Prospects for Xenotransplantation
Scientific Aspects and Ethical Considerations

Part Two

Anthropological and Ethical Aspects

Besides the scientific and technical aspects of xenotransplantation described in the first part of this document, anthropological and ethical considerations are alsoinvolved.

The purpose of this second part is to explore these considerations, albeit by way of a brief overview.

Preliminary issues

In addition to the problems raised by every transplant, it seems us that there are three issues specifically related to xenotransplantation: 1) the acceptability of man's intervening in the order of the creation; 2) the ethical feasibility of using animals to improve the chances for survival and well-being of human beings; 3) the possible objective and subjective impact that an organ or tissue of animal origin can have on the identity of the human recipient.

Human intervention in the created order

7. To begin with, we would like to deal briefly with a fundamental question that, generally, is posed by the different religious traditions, albeit with different accents: this concerns the possibility itself that man may licitly intervene in the realities that exist in the universe in general and, more particularly, in those things that concern animals.

In view of the more specifically theological nature of such a question, we deem it useful to offer a short summary of the Catholic position on this question, applying the language and the methods proper to theological anthropology.

By what right can humans, whom God created as female and male, and whose full human dignity must be recognized at every stage of life, intervene in the created order, perhaps even modifying some of its aspects? What criteria must be adopted and what limitations must be introduced?

From imagery of the account of creation "in six days"50, it is evident that God established a hierarchy of values among the various creatures. Moreover, this hierarchy also emerges from a rational consideration of the transcendent richness and dignity of the human person.

Man, created "in the image and likeness of God", is placed at the centre and at the summit of the created order, not only because everything that exists is intended for him, but also because woman and man have the task of co-operating with the Creator in leading creation to its final perfection. "Be fruitful and multiply, and fill the earth and subdue it" (Gen 1:28): this is the mandate that God gives to human beings, "dominion" over the created order, in his name. In this regard, Pope John Paul II writes in his encyclical "Laborem Exercens": "Man is the image of God partly through the mandate received from his Creator to subdue, to dominate, the earth. In carrying out this mandate, man, every human being, reflects the very action of the Creator of the universe"51.

This, therefore, is the deepest meaning of the action of man in relation to the created universe: certainly not that of arbitrarily "lording it over" the other creatures, reducing them to humiliating and destructive slavery in order to satisfy any whim that he may have, but to guide, through his responsible work, the life of the creation towards the authentic and integral good of man (the whole man and every man).

Certain documents of the Second Vatican Council had already affirmed this truth. In "Lumen Gentium", for example, we read: "Therefore, by their competence in secular disciplines and by their activity, interiorly raised up by grace, they (the laity) must work earnestly in order that created goods through human labour, technical skill and civil culture may serve the utility of all men according to the plan of the Creator and the light of his Word. May these goods be more suitably distributed among all men and in their own way may they be conducive to universal progress, in human and Christian liberty"52. Also the decree of the Second Vatican Council on the apostolate of the laity takes up this idea when it asserts that "this natural goodness of theirs (of the realities that make up the temporal order) receives an added dignity from their relation with the human person, for whose use they have been created"53.

In summary, therefore, there should be a reaffirmation of the right and duty of man, according to the mandate from his Creator and never against the natural order established by him, to act within the created order and on the created order, making use as well, ofe other creatures in order to achieve the final goal of all creation: the glory of God and the full and definitive bringing about of His Kingdom, through the promotion of man. The words of St. Irenaeus of Lyons still ring out with all their truth: "Living man is the glory of God and man's life is the vision of God"54.

The Use of Animals for the Good of Man

8. For a theological reflection that will help to formulate an ethical assessment on the practice of xenotransplantation, we do well to consider what the intention of the Creator was in bringing animals into existence. Since they are creatures, animals have their own specific value which man must recognize and respect. However, God placed them, together with the other nonhuman creatures, at the service of man, so that man could achieve his overall development also through them.

