4. What are the Risks?

Cross-species infection

The main risk for a person receiving animal transplant therapy is that the transplant might not function properly. However, there is also a risk that one of the wide range of viral, bacterial and other infections known to occur in the source animals will infect the transplant recipient, causing disease (sometime called xenosis). Some cross-species infections are caused by bacteria, viruses and prions, that move from animal to animal and then across to humans. HIV is one example, being a human version of SIV, which is caught from infected chimpanzees. The same problem occurs for human-to-human trans-plantation, and transplant recipients have contracted infectious diseases from donor organs and tissues.

Unfortunately, for both human-to-human and animal-to-human transplantation, the potential for an infection to occur is increased by the drug treatment that transplant patients receive to suppress their immune systems and help prevent rejection of the transplant. However, researchers believe that the risk of infection by pathogen-caused animal diseases would be minimised in the same way as for human infections: by rigorous screening of source animals and appropriate treatment of transplant recipients if an infection occurs.

While known animal infections may not pose a serious problem, xenotransplantation does carry another potential risk that has more serious implications for both the individual patient and the wider community. This is the risk that a previously unknown disease, or a new form of a known disease, might emerge and infect recipients of animal transplants and subsequently spread to close contacts and the general public, causing a serious new epidemic. It is for this reason that consideration of the risks of the procedure need to go beyond an individual's assessment of the personal risk they are willing to take.

ERVs

A group of viruses called endogenous retroviruses (ERVs) are of particular concern. Instead of actively causing infections like other retroviruses, the endogenous retroviruses remain dormant in their host - embedded in the genetic material - not causing any obvious signs of disease. However, they may be activated occasionally, and it is possible they could then infect other animals, including different species. Little is known about what might make endogenous retroviruses become active but, if an animal transplantation product contains an endogenous retrovirus, there is the potential for it to activate at any time in the future and infect the transplant recipient (see Figure 2). Such an infection could spread to close contacts of the recipient (for example, medical staff, family, friends) and, in the worst case, to the general population. These ERVs cannot be screened out.

Figure 2: Possible activation of an endogenous retrovirus

See figure at its full size (including text description).

PERVs

Most pigs have a retrovirus called porcine endogenous retrovirus (or PERV). In 1997 researchers reported that when they mixed pig cells with human cells in the laboratory, some human cells became infected with PERV. The first evidence of cross-species transmission of a retrovirus during a transplant occurred in 2000, when a study found transmission of a PERV from pancreatic pig cells into immunosuppressed diabetic mice. This raises the possibility that the recipient of a pig transplant may be infected with PERV, or with another, currently unknown, infectious disease agent. Some retroviruses have been associated with cancer.

Many researchers consider that the risk of a new infectious disease emerging as a result of xenotransplantation is very low. More than 200 human patients have received pig transplant therapies and none have become infected with PERV or other new infectious agents. However, such an event cannot be completely ruled out and the consequences, were it to happen, could be serious.

Such risks must therefore be assessed and weighed against the potential benefits of xenotransplantation. It is impossible to generalise the level of risk associated with xenotransplantation research, which must be assessed over the long term. The precise risk will vary from one procedure to another, depending on a range of factors including the following:

• The amount of direct contact between animal and human tissues - this may be zero for some external procedures, such as liver perfusion devices, where the animal liver cells are contained within the device and separated from the patient's blood by a membrane. It may also be minimal in some cell therapies where the cells are contained in an organic capsule, such as collagen. However, in the case of organ transplants, direct contact would be considerable. The immunosuppression required following whole-organ transplants following such procedures also increases the risk of infection, due to the weakening of the recipient's immune system.
• The length of time the animal and human tissues are in contact - this may be very short for external therapies, and long term for cell and organ transplants.
• Detailed information about any retroviruses or other infectious agents that the source animal carries.

Informed consent

As we have seen, the risks to the recipient are that the transplant will not work, or will worsen their condition, and that the transplant will infect them. The existence of risks does not in itself mean that xenotransplantation should be rejected. Most standard surgical operations, especially those performed under general anaesthetic, carry some risk. So long as the recipient is aware of the risks, and there is sound evidence that the risks are outweighed by the potential benefits, the familiar idea of informed consent can be applied.

In New Zealand, the Code of Health and Disability Services Consumers' Rights establishes the rights of the consumer to make informed choices about the delivery of health services - including clinical trials. For informed consent to be obtained, information on the procedure, including any known risks, needs to be provided to the subject. In the case of xenotransplantation, the patient would need to be informed of the risks of cross-species infection, even if these risks were not quantifiable.

It is highly likely that any xenotransplantation research carried out in New Zealand would be therapeutic (expected to benefit the subjects) rather than done on healthy subjects. Before being permitted, there would be a scientific review of the pre-clinical data by an expert group, and then review by one of New Zealand's seven new Health and Disability Ethics Committees.

Public health risks

If the xenotransplant procedure involves a risk not only to the recipient but also to close contacts - and in the worst-case scenario of an epidemic, a risk to everybody - individual consent becomes insufficient. The ethical question then becomes: is it right to impose risks on people without their consent? Are the risks of xenotransplantation so great as to make the procedure wrong without the consent of the whole community? How are we to weigh the risks of potentially saving the life of a person with kidney failure against the unknown risks of an epidemic?

There is also the question of how far the need for consent should extend. For example, should it extend to clinical staff involved with the procedure? If they refuse to be involved and the patient dies as a consequence, what would this mean? Should close contacts of the potential recipient also be asked to consent?

It is obvious from these questions that, unlike the situation with other new medical procedures, the risks of xenotransplantation potentially include the whole community. It is for this reason, in particular, that it is crucial that people have the chance to think about the benefits and risks, to discuss their feelings, and to be kept informed and involved in decisions made about xenotransplantation. In Part Two we turn from descriptions of the more technical aspects of xenotransplantation to look at the cultural, ethical and spiritual aspects, and then in a later section we return to the problem of weighing individual benefits with public risks.

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