Everything You Always Wanted To Know About Sleep (But Were Too Afraid To Ask)

This post is perhaps not my best post, but is, by far, my most popular ever. Sick and tired of politics after the 2004 election I decided to start a science-only blog - Circadiana. After a couple of days of fiddling with the templae, on January 8, 2005, I posted the very first post, this one, at 2:53 AM and went to bed. When I woke up I was astonished as the Sitemeter was going wild! This post was linked by BoingBoing and later that day, by Andrew Sullivan. It has been linked by people ever since, as recently as a couple of days ago, although the post is a year and a half old. Interestingly, it is not linked so much by science or medical bloggers, but much more by people who write about gizmos and gadgets or popular culture on LiveJournal, Xanga and MySpace, as well as people putting the link on their del.icio.us and stumbleupon lists. In order to redirect traffic away from Circadiana and to here, I am reposting it today, under the fold.

[This is also the post included in 'The Open Laboratory 2006', the anthology of best science blogging]

What are you doing up so late, staring at the computer screen reading this? For that matter, what am I doing up late writing this at 11pm? Are we all nuts?

Until not long ago, just about until electricity became ubiquitous, humans used to have a sleep pattern quite different from what we consider "normal" today. At dusk you go to sleep, at some point in the middle of the night you wake up for an hour or two, then fall asleep again until dawn. Thus there are two events of falling asleep and two events of waking up every night (plus, perhaps, a short nap in the afternoon). As indigenous people today, as well as people in non-electrified rural areas of the world, still follow this pattern, it is likely that our ancestors did, too.The bimodal sleep pattern was first seen in laboratory animals (various birds, lizards and mammals) in the 1950s, 60s and 70s, i.e, before everyone moved their research to mice and rats who have erratic (un-consolidated) sleep patterns. The research on humans kept in constant conditions, as well as field work in primitive communities (including non-electrified rural places in what is otherwise considered the First World) confirmed the bimodality of sleep in humans, particularly in winter.

Larks and Owls

There is a continuum of individual sleep patterns ranging from extreme "larks" who fall asleep at the first inkling of dusk but wake up before dawn, all the way to the extreme "owls" who stay up quite late and wake up once the day is in full swing, and of course everything in between. No matter where you are on this continuum, you tend to sleep more during the winter long nights than during the short summer nights.

The genetic basis of extreme "larkiness" has been elucidated. It is a mutation in a phosphorilation site on the protein product of the core-clock gene period (per). A phosphorilation site on a protein is a place where another protein may add a phosphate group. Phosphate groups are ubiquitous sources of energy in biology (remember ATP from high-school biology? That's it!). Thus, an addition of the phophate may make it easier for the protein to react with another molecule. That other molecule may give it stability, or destroy it, or allow it to move to another part of the cell. In the case of period, it appears that lack of the phosphate group allows the protein to move into the nucleus sooner than normal where it blocks transcription of its own gene.

Of course, we are talking statistics here: hundreds or thousands of period proteins per cell, several thousand pacemaker clock-cells in the suprachiasmatic nuclei, plus trillions of peripheral clock-cells all over the body: each of these molecules has a statistical chance of moving back into the nucleus sooner than in a person without a mutation. Moving sooner into the nucleus means that the inherent ("freerunning") period of the clock is shorter. In most people it is about 24-25 hours long (when measured in completely constant environmental conditions, i.e., no light-dark, temperature, sound, or social cycles). The "owls" have longer periods and "larks" have shorter periods. Period determines phase relationship between the internal clock and the environmental synchronizing cue (e.g., the light-dark cycle), thus longer the period of the clock, later the clock will trigger waking up in the morning or feeling sleepy in the evening, and vice versa. People like me go to bed at 4am and wake up at noon. People with the extreme lark mutation wake up at about 4am, but are real party poopers, snoozing at 7pm or so. The whole continuum is believed to be determined by similar small mutations in which just a single DNA base-pair is replaced in one of the clock genes (12 such clock-genes are known so far to operate in mammals).

During a normal night's sleep, REM occurs every 90 minutes or so. As the night progresses, the REM episodes get longer and the non-Rem periods in-between become shorter (thus still adding up to 90 minutes) as well as shallower. Thus, the really deep sleep (e.g, Stage 3) occurs only during first 1-2 cycles early in the night. Lack of Deep Sleep results in tiredness. Usually adults wake up from REM (children do not), unless waking is forced (e.g., alarm clock). Research on relative roles of REM and NREM in consolidation of memory is very controversial (look for Jerome Siegel on Google Scholar). Growth Hormone surges during episodes of Deep Sleep, and falls during REM, and is almost undetectable during wakefulness.

