Aug. 16, 2001 -- Her name is Xena, but she’s no warrior princess.
Xena is a scrappy, black-coated piglet born from a white-coated sow. As a swine produced by cloned genetic material from fetal pig cells, Xena represents the latest living milestone in the rapidly evolving field of genetic cloning.
She is named after the field of research that scientists hope her birth might advance — xenotransplantation — the use of genetically modified animal organs for transplant into humans.
“By bringing animal organs one step closer to being transplanted into human beings, we hope to one day overcome the desperate shortage of donor organs,” says Elizabeth Fagan, a professor of medicine and pediatrics at Rush Presbyterian at St. Luke’s Medical Center in Chicago.
Pig tissue and organs, particularly the liver, are thought to be similar to human’s and hold the best possibility for human transplant. But Fagan explains that even with the successful cloning of a pig, scientists still must find methods of ensuring pig’s organs aren’t rejected in the human body and are able to function in human hosts.
“Regardless if they’ve cloned a sheep or a pig, we don’t know how the organs handle human material because pigs don’t go around eating caviar or french fries or drinking alcohol,” she says.
Xena Not the First
Xena isn’t the first cloned pig to enter the world. That honor belongs to a litter of five cloned piglets born in March at the Scotland-based PPL Therapeutics — the same laboratory that produced another famous female, Dolly the cloned sheep. The procedures both groups used are being published separately this week in two major science journals.
In this week’s issue of Science, lead author Akira Onishi of the National Institute of Animal Industry in Japan explains his team used the same techniques developed by researchers at the University of Honolulu to clone mice.
To create Xena, scientists used a needle-like pipette to inject genetic material from fetal pig skin into eggs that had been stripped of their own genetic material. Next, the team stimulated the injected eggs with an electrical pulse that triggered them to develop into embryos. Those embryos were then transplanted into four surrogate sows.
Healthy and black-coated, unlike her white-coated surrogate mother, Xena was the one successful birth of 110 transplanted embryos.
When researchers cloned Dolly the sheep, they fused entire cloned cells into empty host eggs. Researchers on Xena’s team believe their technique of injecting only genetic material will allow scientists more flexibility in the future to manipulate the genetic material of pig cells and effectively engineer transplant-safe organs.
“With microinjection you can be quite selective about genetic transfer,” co-author Anthony Perry of Rockefeller University said in a Science news release. “You can separate the chromosomes out and avoid contaminating the egg with the rest of the material from the donor cell nucleus.”
But scientists with the Scotland-based PPL Therapeutics contend the success rate for the procedure that created Xena remains too low. To ensure more successful fertilization, scientists at PPL Therapeutics added a step to the cloning process. Rather than electrically stimulating the cloned egg to develop, they inserted the cloned material into the shell of a fertilized cell, or zygote. The scientists describe their procedure in this week’s electronic version of the journal Nature.
“It’s a bit more labor intensive, but if you look at our success numbers, it’s a more efficient method,” explains Ron James, managing director of PPL Therapeutics. He points out that this method created five healthy piglets last March, as opposed to one.
Efficient cloning may become an important factor in the future if and when scientists are able to use pig organs for human transplant. About 180,000 people around the world are estimated to be waiting for an organ transplant, but fewer than one in three will receive one because of the widening gap between supply and demand. Many see organs derived from pigs as a solution to the problem.
Research is already under way to manipulate genes responsible for organ rejection. Once scientists find a way to turn off organ-rejecting genes, they hope to clone pigs with genetic material that is missing those genes. But as a Nature study points out this week, organ rejection isn’t the only concern. Transferring pig organs may also introduce contagious diseases to humans.
Danger of Disease
Daniel Salomon of the Scripps Research Institute in La Jolla, Calif., and colleagues found that human cells can be infected with viruses that exist in all pig cells, called porcine endogenous retroviruses or PERVs.
“Xenotransplantation falls into the category of hazard where, although the risk is probably low — and the benefit to individuals undoubtedly substantial — the public consequences could be catastrophic,” wrote Nature’s editors.
Guidelines surrounding xenotransplantation research by the U.S. Food and Drug Administration have stiffened since 1996 because of such fears. And earlier this week, the director of Scotland’s Roslin Institute, which has been associated with PPL, said it would re-direct funding away from its pig-cloning program.
Scientists say it may be a long time anyway before researchers confront the possible side effects of xenotransplantation. Xena the cloned pig may represent a big step, they say, but there are many more to come before any animal’s organ is made “user friendly” for people.
As John Brems, the director of transplantation at Layola University Medical Center in Chicago, says: “Pigs walk on all fours. If we put their organs in an animal that walks standing up, there are a lot of differences there — a lot of obstacles to overcome to ensure they’ll work.”