Our Charter

Preamble

APAAX is an international alliance opposed to the use of animal organs, tissues and cells for transplantation into humans, commonly known as xenotransplantation.

APAAX believes that xenotransplantation (XT) represents a dangerous and unethical development in medical therapy and that it is being promoted ahead of safer, cheaper and more reliable alternatives.

Aims

• To inform the general public in Australia and in other countries, of issues that continue to be ignored by XT researchers and proponents.
• To provide information about better health and research options.
• To point out alternatives to XT either available now or currently being developed.
• To influence public policy by ensuring that all issues of safety, efficacy, costs and ethics are considered carefully by health authorities.

Rationale

Xenotransplantation research

Researchers are investigating the following animal-to-humans therapies. APAAX considers that each of these methods has unacceptable outcomes.

Whole organ transplants from pigs to humans
Pigs are being genetically modified in an attempt to reduce or prevent rejection of their organs when transplanted into humans. Even if this prevents immediate (acute) rejection, subacute and chronic rejection problems are unlikely to be overcome and the available scientific evidence is too weak to be relied on as a basis for further research.

Cell Therapies
XT islet cell therapies have so far shown only limited efficacy and are not without risk.
There are many alternatives to animal islet cell therapies for diabetes (including human islet cells or insulin pumps) that have shown promise in terms of safety and efficacy.

External Therapies
Although external therapies that use animal tissue, such as liver assists and burn treatments, are considered less risky than whole organ transplants or XT cell therapies, they have their own associated risks as well as efficacy limitations. Many alternatives have either been developed or are under development.

Risks of Xenotransplantation

XT carries risks to the individual recipients, to their immediate contacts and ultimately to the general population.

• Subtle protein differences between pig and human tissues will continue to provoke powerful immunological responses in graft recipients irrespective of the number of genetic modifications/gene knockouts achieved.
• There is a serious risk of a viral infection which has never previously occurred in humans spreading from the source animal to the person receiving a transplant (zoonotic infection).
• The risk of zoonotic viral infection is not limited to the recipient. It could easily spread to close contacts and the wider community. As a new type of virus, it may not be containable.
• As viruses and other infectious agents remain viable in pig cells indefinitely and activate through mutation, and/or recombination with host viruses, at no stage can these agents be declared safe in human beings.

It has been shown that the ubiquitous pig virus PERV (porcine endogenous retrovirus) is able to infect human cells. Variants of PERV in transplanted pig cells will continue to be an unquantifiable risk.

Financial costs of Xenotransplantation

The costs of developing and maintaining XT therapies will be vastly higher than the costs of extending the scope of human tissue transplants and existing human-to human transplant technology.

• If xenotransplantation reaches mainstream medical application, it will require its own immensely expensive infrastructure to maintain vast pig populations in sterile conditions.
• Because of the risk of novel zoonotic viruses infecting human beings, substantial monitoring over the life time of all graft recipients will be mandatory.
• Governments will face potentially massive costs in containing the spread of and treating the effects of "new infections" from zoonotic viruses.

Alternatives to Xenotransplantation

Some alternatives to XT already exist and with the rapid advance of new technologies, XT cell therapies will soon be superfluous. Furthermore, alternative technologies will require a fraction of the cost to develop and incorporate into mainstream medicine without incurring unnecessary risks.

Prevention of disease

• Poor lifestyle and environment contribute to many of the diseases that require organ, tissue and cell therapies. Prevention of disease through healthier lifestyle could dramatically reduce the need for organs and cell therapies.
• A high percentage of liver transplants are preventable.
• There are ways of potentially preventing Type 1 Diabetes. These include vaccination, insulin inhalation and ensuring adequate vitamin D intake.
• Type II diabetes incidence, a common cause of kidney failure, could be prevented and reduced through improved diet and exercise and without medical intervention.

New technologies

• Stem cell research offers many clinical advantages over XT, e.g. no need for immunosuppressants and no risk of infection.
• Surrogate cell research essentially involves engineering a cell derived from tissue from the patient and then ensuring it produces the protein that is lacking in the patient.
• Insulin inhalation has been found to be a more effective treatment than insulin injection and is preferred by patients who have type I diabetes
• Human-based cell therapies are due to reach widespread clinical application with some researchers already saying that XT is not a necessary stop gap solution.
• For the treatment of burns, a dermal substitute based on a biodegradable segmented copolymer has been used to create synthetic scaffolds.
• Liver transplantation for the treatment of chronic liver failure (CLF) is set to be revolutionised by the recent discovery of liver stem cells.