It should be noted that this role of "service" rendered to man by other creatures occurs in different ways according to the cultural advances of humanity. Limiting ourselves to scientific and technological progress in the biomedical field, the service of animals to man represents a totally new application in xenotransplantation, which, therefore, in principle is not in conflict with the order of the creation. On the contrary, xenotransplantation represents for man a further opportunity for creative responsibility in making reasonable use of the power that God has given to him. Furthermore, even if one limits oneself to a purely rational analysis, without desiring to make use of theological reasoning, one can reach the same conclusions on a practical level.

A simple look at humanity's long presence on the Earth is sufficient to show an irrefutable fact clearly: it is man who has always directed the realities of the world, controlling the other living and non-living beings according to determined purposes. It is moreover in its relationship with man that the axiological measure (moral value) of every existing reality is revealed in a universal harmonic and orderly design that indicates all the fullness of the sense of reality.

In particular, man has always made use of animals for his primary needs (food, work, clothing, etc.) in a sort of natural "cooperation" that has constantly marked the different stages of progress and the development of civilization. Such a position of "excellence" is a witness to and also demonstrates the ontological superiority of mankind over the other beings of the earth; this superiority is founded on the very nature of the human person, whose rational and spiritual dimensions place man at the centre of the universe, so that he may use its existing resources (including animals) in a wise and responsible manner, seeking the authentic promotion of every being.

To analyse more deeply the point under discussion, two issues of an ethical nature must be addressed. First, there is the question of the use of animals in order to improve man's chances of survival or to improve his health; the obvious starting point here is the particular way in which one views the relationship between man and animals55. Second, there is the question of the acceptability of breaching the barrier between animal species and the human species.

With regard to the first issue, contemporary thinking includes two opposing and extreme viewpoints56. There are those who believe that animals and man have equal dignity and those who believe that animals are totally at the mercy of the man. In the former case, the use of animals is seen as speciesism or tyranny of man over animals. Even reducing human suffering could not justify the use of animals unless the contrary possibility was also allowed. In the latter case, man can use animals arbitrarily without being limited by ethical considerations.

9. From our point of view, supported by the biblical perspective that asserts, as stated above, that man is created "in the image and likeness of God" (cf. Gen 1:26-27), we reaffirm that humans have a unique and higher dignity. However, humans must also answer to the Creator for the manner in which they treat animals. As a consequence, the sacrifice of animals can be justified only if required to achieve an important benefit for man, as is the case with xenotransplantation of organs or tissues to man, even when this involves experiments on animals and/or genetically modifying them.

However, even in this case, there is the ethical requirement that in using animals, man must observe certain conditions: unnecessary animal suffering must be prevented; criteria of real necessity and reasonableness must be respected; genetic modifications that could significantly alter the biodiversity and the balance of the species in the animal world must be avoided57.

The theological and moral point of view sees no substantial problem in the utilization of different animal species (nonhuman primates or nonprimates), but leaves open the question of differing levels of sensibilities between animals of different species and that of equilibrium among species and within a species.

The point should also be made that Catholic theology does not have preclusions, on a religious or ritual basis, in using any animal as a source of organs or tissues for transplantation to man58. The question of the acceptability of an animal organ, - once it has been established that personal identity is not affected by xenotransplantation, and once all the general ethical requirements of transplantation have been met - becomes cultural and psychological. Therefore, it may be possible to overcome initial misgivings by providing the necessary support in an effective manner.

Xenotransplantation and the Identity of the Recipient

10. In addition to considerations of a theological nature, and perhaps even before these are made, an ethical evaluation of the practice of xenotransplantation must be measured against current anthropological findings, especially that branch of philosophical anthropology that deals with personal identity. Any ethical appraisal of xenotransplantation must ultimately address the question of whether the introduction of a foreign organ into the human body modifies a person's identity59and the rich meaning of the human body? And if the answer is affirmative, one must ask up to what point is such modification acceptable.

Certainly, the concept of "personal identity" is replete with implications and subtleties of meaning, given the different contributions of philosophy and science60. More concisely, in keeping with the scope of this document, we can indicate personal identity as the relation of an individual's unrepeatability and essential core to his being a person (ontological level) and feeling that he is a person (psychological level). These characteristics are expressed in the person's historical dimension and, in particular, in his communicative structure, which is always mediated by his corporeality.

