At some time of our life, we have all felt unaccountably sleepy during the day – often as a consequence of jet-lag – but for some unfortunate people excessive sleepiness is more of a problem. Take Claire, for example, who abruptly and embarrassingly falls asleep at inopportune moments and is quite unable to do anything about it. She also once laughed so much at her friend’s joke that her legs gave way and she collapsed on the floor; indeed any form of excessive excitement or strong emotion can cause a loss of muscle tone so profound that she becomes floppy and falls over. Claire suffers from a chronic sleep disorder known as narcolepsy that is characterized by excessive daytime sleepiness despite adequate night-time sleep. The lack of muscle control she experiences is known as cataplexy and arises because the inhibitory pathways that prevent us moving during sleep are inappropriately switched on during wakefulness or very early in the sleep cycle.
A group of scientists led by Emmanuel Mignot investigated a strain of Doberman pinscher dogs that suffered from the same condition as Claire. Spotting a special food treat, one of these dogs will rush happily over and take a few mouthfuls, but after a few seconds will be so overcome by the excitement that it loses control of its limbs and collapses. The condition is inherited and by laboriously searching for the gene involved scientists identified a chemical called orexin (or hypocretin) that helps stop us falling asleep. This is produced by a small region of our hypothalamus and keeps us awake by stimulating electrical activity in other regions of the brain. If you lack the ability to make orexins, or you have insufficient orexin receptors (as the Doberman dogs did), you will fall asleep involuntarily.
Sleep is a universal imperative. All animals sleep, even insects and fish, and while we proverbially manage an average of eight hours a night, some creatures sleep for far longer. The champion is the two-toed sloth, which sleeps as much as twenty hours each day. Mammals that live in the sea would drown if they fell sleep underwater, so they rest half of their brain at a time, with one side remaining awake while the other is deeply asleep. So too do many birds, which often sleep away the night with one eye open, keeping watch for predators.
Quite why we sleep is still something of a mystery, but there is evidence that one reason is that it is important for memory consolidation. As you will no doubt already know from experience, without adequate sleep our ability to remember things diminishes. Strikingly, even a short nap can help with learning a new task. One hypothesis is that while we are laying down long-term memories, and consolidating and organizing new knowledge, it is important that there is no new input to confuse things. Cut off from the outside world, memories can be replayed, strengthened, stored or discarded more easily. Some evidence in favour of this view comes from the finding that during sleep hippocampal ‘place cells’ fire in a coordinated fashion that suggests the spatial reference map that is formed in the brain when an animal is exposed to a new environment is being replayed. It is as if the brain is remembering its earlier experience – although whether this replay is associated with the consolidation of memory or the transfer of memories out of the hippocampus to areas of the brain where memories are stored is still unknown.
Whatever its actual function, sleep is essential, for without it we soon die. Sleep, then, is very far from the ‘little slice of death’ that Edgar Allan Poe bewailed. Nor is it a nightly waste of time. Rather, as Shakespeare put it, it is ‘the chief nourisher in life’s feast’ and we should endeavour to make sure we get enough.
The God of Dreams
Once, when I was a child, my whole family came down with severe gastroenteritis. Both my parents and my siblings were hors de combat and I was the only person available to collect the medicine. We lived in an isolated village and there were no buses running at the time, so I jumped on my bicycle and pedalled the five miles to the doctor’s surgery. I was given a large glass bottle of kaolin and morphine that I stuffed in my jacket pocket. The journey back was something of a nightmare as it soon became clear that I too was suffering from the vomiting bug and I had to stop several times to throw up on the verge. I arrived home completely exhausted. My mother immediately gave me a large dose of medicine, but, being ill herself, she did not think to shake the bottle first. During the long journey, the kaolin had settled to the bottom and floating at the top was a (weak) solution of pure morphine. Morphine, named after Morpheus, the Greek god of sleep, is a powerful sedative and I slept for twenty-four hours.
