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Online Extra: Side of Valves, Hold the Bacon


On a scenic stretch of the Blue Ridge Mountains, the stench of pigs wafts from a nondescript barnyard near Blacksburg, Va. David Ayares, chief executive of biotech startup Revivicor, trudges from pen to pen in his mud-stained boots, lovingly eyeing rows of suckling piglets.

"Those are knockouts," he says gesturing towards one pen. The term describes the pigs' tweaked DNA -- not their ravishing pink physique. It is also a metaphor for this farm's grand mission: to breed pigs that can donate their organs to humans.

PORCINE PARTS.Ever since the first organ transplant was performed in 1954, there have never been enough human donors to meet the demand. And the problem is only getting worse. So far this year, 16,445 transplant surgeries have been performed, but 95,919 patients are on the waiting list, according to the United Network for Organ Sharing.

Every day, 17 people die waiting for organs. "The numbers are staggering," says Marlon F. Levy, surgical director of transplantation at Baylor University All Saints Medical Center in Fort Worth.

In theory, pigs should be ideal organ donors. Their hearts, livers, and kidneys are about the same size as ours, and they work much the same way. But there are a few key differences between pigs and people that have made the dream of turning porcine parts into lifesavers -- otherwise known as xenotransplantation -- difficult to pull off.

One problem is that their organs house a sugar molecule that causes people's immune systems to go haywire. The pigs from Revivicor and other companies don't have the deadly molecule. The organs have only been tested in other animals so far, but the results are promising: Monkeys with the new pig organs can survive for months, as opposed to just hours with organs that contain the problematic sugar.

SILENCING GENES.Still, knocking out one trait isn't enough. For their organs to last years in humans, pigs will have to be made even more like us. Revivicor is now adding a human gene to some of its pigs that helps to prevent deadly blood clots from forming in and around the organs after they're transplanted.

They're also working to eliminate a pig virus that some transplant physicians fear could be passed along to humans. Using an emerging technique for silencing genes that contribute to the virus, Revivicor hopes to zap it altogether.

The payoff could be sizable. Ayares says it's too early to estimate how much Revivicor cold reap from its reengineered pigs, but Elliot Lebowitz, who recently started a company to commercialize Harvard University's humanized pigs, estimates viable organs could sell for $50,000 a pop. Considering that right now there are nearly 67,000 patients in the U.S. waiting for kidneys alone, "you get into the billions very quickly," he says.

BACK ON BOARD.Problem is, the deep-pocketed investors needed to fund the early research have bolted out the barn door. In the late 1990s pharma giants Baxter International (BAX) and Novartis (NVS) made multimillion-dollar bets on xeno. After the task proved harder than expected, both companies pulled out in 2004.

That turned off venture capitalists such as Paul J. Schmitt of PA Early Stage Partners in Wayne, Pa. Schmitt was once CEO of DNX, which formed a xenotransplantation joint venture with Baxter. Even though he was a pioneer in the field, Schmitt hasn't funded the new crop of xeno startups for fear he won't be able to cash out until some big health-care companies climb back on board. "We're seeing a big chill," he says.

As the scientific community struggles with the challenges of building these new organ farms, many patients are eager to reap the benefits. One who has already gotten a taste of the future is Robert Pennington, a 25-year-old veterinary assistant in Addison, Tex. In 1997 he was in acute liver failure and near death when Baylor's Levy hooked him up to a transgenic pig liver, which kept him alive for seven hours until a human donor was found.

It could be a while before more such human trials are performed. Still, Pennington, who says his health is "perfect" today, is adamant that the xeno dream be kept alive. "I'm a believer," he says. "Research like this saves people's lives." By Arlene Weintraub in New York


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