By S.I. Rosenbaum \ Photos by Peggy Peterson


To begin with, they shared a brain.

It sat between them on in a tray, smelling of fixative agents. They’d already begun cutting into it, and it had flopped open, exposing the hypothalamus.

Jean Bennett and Albert Maguire were both first-year medical students at Harvard, but Bennett already had a doctorate in zoology. Maguire felt he had to make a grand gesture to catch her eye. He took her gloved hand and gently poked her finger right into the bundle of nerves at the rubbery center of the hypothalamus—the pleasure center.

“That’s my favorite organ,” he murmured.

Instead of recoiling, she wiggled the finger in his grasp. She looked at him.

“It’s my second favorite organ,” she replied.

And that was that.

“As you can tell,” she says, “I fell for Al’s sense of humor.”

“I was especially happy to find out someone else hadn’t used that pickup line on her before,” he says.


They tell this story, their meet-cute, with relish—swapping punchlines like the long-married couple they are today. After more than 30 years of an extraordinary partnership, Bennett and Maguire have hit a lot of traditional milestones: They have the house, three kids and two dogs. But they’ve also collaborated in ways few married couples have. The dogs were originally laboratory subjects, and the children grew up listening to their parents talk over experimental medical procedures at the dinner table.

Working in tandem for decades at the Perelman School of Medicine at the University of Pennsylvania, Bennett and Maguire became pioneers in the field of gene therapy—a discipline that was science fiction when they met. In December, they hit a milestone unique to them: The Food and Drug Administration (FDA) approved their treatment for a form of inherited blindness, the first such treatment for a genetic condition ever approved in the U.S.

“By putting our two experiences together and our perspectives on things,” Bennett says, “it really propelled us much further than either one of us could go alone.”

Seeing Eye to Eye


They were still newlyweds—and still med students—when Maguire asked Bennett the question that would change the course of their lives.

She had told him about her postdoctoral work studying molecular biology. She’d been intrigued by the potential to treat genetic diseases by going to the source—replacing a patient’s warped genes with a clean copy. At the time, no such therapy existed, but she could see that it was coming, and she wanted to be ready. That’s what had led her to augment her PhD with a medical degree in the first place.

Maguire, meanwhile, in training to become a retinal surgeon, was working with patients who were slowly going blind because they’d inherited flawed copies of a single gene.

Do you think, he asked his wife, that we could develop gene therapy to cure inherited forms of blindness?

Her answer sealed their fate: “Sure,” she said.

At the time, neither of them quite realized what a challenge they were taking on. It was “like thinking you wanted to go to the moon in 1950,” Maguire says in retrospect.


“We were so naive that it didn’t scare us,” Bennett says.

Besides the hefty technical challenges ahead of them, they also had to learn to work as a team. Their first attempt at collaboration was rocky: Maguire, who had never worked as a researcher, was frustrated when their work didn’t yield immediate results.

“Research requires an extraordinary amount of patience,” Bennett says. “But when it comes to surgery he has more patience than anyone I’ve ever seen.”

“I have the ability to concentrate intensely for short periods of time,” Maguire says. “She can do that for years.”

The Goal in Sight

By the 1990s, Bennett and Maguire had been recruited to Penn’s Scheie Eye Institute. All around them, technology was catching up with their ideas: Genes for different forms of inherited blindness were being identified, and scientists were creating transgenic mice with those same mutations, as well as perfecting techniques for inserting genes in viral vectors that could be used to “infect” an animal cell with those genes. At first, the couple experimented on congenitally blind mice. But by coincidence, it turned out that Penn’s veterinary school housed a colony of blind dogs.

The human condition equivalent to the dogs’ genetic defect is known as Leber's congenital amaurosis (LCA), a severe, progressive inherited disease. People who carry the malformed gene, RPE65, are born with poor vision and eventually lose their sight entirely. The effect on the dogs was much the same—and unlike humans, the dogs couldn’t use technology to help them get around.

