Stanford’s Initiative to Cure Hearing Loss

well thank you very much Nora it's delightful to be here on a winter evening and as a winter evening even though I'm an otolaryngologist my own larynx is slightly less than in peak performance at the moment so if you hear me a little raspy I'm getting a little weak god forbid some of you have hearing loss my usual ear doctor projection is toned down a little bit now there are three parts to what I like to share with you this evening the heart of this is to tell you about an initiative which we hold very dear and we're very excited about which we've recently formed which is a ten year initiative which seeks to cure hearing loss major forms of hearing loss in a way analogous to the way we have cured polio or the way we have cured smallpox and I'm going to tell you more about that large scale integrated research initiative in a little time but first to help you understand the why and wherefore about it I'm going to teach you a little bit about the human ear and how we hear and how hearing goes wrong and then we're going to talk about the initiative and I'm going to explain to you about the science of regeneration not starfishes building another limb but actually how the human ear potentially can be rebuilt and repopulated with the cells necessary for hearing and then finally if we after our discussion if we have a little time for some fun I'll tell you a little some neat things coming about devices that fit into the ear not just for hearing but that guy walking down University Avenue throwing his arms in the air is not necessarily schizophrenic anymore they're often talking on a Bluetooth and that means a great deal going forward and we could talk about that now this is the human ear of course and the ear has three parts it has an outer part that consists of the ear canal and the ear drum three little bones that carry the vibrations from the eardrum to the inner ear a cochlea which looks like a snail that takes those vibrations and converts it into nerve impulses and sends those on to the brain where they're then understood as a sound now just to give that sense you see the vibrations of the air striking the eardrum going through the cantilever chain to the inner ear and the inner ear breaking up all the different notes on the piano keyboard and presenting them on to the nervous system in the brain now you're looking now at the middle ear and this is consists of the eardrum and the three bones and basically what it does is it gathers in vibrations in the air from a very wide surface and it concentrates it on a very small surface and pumps it into the fluid filled inner ear the name of this structure is the cochlea which is simply greek for snail you'll find most medical terms refer to some kind of food or a common object even though they sound very fancy as a matter of fact I had a call from a patient in Athens and I had to explain you know I'm an otolaryngologist that means an ear nose and throat doctor and she sort of said huh of course I know I'm Greek so this is the human cochlea and you can see it is a spiral with 2 and 3/4 turns and a couple of different chambers the vibrations flow upwards and back and they're displacing this membrane in the center where the sound sensing cells live called the organ of Corti and if you think about it this is the cochlea splayed out and imagine the way vibrations go up if I took a jump rope and tied it to the other wall and started to go back and forth and did it at the same rate eventually you'd have a standing wave and that's just what happens in the inner ear and every sound has a unique standing wave now as you might imagine human speech or music has many many different waves all together in a very complex pattern and here you can see that a low frequency okay a low frequency has a certain unique area in the cochlea and a high frequency a unique area now we're taking a microscopic glimpse inside the business end of the inner ear and you might say why am i showing you this I'm showing you this because it's very relevant to what I'm going to tell you about how we fix broken ears and what future science brings this is the organ of Corti with the hairs now what those hairs do is they take the vibrations and they convert those vibrations into nerve impulses that are understood by the brain now the cochlea is like a battery you think of these little hair cells we've got engineers right this is the Silicon Valley anybody who's not an engineer raise your hand I'm just kidding so these are variable potentiometers basically there's an electric charge and when the hair bends current flows through as you see depicted by the battery now here you can see the human organ of Corti drawn beautifully by a wonderful artist I've been working with for many years by the name of Christine gray lab and you can see that there are rows of outer hair cells and three rows three rows of outer and one row of inner hair cells and the bottom of the hair cells attached the nerve fibers that are part of the hearing nerve enroute to the brain and here's an animation done by my colleague Nicholas Blevins Nicholas Blevins is a brilliant ear surgeon but he also is a very skilled three dimensional rendering specialist and he does these animations so you can see the hair cells inner and outer moving back and forth and that's how the inner ear takes vibrations and turns them into nerve impulses and this just shows the ranks of hair cells the way they exist in the inner ear and hair cells are contractile you see bouncing back and forth when you stimulate them they're like little muscles forgive the rock music and in fact we have a wonderful auditory research group at Stanford we have about 70 people doing research on hearing and seeking to restore it this is Tony Richie who is a physiologist of here and he made a fundamental discovery which was listed as one of the top ten discoveries in all of science at Stanford in the last few years and this was about ways that these hairs actually cause sound to be passed on to a nerve now once the sound passes from the hair cells it goes down little fibers into the nerve and from the nerve it passes up through the brainstem and to the brain to be understood as a sound and then integrated with vision and integrated with the language sense to give you an image of what it means and to understand it now let's begin talking about sound and how hearing is tested hearing is tested in a soundproof room by a professional called an audiologist to understand hearing you need to have some conversin see with sound now I'm speaking at perhaps about 70 decibels the threshold of hearing for a healthy young person is about zero decibels I didn't say a teenager because they all listen to amplified music with their iPods and they start to lose hearing when they're teenagers these days as we'll talk about later and then of course a very loud sound like standing next to a jet airplane on takeoff is in the order of a hundred and thirty decibels and if you were to stand there all day you'd rapidly lose your hearing now we we measure hearing loss just like they do in vision you know envision it's 20/20 right you can see 20 millimeters at 20 feet well there's no exactly 20/20 in hearing but 0 to 25 is normal it's kind of like golf low number wins right if you're over 90 you have very severe hearing loss which means before you just hear a sound it has to be extremely loud now there are two things with hearing and everybody here who is over the age of 50 knows this one is how loud is it and two is how clear is it so we all go to restaurants especially older men including me and everybody's talking and I know they're talking I just can't make out half the time what they're saying so clarity is very important and we also test