The Danger Within Us

by Jeanne Lenzer

  Braunwald was an overachiever from a very early age, and it seemed preordained that he would rise to the top of any field he entered. Born in Vienna, Austria, on August 15, 1929, he described his childhood as “idyllic.”16, 17, 70, 71 His parents began taking him to the opera when he was just five—a pleasure he continued to enjoy throughout his life. “I felt totally secure,” he said. “I had private piano lessons, I had an English tutor, and I went to a very good school…my mother would take me to the park and I would be in my Lord Fauntleroy outfit, including the white gloves. The University of Vienna was just two or three blocks away. We would take a walk, and she would point to the University and say, ‘You’re going to be a professor here.’”

  In school he showed a fierce drive to succeed. While other youngsters his age took welcome breaks from school and homework, Braunwald shuttered himself in his room, studying with a single-mindedness that set him apart. Even family gatherings and games failed to lure him away from his studies.

  Braunwald’s family narrowly escaped the Nazis, moving first to London and then to New York in 1939, when he was a child. Four years after the family settled in Brooklyn, Braunwald had adapted to his new environment well and was an outstanding student. He graduated first in his eighth-grade class, and in 1944, at the age of fourteen, he won admission to Brooklyn Technical High School, an elite school focused on engineering, math, and science. He raced through his course work, ultimately opting for a “diploma mill” to graduate, then, at sixteen, he began college at New York University. By his own account he studied “about a hundred hours per week,” earning straight As. It was at NYU that he would meet his future wife, Nina Starr, who would go on to become the first female heart surgeon. His sole escape from long hours of study was to sneak off to the opera with Nina.

  Although he originally wanted to be an engineer, he realized he lacked the manual dexterity required to do drafting and shop work. So he switched his career goals and decided to go into medicine. Once again, Braunwald leaped ahead in his studies. At the age of nineteen, just two years after starting college, he entered NYU’s medical school. In 1952, he received his MD, graduating first in his class. As an intern, he recalls, “I read when other people were too tired to read.” He was on his way to becoming one of the most well-known men in medicine.

  After considering a number of specialties, he ultimately settled on cardiology, a field he said was closest to engineering: “In cardiology, I deal with pumps, which is like mechanical engineering. But I also deal with electricity, so there’s a bit of electrical engineering, too.”

  While excited by the challenges, Braunwald was also troubled by some of the practices he saw as a medical student. Early in his training, he recalls walking to Bellevue Hospital and seeing doctors in their white lab coats hurry past homeless people lying on the street. Later, while in training as a resident at Johns Hopkins Hospital, he had his first encounter with segregated wards. There were two separate training programs: doctors in training in the Marburg service provided care to private patients, while those in the Osler service provided care to all patients. Braunwald applied only to the Osler service. Patients were segregated there, too, in four large wards divided by race and sex. Even blood was segregated, and Braunwald was disturbed that although the blood of white donors could be given to African Americans, the reverse was not true. The concept of a white person’s “racial purity” being “contaminated” by black blood was likely evocative of his narrow escape from the Nazis as a child.

  Despite the blatant class and race divisions at Johns Hopkins, Braunwald was impressed that all patients were addressed as sir or Mr. or Miss or Mrs.—but never by their first names, as was so often the case at other hospitals (unless the patient was a well-off white male).

  Medical research was Braunwald’s greatest passion. At the impossibly young age of twenty-eight, he became chief of the section of cardiology and subsequently the clinical director of the National Heart and Lung Institute, which in later years became part of the federally funded National Institutes of Health (NIH). His arrival there coincided with what are often called the golden years of the NIH: 1955–1968. Funding soared during that period, rising from about $100 million to more than $1 billion per year. The NIH was an exciting and prestigious perch, and Braunwald reveled in his research collaborations with other scientists there.

