Understanding the Bioethics of Xenotransplantation

Whitney Elaine

Reviewed by Jessica Hwang

Dissecting Bioethics

Written on February 22, 2024

Understanding the Bioethics of Xenotransplantation

Transplanting live cells, tissues, or organs from one species to another is known as xenotransplantation. It covers transplants from animals to humans, which can be done in a variety of ways:

• Solid animal organ transplantation (hearts, kidneys, livers, etc.)

• Cell treatments, like the transplanting of pig pancreatic islet cells and neural cells;

• Utilizing living animal cells in gene therapy; incorporating animal cells into medical devices like extracorporeal livers.

Typically, pigs are the preferred donor of tissues and organs in animal-to-human xenotransplants because they are easy to produce, have organs that are the proper size for humans, and are less likely to spread illness than primates. 

Possible Applications for Xenotransplantation

Frequently, people face death while waiting for a suitable donor due to a global shortage of human donor organs available for transplantation. Researchers view xenotransplantation as a way to address the ongoing organ donor shortage. Research on organ xenotransplantation conducted abroad has focused on the transplanting of pig hearts, livers, and kidneys into people and primates, including chimpanzees and baboons. Additionally, studies have been done on xenotransplantation as a treatment for degenerative neurological illnesses. One such study involved injecting fetal pig neurons into the brain of a Parkinson's disease patient to enhance dopamine production.

Research into xenotransplantation as a diabetes treatment is underway in New Zealand. Diatranz, an Auckland-based startup, has been investigating the potential of using pancreatic cells from pigs to treat Type 1 diabetes. Through the use of a barrier, pig pancreatic islet cells—which make insulin—are encapsulated in the Diatranz procedure. A two-week old piglet's pancreas cells are transplanted into a tiny container that was surgically placed into the patient's belly. When these cells get older, they might start producing insulin.

Safety and Medical Concerns

Researchers are attempting to use xenotransplantation to address two significant medical issues. The individual's immune system rejecting the animal tissue or organ is the first of these. When monkeys get organ transplants from pigs, their bodies quickly reject them due to various immunological responses. Researchers have cloned and genetically altered a type of pig to reduce the immunological reaction that pig organs cause in recipients. Organs from these pigs have a longer survival period in non-human primates than in pigs that have not undergone modifications, but it is still shorter than in transplants from humans to humans. Additionally, studies into the creation of immunosuppressive medications to lessen rejection are still ongoing. Due to their interest in the medications required to sustain xenotransplantation, a number of significant pharmaceutical corporations are involved in the practice.

The potential for cross-species infection is the second significant medical safety concern associated with xenotransplantation. Researchers are particularly divided on the possibility of pig retroviruses activating in humans. A retrovirus is a type of virus that reproduces alongside the cell it infects by inserting itself into the DNA of the host cell. Thus, even though the retrovirus may not harm its host organism, it is present in every cell in the body.

Porcine endogenous retroviruses (PERV) are retroviruses that are encoded by sequences in pig DNA. While they are safe for pigs, they may be harmful to people. To ascertain whether PERV infection presents a genuine risk to the human population through xenotransplantation, a significant amount of research is being done. The fact that infection might not show symptoms for years after the recipient receives the transplanted animal organ complicates the research, which is yet inconclusive.

Researchers and government agencies are well aware that HIV is a retrovirus that was present in a monkey species without causing any harm before making its way into the human population and causing AIDS. Not a retrovirus, BSE was thought to pose no serious threat to people until it was introduced into the human population through cows and became known as Creutzfeldt-Jakob Disease. At this point, it is not possible to rule out the likelihood of a similar incident involving a PERV infection spread through xenotransplantation. Thus, complicated safety and ethical questions are raised by human clinical xenotransplantation trials.

Informed Consent and Confidentiality

Although xenotransplantation may help an individual, there may be a risk to public safety due to the spread of pig retroviruses to other parts of the community. It is widely believed that recipients of xenotransplants would have to accept lifelong restrictions that would severely restrict their freedom in order to safeguard family members and the community. Some of these restrictions include never leaving their nation of origin, being watched by authorities, not having children, and disclosing the identities of their sexual partners to the authorities.

For patients of xenotransplants, a new type of informed consent is necessary because the hazards affect not only the patient but also other individuals.These include healthcare workers and medical staff, because when performing xenotransplantation procedures, medical practitioners may be exposed to zoonotic infections, which are illnesses that spread from animals to people. To preserve their health, appropriate safety precautions and procedures are crucial. In addition to that, close contacts, family members and members of the patient’s community also ought to be informed as family members and caregivers who are in close proximity to the transplant recipient may be exposed to any infectious pathogens that are spread during xenotransplantation. For these people, monitoring and education about possible risks are essential. As for the patient’s community, the human population may become infected with new viral strains as a result of xenotransplantation.

An infectious agent may be dangerous to the public's health if it breaks free from containment and spreads. Outbreak prevention requires close observation, prompt detection, and vigilance.

The assent of each patient to take part in a clinical study or treatment is the key component of the traditional informed consent approach. Informed consent must involve not only the recipient of the xenotransplant but also additional individuals who must be monitored.

For xenotransplant recipients, the standard demand for patient-doctor confidentiality will also need to be modified. This includes changes to how family and close friends can participate in the consent procedure, for instance. In certain circumstances, such as when they receive xenotransplants, it might also be necessary to require recipients of those transplants to disclose their medical status.

It might also be necessary in some circumstances—like when they're trying to enter another nation—to make xenotransplant recipients disclose their medical history. Will the recipient of a xenotransplant need to have that information noted in their passport?