To gauge their impairment, Bennett did a simple test, putting the dog in an obstacle-strewn room and calling it to come. The dogs blundered and stumbled around, unable to see their environment. Bennett felt sorry for them. “Dogs are so visual,” she says. “When you saw these blind animals, you wanted to help them and allow them to see a squirrel and run after a squirrel.” Instead, the blind dogs seemed listless. “These poor creatures, they would just sit there.”

They dove into research but tried not to let their project take over their personal life, limiting the amount they talked about work at home with their kids—who nonetheless learned to roll their eyes when one of their parents slipped up and started discussing retinas at the dinner table.

Maguire initially treated three dogs, injecting a virus into one of their eyes. The virus had been designed something like an M&M: Once inside a cell, its protein shell melted away to leave only a snippet of DNA that could make the enzyme the dogs’ cells couldn’t make on their own.

Days after the injection, a lab tech reported the dogs were turning in circles: It seemed like they were trying to look around them with the eye that had been treated. Within weeks, electroretinograms confirmed that the dogs could see. More impressively, when Bennett ran them through the obstacle course again, they were able to navigate it safely and quickly.

It was a successful trial. The only problem was that Bennett and Maguire were having trouble maintaining a proper scientific distance: Both dog lovers, they found their post-surgery subjects hard to resist.

“Once the dog licked my face, wagging its tail—you’re done with, it’s over,” says Maguire.

Adopting a dog who has been part of an experimental gene therapy trial was not easy, they found. “People were worried about gene transfer,” says Bennett. “Is it going to escape the dog, is it getting into the drinking water? … We really didn’t know.” They had to do more research to make sure that once the virus got to the dogs’ retinas, it stayed there. Armed with their data, they argued their case to the provost.

Venus and Mercury, lab animals no more, ended up going home with them.

“They’re the nicest, sweetest animals you can imagine, they’re just the sweetest dogs,” says Maguire. “I mean, everybody says that about their dogs—but they really are.”



Jean Bennett, MD, PhD

F.M. Kirby Professor of Ophthalmology
Director, Center for Advanced Retinal and Ocular Therapeutics

Studies molecular genetics of inherited retinal diseases


Swedish Briard Dog
Female, Age 10

Enjoys sitting beside Bennett as she plays the piano


Albert Maguire, MD

Professor of Ophthalmology
Retinal surgeon at Penn and CHOP

Led clinical trials for therapy now known as Luxturna


Swedish Briard Dog (puppy to Venus)
Male, Age 8

Enjoys exploring new smells and drinking out of the toilet


More than a decade after Maguire and Bennett treated their first dog, a young woman named Katelyn Corey lay in a hotel room with bandages across her face. Behind the bandages, she was seeing something strange: flashes of light, like little sparks.

Corey had been born with LCA. Her vision had never been great, but she had learned to cope with it, using large-print books, writing with a Sharpie instead of a pencil, color-coordinating her clothes. When she was 15, she and her family sought to enroll in an early phase clinical trial of Bennett and Maguire’s gene therapy, but her vision at that time was too good to qualify her for the experimental procedure. By the time she got to college, however, her vision was getting rapidly worse. “I’d adapted to how to take notes, how to study, all those years in high school,” she recalls. “But now it wasn’t working anymore.”

She knew she would eventually become totally blind, and she knew she’d find a way to cope with that too, one way or another. But in 2012, her sophomore year, she decided to give herself six months to find a treatment—a last-ditch effort to save her sight.

She found her way back to Bennett and Maguire. This time, she qualified.

The couple had finally moved to human trials in 2007, after the nearby Children’s Hospital of Philadelphia (CHOP) had invested in creating a Center for Cellular and Molecular Therapeutics. The then-head of that center and a professor of Pediatrics at Penn, Katherine High, MD, had knocked on Bennett’s lab door one day and asked if she wanted to run a clinical trial to use gene therapy to treat congenital blindness. “I don’t think I even called Al to ask him,” Bennett recalls. “I just said yes.”

