Eugene Braunwald Escapes From Austria
Robert M. Califf, MD: I'm Rob Califf. Welcome to our "Life and Times" show, which covers the lives of famous cardiologists and their accomplishments. Our goal is to provide insight into what makes people tick. It might give you some pointers if you are developing a career, thinking about what to do in the future, or even improving the way you interact with others to get things done in cardiology.
I'm really lucky to have Gene Braunwald with me today, someone who has mentored more people than any other person in the history of cardiology.
I would like to start at the beginning. I spent a week in Vienna playing golf about 2 months ago. We have an international competition among cardiologists. I had never spent a lot of time in Vienna other than to go to a meeting. It's a beautiful place, but also has some very ugly history that you were a part of. What did you take away from that early experience?
Eugene Braunwald, MD: Vienna is a splendid city. I go back there every year or two, and I'm going back in November. It means a lot to me.
We left Vienna in 1938 under very difficult circumstances. What was disappointing was not so much that the Nazis took over, but that they were received with open arms by the Austrian population. That was a shock. I was eight and a half at the time, but my parents' phone never rang again. My father was fifth-generation Viennese and had gone to school there and had many friends. It was a sudden cut-off. Things got much worse, but we were able to escape.
The charm of the city persists. I have very good friends there, and I love going back. I like Salzburg even better.
Dr Califf: We were staying at a hotel in City Center and walked through that square where Hitler gave his address. It's unbelievable. You said it well. Given how nice the people are there, how could this happen? Times were tough for everyone then, so it was easy to turn on people.
Dr Braunwald: Yes, it was. The Depression hit Europe even more than it hit us in the United States. There were a lot of pent-up emotions, and this seemed like a simple way forward.
A New Start in the United States
Dr Califf: This must have left an amazing imprint on your whole family, but your immediate family all got out. Did it change the way your parents interacted with you?
Dr Braunwald: My parents were 35 and 34. By our standards (certainly by my standards), they were very young people. Growing up in this country, my parents were pretty cynical about the news. They had been burned so hard, and that had an effect. As they got older and as I became an adult, they mellowed. So it took them about 30 years. They became part of American society.
Dr Califf: What did your parents do for a living?
Dr Braunwald: My father was in wholesale clothing, both in Vienna and then in the United States. He had to start again from the bottom. He started in a very primitive way as a door-to-door salesman. He had to put food on the table, but from that he built up a very nice business. My mother stayed home until his business was established, and then she worked with him.
Dr Califf: Do you have brothers and sisters?
Dr Braunwald: I have a brother. He became a physician as well—a hematologist.
Dr Califf: You must have been driven to succeed, having that background. When you came to the United States and were in school, did you feel that you were different?
Dr Braunwald: I felt that I was different, and people perceived me as such. I have had a lot of lucky breaks, and one of them was timing. I started college in 1946. World War II ended in 1945. A tremendous rush of veterans were coming back—people in their late 20s. They had to catch up. They had spent time fighting. They were determined to get an education, and so college and medical school were accelerated. I graduated medical school at age 22. That gave me some extra time.
Dr Califf: My dad went over and fought in the Battle of the Bulge. He was in college and came back and finished his education at Clemson. That must have been an amazingly intense time for education, because these people had seen things that they would have never imagined.
Dr Braunwald: Post-World War II was a period of tremendous growth in this country. A lot of people say that Roosevelt didn't get us out of the Depression. It was World War II, unfortunately, that got us out of the Depression. Then things really took off.
Medicine and Music
Dr Califf: Where did you do your university training?
Dr Braunwald: I was at New York University (NYU) for undergrad and medical school. I served on the board for 7 years.
Dr Califf: I've recently seen NYU in Abu Dhabi of all places, where we're doing some work, and they have a facility there. Do you think that's a good idea?
Dr Braunwald: I don't know what the motivation is. I look at that very carefully. It's fashionable now.
Dr Califf: What influenced you at age 22 to pick a specialty? At that time, specialists were not that numerous, were they?
Dr Braunwald: No. We think about research opportunities for students that virtually all medical schools are encouraged to offer. It wasn't like that for the class of 1952.
