These Little Pigs Cry "Transplant"?

This genetically engineered and cloned piglet is a step toward overcoming the genetic obstacles that make animal-to-human organ transplants so tricky. © Science

The successful birth of four genetically engineered and cloned piglets, reported by the journal, Science, on the Science Express web site on 3 January 2002, may pave the way for more successful transplants of donor animal organs (xenotransplantation) as replacement organs for humans. Animals like pigs could provide an alternative source of transplant organs in the face of a continued human organ shortage, but immune rejection has significantly slowed the use of animal organs. Over 75,000 Americans are currently waiting for an organ transplant.

Now, Randall Prather of the University of Missouri-Columbia and colleagues have overcome a major xenotransplantation obstacle by genetically engineering pigs to partially lack the gene involved in this hostile immune response. The researchers "knocked out" one copy of the gene for a sugar molecule called alpha (1,3) galactosyltransferase. Normally, human antibodies latch on to this molecule, which rests on the surface of pig organ cells, and kill the cells, causing acute organ rejection.

Quick Time Movie Download video of cloned pigs. (2.7 MB) Courtesy of U. of Missouri

The researchers fused these "knockout cells" with pig eggs to create cloned embryos that were implanted in surrogate sows. The four live piglets resulting from this process lack one copy of the sugar molecule gene, and the researchers hope someday to create pigs that lack both copies of the gene. Pigs that completely lack the gene could provide replacement organs that aren't attacked by human antibodies. The cloned pigs may also serve as models of genetic modification for other medical or agricultural purposes.

The type of pigs used in this study come from a unique line of miniature swine that may have another xenotransplantation advantage: laboratory tests show that cells from this line of pigs don't seem to have the capacity to transmit HIV-like porcine endogenous retrovirus (PERV) to human cells. Although the risks of PERV transmission to humans is still uncertain, use of these mini pigs could help minimize any potential problems.

Among the four live piglets, Prather reports that overall health appears to be good, although one animal had an eye defect and small ear flaps.

-- Becky Ham