In the morning, our body prepares us for waking by increasing blood levels of ACTH and cortisol (leading to preponderance of heart attacks at waking time). Our body temperature is the lowest just an hour or two before waking and highest an hour or two before falling asleep. If you feel a chill sometimes when you are up at strange times, it is because your clock is at a pre-waking (late-night) phase.

Melatonin is secreted only at night (circadian clock time) and is not dependent on sleep. However, bright light tends to reduce melatonin levels. In summer, nights are short, thus the duration of the melatonin "signal" is short. In winter, nights are long, thus the duration of the melatonin "signal" is long. The duration of the melatonin signal is the cue that the circadian clock (this is in mammals only) uses to detect season, i.e., the changes in photoperiod (daylength) - information important for timing of seasonal events, e.g., molting, migration, hibernation, reproduction. Humans are only mildly seasonal - our ancestors about 70 million years ago were living in little holes in the ground, were tiny, were nocturnal, were seasonal breeders, and were hibernators. Some traces of our ability to measure photoperiod are retained in "winter blues", or Seasonal Affective Disorder (SAD). It is almost a form of hibernation.

Phase-disorders of the circadian clock (i.e., extreme larks or owls) can have a similar effect by tricking the melatonin signal (or the reading of the signal by the clock) into believing it is always winter, thus time to be depressed. Lithium treats depression by affecting the period (thus indirectly phase) of the circadian clock (both in vivo and in vitro). In bipolar disorder, manic episodes are characterized by phase-delays and depressive episodes by phase-advances of the diurnal sleep-wake and activity patterns. In a way, phase-delayed people are constantly in the depressive phase of the bipolar disorder.

Treating Extreme Larks and Owls

Trying to regulate sleep-time with melatonin supplements can be tricky. If you are phase-delayed, thus producing melatonin in summer from 2am until 10am, if you take a melatonin pill at 10pm in order to go to sleep earlier, your clock will see a winter-like melatonin signal of 12 hours duration (10pm-10am) and will make you depressed within a couple of days.

The best way to shift a clock is by using bright light. Instead of buying a $500 light-box, you can, for much less money, build your own for a fraction of that money. You need a piece of board, 3-4 strong neon lightbulbs, balasts, a switch, a plug, and some wires. An hour of fun, and you have an apparatus that is just as good and effective as the hifallutin corporate gizmo. Use the light box at appropriate times (dawn for owls, dusk for larks). If you are an extreme owl, when you first get up in the morning, immediately go out in the sunlight (that is thousands of lux of light energy, compared to hundreds from a lightbox) for a jog with your dog. If you do not have a dog, buy one - that will force you to go for a walk early in the morning. Well-scheduled meals also help.

Do not take anti-depressants. They tend to not work for circadian-based depression and may just mask the symptoms (i.e., you "feel" good while your body is falling apart). Do not use melatonin supplements. Do not use alcohol - it may make you fall asleep fast, but the sleep will be shallow and erratic and you will wake up feeling lousy instead of rested. Caffeinated drinks are fine, except during the last 2-3 hours before your intended bedtime, at which time a warm glass of milk may be better.

Make a routine in the evening. The last 2-3 hours before bedtime stay out of the bedroom (bedroom is only for sleep and sex), and switch off all the screens: no TV, no computer, no gameboy. Reading a book while sitting in an armchair in the living room is fine. Just sitting on the porch and thinking will help you wind down. As the evening progresses gradually turn down the lights. Once the bedtime arrives, go to the bedroom, go to bed, switch off the light (pitch darkness) and go to sleep if you can. If you cannot, get up for a few minutes, but keep your lights dim, still no screens, no caffein, no food.

Of course, all of the above are the strategies to shift your clock to a "socially accepted" phase. But you are not crazy or sick. It is the societal pressure to get up at a certain time that is making you sick. Try to get a job that fits your natural schedule. Work at night, sleep during the day (in a pitch-dark, light-tight, sound-proof room) and enjoy life in all its quirkiness.

If you need to go to the bathroom in the evening or during the night, do not turn on the light. Can't you find your vital organs in the dark? If neccessary, a very dim nightlight (or indirect light from the hall) is OK. If you wake up in the middle of the night, do not get up or switch on the light. Have sex instead. Hopefully your partner will enjoy being woken up by your kinky activities. You will both crash into pleasant deep sleep afterwards. If you do not have a partner, just do it yourself without switching on the lights (as I said, you can find your vital organs in the dark). Jocelyn Elders was onto something....