Two years later, they injected their first young-adult human volunteer with the viral reagent.

Safety was the utmost priority in human trials. Bennett and Maguire asked themselves, if one of their kids had LCA, would they let them participate? “We both had to answer that affirmatively,” she says. To make sure their ethical standards were high, she and Maguire waived any chance of financial gain if the therapy proved successful.

Bennett found herself bonding just as closely with her human subjects as she had with their canine ones. “Each one of them is like family with us,” she says. She’s visited their homes, watched their kids give musical recitals. “I feel so lucky to be able to get to know them and be part of their lives and understand how this has affected them,” she says.

Making the trial participants feel comfortable with her also leads to better science, she adds: Patients who felt connected with her would more readily share their experiences.

Maguire, on the other hand, kept his distance. “I think a huge part of success for the trial was my wife and her connection with the patients in the study,” he says. “But I’m also their doctor, and as a surgeon you have to have this space where I’m not too close to them.”

By the time Corey enrolled, the trials were in Phase III—the last phase before a treatment can be approved by the FDA. (That possibility in sight, High left CHOP and Penn in 2013 to become president of Spark Therapeutics, a new startup company spun out of CHOP, where Bennett, Maguire, and their teams still collaborate.)

Corey was initially randomized into the trial’s control group. A year later, she was finally offered the real gene therapy. When her bandages were removed, she was amazed to find that her sight was better—not just better than it had been before the treatment, but better than it had ever been in her life.

“Things were brighter, sharper,” she says. The world was in color instead of black and white. Outside her hotel window, there was a light she’d thought was the moon; now she realized it was the clock tower in Philadelphia City Hall. Even indoors, there was enough light to see by: “The fact that that light was coming into the hotel room and causing it to be light in there—that was and still is crazy to me,” she says.

A few days later, she turned 21. At a follow-up appointment, Maguire gave her a bottle of Prosecco that he and Bennett had gotten for her.

“Do you think this is a good idea?” Corey asked. She was still on prednisone from the surgery.

Back at the hotel, she and her parents toasted over birthday cake.

Eyes on the Prize

Corey, now 25, testified before an FDA advisory panel in October. “I just want you to know that this was significant to me, significant in the way that I live and plan my life,” she told the regulators. “I can finally live my life the way I want to.”

Also testifying that day was the most famous trial participant, “America’s Got Talent” contestant Christian Guardino. His successful treatment had brought the trial popular attention from new quarters. “Gene therapy has made my world literally so much brighter,” he said. “I'm even able now to walk around freely on stage and perform, and not just stand in one spot.”

Two months later, Bennett got the call: The advisory panel had voted unanimously, and their treatment regimen, now readied by Spark for commercialization and branded as Luxturna, had officially been approved.

She and Maguire were thrilled. Their decades of work had finally paid off. Over a thousand people in the U.S. would have a chance at restoring their vision.

Katelyn Corey

Katelyn Corey, now 25, testified before an FDA advisory panel in October 2017. “I can finally live my life the way I want to.”

Mere weeks later, Bennett and Maguire already have their sights set on new challenges and questions. If they treat children early enough, can they totally prevent the disease? Do repeated treatments increase the effect? And there are other forms of inherited blindness they want to try treating, forms that will require entirely new methods.

Meanwhile, at home, they’re just a normal couple with hobbies, some shared, some separate. She plays the piano; he paints portraits of cows. And they keep bees. They have five hives.

Keeping busy with their own pursuits, Bennett and Maguire also see the broader implications of the FDA’s ruling in December. The decision marked a milestone for gene therapy as a field. It was the first time the FDA had approved a genetic treatment for an inherited condition—finally realizing the vision Bennett, Maguire and their colleagues had back in the 1980s. And it paves the way for more such therapies.

“It now sets a path for others to follow going forward, where there was none before,” Bennett says. “This is looking way down the road, but maybe not as far as you think.”


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