Sleep Revolution: Studies and New Technologies - Emmanuel Mignot
Thank. You a Pyrrhic yes, I won't talk to to, you about dogs, but you, know. My. Dog is stayed at home sleeping. But. It's true that I worked a little bit in, dogs, with this strange, disorder, called narcolepsy but. Today I'm going to talk to you more about the future of sleep technology, because, I think from, what we already heard you, know it's very clear that there, is a. Lot. Of new information that's coming about the, biological mechanism. That. Are generating. Sleep in the brain and how important. Is sleep for general health for. The regulation of pretty much everybody. Function. You. Know just to give you an example we. Can actually measure the expression, of genes in the liver and we, know that the expression of genes is the liver depends. Of your, circadian timing, your circadian clock but also how much you slept so. The outer body is really regulated, by sleep and circadian rhythm. Ii, so. I believe, that what. Is interesting about sleep and that's really recapping, what we heard already is that first it's a really an opportunity for, major. Discovery. I mean I you. Know I'm trainers of psychiatrist, and I go to parties you know and like all of you and I go to a party when I'm psychiatrist these. Are people love me too much or they, are afraid but, when you talk about sleep immediately, everyone, is interested, everyone wants to talk about their sleep so, always I have a friend that snores, too much that doesn't sleep I mean you usually are pretty much the hero of the party very quickly and very often so, it's a really good job to be able to sleep doctor, and. At. The same time you, know what's amazing about sleep, is where as we really know and Russell. Didn't talk too much about that quite a bit about, the molecular mechanisms. That regulate circuit and clock he. Mentioned, the fact that there is a circadian. Nuclei. Just, located just close. To the eyes that receive. Light input, and regulate, also circadian timing of your entire body so suprachiasmatic, nucleus. And. We know that inside the suprachiasmatic nucleus. Is of protein and genes that. Have a very specific rhythms, at last 24, hours they. Repress themselves, they go outside of the nucleus of each cell and, that they go back and it takes 24 hours to do the wall rhythm and every. Cell of the body has a circadian, clock and then. This particular, nucleus, that's connected, to the ice so that light. Can reset your circadian. Clock when you travel you, know gets synchronized. All the little clocks of your body and we know really a lot about it but, curiously. What we don't know a lot, about is a second, part of the equation which, is really what he calls a sleep debt or asleep on your status we, really don't understand, why the more, you stay awake the, more tired you are we. Understand, why at some times a day you're awake and some times a day you are asleep. But, we don't really understand, why when you stay awake longer and longer you it's, actually a torture, you're not past a certain time you know everything, is dysfunctional and, in fact it animals you die and as you probably know, of course it's a form of torture, so.
Clearly Just, this simple, fact why do we need to to, just rest regularly, is not very clear, especially. At the molecular level so for, me is that's one of the main reason we want to study sleep is just a mystery of sleep is one of the I think last remaining, mystery, in biology today. The. Second reason is that was very well covered by Raphael is that you, know there is pretty much you know one quarters, of world population that, has a sleep problem we heard about sleep apnea which is very common and predisposed, to cardiovascular disease and, some. Yeah and and mental, disorder, I think Russell. Kind, of mentioned that even in the context of schizophrenia, they, might be even more complex so sleep disturbances. But it's very clear that, we know now that insomnia. Is a frequent, precursor, to depression, that, we know that it's not just that being. Depressed you don't sleep well in fact not sleeping well contributes. To creating depression. And new. Models now that really proves that of course ret pathways goes both ways so it's not just you. You don't go well in your mood, and then you don't sleep well it's, also that you don't sleep well and it starts to eat up your mood. This. Restless, leg syndrome and. Periodic, movements, we, have also heard that it's you know kicking during your sleep and that's, frequent, in a lot of people and in some people it's so severe, that in the evenings, they, feel that they have to move their legs and. So. They can't fall asleep and in. Some people it can be really excruciating then. Besides the people who don't sleep enough there are also the people's feels that they don't sleep well at night there are a lot of people also that feel very tired, during. The day and fall asleep I. Think, we hurt sleep apnea I can be a cause of it but also there are some people we don't know why is they're just tired and that's, one of my specialties, it's narcolepsy, is one of these disorder since. There is we shift. Workers, and people would just have, to work at wrong time of the day and night and that disrupt, completely, their sleep and we know also that it has a lot of health consequences, so. Because, of this sleep a lot of people with sleep problems we just absolutely, need to understand that better and then, of course there is also a large health and economic, impact. Because more and more people work around the clock, at. Night and we. Know again that disrupting. Circuit and resume and sleep increases all kind of diseases metabolic syndrome. You can you have an increased risk of gaining weight you even have an increased risk of cancer in many studies it's. Clear that sleep is really affect, both, the brain and the body in very very complex way so, for this reason I think you know we more. And more people are now realizing that there's a sleep revolution, that we really need to figure out what's happening in one third of our life