Cloned Pigs May Offer Humans Organs
Feat seen as step toward animal-to-human transplants.The cloned piglets, named Noel, Angel, Star, Joy and Mary, were created by PPL Therapeutics, the company that brought Dolly the sheep into the world.
In what many experts say is a major step toward producing a virtually unlimited supply of human transplant organs, two rival teams of scientists have cloned piglets lacking one of the two genes that prompt the human immune system to reject swine tissue. But some expressed reservations.
Pigs are considered a possible good source for organs, as they are readily available, easily bred and are about the same size as people.
Researchers said the achievement, announced by two competing labs, advances the day when herds of special swine could be used to grow lifesaving replacement organs for humans with ailing hearts, kidneys, livers and lungs.
“For the field of xenotransplantation (transferring an organ from one species to another) it is a very important advance,” Dr. Jeffrey L. Platt, head of transplantation biology at the Mayo Clinic in Rochester, Minn., said Wednesday. “It is not the final hurdle, but it is very important.”
The cloned pigs are missing a copy of a gene that animals have but that humans and some monkeys do not. The gene produces an enzyme called alpha 1,3 galactosyltransferase, which causes animal organs to die quickly when transplanted into humans.
It is the biggest barrier to animal-to-human transplants.
But two separate groups announced they had “knocked out” this gene in pigs and then cloned the pigs, to create litters of both genetically engineered and identical piglets.
Liangxue Lai, Randall Prather and colleagues at the University of Missouri and at Immerge BioTherapeutics in Charlestown, Massachusetts, said they had created four cloned piglets that were missing one copy of the gene.
“The four piggies we have are very healthy,” Prather, who was one of the first scientists to clone pigs, in 2000, said in a telephone interview.
His team’s announcement is published in the journal Science, in its online version.
FIVE PIGS PRODUCED IN VIRGINIA
On Wednesday, PPL Therapeutics in Scotland, the firm associated with the scientists who cloned the first adult mammal, Dolly the sheep, said its researchers had produced a litter of five cloned pigs, also missing one copy of the gene. They were born at the company’s farm in Virginia.But the researchers acknowledged that it will take more work to create true “knockout” pigs — animals with both copies of the gene removed.
Because only one copy of the gene is missing, the pigs still produce the enzyme and thus are not suitable themselves to use for transplants, Prather said.
“What we will be able to do is do inbreeding, and get an animal where both (copies of the gene) are knocked out,” Prather said.
“The point is we have introduced the (genetic change) into the population and now we can use conventional breeding to make more. We won’t have to clone again. Once you have it, it is there, and you can just use conventional breeding.”
Ayares said his team already has mother pigs pregnant with males that carry only a single copy of the gene. He said these animals will be born later this year and then mated with the females that were born on Christmas Day.
If both parents lack one copy of the gene, there is a one-in-four chance that one of their offspring will have no copies of the gene, Ayares said.
More than 70,000 Americans and hundreds of thousands of people around the world are on waiting lists for new organs, but there are not nearly enough to go around. An estimated 10 people die every day in the United States alone while waiting for a heart, liver, kidney or other organ.
Pigs are considered a possible good source for organs, as they are readily available, easily bred and are about the same size as people. Heart valves from pigs, which contain no cells but simply cartilage, are already very widely used in people.
QUESTIONS REMAIN
But some raise ethical questions about cross-transplanting body parts from one species to another. And others wonder if there’s a risk of simultaneously transmitting pig viruses to humans.Besides the enzyme, the other barrier to using pigs as sources of tissue and organs has been viruses that exist in all pig cells, known as porcine endogenous retroviruses (PERVs).
Experiments have shown that PERVs can be transmitted to human cells, although no one knows if they would cause disease in a human.
But Prather said his team had used miniature swine, a breed of pig specifically studied for human transplants. And in August 2000, Charlestown, Massachusetts-based BioTransplant Inc. said it had bred miniature swine that carried the viruses, but that did not transmit them to human cells the way normal pigs do.
The teams independently predicted that it will be about four years before swine herds are developed that could be used to grow organs for human transplantation.
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