Sleep

Startling revelations are emerging from research into sleep. The demands of modern life mean that we've forgotten what it is to be awake. .
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I slept badly again last night. Perhaps you did, too. I was in a strange city and in a strange bed filled with the overabundant warmth of a hotel room. At home, I often come awake for an hour or two in the early morning. A thread of thought - the merest particle of wakefulness - presents itself, and soon the bedside light is on and I'm reading again or lying in the dark, thinking.

I often put off going to bed for no good reason. Like a kid with an 8.30 bedtime in the eternal twilight of summer, I can't quite bear to quit consciousness. The itch of waking won't subside. This is an old and by now not particularly troublesome habit, though its effects grow more pronounced the older I get. Like almost everyone, I borrow more from sleep than I can ever hope to repay, and I can feel the debt being exacted whenever my attention dissipates. There are days when I wonder what it feels like to be fully awake.

You may have wondered the same, too. Almost everyone I know complains about sleep, and the refrain is usually "not enough". It's a subjective estimate, but accurate as far as it goes. The problem of sleep curtailment in late-20th-century Western society is "so big", one prominent sleep researcher told me, "that people just can't digest it. If you were to take people off the street, the vast majority would be sleep-deprived."

There is a sense among many students of the subject that sleep deprivation is reaching crisis proportions. People don't merely believe they're sleeping less; they are sleeping less - perhaps as much as one and a half hours less each night than humans did at the beginning of the century - often because they choose to do so.

In the last decade, the number of sleep-disorder clinics in the United States, for example, has grown to an estimated 1,500. Despite this growth, it is only within the past year that the American Medical Association has recognised sleep medicine as special. At the University of Chicago Medical Center, Eve Van Cauter, a research professor of medicine, argues that, besides simply sleeping less, humans are no longer subjected to seasonal changes in the lengths of day and night. The seasonal fluctuations in conception rates associated with long winter nights, plainly evident before World War I, have essentially disappeared. We live in an artificial environment with an altered light-dark cycle, including, obviously, less exposure to true darkness and, perhaps not so obviously, less exposure to bright natural light because so many people work indoors. Shift workers, especially, experience higher rates of gastro-intestinal and cardiovascular disease, as well as depression and infertility.

"The behavioural curtailment of sleep, the deletion of rest," Van Cauter says, "is something that is unbelievably common. It probably has enormous health implications." Yet no one has done the long-term epidemiological studies needed to discover the effects. Like every scientist I talked to, Van Cauter regards as utterly unfounded the recent fascination with melatonin as a sleeping potion and all-purpose medicament. (In America, you can now buy melatonin pills even in airport gift shops, thus creating an enormous uncontrolled experiment with a substance that is being used in a test study in the Netherlands as a contraceptive agent.) But, as Van Cauter says: "If people didn't have a problem with sleep, melatonin wouldn't sell."

More and more, it seems, the convergent Western cultures of work and entertainment aspire to make machines of us all. There is a profound reluctance in the business world even to acknowledge the subject of sleep loss. Hearing people talk about their sleeping habits is a little like hearing them talk about their digestion. An unexpected note of pride creeps in. Some people - a tiny minority - worry that they sleep too much to prosper in these frenetic times. The only individuals who seem content are the ones who cheerfully announce how little sleep they need, and they are often making it up. How we sleep is widely, if implicitly, taken to be an index of things that have little to do with sleep - emotional balance, competitiveness, sensitivity, toughness.

The poet Sir Philip Sidney called sleep "the poor man's wealth, the prisoner's release, the indifferent judge between the high and low". But it's easier, I've found, to say what sleep is - to name it metaphorically - than to state what it does or what the widespread effects of gradual, long-term sleep loss in our society might be.