Morphine is not only a sedative. It also produces relaxation, induces a state of delightful, dreamy euphoria and has the great virtue of relieving pain. It has been used for thousands of years, as both a medicinal and a recreational drug, in the form of opium, a crude extract of the opium poppy, Papaver somniferum. As the seventeenth-century physician Thomas Sydenham said, ‘among the remedies it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium’. Historically, a mixture of opium and alcohol called laudanum was used to treat a variety of ailments and as a consequence many people became addicted, including the poet Samuel Coleridge, who is believed to have written ‘Kubla Khan’ while under the influence of the drug. Others took it for pleasure. Thomas de Quincey wrote in his famous Confessions of an English Opium Eater, ‘I, wretch that I am, being so notoriously charmed by fairies against pain, must have resorted to opium in the abominable character of an adventurous voluptuary, angling in all streams for a variety of pleasures.’
Like other addictive drugs, morphine stimulates the reward centres of the brain, and when taken to excess produces feelings of pleasure so intense that when the ‘high’ wears off the addict craves for more. Its use has led to more than individual misery. By the late eighteenth century, a lucrative and cynical trade had grown up between Britain and China, brokered by the East India Company. Tea, at that time produced only in China, was in high demand in Britain. China demanded payment in silver, but as this was expensive British merchants gradually switched to trading opium for tea. It was trafficked in surreptitiously from India by an indirect route. This proved disastrous for China, as its addictive nature created an instant demand for opium and much of the peasantry and army became incapable of work or combat as a consequence. When China prohibited its sale and requested the illegal imports be halted, Britain, mindful of the economic value of the trade, refused. The issue escalated into the infamous Opium Wars, led to Hong Kong being ceded to the British, the establishment of tea plantations in India, and new trade treaties. Tea, in its own way, appears to be almost as addictive as opium (at least to the British).
Morphine and heroin, to which it is structurally similar, belong to a class of drugs known as opiates. They bind to opiate receptors in the brain and spinal cord, thereby shutting calcium channels and inhibiting transmitter release and neuronal electrical activity. It was musing about why we actually have opiate receptors in the first place that caused John Hughes and Hans Kosterlitz to speculate that the body might produce its own opiates. That led to the discovery of endorphins (the term derives from endogenous morphine), chemicals produced by the body that are released in response to pain. They are also the chemicals that produce the feeling of wellbeing you get from running and other forms of intensive exercise.
Like synthetic opiates, endorphins suppress electrical impulses in pain nerve cells. If you have ever seen a twitch put on a horse you will know just how powerful endorphins can be. The twitch is a loop of rope that is twisted around the animal’s sensitive upper lip and is often used to quieten a restive horse while it is being shod or examined. As the rope – and the lip – is twisted and tightened, the horse appears to almost fall asleep: it stops dancing around, its head droops, its eyes glaze over and it stands quietly. It does so because its system is flooded with endorphins, released in response to the intense pain produced by twisting its lip. Acupuncture also triggers endorphin release, which may explain why some surgical operations can be performed without anaesthesia.
Knockout Drops
Humphrey Davy was
a self-experimenter extraordinaire. Undeterred by almost killing himself by breathing pure carbon monoxide, he went on to investigate the physiological effects of many other substances. Around 1799, he discovered that nitrous oxide – previously believed by some to be a lethal gas – induced euphoria and uncontrollable outbursts of laughter, and led him to dance around his laboratory like a madman. He christened it laughing gas. Inhaling nitrous oxide soon became part of his daily routine. Strangely, however, despite the fact that Davy recognized that the gas took away the sensation of pain and even induced the loss of consciousness he never seemed to appreciate its potential as an anaesthetic.
