The interview with Russell takes place in the iconic Brasenose College (where the professor is a fellow). Professor Russell Foster is Head of the Nuffield Laboratory of Ophthalmology and Director of the Sleep and Circadian Neuroscience Institute at the University. The interview discusses sleep: what is it? Why do we get disrupted sleep? Do animals? And what can we do to give us the best chance of some decent slumber?
Could you sum up the broader context of research into sleep, and where your research figures in that?
'Fundamentally, what I'm excited about and trying to understand is how the core mechanisms of sleep and 24-hour circadian rhythms are generated and regulated within the central nervous system, and then use this fundamental knowledge for translational studies – to inform therapeutic approaches that will improve the quality of life for individuals and their family across a broad spectrum of health conditions where sleep is severely disrupted, from eye disease to mental illness.
For example, we discovered that the eye contains a third light sensor. We’ve known about rods and cones for about 150 years. But we discovered that there’s another light sensor within the eye that is used to lock the body clock and the sleep–wake cycle on to the external world; without it we will drift out of cue.
'For example, we discovered that the eye contains a third light sensor. We’ve known about rods and cones for about 150 years. But we discovered that there’s another light sensor within the eye that is used to lock the body clock and the sleep–wake cycle on to the external world; without it we will drift out of cue. The adaptive advantage of having an internal clock is to anticipate and prepare for the varying demands of activity and rest across the 24-hour day, and to ensure that all our internal biology is appropriately aligned to the other parts for peak performance. Without the daily signal that the dawn/dusk cycle provides our biology becomes disconnected from the external world and our internal physiology drifts apart – which is what we experience during jet-lag. So, for example, if our internal body clock during sleep can anticipate that we need to be awake and active in 3 hours’ time, physiology can be cranked up in anticipation of wake. Glucose levels and metabolism go up, alertness goes up so that we are ready for action with the new day. If we simply waited until the change in the light level, then we would waste a lot of time preparing for, rather than exploiting the opportunities of, the new day. So we have this clock which fine-tunes our physiology and we showed that it is aligned to the dawn/dusk cycle by a non-visual photoreceptor within the eye. The rods and cones of the retina provide us with our sense of space or vision, but a small number of photosensitive retinal ganglion cells (pRGCs) detect the overall amount of light in the environment and then align the body clock – providing us with our sense of time. It was an amazing discovery – mice and humans entirely lacking their rods and cones can still set their clocks to the external world.
What that means, of course, is that you can be visually blind, you can have absolutely no image detection whatsoever, and yet you can still regulate your body clock.
'What that means, of course, is that you can be visually blind, you can have absolutely no image detection whatsoever, and yet you can still regulate your body clock. So we are trying to get this message out into the broader world of clinical ophthalmology, and my colleagues in the Oxford Eye Hospital are helping me to do this. For example, patients with advanced genetic diseases of the rods and cones will go blind but the pRGCs (the photosensitive retinal ganglion cells) may still be working. If this is the case then these individuals need to be told to seek out sufficient daytime light to regulate their sleep–wake cycle. Frequently, under these circumstances, patients will be told "There’s nothing more I can do for you." Without the appropriate advice, such patients will get up and go to bed later and later each day – they will drift through time. In some cases it is even more terrifying as patients may be told, ‘Your eyes are no good to you, you can’t see to look after them, they are a potential source of infection, so let’s take them out.’ So, unwittingly, the ophthalmologist may deprive an individual of their sense of time and plunge them into a world of constant jet-lag.
'So that’s one of the findings of my research. Another, more recent, example is that sleep disruption is always found in some form with psychiatric illness: schizophrenia, bipolar, depression are absolutely characterised by sleep disruption but this had not been properly researched and was largely ignored in clinical psychiatry. We systematically looked at sleep disruption in several patient groups, most notably schizophrenia, and the level of disruption is truly astounding – the sleep cycles of these individuals are smashed. Such observations, and the increasing understanding of the neuroscience of sleep generation, led me to propose that the neural networks in the brain that generate both sleep and mental health overlap, so that a defect in a neurotransmitter system that predisposes an individual to mental illness will almost certainly also have a parallel impact upon sleep – these two critical behaviours draw from the same common pool of neurotransmitters.
