Xenotransplantation Discussion Scenario

 

What is xenotransplantation?

 

Xenotransplantation involves transplanting animal organs, tissues or cells to replace failing organs or treat diseases in humans. Transplants involving whole organs are called solid organ xenotransplantation.

Introduction

Welcome to the Discussion Scenarios. The five scenarios in this section present many of the ethical issues that come up in connection with some uses of biotechnology. You've entered a discussion about xenotransplantation.

This scenario raises a series of questions to help you consider different points of view on the ethical issues associated with xenotransplantation. The questions aren't intended to lead you to a set of answers. The purpose is to encourage you to think about the issues from a variety of perspectives.

These Discussion Scenarios do not address all the ethical issues or concerns related to this technology. We may not have asked all the 'right' questions to help bring the issues to light, and we realize that no choice of questions can be truly "ethically neutral," to the extent that we are raising some issues and leaving out many others.

This is why the questions are intended as a starting point for a broader look at the issues associated with xenotransplantation.

We'll be revising the questions over time, so we encourage you to get back to us with new issues that you consider important.

There are many situations where what we want as individuals may not be the same as what we expect our government to do. As you read the Discussion Scenario, think about which questions should be left to individuals or companies to decide, and which ones should be answered by society as a whole.

We also look at two different philosophical viewpoints that underlie ethical decisions. In one of these traditions, decisions are evaluated based on their consequences. In the other, choices are based on a set of principles, regardless of the consequences. As you read the Discussion Scenario, think about how these philosophical approaches and different kinds of information can help you reach your own conclusions on the ethics of xenotransplantation.

The current organ shortage.

 

Donated organs are currently in very short supply, in Canada and around the world.Kidneys, in particular, account for 62% of organ transplants in Canada, and more than 80% of the people on Canada's organ waiting lists need a kidney. In 1997, 725 kidneys were transplanted from human donors who had died, 285 came from live donors (usually patients' relatives) - and 2,528 Canadians were still on waiting lists.In the United States, after 11,900 kidney transplants (4,016 kidneys from live donors) in 1998, 42,364 people were still waiting.

The world is also facing a shortage of other organs. In Canada, for example, 161 heart transplants were performed in 1997, leaving 112 people on waiting lists. The United States saw 2,340 transplants in 1998, with 4,185 people remaining on the list.

Possible solutions to the organ crisis:

 

• A more intensive effort to build better understanding of the factors (including exposure to toxins, drug use, and infection) that can cause organ failure.
• A prevention campaign based on public awareness to reduce the need for costly transplants, and for other medical efforts that deal with organ failure after the fact.
• Efforts to increase the supply of donated human organs can be expanded by recruiting more donors, and by making the organ donation process more efficient. Canadians who died in 1997 had filled out organ donation cards at a rate of 24.4 per million population (PMP); the rate in the United States was 30 PMP in 1998.

By contrast, Spain increased its human kidney donation rate to 46.6 PMP, the highest in the world, by recruiting donors more aggressively and introducing a more integrated organ procurement, transport, and preservation system. But Spain still has a waiting list for organ donations, and many experts believe the demand for organs will never be met by prevention efforts combined with human donations. To reach Spain's level, Canada would have to double its collections from donors who are deceased, and the United States would need a two-thirds increase. Even at that rate, Canada would still have had 1,869 people on its waiting list for kidney transplants in 1997, while the US would have had 37,992 on its list in 1998 - suggesting that a major organ donation campaign would only reduce waiting lists by 26% and 10.3% in the two countries.

These figures indicate that other strategies or technologies will be needed to clear the organ donation backlog. Some of the research possibilities include:

• New ways of reducing the rate of failed transplants;
• Mechanical hearts and other artificial organs;
• Tissue engineering technologies that may some day offer biological substitutes for failing organs (research in this area is in preliminary stages);
• Human embryonic stem cell (ES) therapies that might eventually be used to regenerate organs (research in this area is also very preliminary, but some scientists are hopeful that these cells may eventually be used to reconstruct organs);
• Development of suitable animals and procedures for solid organ xenotransplantation.

Although most of these technologies fall outside the scope of this Discussion Scenario, each of them carries its own set of benefits, risks and questions. For example, a risk in the use of embryonic stem (ES) cells is that they may give rise to some cancers, and the practice of collecting cells from human embryos raises ethical concerns. Of the five options, solid organ xenotransplantation is closest to being tested on humans. While xenotransplantation may not solve the organ shortage by itself, it is one of several technologies that, if successful, could play an important role.

