Sleep Series Episode 1: How Does Sleep Work? (w/ Prof. Russell Foster)

This is the first episode on our special mini-series on sleep. Professor Russell Foster is Professor of Circadian Neuroscience, Director of the Nuffield Laboratory of Ophthalmology and the Head of the Sleep and Circadian Neuroscience Institute at the University of Oxford. He is the author of the Sunday Times bestseller 'Life Time'.

In this episode, we take a whirlwind tour of how we’ve developed circadian rhythms and how they orchestrate pretty much every function in our body. We turn the focus onto sleep, of course, and speak about the impact of shift work, what is known about the sleep disruption in mental illness (chicken or egg?!) and much more. 

You can see more of Prof Foster's research at https://www.scni.ox.ac.uk/

Interviewed by Dr. Anya Borissova with Dr. Rosy Blunstone. Dr. Borissova is an academic psychiatry registrar at the South London and Maudsley Trust. Dr. Blunstone is a psychiatry and psychotherapy registrar in London. 

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Transcript

Anya: [00:00:00] Hello everyone. Welcome back to The Thinking Mind Podcast. My name is Anya. I'm a psychiatry registrar working in South London alongside my clinical work. I'm very interested in research and my work there mainly focuses on improving treatments for depression. Today I am speaking to Professor Russell Foster, together with Rosie, who is one of our team members on the Think You Mind podcast. Rosie and I have been putting together this series on sleep of which Professor Russell Foster has agreed to be part of. We're very excited to speak to him today, all about circadian rhythms and how these help to regulate our sleep WIC cycles, and really the impact that they have on all of our bodies.

Professor Russell Foster is a professor of circadian neuroscience and the head of the Department of Ophthalmology at the University of Oxford, as well as being a fellow of the Royal Society, the Royal Society of Biology and the Academy of Medical Sciences. He's also a commander of the British Empire, CBE, for [00:01:00] services to science.

Our conversation today spans what circadian rhythms are, how they work in the human body, the importance of light, and we bust some myths, but also affirm. Some parts of conversation about the importance of morning light. We talk about shift work and its impact on our bodies, and we talk about the interaction between circadian rhythms and our mental health.

We really hope that you enjoy this episode as always, please do send us feedback. We love to hear from you. If you appreciated this episode or the other ones, please do give us a rating or a comment wherever you listen, as this helps other people to find the podcast.

Sit back, relax, and enjoy. Hello [00:02:00] everyone. Welcome back to the podcast this week, professor Russell Foster. Thank you so much for joining us today.

Russell: Absolutely delighted. Good to see you both.

Anya: We, so we are here to really get into circadian rhythms and why they're so important, and I hope that we can really traverse the whole realm of what circadian rhythms are about, why they're so important to our health, how they impact on really every aspect of our lives.

And I guess to begin with, what we like to try and do is, is go back to where things started. And so we, Rosie and I would just really love to know how were you first drawn into this world? What, what pulled you to look at circadian rhythms?

Russell: Well, I guess it was three things. First of all, we had some incredible undergraduate le lectures. I was, I was doing zoology at the University of Bristol and a, and a chap called Mike Men came over from the states and he, he is. Just amazing chap, sadly, died a few years ago, and he gave us some of these inspiring lectures on these internal body clocks and how they were timing everything.

Then my [00:03:00] undergraduate, my third year project was actually on, on light systems, but not the light sensors in the eye, but in fact, this was the pineal photoreceptor of a, of a tadpole, and it's involved in lots of non-visual tasks and perhaps the regulation of circadian rhythms. And that sort of set the stage for my PhD work, which was how do birds detect day length to regulate their annual reproductive cycles?

And to detect day length, you need a circadian clock, which measures the duration of light and dark. And knowing that information and whether the days are getting longer or shorter, you can trigger your reproductive system. So it, I, I sort of was interested in photoreceptors and clocks and, and I, ironically, my PhD was on a, on a, a seasonal.

But regulated by a circadian 24 hour clock measuring light and dark.

Anya: Mm. So, guess this is gonna start to get into the crux of really what, what we're [00:04:00] talking about when we say circadian rhythms and, and what kind of rhythms exist in our 

bodies. 

Russell: Yeah. 

Anya: And I guess there's a line at the end of your book that is something like what we do when really matters.

Russell: Yes, 

Anya: And I wonder if we could start there by trying to understand, so what, what are these rhythms about?

What, what should our, what should our average listener know about our rhythms that they may not.

Russell: Well, I think picking up from that point, um. If you think about what our biology is obliged must do, it must deliver the right stuff at the right concentration to the right tissues and organs at the right time of day to allow us to be fine tuned, ideally adapted to the very demands of sitting on a planet that revolves once every 24 hours.

And if you think about it, the, the, the, the, the difference between day and night is profound. During the day, there's lots of light and potentially damaging ultraviolet light, and it can be [00:05:00] very hot during the night. There's no light, of course, and, and it can be extremely cold. And so we have to fine tune our biology to cope with those varied demands and an internal biological circadian clock as essentially adjusting, fine tuning our biology to those varied demands of the 24 hour light dark cycle.

And indeed, without it. Our 24 hour rhythms just collapse and fall apart, including our sleep, which I know we'll get to fairly short, uh, fairly shortly. Uh, so really it's, it's this remarkable internal timer that's really tweaking everything that we do

Anya: And how does it work? What, what, what is happening in the.

Russell: Yeah. So, so yeah. So where to start? First of all, in mammals, where is the clock, which is what I was involved in when I first moved from my PhD work and, and early postdoctoral work, went over to the [00:06:00] University of Virginia and worked with Michael Manka. That person who'd given me those under, given me those wonderful undergraduate, um, lectures.

And he became this, this fantastic mentor, and I joined a project which was trying to identify what the master clock was within the body. And it was thought to be a structure, a small structure that sits on top of the optic nerves as they go into the brain and they fuse, and it's called the supra charismatic nuclei or SCN In humans, there's about a hundred thousand cells in total.

And the project I joined was looking at a mutant hamster. I, I, I, I promise I'll explain this. There was a mu mutant hamster, which, which had a, had a, a clock of about 20 hours. And so what what became clear is if you put that mutant, SCN. Into a normal hamster. It was converted from a 24 hour animal into a 20 hour [00:07:00] animal.

And that was the final bit of proof that, that Martin and, and, uh, who led the project and, and Mike Manka and I was involved, showed that this, there is a master clock in the break. And at that time, and we were talking about, what are we, uh, 1990 some, something like that. And we thought, well, what this thing did this, this structure, there were cell cell connections and the 24 hour oscillation was an emergent property of cell cell.

Nerve cell, nerve cell interaction. And in those days, we were talking to people who were working on swimming rhythms. You know, if you think of a shark swimming that beautiful oscillation and, and people have worked out the circuitry in the spinal cord that generates that oscillation. And we thought, well, that's what the clock must be like.

You know, it's a, it's a, it's a cell cell interaction and then it became clear we were wrong. Yes, there is a master clock, but each one of those cells in the SCN is capable of [00:08:00] generating a 24 hour oscillation. So that became clear and, and it was really first worked out in a fruit fly, not in, not in mammals or mice, uh, that there are clock genes which are turned on.

They produce clock proteins. They form a complex, which then, which then moves into the nucleus. And then turns off her own gene, though that protein complex is then broken down and then the genes can start, um, know, uh, producing more protein, uh, uh, and the whole cycle. See, you have a cycle, uh, a 24 hour cycle of protein construction and then degradation, and that's the heart of the, the clock.

And you find that in every cell in the SEN. And what we thought then was, okay, well all these cells are connected and they then force a 24 hour rhythm on our biology, whether it be hormone levels, whether it be sleep, whatever. We got that wrong too, because then it became clear that every cell in the body has the capability of generating a 24 hour oscillation.

So [00:09:00] this structure within the brain, this SCL, is acting a bit like the conductor of an orchestra producing a regular temporal beat from which all the component parts of the body. The members of the orchestra are aligning their rhythmicity with respect to that master clock within the brain. 

