The Secret World Of Sleep

Tales of Nightmares and Neuroscience

Guy Leschziner

• Publisher: Simon & Schuster UK
• Year: 2019
• Print ISBN: 9781471176388
• eBook ISBN: 9781471176371
• Topic: Medicine
• Subtopic: Sleep Medicine

*As featured on Steven Bartlett's Diary of a CEO podcast* For those fascinated by neurology and for fans of The Man Who Mistook His Wife for a Hat comes a powerful exploration of the mind during night time. Here are the mysteries of sleep, explained – from known conditions to the extreme. 'The Secret World of Sleepinterweaves bizarre real life stories with cutting edge neurological science in the true tradition of Oliver Sacks. A fascinating read.' Martha Kearney, BBC Radio 4 World-renowned neurologist and sleep expert, Doctor Guy Leschziner, takes you through various sleep conditions and how they arise and affect people. Insomnia, narcolepsy, night terrors andapnoea are just some of the conditions afflicting those struggling with sleep. Then there are the extreme cases. The people frightened into paralysis by hallucinations. The woman in a state of deep sleep who gets dressed and goes for a drive. The teenager with 'Sleeping Beauty Syndrome', stuck in a cycle of excessive unconsciousness. The man who cleans out kitchens while 'sleep-eating'. Withcompassionate storiesof his patients and their conditions, Leschziner illustrates theneuroscience behind our sleeping minds, revealing the many biological and psychological factors necessary in getting the rest needed for health and happiness. Pick of the Best Paperbacks - Sunday Times
Best January Paperbacks - The Times
Must Read Brain Books 2019 - Forbes Magazine
The Best Neuroscience Books of 2019 - The Scientist Magazine
The Best Books of 2019 - New Zealand Herald
Best 100 Summer Reads 2019 - Sunday Times
Week's best Science Picks - Nature
Books of the Year 2019 - Irish Independent

1

GREENWICH MEAN TIME

If you have ever been on a long-haul flight crossing time zones, the feeling of jet lag will be all too familiar. You know something is amiss: you feel sluggish and detached from your environment; the bright sunshine of your destination is discordant with your yearning to be tucked up in bed. There is the nausea of needing to stay awake when every fibre in your body craves sleep, or the incongruity of being wide awake at 2 a.m. while the world around you slumbers, and all you can think about is breakfast. Thankfully, your body soon adjusts, and within a few days you are back in tune with life around you. But imagine if that was how you felt all the time, that it was the reality of your daily life, and there was no hope of recovery.

I first meet Vincent, and his mother Dahlia, at Guy’s Hospital. He is sixteen years old, and this particular clinic is specifically for teenagers transitioning from the sleep services in the children’s hospital to the adult world. Typically, this clinic is full of children with narcolepsy or severe sleepwalking. But Vincent is not typical in this regard – or, indeed, any other. He is a shy and reserved teenager, not particularly tall but stocky and well-built. I learn that this is testament to his enthusiasm for boxing. Dahlia, in contrast, is bubbly and very talkative. Originally from South America, she speaks English fluently but with a strong accent and at a machine-gun pace. For the most part, Vincent sits there quietly as Dahlia tells me the story of the past few years, only interrupting when his frustration bubbles over. When he does talk, he is slow and hesitant; he occasionally finds it difficult to find his words.

Between them, they paint a picture of Vincent’s life.

Vincent first became aware of some difficulties with sleep at around the age of nine or ten, but it was really only at the age of thirteen that his problems became much more evident. Dahlia thinks it started after Vincent had two operations on his hip, the second to remove metal plates inserted during the first procedure.

‘Well, it was kind of gradual. At first I didn’t really know what was happening,’ Vincent tells me. He was initially finding it harder and harder to fall asleep, drifting off at three or four in the morning. ‘The first time I properly realised it was a problem was when I was always trying to go to sleep, and then I started seeing the sun rise every time.’

It quickly got to the point where Vincent would be wanting to fall asleep at eleven in the morning and wake up at nine in the evening. Unsurprisingly, his schooling quickly began to suffer. ‘I really missed a lot of school. At first I didn’t want to tell anybody that I was having trouble sleeping, because they would just think that I’m lazy. So I just told them I was unwell a lot.’

For Dahlia, this time in their lives still stings. ‘I started to notice when I was trying to wake him up to go to school that I could not wake him for love nor money. I would shake him, but just not be able to get him up. I was so confused because he had never been late for primary school. Never! I thought I was being judged as a mother. Possibly Vincent thought he was being judged as a student too. I got into so much trouble with his school. I was fined for Vincent’s poor attendance!’

