Opinion: Xenotransplantation: medical advance denied

By Bob Elliott

In the context of treatment for human disease, xenotransplantation involves the transplantation of normal living organs, tissues or cells from animals into humans who suffer disease resulting from damage to the corresponding body parts. It can also refer to transplanted human cells grown on animal cell substrates ex vivo.

The use of animal cells as donors is attractive as human donors are scarce. There are however, some reservations. The two major medical concerns are the swift rejection of animal derived transplants and the real possibility of harm from infections introduced by such transplants. There are also ethical concerns about the use of animals for ‘spare parts’ and a spiritual concern about ‘human identity’.

This has led to a moratorium on xenotransplantation in countries such as Australia and Canada. In other jurisdictions, such as the USA, European Union, New Zealand, China and many other countries, guidelines have been compiled to limit precocious research and treatment.

Is the moratorium here justified? The answer comes down to whether potential benefit exceeds potential risk. If non-hypothetical risks do indeed exist, they should be quantified as much as is feasible. Similarly, likely efficacy needs to be quantified. The balance of risk and benefit can then be assessed and a rational decision to proceed to clinical trial made.

The principal risk is that of infection with animal endogenous retroviruses. This has occurred in the past in the case of primate donors and the practice has been subsequently banned. However, all non-primate animals and the viruses that infect them have surface antigens not found in primates. This means we are inherently less likely to catch most non-primate viruses but are sensitive to primate viruses.

The risk of human infection with porcine endogenous retrovirus (PERV) has been thoroughly researched. Not all pigs are capable of producing infectious virus from the genomic provirus, or if they do, of producing virus capable of recombination with human viruses or subtype recombinations. Furthermore, full length retrovirus has been injected intensively on many occasions in the same individuals (such as haemophiliacs treated with porcine derived clotting factor) without infection.

Many hundreds of pig cell transplants into humans or primates have been carried out without causing infection. Indeed, it appears that no animal has ever been productively infected with porcine retroviruses despite thousands of attempts, even including several species of immune suppressed primates with human adapted pig retro viruses or virus producing cells.

Infection with ‘unknown’ pig viruses has also been brought up as a possibility. Xenotransplantation does not provide additional risk of infection from such hypothetical agents compared for example with pig farmers or abattoir workers. Infection from other known agents can be eliminated by sourcing donor animals from defined pathogen free animals.

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Efficacy of xenotransplantation of organs into primates or humans has not been demonstrated beyond a few weeks or months, and this form of transplantation trial in humans cannot be sanctioned as yet. On the other hand, there have been scientifically substantiated reports of long-term successful cell xenotransplants.

These include pig insulin producing cell clusters (islets) into primates, including humans, using immuno isolating permselective alginate coatings and novel generalised or localised immunosuppressive agents. Sertoli cell co-transplantation is an example of the latter. Genetic modification of pig donor cells may enhance the avoidance of rejection.

In 1996, a longstanding Type 1 diabetic was given about a million porcine islets in prototype microcapsules. Function was clinically apparent for about a year, and 10 years later live insulin-producing cells were recovered from his abdomen and pig insulin could be found in his blood. In a similar study started by Living Cell Technologies in Russia in 2007, two of seven diabetic patients who received a more advanced product have become insulin independent, and four of the other five are still showing substantial clinical benefit.

Where to, then, with the current moratorium on xenotransplantation in Australia? The major risk bogey – infection with pig endogenous retroviruses – is hypothetical and now perceived as ‘vanishingly small’ and demonstration of benefit has been substantiated. As such, I strongly believe that the moratorium on trials of cellular xenotransplantation is no longer appropriate.

‘Duty of care’ is a major responsibility not only of practising health members and researchers, but also health administrators. To unreasonably deny people with diseases such as diabetes and Parkinson’s Disease the hope of better treatment gained by xenotransplantation research is unethical.

Disease sufferers who volunteer for such limited trials may be the best to decide on whether cultural and spiritual considerations affect them, although xenotransplantation outside of limited clinical trials may require wider public consultation.

Dr Bob Elliott is the founder of Living Cell Technologies, which recently began trials in New Zealand of DiabeCell, which uses transplanted pig cells to treat diabetes.

This feature appeared in the September/October 2009 issue of Australian Life Scientist. To subscribe to the magazine, go here.