>> from our studios in new york city, this is "charlie rose." >> to be blind is not miserable not to be able to bear

blindness, that is miserable. on milton wrote that. more than 285 million people live with visual impairment. in recent years they have been breakthroughs in our understanding and treatment of blindness. sanford greenberg lost his vision to ball, at the age of 19. he is chairman of the board of governors at johns hopkins wilbert eye institute. he joins me to talk about his experience and his mission to end blindness. >> plus jean bennett of the university of pennsylvania. once again, eric kandel a howard hughes medical investigator. i began as i always do with my rent air to review our subject tonight. >> the last program we did was a new approach to the treatment of deafness.

tonight were going to consider new approaches to the treatment of blindness. as is the case with deafness, blindness is not a life-threatening situation but in some ways is more disabling as deafness because, as you pointed out, there are number of very important blindness conditions for which there is no treatment. why is that so? unlike deafness, the sensory organ for vision, the retina which is evident of the lower image which shows the eye, that is the most complex since organ that we have. it is not a peripheral organ. it is actually part of the central nervous system that is an extension of the central nervous system and as a result it has a complex structure. it has a small area and the center that is clear in that image which is called the ma

culqa. -- macula. if i turn my head toward you, my eye focuses on you and the macula really analyzes your features. the cells of the macula are sensitive to damage that leads to blindness. at the moment we have no treatment for that, even though this is a point of great visual acuity. blindness is a range of conditions that range from complete to partial blindness. complete line this means that you don't see images you don't see figures are people. you cannot tell the difference between day and night. this is sandy's condition. arsenal blindness varies from having tunnel vision to having cloudy vision to having night

blindness. you can have difficulty with vision from two sources. if you have a damaged individual pathway that goes from the retina into the brain and carla will discuss that more, but were not going to focus on that as it source of blindness. we will limit ourselves to disorders of the retina. as you indicated there are close to 300 million people worldwide that have various degrees of visual impairment. these fall into two categories. treatable diseases and at the moment things that are essentially untreatable. so cataracts, glaucoma, and diabetic retinopathy are treatable diseases. with cataracts you have cloudy vision with paul, you have time of vision and with diabetic retinopathy, you have guilt -- difficulty with side vision. what i find tragic is that there are still a number of people who suffer from these conditions.

this is a graph only of the developed world, the united states, canada, and europe. these are preventable diseases. in the underdeveloped world, these are major forces of blindness. in the developed world, the major problem is macular degeneration. as we indicated the form that accounts for most of it is really sort of an age-related disorder in which people really lose a lot of their vision their visual acuity. in the past come the only thing you could do for people like that is to give them nonvisual guys, teach them how to read braille, a seeing eye dog handrails in their apartment. and speech compression devices which make it easier for them to handle auditory information.

but recently this has changed. we are sitting here in the midst of a revolution in the treatment of macular degeneration and it opens the treatment of many kinds of blindness. that is because three major development have occurred. gene therapy, stem cell therapy and retinal chips. gene therapy is an attempt to replace a defective gene with a normally functioning one. one can insert a normal functioning gene into the cell and in many cases remedy the situation. with stem cell therapy you're not simply rescuing the gene your rescuing the whole cell type. for the last 15-18 years it has been possible for to take one differentiation of stem cells and take on the properties of any cell in your body and get them to be retinal cells of various kinds and replace the

defective cells. with retinal chips, you implant that deep in the retina and stimulate directly electrically, pathways that lead to the brain. we have with us, by coincidence, the three pioneers of this area. jean bennett has pioneered the study of gene therapy. steve has pioneered the study of stem cell therapy. we have one of the outstanding leaders in developing retinal chips, these microchips that are amazing for people who cannot respond to these other treatments. we also have two other people here, carla schatz is a leader in the study of digital therapy and she would explain this to

us. my friend sandy here is amazing. as you pointed out, is a college undergraduate had a severe case of glaucoma from which he became blind. he will tell us what it's like to be blind. but the amazing thing to me about sandy is, despite the fact that he has this tremendous handicap, he is a remarkable human being. he has had a rich happy, and productive life. he has invented tanks and now he has recently become to think of how he can help other people who are blind to make their life that are. >> it's great to have you at this table. talk to us about becoming blind and the whole sense of the journey for you. >> even after 50 years, i can still feel what it was when i went blind. for many months, i had declining

