Katherine High, AB 1972

After graduating from Harvard with a degree in Chemistry, I went to medical school at UNC Chapel Hill and trained in internal medicine and later pursued a hematology fellowship at Yale. I worked on the regulation of expression of the globin genes, which were the first genes that were cloned, and then took my first faculty position at  Chapel Hill in a large research group working on blood coagulation and hemophilia. We were doing lots of structure-function work, and that’s when I started working in gene therapy. I was cloning dog Factor IX  in pre-PCR days and elucidated the genetic defect in a canine model of hemophilia.

I then came to Children’s Hospital of Philadelphia to begin working on AAV (adeno-associated virus) therapy and many subsequent clinical trials. I spent most of my career in the lab, and only in the last 15 years or so have I shifted more to clinical investigation. In 2013, it became clear that our gene therapy programs would need to partner with a pharmaceutical company or become one ourselves. And so, we formed our own company strictly devoted to gene therapy, Spark Therapeutics.

I was a Howard Hughes Investigator at the time, but I eventually retired from Penn to fully run the company. In 2017, we got the first approval of a gene therapy for a genetic disease in the United States, for a rare form of congenital blindness. In February 2020, I left Spark and only recently have joined another biotech company.

I’ve worked on hemophilia for so long, and one of the most satisfying things to me was when we had our first patient enrolled in a trial begin to show signs of improvement. He was a 23 year old nurse with two small children, and growing up he needed infusions of clotting factor concentrate twice a week. If you’re taking infusions twice a week, you always have to worry about scheduling the infusions. You have to plan your life around your factor levels.

After receiving the vector gene therapy in our trial, he never had to worry about infusions or bleeds again. His factor nine level slowly came up and just stayed there. It was a beautiful, beautiful result, and it made a profound difference in his life. When his levels came up, I almost cried. Really, I sweated a lot in the first several weeks after he was infused because I could not believe what was happening as I pored over every lab result.

Dr. Kathy High with two of her children at the ringing of the Nasdaq bell for Spark Therapeutics (PC: https://www.ashclinicalnews.org/spotlight/pulling-back-curtain-katherine-high-md/)

When these results were published in the New England Journal of Medicine in 2017, and we got this result over and over after so many years of hard work, it was… I simply cannot describe the feeling I had. I called and talked to my kids telling them all those years working for hours and hours and missing school plays was worth it in the end. It’s been incredibly meaningful to work in this field, and truly the most gratifying thing in the world is doing work you believe in with really smart people you respect. You can’t ask for a better job than that.

Kathy High MD 

AB 1972 | Chemistry

Emeritus Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania

Co-Founder Spark Therapeutics

President, Therapeutics Asklepios BioPharma

Interviewed and Compiled by Felicia Ho