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50 Years since the first heart transplant: What a piece...

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50 Years since the first heart transplant: What a piece of work is a man!

The 50th anniversary of the first successful heart transplant encourages J. BROOKS SPECTOR to look back at Dr Chris Barnard’s unprecedented medical moment – and to think about what happens next. Shades of the final scenes in the Robin Williams film, Bicentennial Man, perhaps?

O my heart! Be still already!
Why are you pounding so savagely?

It is the will of heaven
that I should leave her.
And if your young life gave you
nothing but delusion and pain,
it still gave her joy,
so let it be lost!…
To my heart! Be still already!’

(Music by Franz Schubert, text by Ernst KF Schulze)

This week marks the 50th anniversary – 3 December 1967 – of the first successful heart transplant, the removal of the still-beating heart of Denise Darvall (who had been rendered brain dead in a motor vehicle accident) and its placement into the chest of Louis Washkansky, in a triumphant culmination of techniques developed by scientists and doctors around the world. The charismatic South African surgeon, Christiaan Barnard, led this first operation together with his team at Groote Schuur Hospital in Cape Town.

Barnard’s success and the global clamour that operation generated for more transplants, even though Washkansky passed away a few months later from the complications of pneumonia, soon led to surgical teams in America and elsewhere to emulate Barnard’s path-breaking efforts.

In fact, so widespread have such operations now become that rather than a heart transplant being a one-of-a-kind, revolutionary surgery that merits banner headlines and breaking news reports on television, a heart transplant is now rather routinely carried out (assuming a suitable donor is available) when a patient suffers from end-stage heart failure or severe coronary artery disease, when all other medical or surgical treatments have failed.

In current surgical practice, the most common procedure for a heart transplant is to take a functioning heart (with or without any transplantation of a lung or lungs) from a recently deceased organ donor and place it into the receiving patient’s chest. The patient’s own heart is usually removed and thus replaced with the donor’s heart. Less commonly, the recipient’s diseased heart is left in place to support the donor heart.

Around 3,500 heart transplants are now performed every year in the world – with more than half of those now taking place in the US. With current post-operative treatment protocols, survival periods now average some 15 years.

Cedars-Sinai Medical Center in Los Angeles currently is the largest heart transplant centre in the world, with doctors there carrying out more than 130 adult transplant operations in 2015. However, the orders of magnitude disparity between the number of people qualifying for a transplant on grounds of medical necessity and those actually receiving them has been encouraging researchers to investigate laboratory-created parts or the transplantation of non-human hearts into humans, even if, to date, the latter such procedures have not yet been successful.

Well before Barnard and his team’s operation, physicians had discussed whether heart transplantation could be a real possibility for over half a century before that ground-breaking 1967 moment. In one of the earliest papers on this topic, back in 1907, by medical researcher Simon Flexner (a key figure in the growth of Rockefeller University as a pre-eminent scientific research institution), Flexner had argued that, in the future, surgeons could substitute diseased organs with healthy ones – including replacement of arteries, the stomach, the heart and the kidneys.

Then, in 1964, James Hardy, of the University of Mississippi, had transplanted a chimpanzee heart into a dying patient. Although the simian heart beat for over an hour, the patient passed away without ever regaining consciousness. Hardy, despite having gained admiration for his successful lung transplant a year earlier, received the hard edge of “icy disdain” for his chimpanzee heart transplant, especially since the consent form had unfortunately failed to indicate that the transplant tissue might not be human.

When Barnard and his team had had their success, they were building on techniques developed earlier by Drs Norman Shumway and Richard Lower. In fact, Shumway and his team carried out the first successful US heart transplant just a month after Barnard’s operation and British doctor Donald Ross and his team did their first heart transplant in the UK five months later than that. By the end of that year, surgeons around the world had carried out more than 100 such transplants, although two-thirds of such transplant recipients died within just three months’ time. Eventually, the next big advance in this surgery was the wide availability of the drug cyclosporine. This led to a need to use lower doses of corticosteroids in suppressing transplanted tissue rejections.

Despite the increasing success of such operations, transplants are not yet problem-free. Post-transplant complications include infection, sepsis, and organ rejection, as well as side effects from all the immunosuppressive medications. Those latter medications are crucial since the transplanted heart originates from another organism and the recipient’s immune system typically attempts to reject it, even with close attention to tissue matches.

Because rejection risk never fully goes away, any recipient of a new heart must take immunosuppressive drugs forever, even though these drugs may also contribute to increased chances of infections or even the development of certain cancers. Recipients may also end up with kidney disease from the side-effects of immunosuppressant medications. However, advances in reducing complications due to tissue rejection have lowered rejections significantly.