And, and so, uh, yeah, it, it was a, an extraordinary time where fundamental, you know, we, our, our, our, you know, every meeting you went to there was something completely new, which broke down our existing understanding.

Now, I moved rapidly from the master clock, which is the project I sort of, uh, was involved in when I first moved to the States to really, I wanted to understand how light, uh, sets this internal day to the external world. 'cause without that adjustment. This internal clock this time is no use whatsoever.

Classic, uh, example, we jet lag. I mean, you know, jet lag is a complete mismatch between the internal day and the external [00:10:00] world. And we get over jet lag primarily, although not exclusively by exposure to the light dark cycle. And I wanted to know how the eye was doing this. We knew it was the eye because in blind people with no eyes, they couldn't regulate their clocks.

They would drift through time. And most human clocks were a little bit longer than 24 hours. So they get up a bit later and later and later each day. And if you covered up the eyes of a mouse or a hamster or whatever, they would again drift through time. So what is it now? The thing that puzzled me and going back to my undergraduate.

Days. I had a wonderful mentor, again called John Liko, who wrote this amazing book called The Ecology of Vision, and its central tenant was, sensory systems are exquisitely tuned to the demands of their sensory task. Now, that's kind of obvious, but if you think about it, what the visual system has to do and the, and the rods and cones of the eye is grab light in a fraction of a second.

Forget they've seen the light to build an image of [00:11:00] our world. And that's why, you know, when we look around, um, we don't get this smear of light. We get, you know, sharp images. But what the clock needs is an overall measure of brightness within the environment at dawn and dusk to set the clock. And I couldn't understand how, how the visual system, as we understood it, could convey that information to the clock in the brain.

And so we started using mice with hereditary retinal disorders where the visual cells, the rods and cones had been, had, had, had been lost largely, and they were being used to study human eye disease. So, you know, the models were kind of there already. And to our absolute amazement is that these visually blind mice could regulate their circadian system, align that internal clock to the external world perfectly.

Normally, not just they could do it, they did it with the same light sensitivity as an as, as a mouse with their rods and cones. And this [00:12:00] suggested that there was something else in the eye. I remember going to these vision meetings in the early days and saying, you know, so the data are consistent with a, a third unrecognized receptor in the eye.

And I remember. Two instances. One person when I said this stood up and looked at me and I thought, oh, they're gonna ask a question. They just looked at me and said, bullshit, and walked out. And somebody else at the end of a of a, of a talk. Said, are you seriously telling us that after 150 years of studying the eye, you have found something new?

There's something all the rest of us have missed. And of course, I was young and full of sort of vigor and I said, yes, uh, I you've missed it. And I'm not sure I've had the same courage these days. I think youth is really important in science and maybe a certain level of arrogance. Um, and so that led to the discovery of this, this third receptor.

And that's what we've be, I've been studying in, in various forms ever since. I mean, the most recent [00:13:00] work is trying to understand the, how these and their, and their course photosensitive retinal ganglion cells. So the ganglion cell layer of the retina is, is, is, is the layer that that sends all the projections from the eye to the brain that form the optic nerve.

And about one out of every hundred of those ganglion cells is directly light sensitive. And now we've been working how those light signals interact with that molecular clockwork and, and keep the rhythm adjusted to the outside world. And, uh, we can come back to some of the, the treatments we're trying to develop, uh, u using that fundamental knowledge.

So, so what you've got is a master clock in the brain. In the SCN, it's coordinating a rhythmic activity of all the, the, the, the cells, you know, the rhythmic cells within the body largely, but, but that master clock is in turn set to the outside by specialized non-visual photoreceptors within the eye. So we've come, let's see, 40 years or so, uh, an awfully long way.

Um, and of course in 20 17, 3 of my [00:14:00] colleagues, young, uh, Ross Bash and Hall got the Nobel Prize for discovering how the first clock worked. And as I mentioned, it wasn't in a mammal, it was in the fruit fly. And what's, I think also fascinating is that the genes and their proteins that. Make a clock tick in a fruit flight are broadly simmer across the entire animal world, including us.

Service in, you know, the whole, it flies are separate to us by what, 500, 550 million years. And yet the building blocks of the clock have been broadly conserved. Now, how we animals build our clocks is different from fungi and from plants and indeed bacteria, but they're all based upon sort of a feedback loop using different genes and different proteins.

So it seems to be something that's absolutely fundamental and one of the very earliest sort of evolutionary features of life on Earth. And indeed when they were looking, [00:15:00] when they are looking for, for life on Mars, they're looking for the rhythmic production of organic molecules in, in, in, in the soil of Mars to see if there's gonna be a clock.

Because Cox are regarded as sort of a ubiquitous feature of life in general.

Anya: Gosh, so 

Russell: Sorry that was a a stream of consciousness.

Anya: no, it's, I, but yeah, I think it, I think the, the kind of, the importance of it, like you say, that this is something that's so conserved across. Really everything that's on this planet speaks to how, how specific and personal it is to the way that our planet moves around the sun.

Rosy: Is there a part in the book that you talk about? Um, the gut microbiome and the 

fact 

Russell: Oh, yes. 

Rosy: that, 

our gut clock can, can interact with bacterial clocks and vice versa.

Russell: since, since Lifetime was written, you know, that science in the past two or [00:16:00] three years has really rocketed forward, and it does seem that the clocks of bacteria in the gut communicate with the clocks in the gut lining, and that changes their biology and the absorption of certain substances from, from, from the digestive system.

There's now even evidence that the microbiome can influence brain activity. Now, I think it's still early days and what the pathways are, it remains sort of somewhat unclear, but yeah, I mean the, the, the, the gut, the, the bacteria that, uh, we carry around in our, our guts, they have clocks and they're talking to our clocks and the good bacteria are making us healthy and the bad bacteria don't help us much. So it's good to get that, that, that microbiome, right? And as, as I say, it's an incredibly interesting area and there's lots of experiments we've got to do. I mean, I'm really fascinated about looking at the, the gut biome of night shift workers, for example. You know, is it disrupted? Like, like their, [00:17:00] um, body cocks are, what about airline pilots?

What about, you know, aircrew and all, and all it's gonna be. So it's a such a brilliant area. It's one of those, again, I think we've been so fortunate in, in our field. 'cause there's all these, you know, little explosions of new knowledge, which then lead you down completely different avenues, which you hadn't really thought about before.

Yeah. New photoreceptors, subcellular, molecular clocks signaling to the rest of the body coordinating things. And now we've got bacteria, uh, contributing this whole network of biological rhythmicity.

Anya: And I mean the, the relevance of that rhythmicity, I mean, you're sort of talking about every cell in the body working to a rhythm that is directed by the. By the SCN overall clock, I mean, what, what level of operation are we talking? Sort of what are the things in our body that show a 

rhythmic 

activity? 

Russell: It's about, it's most things. I mean, essentially what you have to do is compartmentalize particular [00:18:00] biological process processes to a particular time. What you don't want to do is keep on oscillating between different, different sorts of things you say, right? So I'm active during the day. I'll have degraded certain metabolic pathways.

I'll have produced toxins. What I'm gonna do during the inactive phase sleep, and we can talk about sleep in more detail in a second, is then rebuild those metabolic pathways and repair those, those pathways and get rid of the toxins. So it makes it efficient. You compartmentalize biology at a specific time of day.

As I say, I, if you're, if you're constantly oscillating between different states, it becomes deeply inefficient. So, yeah. Um, so it's just about everything. I mean, I, I, I, I can't think of a process that isn't regulated it, that doesn't have a, an influence of internal time. It's utterly pervasive.

Anya: And coming back to the photoreceptors and light. I mean, I think, again, just [00:19:00] to underline for anyone who maybe tuned off and started to make that cup of coffee, 

like the,

the, 

Russell: Sorry. Was it bad? 

Anya: no, no, no. Whilst I've been talking whilst the, the, um, the kind of, the significance of this really can't be understated, as in when I sort of, you know, was reading your work and I was just like, there's a third receptor in the eye.

