Cape Town, 3 December 1967
As Ann Washkansky drove home one December afternoon after visiting her husband in hospital in Cape Town, she came across the scene of an accident. A large crowd had gathered, and a body lay in the road covered by a blanket. The dead woman’s daughter lay prostrate beside her, with paramedics frantically trying to save her life. As police beckoned to Mrs Washkansky, urging her to drive on, she had no inkling that twenty-four hours later the young girl’s heart would be beating in her husband’s body.
The operation in which this tragic coincidence turned into a surgical miracle is now the most famous in history. In the early hours of 3 December 1967, Christiaan Barnard became the first surgeon to transplant a human heart. Half a century later, few people remember more than this impressive fact. Some may recall that the patient’s name was Louis Washkansky and that he lived for a few weeks; or that the world rejoiced and celebrated Barnard, a genius whose feat heralded the era of the heart transplant.
The truth of the matter is more nuanced, and far more interesting. Barnard was an accomplished clinician with undoubted star quality, but he was not even the first surgeon to give a patient a new heart. While he became, overnight, the most famous doctor on the planet, the names of the researchers who had made transplantation a reality remained unknown to the public. It would be natural to assume that the procedure was technically difficult; but, as Åke Senning observed, ‘One must merely sew. And when one knows where to sew, there is no problem.’1 Nor was the achievement universally acclaimed: some physicians felt it happened far too soon, while others had grave reservations about its ethical implications. The ensuing debate lasted several years, and changed the very definition of what it is to be dead or alive.
Like the Moon landing two years later, Barnard’s operation was seen as emblematic of the modern age, a triumph of cutting-edge technology over the natural limitations of human life. One commentator heralded ‘the opening of a new era in medicine … an era as significant as the age of the atom’.2 But optimism soon gave way to crushing disappointment. Dozens of surgeons began to transplant hearts, but only a handful of their patients survived more than a few weeks. By 1970 most had abandoned an operation that had promised so much and delivered so little. For years afterwards only a handful persevered; the ‘new era’ did not begin in earnest until the 1980s, when improved knowledge and a novel wonder drug finally made cardiac transplantation a valuable and reliable operation.
In retrospect it is tempting to see the first human heart transplant as the apotheosis of cardiac surgery, the ultimate peak which the profession was trying to scale. In truth, few were interested in attempting this bold step, which was part of a much broader enterprise involving specialists in many different branches of medicine. Their goal was to show that when parts of the body were beyond repair they might be replaced – new organs substituted for old, just as a mechanic replaces a faulty component in a car engine. Attempts to do so date back at least two millennia to ancient India, when Sushruta described the use of skin grafts during rhinoplasty, surgical reconstruction of the nose.3 In the sixteenth century the Italian surgeon Gaspare Tagliacozzi also became celebrated for his skill in this procedure, using a flap of skin from the upper arm to repair noses mutilated in combat. While the results were often excellent, Tagliacozzi noticed that the operation only worked if the patient’s own tissue was employed: a graft taken from a donor soon withered and died. Using somebody else’s skin was ‘difficult and almost impossible’, he wrote; ‘The singular character of the individual entirely dissuades us from attempting this work on another person.’4 He had hit upon the central problem of transplantation: rejection. The body recognises foreign tissue as alien and wages war against it. More than four hundred years later this remains the single most challenging aspect of transplanting organs from one body to another.
With the advent of anaesthetics and aseptic technique in the nineteenth century, surgeons were able to attempt more ambitious reconstructive operations. They achieved wonders in piecing together bodies mutilated by injuries or deformed by tumours, but attempts to replace lost skin with grafts were always unsuccessful. Russian surgeons even tried to use skin taken from dogs, frogs and chickens to repair burns in human patients, with universally disastrous results.5 In the 1880s the scope of these experiments broadened, as researchers began to investigate the possibility of transplanting endocrine tissue – hormone-producing glands such as the thyroid, testicles and ovaries – from one individual to another in order to treat infertility and cases of thyroid deficiency. But in the closing years of the century, when surgeons discovered a way of suturing blood vessels together, a far more exciting possibility presented itself: transplanting an entire organ and connecting it to the patient’s own circulation.
The first to demonstrate that this was not an outlandish dream was the Austrian Emerich Ullmann. In 1902 he transplanted one dog’s kidney into the neck of another; since the experiment was merely intended to demonstrate the feasibility of the procedure he left the recipient animal’s own kidneys in place. The neck was chosen because its arteries and veins lie close to the skin, considerably simplifying the operation. He attached the donor kidney to these vessels and sutured its outlet duct, the ureter, to the external wound. Urine dripped from the opening, proving that the organ had a good blood supply and was working as usual.
A few months later Ullmann attempted to treat a woman suffering from renal failure by transplanting a pig’s kidney into her elbow, but inevitably the operation was a failure. This did not deter others from attempting similar procedures: the Frenchman Mathieu Jaboulay used pig and goat kidneys in humans, while the German Ernst Unger tried those of an ape.6 In 1906 a surgeon in New York, Robert Tuttle Morris, announced what appeared to be a major breakthrough in transplant surgery. Four years earlier he had replaced the diseased ovaries of a young woman with those of a donor; on 15 March his patient gave birth to a healthy daughter.7 The implications were immense: if the fertilised egg had come from the new ovaries, the child was biologically the donor’s rather than that of the woman who had given birth to her. Most experts today believe that Morris had unwittingly left behind some of the woman’s own tissue when removing her ovaries, and that this was the source of the ovum; since DNA testing lay many decades in the future it was impossible to establish who the child’s mother really was.8
The most thorough of these early transplantation researchers was Alexis Carrel. As the pioneer of blood-vessel surgery he was uniquely well equipped to perform such intricate procedures, and his boundless imagination allowed him to see possibilities that others did not. With his collaborator at the University of Chicago, Charles Guthrie, he succeeded in removing the heart of a small dog and attaching it to the blood vessels in the neck of a larger one. An hour after the operation it began to beat spontaneously, and continued to do so for another two hours. Between 1904 and 1907 Carrel and Guthrie attempted all manner of experiments. They transplanted lungs (both with the heart and without), kidneys, thyroid glands and entire limbs.9 Most spectacular of all, in 1908 Guthrie created a two-headed dog, transplanting one animal’s head on to the neck of another. The grafted head reacted to light and sounds and appeared to be conscious for three hours before it was – mercifully – put to sleep.10
While some researchers performed such trials as a way of investigating the function of individual organs, Carrel made clear that he saw transplantation as a serious therapeutic option. He pointed out that contemporary surgery was by and large limited to extirpation – cutting out diseased tissue. ‘On the other hand,’ he wrote, ‘when the extirpation of an organ is necessary the ideal treatment would be the immediate transplantation of a sound organ to take its place.’11
This was fantastical stuff, and it reached wider attention in 1907 when Simon Flexner, the director of Carrel’s research institute, told a meeting of the American Association for the Advancement of Science that replacing diseased organs would one day be a possibility.12 The press reacted with astonishment: ‘May Transplant the Human Heart’, read one headline.13 The news also inspired what may be the earliest work of fiction about a heart transplant, a short story by the English writer Edgar Jepson. In ‘The Rejuvenation of Bellamy Grist’, an elderly American poet becomes the first human to undergo the operation, receiving the heart of a chimpanzee called Moko. He is restored to such robust health that other leading citizens sign up for the procedure, their hearts ‘worn out by our strenuous American life’. Problems emerge, however, when the austere poet begins to climb trees and produce works with titles such as ‘Ode to a Ripe Banana’ and ‘The Joy of Nuts’.14 The effect is comical, but Jepson was articulating the fears of many who still believed that the heart was the repository of the soul, and that a patient given a new one would in some way take on the characteristics of the donor.
