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ss nucleus - autumn 1994,  Organ Transplantation

Organ Transplantation

This article is a joint submission by three authors:- David Cranston is Consultant Urological and Transplant Surgeon at the Oxford Transplant Unit. Churchill Hospital. Oxford - Andrew Parry is Senior Registrar at the Transplant Unit Papworth Hospital Cambridge - John Dunning is Senior Registrar at the Cardiothoracic Surgical Unit. John Radcliffe Hospital. Oxford.

Introduction

Transplantation involves taking a section of tissue or complete organ from its original natural site and transferring it to a new position. This term, like its synonym 'graft' was borrowed by surgeons from horticulture.

The term autotransplantation is used if an organ is transplanted into a different site in the same individual (a kidney with a long section of damaged ureter moved down to the iliac fossa). Autotransplantation refers to transplantation of an organ from one individual to another of the same species (one person to another). Xenotransplantation involves transplantation between different species (pigs to humans).

The first successful human kidney allograft was carried out between identical twins in Boston in 1954 by Joseph Murray and his colleagues.[1] It was met with spectacular success because it bypassed the immunological problems of rejection since it took place between one identical twin to another. For his pioneering work in transplantation, Joseph Murray shared the Nobel Prize for medicine in 1990.

Apart from results with identical twins the early days of transplantation were fraught with poor results due to the problems of rejection. While this is still a major problem, a number of factors, including the advent of modern immunosuppressive drugs such as cyclosporin have improved the results considerably (Table 1).

Table 1 - Results of whole organ transplantation

Graft survival 1 year 5 year
Kidney 85% 60-70%
Liver 80% 70%
Heart 80% 60%
Heart Lung 60% 40%

Ethical issues in transplantation

Transplantation of an organ or tissue from a dead to a living person presents no ethical problem per se. With few exceptions religious groups, Christian or non-Chnstian, have recognised the worth of such transplants. Questions tend to arise from factors other than the transplant itself. They include brain death, elective ventilation of potential donors, opting in or opting out of organ donation, the use of living related and unrelated donors, the sale of organs, the cost of transplantation in a world of finite resources, and the use of organs from animals. The use of foetal tissue in the treatment of conditions such as Parkinson's disease raises further issues.

This article looks at a few of these areas.

The Bible does not say a lot about transplantation although the Old Testament has a great deal to say about the moral responsibilities of the individual, and the controlling theme throughout the New Testament is that the Christian has to be Christ-like in his attitude and behaviour. Jesus is the model and example for the Christian. He left the glory of heaven because of his great love for us which led him to the cross. His command is for us to love one another as he has loved us. This attitude should help guide those who are involved in all aspects of transplantation, from approaching relatives to request organs, to surgeons who are involved in living and cadaveric organ donation. In cadaveric donation in particular, respect for the dead person and for the local theatre staff who may be new to the procedure is of paramount importance.

Brain death

It is impossible to discuss transplantation without considering brain stem death. The majority of cadaveric donor operations are carried out on brain stem dead patients, on life support machines (an interesting contradiction in terms). Dr Christopher Pallis, a respected neurologist and one of the leading writers in this field, defines death as follows:

'There is only one kind of death. The irreversible loss of the capacity for consciousness combined with the irreversible loss of the capacity to breath (and therefore sustain a spontaneous heartbeat)' [2]

Death can be due to intracranial or extracranial catastrophes, the latter leading to circulatory arrest which is only lethal if it lasts long enough for the brain stem to die. Thus alt death is brain stem death.

It is very important to emphasise the fact that brain stem death did not evolve to satisfy the needs of transplant surgeons, but in response to the increasing medical technology that is now part and parcel of all intensive care units. lf transplantation was superseded tomorrow by better treatment of organ failure, patients who are brain stem dead would still occur wherever intensive care units are established and ventilators would continue to be switched off.

The code of practice in the treatment of these patients was evolved at Harvard 1968, Minnesota

1971, and by the British Royal Colleges 1976 and 1979.[3,4]

The brain stem tests are as foolproof as anything in medicine can be. They involve three phases, three 'sieves' through which the patient must pass. Firstly the diagnosis must be established, in a patient in a coma on a ventilator. Secondly endocrine, metabolic causes and the effects of drugs and hypothermia must be excluded. Only then may the tests be done. These consist of tests of apnoea and brain stem reflexes. They are done by two clinically independent doctors who have been registered for five years or more and have experience in intensive care. The transplant team will not be involved at this stage. What if there is any doubt over these tests? It has been rightly said that 'Where there is doubt there is no doubt because one does not diagnose brain stem death'.