Imagine a world with no artificial illumination, only the light of day and the dark of night, a planet where the intensity of light varies predictably in ways that are connected to, but not caused by, the passage of time. Imagine, too, that over billions of years, organisms evolve that reflect in their bodily systems the relation between light and time in their environment. They develop sensors (eyes) to register the presence or absence of light. They develop internal clocks - genes and cells and clusters of cells capable of generating a biological night and a biological day. They develop pathways along which these sensors and clocks can communicate. Even if light were to disappear for weeks or months at a stretch, the rhythms of biological day and night - what scientists call circadian rhythms - would still be produced at precise intervals within the bodies of these organisms. But biological time and external light aren't completely independent. Sunrise and nightfall re-calibrate the internal clocks of these creatures, so that in winter their biological night is long and in summer it is short. Call this life on earth, 40,000 years ago.

Now imagine one such organism with the temerity to light up the night. It fashions lamps of pitch, animal fat, petroleum, inert gases. It ignores what its cells still remember, that light - even artificial light - has the power to regulate biological clocks. It begins to pretend that every night is a midsummer's night only a few hours long. A society full of beings like this would be able to accomplish remarkable things with the extra time it had on its hands.

But what it would never, ever, elect to do again is turn out the lights and roost when the chickens roost. The one thing this society seems to have wanted all along was to stay up way past its evolutionary bedtime. But the clock we are trying to fool is our own clock, our inherent circadian rhythms.

William Dement has for many years been one of the pre-eminent sleep researchers at Stanford University in the United States. In 1951, when he was a medical student, Dement joined the sleep lab run by Nathaniel Kleitman, a professor of physiology at the University of Chicago Medical School and to many the father of modern sleep research. Just after Dement's arrival, a graduate student in Kleitman's lab named Eugene Aserinsky discovered, in his sleeping research subjects, rapid eye movement, or REM. It was an enormous discovery, after which, Dement has written, "it was, thus, no longer possible to think of sleep as one state". (REM sleep in adult humans constitutes 20 to 25 per cent of a good night's sleep. The rest of the sleep cycle is made up of four non-REM stages, the most important of which, some researchers believe, is slow-wave sleep, also about 20 to 25 per cent of a night's sleep.)

In his opus, Sleep and Wakefulness, first published in 1939, Kleitman defined sleep as "a periodic temporary cessation or interruption of the waking state, the latter being the prevalent mode of existence for the healthy adult". This has a strangely normative ring to it. It supposes that sleep is largely an abeyance of what makes humans human.

The trajectory of Dement's career since suggests the sweeping changes that have occurred in the understanding of sleep. Doctors can now bring about what Dement calls "a miracle of restoration" to many patients, including those who suffer from obstructive sleep apnoea, a chronic, pharyngeal blockage of normal breathing during sleep, which affects between one and four per cent of adults.

Much of the early sleep research in this century was based on the assumption, as one biologist put it, that "humans had potentially evolved out of the constraints of the environment". But what if sleep is a physiological product equivalent to consciousness and not just a state of suspension in which the mind is suddenly untrammelled?

In the early 1970s, it was discovered that in the rodent hypothalamus, a small cluster of perhaps 10,000 cells, called the suprachiasmatic nucleus, or SCN, plays a major part in controlling the alternation between biological day and night. The SCN receives light input from retinal ganglion cells, and so it is able to adjust the body clock using the external rhythms of night and day. If you damage the SCN in rats, you change the distribution (but not the quantity) of their sleep.

The hypothesis, based on increasingly strong evidence, is that in humans, too, the SCN is one of the major centres where circadian rhythms are produced. Circadian rhythms attune the human organism to the external environment, but they also co-ordinate the internal operations of the body. To argue that humans have somehow evolved away from the constraints of their environment ignores the fact that the human body is always to a certain extent producing its environment - a bodily environment that is extraordinarily stable.

Dr Wallace Mendelson, a psychiatrist, is a co-director of The Sleep Research Laboratory at the University of Chicago and the president of the Sleep Research Society. For a decade, Mendelson studied the molecular workings of sleeping pills. He is looking, he told me, for more powerful and safer sleeping pills.

