Interview with Prof David KC Cooper

EIC: WHERE WERE YOU BORN AND WHAT DID YOUR PARENTS DO? DKCC: I was born in Bexleyheath, which is in Kent just a few miles Southeast of London. When I was aged 7 years, we moved a few miles to Bromley, another London suburb in Kent. My father was a businessman and ran his own small engineering company and my mother stayed at home to care for my older sister and me (as a ‘homemaker’). EIC: WHEN DID YOU DECIDE TO BECOME A DOCTOR? DKCC: I was always in the ‘arts’ stream at school, but at 16, after a visit to the local hospital, I decided I wanted to be a doctor. However, the only science subject I had studied was biology and I had even given that up at 15. At that time, the University of London medical schools offered a 1-year preliminary course for candidates like me to study chemistry, physics and biology to the university entrance level before moving on to the medical course. I applied to several medical schools and was offered a place at Guy’s Hospital Medical School, which was convenient to get to from my home and in which I had been a patient a couple of times in my childhood. Many years after I graduated, Guy’s and two other hospital medical schools became absorbed into King’s College London. EIC: WHAT WERE YOUR AIMS AFTER YOU QUALIFIED? TELL US ABOUT YOUR EXPERIENCE WITH LORD BROCK AND DONALD ROSS AT GUY’S? DKCC: As a medical student, I had become greatly influenced by the innovative and exciting work of the two heart surgeons at Guy’s, Sir Russell Brock (later Lord Brock) and Donald Ross, and decided that I would like to train in heart surgery. At that time, Brock and Ross were among the leading heart surgeons in the world. Not only were they establishing the field of open-heart surgery in the UK, but their group was one of the few that had established an active research laboratory, and this emphasis on research greatly appealed to me. EIC: YOU WENT TO DO A PH. D. AT THE NATIONAL HEART HOSPITAL AFTERWARDS AND WERE THERE DURING THE FIRST HEART TRANSPLANT DONE IN THE UK. COULD YOU TELL US SOMETHING ABOUT THIS? DKCC: After junior surgical training appointments and a year teaching anatomy at Harvard Medical School in Boston, I decided to gain some experience in research. I was fortunate to be appointed as a research fellow at the Institute of Cardiology at the National Heart Hospital (NHH) in London, where Donald Ross spent part of his time as the senior surgeon. He and his colleagues had set up a research program to investigate transplantation of the heart and lungs. This was in the summer of 1967, several months before Christiaan Barnard carried out the world’s first human heart transplant in Cape Town. It was a privilege to be present as an observer at the first heart transplant carried out in the UK in May 1968, the world’s tenth heart transplant. By chance, one of Barnard’s team was visiting Donald Ross (a South African contemporary of Barnard when students at the University of Cape Town Medical School), and it was very exciting for me, as a young trainee, to have the opportunity of discussing the topic with them. After 3 years in research (which I submitted for the PhD degree), I completed my general surgical training at Addenbrooke’s Hospital in Cambridge, where I worked with Sir Roy Calne, another Guy’s alumnus and a major pioneer in the field of kidney and liver transplantation, who also greatly influenced my future career. While in Cambridge working first at Addenbrooke’s and later at Papworth Hospital, a cardiac and thoracic surgical centre where I assisted Sir Terence English (yet another Guy’s alumnus) to establish a new heart transplant programme, I was invited to supervise the medical students at Magdalene College in anatomy. Eventually, I became the Director of Studies in Medical Sciences and a Fellow of the College. Because there were only a small number of medical students at Magdalene, I could combine my teaching with the demands made on me by my training in surgery. Magdalene opened up a new world to me. As I was still unmarried, I lived in the College and had the privilege of dining in the candlelit 17th-century hall every evening in the company of professors and scholars in many non-medical subjects, which was a wonderful experience. I only left when I was offered a faculty position at the University of Cape Town in 1980. EIC: WHY DID YOU LEAVE AND JOIN CHRISTIAAN BARNARD? DKCC: I was very keen to obtain an ‘academic’ position in cardiac surgery, where I could combine clinical surgery and research, but there were only three such positions in the UK at the time so I had to look elsewhere. In view of my interest in heart transplantation, I wrote to Barnard and asked him