We had a new associate dean for education, which is the first time that position was established. Timing is everything. It was the year before I went into my senior year, and he changed the curriculum and opened up 3 months of elective with opportunities for students to do research. He asked me what I was interested in. I had been interested in cardiovascular physiology as a freshman physiology student, and had aspirations for engineering when I was 16 because that was a pretty hot thing during the war. So the idea of hemodynamics, pumps, and so forth with the heart seemed natural.
I was the first student to do a research elective in a cardiac catheterization laboratory. There were 12 cath labs in the country. Ludwig Eichna was the leader of the laboratory, and he was studying the hemodynamics of heart failure.
Dr Califf: So you started with a human model. Did you work and study all the time, or did you have hobbies?
Dr Braunwald: I have always been interested in music as a consumer (not a performer). I had the unusual opportunity of taking a couple of music courses as an undergraduate. One of them was in opera. My parents were music buffs, and they took me to the Vienna Opera when I was 5 or 6 years old. When I took this opera course at NYU, the professor had a connection with the Metropolitan Opera. He let us carry spears. So I made my debut carrying a spear in Aida. It was a dollar a night, which at current rates of inflation would be about $500 now.
I did that many times while I was in college and even at the beginning of medical school. Then things got too busy, but I have always enjoyed music. I have a wonderful CD collection and enjoy the opera. I also enjoy chamber music now.
Doors Open to the NIH
Dr Califf: So there you were, studying human heart failure at age 22. That in itself is remarkable. Did you run into Eugene Stead at that time? He was studying heart failure down where I'm from.
Dr Braunwald: Yes, I did. He was an early hero of mine because in the papers that Eichna gave me were some very seminal papers by Warren and Stead. It took me a number of years to realize that they had been at the Brigham and Women's Hospital before they went to Emory University, and Stead had been at Emory before he went to Duke. They have both been heroes of mine for a long time.
Dr Califf: Eugene Stead was such an interesting man. He lived into his 90s, and every Christmas he would write me a handwritten letter telling me everything I had done wrong in the previous year, but in a very helpful way.
So you went from research into more clinical training. How did it work at that time?
Dr Braunwald: I had an internship residency. Then, a strange thing happened. The Korean War reared its head, and I was at Mount Sinai doing my clinical training. This will sound incredible, but the chief of medicine refused to let me finish my training because he was convinced that I would be drafted and disrupt the schedule.
It turned out to be a lucky break. During that year when I thought I was going to be drafted, I got married to Nina, a classmate who was a surgical resident. I went back to Bellevue, but not to Ludwig Eichna's laboratory. At that time, Bellevue was a 4000-bed hospital, and it had a Columbia service and a NYU service. The Columbia University service had a cath lab, so out of the 12 cath labs in the country, two were at Bellevue Hospital. The other lab was run by André Cournand, who was the father of cardiac catheterization and who, a year after I was there, won the Nobel Prize. There is no connection between the two, but it was a tremendous opportunity and he was a very stimulating person.
That experience opened the door for me at the National Institutes of Health (NIH). For anyone who had academic aspirations, the NIH was just building the clinical center, which was growing and had to be staffed. The competition for getting into the NIH was fierce. It was a "uniformed service" hospital—the public health service—although I never wore a uniform. The competition was fierce, but the fact that I was finishing the fellowship with André Cournand opened that door to me.
I was interviewed by Robert Berlin. He said, "Would you wait outside for a few minutes?" He made a call, and then said, "Come in. You're in." That's how I got to the NIH. I spent 13 years there, and then finished my clinical training at Johns Hopkins.
Dr Califf: At the NIH, were you doing clinical care?
Dr Braunwald: Yes, I did a lot of clinical care and clinical cardiology. After about 6 years there I became chief of cardiology, and looking back on it, it was probably the most productive time of my professional life.
Dr Califf: I have heard stories that there are Saturday morning meetings to go over research data.
Dr Braunwald: Saturday morning meetings—that was nothing. There were Sunday night meetings. We worked very hard. We think about how careful we have to be about resources. There was a period there when you could get anything reasonable, and a few unreasonable things.
The annualized growth of the NIH budget during the 1960s was in the low 20% range. They were building extramural programs all over the country. They had lots of hungry people in the intramural programs, and that really shot up. Then, as people left that, it populated the rest of the culture.
I was one of the people who grew up in the system there. I started in the clinical center before it was physically complete. By the time I left, it was more than physically complete, and there was a good turnover.
Taking Pride in Accomplishments
Dr Califf: What was your most significant accomplishment at the NIH during that time?
