Sir Peter J. Morris, AC, FRS

FigureTransplantation: What Event or Person Led You Into the Field of Transplantation? PJM: There was no single event, but perhaps a few fortuitous events pushed me into transplantation. I had a general surgical training in Melbourne, Australia, then in the United Kingdom, and after that at the Massachusetts General Hospital (MGH) Boston. While I was in London, I was a resident surgical officer at the Royal Postgraduate Medical School at the Hammersmith in 1962 for 6 months where an embryo transplant unit had started under the direction of Professors Ralph Shackman and James Dempster. During that time, they carried out the first living unrelated transplant. The donor and the recipient were both doctors and were in general practice together as partners. I was not involved directly but did follow the whole event with some interest. The only immunosuppression in use at that time was total body irradiation which the recipient, Dr Clarke, received. Unfortunately, he died about 1 month after the transplant. The 2 general practitioners were enormously popular in their area in Berkshire and a fund was set up in memory of the recipient known as the Doctor Clarke Fund to support research in renal disease. Some 13 years later, when I came to Oxford to the Nuffield Chair of Surgery with plans to establish a transplant program, the trustees of the Doctor Clarke Fund handed it over to the University of Oxford for me to use for research purposes. It remained a very viable and very much-used fund to which all patient and family gifts were made until I retired in 2001. I left the UK at the end of 1963 to become a senior surgical resident at the MGH in Boston, where Paul Russell was the new chief of surgery and was establishing an impressive living-related renal transplant program. After my year as a senior resident, I moved into research with Jack Burke, a lateral thinking surgeon who, while working at the Lister Institute in London with Sir Ashley Miles, did the seminal experimental work that established the rationale of administering preventive antibiotics before the operation in patients undergoing potentially contaminated surgery. I was working in the laboratory on factors influencing infection and inflammation in the guinea pig, and indeed first used an antilymphocyte globulin to study the response to Staphylococcal infection in the absence of leucocytes.1 Sometime in 1966, Maurice Ewing, the professor and chief of surgery at the Royal Melbourne Hospital within the University of Melbourne, asked me to return to a position in his department. The Royal Melbourne had a new renal transplant program under the direction of Professor Priscilla Kincaid-Smith and Dr Vernon Marshall. I went, with Paul Russell’s advice, to visit Bernard Amos at Duke and Paul Terasaki at UCLA who were using cytotoxic techniques for the primitive typing that was in an early stage of development. I was also aware that Jon van Rood was coming to type their living-related donors and recipients using leucoagglutination. After exploring all options, I decided that the technical aspects of Teraksaki’s microcytotoxic technique were way ahead and pursued that line of endeavor for serological tissue typing. My career was then reinforced by a late call in 1966 to go down to the Medical College of Virginia (MCV) where David Hume had moved as chief of surgery from the Peter Bent Brigham in Boston to establish arguably the major transplant program in the world at that time. He wanted me particularly to set up a tissue typing program and thus, I was now definitely committed to the field of transplantation. Transplantation: When Did You Publish Your First Paper and What Was the Paper You Were Most Proud of Writing? PJM: I published my first paper in Gut in 19652 describing a unique family over 3 generations that I had come across in Southampton (my last post in the UK) in which 8 members of the family had ulcerative colitis, and there was a suggestion from the pedigree that the disease was determined by an autosomal dominant gene. The paper I was probably most proud of writing was the first description of cytotoxic antibodies occurring after renal transplantation and appearing to be associated with acute rejection.3 Subsequently, I showed that most of these antibodies were donor specific.4 This was a major event at the time as antibodies were not considered to play any role in rejection. Another paper that I published soon after returning to Melbourne University was a retrospective review of the impact of blood transfusions in dialysis patients on the outcome of a subsequent renal transplant. This study showed that there appeared to be no associations between the number of transfusions that a patient received and either sensitization or acute rejection, and indeed I speculated on the possibility that the prior transfusions might have induced a degree of partial tolerance.5 Although not published in a high-ranked journal, this is one of my favorite personal articles. Transplantation: Who Were the People Who Had Most Influence on Your Career? PJM: In addition to Jack Burke and Paul Russell, I would like to mention Drs. Tom Rowntree, Jack Burke, Claude Welch, David Hume and Professor Maurice Ewing. Tom Rowntree, consultant surgeon at the Southampton General Hospital was the most brilliant trainer that I was ever fortunate to work with. Dr Claude Welch, the senior clinical professor of surgery at the MGH had come to Melbourne in 1960 as a visiting professor at St. Vincent’s hospital where I was a surgical registrar at the time. In those days, visiting professors came for a month and operated every day of the week, and I was responsible for the organization of the lists and assisting him in every procedure. What amazed me, at the time, was that he said please and thank you to the scrub nurse, to me, and anybody else involved during the operative procedure. I well remember that the first operation he did with an enormous gallery was a partial gastrectomy; and despite all the courtesies, which I had not seen before in theatre, he still had completed the operation in 1 hour and 20 minutes. I regarded him as the proper model for a surgeon. Jack Burke was always full of original ideas and I learnt a lot about research techniques from him. David Hume was a charismatic person and not only a very good surgeon, but also what we would now call a clinical scientist. While working with David Hume at the Medical College of Virginia we experienced several hyperacute rejections. The patients proved to have donor-specific antibodies and a positive crossmatch, performed after the event. These cases and several others were written up by Mel Williams and ourselves in the New England Journal of Medicine in 1968.6 Finally, Professor Maurice Ewing, head of the Department of Surgery at the Royal Melbourne Hospital at the University of Melbourne, was another big influence as he provided me with the means and laboratory space to establish tissue typing and transplantation immunology laboratories. It was here that together John Fabre, a PhD student, and I first