Since Foster’s discovery, scientists have found that we have body clocks not just in the brain but all over—in our pancreas, liver, heart, kidneys, fatty tissue, muscle, virtually everywhere—and these operate to their own timetables, dictating when hormones are released or organs are busiest or most relaxed. Your reflexes, for instance, are at their sharpest in mid-afternoon, while blood pressure peaks toward evening. Men tend to pump more testosterone early in the morning than later in the day. If any of these systems get too out of sync, problems can result. Disturbances to the daily rhythms of the body are thought to contribute to (and in some cases may directly account for) diabetes, heart disease, depression, and serious weight gain.*2

  The suprachiasmatic nuclei work closely with a nearby and long mysterious pea-sized structure, the pineal gland, which is more or less in the middle of the head. Because of its central location and its solitary nature—most structures in the brain come in pairs, but the pineal stands alone—the philosopher René Descartes concluded that the pineal is where the soul resides. Its actual function, to produce melatonin, a hormone that helps the brain track day length, wasn’t discovered until the 1950s, making it the last of the main endocrine glands to be decoded. How exactly melatonin relates to sleep is still not understood. Melatonin levels within us rise as evening falls and peak in the middle of the night, so it would seem logical to associate them with drowsiness, but in fact melatonin production also rises at night in nocturnal animals when they are most active, so it is not promoting sleepiness. The pineal, in any case, tracks not just day/night rhythms but also seasonal changes, which are really important for animals that hibernate or breed seasonally. They are consequential for humans, too, but in ways that we mostly don’t notice. Your hair grows faster in the summertime, for instance.

  As David Bainbridge has neatly put it, “The pineal is not our soul, it is our calendar.” But it is also a very curious fact that several of our fellow mammals—elephants and dugongs to name just two—don’t have pineals and don’t seem to suffer for it. In humans, the seasonal role of melatonin is not entirely clear. Melatonin is a more or less universal molecule; it is found in bacteria, jellyfish, plants, and almost anything else that is subject to circadian rhythms.*3 In humans, production falls significantly as we age. A seventy-year-old produces only a quarter as much melatonin as a twenty-year-old. Why this should be, and what effect it has on us, remain to be determined.

  What is certain is that the circadian system can get seriously confused if its normal daily rhythms are disturbed. In a famous experiment in 1962, a French scientist named Michel Siffre isolated himself for about eight weeks deep inside a mountain in the Alps. Without daylight, clocks, or other clues to the passage of time, Siffre had to guess when twenty-four hours had elapsed and discovered to his astonishment that when he had calculated thirty-seven days to have passed, it was actually fifty-eight. He became hopeless at gauging even short increments of time. When asked to estimate the passage of two minutes, he waited more than five.

  In recent years, Foster and his colleagues have come to realize that we have more seasonal rhythms than formerly thought. “We’ve been finding rhythms,” he says, “in lots of unexpected areas—self-harm, suicide, child abuse. We know it is not just coincidental that these things have seasonal peaks and troughs because the patterns are six-month-shifted from the Northern Hemisphere to the Southern.” Whatever people do in a northern spring—like commit suicide in greater numbers—they do six months later in the southern spring.

  Circadian rhythms may also make a big difference to the effectiveness of the medications we take. As the Manchester University immunologist Daniel Davis has noted, fifty-six of the one hundred bestselling drugs in use today target parts of the body that are time sensitive. “Around half of these bestselling drugs stay active in the body for only a short time after being taken,” he writes in The Beautiful Cure. Take them at the wrong time and they may well be less effective, or possibly not effective at all.

  We are really at the beginning of our understanding of the importance of circadian rhythms for all living things, but as far as we can tell, all organisms, even bacteria, have internal clocks. “It may be,” as Russell Foster says, “a signature of life.”