  Yet in many ways, medical research was still in its infancy, with few doctors trained in research methods, and Braunwald wanted to bring some of his training at the NIH to the broader medical community. So in 1968 he left the NIH to become the first chairman of the department of medicine at the University of California San Diego School of Medicine, where he hoped to create what he called triple threat physicians—doctors who could teach, conduct research, and practice bedside medicine.

  In another step up the ladder, he moved back to the East Coast in 1972 to become a professor of medicine at Harvard Medical School. That same year, he served on the President’s Advisory Panel on Heart Disease. The living Nobel Prize winners in physiology or medicine named him the “person who has contributed the most to cardiology in recent years.”72 He wrote more than twelve hundred scholarly articles and served as the editor of the primary textbook used by medical students and doctors around the world: Harrison’s Principles of Internal Medicine. He remains the editor of Braunwald’s Heart Disease, which is widely considered the bible of cardiology.16, 17, 70, 71

  One of the many young physicians whose lives were affected by Eugene Braunwald was Jerry Hoffman, who met Braunwald in 1970 at the UCSD School of Medicine. Hoffman recalls his first impression of Braunwald: “I had no doubt at all that he was brilliant and incredibly accomplished. In virtually every aspect of cardiology he had made enormous, seminal contributions. He was in some ways an excellent teacher as well as such a giant figure in American medicine. I’ve never forgotten the lessons he taught us about cardiac pathophysiology because he made the concepts—many of which were based on work he himself had done—clear and understandable.” *

  But Hoffman also recalls of Braunwald:

  He was imperious, and certainly no one would have dreamed of talking back to him or questioning anything he said. His personal manner was extremely cold and off-putting, and he tolerated not even a hint of a challenge to authority—which I have long since come to believe is a terrible barrier to real learning. I’m pretty sure most if not all of us—residents and fellows and even faculty as well as bottom-of-the-pile students like me—felt not merely intimidated but actually demeaned by the way he talked down to us.

  Hoffman never forgot the lecture Braunwald delivered on angina pectoris—the name for chest pain associated with coronary artery disease:

  Angina was obviously a very important topic—and the lecture was given by Braunwald himself. So there we were seated in the auditorium, in our little white jackets, and everybody was nervous in front of Braunwald, who was always so stern. He brought in one of his patients, a retired navy admiral, to show us how to take a history from a patient with chest pain. There was one student in our class who always read ahead so that he could ask questions to show that he already knew more than was expected of us. He’d obviously read about how heart disease could interfere with physical activity—including sexual activity—so he asked the admiral something about his sex life. The admiral responded with a little joke, and everyone laughed. It was a nice moment and a relief from the general tension that was always considerable when Braunwald was at the podium.

  But after the admiral left the room, Braunwald ripped us a new asshole. He told us how humiliating and puerile our behavior was, tittering like little children about sex—he let us know in no uncertain terms how ashamed of us he was.

  During the lecture, Braunwald had made a point of teaching the students about the so-called Levine sign, a classic gesture made by patients who have coronary chest pain to describe their symptom. He asked the admiral to point with one finger to the place where his chest hurt. But instead the admiral
balled up his fist and placed it over the center of his chest, saying it wasn’t in just one spot. Braunwald exclaimed, “That’s it—Levine’s sign! When he put his hand to his chest like that and turned it into a fist, covering an entire area. If there’s one thing I want you to remember from this lecture, it’s what it means when a patient makes a Levine sign.”

  After the lecture, Hoffman and a friend found themselves waiting for an elevator with Braunwald and his cardiology fellow, who was furiously brownnosing Braunwald. Hoffman says, “He was telling Braunwald what a fabulous, wonderful lecture he had given and that none of us would ever, ever forget the Levine sign.”

  Hoffman waited a few beats, then turned to his friend and said in a stage whisper, “What was that thing, you know…that the patient did with his fist?”

  Braunwald was not amused. “He turned around and glared at me, and it was clear that if he could have crushed me at that moment, like the cockroach he surely considered me to be, he would have.”