I mean, anyone who's done, you know, a level biology will have learned about rods and cones, and I think we'll be astounded again. You know, if they didn't know, they'll be like, oh my gosh, there's this third thing that wasn't mentioned. But that is so, so crucial and it's, it's such a huge, you know, monumental finding, um, and like sort of monumental change to, to science.

And I guess what, so we, we've talked about the rhythm that is just occurring in our body, but can you talk about the. The light and how it affects it, sort of what the entrainment is about.

Russell: So the. The [00:20:00] clock responds to light in a different way, at different times. So dusk, light delays the clock. We get up later, we go to bed later, morning, light advances the clock. We go to bed earlier and, and, and, and, and we get up earlier. So, so when we're all, you know, agricultural workers, sort of 200 years or so ago, we were experiencing a symmetrical, uh, a dawn dusk exposure.

So advancing and delaying. So, so the clock was basically kept on time. What's happened, of course, uh, and, and I read some statistics fairly recently suggesting that only 2% of the British population are in agriculture and fisheries. So these are the people that would spend, so the rest of us. 95, 90 8% are inside.

And so we are not getting that natural light dark cycle. And so we are not getting the appropriate cues that lock the internal day onto the external world. And so that's really important. We did a, a [00:21:00] wonderful experiment, um, which was, um, you've heard of chronotypes morning people and evening people, and we looked at university students in Perth, in, in Australia, in, uh, in the east, uh, i, I I in, in Melbourne, in Germany, in the uk, in the Netherlands.

And we looked at the amount of time spent outside and when, and whether there they're a morning type. Or an evening type. And what became very clear is that the evening types were missing morning light, which would make them get up earlier and go to bed earlier. So they were sleeping through morning or you know, the early part of morning, and then they were out late in the afternoon.

In the evening they were getting evening light, which was delaying the clock. So part of our, our morning ness, eveningness is influenced very much by when we see light. So that's, that I think is, is really fascinating. But, um, one of the things that's been come [00:22:00] clear is that, okay, dawn and dusk is when you shift the clock, but how much light do you see during the middle of the day can sensitize the clock to light.

So some experiments, uh, by several researchers around the world have shown that if you're under dim light during the day, your clock is more sensitive to light in the evening. And therefore more likely to be disrupted by sort of room lights and stuff like that.

But if you're getting moderate levels of light during the day, the, I mean, 500, 600 lux, and on a outside, even on a cloudy day, you're going to be getting 10 to 20,000 lux.

So it's not that bright, but, but that will. That that five 600 lux during the day will desensitize the clock to light in the evening. And that's been part of the confusion about, you know, about looking at a Kindle, for example. Um, you know, you you read the press reports and say, if you look at a Kindle, you're going to disrupt your circadian rhythms.

Well, it was an artifact of the way the [00:23:00] experiments were done. People kept under dim light during the day, and then they were looking at a Kindle for four hours in the evening before they went to bed. And it had some effect. But when the experiments were repeated by another group and they gave them, uh, these individuals sort of f as I say, five, 600 lux during the day, all the effects were completely abolished.

So this is, this, this is a, a, a bit of a problem because, you know, there are recommendations out there saying, well, you shouldn't see, you know, I think it was 30 luxe, two hours before you go to bed. Now that's, that's based upon the lab experiments, not the field experiments. And I think that's. Tantamount to perhaps even slightly irresponsible because if you are elderly, um, and you're wandering around and you know, your eyesight's not so good, perhaps 30 luxe is really quite dim light, and the chances of tripping and falling or having accidents would be increased by that sort of dim light.

So. Humans are immensely variable in terms of their circadian [00:24:00] architecture, their sleep architecture, their light sensitivity. There's a 50 fold difference of people of the same age in their sensitivity of, of, of the effects of light on the clock. So it's not straightforward. And, and by, and I think one of the frustrations I find at the moment is that people take a huge group of, group of individuals, then they, they say, ah, this is, this is the, this is the, the average.

And then they try and apply that average to the population. And of course, it's a bit like trying to make everybody wear the same shoe size. It's nonsense. Um, and I think we've gotta be much more sensible about how we, how we think about those big data sets. Yes, it's an average, but it doesn't necessarily mean that that's what everybody should be doing.

It's huge individual variation. And we've gotta, we've gotta start taking that, that variation seriously.

Anya: So coming back to the, the sort of 530, you know, these different guidelines about what you should do in the morning, what you should do in the evening. Based on [00:25:00] your work, what, what is a sensible approach to, to light across the day in terms of a 

sensible 

cycle? 

Russell: I think it's important to get morning light. Morning light in particular, because remember that's the light that makes you get up a a bit earlier. 

Um, now the humor body clock for 90% of us is slightly longer than 24 hours. So under complete con darkness, we be getting up a little bit later and later and later.

So we need a daily advance. We need that morning light to sort of push that slightly long clock to make it make it exactly 24 hours. So if you can get out, go outside. I mean, what I think a lot of people do, including myself, is not, you know, go straight to work and then go straight into a building, is I will, I will, will park the car or get off the tube or the bus and, and have that 30 minute walk outside before going, you know, getting into, into work.

So try and get morning light exposure. It's interesting that, um. [00:26:00] And I dunno how good the data are, but, but it's often talked about that, um, people who own dogs have better sleep wake cycles, better timing. And I don't think it's because they're just acting as a companion animal and making you feel, you know, more relaxed.

I think it's 'cause you have to get up, get out first thing in the morning and empty the things out. And so you're getting your, so you're getting your photon shower, um, as a result of walking your work, walking your dog. But yeah, but seriously, getting out, getting there. Also, as we, as we touched on getting light during the day is important.

I mean, most of us could, could in theory, go to work in the dark or at least on the tube, very short walk. And then you're in a house, a a house or, or a building all day. And so it's really important to also to see some light outside during the day. So go outside for lunch if you can. I'm, I'm talking to some architects at the moment and, and, and, and they're read.

Doing their buildings. And I'm sort of saying, look, what you've gotta do is, obviously you've gotta [00:27:00] think about dawn and dusk, but that's probably more in the home

environment, you know, and how you get to work. But during work, there should be spaces where people can either go outside or there's an atrium or where they have their lunch, that that should be flooded ideally with as much natural light as possible.

And, and so I think pe, you know, architects are beginning to take this sort of thing really seriously. I mean, in the past, you know, light was considered a, a, a, an irritant, you know, oh, well we just built the space and fill it, fill it with our, with our uda with them. Artificial light and, and natural light wasn't really a thought of as a feature, but it is increasingly being recognized as an important feature of modern buildings, which is great.

Anya: I mean, what's the, and you, you're talking a lot about getting outside. What's the deal with windows and sort of, you know, having,

Russell: Yeah. 

Anya: having good windows in the morning, but is it.

Russell: It's, it's really, it's a really important issue. And in fact, there are some proposals for energy conservation for [00:28:00] all new builds in London, to have much smaller windows. And I, I just wonder about the, just the sense of this, I mean, yeah, if you think about the windows in a Mediterranean country, they're huge.

They're beautiful, they're big, and they have shutters. So it's not surely beyond the, the wit of individuals to, to develop something rather than the, the knee jerk reaction, which is I think, slightly irresponsible of having tiny windows. You, you do need, um, to get that. Uh, and so in the morning, if you can't get outside, sit next to a window.

The other thing that people can do is they can. Uh, uh, uh, get a luxe meter downloaded onto their smartphone to make sure that they're getting, you know, the, so in the morning, for example, around 10,000 luxe for 30 minutes is really fantastic. So sit my by a window, you'll probably get something like 3000 luxe or go outside.

So, so these are, these are key things that we all really need to do. The nursing home I think is a [00:29:00] particularly interesting one, and colleagues in the Netherlands have increased the amount of light in the day areas and. Try to impose darkness in the bedrooms at night and have stabilized sleep wake rhythms rather beautifully and critically in those individuals showing mild dementia cognition improved by nearly 10%.

