The future of hearing loss
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This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. I thought it would be good to revisit the original intent of this show. In 2017, when we started, we wanted to create a forum to dive into and discuss the motivations and the research that my colleagues do across the campus in science, technology, engineering, medicine, and other topics.

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About 50% of hearing loss is caused by genetic mutations. And if we send people for genetic testing, then we get the precise diagnosis in about 50% of people. And in another 50%, we get a very indeterminate answer. In fact, there can be hundreds of what are known as variants of unknown significance. So as the name implies, we don't know what they mean.

But now with the use of AI, we can actually determine which of these variants of unknown significance are actually significant. So it helps us establish a precise diagnosis in people who did not have that type of diagnosis before.

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Today, Tina Stankovich from Stanford University will tell us about hearing loss. It's one of the most common disabilities, but new developments in AI and stem cells gives hope for better understanding and better treatments. It's the future of hearing loss. Before we get started, another reminder to rate and review the show, especially if you're enjoying it, so that other people can find out about it and enjoy it.

So hearing loss is a big problem in the United States and across the world. It's one of the most common disability claims and it can really affect your life with emotional isolation and problems with communication. The question is, what can we do about this? Ear cells don't regenerate after damage and so in the past you've just been out of luck if you lost your hearing from loud noises or from injury.

However, there are new things coming about. There are stem cells that are allowing us to grow and understand how the cells in the ear work. There are new surgeries and there's AI which is pouring over the records, the medical records of patients to understand how different syndromes of hearing loss might be related and might yield to new treatments.

Well, Tina Stankovich is a professor of otolaryngology and neurosurgery at Stanford University. She's devoted her career to understanding hearing loss and preventing it. She also is interested in new ways to diagnose it and, of course, new ways to treat it. She'll tell us that advances in AI and advances in stem cells have allowed new ways to understand how the ear works and how we may be able to prevent and treat damage to the hearing system.

Tina, what drew you to devote your research and your clinical practice to hearing loss? Well, my love of music drew me into the field of hearing. I played the piano when I was in elementary school. And then, of course, you have to be able to hear to appreciate music. And I have been a dedicated schoolteacher.

scholar of the auditory system ever since I was an undergrad student at MIT, and then continued with my PhD studies at MIT, and then medical school, residency, fellowship, and faculty position at Harvard before moving here four years ago. Wonderful. So what is the status of our understanding and our ability to treat hearing loss in 2025?

Well, it's a frustrating state of affairs because it's a very common disability. It affects one and a half billion people across the globe, which is one in six individuals. And yet there are no cures for hearing loss yet.

We are limited to devices, and primarily there are two types of devices, hearing aids that typically help people with mild to moderate hearing loss, and cochlear implants, which help people on the other end of the spectrum with more severe to profound hearing loss.

But currently, there are no biological therapies and there are really no drugs that are FDA approved for hearing restoration. There's only one drug that was recently approved for hearing protection and for a very specific indication, namely for cisplatin-induced ototoxicity. And that's a cancer drug. Exactly, a cancer drug.

So how are we at understanding the causes for hearing loss? It's very kind of, to many people, they don't understand why this happens. Is it random or are there processes that you can understand? So what is our understanding of the causes? And I'm sure there's several causes for hearing loss.

Absolutely. There are many different causes of hearing loss. They range from genetics to noise trauma to infection to different drugs. We mentioned cancer drugs, but there are other drugs that cause hearing loss, trauma of any kind, many different causes. But right now, we basically lump hearing loss into two broad categories. The first one is called conductive hearing loss, and the other is sensory neural hearing loss.

And we can help conductive hearing loss today. Sometimes we can even cure it surgically. And what that means is that the way we hear is when sound travels down the ear canal, it vibrates the tympanic membrane and that sets in motion the smallest bones in the body. Also known as the eardrum.

The eardrum, exactly. And then the smallest bones in the body, named the malleus incus and stapes, which is the hammer, anvil, and stirb bones. And they set in motion the tiny, well, first the fluids in the inner ear, which stimulates these tiny sensory cells called hair cells. And they release neurotransmitter, which excites the auditory nerve. And then that signal is transmitted to the brain.

So the conductive hearing loss implies that there is a problem with getting sounds to the inner ear. That can be due to a hole in the eardrum or fluid behind the eardrum or a disease process that encases or erodes these hearing bones.

