But Aldini was not the first to use humans. As early as 1798, Xavier Bichat experimented upon bodies of those guillotined during the French Revolution, within forty minutes of their execution. He had no shortage of subjects. His experiments showed that the heart could be excited by electricity when stimulated by direct contact, and they exerted a macabre fascination on the scientific and literary imagination alike.
Equally grotesque experiments were carried out in 1818 by Dr Andrew Ure, which produced as electrifying a reaction in the audience as in the corpse. As Ure describes in his book A Dictionary of Chemistry and Mineralogy, the cadaver was that of an extremely muscular young man who was brought to the anatomy theatre of Glasgow University within ten minutes of being cut down. Incisions were made in the body to enable a battery to be connected, via conducting rods, directly to the nerves. Application of one rod to the spinal cord and the other to the sciatic nerve resulted in violent shudders throughout the body. And, ‘On moving the second rod from the hip to the heel, the knee being previously bent, the leg was thrown out with such violence as nearly to overturn one of the assistants, who in vain attempted to prevent its extension.’ In a second experiment, the rod was applied to the phrenic nerve in the neck. The success of this was ‘truly wonderful. Full, nay, laborious breathing, instantly commenced. The chest heaved, and fell; the belly was protruded and again collapsed, with the relaxing and retiring diaphragm’. Touching the rod to the supraorbital nerve induced the most extraordinary grimaces – ‘rage, horror, despair, anguish, and ghastly smiles, united their hideous expression in the murderer’s face’. Several of the spectators were forced to leave the room from terror or sickness and one man fainted. But worse was to come for electrical stimulation of the ulnar nerve animated the fingers, which ‘moved nimbly like those of a violin performer’, and at one point the arm shook and the forefinger extended and seemed to point at the spectators, some of whom thought it had come to life.
Such spectacles did not help the popular view that all doctors were quacks. Small wonder that Lord Bryon wrote,
What varied wonders tempt us as they pass!
The Cow-pox, Tractors, Galvanism, and Gas
In turns appear, to make the vulgar stare,
Till the swoln bubble bursts – and all is air!
The blasphemous nature of the experiments, due to the possibility of ‘resurrecting’ the dead, also did not go unremarked. Together with Frankenstein’s monster, they gave rise to the idea of the scientist as both ‘mad’ and ‘bad’, an image that pervades the media even today.
With present-day knowledge, the experiments of Galvani and his colleagues are easily explained. The cells of the body do not die when an animal (or person) itself breathes its last breath, which is why it is possible to transplant organs from one individual to another, and why blood transfusions work. Unless it is blown to smithereens, the death of a multicellular organism is rarely an instantaneous event, but instead a gradual closing down, an extinction by stages. Nerve and muscle cells continue to retain their hold on life for some time after the individual is dead and thus can be ‘animated’ by application of electricity. Just as an electric shock will stimulate your nerves so that the muscles they innervate will contract, so too with the nerves of a recently dead corpse. Indeed, the experiments of Ure and Aldini provide a dramatic demonstration of which muscles individual nerves innervate. Nevertheless, the sooner after death the experiment can be implemented, the more likely a response will be obtained.
The Age of Wonder
By the end of the eighteenth century, electricity could be generated, stored and conducted along wires for significant distances. Its wondrous effects excited the interest of scientists and galvanized their research. The culture of the Enlightenment, which dictated that scientific advances should be communicated to the non-specialist, led to spectacular public entertainments that sparked interest in the wider community. Indeed the public science lectures given by the director of London’s Royal Institution, Michael Faraday, were so popular with the wealthy gentry that Albemarle Street became heavily congested, particularly when carriages were collecting people after a lecture, and the first one-way street in the city had to be introduced.
The use of electricity to treat all kinds of medical complaint was widely advocated, as related in Chapter 12. Lightning rods and early batteries offered other practical applications and heralded the dawn of a new electric age. But not everyone was immediately impressed with the possibilities that electricity afforded. William Gladstone, then Chancellor of the Exchequer, once visited Faraday’s laboratory. He stood silent for a moment before the scientist’s electrical contraptions and then remarked, ‘It is very interesting, Mr Faraday, but what practical worth has it?’ Faraday was more than a match for him. He is reputed to have replied, ‘Sir, I know not what these machines will be used for, but I am sure that one day you will tax them.’
It was also appreciated that nerve and muscle fibres could be stimulated by electric shocks. Although Galvani’s idea of animal electricity was contested, it was not without support, for it had been known since antiquity that electric fishes could produce a severe electric shock. Furthermore in 1797 the young scientist and explorer Alexander von Humboldt established that Galvani’s and Volta’s ideas were both correct and predicted that every contraction of a muscle would be preceded by an electrical discharge from the nerve supplying it. In this light, the idea that galvanism could animate a lifeless creature, such as Victor Frankenstein’s monster, requires only a small stretch of the imagination. Recording the currents associated with the conduction of nerve and muscle impulses and unravelling the underlying mechanisms, however, had to await the development of suitable instruments and a greater understanding of electricity itself.