if he had an opening in his department, and fortunately, he did. He was without a doubt the most interesting person I have met in my life. He was charismatic, had a great sense of humour, and had an unmatched drive and enthusiasm for cardiac surgery. His great strength was that he had the courage to take a risk, e.g. in carrying out the first heart transplant, backed by an immense capacity for hard work. His weaknesses were several, e.g. impatience with his staff, and a tendency to blame others when a patient did not do well, but in my opinion, they were outweighed by his strengths. Although an Afrikaner by birth, he did not support apartheid and insisted that all his patients, irrespective of race and ethnicity, received the same care. At the time, because of the liberal views of many of its faculty, the University broke many of the government rules. EIC: WHY DID YOU LEAVE SOUTH AFRICA AND MOVE TO THE USA? DKC: When Barnard retired (at the early age of 61), a surgeon from abroad was appointed to take over from him. Barnard accepted an opportunity to act as an advisor to a surgical group in Oklahoma City in USA that wished to establish heart transplantation at its centre. After a disappointing beginning, through Barnard’s recommendation, I and a close colleague of mine in Cape Town were invited to relocate to Oklahoma to help run the programme. Fortunately, our efforts were quite successful. EIC: YOU HAVE BEEN DESCRIBED AS THE ‘FATHER OF XENOTRANSPLANTATION’. WHEN AND WHY DID YOU BECOME INTERESTED IN THE SUBJECT? DKCC: When I was a research fellow at the NHH, I became aware of the need for a source of organs that did not rely on donation by humans, This awareness increased when I worked in Cape Town and, because we had excellent research facilities and baboons as experimental animals, in 1985, I began to investigate cross-species transplantation, i.e. xenotransplantation, using pigs as organ donors. This was the first series of pig-to-nonhuman primate heart transplantation in the world. Despite the fact that pig organs were rejected within minutes, I mistakenly believed that we would solve the problems within 5–10 years. Instead, the barriers were so many that it has taken almost 40 years for us to begin clinical experiments. EIC: WHAT ARE THE MAIN OBSTACLES YOU FACED IN PROMOTING XENOTRANSPLANTATION AND ARE STILL FACING TODAY? DKCC: The major initial hurdle was the hyperacute rejection that occurred from antibody-mediated complement activation, and this was not truly overcome until it became possible to extensively genetically modify pigs to provide their organs with some protection from this immune response. However, there were several further hurdles that had to be overcome, either by more gene editing or by the introduction of novel immunosuppressive therapies. The potential risk of transfer of pathogenic pig microorganisms to the recipient of the graft is now considered to be small. Although several thousand pigs may be required each year to treat a large number of patients on organ transplant waiting lists worldwide, this needs to be considered in light of the fact that in the USA alone more than 125 million pigs are slaughtered as food each year. EIC: WHAT DO YOU THINK IS THE FUTURE OF XENOTRANSPLANTATION? DKCC: I have often referred to xenotransplantation as ‘the next great medical revolution’ because it will not only resolve the donor organ problem, but it may provide pig red blood cells for transfusion, corneas for corneal blindness, and dopamine-producing cells for the treatment of Parkinson’s disease, among many other conditions. In addition, I foresee gene-edited pigs being sources of human albumin and numerous other blood products essential to medicine today. I firmly believe that eventually the pigs will be gene-edited to provide their organs with complete protection from the human immune response and that no (or minimal) exogenous immunosuppressive therapy will be required to be administered to the recipients, However, this will take many years – possibly 20 or more to achieve. I believe that during the next 10 years, xenotransplantation will become increasingly successful and will steadily reduce the need for allotransplantation. The current shortage of organ availability will therefore no longer limit the number of transplants that can be carried out each year. Transplant surgeons and physicians will be in great demand. The need for scientists to resolve the remaining problems will also increase, and so transplantation will become a field of great expansion. I would therefore encourage young doctors and scientists to direct their attention to transplantation. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.