Before he carried out his first human liver replacement operation, the author first explored kidney transplantation as an associate professor in Colorado. The author explained that his involvement in the ‘renal field‘ was to enable him to find ‘a pathway‘ because ‘the road to the liver would lead through the kidney‘. However, despite this strategy, the author recalled that his initial liver transplant trials all failed, a disappointment that he conveyed most poignantly when he said ‘nothing we had done in advance could have prepared us for the enormity of the task’. This early upset was the reason the author said ‘a pall settled over the liver program’, and it was the justification for his three year ‘self-imposed moratorium‘ during which his team ‘increased the pace of kidney transplantation’. It is relevant that this was also when the author realised that ‘the field of clinical transplantation could advance significantly only by the development of better drugs and other treatment strategies‘. This was indeed the understanding that led him to develop an anti-rejection treatment regime which vastly improved the survival rates of his renal transplantation patients – an outcome which he said was better ‘by far than everyone else in the world combined’, and a breakthrough which he said set off ‘a clinical gold rush‘ of new transplant centres (pages 79, 96-100, 105-112 and 123).
The Puzzle People
Author: Thomas E. Starzl
This book is an insider’s account of the origin story of organ transplantation – a breakthrough which the author referred to as nothing short of ‘a very large miracle‘. Written by the pioneer of the field with perhaps the most diverse experience, the book is an enlightening and inspiring story of determination and perseverance in the face of recurrent setbacks. The book describes the uncertain beginnings of organ transplantation, and the tortuous course it took that culminated in the procedure becoming a routine feature of modern medicine. And accompanying the autobiographical narrative are revealing insights into the lives and careers of the other early researchers who the author said ‘made development in this field possible‘. Beyond its depiction of the technical and academic aspects of transplantation, the book is also an inspiring lesson in humanity, the author’s empathy and concern for the welfare of his patients symbolised by his determination to unravel the critical factors that determine the outcome of each puzzling case. And the book’s wide remit is evident in its discussion of such related themes as the ethics of living donation, the evolution of the concept of brain death, and the malign influence of racism and prejudice (pages ix, 3, 59-60 and 145-150).
The biographical account of the book traced the author’s early life, detailing his birth into a complex family with German and Irish ancestry. It also explored his medical education, for example when it narrated how he worked at two jobs to fund his training at Northwestern University Medical School. It was interestingly as a medical student that the author’s interest in research emerged, and this motivated him to spend an additional year carrying out experiments with Horace Magoun, a professor of neuroanatomy who he referred to as ‘one of the world’s leading students of nervous system function’. The author particularly highlighted the great influence Magoun had on him, describing his lectures as ‘supreme examples of clarity‘, his conversations as ‘magic‘, and his research framework as how to ‘get the contextual picture right instead of being diverted into learning more and more about less and less‘. Similarly, the author’s choice of surgery as a specialty was determined in medical school when he worked with the neurosurgeon Loyal Davis, of whom he said ‘I may have learned more about surgery from him than in any other three-month period in my life’. The author also recounted his post graduation surgical training experience which he said prepared him for his future work; for example, he referred to the time he spent at the Johns Hopkins Hospital as ‘the most formative period of my surgical life’. He also emphasised the benefits of the visits he took to the cardiac surgery unit at Minnesota, an experience that enabled him to witness the innovative open heart surgery attempts of such surgeons as C. Walton Lillehei, F. John Lewis and Norman Shumway (pages 11-34 and 39-46).
The author’s path to organ transplantation began when he was a fifth year resident at Jackson Memorial Hospital in Miami where he said he developed a ‘subconscious attraction for the liver, an organ that he characterised as ‘hostile to surgeons’. Noting that the hospital had ‘one of the busiest emergency rooms in the world’, the author said it was there that he mastered the critical skill of repairing large veins damaged by gunshot injuries, and where he carried out the animal portocaval shunting experiments that led him to develop his technique of total hepatectomy. The author noted that this procedure, which made him realise that a removed liver could be replaced, ‘quickly became the worldwide standard‘. It was however only after he took up a full-term surgical post at Northwestern University in Chicago that the author concretised his transplantation interest and proceeded to set up a liver transplantation research unit. Noting that his initial attempts at transplanting dog livers were uniformly unsuccessful, the author recounted how his team gradually learnt ‘how to preserve the transplanted liver during its removal’; how to ‘maintain the recipient’s blood circulation in as normal a state as possible’; and how to ‘solve the problem of vein blockage‘. The progress they made was such that the author became confident liver transplantation was feasible in humans (pages 47-58 and 62-67).