Dr Braunwald: Looking back, I would say that there were two things that I am most proud of. One was in physiology—the determinants of the heart's oxygen consumption. That comes into play so often when we talk about ischemic heart disease and myocardial infarction being the ultimate ischemic episode.
It is something that I worked on when I was a fellow in Stanley Sarnoff's laboratory in 1955 when I first got there, and then when I got my own lab, which was in 1958 to 1959, I continued working on that until I left in 1968. We had a nice body of work. I look back on that with some pride because after I left the NIH, that led to some dog experiments showing that we could influence an infarct. Although it was physiologic research, it was patient-driven. It was not abstruse research.
The second thing that I'm proudest of was the work on hypertrophic cardiomyopathy, although we were not smart enough to call it that at first. I did some of the first hemodynamics with Glenn Morrow, who was a terrific surgeon and a wonderful mentor. I would put Glenn Morrow, a surgeon, at the top of my list of mentors. He and David Sabiston were close buddies. I got to know David through Glenn Morrow.
Dr Califf: Dr Sabiston (I can't call him David) was a straight arrow, wasn't he? He was really determined to have an impact and mentor people.
Sojourn to the Other Coast
Dr Califf: So you were drawn away from the NIH finally to go to sunny San Diego. What was the precipitating factor there?
Dr Braunwald: I became interested in clinical medicine, and I ran the cardiology service. I made rounds 5 or 6 days a week, but I also was interested in general medicine. I had a teaching professorship at Georgetown, and I did medical rounds there for 3 months a year. I had lots of contact with medical students, and there was a new wind blowing in medical education at the time. So I said, "Okay, I have done this." I wasn't going to retire from research, but I was not going to do it 60 hours a week.
Something good came out of that. I went from doing 95% research to 15%-20%, and then I had to choose. When you don't have to choose, it's like going to a buffet and there is just too much to eat. On the other hand, when I had to select one thing and get a grant for it, I chose modification of infarct size. That was the right choice because if I had gone on at the NIH, I would have dabbled in a lot of things.
Of the wonderful people at NIH—John Ross, Ed Sonnenblick, Burt Sobel—most of them came out to California and we were able to continue our work, although I stepped back from a lot of that. I worked with one postdoctoral fellow, Peter Maroko. I went out to California because I liked the new idea of a medical school in which internal medicine was going to have the responsibility of a lot of preclinical education. Now internal medicine does all of that, but there is still basic science to balance.
The organization of the school was neat, and I thought that with the interest that I had in physiology and pharmacology, I could probably teach those subjects. We had a very good person to head infectious diseases who taught microbiology.
We were really a bunch of amateurs. When that charter class graduated, they came in first in the country on their boards. We were not teaching for the boards, but there was a kind of enthusiasm and involvement. We had only 32 students, and we gave them tremendous amounts of attention. But then there came a push and a pull, so I left and went to Boston.
The "push" was Governor Reagan. Within 10 days of Governor Reagan assuming office, he fired the president of the University of California, Clark Kerr, who was a major figure in higher education. Reagan said that there would be no more construction of teaching hospitals. You can be a great hospital without a medical school, but you can't be a great medical school without a great hospital. I saw the handwriting on the wall, and that was the push.
Dr Califf: A footnote about the education: We learned in our Singapore medical school that starting from scratch with people who love to teach is much better than the ossified systems that a lot of our medical schools seem to have.
Back to Boston
Dr Califf: You arrived in Boston and made some fairly dramatic changes.
Dr Braunwald: There was a lot in the department that needed revitalization, to put it politely. I got a bad rap because, looking back, I replaced a number of division chiefs, but I worked very hard to find good positions for them. They all did very well, and I even became friends with some of them after they left. We retained very good relations.
Dr Califf: You made an important point: Most people have a place where they belong, and if you take the time to help them find that place, it's still uncomfortable, but it can turn out to be good for all sides. Your legacy in Boston was all the people whom you mentored. Do you think that's a fair depiction?
Dr Braunwald: I think so. I'm very proud of these people. They have achieved a lot of fame, but how famous they are is not what counts, but rather their accomplishments and the way they have influenced others.
What I took away from my experience at the NIH, and to some extent from San Diego, was that you have to break down rigid systems of education. That's one of the things myself and my partner in crime in Boston, Marshall Wolf, set up. We take that for granted now, in the same way that we take research electives for students for granted, but it was not always so.