Why We Sleep Like This?

A classical sociobiological just-so story posits that this kind of individual variation on the lark/owl continuum had an adaptive function, namely to ensure that at every time of night at least one member of the tribe was awake. Thus some stood guard early in the night, others late in the night, listening to the sounds of the jungle (or savannah, or whatever) while the midnight break is thought to have been used for copulating with whomever also happens to be awake at the time - this was before the social invention of sexual monogamy.

Why did cave-men live in caves? Caves are rare and expensive pieces of real estate. If you find one, it is likely to be already inhabited, thus you need to kick out the old tenants (bears?) in order to move in. Then you have to defend it from others who also want this nice piece of property. And it is difficult to defend a cave - it has one entrance - the rest is a trap. If the intruder is really dangerous you have two options: to go out and be killed outside, or remain inside and get killed in the cave. What is so important about the cave that warrants such a risk? Is it that a possible attack can come only from one side, thus requiring only one guard at a time? Is it that newly naked human animals needed shelter from bad weather that they did not need while they were still furry? Is it to protect the newly acquired fire from being extinguished by rain? Does it make easier the task of keeping the herd of not-yet-that-well domesticated animals all together and preventing it from running away? Possibly all of it - we'll never know - it's a "just-so" story. But do not forget one very important property of the cave: it is dark inside. It is easy to sleep in the dark. Most animals find shelter or burrow when they want to sleep - this is not just to hide from the enemies and weather, but also to hide from the sunlight.

Sleep is one of the strongest human needs. If you have read the last part of my four-part series featured on the previous Tangled Bank, you have read my ideas why we still don't know what sleep is for (though see the current state of knowledge in, e.g., this paper: Origin and evolution of sleep: roles of vision and endothermy (pdf)). While I am not advocating ditching modernity, cutting off electricity and going back to the old sleep pattern, we still do not know enough about sleep in order to make the 24-hour society work for us without too much in the way of health consequences.

Hey, teacher, leave us kids alone (to sleep late)

It has been known for a while that adolescents are quite extreme "owls" no matter what their chronotype may be earlier and later in life (and fortunately, school districts are starting to recognize this). This has been attributed to the surge of sex hormones in early adolescence. Responsiveness of the circadian clock to sex hormones has not been studied much (virtually not at all, though I should be able to publish my data within a year or so, sorry for not being able to divulge more detailed information yet), yet most people in the field believe this to be the case, even if no details are available yet.

Now a new paper suggests that the end of adolescence should be defined as a time when the circadian clock goes back to its "normal" state. But, wait a minute, the hormones do not disappear at that time. Thus, if the clock is responding to the hormones at the onset of the adolescence, does this mean that the end of adolescence should be defined as the time when the clock becomes UNRESPONSIVE to the hormones? How does that happen and how is that triggered?

Anyway, I still have to look at the study itself (this is just a press release). I want to see if females both become "owls" AND quit being "owls" earlier than males [OK, I took a peek at the paper and yes, they do]. Also, in women, hormones (mostly estrogen and progesterone) surge in monthly cycles that end abruptly at menopause, while in men testosterone (mainly) is pretty high (with a small circadian variation) continuously and only gradually declines in old age. The lifelong sex difference they found in the study is quite interesting in this light.

Also, I like the way they tried to tease away social influences from pure biology, though they are correct to warn they do not know in which direction causation flows: do the teenagers sleep late because they party, or do they party because they are wide awake.....and now a closet sociobiologist is waking up somewhere in my head trying to explain why would it be adaptive for teens to stay up late and play, including perhaps experimentation with sex while elders are asleep (squash, bad sociobiologist...go back to sleep...there, good boy)....

Wake Me When It's Over

"Societies define adulthood in different ways, from entering puberty to entering the workforce. But circadian clock researchers now suggest that adolescence ends when we stop sleeping in.Teenagers are more likely to have trouble getting out of bed in the morning than are young children or adults--a finding many studies attribute to a chronic lack of sleep. But researchers at the University of Munich wondered if a more fundamental biological factor played
a role.Using a brief questionnaire distributed in clinics, universities and online, Till Roenneberg and colleagues collected data on sleeping patterns from more than 25,000 people in Germany and Switzerland. As part of their analysis, the researchers determined each person's "chronotype" by calculating the mid-point of their sleep--halfway between going to bed and waking up--on days when the subjects slept as late as they wanted.A surprising pattern emerged. Average chronotypes drift later and laterduring the teen years, but then begin to move steadily earlier after the age of 20, the researchers report in the 28 December issue of Current Biology. It still isn't clear why, says Roenneberg.