the clarity of hearing so this is and what an audiogram test looks like across the top access our frequency just like a piano keyboard the low notes the middle notes and the high notes and going down is increasing loudness so a person with hearing here is normal and here is a severe loss or worse so here's the red right here and the blue left here and this is perfectly normal hearing all the way across the spectrum this would be someone with no hearing whatsoever now what's the most important thing we listen to people talking well human speech is in the range from about five hundred to three thousand cycles perception but what's important to realize is that different parts of speech are different frequencies vowels are in the lower pitches ah e o now consonants are in the higher pitches now we all know that when you get in a noisy place and as you get older your high frequencies go away and that means it's harder to tell the consonant parts of speech so if I say hope soap coke Pope well it's hard to hear that now of course if I say a sentence I went to the bath and picked up the you know it's not Pope you know it's soap so you know what in context you hope at least all right but there are times God so the most common reason we lose hearing and it is a huge public health issue you know as we grow older we lose hearing and as folks get older it begins to be one of those things that makes your world get smaller it's harder to go to restaurants it's harder to go to live theater it is harder to enjoy many friends sitting around a table and that gradual loss of hearing with aging as we live longer and as we as seniors are active and want to live full and diverse lives it becomes a very difficult thing causes a great deal of suffering as we get older now here's what you'll see is that the high pitches way out here begin to go down this may be someone at the age of 40 50 60 and you see it going down and as it goes down it affects more and more the high pitch areas where consonant sounds in speech are located yeah but it never people don't go deaf merely from 18 they become hard-of-hearing and this shows you the average hearing as people get older shown in that way now the second most common cause of hearing loss is simply from working and loud noise or recreational loud noise and you know if you ever listen to rock music did you ever wonder why there are no Piccolo's in a rock band they don't have any high pitch hearing laughs it's all about boom baboom low frequency kinds of things and of course people who've worked in industry especially with loud explosions and impulse noises lose hearing over time and what you see with noise induced hearing loss is a notch in the high frequencies that's very characteristic and if you continue working in a factory or not protecting your ears and listening to music and judiciously loud it will gradually wear away now many of you have taken your grandchildren to the Disney on Ice where it's incredibly loud or something like that and then at the end of going to that concert or at the end of working with the chainsaw in the backyard or a lawnmower that's loud your ears feel a little Hollow and they ring if we did your hearing test right at that time your hearing has detuned and you might look like someone 30 or 50 years older than you really are and some of those hair cells bend over in what's called a temporary threshold shift and if most of you have experienced this and if it's loud enough to do that it's allowed enough potentially to harm hair cells and to cause a gradual deterioration in your hearing and this shows what happens after exposure to a loud noise these are healthy hair cells and here you see they're bent over and over time they begin to drop out and they begin to become formed as hearing deteriorates now hearing loss due to noise is very much preventable simply stuffing cotton in your ears as those of you are in the military right where they used to do that the cotton is like a picture window for sound it just lets everything through but you can go down to the local pharmacy for 99 cents and pick up some foam rubber ear plugs or for about 12 to 15 dollars over the ear muffs and they're very effective at protecting the ears for those of you who are techies um your iPhone can have a little app that measures the decibel outlet it cost 99 cents in the iTunes Store and if you're down with your kids and you're wondering just how loud it is where they are you can actually measure rule of thumb if it's less than 90 decibels on average it's okay if it starts getting up above that it's starting to be of more concern now just a brief mention of some of the causes of hearing loss aside from the two major ones there are of course to keep ear doctors well employed hundreds if not thousands of causes of hearing loss but a fascinating area is genetic hearing loss and a substantial number of children are born with flawed inner ears and develop hearing loss instead of over a 90 year lifespan over a 15 year lifespan and it just like they went through a very rapid aging process others are born deaf or born with ears that are unstable and and are not a very very sensitive to wear and tear from loud noises for example what we now know is that there are over 200 genes that code for deafness in the human genome furthermore it is on all 22 of the chromosomes which tells you throughout all of the human DNA there are unique genes essential for hearing as a matter of fact you might say years ago just a few years ago we all became aware that we'd clone we had sequenced the human genome it was all over the news we sequenced it well what good is it what next well once we've identified the code the DNA code for a gene we can elaborate its protein product and if we know its protein product we know that this particular protein be an enzyme that speeds up reactions or a structural protein we know that that protein was essential for hearing so we have all these sort of Sherlock Holmes clues now this protein in that protein and this are important to how the human ear works from learning that we're getting great insight into the molecular machinery that underlies hearing now an exciting thing is we have a wonderful geneticist Myrna Mustafa who's an auditory geneticists in my department and what has happened now is that you can actually screen using something called a gene chip where with a single drop of blood it will compare a library of known genetic disorders and will be able to screen all of the known kinds of hearing loss quickly and relatively inexpensively it is a junction between solid-state computer type technology along with wet bioscience very exciting possibility now I'm mostly going to be talking about the inner ear because the inner ear we have almost no cures for today not none but almost none on the other hand I'm going to start by talking about the middle ear because you know the great triumph of ear surgery over the last 50 years is that we've conquered almost all diseases of the eardrum and the hearing bones and this type of surgery for this kind of problem is quite routine now it involves operating microscopes some of the operations are done working through the ear canal literally through a tiny little opening doing it's almost like watchmaking if you will very delicate kinds of things you know you look at the tiny little instruments and little scissors these are the size of a head of a pin but it allows us to operate on areas like the human stay Pease bone stay Pease is simply Latin for stirrup as in horse stirrup and here you can see the job of the stay piece just like a piston in a car it gathers the vibration and it pumps that vibration into the fluid filled inner ear now here's a disease called otosclerosis odo ear sclerosis hardening and you can