Statistically, deaths attributable to complications in surgery are now under 10%. Moreover, figures from 2009 indicate that survival rates for transplant recipients are: 1 year: 88.0% (males), 86.2% (females); 3 years: 79.3% (males), 77.2% (females); and 5 years: 73.2% (males), 69.0% (females). Presumably they are better now than in 2009. There is apparently more of a risk for men receiving female hearts than vice versa.

The actual events that led to Christiaan Barnard’s team’s successful operation unfolded in this way. On the afternoon of 2 December 1967, Denise Darvall was out shopping with her parents. A police reservist in a car jumped a red traffic light and ran into Denise and her mother. While her mother died instantly upon impact, Denise survived, but with traumatic head injuries. By a strange coincidence of history, the wife of Louis Washkansky, the patient already in the hospital for imminent heart failure, happened to drive past the accident scene, even as Darvall was about to be taken to the hospital where she was declared brain dead. At that point, doctors began to believe they might have a potential donor of a heart for the struggling Washkansky, when Denise’s father gave permission to remove his daughter’s heart and kidneys for potential transplants.

Denise Darvall’s heart was removed just after midnight, and then a little later, Washkansky was prepped for surgery to receive his new heart. Just before six in the morning, the complex surgery was completed and the surgical team waited to see if the heart would commence beating on its own. Within a matter of a minute or two, the transplanted heart began twitching on its own as Barnard said to his team, “Will this heart be able to beat after being weaned off the machine?” As it began to do just that once the support was removed, Barnard shouted in the operating theatre, “Dit gaan werk!” (It’s going to work!) Almost immediately, the astonishing news flashed around the world.

While, less than a month later, Washkansky passed away from pneumonia, physicians could still hail this first transplant an extraordinary success. As University of Cape Town transplant consultant and critical care medical academic David Thomson explained in a lecture for the Coursera learning site, “Chris Barnard went on to become a household name and travel the world. His second patient, Philip Blaiberg, lived for 18 months. Patients five and six lived for 13 and 23 years, respectively. Dirk van Zyl, the sixth patient, returned to work after three months and never missed a day of work for the next 15 years until his retirement.

Not all cardiac transplant programmes started as successfully, however. Dr Adrian Kantrowitz performed a paediatric cardiac transplant three days after the South African operation at Maimonides Medical Center in Brooklyn, New York. But the patient demise [was] six hours post-op. The patient had been 19 days old, born with a fatal congenital cardiac defect. The donor was born anencephalic, without a brain. Emotions ran high after this event, and there was much criticism professionally and in the media.

There was an impression that the procedure was rushed, that the cardiac transplantation was being used as a status symbol. This was not the case. Dr Kantrowitz’s team had done over 258 cardiac transplants in the animal lab with survivors living beyond two years. Norman Shumway and Richard Lower, who pioneered the operative technique, had done even more, having first described the operation in 1960.”

With his unprecedented surgery, Chris Barnard became a global celebrity in a way few medical specialists have ever achieved in their lifetimes. He was feted internationally, written about everywhere, and photographed with other celebrities – sometimes with particularly attractive female ones. As he remarked later, “On Saturday, I was a surgeon in South Africa, very little known. On Monday, I was world-renowned.”

On the other hand, for some people, there were strenuous moral apprehensions about whether doctors like Barnard were playing at being God with these transplants. Nevertheless, overall, this criticism was tempered by the global public’s fascination with the idea that one person’s heart could end up beating in someone else’s chest. Barnard took to explaining that the heart was nothing more than a very strong, very specialised pump.

Still, for thousands of years the heart had been understood as something very special, a seat for the soul and the body’s veritable life force. And it had been – and continues to be – the image or inspiration for thousands of songs, poems and other meditations, in a way that could never be true of the kidneys or a gall bladder.

Of course, South Africa’s racial history and politics have never been very far from the surface for anything and for heart transplant pioneer Barnard, his deeds and words were no exception. With his global fame, the government of the day pushed him to speak out positively about South Africa, although his increasingly critical remarks about apartheid eventually drove him outside of their charmed circle. As Marina Joubert wrote about him for the IOL newspaper group, “He was fiercely opposed to apartheid and later refused to allow ongoing segregation of black and white patients in his intensive care wards at Groote Schuur hospital. His anti-apartheid views led to ongoing clashes with hospital authorities and politicians.”

Then there has been the controversy over Hamilton Naki. Naki, an African, who had risen to become an especially talented laboratory technician, working under the guidance of Barnard’s surgical team, from an initially lowly position as a gardener at the University of Cape Town. But the claim that he was a cruelly unsung hero of the transplant team in the operating room has become a story that parallels the larger meme of South Africa’s apartheid history. As Elsabe Brits wrote for the Africa Check website earlier this year, “Numerous incorrect reports claiming that he did participate have surfaced during the past two decades. It forced some of the most prestigious newspapers, such as the New York Times, The Economist, the Associated Press, and peer review journals such as the British Medical Journal and The Lancet to publish corrections.”

