5 Pigs Cloned; Transplants to Humans Touted
The British company that helped clone Dolly the sheep announced Tuesday that it has created the first cloned pigs, animals that eventually could be used as sources of organs needed for human transplant.
PPL Therapeutics said five cloned piglets were born March 5 in Blacksburg, Va., ushering in what could be a new era in cell and organ transplants and an end to the chronic shortages of donors worldwide.
Clinical trials on humans could begin in as little as four years, said the company, which hopes to help supply an estimated $6-billion market for organs and a similar market for cellular therapies to treat diseases such as diabetes.
Pigs are the preferred species for “xenotransplantation,” or animal-to-human transplants, because they can be bred quickly and their genetically altered organs are about the same size as human organs.
Tuesday’s announcement sent the Edinburgh-based company’s stock price soaring, but like so many developments in the rapidly changing field of biotechnology, this one raised as many questions about safety and ethics as it seemed to answer.
“It certainly is a positive step if you are sitting in the queue for heart transplants,” said Jon Turney, an expert on bioscience at University College London. “But there are risks that are being widely discussed. Risks such as that pigs are harboring viruses which haven’t yet crossed the species barriers, called retroviruses, of similar origin to the AIDS virus, which was originally thought to come from monkeys.”
As with the birth three years ago of Dolly at the Roslin Institute near Edinburgh, the Scottish capital--the world’s first clone of an adult mammal--the successful cloning of pigs from adult cells raised fears of an unstoppable march toward human cloning, which is banned in both Britain and the United States.
Ron James, managing director of PPL, denied that the new development “takes us a single step closer to human cloning,” adding that pigs represent the only quick solution to a severe shortage of organs for transplant.
“There will always be the naysayers,” James said, “but the vast majority are happy to see the possibility of human survival increased.”
More than 110,000 people in the United States and Europe are on waiting lists for hearts, kidneys and livers. The lists grow each year, while the number of donors is shrinking.
The cloned piglets, named Millie, Christa, Alexis, Carrel and Dotcom, represent the first stage in creating pigs whose organs can be transferred to humans. The company now plans to genetically alter cloned pigs to “knock out” a specific gene responsible for adding a sugar group to pig cells. The sugar group is foreign to the human immune system and therefore provokes it into rejecting transplanted organs.
Three new genes would then be introduced into the cells of the cloned pigs to control the causes of organ rejection. Finally, potential transplant patients would receive a blood transfusion containing the modified cells of the pig supplying the organ. This would serve as an immunization to help the human system absorb the new tissue or organs.
“We have all the pieces of the jigsaw puzzle for the transplant of human organs,” James said.
Alan Colman, PPL’s research director, added, “It is a case of combining the various strategies into one male and one female pig and breeding from these.”
Vivienne Nathanson, the British Medical Assn.'s head of ethics, science and health policy, said the cloning of pigs raises serious concerns about safety. Acknowledging that there is public sympathy for people who die while awaiting transplants, she said that “it is a question of balancing the skepticism with the sympathy” in considering such transplants.
“The viral issue is a real issue, and one thing we must make certain of is that it doesn’t go ahead anywhere in the world until we understand the level of risk that it might lead to,” Nathanson told Channel 4 television in London.
Turney, the bioscience expert, warned that the possibility of activating retroviruses is a risk not just to the patient receiving a transplanted organ but, potentially, to anyone nearby.
PPL spokespersons countered that the possibility of retroviruses or so-called silent viruses being passed from pigs to humans is “hypothetical.”
They also said that all of the piglets are healthy and that independent tests on their DNA had confirmed they are clones of an adult sow.
The pigs were named Millie for the new millennium; Christa for Christiaan Barnard, who performed the first human heart transplant; Alexis and Carrel for Alexis Carrel, who won the Nobel Prize in Medicine in 1912 for his work in the field of transplantation; and Dotcom because “any association with dot-coms right now seems to have a very positive influence on a company’s valuation,” James said.
The method used to clone the five piglets went beyond that used to create Dolly, and a patent application has been filed for the technique, according to PPL. The Roslin Institute says it has British and U.S. patents on the Dolly technology.
The pig-cloning work was carried out by the company’s staff in Virginia with a grant from the U.S. National Institute of Standards and Technology.
The announcement of the successful cloning came as President Clinton and British Prime Minister Tony Blair issued a joint statement urging scientists to allow free access to their discoveries on the makeup of the human genetic code.
They said that refusal to publish findings on the DNA sequence that makes up the human genome could delay development of new drugs to cure or prevent diseases.
Their call was in response to the refusal of private company Celera Genomics of Rockville, Md., to share its findings with the publicly funded researchers of the Human Genome Project. The two are racing to be the first to provide a blueprint of the 50,000 to 100,000 genes in the human body.
Celera says it has spent millions of dollars on its research and that revealing the results would benefit rival companies. It has asked for exclusive rights to its findings for five years.
But Blair and Clinton said understanding the DNA sequence is fundamental to the development of a new generation of medicines and treatments.
Janet Stobart of The Times’ London Bureau contributed to this report.