The healer: Q&A with Jedd Wolchok

Your research yielded fantastic results on a new immunotherapy combination—ipilimumab and nivolumab. Why is this so exciting?
It broke new ground in the treatment of metastatic melanoma and produced durable tumor shrinkage in about half the patients. Ipilimumab is the first in an emerging class of therapies we call “checkpoint blocking agents,” which enhance the immune system’s ability to identify and kill cancer cells. The approval of ipilimumab to treat advanced metastatic melanoma was a game changer not only for the thousands of people fighting this disease, but also for the entire field of oncology. Now our data indicate that when ipilimumab and nivolumab are given concurrently, they may be more effective against metastatic melanoma than either appears to be alone, as each one impacts the immune system in a distinct but complementary way. So there’s renewed hope for patients whose disease has progressed after ipilimumab. Alternative immunotherapies can still work for them.

Who or what was the catalyst for pursuing melanoma research?
Summer of 1984. I had the honor of meeting with Lloyd Old, who was supervising a dozen different labs at Memorial Sloan-Kettering Cancer Center (MSKCC) at the time. He handed me a stack of papers to read and told me to pick the one that resonated, and he’d have me work there for the summer. I had just finished my freshman year at Princeton and the most accessible paper was on a clinical trial on melanoma written by Alan Houghton. As I learned more through the 80s and early 90s and became an oncology fellow at MSKCC, I grew to appreciate what a significant and challenging problem melanoma had become and how there was a desperate need for better answers.

What inspires you most about your research today?
The ability to bring new treatments to people who need them. We now have a spate of new drugs helping more patients than ever before—giving them more time and a better quality of life. I have the extraordinary privilege of trying to help people who are facing a devastating illness. And what more motivation could a person have than to be face to face with someone who desperately needs a better answer? Over the past 17 years, I’ve been able to change the tenor of the conversation I have with patients. It’s gone from “I’m sorry there’s nothing we have that works well” to “We have several options that will extend your survival but we’re trying to do better than that and that’s why you should consider a clinical trial.” The advances accrued over the past decade have fundamentally changed the conversations that doctors can have with their patients.

What is the biggest obstacle that you have had to overcome in your career?
Balancing how much time and energy I have to do the very important job of taking care of sick patients while paying the appropriate amount of attention to the science. In my world they are both so important and finding that balance is extraordinarily difficult. I see patients one day a week and take care of inpatients two weeks a year. But even though clinic is just once per week, people can be sick on the other days and I need the temporal space to help them. If I were seeing patients in the clinic every day, I would not have enough time or capacity to do science, whether that’s clinical, basic or translational science. You need cognitive space. You need creative space. There are precious few places like the Ludwig Center at MSKCC that allow a physician to define their clinical practice and give people that space to really try to succeed in both worlds.

Can you explain what immunotherapy is and why it holds so much promise?
Cancer can be recognized by our own immune systems as something foreign and dangerous that can be gotten rid of like an infection. And immunotherapy is an intervention that aims to recruit a patient’s immune system to do just that. Immunologists have long hypothesized that specific interventions could stimulate and ‘re-educate’ patients’ own immune systems to attack their cancer. Immunotherapies are designed to help activate the immune system by blocking the ‘stop sign’ that prevents immune cells from destroying cancer cells. Malignant cells are able to proliferate because of driver mutations but also because they hide from the body’s immune system. Sometimes the body doesn’t recognize them as foreign and it doesn’t fight them, or the tumors actively thwart an immune response as a means of survival. The goal is to get the patient’s defenses up so cancer is recognized as an invader, and it gets controlled as an infection would.

With immunotherapy, we’ve entered a new era of cancer therapy. It’s helped us turn advanced cancer into a chronic rather than an acutely deadly disease by enabling the immune system to continuously monitor against the reappearance of ‘foreign’ cancer cells.

If you were just named magic czar of all of cancer in the United States, what would you change about the system to move research from bench to bedside faster?
Money. We need more of it devoted to scientific and medical research. The lack of knowledge and lack of effective drugs are obstacles we’ve overcome. We have collaborative and collegial relationships with industry. Contracted research is a thing of the past and we’re now undertaking collaborative research to advance our goals. Too much time and energy is expended on the constant need to secure funding. And unfortunately much of the time spent on it doesn’t bear fruit.

Scientists want to make progress and eliminate the dependence on writing grants. Ludwig understood this four decades ago. I think it’s a big reason why its reach and impact have been so phenomenal. The secret is to identify promising scientists it has confidence in who will make a difference in cancer research, and to put the resources behind them. Instead of worrying about money, all I have to worry about is the next great experiment. Or the therapy or clinical trial. It’s a much more effective use of my time. With this model, Ludwig was ahead of the curve. It’s a wonderful feeling, knowing that all of the projects I am working on right now will continue to develop and grow over the next five years.

Worldwide deaths from melanoma have reached almost 73,000 a year. What steps can be taken to reduce this number?
Use sunscreen and stay out of the tanning bed. There’s no such thing as a safe tan. And getting one—whether artificially or from the sun—is unhealthy, increasing an individual’s risk of developing cancer. In fact, people who begin tanning younger than age 35 experience a 75 percent higher risk of melanoma.

You and Dr. Old shared a love of music as well as both being accomplished musicians. What instrument do you play?
Tuba. I play in a group called the Brooklyn Wind Symphony, a community-based organization. The majority of its members are music teachers who are looking for a way to hone their performing skills. We perform and raise money and support for a public high school in Brooklyn that is a magnet school for the performing arts. We commissioned a new work, Requiem, by David Maslanka, which was performed on June 15. We’re actually the first group from New York to win a performing spot at the Midwest Clinic, an international band and orchestra competition, which will be held in Chicago this December. It’s the World Cup of wind bands and quite an honor.