Father of heart transplantation who also performed the world's first heart-lung transplant
Thursday 16 February 2006
Norman Edward Shumway, heart surgeon: born Kalamazoo, Michigan 9 February 1923; surgical staff, Stanford University Hospitals 1958-93, Assistant Professor of Surgery 1959-61, Associate Professor 1961-65, Professor 1965-93 , Head of Cardiothoracic Surgery 1965-93, Professor of Cardiovascular Surgery 1974-93 (Emeritus); married 1951 Mary Lou Stuurmans (one son, three daughters; marriage dissolved); died Palo Alto, California 10 February 2006.
Norman Shumway was the father of heart transplantation and carried out the research that underpinned the first transplants. He also did the first US heart transplant operation. Later he performed the first combined heart-lung transplant, having established that it was impossible to transplant the lungs without also transplanting the heart.
Shumway had been researching heart transplantation in animals for a decade when he announced, on 20 November 1967, that he was ready to carry out the first human heart transplant and was awaiting a suitable donor. This was reported on news media around the world, including South African radio. The following day, the South African Cape Times announced that a team at Groote Schuur Hospital was on standby to perform a transplant. Christiaan Barnard, who had trained with Shumway in California and learned the techniques he had developed, performed the world's first transplant on 3 December.
In the next few days, Barnard performed a second transplant, and the team in New York did a transplant in an infant who survived for only six hours. Shumway's response to these other operations was to feel relieved that this would probably remove the media spotlight from him. He hoped quietly to perform a series of 10 transplants and publish the results in a medical journal. He carried out his first successful human heart transplant, and the world's fourth, on 8 January 1968, five weeks after Barnard's first operation. The patient was Mike Kasperak, a 45-year-old steel worker.
During this operation, Shumway's assistant, Edward Stinson, recalled that there was an awful moment when they looked at the empty cavity and wondered what they'd actually done. Then, said Shumway later,
we put in the heart and nothing happened. [Then] there were slow waves on the ECG, and then the heart began beating stronger, and then exuberance. We knew we would be OK.
Shumway's hopes of avoiding publicity were thwarted. When the donor had been found for Kasperak, a call went out to the operating room staff, one of whom was at a wedding reception. By chance, a local reporter answered the call and alerted his editors. To Shumway's dismay, the transplant operation was global headline news, and journalists climbed the hospital walls to get a peek at the operating room.
Nineteen sixty-eight was relatively early days for all kinds of organ transplantation. It was 13 years since the first kidney transplant, but that was between identical twins, where immune rejection was not a problem. It was only five years after the first unrelated kidney transplant, and four years after the first liver transplant. Transplantation was held back by the paucity of methods to prevent rejection. Only two anti-rejection drugs were available, and neither was very satisfactory.
After Barnard's operation, surgeons of other nations had jumped on the bandwagon, usually uninhibited by a total lack of clinical or experimental transplant experience. The American surgeon Francis Moore was in London when the first UK transplant was performed. It was followed, he later wrote in his book on surgical history, not by British soft-soaping and undersell, but by boasting and crass showmanship. The surgeons, in full operating regalia, posed on the hospital steps to flag-waving crowds, accompanied by guardsmen in bearskins and a band playing "Rule Britannia" and "God Save the Queen". The event was satirised on the cover of Private Eye.
In the following months, about a hundred transplants were performed around the world. The results of this surgery were mostly disastrous: patients died a few days later of graft-versus-host diseases or overwhelming infection. There was a sense of public revulsion towards heart transplants, and a feeling - probably unjustified - that the relatives of severely injured people were being railroaded into donating organs. There was also an acrimonious debate about what constituted brain death in potential donors. A moratorium on heart transplantation obtained for a decade in most countries and in most of America.
While Barnard went on to a career as a playboy and had affairs with Sophia Loren and Gina Lollobrigida, Shumway worked quietly on, overcoming technical problems and rejection, and became the world's leading heart transplant surgeon. When the rest of the world resumed transplants, 10 years later, Shumway rightly ascribed the turnaround to his "radical perseverance." He applied himself to the careful selection of donors and recipients, made efforts to increase the donor pool, brought about improvements in organ preservation and in heart biopsies, and improvements in anti-rejection drugs.
Shumway soon led the world both in numbers of hearts transplanted, and - more important - in his success rate. By 1991 his department had performed 687 transplants in 615 patients - some patients underwent a second transplant. Over 80 per cent of these were still alive five years later and the longest survival was 20 years.
He had faced a further and more daunting problem. In the late 1980s, the coroner of Santa Clara County, California, which included Stanford, sought criminal charges against Shumway for transplanting organs without an autopsy on the donor, an act that would have made transplantation impossible. Eugene Dong, then a transplant surgeon at Stanford and now a lawyer, recalls the two men shouting at each other in Shumway's office. In the end, the Santa Clara district attorney, Louis Bergma, did not file a criminal complaint, and the California legislature resolved the conflict by defining death as a cessation of brain activity.