There was a long pause in attempts to transplant the heart after the work of Carrel and Guthrie, and when work resumed in the 1930s it was not with clinical use in mind. The brain plays an important role in regulating the heart and its reaction to emotion and stress. Signals generated in the medulla, a region of the brain stem, are transmitted to the cardiac muscle via a pair of nerves, modifying functions including the heart rate. A group led by Frank Mann at the Mayo Clinic in Minnesota wanted to find out how the organ would behave if isolated from the central nervous system, and decided that a good way to do so would be to study a transplanted heart. In experiments on dogs in 1933 they took a heart from one animal and implanted it into the neck of another, attaching its major vessels to the carotid artery and jugular vein. It continued to beat but played no part in the circulation of blood, since the recipient animal’s own heart had been left in place. Hearts transplanted in this way would function for up to eight days, but generally stopped beating considerably sooner. Mann concluded, rightly, that this was not because of any shortcoming in operative technique, but because of ‘some biologic factor’, an incompatibility between the donor tissue and the recipient which would have to be overcome in order for transplanted organs to survive for any length of time.15
Researchers struggled to understand why tissue transplanted from one body into another was quickly rejected, though as early as 1902 Emerich Ullmann had observed that the appearance in the body of foreign cells ‘calls forth ferments into the circulation which destroy the transplanted tissue’.16 In 1941 a government committee formed to investigate the treatment of war wounds asked the British biologist Peter Medawar to find a way of improving the success of skin grafting, a procedure that was badly needed to treat soldiers with extensive injuries. Although the method had been widely used in the First World War, surgeons could not understand why it was so prone to failure. Medawar performed skin grafts on rabbits, and found that if a first graft failed and the animal was given another from the same donor, the second graft died much more quickly than the first.17 He quickly realised what was happening: this was a classic adaptive immune response. The body’s immune system slowly recognised the first graft as alien tissue, and after a few days lymphocytes, white blood cells, began to attack it. Once the threat had been identified the lymphocytes began to produce antibodies specific to the donor tissue, so that if a second graft were attempted it was quickly recognised and rejected. This insight was crucial, because it suggested a way around the problem: if the immune response could be somehow suppressed, the body might tolerate the transplanted tissue indefinitely. Once effective immunosuppressive drugs had been found, this approach underpinned all subsequent attempts at transplantation.
During the 1940s the most exciting research into the transplantation of organs was taking place in Soviet Russia. This work was almost unknown in the West until twenty years later, when an English translation of a book by Vladimir Demikhov revealed the macabre feats that he and others had achieved. In one operation he cut two dogs in half and created a hybrid animal by joining them in the middle.18 More than twenty times he succeeded in attaching a puppy’s head to the neck of a fully-grown dog, creating a two-headed beast which survived for up to four weeks. The transplanted head reacted to its surroundings, lapped from a saucer of milk and snapped its jaws angrily if provoked.19
His longest series of experiments involved giving a dog a second heart, implanted in the thorax, which would play an active part in the circulation. On 31 March 1949 one of these animals was displayed to members of the Academy of Medical Sciences in Moscow. To their amazement he demonstrated that this apparently healthy animal had two heartbeats. The dog was then anaesthetised and its chest opened to show the two hearts beating independently and at different rates.20 Demikhov also performed no fewer than sixty-seven heart-lung transplants and, on Christmas Day 1951, became the first person to attempt an orthotopic heart transplant. His previous transplants had been heterotopic: that is, the organ had been placed in an abnormal location in the body. In orthotopic transplantation the recipient’s own heart is completely excised and replaced by a donor organ, which is sewn into its anatomically normal location. The first operation was a failure, but one later dog survived for thirty-two hours and was well enough to drink and walk around the laboratory.21 ‘These experiments’, he wrote, ‘have shown beyond doubt that from the point of view of surgical technique, such operations are possible.’22
Unaware of Demikhov’s work, several American groups had also made progress with orthotopic transplantation, using a newly discovered drug, the steroid cortisone, to suppress the immune system.23 In 1957 a young surgeon in California entered the fray; though his contribution would later be overshadowed by that of Christiaan Barnard, many still see him as the true father of heart transplantation. Norman Shumway became a doctor – and a transplant surgeon – by accident. Born in Michigan in 1923, he volunteered for military service at the beginning of the war and owing to a shortage of army surgeons was sent to medical school. After qualification he studied in Minnesota, where John Lewis had performed the first open-heart surgery in 1952, and became interested in the use of hypothermia – the focus of his research when he joined Stanford University five years later.
There he was fortunate to meet the ideal collaborator: Richard Lower, six years his junior, whose seventeenth-century namesake had been the first to perform a blood transfusion. In their early experiments Shumway and Lower cooled dogs to well below normal body temperature to investigate the possibilities of hypothermic surgery. This entailed a lot of standing around waiting, and Shumway suggested they spend the time more usefully by removing the heart and then replacing it. It would be good practice for them, but there was also the possibility of conducting ‘bench surgery’ – repairing cardiac defects while the heart was outside the body. Excising the heart entailed cutting through the major vessels – the aorta, pulmonary artery and both venae cavae – as well as the four smaller pulmonary veins. This was simple enough, but when it came to replacing the organ they found that sewing the severed vessels back together was almost impossible. They realised that it would be simpler if they had an extra margin of tissue to work with; after all, a tailor making a jacket sleeve does not immediately cut it to the desired length, but leaves some extra material and trims it when the sewing has been completed. Lower suggested taking a donor heart from a second dog, leaving a good length of the major vessels attached to the organ. This made the procedure considerably easier, since arteries and veins could now be comfortably sutured into their new location.24
Thus did the careers of two of the greatest transplant surgeons begin: through boredom. Finding that the dogs were often well enough to run around after the operation, Shumway and Lower turned their diversion into a major research project. They used the department’s new heart-lung machine to support the dog’s circulation while its heart was being excised and until the new one was in place, and developed a simplified procedure which removed the need to cut and then suture each of the heart’s eight blood vessels. Four of these are the pulmonary veins, the vessels that return freshly oxygenated blood from the lungs to the left atrium. Shumway realised that if they removed the heart by cutting through both atria, he could leave a cuff of tissue containing the ends of these vessels, together with both venae cavae, the veins which enter the right atrium. Instead of suturing six individual vessels, they would only have a single line of tissue to sew, leaving only the pulmonary artery and aorta to be attached. Several researchers elsewhere reached the same conclusion, including Russell Brock in London, who had begun his own animal experiments in 1959.25
Shumway and Lower found that the results were surprisingly good. Even without any attempt to prevent rejection, their dogs lived for as long as three weeks. A transplanted heart had no nerves connecting it to the brain, but it appeared this made no difference to its function. The only significant problem was rejection, and they concluded that if they could only prevent the immune system from attacking the new organ, it should continue to work for the normal lifespan of the animal.26 Their sunny optimism echoed that of Brock, who observed that the heart was, after all, only a pump.27 This would soon become a familiar refrain, as surgeons tried to convince a sceptical public that they would not lose their soul, or their ability to love, should they undergo the procedure.
