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    • Dr. Jean Bennett during her visit to Hopkins in 2020.

Alumni Interviews: A Chat with Dr. Jean Bennett ’72

Asher Joseph ’25
As scientists continue to expand the boundaries of technology, gene modification has become an increasingly common solution to diseases and medical conditions. Dr. Jean Bennett ’72 is a molecular geneticist who studies ophthalmological gene therapy at the University of Pennsylvania, where the impact of her work extends outside of the lab.
Although molecular genetics research was not conducted until the 1970s, Bennett was intrigued by life science from a young age. When reminiscing on her adolescence, Bennett shared, “I knew from the time I was a little kid that I just wanted to learn about how creatures live, how cells survive, how they come together and make an amazing structure.” After her time at Hopkins, Bennett continued her education at Yale just as the study of molecular genetics was beginning to develop. Captivated by the rapidly expanding field, Bennett decided to “follow [her] instincts and learn what was happening at the time,” ultimately leading her to pursue a career in the specialization. Reflecting on her life-long passion for science, Bennett is grateful to have found her calling early, stating, “I really couldn’t imagine going in any other direction.”

Ocular gene therapy, the study of genetic modification in the eye, is a focal point of Bennett’s work. She specializes in curing inherited retinal degeneration, a type of blindness that is passed down by parents and emerges as the carrier grows older. The trajectory of the disease differs from other types of blindness, Bennett explains: “The retina is irreplaceable; the cells that we have as adults are the same as those we start out with, meaning if they are damaged, they’re gone. That’s blindness.” The drug Bennett and her team developed comes in the form of an artificial virus, which replicates the original copy of a gene suffering from blindness. Bennett elaborates, “Because the virus cannot penetrate the eye’s tissue, the virus itself is delivered through a surgical procedure to the area adjacent to the cells that are dying.” The process requires a very fine needle, “about the width of an eyelash,” that inserts the virus under the retina.

Bennett began her work at a time when the technology needed to develop her gene therapy drug was relatively new. “The problem was, we didn’t know what any of the genes were in the retina,” Bennett says,
“so there was nothing to fix. We didn’t know what genes cause diseases, so it required a little bit of time before the tools were available to begin to try to test our theories as science developed.” Emerging experiments such as the Human Genome Project, an international research effort dedicated to mapping human genes, enabled Bennett and her team to move forward with their work. “We could identify different blinding diseases in animal models,” Bennett says. “This allowed us to start figuring out how to operate the surgery to deliver the DNA, what the best DNA configuration was, that the best virus was a recombinant virus, and how to ensure that the gene was functioning.”

From preparing the trials to obtaining approval from the Federal Drug Administration, the process of developing the gene therapy spanned 17 years. Says Bennett: “We had all of the reagents and animals in place ... Then, it showed that we can make blind dogs see, which was really our first eureka moment.” Bennett explains, “It took about five years of laboratory work to figure out what the optimal conditions were, then we moved to human trials.”

In the nearly two decades Bennett has dedicated to her work, the field of molecular genetics has evolved considerably. Bennett notes: “Once you see a blind child see, that really transforms things. I remember people crying when they saw a video of a [formerly] blind child... being able to play baseball or ride a bike down the street after gene therapy.” Bennett recalls the hope this offered to families afflicted by inherited retinal degeneration, and how the treatment inspired them to band together and form Facebook groups and blogs, hosting bake sales to fund further gene research.

Even with all she has accomplished, Bennett continues to look to the future. Pondering what lies ahead, she says, “You are the future. My advice would be to find something that interests you and you are passionate about. Be aware that every field has a huge amount of tedious work, meaning you have to be willing to take the tedious, repetitive stuff and know that it’s going to lead somewhere. You have to have patience.”
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