XENOTRANSPLANTATION: Benefit and Risk Involved

Introduction

• Human organ transplantation is a relatively new field of medicine that is now facing a significant challenge.
• Approximately 10 people die each day waiting for organs to become available.
• These numbers do not take into account the unknown number of people who are not eligible for transplants because of their age or health status.
• The demand for organ transplantation will continue to increase as improved technical skills and anti-rejection medication make transplant a realistic option for groups of people previously considered too vulnerable for example, those with diabetes.
• Also, many other people may benefit from transplantation of cells or tissues to treat countless other diseases such as diabetes, Parkinson’s, Huntington’s, cancer, and injuries to the spinal cord or other organs and limbs.
• Despite significant educational efforts on both the national and local level to increase the awareness of the need for organ donation, the number of people who elect to donate their organs if they were to die remains stagnant.
• Even if all potential donors elect to donate, the supply of human organ donations will continue to fall short of the need.
• One solution doctors along with pharmaceutical and biotechnology companies are investigating to end this acute shortage is "xenotransplantation"

What is ‘Xenotransplantation’?

• Xenotransplantation is any procedure that involves the transplantation, implantation or infusion into a human recipient of either
  • (a) live cells, tissues, or organs from a nonhuman animal source, or 
  • (b) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs.
• The development of xenotransplantation is, in part, driven by the fact that the demand for human organs for clinical transplantation far exceeds the supply. 
• While still in the experimental stages, xenotransplantation is a potentially life-saving option for people with such ailments as severe heart disease and kidney failure.
• Preliminary data from experiments using transplanted pig cells in patients with diabetes and Parkinson’s disease are encouraging.
• According to a 1997 survey by the National Kidney Foundation, nearly two-thirds of the American public accepts cross-species transplantation as a viable option to increase the number of organs and tissue transplanted and lives to be saved.

HISTORY OF XENOTRANSPLANTATION

• Xenotransplantation, a subject of study and experimentation for almost a century, started to receive serious attention from the scientific community in the 1960s as a result of strides made in human-to-human transplantation.
• Between 1963 and 1993, 31 clinical procedures involving transplantation of solid organs from animal donors were performed in the United States and South Africa.
• These were extraordinary events. Physicians performed these operations as bridges to maintain life while awaiting a human donor organ.
• The first experiments in transplanting chimpanzee kidneys into humans were conducted in 1963 and 1964. One of the patients who received chimpanzee kidneys lived for nine months.
• Two of the most publicized xenotransplant operations in the last two decades involved Baby Fae, the infant who received a baboon heart in 1984, and Jeff Getty, an AIDS patient who received a bone marrow transplant from a baboon in 1995. Baby Fae lived with her xenotransplant for 20 days, while Getty rejected the transplanted marrow almost immediately.
• As of October 1998, Getty remained free of baboon-transmitted viruses and showed no signs of baboon bone marrow in his system.
• Researchers are currently experimenting with pigs as sources of organs and tissues for xenotransplantation.
• Studies include the use of pancreatic islet cells and neural cells from pigs for insulin-dependent diabetes and refractory parkinsonism, as well as perfusion of a patient’s fluids through a pig liver situated outside the patient’s body as a temporary strategy to treat liver failure.
• Patients with Huntington’s disease, which is a neurodegenerative condition characterized by uncontrolled movement and mental deterioration, also are receiving modified tissues from pigs as an experimental treatment.
• These studies are still very preliminary in testing the safety and effectiveness of this promising treatment.

XENOTRANSPLANTATION IN MYTHOLOGY

• A review of Greek mythology and of religious tracts—particularly, for example, from the Hindu religion draws attention to the fact that humans have been interested in the possibility of merging physical features from various animal species for hundreds of years.
• For example, the chimera has been used to represent the allotransplantation of organs and cells (transplantation between members of the same species), and the lamassu has been selected as the mythological figure to represent the International Xenotransplantation Association and its official scientific journal.

APPROPRIATE ANIMALS FOR USE IN XENOTRANSPLANTATION

• Scientists and the U.S. Public Health Service advise that domesticated animals such as pigs and cows be considered as potential tissue and organ sources before nonhuman primates, such as monkeys, for a number of health, safety and logistical reasons.
• Pigs are preferred because they mature very quickly, produce large litters and have organs of comparable size and function to human organs in both infancy and adulthood.
• They also can be bred to high health standards in microbiologically controlled environments.
• Monkeys, on the other hand, are undomesticated animals that do not fare well in controlled environments and, therefore, it is difficult to raise them to the same high health standards as pigs.
• Furthermore, their organs are much too small and, like humans, monkeys mature slowly and tend to give birth to one offspring at a time.
• Although humans might reject nonhuman primate organs less frequently and vigorously than those of other species because of their genetic similarities, these similarities could facilitate disease spread between the donor and recipient.
• This threat of disease, and ethical issues associated with the use of non-human primates as organ sources, have led some government agencies to consider banning the use of non-human primates for xenotransplantation.
• For example, the United Kingdom (UK) has banned the use of great apes and strongly protests the use of other primates for this purpose.