vision. my mother and i went to see glaucoma specialists, and he examined me and turned to me with my mother in the room and said well, son, you're going to be blind tomorrow. i guess that was my moment and i think there is a moment that occurs in just about everyone's life, the instant before bad news is given. after which nothing else in your life will be the same and after which you look back on your life and say i didn't realize how good i have had it until now. for that moment, all, for me, was possible, and all was rather self-evidently actual. after that moment, zero

possible, zero actual. one moment you are at the top of your game, and the next moment there is no game. after surgery, i felt empty, even serrated. my vital parts cut out. there was a fair amount of pain in my eyes, but nothing in comparison with the pain in my heart, knowing that my mother had just witnessed her 20-year-old son go blind, his eyes cut open. so there was really no reason to live. so i prayed in my own way. my girlfriend, i was convinced was going to leave me. after all, dropout with no eyes,

no money, no future. but she didn't. and it is really because of her that i am here tonight with you. she and my college roommate, art garfunkel set me on the way out of my horrific wilderness. i returned to columbia, but then something happened that in not too far from where we are sitting tonight, that turned me away from blindness. art and i were walking toward grand central station during rush hour when he abandoned me. so i got down the steps to that hole in the ground on my own grand central station.

i stumbled to the train that got me back to columbia and as i'm going through the large iron gates guy bumped into me and said opops, excuse me, sir. it was of course my roommate and he had not abandoned me he followed me the entire way. as i bumped into his chest, that instant i knew that if i could get through the new york city subway system blind, there were no limitations to what i could accomplish. all was possible for me.

quick so what do you hope for today? >> what do i hope for today? it's that eric and the people who are sitting at this table in my view, in the achievements of human genius, and for them to end this play, and it's been 6 million years since we humans and are bipedal ancestors were afflicted by this thing, it's got to end and a group of us have started something called in blindness by 2020. my family, my college roommates who was a witness to my subway odyssey has been with me and for me since we both entered columbia college together.

we have launched an effort a few years ago to end blindness by 2020. >> what i find very interesting about you, first of all i must say having art and jerry as roommates is a very good beginning for someone from any point of view. how did you accomplish what you accomplished with this handicap? i mean, you went to harvard. you made a major invasion. you have led a rich life. you are happily married. >> my family, my children have stuck by me and these two guys, who as you say, i was really fortunate to meet and we all started columbia together. but it's not all black or dark.

i don't want to leave that impression with you, because when you're not distracted by visual images, you develop a life within your mind. i can see you now, eric, the way i saw art, and you look pretty good. [laughter] >> your mind is playing tricks on you. >> charlie, you look like david. >> you are what we do this television program, so thank you. let me turn to carla. give me an overview so we understand exactly what it is we are talking about in terms of the human eye. >> vision is a really miraculous

process. to hear about losing it is awful very heartrending. thank you so much, sandy, for what you have just said. i want to tell you a little bit about the basic layout of the system before we get into really talking about the eye. vision starts in the eye. light enters the eye and there is a special layer at the back of the eye which is called the retina. but you can think of the retina is kind of a fancy digital camera. the light-sensitive part of the eye, you can think of it like the pixels in your camera, although the pixels are made out of silicon. in your eye, the pixels are specialized nerve cells which absorbed light and convert it to a neural signal. in the information is sent from the retina -- you can see the

arrows -- two structures in the central part of the rain. this is called the central visual pathway. the information from the eye goes to the primary visual cortex. you can kind of think -- again we talk about this digital camera idea. this is kind of like the central processing unit, where a lot of image analysis happens. it starts in the eye, but most of the information processing and data crunching for the visual system is happening in these central visual pathways. you can ask what is the nature of the information that comes out of the eye? what is it like? i was thinking about how to convey it. and cannot do any better than george the rot -- seurat.

