5.12 — Eyesight: Vision’s Visionaries

Host Walter Isaacson and guests discuss the problems that have plagued our vision since the beginning of humanity, and then delve into all the solutions that have been used to correct our vision.
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In this episode:

  • A radical idea: artificial vision (0:00)
  • One of history's most captivating mysteries (3:10)
  • Community ophthalmology (7:32)
  • The quest for artificial sight (12:39)
  • Better vision through augmented reality (17:36)
  • Gene therapy for the eyes (22:58)
  • Lifting the veil of darkness (28:34)

Vision loss has affected humanity since the beginning of time. With recent innovations, however, we can improve vision like never before and even give sight to the formerly sightless. Find out how scientists are doing this, and what else is possible in the future, on Trailblazers.

More stories about vision:

“This was actually science fiction. We made it science reality.”

— Mark Humayun

Guest List

  • Michael Marmor is an MD who trained at Harvard University and Medical School, and is Professor of Ophthalmology Emeritus at Stanford University. He has written over 250 scientific papers about the retina, but is also known for studies on ophthalmic history and on vision and eye disease in art. He has written 3 books about art, and one about the historical foundations of ophthalmology.
  • Lisa Nijm is a board certified corneal surgeon at Warrenville Eyecare & LASIK, licensed attorney, innovator and professor at University of Illinois Eye & Ear Infirmary. She leads Women in Ophthalmology as its CEO, has taught over 2500 ophthalmologists, and mentors physicians through MDNegotiation.com.
  • Mark Humayun is an ophthalmologist, engineer, scientist and inventor working on the world’s first retinal implant. He is a university professor with joint appointments at the Keck School of Medicine of USC and the USC Viterbi School of Engineering.
  • Drew Perkins is the co-founder and CEO of Mojo Vision. Mojo Vision is developing Mojo Lens, the first true smart contact lens.
  • Jean Bennett is the F.M. Kirby Professor of Ophthalmology in the Perelman School of Medicine at the University of Pennsylvania. She is an internationally-recognized pioneer in the field of gene therapy and has dedicated her career to restoring eyesight in the blind.

Walter Isaacson:

The year is 1992, a young doctor named Mark Humayun walks into an operating room at the Duke University Eye Center in Durham, North Carolina. On the operating table lies a man who’s been blind for 50 years. He has a rare genetic disease. The anesthesiologist numbs one of the patient’s eyes and Humayun begins to operate.

Walter Isaacson:

His goal is to attach electrodes to the man’s retina and see if he can stimulate this small, but vital part of his eye, which has been dormant for half a century. It’s the first step of a radical new idea. Artificial sight.

Walter Isaacson:

A few years ago, Humayun watched neurosurgeons use electrodes to stimulate a patient’s brain. That patient reported seeing little spots of light during the surgery. That piqued Humayun’s curiosity. “Spots of light,” he wondered, “Are those electrical currents stimulating the retina? Could this be a cure for blindness?” Now he finds himself putting his theory to the test. … But something’s wrong.

Walter Isaacson:

He’s been able to attach the electrodes to the retina with a tiny surgical incision. The electricity is flowing, but there’s no response from the eye. Humayun checks his circuits again, he switches frequencies, nothing.

Walter Isaacson:

The surgery is incredibly delicate and now, in the operating room, things are getting tense. Humayun tries one more time, going through his frequencies hertz by hertz. He wonders aloud, “Where are those spots of light?”

Walter Isaacson:

Suddenly, like a flash his patient speaks, “Doctor,” he says, “Are you talking about that little dim light? It looks like a candle far off in the distance on a dark night.”

Walter Isaacson:

Humayun jumps, “Where?” He says. “Tell us how often you see it?” And in that moment, in that tiny distant flicker of light artificial sight is born … And today it’s just one of an array of remarkable innovations transforming our understanding of vision and blindness.

Walter Isaacson:

I’m Walter Isaacson and you’re listening to Trailblazers, an original podcast from Dell Technologies.

Speaker 2:

Where lies the way? Optical science holds the answer.

Speaker 3:

It is well for us to know that our eyes are one of our greatest gifts.

Speaker 4:

General health [inaudible 00:02:55] so dependent on how well we see.

Speaker 5:

With the aid of ingenious scientific instruments.

Speaker 6:

Science observes and analyzes the struggle against disease.

