The Dialectic Nature of Xenotransplantation

The great physicist Niels Bohr stated that there are “. . . two sorts of truth: trivialities, where opposites are obviously absurd, and profound truths, recognized by the fact that the opposite is also a profound truth.”1 This statement explains the dialectic nature of scientific controversy that is part of the discussion of xenotransplantation. Technologic and immunologic progress has allowed transplantation to be performed with relatively low risk, and human donation now is well accepted. But controversy surrounds the ethics and science of xenotransplantation. It is, perhaps, the intertwined relationship of man and animal that has led to the thesis of xenotransplantation. Man’s obsession goes back more than five millennia and is exemplified in art, mythology, and religion. Examples of man’s convoluted identity with the animal are found in every culture and religion: the Egyptian Sphinx sculpted in 2,650 BC; the Roman centaurs; the Greek god Pan, the god of fields, forests, flocks, and shepherds; African tribal art; and on the South American continent, Incas and Aztecs incorporated human and animalistic parts in their pottery and carvings. The first recorded xenograft is found in Indian mythology.2 The story is told that the Lord Siva, in a fit of rage against his wife Parvati’s guard, decapitates him. Parvati, who herself is also a god, threatens to destroy the universe unless her guard Ganesha is brought back to life. Siva is unable to locate Ganesha’s head and sends his assistants out with instructions to return with the head of the first living thing they encounter. And so Ganesha is brought back to life with the head of an elephant. A leap from mythology to physiology might not be as great as one might imagine. Attempts at xenotransplantation actually predated attempts at allotransplantation. As early as 1804, experiments were performed using autogenous and xenogeneic skin transplants in sheep. In 1896, a sheep’s urethra was used to repair a stricture of a human urethra, and during this same period xenografts were used in corneal transplants. In the early 20th century, animalto-human renal transplants were being reported by Jaboulay and his assistant Alexis Carrel.3 Carrel further developed this research and performed experimental transplants of vessels, kidneys, thyroid, ovary, and limbs. He was awarded the 1912 Nobel Prize for Physiology and Medicine for his work with transplantation and vascular surgical techniques. Jaboulay and Unger also attempted kidney transplantation from animals to humans in 1906 and 1920, respectively (Table 1). Research continued sporadically until the early 1960s, when the success of allografts, resulting from the development of effective immunosuppression, increased the demand for human organs which were in limited supply. Increased demand for organs led to the rekindling of interest in xenotransplantation (Table 2). Reemtsma4 and Starzl and associates5 were modern pioneers in the field of xenotransplantation with their primate-to-human renal transplants, which resulted in patient survival of up to 9 months. With the introduction of each new immunosuppressant, new clinical trials in xenotransplantation were initiated. This discourse is not a consequence of the introduction of a new immunosuppressant, but, rather, it is the result of advances in genetics and immunology that alter the immunologic status of Presented at the American College of Surgeons 83rd Annual Clinical Congress, Chicago, October 1997.