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Katherine High, MD, Awarded Esteemed CHOP Gold Medal

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May 12, 2022
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Kathy High, MD

Kathy High, MD, received the CHOP Gold Medal on May 10

Katherine High, MD, one of gene therapy’s pioneering proponents, received Children’s Hospital of Philadelphia’s Gold Medal Award May 10. The award recognizes Dr. High’s longstanding dedication to the development of gene therapies for genetic diseases and revolutionary work bringing these treatments from the bench to the bedside for children around the globe. Beginning her career as a hematologist in the 1980s, Dr. High joined CHOP in 1992 to study adeno-associated viral (AAV) vectors – work that later evolved into the clinical translation of potential gene therapies for a variety of inherited disorders.

Believing in the potential for gene therapies to change children’s lives, Dr. High established CHOP’s first vector production facility through the Raymond G. Perelman Center for Cellular and Molecular Therapeutics (CCMT). As CCMT’s director, she nurtured a community of scientists set on developing novel therapies for genetic diseases. In 2013, when CHOP helped launch Spark Therapeutics, a pharmaceutical company centered on fast-tracking life-saving gene therapies, Dr. High became one of its scientific leaders. It was there that decades of Dr. High’s gene therapy research with CHOP and University of Pennsylvania colleagues culminated in the first U.S. Food and Drug Administration-approved gene therapy for an inherited form of blindness.

In this Q&A, Dr. High tells her story as a gene therapy pioneer in her own words – from the choices and chances she took, to the individuals who supported her along the way, to the role that CHOP played in the framework of her career.

Kathy High, MD

Kathy High, MD

You worked at CHOP for more than 20 years. What does this Gold Medal mean to you?

I gained a great deal from the part of my career that took place at CHOP. Besides helping me focus on my research, CHOP was unstinting in providing support to me at crucial junctures when I needed to take the next step in my work. They have a real focus and interest in work that begins at the bench and eventually moves to the patient, and therefore I always found in CHOP’s institutional framework a great deal of support for translational work, which is key.

Could you give us some examples of how CHOP uniquely supported your work?

In the late 1990s, there were some controversial clinical trials in the field of gene therapy and most companies, including the one making our clinical-grade vector for our hemophilia trials, turned away from the field because they couldn’t raise money to continue the work anymore. I went to CHOP leadership and asked, ‘Would you let me make clinical grade vectors in the hospital?’ Steven Altschuler, MD, CHOP’s CEO at the time, responded, ‘Let me think about it. Come back in a week.’ I was already thinking of a plan B when one week later, to my everlasting surprise, Dr. Altschuler said to me, ‘Here’s what I think. If gene therapy works, it will be life changing for pediatric hospitals.’ He agreed to support it on one condition: I would have to work on diseases other than just hemophilia that affect the pediatric population.

So, in 2004 we set up the CCMT and through that, the vector production facility. This was all made possible by CHOP’s decision to support what we were doing. And when I look back on things, I consider that the single most surprising decision at a time when support for gene therapy had waned. CHOP decided to support it because Dr. Altschuler, who was a pediatrician himself, understood and grasped the fact that if this works, it will make a big difference for children’s hospitals.

As another example, when we began gene therapy trials for inherited blindness in a collaboration with Jean Bennett, MD, PhD, at the University of Pennsylvania, we wanted to include children at the very beginning. The head of the CHOP Institutional Review Board at that time, Mark Schreiner, MD, worked with us extensively to develop a presentation for the NIH Recombinant DNA Advisory Committee that would convince regulators that our proposed trial carried the prospect of direct benefit for each child. We were successful.

Can you speak a little more about establishing the CCMT and eventually leading SPARK Therapeutics?

I came to CHOP in 1992 to work on AAV (adeno-associated virus) therapies, and in 2002, I was named a Howard Hughes Medical Institute Investigator while also continuing at CHOP. As mentioned earlier, I established the CHOP CCMT in 2004 to create a base for researching cell and gene therapies that would address diseases in the pediatric population. That was the vehicle through which we established the Clinical Vector Core. We recruited J. Fraser Wright, PhD, as CCMT’s head of manufacturing. Dr. Wright did the job at CHOP for a long time – he set up a facility, competed for a National Institutes of Health grant to support the production facility, and hired many of the people who work there now. Then, in 2013, CHOP was contemplating spinning out a biotechnology company centered on our gene therapy programs; this would eventually become Spark Therapeutics. I began first as an adviser to Spark, and in 2014, I left CHOP to become Co-Founder and President.

You’ve had a successful career! Can you talk about some of the challenges you encountered along the way?

When I tell my story from a wider vantage point, it looks like it moved along smoothly. But I never felt that way at the time – in fact there were a whole series of decisions that were balanced on a knife’s edge, and I could have gone one way or the other. I’m sure that most people’s careers look like that when they think back on it.

When I was an assistant professor, the departments of medicine were overwhelmingly male. And so when I joined CHOP and there were a lot of women in leadership positions, that was wonderful, and that made a great deal of difference to me. When I moved to a biotech company, and we were going around raising money, there were not many women sitting in investor seats. I would always feel so relieved when we would go in to make pitches and there would be one woman. To me, that was one of the great things about CHOP.

You’ve come a long way since researching hemophilia in a lab in the 1980s. Why did you choose to study hematology in the first place?

I was a chemistry major as an undergraduate, and I was struggling to figure out whether to go to graduate school or medical school. And the first year that I was out of college, I worked in a research lab at Massachusetts General. I was synthesizing chemical compounds and liked the work. So I thought, OK, well, medical school might not be so bad. So I went, but in the first few years I really didn’t like it and decided I would take a year off and go back to the chemistry lab. The head of the lab said, ‘My advice to you is go back and finish medical school. I will help you get a good post-doc based on the work you’ve done in the lab here. And then if you think you have any deficiencies in your background, you can just take courses while you’re a postdoc.’ I found that when I went back to medical school, however, I really enjoyed it. I did a residency in internal medicine and wanted a subspecialty where I could use my chemistry background, with a heavy lab component to it.

Do you have any advice for aspiring young scientists?

Well, the only thing that I can say is that I really loved what I was doing, and that if you’re doing something that you love, it doesn’t feel like work. I have three kids, and I always used to wonder when they were younger, ‘Will my work ever matter to me as much as they did?’ In a weird way, your work becomes like the fourth child, and you love it in a way that’s not like you love your children of course, but you love it as if it were a living thing. Because it feels like a living thing and of course is composed of many other living people. So I think that if you’re doing something you love, you know, it’s not really like work.