The BBC’s ‘Horizon: Mend Me’ programme, aired this week, was a whistle-stop tour through the outstanding –and often unsettling– progress made in the field of organ transplantation. Introductory scenes included jarring images of a young man who had had his face entirely burnt away. Even the presenter Michael Mosley, presumably hardened to horrific injuries during his time as a medic, winced at the horrific damage. This patient was a candidate for a full face transplant, an amazing illustration of how far surgeons have come in the past few decades.
Although the concept of transplantation had been pictured for centuries, it took until the mid-20th century for it to approach any semblance of reality. From the end of the Second World War surgeons zealously raced to be the first to successfully perform an organ transplant. They experimented on healthy animals and their own seriously ill patients. All died after surgery. Such abandon would be shocking today, but as the surgeon Francis Moore put it, the patients were dying anyway and they ‘at least deserved a try’. The grafted organs were rapidly destroyed, in a process that was poorly understood – immune rejection. A successful transplant appeared a pipe dream
It took the insight of Joseph Murray to dispel the air of scepticism and failure. In 1954, Richard Herrick came to Dr Murray, desperately seeking treatment for the renal disease that was killing him. He mentioned that he had a healthy identical twin. Murray correctly inferred that the risk of severe acute rejection would be far less severe in a graft involving tissue from a donor closely related to the recipient. The resultant operation gave the world’s first successful organ transplant; history was made.
Murray made further headlines by pioneering transplants between non-related donors; this had previously been an utter failure. During organ rejection, the immune system does what would normally be beneficial; ridding the host of the foreign body (in this instance, the life-saving new organ). The patient is likely to die from their own over-exuberant immune response. Murray used strong drugs to suppress the immune system; the donor organs avoided destruction, and some patients survived, although others died from drug toxicity. The success was a major milestone, and he was rewarded for his efforts with a Nobel Prize in 1990.
Transplant rejection remains a significant obstacle facing surgeons today, despite finely-tuned drug administration. Anti-rejection programmes are not always successful. Murray’s early operations had a high mortality rate; not from organ rejection, but from immunosuppressant toxicity. Techniques and instruments continue to advance, the operative procedures possible become ever more intricate, but this sophistication cannot escape the potential death-knell of a patient’s own immune system.
The improvement in kidney transplant success rates led to attempts to transplant that most symbolic human organ, the heart. The first human heart transplant was performed by Dr Barnard in South Africa in 1967, but the patient died shortly afterwards, from a secondary lung infection he could not fight off whilst on strong immunosuppressants. This did not temper surgeons’ enthusiasm, and over a hundred procedures were performed worldwide shortly afterwards, with a ‘100% mortality rate…that was a disaster’ – Dr Francis Moore. The cardiac surgeons ‘wanted to show they could also transplant a heart’; but did not appreciate the dangerously high levels of anti-rejection drugs required for a heart transplant compared to a kidney transplant. This period in the history of transplantation was a slow one, at least until the discovery of the selective immunosuppressant compound ciclosporin. This was the surgeons’ saviour; it allowed the host immune system to survive, without the catastrophic attack of the new organ. This discovery enabled multiple organ transplants; the transplantation field grew at an astonishing rate from the 1970s.
Today over 30 000 organ transplants are performed annually in the US alone. But the World Health Organisation puts the number of successful candidates awarded a kidney transplant at just one in ten. Today, the problem is usually not one of surgical technique, but that of demand far exceeding supply. Many thousands of people die every year whilst awaiting an organ. The NHS organ donor scheme acts to address this shortage but some politicians believe that an ‘opt-in’ policy just isn’t enough. Time will tell whether the UK changes policy in this regard. However, we have certainly advanced from the earliest transplants, which were often performed using ‘donor’ organs from a rather grisly source, the guillotines of French prisons. As Charles Dubost, a surgeon based in Paris in the 1950s, succinctly put it: “he’s dead, no head, you can take the kidneys!”
The BBC feature did not shrink away from portraying recent scandals in the field of organ transplantation, further tackling the issue of donor consent. The notorious New York ‘body snatcher’ Michael Mastromarino stole thousands of body parts from corpses and sold them on for a multi-million dollar profit. The bodies he used were subsequently doctored to appear acceptable to relatives before their burial. X-rays of exhumed bodies revealed that Mastromarino and his team had replaced their bones with sections of PVC pipe. This case is far from isolated. Similar scams, this time involving live donors, have been reported across the globe. Some people see a kidney as dispensable, worth sacrificing for quick cash. In particularly disturbing scenarios, impoverished people have been drugged and unknowingly operated upon, for the benefit of a rich recipient. Such occurrences have tarnished the wider image of transplant medicine in recent years. But its importance in saving thousands of lives means that the field will only continue to thrive.
Science still has many questions to consider in the field of transplant medicine. Indeed, the definition of death itself has had to be rewritten. Traditionally, doctors signed a patient’s death certificate as soon as their heart stopped. This was reconsidered in the light of transplant technology and today organs may be harvested from the point of brain death. As long as the heart continues to beat, the organs for transplant are still perfused and healthy.
Remarkable progress in a short time-frame is often the case in medical research, as the final aspect of this programme illustrated. Xenotransplantation in genetically engineered animals has been a recent technique trialled. The first pig-human heart transplant will occur this year, representing a truly astonishing leap from the failures of the 1960s. Furthermore, stem cell research gives the tantalising possibility of organs ‘on demand’; our own cells could theoretically be used to generate new healthy organs. The practical considerations are vast, but labs world-wide are working on this possibility. Dean Third, a man with dilated cardiomyopathy, visited Dr Doris Taylor in her Minneapolis laboratory. Taylor is a researcher hoping to ‘build hearts’ in the lab for transplant. As Dean said upon seeing her work, ‘you’re creating hope for hundreds of thousands of people’.
Future advances will work to satisfy such hopes. This Horizon programme allowed viewers to marvel at medical ingenuity, whilst still appreciating the huge patient sacrifices that have enabled, and will continue to enable, such stories of success as Dr Murray’s.
-Sophie McManus, 2nd year studying Biomedical Sciences at Magdalen