Why We Sleep

by Matthew Walker

  Once the flu virus had been satisfactorily boosted up the nostrils of the participants, Prather then kept them in the laboratory for the following week, monitoring them intensely. He not only assessed the extent of immune reaction by taking frequent samples of blood and saliva, but he also gathered nearly every glob of nasal mucus that the participants produced. Prather had the participants regimentally blowing their noses, and every drop of the product was bagged, tagged, weighed, and analytically pored over by his research team. Using these measures—blood and saliva immune antibodies, together with the average amount of snot evacuated by the participants—Prather could determine whether someone had objectively caught a cold.

  Prather retrospectively separated the participants into four sub-groups on the basis of how much sleep they had obtained in the week before being exposed to the common cold virus: less than five hours of sleep, five to six hours of sleep, six to seven hours of sleep, and seven or more hours of sleep. There was a clear, linear relationship with infection rate. The less sleep an individual was getting in the week before facing the active common cold virus, the more likely it was that they would be infected and catch a cold. In those sleeping five hours on average, the infection rate was almost 50 percent. In those sleeping seven hours or more a night in the week prior, the infection rate was just 18 percent.

  Considering that infectious illnesses, such as the common cold, influenza, and pneumonia, are among the leading causes of death in developed countries, doctors and governments would do well to stress the critical importance of sufficient sleep during the flu season.

  Perhaps you are one of the responsible individuals who will get a flu shot each year, boosting your own resilience while adding strength to the immunity of the herd—your community. However, that flu shot is only effective if your body actually reacts to it by generating antibodies.

  A remarkable discovery in 2002 demonstrated that sleep profoundly impacts your response to a standard flu vaccine. In the study, healthy young adults were separated into two groups: one had their sleep restricted to four hours a night for six nights, and the other group was allowed seven and a half to eight and a half hours of time in bed each night. At the end of the six days, everyone was given a flu shot. In the days afterward, researchers took blood samples to determine how effective these individuals were in generating an antibody response, determining whether or not the vaccination was a success.

  Those participants who obtained seven to nine hours’ sleep in the week before getting the flu shot generated a powerful antibody reaction, reflecting a robust, healthy immune system. In contrast, those in the sleep-restricted group mustered a paltry response, producing less than 50 percent of the immune reaction their well-slept counterparts were able to mobilize. Similar consequences of too little sleep have since been reported for the hepatitis A and B vaccines.

  Perhaps the sleep-deprived individuals could still go on to produce a more robust immune reaction if only they were given enough recovery sleep time? It’s a nice idea, but a false one. Even if an individual is allowed two or even three weeks of recovery sleep to get over the assault of one week of short sleeping, they never go on to develop a full immune reaction to the flu shot. In fact, a diminution in certain immune cells could still be observed a year later in the participants after just a minor, short dose of sleep restriction. As with the effects of sleep deprivation on memory, once you miss out on the benefit of sleep in the moment—here, regarding an immune response to this season’s flu—you cannot regain the benefit simply by trying to catch up on lost sleep. The damage is done, and some of that harm can still be measured a year later.

  No matter what immunological circumstance you find yourself in—be it preparation for receiving a vaccine to help boost immunity, or mobilizing a mighty adaptive immune response to defeat a viral attack—sleep, and a full night of it, is inviolable.

  It doesn’t require many nights of short sleeping before the body is rendered immunologically weak, and here the issue of cancer becomes relevant. Natural killer cells are an elite and powerful squadron within the ranks of your immune system. Think of natural killer cells like the secret service agents of your body, whose job it is to identify dangerous foreign elements and eliminate them—007 types, if you will.

  One such foreign entity that natural killer cells will target are malignant (cancerous) tumor cells. Natural killer cells will effectively punch a hole in the outer surface of these cancerous cells and inject a protein that can destroy the malignancy. What you want, therefore, is a virile set of these James Bond–like immune cells at all times. That is precisely what you don’t have when sleeping too little.