Speaker 7:

As we contemplate the blind, we realize.

Speaker 8:

That optical science is indispensable.

Walter Isaacson:

Blindness is one of history’s most captivating mysteries. Some fear it, others ponder its origins, some even flourish without sight.

Mike Marmor :

The great English poet, John Milton was totally blind when he wrote Paradise Lost.

Walter Isaacson:

Mike Marmor is a professor of emeritus of ophthalmology at Stanford university.

Mike Marmor :

He wrote a famous poem in which he started “these eyes though, clear to outward view of blemish or of spot be reffed of light. They’re seeing half forgot.”

Walter Isaacson:

Vision loss is as old as old age. For some kinds, we’ve been able to create clever solutions to correct minor vision impairments. Like near-sightedness. We made strides as early as the 13th century when glass making craftsmen in Italy invented the first spectacles, but near or total blindness has mystified us for centuries. Leonardo DaVinci was the first to suggest that the eye actually received light so that the mind could see.

Mike Marmor :

Then in 1583, a Swiss anatomist, Felix Platter first effectively dissected eyes and showed that the retina, this large layer of tissue covering the back of the eye was actually an extension or a continuation of the optic nerve. And it was retina, not the lens or something in the humors, which is really the seat of vision.

Walter Isaacson:

The retina is one of the most intriguing organs in the human body, a thin blanket of tissue about the size of a quarter, the retina has hundreds of millions of photoreceptor cells called rods and cones. They convert light into electricity and then send signals up the optic nerve to the brain. So it can interpret what we see and when these rods and cones deteriorate with age, or if they are malformed due to a genetic disorder, we lose our vision.

Mike Marmor :

The retina in your eye is not like skin. It is actually the brain and it does not regenerate or regrow, which is the problem when it’s damaged through macular degeneration or through injury or through retinal detachment.

Walter Isaacson:

Platter’s observations pried open the window to the retina and doctors could finally begin to ponder the diseases that cause blindness. But before the 19th century, we can only study the retina by dissecting it. We couldn’t look into the eye and observe what was happening in real time. Then in 1850, a German physiologist named Herman Von Helmholtz invented a simple put brilliant instrument. He devised a handheld mirror that reflected candle light into a patient’s eye, along the exact access of a doctor’s point of view. He called it an ophthalmology scope.

Mike Marmor :

And ophthalmology was transformed. Now people could see inflammation cloudiness inside the eye. They could see a detachment of the retina. They could see scars on the retina. They could see cupping of the optic nerve, damage to the optic nerve, and bad glaucoma. They could recognize signs of disease inside the eye and over the next century and a half to the present day, ophthalmology grew and flourished as a scientific field.

Walter Isaacson:

When instruments and surgical techniques allowed us to reach the retina we finally started to understand the biological function of rods and cones, and this paved the way to some extraordinary achievements in the 20th century. But one of the most important innovations of the modern era wasn’t technological, it was social. And it took an unlikely visionary to come along and change the way we think of eyecare and blindness, someone who declared simply but boldly that eyesight is a basic human right. Her name was Patricia Bath.

Lisa Nijm:

She did her internship between Harlem Hospital and Columbia University. And she made the observation at the eye clinic in Harlem that about half the patients were blind.

Walter Isaacson:

This is Lisa Nijm. She’s a board certified ophthalmologist and the CEO of Women in Ophthalmology. Nijm explains that while Patricia Bath was in medical school in 1970, she began to notice that eye disease didn’t affect everyone in the same way.

Lisa Nijm:

In contrast, at Columbia, there were very few obviously blind patients. So she took this observation and conducted a retrospective epidemiological study, which documented the blindness among African-Americans was actually double that of Caucasians in that area. And she reached a conclusion that the high prevalence of blindness was due to lack of access to ophthalmic care and she worked to change that. As a result, she actually proposed a new discipline known as community ophthalmology, which is now operative worldwide.

Walter Isaacson:

Community ophthalmology was a radical idea in the 1970s. At its heart it emphasizes that eye disease and blindness are not simply mysteries for doctors to solve alone. They require mobilizing our entire society. Throughout the 1970s, bath challenged her field to get better at preventative care. She worked tirelessly to integrate ophthalmology and to public health care and public schools. Today, we take it for granted that children are tested early for vision impairment and seniors are screened regularly for signs of blindness causing disorders, such as glaucoma, cataracts, diabetes, and retinal disease. But that wasn’t the case until Patricia Bath came along. In 1976, she co-founded the American Institute for the Prevention of Blindness and became the first female faculty member as a prestigious Jules Stein Eye Institute at UCLA.