to, really, improve. Their health of the general population and it's, not just sleep, is not just, nothing. Happens so, what, is also very incredible. In sleep and that's I think the luck that, that I have to be here today is that we are really living your revolution, right, now in. The field of sleep and the, reason is that it's, really at the confluence of several revolutions some, of them that are general set up apply, not only to sleep but, to many other problem, in medicine but. Also specific. Revolutions. That are ideal for sleep, so. One of the revolution, is in neuroscience, you know the fact that now we can more and more create this genetically. Modified, animal, and, we can study sleep, in animal models more and more easily there. Is also a. Revolution. In the, genetics. And proteomics. So, genetics, you probably know now that we know the entire sequence of the genetic of the human, body and I don't know I think in France it's actually not allowed but in the u.s. there, is this famous company, called 23andme, and it, all kind of irritates, company, where you just spit in a tube you send, and they can screen. All your DNA, for all kind of genetic markers for many many diseases and, very. Soon now it costs only a million it, cost only $1,000, to sequence, and enter genome so, very very soon we'll all have our genome sequenced and indeed.
I Mean you also hear in the news that you, have to make sure not to leave your DNA in the wrong places otherwise, and, do something wrong with the West you will surely end up in jail and, I, will talk a little bit about the proteomics revolution. Then, there is a revolution. In analytics. Some, of you may have heard of artificial, intelligence, and machine learning, now. Computers, are so powerful that I can start to make. Provisions. And and. Deductions. Very, similar, to the way human predict. And in fact do better than humans and this, is uniquely. Effective. In the study of sleep and then, finally, and that's probably where dream is ahead is this, revolution. Of hardware that, now more and more scenes can become smaller, and smaller there, is smaller and smaller material to. Study. You. Know the but body signals in, a way that's novel and that will allow all kind of new. Application. So. In terms of just, you, know the new technologies, that are applied in animals, these are a few of them one, of them that's very famous, that probably some of you may have heard is called Chris, cast 9 many. People think that these people will have the Nobel Prize it was so basically. A an. Enzyme, that allows to cut the DNA wherever, you want and change, it edit it the way you want so for. Examples are a lot of people is now being used if you have certain metabolic disorder, in your blood you, can just take your blood and yet fix the DNA where there is a mutation and Riaan directed and then, you hope that it could choose her the disorder, so it allows to really start to manipulate the, DNA in very, large scale and that allows to test a lot of genes and what they could do for in in sleep and in other areas of of medicine, then, there is also very. Excitingly, more, and more technology, that, allows to, visualize. The brain in, transparency. In animals if in, fact in certain fish like the zebrafish they, can be transparent. They are transparent until they're about one month old, and you can actually create like this neurons, that are fluorescent. And you can see them grow, you. Know during wakes they establish, new connection, and then during sleep they reduce a connection, so you can even study our sleep memory, and the synapse formation kind, of interact, and that's. One, way that we can show for example that sleep is so important for memory and for, consolidating. What you learn during the day so, there's really a revolution, in in animal, studies but. That I think applies, not only to sleep to many other area of Medicine. So. This. Is definitely maybe. A revolution. Where were dream and reason as a most playing, the most crucial, role is as, was mentioned right, now for example what. Raphael told, you in, his study in this. 2632. People. Eat. Really, people went through this or, a story, here, where you are completely in. A wire hub with all these wires and you have a box and you can't move and they are murdering how you breathe or your oxygen so, it's very uncomfortable and, the main signals, that you measure are, your brain waves which, are really important, because it's your brain activity and it really shows. If you're real sleep is disturbed, everything. Else is a proxy, of really, your brain activity and that's called. The electroencephalogram. And then, it merge your breathing why because, sleep apnea is so important a lot of people have this, and. We want to know if it if, people have it because that's one of the main problem, it's a general population, then, we measure leg movements, because we have seen that people kick, their legs and, that can be also disrupting, their sleep. So that's a wall montage, that we have and, clearly. Now I mean there's no reason why. This should. Not be transformed. In the future, into things that are much more simple, right, now I think dream is really in the middle of that revolution, and as, you see it's already. Doing. Pretty much the same thing as all this but. With a much simplified device. That. Can be worn day. After day and that's another very big advantage is that, right now we just do this only one night and it's. Not in your bed well, of course with a dream band you can do that at. Home and you can do that every night after every night but, I think even in the future and I'm sure that rhythm, will be part of that further evolution, you. Know the I mean this field is completely exploding. So, for example, there is new skin like material, like I showed you here that's being developed that, can actually conduct electricity. It's. This, is a future, it's not working yet but a lot of people are really working on this new biomaterial. Instead, of using silver electrodes, you, could really use new polymers, that can actually, conduct.
