bowes Welcom. Nowadays, we're very familiar with the idea of research going on in a pharmaceutical company. At that time, it was completely novel. And, of course, for somebody who was interested in chemicals,

working in the pharmaceutical company, he had access not only to chemicals, but to chemists who would make specific chemicals for him. He increasingly found that there was one particular chemical called acetar-colin, which mimicked the effects of this parasympathetic, the slowing down part of the autonomic nervous system. And every way he tested it,

it looked as if acetar-coline was exactly the effect. the same. The effects of astralcholine were the same as a parasympathetic nervous system. And therefore, one conclusion would be that the parasympathetic nervous system works by releasing astralcholine. There was a problem. And it was a big problem. Ashtar colin didn't occur naturally. It wasn't, sorry, it wasn't known to occur naturally. It was just a synthetic oddity that a chemist made for Henry Dale to try. And so although there was some very convincing evidence that acetal colin was important, people disliked. dismissed the idea. And Henry Dale himself was obviously skeptical. Just before the First World War, he did actually find acetal coline occurring naturally, but this was just in the fungus. And that didn't really change people's minds very much. Just after the First World War, an Austrian pharmacologist Otto Lervey did some further, very convincing experiments that a chemical was involved in neural transmission. And in 1929, Henry Dale finally found acetal coline in an animal.

body. He wasn't looking for acetal coline. He was actually looking for another chemical histamine, but he found astralcholine. And this really was the final piece in the puzzle. Everything else then made sense. The evidence that asthmolone mimicked, the parasympathetic nervous system. It was a chemical neurotransmitter. It was found in the body. And therefore, a flood of experiments in the next three or four years went ahead to show that astalcoline was a transmitter. And Colin Blakemore, in the 1950s, a couple of British scientists a set to finally solve the problem of how nerve signals were transmitted. They won a Nobel Prize for it. What did Hodgkin and Huxley discover?

And how does that, did that solve everything or have we a way to go? Well, we're now switching back to the electrical ideas. There is, as you say, this detective story, chemistry, electricity, you know, who's the culprit? And the answer is both. Electricity in the nerve fibres, as Galvani had said, and then chemistry in the synapses for communicating between one cell and another. But Hodgkin and Huxley's great contribution was to show, in beautiful detail.

I mean, it's just the most wonderful example of mathematics applied to biology, but very clever experiments as well, to show the way in which the nerve impulse is produced in a nerve fibre and then transmitted along the fibre. See, there's this paradox which the German physicist Helmholtz had shown in 1830s,

that impulses travel quite quickly along nerve fibres, but not as quickly as electric current. I mean, electric current along a copper wire goes almost at the speed of light. But Helmholt showed that nerve impulses go along with, you know, a few metres a second. Fast, but not fast enough to be an electric current. That'd be something else. An active process going on.

And in fact, nerve impulses became called action potentials because of that. Changes of polarisation of the nerve membrane, of the voltage across the nerve membrane. And what Hodgian and Huxley did in Cambridge was to do a beautiful experiments in which they could freeze the nerve impulse. One of the problems about studying nerve impulse is that it is all over quite. quickly in a thousandth of a second. They discovered electrical ways of clamping the electrical properties of nerve membranes in squid axons, these giant

axons, and then studying the process in the static condition. And they showed basically that there are two processes going on, which means there must be two sorts of mechanism in the nerve membrane, which are selectively permissive to the flow of two different

kinds of charged ions, sodium ions and potassium ions. And the initial change of potential in this of the real pulse is caused by channels opening in the membrane which allows sodium to flood in to the nerve and change the potential inside it. In fact, to de-polarizing, making more positive inside. And then after a delay, the opening of another set of channels which allows potassium, a little bit of potassium, to go out to reverse it, switching on and switching off the nerve impulse in about a thousandth of a second. Just beautifully elegant experiments, then mimicked by

by modelling, by mathematical modelling, which match beautifully the data to show the characteristics of these channels. Can I go back to the beginning when Colin Blakemore said this was a thing for the end of the programme? When I tapped the table and said, well, what impulse is it that makes me tap the table in the first place?

Would any of you like to rise to that? One thing which strikes me from our conversation is that we're scientists are using a whole range of different techniques. We've got chemistry, we've got physics, we've now got mathematics and we still are a long, long, long way from understanding several of the problems.

We know a lot more about structures. We know a lot more about the communications, but we're still somewhere in Hitler that Colin would agree. I mean, it really goes back to Descartes, doesn't it? So why do I tap the table quickly, Tilly, we're nearly finished? You tapped the table just because you wanted to give us something to talk about. Yeah, but we haven't had time to talk about it properly. There's another programme, though.

You're backing off. But never mind. Thank you very much, Tilly, Tansy, Livia, Nutton and Colin Blakemore. Next week we'll be talking about the medieval Jewish philosopher Maimonides. Thank you very much for listening. If you've enjoyed this Radio 4 podcast, why not try others, such as Thinking Aloud, where Laurie Taylor discusses the latest social science research. To find out more, visit bbc.co.com.uk forward slash Radio 4.