It's All In Your Head — Longwood Seminar

welcome to our third Longwood seminar of 2013 my name is Katie dubov communications specialist here at HMS Gina billed the associate dean for communications and external relations is travelling for a conference today so I'm delighted to be able to welcome you here tonight on her behalf I've likely spoken with or emailed with many of you about the seminar so I'm very very happy to see you here tonight as I mentioned this is our 13th year offering the mini-medical program at HMS and once again our seminar topics this year were chosen by voting so thank you to everyone who voted on Facebook and by email we received more than 500 votes this year which is really exciting and this particular topic learning more about the brain was certainly one of the most popular tonight's topic is also very timely many of you may have seen the exciting news today that President Obama just announced a 100 million dollar initiative to study to map the brain to learn more about the circuitry I'm so we're really excited about that here at Harvard and we hope that you will also join us for our fourth and final seminar of 2013 beyond belief exploring the connection between personal beliefs and physical health which will be held three weeks from today on Tuesday April 23rd for those of you who have attended the sessions previously you're likely already aware of the following announcements but I'll go through them quickly before we kick things off if you attend three or more seminars you're eligible for a certificate of completion so if you were here for the first two nights and you're here tonight then you're already well on your way to receiving that certificate and you'll be able to pick it up at the last session on April 23rd but unclaimed certificates will be mailed so if you're unable to attend the last session please make sure that you leave your address with us on an index card or a blank sheet of paper out in the lobby and we'll make sure that we mail it to you we are proud to let you know that we're also live streaming this event as we did for the previous seminars so we welcome those who are watching online if you have family members or friends who are unable to get into the seminars this year we encourage you to let them know that will also be live-streaming the fourth and final session please be aware that we'll be videotaping tonight's session as well and I want to remind those of you sitting in the front that you may appear in the video we are also happy to let you know that the two previous videos from this year are already posted on our website and our YouTube channel so if you miss those sessions I encourage you to check those videos out whenever you have a chance you may have also noticed this year that in an effort to support Harvard sustainability goals we did not print the Supplemental reading packet this year but you can find it on our website and if you don't own a computer then we encourage you to talk to a member of our staff who can give you a handout with local libraries and some information about where you can access the packet as many of you know teachers can earn professional development points by attending all four sessions you need to fill out an evaluation for each one and you can either hand that back in to us tonight or you can mail it back to our office members of our staff will be circulating throughout the evening to collect your questions on the index cards that you received when you checked in so we're really looking forward to an engaging Q&A later tonight you may have also heard that we now this year have a mobile application for iPhone and Android devices which is really exciting the app features the schedule of the location of the seminars a link to the website to download the materials and we encourage you to also check that out on our website as we've done all season this year and last year we'll be live tweeting throughout this seminar tonight so if you're on Twitter we encourage you to join the conversation by using hashtag HMS MiniMed and finally out of courtesy to our speakers and your fellow attendees please remember to turn off your cell phones and if there are seats next to you we encourage you to move in to make some room for other people in the aisles tonight's seminar is called it's all in your head building better brains through neuro engineering the brain is a fascinating and complex organ but how does it work interconnect with the rest of our body scientists today are making groundbreaking strides and understanding the circuitry in the brain and this knowledge and how this knowledge can be used to repair or regenerate damaged cells we have many internationally recognized experts at Harvard who are studying this fast evolving field and it's a privilege to have three of them here tonight to share their insight about a couple of ways that the brain impacts our bodies specifically how the body deals with pain and with hearing and hearing loss dr. Clifford Wolfe is a professor of neurology and neurobiology at HMS and Boston Children's Hospital dr. Albert edge is an associate professor of otology and laryngologist asakusa's ayan Ear Infirmary but first it is a privilege to introduce tonight's moderator dr. Joseph B Martin dr. Martin is the Loeffler professor of Neurobiology at HMS he also served for 10 years as dean of the faculty of medicine at Harvard Medical University from 1997 to 2007 during his tenure as dean dr. Martin helped to establish the dana-farber Harvard Cancer Center an innovative collaboration which brings together 7 Harvard affiliated institutions focused on diagnosis prevention and treatment of cancer he formed the ha Road Harvard neuro Discovery Center and led the creation of the department of systems biology at HMS additionally in 2003 he dedicated the new research building the very building where we are here tonight dr. Martin is the author of more than 300 scientific publications and several books the most recent one is alfalfa - IV memoir of a Harvard Medical School Dean which was published in 2011 thank you all for being here and I hope you enjoyed tonight's program let's give a warm welcome to dr. Joseph Martin thank you very much Katie for that wonderful introduction to all of us and to tonight's program and thank you all for joining us this evening I understand that these courses that you some of you have attended many times have been really quite informative and successful over the years and we're grateful for your interest and attention and I'm always amazed when I hear how access to this kind of information is available now you can Twitter you can put a media you could take my picture and put me on Facebook all this stuff with ten years ago no one knew anything about so you've heard the organization of the program I want to just spend a few minutes perhaps 10 or so creating a kind of framework or an architecture for how one thinks about the nervous system before we go into two very interesting and special aspects of the function of that nervous system and I'd like often to begin with this wonderful picture from Salvador Dali I'm sure all of you are familiar with it it's called the persistence of memory if you actually go to the Museum of Modern Art in New York you'll be surprised at how tiny it is it's really quite a small painting but it's become very famous for the soft clocks measuring time in a way that perhaps our brains attempt to do let me begin with the fundamental element of the nervous system which is called a neuron and it's a neuron that has given rise to the term neural science neural engineering neuroethics neuropsychology all of these areas that now are blossoming in our research and in our public awareness the manor on is that consists of the following components you'll see the cell body on your left with the nucleus oh it's like any cell in the body it has a Duke leus where the DNA is stored it is different than many cells in the body by having a long extension called the axon that goes from the cell body and which ends as shown by a distributed series of endings in an axon terminal which we'll see in a moment connects to another brain cell the dendrites are the receiving components of the nerve cell and the axon is the output so you have in a sense a generator an electrical generator which consists of a body receiving information through its dendrites and then sending them out along the axon to the axon terminal there's a picture of what a neuron actually looks like and you can see the extraordinary complexity of all of the components reaching out here which are part of the dendritic tree and this is actually a picture that was taken to show calcium uptake when the neuron fires and you can see here the nucleus featured by the calcium around it and each of these dendrites has little knobs on it which are called Bouton's or synapses which I'll illustrate for you in a moment in fact here it is so if you take this first cell at the upper left you can see that it consists of connections coming in the dendrites at the axon which takes in some cases a very long trajectory and then it tends to end mostly on the finer dendrites of the next cell so that the discharge from this cell which is associated with a an electrical