Counting Sheep: The Science and Pleasures of Sleep and Dreams

A waking death

We term sleep a death, and yet it is waking that kills us, and destroys those spirits that are the house of life.

Sir Thomas Browne, Religio Medici (1642)

What happens when sleep deprivation is taken to the extreme? If a slight insufficiency of sleep makes us feel unwell, would a prolonged absence kill us? Setting aside purely anecdotal accounts, science has unsurprisingly not investigated whether forcibly depriving humans of sleep is fatal. Ethical committees would tend to frown upon applications from scientists proposing to test this experimentally. But the evidence from other species is clear. Animals that have been experimentally deprived of sleep for long enough invariably die. There is no reason to suppose that humans are fundamentally different.

Some of the earliest experiments on extreme sleep deprivation were performed in the late nineteenth century by a Russian scientist called Marie de Manacéïne. She deprived puppies of sleep by keeping them constantly active. They all died within four or five days, despite every effort to keep them alive. The younger the puppy, the more rapidly it succumbed. Marie de Manacéïne also noticed a progressive decline in the body temperature of the sleep-deprived animals, a phenomenon that is now known to be a standard symptom of prolonged sleep deprivation in humans and other species. She concluded that sleep was even more crucial for survival than food:

As a rule, the puppy deprived of sleep for three or four days presents a more pitiful appearance than one which has passed ten or fifteen days without food. I can speak from observation, as I was obliged to make experiments on the results of want of food as well as of sleep, and I became firmly convinced that sleep is more necessary to animals endowed with consciousness than even food.

Italian scientists working at the end of the nineteenth century kept adult dogs awake by making them walk. The sleep-deprived dogs all died after 9–17 days, regardless of how much food they ate.

One objection to experiments such as these (apart from the obvious ethical one) is that the scientists had to use increasingly stressful methods to keep the animals awake, so perhaps it was the stress that killed them rather than the sleep deprivation itself. Prolonged stress can impair the immune system and make an animal more vulnerable to infection. However, more recent research has managed to sidestep this methodological problem.

In a long series of experiments, Alan Rechtschaffen and colleagues at the University of Chicago systematically investigated how prolonged sleep deprivation affects rats. They used an experimental procedure known as the disc-over-water method, which works like this. Two rats – the experimental subject and the ‘yoked control’ – are placed on a turntable mounted over a shallow bath of water. The brain-wave patterns of both animals are continuously monitored to detect the onset of sleep. When the experimental rat’s brain waves indicate that it is falling asleep, the turntable automatically revolves slowly, waking the unfortunate rat and forcing it to walk in the opposite direction to avoid being pitched into the water. The control animal, which is on the other side of the turntable and separated by a partition, receives precisely the same treatment at precisely the same times. The crucial difference is that the turntable movements are unaffected by its sleep. The control animal is therefore able to get some sleep when the experimental animal is awake. This cunning technique has the advantage – from the human experimenter’s point of view – of preventing the experimental subject from sleeping without having to subject it to other noxious stimuli.

Rats that are prevented in this way from sleeping invariably die after two or three weeks. The control animals, which experience the same stimuli but not the complete loss of sleep, survive and display relatively few symptoms. Before they die, the sleep-deprived rats all exhibit the same horrible syndrome. This is characterised by a debilitated appearance, skin lesions, increased food intake, weight loss, increased metabolic rate, increased levels of the hormone noradrenaline, and declining body temperature. Some of these changes are symptomatic of excessive heat loss from the body, which has led some scientists to suggest that sleep is crucial, among other things, for the regulation of body temperature.

A progressive rise in metabolic rate (the rate at which the body consumes energy) is an early symptom of sleep deprivation. Sleep-deprived rats eat more to compensate for their rising energy expenditure, but their weight and body temperature nonetheless continue to fall. Feeding them an easily digestible diet helps to slow this process somewhat, but it does not prevent them from dying. An increase in appetite is one of the less obvious effects of sleep deprivation in humans as well. Might it be that chronic sleep deprivation is one of the factors helping to fuel the epidemic of obesity that is currently sweeping the USA, UK and other industrialised nations?

Body and soul

Health may be as much injured by interrupted and insufficient sleep as by luxurious indulgence.