Electricity, And murder as well as as electrodes. Then. There is of course a world point of trying to make the components of electronics, smaller and smaller and also, taking less and less battery and that's, also something, that's really moving, very fast and then, I will, mention a little bit about the automatic, analysis, of sleep. So. This is an example of the type of new, materials. That are being developed for example at Stanford we worked with someone. Called Zenon bow who, works completely. In this area of creating these new polymers, that, can capture you. Know the activity, of muscles, or the act or eg activity, and, then. In terms of machine learning so, that's another, big revolution, I mean you probably hear, a lot about machine, learning and artificial intelligence but. For sleep it has not been a pre-k applied. Yet and, we. Know already that it works incredibly well so, here are you, know the examples, of sleep EG so how the sleep waves look, in different, configuration. When you're awake or sleep and normally. The. Way when we have patients. That go to a sleep, and, all, these wires, in, the mornings there is a technician that comes and looked page by page you, know fine screen by screen and, then, looks out this is stage one other, person, is sleeping other, person, is sleeping more deeply other person, is dreaming because it's in REM sleep and they annotate, they just write, down what. Kind of stage of sleep it is and then, at the end and also look if there is happening by, looking at the breathing if people stop breathing if the oxygen drops and they count the number of apnea the number of leg movements, and that's, what's happened, I mean actually. There is one million, people. That undergo, sleep study in the US every night every year so, you see it's really a huge market, in fact even sleep clinics, I mean, it's, big I mean our sleep clinics is eight thousand patients every year and it's just one of many, many in the US and there. Are all these technicians I just read, these things you, know night after night not, very smartly, you know I recognize this pattern and we, have shown for example that, using, this, new neural, network of machine learning, convolutional. Network you, know you can actually train this network, to recognize, the patterns that humans do and actually, at the end I do better than humans, we, know that when, when you do this what's very nice is with the machine learning not only you, can score the different type of sleep but, you can actually even give probability. So. For example here you know it you, know all, the humans said that it was awake like it was sick scores that says there was about 5 out, of 6 that says that a person was awake and then, here's a machine learning gives your probability of being, awake and then, you see it's really denticles, the way you know their scores. Which, don't always agree kind, of decide if you're asleep or awake versus. The machine learning so I think in the future very soon actually there, won't be all these technicians that will be reading all this, recording. It will done automatically, it will be sent on the internet and then, a machine learning will just, score. Every single time ethically and it would be probably we, know it will be better than humans the. Second area of revolution, so there, is a revolution, of hardware, analytics, that, I see the future with something. At night it. Goes straight on the internet on, a computer, and it scores it automatically, and send, it back to the doctors that looks at it and makes some recommendation. And maybe send it directly to the patient. The second big revolution, I mentioned, is genetics, why. Is genetic, interesting, because the genetics, is that the source of things, you. Know when you are you. Are born with your genes they. Cannot be modified by the environment so. If you find that a gene is associated with something it. Has to be causal, like. For example there is a particular, gene that associated, with Alzheimer disease that's. Called a puii if, you are born with it you have about twice more chance of developing Alzheimer's disease, that means that this gene has to cause an Alzheimer, disease because. It, cannot. Yes, there is no other way you are born with it it's, almost like. A randomized, trial so. When, you don't know anything about a trait, or disease now. What people do is a genetic, analysis, where, they take blood samples and, then, they study all the genes and they try to see, the relationship. Between different, genes and a. Disease. Or a trait. And curiously. This has not been done very much in sleep that's. A study that we did in in. Narcolepsy. So, narcolepsy is this weird disorder, when people fall asleep all the time they, are tired all the time and they go into dreaming, very quickly so, they have a lot of nightmares and and they, sometimes they are paralyzed when they wake up it's, a very severe disorder that's my specialty, probably, none of you have narcolepsy, but, it's.
