Thomas Earl Starzl, the father of transplantation (March 11, 1926-March 4 2017)
By Prof. Em. Jan P Lerut
March 2016… the transplant community celebrated with pomp the 90th birthday of transplantation pioneer, Th. E. Starzl. More than 400 surgeons and scientists originating from all over the United States and from all five continents met in Pittsburgh to pay tribute to their mentor, teacher and friend. The ‘Starzl family at large’ experienced a once in a lifetime event ending with a thoughtful, but typical ‘Starzl speech’ about past and future, including a humoristic but realistic view on life and ageing. After three remarkable birthday parties gathering medical and paramedical staffs as well as several patients (‘his heroes’) and their families, everyone returned home content to have met ‘their spiritual father’… to have dug up old memories. Hands were shaken and, considering his excellent status, plans (or dreams) were already made to meet again in five and, why not, in ten years from then.
March 4, 2017 (one week before his 91st anniversary)… the transplant world waked up by the sad news about the unexpected, sudden, death of Th.E. Starzl.
Without any doubt Th. E. Starzl has been one of the most influential personalities in medicine of the second half of the 20th and the beginning of the 21st centuries. His relentless search for innovation indeed changed forever the way surgery and medicine should be conceived. His personal and scientific life was a continuous search to improve patient care taking thereby into account the highest moral and professional standards all in the setting of a ‘interdisciplinary matrix’. Due to its everlasting endurance and determination, the initially highly controversial field of organ transplantation became rapidly accepted as a leading discipline at university and academic levels.
After a promising start in neuroscience (!) research, his brilliant career focused on research in liver pathophysiology, liver and pancreas metabolism, development of safe(r) surgical techniques to replace the diseased liver, improvement of organ preservation and procurement, definition of brain death, modulation and best use of immunosuppressive drugs (termed by him as the multiple-agent techniques of immunosuppression), reversibility of immune allograft rejection, xenografting and finally the discovery of micro-chimerism, a finding fundamental to explain ‘allograft accommodation’ and tolerance. All these discoveries were in the forefront of medical developments and all became applicable to all other types of organ transplantation. The micro-chimerism Lancet paper became the most frequent cited article in transplantation literature. This ‘countercurrent’ finding led to the ‘conceptual unification‘ of solid organ and bone marrow transplantation and also laid the foundation for immunosuppression minimization and withdrawal strategies, which are fundamental to counteract the many (also lethal) side-effects of life-long immune suppressive therapy.
His initial research and, mostly disappointing, clinical experiences intuitionally led him to rapidly understand that the road to successful liver transplantation necessarily needed to pass through the (surgically simpler) model of kidney transplantation. The detailed clinical observations of his early renal patients, hospitalized in the largest renal transplant unit worldwide at that time, made him also the real founder of renal transplantation, a merit often forgotten by the younger generations of surgeons and nephrologists! Once the surgical techniques refined and the immune rejection of the kidney mastered by using the ‘steroids plus azathioprine secret’ and the anti-lymphocytic serum ALG, liver transplantation evolved within five years from a ‘wild science fiction view’ to a clinical reality. Several years of round-the-clock (dog and pig) laboratory and clinical work made the ‘impossible’ operation possible… the first liver transplantation being performed March 1, 1963, the first successful one in July 1967… and the procedure being recognized finally in 1983 at the NIH Consensus Conference as a valuable therapy for patients with end-stage liver disease.
The early Denver experiences related to renal and liver transplantation were compiled in what I would call ‘the old and new testaments’ of transplantation medicine. The textbook ‘Experience in renal transplantation’ and its companion ‘Experience in hepatic transplantation’, edited respectively in 1964 and 1969, an era in which both types of transplantation remained highly controversial, give a detailed, 936 pages long, information about outcome of 74 kidney and 29 liver transplantations only, including six renal and one liver xenografts (!). These books are not only the most frequent cited books in history of medicine but most of all they witness for all future generations the meaning of honest (triumphs and defeats being equally reported!) and in-depth analysis of both experimental and clinical research (all surrounding events, such as coagulation disorders and de novo tumor development were as well analyzed!) as well as of excellency in translational research. The ‘embryonic’ 1958-1990 Denver transplantation experience rapidly became full grown after his move to the University of Pittsburgh in December 1980. The efficacy of the calcineurin-inhibitor Cyclosporine and of, its’ ‘improved version’, Tacrolimus (almost exclusively tested by Starzl’s team) not only remarkably improved survival curves and quality of life of the recipients, but also allowed to embark on the ‘forbidden’ multi-visceral and intestinal transplantations. Being heavily criticized at that time to have monopolized the use of the Japanese ‘million dollar drug’, one has to admit that this approach is still a premium example of how a well conducted ‘investigator driven study’ is capable to reshape in a very short and thus efficient way the practice within a given medical field… a lesson not to be forgotten in an era where clinical research is too often dominated by (paralyzing) ‘industry driven studies’ and ‘trialomania’! The FK506 and other captivating stories are uniquely described in his bestselling autobiography ‘The puzzle people, memoirs of a transplant surgeon’. Reading this book is a must for every individual involved in transplantation!
