Safety fears grow over pig transplants

DOCTORS have warned that the public could be put at risk by animal- to-human organ transplants, despite the latest attempts to devise strict guidelines limiting the practice.

Last week, Imutran, the British company which took the world by surprise in 1995 when it announced it was ready to put a pig heart into a human, said it was preparing to use a pig liver to treat a human patient. On this occasion it was planning to connect the pig liver to the recipient outside the body, using the same principle as a dialysis machine, until a human liver was available.

Dr Corine Saville, chief operating officer at Imutran, told BBC Radio 4's Today programme that the company would apply for a licence to do it "when we think it is justified on the basis of the science", adding, "I would expect we are talking a matter of months to years rather than weeks."

Three years ago, the Conservative government, surprised by Imutran's moves, swiftly organised a national advisory group headed by Ian Kennedy, Professor of Medical Law and Ethics, which placed a moratorium on clinical trials. More research, it said, was needed on the danger of passing pig viruses to humans.

On the same day as the company's latest announcement, Frank Dobson, the Health Secretary, launched new guidelines on animal to human, or xenotransplants, directing anyone wanting to carry out such an operation to get the go- ahead from him and the UK XIRA, a regulatory body set up a year ago.

Imutran, a Cambridge-based company owned by drugs giant Novartis, has overcome the first barrier of organ rejection by genetically modifying pig organs with human genes. The pig hearts express human proteins at their surface which are accepted by the human immune system. In trials, monkeys transplanted with genetically modified pig hearts survived for 60 days.

But the real concern for scientists now is the danger of pig viruses being passed across the species to humans. Professor Robin Weiss, of the Imperial Cancer Institute, said: "We knew there were six companies at the forefront of xenotransplantation and none of them was really saying there is a problem about viruses. We had the techniques so we started the research hoping that the viruses would not infect human cells in culture. Unfortunately they did."

Prof Weiss and his team were particularly concerned about one group of viruses known as endogenous retroviruses - "sort of second cousins of HIV" - which are inherent in many animals including humans. They found that two of three of a particular cell line of retroviruses could infect human cells in culture.

"The real ethical issue surrounds the question of what if the virus started spreading from the recipient to his or her sexual partner, children, and then became a human epidemic," said Prof Weiss. "People say that is too far-fetched, but then you can ask where did HIV come from?"

Pigs are being studied as a source of organs for human transplant for one simple reason. The supply of organs for transplant is falling, partly due to the success of road safety campaigns, yet 6,000 people are on the waiting list at any given time for replacement organs. Government figures show that more than 200 people die each year awaiting heart, liver, lung or heart-lung transplants. In 1997, there were 5,732 people awaiting kidney transplants but only 1,635 were carried out.

Using pig organs and tissue in humans is not new. Imutran is now undertaking a retrospective study of 160 patients around the world who have been exposed to pig organs in operations to find evidence of infection or disease. In the United States, pig neurone cells have been used to treat Parkinson's and Huntington's disease sufferers and, in Russia, children with septosemia have had their blood filtered through a pig liver to remove bacteria.

So far there is no evidence of infection in the blood samples of these patients. Imutran's research data will be independently verified and presented later this year.

In addition to the spectre of a pig virus pandemic, there are also moral questions raised about the use of genetically modified animals in humans. The Rev Professor Andrew Linzey, animal ethicist and fellow of Mansfield College, said: "I have a fundamental ethical objection to using animals for spare parts. If we can't respect the genetic integrity of a pig, what chance have we got for the human race?

"Even if you take a purely utilitarian view in which you balance the benefits - helping people on transplant waiting lists - and the danger of an unknown, untreatable and uncontrollable virus infecting the whole human race, then surely the risks outweigh the benefits?

"The underlying political reality is that the international companies that have invested millions of pounds in this are now really pressurising government so that they can make a return on their investment."

While the debate on transplant ethics in the United States has been continuous ever since the Food and Drug Administration started to regulate the area after Prof Weiss's research was published in March 1997, there has been little equivalent discussion in Britain.

Alistair Currie of Xenotransplantation Concern said: "Human clinical trials are a matter not of individual choices but of public health, and after the last government's mishandling of the BSE/CJD question we expect this government to recognise their responsibility to maximise public awareness of the risks, as well as the possible benefits of xenotransplantation."

An Imutran spokeswoman said the company would "proceed cautiously" but the warnings of Aids and BSE still loom large. As Prof Weiss points out: "New medical procedure is never entirely free of risk. We can say we have identified these particular types of virus, and we have tight mechanisms for looking at them, and we might be able to knock some genes out, but you can never be watertight against what you have not yet discovered."