France and the Early History of Organ Transplantation

FRANCE AND THE EARLY HISTORY OF ORGAN TRANSPLANTATION THOMAS E. STARZL* The different starting points and uneven emphasis of historical accounts of transplantation [1] have tended to obscure the contributions to this field of some of the grand figures of French medicine and science. Clinical transplantation activity began in France within the first few years of the twentieth century when Jaboulay in Lyon [2] and others in France and Germany performed subhuman-primate-to-human kidney heterotransplantation [3-5]. In 1936, The Russian Yu Yu Voronoy of Kiev made the first known attempt at renal allotransplantation [6]. Transplantation lay largely dormant until 1951 when Rene Kuss [7] and Charles Dubost [8] of Paris and Marceau Servelle of Strasbourg [9] carried out a series of cadaveric renal transplantations. The kidneys were removed from convict donors after their execution by guillotine. The next year the French physician Jean Hamburger, working with the urologist Louis Michon at the Hospital Necker (Paris), reported the now commonplace transplantation of a kidney from a live volunteer donor [10]. The pelvic kidney transplant procedure originally used by Kuss and refined subsequently by the French surgeons has been used hundreds of thousands of times since then including for the celebrated identical (monozygotic) twin transplantations performed by Murray (Nobel Laureate 1990) and his associates [11] in Boston. Visitors flocked to France in the early 1950s to learn firsthand from this experience, includingJohn Merrill of Boston, as Hume described in the classical account of his own clinical trials at the Peter Bent Brigham Work aided by project grant DK 29961 from the National Institutes of Health. Essay presented at the 14emes Journées de Chirurgie, University of Rennes, Rennes, France, April 2, 1992. *Pittsburgh Transplant Institute and the Department of Surgery, University of Pittsburgh Health Science Center, Pittsburgh, Pennsylvania 15213. (Reprint requests: Department of Surgery, 3601 Fifth Avenue, 5C Falk Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.)© by The University of Chicago. All rights reserved. 0031-5982/93/3701-0838$01.00 Perspectives in Biology and Medicine, 37, 1 ¦ Autumn 1993 | 35 Fig.1 .—Left—Rene Kuss (1913-----), approximately 1966, and right, Jean Hamburger (1909-1992), approximately 1985. Hospital [12]. The extensive discussion of the French experience by Hume was typical of this man whose awareness and acknowledgment of other people's work was noteworthy throughout his illustrious career. As important as these and later contributions of Kuss [13] and Hamburger [14] were, the scientific basis for transplantation in France went far deeper. The roots of histocompatibility research were nourished in France byJean Dausset (Nobel Laureate 1980) [15]. In addition, George Mathe, the father of cell transplantation, was part of the Paris clique of the 1950s and early 1960s. The skills necessary to transplant the kidney (the only candidate organ until the 1960s) were applications of what were becoming conventional surgical practices after World War II. The vascular surgical technology came from the Frenchman Alexis Carrel [16] and had a pervasive effect on essentially all surgical specialties. Although Carrel understood that transplanted organs were not permanently accepted, the biologic specificity of the field of transplantation was defined by Medawar when he showed that rejection is an immunologic event [17, 18]. In retrospect, every further development was a logical and inevitable step from this beginning. If rejection was in fact an immune reaction, what could be more logical than to protect the organ transplant by weakening the immune system? Medawar's conclusion about the nature of rejection was strengthened when it was shown more than forty years ago that adrenal corticosteroids [19, 20] and total body irradiation [21], which already were known to diminish immunologic responses, significantly prolonged skin graft survival. The relatively modest delay of rejection of rodent skin grafts made possible with corticosteroids and total body irradiation was not an open invitation for clinical application. Nor was there a clinical mandate in the 1953 article by Billingham, Brent, and Medawar [22] that described permanent skin graft acceptance in a special circumstance not involving iatrogenic immunosuppression. The unique circumstance was the inoculation of fetal or perinatal mice with immunocompetent spleen cells. Instead ofbeing rejected, these cells survived and endowed the recipient with the ability in later life to accept other...