His unique interest in liver transplantation, an operation initially conceived to treat (non-resectable) hepatobiliary cancers, also led to a major change in the practice of liver surgery. The right and left tri-segmentectomy eventually combined with resection of the caval vein substantially expanded the boundaries of hepatobiliary oncology.
The impact of both his ground-breaking work and his ‘contagious charisma and attraction’ was enormous. It resulted not only in one of the most prolific scientific productions ever (with more than 2200 publications he was the most cited scientist in clinical medicine; in 1991 he published a paper every 1.8 days!) but – even more importantly – it resulted in the training of numerous fellows coming from all over the world making Pittsburgh the world transplant Mecca in no time. Until the end of the 20th century, almost every liver transplant program in the world could trace its paternal or grand-paternal lineage to Dr. Starzl. His ‘extra-ordinary’ mentorship allowed, directly or indirectly, to hundreds of thousands end-stage diseased patients to benefit from a new life!
Needless to say that numerous, national and international, honorary degrees (including the ESOT honorary membership), distinctions and awards were given to him as a token of appreciation, read admiration for his lifetime achievements…he received them all but one, the Nobel prize. When looking back at his career and impact on the development of modern medicine – and not to forget modern life (he was ranked no 213 of 1000 men and women who shaped the millennium) – it is hard to understand how the Nobel prize committee omitted to recognize such an important service to humanity.
Besides being a pioneer, a medical genius and a legend, Starzl was also a great human, a great humanitarian. All who worked with him will remember his unlimited empathy, respect and engagement for his collaborators, from the lowest to the highest ranked level, and, even more so, for his patients, their families and, importantly, also the donor families. The patient was always central in his doings, encompassing thereby all cultural, religious, gender and racial boundaries. The core value of his medical and human behavior was never business, but always a patient-driven medicine based on correctness, altruism and public trust. All who worked with him will also remember his unlimited memory going from remembrance of first names and even blood groups (!) of his patients via (un)usual anecdotes to details about every single operative event, being it a success or a disaster. He also had a remarkable capacity to keep track of the accomplishments, successes and disappointments of all his scholars and mentees on a worldwide scale… it seemed to many of us that he wanted to be assured that as many patients as possible could (indirectly) take advantage of the right application of his wisdom, advice and teaching. His concern, already expressed as early as 1974, for the real need of transplant centers and their optimal localization, the need for adequate training of a sufficient number of transplant surgeons but also the fear for a superfluity of transplant surgeons have to be seen in this context.
When giving his presidential address at the 1974 inaugural meeting of the American Society of Transplant Surgeons, Starzl quoted these prophetic words from the distinguished scientist and historian, TS. Kuhn: “progress consists of a series of great and small revolutions against authority. A great advance necessitates the overthrow of an established dogma, and when that occurs the advance itself becomes a new dogma to which advocates flock. It is natural for those disciplines to become protectors instead of improvers of the status quo, guardians of the past instead of seekers of the future”. These prophetic words could simply not summarize better what has been the trailblazing input of Th. E. Starzl on today’s (transplantation) medicine.
Without any doubt Thomas Earl Starzl was an exceptional scientist, an exceptional human, a man ‘hors pair’ who will be missed greatly by his beloved wife Joy, his family as well as by the worldwide transplantation community. Let the fact that his achievements will endure in lives of countless patients and in the work of countless persons he influenced be a comfort to handle his unexpected passing away.
Prof. Em. Jan P LERUT,
Starzl Unit Abdominal Transplantation,
University Hospitals Saint-Luc, Université Catholique Louvain,