potential that travels down the axon when it reaches the synapse it actually acts through an electrical chemical connection meaning that as the neuron depolarizes and loses its electrical charge it releases into the synaptic cleft transmitters chemicals which then act upon the post synaptic area to elicit a either excitation to turn the next cell on or inhibition to turn it down and so of all the neurotransmitters in the brain of which they're probably close to now they all tend to have either excitatory or an inhibitory component to regulate the overall neural networks so a brain complexity more marvelous than the universe the estimates are that there are a hundred billion nerve cells it's sort of what we spend every year in dollars for Medicare no one's counted them this is an estimate there are estimates that each neuron has anywhere between a thousand and ten thousand of those synaptic connections on its dendrites or on its act on its axial meaning that there are between ten and a hundred trillion connexes potentially active in the living brain there are a thousand proteins that are present in that synapse that we saw a moment ago that can act to modify both the process of release of the transmitter and to act upon the subsequent effects upon the second neuron in the circuit and very important as you'll hear from our talks tonight is that there is minute-to-minute regulation or modulation of the synaptic strength between those cells which is evidenced in changes in number in size and in shape so that when you leave this lecture tonight your brain will be different than when you came unless you don't remember anything you will in the process of forming memories actually change the biochemistry in your brain the wiring that connects the nerve cells to each other particularly in a region called the hippocampus which is a change that will live for the rest of your life in modified form you may forget tonight but much of what you experienced you go on to remember fortunately not everything you couldn't possibly manage that so we live with the concept of a wet brain it's this is not a computer this is a self-correcting instantaneously potentially modifying structure that lives within the environment that it receives information problem and we will tonight hear about two of those information systems one the pain system or the way in which we perceive unpleasant events and secondly hearing how we perceive the sounds that are about us now the brain is complicated in this slide which is borrowed from my colleague David Cardozo here who is one of our wonderful teachers in the neuroscience course shows on the Left Vesalius who was one of the first people to specifically detect and describe all the components of the human nervous system and you can see that was in 1543 just about 30 years after Michelangelo did the Sistine Chapel so through dissections of humans he was able to show that the brain that the nervous system and the human consists of the brain of a spinal cord that comes down the backbone and then nerves that go out to the arms and to the legs and so you can say when you suffer from sciatica which pain may be felt down here in the foot that it can be due to some interruption in the function of the nerve fibers up here as they leave the spine to enter into the lake and shown here on the right is a view of the brain itself with some of the names now shown the cerebral hemisphere this would be the left cerebral hemisphere this is where language in most people resides the frontal lobe the temporal lobe the brain stem and the cerebellum and the anatomy of the nervous system which our students learn in second-year is of course extraordinarily complicated and detailed to understand all the connectivities that go on between the cerebral hemispheres left and right between their connections to the brainstem to the basal ganglia and to the spinal cord and on down to the muscles now let me just take one little piece I showed you back here where the cerebellum is so to give you an example of the intricacy of how the brain is these fine let's take a look at this one cell a cerebellar Purkinje neuron which lines a particularly R in the cerebellum the function of which is to coordinate movement so that when I take this pointer in my hand and I go up and I want to show your dendrites that system of Purkinje cells in the cerebellum help me aim correctly so that I can actually judge where I want to go or I could put it up there and you know generally hit what I was aiming at this particular cell is one of the most complex here's the cell body sometimes called the soma here's the axon or the output and look at the remarkable spread of all the dendrites that are the input for the integration of the connectivities from the rest of the brain that are going to tell this cell how it should respond in relation to a complicated act like a smooth movement to a point in space now let's just blow it up perhaps ten twenty thousand times take a little piece here shown by the red circle and look in the electron microscope and here you will see a dendrite this is now a single dendrite one of those spicules sticking out from the cell body from one of the branches of it and here you can see coming in an axon which is making connections here to a spine which is one of the pieces of the dendrite that sticks out where most of the connectivities occur at what we call synapses there are many examples now of extraordinary moments and discovery that relate to the potential for future understanding of neurologic and psychiatric diseases and I just show you this one which is from paper in science in 2007 by Ken Garber just pointing out that again looking at the proteins that are associated between here a presynaptic axon that's ending here on a postsynaptic cell you can see the names they don't matter person specifically but there have been now identified instances of autism with the full spectrum disorder that we recognize in genetic mutations that involve proteins like neural ligand or neural interaction meaning that a defect in the function of a small protein at a synaptic cleft can be sufficient by interrupting the wiring of the systems within the brain to cause the complex psychological disorder like autism finally I just wanted to show you that there are many different kinds of brains within the animal kingdom you'll notice here the human brain Illustrated just below the dolphin brain and the point of this slide is to show you that in fact the human brain is not the biggest in the animal kingdom by far here is the size in comparison to the human brain of the dolphin brain shown here and a lot of effort now is made in neuroscience to try to understand the behavioral differences that exists between various members of the animal species and ourselves and I would leave you with the last slide comparing the anatomy of brains and dogs and men you can read that yourselves so let's turn now to our first speaker who's already been introduced cliff wolf is going to tell us about some of the you're not listening this is from another talk cliff wolf was already been introduced to you and he's going to tell us something about the remarkable way in which information from a particular set of sensory inputs occur that help us understand among other things in the nature of pain so cliff I think they'll put yours up right away thank you all very much and thank you very much dr. Martin ladies and gentlemen it's a real pleasure to be here as Katie pointed out this is a very special day because indeed our president announced this new initiative to study the brain to spend a hundred million dollars and one may ask why now when why should this be one of our top priorities and part of it certainly is that the brain is the new undiscovered territory this is this is the the new West that we need to discover and understand that that certainly is a big drive and I make no excuse for it and neither did Barack Obama he said he is all in favor of basic science using modern technology to understand how our brains work and what what greater challenge could there be but there's another element to it and that is what we call translational medicine which is to exploit the understanding that we get from the study of brain mechanisms for the development of new therapies and what I'd like to do today is just to give you a flavor of that related to some of the work that we do and the the particular challenge that we set ourselves was related to the sensation that we call pain this unpleasant sensation that we we feel when we are hurt or saw and I'd like to explain a little bit about what pain is and how we can potentially target pain in a very selective way in a way that has not ever been possible before and the major theme really is that new approach to the management of pain is only possible from studying the way in which pain operates it and that surely is going to be the answer to many neurological diseases so if we look at the pain system here in its most simple you should by now be fully trained near anatomist you have no better teacher than the former dean of Harvard Medical School who is pointed out the brain over here and this is where we have the conscious awareness of sensations this is our