Vincent also recalls feeling judged: ‘The school, my dad and friends found it hard to understand.’ Some people, including his father, from whom Dahlia is separated, raised the likelihood that it was simply a case of a typical teenager oversleeping, or that it was psychosomatic. In fact, I think Vincent’s father still considers this to be the case. On one occasion, I spoke to Dahlia on the telephone and I could hear him in the background, arguing with her that there was no medical issue.

Dahlia knew that there was more to it than teenage sleep patterns, however, and as Vincent’s school attendance dropped further, she sought medical advice. Dahlia recalls taking Vincent to see their family doctor. ‘We went maybe about seven or eight times, a few months apart, just to say Vincent has a problem with sleep. [We got] the usual recommendations – give him a hot milky drink before bedtime, no screens at night – all of that. Lavender oil . . .’ she scoffs.

The problem nevertheless persisted, and eventually Vincent was referred to a paediatrician. It was at this point, some two years after he had realised he had a problem, that Vincent finally received a diagnosis: Vincent’s internal body clock seemed to be set at the wrong time. Rather than being attuned to the world around him, he was told by doctors that his own body clock was running several hours later than everyone else’s. He was diagnosed with delayed sleep phase syndrome.

* * *

We are all children of the sun. We are enthralled by it, and enslaved by it; we march to the beat of the sun’s drum. Our sleep patterns are defined by the 24-hour rhythm of the rotation of the earth and our exposure to the sun’s light. This makes total sense: to be awake and foraging for food when it is light and we can see prey and predators, and to sleep when it is dark and we are vulnerable to predation, seems crucial to our survival. It is not only our sleep that is defined by this rhythm, however.

Type ‘circadian rhythm’ – from the Latin for ‘about a day’ and the name for this 24-hour cycle – into PubMed, the most widely used search engine in the life sciences and medicine, and it will return over 70,000 hits – papers with titles ranging from ‘Biological clocks and rhythms of anger and aggression’ and ‘Circadian regulation of kidney function’ to ‘Biological clocks: their relevance to immune-allergic disease’. Our 24-hour rhythm influences our brain, our gut, our kidneys, our liver and our hormones – every cell in our bodies. In fact, remove a cell, place it in a Petri dish, and it will demonstrate a 24-hour rhythm in some form or other. Indeed, 40 per cent of our genes that encode proteins are under the regulation of this circadian rhythm.

It is not simply a matter of exposure to light, though. The sun is not the metronome that keeps this rhythm going – at least not any more. Put humans in dim light, without any exposure to the rising and setting of the sun, and the rhythm will continue.

In the 1930s, Nathaniel Kleitman, one of the founding fathers of modern sleep science, experimented on himself and others in the depths of Mammoth Cave, Kentucky, the longest known cave system in the world. Deep underground, without light and without fluctuations in temperature and humidity, he tried to impose a 28-hour cycle, but found he could not. Even in the absence of the external cue of the sun’s light, body temperature, sleep and other physiological parameters retain this 24-hour rhythm, implying that somewhere within us is a clock that keeps time.

It also seems that this clock is common to all life on this planet. Bacteria, single-cell organisms, plants, flies, fish and whales – they all have this endogenous clock. For some lifeforms, the need for this clock is clear. But why should bacteria need to know what time it is, or indeed plants? Plants certainly need to know when the sun is shining, to know when to open their leaves and photosynthesise, but this does not need to be guided by an internal clock; simply detecting light would be enough. And why should fish living in cave systems, blind and not exposed to the light of the sun for thousands of generations, hold on to this clock? The fact that they do implies that this circadian rhythm is hardwired into the very essence of life, that since the existence of the last ‘universal common ancestor’, the very origin of all lifeforms on the planet, there has been an evolutionary pressure and natural selection acting to maintain this endogenous clock.

At the most simple end of life as we know it, bacteria and algae, it is difficult to know what this pressure might have been, however. It has been proposed that the origins may lie in a desire to avoid cell replication, which involves the copying of genes, during times of exposure to ultraviolet radiation, known to produce mutations. A more widely accepted hypothesis is that these rhythms evolved to control the production of genes that pre-empt and counteract daily fluctuations in oxygen levels and the damage that oxygen does. The circadian rhythm may in fact date back to the Great Oxygenation Event, approximately 2.45 billion years ago. This time period is defined by the evolution of bacteria called cyanobacteria, believed to have been the first microbes to achieve photosynthesis – the conversion of carbon dioxide to oxygen using energy from the sun’s rays. At that time, atmospheric oxygen levels were low, and any free oxygen quickly became chemically bound to other substances. But the sudden rise in free atmospheric oxygen caused by cyanobacteria is thought to have provoked one of the largest mass extinctions in the history of the world, killing off most organisms for whom oxygen was highly toxic. Surviving organisms needed to develop mechanisms to protect themselves from the dangerous effects of free oxygen. It is thought that this need for protection resulted in the evolution of proteins called redox proteins, which mop up the toxic by-products of chemical reactions involving oxygen. The theory suggests that by predicting sunlight, and knowing when oxygen levels are going to rise, organisms can protect themselves from toxic damage, by generating these proteins at an appropriate time of day. But the truth is the origins of the circadian rhythm remain a mystery.