The first year I was there, I recruited four interns into the research residency track. One is now the editor of the New England Journal of Medicine. The second year, four interns were recruited into the research residency track; one of them is the current president of the Dana-Farber Cancer Institute and the former chairman of medicine at Johns Hopkins (Edward Benz Jr.).
In my early years at the NIH, I learned that if you have somebody in their 20s who is energetic, you can grow simultaneously in two areas. You don't have to partition the time. You have to arrange it so that their laboratory work is a continuation of what they did for a PhD or for an elective year, and it has to be nearby. You can't send them to the Massachusetts Institute of Technology or to Chicago to do their research. It has to be local, and they have to maintain some clinical contacts.
These research residents—they were called "hemi-docs"—had to maintain a clinic and spend one night in the emergency room for 6 months of the year that they were in the lab. Their mentor had to give them a technician to assist them during the six months that they were on the wards.
Dr Califf: Is there a general principle here? Why is it that we partition things? In medical schools now, the students know nothing about research. You say that it's not lockstep now, but most medical schools have a 4-year curriculum. The students may take electives in clinical matters, but they are relatively ignorant about the research world.
Dr Braunwald: Many medical schools now are chartered to produce family physicians, and I don't dispute that. We do need more general internists in the country, but people should be stimulated when they go to medical school. It should not be a vocation. It's a profession. There are many opportunities to go in multiple directions.
The following year, at the Brigham and Women's Hospital, we set up the first family practice internal medicine program. We had both ends of the spectrum. That has been the most rewarding part of my life.
How to Recognize and Nurture Talent
Dr Califf: What about the principles of mentoring people to become leaders? Is there a secret sauce? What do you have to have in your mind if that is a goal?
Dr Braunwald: The first thing is not to compete with them. That comes up much more in the research world than in the clinical world. It begins with selecting people, and comes back to the experience I had as a very young chief of cardiology in selecting people. I had a great mentor there in my boss, the director of research Robert Berliner, who taught me many tricks, such as how to read an application. It is not the genealogy of the person, but what knowledgeable people say about the candidate rather than having gone to the best schools or having the highest grades.
Dr Califf: I remember you telling me that about Marc Pfeffer, who didn't come from Harvard. Can we get that kind of truth these days? It seems that in the legal environment, people are afraid to say what they really think.
Dr Braunwald: We have to do due diligence. It's more than superficially what someone writes on a piece of paper. We have to dig. You need a good Rolodex. You have to know who to call and who you can rely on.
I discovered Marc Pfeffer. He gave a talk at an American Heart Association meeting when he was an MD/PhD student in Oklahoma.
Dr Califf: You saw his talent?
Dr Braunwald: Yes.
Dr Califf: One of my mentors is Lloyd "Holly" Smith, who has said almost exactly what you are saying. He gives a talk on what he calls "academic sex." The point is that you are developing progeny. I love what you said about not competing with them because once you start that, you have an unhealthy situation.
We could talk about a lot of people whom you have mentored with great success. Do you look back and see any mistakes that you made during that era?
Dr Braunwald: I had a postdoctoral fellow who committed fraud in my laboratory. That was not a good period. I learned a lot from that, the most important thing being that if someone finds something that is three standard deviations from the expected, the burden is on them to prove that they are innocent as opposed to the other way around. In our judicial system, we say that you are innocent until proven guilty. When you have done something that is far outside the realm of normal, you can't justify it as an aberrant event that happened because of particular pressures and so forth. That was the major lesson that I learned.
Dr Califf: I have had that experience in the institution, and gotten 60 Minutes time because of it. It seems that in the culture, we have to be more diligent when people are outside the bounds. They might be brilliant and different, but we have to find that out.
Starting a Secret Society?
Dr Califf: Something that still fascinates me is the formation of Partners. You have had a great academic career. You have run a department of medicine. Then you see a need for a different business entity. Is it true that you all met secretly many times and hatched this plot with a small group of people?
Dr Braunwald: Yes. We kept it in confidence. There were six of us from Massachusetts General Hospital and Brigham and Women's Hospital—the chairman of the board, the chief executive officer of the hospital, and they selected one physician. I was the person they selected from Brigham and Women's Hospital. It didn't seem like that big a deal at first because we didn't meet for more than 15 hours in total over the course of about 6 months. We basically wrote down a set of principles.