he has broken up the visual world into 2000 the thoughts of visual color. if you stand up really close and put your nose to the painting basically you will just see a lot of dots. the remarkable thing is if you stand back away from the painting, what you actually see is a seated woman. if we talk about this idea of the retina versus the central visual pathway, the retina is sending thousands of thought to the central visual pathways. in fact each. is carried by a single nerve fiber and there are about a million of these nerve ivers going to the central visual pathways. so it is the job of the retina to deconstruct the visual world into a pixelated view of the world. so thousands of pixels. it is to job of the central visual pathway to reconstruct

the world by making a kind of seamless view of the world, connecting the dots that. we really need are central visual pathways to appreciate that this is a woman seated but we only need are retina to appreciate the dots. so this is kind of that seeing starts in the eye, but really it's the computing power of the retinal system that is needed for what we call visual perception. you need the central pathways for visual perception. damage to any part of this pathway will produce blindness. so damage to the eye will produce blindness and also damage to any of these other connections will produce blindness. what we want to talk about today is blinding eye diseases. i would like to get a little more nitty-gritty and talk about what is in the eye. if you look on the left, you see

that light comes through the lens, and just like a camera, the lynn is focusing light on the back of the eye on the structure called the retina. you see that the back of the night, the retina, is not uniform. there is a dip or a hit that is present in the eye. this is called the macular region of the retina. it is in this region that we have our highest resolution vision. it is also the part of the retina that lets you see in color. the other part of the retina outside the macula is called a peripheral retina. this is the part that lets us see in the dark. this is lowlight vision. if you have ever looked at a starry night, you notice that if

you don't point your eye directly at the star, you look a little offkilter and the star gets brighter. that is because you're using the peripheral retina which has very high sensitivity for light that isn't as good for high resolution images. so we have these two aspects of the retina. the last thing i want to talk about is what are the types of neurons that are in the retina. we can look at a blowup of this macular region and there aren't specialized nerve cells in the retina that are capable of converting light energy to a neural signal. those are called the photoreceptors and there are two kinds of photoreceptors. there are the rods and there are the commons. the cones are the photoreceptors -- rods and cones. the rods are in the macula. the rods are the odor receptors

in the peripheral retina and they are essential for high sensitivity vision. the next step of visual information processing is that the information from the photoreceptors is passed along to the bipolar cells. from the bipolar cells, the information is passed along to the ganglion cells. they are the nerve cells that send their long fibers out into the optic nerve and into the optic track, into the central visual pathways. the last important point i want to make is there is another critical cell type in the retina, called the pigment epithelium. those cells essentially divide crucial support and nutrients to the photoreceptors. they are really essential for

photoreceptor health and survival. several blinding eye diseases involve -- and their treatments involved, these pigment epithelial cells in the retina. i think they will feature quite large in our conversation. >> that is enormously helpful. that gives an understanding of how important the pathways are.

>> i want to come now to jeanne we mentioned gene therapy and stem cell therapy. how can gene therapy be helpful? >> carl has debt -- set the stage for this perfectly. she explained the nerve function for the photoreceptors providing nutrients to those cells and taking away waste products. the two cell types are interdependent. if there's a problem and function of one particular gene and one of those cells, it affects the other cells secondarily. in the next image is an illustration of one particular

example where a mutation can cause disease in both of these cells. you see some pigment epithelium cells next to the photoreceptor cells which are so often because they are sickly. they are accumulating lipid droplets because they have a mutation which prevents them from forming a particular form of vitamin a derivative which they normally supply to photoreceptors which is essential to vision. otherwise they cannot respond to light and there is no vision. this makes them sick and they die off is the person ages. and the same thing can go on if there is a mutation, it can cause disease in the epithelium. knowing this and knowing the

genes which cause these diseases, it's possible to intervene. i like to give you an example of one disease which is one of the most severe forms of retinal degeneration. mainly because it is manifest first in babies. it is present in birth and it's usually the parents who first noticed that the children are not responding to visual cues toys or shiny objects or smiles. instead the children have abnormal, roving eye movements because the retina -- the brain is not giving signals back to the eye muscles to tell them to hold still. this has been studied carefully over the past few decades or so. we now know there are about 19 different genes at can give rise to the same phenotype. we have studied one called

