 It's a real privilege to spend an evening with a group of experts in sleep science, the history of sleep and the opera of sleep as you'll discover later on. There will then have be three breakout rooms. One the Chaucer Room where you'll be able to hear some of the British Library's collection of sleep sounds. The Bronte Room, they will be taking you through the answers and the explanations to the sleep quiz. But you needn't keep your questions just to the sleep quiz, they know everything about sleep, so ask them everything about sleep. And in the Elliott Room there will be my friend and colleague Chiara Ambrosio who will take you through some of the historical representations of sleep in art, some of the uses of sleep in politics and some of the representations of sleep in literature. I'm very happy to be able to welcome Professor Russell Foster who's the Chair of Circadian Neuroscience and Chair of the Nuffield Laboratory of Ophthalmology at the University of Oxford. He's a fellow of the Royal Society, has been since 2008, was elected for his work on circadian cycles and he's a fellow of the Academy of Medical Sciences, so no pressure but this should be pretty good. Russell Foster. So, let's kick off with an overview of sleep and clocks. And the first thing I want to emphasise is that in terms of our entire life activities, so the entire activities across our life, 36% of our life will be spent asleep. 36%, which means if you live to be 90, then 32 years will have been spent asleep. Now that's an incredible, that's a prodigious amount of time, apparently doing nothing. And it's remarkable when you compare it to all of the other lifetime activities. Work related is 16%. Watching TV is 11%. Household work, 8%. I have to say in my household I don't think anything near 8% gets done, it's particularly when the kids are home. But the point I want to try and make is that this is the single most important behaviour that we experience. And of course part of the theme of this evening is that this is a behaviour that completely dominates our lives and yet we take it for granted and largely ignore it. Okay, it's an absolutely obvious statement to make, but the transition from the wake state to the sleep state is also profound. It's the biggest switch in neural systems, in metabolic systems, in everything you can think of going in one direction and then right over to the other. And we're going to talk a little bit more about this later, but what's going on during sleep is turning out to be incredibly interesting. So information processing in the brain, memory consolidation, tissue repair, metabolic rebuilding of metabolic pathways, energy replacement, the clearance of toxins that build up during the wake state are then prepared, packaged and then seem to be detoxified ready for voiding during activity the next day. One of the really exciting areas of neuroscience is that if you want to come up with innovative solutions to complex problems then it's now very clear that a night of sleep can hugely enhance the brain's capability of doing that. So we really need to take sleep very seriously. Okay, let's now consider the role of the eye. We said that the eye plays an absolutely critical role in setting the clock and then the whole of this system to the external world. So the eye is critical and it's exposure to the light-dark cycle which is so important. Now let me emphasise, here's the eye detecting the light-dark cycle going to that master clock within the brain. And what we see here is a cartoon and each line represents a day and the wake-sleep cycle is nicely consolidated, it's entrained. Now if you have no eye, you've lost your eyes as a result of some gasey accident, then your ability to regulate your clock is gone. You will spend the rest of your life getting up later and later and later and later. You can no longer coordinate to the external world. So the eye is obviously critically important in this resetting process and I spent the last 20 years trying to understand how the eye regulates the clock. So if you have a bit of a closer look at the eye, this is hopefully familiar to many of you. These are the photoreceptor cells, the rods giving us our sense of dim light vision, the cones, our sense of colour. This is the inner retina during the first stage of visual processing before a signal is generated in these ganglion cells. They send their projections via their axons from the optic nerve off into the brain. Now what turned out to be truly extraordinary and I'm afraid I'm now summarising 20 years of work in 30 seconds, is that we discovered that you can lose all of your classical visual cells, your rods and cones, your got no sense of light detection whatsoever and yet, if you're exposed to a light dark cycle, you can still regulate your clock perfectly well. What we discovered is that there's another class of light sensor photoreceptor within the eye and it's based upon about one out of every hundred of those ganglion cells that form the optic nerve, is directly light sensitive using a blue light sensitive pigment and we call these the photosensitive retinal ganglion cells. Oh, I'll just show you what they look like. Aren't they beautiful? There's one and all the little fibres are directly light sensitive and if we look at a sort of an arc of the eye, here's individual cell bodies and they form this sort of photosensitive net that essentially captures light, brightness from the environment and sends that off into the brain and the biological clock setting it to local time. Big clinical implications about all of this, of course, because what it means is that visual blindness need not result in loss of all light detection by the eye. However, sleep and 24 hour rhythms are ignored in clinical ophthalmology. Simply hasn't got there yet. I am fortunate enough to work in Oxford and my colleagues in the Oxford Eye Hospital, notably Susie Downs, and we're working together as quite a big team of us now asking the question, what is the impact of eye disease on humans and their sleep weight biology? And I just want to illustrate some of the importance of the data that's emerging. There are patients of course with genetic diseases whereby the visual cells are gone or largely gone and they have no visual responses at all and yet their photosensitive retinal ganglion cells are there and they're working but nobody's bothered to look for that. And so under these circumstances of course what the ophthalmologist needs to say is get out there, expose your eyes to sufficient daytime light even though you're blind so that you can set the clock to the external world, otherwise you'll drift endlessly through time. It gets even worse because there's a tendency to say, well, your eyes look a bit odd, they're not really very attractive, why don't you just pop some dark glasses over them so the rest of us don't have to sort of watch all this. And frequently there are good reasons why you wear dark glasses but a lot of the time it's aesthetic and it gets even worse than that because there has and there still is a tendency to say, well, your eyes are no good to you, you're blind, they're a source of infection, you can't