Xenotransplantation: overview of the key issues

Organ transplantation is the method of choice for the treatment of many diseases involving failure of organs such as heart, liver or kidney. However, the success of the procedure and falling donor rates have resulted in a worldwide shortage of organs for allografts (human donor to human recipient). Xenotransplantation (transplantation of organs from other species to humans) is now seen as a solution to the problem. Several issues have to be considered in choosing the appropriate species, and on the basis of physiological, biological and ethical considerations the pig would seem to be the most suitable donor, a further advantage being that they can be genetically manipulated to make more suitable donor 'transgenic' pigs. "Medicine is on the verge of its next great revolution — xenotransplantation" is the first statement made by Cooper and Lanza in the preface to their book XENO: the Promise of Transplanting Animal Organs Into Humans, and the recent announcements of successful pig cloning by three independent centres indicate that this revolution may be here sooner than anticipated.

The first issue addressed by the authors is the number of potential beneficiaries of xenotransplantation. Although the number of patients on current transplantation waiting lists is often cited as a case for xenotransplantation, Cooper and Lanza argue that these figures may be a gross underestimation of potential beneficiaries, as to become a candidate on these lists often requires the chance of a successful transplant. If borderline candidates who are currently excluded were to be included, the number of potential recipients would at least double. The authors then systematically examine both the positive and negative aspects of xenotransplantation with ample detail and in a very readable style. They present many hypothetical situations to emphasize their arguments in a narrative form that could well have been written by Robin Cook, who contributed the foreword to this book. The immunology of xenograft rejection is a dynamic field, and Cooper and Lanza do a creditable job of describing this in a way that allows a non-scientist to appreciate the key issues.
Allotransplantation techniques have progressed to the stage at which satisfactory graft acceptance and survival can be achieved by judicious choosing of donor and recipient coupled with appropriate patient management and immunosuppression. In contrast, the proposed use of pig organs has reintroduced several immunological problems that have been solved for allotransplantation. The principal immunological barrier is the immediate rejection of pig organs by a process called hyperacute rejection, and only after this barrier is overcome can we fully appreciate and study the subsequent immune responses. This barrier will realistically be crossed only by genetic engineering of the donor pig.
Genetic engineering has brought both promise and controversy to many potential medical treatments, and xenotransplantation is no exception, particularly as it involves not only the introduction of human genes into the pig germ line, but also cloning of pigs to inactivate certain genes and allow acceptance by the human immune system. The authors present a frank discussion and valuable information that will allow the reader to understand several of the ethical and potential legal issues associated with genetic engineering and xenotransplantation. An important concern with the production of a genetically engineered pig that will be tolerated by the human immune system is the release of pig pathogens, particularly retroviruses, which could lead to epidemics. In the trials to date no transmission of infectious disease has been reported, and the authors conclude their discussion of this issue by saying that "the likelihood of endangering the public health by xenotransplantation is remote".
A significant issue raised by Cooper and Lanza is what criteria will be used to choose human recipients once clinical trials commence. This is particularly relevant, especially if one considers that xenotransplantation has already lead to the "unfortunate" deaths of human patients, and that it is likely that the early trials will not lead to long-term graft survival. It should be borne in mind that the earliest allotransplants were also unsuccessful, but that each transplant provided valuable information that eventually led to success. It is anticipated that xenotransplantation will follow the same path, with ultimate success built on previous failures. Indeed, the current state of xenotransplantation can be likened to the initial allotransplants, as the introduction of clinical allotransplantation as a new medical procedure at the present time would almost certainly raise similar objections and concerns.
Throughout their book Cooper and Lanza draw attention to the fact that xenotransplantation has to face many hurdles before it becomes a clinical reality, not least of which is public awareness and acceptance. Indeed, many of those involved in xenotransplantation research have consistently voiced concerns about the necessity of informing the public about the various issues of xenotransplantation. However, although this requires educated debate of all the relevant issues, it is often difficult for the 'non-expert' to know where to obtain sufficient relevant information to form a judicious opinion. This well-timed book goes a long way to providing such information.

Category: 30. Xenotransplantation