retinal pigment epithelium and it's one of the more common forms of this condition. there happens to be in animal model of this disease. puppies that are born with the spontaneous mutation are born blind. we began our work restoring vision to them and reason, it would be great to do this with children. so how would you carry out gene therapy? dna is very highly charged. that is a problem for getting a normal copy of dna across the cell membrane. you have to be able to encapsulate the normal copy of the gene inside what is called a recombinant virus. we have taken essentially the shell of a virus and package it with the normal copies of dna.

that dna is then injected into the space between the neural retina and the nerve cells exposing themselves to the experimental reagent. in the next image, you can see a close-up of the virus entering the sub retinal space. the dna goes into the nucleus of the cells where it sets up shop and starts encoding the protein that is missing, which happens to be rp-65 in this instance. this is a very stable effect in the first animals that we studied after one single injection the protein was produced and the dogs could see after 11 years. so the next question is, how does this work in children?

the bottom line is that we have run a clinical trial using gene therapy for this condition and had found that all of the children involved in the study can now leave essentially normal lives, whereas when i walk into the hospital using a cane or holding their parents hands because they could not see well enough to navigate, they can walk independently. they can sit in a classroom and read books and see what the teacher is riding on the board, play sports, etc.. i like to show you an example of one of the children. you're going to see a video image in a minute of a little eight-year-old boy who is one of the first children in the world and rolled in a gene therapy clinical trial for a nonlethal disease.

he is shown three months after he received a single injection in one of his eyes. it happened to be his left eye. in this video, his injected i is patched. what you will see when the video plays is that the boy is put through an obstacle course in the hospital exam room. it is full of arrows and obstacles that he is supposed to avoid and navigate its way around the course and find a door. what you can see in this video is the boy takes us that and he doesn't know what to do because he cannot see anything. it talks through this video and you can hear what he says. he has to be co-. he takes a step and he bumps into the object in front of his

eyes because he cannot see it. he goes off course immediately. it takes him a total of 17 minutes to make it through this course. on the other hand, once his own injected i is patch and he's using his newly injected eye, he is walking to the same course stepping over an object in his path, avoiding all the obstacles, confident, and makes it to the end of the course without any problem whatsoever. so how does it translate to his daily life? this is what is so fantastic. this child came in using a cane and could not walk around. he's now riding his bike to his friends houses, playing baseball on his little league team hammering objects, playing video games, hitting targets with rocks maybe doing things his parents would rather him not do, but essentially leading a normal

life. >> to whom is that trait -- that treatment going to help? what kind of blindness? >> this treatment will be effective for individuals who have mutations in the rp-65 gene. if they had a mutation in a different gene, that would not be effective. however, the exciting enough that the same sort of approach can be used to intervene with other diseases due to other mutations. there are now at least a dozen other targets out there, several of which are now in human clinical trials with very exciting results. >> we are all learning from jean peavy >> this is not restricted to the eye. gene therapy is the use of ferry us -- various methods.

>> gene therapy is now in the late stage of clinical trial development and showing remarkable efficacy and durability, meaning it's working well within the clinical trials guidelines. didn't sell or regenerative medicine is different. the studies are early and they hold rate hope when promised. they are in the earliest stages of development. i would characterize them as highly experimental. the first stage of any new trial , our hypothesis centers on the idea that we could replace cells. we could take us dim cell that is capable of becoming any type of cell in the body. we can take a stem cell, coax it into becoming a retinal epithelial cell and then take those differentiated cells and

injected them into patients who are missing those with the hope of rescuing or restoring vision. we seek to transplant these epithelial cells and thereby replace the diseased cells. >> she is treating it individual gene in the pigment epithelium. he is replacing the whole population. >> trying to replace it. in macular degeneration, the epithelial cells are lost and were trying to replace them using a strategy similar to jean and her team. we induced the differentiation and coax them into becoming you be retinal epithelial cells. then we optimize and harvest them at a time when they are most likely to succeed in transplantation. in the next slide you can see what we're doing here is through surgery, we're transplanting

them into the same base that jean is using in her gene therapy trials to replace the cells. then they rescue or restore vision by taking care of the photoreceptors that are adjacent. it's a surprisingly straightforward method by which stem cells can be induced into certain cell types. its relatively low hanging fruit in terms of easy to induce the transformation to a terminally offering shaded cell type. they are attractive targets for stem cell ceremony. it has no synaptic connection. it is surgically accessible.