see the hard the ear around the stay peas bone so that when the eardrum vibrates that stay peas bone is now resisted from the calcium and we can take and remove the upper arch of the stay peas and replace it with a little piston and I'm going to show you some new drawings that Chris gray laughs and I have just done in recent ones to give you a little feeling for how this is done here's the ear canal and ear drum here's the hammer the anvil and the stirrup now we've moved the ear drum aside and the surgeon is measuring from the second bone the incus to the footplate the bottom of the stay peas were then severing the joint you have to remember the size of this is the fraction of the size of a head of the pin we're then checking that the other two bones work we're move a little tendon remove the upper part of the arch with Chris's art you can imagine it going click here with the drill this drill is 0.6 millimeters in diameter and then placing a tiny piston and then crimping that with a little clever tool that allows you to tighten it and then here we are at the end and when this ear drum is put back in position and vibrates the linkage goes through this artificial hearing bone to the inner ear and has a very high likelihood of restoring normal hearing if Beethoven were alive today we probably could have brought back his hearing although I understood he did his ninth symphony while completely deaf which is extraordinary now other hearing bones can be replaced as well you see these little replacement prosthesis they're usually made of titanium today so that we're not talking about problems with the hearing bones because we can fix those with today's technology similarly if you have a hole in the eardrum we can go in behind your ear and take a little lining of the muscle a gray membrane that's just the right shape for the eardrum move the eardrum aside place a little bed to support it and then put in the membrane lay back to your drum and you see the membrane here 95 the time we can fix broken eardrums routinely today and sometimes we need to use fancy things like laser beams and the reason for that if we're touching the hearing bones here's the upper part of the state piece every time the surgeon touches it it's like an explosively loud sound and it could injure the inner ear so the beauty of the laser the laser is not a miracle beam it delivers heat in a very precise way but when you touch something with the laser it doesn't make a vibration the way it would if it was your hand now many of you may have heard about cochlear implantation so earlier I told you there wasn't a great deal we could do for inner ear hearing loss but I will tell you that total and abject deafness has already been cured in large part if a child is born deaf today they don't need to learn sign and live in a deaf institution for special education now listen deaf culture I celebrate deaf education and sign language in its own sense can be wonderful but if your child only knows how to sign you can't go to Safeway and ask how much canopy's is you know it's not an oral widely used language there is a device called the cochlear implant which is a multi-channel electrical wire that goes into the inner ear and it stimulates the hearing nerve now here's something that's really key to understand and why our whole initiative to cure hearing loss will work and that is that even though people talk about nerve deafness it isn't nerve deafness deafness is almost always loss of those little hair cells the sound sensing cells within the inner ear and what this device that's grown up over the last 30 or 40 years does is it has little electrodes that directly stimulate the nerves of hearing bypassing the need to have hair cells these adults and children if you're totally deaf it will bring back hearing but let me be clear it brings back partial hearing it doesn't bring back normal hearing it's also a very expensive and fancy device that requires surgery and this just shows a little bit putting this as the device against the head showing how the wire is uncoiled within the cochlea now I want to share with you the main reason we're here tonight which is the Stanford initiative to cure hearing loss this is an initiative which is large-scale it involves a number of disciplines and our goal is to within a ten year period to bring to clinical trials a cure for sensory inner ear hair cell deafness now Helen Keller had a unique perspective she said you know blindness separates us from things but deafness separates us from people the ability to hear our fellow man is central to what we are as human beings the ability to communicate with friends and family and co-workers to listen to music is essential the loss of hearing is a great isolator two or three out of every thousand children are born deaf half of all seniors over the age of 70 have very significant hearing impairment and that can contribute to depression and isolation there are about 36 million Americans with significant hearing loss and there are hundreds upon hundreds of million around the world in children hearing loss impairs the ability to learn it limits ultimate occupational choices and it leads of course potentially to social isolation now our initiative to cure hearing loss is not like most scientific initiatives most scientific research goes on in incremental ways the war on cancer been very productive over the last 30 years but billions upon billions of dollars are spent every year and yes we're making inroads into childhood leukemia yes we're making in lodz into breast cancer however we have not categorically and fundamentally been able to cure cancer yet but we believe where we are today in 2012 with what we have learned in with breakthroughs in the last decade that we sit on the cusp of a time through regenerative means that we believe that we can categorically cure a large percentage of inner ear hearing loss whether they be children or adults in time now I don't mean that's going to be in the next five or ten years I think we're going to begin in the next five or ten years but I am quite confident but by the time some of your grandchildren and children are of age that we will have the ability much as we can already for disorders of the eardrum and hearing bones that the much larger number of people with inner ear losses we can cure them now this book stem cell for dummies you have to realize I'm a surgeon and I teach this to surgeons so I like to call it stem cells for surgeons and they're about equivalent don't quote me now what does the stem cell alright a stem cell is a spherical cell which when injected into a laboratory animal produces a scientific paper actually what not exactly okay now what a stem cell is it is a what's called a pluripotent a cell which if it is manipulated by clever molecular steps can make many different types of tissues now when you are in embryo when you were developing inside your mother you had many primitive cells that became brain or heart or bone and in fact you have them in your body at all times everyone in this room have stem cells of one kind or another in their body you are constantly producing blood cells and you do that from stem cells that exist in adults in your bone marrow now I'm going to go back to what we looked at before this is the healthy organ of Corti with hair cells and here we are having lost the outer hair cells this is someone who's starting to get pretty seriously hard-of-hearing here is someone with no hearing at this frequency and if it would look like this with no hair cells throughout the cochlea you would be utterly deaf so here's our challenge we have all these nerve fibers over here but this epithelium lacks cells so we need to be able to restore the hair cells there and this is just my colleague dr.