So not only did they improve sleep by simply giving brighter light during the day, darkness at night, uh, you know, a good signal to the clock, but it actually impacted upon cognition. So I, I think, I think we should be taking it seriously at every level classrooms, you know. Um, and, and another area you were talking about windows.

Well, there's this meeting I was at recently. There's some really lovely data about. The, the biological advantage of a view, so it's not interacting with the circadian system, but it is having an important effect upon a one's cognition and one's level of anxiety. I mean, a view is [00:30:00] considered to be very positive, interestingly. In the, and, and this, this came outta this meeting in the US in the 19, late fifties and sixties. Classrooms were being built without windows at all. And the, the, the logic was, oh, it'll, it'll distract the pupils and the, you know, they'll just gaze outside. Actually windows improve educational performance.

But the secret agenda was they were gonna use classrooms as nuclear shelters, and you don't want windows in nuclear shelters. So, so this sort of trend of excluding light from classrooms in particular sort of started in the fifties and sixties and, and the, and I said the subtext was as a, to, to develop nuclear shelters, which is kind of interesting.

Uh, the one thing about windows though, that we don't talk about, and that's the, the, the fact that all domestic glass locks UVB light. And UVB light is what the [00:31:00] skin needs to get to kick off vitamin D synthesis. And so even by sitting at a window, you might get enough light to regulate the clock, but you will not be getting the UVB to make vitamin D.

And this is one of the things that turned up with COVID. People were spending all their time inside, and if they weren't taking vitamin D supplements, then uh, they, they were getting vitamin D deprived. So yeah, again, getting outside, getting relatively short exposure to natural light will give you the vitamin B, uh, that, that you like during most of the year.

But in winter it's a bit more tricky. And, and certainly for, for women who are pregnant, the advice is. Take supplementary vitamin D three 'cause you're not gonna get it if you're, you know, um, uh, because it's being filtered out by glass. Interestingly, and this is a little aside, there's a rather famous, um, aquarium in the United States, and they built a great glass dome to have a tropical house by the side of this aquarium.

And [00:32:00] at one point, all the, the, the lizards, the reptiles, these lovely iguanas were dying and falling off their pers and, uh, they thought, oh, they've got a virus. And then somebody realized that of course the glass they'd used wouldn't transmit UVB and the reptiles needed vitamin D and they weren't getting it and they died.

Um, now that's an extreme example, but it's, it's, it's just illustrates the fact that we overlook Yeah. The, we, we've retreated inside. We've essentially. Gone back to being caved dwellers. And we've, we've just because we can see the light, we think that's enough and we're getting all the, all the elements of light.

And we're not, I mean, if you look at the, again, get your luxe meter on your smartphone, it's so fascinating. Go to the window and you'll get about 3000 luxe. The time you're in the middle of the room, it's dropped to a hundred to 200 luxe. So although the visual system is fine, the clock needs relatively bright light for a long time to set the clock.

So that's why we need to get [00:33:00] decent exposure to light.

Anya: And then take us through Dusk and Knight. What, what is the sort of reality away from newspaper headlines?

Russell: Yeah. So one of the interesting things is that as the sun sets, the light has to travel through more of the atmosphere. 

So when you look at the horizon, of course it's red, but because short wavelength, light is scattered more. Blue light, the dome of the sky becomes enriched with blue light. So we, we'd think of sunset as being, you know, orangey red, but actually just look up a few degrees.

And of course it's blue. And interestingly, those new photoreceptors we discovered are maximally sensitive at 480 nanometers, which is the blue of a, of a beautiful blue sky. And, and so, so I mean, it's, it's, it's hand waving. If you were [00:34:00] going to design a system that was gonna be maximally sensitive to dawn and dusk, that's where you'd put its sensitivity.

So, yeah. And some interesting studies have shown that in lamps that rather than just sort of bedside lamps that, that, that, that wake you up, these sort of sad lamps and things like that, if you actually ramp them up slowly, over 30 minutes, it's much more effective at setting the clock than simply sh just turning it on.

So yeah, the dynamics of the light changes at dawn and dusk are, are important. We've, we've got some idea, but not a complete understanding of what, what, what's going on there.

Anya: And Kindles at night, laptops at night, phones at night. I mean, you, you, you sort of, you talk about the alerting effect just of, of them, but in terms, is there something that they can do to the clock 

and the blue light keeps us awake and it's terrible and

Russell: And there's, yeah, there's so much about this blue light and [00:35:00] largely nonsense. So smartphones, computers, kindles, they can have an alerting effect upon the brain. If the light is bright enough, it can increase alertness and delay sleep. But it's largely the social media impact. It's the sort of anxiety inducing, it's that sort of alerting effect light itself.

There's very little evidence that in the real world that a light from a Kindle or a screen is gonna have a big effect upon the clock. And particularly if you're gonna see natural light the next day, any subtle effects of delaying the clock in the evening will be hit, uh, because of the advancing effects of light first thing in the morning.

So again, that's a good reason to get outside, but, but. I, I mean, I mean, I got quite irritated with, with sort of that aspect of, uh, these devices because, because it's out there. People say, I can't look at a Kindle. I mean, I, I gave this talk on, on Saturday and so many people said, I can now tell my wife it's [00:36:00] okay to look at a Kindle to relax and go to sleep.

And broadly speaking, yes it is. I mean, the Kindle data, as I say, I mean, I probably should unpack that experiment in more detail. And so what happened is in the first experiment, people were asked to look at a Kindle on its brightest setting for four hours immediately before bedtime on five consecutive nights.

So that's quite a hit after five nights. And, and during the day, those individuals were kept under 90 lux. So dim light, the Kindle was producing about 30 lux at the end of five. Nights of reading a Kindle sleep onset was delayed just statistically significantly by nine minutes, and as one of my colleagues at the time said, well, that may be statistically significant, but that's biologically meaningless now. There was an effect upon the hormone melatonin. It was suppressed, and it was shifted, but it illustrates the point that, of course, melatonin is not a sleep hormone because it didn't correlate with [00:37:00] a sleep weight timing. It's a modulator of sleep. And then there was this really important experiment by a Scandinavian group.

Who gave people not 90 lux during the day, but six hours of five to 600 lux and all the effects on both melatonin and even the tiny effects on, on, on, on delaying sleep onset were completely abolished. So, so. You know, we've gotta be very careful about the recommendations we build upon just lab-based experiments.

I mean, what was also interesting at this meeting in, in Copenhagen, uh, uh, a few days ago, was some new technology whereby you can, you can clip a little light meter on somebody's sort of shoulder, which will measure the spectrum, the intensity, and actually some physiological parameters. So if we want to do the field experiments of light exposure, when we get it, what time and its impact upon our biology and our reaction times, for example, and our cognition, all the technologies there, we can [00:38:00] do the field studies on humans to develop evidence-based, um, guidelines.

And, and so I think again, when at another exciting time, we another step forward in the whole field of making this, this biology relevant to, uh, the built environment.

Anya: And we've started to bring in sleep as we talk about these rhythms. And, you know, sort of the, one of the big things about circadian rhythms, aside from everything else that it's doing in the body, is its impact on our ability to sleep. People will know that this, this episode will be part of a series. So we sort of have some, some more specific episodes just about insomnia and sort of just about sleep disorders.

But I guess if we talk about this interaction between circadian rhythms and sleep, and, you know, Rosie and I were just talking, Rosie's just come off night shifts and sort of the, the ways of which we can make things go wrong for ourselves. And what kind of living life, not in line with our, uh, planetary circadian rhythms.

What, what can that do?[00:39:00] 

Russell: Well, so if we kick, if we kick off with an understanding of the biology of sleep. So what we've got is, is almost a flip flop between the conscious wake state, where, where the brain is being bathed in a whole bunch of excitatory neurotransmitters regulated by key structures within the brain. And that will then flip to the, uh, sleep state where another bunch of, uh, pathways will reduce largely that neurotransmitter release to the, to the cortex, to the cognitive areas of the brain, and also sort of interact with the midbrain.

