FIRST PART
Scientific Aspects

Historical background

1.

 To date, there is only very limited experience in transplanting xenogenic organs or tissues to humans. The attempts made in the 1960s and early 1970s used immunosuppressive therapies on the recipient to prolong survival of the organ. The most striking success was the nine-month survival of a chimpanzee kidney transplanted into a human by REEMTSMA and colleagues.(²) In the 1980s, a baboon heart was transplanted to a baby (Baby Fae) that survived briefly;(³) however, rejection occurred within a few weeks. In the 1990s, baboon livers were transplanted in two patients by STARZL and colleagues.(⁴) Those patients survived for 70 days in one case and 26 days in the other.

The first patient was placed on an oral diet on the fifth post-transplant day and spent most of his time in a regular ward, leaving the hospital briefly on one occasion.(⁵) However, in one of the two cases, a baboon pathogen (cytomegalovirus) was apparently transferred to the patient, even though this did not result in a disease process.(⁶) However, in both patients there was evidence of an adequately functioning liver mass, sufficient to sustain life. The baboon livers led to the presence of baboon proteins synthesized by the liver; in some cases those proteins assumed the blood levels that are characteristic of the baboon and not of the human. Possible molecular incompatibility of those proteins poses a potential problem of functionality for humans.

Transplants have also been attempted using pig hearts (three cases) or livers (one case); in no case did the recipient survive more than 24 hours.(⁷)

While non-human primates have been preferred in the past as source organs for humans, at present the scientific community and the regulatory agencies in those countries which are addressing the issue have ruled out the use of such source animals both because of the increased risk of transmission of infection and because of a variety of other ethical and practical concerns.(⁸) As a consequence many researchers have settled on the use of pigs as a potential source animals for xenotransplantation.(⁹) The use of genetic engineering has resulted in significant improvement in survival time for a pig organ in a non-human primate receiving immunosuppression.(¹⁰) However, the survival time of such organs does not yet approach that of human organs transplanted to other humans (allotransplantation). Therefore, certain barriers to xenotransplantation remain.(¹¹)
Further genetic engineering of source animals and/or use of additional/new immunosuppressive agents are the two approaches that are considered most likely to prolong the survival of a xenotransplant.(¹²) Clearly more research in xenotransplantation is needed and should be done.