Heart transplant researchers were also buoyed by developments elsewhere. Attempts at kidney transplantation had recently intensified, and in 1951 French surgeons performed a number of operations using kidneys taken, controversially, from the bodies of guillotined criminals. These attempts all failed, but in Boston three years later the plastic surgeon Joseph Murray, who had become obsessed with the challenge of human organ transplantation, achieved the first successful kidney transplant. Luckily he did not have to worry about rejection: his patient, Richard Herrick, had an identical twin, Ronald, who was willing to donate one of his own kidneys. Since the brothers were genetically indistinguishable, Richard’s immune system did not recognise the new kidney as alien tissue and he made an uneventful recovery.28 Rejection remained an apparently insuperable problem, but this was an immense achievement nevertheless: Murray succeeded in conquering numerous technical difficulties which had baffled earlier surgeons. Richard Herrick was the first long-term survivor of a transplant operation, living for another eight years. This was well publicised, and rightly so: it was proof that giving a patient a new organ could have dramatic results.fn1
By 1964 Shumway felt that the surgical elements of the operation had been perfected: cutting out a diseased heart and sewing in a new one was a relatively straightforward technical procedure. Encouragingly, new drugs and radiotherapy had reduced the incidence of rejection in kidney transplantation, developments which led Shumway to conclude that cardiac grafts were ‘just around the corner’.29 Indeed, a team led by James Hardy at the University of Mississippi was already rehearsing for the great moment. The previous summer Hardy had performed the world’s first human lung transplant on John Richard Russell, a fifty-eight-year-old convicted murderer suffering from cancer. The new lung (taken from an emergency-room patient who had died from a heart attack earlier that day) worked well, but Russell died eighteen days later from a pre-existing kidney complaint.30 Hardy had been working on heart transplantation since 1956, and few in the field possessed such wide-ranging expertise. From December 1963 he and his team were on the lookout for a suitable patient: somebody in terminal cardiac failure who could not be helped by any conventional treatment, but who might be saved by a new heart.
On 18 January 1964 newspapers worldwide published a sensational story under the headline ‘Human Heart is Transplanted’:
A bold attempt to give a man another heart was made by Mississippi surgeons Friday. The transplant worked for an hour. It was the first known successful human heart transplant in the world … The heart came from a dead man. It was revived and transplanted into the chest of a man dying of heart failure.31
This was complete fiction. A member of the hospital staff had given the press a tip-off, having discovered that Hardy’s team had a patient and a donor heart and were all set to operate. But the transplant never took place: when Hardy opened the man’s chest he found that a simple surgical repair would be enough to help the patient.32 This was all useful experience, however, as the team had gone through every stage of the transplant protocol except the actual procedure.
Less than a week after this dry run Hardy was able to perform the operation in earnest. On 17 January, Boyd Rush, aged sixty-eight, had been admitted to the hospital in a sorry state. After years of high blood pressure his circulation was so poor that he had developed gangrene in both legs, which had to be amputated. A cardiologist concluded that his case was hopeless without a transplant, and on the evening of 23 January his heart started to fail. Hardy had three potential organ donors lined up, young patients who were dying from brain damage and being kept alive on ventilators. He realised that if he turned off one of these machines to obtain an organ he risked prosecution for murder, and decided that he would only use a heart from a donor who had died naturally. He knew the chances that this would happen at just the right moment were minimal; so he had a contingency plan.
A few weeks earlier Hardy had paid a visit to Keith Reemtsma, a kidney-transplant surgeon in New Orleans. The only patients it was possible for him to operate on were those with a close relative willing to donate a kidney, which meant that very few transplants took place. Reemtsma decided to use kidneys from primates in order to increase the numbers who might benefit from the operation – an easy thing to do, since in the early 1960s the sale of monkeys, chimps and even big cats remained unregulated. It was a controversial procedure, but the results surprised everybody. One patient, a dock worker called Jefferson Davis,33 lived for two months with the kidneys of a former circus chimpanzee, while others were given organs from baboons and monkeys.34 Hardy was impressed by what he saw, and it occurred to him that in extremis a primate heart might be an acceptable back-up should a human organ not be available. He bought four large chimps and, to test his hunch, measured the cardiac output of the biggest of them, a hefty specimen of over 100 pounds. At 4 litres per minute it was low by human standards, but he concluded that if it were really necessary it would suffice for a small adult.35
As Boyd Rush’s heart failed his blood pressure plummeted, and his breathing could only continue with mechanical help. Hardy went to check on the condition of the prospective organ donor, and found that he was unlikely to die imminently – they would not be using his heart that night. Instead the largest chimpanzee was tranquilised and prepared for surgery. Hardy reasoned that his patient had lost both his legs, reducing the volume of blood in his body, so the chimpanzee heart might be just enough to keep him alive. When Rush arrived on the operating table his pulse was irregular and his blood pressure almost non-existent. He was comatose and barely needed anaesthesia. His heart arrested as Hardy was opening his chest – with not a minute to spare they succeeded in attaching him to the heart-lung machine.
With the patient safely on the pump, Hardy summoned his staff to the operating theatre to decide what to do next. They could either turn off the heart-lung machine and let their patient die, or transplant the chimpanzee heart. After a quick discussion the five senior staff took a vote: four were in favour of continuing with the chimp heart, and one abstained.36 While one team went into the adjoining room to open the animal’s chest, Hardy excised Rush’s failed and useless organ. He looked down with awe at a sight he was the first to see: a living patient with a hole where his heart should be.37 The chimpanzee’s heart was handed to him in a metal bowl. It had been rinsed out with a cold solution and was now being perfused with human blood. It took forty-five minutes for Hardy to sew it into place. As the new heart was rewarmed to normal temperature it began to quiver. Hardy gave it a single shock with the defibrillator, and after a short hiatus it leapt into a regular and powerful beat. The initial signs were encouraging, but Hardy soon realised the ape’s heart could not cope with the job it was being asked to do. After watching it struggle for an hour he gave up hope of seeing his patient regain consciousness.38 As the chimpanzee heartbeat faded away, so did the life of Boyd Rush, the first human to receive a new heart.
When Hardy looked up from the table he was surprised to find the room full of people, many of whom he did not recognise. More than twenty-five uninvited guests had talked their way in, keen to see history being made. Realising that the operation would soon be common knowledge, he arranged for the hospital authorities to issue a brief press release stating that a heart transplant had taken place. No mention was made of the chimpanzee, leading many in the press to speculate about the identity of the unnamed donor, and beginning a long and dishonourable tradition of heart transplant PR disasters. A second statement was hurriedly published to clarify matters.
Hardy had thought long and hard before proceeding with transplantation, and solicited advice from many of his colleagues. He was taken aback by the hostility the operation aroused in America, with surgeons and the public alike uniting in condemnation. In his memoirs, written twenty years later, Hardy recalled that it was ‘as if there had been a recent bereavement in the family, for the lung and heart transplants were never mentioned by friends’.39 It was apparent that he had broken a taboo, and Hardy decided not to involve another patient unless there should be a palpable change in the public mood. Two thousand miles away in Stanford, Norman Shumway had followed developments with interest before coming to the same conclusion.
Though would-be heart transplanters kept a low profile for the next few years, important work was being done behind the scenes. Experimental animals started to live for dramatically longer, thanks to improved management of rejection. Richard Lower discovered that the powerful immunosuppressive drugs often caused dogs to die from infection, and began to use them only if rejection was detected.40 He and Shumway subsequently kept one animal alive for a year with a new heart.41 Their collaboration ended in 1965 when Lower moved to Virginia, where he performed a mirror image of James Hardy’s feat by transplanting a human heart into a chimpanzee. This may seem a macabre thing to do, and Lower was so worried about adverse publicity that he never reported it, but it was a significant achievement. It was the first time that a beating human heart had been deliberately stopped and removed from a cadaver, sewn into another body and restarted – and it kept the ape alive for several hours afterwards.42
Meanwhile a surgeon in Brooklyn, Adrian Kantrowitz, was having notable success in transplanting puppy hearts. Despite the difficulty of working with such tiny organs, most animals survived the procedure. No effort was made to prevent rejection, yet some lived for several months.43 Kantrowitz believed this was because the puppies’ immune systems were still developing, and reacted less aggressively to foreign tissue – which seemed to bode well for the possibility of heart transplants in small babies. By early 1966 he felt that he was ready to operate on an infant. The ethical situation was less fraught than with adults, since the babies who would be candidates for a transplant were those born with major congenital heart defects which were otherwise impossible to treat, and whose life expectancy was measured in weeks or days. As for donors, Kantrowitz chose to use only anencephalic infants, those born with most or all of their brain missing. Since these babies could neither feel pain nor sense their surroundings, and usually died within hours, there were likely to be few moral qualms about their role as organ donors.
