Grand Challenges in Organ Transplantation

The modern era of organ transplantation was pioneered at the Peter Bent Brigham Hospital in Boston by physician-scientists John P. Merrill (nephrologist), and Joseph E. Murray (surgeon). Their joint effort led to the first successful human kidney transplantation between identical twins (1954), the first allograft between fraternal twins (1959) and the first kidney allograft from a cadaveric donor (1962). Other landmarks in transplant history include the first successful human liver (1967) and pancreas (1968) transplants, the first transplantation of the heart (1967), lung (1983), intestine (1987), and more recently hand (1998), facial tissue (2005), and the uterus (2013). Hematopoietic cell transplants were implemented in 1957 using bone marrow grafting in cancer patients. After the mechanism of acute graft rejection was confirmed to be immune-mediated, the application of immunosuppressive drugs (corticosteroids, calcineurin inhibitors) and biological modalities (e.g., polyclonal and monoclonal antibodies) paved the way for transplantation to become the standard of care for patients with end-stage organ diseases. Several Nobel Prizes have been awarded to transplant “founding fathers,” Peter B. Medawar and Frank Macfarlane Burnet (1960), Baruj Benacerraf, Jean Dausset, and George D. Snell (1980), as well as Joseph E. Murray, and E. Donnall Thomas (1990). The Lasker Award was shared by Thomas E. Starzl, and Roy Calne in 2012. Organ transplantation remains one of the most spectacular and consequential fields in 21stcentury medicine, integrating advances in surgery, immunology, genetics, pharmacology, intensive care medicine, epidemiology, and ethics. The idea of prolonging life and wellbeing through organ transplantation captures worldwide attention of medical practitioners, students, and scientists alike. Today, organ transplantations are a common feature of medical practice in developed countries and increasingly in developing countries, and new advances in the field are frequently reported in the lay press.