the the the point at which we are aware of a sensory experience and the way the sensation occurs is that there are specialized operators in the periphery in in the at which which had the capacity to convert external stimuli into electrical activity that travels through the nervous system to towards those centers in the brain that leads to the this conscious awareness of the pain sensation so if you imagine a touching something too hard to exposed to a flame this will activate a series of signals that will flow through the brain and will eventually have this particular sensation of pain why do we have it what what is the purpose of pain well pain is an early warning device system it informs us of danger in the external environment and there are some unfortunately individuals who are born without the capacity to feel such pain and they not surprisingly damage their bodies when they drink something they cannot just distinguish being in something that is warm or scalding heart they went when they eat cannot differentiate between chewing meat or their tongue and which they destroy so pain is an absolutely essential part of the way in which we are able to safely navigate the external environment and yet I like any danger system there it is there to protect us but there may be false alarms and a false alarm is a situation where this pain system is activated in the absence of any danger signal and that is in in some the key element of chronic pain persistent pain that is warning us of present of danger that is not actually there it is a disease state of the nervous system and what I want to describe to you is how we can potentially target the system in a way that we can control it in in in a very selective way so here here we we've learnt about neurons and these are the neurons that mediate the transfer of information from the periphery to the central nervous system and in essence these simplest features of these sensory fibers is that there are two systems there's a system of neurons that are I will call small and those that are large the large ones are designed to detect innocuous stimuli the kind of stimulus that would be generated by touching the skin by vibration and what we call tactile stimuli and so these are obviously do not produce pain and then the small set of sensory fibers are activated by intense stimuli these may be intense temperatures either hot or cold they may be intense mechanical stimuli such as pinprick or noxious chemicals and these activate these small sensory fibers the information is transferred by electrical activity to the central nervous system generates activity in a sending pathways to the brain where we now are aware of this this peripheral stimulus and the challenge that we set ourselves is can we switch off this pathway the small pathway that generates pain while leaving the large pathway that generates innocuous sensations intact now if we actually look at what these sensory fibers look like this is what we call the dorsal root ganglion and this has the cell bodies or the soma a term that dr. Martin mentioned of the sensory neurons that I described and we have techniques to identify these two sets of neurons we the the small neurons over here are the pain neurons if you like these are the pain fibers that are activated by noxious stimuli whereas the large sensory bodies over there are those that mediate the innocuous and and that our challenges is their way to target only these small pain neurons leaving the other ones intact now the way we do which we try to do this at the moment is to use a chemical called lidocaine and lidocaine as you anyone has been to the dentist and haven't had an injection of what local anaesthetic is aware of this chemical because it's a very potent animal local anesthetic and a local anesthetic means it produces total anesthesia it eliminates all sensation and it does this by blocking the electrical activity the electrical signals that are that carry the information from the periphery to the central nervous system and it does this by targeting a particular protein called sodium channels and the sodium channels essentially are the batteries within the nerve fibers that carry this information and this is the electrical signal which is switched off by lidocaine now lidocaine this is this actual chemical structure has a particular property which is that at normal pH it exists in two forms it exists largely most of it in our if injected in into our bodies in a charged form a protonated form and a small minority about 15% of it is in in an uncharged form now why is this important well the it so happens that the site on the sodium channel where lidocaine acts to block electrical activity in the nervous system is on the inside of cells so in order to gain access to that the lidocaine has to come from the outside of the cell to the inside of the cell and it turns out that the only way it can do that is by diffusing through the membrane of neurons and in order to do that this is a lipid environment it the only form of lidocaine that can do that is the deprotonated or the uncharged form so you have I mentioned there was a charge form which is the majority of the lidocaine and an uncharged form well it's the uncharged form that diffuses through the membrane of the neuron gets into the inside of the cell and then access to the sodium channel where it can block it and produce its its effects on reducing excitability of the neuron so here's a recording from a neuron we have a measure of its excitability we put on lidocaine here and essentially we switch off immediately the sodium channel activity and it the switch off occurs within a few thousandths of a second of the application of the lidocaine and when we switch when you take away the lidocaine then the activity returns so this this effect is is almost binary and the president's in the presence of lidocaine there is no activity in its absence the activity returns now if we inject lidocaine in in the human or in a in a mouse we can we observe the effects of blocking electrical activity so in this particular case we've injected lidocaine to one of the peripheral nerves that dr. Martin pointed out and when we do so there is a complete loss of the responsiveness of that mouse or of a human if you did it in the in a subject to heat pain sensitivity so if and this effect the details are matter but the important thing is to notice this effect is very short lasting it's very dense it completely shuts off the capacity of the animal to react to a noxious heat stimulus but the effect is over within an hour the same is for pinch and in addition there is block of the motor axons the axons that carry information from the spinal cord to muscles that cause them to contract so you have a situation where there is loss of sensitivity as well as motor function the the hind poor of a mouse in this particular instance is paralyzed but the effect is very short lasting so essentially the lidocaine is a very blunt tool it's non selective it blocks the small fibers which we want because we want to block pain but it also blocks the large fibers and therefore causes a complete loss of sensation and again we go to the dentist we have our shot of lidocaine that certainly moves the pain but you all know you feel numb and you're drooling and your mouth your mouth is paralyzed because of this non-selective action of lidocaine on all neurons so the challenge that Bruce beam is one of my colleagues at Harvard Medical School and a postdoc in my lab Alex bench doc said our cells was to say could we silence only pain fibers leaving the low threshold fibers that generate innocuous sensations intact and leaving motor axons intact so that instead of producing local anesthesia which as I indicated earlier means a total loss of sensation whether we could produce local analgesia which is only a loss of pain sensation so how to do this well we looked at lidocaine and we said we know that it exists in these two forms a charge form and an uncharged form well I've indicated before that the charge form can't get through the membrane it the lipid environment the membrane is is not compatible with charge molecules and therefore it stays outside and as a consequence if we take lidocaine and just add on a quaternary aiming group over here which makes it permanently charge we now have a lighter came drug that is totally ineffective it cannot diffuse through the membrane it cannot block sodium channels it cannot block excitability of the neurons and therefore it is a completely useless drug and AstraZeneca in their wisdom designed this drug as a potential local anaesthetic about 25 years ago and discovered very quickly it was absolutely useless however it has a very useful property which is that if you put it inside a cell it will block the sodium channels and we electrophysiologists who study the excitability of the nervous system have a trick we can put an electrode against a neuron we can then exert a little suction force on the the electrode which breaks the membrane over here you can see it's broken over there and if we have light this charge lidocaine in the the this electrode it will diffuse from the electrode into the cell and if you do that here's the electrical activity of the