Blevins illustration in animation of how hair cells die the outer hair cells and then the inner hair cells and then the nerve fibers lie there waiting for us to bring something back now you might say why the year I mean they're all these organs in the body we're always talking about regeneration of the brain in the heart and the spinal cord and things like that well tell you why most organs in the human body when they're lost take for example the liver if you've lost your liver all you have is a scarred hard little rock hard ball with no architecture remaining no collecting ducts no bile conduits whereas when you've lost your inner ear the elegant cochlear spiral remains the hearing nerves are splayed out like a piano keyboard in it from all the frequencies it sits there ready with its architecture preserve the target to restore this organ to function is a much lower bar than it is for many other organs now what are some of the concepts that we use so imagine this membrane of hearing cells of hair cells and the black areas are damaged you've lost those hair cells so one of the concepts is to regenerate and re-implant now for those of you interested in Rogaine and baldness that's not the hairs I'm talking about I'm talking about specialized sound sensing cells in the inner ear now conceptually in a very simple sense there are several ways one could do this one could take these scar membrane cells and trans differentiate them using molecular triggers and special markers to change them into a hair cell the problem with that is you would run out of cells pretty quickly even better is proliferation you see this scar cell is being manipulated to divide and the daughter cell becomes a hair cell this just gives an illustration of that from dr.

Blevins showing how in a deaf ear we've manipulated this is all conceptual of course and how a nerve fiber you might say god that's a miracle why would the nerve fiber do that I'm here to tell you that when you implant a stem cell into the ear and it differentiates into a hair cell the nerve fibers grow and link up with it it's a God down miracle but that's what happens now how would you go about doing this now it turns out there are a series of different methods that you could use in regeneration and I'm going to share with you these now our initiative engages a series of different lanes if you will we have groups of scientists working in gene therapy and molecular modulation I'm going to explain all these developmental master jeans and even electronic things we're going to focus our our efforts in all of these areas and the ones that look most promising we're going to concentrate our resources to move forward now the first I'm going to mention is gene therapy what you see depicted here is a virus with a little snippet of DNA within it and that virus is going to attach and communicate and here you see the virus attaching to the scar membrane injecting a specialized piece of DNA which leads to the cell transforming into a hair cell this is not science fiction this is science fact even better though when you take a virus and you put it in the human body you'd like it to stay where it started you know you don't want that virus injecting DNA where you don't want it to go and it's very hard to keep a virus put in the body in one spot so what we are looking for our molecular switches that is to say small molecules small peptides which are biologically active that will actually cause things to happen within the cell now you might say what things think about it this way a baby an infant at the two cell stage right has in the DNA all of the instruction set necessary to build a whole human being you have that in every cell in your body in fact today but it's all been switched off now what we've learned about the development of the inner ear and the way that it happens in embryology inside a woman building a baby is that those steps and stages can be rekindled in adult cells it's very exciting and furthermore excuse me it's okay I get it so what happens when you operate today become popular so that let me go back to this because you might think that for those of you inclined to understand biology you might think the steps in human development to build an inner ear a cochlea within a fetus are very very complicated and include a credible number of substances that have to appear and then stop and new substance come in and that if you did it wrong you we would all have two heads and three fingers right it would all be wrong but it turns out that there are master developmental regulatory genes in this case something called a tonal homolog one or 801 which is drawn huge attention because if you switch that gene on in in a cell in the inner ear there's a self-organizing cascade of molecular events that lead to the formation of a hair cell furthermore Stephan Heller who heads my lab has found ways of doing this in these cells that used to support hair cells where the hair cell has died that can be manipulated to turn into hair cells and function now everyone knows about stem cells but that's a very simplistic concept so what we're really talking about here is cellular therapy but many of the cells that I've been telling you about are actually the cells within your body that can be influenced to change and proliferate downlines productive to replace lost things now cellular therapy talks about bringing in we've all heard embryonic stem cells for example from an embryo and you know people have looked at umbilical cord but more and more we're talking about induced pluripotent cells what the heck is that taking something from your body skin fat and from that teasing out cells that are mature and bringing them back to a pre primitive state and then from that state proliferating them and then bringing them back up to the end product that you want to make so the likelihood in the future is that stem cells will be about taking the person in need of somethings own cells and converting them across to form the tissue that you need so this shows a stem cell transplant coming into the scar membrane in the inner ear and repopulating hair cells now there are a number of ways those stem cells might get there we might inject them in the ear and they would be designed to attach to the scar membrane one place or another they might be injected in the bloodstream and of special affinity markers for the cochlea and you know there are other things that are coming about through this for example there are many medications and chemicals that will damage the ear and our group is working on blockers that are designed to protect the hair cells which are damaged to protect them without a protective substances right so that you don't lose it to begin with now I'd have to say that based on what we know as of today that I am greatly optimistic that in time that we will overcome inner ear hearing loss I don't know whether it will be through stem cells or whether it'll be through molecular modulation by that I mean I should explain that there are functions in the cell for example the gene I told you that gene that master regulatory gene that gene may be switched on may be up regulated by a small molecule and you know there are now machines that will search through libraries of a hundred thousand or three hundred