'So how can we test this idea? We reasoned that if we take a gene that has been linked to human schizophrenia, and then we mutate the same gene in a mouse, then we should see a defect in the mouse’s sleep–wake pattern. And by god we showed this link! And now we’re looking at a whole range of genes; some do, some don’t. What’s fascinating is that some of the genes that have been shown to be critically involved in the sleep timing systems have also now been linked to various form of mental illness. In addition, we have looked in teenagers who are at risk of developing mental illness. Our hypothesis was that if there are common and overlapping pathways between mental illness and sleep disruption you may see sleep disruption in “at risk” individuals prior to any clinical diagnosis of mental illness. Working with my colleague Professor Guy Goodwin in psychiatry this is exactly what we found. While the origins of sleep disruption in mental illness may arise because of overlapping pathways, it is also likely that the sleep disruption may make the mental illness worse and the mental illness further disrupt sleep. This has also been shown to be true. Another colleague in psychiatry, Dan Freeman, has shown that the partial improvement of sleep disruption in schizophrenia can reduce significantly the level of delusional paranoia. This is a particularly important finding as it suggests that the sleep systems represent a new therapeutic target for dealing with some of the symptoms of mental illness. Stabilise sleep and it can actually reduce some of the symptoms of mental illness – that is remarkable!
Stabilise sleep and it can actually reduce some of the symptoms of mental illness – that is remarkable!
'Who would have thought that ophthalmology and psychiatry would ever share the same research space? But they do, because they are all united by an understanding of the fundamental neuroscience of sleep generation and regulation.'
Do animals have sleep problems or is it peculiar to humans?
One of the problems of studying sleep in animals is that the techniques to study sleep can actually interfere with sleep behaviour. My colleague Stuart Peirson and I have developed a new video-based system for monitoring the sleep patterns of mice. This camera-based system is completely unobtrusive, and Pat Card at the MRC Harwell Institute and I have identified mice with genetic defects that profoundly disrupt their sleep. To date, three new sleep mutants have been identified, which is telling us lots of new things about how sleep is generated in the brain. So yes – animals, like humans, can have sleep problems.'
What are we doing when we sleep? What’s its function? Is there an evolutionary component?
'Not everyone will necessarily agree with my explanation – but here we go! All life on the planet has evolved a 24-hour timing system, which we use to fine-tune our physiology to the varying demands of activity. Essentially, each species has made an “evolutionary decision” to be active at a particular part of the day. And, as a result, that species will have evolved key evolutionary specialisations. We’re day active, and we have an eye that works well during the day but is far less efficient at night. But many animals, such as owls or bats, have eyes and other sensory systems adapted to the dim light conditions at night. Once you've committed to that evolutionary decision, you’re stuck – being active at a particular time of day, when you can function well, and inactive another time when you would be at a distinct disadvantage. At the same time, the body has to perform a critical and large number of essential housekeeping functions. For example, if an animal has a big brain, it needs to process the information it has received during the day: make decisions about what to turn into stored memories and how to use the new information for forward planning. For any animal, being active will generate toxins which can then be processed and eliminated during inactivity; metabolic pathways used-up during activity can be rebuilt during rest; food consumed during activity can be turned into stored reserves during rest etc. These are all critically important housekeeping functions that need to be undertaken at some point over the 24-hour cycle, and they will be allocated to the most appropriate phase of rest activity cycle. So what is sleep? My definition would be as follows: sleep evolved as a species-specific response to a 24-hour world. During sleep – a period of physical inactivity – individuals avoid movement within an environment to which they are poorly adapted, but then use this time to undertake essential housekeeping functions demanded by their physiology.'
During sleep – a period of physical inactivity – individuals avoid movement within an environment to which they are poorly adapted, but then use this time to undertake essential housekeeping functions demanded by their physiology
Do you think our attitude to sleep has got worse with digital devices and the increasingly international nature of work?
'I think that people are now beginning to understand that sleep is important. Are they doing anything about it? No, not yet. Sleep is critical for our cognitive health and, if you want a workforce that is creative and can solve problems, then the brain that has slept will be far superior to the tired brain. It really is an extraordinary thing that in the developed and developing nations, which depend so critically on our ability to process information and come up with solutions to complex problems, the one thing we do is deny ourselves sleep! I should also add that sleep affects our overall health. A large number of studies have now shown that disrupted sleep, such as in shift-workers, can lead to a multitude of problems ranging across suppressed immunity, greater risks of cancer, an increased risk of coronary heart disease and even metabolic disorders such as diabetes II.'