Kantrowitz came very close to being the first surgeon to perform a human-to-human heart transplant. In May 1966 he had identified a possible recipient, a baby boy with a catastrophically malformed heart. A few weeks later a hospital in Oregon responded to his plea for donors, and an anencephalic baby was flown all the way to New York. On the morning of 30 June the donor’s heart stopped beating, and everything was made ready for surgery – but it had been starved of oxygen for too long to be restarted, and Kantrowitz abandoned the procedure. Although several other donor infants were found, they could never be matched to a suitable patient, and it was not until late the following year that Kantrowitz and his colleagues had a chance to try again.44
As 1967 drew to a close three American surgeons were on the brink of making history. Shumway, Lower and Kantrowitz had all performed hundreds of heart transplants on animals, thoroughly investigated the management of rejection and assembled expert teams able to deal with every aspect of the operation and its aftermath. More or less everybody in the medical profession imagined that one of them would be the first to take the momentous step of transplanting a human heart. And then on 4 December came the news that nobody was expecting: a surgeon in faraway South Africa had beaten them to it.
Christiaan Barnard was certainly an outsider in the world of transplantation. Few outside Cape Town knew he was even interested in the subject; he had done little research and published nothing about it. Born in 1923 in the vast open spaces of the Karoo, the desert heartland of South Africa, Barnard was the son of a priest in the Dutch Reformed Church who tended a large congregation drawn from the impoverished Cape Coloured community. Living in relative poverty and surrounded by his father’s parishioners, Christiaan grew up without any of the racial prejudice so common among white South Africans at the time – a fact reflected in his later refusal to segregate his surgical wards by race, as the government demanded. After training as a surgeon he performed important research into intestinal atresia, a congenital abnormality in which part of the bowel is narrowed or missing. He proved the cause of this condition by operating on canine foetuses as they lay in the womb,45 an extraordinary feat which later made possible the entire field of surgery on unborn infants.46
Partly on the strength of this work, Barnard won a scholarship to continue his training in Minnesota, where he was given the best possible grounding in open-heart surgery by the pioneer in the field, Walton Lillehei. When he returned home two years later the chief of surgery, Owen Wangensteen, was so impressed with his protégé that he raised funds to buy a heart-lung machine so that Barnard could establish an open-heart programme at Groote Schuur Hospital in Cape Town – the first in Africa.47 Barnard did not disappoint: with his brother Marius, also a surgeon, he was soon performing some of the most difficult cardiac operations on children, with results as good as any in the world.48
Marius worked closely with Christiaan for thirteen years and took part in the famous transplant, yet chose never to assist him at the operating table. He described his first few months working for his brother as ‘utter hell’, and was appalled by Christiaan’s belligerent behaviour towards his staff.49 He was not alone in his opinion that Christiaan was not a naturally gifted surgeon, even describing him as ‘cumbersome’ – but any deficit in talent was more than made up for by his unshakeable perfectionism. And he was not short of self-belief: ‘I have a tremendous ego, I know that, and I must feed it, or I become miserable and unhappy,’ he told one interviewer.50 Though urbane and charming, he was uncompromisingly, obsessively competitive. When his teenage daughter Deirdre emerged as a talented international water-skier, Barnard brought the same unwavering fanaticism to her coaching. In a revealing passage from his autobiography he recalled his frustration when he realised that she had not inherited this ruthless streak: ‘I had failed to transplant into her my own hunger for victory. She was still not going to beat her fists and cry if she lost … She would never make it.’51
Barnard’s interest in the possibilities of transplantation was aroused in 1962, when a South African newspaper reported Demikhov’s creation of a two-headed dog. He immediately went to the animal laboratory to repeat the experiment, an exploit that earned him considerable local notoriety. The following year he performed a heart transplant on a dog and predicted in a talk to students at the University of Pretoria that the operation would soon be possible in humans52 – but made no serious effort to begin a concerted programme of research. That all changed in the summer of 1967, when he travelled to America to visit several transplant specialists and find out what progress was being made. Soon after his return to Cape Town he decided to perform a kidney transplant as preparation for the more technically complex procedure with a heart: it would give him an opportunity to test the anti-rejection protocols he had learned in America. As a dry run it could not have gone better: the patient, a middle-aged woman called Edith Black, made an excellent recovery and lived for another twenty years.
After this success Barnard was buoyant. Colleagues were less enthusiastic about the possibility of a heart transplant, but his enthusiasm brooked no argument. Any initial reluctance was not reflected in the care they paid to the necessary preparations, which were meticulous. Barnard’s team included consultants in every relevant specialism, as well as experts in rejection, tissue compatibility, infection, and pre- and post-operative care. There was, however, one curious omission. While Shumway, Lower and Kantrowitz had practised the operation hundreds of times on dogs, Barnard seemed to think such rehearsals unnecessary. Marius did perform a number of canine transplants, but regarded them as personal practice in general cardiac surgery. Christiaan later suggested in self-justification that these experimental operations were a significant part of the hospital’s preparations for a human transplant, a claim Marius treated with derision.53
In October Barnard decided that his team was ready. After much persuasion the director of the hospital’s cardiac clinic, Velva Schrire, agreed to let him know if he came across a suitable candidate for a heart transplant. A month later Schrire summoned Barnard to his office to tell him that he had found one. His name was Louis Washkansky, a fifty-four-year-old grocer with a litany of health problems. Diagnosed with diabetes in 1955, he had since had three heart attacks and been repeatedly hospitalised. He was so ill that the slightest exertion made him breathless; his damaged heart had ballooned to a grotesque size. So poor was his circulation that he had developed severe oedema, swelling caused by fluid retention, which had to be drained using tubes inserted into his legs.54 When Barnard watched an X-ray film of Washkansky’s heart in action he was shocked: two-thirds of the muscle of the left ventricle was dead and useless, and the coronary arteries were almost obliterated.55 Barnard could barely believe that he was still alive.
Given this bleak outlook, it is hardly surprising that when offered the extraordinary possibility of a new heart he accepted without hesitation. All that remained now was to find a donor organ, and after one false alarm they found one. On the afternoon of 2 December a local family, the Darvalls, went out to visit friends, stopping en route at a bakery to buy a cake. As Mrs Darvall and her twenty-four-year-old daughter Denise crossed the road they were hit by a car. Mrs Darvall was killed instantly, and Denise suffered a terrible head injury. Though an ambulance arrived within minutes, it was soon apparent that nothing could be done for her. At the hospital a few miles away the news was broken to her father, who readily agreed that her organs could be used for transplantation.
Marius Barnard and his wife were at home that evening celebrating their sixteenth wedding anniversary when he received a phone call from his brother summoning him to Groote Schuur. When he arrived at the hospital Denise Darvall had already been seen by a neurosurgeon, who confirmed that she was beyond medical help. With everything in place, Washkansky was taken to the operating theatre at 12.50 a.m. and anaesthetised. In the room next door Denise Darvall lay on the operating table, dead but not-dead, her heart still beating but her brain no longer functioning. Marius took charge of preparing her for the procedure while Christiaan began the transplantation operation on Washkansky, opening his chest and inserting cannulas for the heart-lung machine. By 2.20 a.m. he was ready, and a message was sent next door for Denise Darvall’s artificial respirator to be switched off. Twelve minutes later her heart stopped.56 Immediately her chest was opened and she was connected to the heart-lung machine, which cooled her blood to preserve her organs. Christiaan cut through the major vessels of the heart and placed the precious object in a bowl of cold preserving solution, before carrying it next door, where it was immediately perfused with blood from the pump.
