Xenotransplantation

In an attempt to prevent hyperacute rejection of pig organs by humans (Chapter 2), pigs have been made transgenic for the expression of human complement proteins, which are involved in regulation of the immune response (Cozzi and White, 1995; Tu et al., 1999; Cozzi et al., 1997; Byrne et al., 1997; Cowan et al., 2000). No phenotypic abnormalities have been reported in pigs as a result of the expression of transgenes for these human proteins, although, since the pigs are produced by microinjection, there are the usual inefficiencies in terms of the number of embryos microinjected relative to the number of transgenic animals born (Tu et al., 1999; Niemann and Kues, 2000).

Research is underway to produce pigs that, in addition to carrying complement transgenes, have both copies of the gene encoding the enzyme that produces the antigen associated with rejection knocked out. The animal welfare implications of this genetic manipulation are unknown; however, the knockout, which causes changes in cellular carbohydrate structure, potentially could have deleterious physiologic effects on the animals (Dove, 2000) and also render them susceptible to infection with human viruses (Chapter 2).

An important animal welfare concern related to xenotransplantation is the management and housing of pigs intended for use as organ sources. To minimize the potential for transmission of disease to human recipients, only specific pathogen free (SPF) pigs are used. SPF research animals are used in other contexts besides xenotransplantation, but their use raises several animal welfare issues. SPF pigs are born by hysterotomy or hysterectomy, and then are reared in isolators for 14 days before being placed in the source herd or in the xenotransplantation facility. The natural weaning age for pigs is about eight weeks (three to four weeks in commercial practice), and piglets subjected to extremely early weaning like this are known to develop abnormal behaviors (Weary et al., 1999). Older pigs intended for testing or organ donation might be housed in social isolation in unusually barren (i.e., easily sanitizable) environments. Pigs are extremely social animals that, when given the opportunity, will spend considerable time each day foraging, and that develop abnormal behaviors in confinement if not given the opportunity to root or build nests. In the United Kingdom, the Home Office Code of Practice (Her Majesty’s Government, 2000) for organ-source pigs, while recognizing the importance of maintaining biosecure facilities, nevertheless recommends that such pigs be housed in stable social groups, and provided with environmental enrichment such as straw or other material suitable for manipulation. The Code requires justification if the animals’ behavioral needs are to be compromised for a xenotransplantation protocol. There are no comparable standards for pigs intended for xenotransplantation in the U.S., and the lack of standardization of housing and care among U.S. facilities for these pigs is a source of concern. Although there are many forms of environmental enrichment available that are



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