we can get to it surgically, relatively safely. doesn't require synaptic connections. we can turn them into essentially brand-new cells and give someone a fresh layer of the cells that can -- we have translated a number of patients these early studies seems safe and sane to be giving a signal there might be some restoration of vision. i want to share with you the first patient i would transplanting, a young lady who was a set designer. she lost her vocation because of her blindness. >> when i was younger, i played a lot of competitive tennis. when i was in my later teens, i started playing a little more poorly. seeing the lines are the ball not quite as precisely was a

little more difficult. i woke up one morning and looked across my room and i have a piece of furniture that that was a large armoire was a lot of car detail on it. i had my head to the side and opened my operated eye and look at it. for the first time i could see the detail in it that i had not been able to see from the distance i was lying down. after that i just got up and darted looking at everything around the house, looking at the grass, looking at everything with one eye and then the other eye. they only operated on the one night. i could see it a lot better than i had before and i thought maybe there was something here that was really going to work. it was pretty exciting. >> how long will it be before you operate on the other i? >> a long time. we are very careful and divided

by the ethics committee. only the worst i, when we are not certain about safety. we are far from doing both eyes, but we have certainly given this opportunity to a number of patients. about -- between 20 and 30. they are actually the heroes. they're the people who willingly go into this with huge risk. >> the risk in stem cell therapy are enormous. we are careful about making certain that we differentiate the cells, but it could turn into anything. plus the body could reject. so we have been very lucky to have a heroic group of patients is simply volunteer -- essentially volunteered to put themselves in harms way.

>> there are people that don't qualify for gene therapy are stem cell therapy, and you have stepped forward to use the technology. >> what do you do if all the photoreceptors are gone, there is nothing to treat anymore? what you can do is replace -- we build a chip that has little photodiodes in them, and each photo diode takes a spot of the image and amplifies it and sends an electric signal back. it's kind of a replacement of the photoreceptor. how does it work?

the chip is a little bit like the camera chip in an iphone. it has 1500 photo diode. point by point the images analyzed and turned into a mirror image and the cells first emulated point by point. then it sends the image through the optic nerve through the retina back to the central visual system. what we see on the left is again the retina, and we put the chip right beneath the macular

region. now the brain has to learn to see that things. there is a tiny, yellowish foil cable with treated gold wires going under the retina to the top of the eyeball, crossing that i am coming out to a power supply that goes back to the ear. i will come to that in just a moment. let's first look through the right side onto the retina. on the very right you see the optic nerve. it, the patient looks into the world and this yellowish cable is the power supply and the

lines to control the chip. there is a camera chip in the eye and a little cable that goes up to a receiver behind the ear. it has a white dot in the center which is a magnet. on the right side you see the patient, if he wants to switch on the chip, he simply clips the antenna coil behind that year is the size of a one dollar coin. in his hand he has a power box of the 10 control brightness or contrast. this cable powers the antenna. this reminds us a little bit about the cochlear implant. this is much more complex

because in hearing, we have a single signal in time to analyze. here you have to have 1500 points to address at the same time, so it's much more complex and difficult. >> when you speak, there is a sequence to the sounds. that is much easier to analyze. if you look at the painting in which you have to simultaneously analyze all the components of the image. it's much more difficult. >> how many dots are there? i don't know several thousand. probably 20. fall on one pixel so the image is not colorful anymore because it all mixes into great.