This was the point of no return; but having now seen Washkansky’s ruined heart at close quarters Barnard knew that without a transplant he was finished. Bypass was begun, and Washkansky’s body cooled to 30°C to protect his brain from damage during the long procedure. After placing a clamp across the aorta to exclude it from the circulation, Barnard cut through the vessel just above the opening of the coronary arteries. The pulmonary artery was also severed, and then Barnard cut away the rest of the heart, leaving a cuff of tissue, the portions of the atria containing the ends of the venae cavae and pulmonary veins, in situ. He placed Denise Darvall’s heart into the chest and began to cut into the left and right atria, making holes to match the tissue that he had left behind. Washkansky’s diseased organ had been far larger than the new one, so he trimmed the cuff to ensure that it would fit. Then he began to stitch, attaching the left atrium and then the right with two layers of sutures. The pulmonary artery was next to be attached, and finally the aorta was trimmed to length and sutured. When Barnard was satisfied that his stitches were airtight the clamp across the aorta was released, allowing Washkansky’s blood to flow into the new heart muscle for the first time.
The transplant was now complete, but the team had to wait for Washkansky’s body to be returned to normal temperature before they could find out whether the new heart would work. After a tense half-hour the anaesthetist Joseph Ozinsky finally announced that the temperature in the oesophagus had reached 36°C.57 Barnard applied the paddles of the defibrillator to the quiescent organ, which jolted as a pulse of electricity passed through it. There was a breathless pause, and then the heart contracted for the first time in its new body. ‘Dit werk,’ Barnard said quietly in Afrikaans: ‘It works.’58
It was 5.52 a.m. Barnard and his team had been operating for four and a half hours, but there was much still to do. It took three attempts to wean the patient off the heart-lung machine and demonstrate that the donor heart would support Washkansky’s circulation on its own. His chest was closed, and anaesthesia was finally stopped at 8.30 a.m.59 The patient was now attached to a drip containing powerful steroids which would suppress his immune system, reducing the chances of rejection. When all were satisfied that Washkansky’s vital signs were stable he was taken to a room specially prepared for him. Because of the dangers of infection the most stringent precautions had been taken: every object, from the mattress to the walls, had been scrubbed with disinfectant, and any staff who were to come into contact with the patient screened for possible bacterial contamination. This sterile cell would be Louis Washkansky’s home for the remaining eighteen days of his life.
An exhausted Barnard had barely returned home before the media frenzy began. It was the biggest news story since the assassination of President Kennedy: within hours the world’s media had descended on Cape Town. The operation was meant to be a secret, and it remains a mystery how the press found out: Marius (and many others) suspected Christiaan had tipped them off, but the surgeon always fiercely denied having done so.60 Louis Washkansky instantly became the world’s most famous patient, with constant bulletins on his condition. The early reports were encouraging: within a few days he was sitting up in bed and talking to his nurses, while the symptoms of heart failure had started to subside. The function of his other organs steadily improved, indicating that his circulation was drastically better. When he was well enough Barnard allowed him to give interviews. It was natural that there should be huge interest in his condition, but the hospital allowed access to their patient on a scale which would not be contemplated today: Washkansky was visited by cabinet ministers, photographers, newspaper journalists and representatives of all the major broadcasting organisations.61 He coped with these invasions with good grace, although he bridled when a BBC interviewer asked how he, as a Jew, felt about receiving the heart of a Gentile.
On 15 December, twelve days after the operation, Washkansky was allowed out of bed, but later that evening came the first signs that all was not well. He started to have difficulty breathing, and an X-ray showed a shadow on his lungs.62 The diagnosis was pneumonia, and because tests failed to identify any infectious agent Barnard decided this was a sign of rejection – a crucial mistake. In fact Washkansky had an infection which had migrated from a wound in his leg and needed antibiotics; instead he was given a larger dose of anti-rejection drugs, further depressing his immune system at just the moment it was needed to fight the bacterium. Barnard can be forgiven for this error: distinguishing between the symptoms of rejection and infection is still one of the biggest challenges for the transplant surgeon, fifty years later.
By the time Barnard’s team realised the true cause of Washkansky’s pneumonia it was too late. They threw the pharmacological kitchen sink at the infection, but he continued to deteriorate. On 21 December, eighteen days after the transplant, he finally succumbed. Washkansky’s family received condolences from thousands of people who had never laid eyes on this remarkable patient, let alone met him.
Barnard was devastated. He attended the post-mortem, but was overcome with emotion and had to leave the mortuary. Though it felt like a failure, the pathologist’s findings showed that the operation had been a success. The cause of death was pneumonia; although there were signs of rejection, these were trivial and had not affected the outcome.63 If the infection had not supervened, Washkansky apparently might have lived for considerably longer.
While the operation prompted adulation in the media, the reaction of most surgeons was bewilderment. In New York, Adrian Kantrowitz learned of it from his daughter, who had heard the news on the radio. He was stunned: Lower or Shumway would have been no surprise, but Barnard was not the name he expected.64 He had a baby awaiting transplantation in his hospital, and was worried that proceeding with the operation would be seen as rushing to get in on the act. But on 4 December an ideal donor, an anencephalic infant, was transferred to Maimonides Medical Center and he decided to go ahead. Two days later he operated, but his tiny patient, a two-week-old baby boy, lived only a few hours before the transplanted organ failed.65 In early January a second, adult, patient died just a few hours after the operation.66 Although Kantrowitz had emulated Barnard’s achievement, he was the first of many to discover how elusive ultimate success could be.
Norman Shumway joined the transplant club within days, but his first patient, a fifty-four-year-old man, fared little better than those of Kantrowitz. Remarkably, the operation took place less than twenty-four hours after the patient had been admitted to hospital in terminal cardiac failure. The donor heart came from a forty-three-year-old woman who had suffered a massive stroke. The operation on 6 January went without a hitch, but complications began within hours and never receded. Infections and gastrointestinal bleeding followed, and he died a fortnight later.67
In early February Barnard flew to London to take part in a television debate, a special edition of the BBC’s science magazine Tomorrow’s World entitled ‘Barnard Faces His Critics’. It was an extraordinary occasion. A large studio audience included many of the most eminent British surgeons and physicians, as well as several outspoken opponents. The questioning was not entirely friendly: five more transplants had been performed since Barnard’s first operation, only one patient was still alive, and public opinion was beginning to turn. Some of the most biting criticism came from another transplant surgeon, Roy (later Sir Roy) Calne, who at the age of thirty-seven was widely regarded as Britain’s leading expert in the field. As the discoverer of the first effective immunosuppressive agent, azathioprine, he had already begun kidney transplantation and later that year would become the first European to transplant a liver. Although supportive of the decision to perform the operation, he condemned the ‘nauseating’ publicity that had accompanied it, and attacked the decision to publish photographs of patient and donor. Still more hostile was the writer and broadcaster Malcolm Muggeridge, a devout Catholic whose comments were coloured by his religious convictions. Describing transplantation as ‘deeply repugnant’, he wondered ‘what the fury of Heaven would be at the notion that our bodies are collections of spare parts’.68
Such voices were, however, in the minority. Another heart surgeon, Donald Longmore, dismissed the ‘phoney’ ethical arguments and emphasised the exciting possibilities of the operation. He introduced one of his own patients, a retired milkman called Bill Bradley, who was brought on stage in a wheelchair. The raucous audience fell silent as he explained softly that he had been waiting five years for the possibility of a new heart. ‘I will take it tomorrow, given the opportunity,’ he said. ‘I can become a new man, I can live a life, instead of this.’ A sometimes fractious debate ended with a dose of sobering reality.
