American Journal of Law & Medicine

Ethical and legal issues in technology: xenotransplantation.

I. TECHNOLOGY: BENEFITS V. RISKS

The development and application of technologies will arguably be the major driving force for the evolution of world society in the first part of our new century. In medicine, agriculture, material science, communications and a host of other areas, new technologies promise unimaginable changes in our lives. And yet, in the midst of the euphoria surrounding this rush of invention, there is concern. When asked, people often say they are scared of what they do not know and scared of today's pace and power of invention. Putting aside the voice of the modern Luddite, it appears that while few want to stop the rush toward more and better technology, there is apprehension about the potential risks of the new technologies--risks that have not been sufficiently considered.

Among these concerns are the legal repercussions of this technologically enabled time. Today's legal concepts, procedures, and structures are insufficient to keep pace with technological advance. Our legal systems need to develop to ensure that technology serves as many people as possible and disservices as few as possible. As Albert Einstein said: "Never forget this, in the midst of your diagrams and equations: concern for man himself and his fate must always form the chief interest of all technical endeavors."(1)

This article discusses the exceedingly difficult decision-making processes, legal and otherwise, that must balance the potential benefits and the public's feelings and fears. In doing so, we recognize the need to assess the benefits and risks of technologies, even if those benefits and risks are ill-defined. We must learn to bring stakeholders together so that a consensus can be reached on how to develop and apply a given technology. We must respect each stakeholder for his or her individual opinions and obligations.

In many ways, such a discussion revisits the age-old issue of societal vs. individual rights. For any given technology, there will be those who stand to benefit significantly and others that will gain nothing despite sharing the risk. The issue becomes even more complicated when we realize that so often the potential risks are global whereas the opportunities are national. This need for technology-based risk/benefit analyses on a global level is perhaps the primary ethical dilemma of our global society as we enter this new century. While this challenge could be discussed in many ways, we have chosen to illustrate this challenge by focusing on xenotransplantation.(2)

A. XENOTRANSPLANTATION.

Transplantation of organs such as the kidney, heart, liver and others has been one of the remarkable successes of modern medicine in the last half century. For patients with many different diseases, transplantation has become the therapy of choice, and in some cases the only life-saving treatment. Solid organ transplantation is a victim of its own success. As more and more patients have benefited from organs received from either recently deceased or living organ donors, the demand for more organs has grown much faster than the supply. Many thousands of individuals die each year because no human organ is available. This imbalance stimulated researchers in the field of transplantation to return to the notion that perhaps organs from other species can substitute for human organs. While xenotransplantation is not a new idea, the very few clinical trials of the 1960s and 70s were largely unsuccessful and xenotransplantation was discarded after a series of well-publicized patient deaths.(3) There was reason, however, in the late 1980s to try again. First, the immunosuppressive drugs used to prevent a patient's immune system from rejecting a human donor organ have been improved such that they may prevent xenograft rejection.(4) Second, and perhaps more important, was the newly found ability to genetically modify the donor animal. Genetic engineering held out (and still does) the hope that the donor animal could be altered to make it less foreign and more acceptable to the human recipient.(5) With these two developments, scientific, medical and commercial attention has returned to the possibility of thousands of specially bred animals providing a near limitless supply of organs for human clinical treatment. The pig has emerged as the donor of choice.(6) Its similar size and anatomy, abundance, agricultural familiarity and historical acceptance make it a strong candidate.

1. Potential Benefits of Xenotransplantation.

Most agree that we are not yet at a stage in our research where a pig organ could be transplanted successfully into a human. Let us for a moment assume that we can successfully perform pig-to-human transplants. If this were tree, we would potentially be able to treat all patients currently waiting for these organs. Indeed, we could expand the criteria for potential recipients--criteria that are for the moment artificially limited by the shortage of human organs. Putting aside economic restrictions and global access to health care, the number of people that would benefit from xenotransplantation would be many thousands every year.(7) And assuming an efficacy similar to today's human-to-human transplants, these patients would enjoy an excellent quality of life. Anyone who has known a kidney transplant patient who previously underwent dialysis for the treatment of kidney failure will appreciate the magic of organ transplantation. The quality of life is incomparable; those with a transplant say they remember what life was really like when they were well. As potential risks are considered, the potential good must never be forgotten--there is no doubt that successful, widespread xenotransplantation could be a wonderful development.