But the bigger problem is the sensory neural hearing loss. And that's the type of hearing loss that typically originates in the inner ear. And this is a challenging problem because today we can't tell any living individual what exactly is wrong in the inner ear because the imaging tools are not there yet. And we cannot biopsy this tiny organ to see

obtain tissue to establish a precise diagnosis. So you have to mostly tell what's wrong by the functional capacity of the patient. Can you hear this? Can you hear that? What are the volumes? And you'd like to be able to kind of objectively assess the health of this inner ear neural system.

Absolutely. And this is so challenging because the human inner ear is a very tiny organ. And just to give you a flavor for the scale, if you look at a penny, then you'll notice that Lincoln is on a penny. And the human cochlea, which is the spiraling organ and the hearing part of the inner ear in cross section, is the size of Lincoln's upper face on a penny.

So within this tiny organ, there are more than 30 different cell types and there is fluid as well. So within the human inner ear, the total volume of fluid is the equivalent to just three raindrops, about 140 microliters.

And these are the things that you're actually doing surgery on, which is just a miracle in itself. Do you use robotic-assisted surgery, or is it all still your hands? We do both, and this is primarily for cochlear implant insertion. So the cochlear implant is a device that electrically restores hearing by directly inserting

stimulating the auditory nerve. So it bypasses all cells that are not working in the inner ear and it can be inserted manually, which is what we do most of the time. And now robotic insertion has become available and we are eager to adopt that.

Great. Okay. So before we get into the exciting new technologies and research efforts that I know you're working on, I just wanted to ask about tinnitus or ringing in the ears or buzzing in the ears. Is this related to hearing loss or is it an entirely different problem? It's absolutely related to hearing loss in the vast majority of people. In fact, a very sure way to get tinnitus is to be exposed to loud noise.

In fact, hearing loss and tinnitus are the two most common disability claims of veterans. So the way we think of tinnitus is that it's a phantom sound produced by the brain, typically because of injury to the inner ear. And we know that's the case because with cochlear implantation that we just talked about, we can improve hearing.

tinnitus in 75% of patients and in 10% of them it completely goes away which tells us that if we restore the periphery if we rehabilitate the inner ear the brain will adjust and recalibrate and tinnitus can go away

Great. Okay. So now having established this, thank you very much. This was a wonderful tutorial. So I think we all feel like we're experts now, or let's be a little honest. We understand the issues. Tell me, I know that you've written about and you've used many new emerging technologies to try to understand this exquisitely small and powerful system. What are some of the technologies that are emerging that make you optimistic about the future for both treatment, diagnosis, and prevention?

There are many, and this is such a great question, and they include...

stem cells, which we can use not only to understand the disease mechanisms in people, because now there are ways to just take a little skin biopsy or blood and convert these cells into induced pluripotent stem cells, which we can then differentiate into inner ear cells and organoids. I was going to ask you about that. So that's amazing. You do have protocols for making exactly the kind of cells that you're interested in from these

Sometimes they're just skin cells that have been modified to become pluripotent stem cells. So that's amazing.

Yes. Well, Yamanaka, who figured out how to turn any cell in the body into a stem cell, won a Nobel Prize for that. So that's by now routine. However, what is challenging and still being developed is to discover protocols that lead to specific cell formation after it uses pluripotent stem cell development.

And so this is what we and others at Stanford and across the world have spent a lot of time developing these protocols that can robustly and reproducibly generate cells of interest. But this is an ongoing effort. So it's by no means a solved problem. But it makes me excited about the future because we can imagine that we'll be able to develop protocols

personalized therapies guided by what we find in any given individual. So that's one example of a super promising technology. Another one is AI. Of course, here at Stanford, we are ground zero for AI.

AI development and that's really changing how we think about disease mechanisms, how we incorporate it in our workflows. We are now collaborating with Google to

Use novel large language models that have been trained on clinical and scientific data sets to answer problems that have been unsolved in the auditory field and beyond. Other examples of exciting technology that we are using is high resolution optical cameras.

imaging of the inner ear that's based on both two-photon microscopy and optical coherence tomography.

gene therapy is really gaining momentum with the first demonstration of the feasibility of gene therapy for human hearing loss just last year. And it's super exciting that lots of these developments are happening right here on Stanford campus as a part of the Stanford Initiative to Cure Hearing Loss.