It must be affirmed, then, that personal identity constitutes a good of the person, an intrinsic quality of his very being, and thus a moral value upon which to base the right and duty to promote and defend the integrity of the personal identity of every individual.

We can therefore conclude that, in general, the implantation of a foreign organ into a human body finds an ethical limit in the degree of change that it may entail in the identity of the person who receives it.

11. Such a modification, as already noted, affects the historical dimension of the person, and thus the individual's communicative structure as mediated by his corporeality.

In light of a renewed appreciation of the body and of the symbolic understanding of it that much of contemporary anthropology offers, it should be observed that not all organs of the human body are in equal measure an expression of the unrepeatable identity of the person. There are some which exclusively perform their specific function; others, instead, add to their functionality a strong and personal symbolic element which inevitably depends on the subjectivity of the individual; and others still, such as the encephalon and the gonads, are indissolubly linked with the personal identity of the subject because of their specific function, independently of their symbolic implications. Therefore one must conclude that whereas the transplantation of these last can never be morally legitimate, because of the inevitable objective consequences that they would produce in the recipient or in his descendants61, those organs which are seen as being purely functional and those with greater personalized significance must be assessed, case by case, specifically in relation to the symbolic meaning which they take on for each individual person62.

12. The questions and issues connected with the defence of the personal identity of the recipient patient is a central point not only for philosophical anthropology but also for moral theology, as is demonstrated by certain official pronouncements of the Magisterium on xenotransplantation, which see this as one of the fundamental criteria for the moral legitimacy of xenotransplantation. First Pius XII (Address to the Italian Association of Corneal Donors, Clinical Ophthalmologists and Legal Medicine, 14 May 1956), and more recently John Paul II (Address to the Eighteenth International Congress of the Transplant Society, 29 August 2000, n. 7), have clearly upheld the moral legitimacy, in principle, of this therapeutic procedure, on the condition that "the transplanted organ does not affect the psychological or genetic identity of the person who receives it" and "that there exists the proven biological possibility of carrying out such a transplant with success, without exposing the recipient to excessive risks".

We may observe here that together with the defence of personal identity, these pronouncements of the Magisterium indicate a second criterion for the moral legitimacy of xenotransplantation: health risk. We shall discuss this in greater detail shortly.

With regard to all other issues, from the standpoint of moral theology, the ethical conditions required for every other kind of transplant apply also for xenotransplantation63.

Bioethical Issues

Further investigation and clarification is needed for a wider bioethical analysis. The ethical evaluation of the practicability of xenotransplantation, in light of the current situation as summarized in the first part of this document, requires the consideration of a whole series of factors, some of which are derived from the general moral norms valid for all transplants, and others of which are morespecifically related to xenotransplantation64.

The Health Risk

13. As previously stated, one of the fundamental ethical questions that should be examined when judging the legitimacy of xenotransplantation is that of the health risk involved in such procedures. This risk is dependent on various factors which cannot always be predicted or assessed. Before going on, therefore, it may be useful to recall some general aspects of the ethics of risk.

Risk -- understood as an unwanted or damaging future event, the actual occurrence of which is not certain but possible65 -- is defined by means of two characteristics: the level of probability and the extent of damage. The probability of the occurrence of a certain damaging event in particular circumstances can be expressed as a risk percentage or as a statistical frequency. Furthermore, the presence or absence of certain chance factors of risk can sometimes alter the probability that a certain event will take place. The extent of the damage, in contrast, is measured by the effects that the event produces. Naturally, a very probable risk is easily tolerated if the extent of damage associated with it is very small; on the contrary, a risk that causes a high level of damage, however improbable, gives rise to much greater concern and require greater caution.

It is important to distinguish between a probable event (albeit with varying degrees of probability) and an event that is only hypothetical; this latter is an event which is not theoretically impossible but which is so improbable as to require no change in behaviour or choices.

Together, these two criteria - probability and extent of damage - define the acceptability of the risk, as reflected by the risk/benefit ratio. Only when a risk can be concretely assessed it is possible to apply criteria for evaluating its acceptability.