Nineteen sixty-eight was to become the most tumultuous year in the history of heart surgery. Suddenly everybody was performing cardiac transplants. As Adrian Kantrowitz noted in a special edition of the American Journal of Cardiology, ‘It is unusual that a new surgical procedure, experimental in nature, has been so quickly taken into clinical practice in so many divergent centres throughout the world.’69 By the end of October more than sixty operations had taken place, in India, Venezuela and Czechoslovakia as well as leading centres in America and Europe.70 Many of these should never have gone ahead, performed by surgeons with trivial knowledge of the procedure in hospitals where there was little or no understanding of the complexities of rejection. As one eminent American surgeon, Lyman Brewer, pointed out, the operation had become a status symbol for those seeking the adulation and publicity that came with it.71
The most prolific of the early transplanters was Denton Cooley, who candidly admitted that he regretted not having been the first. His reaction to news of Barnard’s operation was to send a telegram of congratulation, goading his colleague with the prediction that he would soon be reporting on his first hundred cases.72 It was not until May that he performed his first, on a forty-seven-year-old accountant who did quite well until rejection set in six months later; a repeat transplant also failed, and he died shortly afterwards.73 Cooley – who prided himself on his speed and accuracy – took a mere three hours to complete an operation that had taken Barnard eight. He was intoxicated by the acclaim that followed, admitting to a colleague that he relished the public perception that he was a ‘supersurgeon’: ‘Overnight’, he said, ‘the surgeon becomes some sort of deity!’74 By the end of the year Cooley had performed eighteen operations, including one heart-lung transplant on a two-month-old girl.75 But only six of his patients were still alive, and the longest any of them survived was little more than a year.
If these results were not particularly impressive, the overall picture was hardly more encouraging: a survey compiled in December 1968 found that fewer than half of the sixty-five patients given a new heart in the preceding twelve months were still alive.76 So poor were the early results that heart transplantation might have been quickly abandoned had it not been for one beacon of hope: Christiaan Barnard’s second patient, a retired dentist called Philip Blaiberg, who lived for more than nineteen months. After a long and arduous recovery he became the first transplant patient to leave hospital, but not before he had had the unprecedented experience of holding his own, dead heart. This encounter provided the title for his book, Looking at My Heart, in which he recorded his astonishment at becoming an international celebrity; daily bouquets of flowers arrived at his flat and he received endless offers to give talks and appear on TV.77 As the world gradually became aware that most transplant patients survived for only a few miserable weeks in hospital, pictures of this amiable South African strolling in his rugby-club blazer, and even swimming in the sea, gave a hint that transplantation might one day fulfil the exalted expectations of the public.
With doubts emerging about the worth of the operation, there was also growing disquiet about the ethical questions it raised. Of particular concern was the status of the donor. A heart only remained viable if taken from the body a short time after it stopped beating. Surgeons quickly realised that the ideal donor would be a young person who had suffered a brain injury of some kind. A young body was more likely to have healthy internal organs, and a head injury would often leave the heart unaffected. There was another advantage, too, but one that created an ethical minefield. Modern medical technology such as mechanical ventilation often made it possible to keep the heart beating for some time, even when the brain was catastrophically damaged. A potential donor might therefore be left on life support until surgeons were ready to perform a transplant. But was such a patient alive or dead? By the 1960s, many doctors were satisfied that absence of brain activity was a conclusive sign of death, but among the public it was generally believed that anybody with a beating heart was still alive. Even if it were accepted that a person’s brain was dead, it was not clear whether it would be morally defensible to take out a heart that was still beating, or to turn off a ventilator so that it stopped.
Worse, the law had not kept up with recent medical developments. In 1963 a young man from Newcastle was assaulted and suffered fatal head injuries. When he stopped breathing he was put on a ventilator; his wife, when told that his condition was hopeless, gave permission for doctors to switch off life support and remove a kidney for transplantation. The man’s assailant was arrested, but attempts to try him for murder failed: the court ruled that the victim had died at the hands of the doctors who turned off his ventilator, so the defendant could only be convicted of common assault.78
Similar problems beset Donald Ross when he performed the first heart transplant in Britain – and the tenth anywhere – in May 1968. Press interest was overwhelming, and photographs of Ross and his team standing beaming on the doorstep of the National Heart Hospital were on many front pages. But a note of uncertainty had crept into the coverage. The Times printed a sceptical article by its medical correspondent under the headline ‘British Heart Transplant May Be Too Early’.79 The Guardian quoted a consultant cardiologist, Donald Scott, who condemned the operation as ‘almost amounting to cannibalism’.80 The fuss did not appear to bother the patient, forty-five-year-old Frederick West, who cheerfully admitted that he was not interested in the details of the procedure. He made an excellent recovery at first, and was able to drink sherry with his wife three days after receiving his new heart, but died on 18 June after suffering blood clots on the lungs, an avoidable consequence of the technique employed to stitch in the new heart.81
Within weeks of the operation Ross and his team were facing calls for their prosecution. The source of the donor heart was Patrick Ryan, a labourer who had been fatally injured when a concrete slab fell on his head. His heart stopped in the ambulance but was restarted, and he was kept on a ventilator until the surgeons were ready to remove his heart. Some questioned whether the doctors had in fact killed him to harvest his organs, and there was considerable media coverage of the ensuing inquest. This was heard in front of a jury and there seemed a genuine prospect that it might give a verdict of unlawful killing. On the stand, one of Ross’s colleagues, the surgeon Donald Longmore, produced Ryan’s skull from his briefcase, demonstrating that the injury had removed the top half of his brain.82 The coroner accepted the medics’ assertion that Ryan had died in the back of the ambulance, and the jury returned a verdict of accidental death.83 Ross and his team were off the hook, but the controversy showed no signs of abating. A few months later Ross sent a circular to several hospitals asking staff to notify him if any suitable heart donors were admitted. The head of the intensive care unit at St Thomas’ Hospital reacted furiously, denouncing the ‘gang of vultures’ waiting to snatch out his patients’ organs.84 This echoed the sentiments of the cartoonist Gerald Scarfe, who had depicted Christiaan Barnard as a sharp-beaked vulture ripping the heart from a living patient.
Medics knew they had a problem, and steps were finally taken to ensure that such cases would not arise in future. On 5 August two organisations independently released ethical guidelines intended to clarify the main issues surrounding death. Delegates at the World Medical Assembly in Australia issued a document known as the Declaration of Sydney, which acknowledged that death was not a clear-cut process: tissues often continued to function for hours after the death of the individual. This was significant, since it gave physicians justification for declaring a patient dead before the heart had stopped beating.85 Still more important, however, was the report of a committee from Harvard University published the same day. It called for a new definition of death that would be enshrined in law. The key criterion was to be the status of the brain: if the central nervous system was dead, so was the patient. Brain death could be diagnosed if the patient was unresponsive, could not move or breathe, and lacked normal reflexes (for instance, if the pupils no longer reacted to light). Crucially, the committee proposed that a respirator should only be turned off after death had been declared – this would protect doctors from the possibility of legal action.86
The Harvard report had profound consequences, particularly in the US, where a new definition of death was eventually enshrined in federal law in 1981.fn2 87 It came too late, however, to prevent one of the most notorious episodes in the history of transplantation. On 8 August 1968 the Japanese surgeon Juro Wada performed his country’s first heart transplant, using an organ taken from the body of a boy who had drowned while swimming. It was later alleged that the donor was still breathing when he reached hospital, and that Wada had given him a muscle relaxant to hasten his death. He then declared the boy brain-dead – a gross violation of a principle established elsewhere that the person certifying the death of a donor should not be the surgeon wanting to use their organs.88 The recipient died three months later, prompting a criminal investigation which eventually saw Wada charged with murder, professional negligence and the illegal disposal of a body.89 The case failed through lack of evidence, but its effects were chilling. Public trust in the medical profession plunged, and further operations in Japan became impossible. It was not until 1999, more than thirty years later, that the next heart transplant took place there.90
This was an isolated incident, but enthusiasm was waning elsewhere too. After the peak of 1968, the ‘year of the transplant’, there was a steep fall in the number attempted. In December 1970 the American Heart Association compiled the results of all 166 reported transplants and found that only 23 patients were still alive. Surgeons were realising that while the procedure itself was technically straightforward, ensuring the patient’s survival thereafter was a formidable challenge – one requiring expertise which only specialist centres could offer.