And this is a highly collaborative group that includes more than 100 researchers with broad and deep expertise in lots of complementary fields that range from what I already mentioned, stem cell biology, regeneration, genetics, genetics.

drug design, and even mathematics and computational modeling. But of course, we work in the bigger ecosystem, not only here in Silicon Valley, but also nationally and internationally. And since you asked me about coming to California, I have to say that I really

was really struck by the majestic redwood trees. Of course, the redwood is in our university's logo. And these are the tallest living creatures that have ever existed on the planet. And what I find remarkable about them is that they live in groves or family circles.

where they support each other, not only through the roots, the network of roots, but also they shield each other from winds. So this is how I think about people working on hearing therapies, hearing cures, where

all of us together at Stanford nationally and internationally have to collaborate to accelerate progress. Great. Thank you very much. And so going back to some of those technologies, because I think this is what fuels these exciting collaborations, and I have questions about all of them, but let me

The first one is you talked about the stem cells and getting like cells from the ear, but it strikes me that there's a special challenge because these cells function in a very special environment. You mentioned the cochlear, which basically looks like a conch. It looks like a helical shell. It occurs to me that you have to kind of create a three-dimensional environment for these cells so that they can kind of start to approximate their function. So how...

Is that what on the agenda is creating the three-dimensional milieu so that we don't just have the cells, but we have them in the correct position relative to one another and relative to the fluid and the bones and all the other pieces of the cochlear? Absolutely. That's a great question. And certainly lots of work is invested trying to solve those problems. And I'll just touch upon two things that you mentioned. One is fluids and the other is bone.

Because both are unique in this very special organ. The fluids in the inner ear, there are two types. One is called paralympic, and that's very similar to extracellular fluid everywhere else. However, there is this other fluid, which is called endolymph, and it's very high in potassium. Normally, you find potassium at high concentration levels.

inside of cells, not outside of them. And this high potassium concentration combined by energy pumping into the space generates a biological battery, which is truly remarkable and doesn't exist anywhere else in the body. So within the inner ear, there's this biological battery of 100 millivolts of positive potential that

that is driving ions through sensory cells to improve their sensitivity. And it actually allowed the hearing process to occur. And this is the most sensitive sensory organ. And we can detect sub angstrom displacements. So that's about fluids. And then you mentioned the bone and what's really special about that bone that surrounds the inner ear. It even has a special name. It's called the OD capsule is that it,

it's fully developed in the womb, in utero. So when that bone fractures after birth, if there is a trauma of any kind, it never heals. You can see that fracture line forever. And what's normal in other bones, namely bone remodeling, because if someone breaks a bone and then it remodels and your bone forms and it heals,

That is abnormal in this bone. If this bone starts to remodel, then it leads to disease, including hearing loss. So you are absolutely correct that dealing with this very special, unique milieu, very tiny spaces requires precise approaches, technology development,

But we as a field have been at the forefront of technology development and adoption. And I'll just give you an example that it was two ear surgeons who, 100 years ago, were the first to introduce a microscope into the operating room. These were Nilen and Holmgren in Sweden. And now...

You can't imagine doing anything delicate without the use of a microscope in all of surgery, ranging from microvascular reconstruction to surgery.

Neurosurgery. So, again, I think by solving these super challenging problems, the fact that the organ is tiny, that it's encased in the hardest bone in the body, that it's located deep in the base of the skull, we can't see the way you can see the eye, we cannot biopsy directly, is actually impossible.

accelerating progress. It's fueling our not only curiosity, but inventions to solve some of these problems. But that's why it's been a challenging nut to crack. This is The Future of Everything, and we'll have more with Tina Stankovic next.

Welcome back to the Future of Everything. I'm Russ Altman, and I'm speaking with Dr. Tina Stankovich from Stanford University. In the last segment, we went over the basics of how the ear works, some of the problems that we face, and some of the new technologies that are giving us hope for new kinds of treatments.

Now, Tina, you mentioned AI and a collaboration with Google, but I wonder if we could just talk a little bit more about what kind of problems did the AI help you address? I think you said you were looking at medical records and asking questions. I think it'd be really fun to see how it actually helped you.

