XENOTRANSPLANTS

Xenotransplantation (the transplanting of an organ from one species into another) is not a new idea - having been performed between animals of different species and from animals to humans since the begining of the 20th century.

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KIDNEYS

In 1902, Emerich Ullmann, Chief Surgeon at Spital der Baumherigen Schwetern, Germany, removed the kidney from a dog and transplanted the organ into a goat - unsuccessfully(1). Three years later, in 1905, Princeteau, in France, wrote of a child with kidney inefficiency receiving some slice of  a kidney from a rabbit - the child died 16 days later of congestion of the lungs(2). Around this time, Mathieu Jaboulay, in Lyons, France, transplanted a kidney from a pig into the arm of a human, and grafted the kidney of a goat into the thigh of another patient - both recipients "survived" for less than an hour after the operation(3). In 1909, Ernst Unger, of Berlin, Germany, transplanted the kidneys of a fox terrier into a boxer dog - urine flowed for only two weeks(4). On 10 Dec 1909, Unger grafted a kidney from a stillborn baby into a baboon - which died shortly afterwards(5). At the end of 1909, Unger transplanted the kidney of an ape into the thigh vessels of a woman - no urine was produced(6). Reviewing the early work, Guthrie, of Hull Physiological Labs, Chicago, wrote in 1912 "no-one, although many experiments have been reported, has yet succeeded in keeping an animal alive for any great length of time which carried the kidney, or kidneys, of another animal after its own kidneys had been removed"(7); and Yu Yu Voronoy, who had read of Jaboulay`s, and of Unger`s, experimental xenotransplants wrote in 1936 "Transplantation of primate organs [as conducted by Unger] and, above all, of domestic animals such as goats and pigs [as conducted by Jaboulay] have failed utterly. The only source of grafts is cadavers since the donor does not suffer a loss"(8).

Experimenters during the 1920s included Williamson, of the Division of Experimental Surgery and Pathology at the Mayo Foundation in America, who grafted the kidneys from two goats into two dogs - both recipients died within minutes(9). In 1923, Neuhof transplanted the kidney of a lamb into a human - the patient died nine days after the operation(10).

No further work on kidney xenografts was performed until the 1960s - when, at the begining of the decade, Roy Calne (now Sir) reported on having transplanted the kidney of a goat into a dog - 90 minutes after the operation, the dog became pale and cyanosed(11). In 1963, Claude Hitchcock at the Hennepin County Hospital, Minneapolis, USA, transplanted the kidney of a baboon into a 65-year old woman - the organ worked for just four days; and in the same year, Keith Reemtsma, working as a surgeon at Tulane University School of Medicine, USA, transplanted both kidneys from a chimpanzee into Jefferson Davis - who died nine weeks later of pneumonia, as his resistance to infection had been weakened as a result of the anti-rejection drugs he had been  given(12). Reemtsma tried five more times - transplanting kidneys from chimpanzees into humans - four died with weeks, one lived for nine months(13). In 1964, Thomas Strazl, in Denver, Colorado, USA, transplanted kidneys from six baboons into six humans - each xenotransplanted organ rejected within weeks of the operation(14). In 1966, Pereper and Najarian transplanted kidneys from pigs into dogs, and from dogs into pigs - all of the recipient animals became pale and cyanosed. Pereper and Najarian tried transplanting kidneys from sheep into goats - the goats died within two days(15). Also in 1966, H Gerwurz grafted the kidney of a sheep into a dog - the kidney was rejected within minutes(16). Raffaello Cortesni, of Italy, conducted anumber of transplants with chimpanzees before, at the end of the 1960s, he transplanted the kidney of a chimpanzee into a 19-year old man - who was dead less than a month after the operation(17).

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HEARTS

In Jan 1964, James Hardy, of the University of Mississippi Medical Center, Jackson, Mississippi, USA, transplanted the heart of a chimpanzee into a 68-year old man, Boyd Rush. The chimp`s heart was started with a defibrillator and did beat - but not for long, and two hours later, Rush was allowed to die(18). In 1968, Denton Cooley, in Houston, Texas, USA, transplanted the heart of sheep into a dying man(19) - who died instantly(20). Also in 1968, in the UK, the heart of a pig was transplanted into a human - the organ failed immediately(21).

Christiaan Barnard, who, in 1967, had perfomed the first human-to-human heart transplants at the Groote Schuur Hospital, Cape Town, South Africa(22) performed two xenotransplants in 1977. He transplanted the heart of a chimpanzee into a 26-year old woman - who lived for six hours; and transplanted another chimpanzee`s heart into a 59-year old man - who lived for four days. On both occasions, Barnard had placed the heart of the chimp alongside the patient`s own heart(23).

From the mid-1970s, Leonard Bailey had been involved in xenotransplants at Loma Linda University Medical School, Los Angeles, USA - and had transplanted heart from lambs and piglets into goats(24). In a seven-year period (1977-1984), Bailey performed almost 160 cross-species transplants(25).Out of all of his animal xenografts, only one xenograft "succeeded" - between closely-related sub-species of goat - which lived for six months(26).

