XENOTRANSPLANTATION: The Benefits and Risks of Special Organ Transplantation
Researchers are currently experimenting with pigs as sources of organs and tissues for xenotransplantation. Studies include the use of pancreatic islet cells and neural cells from pigs for insulin-dependent diabetes and refractory parkinsonism, as well as perfusion of a patient’s fluids through a pig liver situated outside the patient’s body as a temporary strategy to treat liver failure. Patients with Huntington’s disease, which is a neurodegenerative condition characterized by uncontrolled movement and mental deterioration, also are receiving modified tissues from pigs as an experimental treatment. These studies are still very preliminary in testing the safety and effectiveness of this promising treatment.
Appropriate Animals for Use in Xenotransplantation
Scientists and the U.S. Public Health Service advise that domesticated animals such as pigs and cows be considered as potential tissue and organ sources before nonhuman primates, such as monkeys, for a number of health, safety and logistical reasons. Pigs are preferred because they mature very quickly, produce large litters and have organs of comparable size and function to human organs in both infancy and adulthood. They also can be bred to high health standards in microbiologically controlled environments.
Monkeys, on the other hand, are undomesticated animals that do not fare well in controlled environments and, therefore, it is difficult to raise them to the same high health standards as pigs. Furthermore, their organs are much too small and, like humans, monkeys mature slowly and tend to give birth to one offspring at a time. Although humans might reject nonhuman primate organs less frequently and vigorously than those of other species because of their genetic similarities, these similarities could facilitate disease spread between the donor and recipient. This threat of disease, and ethical issues associated with the use of nonhuman primates as organ sources, have led some government agencies to consider banning the use of nonhuman primates for xenotransplantation. For example, the United Kingdom (UK) has banned the use of great apes and strongly protests the use of other primates for this purpose.
Addressing Organ Rejection
Rejection, in which the recipient’s body attacks the new organ like an infection, is the greatest practical obstacle to xenotransplantation. Traditionally in transplants of organs from one human to another, drug therapies, such as cyclosporine, are used to suppress recipients’ immune systems in order to allow transplanted organs to function without being attacked and rejected as foreign. In xenotransplantation, a more aggressive defense mechanism called "hyperacute rejection" occurs when tissue not recognized as human is introduced to the body. In a matter of minutes, an individual’s immune system sets out to destroy the transplanted organ.
One technology being developed to overcome such organ rejection is the breeding of transgenic pigs. These genetically-altered pigs express specific human proteins that make it more difficult for the human immune system to identify the porcine organ as belonging to a different species. A transgenic pig is bred by injecting a small amount of DNA (or genetic material) mimicking a human gene sequence into a fertilized pig egg and then implanting that egg into a sow leading to the pig’s birth. As demonstrated in recent studies, this technique has addressed hyperacute rejection in nonhuman primates that received organs from transgenic pigs.
New cloning techniques may further enhance the immunocompatibility of pig organs by eliminating the pig gene-products that cause hyperacute rejection. In theory these developments should mean that once transplanted, animal organs could be treated in the same way as human organs, with the use of standard immunosuppressive regimens.
Addressing Potential Risk of Infection
The transfer of infectious diseases between animals and humans, or cross-species infection, remains an important area of study even though risks have been reduced. In 1997, it was reported that two of four variants of the porcine endogenous retrovirus (PoERV) could infect cultured human cells in test tubes. An endogenous retrovirus is a type of virus that exists as part of the DNA of all mammals and is passed down to offspring over successive generations without causing harm. This earlier report does not indicate if viral transfer would occur as a result of a transplant or whether, if it did happen, it would cause any disease.
Xenotransplantation opponents voice concerns regarding the unpredictable nature of microorganisms. They point to existing human viruses suspected to have originated in animals -- human immunodeficiency virus, simian immunodeficiency virus and bovine spongiform encephalopathy (BSE), in which people developed Creutzfeldt-Jakob Disease, the human equivalent to BSE. They express concern that xenotransplantation puts society as well as the individual recipient at risk for disease.
