**2. Early beginnings**

Examples of xenotransplantation can be found recorded as early as the seventeenth century, in which the transfusion of blood from animals into human patients was described [1]. In the eighteenth century, more complex tissues such as skin were tested as grafts in human patients [2]. In 1905, Princeteau transferred rabbit kidney sections into a child with immediate positive results, however, after 16 days the child died of pulmonary complications [3]. Soon thereafter, two kidney xenotransplants were attempted, with one patient receiving an organ from goat, the other from pig. Unlike Princeteau's experiment, neither organs functioned and both apparently failed due to thrombosis [4]. Similarly, an attempt by Unger in 1910 to transplant kidneys from a chimpanzee into humans led to failure due to thrombosis in about a day [5]. In 1923, Neuhof transplanted a kidney from a lamb into a human patient, allowing the patient to survive 9 days [6].

In the early twentieth century, an odd offshoot of xenotransplantation was created due to interest in "rejuvenation" via transplant of animal testis in human males, as demonstrated by Voronoff in Russia [7] and Brinkley in the US [8] using chimpanzee or goat testis, respectively. So popular was the use of goat testis in the US, an entire radio empire was built around advertising the services, with many patients claiming enhanced fertility and sexual function [8].

The field of immunology developed in parallel with surgical approaches to xenotransplantation. As the mechanisms of immune rejection were better defined, the enormity of the challenges facing transplant of organs between members of the same species were recognized. During and after WWII, pharmaceutical companies created a series of increasingly effective immunosuppressive drugs which could inhibit some rejection responses, renewing interest in xenotransplantation.