  * * *

  —

  The suprachiasmatic nuclei don’t entirely account for why we get sleepy and want to go to bed. We are also subject to a natural sleep pressure—a profound and eventually irresistible urge to nod off—governed by something called sleep homeostats. The pressure to sleep grows more intense the longer we stay awake. This is in large part a consequence of an accumulation of chemicals in the brain as the day goes by, in particular one called adenosine, which is a by-product of the output of ATP (or adenosine triphosphate), the little molecule of intense energy that powers our cells. The more adenosine you accumulate, the drowsier you feel. Caffeine slightly counteracts its effects, which is why a cup of coffee perks you up. Normally, the two systems operate in synchronicity, but occasionally they deviate, as when we cross several time zones on a long-distance plane flight and we experience jet lag.

  Exactly how much sleep you need appears to be a personal matter, but nearly all of us fall somewhere in the range of a nightly requirement of seven to nine hours. Much depends on age, health, and what you have been up to lately. We sleep less as we get older. Newborns may sleep for nineteen hours a day, preschoolers for up to fourteen, young children for eleven or twelve, teens and young adults for ten or so—though they, like most adults, may not get all that they need because of staying up too late and having to rise too early. The problem is particularly acute for teenagers because their circadian cycles can be up to two hours adrift from those of their elders, turning them into comparative night owls. When a teenager struggles to get up in the morning, that isn’t laziness; it’s biology. Matters are compounded in America by what The New York Times in an editorial called “a dangerous tradition: starting high school abnormally early.” According to the Times, 86 percent of U.S. high schools start their day before 8:30 a.m., and 10 percent start before 7:30. Later start times have been shown to produce better attendance, better test results, fewer car accidents, and even less depression and self-harm.

  Nearly all authorities agree that we are sleeping less than we used to at all age levels. According to the journal Baylor University Medical Center Proceedings, the average amount of sleep people get on a night before work has fallen from eight and a half hours fifty years ago to under seven now. Another study found a similar decline among schoolchildren. The cost to the U.S. economy of all this tossing and turning has been estimated at more than $60 billion from absenteeism and diminished performance.

  Between 10 and 20 percent of adults in the world suffer from insomnia, according to various studies. Insomnia has been linked to diabetes, cancer, hypertension, stroke, heart disease, and (not surprisingly) depression. A study in Denmark, noted in Nature, found that women who regularly worked night shifts showed a 50 percent greater risk of developing breast cancer than their counterparts who worked by day.

  “There’s also now good data to show that sleep-deprived individuals have higher levels of beta amyloid [a protein associated with Alzheimer’s disease] than those who have slept normally,” Foster told me. “I wouldn’t say that sleep disruption causes Alzheimer’s, but it is probably a contributing factor and may well speed the decline.”

  For many people, the principal cause of insomnia is the snoring of a partner. It is a very common problem. About half of us snore at least sometimes. Snoring is the rattling of the soft tissues in the pharynx when one is unconscious and relaxed. The more relaxed, the greater the snoring, which is why drunken people snore particularly robustly. The best way to reduce snoring is to lose weight, sleep on your side, and not drink alcohol before retiring. Sleep apnea (from a Greek word meaning “breathless”) is when the airways become obstructed and victims either stop breathing or nearly stop breathing while asleep, and it is more common than generally appreciated. About 50 percent of people who snore have some degree of sleep apnea.

  The most extreme and horrifying form of insomnia is a very rare condition known as fatal familial insomnia, which was first medically described as recently as 1986. It is an inherited disorder (hence, familial) that is known to affect only about three dozen families in the world. Sufferers simply lose the ability to fall asleep and slowly die of exhaustion and multiple organ failure. The disease is always fatal. The destructive agent is a type of corrupted protein called a prion (short for proteinaceous infectious particle). Prions are rogue proteins. They are the wicked little particles behind Creutzfeldt-Jakob disease and mad cow disease (bovine spongiform encephalopathy) and some other horrible neurological illnesses, like Gerstmann-Sträussler-Scheinker disease, that most of us have never heard of because they are mercifully rare (but without exception very bad news for coordination and cognition). Some authorities think prions may also have a role in Alzheimer’s and Parkinson’s diseases.*4 In fatal familial insomnia, prions attack the thalamus, the walnut-sized body deep in the brain that controls our autonomic responses—blood pressure, heart rate, the release of hormones, and so on. How exactly prion disruption interferes with sleep is unknown, but it is a wretched way to go.