It had occurred to me that humans, in addition to their other sleep problems, are notoriously inaccurate witnesses of their own repose. Mendelson cited, for my consideration, a perplexing subgroup of insomniacs, a highly unusual example of the trouble humans have in estimating their sleep. "These are people," he said, "who come to the doctor bitterly complaining of insomnia. So you do a study on these persons. You turn out the lights, and five minutes later their eyes are closed, they're breathing slowly and quietly, they're not moving, and their EEG [electroencephalogram] is showing a sleep pattern. They stay that way for eight hours, yet you wake them up in the morning and they say: `See? I told you I wouldn't sleep.'

"I gave poor sleepers a placebo one night and a sleeping pill the next. Basically, when you gave the insomniacs a placebo and woke them and asked, `Were you awake or asleep?' they said, as predicted, `I was awake.' When you gave them a sleeping pill and woke them and asked them the same question, they said, `I was asleep.' The theory we're beginning to operate under is that maybe what sleeping pills do to the EEG is less important than the fact that they change your perception of whether or not you're awake."

Perhaps the task of the next generation of sleeping pills will be to produce the illusion that we have slept well and deeply when in fact we have not. This would make sense if the consequences of sleep loss were more benign. But the penalties for what might be called catastrophic sleep loss are well known. Allan Rechtschaffen, who is about to retire as head of the University of Chicago Sleep Research Lab, has done a famous series of experiments in which rats were wakened to death. Rats deprived of total sleep died in two and a half weeks, after their thermoregulatory systems collapsed. Rats deprived of REM sleep died in five weeks. (No one knows how soon a rat would die if, like the insomniac subgroup Mendelson described, it merely believed it had been deprived of sleep.)

I asked Rechtschaffen the question that had begun to prey upon me: What is sleep for? "Sleep facilitates survival. That's the bottom line. What is it about sleep that's essential for survival? That's the key question." He paused, ruefully, and then said, "I can't answer that. We have a lot of leads about what the function of sleep might be. But we haven't nailed it down. So that a third of our lives still remains for the most part a mystery."

Underlying all the intricacies of the human circadian system, and all the atemporal elements in modern life that affect our natural periodicity, there is, of course, the greater periodicity of the human organism, the passage from birth to death, to be reckoned with. Mary Carskadon's office is in the Bradley Sleep Lab of Brown University's Butler Campus, in Providence, Rhode Island. Carskadon studies the sleep patterns of middle-school and high-school students.

The research question that drives her is all too familiar to parents: Why has this bright, happy child who used to be raring to go at 6am turned into this morose adolescent you can't get out of bed? Carskadon says: "It became really evident as I looked at surveys gathered here at Brown that there's a clear delay in the timing of sleep across early adolescence. We'd thought that this was all due to psychosocial factors. For example, most parents hold out staying up later as a reward. Going to bed early is a punishment. I became intrigued by the possibility that there might actually be a biological process going on as well. It's a big shift. It's a very salient phenomenon."

Carskadon's hypothesis is that the entry into adolescence, and the dislocations of mood and conduct associated with it, mark the maturing of the circadian system. "We see that same pattern," she says, "throughout the rest of adulthood - what we call a midday trough." That is the period roughly between 1pm and 4pm when sleep looms, existence pales and, not coincidentally, there is a significant rise in the number of traffic and industrial accidents. (A parallel trough, familiar to anyone who has known the despair of early morning, occurs between 1am and 4am, the time when humans are likeliest to mourn credit card debt and to die.)

In their sleep patterns, as in almost everything else, adolescents are making the passage to adulthood, which is why they seem so odious to adults and to one another. But that passage has, in fact, already begun in the darkness of the womb. Steven Reppert, a paediatrician who runs the Laboratory of Developmental Chronobiology at Harvard Medical School, says, that "many years ago", by which he means recently, "we discovered that the biological clock in the SCN is actually working in the foetus. We did a number of experiments showing that the foetus was always in time with the mother."

