Heart--A History Page 10

  Werner Forssmann, circa 1928 (Courtesy of The American Journal of Cardiology 79, no. 5 [1997])

  Nothing in Forssmann’s background could have predicted such brazen, almost criminal action. He was born in Berlin on August 29, 1904, the only child of a lawyer and a homemaker. Blond and blue-eyed, he was raised in a Prussian household with Prussian rules and a Prussian respect for law and order. His father was killed in battle during World War I, leaving his mother and grandmother (a woman he affectionately referred to as “old corset bone,” because she was so rigid) to supervise his early education. However, it was his uncle Walter, a small-town physician with whom Forssmann made house calls in a yellow two-horse carriage, who encouraged him to study medicine. His hard-nosed uncle did not tolerate squeamishness. He once made the teenage Forssmann go to the local prison to cut down a prisoner who’d hanged himself in his cell.

  In 1922, seven years before his tryst with Ditzen, the eighteen-year-old Forssmann entered medical school at the University of Berlin. In his first year, he was nauseated by animal experiments; like many, the wobbly youth did not enjoy pithing frogs. In the anatomy lab, Forssmann later recalled, a professor once joked that “the only way to a woman’s heart is through her vagina. You go from the uterus and the Fallopian tubes to the abdominal cavity, then via the lymphatic space into the lymphatic vessels and veins and thus to the goal!” Perhaps this, Forssmann cheekily wrote, is what inspired him in his later attempts to reach the heart through the vascular system.

  In his first year in medical school, Forssmann became fascinated with the heart, particularly the experiments of the French scientist Claude Bernard, widely considered the father of modern experimental physiology. Bernard measured pressure in the cardiac chambers of horses and other animals by inserting rubber catheters through blood vessels and into their hearts. (In fact, he coined the term “cardiac catheterization.”) Bernard’s animal studies convinced Forssmann that inserting a catheter into a human heart would also be safe. The young medical student wanted to check the heart’s pressures and flows, to understand and operationalize its basic functions, as one would a complex machine. No doubt he wanted to expunge the heart of its emotional connotations. But the idea that the human heart was just a pump, like an animal’s, was still anathema.

  After graduating in the spring of 1928, Forssmann joined the surgical staff at the Auguste-Viktoria Hospital in Eberswalde. Not long after beginning his internship, Forssmann mentioned his interest in cardiac catheterization to his chief, Richard Schneider, a modest and reserved administrator who was also a Forssmann family friend. The young intern described an audacious plan to insert a thin, flexible tube into a vein and advance it along the superior vena cava and into the right side of the heart. Moreover, he wanted to do this on a living person: himself. Schneider immediately nixed the plan. The human heart was an inviolable sanctuary; invading it with a foreign object was a medical and cultural taboo. Like most mid-level academic administrators, Schneider had no appetite for such adventure. “Remember your mother,” the chief cried. “Imagine how it would be if I had to inform this lady, who has already lost her husband, that her only son had died in my hospital as a result of an experiment which I had approved.” However, Schneider was reluctant to discourage Forssmann completely. He suggested trying the procedure on animals first.

  But Forssmann—brash, ambitious, and naive to the ways of academia—did not drop the idea. He persuaded a fellow intern, Peter Romeis, to help him perform the experiment. A week before his jaunt with Nurse Ditzen, the story goes, he met Romeis in an operating room at the hospital. With his colleague’s assistance, Forssmann made an incision in his left arm and inserted a rubber bladder catheter into the antecubital vein, which drains blood from the hand. Unfortunately, the thirty-five-centimeter catheter wasn’t long enough to reach the heart. (The typical distance from hand to heart in an adult is sixty to eighty centimeters.) When Forssmann insisted on walking to the fluoroscopy lab to take an X-ray to document the catheter’s position, Romeis panicked and yanked the catheter out.1 He later said that he’d always found Forssmann to be “a rather queer, peculiar person, lone and desolate, hardly ever mingling with his coworkers socially. One never knew whether he was thinking or mentally deficient.”

