Imagine a pig farm with a difference. Instead of snuffling around in the mud and feeding from troughs of potato peels, pigs are housed in a series of dormitory-like rooms. They live in a strictly controlled environment, with a regular check on water quality. Fed only on vegetables, these pigs are sparkling clean - the ultimate in porcine pampering.
Sounds a little Orwellian? In fact, it is the pig-breeding warehouse of an international drug company. The sterile conditions are not because of drug testing, but because these pigs organs are destined for transplantation into humans. The era of xenotransplantation has arrived.
Allotransplantation (human-to-human organ transfer) has been a huge success since it was pioneered in the 1950s. Xenotransplantation (animal to human) is the next step forward in the ever-changing world of transplant surgery, and has come about because of a global shortage of human organs.
There is a 10-year waiting list in southern Italy for kidney transplants. UK figures for major organ transplants (see graph) illustrate the imbalance between supply and demand which is experienced in many Western countries. It is estimated that 45,000 Americans could benefit from heart transplantation, yet only 2,000 human hearts are available annually.
Although previous research efforts had focused on using ape and baboon hearts - the first heart transplant using a chimpanzee as a donor took place in 1964 at the University of Mississippi - objections by the animal rights lobby mean that pigs rather than primates are now the front runners as the source of organs.
While it is true that pigs are less compatible with humans than are monkeys, they can be genetically manipulated to produce organs less likely to be rejected on transplantation. Pigs quickly grow to full size, produce larger litters and can be reared in germ-free conditions. Biotechnology companies certainly believe in the future of pig-to-human transplantation; they are investing millions of pounds in developing genetically modified animals.
There is a huge amount of hope and hype surrounding xenotransplantation. The process is not entirely novel, as pig heart valves have been used to replace damaged human ones without any ill effect. However, heart valve tissue is essentially inert and unlikely to provoke a severe response from the immune system, so a big question remains: will entire hearts, kidneys and other organs be met by the same passive response?
Probably the issue of most concern to potential recipients is the range of medical problems associated with pig-to-human transplantation. First there is the challenge of overcoming rejection. Second, will the pig kidney be able to perform all the functions of its human counterpart? And is there a danger of introducing new and dangerous infections into the human race?
Rejection of transplanted organs can occur, even when genetic compatibility is maximised, as in the case of sibling donations. In kidney transplants, rejection is managed using powerful drugs, which suppress the recipients' immune system. When first developed, these drugs suppressed function in an indiscriminate way; now it is possible to inhibit the unwanted effects without jeopardising aspects of immune response which are essential for day-to-day living.
Dr Jeffrey Platt, an immunologist at Duke University Medical Centre in the US, has been at the centre of scientific breakthroughs in the immunology of transplant surgery. "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," he explains.
Platt and his colleagues use a three-pronged approach to try to eliminate the need for immune-suppressant drugs. They introduce human genes into the donor pig - this stops hyperacute rejection (the immune system's initial response to foreign material). Certain pig genes flag the organ as foreign, so removing these from the specially-reared animals is also important.
The third major area of research is in the field of vascular rejection. This occurs weeks to months after transplantation. Basically, the blood-clotting system goes into overdrive within the foreign organ, causing massive clots. The new organ ends up starved of its own blood supply.
Whether animal organs can replace the physiological function of human organs ones is another key area for research. One biotechnology company reported to a recent meeting of the US Food and Drug Administration (FDA) that pig-to-primate kidney transplants function well on several levels. However, they were incompatible with respect to a substance called erythropoietin, essential to the manufacture of new red blood cells by the body. There may be other "mixed" physiological signals, yet undiscovered, between pigs and humans, including factors that control the health and function of the bone marrow and liver.
Researchers are predicting pig-to-human transplants of heart, kidney and lungs. Whole organ liver transplants will almost certainly not be possible, due to the many differences in protein manufacture by porcine livers.
The biggest area of concern to both doctors and patients is the possibility that xenotransplantation might create a new infectious disease epidemic. Two years ago, the risk was regarded as so great that the FDA placed a hold on clinical trials involving cellular xenotransplants. That action followed the discovery that a pig virus could infect human cells in the laboratory.
These retroviruses are found in the genetic material of mammals and so cannot be "bred out" of xenoptransplants. Although there is no current evidence of porcine retrovirus infection in human recipients of transplanted pig tissue, the old adage, "absence of evidence does not mean evidence of absence", is particularly relevant here. The nightmare scenario for society would be the creation of another HIV-like epidemic, whereby a pig retrovirus could sweep around the world after its introduction to humans by way of xenotransplantation. However unlikely this possibility, it is extremely important that the risks are fully debated before the green light is given for pig-to-human transplants.
Which brings us to the ethical issues involved in allowing animal organs into the human race. Animal rights activists may not be appeased by claims that pigs are already bred for human consumption and so represent a "better" choice than apes or monkeys. The genetic alterations necessary to prepare organs for transplant may be equally unacceptable. The complexities of informed consent for human research subjects must be addressed. The public has a right to debate all these issues before biotechnology companies go further with xenotransplantation.
For the many people worldwide who are waiting for a new kidney and wishing for an end to daily dialysis, these ethical concerns may seem academic. As one patient put it to me recently, the trauma of receiving an animal kidney may be less than the guilt associated with benefiting from another person's death.
What is the situation in Ireland? According to David Hickey, consultant renal transplant surgeon at Dublin's Beaumont Hospital, we are in the enviable position of being number one in the European league table for the supply and demand of human kidneys. "We carry out at about 50 kidney transplants per one million population at present, with no shortage in organ donors," he says. "This compares with a four-year waiting list in Britain." The same statistics apply to the availability of other donor organs, so that, from a demand point of view, we are unlikely to be at the forefront of pioneering xenotransplant surgery.
At the same time, it would be mistake to absent ourselves from the worldwide discussion on this issue. Whatever regulations eventually come into force are likely to be driven by Europe, and our present lack of demand for animal organs may not last for ever.
So will xenotransplantation become routine? According to one veteran transplant surgeon: "Xenotransplantation is just around the corner - and always will be." However, David Hickey feels the answer is almost certainly yes. He believes that we will see xenotransplantation in Europe within the next five years.