spiked-science | Article | Pig organ transplants: you could die waiting

The use of animal cells and tissues in human organ transplants could be the best hope for the majority of patients waiting for transplants. So why have the US authorities placed clinical trials of pig xenografts on hold?

Every year, almost 10 percent of people awaiting a heart transplant die because no organ is available. In the USA, as many as 50 000 people die every year waiting for heart transplants. In the UK, 10 months into the year 2000, 1900 people had received transplants from 649 donors. Yet there remained 5700 people still in need of a transplant, (1) and most would die waiting.

Consider the emotional and physical toll of simply waiting. To hold on 10 years for a kidney transplant is not unusual, and during that time the patient must undergo four hours of dialysis three times a week and maintain a heavily restricted diet. The potassium content of a banana will kill a patient with kidney failure. The wait and death toll would be reduced if more donors came forward, but even under the most optimum of circumstances and the maximising of the potential donor pool, the supply of transplantable organs will never meet the demand.

It is this pressing need for an increase in the supply of donor organs that has provided the impetus for investigating xenotransplantation: the grafting of animal cells and tissues into humans. Writing in the journal Science in 1999 (2), Robin Weiss of University College, London has described the future of xenotransplantation as one with an 'uncertain peril and certain promise'. The promise is that of a virtually limitless supply of cells, tissues and organs for a variety of therapeutic procedures including transplantation. The peril includes imperfect function of those organs, immunological rejection and the transmission of harmful viruses. The transmission of viruses is perceived as the greatest threat and has received the most attention from researchers.

Pigs are potentially a safer source of organs than humans

For various reasons, including size of organs, matching physiology, practical matters of husbandry and ethical objections to the use of primates, pigs are the most likely source of donor organs. Most potential pathogens can be eliminated from the donor animals through the use of closed breeding, barrier air filters and other strict biosecurity measures during preparation. These procedures make pigs a potentially safer source of organs than humans because pathogens such as cytomegalovirus and Epstein-Barr virus, which are a common cause of mortality in the post-transplant patient, can be eliminated from pig but not human donors.

Porcine endogenous retrovirus, so called PERV, however, cannot be removed. PERV is a retrovirus that is integrated into the genome of pigs, which cannot be eliminated through any known breeding mechanisms or other extraction procedure. The risk of PERV infection in a human recipient of a pig organ prompted the US Food and Drug Administration (FDA) to place pig xenograft trials on hold until the risk could be adequately assessed.

PERV poses a particular hazard. Cross-species transmission of a virus can be devastating because the immune system is naive to the new attack and few viruses are amenable to therapy so that any PERV infection would be difficult to treat. Examples of newly emerging viral diseases in humans include AIDS and Ebola. The possibility of unleashing a new AIDS on the planet has understandably given scientists pause for thought.

Yet a team of American and European scientists from the Novartis foundation and from universities including Glasgow, St Petersburg and Montreal directly investigated this possibility, in a study of 160 patients who had been treated with living pig tissue including skin grafts, blood products and the transplant of nervous tissue into the brain (3). No PERV infection was detected in any of the patients, including those who were pharmacologically immunosuppressed and were therefore placed at greater risk of infection. PERV was not detectable in any patient despite the presence of pig cells observed in 23 patients up to 8.5 years after the original procedure.

These findings demonstrate that infection from PERV is either not occurring, is occurring and is being removed by the recipient's immune system, or is occurring at a very low level that is beyond the limits of our current detection techniques. PERV cannot be considered highly infectious and, if transmitted at all, cannot be highly aggressive as there was no detectable illness, side effects or other morbidity even in those patients that had received their therapy many years earlier. The possibility of a very low level of infection with a long latency to disease was not ruled out by this study and cannot be ruled out by any study excepting a monitored clinical trial of xenotransplantation.

A thoughtful process of trial and error characterises the emergence of all complex fields of medicine with the full knowledge that failures and setbacks are bound to occur. Xenotransplantation is no exception. The first recipients of pig organs will need to submit to a high level of vigilance to assess retroviral infection. The implications for the individual and his or her intimate contacts will be profound but are likely to be preferred to years of waiting followed by almost certain death. The risk to broader society will be much more remote than that to the individual because, unlike those exposed to HIV, recipients of pig organs will be a known and already highly monitored section of the population.

Both the FDA and British authorities are moving towards approval of small-scale human trials of xenotransplantation and their efforts need applause and encouragement. The alternative is to abandon xenotransplantation and forever deny a therapy that could save tens of thousands of lives.

Stuart Derbyshire is an assistant professor in the University of Pittsburgh Department of Anaethesiology. He is a contributor to Animal Experimentation: Good or Bad?, Hodder Murray, 2002 (buy this book from Amazon (UK) or Amazon (USA)).

Read on:

Animal research: a scientist's defence by Stuart Derbyshire

Andrew Blake: 'Animal research is the only hope for people like me' by Brendan O'Neill

(1) Statistics of the number of people requiring and receiving heart transplants are available from the United Kingdom Transplant Support Service Authority

(2) Robin Weiss was writing in Science in 1999, issue 285

(3) See 'Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue', Paradis K, Langford G, Long Z, Heneine W, Sandstrom P et al, Science 1999, issue 285 here