  Jerry Hoffman’s irreverent bit of nose thumbing revealed an iconoclastic side to his own personality that we’ll encounter again in a very different context later in this book. But the story also shows us something about Eugene Braunwald—a brilliant, innovative medical thinker not greatly endowed with the gifts of humor, humility, or self-doubt…which may help explain some of the unfortunate byways into which he would later wander and into which he would help steer a significant portion of the American medical establishment.

  Braunwald did much more than simply conduct his own program of medical research. In 1984, he founded the Thrombolysis in Myocardial Infarction (TIMI) Study Group, which would grow into a multibillion-dollar multinational research organization with eight thousand researchers in fifty-two countries and more than three hundred thousand human test subjects enrolled in clinical trials.73, 74 Braunwald seemed to be everywhere, and his accomplishments were praised as unparalleled.

  His most important research contributions have been in four areas: diseases of heart valves, heart attack, an unusual condition now known as hypertrophic cardiomyopathy (HCM), and congestive heart failure.

  The discovery of HCM resulted from one of the most frightening moments of Braunwald’s career.17 Back in 1958, he had been working on aortic valve disease at the National Institutes of Health, the epicenter of medical research in the US, with Andrew Glenn Morrow, a heart surgeon. The aortic valve keeps oxygenated blood flowing forward from the left side of the heart to the rest of the body. If the valve becomes hardened and stiff, it restricts the forward flow of blood, depriving the brain and body of oxygen. The result can be chest pain, congestive heart failure, syncope (passing out), and even death if it is left untreated.

  Sometimes the aortic valve fails to close properly after the heart contracts, allowing blood to flow in the wrong direction, back into the heart, also depriving the brain and body of oxygenated blood. Less commonly, a fibrous ring just below the aortic valve can interfere with the forward flow of blood. Each of these malfunctions causes distinctive changes in the pressure gradients inside the heart. By measuring the pressures, Braunwald and Morrow could determine the diagnosis. Morrow depended on Braunwald’s findings to plan the appropriate operation.

  But all seemed to go horribly wrong one summer day in 1958, when Morrow angrily summoned Braunwald to the operating room. Braunwald arrived to find a young man lying on the operating table, his rib cage cut and his chest splayed open. His heart, an organ never meant to be exposed to the external world, was on display: red and still—paralyzed by a flood of potassium that was allowing Morrow to perform surgery. The man’s blood was being pumped through a cardiopulmonary bypass machine that artificially oxygenated his blood.

  As the young man lay unconscious on the operating table, Morrow said, “There’s a terrible screw-up here. I opened this guy’s heart, and I just can’t find anything wrong with it.”

  Braunwald was confused. He recalled listening to the patient’s loud heart murmur and hearing that he was short of breath prior to surgery. He had analyzed the pressure tracings from the patient’s cardiac catheterization. The pressure gradient indicated some sort of obstruction just below the aortic valve.16

  Yet when Morrow opened the man’s chest, the aortic valve itself was normal—and when he poked his finger through the valve, to the subaortic area, there was no evidence of a fibrous ring. Nothing was wrong.

  Braunwald was horrified. It was as if he had sent the wrong patient to surgery. Worse, in 1958, getting a patient’s heart restarted was not a sure thing. These were still the early years of cardiopulmonary bypass, and the techniques of stopping and restarting the heart were in their infancy. The bypass machine, developed in the early 1950s, had such a poor record initially that William S. Stoney, a cardiothoracic surgeon, reported in the prestigious medical journal Circulation: “The first attempts at cardiopulmonary bypass during those years were a series of disasters with an appalling mortality rate. During [the] four years between 1951 and 1955…of the 18 patients reported to have had an operation using cardiopulmonary bypass at 6 different centers…[there was] only 1 survivor.”75

  To lose a patient during a necessary surgery was one thing; to lose a young man who never needed surgery in the first place would be devastating.

  Braunwald felt sick.

  As Braunwald left the operating theater, he made a plea: If Morrow could get the young man’s heart beating again, would he please stick a needle in the man’s left ventricle to see if Morrow observed the pressure gradient Braunwald had found during his catheterization?