Lisa Nijm:

And she did this at a time when there were not very many female physicians let alone minority female physicians as role models to look up to.

Walter Isaacson:

Bath’s determination to eradicate blindness reached its climax in the 1980s. When she turned her attention to cataracts. A cataract is a clouding of the lens in the eye due to aging, leading to distorted vision and often blindness. It affects millions of Americans every year and is perhaps the leading cause of blindness in human history.

Lisa Nijm:

Cataracts are the most common cause of reversible blindness. I think Dr. Bath focused on cataracts because it underscores the critical role vision plays with quality of life and healthy aging. Data shows that elderly patients are 60% less likely to suffer hip fractures after they have cataract surgery. So improved vision means a greater chance of retaining independence for elderly adults, having a chance to be more physically fit and having better mental health.

Walter Isaacson:

Before the 20th century the only way to treat cataracts was a risky and painful surgical procedure in which a needle was used to Pierce the lens and dislodge the cataract from the field of vision. Better treatments were introduced in the 1950s and sixties. But bath wondered if laser technology could further revolutionize cataract surgery. Then in 1986 bath invented a device called the laserphaco probe. The laserphaco uses a laser to vaporize and remove all traces of a cataract. The surgery proved to be virtually painless and could even restore sight to people who’d been blind for years.

Lisa Nijm:

The thought of using a laser to remove cataracts was very novel at the time. I think her work opened the door for innovators to keep pushing the envelop, to find new ways to utilize technology and lasers, to improve cataract surgery.

Walter Isaacson:

In 1988 bath became the first African-American woman to receive a patent for a medical device yet another achievement and a remarkable career of ophthalmology. Today Champions for Change are building on the legacy of Patricia Bath by breaking new barriers. And that includes Mark Humayun, who hasn’t given up his quest for artificial sight. After Humayun was able to make a man who’d been blind for 50 years, see spots of light, he turned to his next challenge. He wanted to engineer a device that could live on the damage retina and replicate what it does. In fact, he needed to invent two devices, a microchip with electrodes to be implanted on the retina and the a mounted on a pair of glasses that could communicate with the implant. As it often does, inspiration came from a related technology. In this case, Humayuns studied cochlear implants, devices placed in the ear to stimulate damaged cells and overcome hearing loss.

Mark Humayun:

We literally reconfigured a cochlear implant, such that it would receive information from the glasses and then stimulate the retina. So instead of going into the ear, it would go into the retina and that showed us for the very first time that you can attach electrodes, that they’ll stay there, and they can actually stimulate and create vision. This was another defining moment.

Walter Isaacson:

In 2002, now at the university of Southern California, Humayun implanted the first microchip with 16 electrodes onto the retina of the same blind patient he operated on in 1992. Humayun promised the man that if he was able to invent the implant, he’d be the first person to get it.

Mark Humayun:

And I still remember clearly to this day, we had this large letter H and we wanted to know, can your patient actually see form visions? See the form of this letter H and I still remember again, struggling and struggling and struggling, but then, the patient says, oh, are you talking about these two vertical lines that are connected by a horizontal line? And we were like, well, what is that letter? And what I learned is because he hadn’t read any letters in such a long time, it wasn’t so obvious that he should just blurt out that it’s H

Walter Isaacson:

The biggest breakthrough came in 2013 when the FDA approved a new version of the implant. The updated device has 60 electrodes and communicates wirelessly with the camera in the glasses via a short wave radio frequency. The camera sends a signal to the implant with visual information. And the implant does what the retina used to do. It converts light into electrical signals and sends them up the optic nerve to the brain. Humayun’s retinal implant isn’t perfect yet, but it allows a blind patient to distinguish contrasting patterns, outlined shapes, and movement in the world around them. And an algorithm helps them interpret those images and learn what they are. The results have been inspiring. Several of his patients reported being able to experience the sight of fireworks on the 4th of July for the first time.

Mark Humayun:

They can actually see the fireworks go up and the little streamers coming down, another patient told me this was really the first time she could actually look at the lights on a Christmas tree. Another story is a grandmother who was able to play with her grandson and that kind of story is very special.

