Xenotransplantation

Xenotransplantation involves the use of live, non-human animal cells, tissues and organs in human patients. The practice is now likely to become more widespread in clinical research. In the USA, clinical research is subject to FDA guidelines as interpreted by Institutional Review Boards (IRB) and Animal Research Committees (ARC). An Advisory Committee within the Department of Health and Human Services is likely to coordinate any modification of guidelines and practice, following the outcome of future xenotransplantations. The ethical guidelines and concerns regarding neural xenotransplantation can be examined with regards to issues that involve general xenotransplantation and those which specifically touch upon neural xenotransplants.

Ethical Concerns Regarding Xenotransplantation

It should be noted that while biological phenomena are studied and harnessed, ethical considerations are arrived at and practiced largely on basis of opinion. Ethical issues have a certain fluidity in time, and anomalous or incongruous ethical circumstances can arise. Ethical concerns of xenotransplantation include the risks to the general public; risks of cross over infections from animals to patients; how informed consent is possible with such indeterminate risks; issues of justice and the availability of procedures, based on need and not finances; animal welfare issues; religious morals; and the psychological or social issues created by placing animal organs in human patients. Because of public health concerns about long-term retro virus infection, life-long monitoring of patients is anticipated. This review will focus on only a few questions and provide appropriate points of discussion to provoke further examination of the issues.

Is There a Need for Xenotransplantation?

Q: Is there a need for xenotransplantation i.e. whether the current and future needs for organ transplants can be met by other means?

Currently much human potential transplant material is lost to use in two principal ways. First, not every member of the population that considers human organ-doning acceptable carries a doner card. Second, the wishes of the next of kin can supersede those of the recently deceased, preventing organ-doning in circumstances where there is ambiguity in determining exactly what the organ donor was permitting. It is possible to counteract the above by a) moving from the current "opt in" organ donation scheme to an "opt out" one, and b) raising the status of the deceased’s wishes over those of his or her next of kin. The above strategies, though controversial in their own right, might well be sufficient to negate much of the current demands. Given this, the question arises as to whether or not to pursue the idea of minimizing xenotransplantation through the use of volunteered human organs.

What Are The Risks of Infection?

Q: What about the risk of infection between animal-to-human transplantations?

To guard against potential animal-to-human infection, recommended guidelines for human clinical trials address four major areas.

1. Procedures must be developed in order to screen source animals for the presence of infectious organisms and consideration of the development of specific pathogen-free animals.
2. Secondly, continued surveillance of patients and periodic surveillance of their families, health care worker, and others to check for evidence of infectious disease is important.
3. Thirdly, an establishment of tissue banks containing tissue and blood samples from source animals and patients should be created.
4. Lastly, there should also be an establishment of national and local registries of patients receiving xenotransplants, with a special effort to coordinate with international registries and data bases.

Is Genetic Modification Ethical?

Q: Is it ethical to use, to modify genetically and to breed animals so that their organs may be used for transplantation to humans? Whether the issues are different from those involved in the breeding of animals for food? Whether different issues apply for different animals?

There is no difference in the ethics of breeding animals for food as opposed to producing them specifically for organs for transplantation. That is not to say that it is right or wrong, just that when debating ethical considerations over the use of animals it would be illogical to use different criteria for the different uses to which the animal is to be used, given that the fate of the animal in each case is identical (i.e. that it is sacrificed).

Turning to the question of genetic modification, there is little difference between this type of creation of new strains and breeding. Though the mechanism for the former is undertaken typically through the addition of new DNA, while the latter is through the generational editing of DNA: both practices alter the animal’s genetic make-up. However, this is not to say that there are no ethical concerns, but that such concerns have their counterparts on either side of the breeding/genetic-modification fence. (For instance, what right do humans have for killing animals, irrespective of whether it is for food or xenotransplantation?) Clearly to create a genetically modified animal that suffered would not be ethically justifiable, as equally would it be to breed a creature that suffered. Indeed, it is of concern that some breeds of pet are more prone (as a result of their breeding) to disease and discomfort. Similarly, some agricultural animals have been bred for such a level of production that arguably suffering is either taking, or is close to taking, place. In short, while genetic engineering is ethically no more or less of concern than breeding, there are still ethical considerations to take into account regarding xenotransplantation.

Finally, there is the question of whether different issues apply for different "animals" (presumably "species" as opposed to agricultural or biomedical animals). Here the answer is yes: different species do warrant different ethical considerations. This view is largely adopted by scientists and the public. The public is more concerned over the laboratory use of feline and canine mammals, than rats, and more over rats than the fruit fly, Drosophilia. Given the above, the greatest ethical concern is the use of primates. This is primarily due to their similarity, evolutionary proximity, to ourselves and to a lesser extent to a perceptual awareness. This issue is currently an issue of controversy today and more discussion needs to take place regarding the ethics in experimenting on primates.

Ethical Concerns Specific to Neural Xenotransplantation

Ethical guidelines for neuro-xenotransplantation are similar. Animal studies have shown that a preparation containing fetal mesencephalic dopaminergic neurons induce a long term recover of motor deficits. Clinical trials are being run, in the hope of therapies for Parkinson’s and Huntingdon’s disease. The Network of European CNS Transplantation and Restoration (NECTAR) addressed the fear that the consequent increase of demand for fetal neural tissue might increase restore to elective abortion, and even to elective conception with this in view. NECTAR guidelines were adopted in Milan in 1992 and published in 1994 with a commentary. The recommendations involve tissue may be taken only from dead embryos of fetuses, whose life may not artificially be prolonged to yield usable material. Neither the decision to terminate nor the timing and method of termination may be influenced by the transplant interest; and maternal consent must not be sought for the second until she has already consented to the first. The popular fear of transplanting of whole brains, or of "personality transfer", is excluded by the rule that only suspended cell preparations or tissue fragments may be transplanted.

Summary

The government has proposed a ban on human clinical trials until safety and efficacy can be assured. But the question arises: what assurance can there be without trial? As a result, trials are conducted abroad and, it appears, some successfully. In fact there can be no innovation without risk; there are limits to what can be assured. If the risk is simply personal there is no moral reason why a patient, suitably advised, should not be free to accept it. It the risk were social, there are grounds for restraint.

The concept of neural xenotransplantation has come to significant attention largely because of the public interest in the amelioration of degenerative diseases of the central nervous system, particularly Parkinson’s disease. Ethical problems raised by transplantation have been reviewed in a number of forums and numerous additional articles on the subject. The above ethical discussion provides a basis for continued discussion regarding the need for understanding the background of ethical and policy questions as presented here. Neural xenotransplantation may be beneficial and feasible if ethical guidelines and quantitative requirements can be met.