Rare But it's quite interesting and, when. You do a genetic, scan of all this, the. People with narcolepsy like, several thousands. Versus, controls, you see this big peak here, it's a correspond, to region of the genome where, is different, between control, and narcoleptics. And then, the names. Here are the different genes that, you find and when you look at this gene you if, you were to look at a catalog you, can see immediately that all these genes are related to the immune system to. The ways the, sis. The body, fights infection, you know some of these genes are involved in autoimmune disease, or in infection. So. You may say why a brain disorder like narcolepsy, would have something to do with with. Infections. And in fact now we know, that the, explanation, for this is that narcolepsy. Is an autoimmune disease, probably. Where some people get the flu it's, probably caused by the flu and then, the, flu some people try to fight against the flu with an immune response like. All of us but in some cases it turns, wrong, and it attacks your own brain and, attacks brain, cells that contain a certain chemical calorics, in hypocretin. And then, once this, cells are dead you, have narcolepsy so. This, was just to illustrate that, by doing this genetic, analysis, even if you know absolutely nothing about, a condition it, may give you total Nuvo novel insight into it so, similarly, now people are starting to do this, kind of studies and insomnia, and depression and. This. Way because we are born with gene you can actually demonstrate, that. Insomnia. Is partially. Involved, so genetic predisposition, of insomnia, is causal. To the genetic predisposition to, depression, so that's why genes are so powerful because, it gives you an idea of the causality pathway. So. In fact to try to address this we have started we are studying something, that I think will be very complimentary, to a dream is really doing. Right now, where. We are I think. This PhD, is big that, is that I described is going to disappear, is, a dream, we'll kill it or, someone. Else will kill it because you. Know it's very cumbersome, it's, very expensive, you know and it doesn't make really much sense so, truth of the matter is the only thing you murder is if people have sleep apnea and I. Think just murdering if you snore I mean I think I'm sure there are some wives. Here that can, see their husband on, they. Don't really, need to have any tests to know that their sleep but they're unfortunately. So. You, know I think it's over killing, sleep. That. We put two murderers sleep apnea and we. Need to go fast to captors, is very rich information, before it disappears, I think and is replaced by some test and. I. So. This is a goal of this studies. We are going to study 30,000. People and we, are going to study their genetics, and we, are going to have all their sleep monitoring, the heart rate everything, during the night I like, to say that what's very nice during the night is that you almost have a check-up of your brain health because.