William Kitchiner, The Art of Invigorating and Prolonging Life (1822)

What of people? Research on humans has stopped short of the lethal sleep deprivation imposed on rats and puppies, but it has delved systematically into the consequences of a few days’ sleep loss. The results consistently show that moderate sleep deprivation has pervasive effects on the human body as well as the human mind. Sleep loss impairs vision, for example, causing blurring and errors in judging distances. It also triggers the familiar decline in body temperature that Marie de Manacéïine observed in her puppies, together with a reduction in blood glucose levels and changes in various hormones.

Set against this, sleep loss has surprisingly little impact on our ability to keep moving around and doing physical work. Moderate sleep deprivation does not greatly diminish our capacity for labour. Physically fit young adults can withstand several days of sleep deprivation without a substantial deterioration in their muscle strength, muscle endurance or cardiovascular responses to exercise. In one experiment, for example, the exercise capacity of young women was assessed following 60 hours without sleep. The sleep deprivation had no significant effect on their aerobic capacity or their endurance for exhausting exercise. In another study, researchers monitored two men while they played a marathon tennis match lasting a week, during which time the players got very little sleep. Although their mental performance deteriorated during the match, the players were able to sustain a high level of physical work. Our muscles can mostly keep going even when our brains are flagging.

Sleep deprivation does disturb many aspects of physiological functioning, however. Breathing is one example. A single night of sleep loss impairs breathing in healthy people, provoking a small but significant reduction in the maximum amount of air that can be exhaled after maximum inhalation. Sleep loss also leads to a substantial blunting of the normal respiratory responses to reduced blood-oxygen levels. After 30 hours without sleep there are marked deteriorations in the strength and endurance of the muscles used for breathing – as revealed, for example, by a reduction in the time for which people can breathe in against a sustained pressure. Such changes could be important in patients with respiratory diseases, who often suffer from chronic sleep loss. Sleep deprivation also slows the rate of cardiovascular recovery from intense exercise. When someone has been deprived of sleep for 24 hours, their breathing rate and oxygen uptake after a burst of intense exercise remain higher for longer.

Sleep loss is accompanied by many changes in body chemistry. People who have been kept awake for more than three days have altered liver functions, marked by large increases in the levels of key liver enzymes, changes in various types of fat and a rise in the amount of phosphorus circulating in the blood. Thyroid hormone levels are affected and biochemical changes can be detected at the level of gene activity.

Glucose metabolism is particularly perturbed by sleep loss. Healthy young men whose sleep was experimentally restricted to four hours a night for six nights became less tolerant to glucose. They took 40 per cent longer than normal to regulate their blood-sugar levels after eating high-carbohydrate food, and their ability to produce insulin fell by nearly a third – a condition resembling the early signs of diabetes. These abnormalities vanished after the men had slept for 12 hours. Fatigue-induced physiological changes like these could contribute to the development of chronic conditions such as diabetes, obesity and high blood pressure, all of which are associated with a shortened lifespan.

Sleep, immunity and health

Our foster-nurse of nature is repose.

William Shakespeare, King Lear (1605–6)

Some of the most interesting, least well understood, and potentially important consequences of sleep deprivation are found within the immune system. In short, lack of sleep can impair the body’s immune defences and thereby make us more susceptible to infection by bacteria, viruses and parasites.

The evidence comes mostly from research with other species. In one experiment, for example, mice that were immunised against the influenza virus were resistant to infection if they were exposed again to the virus a week later. But if the immunised mice were deprived of sleep for seven hours immediately after being exposed to the virus, they were no more resistant to infection than mice that had not been immunised at all. A mere seven hours of sleep deprivation disturbed their immune response enough to erase the benefits of immunisation.

Some scientists have suggested that one reason why prolonged sleep deprivation is ultimately fatal is that it breaks down the animal’s immune defences, making it vulnerable to infection by any opportunistic bacteria and viruses that happen to be in the vicinity. Experiments with rats have shown that following severe sleep deprivation, the lymph nodes and other organs are invaded by potentially dangerous bacteria, which appear to have migrated there from the intestines. However, the role of infection in killing sleep-deprived animals remains a controversial issue.