Ethics of xenotransplantation

 

Transplants between humans (allotransplantation) are considered a very successful treatment for severe organ failure. At present, 95% of patients who receive kidney transplants from deceased donors live at least one year, and 81% live at least five years. If xenotransplantation were this successful, it could virtually eliminate the need for organ waiting lists. And with an estimated market of 100,000 patients a year, this option could make a major contribution to job creation, economic growth, and profits for the companies that develop the technology.

But there are risks and ethical questions to be considered. An animal virus passed on to a human patient through a transplanted organ, if harmful, could cause a major epidemic. At a time when the likelihood of this outcome cannot be measured, the ethical challenge is to balance the possible consequences for society against the potential benefits of the technology to the individual.

Quality of life is another important concern. While allotransplantation is often seen as the best option for patients with severe organ failure, the treatment still has a drastic impact on their lifestyle. And since transplanted organs may not survive as long as the patients who receive them, a transplant isn't always a permanent solution - while 81% of kidney recipients survive at least least five years, only 61% of the kidneys last that long.

The high cost of xenotransplantation might raise ethical questions related to the allocation of scarce public health care dollars, and some people may be concerned about the impact of xenotransplantation on human and animal dignity.

With these ethical issues in mind, this Discussion Scenario considers xenotransplantation from three perspectives: the Patient, the Patient's Neighbour, and Regulators and Policy-makers.

Scenario A : The Patient

 

Andreas, 12, has had kidney disease for most of his life. Since health problems prevent his parents from donating their kidneys, Andreas has been on a waiting list for a donated human kidney.

While a kidney transplant is considered to be the best possible treatment for Andreas' condition, there are drawbacks. Because a person's immune system will attack any transplanted organ;

immunosuppressive--also called "anti-rejection"-- drugs are needed to suppress this immune response. This has the side-effect of weakening a patient's overall immune system which makes him or her more susceptible to infection. Transplant recipients must use anti-rejection drugs for the rest of their lives and cannot expect a normal lifespan. While 81% of kidney recipients survive at least 5 years, 61% of kidneys last that long. These benefits and drawbacks to human-to-human transplantation will likely also be present for xenotransplantation.However, receiving a transplanted organ would bring Andreas much closer to leading a normal life, and would avoid his having to undergo daily dialysis treatment, which presents extreme physical and emotional challenges not only to Andreas, but also to Marta and Antonio, his parents.

Under the circumstances, if xenotransplantation was approved for human s , Marta and Antonio would want their son to participate. However, they know that extreme caution must be exercised before involving a child in a major experimental procedure like xenotransplantation. How should a 12 year old like Andreas participate in the decision of whether to go ahead with a xenotransplantation procedure?

(i) Acceptable survival rates in animal experiments

 

At this point, there have been no experimental trials in solid organ xenotransplantation that involved humans. Marta and Antonio have been keeping up with advances in xenotransplantation and are aware of animal-to-animal experimental xenotransplant trials that are currently going on (e.g. pig organs to monkeys).

However, they are aware of the difficulties inherent in deciding when the procedure is safe enough for clinical trials. Currently with human-to-human transplantation, 61% of transplanted kidneys last at least 5 years. What survival rates for animal-to-animal xenotransplant experiments would be acceptable before human trials should be allowed?

(ii) Infectious risk

 

Marta and Antonio are also aware of the infectious risk associated with xenotransplantation. Right now, pigs seem like the most likely candidates as organsources, and some pigs have been found to harbour porcine endogenous retroviruses (PERV). PERVs are harmless to the pigs that carry them, but their effect on humans is unknown. It is not known whether PERVs can infect Andreas' cells if they are carried into his body by an affected pig organ. And if PERVs could infect Andreas' cells, it is not known whether they would be harmful to him. Finally, it is not known whether PERVs could spread from xenotransplant recipients like Andreas to people who frequently come into close contact with him, and through these contacts to members of society at large. These risks about the infectious potential of pig pathogens, the potential severity of such infections and the potential for the wider spread of an infectious agent like PERV in the human population, is presently unknown.

Attempts to address these issues, are being made by regulators at the national levels (Canada and the United Kingdom , for example) and at the international level through the World Health Organisation (WHO) andOrganization for Economic Development (OECD). Efforts are being made to manage and minimize the risks--potential source animals are born and raised in bio-containment facilities (there are tight restrictions on the types of biological entities that may enter and leave), are tested frequently for infectious agents that cause disease in pigs, and their contact with humans is minimized.

