Introduction Xenotransplantation is the use of live animal organs, tissues, or cells in human transplant operations. It has been hailed as a great advance – a solution to the shortage of donor organs available for desperate patients. However, fears that it could result in the transmission of animal diseases to humans or produce unforeseen effects have led to it being made illegal in the UK and, except for one clinical trial, it is banned in the USA. Scientists wishing to perform xenotransplantation experiments in the UK must obtain special permission from the government. Xenotransplantation includes the transplanting of bone marrow to assist AIDS patients and other immunosuppressed groups, and of pig fetal neural tissue to assist people with Parkinson's disease.
History of transplants Transplant operations are not new: the moving of kidneys from one human to another has been going on since the early 1960s, and heart transplants became common in the 1970s. There have also been experimental transplants of animal organs: 30 years ago a young woman survived for nine months after having received chimpanzee kidneys. The survival rate for transplant recipients is now good enough for the technique to be considered fairly routine. Yet, while the medicine has improved, one problem has remained: the waiting lists.
Using animal organs? The shortage of suitable human organ donors is getting worse. Organs for transplanting must be taken from healthy, recently dead, cadavers. This means that donors are usually patients in intensive care units who have died as a result of trauma, are brain-stem dead, have organs in good condition, and have next-of-kin amenable to removal of those organs. This is quite a rare combination, and several factors are making the situation more difficult: the population is ageing, roads are getting safer (reducing the number of donors), and post-operative treatment is improving the survival rate, making the transplant option yet more attractive. If we could use animal organs safely, the waiting lists could be cut almost instantly. The human immune system is primed to attack anything the body thinks is foreign. Ordinarily, a pig heart placed inside a human would be dead within five minutes – and so would the patient. But here has been a scientific breakthrough: pigs can be genetically engineered so that their hearts carry human signals. If such a heart were placed in a human, the immune system would not react, at least not strongly enough to cause rejection.
The scientific background The last few years have seen an astonishing growth of a new technology, loosely called ‘biotechnology’ or ‘new genetics’. Cloning, gene testing, gene therapy, and genetic engineering are just a few aspects of what can now be done, and all of these techniques rely on the fact that scientists can identify genes, cut them up, and move them around, even from species to species. The manipulation of genes – whether plant or animal (and that includes human) – is nothing new. In the past, however, the manipulation was done simply by breeding. Cattle herds have been selectively bred for decades, with farmers selecting for breeding the individuals that have the desired milk or beef characteristics. The same goes for plants: gene manipulation of plants has been going on ever since agriculture started. What is going on currently is fundamentally different, for two reasons. First, we are now able to manipulate genes in the laboratory, not just in the farmyard. We can insert the genes we want into animal eggs, just before fertilization. In other words, we can fiddle around with genes without having to go through the natural process of sexual reproduction. Secondly, and more importantly, we can now move genes from one species to another. We can do something nature rarely does: cross the species divide. We are able to put human genes into pigs, specifically genes that make the heart signal: ‘Yes, I am a human heart’. The scientific problems are not negligible. Clinical trials are not yet authorized, let alone under way, and there are many unanswered questions. For example, a pig lives for 20 years. Could a pig heart last for 40 years? No one knows. Then there is the question of pathogens in pigs. A pig heart xenograft is a living thing – you cannot kill all the germs in it by dunking it in disinfectant, or by heating it to 100°C. Scientists hope that a pig carefully bred in sterile conditions might not carry germs. Yet retroviruses – germs that actually copy themselves into the DNA and remain dormant for generations – would be much harder, if not impossible, to get rid of.
Is it ethical? A quick response to the question ‘Do you have a problem with xenotransplantation?’ might be ‘Why? It's no different from eating bacon’. Yet, as usual with ethical issues, these matters are not straightforward. They concern animal as well as human rights. Apart from saving lives, the use of animal organs could help bring about an end to such practices as the selling of human organs, which is legal in India, and the use of organs of executed prisoners, which occurs in China. However, xenotransplantation requires that pigs be conceived by in vitro fertilization, born by hysterectomy during which the sow is killed, fed by white-gloved assistants, and quartered in a sterile environment with a mesh floor to prevent faecal build-up. The debate is whether this sort of life is any worse than that of the average farm pig. Then there is the issue of how we feel about our own bodies. Is there a problem with a technology that will allow us to replace organs as if they were spare parts? At present, it is predicted that the use of xenografts will help terminally ill patients – in other words, save lives. Yet xenografts could be used as treatment – for instance, to assist those with a genetic disposition to heart disease. Uncomfortable scenarios rear up here: what about transplants for athletes, or for those who want to spend money extending their life? Where new technology beckons, money follows not far behind. The new genetics is an area absolutely in the grip of business – for the simple reason that genetic engineering is expensive and the medical spin-offs amazingly profitable. Xenotransplantation is no exception; indeed, the main player in British xenotransplant development is Imutran Ltd, a Cambridge-based company owned by Sandoz Pharma AG, Switzerland. The money men are already licking their lips: Salomon Bros, a Wall Street investment company, has affirmed that the demand for organ transplants by the year 2010 could be worth US$6 billion – tempting pickings if the scientists, the doctors, and the regulatory bodies give xenotransplantation the green light.