established the renal transplant model in the rat, and produced allograft tolerance both by passive enhancement and prior blood transfusions.7,8 Needless to say, I was heavily involved in the clinical transplant program as well as carrying out a good deal of general and vascular surgery, as surgeons of my vintage always did in those days. Transplantation: What Was the Best Experience in Your Career? PJM: I would say that my marriage to Jocelyn over 50 years ago was the most memorable occasion, but professionally I think the 1 event that I was most excited by was to hear that I had been elected as a fellow of the Royal Society in 1994. It is a rare event for a clinician, much less a surgeon, to be elected into this premier scientific society of the United Kingdom and the British Commonwealth. When I got the news I was playing golf at Augusta National, the home of the Masters Golf tournament, but sworn to secrecy and was not able to celebrate with my host and friends in the golfing group! Another event that gave me great pleasure was to be elected as president of The Transplantation Society in 1986 and later, the award of the Medawar Prize in 2000. I am enormously proud of all the people who have worked in my Oxford Department from all over the world. It would be invidious to single out individuals, but it is worth noting that at the last count, we could claim over 40 professors of surgery and transplantation, and others who had reached the top as professors in nephrology, immunology, and even one as professor of genetics. Transplantation: What Do You Most Like to Do When Not Working? PJM: In my early days it was playing cricket—for a while I had played professional cricket at district level in Melbourne and continued that on a social level in Oxford. Then I found it was a bit too time consuming, but I was also playing a fair bit of tennis. Indeed every year Roy Calne’s department in Cambridge and my department in Oxford competed for a tennis cup that was a tensely fought battle alternating between Oxford and Cambridge. Before the match we always had a scientific symposium and after the match either Roy Calne or I hosted everyone at our homes. Later on, I renewed my interest in golf and indeed, I got my handicap down to 8 or 9 as I recollect when I was 60. Sadly, now my back has stopped my golf and my exercise is restricted to gentle walking with a stick! Transplantation: Where Do You Expect the Greatest Advancement in the Transplantation Field in the Next 10 Years? PJM: I have spent much of my career working on the induction of tolerance, and I am reminded that in 1970, when John Fabre and I first induced tolerance to a kidney allograft in the rat by a prior blood transfusion, I had made the comment publicly that within 10 years we would be producing tolerance in patients. The MGH group, led by David Sachs and Ben Cosimi, have in fact produced tolerance in selected patients with what would be considered a fairly heavy immunosuppressive protocol around the time of transplantation that is encouraging, but it is not suitable for general use.7,8 However, I do think that tolerance will be produced in the clinic on a routine basis in due course. There is a lot of work directed at the influence of regulatory T lymphocytes in the clinic to which Kathryn Wood and her group have made major contributions.9,10 There is now a large multicenter study run out of Regensburg, Germany by Professor Edward Geissler looking at infusion of regulatory T cells into patients receiving a living-related transplant. The first patients from Oxford have been recruited and treated. Although this approach may require much more work, I suspect it may be successful in the future—perhaps more likely to be so in liver transplantation than in renal transplantation. Transplantation: What Was Your Experience With the Journal? PJM: I was asked by Richard Batchelor in 1976 to become an Associate Editor, modeled on the role of the inimitable Mary Wood who served in that role for Tony Monaco in Boston. Later I became a full editor and succeeded Richard Batchelor as senior editor in Europe in the 1980s. When Tony and I retired as senior editors, we were made responsible for special features—a new venture to include overviews and for a, for example. Jim Mulligan was our publisher and a very good relationship between Lippincott Wilkins and Williams and us resulted. Transplantation: What Would Your Advice be to the Young Medical Students Seeking Your Opinion on Getting Into This Field? PJM: Medical student and residents, whatever specialty they are hoping to enter, be it general practice or a specialty such as surgery, medicine etc, should like people. If they do not have that sort of personality then they are not going to be a good doctor. You do not have to be a rocket scientist to be a good doctor, but you need common sense and to like people. With respect to transplantation, I think medical students can be attracted to the specialty not by the clinical side itself but by the related research that should be part of the practice of organ transplantation. Transplantation: What Is Your Advice to the Young Clinician/Scientist in Transplantation? PJM: Basically you should not only be interested in the technical aspects of an organ transplant, but in particular, to the immunological, physiological, and genetic determinants of outcome in patients receiving an organ transplant. If a clinician can be involved in various research projects in an academic transplant program, he or she will have a very satisfying life. What makes the job so interesting and rewarding is that you are not only enhancing or even saving the lives of your patients, but also there is the associated research that is, and will be, required for many years to come. And, transplantation research has wide applications: for example my involvement in the early times of HLA led me into studies of HLA and disease and the use of HLA as a genetic marker in anthropological studies in New Guinea, Fiji and South East Asia. Overall, I could not imagine a more exciting and rewarding career. Transplantation: What Do You Do Now? PJM: I am retired from clinical practice. Around the time I was due to retire from the Nuffield Chair of Surgery at the University of Oxford in 2001, I was elected as the president of the Royal College of Surgeons of England. This was a fulltime job for 3 years, and very political and frankly as busy as being the chair of surgery! After that, I received a grant to establish a Centre for Evidence in Transplantation (CET) (www.transplantevidence.com) and as director, this has been my major activity for the last 10 years. It is based in the Royal College of Surgeons, the London School of Hygiene and Tropical Medicine, and the University of Oxford. The CET evaluates the quality of evidence in organ transplantation with regular systematic reviews of controversial topics and in addition has established an electronic library of all randomized controlled trials in organ transplantation plus selected systematic reviews. It is easy and quick to use and is spreading rapidly though the transplant world.