Cloning the New Babes

By Jeffrey Kluger

Dolly was once an awfully lonely sheep. When the famously cloned animal made headlines in 1997, she was the only mammal ever to be manufactured from the cell of an adult donor. Since then, the clone ranks have swelled, with mice and cattle also toddling out of the labs. Last week cloning technology took another step forward when an international biotechnology company announced that it had created a litter of five genetically identical piglets, and that it had a pretty good idea of how they could one day be used: as organ donors for ailing humans.

The idea of turning pigs into tissue factories has been around for at least 30 years. Pigs breed easily and mature quickly, and their organs are roughly the same size as those of humans, meaning operations can be performed with a relative snap-out, snap-in simplicity. The problem is, once the donor organ is stitched in place, the body rebels, rejecting it even more violently than it would a human graft. "A pig heart transplanted in a person would turn black within minutes," says David Ayares, a research director with PPL Therapeutics, the biotech firm based in Scotland, New Zealand and Virginia that helped clone Dolly and also produced the piglets.

What causes porcine organs to be rejected so quickly is a sugar molecule on the surface of pig cells that identifies the tissue as unmistakably nonhuman. When the immune system spots this marker, it musters its defenses. PPL scientists recently succeeded in finding the gene responsible for the sugar and knocking it out of the nucleus of a pig cell. Their next step would be to extract that nucleus, insert it into a hollowed-out pig ovum and insert the ovum into the womb of a host sow. The sugar-free piglet that was eventually born could then be cloned over and over as a source of safe transplant organs. "The idea is to arrive at the ideal animal and repeatedly copy it exactly as it is," says Dr. Mark Hardy, director of organ transplantation at New York-Presbyterian Hospital.

The cloned piglets PPL introduced to the world last week were created in just this way, though for this first experiment in pig replication, the scientists left the sugar genes intact. "We wanted to work with pristine cells to make sure our cloning technique would indeed work," says Ayares. Now that they've proved it does, the scientists plan to raise the bar and try the same procedure with modified genes.

Despite this recent success, PPL is not likely to be setting up its organ shop anytime soon. Knocking out the key sugar gene solves only the problem of short-term rejection. Long-term rejection, caused by blood coagulating around the new organ, requires that researchers re-engineer an entirely different set of genes that code for anticoagulants. But even this would not be a perfect solution, and recipients of pig organs would probably still have to take the same rainbow of antirejection drugs recipients of human organs must now endure.

Nonetheless, Ayares is optimistic, insisting that pig organs could be available in as little as five years. Hardy believes that whenever the tissue does come along, it will at first be rather small-bore stuff--pancreatic islet cells for diabetics, say--rather than hearts, kidneys or lungs. Whatever it is, even a little new transplant material is a big improvement over what's available now, and for gravely ill patients awaiting a donor, that's no small thing.

--With reporting by Alice Park/New York

With reporting by Alice Park/New York