In Oct 1984, Bailey obtained permission from the parents of a baby girl - known only as "Baby Fae" - to allow him to transplant the heart of a baboon into her, and set about trying to match the immune system of a baboon with that of the baby. On 26 Oct 1984, Bailey placed "Baby Fae" on a heart-lung machine, removed the heart of a 7-month old female baboonand grafted it into the baby - within four hours of the start of the operation, the baboon`s heart was beating inside "Baby Fae". As time went on, it was thought that the baby`s body was rejecting the transplanted heart so the doseage of anti-rejection drugs was increased. A few days later, her kidneys failed and then her heart. On 15 Nov 1984, "Baby Fae" died - but it was not organ rejection which had killed her. The cause of death was a mis-match of her blood and that of the baboon. Bailey was aware of this mis-match of blood, but as the tissue of the baboon matched, to some extent, that of the child, he decided to go ahead with the xenotransplant anyway(27).

refs

1. Ullmann,E. Annals of Surgery. vol 60. 1914. 

2. Princeteau,MJ. J Med Bordeaux. vol 26. 1905.

3. Hamilton,D. in Morris,P [ed]. Kidney Transplantation: principles & practice. WB Saunders Co. 1988.

4. Winkler,E. J of History of Medicine. vol 37. 1982.

5. Hamilton,D. in Morris,P [ed]. Kidney Transplantation... WB Saunders Co. 1988.

6. Unger,E. Berlin Klin Wschr. vol 1. 1909.

7. Guthrie,C. Blood Vessel Surgery & Its Application. Longman,Green & Co. 1912.

8. Voronoy,YY. Siglo Medico. vol 87. 1937.

9. Williamson,CS. J of Urology. vol 16. 1926.

10. Neuhof,H. Transplantation of Tissue. D Appleton & Co. 1923.

11. Calne,RY. Br J of Surgery. vol 48. 1961.

12. Stark,A. Knife to the Heart - the Story of Transplant Surgery. Macmillan. 1996.

13. Reemtsma,K et al. Annals of Surgery. vol 184. 1964.

14. Starzl,T. in Hardy,MA [ed]. Xenograft. vol 25. 1989.

15. Pereper,RJ. najarian,JS. Transplantation. vol 4. 1966.

16. Gerwurz,H. Annals of NY Academy of Science. vol 129. 1966.

17. Stark,A. Knife to the Heart... Macmillan. 1996.

18. ibid.

19. ibid.

20. Working Party on Xengrafts report. 1997.

21. Cooper,DKC et al. Xenotransplantation. Springer-Verlag. 1991.

22. Najarian,JS. Simmons,RL [eds]. Transplantation. Lea & Febiger. 1972.

23. Stark,A. Knife to the Heart... Macmillan. 1996.

24. ibid.

25. New Scientist. 29 Nov 1984.

26. Sharpe,R. The Cruel Deception. Thorsons. 1988.

27. Strak,A. Knife to the Heart... Macmillan. 1996.

RISKS of XENOTRANSPLANTATION

Much attention has been paid to the pursuit of adapting the organs of pigs for transplantation. Whilst much of this has focussed on the ethical considerations of the suffering of the animals involved in experimental techniques - particularly as primates have been the recipient species - little has been mentioned of the potential risks and harm to people if the procedure is to adopted for human transplantation.

Medical professionals have warned of the hazards of infections - not least viruses - passing from animals to humans, and that this could be extenuated in an animal-to-organ transplant. Many of these comments have appeared in newspaper - reaching a mass media.

"Most new pandemics arise through inadvertent transmission of viruses from another species to humans"(1).

"Parasites of all kinds - whether viruses, bacteria, protozoa, worms or whatever - have switched hosts before and will do again... It is harder to assess the chances of a virus spreading once it has found lodging in a human... a virus, once in the human population, may spread. As the numbers of organ recipients grows, sowill the danger of their passing a virus to a wider population... diseases that are harmful to their usual hosts may not be harmless in a new one"(2).

"A virsu can be most deadly when it has jumped to a new host species... Dr Johnathan S Allen, who works at the Southwest Foundation for Biomedical Research in San Antonio has sounded an alarm about the theoretical risk that known or unknown viruses could infect human recipients, then be transmitted to other people"(3).

"Any pig we use for transplants would have to be screened very carefully for known viruses. The cornern is over the unknown viruses. The recipient of the organ might be prepared to take the risk. But what happens if a virus becomes a human epidemic?"(4).

"Suppose research finds horrendous rejection problems. That for me would mean we say `no` [to human trials]. Suppose research shows retroviruses from pigs can be transmitted to human tissues in the lab. Without wishing to create a doomsday scenario, there is a possibility that not only could this lead to particular infections in the [human] patient may pass on the infection to a wider public"(5).

"All animals - pig included - harbour quiescent viruses within their genetic material. These viruses, while dormant in their host, may become more lively when transplanted into a different species"(6).

refs

1. Science. vol 265. 1994.

2. The Economist. 21 Oct 1995.

3. Herald Tribune/ 11 Jan 1996.

4. The Times. 16 Dec 1996.

5. The Guardian. 16 Dec 1996.

6. The Times. 17 Jan 1997.

7. The Economist. 18 Jan 1997.