Any clock needs to be adjustable or reset, like a horologist tinkering with the pendulum of a grandfather clock to keep it running on time. The circadian rhythm, particularly for more complex organisms, needs to be tweaked according to the changing patterns of our seasons. Over the past few decades, our understanding of how this occurs has advanced. We are now aware of the influence of environmental cues or influences that gently nudge our circadian rhythms forward or back. These are termed Zeitgebers – ‘givers of time’ in German. Left to its own devices, the human circadian rhythm is set to 24.2 hours, and without Zeitgebers we would eventually find our internal clock drifting relative to the world around us. Our internal clock is sensitive to temperature, physical activity and eating, but by far the most potent Zeitgeber is light – particularly light at the blue end of the spectrum, like sunlight. While our circadian clock has proved itself independent of the sun, therefore, it is still its greatest influence.

The Royal Observatory, Greenwich, only a few minutes’ train ride from the Sleep Disorders Centre, Guy’s Hospital, sits atop a hill overlooking a large loop in the River Thames. From the thirtieth floor of the hospital, I can see the hill rising slowly towards south-east London, but cannot quite make out the building between the forest of ugly 1960s towers and new skyscrapers. On the roof of the observatory, a large metal mast with a weather vane on its tip juts into the typically grey London sky. On this mast, a large red ball, several feet in diameter, is impaled. Every day, at 12.55 p.m. Greenwich Mean Time in the winter, British Summer Time in the summer, the ball rises halfway up; then, at 12.58 p.m., ascends to the top. At 1 p.m. exactly, the time ball drops down the mast. In the present day, the area around the observatory is dominated by the skyscrapers of Canary Wharf, the main financial district of London, looming over the city from across the river. In the mid-nineteenth century, however, the Thames below would have been chock-full of sailing ships, ferrying the lifeblood of trade through the British Empire. Hundreds of telescopes would have been focused on the time ball of the observatory, waiting for the ball to drop. This would be the sailors’ opportunity to reset the chronometer on board each ship to Greenwich Mean Time, crucial for the calculation of longitude on their journeys to the East Indies and beyond.

Like the chronometers on these ships, there are multiple clocks within the human body, but the seat of the master clock – the large red ball of the Royal Observatory – in humans, and indeed all vertebrates, is a tiny area of the brain called the suprachiasmatic nucleus. This tiny area, comprising a paltry few thousand neurones, sits in the hypothalamus, immediately above the optic chiasm, where the optic nerves carrying information from the eyes merge. This tiny nub of tissue is the control room for all circadian rhythms throughout the body, and destruction of the suprachiasmatic nucleus results in the loss of this rhythmicity.

Within the neurones of the suprachiasmatic nucleus, a complex dance occurs on a daily basis, with several genes with names like CLOCK and Period interacting with each other, feeding back to each other, conducting the ticking of our clock. But light, as a Zeitgeber, sways this dance, tweaking it forward or back. In the retina, at the back of the eye, in addition to the rod and cone cells responsible for converting light into vision, are cells known as retinal ganglion cells. A few of these cells have no contribution at all to vision. Their purpose is instead to conduct signals to the suprachiasmatic nucleus, through a direct projection called the retinohypothalamic tract. And it is through this pathway that light influences the rhythm in the suprachiasmatic nucleus, affecting the phase, the relationship of the 24-hour rhythm to the outside world, and the amplitude, the strength with which this rhythm runs. For people without any vision, the control of the circadian rhythm can be problematic, as we will see later.

* * *

The paediatrician’s diagnosis in Vincent of delayed sleep phase syndrome is a common one. For those with this condition, their circadian rhythm runs behind that of the outside world. While most people want to go to sleep between 10 p.m. and midnight and wake between 6 and 8 a.m., people with delayed sleep phase syndrome may want to sleep at 3 a.m., sometimes as late as 7 a.m., and wake up seven or eight hours later. If they get this amount of sleep, then they feel fine. Unfortunately, life often gets in the way of sleep, and within the constraints of modern society, holding down a job or getting an education is difficult, if not impossible, on this sleep schedule.

To some extent, having a tendency to want to wake up early and go to bed early, or wake up late and go to bed late, is normal. There is a broad spectrum of chronotypes – a person’s preference to go to sleep and wake up at a particular time. At the extremes of ‘morningness’ or ‘eveningness’ are those individuals known as ‘morning larks’ or ‘evening owls’. People with delayed sleep phase syndrome can be considered extremes of the extreme, ‘evening owls’ whose circadian rhythm is so delayed that it has negative consequences on their life.