cell before and then after and you can see it's completely eliminated so that this charged form of of lidocaine which is called qx3 1-4 can act provided it's inside the cell but normally it does not act because it cannot diffuse through the membrane so the question then we had was is there a way that we could possibly deliver qx3 one for the permanently charged form of lidocaine selectively only into pain fibers how to do this how how to even conceive of a way to do this well we've heard that one of the themes of the this this evenings presentation is neural engineering and I'm going to introduce a form of neural engineering that doesn't require a device it doesn't require any machine or any material it's a form of mirror engineering that just requires a good idea and the good idea was to use what is there already in the body what I mean by that well let's go back to how we feel pain this is what how Rene Descartes or a great French philosopher about 400 years ago this is the way and he the way in which he saw pain was perceived again to have a noxious stimulus it acts on he didn't appreciate there were neurons or there was just a bit he knew there was some signal that was generated he thought that the the conscious awareness of pain occurred like a little bill that rang in the pineal gland so if he's he didn't get everything right but essentially he had the notion that noxious heat would activate a sensory flow of information that would cause pain how does this actually happen well it this is a model of the peripheral end of a pain fiber in the skin and this pain v expresses a protein called trip v1 which is an ion channel and this ion channel is activated by noxious heat so when this channel is heated up to a temperature of about 42° it opens and that opening allows ions to travel across the membrane which depolarizes the membrane generates an action potential and carries that that current of information after the brain so this is what we call a transducer it transducers heat into electrical activity and it does it by opening a channel which is called trip v1 now the extraordinay thing about trip v1 is that it's not only activated by noxious heat but it's also activated by capsaicin which is the pungent and granted ingredient in Chili Peppers now that's not too surprising if you think about it when you eat a very hot chili pepper and why do we call it hot that's not because it's actual temperature it's because the sensation that it generates is one of heat why is that so well the answer is really quite simple capsaicin activates trip v1 which is exactly the same protein that noxious he does so the reason we feel that sensation has been hot is because we are activating pain fibers that would normally only be activated by noxious heat stimuli so now we have a chemical means of activating pain fibers in a very selective way now this is what trip v1 actually looks like this is the membrane this is the ion channel and this is a show at an atomic level what does a nine channel looks like now the important feature in fact the only feature you need to know about this is that trip v1 is a large pore channel which means that it has a large hole when it opens up in the membrane and what our idea Bruce Bennett and myself was could we use trip v1 as a drug delivery mechanism to get our charge form of lidocaine qx3 and for from the outside of a neuron to inside of the neuron and that really was our neural engineering instead of using a drug delivery device that was something that was manufactured our drug delivery device was an ion channel that was present naturally in the body a ion channel that had a pore that was large enough to allow this small dread like compound to move from outside the neuron to to inside and this essentially was was the conception which is that if we had our charge form of qx3 one for outside of a nerve fiber then it would be inactive as I've described but if we combined the presence of the charge form of lidocaine qx3 1/4 with capsaicin which I've told you activate strip v1 then the capsaicin would open the trip v1 channel and this pore of the trip v1 channel is large enough to allow the qx3 1-4 to move from outside the cell to inside where it can now block the sodium channel over here and produce a block of excitability in in the neuron but the beauty of this is that this will only work on those cells they express trip v1 and trip v1 is only expressed on pain fibers that respond to noxious heat so this this treatment of combining capsaicin with QX 3 & 4 will get QX 3 1 4 only into those pain fibers that are noxious heat detectors so we potentially have our selectivity here does it work well we studied this first in cultures of neurons where it's possible to take the neurons put them in a dish we have the large neurons which are the ones that mediate innocuous sensations and here's a small one which is a pain detecting your own and what we've done here is we've combined qx3 one for the charged the permanently charge form of lidocaine with capsaicin in the control situation we have a measure of the excitability of this neuron and then we do put on this combination and in a matter of seconds you can see the excitability reduces and by a minute it's completely eliminated so in this small little neuron we are able to switch off the excitability of this neuron and it becomes in excitable and unable to transfer information whereas when we look at the large neuron which would be activated by touch or vibration there is no effect whatsoever doesn't matter how much qx3 and foreign capsaicin you put in the solution this does not change the excitability of this neuron because this cell does not express trip v1 the noxious heat detector or the capsaicin receptor so we've got our selectivity by using the differential expression of a key protein that is only present in this neuron and not in that neuron and furthermore we've done this by virtue of the fact that the trip v1 has a large pore so when it is activated it can allow delivery of our drug only into these cells does this work well again we go back to our preclinical models in mice we now inject capsaicin by itself this pungent in ingredient and it produces no change in payment behavior we inject the qx3 1-4 by itself it is absolutely no effect exactly as one would predict because it cannot cross the membrane of neurons to get inside it but when we do the combination of the charged form of lidocaine QX 3 & 4 plus capsaicin we now get a very high level of blockade of of in this case responds to pinch and I mentioned earlier when you inject lidocaine the effect is over within an hour as you can see here there are this combination effect has a duration that is much much much longer than lidocaine and the reason for that is because the qx3 1/4 is trapped in the pain fibers it gets only it gets it only gets into the the pain fibers but once it is there it is trapped and has a very long lasting effect so this idea once it was proved resulted in paper that the three of us published in in nature which was very exciting at that time I was happened to be in the department of anaesthesiology at Mass General Hospital and the the journal anesthesiology which is the the major journal of anesthetists ask the question is regional blockade of only pain v as possible I think our data show that it is my colleagues were very worried as Anissa tiss this may mean they were put out of business well that's science and the hope is that by understanding the mechanisms of the nervous system we truly can make a major impact on on the treatment of neurological disease and we hope in in collaboration with partners in the pharmaceutical industry that this conception this idea this notion that we can deliver drugs in a very specific way to only specific subsets of sensory fibers to produce local analgesia will turn into a new form of therapy thank you thank you very much Clifford for that great talk I have some great questions here on cards keep the cards and letters coming and we'll try and respond to some of them the next speaker is Albert edge who as you've heard is at the mass eye and ear doctor edge first came to Harvard Medical School as a postdoctoral fellow in the 1980s he worked as the Joslin Diabetes Center for many years left for a while to become involved in some projects in in in the biotech industry and then came back in 2003 to the mass eye and ear and his particular interest is in trying to discern effective ways to restore hearing in those of us who have shouldered the effects of loud noise or aging or whatever by using stem cells it's a very exciting area of recent development in the stem cell world so dr. edge well thank you thank you very much for the introduction and thank you all for coming I think the dr. Martens introduction and dr. will stock are perfect sort of for coming before my talk because many of the themes are quite similar we're switching to a different system now but we're going to talk about the cells that transfer information from the ear the sound information to to the brain and I thought I would first start and this my what I want to talk about today is also what dr. Wolfe called translational in that I'm going to really talk about some of the work that we've