As a father, I can only imagine the Gliddens’ agony. I can see them racing across the flat Minnesota landscape that winter, sick child in tow, the white dashes on the straight road extending like a zipper to the horizon. They were still mourning their daughter and were desperate to avoid another young death in their family. Their hearts were full of fear—the worst kind, of love about to be snatched away—but courage, too: the courage to go first, to offer up their little boy for a chance, however small, at a normal life, and perhaps for the sake of science as well.
Lillehei’s experiments are a painful reminder that innovation and expertise in medicine are earned on patients, and unfortunately there is always a learning curve. How to protect patients while doctors learn is a conundrum still faced in all areas of medicine. For example, in the early 1990s, a hospital in Bristol, England, introduced an innovative operation to correct a congenital heart abnormality in babies called transposition of the great arteries. Before this, newborns with this condition were treated with a palliative procedure that had poor long-term outcomes. Children at the hospital ultimately benefited from the innovation, but a heavy price was paid. The death rate for babies in the first few years after doctors started doing the operation was many times higher than with the palliative procedure. Commenting on the poor outcomes, a pediatric surgeon wrote that it was understood “there would initially be a period of disappointing results.”
Observers were aghast, however, calling for a moratorium on the procedure. They argued that surgeons with children’s lives in their hands should not take on more than they could handle. How then, surgeons responded, do we innovate? For a new technology, there is no opportunity for rehearsal. For an innovation to benefit patients, there has to be a first time.
There seems to have been no hand-wringing on Lillehei’s part, no soul-searching about how to protect babies and children while he learned on them. The kids, Lillehei knew, were doomed anyway, justifying the risks. But he underestimated the backlash. Even the hospital was against him. In the afternoon before the operation, Cecil Watson, chief of medicine, and Irvine McQuarrie, chief of pediatrics, wrote a letter to the head of the medical center demanding that the surgery be aborted. There was too much to lose, not just a little boy and his healthy father, but also the hospital’s reputation as the first heart institute in the country. It had taken years to earn this title, and they were not about to let a young upstart surgeon slow their momentum. However, the director, Ray Amberg, refused to intervene. He would not get involved in medical matters, he said, giving Lillehei a de facto green light to proceed.
The operating theater that late-March morning was packed with onlookers. Lying on a table was Gregory, still clutching his teddy bear. An injection of sodium pentothal rendered him unconscious. After a breathing tube was inserted, Lillehei worked quickly. He made an incision across the tiny chest. He split the fragile breastbone. Once the walnut-sized heart came into view, he called for Lyman, the father, who was wheeled in by stretcher and placed three feet from his son. He, too, was quickly sedated, but only lightly, lest the medicine in his bloodstream poison the boy. Watching them, Lillehei knew that if his technique did not work, father and son could very well be buried this way.
Lillehei inserted plastic catheters into Gregory, while his assistants inserted separate catheters into Lyman. The boy was then connected to his father, vein to vein, artery to artery, via a beer hose passing through a Sigmamotor milk pump. Lillehei’s team had to be careful: too little blood through the pump would result in oxygen deprivation to Gregory’s organs; too much could cause brain swelling and tissue edema. After the pump was turned on (and confirmed not to leak), Lillehei tied off all inlets and outlets to Gregory’s heart, isolating it from the circulation. At that point, Lyman Glidden’s heart and lungs were keeping both father and son alive—just as a mother’s would for her developing child.
For thirteen and a half minutes, well past the time that hypothermia could afford, Lillehei operated on the bluish plum in Gregory’s chest. He cut through the outer wall of the heart. With a relatively bloodless environment, visibility was good. He quickly found the VSD. It could have been any number of morphologies—a single hole, a tear, a flapping membrane involving the valves, even a Swiss cheese pattern—but fortunately for Lillehei (and his patient) that day, it was an isolated dime-sized hole high up in the ventricular septum. He sewed it closed with a dozen silk stitches.