In those days, surgeons and immunologists were feeling their way in trying to establish the dose of immune-suppressing drugs, which were needed if the transplanted organ was not to be rejected by the patient's body. Too little, and the patient rejected the transplant; too much, and they were susceptible to life-threatening infections. Shumway improved survival by devising a technique for spotting early rejection, putting a catheter into the heart and removing a tiny piece of tissue for examination. When signs of rejection were spotted he increased the dose of drugs.
At the same time, progress was being made in immune-suppressing drugs. Early heart transplant patients were treated with azathiaprine, only the second immune-suppressant drug, discovered in 1957. The perfect drug needs to suppress the immune response that would reject the transplanted organ, without having extensive adverse effects. A prescient scientist from the drug company Sandoz realised that the ideal substance would probably be derived from a fungus found in soil. The company therefore asked all its employees to bring back soil samples whenever they took a trip abroad. A few years afterwards, after literally thousands of soil samples had been analysed, Sandoz scientists found a better drug, cyclosporine, in a soil sample from a Norwegian fjord. They developed a technique of manufacturing it.
Its potential in transplantation surgery was soon established by the British transplant surgeon Sir Roy Calne, who persuaded Sandoz to part with a small quantity. It proved more effective and safer than azathiaprine, and it revolutionised transplant surgery. Sandoz thought cyclosporine was not commercially viable as the transplant market would always be too small and therefore had no plans to market it, but found they were besieged by requests for samples. Calne later said in an interview that he had "spent a long time trying to persuade my cardiac colleagues here [Cambridge] to use it in their patients, and they wouldn't". Shumway's team, however, were enthusiastic. They began to use the drug, initially in animals, after a member of Calne's team gave a talk at Stanford. They were the first cardiac team to do so. Cyclosporine is still in use today.
Norman Shumway was born in Kalamazoo, Michigan. His father kept a creamery. He enrolled at Michigan University to study law and was drafted into the army two years later. The military gave him an aptitude test that indicated an interest in medical matters, and asked him to tick a box to choose between medicine or dentistry. He chose medicine and was sent to an army premedical training course at Baylor University in Waco, Texas. This did not lead to a formal qualification but he qualified MD at Vanderbilt University, Tennessee, in 1949.
As soon as he qualified, he entered the surgical research programme of Owen Wangensteen in Minnesota. Wangensteen was the US leader in surgical research in the Midwest and many famous surgeons, including Christiaan Barnard, trained under him. Shumway researched the effects of temperature on disturbed rhythms of the heartbeat, which was important as the heart has to be cooled for open-heart surgery and transplantation. He earned his PhD in cardiovascular surgery in 1956. During this time he took two years out, serving in the US Air Force.
In 1958 he moved to Stanford University in California. He was soon joined by another heart surgeon with an interest in transplantation, Richard Lower, a graduate of Cornell and Washington universities. In 1959 they successfully removed a dog's heart and sewed it back, and in December that year they performed the first successful experimental transplant, in a dog, proving it was technically possible and that the heart would function and the circulation would be maintained. The dog lived for eight days. Subsequent dogs had a 60-70 per cent long-term survival rate.
Around this time, other centres were experimenting with artificial hearts in animals, but Shumway was vigorously opposed to this as a long-term solution for heart disease. He considered, rightly, that they would be an easy target for infection and blood clots. Some are in use today as short-term treatment for patients awaiting transplants.
Shumway's interest in transplantation surgery had been inspired by two Nobel prizewinners - Joe E. Murray of Boston, whose team did the first kidney transplant between twins in 1954, and, Sir Peter Medawar, a pioneering British immunologist, of whom Shumway said,
Being in his presence would just send thrills up your spine. He was so incredibly friendly, yet intelligent beyond anything I've ever seen.
He became chief of cardiothoracic surgery at Stanford in 1965, and served as head of department until his retirement in 1993. He lectured and wrote extensively, and trained surgeons from all over the world. He also developed lung transplantation. After it became clear that it was impossible to transplant lungs without also transplanting the heart, he and his colleague Bruce Reitz performed the first heart-lung transplant, in 1981. The patient, Mary Gohlke, a 45-year-old advertising executive, lived for five years.
Shumway performed or oversaw 800 heart transplants. He also advanced the treatment of congenital heart malformations in children, and the treatment of aneurysms and valve disease in adults. He improved techniques for storing transplant hearts when they were in transit between hospitals. At a 2003 Stanford reunion he told a crowd of transplant patients that it was "gratifying to see the changes that have made this [heart transplant] an almost ordinary experience".
Norman Shumway was a modest, self-effacing person with a light sense of humour, a contrary streak, and irreverent spirit. He always used humour, and delegated responsibility to his trainees. He was one of the first to alternate his trainees through cardiac and general surgery, a practice that has now become standard in the United States. One of his trainees did a heart transplant before he did a hernia operation. He would put the trainee in charge of the operation, and only take over if the other surgeon erred.
He received honours and honorary degrees around the world. Late in life he wrote to Baylor University in Texas, where he did his army medical training, asking if he could obtain their undergraduate degree. University officials said he could if he took courses in religion and the history of Texas. He declined.
Shumway officially retired in 1993, the year in which he stopped operating, but he continued to lecture and write: the last of his 447 research papers was published in November 2005. In retirement he also improved his game of golf.
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