done to move towards cures for for hearing loss and to set the stage for that many of you know that that hearing loss is very common but you may not realize how common it is it's close to 50 million Americans have significant hearing loss around the world the numbers is closer to 300 or 350 million people who have serious or some some moderate to severe hearing loss some of that is age-related so that in in older people this hearing loss becomes extremely prominent it's also a problem in in newborns genetic forms of deafness which is which are which are actually quite common and and a lot of that is is caused by exposure to loud sound and I'll actually summarize causes hear noise trauma or loud sound is a major cause of hearing loss this isn't just something that parents tell their kids you know turn down that music or turn down that that iPod it's a real thing and there's a lot of evidence from from labs around the world showing that that loud noise really does negatively affect your hearing in the long term there are certain drugs that are that have been used to treat other diseases which can actually have a negative impact on hearing these aren't used so much anymore in the United States although there are certain diseases in which these antibiotics are used and can cause hearing loss and there's some cancer drugs that can also cause hearing loss probably the major cause in terms of numbers of people is is aging and I'm sure most of you know someone or have a friend or family member who's been affected by that and I mentioned genetic factors and a number of diseases which can also cause hearing loss so what's what's interesting to us as scientists is that we really understand a good deal about what actually goes wrong when hearing is lost and so I'm going to spend the first couple of minutes just orienting you to the neurons and receptor cells in the ear which are different from what we've been hearing about but but similar in many ways and then show you about two approaches that we've taken to trying to replace some of these cells so just to begin that or orientations here's the external ear and the ear drum the middle ear is where these bones are that actually vibrate in response to sound waves but the real action occurs in here and what's called the inner ear which is actually deep inside the skull and it's the location of the cochlea which is this kind of snail shaped dividing organ shown here and which contains these cells which I'll tell you a bit about called hair cells which are really the sounds the the cells that first detect sound and like the other systems that dr. Martin introduced here's our ear again and through a series of steps and sort of relay stations within the brainstem and then working all the way up to the auditory cortex this sound information is interpreted in your brain so that you can speech and music and figuring out that that a truck is approaching these hair cells are so called because here these three red cells and blue cell are what we call hair cells and if we look at the very top of these cells they have these structures which we call stereocilia which are hair like structures that's why they're called hair cells but this is microscopic you can't see this unless you're looking through a microscope and they're connected by little structures protein structures called tip links and there are a number of people working on how hearing actually works and they think that vibration of these stereocilia actually opens a channel not unlike the trip channels that dr. Wolfe was just talking about which allow ions to rush in and create an electrical potential so you've heard this from each of the three speakers tonight that electrical activity is what that then gets transmitted to the brain and that happens in the inner ear by transfer of that electrical information from a hair cell this blue cell here is called an inner hair cell these three red cells here are called outer hair cells and that happens through a synapse which you've heard about several times today chemicals are released from from the hair cell which excite the auditory nerve and then that auditory nerve leads to the brain to bring the information there and so if we actually look a bit at these outer hair cells these cells are actually like little muscles they actually contract in response to sound and they actually form what we call the amplifier of the inner ear whereas the inner hair cells transmit the sound after it's been amplified by outer hair cells via the auditory nerve to the brain in hearing loss if we look again at the same sort of cartoon depiction of the inner ear there are two two cell types that I've talked about and both the loss of either of those can cause loss of hearing so here we illustrate loss of the nerve fiber and there's some forms of hearing loss in which that nerve fiber is gone but the hair cells are still intact and this person will definitely be deaf and the other type is loss of hair cells so now we have an intact auditory nerve but the hair cells are gone and again this this these are these are both called sensory neural hearing loss the only treatment that we currently have for this type of hearing loss are hearing aids which most of you know about and cochlear implants which are a bioengineering approach to treatment of loss of hair cells so a cochlear implant it's a device that actually gets implanted into the skull and which detects sounds very much like the hair cells detect the sound and then transmit an electrical signal to the auditory nerve so that that can be communicated to the brain now that's all I'm going to say about cochlear implants because our interest is actually not in using devices to try to restore hearing but in fact to try to replace the lost neurons and lost hair cells and the way that we do that is by using technology which comes from from stem cells and so I'm going to spend a couple of minutes showing you what what that involves and then I'll basically show you the results of two experiments in which we've had some success now in replacing these two cell types but first let me quickly show you some older data not not from my lab but from from a number of publications by others which illustrate an interesting phenomenon chics these are these are birds these are actually young young chickens spontaneously regenerate they'll replace hair cells after hair cells are damaged so here we see a chicken inner ear the little white spots that you see are actually those hair bundles that I showed you before after noise damage after exposure to noise you can see there's a large area here of damage and over the course of the next few weeks those cells are completely replaced and the hearing in these animals and this is also true in fish is completely restored the process by which that occurs is as shown here these purple cells this is sort of a simplified ear of a chicken it's less complicated than ours so here the hair cells in the chicken here's a hair cell dying and their cells underneath those hair cells which have some properties of stem cells we call these actually supporting cells which can go through division so here we see the the DNA replicating itself and two new cells arising from a single cell and as we go from left to right here complete restoration of the original structures so by by two processes dividing the cell and then what we call cell differentiation so we start with these gray cells and we get a new gray cell and the new purple cell so in Chicks both of these processes go on but in humans and actually in all mammals this does not occur at all so once we lose our hair cells they're not replaced so I just want to show you again what these hair cells look like in a mammal so here's this snail shaped organ the cochlea and they're arranged in sort of this spiral but what we have here are this row of what are called the inner hair cells and three rows of outer hair cells these are the cells that I showed you can actually expand and contract to amplify the sound and these are the cells that transmit that sound to the brain and when we look at these in the laboratory we usually use fluorescent more purrs and so you're gonna see me show these a couple of times so that you can follow me these are the outer hair cells in three rows with a green fluorescent marker in them and the inner hair cells which are shown here and here also with a a green fluorescent tag now let me just spend 30 seconds talking about stem cells and the concept of stem cells most of you are probably somewhat familiar with this that there are various types of stem cells and I won't go into that today but what makes stem cells powerful is their ability to become different types of cells in fact all of the different types of cells in the body and so various labs around the world have shown that we can make neurons from stem cells and one way that we hope we'll be able to treat neurological disease in the future is actually to transplant those new neurons into people with with various diseases and so in the I'm going to now show you these these two experiments that I mentioned one in which we're trying to replace the neurons and one in which we're trying to replace hair cells so the approach that we use for trying