What are your personal tips for a great night sleep?
'Be sensitive and alert to how much sleep you really need. Assess whether you are the sort of person that needs to go to bed early or late or who needs lots of sleep or significantly less than 8 hours. Your sleep pattern at the weekends or when you go on holiday is a good way to unmask your true sleep needs. And, if you're not getting enough sleep, you need to make an effort to get more! It is not a luxury or an indulgence but a fundamental biological need, enhancing creativity, productivity, mood and the ability to interact with others.
If you are dependent upon an alarm clock to get you out of bed; if you take a long time to wake up; if you feel sleepy and irritable during the day; if your behaviour is overly impulsive, it means you are probably not getting enough sleep. Take control. Ensure the bedroom is a place that promotes sleep – dark and not too warm – don't text, use a computer or watch TV for at least half an hour before trying to sleep and avoid bright lights. Try not to nap during the day, and seek out natural light in the morning to adjust the body clock and sleep patterns to an earlier time. Avoid caffeinated drinks after lunch.
'So take control of your sleep: you’ll be a happier, healthier person as a result.'
Why do some people need more sleep than others?
'There are two really key regulators of sleep. One is the body clock, which tells our physiology and behaviour when it is a good time to be awake or asleep. And, as we discussed, the internal day is normally locked onto the external world. But then there's another important driver of sleep – which is the intuitive part about sleep, often called "sleep pressure". This builds up the longer you've been awake and then dissipates when you are asleep. So the clock and sleep pressure act together to determine when we sleep and how long we sleep. The sleep pressure builds during the day, but we don’t fall asleep because the clock is saying “keep awake”; but in the late evening, when the clock says “ok, sleep”, we go off to sleep. Sleep pressure is due to the build-up of multiple substances in the brain, one of which is adenosine. Some individuals seem to have receptors that are particularly sensitive to adenosine and so tend to sleep earlier and longer. The reason coffee works is that it blocks those receptors that bind adenosine, so that’s why you feel more awake after that cup of coffee.'
As well as psychiatric disorders, what other, more day-to-day issues can lack of sleep bring on?
'Poor sleep is definitively linked to hunger. Even with relatively short periods of sleep disruption, you start releasing the "hunger hormone" ghrelin. As a result, your metabolic axis can change very markedly over a short space of time. You develop cravings for carbohydrates, particularly sugars. On a sustained basis, all this can predispose you to obesity and clinical diabetes. Studies from the USA have shown that insufficient sleep is directly linked to the chances of weight gain and obesity.'
All these sleep disorders indicate you’re not quite at one with the timing of the world, if your body clock does not match the external world. Do you think that being able to sleep well is a function of being well integrated in your surroundings?
'I think that’s right. It sounds awfully like “dream catchers” and "crystal waving", but it is about being tuned in to the demands that you’re placing on yourself. The demands that your body simply has in order to function effectively and you’ve got to take those body demands seriously.'
How did you come to be at Oxford, and which departments have you worked in? What has it been like?
'I moved my laboratory to Oxford because I wanted to take part in translational research, and more specifically translational neuroscience. By that, I mean using our fundamental understanding of biological processes within the brain to inform our mechanistic understanding of neurological disease, new therapeutics, health and quality of life. And I did that because my work is fundamental neuroscience, and I could see lots of opportunities at Oxford where this research could be placed into a broader clinical context. And what Oxford does, in my view, better than almost any other institution in the world is bring together basic scientists and clinical scientists. There is a robust culture of sharing ideas and of basic and clinical scientists working together. Translational biology has always existed, to some extent, at Oxford. Indeed, you could argue that evidence-based medicine originated in Oxford because highly motivated individuals, passionate about what they do, have always been attracted to the place to share ideas and new methods and approaches. This was clearly recognised by the recent Research Excellence Framework assessment, which not only ranked Oxford as the highest-achieving institution overall, but ranked psychology, psychiatry and neuroscience as the best in the UK.'
Russell Foster was awarded a CBE in the New Year Honours 2015.