In yet another example of how a British discovery was subsequently exploited to great effect by entrepreneurs in the United States, it was a group of US dentists, searching for a means of extracting teeth painlessly, who introduced general anaesthetics for pain relief. One of the first to do so was Horace Wells, who trialled nitrous oxide first on himself, and then on his patients. Confident of its virtue, he gave a public demonstration of a tooth extraction under ether anaesthesia to a class of medical students in Boston in 1845. It was not a success, as the gasbag was removed too soon, the patient yelped with pain and the watching students jeered and booed. Wells was so disheartened by the affair that he gave up dentistry, became addicted to chloroform, and threw sulphuric acid at two prostitutes while under the influence of the drug. When he realized what he had done, he committed suicide. Wells’s misery was compounded by the fact that his colleague, William Thomas Green Morton, performed the first successful public operation on a patient under ether anaesthesia in Boston just a year after his own abortive attempt. Unlike Wells, Morton was widely lauded. He was far less popular, however, for his attempts to make money from the process: his patenting of the use of ether as an anaesthetic caused a public outcry and his demand that Congress pay him 100,000 dollars as a ‘national recompense’ for his invention was met with scorn.
Because ether tends to irritate the lungs (and explodes easily), James Simpson, a Scottish obstetrician, subsequently introduced the use of chloroform to ease the pain of labour. Although some opposed the practice, citing the teachings of Genesis in which God tells Eve, ‘in sorrow thou shalt bring forth children’, its use received a considerable boost when it was administered to Queen Victoria on 7 April 1853 during the delivery of her eighth child, Prince Leopold. The British Medical Journal commented, ‘the Royal Majesty of the patient, and the excellence of her recovery, are circumstances which will probably remove much of the lingering professional and popular prejudice against the use of anaesthesia in midwifery’. Fascinatingly, the Court Circular reports that during the birth the Queen was attended not only by her doctors and a nurse, but also by Prince Albert, proving him to have been a thoroughly modern husband.
A good general anaesthetic needs to induce loss of consciousness, loss of pain sensation (analgesia), immobility and preferably also amnesia so that you fail to remember the experience. All of this must be achieved without affecting the heart and, if possible, the respiratory muscles, and without causing vomiting or long-lasting neurological complications. And of course it must be easily reversible. Not all of these attributes are necessarily found in a single drug. Ether and chloroform are effective anaesthetics, but they are far from perfect, and today vapours such as isoflurane and sevoflurane, or injected drugs like propofol, are usually used to induce loss of consciousness and amnesia, with other drugs being used to produce analgesia and muscle relaxation. Interestingly, nitrous oxide gas still has a useful role in many cases.
As a general anaesthetic takes effect, you first enter a sedated state: you become drowsy and even if the anaesthetic is removed you will remember little of the experience. Gradually, you fail to respond to verbal commands and drift into unconsciousness. Surprising as it may seem, you then enter an excited state characterized by uncontrolled movements and irregular breathing. Subsequently your muscles relax again, breathing becomes regular, eye movements cease and you are now so fully asleep that a surgeon can perform an operation without causing pain. At this stage, brain scans show that metabolic activity is uniformly suppressed across your brain, suggesting that all brain regions are affected. It seems there is no brain region that is especially sensitive to general anaesthetics. Frustratingly for neuroscientists trying to identify where consciousness arises in the brain, it has not been possible to identify an area whose activity ‘winks out’ just as consciousness is lost.
Despite the fact that general anaesthetics are administered to thousands of people throughout the world every day, we still have only a limited idea of how they work, and how they induce unconsciousness remains one of the great mysteries of neuroscience. Current evidence suggests that they suppress brain electrical activity by interacting with ion channels. It is suggested that they stabilize a particular conformational state of the channel by occupying gaps in the protein molecule itself or by intercalating between the protein and the lipid membrane in which it sits. Some anaesthetics seem to open ion channels that suppress the electrical activity of brain cells, such as GABA channels, glycine receptors and potassium channels. Other anaesthetics block synaptic transmission by inhibiting the function of excitatory glutamate receptors. The fact that both excitatory and inhibitory neurones are affected fits with the general suppression of electrical activity seen in brain scans.
