Research Progress: Pig
Cloning for Organs:
Target is Gene that Leads to Organ Rejection
January 3, 2002' 2:50 PM EST; Columbia, Missouri (CNN) -- Researchers say they've taken a major step toward cloning pigs whose hearts, lungs, and kidneys could be safely transplanted into humans. Such organs would save the lives of thousands of critically ill people who cannot get transplants because of the shortage of human organs.
Using the same cloning technique that created Dolly the sheep, scientists say they produced four piglets without one of two genes that lead to the massive rejections that have plagued efforts at xenotransplantation -- the process of replacing human organs with animal organs. "We've knocked out one copy of the gene known to cause this immune response," said Randall Prather at the University of Missouri-Columbia, who performed the nuclear transfer that produced the piglets. "Now we have to do other studies to make the double knockout." The two genes are actually copies of the same gene, known as GATA1.
"This is a major, major step in our attempt to be able to come up with an animal that can be used for transplantation," said Dr. Goran Klintmalm of the Baylor Institute of Transplantation Sciences "They've knocked out the protein that identifies the organ as being a pig organ rather than a human organ, so it's a very significant advance."
Researchers predict it will be only a matter of months before they genetically engineer piglets without either copy of the GATA1 gene. The next step will be to test the organs by transplanting them into non-human primates. "We think if everything is successful with what we think are the major issues, in [2 - 3] years we'll be able to develop a program to test the organs in small numbers of human patients," said Julia Greenstein of Immerge BioTherapeutics, a company created to lead the research project.
Initially, researchers think the piglets' hearts, lungs, and kidneys could be transplanted into humans. Currently, about 75,000 Americans are on transplant waiting lists. Most people die waiting for an appropriate organ. While the demand for organs increases every year, the supply of human donor organs has remained relatively stable. Even if animal-to-human transplants become feasible, there are still likely to be questions about whether such procedures are morally acceptable. "Most transplant patients would have no such qualms," researchers say. "When you talk to patients and see surveys done with patients on organ waiting lists, if they're shown to be safe and effective, I think the population that has end-stage organ disease don't have a huge problem with animal organs for transplantation," Greenstein said.
Researchers produced seven piglets, but three died. One of the four living piglets was born with an ocular defect and small ear flaps. "The deaths appeared to be caused by classic nuclear-transfer problems, such as respiratory distress, immaturity at birth, and heart problems," Prather said. That points to another question that must be answered: Could the organs in the genetically engineered piglets be flawed? "We can only speculate at this time because we simply don't know," Klintmalm said. "The only way to get the answers is to do studies and see how it works out."
Another major concern with animal-to-human transplants has been the theoretical threat of transmitting dangerous animal viruses to humans. With pigs, the specific concern has been the potential spread of Porcine Endogenous RetroVirus -- or PERV -- a naturally occurring part of pigs' genetic makeup that appears to cause no harm to pigs, but may play a role in resistance to infection. Greenstein said researchers were able to find a strain of miniature pigs that, "while they have PERV, don't appear to be capable of infecting that virus into human cells, so we think that means these pigs will have a potential safety advantage with regards to PERV."