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Objectives of the Workshop

DAVID HARPER

Chief Scientist, Department of Health, Skipton House, 80 London Road, SE1 6LW London, United Kingdom

On behalf of the Working Party on Biotechnology, it is my pleasure to welcomeyou to New York. Thank you for having accepted our invitation to convene here todiscuss a wide range of important issues associated with transplantation technology.The focus of the workshop is xenotransplantation—the transplantation of cells, tis-sues, or organs from other species into human patients.

We have an ambitious program ahead of us and a hard task: to discuss and formu-late an OECD opinion on current developments on xenotransplantation to be con-densed in a series of policy considerations for OECD member countries.

The OECD appears ready for this debate; many of you here belong to advisorygroups or committees that have or are about to formulate guidelines on this new tech-nology. We have gathered here leading experts and representatives from 17 OECDmember countries, from Cameroon and from the Sultanate of Oman. We wish tobuild our discussions on your experience.

The goal of this presentation is to help steer this workshop towards a useful out-come for the OECD and the international community as a whole.

In broad terms, the objective of this workshop is to guide OECD member coun-tries towards international coordination and the establishment of coherent interna-tional policies and regulations on xenotransplantation.

To help achieve this objective, I will attempt to outline some of our most imme-diate preoccupations.

THE CORE OF THE PROBLEM: THE SHORTAGE OF ORGAN DONORS

Today transplantation is considered an accepted practice to treat patients withend-stage organ failure where treatment with drugs or restorative surgery is not fea-sible. Because of important breakthroughs in tissue typing and immunosuppressantdrugs, it is now possible to transplant approximately 25 different organs and tissue,including bone and cartilage, bone marrow, skin, cornea, heart, heart, heart–lung,kidney, liver, lung, and pancreas. Furthermore, survival rates have greatly improved.Eighty percent of kidney transplant recipients live for at least one year, and morethan 60 percent live for at least five years. Other transplants are not as successful,but even in the least successful cases, more than 50 percent of recipients live forlonger than five years. More than one million people worldwide have benefited fromsuccessful organ transplantation. Transplantation technology has, however, becomea victim of its own success.

A consequence of the successful advances in organ transplantations is that de-mand for such treatments, and consequently for human organs, is increasing. Cur-rently this demand cannot be adequately met because of the shortage of organ

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donors. The imbalance between supply and demand leads to different technical andethical problems that will need a solution.

THE BURDEN AND THE ALTERNATIVES

This symposium will attempt to discern the actual burden to society of diseaseswhere xenotransplantation may have a role as well as to consider the alternatives thatexist to alleviate organ shortage. Countries such as Austria which have “presumedconsent” laws that do not require the next-of-kin to be notified or to give their con-sent to organ donations from the newly dead generally have higher donation ratesthan do countries such as the United States, where informed consent is required. Dr.Miranda will discuss the measures taken in Spain to boost the low rates of cadavericdonations. Today Spain has one of the highest rates of organ donations in theworld—27 per million inhabitants.

What are the available or possible alternatives derived from recent technologicaladvances? This brings us to the main focus of this symposium: xenotransplantation.

Recent advances in biotechnology have meant that transplantation of animalcells, tissues, and organs could become a clinical reality in the future. Thus, xe-notransplantation could become a means to alleviate the chronic shortage of humanorgans.

UNDERSTANDING THE RISKS

An understanding of the risks and the ethical and socioeconomic implications ofxenotransplantation is still evolving. The concern that animal viruses might be trans-ferred along with organs and might jump species barriers has stirred significant in-ternational debate and many questions remain unanswered.

This symposium will discuss xenozoonotic disease risk and will note which pub-lic health tools are currently available or are being developed to prevent the risk ofinadvertent transmission of infectious agents into xenotransplant recipients. It willalso address the chance of subsequent secondary transmission of infections to thewider human population. And it will consider whether animal cells, tissues, and or-gans are, or could become, compatible with the human immune system and physiol-ogy.

Informative analogies will be drawn between human gene therapy and xenotrans-plantation. Since its inception, gene therapy has raised concerns regarding the poten-tial emergence of replication-competent viruses and insertional mutagenesis.Infectious disease consequences would affect not only the individual patient, butalso the population at large.

In 1995 the OECD organized a workshop in Ottawa to discuss these and other is-sues related to gene therapy. Today, we take advantage of that experience by review-ing together with Dr. Nevin similarities in the two fields so that it will not benecessary to reinvent regulatory mechanisms where specific frameworks and poli-cies have already proven successful.

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ISSUES OF PRIMARY IMPORTANCE

In this context, and from an OECD perspective, the following issues are of pri-mary importance:

The public health tools currently available or being developed to reduce or elim-inate the risk of inadvertent transmission of infectious agents into xenotransplant re-cipients need to be identified

The features of a compatible international framework to detect, identify, monitor,evaluate, and manage xenozoonotic risk ned to be determined.

How the OECD and other international organizations could assist the develop-ment of international public health tools in xenotransplantation needs to be dis-cerned, particularly with regard to international surveillance, safety assessment,including monitoring of health events, and the assessment of patient outcomes.

Many OECD member countries have set up advisory committees on xenotrans-plantation, and opinions vary. In Europe, the most stringent positions, echoed by re-cent debates within the Council of Europe—as Dr. DeSola, Secretary of theCouncil’s Steering Committee on Bioethics, will report—call for a hold on clinicaltrials until further research shows that the technology is safe and offers real benefits.

Discussions on safety will consider the limitations of currently available toolsand should assist the international community in addressing the question of defini-tion and quantification of risk. However, discussions on safety have, even if under-standably so, overshadowed other important issues. International frameworks andinfrastructures (such as mechanisms for international surveillance and their manage-ment) needed to take the technology forward have not yet been adequately identified.And so our goal is to determine how international organizations can enable the es-tablishment of effective frameworks and infrastructures.

ETHICAL ISSUES

A number of ethical issues will be considered:If xenotransplantation becomes clinically viable, the technique may be capable of

alleviating the suffering of persons with specific medical conditions and may add totheir quality of life, possibly prolonging their life. Thus, for the many who are inneed of a transplant, xenotransplantation could become an answer to their needs.

However, because of the conditions in which animal donors will most probablyhave to be bred and kept in order to comply with possible GMP guidelines, there area series of animal husbandry and welfare issues that need consideration.

Many ethical and legal issues are raised by the potential clinical application of xe-notransplantation. We will attempt to address some of these issues by reviewing theworks of a number of international bioethics committees and expert institutions. Wewill learn about the opinions expressed by other international fora and committeeson animal welfare, accessibility, equity, and acceptance.

ECONOMIC DIMENSIONS

Finally, there is an important economic dimension to the problem: Currently ap-proximately 700,000 patients world wide undergo dialysis at an annual cost of ap-

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proximately 19 billion U.S. dollars. The transplant market, including all organs andassuming availability of organ donors, is a 10-billion dollar business.

Transplantation is estimated to produce a savings of nearly 60 percent over totalmedical expenses for a patient with renal disease when compared to the cost oflife-long dialysis. So if xenotransplantation proves successful, the international mar-ket may be worth up to 6 billion dollars in 2010. The economic implications of thisfor both industry and health care providers are significant.

Issues that will be addressed in the final economic forum are resource allocation,the costs of organ procurement programs and their management, and the costs of reg-ulatory oversight.

Can we forecast these costs? And who will bear the burden?