So you get these two states of sleep, which is non rapid eye movement, sleep and rapid eye movement sleep. And associated with rem you've got that paralysis from from the neck down, which it probably stopped us acting out our, our dreams 'cause we have our most vivid and complex dreams during REM sleep.

And there's a condition called, as I'm sure you're aware, called Run behavioral disorder. Which [00:40:00] is where that paralysis doesn't occur, and people can act out their dreams. And there's a famous case fairly relatively recently where, uh, a uh, an individual in Wales murdered his wife. Uh, he was having an episode of REM behavior disorder.

He thought that his wife was, uh, uh, an intruder breaking in. And so he, he sort of stopped them and, um, uh, he killed her crown prosecution said. Not in control of his ties, so would not be prosecuted. And the only thing he remembers is this vivid dream of an intruder, uh, co coming in, in, into, into the room.

It's, it's really distressing. You also have, interestingly, this lack of atonia, this muscular paralysis in certain neurodegenerative diseases. So Parkinson's, Alzheimer's, Alzheimer's, dementia in particular, uh, some re behavioral disorder ha has been noted. Okay, so you've got these two different states, uh, of sleep, broadly speaking and what's controlling it.

And there are two processes. [00:41:00] One is the circadian system and one is the intuitive part of, of sleep perhaps, which is the longer you've been awake, the buildup of sleep pressure, the more you need to sleep. So what happens during the day? The sleep pressure, pressure as as we are awake, builds and builds and builds and builds.

Then when we're asleep, that pressure dissipates. One of the agents of sleep pressure is a substance called adenosine, which builds up, and of course, coffee works because it's an adenosine antagonist. It, it antagonizes the receptors that detect the sleepiness within the brain. So that's why a cup of coffee makes you feel more alert.

But, but, so, but that's not the whole story. You've got that buildup of, of sleepiness during the day, and by mid-afternoon it can be incredibly high. So why don't we fall asleep? And that's because the clock is producing a wakefulness drive, which ideally keeps up and exceeds that pressure [00:42:00] for sleep. So you've, you've got almost an antagonistic system, sleepiness, sleep pressure, substances like adenosine, and then the clock saying, Nope, this is the time you need to be awake.

This is not a good time to be asleep. And so, so counteracts that sleep pressure Now as we approach sleep. Sleep pressure's really high. We're still not going to sleep because the wakefulness drive is really high. So ironically, the wakefulness drive from the clock is at its highest. Just before we go to sleep, fall asleep, the clock says, okay, brain, body.

Now it's time for sleep. The wake wakefulness drive from the clock drops, the sleep pressure kicks in, and then we can have that sustained period of sleep. Where the wakefulness drive is low, the sleep pressure declines. But as we approach morning, the wakefulness drive then begins to kick in. The sleep pressure is very low, and that's why we wake up.

So you've got these two sorts of drivers. Now for, for night shift workers, the [00:43:00] assumption was always that the body will adapt to the demands of working at night. And it doesn't, broadly speaking, and it doesn't because of light exposure. So the clock is still locked onto the light dark cycle. So you're going to, to work, uh, probably during the light or driving home from work during the light.

Um, so that's setting the clock and you're under dim light in the workplace. And some studies from Harvard did a lovely experiment showing that if you take night shift workers. You increase the light in the workplace to a couple of thousand lux, then hide them from natural light during the day, then you, they will shift in the same way you get over jet lag.

But of course, for all practical purposes, you, you can't do that. So what the night shift worker is facing is their circadian drive for sleep is high at night when they're being forced to work. And then of course, the sleep pressure builds and builds and builds. So the sleep pressure's really [00:44:00] high. And so they get home and they, they, they, they ideally, and Rosie you might be able to comment on this, you can fall asleep fairly quickly once you get home.

But because the clock is saying no, it's daytime. You should wake up the duration of that sleep. Even though the sleep pressure is high, it can't be effective because the clock is saying it's daytime. You should be awake. So many people on the night shift trying to sleep during the day get perhaps four or five hours.

So they're not getting very much sleep during that. So, so one of the rules of thumb is that after the night shift, get home as soon as you can and get your sleep in there, because that's when, you know, the circadian drive for wakefulness is, is, is before it properly kicks in. Now, of course, for practical purposes, that often doesn't work.

Many people who do night shift work do it because they want to combine a career with a family. So they get the kids off to bed, um, go on the night shift, then they get back home, they get the kids off to school, [00:45:00] and then they can think about having some sleep. And of course that's not ideal. So the, the, the demands of work night shift work and family are often.

Really in opposition and because essentially what you're doing during the night shift is forcing your body to be awake. When it actually, the biologist saying you should be asleep can be very distorting and potentially quite damaging. So if we look at the impact of sleep loss and um, circadian rhythm disruption, it's a, a term we've, we've called scarred sleep and circadian rhythm disruption.

We, we got that acronym because we were writing a grant and there was a word limit and sleep and circadian rhythm disruption is full of, scarred is one. So, you know, but, but it's interesting 'cause everybody now uses as a shorthand 'cause it's very difficult to disentangle. The, the disruption associated with la lack of sleep and the disruption, um, as a result of that misal [00:46:00] misaligned, um, biological clock.

And if we think about some of the consequences of, of scarred, then we can think about emotional, cognitive, and long-term physi, physiological, uh, responses. So if we think about our emotional responses, fluctuations in mood, irritability, anxiety, loss of empathy, really very interesting one, you fail to pick up the social signals from your, your, your partner, your, your, your family, friends, colleagues.

In fact, interestingly enough, the divorce rate is significantly higher for night shift workers. Compared to the same job on the day shift. In fact, some studies from other states have shown that the divorce rate in some sectors can be six times higher for night shift work compared to day shift work.

Because of this complete distortion of one's emotional responses, I was talking about the sort of stuff, uh, to a group of minors and their partners in Northwest Australia, the Pilbara area. And I was saying, you know, [00:47:00] all about these emotional changes and this, this, this lady in the audience started sobbing, crying, and saying, oh my God, I've been so mean to my partner because I had no idea that, you know, his irritability, his, his, his loss of empathy, you know, he, his negativity was actually a consequence of the night shift work, not him turning into a monster.

And, and there's a very important ed educational piece, which we should come onto. So there's those emotional responses. Negative salience is also. Really interesting, which is the tired brain remembers negative experiences, but not the positive ones. So one's whole worldview is biased, you know, the tired brain remembers negativity.

So that's some of the emotional stuff. The cognitive response is, is obviously overall cognitive performance. The ability to multitask is interesting. You know, what we're good at doing generally is identifying what's important that we need to resolve [00:48:00] and ignoring the other stuff. And of course that's multitasking, but we are very bad at that when the brain is tired.

And so we, it all becomes a bit, you know, you've become a bit gridlocked. I, I dunno what decision I need to make, type stuff. Concentration, communication, decision making, all of that, uh, creativity all go. And then if we think about longer term night shift work, uh, where the data are really quite clear, particularly on, on night shift nurses where there's been a great deal of study.

Obviously daytime sleepiness, microsleep. So, uh, over a hundred thousand crashes on the American motorway system are associated with falling asleep at the wheel because of microsleep, these uncontrollable, and I think. Sadly, we probably all experienced it at one time or another and it's a hell of a shock 'cause you are uncontrollably.

And of course that becomes, these, these sorts of crashes are very bad because you've fallen asleep and you are asleep when you crash, so you're not able to put the brake on or anything [00:49:00] else. So they're, they're really debilitating crashes. So one of the things about short-term sleep loss. Kind of okay. A bit other than the emotional and cognitive responses.

But, but to stay awake day after day, uh, year after year, you are turning on the stress axis. Now, stress is useful, of course, short term. And, and, and the analogy is a bit like an engine. You know, you put it into first gear and you've got that acceleration. Get away, leave the engine in first gear, and it falls apart.