to replace neurons was to first as I said make neurons from stem cells in the laboratory and then to actually transplant them and this shows you a little bit about the neurons that we made you can recognize these now from the proceeding information that you receive so here's the cell body or the soma here are some axons protruding from these neurons but these are neurons that we've made from stem cells and this is an experiment we did just to prove to ourselves that these were actual neurons they look like neurons and if we measure their electrical activity they respond like neurons and so what we've done is to take the these three rows so now the hair cells are in blue here and the neurons are in in green so the brain would be over here on the left and the ear is over here on the right and we did some experiments still in a dish in which we first removed the neurons and then added our neurons that we had made from stem cells and when we did that we could see that these stem cell derived neurons sent out these processes and they seem to know where to go so they're going to the hair cells which is where we want them to connect so that they can respond to sound and we then when went ahead to try to reproduce this in an actual animal in a mouse that was deaf after exposure to loud sound and so these animals are our deafened at day zero of this experiment after a little more than a week we put in the new cells by a surgical procedure and then we look to see whether we can find the cells and to see whether the cells are doing anything to treat the deafness in these animals and what you can see here is here here's a mouse ear from a deaf mouse in which the neurons are completely gone so the hair cells that I've shown you a couple of times are still there the three rows of outer hair cells and I hope you can see a row of the inner hair cells here these are just the name of the of the new neurons that we put in derived from the stem cells and we can see that the they reproduce the pattern of the original neurons and go and connect in this case to these inner hair cells and if we look even more closely here zero in on the place where we would hope that there would be a synapse forming this is a little bit difficult to see but the blue and the red dot the the blue dot is actually in the hair cell and the red cell is in the neuron and so this is diagnostic for us that synapse has been formed so these new neurons that we make from stem cells find their way to the hair cells and actually form and I won't go over the details here but this is the way that we measure a hearing in a mouse you can't play a tone to a mouse and ask him to lift his paw when he hears it so we have ways of doing that which essentially involve administering a sound to the ear and then measuring the electrical activity in response to that sound and and what we show here is that in our deafened animals over time there's a decrease in hearing and a slight increase in improved hearing in these animals where we have transplanted these new neurons and so this is the first step in terms of neural replacement as a potential future treatment for for hearing loss and the second set of experiments that I'm going to show you are to replace the other cell type that I mentioned the hair cells and we take a quite different approach here first of all we've identified stem cells in the ear and so rather than using stealth cells that we're putting in from outside we're actually going to try to stimulate those what we call endogenous stem cells the cells that are right there in the ear and see if we can get them to make new hair cells they don't do it on their own but we wondered if we could use a drug to stimulate those stem cells in the year to become new hair cells and so the procedure here would be actually eventually we haven't obviously done this in human patients yet we've only done it in mice but the idea would be to inject a drug and we actually do put it in locally rather than as a pill for the time being that's that's been the best approach so we put the drug right right into the inner ear and then we measure new hair cells and recovery of hearing and just to give you a feel for how this is done since there are no drugs that can do that currently we set up what we call it a screen to look for molecules that might have this property and the way we do that we can sort of ignore the details here but we set up a reporter what we call a reporter system that lights up when we see a molecule that's making a new hair cell and this is done and the concept here is that we're starting with a stem cell and if we pick and that stem cell can become many different cell types but we're trying to affect sort of a series of binary switches to end up with with a hair cell the way we do that is actually using robots to screen through thousands and thousands of molecules this shows such a robot that says 384 pins here stainless steel pins which dip into a dish with 384 Wells each of which has a different chemical in it and so we can then use that assay to ask whether any of those drugs are working to make new hair cells and we found some molecules that that do that in fact and so here again our is our row of inner hair cells in three rows however hair cells when we put one of these drugs on the ear you see something unusual happens we get extra rows of outer hair cells and so it looks like this is a drug that actually makes new hair cells this is in a dish in a in a newborn animal actually and we did a similar experiment but actually first damaged some of the hair cells so instead of three perfect rows of hair cells you'll see that some of them are damaged here and we use this same compound and saw that we were getting new hair cells in this experiment that we did in a dish so we then went on to try this in actual animals so mice that had been been deafened similar to what we did with the with neurons and again if we look over here this has control but what this means is that this is the deafened animal there if you just look at these green spots here these are now the hair cells so we still have our row of inner hair cells on the top but a very much disrupted number of outer hair cells here and after treatment of these animals with the drug and then waiting for several months we found a partial replacement not complete but pretty good replacement of of those hair cells we went on to look at whether these ears could hear whether we had restored any hearing in those ears and again the details here aren't important except that what what we do here as I said before is administer a sound and then measure electrical activity and what we found this is an untreated this is a damaged but untreated ear on this side and you can see there's a change and this is actually measuring that the amount of sound that it took for this for this animal to respond and so this animal is completely deaf it's really has no response at all and this animal now does respond to fairly loud sounds and so we've managed to again partially restore hearing in a completely deaf mouse this time by replacing hair cells with a drug and in the previous work by replacing neurons by stem cell transplantation and just to give you a feel for for how this might go in the future and then I'll finish up here you know how would you deliver a drug to the ear we hope that we would have something that would be a pill there's also the possibility of ear drops which are put into the outer ear another way is what we call a trans tympanic injection which is an injection actually across the eardrum which can also be done and that's actually what we did in the mice and so that's a viable way of delivering a drug to the ear and ultimately we hope that we will have ways to actually deliver these drugs directly to the inner ear and so to conclude as I said we were interested in replacing these two critical cell types for hearing the receptor cells for sound and the neurons that transmit that signal to the brain and I showed you that both of these can be lost and caused cause deafness and we've now been successful and partially replacing some of the hair cells and in partially replacing some of these neurons so thank you very much so I'll invite dr. wolf and dr. edge to take chairs at the at the table here and perhaps we can turn up the lights a bit so you could all see each other there's some great questions here and I'm going to start with one for dr. wolf which is really a very fundamental issue about how the brain works and which he is an expert on the question is how is the electrical or the neural impulse generated inside a neuron is fundamental to the operation of the nervous system and the membrane of the of neurons is this lipid structure which separates two environments there's the extra cell environment and the intracellular environment and they have different ionic compositions and this really acts as a battery so there for example is a lot of potassium intracellularly and less extracellular and the reverse for sodium and when I'm channels open when these channels open such as the sodium channel this allows the ions to move down their gradient and these are charged ions they carry charge with them and it is this charge which is the electrical