  * * *

  —

  Another disorder that disrupts sleep is narcolepsy. It is commonly associated with extreme drowsiness at inappropriate times, but many with the condition have as much trouble staying asleep as staying awake. The condition affects four million people around the world. It is caused by a lack of a chemical in the brain called hypocretin, which exists in such tiny amounts that it was only discovered in 1998. Hypocretins are neurotransmitters that keep us wakeful. Without them, sufferers may abruptly nod off in the middle of a conversation or while eating, or slip into a kind of twilight state that is closer to hallucination than to consciousness. Conversely, they may be quite exhausted but unable to sleep at all. It can be a miserable condition, and has no cure, but mercifully it is quite rare, affecting just one person in twenty-five hundred in the Western world.

  More common sleep disorders, collectively known as parasomnias, include sleepwalking, confusional arousal (when the victim appears to be awake but is profoundly muddled), nightmares, and night terrors. The last two are not easily distinguished except that night terrors are more intense and tend to leave the victim more shaken, though curiously victims of night terrors very often have no recollection of the experience the following morning. Most parasomnias are much more common in young children than in adults and tend to disappear around puberty, if not before.

  The longest anyone has intentionally gone without sleep was in December 1963 when a seventeen-year-old high school student in San Diego named Randy Gardner managed to stay awake for 264.4 hours (11 days and 24 minutes) as part of a school science project. The first few days were comparatively easy for him, but gradually he became irritable and confused until his entire existence was a kind of hallucinatory blur. When he finished the project, Gardner fell into bed and slept for 14 hours. “I remember when I woke up, I was groggy, but not any groggier than a normal person,” he told an NPR interviewer in 2017. His sleep patterns returned to normal, and he suffered no noticeable ill effects. Later in life, however, he experienced terrible insomnia, which he believed was “karmic payback” for his youthful adventure.*5

  * * *

  —

  Finally, we should say a word about that mysterious but universal harbinger of weariness, the yawn. No one understands why we yawn. Babies yawn in the womb. (They hiccup, too.) People in comas yawn. It is a ubiquitous part of life, and yet what exactly it does for us is unknown. One suggestion is that it is somehow connected with shedding excess carbon dioxide, though no one has ever explained in what way. Another is that it brings a rush of cooler air into the head, thus slightly banishing drowsiness, though I have yet to meet anyone who felt refreshed and energized after yawning. More to the point, no scientific study has ever shown a relationship between yawning and energy levels. Yawning doesn’t even correlate reliably with how tired you are. Indeed, when we yawn the most is often in the first couple of minutes after rising from a good night’s sleep when we are at our most rested.

  Perhaps the least explicable aspect of yawning is its extreme infectiousness. Not only do we more or less have to yawn when we see others do so, but just hearing or thinking about yawning causes us to yawn. You will almost certainly want to yawn now. And frankly there is nothing wrong with that.

  *1 Aserinsky was an interesting, if restless, fellow. Before coming to the University of Chicago in 1949 at the age of twenty-seven, he had attended two colleges and majored successively in sociology, pre-med, Spanish, and dentistry without completing his studies in any of them. In 1943, he was drafted into the army and, despite being blind in one eye, passed the war as a bomb disposal expert.

  *2 Even our teeth mark the passing of time by acquiring daily microscopic accretions, not unlike tree rings, until they stop growing at about the age of twenty. Scientists count the rings in ancient teeth to work out how long it took children to grow up in the very distant past.