Ethical issues raised by Xenotransplantation

People have wide-ranging opinions about the acceptable limits of the whole field of genetic technology and these unresolved issues for humans and animals apply equally to XT. The following issues specific to XT should also be considered.

For people

• Individual and institutional religious belief world-wide is divided over whether XT qualifies as an ethical medical application.
• There is a risk of the spread of zoonotic disease throughout society, to individuals who have never given consent for such practices and who remain unaware that this may occur.
• It is unlikely that there will be a fair distribution of limited medical resources if this highly expensive therapy proceeds - inevitably this therapy will predominantly go to those with the ability to pay but with major hidden subsidies from governments and others. Thus this will most likely result in an unfair distribution of scarce health resources.
• Whether it is possible for a person suffering a life-threatening illness to evaluate the risks and appreciate the long-term implications involved in accepting a non-human organ and thus to give informed consent to the procedure.

For animals

• Many people consider it unethical to involve countless animals in animal to animal tests given the unlikelihood of animal to human transplantation procedures successfully taking place
• In addition to the existing ethical problems involved in using animals in such procedures, a further dilemma faced is the incorporation of human genes into pigs making them partial humans. What will be the position on the rights of partial humans?

References

Collignon P, Purdy L. Xenografts: are the risks so great that we should not proceed? 2001 Editions scientifiques et medicales Elsevier. SAS

Ryan EA, Lakey JR, Paty BW, Imes S, Korbutt GS, Kneteman NM, Bigam D, Rajotte RV, Shapiro AM. Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes. 2002; 51:2148-57

Hammer C. Xenotransplantation for liver therapy or: Can porcine hepatocytes generate physiological functions sufficient for a human patient in ALF? Int J Artif Organs. 2002 25:1019-28.

Lavillette D, Kabat D. Porcine endogenous retroviruses infect cells lacking cognate receptors by an alternative pathway: implications for retrovirus evolution and xenotransplantation. J Virol. 2004; 78:8868-77.

Peck et al 2003 In vitro-generation of surrogate islets from adult stem cells, Transplant Immunoassay 12: 259-272;

Okitsu et al.,Transplantation of reversibly immortalized insulin secreting human hepatocytes controls diabetes in pancreatectomized pigs. Diabetes 2004 53:105-112)

Priscilla A. Hollander, Lawrence Blonde, Richard Rowe, Adi E. Mehta, Joseph L. Milburn, Kenneth S. Hershon, Jean-Louis Chiasson, and Seymour R. Levin Efficacy and Safety of Inhaled Insulin (Exubera) Compared With Subcutaneous Insulin Therapy in Patients With Type 2 Diabetes: Results of a 6-month, randomized, comparative trial. Diabetes Care 2004; 27: 2356-2362.

Zella JB, McCary LC, DeLuca HF. Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus. Arch Biochem Biophys. 2003; 417:77-80.

Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001; 358:1500-3.

No authors listed. Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. Diabetologia. 1999; 42:51-4.

Hunkeler D, Rajotte R, Grey D, Morel P, Skjak-Break G, Korbutt G, Gill R, Oberholzer J. Bioartificial organ grafts: a view at the beginning of the third millennium Artif Cells Blood Substit Immobil Biotechnol. 2003; 31:365-82

El-Ghalbzouri A, Lamme EN, van Blitterswijk C, Koopman J, Ponec M. The use of PEGT/PBT as a dermal scaffold for skin tissue engineering. Biomaterials. 2004; 25:2987-96.

Theise, ED, R. Saxena, R, Portmann, BC, Thung, SN, Yee, H, L. Chiriboga L, et al. The canals of Hering and hepatic stem cells in humans. Hepatology 1999 30 6:1425-1433.

Clare S, Humphrey H Organogenesis and Tissue Engineering in Transplantation MedicineTransplant Immunology 2004; 12:273-288

Manez R, Lopez-Pelaez E, Centeno A, Herrera JM, Juffe A, Domenech N, Harrison R, Schuurman HJ. Transgenic expression in pig hearts of both human decay-accelerating factor and human membrane cofactor protein does not provide an additional benefit to that of human decay-accelerating factor alone in pig-to-baboon xenotransplantation. Transplantation. 2004; 78:930-3.

Animal Protection Institute, Xenotransplantation

Willett WC Lessons from dietary studies in Adventists and questions for the future 2003; Am. J. Clin Nutr. 78(suppl):539S-543S