Like so much else in our lives, sleep is disrupted by the process of growing old. "As we age," Eve Van Cauter had explained to me, "we lose the ability to produce deep sleep, and the intensity of the deep sleep is less. The initiation of deep sleep is associated with the release of human growth hormone and of prolactin. Particularly for older adults, in their seventh decade or so, there may be zero minutes of deep sleep and there may be zero micrograms of growth hormone being secreted."

Not much is known about the role of prolactin, except in pregnant women. According to the Encyclopedia of Sleep and Dreaming, edited by Mary Carskadon, it is "the most important hormone for production of casein, the essential protein in human breast milk." Human growth hormone controls the ratio of fat tissue to muscle mass, and it also affects bone metabolism, immunomodulation and other functions.

The quality of sleep in humans begins to deteriorate as early as the late 30s, and, when the quality of sleep goes, so goes its restorative effect on the endocrine and cardiovascular systems. And, as sleep deteriorates, so, too, does one's emotional state. "I think it's not an unreasonable hypothesis," Van Cauter said, "that a lot of the effects of ageing, including geriatric depression, could be ultimately traced to a sleep deficit."

"All wakefulness is sleep deprivation," William Dement said to me. This was a phrase I would hear in my head for weeks, and it came to mind again as I sat in an office belonging to Joseph Takahashi, a professor of neurobiology and physiology at Northwestern University and a member of the National Science Foundation Center for Biological Timing. Takahashi has carried the search for the physical source of circadian rhythms down to the genetic level, the elemental substratum of organic life. His experiments have shown that there is a genetic as well as an environmental limit to the circadian rhythms at work.

I was looking at the activity record of a mouse. If a mouse is exposed to regular 12-hour periods of light and darkness, its activity record usually looks like perfectly vertical alternating bands of white (rest) and black (running) across a 48-hour span. (The hours are plotted on the horizontal axis, the days on the vertical axis.) But, if the mouse is left in darkness for many days, its internal clock is not reset by light, and it adheres to its natural cycle - "free-running rhythm", as the sleep people say. The average free-running circadian period for the strain of mice in Takahashi's lab is 23.7 hours.

Because each activity episode and each sleep episode begins slightly earlier than it did the day before, the vertical bars on the activity record of a normal mouse kept in constant darkness will drift to the left as the days pass. For humans, the free-running circadian period is about 25 hours, which means that in a similar experiment the vertical bars on a human sleep activity record would drift to the right.

I bother to explain all this because in Takahashi's office I was looking at an activity record that was shocking. It seemed almost ordinary for the first 20 days, while the mouse that produced it was on a fixed light- dark schedule. But when the lights were turned off for good, the cycle lengthened to 28 hours, and then it exploded. Suddenly, the activity record looked like noise, an incoherent flickering of abbreviated light and dark dashes scattered all over the page for all the subsequent days of the experiment. This mouse plainly lacked any circadian guidance in the absence of environmental cues. It had failed to generate its own temporal environment.

You can produce a similar effect in a rat by altering its brain, removing the SCN. But this mouse, whose SCN was intact, had two copies of a mutant allele of the "clock" gene. Now they have found the gene. It is extremely likely that in humans, too, there is a clock gene, probably on chromosome 4.

I found myself staring, in Takahashi's office, at the white space on the activity record of a normal mouse, which I had been using for comparison. The white space represents light, and light, on a human activity record, means waking. The white space seemed to be posing a question of its own: What is waking for? Because we oscillate between sleeping and waking. Stop oscillating and you're dead. It had become apparent to me that the circadian system - of which sleep, like the full moon passing across the night sky, is only the most visible marker - is an enormously subtle means of integrating environmental input with a complex suite of physiological outputs.

I had just become used to the idea that sleep is a physiological artefact of the circadian system when I realised that waking - consciousness - is not merely the transparent state of being it seems to be. It, too, is being generated by the body's circadian rhythms. It has a shape and a hormonal substratum all its own. This was not necessarily news, but it reminded me a little of the moment when you first realise that the eye is not a window, even into the soul, but an organ with its own opacity.

It makes you wonder.