2
Molecular Pores
The American quarter horse
known as Impressive,
the shivering pig,
a whole herd of goats
in Texas, and some
among you in the front row
with your various flaws
will feel the pang of recognition,
a flutter in the ion channels,
as you watch me fall down.
Jo Shapcott, ‘Discourses’
During an oral examination at Oxford University around 1890, a student was asked if he could explain electricity. He replied nervously that he was sure he once knew what it was – but he had forgotten. ‘How very unfortunate’, remarked the examiner, ‘Only two persons have ever known what electricity is: the Author of Nature and yourself. Now one of the two has forgotten.’
Today, we are all very familiar with electricity as it powers our industrial society. Almost everything we use – our transport, lighting and communications devices, even the computer I am writing this on – runs on electricity. But what is less widely recognized is that we too are electrical machines and that electrical currents lie at the heart of life itself. In turn, these currents are due to the activity of ion channels. To appreciate how it has been possible to leap from Galvani’s experiments with frogs’ legs to our ability to treat diseases of electrical activity like epilepsy – or the neonatal diabetes from which James suffers – it is necessary to understand what ion channels are and how they contribute to the electrical responses in cells.
For more than a century and a half after Galvani, scientists laboured to measure the electrical impulses of our nerves and interpet what they meant. It took even longer to detect the ion channels that are responsible – but their discovery transformed our understanding. The concepts I had struggled with as a young student, and that caused me many sleepless nights (especially around the time of the examinations), suddenly became crystal clear. This chapter therefore jumps straight to the present day and provides a state-of-the-art picture of how ion channels work. But first it is helpful to consider what electricity is and how the electricity in your head differs from that supplied to your home.
The Holy Trinity
El
ectricity is a form of energy that is based on electric charge, one of the most fundamental properties of subatomic matter. The electric currents that flow through the wires in our houses – and along our nerves – are quantified in terms of three basic units: the amp (A), the volt (V), and the ohm (Ω). They are named after a triumvirate of great eighteenth-century European physicists: the Frenchman André-Marie Ampere, the Italian Alessandro Volta and the German Georg Ohm. Current is measured in amps, resistance to current flow in ohms, and voltage, the force that drives the current flow, in volts.
The flow of electric current through a wire is often explained by analogy with the flow of water through a pipe. In electrical terms, the current corresponds to the rate at which a stream of charged particles moves, with one amp being the equivalent of approximately six million million million (6x1018) particles per second.
Resistance is a measure of the ease or difficulty of flow. Narrowing a pipe will restrict the flow of water, whereas increasing the pipe’s diameter will increase water flow. In an electric circuit, materials that offer little resistance to current flow, such as metals, are called conductors, whereas those that resist the flow of current (like paper or air) are known as insulators. Grasp the bare wire of an electric fence and you will get an unpleasant shock, but you will feel nothing if you instead take hold of one of the insulated handles that enables you to open the gate in the fence.
The voltage difference between one point and another is equivalent to the difference in water pressure that causes water to flow from one region to another. Essentially it is the force that drives the current flow. It is also sometimes called the electrical potential difference (or potential for short). Providing two points are not connected, no water will flow between them, and in an analogous way an electric current will only flow when a circuit is complete. This is why there can be a huge voltage difference between a thundercloud and the ground, but no current flows until the lightning bolt jumps the gap. It also explains why electrons do not move along a wire unless the electric circuit is complete, and thus why your desk lamp does not light up until you flick the on/off switch that links the wires. Just as increasing the water pressure will increase the flow of water, so boosting the voltage increases the current. Increasing the voltage supplied to the lamp, for example, will make it shine brighter.
Ground (or earth) is defined as the lowest point of voltage and, like water, current will always flow to the lowest level. This was appreciated early. In 1785 Joseph-Aignan Sigaud de la Fond was bewildered to find that although he had a highly charged Leyden bottle and a chain of sixty people holding hands, the shock was not felt by more than the first six. Why it stopped at the sixth man was a mystery, and it was argued that there must be something peculiar about him. The favoured hypothesis was that the young man in question was not endowed with ‘everything that constitutes the distinctive character of a man’ – not, in other words, in full possession of Nature’s attributes. Gossips quickly spread the idea around Paris that it was impossible to electrify a eunuch.