  Though the practice has been largely hidden, self-experimentation in medicine has a long history. Through the centuries, as the journalist Lawrence Altman has detailed, doctors and scientists have often decided to do research first on themselves. Some have done so for moral reasons, wanting to assume an experiment’s risk before imposing it on others. There were also practical considerations: identifying subjects to participate in research isn’t always easy. In the eighteenth century, for example, John Hunter, physician to King George III, intentionally injected his own penis with the purulent discharge of a patient with gonorrhea to investigate the transmission of that disease, contracting both gonorrhea and syphilis (the patient apparently had both). A hundred years later, Daniel Carrión, a medical student in Lima, injected himself with the blood of a boy with verruga peruana, then a common disorder in Peru, to prove that verruga and “Oroya fever” were manifestations of the same infection. Carrión fell into a coma and died thirty-nine days later.

  Whatever Forssmann’s motivations, he eventually sweet-talked Ditzen, the surgical nurse who held the keys to the supply closet, into getting him a longer catheter, prowling around her “like a sweet-toothed cat around the cream jug,” as he later wrote. A week later, on the afternoon of May 12, 1929, while his colleagues napped in their call rooms, he was ready to try again. Ditzen believed she was going to be Forssmann’s first subject. Forssmann had a different idea.

  After slicing open the skin over the elbow crease of his left arm, Forssmann widened the wound with metal forceps to get a better view. He dissected down to the antecubital vein, periodically dabbing the oozing blood to clear the view. He pulled the vein up taut to the skin surface; it had the color and consistency of an earthworm. He must have tied off the vein upstream from where he was going to cut to minimize bleeding. Then he transected the vein. It quickly drained of blood, collapsing on itself like a flimsy membrane. Forssmann inserted the sixty-five-centimeter catheter provided by Ditzen into the hole and advanced it. He later said that he experienced a warm sensation as the flexible tube scraped along the walls of his veins, as well as a slight cough, which he attributed to stimulation of the vagus, the main parasympathetic nerve in the body. With the catheter dangling out of his bleeding arm, he released Ditzen, who had apparently been protesting and struggling to get free, and ordered the angry nurse to follow him to the fluoroscopy lab to help him take a picture. Perhaps realizing they were about to make history—or maybe out of fear of the self-butchering intern—Ditzen acquiesced. They slipped downstairs. In the fluoroscopy lab, Forssmann lay down on a stretcher, while Ditzen held a mirror in front of him so that he could observe the catheter tip on a camera screen. The first X-ray showed that the catheter had not yet reached its destination, so Forssmann pushed it even farther until his arm had swallowed nearly all of it. In the middle of all this, Romeis, Forssmann’s colleague, hair tousled and still half-asleep, burst into the fluoroscopy lab and tried to stop Forssmann. Apparently, the word around the hospital was that Forssmann was trying to commit suicide. Romeis found Forssmann silent and pale on a gurney, sheets soaked with blood, catheter still in his arm, staring up at the ceiling. “What the hell are you doing?” he cried. Forssmann wrote that he had to give Romeis “a few kicks in the shin to calm him down.” As Forssmann pushed in the last few centimeters, the catheter tip clearly passed under his armpit and into the right atrium. It was a seminal moment—a violation, really—that philosophers and physicians had awaited—indeed feared—for centuries. Ditzen and a flabbergasted radiology technician snapped a photograph to document the catheter’s position. Then Forssmann pulled the tube out of his body.

  When he learned what Forssmann had done, Schneider was incensed at the disobedience, even as he ack
nowledged (over drinks at a nearby tavern) that Forssmann had made an important contribution to medical science. “Say that you tried it on cadavers before you did it on yourself,” Schneider urged, hoping to keep Forssmann from appearing like a nut to the scientific community. In any case, there was nothing at Eberswalde for his protégé. He suggested Forssmann transfer to a more research-oriented facility to pursue his interests.

  A few months later, Forssmann took an unpaid position at the Charité Hospital in Berlin. In November 1929, his self-experiment was published in Klinische Wochenschrift, a leading journal. The paper, “Probing the Right Ventricle of the Heart,” received widespread press coverage, but Forssmann was ridiculed as a quack in the medical world. There were no obvious applications of his procedure—this would change within a few years—and Forssmann’s fanciful proposal to use cardiac catheterization for metabolic studies or cardiac resuscitation did not gain him any supporters. Moreover, Ernst Unger, a leading German surgeon, falsely claimed that he had already performed cardiac catheterization many years before and that Forssmann had not properly acknowledged his work, a claim that was repudiated by Klinische’s editor. With controversy swirling around him, Forssmann, just twenty-six years old, was fired. His chairman, Ferdinand Sauerbruch, one of the leading academic surgeons in Germany, reportedly told him, “You qualify to work in a circus, not in a reputable clinic.”