Circuit used for Lillehei’s first cross-circulation operation (Created by Liam Eisenberg, Koyo Designs)
After he was done, Lillehei’s assistants released the tourniquet around Gregory’s venae cavae, allowing blood to return to his heart. Almost immediately—and to everyone’s surprise, none more than Lillehei’s—it started to beat vigorously. The milk pump was turned off, father and son were quickly separated, and their wounds closed. Lillehei and a relieved assistant reached across the boy and shook hands. The patients were sent to separate recovery rooms. A few hours later, Lillehei informed Frances that her husband and son were awake and intact.
For the first few days, Gregory’s postoperative course was smooth. Though groggy from painkillers, he drank milk and took some bites of poached egg and Cream of Wheat. But pneumonia, “the old man’s best friend,” as Osler once said, set in. Gregory’s lips turned blue, and his breaths quickened. His trachea was suctioned constantly of bloody mucus. Though he received the most powerful antibiotics, his condition worsened. Near the end, anesthesiologists were squeezing oxygen from a bag directly into his lungs. On the morning of April 6, 1954, eleven days after the historic operation, Gregory Glidden’s heart finally stopped. An autopsy showed the cause of death was a chest infection. His VSD remained closed.
Despite the setback, Lillehei decided to perform another VSD repair two weeks later, this time on a four-year-old girl named Pamela Schmidt who had lived in an oxygen tent for almost a year. She was battling pneumonia when Lillehei first met her, so he had to wait for penicillin to do its job. During the four-and-a-half-hour operation, Schmidt’s heart was separated from her circulatory system for nearly fourteen minutes. But this time, Lillehei’s patient survived the surgery. Her father, the donor, also recovered uneventfully.
On April 30, 1954, Lillehei held a press conference in Minneapolis to describe his cross-circulation technique. He showed slides describing the pathology of the VSD and talked about his failed first attempt on Gregory Glidden. Then he introduced Pamela, a brown-haired beauty, who was pushed across the stage in a wheelchair. The reporters were thrilled, and Lillehei’s operation became a worldwide sensation. Time called it “daring.” The New York Times deemed it “impossible.” London’s Daily Mirror proclaimed it “as extravagant and fantastic as any ever written in a shilling science thriller.” Pamela became a national celebrity, too, appearing on television and in a six-page photo spread in Cosmopolitan. The American Heart Association dubbed her “the Queen of Hearts.”
But Lillehei, no stranger to tragedy, did not forget about Lyman and Frances Glidden. A few weeks earlier, unable to afford a headstone, they had buried Gregory in an unmarked grave next to his sister. On May 4, Lillehei sent them a letter. “It is still a source of bitter disappointment to me that we were not able to bring Gregory through the post-operative period after the operation had seemingly gone so well,” he wrote. “I do wish to tell you again that had it not been for the encouragement gained from Gregory’s operation, we would not have had the courage to go ahead … I feel greatly indebted to both of you.” Perhaps the world did, too.
During the spring and summer of 1954, Lillehei was the only person on the planet performing advanced open-heart surgery. His surgical suite, according to a visitor, the British cardiac surgeon Donald Ross, “was like a circus. There was a large gallery in the operating room with about fifty people. People were rushing in and rushing out … The operating room was chaos, with pipes and tubes everywhere.” But his patients did well.
However, that autumn, Lillehei went through a spel
l of extraordinarily bad luck. Six out of seven cross-circulation cases ended in death. In one operation in October, a donor mother suffered severe brain damage after an anesthesiologist inadvertently injected air into her IV line. Tense colleagues whispered that Lillehei was a “murderer”; no one could stomach seeing little babies die. In response, Lillehei reportedly said, “You don’t venture into a wilderness expecting to find a paved road.”
Lillehei continued to use cross-circulation for several more years, correcting increasingly complex congenital defects. He searched for voluntary donors in unusual places, including the state penitentiary. When white inmates refused to serve as a donor for a black man, Lillehei decided to use a dog’s lung to oxygenate that patient’s blood. The man quickly succumbed on the operating table.