Sleep loss impairs the human immune system as well. Even modest sleep deprivation evokes measurable changes. One night of sleep loss lowers the activity of natural killer cells and reduces the numbers of several different types of white blood cells circulating in the bloodstream. (Natural killer cells are a special type of lymphocyte, or white blood cell, that attack virus-infected cells and certain types of cancer cells.) Depriving healthy adults of sleep for seven hours on one night suppressed their natural killer-cell activity by 28 per cent. It bounced back to normal after a night of uninterrupted sleep. Moderate sleep loss will also reduce the body’s production of interleukin-2, a chemical messenger substance that plays an important role in regulating immune responses. After two or three days of sleep deprivation there is a marked decline in the responsiveness of lymphocytes and an even bigger fall in the activity of natural killer cells.

Sleep loss might play a role in the well-established connection between severe depression and impaired immune function. Depressed people generally sleep badly and have poorer immune responses. The more disrupted their sleep, the bigger the decline in their immune function. One study, for example, found that people who were suffering from depression following bereavement had fewer natural killer cells. The bereaved subjects were troubled by intrusive thoughts that often woke them or kept them awake during the night. The extent of the reduction in their natural killer-cell numbers was correlated with the amount of time they spent awake during the night: the more troubled someone was by their loss, the more disrupted their sleep and the fewer natural killer cells circulating in their blood. Sleep deprivation could be one of the mechanisms by which depression makes people more vulnerable to illness.

The relationship between sleep and immunity works in both directions. Not only does sleep affect the immune system, but the immune system also affects sleep. The immune reactions triggered by infection and illness can elicit alterations in sleep patterns. That is why infections are often accompanied by lethargy, loss of appetite, depressed mood and general malaise. Animals infected with influenza virus display a large increase in sleep about 24 hours after exposure to the virus. These changes in wakefulness are part of the body’s defence mechanisms and assist the recovery process. Human experiments, in which noble volunteers were injected with bacterial toxins, found that sleep is highly sensitive to the activation of the immune defences. Low-level infection tends to promote deep sleep. However, a full-blown infection accompanied by fever induces lethargy but typically disrupts sleep. You might have noticed that you sleep more deeply for a night or two when your body is fending off a potential infection, whereas when you are in the throes of a galloping illness you feel exhausted but lie for hours without sleeping.

The immune response to infection stimulates the release of chemical messenger substances that act on the brain to induce malaise, drowsiness, loss of appetite and sleep. During infection, a substance known as interleukin-1 stimulates the brain to induce deep sleep, while other interleukins trigger the fever that often accompanies infections. They do this by adjusting the brain’s temperature control centres – in effect, putting the body’s thermostat on a higher setting. That is why we feel hot and sleepy when we have a bad infection. The fever response is a defence mechanism found in all animals: the rise in body temperature makes life harder for the offending bacteria or viruses, and the lethargy forces the infected organism to curl up in a dark corner and sleep until it has recovered. It all makes good biological sense.

The brain and the immune system are interconnected through an elaborate network of chemical and neural communication channels. One important link between sleep, immune function and psychological stress is the steroid hormone cortisol. Sleep deprivation and prolonged stress both provoke an increase in the level of cortisol. After one night of sleep loss, your cortisol levels would typically be raised by about 45 per cent the next evening. It is not good to have elevated cortisol levels for too long, since cortisol has a powerful suppressive effect on the immune system. The functioning of the immune system is also intimately bound up with the 24-hour sleep – wake cycle and the circadian rhythms in hormone levels. Various aspects of immune function fluctuate in tune with the circadian cycle. Anything that disrupts the normal cycle of sleep and wakefulness therefore tends to disturb the immune system, with potential consequences for the body’s ability to defend itself against infection and disease.

The intimate relationship between sleep and immune function takes on a potentially huge practical significance when you consider how widespread sleep deprivation has become in society. Tired people are more likely to become sick people.

The Battle of Stalingrad

O, I have passed a miserable night,

So full of fearful dreams, of ugly sights

William Shakespeare, Richard III (1591)

Prolonged sleep deprivation, uncontrollable stress and starvation make a lethal cocktail, as Hitler’s troops found to their cost during the Battle of Stalingrad in World War Two. In June 1941 German forces invaded the Soviet Union and were soon threatening Moscow. The capture of Stalingrad on the River Volga became a key strategic objective. Stalin decreed that the city must be defended to the bitter end. The titanic struggle that ensued cost the lives of at least 800,000 Axis soldiers and 1.1 million Soviet soldiers.