Establishing a monitoring system and imposing obligations on xenotransplant recipients and their close associates present intricate ethical and legal dilemmas. These problems must be resolved as part of building a regulatory infrastructure, and in the end, both international legislation and national regulation may be needed.

Control of Heterologous Transplantation

It is thought that there is a slight but real risk of cross-species infection to the general populace. Clinical trials are conducted under stringent regulatory guidelines and with regulatory agency clearance in the countries where they are currently underway. For instance, in the UK, xenotransplantation involving human subjects requires approval from the UK Xenotransplantation Interim Regulatory Authority. The Food and Drug Administration plays a similar duty in the United States.

In Canada, xenotransplantation has been the subject of substantial public consultation. The primary outcome of the consultation was the realization that most knowledgeable Canadians would rather solve organ donation difficulties in other ways than xenotransplantation at this time. The results of the consultation indicate that Canadians, including those who support xenotransplantation, think it is crucial to establish a stringent regulatory framework before taking any further step.

There isn't a similar regulating agency or framework in New Zealand as there are in the UK or the USA. Although xenotransplantation will be one of the many topics on the bioethics committee's agenda, there hasn't been much public participation in the conversation about it. In light of that, it will be just one of many things on the bioethics advisory body's agenda when it is constituted in response to the Royal Commission on Genetic Modification's recommendations.

The Director-General of Health rejected Diatranz's application in July 2001 to conduct clinical trials of their diabetic medication in New Zealand based on the Gene Technology Advisory Committee's (GTAC) recommendation. The application had flaws, and approval was denied due to insufficient knowledge of the risks associated with retrovirus infection. The Health Research Council further informed the Minister that unless a regulatory framework is in place and public input on xenotransplantation has been received, it would not be acceptable to permit clinical trials.

A Supplementary Order Paper establishing temporary restrictions on xenotransplantation was brought into Parliament in mid-December 2001. A Parliamentary Select Committee was tasked with reviewing the proposed law; the committee returned its report to Parliament on March 28, 2002. The Committee endorses measures to restrict the use of human subjects in xenotransplantation in their report, including requiring the Minister of Health's consent before beginning any clinical trial. The proposal must have sufficiently addressed any threats to the public's health and safety as well as any ethical, cultural, or spiritual considerations in order for it to be approved. The report has rejected a proposal to exempt the Diatranz clinical trials from the legislation. The legislation's proposed timeline, which expires on June 30, 2003, but may be extended by Order in Council to June 30, 2005, has also received approval from the Select Committee.

Parliament will consider the proposed legislation and the report of the Select Committee at the end of April. If the legislation is approved, it will give the bioethics advisory council time to evaluate the moral, cultural, and spiritual implications of xenotransplantation; it will also give the public time to be consulted and give time to build a legal framework. Diabetics are furious about the new regulation because they believe the Ministry of Health is being unduly cautious. Patients with diabetes who participated in clinical trials conducted in the middle of the 1990s before the Ministry of Health stopped them have openly discussed the advantages of the treatment and expressed dissatisfaction with the state of affairs. Diatranz has conducted clinical trials in Mexico in the past and is currently hoping to carry out a similar mission in the Cook Islands.

Animal Welfare

Animal welfare organizations are putting pressure on governments worldwide to improve the treatment of animals involved in xenotransplantation experiments. Prominent xenotransplantation firms, like Novartis subsidiary Imutran, have faced accusations of deceiving the public about the pain inflicted on animals during research. Strong opposition exists against the international apprehension and transportation of primates for the purpose of conducting such research. In 2000, the Daily Express newspaper and a British animal welfare group made documents from xenotransplantation studies public. They dubbed these documents "Diaries of Despair." These records showed that baboons and monkeys were dying days or weeks after having organ transplants from pigs, and that the animals suffered greatly in the interim before passing away.

The Animal Welfare Act (1999) governs animal welfare in New Zealand. The physical, medical, and behavioral needs of animals are covered under the "Duty of Care" that this law lays out. Additionally, it permits the "Duty of Care" to be partially suspended while conducting research as long as certain requirements are fulfilled. All organizations conducting research on animals, be they businesses, academic institutions, or research committees, are obliged to have an established Code of Ethical Conduct and an Animal Ethics Committee that grants permission for the research. Using animals in ways that violate the Code of Ethical Conduct carries severe consequences. Although this method won't address the concerns of animal rights activists, it should ensure that animals used in xenotransplantation in this nation are treated ethically. Animal welfare activists who are against all vivisection will not have their concerns addressed by this system, which should ensure the moral treatment of animals used in xenotransplantation in this nation.

Summary

Xenotransplantation presents obstacles to our way of thinking and doing. It calls into question our empathy for people suffering from ailments that xenotransplantation might be able to treat. Research and discussion are still needed to determine the extent of risk to the larger community. Concerns over the usage of animals and their wellbeing in connection to benefits to humans also exist.

Xenotransplantation provides immense hope to diabetics who must undergo the daily insulin ritual and transplant surgeons whose patients perish waiting for organs. For those tasked with maintaining public health, the potential for retrovirus transmission indicates that xenotransplantation carries some risk. It is exploitative and unethical in the eyes of animal activists.

Each of us must face our own personal feelings regarding the usage of organs or tissue from animals in our bodies.

The foundation of both our individual and group responses is our comprehension of the role that humans play in the creation. Above all, however, xenotransplantation, like other biotechnological practices, poses new concerns about the lengths we will go to in order to prolong our lives or enhance our quality of life.