After the second set of tests has been done a death certificate can be issued, and turning the ventilator off at this stage is not withdrawing treatment and allowing the patient to die, but it is ceasing to do something useless to someone who is already dead. Keeping the patient on a ventilator at this point raises hope where there is no hope.[5]

Dr Martin Colebrook, a family doctor in Bedford wrote poignantly of his Son's death in a motor cycle accident:

'1 can only say that for us to sit with Nic while he was like that (on a ventilator) and then, when we felt it appropriate, to say 'God be with you' (the full meaning of 'goodbye') was infinitely preferable to witnessing him rattle into cardiopulmonary arrest. Our last impression is of him asleep rather than dead, and we are thankful.[6]

Health economics financial pressures

In health care systems throughout the world, cost effectiveness is becoming a major driving force for directing strategies of health care. The resources available for administering health care are finite, forcing difficult choices to be made in the use of finances, in the use of time, and ultimately in which patients are treated and in what way. As medical knowledge advances, public expectations rise and pressure mounts to provide more and more from the same resources.

Transplantation is often considered to be an expensive option, but it is often more cost effective than other treatment options, when the cost of drug bills, repeated hospital admissions, dialysis (for renal failure) and a high level of dependency in the community are considered.

In transplantation as in other branches of medicine one must remain realistic in the aims and offers given to patients. Much of medicine is palliation rather than cure, and transplantation is not without its problems and complications. It may be presented by the media as a panacea, but we do our patients no favours by perpetuating this error. In modern medicine a great disservice has been done by presenting death as a failure. Too often patients cling to life at all costs and one needs to learn to allow people to die with dignity, from end stage organ failure as much as from any other disease.

Health economics the shortage of available organs

The number of available organs falls short of those required. For example in the field of heart and lung transplantation 456 organs were transplanted in the United Kingdom in 1992 while the waiting list had grown to 750 patients. In 1993 in the USA, approximately 1 in 20 kidney patients, 1 in 5 liver patients, 1 in 4 heart patients and 1 in 3 lung patients died waiting for the appropriate transplant. Careful pre-operative assessment of the potential recipients is crucial to exclude those who are likely to develop such a cascade of post-operative problems that they become more incapacitated than before. For such patients transplantation would be an unfair option, both for the individual in question and also for other patients who would be denied a transplant.

When the appropriate parameters have been matched (blood group, size, tissue type, cytomegalo-virus status), there still may remain a choice of recipient. Who is transplanted first? Those waiting longest? The sickest, who on the one hand may not survive until the next opportunity, but on the other hand have a much higher mortality rate than the less sick patient? Should a 19 year old in his formative years be preferred to a fully trained 49 year old with dependent children? Does the society which pays for the transplant have the right to demand some return for its investment? All these issues are considered when making a final decision, and in each case the relative weights attached to each will vary; there are no right or wrong answers.

Living donors

The continuing limitations in the number of cadaveric organs, along with better results, have encouraged the taking of one organ from living donors where humans have two, such as kidney transplants. In renal transplantation for example, the 1 year graft survival is 93% and at 5 years 85% compared with 83% and 68% respectively for first cadaveric grafts.

Lobes of the liver or lung have also been used. A very particular example is the 'domino' procedure in heart-lung/ heart transplantation. Here the heart and lungs from a donor are transplanted into a recipient with a good heart and diseased lungs (prognostically better than just transplanting the lungs). The good heart from the recipient is then transplanted to another patient with a diseased heart.

All operations involve some risk to life, and only in exceptional circumstances can this risk be justified in a person who is both fit and healthy. Furthermore it puts intense pressure on the surgeon who is operating on a person who does not need an operation and will not benefit physically from it.

Some theologians speak of the principle of fraternal love or charity justifying the transplant as long as there is only limited harm to the donor. They distinguish between anatomical integrity (the physical integrity of the body) and functional integrity (the efficiency of the body).[7] Losing one kidney leads to a lack of anatomical integrity but not functional integrity because the efficiency of the body is not impaired. However loss of a cornea (for example) leads to a lack of functional integrity as well as anatomical integrity as the efficiency of the body is impaired by a loss of depth perception.

