Pulling Back the Curtain: Katherine A. High, MD

Katherine A. High, MD
Dr. High is co-founder, president, and chief scientific officer of Spark Therapeutics in Philadelphia.

In this edition, Katherine A. High, MD, talks about her work in gene therapy, her love of reading, and the importance of “getting things done.”

What advice would you give to early-career hematologists and trainees?

I would share something that a senior professor told me early in my career: If you’re really trying to solve a problem (in my case, that’s finding a gene therapy for hemophilia), remember that you own all the problems – not just the problems that you like, or the problems that are most interesting to you, but all of them. If it’s in the way, you own it. It has shaped how I tackle difficult problems in my research.

When you were a kid, what did you want to be when you grew up?

I wanted to be a chemist. When I was 10 years old, Santa Claus brought me a chemistry set for Christmas, and I spent endless hours doing the experiments outlined in the accompanying manual. It was so much fun!

And as I got older, I realized that I loved studying, particularly German history. So, I guess I also imagined having a career as a history or language professor. I’d still like to learn to speak German fluently someday.

What was your first job?

The first job that I was paid for was working at a bookbinder during the summer after my senior year of high school in Greensboro, North Carolina. This bookbinder had state contracts for rebinding older textbooks.

That’s an unconventional summer job – how did you come to work there?

Dr. High with her two youngest children on the day that Spark Therapeutics rang the opening bell at Nasdaq.

Because the textbooks needed to be ready before the start of the next school year, the summers were a busy time for the bookbinder. It wasn’t a particularly complicated interview process: The company made their hiring selections by administering a written test and assessing our manual dexterity; they made a composite score from those tests and simply drew a line under the names with the highest scores. After I started working there, I learned rapidly that all that really mattered was the manual dexterity.

Fortunately, it was one of the few places hiring teenagers that paid minimum wage, unlike many of the typical teenager jobs (lifeguarding, babysitting, or bagging groceries) in those days. So, bookbinding was a very attractive option. As many first jobs are, it was also a great learning experience.

“If you’re really trying to solve a problem, … remember that you own all the problems – not just the [ones] that you like.”

After you graduated and went to medical school, did you have any mentors who helped to shape your career?

When I was doing my hematology training at Yale University, I worked in the lab of Edward J. Benz, Jr., MD. After leaving his position at Yale, he went on to serve as chairman of the Departments of Medicine at the University of Pittsburgh and Johns Hopkins University, as well as president and chief executive officer of the Dana-Farber Cancer Institute.

After working in his lab, I sought his guidance when I contemplated any move or change in my career’s direction, and he always offered sound advice.

What advice would you give to early-career hematologists and trainees?

I would share something that a senior professor told me early in my career: If you’re really trying to solve a problem (in my case, that’s finding a gene therapy for hemophilia), remember that you own all the problems – not just the problems that you like, or the problems that are most interesting to you, but all of them. If it’s in the way, you own it. It has shaped how I tackle difficult problems in my research.

What career accomplishment are you most proud of?

For the last 25 years, my career has focused on gene therapy for inherited diseases. December 2017 was an important month in my career: First, in early December, the clinical study of gene therapy for hemophilia that our company sponsored was published in The New England Journal of Medicine, along with an accompanying editorial. The circulating levels of clotting factor that we achieved allowed the participants in the study to lead active lifestyles without the need to take any clotting factor.

This work has made a real difference to the people who volunteered to participate in the trials and the results have far-reaching implications for the larger hemophilia patient population.

Then, later that month, the biotech company that I cofounded, Spark Therapeutics, received regulatory approval for the first adeno-associated viral (AAV) gene-therapy product in the U.S., for a rare form of congenital blindness. I’m extremely proud of that.

On the other side, have you ever had any major disappointments in your career – and how did you handle them?

There were many disappointments on the nearly 20-year road to developing that gene therapy for hemophilia and publishing those exciting results. In each case, I tried to carefully analyze the situation so that I could learn what went wrong and then move forward – and try to avoid repeating those mistakes. When something that you believe in and have personal conviction about doesn’t work out, it’s hard, but you have to be persistent.

But don’t give up and don’t get discouraged. Much of your success will be determined by your ability to represent to others the excitement you feel and the importance of the work; it’s easier to accomplish your goals when you really believe in what you’re doing.

From the beginning of your career to today, how do you think hematology and medicine have changed?

The most obvious way is that our understanding about the basis of many diseases has expanded immensely. If I think about what was written in hematology textbooks when I was a fellow, and what’s written in the textbooks today’s fellows are looking at, it’s profoundly different.

Dr. High receiving an honorary degree from the National University of Córdoba in Argentina.

During my training, the coagulation factors VIII and IX had just been cloned. Now, we have recombinant clotting factors and we understand, in exquisite molecular detail, the mutations that cause hemophilia A and hemophilia B. I think that, over the span of my career, the hematology textbook has undergone frequent revisions.

In a typical workday, what is your rose and what is your thorn?

That I work at a biotech company that I co-founded means there is always something to look forward to. The best part of going to work is the people with whom I work: They are physicians and scientists who are all working towards a common goal of moving therapeutics, particularly gene therapies, to the next generation. We are all interested in finding long-term treatments for serious diseases and coming up with great solutions to tough problems.

The worst part of my day is an unfortunate side effect of our successes: Our company has grown rapidly, with locations at several sites in West Philadelphia, so getting from one place to another has become much more complicated than when we were all in the same building.

What do you do when you’re not working or navigating traffic? Do you have any hobbies?

I read a lot. I suppose I still love studying, so I enjoy reading history, biographies, and fiction. I also try to reread works that meant a lot to me when I first encountered them.

I have several favorites, like The Odyssey by Homer and Kristin Lavransdatter by Sigrid Undset, who won the Nobel Prize in Literature in 1928. Kristin Lavransdatter is a trilogy of historical novels tracing the life of a woman in Norway in the 14th century. I know that when people read that description, they might think, “How could that be relevant to anyone today?” But so much of her experience resonates with the modern reader, and it has something to communicate about every phase of life. The way the author writes makes you care deeply about the long list of characters. I learn something new every time I read it.

I also like to swim, and, as I mentioned earlier, I am committed to the idea of trying to study foreign languages. But, I must say that my life has crowded out earnest attempts in that space.

What is your biggest pet peeve?

It has changed over the years, but the one thing I have constantly found irritating is people who just can’t get things done. Fortunately, I don’t encounter too many people like that anymore, but earlier in my career when I was responsible for training young investigators, I found out that I don’t have much patience for that quality! Getting things done requires a combination of the ability to prioritize activities to reach a goal, and the ability to be resourceful if the obvious solution isn’t close at hand.

When I became a parent, one of the things I was afraid of was that I would raise children who couldn’t get things done – but I’m proud to say I didn’t!

What’s one thing most people might not know about you?

One of my daughters, Sarah Steele, is a successful actress. Her first film role was as Adam Sandler’s daughter in “Spanglish,” and a few years ago, she starred in the Tony award–winning play “The Humans,” first off-Broadway and then on Broadway. She also was on the television show “The Good Wife,” and now stars in its spin-off, “The Good Fight.”

What person from history would you like to have dinner with, and what would you ask?

I’d love to talk to Winston Churchill. He has a great legacy, but he was a complicated man and there are many opinions about him. I would ask him why he was so sure of the course in 1940, and what motivated his actions.

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