Walter Isaacson:

For Humayun and his colleagues it’s taken nearly 30 years to get where we are today and there’s room for the technology to grow. Improvements to the software will eventually allow patients to see colors, increase vision clarity, and even zoom in on objects from far away. Humayun named his implant the Argus after the many eyed giant from ancient Greek mythology,

Mark Humayun:

So it kind of reminds me of that mythical aspects of this whole project. How everyone said this cannot happen. You can’t put electrodes in the eye, it’s too delicate. How could you possibly replace hundreds of millions of photo receptors with only 60 or 16 electrodes. Patients won’t see anything but a big flash. They’ll never be able to get used to it and on and on and on. So it really, this was actually science fiction and I made it science reality.

Walter Isaacson:

Turning science fiction into fact is something Humayun shares with other modern innovators. Just a few hours up the road from USC and Saratoga, California. Another team is working on a solution to blindness and they plan to do it by harnessing the power of augmented reality.

Drew Perkins:

When you bring incredible people together, you can solve incredibly daunting challenges.

Walter Isaacson:

Drew Perkins is a co-founder and CEO of Mojo Vision. He’s built a successful career as an entrepreneur, but had never thought about vision impairment until a few years ago, when it touched him personally.

Drew Perkins:

I started to have vision problems. And I realized that it wasn’t just that my myopia was getting worse like it had been for 30 years and it was something different. And I went to the optometrist and he said, “yep, you have cataracts.”

Walter Isaacson:

Perkins had successful cataract surgery, but like many other patients, his vision wasn’t perfectly restored. He had trouble seeing objects at a middle distance and he found it hard to see clearly at night or in a dim light.

Drew Perkins:

I thought, why isn’t there better technology? Why was it that 40 years ago, I watched the $6 million man on TV and they had bionic vision. Then why don’t we have that today? I thought, when I do my next company, I’m going to see if I can invent that.

Walter Isaacson:

Millions of Americans, whether the result of aging or genetic abnormality suffer from partial blindness. Think of a cozy dimly lit restaurant. When you walk in, if your vision is fully functional, your eyes adjust to the low light and you can read the menu or glance around and find the restroom. But for many people, low light is a serious impairment after all the retina needs light to create vision.

Drew Perkins:

And so if you can make this so that the image you’re seeing is brighter. If you can make it have higher contrast, you can pick out the edges and do edge highlighting, highlight letters that you’re looking at, and the words that you’re looking at, you can help people that have poor vision see better in those types of environments.

Walter Isaacson:

Perkins started thinking augmented reality might be the right technology to help do this. He knew that AR requires a led display such as an iPad screen or a headset, but Perkins wanted to invent something less cumbersome, a device so small that you don’t even notice you’re wearing it. And then it hit him. Something like that already exists. It’s called the contact lens. By chance Perkins was introduced to the man who had become his co-founder Michael Deering, an engineer who had patented several kinds of miniature led displays. Together they spent the past few years figuring out how to create an AR display that can fit onto a contact lens.

Drew Perkins:

Each pixel is less than one micron, tiny, tiny little pixel. It’s thousands of times denser than your iPhone. And we’re able to make these displays. And once you have pixels that small, you can shrink the whole display to something that is less than a millimeter in size. And at that point you can put it to the contact lens and it will be practically invisible to either the wearer or to somebody looking at the wearer.

Walter Isaacson:

That tiny display, no bigger than a grain of sand sits in the middle of the contact lens. It directs incoming light to a specific area of the retina where the rods and cones are still healthy. The image sensor with its microscopic pixels can detect the faintest details and with a wireless processor connected to your iPhone or the cloud, it enhances those details for the retina, making it possible to see an augmented reality of the world around you. Even more incredible the interface is entirely controlled by the movement of your eye, wherever you look, whether it’s a dimly lit menu or a distant road sign that tiny sensor locks on and enhances the image. While Mojo’s prototype is still a few years away from being deployed Perkins is already thinking about the next generation upgrades. Future versions of the device may be able to magnify objects, adjust colors for those with colorblindness and let you see in the dark.

Drew Perkins:

And the process of giving all these super powers we’re going to reinvent literally man’s relationship with technology. Our goal really is to improve the human condition and being able to help everybody lead a normal life. And I think that the Mojo lens is going to be able to do that better than just about anything that’s come before it.