Lastly, it is necessary to distinguish acceptability from what we can define as the acceptance of the risk, as defined by the reaction of the individual or of the general public to the existence of the risk. This is a response that has a significant subjective component, one which is not always completely thought out and which is influenced by culture, by the information available and how it is understood, by the way in which the information itself is communicated, and by common sensibilities66.

In the absence of data that allow a reliable assessment of such a risk, greater caution should be used; this does not necessarily mean, however, that a total moratorium should be placed on all experimentation. Indeed, to move from ignorance to knowledge, from the unknown to the known requires the exploration of new approaches which in all likelihood, especially during initial experimental stages, will not be without risks, at least potentially. In this situation, therefore, the imperative ethical requirement is to proceed by "small steps" in the acquisition of new knowledge, making use in experiments of the least possible number of subjects, with careful and constant monitoring and a readiness at every moment to revise the design of the experiment on the basis of new data emerging.

It is important to consider the distinction between risk assessment and risk management. To achieve an ethical assessment, both elements must be carefully examined.

14. This general discussion of the ethics of risk must now be applied to the specific case of xenotransplantation.

First of all, we note that there are issues connected with xenotransplantation, such as the probability of rejection and the increase in the probability of infection because of immunosuppressive therapies, about which some degree of knowledge already exists, although further study is necessary. The data which the scientific community already possesses, together with new data being gathered, can help to establish the threshold of risk that must not be crossed if a transplant operation to be considered morally acceptable.

More complex and uncertain is the assessment and evaluation of risks connected to one specific aspect of xenotransplantation: the possible transmission to the recipient of infections arising from the xenotransplant (zoonoses) by known or unknown pathogenic agents which are not harmful to the animal but which are possibly dangerous for man. Such infections could escape detection, with the consequent possibility of the spread of the infection to those having close contacts with the patient, leading eventually to its being spread to the entire population.

Since clinical experience of xenotransplantation is quite limited and certainly insufficient to provide reliable statistics on the realprobability of occurrences and spread of infections, any decision concerning clinical development of the new therapy can only be based on hypothesis. There is, therefore, an ethical requirement to proceed with the greatest caution.

When the moment for clinical application of xenotransplantation arrives, it will be necessary to select patients carefully, based on clear and well-established criteria67, and to monitor the patient very closely and constantly. One must also contemplate the possibility of placing the patient in quarantine to prevent the epidemic spread of an infection. Arrangements for some kind of monitoring of those having close contacts with patient should also be made.

Moreover, during the experimental phase of clinical trials, patients should agree not to procreate because of the possible risk of genetic recombination that could affect the patient's germ cells. Sexual abstinence would also be necessary to avoid the venereal transmission of possible viruses.

In the clinical application of xenotransplantation, psychology should also play an important role. It should address the probable repercussions for the recipient's psyche of the (e.g. because of the modification of one's "bodily schema") arising from the acceptance of a foreign organ68, especially when it comes from an animal69. In the post-transplant stage, psychology must also provide clinical support the for the patient in the process of integration.


15. The use of organs from engineered animals for xenotransplantation raises the need for certain reflections on transgenesis and its ethical implications.

The term "transgenic animal" is used to indicate an animal whose genetic make-up has been modified by the introduction of a new gene (or genes). In contrast, the term 'knock out' is used to designate those animals in which a given endogenous gene (or genes) is no longer expressed. In either case, such animals will express particular characteristics which will be transmitted to the offspring.