Will there someday be humans who are born with a purposely altered clock gene? Will we go that far to accommodate a sleepless society? Perhaps. But perhaps there is a simpler, already innate solution to the problem of sleep curtailment, one that depends on our oscillatory nature. Modern sleep - severely delimited sleep - is largely a cultural product. It is only, at most, a few centuries old, a result of our profound conviction that we can control the details of our biological destiny. But what did sleep in the era of our evolutionary emergence look like? What was sleep like before television, before electric lights, before the industrial revolution, before agriculture?

Something like an answer has been provided by Thomas Wehr, who is chief of the Clinical Psychobiology Branch of the National Institutes of Mental Health in Bethesda, Maryland. While Wehr was studying melatonin secretion, he found himself wondering: Have humans preserved a mechanism for perceiving seasonal change, the way animals have? To answer this question, he devised an experiment in which volunteers subjected themselves in the laboratory to a sleep schedule based on the duration of a midwinter's night at the latitude of Washington - about 14 hours. In other words, they spent 14 hours in darkness, from 6pm to 8am, every night for at least a month, just as the aboriginal occupants of Lafayette Park would have done every winter until they died of malaria.

"We decided," Wehr told me, "to take a more general look at what human biology could be like in a longer night - to re-animate a prehistoric mode." What Wehr found was remarkable. The first night, the volunteers slept 11 hours, and, in the first weeks of the experiment, they repaid 17 hours of accumulated sleep debt - ie, they slept 17 hours longer than they would have called normal for the same period. It took three weeks for a sleep pattern to stabilise, and, when it did, it lasted about eight and a quarter hours per night. But it was not consolidated sleep. Over time, Wehr explained, "another state emerged, not sleep, not active wakefulness, but quiet rest with an endocrinology all its own."

Each night, the volunteers lay in a state of quiet rest for two hours before passing abruptly into sleep. They slept in an evening bout that lasted four hours. Then they awoke out of REM sleep into another two hours of quiet rest, followed by another four-hour bout of sleep and another two hours of quiet rest before rising at 8am. This pattern of divided sleep, separated by rest, is called a bimodal distribution of sleep, and it is typical of the sleep of many mammals living in the wild, which is to say that it is atypical of humans living in modern Western society. Yet bimodal sleep, punctuated by quiet rest, was a pattern to which modern Americans reverted almost as soon as they were given the chance.

"In healthy people," Wehr remarked, "this bimodal pattern of sleep would be called a sleep disorder, although the resemblance to animal sleep confirms its naturalness. And, as people get older, they revert to this pattern of divided sleep. Perhaps it gets harder to override it."

I asked Wehr whether any of his subjects had gone crazy lying in the dark during those long nights. None had. "Anyone could do it," he said. And, having done it, not only did Wehr's subjects "feel more awake, they were more awake".

What has been sacrificed as human sleep has become more and more condensed and less and less seasonal is an open question. Living year-round on midsummer time, with long days and short nights, "has obtained," Wehr writes, "for so many generations that modern humans no longer realise that they are capable of experiencing a range of alternative modes that may once have occurred on a seasonal basis in prehistoric times but now lie dormant in their physiology."

While humans worry about how much further we can compact our actual sleep time, we've already jettisoned six nightly hours of quiet winter rest. In a most meaningful sense, those are transitional hours. Once in the night and once in the early morning, Wehr's volunteers woke out of REM sleep, which is strongly associated with dreaming, into a period of quiet wakefulness quite distinct from daytime wakefulness. Perhaps as we've learned, over time, to sleep a less characteristically mammalian sleep, we've also learned to sleep a less human sleep.

"It is tempting to speculate," Wehr writes, "that in prehistoric times this arrangement provided a channel of communication between dreams and waking life that has gradually been closed off as humans have compressed and consolidated their sleep. If so, then this alteration might provide a physiological explanation for the observation that modern humans seem to have lost touch with the wellspring of myths and fantasies"

@ New York Times Magazine, 1997

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