The British firm that cloned Dolly the sheep said Tuesday that it has taken a further step by breeding the first clones of pigs, in what experts said could be a “profoundly important” advance toward the goal of modifying animal organs for transplant to humans.
Some researchers criticized the decision by PPL Therapeutics Inc. of Edinburgh, Scotland, to release news of its achievement before the work has been vetted by other scientists and published in a professional journal.
The hurried announcement paid off, as PPL stock rose 19 percent on news of the cloning.
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Yet the Blacksburg, Va.-based team that produced the piglets–named Millie, Christa, Alexis, Carrel and Dotcom–is a respected group that has been on the verge of such a feat for some time, experts said.
The goal of cloning pigs has been a Holy Grail for researchers working on xenotransplant-ation–the use of animal organs for transplant to human beings–in large part because the risk of passing diseases from pigs to people is less than the danger from primates such as baboons. Cloning also provides ways of genetically engineering animals to be compatible with the human immune system with a level of precision that’s impossible using current genetic methods, scientists said.
“This is excellent news for all of us in the field of xenotransplantation,” said Dr. Robert Lanza, vice president for business and scientific development at one of PPL Therapeutics’ competitors, Worcester, Mass.-based Advanced Cell Technologies. “There’s going to be a lot of pressure for other teams to get their projects up and going.”
Although experts say the first human clinical trials of xenotransplantation are at least two years away, genetically engineered pigs could one day eliminate current shortages of human donors of livers, kidneys and hearts.
As many as 68,000 people in the United States and 50,000 in Europe are waiting for transplants, and demand is growing by 15 percent a year while the number of donors is dwindling.
Professor Nadey Hakim, surgical director of the transplant unit at a leading London hospital, said: “If they have successfully cloned pigs, we could potentially have an endless supply of kidneys, hearts and livers for transplantation.”
At the moment, xenotransplantation is banned by the American and British governments because of the fear that animal viruses might be transmitted to the human recipients.
That concern abated somewhat last year with the release of a study co-authored by the Centers for Disease Control and Prevention showing that certain retroviruses common in pigs did not appear to cause infection in people who received pig heart valves or similar tissue transplants.
In addition to having fewer disease risks than primates, pigs would be a more ethically acceptable source of organs because they already are bred for food, researchers say. Still, Michelle Thaw of the Anti-Vivisection Society in Britain deplored what she said was a move toward “using animals as spare parts.”
A major goal of pig cloning is to produce “knockout” pigs that lack a gene thought to produce a sugar that causes the human immune system to attack pig tissue.
Although researchers have produced such knockout pig cells in the laboratory, they have not been able to extend the technique to entire animals with current genetic engineering techniques. Cloning should allow scientists to use the knockout cells to create whole genetically modified animals, which could then be bred naturally with the new traits.
Making the pig clones called for overcoming hurdles of basic animal husbandry as well as sophisticated cell biology.
Unlike other mammals such as sheep, pig sows need at least three gestating embryos to maintain a pregnancy, according to David Ayares, vice president of research and development at PPL and leader of the team that bred the pig clones. It took many attempts to get enough piglets to mature at the same rate and survive to term.
Pig egg cells are also fragile, requiring changes in the method of nuclear transfer that was used to clone Dolly.
The technique involves removing the nucleus of a cell from an adult animal and implanting it in the “husk” of an egg cell, which is then put into a solution of salts. The cell divides like a normal embryo.
“Solving nuclear transfer in pigs was quite a challenge,” Ayares said. PPL has applied for a patent of the technique used to clone the piglets, which were born March 5.
Other companies working on pig cloning include Advanced Cell Technologies and Charlestown, Mass.-based BioTransplant Inc. PPL Therapeutics is the commercial spinoff company of the Roslin Institute in Edinburgh that carried out the cloning of Dolly.
Although the PPL team’s success appeared legitimate, many researchers say announcing such results before they have been published amounts to a dangerous shortcut around the formal process of scientific peer review.
“I hope this isn’t a trend,” said Lanza of Advanced Cell Technologies. “Publication by press release is not desirable.”
Still, Lanza said, “They’re a really reputable team. We’d had some advanced pregnancies ourselves, so we knew it was a doable feat. I think they wanted to put their flag in the ground.”