As we have already observed, the possibility of effecting out such genetic modifications, using genes of human origin as well, is morally acceptable when done in respect for the animal and for biodiversity, and with a view to bringing significant benefits to man himself. Therefore, while recognizing that transgenesis does not compromise the overall genetic identity of the mutated animal or its species, and reaffirming man's responsibility towards the created order and towards the pursuit of improving health by means of certain types of genetic manipulation, we will now enumerate some fundamental ethical conditions which must be respected:

  1. Concern for the well-being of genetically modified animals should be guaranteed so that the effect of the transgene's expression -- possible modification of the anatomical, physiological and/or behavioural aspects of the animal -- may be assessed, all the while limiting the levels of stress and pain, suffering and anxiety experienced by the animal;
  2. The effects on the offspring and possible repercussions for the environment should be considered;.
  3. Such animals should be kept under tight control and should not be released into the general environment ;
  4. The number of animals used in experiments should be kept to a bare minimum;
  5. The removal of organs and/or tissues must take place during a single surgical operation;
  6. Every experimental protocol on animals must be evaluated by a competent ethics committee.

Informed Consent

16. In the ethical discussion on xenotransplantation, the subject of informed consent also deserves special attention70.

Given the animal source of the organs which will be transplanted, this issues concerns only the recipient and, secondly, his relatives. At the outset the recipient should be given every information regarding his pathology and its prognosis, the xenotransplant operation and subsequent therapy, and the probability of success and the risks of rejection. Special attention should be paid to making sure that the patient is informed about the real and hypothetical risks of zoonoses, in light of current data, and about the precautions to be adopted in the case of infection (in particular the possible need for quarantine, which involves avoiding physical contact with others while the risk of contagion is present). The patient must also be informed about the need to remain under medical supervision for the rest of his life, so that the necessary constant monitoring following the transplant may be carried out. In addition, adequate information on possible alternative therapies to xenotransplant therapy should not be withheld.

This informed consent on the part of the patient should be understood as personal. For this reason, minors and those unable to give valid consent are to be excluded from the experimental phase.

However, if a patient incapable of giving valid consent should find himself in a previously unforeseen situation where there is danger of imminent death, recourse may be made to a legal representative (e.g. in the hypothetical case of a life-saving xenotransplant as a temporary solution for a patient in a coma), provided that the medical procedures to be used offers a reasonable hope of benefit for the patient.

The patient's relatives should also be informed about what the transplant could entail regarding their contact with the patient and about the possible risks of contagion should an infection, as mentioned above, set in. In a strict sense, however, consent cannot be requested from them, since it is the patient who is ultimately responsible for the choices concerning his own health.

Allocation of Health Care Resources

17.Xenotransplantation certainly represents a form of possible treatment requiring a great outlay of both health care resources and economic resources71. For this reason, some people have expressed doubts about its ethical validity; given the large amounts of resources that it would take away from the other forms of therapeutic treatment and from other area of research, they consider both the uncertainty about its success and the risk entailed to be excessive. Faced with these doubts, it is important to remember that, even taken into due consideration the costs-benefits balance, the huge amount of health care resources used in this case is justified by the urgent need to try to save the lives of so many patients who would otherwise have no chance of survival.

It should also be added that as long as xenotransplantation on man remains at an experimental stage it should not be subject to the criteria applied to treatment in strict sense; rather it should be evaluated according to the criteria used for trials. Therefore, the foreseeable collective benefits that it may accrue in the future should also be taken into account. We do well to recognize here that the research into xenotransplantation which has taken place so far has also brought about greater medical knowledge in the area of allotransplantation.

Patentability and Xenotransplantation

18. Research on xenotransplantation has hitherto in large measure been carried out largely by private pharmaceutical companies which have committed substantial economic resources to this endeavour; they have also been providing financing to public institutions for the purpose of obtaining better therapeutic results. It is therefore reasonable for them to expect an economic return on the investment made; one of the possible ways to do this is by acquiring patents.

From a formal point of view, there is no technical or legal obstacle standing in the way of the patenting genetically engineered animal organs intended for transplants72. It should be emphasised however be that the norms drawn up by the European Community to regulate this matter could not, at the time they were being drafted, take into account the use of such organs for transplant from animal to man, since this therapeutic procedure had not yet been accomplished in clinical practice. We therefore stress that, given the extraordinary financial commitment that has been made, now is the time to reconsider - or rather to be more precise about - the specific norms that apply.

