TMC Interview

Ronald A. DePinho, M.D., president of The University of Texas MD Anderson Cancer Center, sat down with Texas Medical Center Executive Vice President and Chief Strategy and Operating Officer William F. McKeon to look back on the influences that led him to medicine, and how passion and dedication drive the MD Anderson team in their battle against cancer.

Q | Tell us a bit about your upbringing and the influences that shaped your life.
A | We’re all shaped by our past in a profound and enduring way. We are the product of our culture, our family core values and our educational experience provided by devoted mentors. There are really three major forces that shaped my life and my current position.

The first one, of course, is my family. My mother and father came from a very poor background in Portugal, with limited opportunity. My dad, at age 17, left for Brazil as a means of supporting the family back home. Although he had limited education, he was driven and creative and became reasonably successful in providing some resources to the family back home. But, the opportunities were limited there as well, so he decided his best way to help his family was to come to the United States. The only problem was that he did not have a formal invitation. Rather, he ended up a stowaway on a ship, in a box for 13 days, and eventually made it to the New York Harbor. He worked construction in the Bronx, right across the street from Fordham University, where I would go to school years later. He shared with me his dreams of those early years of sending his children to college. He would confidently tell his roommate, ‘I’m going to be sending my children there [Fordham].’ Three of his five children graduated from Fordham College.

With the U.S. entering World War II, his love of country and all that it stood for inspired him to enlist and earn his citizenship. He fought on the Italian front and was one of the few to come back alive from his company. Following his return to the U.S., he built a construction company, got involved in real estate and started a family. When he reached a certain level of stability, he focused his attention on helping others in need. Driven by Christian values, he would identify families with limited opportunities in other parts of the world and sponsor them to come to the U.S. He did this for many families residing in Africa, South America and Europe. They would come one by one, and he would get them integrated into our country. Many were afforded the opportunity to live the American dream.

That example had a profound impact on me. There are some really heart-wrenching stories. Families that were wiped out by war or suffering from lack of opportunity—in some cases, he supported families for years. He was truly altruistic and expected those core values of us. We were expected to serve, especially among those who are underserved and might not have the same opportunities.

My second influence derives from a string of dedicated teachers, particularly in high school, who inspired me to apply myself and learn. A seminal event for me was the dissection of my first frog, after which I wanted to know everything about how the organ systems work and how this miracle of complexity enabled an organism to function.

I gravitated toward trying to understand why. I loved biology, and I also loved helping others, so I concluded that the right profession for me was a physician.

The third major influence in my life was my martial arts instructor, Master Ik Jo Kang, a political refugee from Korea and self-made man who had the gift of inspiring others to do the impossible. Martial arts has endured for more than 3,000 years—based on its ability to transform individuals. The practice instills principles of courage, humility, respect, discipline and a hard work ethic to foster inner balance and a positive attitude. I was 16 when
I started, training five hours per day. That experience generates fortitude, discipline and the ability to deal with crises in a stable and thoughtful way. That had a profound impact on who I am today. So, it was the influence of my father, my teachers, and my martial arts teacher—all of them gave me attributes that positioned me to contribute to my profession and serve others.

Q | What led to your passion for cancer? Was it your research that led you there? Was it the loss of your father to cancer?
A | First and foremost, I loved clinical medicine. I loved the relationship one develops with the patient and the ability to really help a patient. I then became increasingly interested in understanding the ‘why’ of disease.
I wanted to complement my clinical experience with a scientific career. I wanted to go beyond caring for disease and strive to understand disease at a level that would lead to prevention or cure. My pursuit of fundamental science was born, prompting my pursuit of a dual physician/scientist career.

I was very interested, as a physician and scientist, in bridging the divide, so I took time off from being a clinician and I worked full time in a laboratory and eventually returned to a dual career. I was very fortunate to have great mentors who helped me attain a level of competence in both arenas.

Then I had the unfortunate experience of losing my father at a time when my lab was making meaningful scientific discoveries, but none of those insights were able to impact his disease. I felt a profound level of disappointment that I couldn’t help him and other patients suffering from cancer. His passing had a significant impact on my career, as it solidified my interest in not simply doing science, but doing science that mattered for patients. From that point on, everything we did in the lab was driven by the question of whether a discovery would help patients. With our new knowledge, what can we do to take the next step in the translational process? That impacted my orientation of science in general, but also the emphasis on cancer and its translation into applications that would reduce the pain and suffering from cancer.

