Circe, Cassandra, and the trojan pigs: xenotransplantation. (2004)

SUPPOSE YOU NEED a transplant, a new heart or kidney. Rather than wait for an altruistic human donor to die or a living relative to volunteer a kidney, you may one day book in for elective surgery to receive an organ freshly taken from a specially bred pig. The transplant surgeon, assisted by the anti-rejection potion prepared by immunologists, represents our modern day Circe, who conjures the metamorphosis of the patient whose mind remains human as ever. I have found myself playing the role of Cassandra, prophesying doom largely unheeded by the surgeons. Ideally, the source animal will be reared in specific pathogen-free conditions and should therefore be much less of an infection hazard than a free range human donor who might be infected by HIV or hepatitis viruses, and certainly will be carrying several kinds of herpesvirus. But certain porcine viruses, the paleontological ones, cannot be eliminated; they reside within the pigs' DNA, but like the Greeks hidden inside the Trojan horse, they may emerge once the pig tissue or organ is taken into the human body. Xenotransplantation-the transfer of animal cells, tissues, or organs into humans-poses a number of problems: ethical, physiological, immunological, and microbiological. Nevertheless, xenotransplantation is being explored in several ways with the aim of improving human health. Bovine and porcine heart valves have been used in cardiac surgery for more than thirty years, but these valves do not represent living tissues; they are pickled first, contain very few cells, are not rejected, and do not release viruses. More recently, clinical trials of live cellular therapies have been undertaken. Fetal pig neurons inoculated into the human brain might ameliorate degenerative conditions such as Parkinson's and Huntington's diseases (Fink et al. 2000). Cells from the islets of Langerhans of the pig pancreas may be useful in treating type 1 diabetes, since porcine insulin works in humans (Groth et al. 1994). Pig liver cells have been used extracorporeally as the equivalent of a dialysis machine in order to tide over patients with fulminant liver failure until either their own liver recovers or a human transplant becomes available (Chen et al. 1997). Whole organs from animals, however, present greater technical hurdles for controlling rejection, although genetically modified pigs may well provide the answer (Platt 2003)-and additional infection hazards (Weiss 1998). In fact, the transfer of animal cells into humans has been practised experimentally for centuries. In the sixteenth to eighteenth centuries, sheep blood was occasionally transfused into patients (fig. 2), if only to replace the human blood extracted by the application of leeches. Samuel Pepys gives a graphic account of the treatment of a mental affliction in his diary for 1667 (Scott 2004). Fellows of the Royal Society in London differ in the opinion they have of the effects of it; some think that it may have been a good effect upon him as a frantic man; others, that it will not have any effect at all. Pepys later reports that the treatment did the patient no harm although was still cracked a little in the head and he had but 20 shillings for his suffering it. The ethics of paying the man to undergo experimental therapy was of no concern to Pepys, only how little money received. In the United States, animal to human blood transfusion was attempted during the eighteenth and nineteenth centuries (Schmidt 1968). Such transfusions probably did more harm than good because humans have a blood group incompatibility with domestic animals that causes hyperacute rejection. In 1901, Karl Landsteiner published his Nobel Prize-winning discovery of the ABO histo-blood group incompatibilities. The ABO system comprises carbohydrate antigens on the surface of red blood cells and other tissues. Humans make natural antibodies to the blood group they do not possess. Thus a group A person makes anti-B, a group B person anti-A, and a group O person both anti-A and anti-B. …