The highlight of the book is probably its description of the author’s recommencement of human liver transplantation, a step that he said was made possible by the ‘accretion of small details in surgical skills and post-operative management‘; the development of a triple immunosuppression therapy regime which included anti lymphocyte globulin; a better understanding of the contribution of tissue typing; and improvement in the techniques of organ procurement and preservation. Although all his initial seven patients died, the author argued that some of the subjects lived ‘long enough to demonstrate convincingly the potential value‘ of the procedure. The successful outcome of his subsequent trials justified this contention, and the book portrayed how this landmark achievement set off ‘a ripple effect’ that made feasible the transplantation of other organs such as the heart and the pancreas. Whilst this success made ‘the smouldering embers in other speciality centers burst into flames’, he called this ‘a pyrrhic victory‘ because ‘the rush of enthusiasm was replaced by reality‘ as ‘many of these attempts failed’. The author explained that at this point, ‘liver transplantation was a feasible but impractical way to treat end-stage liver disease because the triple immunosuppression combination ‘was not good enough‘ – a situation that he said resulted in a decade-long ‘deadly inertia‘ in organ transplantation (pages 133-139, 163-166, 169-170 and 177).
The single innovation that eventually enabled long-term survival of transplant recipients was the development of cyclosporine, an immunosuppressant that was ‘discovered by workers at Sandoz Corporation‘. In exploring this revolutionary drug, the author described how immunologist Jean Borel demonstrated that it primarily suppressed T helper lymphocytes – a feature that he said enabled it to bypass ‘the nonspecificity of previous therapy’. It was however to transplant surgeon Roy Calne that the book attributed the most credit for the practical use of cyclosporine. Describing Calne as determined, courageous, intelligent and skilful, the book recounted his long involvement in the field – initially in kidney, and later in liver transplantation. The narrative showed how Calne convinced Sandoz executives not to discontinue the development of cyclosporine, and it described how he went on to demonstrate its benefits in clinical trials. Calne was also responsible for identifying the renal toxicity of cyclosporine – an adverse effect that the author’s group later showed could be mitigated by combining it with steroids. Referring to this breakthrough as the launch of ‘the cyclosporine era of transplantation’, the author reported his subsequent success with the drug in liver transplantation, remarking that ‘we had never seen so little trouble before in eight consecutive liver recipients’. This, he added, resulted in a ‘stampede‘ to develop other liver transplant centers (pages 188-190 and 209-214 and 221).
Apart from its dull diagrams and terminally redundant themes, this book is an excellent adventure into one of the most important breakthroughs in medicine. The writing is lively, the scenes dramatic, and the prose simple. The author’s frequent human angle anecdotes also symbolised his humane personality and greatly enhanced the book. His commentaries on the somewhat malevolent influence of research funding on the behaviour of researchers, and on the intricacies of the politics of healthcare, are as relevant today as in his days. The inspiring tone of the book is equally matched by its downbeat realism of the challenges and failures that initially beset ultimately successful clinical research projects.
By providing a front-seat and first-hand account of the steps that incrementally advanced the field of organ transplantation, this book conveys invaluable historical and clinical lessons. And by chronicling the dual hardships and successes that characterised his transplant journey, the author has done a great service for all doctors at the cutting edge of medical progress. His reflective insights into the philosophy of medical scientific progress are also gems of contemporary value. And in his unprejudiced attitude and open-mindedness, the author has set a benchmark not just for healthcare but for society as a whole. The book is a refreshing and revealing look at a critical medical advance, and I recommend it to all doctors.
Publisher, Place, Year: University of Pittsburgh Press, Pittsburgh, 1992
Number of chapters: 28
Number of pages: 370
Star rating: 5