Xenotransplantation 30/7/03. By Richard Twyman Transferring tissues or organs from one species to another.

When an organ fails, the best treatment is to introduce a healthy replacement organ, ideally from a compatible human donor (an organ transplant). At the current time, however, there is a chronic shortage of organ donors resulting in long waiting times and many unnecessary deaths.

One possible solution to this problem is to use animals as donors. The transfer of organs, or of any other tissue, from one species to another is known as xenotransplantation. Although this sounds like a futuristic idea, xenotransplantation has a long history. The first record of such an operation in humans dates back to 1682 when part of a dog's skull was used to repair the broken skull of a Russian nobleman.

The first successful organ xenotransplants were carried out in 1963, when chimpanzee kidneys were transplanted into 13 patients, one of whom survived for over nine months. The first cardiac xenotransplant was carried out in 1964, again using a chimpanzee donor. Only eight such operations have been attempted to date, and none of the patients have survived for very long. The longest survivor was baby Fae, who received a baboon heart in 1984 and lived for 21 days. As well as primates, pigs and sheep have been used as donors.

The major technical problem with xenotransplantation is rejection of animal tissue by the human immune system. Cells from monkeys, pigs and other mammals carry non-human antigens and are therefore regarded as foreign invaders. This results in a series of immune reactions against the donated organ.

The first reaction, known as hyperacute rejection, occurs minutes to hours after the transplant. It involves a collection of proteins called complement, which bind to the surface of foreign cells and break open their membranes. The complement reaction is stimulated by immune cells and free-circulating antibodies that recognise foreign antigens on the surface of the donor organs. Current research has focused on strategies to suppress hyperacute rejection.

Feature: Genetic modification of pigs for xenotransplantation

If hyperacute rejection can be avoided, there are other, equally difficult obstacles to overcome. Delayed rejection occurs after a few days and involves the recognition of foreign tissue by macrophages and natural killer cells. It may be necessary to train the recipient immune system to develop T-cell tolerance of the foreign organ, i.e. to regard it as 'self'.

As well as these technical difficulties, there are many ethical concerns about the use of animal organs in humans. Some of these objections are based on points of principle, but others represent more concrete fears about safety. For example, it may be possible for animal viruses, which are harmless to their natural hosts, to jump to human recipients and cause new diseases. In particular, much research is being carried out on a family of viruses called porcine endogenous retroviruses. There is no current evidence that such viruses can cause diseases in humans but it is possible they could adapt over time and become more harmful.

The potential benefits of xenotransplantation to individual patients must therefore be weighed against potential risks affecting the entire human population.

Image credit: Anthea Sieveking