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Thomas Earl Starzl, MD, PhD, Transplant Pioneer, Polymath, Mentor, March 11th, 1926–March 4th, 2017

Fung, John J. MD, PhD

doi: 10.1097/TP.0000000000001731
In View: Obituary
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Correspondence: John J. Fung, MD, PhD, Division of Transplant Surgery, University of Chicago Medical Center, 5841 S. Maryland Avenue, MC 5027, Chicago, IL 60637. (jfung@surgery.bsd.uchicago.edu).

Thomas Earl Starzl, MD, PhD was best known for his contributions to the field of organ transplantation, and often referred to as the “father of transplantation”. He pioneered many facets of transplantation, including immunosuppressive drug development, organ preservation, tissue matching, surgical transplant technology, and developed the team approach to organ transplantation; thus paving the way for the success and acceptance of heart, lung, pancreas, intestinal, liver, and kidney transplantation. The international impact of the fruits of seven decades of commitment to transplantation is shown by estimates of over 600 000 Americans and millions of patients around the world that have received a life-saving organ transplantation.

Thomas Starzl was born on March 11, 1926, in Le Mars, Iowa, the son of newspaper editor and science fiction writer Roman Frederick Starzl and Anna Laura Fitzgerald. He attended Westminster College in Fulton, Missouri and studied biology before attending Northwestern University Medical School, where he earned both a PhD in neurophysiology and an MD with distinction. Dr. Starzl then completed his surgical training at Johns Hopkins Hospital in Baltimore and Jackson Memorial Hospital in Miami before completing training in thoracic surgery at Northwestern University. In 1959, he was awarded a Markle Scholarship, which allowed him to pursue his newly discovered interest in liver physiology and the role of hepatotrophic substances in portal blood. This eventually led him to liver transplantation as an extension of his surgical modifications in liver blood flow. In 1961, Dr. Starzl was recruited to the University of Colorado School of Medicine as an Associate Professor in Surgery and was promoted to Professor of Surgery in 1964. He was Chief of Surgery at the Denver Veterans Administration Hospital from 1961-72 and was Chairman of the University Department of Surgery from 1972-80. During this time, he would launch human kidney and liver transplant programs, elucidate therapeutic immunosuppression principles that were generalizable to all other kinds of allografts, and lay the foundation for a new field of medicine. Dr. Starzl joined the University of Pittsburgh School of Medicine as Professor of Surgery in 1981. Until 1991, he served as Chief of Transplantation Services at Presbyterian University Hospital (now UPMC Presbyterian), Children’s Hospital of Pittsburgh, and the Veterans Administration Hospital in Pittsburgh, overseeing what became the largest and busiest transplant program in the world. He is credited as having trained over 1 000 medical and surgical transplant specialists over his 50 years in clinical medicine, many of who have gone on to successfully develop their own transplant programs around the world.

Dr. Starzl’s unique accomplishments included the world’s first series of successful kidney allotransplantations (1962-3), and the first-ever successful liver (1967), abdominal multivisceral (1987), pancreatic islet transplantations (1990) and xenotransplantation (1992). His achievements depended on his strategies of drug immunosuppression. In the first version, azathioprine and prednisone were combined, and in the second, antilymphocyte globulin (ALG) was added. Using the triple drug regimen of azathioprine, prednisone, and ALG, he produced the first successful human liver recipients in 1967. His substitution of cyclosporine for azathioprine (1979), and then his subsequent substitution of tacrolimus for cyclosporine as the baseline immunosuppressants (1989) in his therapeutic algorithms, resulted in step-wise survival improvements with all organs. The worldwide adoption of tacrolimus as the primary immunosuppressant in all solid organ transplantation is vindication of his approach to transplant patient care.

Dr. Starzl’s contributions to organ procurement and preservation were also critical components of the new field. In 1958, he introduced the intravascular infusion of chilled fluids for preservation of canine liver grafts, a practice that he then adapted (1962-63) for protection of human kidney grafts. Intravascular cooling remains the first step in organ preservation. When it became obvious that transplantation of all vital organs was achievable, Starzl developed procurement techniques with which all organs are cooled in situ and rapidly removed in a bloodless field. Sharing of organs from a common donor by widely separated recipient teams then became economical and practical.

Dr. Starzl also played a key role in human tissue (HLA) matching. Not only did he show for the first time, that perfect HLA matches improved outcome but also that good organ and patient survival was possible with lesser degrees of matching with appropriate immunosuppression. His seminal contribution to matching was the avoidance of antibody-mediated hyperacute rejection with his ABO blood group compatibility guidelines (1964) and use of the cytotoxic antibody crossmatch developed with Paul Terasaki in 1965.

Dr. Starzl’s liver research established the new field of hepatotrophic physiology and his seminal paper on the central role of the liver in cholesterol metabolism established the basis for current treatment of hypercholesterolemia. However, his supreme contribution to clinical science was to unravel the mechanisms of engraftment. This hinged on his demonstration in 1992 that the tissues and/or blood of his long-surviving kidney and liver recipients had low level donor leukocyte chimerism (microchimerism). The discovery mandated a transformative paradigm shift in transplantation immunology and in immunology overall. In 1998, his transplant paradigm was generalized (with Rolf Zinkernagel) to the immunology of infection, cancer, and self-nonself discrimination (autoimmunity). The paradigm explained numerous previously enigmatic observations with both organ and bone marrow transplantation, upheld Starzl’s long-held conviction that organ engraftment is a form of variable tolerance, and has provided a rational basis for improved immunosuppression strategies.

Dr. Starzl was a member of more than 40 professional journal editorial boards and authored or co-authored more than 2300 scientific articles, four books, and 300 book chapters. He was awarded 26 honorary doctorate degrees in 10 countries that have been conferred in “Law”, and “Humane Letters” in addition to “Medicine” and “Science”. Dr. Starzl was the most highly cited clinical scientist of the 20th century (Institute of Scientific Information [ISI]. The magnitude, profundity, and impact of his productivity has been assessed in the website http://www.starzl.pitt.edu/people/index.html, which is based on the Archival collection donated by Dr. Starzl to the University of Pittsburgh.

Dr. Starzl celebrated his 90th birthday surrounded by his former fellows, colleagues, friends and family (see photo) and continued to work until his untimely death on March 4, 2017. He is survived by his wife of 36 years, Joy Starzl; his son, Timothy Starzl and his grandchild, Ravi Starzl, PhD. He was preceded in death by his daughter, Rebecca Starzl, and his other son, Thomas F. Starzl.

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