Dr Califf: And you didn't hire a consultant to do it for you?
Dr Braunwald: We did have a legal consultant because there were issues of governments and fiduciary responsibility, and many things that I didn't understand. It was a time when we felt that the hospitals were emptying. Both hospitals had lost about one third of their patients. If you look back on the history of that period, which was in the fall of 1993, the low point in the combined census was the week that we signed the deal. Then it bottomed out, and patients started flowing back because several small hospitals in the state of Massachusetts closed.
Dr Califf: Necessity is the mother of invention. Were other societal factors playing into it? Are you happy with where Partners is now?
Dr Braunwald: I'm moderately happy. There could be greater synergies. There are some, but they have not taken full advantage of each other.
Early Translational Research
Dr Califf: You have described eloquently how you got involved in thinking about infarct size and the way myocardial infarction happens, but when you started, you weren't thinking about blood clots, were you? When did you get into the thrombus? I still remember as a medical student, I was taught that blood clots didn't cause heart attacks. Shortly thereafter, we were doing angiograms, and then the TIMI trials started.
Dr Braunwald: Marcus DeWood was the turning point. The other was an error because people looked at a postmortem, and a lot of fibrinolysis goes on postmortem. Obviously, not every infarction is thrombotic, but the large ones are.
Dr Califf: My perception of you is that you follow things very closely on a wide angle. You pick up things that are happening, and then move on them. So you didn't discover that thrombus causes heart attack?
Dr Braunwald: No.
Dr Califf: But when you saw that you were prepared, like a Boy Scout.
Dr Braunwald: Yes. In a paper[1] that we published in 1971 (with first author Peter Maroko), we stated explicitly that if it were possible to increase perfusion and also reduce demand, we could make a very big difference.
Curiously, I knew about streptokinase because the discoverer of streptokinase was William Tillett, who was chairman of medicine at NYU when I was a student, and Sol Sherry was his research fellow. They were giving streptokinase to patients at Bellevue who had fibrothorax.[2] These patients had pneumonia and organized pleural obliteration, which they treated. He did some preliminary studies of intravenous streptokinase.[3,4] Chazov took the big step of giving it intracoronary.[5]
Dr Califf: You didn't start out as a trialist, but you are one of the biggest clinical trialists now. What happened? How did you become so interested in clinical trials?
Dr Braunwald: What got me interested in clinical trials was the TIMI study.[6] I began to see the problems with surrogate endpoints. Physicians gave digitalis for historic reasons (it might cause less ankle swelling), but pharmacologists had strung up both amphibian and reptile hearts, and when they added digitalis to the perfusate, the hearts contracted better. That was sufficient. Now we laugh at that.
Dr Califf: That was translational medicine back then.
Dr Braunwald: Yes, that's right, but it became very clear that it was going nowhere. That's why I began to do clinical trials. The first major trial with surrogate endpoints was with Marc Pfeffer and the SAVE trial,[7] giving captopril post-myocardial infarction.
Dr Califf: That's a great story. There was great news this week about advancing beyond angiotensin-converting enzyme inhibitors.
My last question is about the current state of your family. You are very involved with your grandchildren. What is the total count now?
Dr Braunwald: The total count of my grandchildren is seven. My wife is here at this meeting. I have three daughters. One of them is in medicine. Two of them were smart enough to seek other employment. They have blessed me with seven grandchildren. Fortunately, we are all in the same area, although the children and grandchildren are beginning to scatter around. We still have a few at home, but they all seem to return when they are in this country for Thanksgiving. We look forward to that.
Dr Califf: What is in the future for Gene Braunwald?
Dr Braunwald: I like what I'm doing, as long as I feel that I can contribute. It is important to be a careful judge of that. Sometimes it's difficult. I retired from my chairmanship when I was asked repeatedly to continue it, but I felt that I had done that part. It's an internal feeling, but I'm not quite there.
Dr Califf: I look forward to the IMPROVE-IT[8] results at the American Heart Association meeting. You are like an assistant professor looking for the next question to answer. As long as you have curiosity, it's a great thing.
Dr Braunwald: I'm still interested in heart failure.
Dr Califf: Thanks for spending the time with me. Our readers will get a real thrill out of hearing about what you have done and the way you have thought about it.