Despite isolated successes, cross-circulation fell out of favor. “We are still convinced that it is preferable to perform operations … by some procedure which does not involve another healthy person,” John Gibbon, a professor of surgery in Philadelphia who had been working on a heart-lung machine for two decades, declared. Lillehei himself had abandoned the technique by the late 1950s. In the end, he performed forty-five operations with it, with twenty-eight long-term survivors, a mortality rate of 40 percent, which was still better than the natural prognosis of uncorrected congenital defects. In the end, history has judged his work to be a success.
By the mid-1950s, a prototype of a heart-lung machine had been built and was ready to be used on humans. “It would provide surgeons with a dry field for operation, permitting for the first time the fullest use of their most valuable assets—their hands and eyes,” the renowned surgeon Claude Beck said at Case Western Reserve University in Cleveland in 1951. The machine was a massive technological leap, but it required an equally large conceptual jump: that blood could be circulated and oxygenated by a machine; that in the end there was nothing fundamentally special about the human heart.
5
Pump
We are in large part recompensed for the long and difficult hours by seeing the most miraculous change in the children and in witnessing the joy and relief of the parents when they see their children running about happily and without effort like other children.
—Lord Brock, cardiac surgeon, Guy’s Hospital, London
The scale of heart disease in the 1950s was like that of AIDS in the 1980s: a disease that dominated American medicine both clinically and politically. More than 600,000 Americans were dying of heart disease every year. In 1945, the budget for medical research at the National Institutes of Health was $180,000. Five years later, it was $46 million. A large portion went to cardiac research, in part because of political advocacy by the American Heart Association and other lobbies. In 1950, President Harry Truman, in a warning about heart disease starkly similar to the one he delivered about the Iron Curtain spreading across Europe, said that “measures to cope with this threat are of immediate concern to every one of us.”
It still amazes me that so many advances in heart treatment occurred in the decade just after my grandfather died, and so many of them in Minnesota, too, only a few hours’ drive from the hospital in Fargo where I stood with Dr. Shah in the operating room that Christmas morning. Our patient’s open chest was framed by sterile towels, like blue curtains stained with punch. Shah’s red-streaked fingers moved surely, precisely, as if each digit were following a programmed script. We were about fifteen minutes in, the heart quivering in fibrillation, when he applied blade to muscle and sliced open the left atrium. Tears of blood streamed from the slit. He reached into the heart and pulled up on the patient’s infected mitral valve with sutures, urging me to come in closer for a better view. The infected growths on the leaflets were small and white, like a baby’s teeth, and seemingly just as innocuous. It was hard to believe they had almost killed the man.
One thing I’ll never forget is how relaxed Shah appeared. He talked about the town, the weather, his friendship with my parents, residency training, even his belief that elderly patients with less time left to them have a greater will to live than younger patients. He took every opportunity to explain what he was doing, perhaps sensitive about shortchanging my investment of time on a major holiday. There was none of the slow panic I expected after the patient’s chest was opened. At one point, Shah inserted his finger into a bleeding hole and turned to me like a man waiting for a train. “We want to use a tissue, not metal, valve because at his age we don’t want him on long-term blood thinners.” I nodded nervously. I couldn’t believe that even at that tense moment, Shah was trying to teach me something. Of course, he could afford to take his time because the heart-lung machine was keeping our patient alive. Without it, the atmosphere in the OR would have been very different.
* * *
The person who contributed most to the invention of the heart-lung machine was a similarly generous, if ambivalent, soul. Toward the end of his first year at Jefferson Medical College in Philadelphia, John Heysham Gibbon Jr. considered quitting medicine to become a writer, a passion he’d nurtured since his college years at Princeton. His father, a pragmatist, advised him to obtain his medical degree, telling him (in advice that sounds very familiar) that he would not “write worse for having it.” So Gibbon persevered and received his MD three years later, in 1927.