  X-ray image of Forssmann’s self-catheterization, showing a catheter threaded through his arm and into his right atrium (circled) (Reproduced by permission; from W. Forssmann, Klinische Wochenschrift 8 [1929]: 2085–87)

  In January 1930, Schneider allowed Forssmann to return to Eberswalde, where the young doctor resumed his catheter experiments. He finally performed animal studies, keeping experimental dogs at his mother’s apartment, where he would inject them with morphine, put them in a sack, and lug them to the hospital on his motorcycle. Over the following year, Forssmann did more experiments on himself, too, injecting opaque dye into his own heart to better visualize its function under X-ray. Though the pictures were poor and his experiments largely unsuccessful, Forssmann kept going until he had scarred all the usable veins in his arms (as well as butchered a few in his groin). Despite the sacrifices to his body, at surgical conferences Forssmann’s talks would be placed last on the agenda and received little attention. Discouraged by the lack of progress and his work’s chilly reception, Forssmann abandoned cardiology and turned to urology. He eventually went into private practice, like his uncle Walter, in a small town in the Black Forest.

  Forssmann’s self-experiments did not go unnoticed, however. In the late 1930s, two American scientists, André Cournand and Dickinson Richards, working at Columbia-Presbyterian Medical Center and later at Bellevue Hospital in New York City, came across Forssmann’s techniques and applied them to measure cardiac pressures and flows, first in dogs and chimpanzees and later in humans. With war looming, their work was encouraged by the federal government’s interest in supporting research on blood circulation that could help in the treatment of traumatic shock. Over a ten-year period, the Bellevue scientists used modified bladder catheters just millimeters in diameter to study the dynamics of blood flow in patients with congenital, pericardial, and rheumatic heart disease. American cardiology was brought into the modern age.2

  In 1956, nearly three decades after Forssmann’s seminal experiment, Cournand, Richards, and Forssmann shared the Nobel Prize in Physiology or Medicine “for their discoveries concerning heart catheterization and pathological changes in the circulatory system.” In his Nobel lecture, Cournand paid homage to Forssmann, stating that the cardiac catheter was “the key in the lock” to discover the intricate physiology of the human heart. Indeed, cardiac catheterization was undoubtedly one of the greatest medical discoveries of the twentieth century, ushering in numerous applications, such as coronary angiography, coronary stenting, and right-heart studies, that have saved countless from premature deaths. For his part, Forssmann declared that he felt “like a village parson who has just learned that he has been made bishop.” Despite the Nobel Prize, he never returned to cardiac research, however. “The subject had progressed too far,” he wrote, “and when I considered it objectively I was certain I’d never catch up.” He decided “it was more honest to content myself with the role of leading fossil.” Forssmann continued his private urology practice. On June 1, 1979, he died of a heart attack.

  Within a decade after Forssmann’s epoch-making experiment, the taboo about touching the heart had been demolished. Scientists explored every avenue of access to animal and human hearts—under the breastbone; through the ribs; just below the nipple; through the left atrium; through the aorta; through the suprasternal notch, the soft spot above the breastbone and below the throat; and even through the back—giving them unprecedented access to the physiology of a once mysterious organ.

  But as is so often the case in science, once the taboo about touching the heart was breached, it was transformed into something equally inviolable. Accessing the heart’s apple-sized chambers was one thing. Inserting needles into the coronary arteries that supply blood to those chambers was a different challenge altogether. Coronary arteries are small, hardly five millimeters in diameter. When they are diseased with fatty plaque, their diameter can shrink to microns. No one thought that dye could be safely injected into these vessels because it was feared that occluding a coronary artery with a catheter for even a few seconds would precipitate a fatal arrhythmia. Even the fearless Forssmann never messed with the coronaries; they were only studied at autopsy. Though animal studies did not validate doctors’ widespread fears, the human heart was once again believed to be uniquely impervious to intervention. But did it have to remain so? After World War II, the coronary arteries became the new frontier in cardiac medicine, and the holy grail.