2. Potential Risks

One potential risks of xenotransplantation is that a pig virus might infect the human recipient, mutate and spread first to the close contacts of the patient and then to the general population. The genetic coding of pig viruses lie in the DNA of all pig cells, including the cells of the transplanted organ. While we do not know how many pig viral sequences exist that could be of concern to us, we do know from laboratory experiments that some pig viruses can infect human cells. Of course this laboratory demonstration of infection is a long way from the natural world, and a simple, isolated, real life infection is in turn a long way from an epidemic. Nonetheless, the risk, however remote, that a pandemic could result as a consequence of pig-to-human organ transplantation exists. The viruses of most concern, referred to as porcine endogenous retroviruses (PERV),(8) belong to the same family of retroviruses that causes AIDS. Investigators have shown that in the test tube, a pig PERV can infect human cells. PERV's have captured the headlines, probably because it is a relative of HIV and we really have no effective treatment for AIDS. However, one must realize that PERV are not the only infectious particle that could cause trouble. Just over a year ago, 104 pig farmers died and many more became sick due to a previously unknown pig virus.

What is the likelihood that a PERV or other pig viruses would infect a human recipient, cause disease and be transmitted to others? There is no way of quantifying that potential risk. What is known is that if the worst happened, i.e. the PERV did get out into the general population and cause widespread disease, the consequences could be devastating by any measure. Even if we did recognize that a patient had an illness caused by a pig virus, there is no guarantee that we could identify the disease before that patient passed the disease to a close contact or others. Complicating this picture of ignorance is the fact that we have no way of predicting when a virus may manifest itself. The expression of the virus could occur after only a few or perhaps thousands of xenotransplants have been performed. Almost certainly, we would have to perform xenotransplantation on humans to ascertain this risk. And only if a patient became infected would we be able to begin estimating the risk.

3. Different Approaches to the Risk.

How does one balance the clear clinical value of pig-to-human transplants (once the problems of rejection are solved) with this potential, unproven risk to all of humanity? It seems almost an unsolvable problem. Therefore, classical risk-benefit analysis is most difficult in this situation.

Those concerned with this problem can be split into two groups. There are those who are willing to start xenotransplantation to humans once the research warrants it (a judgment that will not have uniform consensus).(9) These individuals propose a cautious approach: an iterative process in which some small number of transplants would be performed and those patients would be watched for some period of time before more transplants are done.(10) If there are no signs of an infection by a pig virus, more procedures could be performed. Over time, this approach would decrease, but not eliminate, the potential risk that an infectious epidemic would later emerge due to a dormant virus that manifests only after many years of residence in the human host.

Others feel that the potential risks associated with xenotransplantation are too great to undertake the procedure.(11) They point out that no matter how small the risk, if a viral outbreak does occur, the consequences could be globally catastrophic. Further, they contend that alternative therapies to transplantation are under development that may not carry such a risk and that may be available as soon as, or almost so, as xenotransplantation.

We have taken neither of the two stands described above. Rather, we emphasize that xenotransplantation represents one of the several new technologies now available or being developed that bring potential risks to the public. When examining new technology, one should differentiate between risks only to the individual who reaps the benefit and risks to the general public.

There is a solution to this dilemma. Perhaps the greatest advance in medical ethics was the introduction of "informed consent" which allowed the patient to decide whether the benefits are worth the risks of a new treatment. In almost every situation, these treatments posed no risk to the public. However, in some cases, we are confronted with potential risk that may be borne by those who would never benefit from the technology or who may not even know about the plans for the technology. We believe in these latter cases, we must extend aspects of the concept of informed consent to the public that is put at potential risk.

We should not discard any technology only because there are perceived potential risks. Nor, however, should we impose potential risks onto an unknowing public. …

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