As with many features of our sleep, it appears that what chronotype we are is to some extent determined by our genes. Studies in twins or in families suggest that up to 50 per cent of our chronotype is under genetic control, and variants in the genes that regulate our circadian rhythm have been associated with both extreme ‘eveningness’ and extreme ‘morningness’. In a familial form of what’s known as ‘advanced sleep phase syndrome’, in which sufferers want to go to bed early in the evening and wake up extremely early in the morning, much rarer than delayed sleep phase syndrome, a mutation in one particular circadian gene, called ‘PER’, has been identified. Furthermore, mutations in another one of these circadian genes, called ‘DEC2’, seem to increase the amount of time we spend awake and reduce the amount of sleep required. For most people, however, it is not these few mutations that influence their wake/sleep pattern, but likely the cumulative effect of multiple milder variants in all of these genes.

Moreover, it appears that shifts in our chronotype also occur as the brain matures. Teenage circadian rhythms will typically shift later in the day, before then shifting back in adulthood. I can see this happening in my older daughter. Prising her out of bed in the morning is becoming increasingly difficult – as is getting her to go to sleep at a reasonable time at night. Undoubtedly this shift in the body clock seen in teenagers is compounded by the use of electronic gadgetry late in the evening. Being glued to your tablet, laptop or smartphone while in bed, as many teenagers are, provides a potent source of light to act as a Zeitgeber and makes this delay worse. This is a real problem. The consequence being that many teenagers, still needing to get up early to go to school, are sleep-deprived, and sleep deprivation is correlated with poorer performance at school as well as behavioural issues and anxiety. Individuals with delayed sleep phase syndrome, however, seem to be particularly sensitive to light exposure and its effects on the circadian rhythm. A burst of light in the evening seems to have a much greater delaying effect on the circadian clock in susceptible individuals than on average.

So, maybe the answer to Vincent’s problem is as simple as cutting out the use of electronic devices at night. Or even wearing sunglasses in the evening to stop as much light as possible, especially blue light, from hitting his retinal ganglion cells. There is only one problem with this solution: Vincent does not actually have delayed sleep phase syndrome. What he has is much rarer.

If you listen carefully to his story, it is readily apparent, because Vincent does not want to go to bed at the same time every night (or day for that matter).

‘Essentially my sleeping pattern shifts constantly, so my body wants to go to sleep an hour later every day,’ Vincent says. ‘So basically if I go to bed at 10 p.m. one day, I’ll be naturally inclined to go to bed at 11 p.m. the next day, and so on.’

For Vincent, this constant shifting in his internal body clock means that bedtime, and by extension waking time, progresses by an hour a day. For a few days of every month, therefore, Vincent is synchronised with the world around him, but he soon shifts out of phase. ‘For a week or so, I will be in social hours, but for the rest of the time, to different extents, I am out of sync.’ At its worst, Vincent is essentially nocturnal and tells me that he can sometimes want to go to sleep at 11 a.m. and wake up at 9 or 10 p.m.

The impact of this shifting pattern is enormous. The result is that Vincent is often incredibly sleep-deprived. For most of the cycle that he shifts through, he finds it difficult to fall asleep at an appropriate time, but is forcing himself to get up in order to go to school. Some days, it is the equivalent of being rudely awakened at 2 or 3 a.m. and then being expected to pay attention in class at 4 or 5 a.m. Essentially, he is almost constantly jet-lagged.

Vincent says: ‘When I’m in school, it can be very difficult to concentrate. One teacher noticed that my reading is particularly slow, and that it affects my processing skills. Sometimes it is almost impossible to stay awake and concentrate, so I could fall asleep during lessons.’

On one of the occasions we meet, it is about 5 p.m., but Vincent is in a phase when he wants to go to bed at 2 or 3 p.m. and wake up at midnight or 1 a.m. For Vincent, his brain is telling him he should be deeply asleep, and according to his body clock it is about 1 or 2 a.m. He struggles to string a sentence together, pausing constantly to find words, trying to get his thoughts in order. It reminds me of times as a junior doctor ...

Table of contents

• Cover
• Dedication
• Introduction
• 1 Greenwich Mean Time
• 2 In the Still of the Night
• 3 Disney Was Right
• 4 Rumblings
• 5 The Sleep-Talking Bus Driver
• 6 Weak With Laughter
• 7 Buzzing Bees
• 8 Seized by the Throat
• 9 Floating Eyeballs
• 10 Jekyll and Hyde
• 11 The Waking Effects of Coffee
• 12 A Peculiar Fairy Tale
• 13 Inception
• 14 Losing Sleep
• Epilogue: Some General Thoughts on Sleep
• Appendix of Diagrams
• Acknowledgements
• Glossary
• Further Reading
• Index
• Copyright