  7

  Stress Fractures

  Every affection of the mind that is attended either with pain or pleasure, hope or fear, is the cause of an agitation whose influence extends to the heart.

  —William Harvey, De Motu Cordis (1628)

  In the catheterization lab, I was able to visualize the consequences—stony plaque, obstructive clot—of coronary artery disease. But why did the disease develop in the first place? This was a question that vexed scientists at mid-century, even as the heart-lung machine was being developed and cardiac catheterization techniques were being refined. (As is so often true in medicine, treatment outpaced understanding.) But by the 1960s, doctors had an idea—albeit incomplete—of the answer. And it came from a study begun in a small town in Massachusetts shortly after World War II that almost single-handedly defines the modern science of heart disease.

  The impetus for the Framingham Heart Study was obvious. In the 1940s, cardiovascular disease was the main cause of mortality in the United States, accounting for nearly half of all deaths. However, what was known about heart disease wasn’t enough to fill even a slim chapter in a modern textbook. Doctors, for example, did not know that myocardial infarction was caused by total or near-total obstruction of a coronary artery. (This mechanism wasn’t even mentioned in popular literature until 1955, when Humbert Humbert in Lolita is said to die of a “coronary thrombosis.”) The jury was also out on whether angina, chest pain caused by decreased coronary blood flow, was a psychological syndrome or a disease based on an organic cause. “Prevention and treatment were so poorly understood,” Dr. Thomas Wang and his colleagues wrote in The Lancet a few years ago, “that most Americans accepted early death from heart disease as unavoidable.”

  One who fell victim to this ignorance was our thirty-second president. Franklin Delano Roosevelt was in poor health for much of his presidency, even though his doctors, his family, and even journalists colluded to portray him as the picture of health. (Few in the public knew, for example, that Roosevelt was essentially confined to a wheelchair after contracting polio when he was thirty-nine.) Roosevelt’s personal physician, Admiral Ross McIntire, an ear, nose, and throat speci
alist, seemed to hardly pay attention to the president’s blood pressure as it rose over his four terms. When Roosevelt began his second term in 1937, his blood pressure was 170/100 (normal today is considered less than 140/90). When the Japanese bombed Pearl Harbor in 1941, it was 190/105. By the time American soldiers landed in Normandy in June 1944, it was 226/118, life-threateningly high. At the Yalta Conference in February 1945, Winston Churchill’s doctor wrote that Roosevelt “has all the symptoms of hardening of the arteries” and “I give him only a few months to live.” Yet McIntire insisted that the president was healthy and that his problems were “no more than normal for a man of his age.”1

  Within a month of Roosevelt’s last State of the Union address, in which he declared that “1945 can be the greatest year of achievement in human history,” his condition had visibly deteriorated. Roosevelt had already been admitted to Bethesda Naval Hospital with shortness of breath, profuse sweating, and abdominal swelling: classic signs of congestive heart failure. Howard Bruenn, one of only a few hundred cardiologists in the country at the time, gave the president a diagnosis of “hypertensive heart disease and cardiac failure.” However, there were few treatments available to him. He put Roosevelt on digitalis and a salt-restricted diet, but Roosevelt’s blood pressure continued to rise. It remained life-threateningly high until April 12, 1945, when Roosevelt died at the age of sixty-three from a stroke and brain hemorrhage. His last words, sitting for a portrait in Warm Springs, Georgia, where he had gone to rehabilitate, were “I have a terrific headache.”

  Though it was a national tragedy, Roosevelt’s death was not in vain. In 1948, Congress passed the National Heart Act, declaring “the Nation’s health [to be] seriously threatened by diseases of the heart and circulation.” Signing the bill into law, President Harry Truman called heart disease “our most challenging public health problem.” The law established the National Heart Institute (NHI) within the National Institutes of Health to promote research into the prevention and treatment of cardiovascular disease. One of the first grants was for an epidemiological study to be conducted by the U.S. Public Health Service.