And that's the problem with stress. Keeping it on and on and on means you're throwing glucose into the circulation. Cardiac output is, is higher. And of course, high levels of cortisol lower the immune system, higher levels of infection, and indeed high rates of cancer. I think it's really very interesting that some studies on, again, night shift nurses have shown high rates of bre, breast cancer, colorectal cancer, uh, in, in [00:50:00] nurses in night shift, long-term, night shift nurses compared to day shift.

And it's probably because the cortisol is suppressing the immune. Mean system, metabolic and AB abnormalities, obesity type two diabetes. You're throwing all this glucose, you're becoming glucose intolerant. And then of course, depression and psychosis, which we, I know we're gonna come onto. And if you are vulnerable to those conditions, depression and psychosis, then sleep disruption can nudge you into a more severe state.

And then of course, dementia. So. What's turned out to be really interesting is there have been these sort of correlations between really poor sleep during the middle years to increased risk of dementia in the later years. And, and, and it hasn't kind of made too much sense. And now we know about this new sort of toxin clearance system called the Glymphatic system, which I'm, you've probably come across, which is a way of getting rid of a whole bunch of toxins, not least those misfolded.

[00:51:00] Proteins that are associated with dementia and Alzheimer's. And if, uh, you don't sleep, then those start to build up within the brain. And this has been shown from both animal models and indeed human studies by, by actually sleep depriving individuals and me measuring the level of these misfolded proteins in the cerebral spinal fluid.

And they are higher, noticeably higher even after just one day. So perhaps the higher rates of dementia in those that slept very badly during the middle years is associated with, um, a, a failure to allow the glymphatic system to work. Now, I wouldn't say that poor sleep scarred is gonna cause dementia, but if you are on that vulnerability spectrum, then it, it may well be a contributing factor.

So that looks like a whole sort of stream of gloom and doom. And to a large degree it is, but it would be. I think irresponsible and naive to say, well, we shouldn't do night shift [00:52:00] work. We're always gonna need, you know, frontline staff, whether it's nurses, doctors, you know, police, fire, and all the rest of it.

But the missing part of the puzzle is that we can mitigate some of the effects of night shift work. So, loss of vigilance. You know, on the drive home there's a study showing that 57% of junior doctors, and these are anes anesthetists, um, on the, on the drive home, had either had a crash or a near miss that's 57%.

So why aren't we saying you've got to use an app on your phone that can measure lateral movement of the car or head nod that can then stop those micro sleeps and, and actually wake you up. And that's just. Common sense you could loss of vigilance in the workspace, high levels of accidents, you could actually increase the light to increase levels of alertness.

That's something that could be done. We've talked about the poor physical and mental health that you get with night shift work, [00:53:00] so why aren't there higher frequency health checks to check if you are on that, you know, developing type two, you're showing signs of depression so you can hit these conditions before they become, before they become chronic.

One, I think very easy area is in the area of obesity. Type two diabetes, metabolic abnormalities. So what food is available to night shift workers? Well, it's vending machines full of chocolate bars, and it's fast food. It's high fat, it's high sugar. And some very nice studies have looked at the chance, the risk of developing type two diabetes over, I think it was five, 10, and 15 years.

And those individuals who ate well, low fat, low sugar, and also exercised, had a hugely reduced risk. So we've gotta get the right food into the workplace. And actually, one of the great things that we, we we're, we're good at in the UK is, is food. So I've, I've always wondered why somebody like Mar [00:54:00] Spencer or S haven't developed a line of food lowfat, low sugar, easy to digest, nutritious that night shift workers can snack on.

Or, or, or eat. And I do feel that employers should. Maybe have free gym membership to encourage their workforce to, you know, go and, and, and, and, and, and keep that exercise, uh, going. The failure to appreciate the consequences of night shift. Many, many employers don't discuss that with their workforce at all.

Um, they need to know the vulnerabilities and the implications, but not just those individuals, but as we touched on the people they spend their lives with, you know, their partners need to know, this person hasn't turned into a monster, but if you do this to your biology, this is what happens. And th they need, you've gotta cut some slack.

And it's really difficult getting those demands of, of, you know, economics to keep a family unit going. And the [00:55:00] stresses and strains that night shift work puts on that family unit. But it should be openly discussed and, and encouraged by the, by the employer. And it isn't at the moment. There's a lot of anxiety and misinformation as we've touched on over apps, you know, so for example, sleeping apps and, and, and, and trackers and things.

Broadly speaking, at the moment, they're absolute nonsense, you know, a bit of fun, but don't take them seriously. Um, and, and they've been developed largely, uh, on a small number of California undergraduates with one night in a sleep room. And, and you know, the algorithm is kind of fixed. And, and, and with a increasing ai, there will be feedback, they will get better, and they do have a role because in the same way that if you want to lose weight, you change your eating, eating habits, you weigh yourself in the morning and you see, oh yes, I've lost a bit of weight.

That reinforces, you know, your, your, your changed eating habits and if you want to have longer sleep or different [00:56:00] timing of sleep, an app could be very useful in that sense. But when they start saying, oh, you had a really bad night and, uh, you know, you this and that, uh, I think it can be again, harmful and and misleading.

We've sort of touched on morning types and evening types, and I think, you know, there's this, maybe some in intelligence thrown into this equation, which is if you are a late type, you get up late and you, you like to work late, you should be kind of on the morning, on the evening shift. You certainly shouldn't be on the morning shift and vice versa.

So, so as I sort of put in the back of, of lifetime, you know, you can chronotype yourself and I think employers should be more flexible about who they put on the night shift versus the day shift. And a final point is that the, the sort of the, the physic, the type two, the, the obesity, the depression, and can build up over time.

So should we limit night shift work to 2, 3, 4 years, then you cycle out of it for [00:57:00] three, four years and then you cycle back into it. So you give the the body time to, to, to, to sort of wind back. Now we don't have evidence that that works. And to my knowledge, nobody's doing those studies, but I, I think on the basis of the biology, we understand that would be a sensible strategy.

The problem, of course, is how do you, how do you compensate people? You know, financially people don't really want to work on the night shifts. Most people don't, but they get paid better. So if you then flip to the day shift, then you're gonna lose income. So that financial equation is really tricky and it needs careful consideration and debate.

But if you are an employer who wants to look after a workforce and optimize productivity, these are the sorts of things. It's in your interest to do, let alone the interests of the of, of, of, of the employee. [00:58:00] Uh, I, I think we need a much more intelligent look at this whole space. And at the moment we are really not, we are not really doing it.

And I think that's a great. Got another stream of consciousness. Sorry, I've, I've, I've bamboozled you.

Anya: No, no, please never. The streams of consciousness is what this podcast is about. Um, I, I'm, I'm wondering if Rosie has this, you know, again, having, if, if there's any thoughts that you want to follow up, um, on the back of that.

Rosy: Well, gosh, so many. And I, I have to say, I was thinking the whole way through my night shift about all the changes that I could feel happening. Um, and I certainly can completely, it being so close to that time, exactly the same of just feeling so desperate to get to sleep in the morning. Um, and then so frustrated through the afternoon that I couldn't sustain that sleep knowing I needed more.

Um, and I also have a young child at home, and so having to balance that it all, it, yeah, that all hits [00:59:00] home. And I think that one of the other things that comes up. That is something that is probably more specific to those of us who work in, um, you know, uh, sort of, um, clinical roles or public facing roles is, you talk about this in the book as well, but people tend to get more sick at night too.

So you have a sort of an unhappy union of very tired and cognitively potentially cognitively impaired 

clinicians or, or workers faced with, um, people becoming much more unwell through the night. And that is also linked with our circadian rhythms, from what I

Russell: yes, absolutely. And, and while we're on that topic, if we think about intensive care, it's about the worst possible environment for sleep and circadian rhythms you could think of. There's no so robust light, dark cycle. Um, and it's been shown that in, in, uh, in, in, um, premature babies in their intensive care, if you impose a like dark cycle, the duration of stay is shorter.