  Morrow did manage to get the man’s heart restarted, and when he did, he fulfilled Braunwald’s request. He pierced the left ventricle with the needle, and to his surprise, he found the abnormal pressure gradient Braunwald had reported earlier. But the finding was puzzling. There was no obstruction. How could this happen? The two men had no way to explain it.

  Shortly after this incident, other patients began to present with the same mysterious problem. Morrow noticed something: although these patients didn’t have any fixed obstruction that could be seen or felt, they did have an unusual thickening of the heart muscle just below the aortic valve. Instead of a fibrotic, or hard and calcified, lesion, what he found was a hypertrophied, or enlarged, muscle that would squeeze so effectively that it created a dynamic obstruction that could be observed only as the heart was beating.

  In 1959, Morrow and Braunwald published their findings in Circulation and named their discovery idiopathic hypertrophic subaortic stenosis, or IHSS.76 Later they would discover that the condition had a genetic component, and the term idiopathic—meaning of unknown cause—was dropped. Ultimately the condition was renamed hypertrophic cardiomyopathy, or HCM. Their work led to new medical and surgical treatments for HCM, which is estimated to affect one in five hundred people.

  Looking back many years later, Braunwald called his work on this condition “the most exciting of my professional life.”70

  Braunwald, now in his eighties, speaks in a gravelly voice with a thick Boston accent. His work on HCM may have been especially exciting, but his greatest achievement, he says, was his insight into the nature of heart attacks and his discovery that their severity could be modified. This was a novel concept at the time, and it came about from one of the most dramatic “aha” moments of his career—a moment that would change how doctors understand heart attacks and would ultimately lead to new treatments for the number one killer in the US…and to the VNS device that would be implanted in Dennis Fegan in 2000.

  Braunwald’s moment of insight came during a chance meeting after he gave a guest lecture in 1967 in Rochester, New York. He was preparing to leave to catch his plane home when Seymour Schwartz, the author of the leading textbook on surgery, approached him. Schwartz asked if he’d be interested in seeing his experiments in treating high blood pressure, which he conducted on dogs. Braunwald agreed and accompanied Schwartz to the dog lab.

  In order to treat high blood pressure, Schwartz
first had to create high blood pressure in the dogs, which he did by surgically removing one kidney from each dog. Then he wrapped the remaining kidney in cellophane, causing it to release renin, an enzyme that triggers a cascade of hormones that regulate blood pressure. Once the dogs became hypertensive, he rigged up a crude electrical device similar to a pacemaker that delivered small shocks to wire leads protruding from the dogs’ necks. The wires were wrapped around the carotid sinus nerves, which are activated via stretch receptors in the carotid sinus, a small swelling in the carotid artery that senses blood pressure. The carotid sinus loop involves a feedback mechanism that stimulates the vagus nerve, slowing the heart rate, weakening the force of the heart’s contractions, and dilating blood vessels. This triad of effects causes blood pressure to drop, thereby treating the dogs’ artificially induced hypertension. If the device worked, said Schwartz, it might be possible to use it to treat high blood pressure in humans.

  This gave Braunwald an idea: since the electrical stimulator effectively decreased blood pressure, it could theoretically reduce the workload of the heart. If that was the case, perhaps it could be used to treat not just high blood pressure but also heart pain, known as angina.

  In an interview with the Journal of Clinical Investigation posted on YouTube, Braunwald relates how he and his wife, Nina, developed a carotid sinus or vagus nerve stimulator that patients could activate themselves if they had chest pain:16

  I came home that evening, and I said to Nina, “Do you think that you could implant [a] carotid sinus nerve stimulator into patients?” And she said, “Why? What for? That sounds nutty to me.” So I told her about the [visit with Schwartz], and she said, “Yeah, I think I could do it.” And…she went to the autopsy room and learned how to dissect out the human carotid sinus nerves…and that isn’t something that is that easy to find.