Teenagers may sleep late because they've been out partying or they may go out because they're wide awake at 11 pm. However, he says, the team also saw a similar pattern in teenagers in rural valleys in South Tyrol--where nightclubs are relatively scarce. There, the average chronotype wasabout an hour earlier, but the overall age pattern was the same. The researchers also saw differences between the sexes, with females having an earlier average chronotype than males until around age 50--consistent with menopause--when the correlation between age and chronotype seems to break down. This suggests, Roenneberg says, that biological factors such as hormones have an important influence on the tendency to sleep late.Sleep researcher Mary Carskadon of Brown University in Providence, Rhode Island, says that both social and biological factors are likely involved. Finding the biological trigger--if any--could lead to a better understanding of
what drives circadian rhythms, she says."

Of course, the study was done on Germans. Even in disco-less South Tyrol there is electricity and modernity. It would be cool to see a similar study performed in a culture where sleep is divided in two parts (late-night sleep and afternoon Siesta), like in Mediterranean and Latin American countries, as well as in a real primitive society in which sleep is divided into two parts (early-night sleep and late-night sleep with a break for sex around midnight).

Societal Constraints

One thing we know is that darkness is an important aspect of the environment conducive to sleep. Silence is another. And we do not need science to tell us this - it's been known forever. I remember, as a kid, learning the "sleep manners", along with learning how to say "please" and "thank you", how not to interrupt adults when they were on the phone, and other early lessons of life. By "sleep manners" I mean behavior when there is someone asleep in the house: one is not to enter the room with the sleeping person, not to switch on the lights, not to switch on the noisy appliances (TV, vacuum cleaner, hair dryer or wash machine), not to talk at all if possible, or reduce it to the briefest quietest whisper if absolutely neccessary. One is to walk around on tiptoes, although the best idea is just to leave the house for a while. There was also a ban on telephone use between 10pm and 8am and again between 2pm and 5pm (so-called "house order"). Sleep was treated as something sacred. Be it at night, or the afternoon siesta, only a life-or-death emergency situation warranted waking someone up.

As Robert Anston Heinlein said:

Waking a person unnecessarily should not be considered
a capital crime. For a first offense, that is.

One thing I noticed upon arriving to the States is that nobody here seems to have any notion of "sleep manners". I have seen (and experienced) many times people barging into the room containing a sleeping person, switching on the lights and TV, talking, even talking to the sleeping person, all the while not being even aware that this is a Big No-No, very inconsiderate, and extremely rude. When confronted, the response is usually very defensive, stressing the person's individual right to do whatever he/she wants and not bother about being considerate about some lazy bum who is sleeping at an inappropriate time. Whoa! Stop right there!

First, individual rights are assumed to mean that you can do whatever you want as long as that does not hurt another person in some way. Waking someone up is harassment - of course it hurts someone. Second, there is no such thing as inappropriate time. If you can, you sleep whenever you can. There is no appropriate or inappropriate time. What do you do if someone is working the night-shift (like my wife often does, and I sometimes do, too)? That person will sleep during the day, so you better shut up. Third, what is this about sleeping being a sign of laziness. The "owls" are constantly being treated as lazy, though they are more likely to be sleep-deprived (cannot fall asleep until the wee hours, then being rudely awoken by the alarm clock after just a couple of hours) and spend more hours awake (and presumably productive) than "larks" do. If you are asleep, this means you need it. If you are rested enough you cannot physically remain asleep or go back to sleep again. You are wide awake. Thus, when you see someone asleep, it is because that person needs sleep right there and then. Sleep is not laziness. Laziness is "lots of front-porch picking".

Pretending that sleep-need does not exist is also institutionalized. I am not talking just about night-shifts and rotating shifts (those will kill you), night flights, being available for communication 24/7, stores open 24/7, etc - those are part of a modern society, will not go away, and we just need to learn how to adjust. I am talking about the building standards. With a huge proportion of the population working at night, why do windows have no blinds? Some old manors do, but new buildings do not. Never. Some have fake blinds, just for show, screwed into the outside walls on the sides of windows, yet cannot be closed. There are no built-in black curtains, or roll-down wooden blinds. It is difficult to find such curtains in stores if one wants to install one. What is going on? I have never seen, heard, read about, or experienced another country in the world in which sleep is not sacred, and blinds are not an essential part of a house.

