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Bryan is a medical journalist and the author of 28 books on science and medicine for adults and children. Clare is co-producer of Carlton TV's "Organ Farm" documentary co-production with FRONTLINE. Bryan and Clare also co-authored the book Organ Farm which draws on research and reporting by the Carlton TV producers for the documentary.

1. Who is waiting for a transplant?

Every year, 150,000 people around the world join the waiting lists for a new heart, kidney or liver. Half die before they can get one. In the USA, about 20,000 people receive an organ transplant each year; in the UK, it's around 2000. In Europe, America, Asia, and Australasia, 21st century transplant surgeons cannot hope to keep pace with demand.

See updated data on the organ shortage compiled by the United Network for Organ Sharing. This site also has information on donating organs and contains archives of articles and the latest news reports on human transplant issues.

A Public Opinion Survey on the Organ Shortage and Xenotransplantation
94% of Americans are aware of the organ shortage; 62% believe xenotransplantation is a viable option to combat the organ shortage. These are some of the top findings in this 1998 National Kidney Foundation survey. Read this press release for more details.



2. Why the shortage?

There are several reasons. Only a small proportion of people die in a way which makes their organs suitable for transplantation - in the hospital, preferably in an intensive care unit, following a road accident or a stroke. Some have not made it clear that they wish to donate their organs when they die, and relatives may be too upset to give permission or doctors too embarrassed to ask.

Ironically, road safety campaigns and improved stroke treatments have helped reduce the supply of organ donors. Yet, success rates for transplant surgery continue to rise. In 1985, six out of 10 people lived a year or more after a heart transplant. By 1997, the figure had risen to 84%. For kidney transplant the figure rose from 70% up to 85% in the same period.

So skilled are the transplant teams that surgeons would operate on older, sicker patients than ever before - if only there were enough human organs to go around.

3. What is xenotransplantation?

In xenotransplantation, organs, tissues or cells from one species are transplanted into animals of a different species. The transplant can be carried out between closely related (concordant) species, such as a human and a baboon, who have a lot of the same genes. Or it can be carried out between "discordant" species, such as a pig and a human, which are not closely related and therefore have fewer genes in common.

The less closely related the donor and recipient species, the more violently the transplanted organ is rejected. This is because all animals have 'flags' on their cells which announce what species they are. Pig cells say 'I am pig', baboons' say 'I am baboon', human cells say `I am human'.

4. Why are transplanted organs rejected?

Nearly all transplanted organs trigger some rejection problems in their new owner, even when they are from the same species. That's why transplant patients take anti-rejection drugs. Only transplants between identical twins are completely accepted.

Rejection occurs because the recipient's immune system recognises that the new organ is not its own. It's foreign.

If the organ comes from a different species it is rejected within a few minutes in a process called hyperacute rejection. Pre-programmed antibodies in the recipient's bloodstream target the xenoantigens - the flags which say 'I am pig' - all over the transplanted organ and trigger a destructive chain reaction. The blood supply to the transplanted organ is blocked, cells die, and the organ stops working.

5. How are scientists trying to prevent hyperacute rejection of xenotransplants?

In 1992, British scientists succeeded in breeding a pig, called Astrid, with human 'flags' on her cells. They put genes (DNA) for the human flags into pig embryos and put them into the wombs of surrogate sows. They had to do it many times before Astrid was born. She was still a pig, but she was a 'transgenic' pig and her DNA was 0.000001% more human than other pigs.

Since 1992, herds of transgenic pigs have been bred in Europe and the USA which have human flags on their cells. But traditional breeding methods mean that some animals have plenty of flags while others don't. It's very hit and miss. However, US scientists are very close to cloning piglets which have human flags on their cells. So they should soon have a reliable source of transgenic pig organs.

6. Have transgenic pigs got rid of the rejection problems for xenotransplants?

No, the longest that monkeys given organs from transgenic pigs have survived is a few months. Although they have human flags that should make them more acceptable to the monkeys than ordinary pig organs, the flags are not, after all, monkey flags. So the organs are still rejected.

7. Why not put them in humans then?

No organs from transgenic pigs have been transplanted into humans. There are strict rules about such operations and surgeons would need to get permission from their national xenotransplantation authorities before they could operate. These authorities want to see better results with transgenic pig organs in monkeys before they will give the go-ahead for human surgery. They are also worried that transplanted pig organs could carry potentially dangerous pig viruses into their human recipients.

8. What are these pig viruses?

In 1997, British scientists discovered that porcine endogenous retroviruses (PERVs) could infect human cells. Every species has its own type of endogenous retrovirus and each is harmless to the species it lives in. PERVs are harmless to pigs and human endogenous retroviruses are harmless to humans. There is no evidence that PERVs are harmful to humans but the fact that they can spread amongst humans is worrying. If they did ever attack our cells, we might not have the defense mechanisms to destroy them.

9. Have PERVs put an end to pig to human transplants then?

No. Since 1997, scientists have been working hard to assess just how big a risk PERVs are. And health authorities in the USA, the UK and other countries have drawn up guidance to reduce the risk of anyone who has a transgenic pig organ passing PERVs on to other people. This includes having regular tests for PERVs, always using condoms during sex, and seeking advice before having children.

10. If pig organs are causing such problems, why not use organs from monkeys and other primates that are more closely related to humans?

Chimpanzee and monkey organs might well have fewer rejection problems than pig organs if they were used for human transplants. But researchers have decided that it would not be right to use our closest animal relations in this way.

11. So pigs don't count?

Although pigs have been used as a source of food for humans for generations, their insulin has been used to treat diabetes, and their heart valves used to replace diseased human valves, some people do not believe that pigs should be farmed so that their organs can be used for human transplants. And animal rights groups have campaigned strongly for xeno research involving animals to stop. They have drawn attention to the unnatural conditions in which transgenic piglets are kept before their organs are used. Hygiene requirements prevent them from staying with their mothers, suckling, or leading normal pig lives.

Animal rights groups have also campaigned against the use of monkeys as recipients for transgenic pig organs in xeno research. In some experiments, pig hearts are attached to the necks of monkeys to watch for signs of rejection and, in all cases, the animals do eventually succumb to rejection.

11. What's the nearest we've got to using transgenic pig organs for human transplants?

Livers from transgenic pigs were used to keep two patients alive in the USA while doctors searched desperately for human organs for them. But that was before scientists discovered that PERVs could infect humans. The two patients - one of them Robert Pennington - were connected to transgenic pig livers on trolleys at their bedside. The pig livers took over the work of their own failed livers, cleaning their blood and keeping them alive. Both procedures were successful and the two patients are alive and well after human livers were found for them and transplanted.

12. Are pigs being used to treat any other human diseases?

Pig brain cells have been used to treat Parkinson's disease and strokes in small numbers of people (see information on the results of these experimental clinical trials). Pig pancreatic cells have also been used to treat diabetes, with less success. In all these cases, the cells used have been taken from ordinary pigs, rather than transgenic animals, since injections of pig cells are not susceptible to the rejection reactions encountered by whole organs.

13. Is xenotransplantation the only solution to the shortage of organs for transplantation?

Transplant specialists are trying to boost the supply of people prepared to donate organs after their death by encouraging them to carry donor cards or join donor registers. In Spain, the supply of organs and the number of transplants carried out each year has increased dramatically since such a scheme was introduced.

In the longer terms, advances in cloning and other technologies may make it possible to grow human cells and even whole organs in the laboratory. But it is likely to be many years before this become a reality.

Xenotransplantation could help provide a solution to the current worldwide shortage of organs for transplantation much sooner than human cloning research.

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