thousand small molecules against this one gene and it's just incredible robotic automated system that will help you identify this now I want to pay homage to Stefan Heller a Stefan Heller was the one who first identified the presence of stem cells within the adult inner ear and he is recognized worldwide as the leader in this field he has built in my department at Stanford Wood is widely recognized as the world's leading program striving to regenerate the inner ear it isn't very often that a search leads to the sunday New York Times article this is about Stefan Heller whence and this was in a Boston newspaper Stanford steel stem cell doc from Harvard our Dean who is from Harvard loved this was also in the Harvard Crimson what's wrong with us we're losing these great people to Stanford you can bleep this off the tape please the daughter there but and this is one of his early paper showing stem cells from the adult inner ear and just a year or so ago a Stephon was able in his lab to create functional stem cells and they're just a huge number of details that I really can't go into tonight but I will tell you in a tree cuz I didn't expect it Stephan Heller is in the back row and a question time you can talk with them so it's not very often it that the doc talks you get some good docs but you don't get world-class scientists very often so thanks for coming Stephon we have a great team of folks that are involved in auditory research at Stanford including people in genetics and physiology and and they all work in a collaborative way together bringing different skills because you know Stefan and his group may produce a cell that as hairs on the top and looks and seems just like a hair cell with this markers but unless a physiologist looks at it and says that thing works electrically like a hair cell and someone who can do hearing testing and an animal to prove that that animal actually has hearing your story you really don't have the full package in that way we even have that rarest of breed the surgeon scientist some of us think that's an oxymoron ourself canceling phrase but we actually have ear physicians and surgeons who are very fine scientists who work together with basic scientists helping to bring these innovations in the basic science laboratory towards human use and some of the things that are being done are developing miniature endoscopes little tiny viewing portals that can look inside the living inner ear this is hair cells within the living animal inner ear these are the blood vessels going directly to where the hair cells live in the inner ear this is Nick Levin and Mark schnitzels research John ogle I is both engineer and surgeon it's a wonderful combination of things and John is able to non-invasively image inside the cochlea using things like optical coherence tomography now it takes a village it's a large group of people sometimes they look like a high school from gun or something but it's an incredibly talented group of people that are involved in this research there are a large number of people coming from all over the world constantly to learn from Stefan and his colleagues if you look at what how this program has grown it started about 2005 and our research expenditures were almost nil at that time the Andrew annual research expenditures are about six and a half million dollars now from this group and this group is rapidly growing and part of the reason we share this with you that if there are those amongst you interested in helping this vision to happen you know research is an engine and it is money which drives the engine forward there's no question that we and other colleagues like us around the world will be able to achieve these goals much better if we have the resources to move this forward we actually have a group of people with means and with friends with means who meet together with us every few months and that we have now this website you have the front page of it about our initiative the Stanford initiative to cure hearing loss and if any of you are interested in helping to talk with us about this we would be delighted to chat with you or have you come and visit our laboratories to learn about it we have actually four endowed chairs that's me just kidding and which is great and you might ask why Stanford you know why is this growing up here why is this growing up now well then now is the easy one the discoveries and the technology have reached a right phase why Stanford we have the world's most sophisticated regenerative medicine Center the law real okay building if you haven't visited it yet has a beautiful Chihuly sculpture in the foyer it has an incredible group of people not just working on Deafness but in many different areas and there are people a large number of them working just on the fundamental biology of stem cells and of regeneration and developmental biology and we very much integrate and work with that group in order to bring that expertise and broader Stanford science to the focus purpose of overcoming deafness we also collaborate as you might imagine with a number of entities across engineering computer science and other areas at Stanford so our overall goal is to cure a deaf mouse in five years and a deaf human intent do you have any questions or any comments and Stephane may I bring Stephan up definitely come on up if you don't mind let's give them a round of applause you're gonna need to stand by the mic Stephan I think questions yes ma'am and I'm gonna repeat them so others can hear yeah the question is can certain diseases such as pneumonia wipe out the hair cells Stephan I'll do that that's a medical one pneumonia itself seldom would the treatment for pneumonia with antibiotics occasionally there are a few antibiotics that might do that now backing up there are many diseases which cause loss of hearing for example people whose kidneys don't work in our on dialysis gradually lose hearing and there are litany of other diseases that do and many other diseases that don't seem to adversely affect the ears for example generally heart disease and diabetes and high blood pressure which are huge health concerns don't really affect hearing yes the question is whether mumps now most you have to be a little older remember measles and mumps because the kids today go what for those because it you know they don't get it today now it turns out measles was the number one cause of acquired deafness and blindness in in rehabilitative centers for children through the 1950s it was a huge scourge mumps interestingly enough is always one ear one testicle and one ear that's why few men were ever made sterile because it's only one side one parotid gland swells up one cheek that's why you look full so mumps can cause it but it's only on one side generally yes ma'am can chemotherapy cause hearing loss the answer is yes certain kinds of chemotherapy can and so one of the things I encourage my patients with pre-existing hearing loss is to mention to their doctors that they have it so that they can choose if possible medications that don't further it in general with chemotherapy it's the Platinum drugs right sis platinum now having said that platinum is a very important drug in the treatment of cancer and we bring many people through treatment with with platinum drugs who have hearing