A world-renowned transplant surgeon, Thomas Starzl (born 1926) performed the first human liver transplant in 1963 and was also a pioneer in kidney transplantation. Starzl's research in chimerism, the coexistence of donor and recipient cells, led to significant contributions in the understanding of transplant immunology, including how and why organs are accepted. He also helped to develop better drugs to make human organ transplants safer and more successful.
Thomas Earl Starzl was born into a prominent Le Mars, Iowa, family of German extraction on March 11, 1926. His father, Roman F. Starzl, was editor and publisher of the Globe Post and, as R.F. Starzl, was one of the early twentieth-century science fiction writers. His father was also a frustrated inventor. His mother, Anna Loretta (Laura) Fitzgerald Starzl, was the center of family life and when she died of breast cancer just before Starzl graduated from college the family disintegrated. Starzl had an older brother, two younger sisters, and from his father's second marriage, a half sister. From the age of twelve or thirteen, Starzl was expected to do his share of work at the paper. His first job was as a newspaper carrier. Later, he became a devil, one of the men who fed giant rolls of paper into the presses. Starzl was also an excellent student and participated in school athletics. While Starzl was sheltered in his small Iowa town, World War II raged abroad.
Upon graduation from high school, Starzl immediately enlisted in the navy and was sent to officers' training school at Westminster College in Fulton, Missouri, in 1944. He returned to Westminster College in the premedical program after his discharge from the navy and graduated with a degree in biology in 1947. He entered Northwestern University Medical School in Chicago, Illinois, in September 1947. After three years in medical school, Starzl took a year off to work with Dr. Horace W. Magouin, a professor of neuroanatomy and a world-renowned researcher of the nervous system with a particular interest in sleep and wakefulness. Starzl developed a recording technique to track deep brain responses to sensory stimuli. According to Starzl in his autobiography The Puzzle People: Memoirs of a Transplant Surgeon, it was like exploring the deep sea for the first time. Starzl and Magouin published their research in 1951. Starzl's work with Magouin earned him a Ph.D. in neurophysiology from Northwestern in 1952, and at the same time he received his medical degree with distinction.
Starzl met one more doctor at Northwestern who had a great influence on his life, Loyal Davis. According to Starzl, he learned more about surgery in three months on Dr. Davis' service than in any three months in his life. Though Magouin wanted him to continue in neuroanatomy and Davis wanted him to remain in his program at Northwestern, Starzl chose to continue his surgical training at Johns Hopkins University Hospital in Baltimore, Maryland, where he completed a fellowship and a residency. Two years into his residency, he married Barbara June Brothers of Hartville, Ohio, whom he had met at Rehoboth Beach, Delaware, six months before. They had three children, Timothy, Rebecca, and Thomas.
After four years at Johns Hopkins, Starzl chose to take a position at Jackson Memorial Hospital in Miami, Florida. He was angry that Johns Hopkins offered him a fifth year, but definitely not a sixth year. He also did not like the regimentation of the program, and he needed a salary to support his growing family. His father was recovering from a stroke and Starzl felt it was time to stop being subsidized by him. Jackson Memorial Hospital had one of the busiest emergency rooms in the United States. Starzl was in on the beginning of both open heart surgery and the dawn of blood vessel surgery. He also set up a laboratory in an empty garage on the grounds of the hospital and experimented with removing the livers of dogs. He was successful and published his results, which quickly became the standard worldwide.
In 1958 Starzl accepted a fellowship in thoracic surgery at Northwestern University. In 1959 he passed the thoracic surgery boards and remained on the faculty for four years. He received two awards that helped to fund his experimental research in techniques for liver transplantation. The National Institutes of Health gave him a five-year grant, and the other was the Markle Scholarship, which induced him to stay in academic medicine. Most surgeons at university hospitals were volunteers and derived their income from private patients. Starzl was the second full-time member of the Northwestern University surgical faculty. That and his grants allowed him to continue his research on liver transplants.
Developed Reliable Management Techniques for Kidney Transplants
After four years at Northwestern, poor working conditions caused Starzl to look for a better position. He joined the faculty at the University of Colorado School of Medicine as an associate professor of surgery in 1962 and became a professor of surgery in 1964. He was to remain in Colorado for 19 years. On March 27, 1962, Starzl performed his first kidney transplant on an identical twin recipient. Soon he became interested in a patient, Royal Jones. The boy, only twelve years old, was running out of places where the artificial kidney machine could be connected. His mother was to be his donor. This would be Starzl's first non-twin transplant. In his autobiography, Starzl said that to abandon Royal was unthinkable in view of the deep commitment made to him and his mother. On November 24, 1962, the kidney transplant was completed along with a combination treatment of irradiation, and the administration of immunosuppressant drugs Imuran and prednisone. The operation was a success. Royal Jones was later to have the first and second kidney transplants replaced, but was still alive when Starzl's autobiography was published thirty years later. Starzl and his research team went on to perform more than 1,000 kidney transplants at Colorado General Hospital and at Veterans Administration Hospital in Denver.
