Xenotransplantation

An aid to ethical discernment

prepared by a working group on behalf of the Church Office of the Evangelical Church in Germany and the Secretariat of the German Bishops' Conference

Joint Texts No.13, 1998

Xenotransplantation

An aid to ethical discernment

1. Latest developments in research

Transplantation of organs from deceased or sometimes also from living relatives (so-called allotransplantation) has become an established procedure to remedy organ failure (such as failure of the kidneys, liver, heart, lungs and pancreas). However, there is a great disparity between the number of people in need of an organ transplant and the number of available organs. The result is a serious prob-lem of how to distribute these organs in a just way.

An increase in organ donations would only alleviate the problem, but not abolish it completely. Alternatives to more long-term graft organ replacement are at present available only for patients with kidney problems (hemodialysis, peritoneal dialysis). However, apart from entailing great encumbrances and limitations for the patients with respect to the quality of life, these therapies are also rather cost-intensive. Only in singular cases, patients with heart failure may be helped to bridge a short time with the mechanical support of an artificial heart. Generally, death is imminent for patients with serious heart, liver or lung problems without transplantation.

Transplanting animal organs into humans (so-called xenotransplantation) could solve the shortage in human donor organs. Approximately 4,000 to 6,000 animals would be required in order to meet the estimated annual demand in graft organs in the Federal Republic of Germany. That way, all patients who live with a medical indication for transplantation could receive a donor organ. In consequence, this would most likely lead to an expansion of the medical indication, so that an increase in the number of transplantations would have to be expected. There might be some medical advantages to transplanting animal organs as a therapy for certain diseases. In almost all instances, allograft hepatic replacements in liver patients with hepatitis B or hepatitis C lead to a resurgence of the disease, while donor organs taken from animals are resistant against the pathogens.

On the basis of current results in research, animal-to-human organ transplants (i. e. xenotransplantation) for the first time now appears a feasible alternative. By introducing human protein molecules into animal organs (producing so-called "transgenic animals"), the immunological reaction can be curbed to such a degree that allows for a well-tolerated immunosuppression to avoid rejection. Scientists involved in the field estimate that a broad clinical application of this method will not be realistic before the year 2010. At the moment, worldwide intense cooperative efforts concentrate on research in the area of xenotransplantation. In Germany, the German research foundation Deutsche Forschungsgemeinschaft has decided to focus on the promotion of xenotransplantation research.

So far, clinical xenotransplants in which animal organs without genetic modifications were used have not been very successful:

  • On 5 November 1963 in Toulane/USA Prof. K. Reemtsma transplanted six chimpanzee kidneys into human patients with kidney failure. The longest survivor died after nine months.

  • Also in 1963 in Denver/USA Prof. T. Starzl transplanted six baboon kidneys, the longest survival time was three months.

  • On 23 January 1964 Prof. J. D. Hardy transplanted a chimpanzee's heart into a human being. However, the organ did not take up its function.

  • In 1968, in South Africa Prof. C. Barnard undertook a heterotopic transplant of a chimpanzee and a baboon heart (creating an organic compound). These hearts are reported to have functioned for one day and for four days, respectively.

  • In 1985 in Loma Linda/USA Prof. L. Baily transplanted a baboon's heart into newborn Baby Fae. The child lived with it for three weeks before it died of multiple organ failure.

  • In 1992 in Pittsburgh/USA it was again Prof. T. Starzl and colleagues who transplanted baboon livers into two patients with hepatic failure due to hepatitis B. One recipient died after 28 days, the other one survived for 71 days.

  • Worldwide, extracorporeal liver perfusions have been carried out. The success rates so far have shown no clinical relevance.

At present, the main problems related to xenotransplantation are as follows: 

  1. The severe acute rejection up to now has not been mastered effectively. By means of physical methods such as hemodilution (i. e. thinning of the blood) or the absorption of antibodies, chemotherapy and the use of genetically modified animals (transgenic pigs that carry human protein on the surface of their cells in order to avoid rejection after being recognized as foreign to the body), apes with transgenic hearts and kidneys have survived implantation for 20 to 70 days. These hearts were connected to the ventral vessels and did not interfere with blood circulation. The graft kidneys were able to keep up a regular excretory function over a longer period of time.

  2. Researchers know very little about immunosuppression, which becomes necessary to contain the rejection of foreign tissue.

  3. The hypothesis was made that in immunosuppression, viruses contained in the genome (retroviruses) are transmitted from pigs to humans. This could lead to unknown diseases in the organ recipient. This assumption has not yet been confirmed by any of the experiments or by experience.

  4. In particular in liver transplants, the compatibility of metabolic functions between the animal's organ and the human organism has not yet been clarified.

Animals that are suitable for xenotransplantation have to be kept in special colonies under sterile or semi-sterile conditions. By means of genetic monitoring their genome has to be freed from retroviruses. Their "genetic skeleton" is to match the human one as closely as possible (histocompatibility). Certain auspicious breeds have to be brought to the adequate size. Further research needs to be done on interactions between animal and human hormones, enzymes and other cell products.

The various breeds of the domestic pig probably make for the best suited human organ resource. It is easy to keep these animals; feeding them is not expensive. Their rapid growth and reproduction are further advantages, for this way there would always be some animals available for transplantation that could be selected according to size, sex and age. In contrast to anthropoid apes, pigs have only very few bacterial or viral diseases and no malign diseases that could be transmitted to humans. Apes must not be used for reasons of species conservation. They are too few in numbers, and their artificial breeding is too laborious. From a zoological stance, other species such as sheep, goat or kangaroo are just as much qualified organ donors as pigs, however, their reproductive cycle is too slow, and it is difficult to rear them in captivity. American breeders have calculated that the costs for transgenic pigs would not be substantially higher than for pigs earmarked for human consumption. In Germany, every year around 48 million pigs are raised to be eaten; for transplants, the maximum number necessary would not exceed 6,000 animals, that is 0.2 ? of the animals for slaughter.

The preparations for painfree organ removal from living pigs, which means anaesthesia and surgery, correspond to the procedures in allotransplantations from living human organ donors. As diseases might occur after a successful transplantation, the documentation of the animal organ donor and the human organ recipient would have to cover a long period of time and would have to be very exact and strict. The animals killed in the process of organ harvesting would have to be destroyed according to legal provisions.




 


 

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