Animal organ transplants
The transplantation of organs from one species to another, for example from a pig to a human, is called xenotransplantation. The term covers transplantation of organs (such as the kidneys or the heart), tissues (such as skin) or clusters of specialised cells (such as brain cells or the pancreatic islet cells that produce insulin).
Xenotransplantation can also involve the infusion or transplantation of body fluids, tissues or cells that have been in contact with the tissues or cells of another species outside the recipient’s body. For example, a person might be treated for liver failure by having their blood passed through an artificial device containing pig liver cells (liver perfusion).
Some non-living devices derived from animals, such as pig heart valves, have been used in humans for many years. Xenotransplants differ from these devices in that they are alive and can perform the same functions as the organ, tissue or cells that they replace.
Xenotransplantation and allotransplantation
Transplantation among members of the same species is known as allotransplantation, and in humans this is a very successful way to treat a variety of illnesses. However, the number of people who need transplants far outweighs the number of human tissues and organs available for transplantation, so many people who could benefit from a transplant wait in vain for a suitable donor. As a result, transplant specialists are considering animals as a possible source of organs and tissues for human transplantation.
The greatest benefit of xenotransplantation would be a potentially unlimited supply of cells, tissues and organs for use in humans.
Recent advances in technology have increased the possibility of successful xenotransplantation and stimulated research in this area. For example, genetic engineering has allowed human genes to be inserted into pigs so that their cells, tissues and organs are less likely to be rejected when transplanted into humans.
However, perhaps the greatest obstacle to xenotransplantation will be the ethical issues that arise from it, such as animal welfare and the issue of scientists ‘experimenting’ on humans to conduct clinical trials. Such ethical issues are subject to ongoing discussion in the scientific community.
How could xenotransplantation help humans?
Xenotransplantation has the potential to treat a wide range of life-threatening or debilitating conditions. For example, it is possible that isolated cells could be transplanted to treat diseases such as diabetes, Parkinson’s disease, Huntington’s disease or strokes.
Another possibility is that xenotransplantation could be used to keep potential transplant patients alive and as healthy as possible while they wait for a suitable human donor. There have been promising results from overseas trials in which isolated pig liver cells were used to treat acute liver failure.
Suitable animal donors
Some overseas research has focused on the use of baboons as potential donors to humans. However, much research has focused on the use of pigs. Pigs are considered to be a suitable species as a source of material for xenotransplantation for several reasons.
- They reproduce quickly and have large litters.
- Their organs are similar in size to those of humans.
- They are easy to rear in conditions free of particular pathogens (disease-causing organisms).
- They can be genetically manipulated to reduce the risk of rejection.
- The risk that they will carry pathogens that can infect humans is smaller than with apes and monkeys. Apes and monkeys have a closer genetic make-up to humans and this increases the risk of a virus being transmitted across species.
Risks of xenotransplantation
The main risk to the recipient of a transplant is rejection due to the patient’s immune response. In human-to-human transplantation (allotransplantation), rejection has been largely overcome by tissue matching of donors and recipients, and by giving the recipient drugs that suppress their immune response.
The risk of rejection in xenotransplantation is more severe because the differences between the donor and the recipient are much greater. The most promising approach at this stage is to genetically modify the source animals so that their organs or tissues do not cause such a strong immune response when transplanted to humans. Scientists have already produced several genetically modified strains of pigs that show promising results.
Viruses
Xenotransplantation also carries some risks for the wider community. The major concern for public health is that xenotransplantation might transmit an infectious agent (such as a virus) from animals to humans. Retroviruses are the chief concern, because there are many examples of such viruses moving from one species to become infectious in another.
Retroviruses do not always cause obvious signs of disease initially. So if a transplant patient became infected with a retrovirus, the virus could spread to that person's family, carers, close contacts and even the general population before it became obvious that an infection had occurred.
The virus that is of most concern in xenotransplantation using pigs as the donor species is the porcine endogenous retrovirus (PERV). PERV is present in almost all strains of pigs and cannot be removed by raising pigs in sterile conditions. Although PERV is inactive, and therefore harmless, in pigs, there are concerns that transplantation into humans may activate the virus, creating a new human disease that could spread to those close to the transplant recipient and eventually to the wider community.
PERV can infect human cells in the laboratory, suggesting that it could infect humans through xenotransplantation. However, according to the National Health and Medical Research Council (NHMRC), studies of about 150 people worldwide who have been transplanted with pig tissue or had their blood pass through pig cells have shown no evidence of infection with a virus or any other infectious agent originating from pigs.
Minimising risks
Although most pigs carry PERV, at least one strain of ‘minipigs’ does not, so researchers are investigating the use of this strain (or breeding others) for xenotransplantation in order to reduce the risk of infection in the recipient.
According to the NHMRC, animal-to-human trials will not be approved in Australia unless there is an appropriate infection control policy in the hospital where the transplant is taking place.
And because the long-term consequences of xenotransplantation will not be fully understood for some years, anyone transplanted with cells, tissues or organs from another species would need to be carefully monitored. Therefore, anyone receiving a transplant would be informed about the potential infectious disease risks and would be asked to support such long-term monitoring.
Animal-to-human xenotransplantation trials overseas
Many western countries have decided to proceed with xenotransplantation research under agreed guidelines.
Some xenotransplantation trials are in progress in the USA and Europe. These trials include:
- transplanting fetal neuronal cells from pigs for the treatment of Parkinson’s disease;
- using genetically modified pig liver for liver perfusion to help treat liver failure;
- using fetal calf adrenal cells for pain relief for end-stage cancer; and
- implanting pig pancreatic islet cells (the cells that produce insulin) as a treatment for insulin-dependent (type I) diabetes.
The future of xenotransplantation in Australia
According to the NHMRC, if xenotransplantation is to become an option for human therapy, research is needed that includes:
- animal-to-animal studies (preclinical studies), in which proposed xenotransplantation procedures are tested on animals (e.g. pig-to-baboon kidney transplant); and
- animal-to-human trials (clinical trials), in which animal products are used for xenotransplantation procedures on human beings (e.g. pig-to-human brain cell transplants).
Animal-to-animal studies are covered by existing regulations for research involving animals. Animal-to-human trials were the subject of draft guidelines developed by a working party of the NHMRC. The guidelines were released for public consultation in July 2002, and were followed by a series of public meetings in Perth, Melbourne and Sydney.
The NHMRC Working Party on Xenotransplantation received 97 public submissions providing feedback. Many people wanted to know more about xenotransplantation and raised issues such as animal welfare and infection risks.
This year, a second discussion paper, incorporating responses from the first round of consultation, is being released by the NHMRC's working party, followed by a second round of public meetings and public consultation.
According to the NHMRC Working Party on Xenotransplantation, the potential benefits of xenotransplantation must be balanced against the ethical concerns raised by the Australian community. The working party is now seeking answers to the central questions of whether the use of animal organs in humans is acceptable to the Australian community and whether suitable guidelines can be developed to make research in this area suitably safe.
Last Reviewed: 31 March 2003
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