Cloning for Organs
With at least 180,000 people around the globe, including more than 3,500 Canadians, awaiting organ transplants, and with donor organs in short supply, animals are an obvious possible alternative source of spare parts for humans. The mammal that has organs closest in size and function to Homo sapiens is the humble barnyard pig. And when researchers are certain porcine organs can be used safely, cloned pigs could provide a bountiful supply of identical, genetically modified hearts, kidneys, livers and other organs for transplantation. But despite scientists' successes in cloning sheep, mice, cattle and goats, turning out carbon-copy pigs proved frustratingly difficult - until now. In reports published last week, research teams from the United States and Japan explained how they produced six cloned female piglets, whose wriggling, snout-nosed existence brought pig-to-human transplants a little nearer to reality.
Scientists celebrated the clonings as a major advancement. "It's a key step," said Dr. Robert Zhong, a London, Ont., transplant surgeon and immunologist, "towards an eventual revolution in organ transplantation." But formidable difficulties remain. Another study published by scientists in La Jolla, Calif., showed that pig viruses can infect human cells - raising the prospect that transplanted animal organs could spread new diseases among humans. Moreover, scientists are still searching for ways of dealing with organ rejection that is certain to occur when animal tissue is implanted in humans. "It could be years before the problems are solved," cautioned a spokesman for the British biotechnology giant Novartis. "We don't want to raise unrealistic expectations - especially among people on transplant waiting lists."
The two cloning teams produced piglets using complex procedures centring on fetal and ovary cells, and using electrical jolts to initiate cell division and the growth of early-stage embryos, with the results being implanted in surrogate mother pigs. The result: five piglets produced in Blacksburg, Va., by Edinburgh-based PPL Therapeutics in March, and another born in Japan earlier this year and named Xena - short for xenotransplantation, the scientific name for organ transplants between species.
Before pigs' organs can help keep humans alive, scientists will have to solve the rejection problem. The solution could come from research by Canadian scientists who are working with genetically altered white pigs raised at the University of Guelph, about 60 km west of Toronto. Bred by the Novartis subsidiary Imutran Ltd. of Cambridge, England, the pigs are not clones - researchers created the transgenic animals by injecting a human gene into pig embryos and letting the pigs produce successive generations through normal breeding. Imutran scientists think the pigs' human gene can trick transplant recipients' immune systems into accepting pigs' organs - instead of responding with hyperacute rejection, the massive attack the human immune system usually launches against alien tissue.
But rejection could still occur, notes Zhong, who is part of the Imutran research program, and the pigs will probably need further genetic modification to avoid that. As well, he added, "we are looking for new drugs to suppress the immune response - the existing ones aren't going to do it when pigs' organs are involved." At the same time, researchers will have to be sure that none of the scores of viruses lodged in pigs' genetic makeup, known as PERVs, will infect humans. "It's possible," said Ian Wilmut, leader of the Scottish team that cloned Dolly the sheep in July, 1996, that "there are pig viruses we don't know about that could be released into the human population." A possible solution, says Imutran's medical director, Khazal Paradis, might involve genetic tinkering to remove the DNA sequences in pigs that give rise to viruses. Given the problems that remain, he predicted, it could be "at least several years before we feel comfortable enough about our program to consider testing it in humans." If pig-to-human transplants are to be the solution to organ waiting lists, that day lies still further in the future.
Maclean's August 28, 2000