We would ask very practical questions such as, ‘Are we systematically converting insights into drugs or diagnostics that can help save lives or prevent diseases from happening in the first place?’ I began studying the processes or the organizational constructs that are needed to systematically enable translation of knowledge. I was surprised to learn of the system’s inefficiencies. The ecosystem allows knowledge that occurs in our academic medical center to eventually reach the private sector, but at each step along the way—clinical research, trials, implementation on a population scale—I thought the handoffs would be more deliberate and organized than they were. I began asking what my team could do to move that forward.

There seemed to be poor coordination between the promise of science and the deliberate application from the private sector in the form of new drugs, diagnostics or devices. I began to consult for large Pharma in an effort to bring the insights in genetics, genomics, and use of engineered mouse models as a means of reducing unnecessary failures in clinical trials.

I learned a lot from that experience and I also learned large Pharma was risk-averse in adopting science-driven drug discovery. Guided by great mentors with entrepreneurial experience, we sought to create companies that would fill this void of science-driven drug discovery to influence rational drug discovery and development on a larger scale. These companies were driven by the idea that strong preclinical science could help reduce the rate of failure for cancer drug development.

Q | From physician scientist to entrepreneur, how much did that experience shape your decision to come to MD Anderson?
A | As a physician, scientist and entrepreneur, I learned a tremendous amount about how drugs get made. The lessons that I learned from mentors in business and operations had a very significant impact on my trajectory. At Harvard, I founded the Belfer Institute for Applied Cancer Science, which, in 2003, was an attempt to bring the best attributes of science, academia and industry together. It was a concerted effort to deliver on discovery, drive opportunities forward and get higher visibility so the launch point of ideas to the private sector would be more productive. We sought to validate or de-validate concepts more robustly before starting a company or licensing a drug.

I learned a lot from that experience—good things came out of it, lessons were learned and it was clearly contributing toward moving the ball down the field for the benefit of patients. When I was given the opportunity to come to MD Anderson, I reflected on my background and the different attributes and experiences I had, and I asked the question of whether or not the institution, which was clearly the greatest institution in the world in cancer science and cancer care, would benefit from someone with my background who would bring new ideas or new ways of approaching things that could better organize efforts to help patients more quickly. I was inspired by MD Anderson’s critical mass, its singular focus, its culture of collaboration, its patient-centric efforts, its research-driven patient care—all of these things were astonishing and inspiring at the same time.

Also, what was happening was a true change in the field, where we were afforded new opportunities in cancer that were truly historic. The cancer genome, the advances in imaging physics and nanotechnology, the ability to sequence genomes at clinically active time frames at an expense that’s man- ageable, the ability to aggregate data and analyze data with artificial intelligence systems. These are all things that came online when I was considering the opportunity—the privilege—of coming to MD Anderson. At this particular point in time, leading MD Anderson was a very compelling opportunity. I was very fortunate to be given the privilege and the honor of leading the greatest institution in the world in cancer care.

Upon arrival here, I met with hundreds of investigators, clinicians and beyond to understand the institution, what its capacity was, what its opportunities were, where its culture and orientation were, and I recognized there was an opportunity to bring the institution and its formidable talent, resources and reach to bear on the cancer problem. I embraced this responsibility and went at it with full force.

Q | MD Anderson has had many exciting and bold initiatives over the years. One was the branding campaign which is one of the most brilliant I’ve ever seen—striking through your name to drive home the concept of ending cancer. There’s also the Moon Shots Program and the concept behind it. Can you talk a little bit about how those concepts came about?
A | First, with respect to the marketing and the branding, those things only work if they’re grounded in reality. You walk the hallways here and whether you talk to the valets, or our volunteers, or our neurosurgeons, or our Board of Visitors, everyone is truly focused on the mission. Everyone understands what we’re doing—Making Cancer History—and we want to end cancer in Texas, the nation and the world.

All that we do is focused on trying to achieve that mission. The credit for the concept of striking through CANCER and Making Cancer History goes to John Mendelsohn and his communications team. The enduring nature of that brand and the true power that it carries rests on the fact that it’s actually who we are. It’s grounded in the reality of the conviction of all the 21,000 cancer-fighting champions of MD Anderson.