  Dr. Michael Irwin at the University of California, Los Angeles, has performed landmark studies revealing just how quickly and comprehensively a brief dose of short sleep can affect your cancer-fighting immune cells. Examining healthy young men, Irwin demonstrated that a single night of four hours of sleep—such as going to bed at three a.m. and waking up at seven a.m.—swept away 70 percent of the natural killer cells circulating in the immune system, relative to a full eight-hour night of sleep. That is a dramatic state of immune deficiency to find yourself facing, and it happens quickly, after essentially one “bad night” of sleep. You could well imagine the enfeebled state of your cancer-fighting immune armory after a week of short sleep, let alone months or even years.

  We don’t have to imagine. A number of prominent epidemiological studies have reported that nighttime shift work, and the disruption to circadian rhythms and sleep that it causes, up your odds of developing numerous different forms of cancer considerably. To date, these include associations with cancer of the breast, cancer of the prostate, cancer of the uterus wall or the endometrium, and cancer of the colon.

  Stirred by the strength of accumulating evidence, Denmark recently became the first country to pay worker compensation to women who had developed breast cancer after years of night-shift work in government-sponsored jobs, such as nurses and air cabin crew. Other governments—Britain, for example—have so far resisted similar legal claims, refusing payout compensation despite the science.

  With each passing year of research, more forms of malignant tumors are being linked to insufficient sleep. A large European study of almost 25,000 individuals demonstrated that sleeping six hours or less was associated with a 40 percent increased risk of developing cancer, relative to those sleeping seven hours a night or more. Similar associations were found in a study tracking more than 75,000 women across an eleven-year period.

  Exactly how and why short sleep causes cancer is also becoming clear. Part of the problem relates back to the agitating influence of the sympathetic nervous system as it is forced into overdrive by a lack of sleep. Ramping up the body’s level of sympathetic nervous activity will provoke an unnecessary and sustained inflammation response from the immune system. When faced with a real threat, a brief spike of sympathetic nervous system activity will often trigger a similarly transient response from inflammatory activity—one that is useful in anticipation of potential bodily harm (think of a physical tussle with a wild animal or rival hominid tribe). However, inflammation has a dark side. Left switched on without a natural return to peaceful quiescence, a nonspecific state of chronic inflammation causes manifold health problems, including those relevant to cancer.

  Cancers are known to use the inflammation response to their advantage. For example, some cancer cells will lure inflammatory factors into the tumor mass to help initiate the growth of blood vessels that feed it with more nutrients and oxygen. Tumors can also use inflammatory factors to help further damage and mutate the DNA of their cancer cells, increasing the tumor’s potency. Inflammatory factors associated with sleep deprivation may also be used to help physically shear some of the tumor from its local moorings, allowing the cancer to up-anchor and spread to other territories of the body. It is a state called metastasis, the medical term for the moment when cancer breaches the original tissue boundaries of origin (here, the injection
site) and begins to appear in other regions of the body.

  It is these cancer-amplifying and -spreading processes that we now know a lack of sleep will encourage, as recent studies by Dr. David Gozal at the University of Chicago have shown. In his study mice were first injected with malignant cells, and tumor progression was then tracked across a four-week period. Half of the mice were allowed to sleep normally during this time; the other half had their sleep partially disrupted, reducing overall sleep quality.

  The sleep-deprived mice suffered a 200 percent increase in the speed and size of cancer growth, relative to the well-rested group. Painful as it is for me personally to view, I will often show comparison pictures of the size of these mouse tumors in the two experimental groups—sleep vs. sleep restriction—during my public talks. Without fail, these images elicit audible gasps, hands reflexively covering mouths, and some people turning away from the images of mountainous tumors growing from the sleep-restricted mice.