here is a movie clip next. >> it is all light up there and lighter there. you have the bricks going across. that is the building there. and up there, it goes up there. >> here she is dumb as she is completely blind. >> she is seeing what, as she described that bridge at oxford? >> that is what she's seeing through the chip can >> you will see on the next image exactly

what that looks like. >> it shows what she is describing. it's really an image consisting of white wide and grayish level. it's probably not much for us since we are seeing so well, but for someone who has been blind, it makes a lot of difference to see at least the surroundings in a blurry grayish like an white way. to be able to be self-confident and walking, many patients are able to see a glass, lift up glass, lift a knife or spoon or something like that. >> who is eligible for this? >> patients who have lost photoreceptors and the retina is still in tact. we have patience with a ready terry retinal degeneration.

there are 4000 here in new york that have such a condition. text-only what you are thinking as you listen to all this. >> it is inspiring. i'm not a guy who likes the "i" word very much. there are millions of these children out there who have zero possible and millions who will be born blind. to make a long story short the people i mentioned before, we have established a prize to in blindness the work that best achieves our objective at developing treatment for eye diseases, $3 million in gold all you and is the prize.

we are doing whatever we can -- in gold bullion. these are without a doubt the leaders. critics what's wonderful about this approach that the three of them are taking is that first of all it shows there is no single approach to cure blindness, because blindness takes many different forms. and it gets progressively more complicated. jean essentially inserts a particular gene into a particular cell type and boom. he takes cases in which you don't even have the epithelial cells. you have lost a good part of the retina, and he stimulates the central connections that lead to the central nervous system. these are progressively -- as we were watching, i was thinking of

a society that worships athletes and celebrities and sports figures, and here we are with scientists and people who are experimenting with their own lives, who give new definition to what it is to be a hero and make real contributions to society, so we are all in your debt. as we run down the clock, let's go to each of you and ask about what you hope is possible from the research you're doing and >> on an immediate level, we're running a phase three clinical trial aimed at getting this material approved as a drug so that people who have this condition can benefit from the intervention. this is being run at children's hospital philadelphia and is the only phase three gene therapy clinical trial going on in the world. there is no approved gene

therapy in the united states and only one other gene therapy approved in the world. we think it could be the first approved gene therapy for a blinding condition and could pave the way for opening the possibilities of developing similar approaches for many other blinding conditions. so we think it is just the beginning. >> i think gene is right. gene therapy is here to stay. it's a little bit like antibiotics -- antibodies were years ago. as far as the stem cells go, i want to continue to emphasize how early it is. i'm very mindful of not increasing patient suffering. there is so much stigma around stem cells. it's worth recognizing the social and political complexities of studying stem

cells. we have had to political leaders that have sort of contributed to this enormously. ironically they are from the -- different political parties. in california arnold schwarzenegger started a program that pave the way for a lot of the work in california. it has allowed us to stand on the shoulders of great scientists in great universities like ucla. the other is president obama. barack obama is very courageous in following the science and supporting the national institutes of health in very complex political and economic times. they have both been really important to us. it's really the team. i cannot do this myself. my hope for the future is that efforts like this, like what you do, this great work, is it allows people to understand the suffering of what sandy has gone

through, and the countless number of people who go blind i necessarily, bringing blindness to the forefront in ending it is my goal as a treating physician. macular degeneration would be of great thing to knock off the podium as the leader of linus. >> we have operated so far about 40 nations. -- operated so far on about 40 patients. only half of them have really useful vision in daily life, but there are more than 40 groups working worldwide on some of these approaches. for those patients like sandy who have lost the optic nerve or other people who have lost the eye, it is possible already in

monkeys to directly connect the impulse to the brain. that may be a way to help those other patients were the reason is not a retinal situation. of course you cannot put only a single ship in the eye but many chips to increase the visual field and you can transform this complicated pick your by computers to simple graphs like sketches or caricatures which can be grasped. there is still a lot of room for improvement. >> thank you very much. thank you for joining us. see you next time. ♪

>> i'm john heilemann. >> and i'm mark halperin and with all due respect to chris christie -- ♪ >> on the show tonight, the boys are back in town. california gets recharged by jerry brown. but first, what does the fox say? mike huckabee's strengths are not just limited to giving advice to survival food pantries. he also does well in iowa.