And I don't [01:00:00] think people have looked at. Death. Um, but certainly duration of stay and, and again, intensive care in, uh, in adults, uh, uh, you know, there's no, there's a failure to have a robust light, dark cycle. And, and of course, by essentially putting the clock into free fall, you know, and biology then becomes, rather than a sort of, as we were saying, doing the right stuff at the right time, it becomes a smear.

So we're actually harming the capacity of the individual's, uh, biology to, to help them. And, and, and there is increasing interest in, in how we can improve the sleep, like dark environment in intensive care where it's really bad, both, of course, for the patient and, and the clinicians

Anya: Mm.

Rosy: Likewise in mental health hospitals, something that comes up a lot is the fact that we routinely wake our patients up at night to check

on them. So in combination with, uh, them possibly already having a disrupted sleep wake cycle, we also interfere with that ourselves too.

Russell: Well, I think, [01:01:00] I think that's incredibly important. And, and of course in psychiatric prisons, I know that that is an issue where, where people are woken up every hour or so, and in another context that could be deemed as torture. But I mean, what we got in terms of the biology, uh, and the relationship between scarred and mental health, mental illness is really fascinating.

I got into this 'cause I was with a psychiatrist, um, in a lift. And, and I, the person in the place will remain, uh, undisclosed. And this person, sort of who, who I'd met sort of in staff meetings said to me, oh yeah, you work on sleep, don't you? And I said, well, yeah, no, yes. Um, and he said, well, well, my patients with schizophrenia don't have a job, so they go to bed late, get up late, miss my clinic and don't have friends.

And I was so incensed by that. I, and I'm, and I'm not a person that gets irritated very easily, but I was very irritated with that. It was such a dismissive, unreflective sort of thing to say. [01:02:00] So I then got together with Eileen Joyce, who's uh, in the Institute of Neurology, and she had cohort of patients with schizophrenia.

We looked at the rest activity cycles of these individuals in their normal home environment. We measured light exposure. We, you know, lots of parameters with age matched, employed individuals and unemployed individuals. So it was quite a big study, and it's one of those, again, pivot points in my career where I, I first got to see the rest activity cycles of those, those, those individuals with a diagnosis of schizophrenia.

And they weren't just bad, they were smashed. They, they were the worst sleep weight patterns I've ever seen, even in a mutant mouse, for example. I mean, this was terrible and it got me thinking that, well, maybe we've been thinking about this slightly incorrectly. And so we produced a very simple con conceptual model because of all those neurotransmitters we, we know about [01:03:00] regulating sleep, circadian rhythms.

And because they, they overlap with the neurotransmitters underpinning. Mental health, perhaps at the core of the system, a change in the neurotransmitter that predisposes you, let's say a change in dopamine or whatever to a mental health state has an impact or so on sleep wake. So at the core, your vulnerability is, is, is could well be because of gene polymorphisms.

Gene associations and whatever. Um, and we, we did quite a few studies on this, taking a gene that being linked to human schizophrenia, mutating it in a mouse, and then that mouse was showing a fragmented sleep weight pattern. I mean, it's really fascinating and, and vice versa. So at the core, there's that overlap between mechanisms, but of course it's, it's much more important than that because once you start the slide of sleep and circadian rhythm disruption, that feeds back via the emotional, cognitive and physiological disruption to exacerbate the mental health and the mental health [01:04:00] because of the psychosocial issues and perhaps even the medication will make the scarred worse.

So you can very rapidly go from that area of vulnerability to move into a much more pathological state because of that feedback loop. But it, it's a very simple model, but it had. But you, there was an explicit prediction. So if we take individuals who are showing scarred and, and the study was done with Dan Freeman, one of my colleagues in psychiatry in Oxford, and you even partially stabilize, scarred in those individuals, and you look at their levels of paranoia and hallucinatory experiences, what happened was in those individuals with partial stabilization of scarred, uh, and I won't bore you with the details, but they showed a drop in both paranoia and hallucinatory experiences.

So an explicit test of the prediction that if you can stabilize sleep, you could reduce the severity potentially in some [01:05:00] areas of, of mental health in the same way, um, light therapy in depression. Has shown to be extremely effective. There's one study which looked at 30 minutes of 10,000 lux in the morning and compared it with placebo, uh, Prozac and, and light therapy by eight weeks.

Prozac was statistically different from placebo by two weeks. VA light therapy was statistically significant from placebo and by eight weeks it was very different, much improved compared to Prozac. Fascinatingly. This research also compare compared light therapy and Prozac, and it looked like the two were additive.

So whether. Light therapy in this contact was acting as a, as a, a, a serotonin selective, you know, SSRI receptor inhibitor or whether there's another mechanism we don't know. But I think what it, it, it, um, [01:06:00] sort of demonstrated is that light therapy in of itself, probably by stabilizing the circadian system morning light, you know, 10,000 lux 30 minutes could actually, uh, improve mental health outcomes.

In this case, it was depression. So I think this is an area that has been. Kind of ignored until very recently. And one of the exciting things is that we've been able to drive this discussion and, and the realization, I mean, it's, it's absolutely fascinating. Ling you know, the father of psych, of psychiatry, you know, back in the 1880s was talking about poor sleep in conditions that we'd now call schizophrenia.

And then it, when the antipsychotics came in, in the sixties and seventies, the poor sleep was, oh, due to the antipsychotics. Even though, you know, a hundred years before, um, almost people were talking about sleep, weight disruption and, and. And if it's not the antipsychotics, uh, then it's the fact that there was no structure to these people's lives.

And I think now sleep is being taken seriously and I think very [01:07:00] excitingly as a new therapeutic target in psychiatry. And I, I think that's really exciting because this is stuff that doesn't require massive new drugs, billions of, of, of, of, of funding. But actually it's stuff that we can do now, um, in many cases, not all.

I appreciate that.

Anya: And I mean, I'll, I'll, I'll follow the, the crumbs you've dropped. I mean, what, what are the things that we could do now? You know, it sounds like just saying to our patients with schizophrenia, well, you need to sort out your routine and go and get a job. Or it actually misses the 

Russell: Yeah, I know. Yeah, absolutely. And, and so what that study that Dan Freeman led was using cognitive behavioral therapy for insomnia, but it was a, it was a digital version. So these are university students with scarred, you know, showing borderline paran. They were, they were showing levels of psychosis and, and, and that digital, a digital approach, even the [01:08:00] smartphone telling them, okay, what you need to do and what was that allowed the study to have thousands of participants.

Now, cognitive behavioral therapy for insomnia one-on-one is effective, but it's so impossible to deliver because of the, the, the time it takes. We've talked about light, um, as being an effective. Intervention. But the last gasp of my career, working with two amazing colleagues, um, Artie Ya Enough, and, and Shiva.

It's taking what we know about that light signaling pathway and going down to, we now understand how the molecular clock is being changed by light. So are there ways drugs which we could use to fool the clock that it seemed light? Now the reason we started on this is because we work on the profoundly blind individuals who have no eyes.

They spend all their life drifting through time. And it's really fascinating talking to these individuals. They say, I can kind of cope with not being able to [01:09:00] see my world. What I can't cope with is constantly being fooled by my body. It, it's as though it's, it's tricking me all the time. And that is immensely destabilizing.

And just a quick story, one chapter. he'd lost his eyes and he said I was not gonna have the messy front yard. So he'd worked out a way of getting the out of the shed and there were borders, so he knew when he'd reached the end of the grass, he could turn it around. So he couldn't see any of this, but he was gonna cut the grass on a regular basis.

And then he was doing this and his wife came down and tapped him on the shoulder and said, it's 3:00 AM you're waking up the neighbors and you know, where somebody's trying so hard to, to be independent and to do the right thing and their body is fooling them. So, so that was our initial motivation for developing.

And we got a drug which has actually got showing, really done all preclinical work. We know the drug is safe, and we're now trying to get the first clinical trials off, [01:10:00] off the ground so we can stabilize sleep, wake, take it at the right time of day. Every day you can, you can take a drifting clock and you can make it 24 hour.