  I then have to describe the only news that could be worse in any story of cancer. When Gozal performed postmortems of the mice, he discovered that the tumors were far more aggressive in the sleep-deficient animals. Their cancer had metastasized, spreading to surrounding organs, tissue, and bone. Modern medicine is increasingly adept in its treatment of cancer when it stays put, but when cancer metastasizes—as was powerfully encouraged by the state of sleep deprivation—medical intervention often becomes helplessly ineffective, and death rates escalate.

  In the years since that experiment, Gozel has further drawn back the curtains of sleep deprivation to reveal the mechanisms responsible for this malignant state of affairs. In a number of studies, Gozal has shown that immune cells, called tumor-associated macrophages, are one root cause of the cancerous influence of sleep loss. He found that sleep deprivation will diminish one form of these macrophages, called M1 cells, that otherwise help combat cancer. Yet sleep deprivation conversely boosts levels of an alternative form of macrophages, called M2 cells, which promote cancer growth. This combination helped explain the devastating carcinogenic effects seen in the mice when their sleep was disturbed.

  Poor sleep quality therefore increases the risk of cancer development and, if cancer is established, provides a virulent fertilizer for its rapid and more rampant growth. Not getting sufficient sleep when fighting a battle against cancer can be likened to pouring gasoline on an already aggressive fire. That may sound alarmist, but the scientific evidence linking sleep disruption and cancer is now so damning that the World Health Organization has officially classified nighttime shift work as a “probable carcinogen.”

  SLEEP LOSS, GENES, AND DNA

  If increasing your risk for developing Alzheimer’s disease, cancer, diabetes, depression, obesity, hypertension, and cardiovascular disease weren’t sufficiently disquieting, chronic sleep loss will erode the very essence of biological life itself: your genetic code and the structures that encapsulate it.

  Each cell in your body has an inner core, or nucleus. Within that nucleus resides most of your genetic material in the form of deoxyribonucleic acid (DNA) molecules. DNA molecules form beautiful helical strands, like tall spiral staircases in an opulent home. Segments of these spirals provide specific engineering blueprints that instruct your cells to perform particular functions. These distinct segments are called genes. Rather like double-clicking open a Word file on your computer and then sending it to your printer, when genes are activated and read by the cell, a biological product is printed out, such as the creation of an enzyme that helps with digestion, or a protein that helps strengthen a memory circuit within the brain.

  Anything that causes a shimmy or wobble in gene stability can have consequences. Erroneously over- or under-expressing particular genes can cause biologically printed products that raise your risk of disease, such as dementia, cancer, cardiovascular ill health, and immune dysfunction. Enter the destabilizing force of sleep deprivation.

  Thousands of genes within the brain depend upon consistent and sufficient sleep for their stable regulation. Deprive a mouse of sleep for just a day, as researchers have done, and the activity of these genes will drop by well over 200 percent. Like a stubborn file that refuses to be transcribed by a printer, when you do not lavish these DNA segments with enough sleep, they will not translate their instructional code into printed action and give the brain and body what they need.

  Dr. Derk-Jan Dijk, who directs the Surrey Sleep Research Center in England, has shown that the effects of insufficient sleep on genetic activity are just as striking in humans as they are in mice. Dijk and his prolific team examined gene expression in a group of healthy young men and women after having restricted them to six hours of sleep a night for one week, all monitored under strict laboratory conditions. After one week of subtly reduced sleep, the activity of a hefty 711 genes was distorted, relative to the genetic activity profile of these very same individuals when they were obtaining eight and a half hours of sleep for a week.

