Novartis To Pigs: Keep Your Kidneys
By Meredith Wadman

(FORTUNE Magazine) – Last month Swiss drug giant Novartis scaled back research on pig-to-human organ transplants, dealing a big blow to the hyped field of xenotransplants (the technical term for animal-human organ donation); Novartis once led the race to develop the procedure.

Novartis is closing its xenotransplant subsidiary, and although some of the work will continue through a new joint venture, the future of the enterprise is precarious at best. In three years, if the new business can't produce strong evidence that xenotransplants can work safely, Novartis will cut off funding. Paul Herrling, Novartis' head of global research, says he's not terribly optimistic, but the company "did not want to simply abandon the approach."

Xenotransplants looked promising in 1995, when researchers at Britain's Imutran announced a breakthrough success transplanting pig hearts into monkeys. Suddenly Babe seemed the answer to a devastating human organ shortage. Novartis (then Sandoz) CEO Daniel Vasella pledged to spend $1 billion on research, then bought Imutran in 1996 to compete with Baxter Healthcare and US Surgical in the xenotransplant race. Company officials giddily predicted mass-market pig hearts and kidneys by 2004. The excitement was furthered by a Salomon Brothers study that estimated a $6 billion market for xenotransplants by 2010.

Now Novartis has shut down the Imutran operation, its optimism dampened by the cold calculus of politics and the fickle finger of scientific discovery. The first blow came in 1997, when scientists reported that a virus found in pig genes could infect human cells in lab experiments. Although there's no evidence that porcine endogenous retrovirus, or PERV, causes disease in humans, Imutran faced enormous scrutiny from government regulators, wary scientists, and anti-xeno activists who fear that animal-human transplants may unleash the next AIDS. An additional headache: Animal-rights activists regularly targeted Imutran's work.

But perhaps the biggest problem was that Imutran's scientists didn't deliver. Vasella bought the British biotech outfit because its researchers had cracked a huge problem; pig organs are usually rejected immediately, but half of Imutran's monkeys were still alive 40 days after the transplants. Unfortunately they were never able to build on that success--when Imutran closed, scientists had been able to get only one monkey to live beyond three months. (Their competitors have done no better; US Surgical dropped out of the race in 1999.) Says Daniel Salomon, an expert in organ transplantation at the Scripps Research Institute in La Jolla, Calif.: "That's a remarkable scientific achievement. But if you are talking about a human trial, that ain't going to cut it."

Despite the grim news, researchers are plodding on, trying to resuscitate hopes for xenotransplants. Scientists working with Novartis' new joint venture have produced a minipig that seems incapable of transmitting the worrisome PERV to human cells in a petri dish. And a strong new competitor has emerged: The cloning of pigs last year by Scotland's PPL Therapeutics has opened up enormous possibilities for modifying pig genes in ways that may let transplanted organs survive immune assault. Meanwhile at Nextran, a Baxter subsidiary, vice president of research and development John Logan stills expects the company to be ready for human trials of pig organ transplants this year or next.

"Everything's okay," says Scripps' Salomon. "We just have to cool it, do some good research, find the next technological edge. In the end the overwhelming donor organ shortage and the misery and death that this brings will drive xenotransplantation forward." We're not sure whether to call that optimism.