And so, in a sense, give people. Make them, you know, to remove the time blindness from these, these, these, these individuals. Now, I think some of the other applications of the drug could be useful, so I, I, I wouldn't. Want necessarily to, to use it in long term in mental health because as if you, as you've sort of talked about, I mean, it, it is problematic, but what you could do is go in and stabilize for a month, let's say, using a drug, get everything aligned, and then then.

The appropriate light exposure, the going outside, the eating regular meals, all of those sorts of signals to stabilize the sleep wake circadian architecture. So I think short term use could be very powerful. And in the same way I, I think in some neurodevelopmental conditions, you see lots of discussion of [01:11:00] autism and other, and indeed in, in dementia as well.

Uh, terrible. I mean, the reason, you know, so many individuals are placed into a sort of a, a nursing home environment is because they're wandering around in the middle of the night, waking up the family. Um, and that's the problem. It's not that they've sort of become a different sort of person. It's because they, they just are disrupting the entire family unit.

But if you could stabilize the sleep wake in those individuals, you delay the time that they'd need to be taken into some sort of more intensive care. And, and, and I, ideally it would be less. Emotionally draining on, on, on the fam family unit and certainly financially draining, uh, as well. So I think it, it's really fascinating.

We, we started with, you know, my, my, my curiosity driven research as a zoologist interested in the mechanisms of how clocks tick and how they're regulated by light. And we've come 40 years later or so to the point where now we can use this curiosity driven [01:12:00] research to develop new therapeutic interventions which have, which could have a huge impact across broad areas of, of, of, of the health spectrum.

And in fact, that's the exciting next phase. So the Ask Gas for what I want to do is now with, with David Ray and other colleagues, we're developing a, a Center for Circadian Medicine in Oxford. So we can then. That embed all of this wonderful science within cardiovascular. So we've got some fantastically interesting studies showing that when you have a stroke, will de will determine the size of the penumbra, the size of the damage.

And if we can identify why there are those differences, we think it may be linked to antioxidants, you can then pop in the appropriate compounds that will limit the size of the stroke in metabolic conditions. You know, we've talked about those sorts of things. We've talked about mental health, we've talked about eyes and the impact of eye disease.

If we can embed clinician scientists and clinician and [01:13:00] nurses in those specialties that understand this stuff and we can get this information embedded within practice. So that's the, that's the last hurrah, uh, for me to, to really use the knowledge to improve, uh, health and wellbeing.

Anya: I mean, that sounds like probably the right point at which to draw to a close. Although, I mean, I, I wish we had hours more because, uh, this, this is, I mean, it's amazing and I think the implications for, for our health, I, like you touched on in your book, really are only just starting to be recognized, uh, or widely recognized.

Um, you know, people are starting to listen and, and I guess it sounds like we need to get 

politicians, employers, all those people to listen as well.

Russell: Well, the politicians are beginning to listen. So we've been doing some work with Law Watson, Tom Watson, and he's been very supportive on the work we're doing with night shift workers. So, um, the nightclub is a, an [01:14:00] organization which I advise the science on and, and active in other ways. But basically it's where you go into the workplace and during the breaks, talk to the night shift workers about, you know, some of the things that they could do to mitigate some of the effects.

So some of our politicians, penny Morant, was very supportive as well when she was in Parliament. So, so it's beginning, I think the difficulty, and you will appreciate this within medicine, is that, and half my family are medics. I mean, you know, three children, two are medics. Um, and you know, the problem is.

They're running as it's the red queen. They're running as fast as they possibly can to stay where they are. If you impose yet another dimension of time and time delivery of therapeutics, and we haven't talked about that, but we know when you get your anti-cancer treatments can, can change survival from 70% to 35% at a different time.

In, in, in, in breast cancer. Breast [01:15:00] cancer, uh, and colorectal cancer changes can go from 40% survival after, uh, uh, five years to 10%. Same drug, same concentration, different time. But trying to introduce that into mainstream medicine is really difficult because everybody is overstretched and to to, to breaking point.

And so I'm immensely sympathetic to, to my clinical colleagues. It, we are asking a lot, but I do think it's. Time we started to push a bit harder. It's, I think, very easy to say. It's just beyond what I can deal with at the moment, but I think we've gotta take it a bit more seriously and find ways in which we can support our clinical colleagues to introduce this into, into the clinical realm.

Um, and I, but as I say, I appreciate it's really difficult. Uh, but, but that's the joy of working together. I think this is a great example where scientists and clinicians and patients can all think about clever ways of resolving some of these issues.

Anya: I couldn't agree more. I think [01:16:00] the case you make in your book, and I think anyone who's had their interest peaked, especially clinicians, uh, around, you know, drug time delivery must go and read that chapter because it's so stark that I think actually, like you say, even though it will require some buy-in effort, the dividends are wild.

Russell: Yes. 

Anya: And so we've, we've gotta, we've gotta do it. We've, we've, we've got to put we, yeah.

Russell: The joy for me was that there are, I think it was about 920 references in Lifetime. Um, and I thought, penguin are never gonna get, let me get away with this. But actually they didn't kick back at all. And the feedback from readers has been brilliant because, you know, I, it was, there was one very memorable one where a wife was saying to her husband about when he should take his antihypertensive.

And he said, oh, for goodness sake, it doesn't matter. She said, well, here's the reference. Go and read the paper. And he'd read the paper and came back [01:17:00] and said, oh my God, yes, there is something in this. And I think, I think that's what's exciting for me as, as a scientist, but also deeply passionate about.

Conveying what we do. In fact, in, in some sense, you know, we are paid by the broader public, therefore we must convey this information to the, to the broader public, but, but empowering individuals with the science and that they can then go to the next stage and go to the original research and then, and then to, to, to a large degree, a, assess the quality of that research and whether it should influence their lives.

Anya: So the information's there, grab it. Um, professor Foster Russell, thank you so, so much for speaking to 

us 

today. 

Russell: It's been my pleasure. Thank you.

Anya: If, if people want to learn more, read more, I mean, your book, of course, your most recent book of course is one place to go, but anything else you'd 

point 

people to? 

Russell: Yeah, I mean there's, there's the, the website, the Sleep and Circadian in Neuroscience Institute. Um, and I mean, again, one of the [01:18:00] joys is that we've, we've built the critical mass of scientists. So we've got Simon Kyle on the human sleep side, Ladowski, working on the fundamentals of the, you know, the neuroscience of Sleep, Stewart Pearson on the mechanisms of light detection and ri zoan on the pharmacology and the, on the cellular molecular aspects of David Ray, you know, on the metabolic aspects.

So we've got this amazing team. Um, and, uh, you know, what gets me outta bed every morning is, is, um, after a reasonably good night's sleep is working with these brilliant individuals. I mean, it's such a joy.

Anya: Amazing. Thank you. And Rosie, is there any sort of final thoughts or points you have? 

Rosy: This has been a fascinating discussion and I'm really hopeful that more people now feel empowered to have a, think about their own lifestyle, their own sleep, and pick up, pick up your book and, and, and, and maybe change their life. At least change their sleep.

Russell: I mean, the part of the motivation for writing it was I was hotly sick of the, the sergeant majors of sleep screaming, [01:19:00] you must get eight hours. You can't do this. And it's, it's, as I said before, it's all about shoe size. You know, one size doesn't fit all. It's, we can, we can work out for ourselves, you know, what we need to do to get the sleep that we need.

And it's not, I think so many people for that sleep is what you get and it's a behavior that we don't have control over and we do to some degree. Um, and, and the fact that it will change as we age and under different sorts of circumstances and it's, and it's, it's time we started embracing sleep. I mean, I think so many people think of it as this rather naughty creature that needs to be subdued and bludgeoned into submission, whereas actually what it needs is just a cuddle.

Um, and, uh, I think that's the metaphor. Perhaps we should end on.

Anya: Amazing. Thank you so 

much. 

Thank you for

Russell: Great pleasure. Okay

thank [01:20:00] you.