At the start of his career, Dr Robert Goetz mentored him and Naki began to learn animal anatomy and to operate on them as well. Professor Rosemary Hickman, a renowned surgeon who knew Naki well, has written, “Naki had an amazing ability to learn anatomical names and recognise anomalies. His skills ranged from assisting to operating and he frequently prepared the donor animal (sometimes single-handedly) while another team worked on the recipient.”

Brits explained that it was in his role as laboratory assistant that Naki became involved with Chris Barnard and his brother, Marius, also a surgeon. Or as a 2014 overview article in The Bulletin of the Royal College of Surgeons of England explained his role, “Naki anaesthetised the dogs for the earlier work in heart surgery in the laboratory, which was on the establishment of open heart bypass, using an external heart pump. This was a finger pump that circulated blood through heat exchangers that were warmed or cooled by huge steel tanks of water. Such pumps were difficult to maintain and often broke down unexpectedly.”

However, for the first heart transplant operation, Marius Barnard told Brits in 2011 that Naki had been at home, asleep, during the initial transplant into Washkansky’s body – not surprisingly given the late night/pre-dawn prepping. For Naki to have participated in the actual transplant operation, given his lack of formal academic credentials in medicine, would have been both illegal and unethical. Still, in the lab, at the experimental surgical operating table, Naki worked on baboons, rabbits, dogs and pigs to advance the work on liver transplants, in particular.

The 2014 British article adds, “As the most senior member in the laboratory, Naki came to be considered its leader and began to impart the knowledge he had acquired to a long series of trainees. He demanded high standards and became a strict taskmaster. Naki demonstrated dissection and surgical procedures to more than 12 trainees who were later to become professors of surgery.”

It is a shame, but perhaps inevitable, given the racialised nature of history in South Africa, that Naki’s actual and important career has been tied up with efforts to give him unearned accolades to drive home the obvious point about the iniquities of South Africa at the time. Brits explained after Naki’s death, “The then dean of UCT’s faculty of health sciences, who knew Naki at the time of the first heart transplant, wrote: ‘It is distressing that a fiction is gathering momentum and tarnishing the name of a highly talented and good man with an untruth. The suggestion that Hamilton Naki performed the donor operation was never mentioned in life by the man himself, by the department of cardiac surgery, or by the university in his citation for his honorary degree in 2003. It was not mentioned at his family funeral, or at the memorial service in the medical school experimental laboratory. The reason for this: it never happened.’ ”

What his very real accomplishments do argue for, of course, is the demonstration of the waste of innate talent and skill as an inextricable part of South Africa under apartheid. Imagine for a minute, instead, what Naki’s accomplishments might have been had he been able to enter medical school and gone on to become a renowned researcher or surgeon.

The team led by Chris Barnard that completed the first successful human heart transplant made medical and scientific history. But how much longer before the transplantation of human organs from one person to another is overtaken by science?

Now, 50 years after the first successful heart transplant, experts believe we may be nearing an era where organ transplantation will no longer be necessary. As Don Galeon reported in this week, citing researcher Stephen Westaby of the John Radcliffe Hospital in Oxford, UK, “I think within 10 years we won’t see any more heart transplants, except for people with congenital heart damage, where only a new heart will do.” He went on to say he has been a great supporter of cardiac transplants, but recent technological developments may well be soon ready with alternatives that could save more time, money, and lives. As Westaby explained, “I think the combination of heart pumps and stem cells has the potential to be a good alternative which could help far more people.”

Galeon notes, “Studies that have been done with stem cells have proven that it is possible to grow organs in a lab, which could then be implanted.” Moreover, “Science has also made it possible to produce artificial organs using another technological marvel, 3D printing. When applied to medicine, the technique is referred to as 3D bioprinting — and the achievements in the emerging technique have already been quite remarkable.”

Successful efforts already include 3D-bioprinted thyroid glands, tibia replacement and a patch of heart muscle tissue that actually beats. Galeon adds, “Other technologies that are making it possible to produce synthetic organs include a method for growing bioartificial kidneys, the result of a study in 2016.” Meanwhile, reports Galeon, Westaby is working on a variety of projects that range from stem cells to reverse scarring in heart tissue and mechanical heart pumps manufactured out of titanium.

Potentially, at least, such developments could help address the backlog of patients desperately awaiting possible donors. In fact, eventually synthetic organs could even be reliably printed on demand for patients. Then we can begin the argument over what, exactly, is the nature of a partially manufactured, retrofitted human? Such a question has been asked for years in sciencefiction, but any real answer still eludes us. Soon enough, however, we may yet have to deal with the legal nature of just this kind of question. Or, as Hamlet exclaims (and asks), “What a piece of work is a man!” DM

Photo: Photo: Dr Chris Barnard.


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