loss by doing things for example like wearing earplugs by using very slow infusion of the medicine making sure you're well hydrated these are things that oncologist cancer specialists know very well but you have to tell them you have hearing loss most doctors don't know they can't tell to look at you by and large yes sir yeah so the question is it sounds like your initiative is on deafness not hard of hearing and the answer to that is our initiative is very much based very much based upon all forms of hearing loss and if you look at hearing loss it's like a pyramid there's a tiny number of people at the top totally deaf and a huge number of people at the bottom mildly affected and then a bunch of people in the middle whose lives are significantly impacted now our goal is to be able to cure aging related hearing loss we want to bring help to millions not to thousands so tinnitus is the question is what about tinnitus tinnitus is ringing in the ear forgive me for just a minute love just tell them call after it's nothing urgent is it it's a patient's family right I'll call after you can cut that from the tape or leave it on there are no HIPAA violations here all right so tinnitus is simply abnormal activity in the hearing nerve you know when a segment of the inner ear has lost its hair cells the nerve fibers going to those become irritable and begin to rhythmically discharge even though no sound is coming into them and because most hearing losses in the high pitches most of us who have tinnitus including me hear a constant high pitch he all the time now there is no medicine or surgery for that however most of us in time just kind of get used to it and it doesn't trouble us some people you know put soft music on in the background when in a quiet room to keep the ears quiet maybe when we can restore hair cells so making those nerve cells happy again that the ringing will go away yes sir so the question was whether the court a organ which is just behind actually the eardrum in the middle ear whether after hearing loss and whether the organs in sight are are are destroyed or degenerated whether it would be possible with stem cells to regenerate this organ and then the the this is our hope this is what we are working toward and then what dr.

Jackler said is the the nice thing with the cordilla organ with the cochlea is that it provides a scaffold the the organ itself is still there but the cells are gone so the only thing that we have to reseed if you can think about just putting in cells that have more juvenile or more more more potential with development that it undergoes a developmental program which reforms the ear as it would form in an embryo this is a dream that's going I mean we will not be able to reach this in one step it's going to be step wise and step wise and then the reason your question was very important with a hard-of-hearing patient which has only lost a few cells and not the whole structure the organ this will be the first group of patients that will actually benefit from this kind of research because getting a few cells back into a into an organ is more simple than getting the whole network of cells to regenerate in there so I think a first step will be to help people who are hard of hearing to give them better frequency responsiveness and an and an ability maybe for hearing aids to work better with them or maybe to replace a hearing aid I don't know I mean we I cannot look into the future but this is a goal for of us and then the next step is to be able to totally rebuild the organ from within but I don't know whether we can achieve this in 10 years 20 years in a decade or two decades but I think we can do the first steps and then in the next couple of years the question is whether or not someone who lost hearing from measles may be able to have hearing restored now contemporary technology excuse me contemporary technology with hearing aids which by the way get better and better they have a terrible reputation but they're coming a long way in recent years and the future is very promising actually for hearing devices but you know the telephone can work only as well as the wire can carry the sound and if the inner ear is fundamentally damaged matter how good the device is it's not going to work this the helping a child who lost the inner ears 30 years ago or 50 years ago from measles who's now suffering in addition from the changes in aging these are exactly the kind of people were trying to help we're not talking about today we're not talking about even tomorrow but we're talking about a reasonably foreseeable horizon using very different techniques that are not available today okay the question was for someone who has a profound one-sided hearing loss that is you said nerve deafness although I will tell you from what I told you it's not nerve deafness almost ever it's usually from the inner ear as of today there are a number of things that can be done with someone with the good ear on one side and a deaf ear and the other half is good well so let me give you a few things and now I'm gonna step back from you know the beauty and dream of exciting research to today's practice alright when a person has a good ear on one side and a bad ear and the other there are three disadvantages one it's hard to tell where sound is coming from because that requires two ears to compare so a person with one good ear and a bad ear is gonna be turning the wrong way sometimes number two when you're good ears on a telephone you're kind of disconnected or if someone sitting on this side and talking with you while someone else comes from that side so it can make it sound like you're ignoring them or being snobbish because it doesn't show that you have a hearing loss so it's good with your friends to tell them but the third thing is the big one to ears filter better in adverse listening situation than one year so when you go in a noisy restaurant things run together when you have only one year now there are a number of clever devices that can help they're not perfect one of them is to take a crossover hearing aid a device that takes the sound from the Deaf side and broadcast it over to a second device on the good side and that will get around the fact that when someone's keeping your good ear busy you're not hearing on the other side there's a very clever device that's just come out called the soundbite where would you imagine the soundbite is positioned on the teeth it turns out the upper teeth root anchors firmly in the bone of the skull and the skull being a rigid body if you vibrated it passes directly up to the ear so that you have a little device on the deaf side that communicates over to the other side to a thing against your tooth that buzzes up to the good ear it's very new it's a little uncertain in the early versions how effective it will be but so far it looks very promising it's something we are one of the beta sites for at Stanford now it is FDA approved but we don't yet have thousands of people wearing it so the question was do iPods cause hearing loss and is that a concern full disclosure I have consulted for Apple before on this the answer is yes they do and that it is of concern when you're standing in an elevator and there's a teenager on an iPod or any listening device and you're hearing