Absolutely. So right now, about 50% of hearing loss is caused by genetic mutations. And if we send people for genetic testing, then we get the precise diagnosis in about 50% of people. And in another 50%, we get a very

indeterminate answer. In fact, there can be hundreds of what are known as variants of unknown significance. So as the name implies, we don't know what they mean. But now with the use of AI, we can actually determine which of these variants of unknown significance are actually significant.

So it helps us establish a precise diagnosis in people who did not have that type of diagnosis before. So that's just one example. And this is certainly a work in progress, but a thrilling direction to pursue. So it can go through large volumes of text and of genetic – even genetic results –

and kind of put together the pieces to say, wait a minute, we're seeing this variant a lot and we don't think it's of unknown significance. We now have a hypothesis that it might be quite significant. - Exactly.

The other thing I didn't get to ask you in the first segment was about regeneration. So you talked about how the bone, that very delicate bone in the cochlea doesn't regenerate. But in general, do the neural cells, can you get a regeneration of your hearing after a trauma or are you out of luck?

Out of luck at this point in humans, unlike lower species like birds and reptiles, the mammalian inner ear does not regenerate spontaneously to any significant degree. That's why it's so important to protect hearing. However, by understanding how birds and reptiles are regenerating their cells, we now know what the key pathways are and we can turn them on in mice.

which means that we can now regenerate sensory hair cells in mice, which is certainly a step in the right direction. But a lot more work remains to be done before this is ready for human use, because humans are not just big mice. Right.

But a very exciting discovery happened here at Stanford Initiative to Cure Hearing Loss, identifying that there is an early step towards regeneration, even in the human inner ear. And this discovery came from studying

inner ear tissue, which we can get from performing surgeries that require drilling through the inner ear. That's called that labyrinthectomy or from organ donors. So these are people who have generously donated their other organs for transplantation. And then at the end, we come in and collect the inner ear tissue by

studying it, we now know that in the human inner ear and in particular in the balance part of it, there is an early initiation of the regeneration process, which makes us optimistic about pushing that forward to really complete it. And of course, a lot more work needs to be done in that direction, but it's a very important direction.

Yeah, the discovery of that early step makes one wonder if we used to be able to regenerate millions of years ago and we lost that capability. And now you and your colleagues are trying to figure out how to turn it back on.

Yes. So I know you also, you care about hearing loss from multiple angles. And one of the things you've written about a little bit is the, not just the communication consequences of not being able to hear, but other consequences on those patients in terms of their general life. And I'm wondering, can you summarize the kind of experience and the kinds of other things that come along with the loss of hearing other than, you know, you just can't hear things?

Absolutely. The main issue is that hearing loss leads to emotional withdrawal, and it really leads to emotional and relational issues. And hearing loss can even be linked to cognitive decline and prior to that, depression. And Helen Keller, who was both

blind and deaf, and she was one of the most celebrated people of the 20th century, said that deafness is a worse misfortune because blindness separates us from things and deafness separates us from people.

And this is what we hear repeatedly. There's huge social stigma associated with hearing loss, in part because the current therapies are not curative. For example, if you have a problem with vision, you wear glasses and they restore your vision to normal. And that's why people wear glasses even if they don't need them as a fashion statement.

But nobody is doing that for hearing aids. And as the name says, they are hearing aids. They aid in listening, but they're not curative. And that's why hearing loss traditionally has been associated with old age. And people don't like that.

And it really impacts beyond what words can describe how people feel and how isolated they can be. And the fact that they live through this invisible disability alone, because if you look at them, they look fine. Yeah. Yeah.

You know, as you were saying this, it struck me that I've seen young people like at schools for the hearing impaired. And, you know, they have a very vibrant culture and they're doing sign language. And like, of course, I don't I don't know for sure, but it seems like because they got it early in their life that they've adjusted. They have friends, they have cultural and

personal connections. But as you say, when the hearing loss comes later in life, especially at a time where learning new things is not as easy, so learning sign language would not be as easy, adjusting to the deficit. Are there specialists who can help people manage the challenges of kind of late onset after a life of hearing to have your hearing taken away? Who can help those folks?