In September 1971 Life magazine published an exposé by Thomas Thompson, a journalist who had spent several months in transplant units in Houston. The cover carried the unambiguous headline ‘The Tragic Record of Heart Transplants: A New Report on an Era of Medical Failure’. Thompson revealed that in addition to the high mortality of the operation, many survivors experienced dreadful side-effects from their anti-rejection drugs: the powerful steroids caused facial swelling, depression and even psychosis.91 What had originally seemed the dawning of a new medical age was now widely regarded as a dangerous and failed endeavour.
In the early 1970s transplantation virtually ceased. In some countries efforts simply petered out; in others a formal decision was taken to abandon the operation. In February 1973 the UK’s chief medical officer Sir George Godber called a meeting of clinicians to discuss the situation, after which a letter was sent to specialist centres recommending they cease all transplants.92 This communication was described as ‘advisory’, but surgeons were in no doubt that it amounted to a prohibition. For the next five years only a handful of brave souls were willing to persist with heart transplants. Shumway and Lower, who had unrivalled expertise in the subtle problems of rejection, were in it for the long haul. Barnard also continued, and his results were better than most: four of his team’s first ten patients lived for more than a year. One of them, Dirk van Zyl, returned to his job within months of being given a new heart, and did not miss a day’s work until his retirement fifteen years later – an indication that transplantees could not only live for a long time, but with excellent quality of life.93
While Shumway and Lower made incremental improvements to their existing techniques, Barnard went in several new directions. In 1974 he began to employ a radical alternative to the conventional transplant method, using two hearts rather than one. The idea came to him after a patient died on the operating table because the new organ could not be started. The man’s son asked Barnard why he could not put the diseased heart back, since at least it worked.94 Barnard realised that this was not as silly as it first appeared. The original heart could be left in place and a donor heart implanted in parallel with it. The new organ would support the old one, possibly allowing it to recover; if rejection set in, the original heart would be able to support the circulation until the episode had been averted. From November 1974 Barnard adopted this approach exclusively; one-year survival improved from 40 to 61 per cent, almost as good as the results achieved by Shumway. Ten of these patients survived even after their donor organs failed, showing that two hearts were indeed sometimes better than one.95
Three years later Barnard attempted to use donor organs from non-human species. This approach, known as xenotransplantation, had been employed by James Hardy in the disastrous first human transplant attempt in 1963. Six years later Denton Cooley had attempted to use a ram’s heart when no human donor was available, with a similarly dismal outcome: it began to shrivel even as it was being sutured in place, and the patient was dead before Cooley could substitute the pig’s heart he had as back-up.96 In London Donald Ross also attempted xenotransplantation in 1968, in an operation that took place before his first human-to-human transplant. Ross intended to transplant a pig’s heart in parallel with the patient’s failing organ, anticipating the approach later taken by Barnard. The evening began badly when one of the porcine donors escaped and was recaptured by Donald Longmore after a helter-skelter pursuit through the streets of central London; a senior nurse, woken by the animal’s squeals, made a complaint to hospital managers, and was distinctly unamused to discover a plate of pork chops on her front doorstep the following morning.97 The operation itself was an abject failure: the patient died within an hour. It was an episode that began as farce and ended as tragedy, and unsurprisingly no effort was made to report it to the wider world.
Barnard was no more successful. His first xenotransplant took place in October 1977 when a young woman undergoing routine surgery could not be weaned off the heart-lung machine. He opted to implant a baboon heart as an adjunct to the failing organ; this was a temporary measure, intended to buy a few days until a human donor could be found.98 The decision prompted a furious row with his brother Marius, who refused to take any part in the operation.99 Barnard succeeded in restarting both hearts, but the patient died after a few hours. A second operation, this time using a chimpanzee heart, took place shortly afterwards; this time the patient lasted four days.100
The final – and most controversial – attempt at cardiac xenotransplantation took place seven years later when a surgeon from California, Leonard Bailey, gave a two-week-old infant the heart of a baboon. Bailey had been investigating the possibilities of xenotransplantation for six years and had succeeded in keeping a goat alive with a sheep’s heart for five months. He believed that enough was now known about the immunological problems for transplant surgeons to risk crossing the species barrier. In October 1984 a paediatrician told him that he might have a suitable candidate. Stephanie Fae Beauclair was less than a week old and had been born with hypoplastic left heart syndrome, a congenital condition which at the time was almost universally fatal. Bailey met her parents and explained that although there was an operation which might improve her prospects, its results were so poor that a transplant represented her best hope. They gave their consent, and blood samples were taken to test for compatibility with a donor organ. Surprisingly, tissue from a baboon provoked a less aggressive response from her immune system than samples from her own parents. The decision was taken to go ahead with the xenotransplant.
The operation on 26 October was an intimidating technical challenge. The donor heart was the size of a walnut, and suturing its tiny vessels without leaving any leaks required dexterity of the highest order. When Bailey shocked the new organ and it began to beat once more the surgical team hugged each other with relief. For the next few weeks newspapers carried daily updates on the condition of ‘Baby Fae’. At first she did well, and within a week was feeding and being held by her mother. Drugs succeeded in quelling an episode of rejection, but on 9 November there were signs that the new heart was beginning to fail. Despite the team’s best efforts she deteriorated steadily and died six days later, having lived for three weeks with the heart of a monkey.101
The sorrow that greeted Baby Fae’s death was accompanied by mounting criticism. Opposition had begun while she was still in intensive care, when a small group of animal-rights activists picketed the hospital holding placards with the legend ‘Ghoulish tinkering is not science’. Anger intensified when it emerged that Bailey had not even attempted to look for a human heart before going ahead; one had in fact become available on the day of the operation.102 Many surgeons argued that a xenograft was doomed to fail: though baboons and humans are genetically similar, tissue from a foreign species was far more likely to provoke acute rejection. In his report of the operation Bailey tried to defend himself from attacks on his clinical judgment. He argued that a newborn’s immune system was poorly developed and therefore more likely to tolerate a xenograft, and pointed to the post-mortem findings, which he said showed no signs of rejection. He suggested that her death was instead attributable to the donor having a different blood type.103 Few shared his opinion, with one expert publically accusing Bailey of ‘wishful thinking’.104
The Baby Fae operation brought an end to the first era of xenotransplantation. Medics realised that they had not yet conquered the immunological barrier between humans and other species – moreover, conventional transplantation was suddenly looking a far more hopeful option. A few months before Baby Fae was born, a surgeon in New York, Eric Rose, had performed the first successful paediatric transplant on a four-year-old boy, James Lovette. Although he later needed a second new heart, James lived into his twenties.105 The story with adults was even more encouraging: increasing numbers of patients were surviving for a year or more after transplantation. The first months were always the most dangerous period for a transplant patient, so keeping significant numbers alive for as long as this gave some hint that indefinite survival might soon become possible, or even routine.
