In memoriam: Sir Roy Calne (1930–2024) – A life in surgery and impact on paediatric liver transplantation in Singapore

INTRODUCTION Professor Sir Roy Yorke Calne, FRS FRCS, a giant in the field of organ transplantation, passed away on 6th January 2024 at the age of 93. He was a visionary whose team at Addenbrooke’s Hospital in Cambridge, UK, performed Europe’s first liver transplantation in 1968.[1] He also experimented with immunosuppressants, pioneering the use of 6-mercaptopurine in canine renal transplant models in 1959 while working at the Royal Free Hospital in London,[2] progressing to azathioprine and cyclosporine in animal models before successfully translating to human organ transplantation. Together with Thomas Starzl, Sir Roy Calne transformed the field of organ transplantation from marginal science into mainstream medical therapy. In the footnotes of such an illustrious academic medical career, it is often overlooked that for a period of time, Sir Roy Calne roamed the wards and corridors of the erstwhile British Military Hospital in Singapore (the current-day Alexandra Hospital) as a medical officer during the 1950s, and would later revisit Singapore in the 1990s to help initiate and establish a liver transplantation programme at the National University Hospital (NUH). A LIFE IN TRANSPLANTATION SCIENCE Sir Roy was born in Surrey on 30th December 1930, and started his medical education at Guy’s Medical School at the age of 16. He recalled being appalled when, as a medical student, he was assigned a 20-year-old patient with Bright’s disease and end-stage renal failure, and was told to prepare the patient’s imminent demise within two weeks.[3] When asked if a kidney graft would have saved the patient, his tutor replied, “It can’t be done.” The experience stayed with Sir Roy throughout his subsequent National Service in Malaya and Hong Kong as a medical officer with the Gurkha unit, before revisiting organ transplantation during a lecture by Peter Medawar on the immunological characteristics of graft rejection. Sir Roy initially started animal work on the Royal College of Surgeon’s Buckstone Browne Farm, attempting various forms of immunomodulation on his canine subjects, such as whole body irradiation prior to renal transplantation, before achieving success with 6-mercaptopurine in 1959.[2] This, unfortunately, did not translate well to his human patients, two of whom underwent unsuccessful transplants in 1960. He subsequently went on fellowship at the Peter Bent Brigham Hospital under Joseph Murray and Francis Moore, where he was introduced to azathioprine. Upon his return in 1963, he commenced practice at St Mary’s Hospital’s kidney transplantation programme, where he replaced whole body irradiation with azathioprine as the immunosuppressant of choice. In 1965, he was appointed Chair of Surgery at Cambridge, where he then performed the first successful liver transplantation in Europe in 1968. Other European liver transplant programmes were started in Groningen, Paris and Hanover, but they were plagued with poor graft and recipient survivals, until the introduction of cyclosporin in 1977.[4] The transplantation programme at Addenbrooke’s Hospital in Cambridge has since grown into a major clinical and research centre. Under Sir Roy’s leadership, the centre performed the first combined liver, heart and lung transplantation in 1987, the first intestinal transplant in the UK in 1992, and the first multivisceral transplant (comprising combined stomach, small bowel, pancreas, liver and kidney grafts) in 1994. Sir Roy was elected Fellow of the Royal Society in 1974, and received his knighthood in the 1986 Birthday Honours. He retired as Chair of Surgery at the age of 68 in 1998 but remained active in kidney transplantation and research well into his eighties. Sir Roy passed away from heart failure on 6th January 2024. IMPACT ON PAEDIATRIC LIVER TRANSPLANTATION IN SINGAPORE The first deceased donor renal transplant in Singapore was performed in Outram General Hospital in 1970, and the Human Organ Transplant Act was introduced in 1987 as an opt-out legislation to expand the cadaveric donor pool in Singapore. In February 1990, the Ministry of Health, Singapore, approved the development of two pilot organ transplant programmes — a heart transplant programme at Singapore General Hospital and a liver transplantation programme at NUH.[5] The Ministry of Health anticipated an annual national requirement of 20 heart transplants and 33 liver transplants. As part of the preparatory work, two members (Dr Susan Lim and Prof Krishnan Prabhakaran) of the liver transplantation team were sent on fellowship to Addenbrooke’s Hospital to train with the Cambridge team. Sir Roy Calne was instrumental in this preparatory work, travelling to Singapore to train the liver transplantation team at the Singapore General Hospital Animal Laboratory [Figure 1].Figure 1: Prof Sir Roy Calne attempting to corral a porcine patient at the Singapore General Hospital Animal Laboratory.The first liver transplantation in Singapore was performed in September 1990 at NUH, where a 25-year-old female patient with autoimmune hepatitis received a cadaveric whole liver graft from a 22-year-old deceased organ donor. Dr Susan Lim was the lead surgeon for the five-hour procedure, with three other surgeons, Prof Abu Rauff, Prof Prabhakaran and Prof Ti Thiow Kong [Figure 2]. The anaesthestists supporting the procedure were Dr Ashok Kumar and Dr Lai Fook Onn.[6] The operation was a success, with the liver functioning well immediately postoperatively; the patient recovered well and celebrated her 50th birthday in 2015.[7]Figure 2: The National University Hospital team behind the first Singaporean liver transplant operation.After Dr Susan Lim went into private practice, Prof Prabhakaran developed the fledgling liver transplant programme further, with the first paediatric liver transplant in 1991, the first living donor paediatric liver transplant in 1996, and the first split paediatric-adult liver transplant in 1997 [Figure 3]. Currently, the organ transplant programme at the National University Centre for Organ Transplantation (NUCOT) at NUH is effectively the national programme for paediatric liver transplantation. The programme recently celebrated its successful 150th liver transplant in 2023. The outcomes of NUCOT paediatric liver transplantation unit are comparable to that of the Scientific Registry for Transplant Recipients in the United States and European Liver Transplant Registry in Europe.[8,9,10]Figure 3: Chart shows the timeline of the National University Hospital Paediatric Liver Transplant Programme.The seed that was planted by Sir Roy Calne so many years ago has continued to bear fruit, as the NUH team has gone on to help set up regional paediatric liver transplant programmes at Dr Kariadi Central General Hospital in Semarang and Cipto Mangunkusumo Hospital in Jakarta, Indonesia. For his contributions to the establishment of the national liver transplant programme, Sir Roy was appointed the Yeoh Ghim Seng Professor of Surgery by the National University of Singapore in 1998, and he had continued to visit Singapore for academic exchanges in subsequent years. In the words of Sir Roy himself, as fondly remembered by one of the co-authors, “If you dare big things, there will be those who will support you, and those who can’t wait to see you fail. The trick is to try anyway.” Requiescat in pace, Sir Roy. Acknowledgement The photo of Sir Roy Calne on page 654 is reproduced with the permission of Cambridge University Hospitals NHS Foundation Trust.