  *3 In the United States, melatonin is commonly taken as a treatment for jet lag or insomnia. It is, as James Hamblin has written, “one of the very few hormones that you can purchase in the United States without a prescription. It is considered a dietary supplement and therefore held to essentially no premarket standards of quality, safety, or efficacy.”

  *4 Prions were discovered by Dr. Stanley Prusiner of the University of California at San Francisco. In 1972, while still training as a neurologist, he examined a sixty-year-old woman who was suffering from a sudden onset dementia so severe that she couldn’t manage even the simplest and most familiar tasks, like how to put a key in a door. Prusiner became convinced that the cause was a misshapen infectious protein which he called a prion. His theory was widely derided for years, but Prusiner was eventually vindicated and was awarded a Nobel Prize in 1997. The death of neurons leaves the brain pocked with cavities, like a sponge—hence the term “spongiform.”

  *5 There have been surprisingly few challenges to the record. In 2004, ten people competed to stay awake the longest for a television series called Shattered on Channel 4 in Britain. The winner, Clare Southern, lasted 178 hours, more than three days less than Randy Gardner.

  17 INTO THE NETHER REGIONS

  On a Presidential visit to a farm, Mrs. Coolidge asked her guide how many times the rooster copulated daily. “Dozens of times” was the reply. “Please tell that to the President,” Mrs. Coolidge requested. When the President passed the pens and was told about the rooster, he asked: “Same hen every time?” “Oh no, Mr. President, a different one each time.” The President nodded slowly, then said: “Tell that to Mrs. Coolidge.”

  —LONDON REVIEW OF BOOKS, JANUARY 25, 1990

  I

  IT IS A slightly startling fact that for the longest time we didn’t know why some people are born male and some female. Although chromosomes had been discovered in the 1880s by the very busy and lushly named German Heinrich Wilhelm Gottfried von Waldeyer-Hartz, their importance wasn’t understood or appreciated.*1 (He called them chromosomes because of how well they absorbed chemical dyes under the microscope.) We now know, of course, that females have two X chromosomes and males have one X and a Y, which is what accounts for their sexual differences, but that knowledge was a long time in coming. Even in the late nineteenth century, scientists commonly thought that sex was determined not by chemistry but by external factors like diet or air temperature or even a woman’s mood during the early stages of pregnancy.

  The first step in solving the problem came in 1891 when a young zoologist at the University of Göttingen in central Germany, Hermann Henking, noticed an odd thing while studying the testicles of a genus of fire wasp called Pyrrhocoris. In all the specimens he studied, one chromosome always remained aloof from the others. Henking dubbed it “X” because it was mysterious, not because of its shape, as is nearly always assumed. His finding generated a ripple of interest among other biologists but seems not to have captivated Henking himself. He took a job soon afterward with the German Fisheries Association, where he spent the rest of his life surveying North Sea fish stocks, and, as far as can be told, never looked at another insect testicle again.

  Fourteen years after Henking’s accidental discovery, on the other side of the Atlantic, came the real breakthrough. A scientist at Bryn Mawr College in Pennsylvania named Nettie Stevens was doing similar work with the reproductive apparatus of mealworms when she discovered another aloof chromosome and—her crucial insight—realized that it seemed to have a role in determining sex. She called it the Y chromosome to continue the alphabetical sequence begun by Henking.

  Nettie Stevens deserves to be better known. Born in 1861 in Cavendish, Vermont (the place coincidentally where Phineas Gage had an iron bar shot through his skull while building a railway there thirteen years earlier), Stevens grew up in modest circumstances, and it took her a very long time to fulfill her dream of attaining higher education. She worked for several years as a teacher and librarian before finally entering Stanford University in 1896 at the advanced age of thirty-five, and she was forty-two and tragically near the end of her short life when she finally earned her PhD. Taking a position as a junior researcher at Bryn Mawr, she embarked on a blizzard of activity, publishing thirty-eight papers as well as discovering the Y chromosome.