What had changed? Many transplant surgeons would say that the crucial breakthrough was the introduction in the early 1980s of a powerful new drug, cyclosporine, which drastically reduced the threat of rejection. But this is only part of the story. As early as 1973 Norman Shumway had been able to report that over a third of his patients lived for two years or longer.106 Much of this success was achieved simply by improving the diagnosis of rejection episodes, and finding a regime of drugs that would treat them. The most important contribution was made by a young surgeon from Northern Ireland, Philip Caves, who joined Shumway’s team as a research fellow in 1971. Shumway was at first perplexed by his new recruit, who shunned the operating theatre in favour of a long sojourn in the library. When Caves emerged several weeks later it was soon apparent that his time had not been wasted: he showed Shumway some little-known research by a Japanese surgeon, Souji Konno, who had devised a method of removing tissue samples from inside a beating heart.107 Caves realised that the symptoms of rejection appeared some time after the white blood cells began to attack the donor organ. By inspecting sections of cardiac muscle through a microscope, he suggested, it should be possible to detect the process even before the patient became unwell. With the help of a technician he designed and made an instrument called a bioptome, a tiny pair of pincers attached to a length of piano wire, which could be inserted into a neck vein and passed down inside the heart. Once there it would snip off a tiny portion of the cardiac wall and retain it for microscopic examination. This process, endomyocardial biopsy, was an immense improvement on existing methods of spotting rejection. Transplant patients were given regular biopsies and if necessary received drugs in doses tailored to the severity of the episode.108 Catching it early meant that most incidents of rejection could be treated without the patient even needing to return to hospital.109 Survival rates soared, and the proportion of patients living for five years doubled to 40 per cent.110
In 1973 Caves received a visit from his friend Terence English. A South African who had nearly abandoned medicine to work as a mining engineer, English was a newly appointed consultant cardiac surgeon at Papworth Hospital in Cambridgeshire. He was surprised to find so many of Shumway’s transplant patients looking happy and well, and deeply impressed when Caves showed him his work on endomyocardial biopsy. English had arrived at Stanford without any interest in heart transplantation, but his friend’s enthusiasm was so great that he left California intent on establishing a new programme in the UK.111 It took several years and endless political manoeuvring, but English eventually managed to persuade the authorities that the time was right to resume transplantation.
Britain’s first transplant since the moratorium took place at Papworth on 14 January 1979. English began to excise the donor heart while a second team prepared the recipient for surgery. He had just finished when he received a phone call from the anaesthetist in the other operating theatre, who told him that the patient had suffered a heart attack while being put to sleep. Although they had managed to resuscitate him, they could not tell whether there would be any long-term consequences. English decided to go ahead with the operation anyway, and though the new heart worked perfectly the patient had suffered irreversible brain damage and died eighteen days later. In English’s words, ‘the shit hit the fan,’ but he was determined to continue despite any public furore.112
His second attempt in August went much better: the recipient, Keith Castle, proved to be the perfect advertisement for transplantation. Waking from the anaesthetic his first question was about the football results; auspiciously, his team Fulham had won their first game of the season 4–3. Later, TV pictures of the cheery south Londoner riding his bike, playing golf and enjoying a pint in his local pub endeared him to the British public and showed how a heart transplant could transform the life of somebody previously unable to walk more than a few steps. Despite failing to heed English’s advice to give up smoking, Castle lived for almost six years.
The following year another British surgeon, Magdi Yacoub, began a second transplant programme at Harefield Hospital, and steadily improving survival rates ensured that official approval – and, more importantly, funding – followed. It was only in 1981, after twenty-nine transplants, that English and his team at Papworth started to use the revolutionary new immunosuppressive agent cyclosporine.113
The story of this miracle drug began in 1969 when H. P. Frey, an employee of the Swiss pharmaceutical company Sandoz, was on holiday with his family in the mountains of southern Norway. Scientists at the firm were trying to develop new antibiotic agents, and members of staff who travelled abroad were asked to fill a small plastic bag with local soil in case it contained organisms with antimicrobial properties.114 The sample brought back by Frey included a fungus identified as Tolypocladium inflatum, and microbiologists found that it produced a substance that was given the code number 24–556, and later named cyclosporine. They were disappointed to find that it had no antibiotic effects, but tests revealed another interesting property: when administered to animals it impaired their immune systems.
Experiments showed that when rabbits were given the substance after kidney transplants they lived indefinitely, while those that received no immunosuppressive therapy died in less than a month.115 In Cambridge Roy Calne tested it in heart transplants on pigs, and found that it greatly increased survival times. His assessment was that it was more effective in suppressing rejection than any other drug his team had tried.116 He began to use it clinically for kidney and liver transplants, but his earliest human patients suffered serious side-effects, including cancer. This problem was eventually solved in Pittsburgh by Thomas Starzl, who discovered that the toxic effects of cyclosporine were mitigated if it was administered in smaller doses as part of a cocktail of drugs.117
Heart surgeons were circumspect about adopting the new drug, waiting until its efficacy had been proved before risking their own patients. The results of clinical trials in the early 1980s were eagerly awaited, and did not disappoint. Cyclosporine was found to be a potent weapon against rejection, significantly improving life expectancy for heart transplant patients: 76 per cent of those given it lived for over a year, compared with 62 per cent of those who were not.118 Many sceptics were finally convinced, and the number of transplants performed each year soared from 182 in 1982 to more than 4,500 by the end of the decade. It became routine for patients to live long and healthy lives, with average survival today more than a decade.119 The most spectacular success story was that of John McCafferty, at time of writing the longest-lived heart transplant patient. When Magdi Yacoub performed his transplant in 1982 he was thirty-nine and near death; a year later he walked the sixty miles from his home in Buckinghamshire to Harefield to raise money for the hospital. He ran half-marathons and competed in the British Transplant Games, and lived for thirty-three years with his replacement heart until his death in February 2016.
Norman Shumway described cyclosporine as ‘an improvement of [a] magnitude that I think we will never see again’.120 So it was, but he was also being too modest about his own contribution. More or less overnight, cyclosporine improved one-year survival by around a fifth; but it had tripled in the decade before that, a period when Shumway almost single-handedly salvaged heart transplantation from the wreckage of its disastrous early years.
It should be acknowledged that Christiaan Barnard’s results were also exceptionally good, with four out of five of his post-1974 patients surviving for over a year. But curiously the pioneer of heart transplantation played only a minor role in its later development. He savoured the fame that his achievements brought him, the endless requests for interviews and the private audiences with President Johnson and the Pope. He became, in the words of a contemporary, ‘a bit of a dilettante and one of the world’s great womanisers’. The slightly rumpled surgeon was transformed into a nattily dressed socialite who visited nightclubs with Sophia Loren and was invited to spend holidays on Peter Sellers’s yacht; his first marriage collapsed after rumours of an affair with the actress Gina Lollobrigida. In the thirteen years that followed the historic first transplant he performed only twenty-one more,121 and in 1983 gave up surgery for good. His reason for doing so was the rheumatoid arthritis which had afflicted him for twenty years, causing severe pain and hampering his ability to operate. But many of his colleagues suspected him of losing interest in surgery long before he finally put down the scalpel.
In retirement Barnard helped to establish a transplant unit in Oklahoma, but his extracurricular activities did little to enhance his reputation. He lent his name to the ‘rejuvenation therapy’ of an expensive health spa, and was paid large sums to advertise a face cream – making scientifically dubious claims that outraged many in the medical profession.122 When he died while on holiday in Cyprus in 2001, the obituaries were fulsome, but paid almost as much attention to the many sexual conquests of the ‘playboy king of hearts’ as to his surgical achievements.123 Never has a surgeon’s private life been so publicly dissected, or their legacy so hotly debated.
Was Barnard right to perform the first heart transplant? Even among surgeons the point remains moot. Several I spoke to felt that he allowed personal ambition to trump clinical judgment, and that he failed to give Shumway sufficient credit for the years of research that made it all possible. Others pointed out that transplantation was inherently a leap into the unknown, and that no amount of animal experimentation would have been enough to show how the human body would react to being given a new heart. Maybe Barnard was not the person best equipped to transplant a heart in 1967 – but he was the first who had the courage to do so. And where he went, others followed.
So much attention has been paid to Christiaan Barnard and his operation in the half-century since it took place that an intriguing fact has been largely overlooked. In the early 1960s many people doubted that transplantation was really the answer to the failing heart. They believed in an alternative – one which promised to be cheaper, simpler and less fraught with ethical difficulties. Millions of dollars were spent in the quest for a reliable artificial heart, a machine that would act as a permanent replacement for the organ. In an age when two nations were racing to put a man on the Moon, designing a simple hydraulic pump for the human body seemed a realistic technological goal. But this exciting undertaking would soon turn into one of the most rancorous episodes in the history of medicine.