POTENTIAL ADVANTAGES OF XENOTRANSPLANTATION

1. No organ shortages

• • Once clinical xenotransplantation becomes available there will be no organ shortages and it will be possible to offer transplantation to all patients in need.

2. Prompt surgery

• • While patients in many countries currently may have to wait for years for a cadaveric organ, all transplantations can be performed promptly and death on the waiting list will be avoided.

3. Liberal age limits

• • Furthermore, with access to pig organs more liberal age limits could be applied, making it possible to accept elderly patients, who are not accepted today.

4. Doing away with legal and ethical problem-

• • Eventually, the use of organs from diseased or live human donors will become obsolete.
  • The many legal and practical problems that are associated with the use of organs from deceased donors will become history, a fact that will be of special importance in countries where removing organs from deceased human beings is made difficult by cultural taboos.
  • Moreover, the inevitable ethical problems that accompany the use of related or unrelated living donors, such as coercion and financial arrangements (including organ commerce) will be avoided.

5. Optimal quality organ

• • Recently, it has become customary to accept non-optimal human organs for transplantation.
  • With the use of pig organs, all organs will be of optimal quality.
  • Furthermore, it will be possible to keep the warm and cold ischemia times to a minimum.

6. Procedure can be prescheduled

• • A further advantage of using pig organs is that the transplant procedure can be prescheduled, allowing for the pre-treatment of the recipient with immunosuppressive agents.
  • Such pre-treatment has recently become practice at some centers with the aim of facilitating tolerance.

7. Alleviate graft rejection

• • Finally, the use of pig organs would make it possible to alleviate graft rejection by modifying the donor tissue through genetic engineering, thereby making the outcome less dependent on recipient treatment with immunosuppressive agents

8. Cost savings

• • Eventually, xenotransplantation has the potential to bring significant cost savings.
  • Thus, the existing organizations for procurement and sharing of organs from deceased donors will become obsolete.
  • The immediate access to pig organs will also result in savings: there will be less need for chronic dialysis treatment and less need for intensive care treatment of patients with end-stage liver, heart and lung disease.

Risk Involved

ORGAN REJECTION

• Rejection, in which the recipient’s body attacks the new organ like an infection, is the greatest practical obstacle to xenotransplantation.
• Traditionally in transplants of organs from one human to another, drug therapies, such as cyclosporine, are used to suppress recipients’ immune systems in order to allow transplanted organs to function without being attacked and rejected as foreign.
• In xenotransplantation, a more aggressive defense mechanism called "hyperacute rejection" occurs when tissue not recognized as human is introduced to the body.
• In a matter of minutes, an individual’s immune system sets out to destroy the transplanted organ.

RISK OF INFECTION

• The transfer of infectious diseases between animals and humans, or cross-species infection, remains an important area of study even though risks have been reduced.
• In 1997, it was reported that two of four variants of the porcine endogenous retrovirus (PoERV) could infect cultured human cells in test tubes.
• An endogenous retrovirus is a type of virus that exists as part of the DNA of all mammals and is passed down to offspring over successive generations without causing harm.
• This earlier report does not indicate if viral transfer would occur as a result of a transplant or whether, if it did happen, it would cause any disease.

Animal Welfare

• The animal rights movement has objected to these advances in medical science, of xenotransplantation, because it ignores the rights of animals.
• They are hostile to the idea of animal farms with genetically modified animals for the purpose of harvesting organs for humans requiring transplant.
• Animals also have rights and it is our moral responsibility to support these rights.
• Such thinking, they argue, stems from a philosophy of anthropocentrism which places human beings at the centre of nature and regards all other living creatures as having only value if they can be of use to humans. 

ETHICAL ISSUES

• In addition to the critically important potential public health issues in xenotransplantation, there are a number of ethical issues that should be addressed.
• These include:
  • deciding upon the fairest way to allocate donor animal organs in a society where thousands of people die while waiting for a transplant;
  • deciding whether or not persons who receive xenografts may be compelled to participate in long term follow-up programs because of the theoretical public health risk from endogenous viruses;
  • developing a carefully constructed ethics concerning the creation and care of those animals that will be created to serve as donors;
  • determining when and under what circumstances children and infants may be considered as recipients of xenografts; and
  • studying the potential emotional impact on people of having had their lives prolonged with donor animal organs.