Dr Harriette Van Spall: I’m Harriette Van Spall, Associate Professor of Medicine and a cardiologist at McMaster University in Canada. I am absolutely thrilled to have with me Dr Eugene Braunwald, Distinguished Hersey Professor of Medicine at Harvard Medical School and founding chairman of the TIMI Study Group. We are here to discuss his life achievements and research advice for young trainees. Welcome, Dr Braunwald.

Dr Eugene Braunwald: Thank you. It's nice to be here.

Dr Harriette Van Spall: I’m so delighted to talk to you in this masterclass. I wonder if you could begin by telling us about your early life—how you came to the United States from Austria and chose to begin studying medicine here.

Dr Eugene Braunwald: Okay. So, until the age of nine, I was born in Vienna and led a wonderful life there. My parents were interested in opera, and they took me as a kid; I went to a wonderful school and had a special tutor in English. Then the Nazis came in March 1938, and we escaped as refugees, ending up in England. We came to the United States after World War II began in 1939. It was a very close call, but fortunately, our nuclear family made it.

We lived in Brooklyn, and I went to Brooklyn Technical High School, which is a terrific school that required a tough entrance exam. From there, I went to NYU and then the NYU College of Medicine. In medical school, they began one of the first elective programs in the country; before that, medical education was straight through without choices. I elected to work in a cardiac catheterization laboratory in 1951. At that time, cardiac catheterization was a tough research procedure, not a diagnostic test. The first project I worked on was congestive heart failure and hemodynamics.

I then went on to my clinical training at Mount Sinai and had three cardiology fellowships: one at Mount Sinai in cardiac catheterization, a second at Bellevue Hospital with André Cournand—the father of cardiac catheterization—the year before he won the Nobel Prize, and then to the NIH, where I worked in more basic cardiovascular physiology. I eventually became head of the cath lab there. Cardiology has been part of my life for 70 years.

Dr Harriette Van Spall: Those are pivotal training experiences in exceptional centers, and I imagine mentorship played a key role. Tell us about how the adversities in your childhood—escaping a time of pain, uncertainty, and injustice—shaped you as a person and researcher.

Dr Eugene Braunwald: I learned two things that were terribly important. The first and most important was family. There were times during that period when the question of separation came up, but my father insisted we stay together, saying, “If we’re going to die, we’re going to die together; if we’re going to live, we’re going to live together.” That imbued a feeling of family cohesion that I have tried to transmit to my children and grandchildren.

The second thing I learned was that it is normal to work very hard. We were very poor, and my parents worked 12- to 15-hour days in both England and New York just to stay afloat. I began to feel that working those hours was normal, and a strange thing happened: I enjoyed it. While colleagues looked for relaxation, for me, relaxation was continuing to work in the evenings and on weekends. Even now, in my 90s, I’m working 12-hour days, six and a half days a week, and enjoying it. I also became immediately very curious; I wanted to answer questions.

Dr Harriette Van Spall: Powerful lessons there. What do you consider your greatest achievements?

Dr Eugene Braunwald: What I am most proud of is the concept of infarct size reduction. Into the late 1960s, the idea was that coronary thrombosis and tissue death happened very suddenly, and you just handled the aftermath. From clinical observation of patients with “stuttering infarcts”—where ECGs with ST elevation would go up and down—I realized it wasn't like a light switch being turned off.

We began experiments in open-chest dogs and showed it was possible to influence the size of an infarction. We found that reducing oxygen demands with beta-blockers or slowing the heart rate reduced infarct size. In 1971, we published the concept in Circulation, stating that rapid reperfusion could salvage myocardium. In 1975, Eugene Chazov, a famous Soviet cardiologist, injected streptokinase directly into an occluded coronary artery and it opened up. We showed that ischemic tissue isn't dead and can regain function when reperfused. While we now use stenting and other techniques, I am proud of that original idea.

Dr Harriette Van Spall: If you had a chance to do your career again, would you do anything differently?

Dr Eugene Braunwald: I spent 35 years in major administrative jobs, including being a Department of Medicine Chairman at both the University of California and Harvard. Looking back, I shouldn't have stayed that long. Those are huge jobs dealing with faculty salaries and hospital administration. I protected at least 25% of my time for research, but I could have had 100%, and that would have been better. Perhaps 10 years of administration would have been sufficient.

Dr Harriette Van Spall: What advice would you give to young researchers starting out in cardiology?

Dr Eugene Braunwald: The most important decision you make is where you do your research fellowship and who you choose as your mentor. People worry about college, medical school, and residency, but none of these matter as much as your research mentor. You must do your homework. Ask people who worked in that laboratory how they did with that person. Sometimes a “big name” is not the right name because they may be too busy or unavailable. You want a mentorship that guides you but lets you grow so that by the end of three years, you are independent.

Dr Harriette Van Spall: What are the biggest research gaps we ought to close in the next five to ten years?

Dr Eugene Braunwald: The most important thing is that we “get rid of cardiologists”—meaning the next challenge is prevention. I am particularly interested in primordial prevention beginning in neonatal life. Using GWAS (genome-wide association studies), it is now inexpensive to perform polygenic analyses on newborns to identify risks for hypertension or atherosclerosis 30 years down the line. We should divert resources to look at prevention at every level, including dietary sodium intake from the beginning.

Dr Harriette Van Spall: Thank you so much for your time. It has been such an honor to learn from you—a source of inspiration who has overcome adversity to shape our careers and the care we provide patients.

Dr Eugene Braunwald: Thank you.

This transcript has been lightly edited for clarity.