Should xenotransplantation become a reality, the benefits to Andreas could be substantial, and society at large also benefits when people with Andreas' condition are closer to leading a normal life. However, these benefits must be weighed against the potential infectious risk. What level of risk to the population is acceptable given the individual and societal benefits of this technology? How can the infectious risk be managed effectively?

(iii) Monitoring challenge

 

So far, regulatory authorities have indicated that a measure that will come into effect as part of any xenotransplantation clinical trial will be mandatory monitoring of initial transplant recipients and their immediate contacts for a very long time--possibly for the rest of their lives. Monitoring would be necessary to attempt to identify and contain viral infection or transmission that might occur as a result of organ xenotransplantation. Monitoring would also include the health-care providers who are involved in Andreas' care. This would likely consist of "tissue banking" where tissue samples from Andreas, Marta and Antonio and others are obtained and stored locally and possibly also as part of a centralized (national) system. Subsequent samples obtained from Andreas and his close contacts would be tested for PERV and other pathogens and compared with the tissue samples on file.

Surveillance activities are likely to be very expensive. How should surveillance be paid for? Even if the cost of surveillance for the patients involved in clinical trials is covered by the company developing the technology, who should pay for ongoing surveillance once the technology is approved for general use?

While Andreas, Marta and Antonio are willing to consent to the surveillance, they are a little uneasy about having their tissue samples--from which genetic information can be obtained--in a centralized databank. What measures must be in place to ensure that only appropriate individuals have access to this information, and only for legitimate purposes? Who are the appropriate individuals and what purposes are legitimate ones? Currently, any publicly funded research that involves the creation of a databank in Canada must comply with article 8.6 of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. These questions would also apply to transplant doctors, nurses and other health workers involved in Andreas' care, as these individuals would also need to be monitored for signs of transmitted infections.

Scenario B. His Neighbour

 

Sarah, who lives next-door to Andreas and his parents, is very concerned about the potential risks of xenotransplantation to her family and her community. She is concerned because her own daughter, Mary, is in Andreas' class at school. She understands why members of Andreas' family are willing to take the risk and submit to lifetime surveillance, but thinks that their actions might put her own daughter--and others in the community with whom Andreas comes into regular contact--at risk. If Andreas were to have the operation, Sarah would consider sending Mary to a different school and would want to have her family undergo medical surveillance as well.

(i) "Societal" Consent Issues

 

This raises the issue of how "societal" consent for the use of xenotransplantation can and/or should be obtained. One of the most basic principles of medical ethics is that a patient's informed consent must be obtained before any medical procedure is carried out. Informed consent means that the patient has freely agreed to the procedure and fully understands the benefits and risks involved. In this case, Andreas' transplantation procedure has risks that extend to other members of society, like Susan and Mary.

What should be the nature of a broader form (a "societal" form) of consent for the use of xenotransplantation? How could such consent be obtained? One suggestion might be the active involvement of the public in policy development with respect to xenotransplantation, including determinations of what results in animal-to-animal xenotransplants are a prerequisite for human trials, etc. Many preliminary forums and consultations have already taken place or are ongoing. See, for example, the report of the National Forum on Xenotransplantation (Health Canada) and the report of the Nuffield Council of Bioethics on Ethical Issues Related to Animal-to-Human Transplants. Health Canada recently held a two day planning workshop on April 10 -11, 2000 to further develop their plan for 'Public Involvement on Xentransplantation'. Please visit Health Canada's Therapeutic Products Programmefor further xenotransplantation information.

(ii) Beyond Andreas' Neighbour--International Implications

 

With international air travel, infectious agents can spread around the world at a rapid pace. This means that the infectious risk of xenotransplantation is a global issue that implicates developed as well as developing countries. The WHO Electronic Discussion Group on International Xenotransplantation Policy Considerations(you may join in if you wish) is an international forum that examines xenotransplantation issues from an international perspective.

Scenario C. The Regulators & Policymakers

 

Because the prospect of xenotransplantation raises issues that go beyond the traditional health and safety considerations that government regulators normally develop and employ, government policymakers and regulators are working together to develop a more comprehensive strategy with respect to xenotransplantation. Hypothetically, they might be faced with the following issues (among others).

(i) Monitoring

 

There may be problems associated with the need for lifetime surveillance. Monitoring the close contacts of transplant recipients (and the recipients themselves) and "banking" their tissue samples for future comparison would require a significant amount of organization and resources at the national and perhaps international levels. What would happen if a recipient (or his or her contact) under surveillance wanted to live in another country that did not have the resources to do this kind of surveillance? Do these people need to get permission from their doctors to travel? Could recipients and their contacts be realistically kept in or out of a country against their will, given that this might infringe upon their freedom of movement?