You Are not moving so, you are just going through a natural program, and dependent. Of any sensory input, so that's one was a way to check that your brain works well and that your general physiology, works well and then, we'll have also some general. Ideas there of, the activity, of people also their face because people who have sleep apnea, of. You have seen that often is when you are obese because. You get a lot of fat in your here. Especially men that's, why you know men put it here that's why they have more sleep apnea than women, and. But. Also sometimes, people that are skinny and children. Also can have sleep apnea it's often because they have a very small job because. If their Joy's like backwards then. You know there is less space and, that can predispose to sleep apnea so we also have a craniofacial picture, of people to, murder Prince position to sleep apnea we, have vigilance. Tests and then. A lot of questions about their sleep and then. We are going to try to correlate, all this with the genetics so. It's a very exciting study, that we are just starting right now. And the last point that I wanted to to, mention this besides the genetics. There's, also another revolution. That's coming is in the past now we good. Thing about genetics. Is you can measure all the genes at once so. That's what makes it exciting is, that you, can. Study all the gene of one, person by sequencing, the entire DNA, but. We couldn't do that for the body constituents. That are called the proteins, that are really what the. Body is producing, with, a gene and is really acting, on your general physiology, right. Now if you go to a doctor. And they, want to check if you have kidney, disease for example, say Mercer a certain chemical in the, blood that's called creatinine, I, mean, oh oh you know there's different specialized, tests for different. Diseases but, now what's happening, which is really interesting is, there is new techniques that is coming onboard we're, similar, to the gene you can start to measure thousands. Of proteins, at once in, a very small volume so. There's a company I work with that's now can murder five thousand, five hundred proteins, in hundred, micro liter and when. You do that it's quite amazing because you can have like a cross, section, of the general health of the person, and also. Because. You measure not only one thing you. Start to have, multiple. Things that create together as I can be indicative of a disease and that has, a lot of power for example this is an example of protein, panels, and certain. Proteins that change with circadian time so, for example here on top you see this dark band. Here that's moving is this a people. That, I've said awake. All for. Two days in, a row and then. You see some proteins that continue, to freak traits and definitely. Of the fact that they have not slept so, this is only related, to a circadian clock so, what we hope is one, day we'll be able to take a blood sample and, then. By measuring all these proteins I will be able to say ah my. Blood I just. Still on California, time because. My profile, looks like I mean.
I Guess unfortunately here, something. Like 3. A.m. or something like that no, actually it's 8. A.m. it's probably, not so bad I should, wake up so. And to give you another example it's quite amazing when you measure all this protein at once we, can for example predict, the age of people I could take now a blood sample of any of you blind. And I, measure with this protein and I do a calculation and then, I can get your age within three years so. It's just to show you that it's. Really, incredibly. Powerful, when you start to be able to measure thousands. Of things at once and we hope to even, find some screening. Tool for sleep, apnea and also sleep disorders, so. I think in general what. Do we want to achieve in the future what, is the future for sleep, I think one of them is that we're going to start to understand, through the genetic and with, this proteomics we're, going to start to understand, really the molecular. Basis of sleep and especially, why, we get tired during the day and also, some, proteins, at credit we sleep apnea we. May very well have some blood, biomarkers. Maybe you will go to the doctor's I take a blood sample and, they, say are you are sleep deprived or your sleep is not good or you have sleep apnea or your circadian clock is misaligned, and then. The second big, aspect, will be most. Of your monitoring, of sleep will be done at home and what, I hope is that, it will not be only for, sleep but, for other things because, I didn't have time to really mention it but as mentioned by Russell, we, know that sleep gets really impaired when you have Parkinson. Disease or, when you have Alzheimer's. Disease, or even depression, and maybe. When if you monitor sleep continuously, in your home in a very convenient, way you, start to see some some. Change and it tells you oh I'm getting in trouble you know I'm going to have depression and then you can intervene even before, oh oh, I'm developing Alzheimer's. Disease and I, think by doing this very sophisticated analysis. That I told you of the sleep, signals we, may have diagnostic, tools that are not only for sleep disorders which, already very frequent, but, even kind of a check-up for brain health and then. Finally, so. Maybe, the most exciting area. Is that, when you murder asleep continuously, you, have the possibility, of acting. On it immediately so. For. Example if, you study sleep and you go into dreaming, we. Know for I just, one example I was discussing we know for example that one of the biggest predictor of suicide, is nightmares, I know. You may not know and Sonya is very commonly occur. Because reside but nightmare, is a very, big predictor. Of suicide, so, maybe you. Know with when. We monitor, dream with. The. Band you can detect REM sleep and then, maybe you can put some nice music or way to soothe, the dream, and then maybe that would have therapeutic, effect. In some patients or sorry people with PTSD were, very bad dreams so, you might be able to immediately act, on the, bad sleep symptoms, as they appear and I think that's a very powerful. Potential. Tool but of course you know I I, was. Charge was talking about sleep of the future so, I'm not saying that this is tomorrow, you, know you're we are scientist in a lot of studies, but, I just wanted to really illustrate the fact that this field is changing really, rapidly and, that the ability to murder sleep continuously. Is probably. Going to revolutionize a, lot how, we view sleep sleep disorders, and maybe even general. Health especially, in the area of psychiatric disorders so. Thank you so much for your attention.