I see some striking parallels between the way this society treats sleep and the way it treats sex. Both are sinful activities, associated with one of the Seven Deadly Sins (Sloth and Lust). Both are associated with the most powerful biological needs. Both are supposed to be a taboo topic. Both are supposed to be done in private, at night, with a pretense that it is never actually happening. Education in sleep hygiene and sex hygiene are both slighted, one way or another (the former passively, the latter actively opposed). Both are thought to interfere with one's productivity - ah, the good old Protestant work ethic! Why are Avarice and Greed not treated the same way? Raking in money by selling mega-burgers is just fine, and a decent topic of conversation, even a point of pride. Why are we still allowing Puritan Calvinist way of thinking, coupled with capitalist creed, to still guide the way we live our lives, or even think about life. Sleeping, whether with someone or alone, is a basic human need, thus a basic human right. Neither really detracts from the workplace productivity - au contraire: well rested and well satisfied people are happy, energetic, enthusiastic and productive. It is sleep repressed people, along with the dour sex repressed people, who are the problem, making everyone nervous. How much longer are we going to hide under the covers?

Perhaps not that long. It appears that we are slowly waking up to sleep problems (pun intended). More and more companies are allowing naps, and even providing nap-rooms. More and more school districts are moving high-school morning schedules later, as during teenage years, under effects of sex hormones, the circadian clocks are all temporarily "owlish". Adolescents are not crazy and lazy - they physically cannot fall asleep at a normal bed time, and physically cannot awake and feel rested early in the morning (elementary and middle school kids can, as their hormones have not surged yet).

It seems political advisors have caught on, too. During the presidential debates I blogged about the likely tacks used by the handlers to get their candidates to be at their peak performance levels in early evening - something apparently more difficult for Bush than Kerry ( see this and this). Battle for More Free Time, including its subset: the Battle for Sleep, is re-entering the political domain again. Check the links to the websites commenting on this newly-brewing movement. And of course, the art of matchmaking is starting to include the lark/owl questionnaire, assuming that people of the same chronotype are a perfect match (I saw this in a magazine in a waiting room, but if anyone knows if online dating services are doing this, please let me know).

Popping melatonin pills is one of the latest crazes. Melatonin failed as a sleeping pill and its uses as a scavenger of free radicals are dubious at best. It can shift one's clock, though. However, it cannot help against jet-lag or effects of shift-work (shift-lag) as melatonin is likely to shift only the main brain pacemaker in the suprachiasmatic nuclei. The problem with jet-lag and shift-lag is dissociation of rhythms between cells in different tissues, i.e., your brain clock may resynchornize to the new time-zone/schedule in a couple of days, the clocks in your heart and lungs in a week, and in your stomach and liver in a month. In the meantime, everything in your body is desynchronized and you feel really bad. If you keep changing your work shift over and over again, you never get to achieve complete synchronization, leading to long-term effects on health, including significant rise in heart attacks, stomach ulcers, and breast cancer.

Well, intercontinental flight is here to stay, and some shift-work is neccessary for the modern society to survive. It is now understood that some people (chronotypes) adjust to night-shifts and even properly executed (non-rapid, phase-delaying) rotating shifts, better than others. People have always tried to self-select for various schedules, yet it has recently started to enter the corporate consciousness that forcing employees into unwanted shifts has negative effects on productivity and safety, thus bottom line. See Chernobyl, Bhopal, Exxon Valdese and Three Mile Island accidents - all caused by sober but sleepy people at about 3am, just like thousands of traffic accidents every year.

So how does the future look like? As usual, don't ask scientists, especially members of the Academy. If you want answers to scientific questions about the future, you have to read science-fiction - this is a sacred duty of all scientists. Cory Doctorow who blogs on the group blog Boing Boing, has written a novel "Eastern Standard Tribe" (you can buy it, or download for free here) that answers just such questions. In the future not so far, people form communities not according to geography, or hobbies, or ideology, but their time zone. Everyone, no matter where on the planet, awake and at the computer at the same time, belongs to a particular Time Zone Tribe. Thus an owl from one country, an average from another and a lark from another will all be typing and reading at the same time, thus will meet in cyberspace and forge alliances against other time-zone communities. Inter-time-zone wars ensue, intrigue and treason happen, boy meets girl...the story is wonderful and will make you think about sleep, and about circadian rhythms, about Internet, and about being human, all in ways you never thought before. Enjoy.