that generates the electrical activity in the neuron so this is the the way in which neurons carry information and it is the most fundamental property of a neuron it's amazing how nature uses simple things like sodium chloride and potassium to produce all of the activities that we're describing for dr. edge this is a very interesting question is the sensation of hearing both contralateral and Epsilon or from both ears do the neural pathways take information from both ears and how does that work yeah that's a very good question maybe I should explain the terminology to those who don't get that so contralateral meaning the sign-ups collateral the same side there are both do occur mostly the signal goes to the other side of the brain so it's it's contralateral but there are contributions from from both sides so as these ascending pathways as we call them in the brain go from the brain stem up eventually to the cortex there is usually crossover of most of the information to the other side no you're not aware of that and you shouldn't be because your brain is is integrating all this this information but that that happens to be how it's set up okay thank you dr. Wolfe how would a patient be treated for pain management with qx3 1 4 and capsaicin example what would be the mode of delivery so the the way in which we envisage it being used initially at least is by injection so instead of an injection of lidocaine there'd be a a mixture of qx3 1/4 or a similar drug it's very unlikely we'd use capsaicin because as you know anyone who's chopped a chili pepper with a slight abrasion it produces very intense pain and while the capsaicin and QX together will block pain there would be a few seconds of very severe pain if you injected capsaicin we have found other ways of opening the trip v1 channel so we would use a non pungent trip v1 activator as well as lidocaine and I would envisage being used in a post-operative setting of exactly like your dentist does at the moment except when you get a shot of this combination you would only have a reduction of pain there would be no numbness and it would last for a very long time so if you had a domino surgery for example you would have pain relief for we estimate for something like 24 hours which hopefully would mean you wouldn't need any narcotic drugs after the up raishin which as people may be aware one of the major problems we have in the health problems we have now is his diversion of morphine like drugs and drug dependence and drug over overdose so if we can come up with a medication that enables us to stop using these morphing like drugs that would be a great step forward dr edge here's an interesting one why am i the only person who has difficulties hearing and understanding when speaking on a cell phone I think for for people who have some hearing loss cell phone uses is extremely difficult so you know obviously it depends on what cell phone you have and how how good your signal is but for for people with with hearing loss understanding speech is really the critical thing and and and it can be very difficult especially usually the complaint is that it's hard to understand speech when there's background noise so if you're in a in a restaurant or a cafeteria you're trying to hear the person across from you but there's other sound coming in that that's one of the first things that is lost the ability to do that when there's a significant amount of hearing loss talking on the phone is obviously a another problem and and actually there are speaking about technology not something that we're doing but there are all sorts of new devices for for the deaf people who are completely deaf to be able to communicate you know with devices that that instantly transmit them a text rather than rather than voice so there are there a lot of advances I think in this kind of communication for the deaf but but yes understanding languages is often the first reason the first sort of symptom that people notice when hearing is getting worse here was one that was addressed to to me how does the brain process short and long-term memory and why do some people have better long-term memory than short-term memory or vice-versa what's remarkable about the sensory experiences that we take part in in our daily lives whether it's vision hearing feeling smelling tasting those are all taken to the brain in the pathways that you've seen described discrete ending in the parts of the brain where those are perceived if an event has a significant emotional component to it or is triggered by the impact of how it connects to your everyday experience in more than just the mundane way of getting on the bus in the morning and traveling downtown and getting off the bus and going to work you don't bother remembering that but if you're involved in an accident on the way to work you'll remember that and the emotional aspects of the event will take a process which collects the information from all over the brain whether it's visual hearing smelling and we'll pass it to a part of the brain called the hippocampus which will strengthen the synaptic connections associated with that memory the visual the auditory all the components and will in strengthening the connections in the brain make that memory potentially retrievable at will subsequently now short-term memory fails in Alzheimer's disease sometimes in head injury sometimes in encephalitis a viral involvement of the brain when the hippocampus itself is damaged and that process of strengthening the synaptic connections is taken away and so a patient with severe Alzheimer's disease has trouble remembering things for more than 30 or 60 seconds and it disappears as we age most of us tend to have a repository of memories that we have thought about over time in many different ways and they tend to stay around whereas the ability to make the new memories which depends upon the hippocampus amplitude in energizing synaptic connection fails here is another one if the pain receptors become selectively blocked during neurologic disorders treatment will the patient be susceptible to difficulties in everyday life such as those you mention at the beginning damaging their body with extreme temperature foods tongue biting not feeling symptoms of other conditions in other words congenital insensitivity of pain is an example of that but how would you take the drugs that you want to use and help make them an effective selectively with the drugs need to be used in a context such as post surgery or during labor where again the patient would not then be exposed to to potential danger in the environment you certainly would not want to switch off the capacity of the individual to react to noxious stimuli we've all the time as we sit here we squirm in our seats not only because we're bored but because we feel discomfort because the blood flow to our skin is disrupted that causes pain we move a network that allows the the blood to be restored so these are absolutely critical and switching of the pain system will have to be done in a in a very controlled fashion and only for discrete periods of time okay doctor edge about hearing in the case of someone with impaired vision or blindness how do you explain the person's superior hearing ability can you attribute it to some physiological change or adaptability well maybe that's a better question for you this the and the reason I say that is this is really a central question I mean I think that that is a real phenomenon and that the brain recently you know within the last 10 or 15 years I think we've discovered how what we call plastic the brain is it really is changing it had been thought that once you had your neurons that's it but there's more and more evidence which maybe dr. Martin can comment on that you do adapt that neurons are constantly being made and and connections are constantly being remade and so in in a in an event of sensory deprivation from one of your senses I think that's I I don't know the scientific literature on that but I'm pretty sure that there's evidence that other systems can ramp up and start to have a have an even stronger sensory ability to yeah I would add two aspects beyond that the first is a developmental aspect if you're born blind the brain actually develops a larger region that is capable of hearing if you're born deaf the brain has a larger area physically for vision now does that happen in the adult yes experiments have shown in the somatosensory or the feeling system that dr. Wolfe spoke of that if you interrupt the input from say part of the hand this has done been done in monkeys this is a kind of work that you can do in in high primates and your measure the loss of the input from the nerve that's been cut and then follow the inputs from the nerves that were not cut right in the same region of the hand you can actually show it they sprout and take over the space that was lost from the nerve that was cut and Mike Marisnick at the UCSF has done fantastic experiment showing that so the brain is capable of recovery of restoration of function through synaptic plasticity when specific sensory inputs are interrupted here's an interesting one how badly does lack of sleep affect the brain each of us will take raccattack it's it's an interesting