see to look after them, why don't we just pop them out and pop one of these in and then of course completely unwittingly what you've done is they're already blind, there's a sense of space but then you've taken away their sense of time as well and this is completely ignored. In the same way, there are individuals whose light sensors are okay but the inner retina breaks down so there's no way that the rods and cones can talk to the brain and you've lost those photosensitive ganglion cells but again all is not lost because there are ways of using drugs to try and hit the clock to consolidate it to restore a sense of internal time. So the point I'm trying to make is that clinical ophthalmology must now understand that the eye not only provides us with our sense of space but also with our sense of time and it's a great example of where our basic science discovery and it's a very simple question how does the eye regulate the clock is transforming the lives of potentially half a billion people worldwide. So with that I'll finish, thank you for your attention. I'd like to welcome Impropera who is the world's only improvising opera company. So what we will do is we will, before an event, on the spot, a sleep opera. We've never done this before, we may never do it again, that's how it goes. What we thought we would do is we would enter the dream world of sleep where illogical things seem to logically fit together which is a pretty good description of the work we do anyway but we thought we would post-justify by wrapping it in a sleep concept. So for that we will need some suggestions. So for example could you give us a name of a person who might not have an opera written about them? Anyone? Felix is correct? Felix is. Could we have a place in the world? Bombay. Is correct it is indeed Bombay. Could we have from this side of the room a phrase that we wouldn't necessarily expect to hear in an opera? Eat your broccoli twice. Thank you. I like your accent. The accent wins, what can you hear what you said? Eat your broccoli. Eat your broccoli is correct. Welcome back. From Russell's talk and from the opera we learned that there's a downside to not getting enough sleep and we learned that we're living in this crazy 24-7 society which is driven by schedules and driven by stimulants and not driven by concern for how we spend 36% of our lives and how we deal with the quality of that large proportion of our lives. And if we think about the cognitive costs of not getting those aspects of our lives correct think about whether you might be working as a shift worker in an airport checking the scans of equipment and luggage or whether you're a radiographer or whether you're just a burnt-out person working at your desk. What we know and this is work from Tara Santhe who's here in the audience tonight is that after one night of sleep you're going to lack of sleep you're going to make lots and lots and lots of errors and that gets worse with subsequent nights of sleep. We know that loss of sleep, we know that not sleeping is a bad thing. What I want to concentrate on is the positive side. What does sleep do that's actually good for you and it makes you smarter? I'll be showing you that it can make you thinner and that you can live longer and have a happier life. Now look at what happens during the night. This is one night of sleep across here and what you do is you go through different phases of sleep during the night's sleep. In between each of these red bars is roughly about 90 minutes and you have periods of deep sleep and you have periods of rapid eye movement sleep and so your brain just doesn't switch off. Your brain is doing something. I said about 80% of your brain is working while you're asleep. Let's look at how the brain can help to make you more smart. Here's something that we like to do in laboratories to give people something called Perdissociate Learning Tasks. So I show you a picture of an aeroplane and a basketball. That's the pair that you associate. I show you a picture of a corn and a dinosaur. That's the pair you associate. I later on give you a test and I'll show you a picture of the basketball and then two pictures of the corn and the aeroplane and you have to say which is the object that's associated with the first. Another kind of test that we like to give people is a test which requires no memory, no association but just tracing, a complete multitask. Mirror tracing, looking in a mirror and tracing something that's in front of you. It's a motor skill. So what happens when we give people these things to learn and then we let them sleep? How does sleep help you to learn these things? What you can see here is that if we have people sleeping early in the evening after learning these two tasks and then we wake them up and ask them to perform them people perform very much better if they've slept in the early part of the night on the Perdissociate Learning Task. If you want people to improve on the multitask but not the Perdissociate Learning Task then you let them sleep in the late phase of the night. So these phases of sleep are associated with completely different cognitive functions. It's not just an off-switch mush in which the same thing is going on all the time. These later phases associated with what we call procedural memory or motor functions and these earlier phases concerned with what we usually think of as clever stuff like learning languages and facts. How do we improve our lifespan? One of the long list of issues that Russell brought up was the effect of poor sleep on lots of aspects of health and he also had on his slides cardiovascular illness. Let's ask, can we have a positive side to that? Does looking after your sleep cycle and your sleep behavior help you to improve your health and protection from cardiovascular disease and coronary disease? So there was a huge study of Greek nappas. Over 23,000 people followed them for over six years. The question of the research was who dies from coronary heart disease? It's a fun game. And what they did was tried to control for all sorts of things like level of income, exercise taken, diet. It really is a very good study. These things are hard to do. But what they found was that the occasional nappas had a 12% lower mortality than baseline than the people who didn't napp at all. The regular nappas had a 37% lower mortality than the non-nappas, which is really significant. It screws up your GDP, obviously. These are not prosperous people. As you'll see in a second, they're in for a hell of a pension crisis. Here's my favourite sentence, and I think it's one sentence from the whole of that paper. Very, very instructive. Amongst men, the napp benefit was stronger when the analysis was restricted to those who were currently working at Enrolment. You could see there are reasons that might be. Whereas among women, a similar analysis was not possible because of the small number of deaths. Greek women who napp are immortal. It's been amazing. It's so good, especially that first tour. It was so brilliant. That's actually the first opera I've ever seen, so I don't know how true that is to real opera, but it was really good, really interesting.