During his internship at Boston City Hospital, he began to toy with the idea of “extracorporeal circulation.” One night, his research mentor, Edward Churchill, had him monitor a dying young woman who had developed a massive lung clot after a routine gallbladder operation. Churchill knew that incising the blood-filled pulmonary arteries to evacuate the clot, an operation called a pulmonary embolectomy, would almost certainly result in fatal bleeding. But isolating the heart to prevent exsanguination was not an option; without oxygen delivery, the brain would get irreversibly damaged within minutes. The pulmonary embolectomy operation was invented in 1908 by Friedrich Trendelenburg, a German surgeon, but none of his patients survived. “Twelve times we have done it at the clinic,” he lamented in 1912, “my assistants oftener than myself, and not once with success.” Noting this horrible mortality, Trendelenburg’s contemporary, the Swedish surgeon Gunnar Nyström, said, “Our rule is not to operate until the patient, as far as is humanly possible to judge, no longer has any chance of returning to life.”1
An early heart-lung machine, circa 1954 (Courtesy of Walter P. Reuther Library, Archives of Labor and Urban Affairs, Wayne State University)
So Churchill, stuck in a surgical catch-22, vacillated. Perhaps the clot would dissolve on its own or crumble and migrate down smaller arterial byways. Perhaps other areas of the lung would increase ventilation to compensate. He instructed Gibbon to notify him when the patient’s condition became so tenuous, so near death, that a Hail Mary operation would be justified. Early the following morning, as the patient’s blood pressure dived and she became unresponsive, Gibbon called his chief. The woman was rushed to the operating room but died on the table.2
Though Gibbon was a stoic researcher more comfortable around pipettes than people, he wept over that young woman. But in her death, he had a eureka moment. “During that long night,” he said in 1970, “helplessly watching the patient struggle for life as her blood became darker and her veins more distended, the idea naturally occurred to me that if it were possible to remove continuously some of the blue blood from the patient’s swollen veins, put oxygen into that blood and allow carbon dioxide to escape from it, and then to inject continuously the now-red blood back into the patient’s arteries, we might have saved her life. We would have bypassed the obstructing embolus and performed part of the work of the patient’s heart and lungs outside the body.”
Gibbon and his research assistant (and wife), Mary Hopkinson, essentially devoted the rest of their professional lives to this goal. His mentors discouraged him, believing that his outsized ambition would be better spent on a less risky project. Churchill himself took a “dim” view of the proposed work. In the medical academy, then
as now, huge outlays of time and money for big ideas were frowned upon. In a publish-or-perish world, you had to get your name in the top journals with regularity. Gibbon’s mentors advised him to pursue iterative problems, problems whose solutions might tweak the existing paradigm but would not try to supplant it.
However, Gibbon had a stick-to-itiveness that was unusual, even for a medical scientist, and so he applied himself and forged on. The result was a thirty-year academic career devoted to one big idea. But it changed medicine forever.
What Gibbon faced was an engineering problem: how to drain blood from the body, oxygenate it in a machine of metal and plastic without forming clots,3 and then pump it back into the body without air bubbles to nourish the vital organs. To solve this problem, he needed animals. He and Mary performed their early experiments on stray cats they plucked with tuna fish bait and a gunnysack from the streets of Boston. They went to the lab early in the morning because the preparations for their experiments took several hours. They would anesthetize a cat, perform a tracheotomy, and connect the animal to an artificial respirator. By mid-afternoon, they were ready to start the main demonstration: sucking blood out of the animal, circulating it through a machine while the heart was stopped, and then pumping it back into the animal to keep it alive. After much trial and error, they settled on the following scheme: isolate the cat’s heart by tying off the major veins and arteries; withdraw blood from a vein in the head at a rate of about half a soda can per minute; pass it in a thin stream down a rotating metal cylinder in an atmosphere of almost pure oxygen, which allowed the blood to pick up oxygen and give up carbon dioxide through diffusion; and finally collect the blood at the bottom of the cylinder, warm it, and return it to an artery in the animal’s leg via an air pump, which Gibbon purchased for a few dollars at a secondhand shop near the hospital. Mary later said, “We would keep the clamp completely occluding the pulmonary artery for as long as we thought the cat could stand it, or nothing went wrong with the apparatus, but things that were apt to go wrong were infinite.”
Heart--A History Page 8
