Clinical organ transplantation is a life-saving procedure for patients with terminal organ failure and requires deceased or living donors. The increasing number of patients with various organ failures and the world shortage of donated human transplantable organs have created a gap between organ supply and demand. This imbalance has resulted in increasing waiting times and death of patients on waiting lists. Xenotransplantation carries the 'hope' of alleviating the shortage of deceased human donated organs, eliminating the need for living organ donation, and the associated commercialization of transplantation and organ trafficking. Recent progress in the field of xenotransplantation has brought this method closer to clinical application, and new clinical trials could be potentially initiated soon.
The earliest example of combining man and animal parts in a medical procedure was in 1682, when a Russian physician repaired a man's skull using the bone of a dog. After the turn of the 20th century, doctors began grafting tissues from animals to humans. A prime example of this being in 1905, when a French surgeon used slices of rabbit kidney to treat a child suffering from kidney failure. As exploration into xenotransplantation continued with other animals such as pigs, goats, lambs and monkeys, doctors began to notice that these transplants would fail in relatively short amounts of time, lasting for only weeks at best. It wasn't until the 1940's, when the cause for these transplantation failures, and thus the most significant setback within xenotransplantation, was identified as a crucial connection between the immune system and the rejection of a transplanted organ (Spital, 1996). Although clearly an experimental procedure, xenotransplantation between closely related species, such as baboons and humans, offers an alternative to allotransplantation as a source of human organ replacement. Alternatives to allograft donors, such as baboon or pig xenografts, require serious investigation if clinical transplantation is ever to meet the current demand and continue the explosive growth pattern it has established over the past quarter century (Cooper et al., 1991). Two of the most crucial risks involved with xenotransplantation are rejection and xenozoonoses. Rejection primarily involves how the immune system uses several lines of defense against infection from foreign organisms like parasites and bacteria, and specifically when the system attacks transplants. "These defense mechanisms are a double-edged sword...in xenotransplantation, we are walking a fine line between asking the immune system to accept an organ from an animal, but still protect us from other threats, such as infectious disease.” To combat this, doctors have been trying various methods of modifying xenotransplantation procedures. One way is to attempt to alter the recipient's immune system to increase transplant tolerance. Another is to utilize genetic engineering to change the organs, cells, and tissues of the donating animal, especially by deleting certain animal genes to be replaced by human genes. An example of this transgenic procedure occured in 1992, when doctors introduced a human gene that directs the production of a human complement-inhibiting protein into pig embryos, in order to prevent human complement proteins from doing damage. While experiments such as these have yet to solve the problem of rejection, the goal is becoming less and less elusive as medicine increases its options for "tricking" the immune system (Wenz, 1995). Even a transplanted human organ, if it does not come from a genetically identical twin, will be met with a rejection response without immunosuppressive therapy. Discordant xenotransplantation, transplantation between distantly related species, is typically accompanied by hyperacute rejection, resulting in damage to or destruction of the organ within minutes after establishing its blood supply within the recipient; "preformed