Attempted First Liver Transplants
Starzl was not satisfied with his success in the field of kidney transplantation. He was still determined to transplant livers. His first attempt was on March 1, 1963, on a three-year-old boy, Bennie Solis, who was born with an incomplete liver. Uncontrolled bleeding killed Solis. Starzl tried again in May of 1963 with a man suffering from cancer of the liver. Starzl tried to solve the bleeding problem by administering huge amounts of fibrinogen, a protein that forms blood clots. The operation appeared to be a success, but the man died three weeks later from complications due to blood clotting.
The paramount problems to be solved were uncontrolled bleeding and tissue rejection. Starzl suspended human liver transplantation to work on these issues. He also worked on the manuscript for his first book, Experience in Renal Transplantation. He also suffered a bout of hepatitis which was all too common at that time for transplant personnel. In 1964 he and his colleagues closed their transplant center for six months in order to set up the first extensive trial of tissue matching ever attempted. Starzl worked with Dr. Paul Terasaki from the University of California at Los Angeles. Terasaki concluded that tissue matching within families was feasible, but that it had limited value with unrelated donor kidneys. It was clear to Starzl and Terasaki that the solutions to organ transplant rejections lay in the development of better drugs and other treatment strategies. Starzl theorized that organ rejection could be controlled by using the steroid prednisone along with Imuran. He soon added the anti-lymphocyte globulin and another immunosuppressant, cyclosporin. The use of this combination of drugs advanced kidney transplantation from an experimental procedure to a standard procedure.
Performed First Successful Liver Transplants
In 1967 Strazl felt that the surgical techniques and immunosuppressant drugs had advanced enough to begin liver transplant trials again. The first attempts were on infants and young children with severe liver disease. Some of the operations were successful, while others failed because of the severity of the illnesses some of the patients had. By the late 1970s the survival rate for liver transplants had risen to 40 percent. Starzl was promoted to chair of the department from 1972 until he moved to the University of Pittsburgh in 1981.
While Starzl's professional life was extremely successful, his personal life was in shambles. His wife of 22 years divorced him intending to marry a wealthy Middle Eastern businessman. He felt that she rightly was tired of being a distant second to his career. His father, who had become totally paralyzed, died at about the same time. Next, his sister, Nancy, died of liver disease and he was unable to get to her in time. His son, Tim, was also hospitalized with an emotional breakdown. In March 1977 Starzl assembled a new research group. One of the researchers was a young woman, Joy Conger, who would become his second wife in 1981.
In 1981 Starzl joined the staff of the University of Pittsburgh School of Medicine as professor of surgery. For the next ten years he oversaw the largest transplant program in the world at Presbyterian University Hospital (UPMC Presbyterian), Children's Hospital of Pittsburgh, and Oakland Veterans Affairs Medical Center. Ultimately, he became the director of the University of Pittsburgh Transplantation Institute which was renamed the Thomas E. Starzl Transplantation Institute (STI) in 1996. In 1998 he retired as director but continued to be active in research.
Performed Successful Baboon-to-Human Transplants
Starzl engaged in significant work during his tenure at the University of Pittsburg Transplantation Institute. He got the National Institutes of Health to approve the drug cyclosporin for liver transplants. In 1984 he helped to get a bill passed by Congress which set up a national system of organ procurement and distribution. He and his researchers have improved the outcomes of liver, kidney, pancreas, and multiple organ transplantations. In 1986 Starzl and his team successfully completed their pivotal work on the anti-rejection drug tacrolimus which has benefited nearly 5,000 patients. To address the chronic shortage of human organs, Starzl and his team have looked into the feasibility of cross-species transplantation, or xenotransplantation. In 1992 and 1993, Starzl and his team performed two successful baboon-to-human liver transplants, making medical history.
In 1990 Starzl underwent coronary bypass surgery. He retired from active surgery and wrote his autobiography, The Puzzle People: Memoirs of a Transplant Surgeon. The idea for the title was given to him by an Indian journalist who asked him if in the next decade a puzzle man with multiple organs from various human and non-human sources would be feasible. After contemplating the idea, he decided that every patient who receives an organ is a puzzle because of all the ways the body has to change in order to accept the gift. Starzl continued to be active in research. He changed his concentration to chimerism, the coexistence of donor and recipient cells. Starzl now believed that the immune system no longer needed to be suppressed. The body could be fooled into believing that the transplanted tissue was not foreign. The trick was to convince both the body's defense mechanism and the new organ that the intruder is really "self," a recognized member of the host body.
Many of Starzl's ideas are still controversial, especially the animal to human transplants. He continues to speak throughout the world and is one of the most prolific writers in his field with four books, 2,076 scientific articles, and 283 chapters.
American Men and Women of Science 1998-99, 20th Edition, R.R. Bowker, 1999.
Notable Twentieth-Century Scientists, Gale Research, 1995.
Starzl, Thomas E., Puzzle People: Memoirs of a Transplant Surgeon, University of Pittsburgh Press, 1992.
The Lancet, December 19, 1992, p. 1524.
Time, Fall 1996, p. 70.
U.S. News and World Report, July 13, 1992, p. 12.
Thomas E. Starzl Transplantation Institute,http://www.sti.upmc.edu (January 8, 2001). □