the noise the music really loud you know that's worrisome it's probably too loud many of us would like to see these personal listening devices limited especially for young people and not reach levels that would never be permitted by occupational safety rules in an industrial setting in Europe they've capped it to 105 decibel output it's a bit higher in the United States now than is in Europe I think that there will probably be some agreements within the industry and some advice coming out of Congress to help limit that to some degree right it is possible to listen to your ear device too loud and cause injury but that's also true with your television it's also true you know with with a normal music player as well it's not unique to ear devices yes so the question is are they safe if you're not listening to I comfortable levels of sound even if you listen to it 24 hours a day 365 days a year don't cause hearing loss it's only when it's above a certain level that way you know one of the tests whether your life has that kind of sound that I recommend to people when you've been out driving and listening to the radio and you've been driving on the freeway at high speed and you get home leave your radio on the next morning when you come out you turn your car on if you go oh my god you've been running too loud because you add the loudness to the sound of the road noise and the windscreen and all that and that can get up to a level that can for vulnerable people if you take a hundred people and put them in a loud factory some people rapidly lose hearing they have ten years some people left steal ears they can be in a factory for years and not have much loss but most of us are in the middle there's some vulnerability and we'll lose hearing yes sir yes of course yes we have a sizable group of ear specialists that do we usually because we're so specialized asking you to see a community your nose and throat doctor first you know but if you really would like to come to the University we're happy to see you we're tending to see more triples and home runs than singles if you will more people with complicated problems or complicated needs but we do welcome especially with our neighbors and friends here around Stanford community we welcome and we'll do our best to to have you see one of our physicians yes so the question is a good one for Stefan and the question was might the techniques for rejuvenation of the inner ear also be used in other senses for example taste so yeah I think the techniques per se are are are generally applicable and I think there are groups working on regeneration of smell regeneration of taste vision hearing and vestibular sense and I think we all learn from each other so advances that are happening in any of these fields will be translated very rapidly to the other field because we are not in a vacuum we will we will know what other people do so people working on taste and I can tell you they're not so many people working on taste I mean the the the the the biggest health issue issues are actually the issues where people work most on and hearing loss leads to more problems for affected people although I wouldn't say that if you lose your taste or your smell which is connected to the taste that this isn't an issue I think if you if you lose I enjoy wine and I enjoy certain things in life and then they just don't taste as good if you if you cannot experience them anymore so in general yes I would say implementing them into a general clinical practice will probably be delayed and and I've come after vision and and and and and hearing I think these are the two major research areas but it's not that people are not working on it okay I'll give you an interesting anecdote about hearing versus taste and I was on a panel a number of years ago where it turns out there's a little tiny nerve called the chorda tympani that goes through the ear and is sometimes injured in ear surgery and it supplies the tongue and there were a number of people from different countries around the world discussing whether that nerve ever got lost in surgery and one of the surgeons was from Paris and what he said was very simply in a Fleshman navel yes sir there is so anyone essentially anybody who has inner ear hearing loss has also in a quiet room a spontaneous noise in the ear there are some medical ear diseases that give low pitch hearing loss and those people instead of hearing a high pitch he they hear all the time and some people have variable tones so if I were to say that three-quarters of people over the age of 70 have hearing loss that's exactly the same as saying three-quarters of people over the age of 70 in a quiet room hear ringing all right they do if you if I put you in a soundproof room and you have gray hair the likelihood is you'll go yeah but you know what I don't think about it there are a few people a few people that the ringing really troubles and it keeps them awake at night and it makes it hard to concentrate and interestingly enough the loudness of that ringing in those individuals is generally no different than what it is in the millions of others whose brain just adapts to it and it doesn't trouble them right so the question is over time does it accommodate in exactly if any one of us at any time in life the ear suddenly goes bitten and makes a loud noise that happens right and you imagine that if you had a loud screaming in your ear all day it would drive you pretty crazy and you'd feel Laozi about it for time and the rare person who has a sudden deafness in the year it's a kind of person I see fairly often often has a very distractingly loud ringing in the ear for time in time number one the ear becomes less irritable and number two the brain listening to a steady repetitive cacophony of nerve impulses with no other meaning eventually turns the attention away from it and that you accommodate can take months but usually accommodate other questions yes ma'am so the question is is it possible to train our ear and in order to protect our hearing well there are certainly wonderful musicians and singers who train their ear beautifully for pitch and to hear things that most of us don't in fact if you think about the brain some people have enormous visual cortices I think the part of the brain and hearing is much greater in musicians and perhaps much less in men than women but that's another story altogether did I answer your question okay yes ma'am so the question is and it sounds like you had many ear infections when you were young and many antibiotics and you're saying you know my hearings a bit off and people have said you could use a hearing aid if you wanted when with all these advances how long should I wait when's the right time three weeks from Tuesday at 2:00 in the afternoon yeah when it comes to science we can talk about probabilities and and you know but the kind of hearing loss you're talking about and I I don't remember the specifics at the moment if you're having trouble in day to day life that's the biggest litmus test so if you're having trouble understanding people at the dinner table you're having trouble at the live theatre you understand a lot of people today wear hearing aids just like reading glasses you put them on when you need them you don't wear them necessarily all the