  Interestingly, the effect went in both directions: about half of those 711 genes had been abnormally revved up in their expression by the loss of sleep, while the other half had been diminished in their expression, or shut down entirely. The genes that were increased included those linked to chronic inflammation, cellular stress, and various factors that cause cardiovascular disease. Among those turned down were genes that help maintain stable metabolism and optimal immune responses. Subsequent studies have found that short sleep duration will also disrupt the activity of genes regulating cholesterol. In particular, a lack of sleep will cause a drop in high-density lipoproteins (HDLs)—a directional profile that has consistently been linked to cardiovascular disease.fn4

  Insufficient sleep does more than alter the activity and readout of your genes; it attacks the very physical structure of your genetic material itself. The spiral strands of DNA in your cells float around in the nucleus, but are tightly wound together into structures called chromosomes, rather like weaving individual threads together to make a sturdy shoelace. And just like a shoelace, the ends of your chromosomes need to be protected by a cap or binding tip. For chromosomes, that protective cap is called a telomere. If the telomeres at the end of your chromosomes become damaged, your DNA spirals become exposed and your now vulnerable genetic code cannot operate properly, like a fraying shoelace without a tip.

  The less sleep an individual obtains, or the worse the quality of sleep, the more damaged the capstone telomeres of that individual’s chromosomes. These are the findings of a collection of studies that have recently been reported in thousands of adults in their forties, fifties, and sixties by numerous independent research teams around the world.fn5

  Whether this association is causal remains to be determined. But the particular nature of the telomere damage caused by short sleeping is now becoming clear. It appears to mimic that seen in aging or advanced decrepitude. That is, two individuals of the same chronological age would not appear to be of the same biological age on the basis of their telomere health if one was routinely sleeping five hours a night while the other was sleeping seven hours a night. The latter would appear “younger,” while the former would artificially have aged far beyond their calendar years.

  Genetic engineering of animals and genetically modified food are fraught topics, layered thick with strong emotions. DNA occupies a transcendent, near-divine position in the minds of many individuals, liberal and conservative alike. On this basis, we should feel just as averse and uncomfortable about our own lack of sleep. Not sleeping enough, which for a portion of the population is a voluntary choice, significantly modifies your gene transcriptome—that is, the very essence of you, or at least you as defined biologically by your DNA. Neglect sleep, and you are deciding to perform a genetic engineering manipulation on yourself each night, tampering with the nucleic alphabet that spells out your daily health story. Permit the same in your children and teenagers, and you are imposing a similar genetic engineering experiment on them as well.

  Part 3


  * * *

  HOW AND WHY WE DREAM

  Chapter 9

  Routinely Psychotic

  REM-Sleep Dreaming

  Last night, you became flagrantly psychotic. It will happen again tonight. Before you reject this diagnosis, allow me to offer five justifying reasons. First, when you were dreaming last night, you started to see things that were not there—you were hallucinating. Second, you believed things that could not possibly be true—you were delusional. Third, you became confused about time, place, and person—you were disoriented. Fourth, you had extreme swings in your emotions—something psychiatrists call being affectively labile. Fifth (and how delightful!), you woke up this morning and forgot most, if not all, of this bizarre dream experience—you were suffering from amnesia. If you were to experience any of these symptoms while awake, you’d be seeking immediate psychological treatment. Yet for reasons that are only now becoming clear, the brain state called REM sleep and the mental experience that goes along with it, dreaming, are normal biological and psychological processes, and truly essential ones, as we shall learn.

  REM sleep is not the only time during sleep when we dream. Indeed, if you use a liberal definition of dreaming as any mental activity reported upon awakening from sleep, such as “I was thinking about rain,” then you technically dream in all stages of sleep. If I wake you from the deepest stage of NREM sleep, there is a 0 to 20 percent chance you will report some type of bland thought like this. As you are falling asleep or exiting sleep, the dream-like experiences you have tend to be visually or movement based. But dreams as most of us think of them—those hallucinogenic, motoric, emotional, and bizarre experiences with a rich narrative—come from REM sleep, and many sleep researchers limit their definition of true dreaming to that which occurs in REM sleep. As a result, this chapter will mainly focus on REM sleep and the dreams that emerge from this state. We will, however, still explore dreaming at these other moments of sleep, as those dreams, too, offer important insights into the process itself.