We are aware of the broad debate underway on the basic question of whether the possibility itself of patenting living beings (even though genetically modified) or parts of them, especially when they contain genetic elements derived from humans (as is the case with animal organs genetically engineered for xenotransplantation into man), is ethically acceptable. We are also aware that there is a difference between a "discovery" (which cannot be patented) and an "invention" (which can be patented). Although it is our view that the transgenic animal as such - and all the more when they are used for transplantation into man - should be considered "nonpatentable", we nonetheless believe that it is not the purpose of present document to address this complex question directly.

Here, we shall limit ourselves to emphasising that, whatever answer may be given to this basic question, it is always necessary - as a bare minimum - to guarantee respect for the fundamental right of every person to equitable access to the health care they may be needed, without discrimination and without being impeded by excessive costs. This applies above all else to accessibility to treatment. This objective - in the hypothetical case of patents connected with xenotransplantation, a procedure which should be viewed from a therapeutic standpoint - can be reached by making appropriate legal requirements apply (for example, the introduction of compulsory licences), thus allowing "production" at accessible prices73 which would hopefully be controlled by supranational body specifically set up for this purpose.

Practical Guidelines

19. Bearing in mind all that has been said above, we can now present a practical approach which will guide the path of research and development in the area of xenotransplantation as applied to man.

Regarding the xenotransplantation of solid organs, it is of course necessary that pre-clinical experiments (from animal to animal) should continue for as long as scientists should require and until repeatable positive results are obtained, results which are considered sufficient to allow trials on man to begin.

When the moment arrives, it will be ethically correct, respecting the rules of informed consent indicated above, to involve initially only a restricted group of patients, patients who cannot be chosen - in the given circumstances - for allotransplantation (whether because of waiting lists or individual counter-indications), and for whom no better alternative treatment is available.

A commensurate moral imperative is that of ensuring careful and detailed monitoring of the individuals who receive a xenograft, a situation which could foreseeably continue for the rest of patient's life, watching for any sign of possible infection caused by known and unknown pathogenic agents.

In addition, every experimental clinical trial should be carried out in highly specialised centres with proven experience in pre-clinical pig-to-primate models; these centres should be authorised and supervised by the competent health care authorities.

The results thus obtained, if unequivocally positive, would constitute the basis for extending the practice of xenotransplantation, making it an accepted surgical therapy.

20. The questions and issues related to xenotransplantation have implications of a very wide social character. There is thus an ethical need to acquire correct information on the topics of greatest public interest with regard to the potential benefits and risks. This information should be communicated to as large a segment of the public as possible. Moreover, by means of debates and public discussions in small and large groups, society itself, through its representatives, should help to identify the conditions under which they would find it acceptable to invest resources and hope in this new therapeutic approach, in light of the scientific uncertainties which are still present and the urgent need to increase the availability of organs which can be transplanted.

A serious ethical commitment on the part of scientists should not neglect to explore therapeutic paths which may represent alternatives to xenotransplantation, such as seem to be promised by many recent discoveries in the field of genetics, as in a longer period the therapeutic use of adult stem cells.

21. With respect to the specific fields of health-related policies and legislation on matters of xenotransplantation, it is our heartfelt hope that the considerations offered in the present document will provide a useful point of reference for all those who -- at an international, national, regional and local level -- are responsible for leading society. Many countries have already developed guidelines to regulate this complex sector, offering helpful operational directives74.

On our part, we do not believe that this document should enter into procedural political-legislative matters. We therefore limit ourselves to emphasizing the importance and desirability that a substantial convergence of international legislation in this area should be achieved as soon as possible, by means of a genuine coordination at the different levels. On the one hand such legislation must provide rules for the continuation of scientific research, guaranteeing its validity and safety; on the other hand it must watch over the health of the citizens involved and the potential risks (especially infective) connected with xenotransplantation. Furthermore it must offer criteria for organizing the necessary information campaigns aimed at the entire population.

We conclude this document with the sincere hope that the effort made on this study by those who have participated in it -- scientists, jurists, theologians and bioethicists -- will represent a concrete contribution to the development of the discussion on the important theme of xenotransplantation. May it also be seen as a further expression of the close attention which the Catholic Church pays on problems related to human disease and suffering.

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