The Duc de Châtres, who had a scientific turn of mind, demanded proof and the requisite experiment was carried out using three of the King’s musicians, with understandable apprehension on the part of both the experimental subjects and the fully endowed controls. To Sigaud’s further bafflement, all three castrati felt the shock. The mystery was only solved when the experiment was repeated many more times and it was noticed that individuals who did not transmit the shock were standing on soggy ground. As wet earth is a better conductor of electricity than the human body, the current preferentially flowed to ground. This is also the reason you get an electric shock when you accidentally touch a live wire: the ground on which you stand is at a lower voltage than the wire in your hand, so that the current flows through you to the ground.
Amps, volts and ohms are bound together in an eternal embrace, as was first appreciated by Ohm. He formulated a famous law, which states that the current (I) is equal to the potential (V) divided by the resistance (R); it is abbreviated mathematically as I=V/R. In other words, provided that the resistance remains the same, increasing the voltage will increase the magnitude of the current that flows. Similarly, if the resistance falls, but the voltage remains the same, then the current will increase. And so on. This simple formula, known as Ohm’s Law, is the key to understanding how nerves – and electricity – work.
Poles Apart
There is a fundamental difference, however, between the electricity that powers our bodies and that which lights our cities. The electricity supplied to our homes is carried by electrons. These indivisible subatomic particles carry a negative electric charge and because opposite charges attract one another (and similar charges repel) electrons always flow from a region of negative to positive charge. Confusingly, we define current as the direction of flow of positive charges, which means that the current in a wire moves in the opposite direction to that in which the electrons flow!
In contrast, almost all currents in the animal kingdom are carried by ions – electrically charged atoms. There are five main ions that carry currents in our bodies. Four are positively charged – sodium, potassium, calcium and hydrogen (protons) – and one, chloride, is negatively charged. Because they are electrically charged, the movement of ions creates an electric current. In the case of positively charged ions, the current flow is in the same direction as the flow of ions, whereas for negatively charged ions (as for electrons) it is in the opposite direction.
It is also worth noting that currents in electric circuits flow along the length of the wire. In contrast, the ion currents responsible for nerve impulses flow across the membranes that envelop our cells, into or out of the cell. Thus although electrical impulses travel along the length of our nerve and muscle fibres, the ion currents that generate them flow at right angles to the direction of travel.
Another difference between the electrical signals in our heads and in our homes is their speed of transmission. An electrical signal in a wire travels at almost the speed of light, which is 186 million miles per second. It’s easy to see this, for when you flick the switch a light comes on at once, and telephones and the Internet provide almost instantaneous communication around the globe. By comparison, the fastest nerve impulses are pitifully slow, crawling along at a mere 0.07 miles a second (120 metres a second). Even the brightest of us cannot think at the speed of light.
As well as being slower, the electrical impulses we generate are also much smaller. Your electric kettle needs three amps of current to run, but the currents that tell your heart when to beat are only a few millionths of an amp. Finally, while energy is needed in both cases, the power – the battery if you will – that drives the current is produced in quite different ways, as explained later.
These differences between animal electricity and that which supplies our homes are simple to state, but took many years to understand. Although the fundamental properties of electricity were understood by the beginning of the nineteenth century, it is only in the last sixty years or so that we have begun to understand the origin of bioelectricity and only in the last fifteen years that we have had a glimpse of what the molecules (the ion channels) responsible for the electrical activity of our nerve and muscle cells actually look like.
The Building Blocks of Life
We are no more than a collection of cells, millions and millions of them – as many as the stars in the galaxy. They come in many different varieties, like muscle cells and brain cells and blood cells, and in multiple shapes and sizes, but they are all the same fundamental entity. Robert Hooke discovered them in 1665 when he was examining a small section of cork under his microscope. He named them cells because they reminded him of the tiny chambers monks lived in, but you’ll get a better idea of what they look like if you imagine the cells of a honeycomb on a much smaller scale.
Cells are teeming with molecules carrying out all sorts of complicated reactions, labouring away at making proteins, replicating DNA and generating energy. H
owever, for understanding the electrical properties of cells we only need to consider the events at the cell surface, as it is here that voltage differences arise and nerve impulses are transmitted.
Each of our cells is surrounded by a membrane that encloses its contents and serves as a barrier to the world outside, rather like the skin of a soap bubble. This membrane is made up of fats (technically known as lipids), which means that it is impermeable to most water-soluble substances. It arises from the simple fact that fats and water do not mix. As anyone who has made a vinaigrette salad dressing knows, over time the ingredients separate into a lower layer of vinegar with the lighter oil floating on top. The phospholipid molecules that make up the cell membrane have water-loving phosphate heads and lipid tails that prefer to avoid water, and they organize themselves into a double-layered membrane in which the water-shy lipid tails are sandwiched inside the bilayer between two layers of phosphate headgroups. Don’t think, though, that membrane lipids are as hard as butter – they are more the consistency of machine oil, so that the proteins that sit in them tend to float about and must be anchored to the cell’s cytoskeleton to keep them in their correct places.
The Spark of Life: Electricity in the Human Body Page 4