Mark Humayun and David Hinton look to stem cells to bring sight to the blind

David Hinton, MD, (left) and Mark Humayun, MD, PhD (Photo by Ryan Ball)
David Hinton, MD, (left) and Mark Humayun, MD, PhD (Photo by Ryan Ball)

Video by Ryan Ball

For years, people were throwing away cells that could bring eyesight to the blind. These dark, blackened cells looked like spots of contamination in the petri dishes in which researchers around the world were carefully nurturing highly purified colonies of human stem cells.

It took Keck School of Medicine of USC scientist David R. Hinton to realize that what appeared to be specks of dirt were actually some of the key cells that enable people to see.

In those seemingly contaminated petri dishes, stem cells had transformed themselves into the specialized cells that support the health of the retina — known as retinal pigment epithelial, or RPE cells. The death of RPE cells is one of the primary contributors to age-related macular degeneration, the leading cause of blindness in the elderly in the Western world.

Hinton has partnered with USC colleague Mark S. Humayun to deliver these RPE cells into the eyes of patients with the most common form of the disease —the atrophic, or dry type of age-related macular degeneration — in a phase 1 clinical trial, scheduled to begin in early 2015 with funding from the California Institute for Regenerative Medicine (CIRM).

Both Humayun and Hinton are principal investigators with USC Stem Cell, a university-wide, multidisciplinary, collaborative initiative working to translate the potential of stem cell research to the clinical imperative of regenerative medicine.

Long roads united these two very different talents at this critical crossroads in their careers.

As a child growing up in Maryland, Humayun watched his grandmother go blind from complications of diabetes. This inspired him to follow in the footsteps of a large family of physicians — including his mother and five uncles — and specialize in ophthalmology.

“For me, it’s always about helping people who are going blind or who have gone blind and trying to restore their sight or prevent their visual loss,” he said.

After earning his undergraduate degree from Georgetown University, he attended Duke University Medical School before obtaining a PhD in biomedical engineering from the University of North Carolina, Chapel Hill.

“I think that ultimately, if you’re going to solve these complex problems, it’s really going to be through the merger of biology and a device,” said Humayun. “That’s really the fundamental aspect of my work: to restore sight and to do it through this abiotic/ biotic interface.”

After completing a fellowship at The Johns Hopkins Hospital, he came to USC in 2001. He currently holds the Cornelius J. Pings Chair in Biomedical Sciences and serves as Professor of Ophthalmology, Biomedical Engineering, and Cell and Neurobiology.

He enjoys an active Southern California lifestyle involving mountain biking, skiing, traveling and playing tennis with his children, and he likes reading popular authors ranging from Isaac Asimov to Malcolm Gladwell.

He also appreciates the unique academic culture of USC. “The ability to do more interdisciplinary work here was something that I could not do when I was at Johns Hopkins,” said Humayun. “And USC was doing more of that work, the interdisciplinary work, especially related to the eye. So that’s what led me to come here.”

In contrast, Hinton’s initial inspiration to enter the sciences was not human, and arguably not even alive. Canadian by birth, Hinton was the son of a microbiologist and infectious disease specialist. He remembers photographing and scrutinizing viruses under an electron microscope in fifth grade.

“They probably wouldn’t let me do that anymore,” he joked.

He earned his undergraduate and medical degrees from the University of Toronto, and completed his residency at the university’s children’s hospital.

“I’ve always had a basic curiosity about how the brain develops, how it works, the ideas of consciousness and all these things, and I trained as a neuropathologist,” he said. “So my original motivation to do eye research is because many people refer to the eye as the window to the brain, and that’s because the retinal cells, the light-sensitive cells at the back of the eye, are derived from the brain and have the same cells of origin. And so you can study the brain by studying the eye.”

In 1985, he won a fellowship from the Medical Research Council of Canada enabling him to spend three years studying anywhere in the world. He chose to go to the California Institute of Technology to explore the development of the fruit fly’s compound eye with late geneticist Seymour Benzer, whose widow Carol Ann Miller is a neuropathologist at USC. This kicked off a collaboration between the two universities.

Hinton joined the USC faculty in 1988 and eventually became the holder of the Gavin S. Herbert Professorship in Retinal Research; a professor of Pathology, Neurological Surgery and Ophthalmology; and the associate dean for Vision Science, specializing in the biology of RPE cells.

Hinton finds equal joy in riding his bicycle along the beach near his Venice home and traveling the world. He once contracted a curable but tough-to-diagnose case of malaria during a six-month adventure in Africa, which he explored by truck while camping out every night. This year, he plans to experience the midnight sun during the summer solstice in Iceland.

He’s also a dyed-in-the-wool Trojan, having spent 25 years on the faculty. “USC is a very highly collaborative institution, and people aren’t so much keeping secrets from one another but wanting to work together to move things forward,” he said. “And that’s one of the things I like best about USC.”

Hinton has been working to perfect the technique for differentiating stem cells into RPE cells since 2006, and he began collaborating with Humayun on the RPE project in 2007. The two had already known each other for a decade, and Humayun had frequently called upon Hinton to examine eye pathology related to various other research endeavors.

Hinton knew without a doubt that Humayun was the man who could engineer a way to implant his RPE cells into patients with atrophic age-related macular degeneration. Humayun had already spent 25 years building the synthetic membrane that he implanted as the Argus II, the world’s first artificial retina restoring some vision to people suffering from blindness caused by the inherited disease retinitis pigmentosa. The Argus II synthetic membrane carries electrodes; the new synthetic membrane will host a population of RPE cells.

“I remember the day,” said Hinton, “talking to Mark and saying, ‘Look, we have to do this project together. We’d be a perfect team.’ ”

Humayun immediately sensed their synergy: “What he brings to the table is really the cell culture and the cell biology aspects of it. And what I bring to the table is more the engineering, the tools and, of course, the clinical practice of ophthalmology.”

Supported by nearly $40 million in CIRM funding, the USC-based project also brings together several other partners from across Southern California in a true interdisciplinary, multi-institutional convergence. The University of California, Santa Barbara, is helping with the differentiation of RPE cells, Caltech is assisting with the development of the synthetic membrane, and City of Hope is manufacturing the actual product that will be implanted into patients in the clinical trials.

The other essential partners are the patients who will participate in the clinical trials.

In total, more than two million Americans, or about two percent of the population, suffer from the advanced form of age-related macular degeneration. Each year, nearly 300,000 of these patients in the U.S. alone watch their worlds vanish as the disease blinds them. Macular degeneration destroys their central vision, leaving them unable to recognize faces, drive, read and lead independent lives.

Currently, there is no treatment for the atrophic form of the disease, which the new RPE implants will target.

“Patients that have been involved in our studies and want to be really are brave,” said Humayun. “They’re truly altruistic, and they want to progress the science. We view them as part of the team.”

These patients are what motivate Humayun and Hinton to contribute the long hours of tireless work year after year.

“The idea of being involved in a project where you can go from conducting a benchtop experiment to treating patients in the near future is something that is really exciting,” said Hinton. “For me, it’s almost a once-in-a-lifetime opportunity to go that whole distance.”

Having achieved a previous success with the Argus II, Humayun knows how rewarding this process can be.

“Some of the greatest things patients have told me certainly come from what they have been able to see and how we’ve been able to help them — for example, never being able to see their grandchildren, and then being able to see them,” he said. “But also what’s very important are certain patients that we haven’t yet been able to help. And so that is, in many ways, equally motivating as seeing the successes.”

Mentioned in this article: Mark Humayun, MD, PhD