The fight for Stalingrad (now renamed Volgograd) began in earnest in the summer of 1942, as the Germans advanced rapidly towards its suburbs. There was fierce Soviet resistance and the fighting dragged on into the harsh Russian winter. By September 1942 the battle was being waged at close quarters among the buildings, cellars, sewers and bunkers of ‘the Stalingrad Academy of street-fighting’.

To increase the pressure on their opponents, the Soviet commanders ordered continual raids to be carried out by night. They did this partly because the Germans lacked protection from their air force at night, but mainly to induce exhaustion among the enemy. To augment the night raids, the Soviets fired flares indicating that an attack was imminent even when it was not. Their air force also attacked German positions every night. The Soviets kept up the psychological pressure throughout the night, with loudspeakers blaring out propaganda broadcasts, surreal tango music, or the sound of a ticking clock. The strategy was highly effective. ‘We lie exhausted in our holes waiting for them,’ wrote one German soldier. The German commanders begged for air support, citing their men’s exhaustion.

The German troops’ health started to deteriorate badly even before the dreadful Russian winter had begun to bite. There was a sharp rise in deaths from infectious diseases including dysentery, typhus and paratyphus. The actual prevalence of these diseases was not much worse than it had been a year earlier, but the numbers of infected men who were dying from them increased fivefold. It was as though the German soldiers had lost their capacity to resist infection. The Russians noticed this phenomenon, which they referred to as ‘the German sickness’.

In November 1942 the Russians launched a huge and ultimately successful counteroffensive that soon had the Germans encircled within the ruined city. But the Germans were under orders from Hitler not to surrender, and so they fought on through December while the Russians gradually tightened the noose. Conditions for the German troops became appalling as their supply lines were cut off and the Russian winter froze them. There was hardly any food and little or no medical care.

In mid-December 1942 the German military doctors in Stalingrad noticed a new phenomenon: more and more apparently healthy troops were suddenly dying for no obvious reason. The Germans were unsure whether the deaths were the result of starvation, exposure, exhaustion or an unidentified disease. A German army pathologist named Girgensohn, who was sent to Stalingrad to investigate the problem, became convinced that a combination of exhaustion, stress, cold and lack of food was responsible for the much higher death rate. The Russian night attacks and round-the-clock activity had caused severe sleep deprivation, and Girgensohn concluded that this had amplified the effects of the food shortage by ‘upsetting the metabolism’ of the exhausted Germans. We know now that one symptom of prolonged sleep deprivation is a marked increase in metabolic rate and hence the requirement for food. Whatever the precise explanation, the pressure was too much for the Germans. In February 1943 the Battle of Stalingrad finally ground to a halt, as the crushed and starving remnants of the German army surrendered.

Sleepless in hospital

I have the feeling that once I am at home again I shall need to sleep three weeks on end to get rested from the rest I have had.

Thomas Mann, The Magic Mountain (1924)

Sleep is good for you and lack of sleep is bad. It therefore seems odd that hospitals, which are supposed to promote recovery, are usually dreadful environments for sleeping. ‘The hospital bed,’ wrote one historian, ‘is one in which normal sleep is forbidden.’ A Punch cartoon of 1906 shows a patient being told to ‘wake up and take your sleeping-draught’. Things have improved since 1906, but not much.

Sick people really do benefit from sleep. We saw earlier how the brain and the immune system respond naturally to infection by inducing sleep. This helps the body cope with disease in several ways. The production of growth hormone occurs mainly during sleep, and growth hormone aids physical recovery by promoting the healing of mucous membranes and in other ways. The hormone melatonin, which is also produced at night, boosts immune responses, inhibits the growth of tumours and enhances resistance to viral infections. Conversely, sleep deprivation impairs immunity and slows the healing process. Given the importance of sleep for recovery, it is ironic that hospital patients are routinely subjected to conditions that make normal sleep almost impossible.

Sick people start with big disadvantages, of course. Pain is a powerful disrupter of sleep. Patients suffering from chronic, severe pain often become exhausted. Disrupted sleep is a common complication of burn injuries, for example. Studies have found that between half and three quarters of burns patients experience significant sleep disturbances. Sleep problems are common among cancer patients too. Fatigue can become one of the most distressing aspects of having cancer, severely reducing the quality of life. While medical treatments for cancer have advanced apace, efforts to improve patients’ quality of life by alleviating their fatigue have lagged behind.