(ii) Allocation of Health-Care Resources

 

A recent OECD study estimated that human-to-human kidney transplantation produces a savings of 63% when compared with lifelong dialysis treatment. The calculation takes into account the costs of immunosuppressive drugs that transplant patients must take for the rest of their lives, but does not account for any social and economic benefits associated with improvements to a patient's quality of life from transplantation.

However, that same study suggested that it is too early to predict the costs of xenotransplantation. The costs of a xenotransplant operation would be comparable to the cost of a human-to-human transplant operation, and the costs associated with lifetime use of immunosuppressive drugs would also be the same. The cost of an organ from a transgenic pig is likely to be high in the early trials, reflecting the cost of innovation required to produce it as well as the breeding and rearing of animals in controlled conditions. There will also be costs associated with the charge of monitoring xenograft recipients, their close contacts, and health professionals for evidence of disease.

In the short term, it seems that xenotransplantation will be expensive. However, if xenotransplantation proves to be safe and effective, several years from now monitoring may not need to be quite as extensive. Thus, if xenotransplantation is successful, its cost would likely diminish over time. That having been said, the costs of xenotransplantation in early clinical trials are likely to be significantly higher than human-to-human transplantation.

The policymakers and regulators must consider organ xenotransplantation in light of its cost to the Canadian public health-care system. Undertaking to use xenotransplantation as part of a solution for the organ shortage could necessarily divert health care funds from the application of solutions to other public health problems which may impact more people and may be less expensive to alleviate.

(iii) Animal dignity

 

Some may have concerns about the raising of animals whose sole purpose is to serve as organ "donors" for humans. Currently, all publicly funded research involving animals--including transgenic animals--must be carried out according to requirements set out by the Canadian Council of Animal Care (CCAC) . The CCAC's policies and procedures are for the ethical treatment of research animals and include requirements on animal living conditions and steps for minimizing pain and distress in these animals during and after experimentation. Are additional requirements needed for animals bred for use in xenotransplantation? How can we ensure that these animals are treated with the appropriate dignity and respect?

Based on personal values, others are concerned because the animals that would be used for xenotransplantation are transgenic. In this case, a human gene has been added that avoids a type of human immune rejection (called hyperacute rejection) that occurs when an animal organ is placed in a human. For information about how transgenic animals are developed and some of their uses, see the Biotechnology Science Centre . Currently, organs obtained from transgenic animals do not avoid all types of rejection, and so anti-rejection drugs are still needed. For more information about human organ rejection, visit the xenotransplantation ection of the Science Centre.

(iv) Effects on Humans

 

There may be psychological impacts for patients who receive animal organs. Relatives of transplant recipients may also be affected psychologically. How should the potential psychological impacts of this treatment be managed?

The advent of new transplant technologies, including xenotransplantation, could have the effect of decreasing human organ donation rates as people begin to perceive the need for human organs as less urgent. However, even if xenotransplantation or other new transplant technologies become a reality, human-to-human transplantation will likely be the preferred option when possible (for one thing, human organs are free, while pig organs or organs generated using other technologies would have to be purchased). How should continued human organ donation be promoted and maintained even if alternative technologies are available?

Ethical questions have been raised about the effects of xenotransplantation on how humans view themselves and their bodies. Margaret Somerville, a Canadian ethicist, asks:

...does [the advent of xenotransplantation technology] take us yet one more step away from an integrated theory of personal identity--seeing ourselves as unique, indivisible human beings--and further along the line of a modular theory of human identity--that we are simply a series of interchangeable parts, and these parts can now include animal parts--and a "gene machine" view of human life? Or could the "miracle" that this technology makes possible deepen our sense of awe and wonder about ourselves, our world, and life in general?

Are such philosophical questions about the nature of human identity best left to the individual, or does society have a role?

(iv) Public consultation

 

To devise appropriate responses to many of the questions raised in this scenario, the policymakers will need to consult the public. Who is "The Public"? How should the government go about consulting the public on this issue? What would be the roles of citizens, governments, industry, non-governmental organizations, academia, ethicists and/or others in such discussions? How can it be ensured that a broad range of perspectives are represented? Given the "borderless" nature of many of the issues related to xenotransplantation (the infectious risks and monitoring challenges being two such examples), which of these discussions, if any, should be carried out on an international scale? How should these international discussions be carried out?