A living related donor (LRD) donates an organ (usually a kidney) to a blood relative. This offer should come from a stable relationship which should survive the emotional turmoil which accompanies the procedure. This may include the guilt of the recipient in putting the donor through a major operation, the feeling of superiority of the donor over the recipient, and most tragically, the guilt of the donor should the graft fail or of the recipient should the donor die from the operation (an estimated risk of 1 in 3000). Careful psychological and psychiatric assessment and counselling are crucial to allow these conflicts to be resolved satisfactorily. Yet if this donation comes as a free gift without any external pressure, with no financial or emotional incentive and without moral blackmail, it should surely be welcome.

Living unrelated donor transplantation is more complicated.

Strictly speaking spouses fall into this category as they are not blood related, and the tissue match is unlikely to be as close as a blood relative even if the blood group is the same. What about other donors? If the donation is unreserved, altruistic and devoid of pressure, financial or otherwise, is it to be condemned, or is it to be commended as following the principles of Christ's teaching?

'Greater love has no one than this, that he lay down his life for his friends' Jn 15:13.[8]

Legally, financial compensation remains limited to expenses arising from the operation, but how easy is this to enforce? Financial pressures are often minor in relation to others that can be brought to bear upon a person. In the UK the British Transplantation Society have a small supervisory committee of three wise persons' and they suggest that all proposed living unrelated transplants (apart from spouses) are discussed with that committee before proceeding with surgery.

The selling of organs is unethical, and the International Transplantation Society took a firm stand against this in I 986.[9]

Xenotransplantation

The consideration of the ethics of xenotransplantation consists of more than a simple analysis of whether or not it is immoral to use animals as a source of organs or tissues for transplantation. The moral acceptance of xenografting will for many people only be possible provided there is no plausible alternative source of transplantable organs or tissues. As discussed above there is little doubt that no initiative will yield additional donors in sufficient numbers to satisfy the demand that current waiting lists place on scarce resources.

The use of tissue from living donors will only ever provide the solution to a handful of patients. Mechanical or artificial substitutes have been suggested as another potential solution, and while great advances have been made, particularly with the artificial heart, the prospect of safe, efficient, reliable and implantable mechanical alternatives still appears to be some years distant.

What animals could or should be used if xenotransplantation became a reality? It is unlikely that primates will ever be used in large numbers since they are scarce, and the species most closely related to man are already endangered. In addition they have highly developed social structures closely resembling man's own. Such features effectively exclude them from serious consideration as mass donors. Far more likely is an animal that is already domesticated, bred easily in captivity and already used in large numbers for food. One possibility is the pig. It is hard to put forward coherent logical arguments against the use of such animals in a meat eating society. Only a few thousand extra animals would be required annually, and the number already killed for food in the United States alone exceeds 89 million each year. Consideration must also be given to the ability of recipients to accept animal parts. Some would say it is unnatural, but there are many things accepted now that only a few years ago were viewed as unnatural, such as anaesthesia and surgery. Support and counselling are required for transplant recipients already and additional support may be necessary.

If xenografting evolves into a realistic therapy, provision must be made for the welfare and health of animals bred, raised and killed to supply organs and tissues to humans. It is interesting to note that Jewish and Islamic leaders agree that organs from pigs could benefit their groups even though they are not permitted to eat the flesh.

Conclusion

Transplantation is here to stay and most members of the Christian community as well as other religious groups welcome it. However there are many different ethical questions that need to be discussed and it is important that all members of the medical profession are aware of them. For those of us in this field or thinking of entering it we should have considered them in greater detail and approach them in the way that we believe Christ would have done.

References
  1. Murray J E, Merrill J P. Harrison J H Kidney transplantation between seven pairs of identical twins. Ann Surg 1958; 148:343
  2. Paltis C. Brain death, the evoiution of a concept. Chapter 6 in Morris P J Ed. Kidney Transplantation Principles and Practice W B Saunders Philadelphia. 4th edition for publication July 1994
  3. Conference of Medical Royal Colleges and their Faculties (UK) BMJ 1976;1:1187
  4. Department of Health and Social Security. The removal of cadaveric organs for transplantation a code of practice HMSO, London 1979
  5. Searle J F. Brain death. Hospital Update I 980 359-368
  6. Colebrook M. Transplantation: a cost/benefit balance or an ethical issue. JCMF 1985;122:8-14
  7. Ashley B M, O'Rourke K D. Reoonstruoting Human Beings. In Health care Ethics, a theological analysis. CHA Publishing St Louis 1989. 3rd Edition p306
  8. Wing A J. Human Kidneys for sale. JCMF 1989; 138:2-5
  9. Morris P J. Presidential address to the Transplantation Society Helsinki 1986
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