Great points. Otologists, so otologic surgeons can help audiologists who fit hearing aids, psychologists and psychiatrists, depending on the severity of the emotional impact that hearing loss has. So basically, social workers can be super helpful. So it's a team of

professionals working together to help individuals. And you bring a great point that people who are born deaf, they belong to the deaf culture with a big D. And in fact, they don't consider their hearing loss a disability. They consider it a unique aspect of who they are. They are not interested in therapies to cure hearing loss because again, they don't consider it as a problem. But anyone who

has head hearing and then loses it, considers that a major handicap. And they would love to have better options than what's available today.

So in the last few minutes, I had two questions. The first is, as you know very well, I recently saw a video about your work that Stanford had posted, and it involved the singer Paul Simon. And I believe he was supporting your center that you described earlier with the multidisciplinary collaborations. And of course, the big irony, as I'm sure you know very well, is one of his biggest song hits was a song called The Sound of Silence. So I'm wondering if you just can tell us a little bit about

Why is Paul Simon so interested in deafness and how did that relationship come about? Well, Paul came to us as a patient and I will let him tell his story. And in the process, he became really interested in hearing research, recognizing the limitations of the current state of the art.

So he has become a wonderful advocate, ambassador, and a supporter. He has given benefit concerts in support of the Stanford Initiative to Cure Hearing Loss, and he has broadened the network of people

who are now interested in hearing and willing to openly talk about it to overcome this enormous stigma. And when someone of his stature in the artistic and the entertainment world is willing to talk openly about their hearing loss and how it impacts them, it really empowers and emboldens others to do the same.

to really galvanize forces to accelerate cures. And a part of the issue is overall limited funding for hearing research because an institute at NIH that sponsors hearing research, it's called the National Institute for Deafness and Other Communication Disorders, is one of the smallest NIH institutes.

Great. Well, it's great to hear that he's involved in. And we will put a link to that video for this podcast so that people who are interested can hear his story. Well, I wanted to end, I know that you care very deeply about prevention of hearing loss, especially from noise and from things that can be controlled. And so I'm wondering if we could end with just your advice about how somebody who wants to protect their hearing, what are some good practices, good habits that they should get into? Sure.

Great question and super important to observe. Do you definitely want to protect your hearing if you're going to any loud events, such as music concerts or sporting events, or if you're using power tools, you can get...

decibel meter on your phone to measure sound levels around you. And a good rule of thumb is that you do not want to be exposed to sound levels more than 85 decibel. And to orient you what this means, I'm now speaking at around 65 decibel. Many music concerts are around 120 decibel, which can literally be deafening. And the

The U.S. holds the world record for having achieved the highest noise levels at a football stadium, which was 143 decibel. And that's louder than a jet engine. So, of course, anybody who goes to events like that can damage their hearing. So we recommend using hearing protection. You should always walk around with earplugs in your pocket. I have my earplugs that I carry all the time.

Excellent. Also, if you anticipate being exposed to these loud events, you should take magnesium. Magnesium supplementation has been shown to protect against noise trauma. And the initial study was actually done in Israel where there is mandatory military service and all these young people are exposed to artillery and training noises. And they were randomized into two groups, those who received magnesium and those who didn't.

and those who received magnesium had less hearing loss. Other things that you can do is a healthy lifestyle in general, because numerous studies have shown that a healthy lifestyle

is conducive to hearing protection. And what does that mean? That means eating foods that are rich in omega-3 fatty acids, such as seeds and nuts, and eating fruits and veggies that have beta-carotene and cryptoxanthin. It also means not smoking and not drinking.

and exercising regularly. And studies have shown that all of these measures actually work. They're modifiable risk factors for hearing loss. And these studies involved hundreds of thousands of people followed for many years and decades.

Another one is if you have a chronic disease like high blood pressure or diabetes, you have to get that under control because if it's not controlled, that also contributes to hearing loss.

And drugs, beware of anything that you ingest. For example, commonly used drugs such as Tylenol or Ibuprofen can increase the risk of hearing loss. In fact, they're the most common modifiable risk factors for hearing loss. But there are other drugs. We mentioned cancer drugs before. There are certain antibiotics like gentamicin or certain diuretics like furosemide. And the list goes on.

Thanks to Tina Stankovich. That was the future of hearing loss. Thank you for tuning into this episode. Don't forget, we have more than 250 episodes in our back catalog on a wide variety of topics that can keep you entertained for hours. If you're enjoying the show or if it's helped you in any way, remember to review it and tell your friends and neighbors all about it.

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