question because it underneath what is the implication why do we sleep if you think about it in terms of the evolution of organisms where the thing the environment is danger within predators and yet we see makes us incredibly vulnerable so what why do we do it why do what there must be something so important that we've that that overcomes our need to protect ourselves and be aware of our environment because sleep in the context of sleep we switch off our awareness of the environment and almost certainly it relates to something that dr. Martin mentioned before which is the way in which we consolidate our memory the way we and what seems to happen is he's mentioned a structure in the brain the hippocampus which receives information during the day and then when we sleep it consolidates it it turns it into permanent changes in the our circuitry so we now have a permanent record of what of the salient features of what happened in that day and this is so fundamental that if you deprive an individual of sleep their behavior begins to deteriorate and in fact if you deprive an individual of something like five days sleep some individuals start to actually die so sleeping is absolutely critical for the normal functioning of the brain I work in the area of pain and what is clear to us is that there is a not surprisingly if you have the severe pain that disrupts your sleep but the reverse is also true that if you have Leslie the or pain gets worse so there are when we talk about pain or hearing or any of these other functions they do by themselves the brain is a very complex organ where there's an integration of activity and certainly sleep is one of those fundamental common features of the brain another question which is is very timely in terms of its importance to patients what is tinnitus some people pronounce a tinnitus but tinnitus is the usual pronunciation and why does it occur with vertigo and loss of hearing is this neuro based or what is the mechanism right right so that that's that's a very good question for those of you who don't know tinnitus is really ringing in the ears and so someone is actually perceiving sound that's not there it's sometimes been compared to the sensation that people have when they're when they've lost a limb but they still perceive that the limb is there so there's something going on centrally again this you know sort of the theme of today is how about how the information gets from the periphery to the to the to the central nervous system there's something that goes wrong in the communication between the ear and the brain in tinnitus tinnitus is actually very poorly understood the the problems of deafness that I was talking about today are very well understood you know we know exactly which cells are involved we know what causes their loss and so we can work in straightforward ways on on cures then the main problem with tinnitus is a clinical entity is that we really the Sun as scientists have very mixed opinions and and really a very poor understanding of what it is and as the questioner asks or states this is true that hearing loss often does go with tinnitus so that's kind of like the phantom limb that I was talking about it it can seem like there's sound even there is no sound and and many patients does these two go together loss of hearing and tinnitus but there's also people who think that that and there's evidence that most tinnitus comes from central mechanisms it's really that the the neurons in the brain are perceiving sound that isn't there even when there's no sensory sensory input and so I would say you know that this is a case in which before really good treatments for tinnitus will be available we need to understand better what it is there there are a lot of drug trials going on right now for tinnitus I've heard that some of them are having some limited success in some patients but generally patients often are treated with anti-anxiety medications which can be very helpful different people react differently to some ringing in the ears some people if it's not too severe can sort of take it in stride others are really driven to distraction by it so you know the best the best treatment we have right now is to try to calm the person down if it's if it's really interfering with their with their life but but I think that this is an important future area of research that that really we're not going to make huge progress until we understand it better thank you here's a very perceptive question how would mapping the brains we heard a big announcement today how would mapping the brain be useful if the brain is always changing a map is a static representation these are if you want to calm it on that well I think the mapping that's true there's there's an anatomical map which is the the connections between the components of the brain and there's a functional map which is the way it operates and I the map that was described today that the president announced that the NIH and other bodies are to fund will be aimed much more at the functional side what what are the codes that enable populations of neurons to operate in a way that generates these complex functions which is our capacity to think to feel to act and what we've managed to do so far is to identify the way that single neurons function and from that we can deduce the way that simple pathways operate what we've been much what we haven't been able to do though is to look at the way in which tens of thousands of the of the of the very large populations of neurons that make up the brain operate together and that's going to require new technology and a whole new kind of mapping and it's and maybe the map is not the best analogy that it's it's because in the end this map is going to be more like a supercomputer whereby there will be in very complex simultaneous operations in in large networks of neurons and it is and that will constitute this dynamic and there certainly will be dynamic functional map so I'm going to use this set of questions as a kind of move to a different set of topics are there specific foods we should eat to maintain a correct protein balance in synaptic gaps is there a diet to reduce sodium channel transmissions of pain that's quite an easy one to answer the answer's no so dietary supplements may be very popular but unfortunately most of them do not do not do much more than have been generate profits for the the companies that sell them and certainly there is no miraculous new dietary food that is is going to reduce pain having said that that doesn't mean that there aren't natural compounds that do effect pain I've mentioned one capsaicin which activates pain and morphine which is extract for poppings which reduces pain and no doubt there will be many more and they are part of the kinds of screening operations that dr. edge described involve compounds from from from natural compounds that we look to see which the ways in which they can act on a nervous system however unfortunately there's no simple dietary compound that is going to switch off the pain system yeah I would agree with that and I would say oh it's not this this kind of advertisement of vitamins or foods that can you know restore your hearing or make your hearing better I think it's I would stay away from that this is a neuro ethics question and I think it has a significant intent behind it knowing that there is a vibrant deaf community composed of phenomenal individuals I cannot see your work is any different than the active practice of eugenics please speak to the neuro ethics of your work to help me and others like me understand how your work is different well this this is a position that I respect and those of us working in in trying to restore things like hearing or vision respect particularly in the deaf community there is in fact a very vibrant community and I think that they are correct in in not wanting to have this have deafness seen as a disease and we try not to speak of it that way on the other hand most of the feedback that I get from the general public about the work we're doing is is extremely positive that you know there are there's a real difference of opinion among the deaf community about you know whether they actually want treatments to cure their deafness or if they feel perfectly happy the way they are using signing and having a community that's really really based on that so I I don't I certainly don't object to that to that view but but my my personal view is that if this is something that that someone feels can help them then it should certainly be made available to them no one's going to force someone to to have a treatment for their for their deafness thank you very much for that thoughtful response well that concludes our question period I apologize to any of you who didn't have your questions selected but these have been a wonderful collection of the kinds of issues that that we as scientists and neurologists face and I thank you so much again for your attention

Channel: Harvard Medical School

Views: 56,501

Keywords: Harvard Medical School, Longwood Seminars, neuroengineering, neurobiology, hearing, pain, Joseph B. Martin, Clifford Woolf, Albert Edge

Id: UundYpS6Ynk

Length: 91min 24sec (5484 seconds)

Published: Fri Apr 05 2013