time but you know a lot of people that have had hearing loss gradually coming on don't realize what they're missing you know often their spouses they're telling you know the typical story as the husband says I don't really have a problem in the wife's going you know he's a terrible problem and so you know just ask your family and friends how much is it bothering and you can always try hearing aids you know by state law you have up to a month after they're fitted to turn them in if you don't want them now what you may be reflecting is a bias from the stigma of wearing a hearing aid let me touch on that you stick a piece of glass and plastic in front of your face right it changes the way you look right but you think somebody wearing eyeglasses is smarter and you think somebody wearing eyeglasses is fashionable you stick a putty colored thing in your ear and you lose 20 points in IQ and you're 10 years older right wrong that stigma just changed you watch all the kids what are the kids doing they're changing it there wearing Bluetooth devices pretty soon wearing a device on your ear is going to be more common than wearing a wristwatch it's gonna become a universal conduit you know 30 years ago we put computers on everybody's desk at home then over the last decade or so we've linked them up and out to the internet but that space between you and the computer that last two feet is still what smith-corona developed in a typewriter a hundred and ten years ago right the man machine interaction is the next new new thing hearing devices the human ear and the human voice will be the first two senses routinely linked man and machine so wearing an ear device for all sorts of reasons it does you don't need a cell phone on your hip I used to have one here you don't need a cell phone on your hip you can have a little thing on your ear cell phone call home voice activation right but that thing that's on your ear can also be your ear pod it can have thousands of songs or audio books it can be your GPS I'm driving down the street to 10:10 main street and it tells me I'll turn turn left in a thousand feet turn left now and I'm walking up to that house John Smith lives there and I say to my ear device John Smith 1212 Main Street what John's wife's name and in my ear comes Mary you have an audio web of course if Mary speaks only Chinese and you have some architectural connection this is coming you speak to me in Chinese and this device will speak to me in a proper British accent or if you prefer Kiwi or an accent from New Orleans this is coming that's gonna take a little time but not that much time before that will come now my point being to your question that once wearing a device on your ear becomes absolutely routine and normal indeed in the central part of day-to-day life there's no stigma to it as a matter of fact grandpa will go to the Senior Center even today and go Hey look at this thing I got man it's the latest you know and be excited about it so the stigma about not wearing it yes sir you look great huh but the stigma for wearing a hearing aid is rapidly going away okay and they're merging the devices today do what Bluetooth devices do they'll communicate with your phone they'll communicate with your iPod so they're really becoming multi-purpose devices in time normal hearing people will wear them all the time and once you've got these things on everybody's ears all you need to do is to build in the necessary amplification for people with hearing loss and it does dual purpose it still won't give you back an inner ear that doesn't work well enough to give you clarity and that's millions of people and that's what we're talking about overcoming but be able with mild losses or losses to the scarring of the eardrum I think we're getting a little bit late Nora how are we doing up to everyone is there a question or two more yes ma'am so the question is if a person sleeps through the radio on all night will it be harmful to the ear no but it might affect your marriage unless he snores in which case he deserves it yes ma'am the first question is when are we going to start clinical trials and the simple answer is absolutely as soon as we can but this is a process that is first led by science and innovation and then leads to very cautious clinical trials and then broadens out now you live in a community where those clinical trials will very likely be tried for the first time in the world so that's an opportunity it is a time away we're at a stage of intensive research I don't mean to kid you that we're around the corner from discoveries that implement to cure hearing loss merely that we have many good sound reasons to feel that that will be coming soon the second question is what's changing and hearing aids and why are they becoming better well most importantly they're beginning to be able to distinguish background noise from human speech that requires very fancy digital processing very quickly when you watch a movie and the speaker's slightly off in the movie drives you crazy so in order to do that you have to have a whole computer built inside this tiny little device at the level of your ear many advances are coming in computer processing and miniaturization today for example they use tricks so a device might have two microphones one facing forward and one facing back and it makes the reasonable assumption that the person you're speaking with is in front of you and the background noise is behind you so it makes a manipulation that de-emphasizes the sound behind and augments the sound in front this is the level that we're at today hearing aids are much better today than they were 10 years ago but they're still not perfect by any means and they are still limited by the fundamental inherent clarity of the ear the very finest piano played loud is going to sound very off to someone now I will tell you that there are new devices coming online and so I'll give you one example can you imagine a photonic hearing aid one that's driven by light so this is to develop it currently by one of our clinical professors in a company called ear lense what they do is make an extended wear contact lens for the ear drum goes way in the ear and on its surface it has a photovoltaic like you'd have on your roof that photovoltaic is hit by two different lasers one laser that's like sunlight it powers it and there's a little micro motor the second laser light goes in and it gives the signal the sound and it powers and runs a motor that directly drives the eardrum fascinating concept in that way and this is under development in a preliminary way it's not yet out but in the preliminary way gives really exciting hearing levels in that way and by having it light driven it gives a tremendous inflammation that information flow and gets rid of all sorts of concerns about radio frequency interference and also it leaves the ear open you know when you put a device in that clogs the ear it's very unnatural for those of you who wear hearing aids you know when you chew your food or hear your self speak it sounds different when you clog your hear right but having your ear open is much better and more natural maybe one or two more questions wrap something for dr.

Heller great thank you very much for coming.

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