Walter Isaacson:

Some of the leading causes of blindness are due to environmental factors like age-related cataracts and poor diet, but there are many more that we’re simply born with. These are the diseases that emerge from our genes.

Jean Bennett:

When I first began studying blindness, there were no genes that had been identified, which caused blinding disease.

Walter Isaacson:

Jean Bennett is the co-director for the center for Advanced Retinal and Ocular Therapeutics.

Jean Bennett:

And gradually with the progress of the human genome project, more and more genes were identified. And now they’re more than 270 different genes, which if mutated can cause blindness.

Walter Isaacson:

Back in the 1990s, there were amazing advances in the science of gene cloning and biologists began to realize that if we could replace defective genes with healthy ones, we could potentially target genetic diseases at the roots. It’s an exciting field called gene therapy.

Jean Bennett:

The success of gene therapy depends upon the ability to efficiently and safely deliver the gene to the target cells. And one of the most amazing developments in the 1990s was the recognition that a virus can be harnessed and the genes which allow it to replicate in a host cell can be removed. And instead, those can be replaced with the genes that you want to insert inside the cell.

Walter Isaacson:

What Bennett is describing is called a viral vector. Think of it as a gene delivery vehicle, biologists can load the vehicle with a clone gene and surgically implant it to replace a defective gene. And here’s where the retina reminds us again, how special it is. In most parts of the human body our cells keep dividing after we’re born. If you deliver a viral vector to most cells, the virus will probably be attacked by the body’s immune system or simply be lost in the shuffle of cell division. But the cells in the retina don’t divide after we’re born. It’s like the retina is a walled garden, a sanctuary where if you deliver a gene on the back of a virus, it will stay where it’s supposed to and nothing will harm it. And this makes the retina perfect for gene therapy.

Walter Isaacson:

In her lab in Pennsylvania Bennett has spent the last decade focused on one particular gene in the retina called RPE 65. A mutation in this gene can lead to a blinding disease called Leber Congenital Amaurosis or LCA, which affects about one in every 40,000 people in the United States. In fact, it’s one of the most common causes of blindness in children. Bennett and her colleagues figured out that there’s actually a similar genetic mutation in some dogs. And this is where they first tested their gene therapy. When she loaded up a replacement gene and delivered it to the dog’s retina, the results were almost magical.

Jean Bennett:

When they received their first injection of the gene therapy region within days, they began to see, they began to notice that the technicians who were taking care of them were walking back and forth in the room. They’d follow them with their eyes and their heads and act like normal puppies. They would play tug of war. They would catch balls that would be tossed to them. Interact with the other dogs. Tails would be wagging. Their whole behavior. Their whole stance changed.

Walter Isaacson:

The success of those early experiments had Bennett feeling optimistic.

Jean Bennett:

But of course our first reaction was, wow, we can make blind puppies see. Wouldn’t it be amazing if we could make blind children see? And we did test it in humans and we tested it in adults and in children born with mutations in the RPE 65 gene, the same gene that causes the blindness in the dogs, and lo and behold, they can see now.

Walter Isaacson:

In 2017, after many clinical trials, the FDA approved this particular gene therapy to treat LCA. The first of its kind. Today, many other therapies are in advanced stages of clinical trials, including those using gene editing or CRISPR technology to do similar things. Bennett believes we’re on the cusp of an exciting new era in the battle against blindness, but she cautions against any premature celebration of finding a cure.

Jean Bennett:

Although the patients that we treated 10 years ago continue to show robust improvements in their vision we don’t know what’s going to happen going forward. This is still somewhat of an experiment and we’re following these patients over time. And we certainly hope that they will show the same level of vision in another 10 or 20 years. So time will tell whether or not this is a cure.

Walter Isaacson:

It’s not hard to look at these doctors and inventors and mistake them from miracle workers. After all, what could be more miraculous than lifting the veil of darkness, but they would all tell you the same thing. There are many challenges ahead and more puzzles to solve. The retina still has much to reveal about itself, but one thing we know way off in the distance on a dark night, at least we can now see little spots of light. I’m Walter Isaacson and you’ve been listening to Trailblazers, an original podcast from Dell technologies. If you’d like to learn more about any of the guests on today’s show, please visit delltechnologies.com/trailblazers. Thanks for listening.