Who Am I?
Precisely what consciousness is has occupied philosophers and neuroscientists for centuries and we still lack a definitive understanding. Yet it is something that each of us is so familiar with and that we all experience. ‘I think’, said René Descartes back in the fifteenth century, ‘therefore I am’. But what, exactly, am ‘I’?
In Descartes’s view, the mind and body were separate entities. But the profound changes in our personalities produced by drugs, disease and brain damage provide abundant evidence that this is not the case – our minds are the product of our brains. Parenthetically, I have often wondered if the Cartesian view may in part stem from the fact that philosophy was once primarily the preserve of men, for the penis often appears to have a life of its own, sometimes refusing to perform when desired or being embarrassingly eager at inopportune moments. Women, on the other hand, whose emotional state is clearly influenced by their hormonal cycle, are constantly reminded of the link between body and mind.
Despite our very powerful sense of self, neuroscience reveals we are no more than the integrated electrical activity of our brain cells. Uncomfortable as it may seem, there is no separate entity, no soul, and nothing that lives on after our death – a fact that catapults science into direct conflict with many religions. So where does it come from, this precarious feeling of ‘I’, this person sitting here inside my head, looking out of my eyes, tapping away at this keyboard, trying to communicate my thoughts to you?
We are not born with a sense of self. Babies are not self-aware, nor do they recognize the thoughts and feelings of others. They develop these attributes gradually. A common way to assess self-awareness in very young children or animals is to test their ability to recognize themselves in a mirror by sticking a brightly coloured label on their head. If they identify themselves they will try and remove the label – but if they see a stranger they will do nothing, or reach out towards the image in the mirror. By this criterion, human children become self-aware between the age of two and three. It seems that our brains must reach a certain stage of development before we are fully self-aware. It is also not an instant ‘awakening’ – psychologists suggest that there are several steps in the development of self-awareness.
The next obvious question is where self-awareness is located in the brain. Is it a distributed entity, involving multiple networks of nerve cells, or does it reside in a specific set of nerve cells? Studies of brain-damaged patients suggest there is no discrete site for self-awareness, because while damage to specific regions of the brain can cause dramatic changes in personality, it does not create a zombie – an individual with no s
ense of self but otherwise functionally normal. Likewise, no one brain region ‘winks out’ concomitantly with the loss of consciousness when you are given a general anaesthetic. The loss of consciousness we experience during sleep is also very different from that of anaesthesia; anaesthesia seems to cause a general depression of electrical activity across the brain, but sleep is an exquisitely regulated active condition. The very different patterns of brain activity during sleep, anaesthesia and wakefulness indicate that loss of consciousness – and by implication perhaps also consciousness itself – may have more than one origin. It also seems to require the integrated activity of many neurones – but exactly which ones is still a mystery.
It is also worth noting that memory is intimately connected with our perception of consciousness. Patients given certain sedatives are able to respond to the doctor’s commands, can feel pain and would probably claim to be conscious if asked. Yet when the drug wears off they remember nothing and will state they were unconscious throughout the operation. A similar phenomenon is found with notorious date-rape drugs such as rohypnol, which can produce profound amnesia. Perhaps, then, one reason that children do not develop self-awareness until the age of two or three is that long-term memories do not appear to be laid down until about the same age – few of us remember anything before we were three.
And yet, you may argue, it feels so real, this individual inside my head. How can it be no more than an illusion? But remember that we are easily fooled. Our brain shapes the way we perceive the world, and the way we react to it. It regularly seduces us into thinking we see or hear something other than we do, for visual illusions abound and attention may wax and wane. Brain imaging even indicates that we may act on a decision, such as whether to press a button with our right or left hand, even before we are aware of having made it. Free will, like so much else, is merely an illusion. It, too, is a construct of our brain.
The Spark of Life: Electricity in the Human Body Page 29