Special Report
Could benefits abound in a brave new world?
’When they offered me the pig, I didn’t think about the fact that it was a pig. I thought, we are losing this battle, and desperate men take desperate measures.”
Mother of a pediatric pig liver bridge xenotransplant recipient1
If the infectious disease risks of xenotransplantation can be met and managed, a new medical era of vast potential may be opening. Advocates of this emerging technology imagine a bountiful resource of carefully raised and screened animals available for long-term organ replacement or at least as a biological bridge for patients awaiting human organs. In addition, cellular transplant studies are under way that hold potential for treating human diseases like Parkinson’s disease and diabetes.
The need is well-documented, as approximately 3,000 people die annually because donor organs are not available. Approximately 48,000 people are now on the waiting list for organs, and the number of people awaiting transplants continues to grow. For example, more than 33,000 patients were awaiting kidney transplants in August 1996.
While cases of whole-organ xenotransplants have drawn the most attention in the past, much of the current research approved or under review by the FDA in phase one safety trials focuses on using animal tissues or cellular materials in humans. This includes using encapsulated pig pancreatic cells to secrete insulin to treat diabetes. Other clinical protocols include the implantation of fetal pig neuronal cells to treat Parkinson’s disease; use of encapsulated fetal calf adrenal cells implanted in the spinal cord for pain relief in end-stage cancer; and use of genetically modified pig livers in the treatment of fulminant liver failure.
Although sporadic attempts by modern medical practitioners to transplant or graft animal organs into humans date back to the beginning of this century, xenotransplantation has been systematically studied by the medical community only since the 1960s, according to a recent report by the Institute of Medicine.1 A brief history of the field includes the following highlights:
• The first modern clinical trials of xenotransplants were performed in patients with end stage renal disease. Organ transplantation was the only option for these patients and the need for donated organs far outstripped the supply.
• In late 1963 and early 1964, a team at Tulane University in New Orleans transplanted kidneys from chimpanzees into six patients, one of whom lived for nine months.
• By 1974, including experimental surgeries performed at the University of Pittsburgh, about 20 patients had received xenotransplants. Many of these grafts appeared to function normally at first, but soon the grafts succumbed to immune rejection. Patients later died either from graft rejection, with loss of vital function, or from infections resulting from the use of large doses of immunosuppressive drugs. A voluntary moratorium was established by the transplant community in the United States due to poor survival rates and the advent of renal dialysis.
• The introduction of new immunosuppressive drugs such as cyclosporine and tacrolimus, improved understanding of graft rejection, and continuing organ shortages were major factors in more recent xenotransplant trials in the United States. In 1985, at Loma Linda (CA) University, a baboon heart was implanted in ’Baby Fae,” a newborn infant who survived four weeks.
• In the early 1990s at the University of Pittsburgh, baboon livers were transplanted into two patients with advanced hepatitis B infection. A third patient with AIDS was implanted with baboon bone marrow that did not engraft. One of the two liver transplant patients survived 70 days and the other survived 26 days. Both patients died of infection due to excessive immunosuppression. A baboon marrow graft was also attempted in 1995, when researchers at the University of California, San Francisco and the University of Pittsburgh conducted the procedure on an AIDS patient in an attempt to bolster his immune system.
Reference
1. Institute of Medicine Committee on Xenograft Transplantation. Xenotransplantation: Science, Ethics and Public Policy. Washington, DC: National Academy Press; 1996.
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