In terms of the Moon Shots Program, this program is a reflection of the historic opportunities in the field. Throughout my career, I’ve had the tendency to look five to 10 years into the future and consider what’s possible. We knew when we started the Human Cancer Genome Project in 2007, that we did not have the technology to sequence the tens of thousands of tumors needed. But we knew if we put our minds and will to a task, we would succeed—history has taught us that when you have a goal and you have ingenuity and determination, you will achieve that goal. You may not know exactly how to get there, but you will achieve that goal. We saw that with the Manhattan Project, we saw that with the moon shot; it was not possible in ‘62 to complete that goal, but we knew it was possible if we put our minds to the task. That’s what Kennedy taught us, that’s what George H.W. Bush taught us in 1989 with the Human Genome Project—again, a daunting task, seemingly impossible, but a decade and $3.6 billion later, we had the blueprint of life for humans. History has taught us if you have a goal and articulate a vision at the appropriate time, you can make a difference.

Reflecting on the status of the field, it seemed to me there was a lot of prosecutable information. We had a lot of understanding of what caused cancer; we had technology that could detect cancer earlier, when the chance to cure it is greatest; and a lot of new clinical proof of concept—this was the game-changer, in my mind. I was seeing the early data that came out in 2009 and recognizing we were experiencing the game-changer on the therapy side. Those were early days, but again, looking ahead and thinking, ‘Well, we now better understand the rules here. Can we build on this?’ That conceptual maturity was coupled with the technological prowess, and there were a couple of things there that were really exciting to me. One was the ability to sequence in real time, for a fraction of the cost and a fraction of the time—that was a game-changer from a clinical standpoint. The imaging capabilities that we had, and the maturing of imaging physics, were game-changers as well, and they were there to better detect disease. The advances in serum proteomics, to detect serum proteins, potentially identify early biomarkers of disease, long before you can even see them by imaging. Things of that nature.

If you look out ahead and ask, ‘If we could detect cancers as early as stage 1 or 2, what kind of an impact would we have? Why aren’t we getting there?’ The opportunities there were obvious. Then, what happened with Watson, and artificial intelligence, and the cloud, and mobile technology; those were obvious, so you look at those and say, ‘You’re well positioned as a field to do things.’ The second question you have to ask is, ‘Are we organized to be able to do that? Is the government or our school system doing what’s possible to prevent disease? Are hospitals and medical centers providing state-of- the-art, evidence-based care? Is the biotech industry using rigorous science to drive the best drugs forward?’ and so on and so forth. If you look at the prosecutable information in hand today and the length of time that infor- mation has been around, you’d have to conclude that there are opportunities for optimization. So, we set out to build teams, infrastructure and resources to accelerate the conversion of knowledge into clinical endpoints that would save lives.

Q | How impactful is it to have MD Anderson, the largest cancer hospital in the world, on the campus of the Texas Medical Center?
A | I think it’s immeasurable. I don’t think MD Anderson would be the powerhouse that it is without other world- class institutions that have made us better. To have the best medical school in Texas right next door in Baylor College of Medicine; to have one of the top children’s hospitals in the country right next to us; to have UTHealth and its multiple institutions from bioinformatics to public health; to have great institutions like Rice and their gifted engineers and academicians; Memorial Hermann and its trauma care; the legacy of Texas Heart Institute, and Cooley and DeBakey and Methodist. We are great because we are the TMC. Any of those institutions benefit mightily by the success and well-being of the other institutions. It’s a symbiotic relationship that has driven our collaboration, our competitiveness to be the best, and the facts speak for themselves. We are an engine for discovery and for delivery, the likes of which the world has never seen. Bobby Robbins’ leadership is taking us to a new level of impact.

Q | Do you have any closing thoughts?
A | We’re at a special point in the history of the field of medicine where we’re very excited about the opportunities for science really changing the natural history of diseases like cancer and heart disease. The greatest challenge and the biggest responsibility we have is to ensure this knowledge is delivered to those in need. It’s not enough to care for folks who can come here and access the world’s best care. We also have to work hard to spread our knowledge and deliver safe, effective care to others through our science and clinical care. The TMC, with its reach and its potential, has an opportunity to level disparities and solve diseases through prevention, early detection and definitive treatment. MD Anderson plays a very special and prominent role in that process when it comes to cancer, for the country and the world, and it’s a responsibility we embrace.

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