Scientists reported Wednesday that for the first time, they used cloning techniques to coax human eggs to generate embryonic stem cells containing the genes of specific patients.
The step, published online in the journal Nature, marks a long-sought, potentially pivotal advance toward the goal of creating genetically matched embryonic stem cells that could be used to treat many major diseases.
The scientists so far have only managed to produce genetically abnormal cells useful for research, but they were confident they could overcome that hurdle.
"This work for the first time demonstrates that the human egg has the ability to turn a specialized cell into a stem cell," said Dieter Egli of the New York Stem Cell Foundation, who led the research.
The research sidestepped fears that scientists had moved closer to human cloning by producing the cells with non-viable embryos.
But the experiments nevertheless have raised a new set of ethical concerns in a field already rife with ethical, moral and political quagmires.
The research was possible because for the first time, scientists paid women for their eggs for human embryonic-stem-cell research, stirring worries about women being exploited and putting their health at risk.
At the same time, the researchers made the cells by producing and then destroying mutant embryos, whose moral status immediately became a matter of sharp debate.
The researchers who conducted the work and others hailed the advance as an ethically defensible, potentially highly significant advance that could lead to producing large numbers of patient-specific cells that could cure widespread suffering.
"Cell-replacement therapy would dramatically change treatment and potentially even cure debilitating disease and injuries that affect millions of people suffering from these diseases," said Susan L. Solomon, who heads the foundation. "There really is a moral imperative to alleviate suffering."
Opponents of embryonic-stem-cell research, however, questioned both the scientific value of the experiments as well as its morality.
"We don't believe you should be creating new beings through this cloning process and destroying them to harvest their cells," said David Prentice of the Family Research Council.
Even some supporters of embryonic-stem-cell research were uneasy about paying women for their eggs.
"It just kind of gets you into the paying-for-organs controversy," said Jonathan Moreno, a University of Pennsylvania bioethicist and author of a new book, "The Body Politic."
"I've always felt it would be better to keep this field out of those areas of debate. We've got enough problems," he said.
Supporters of human-embryonic-stem-cell research consider the field to be one of the most promising in biomedical research. Because the cells are believed to be able to morph into virtually any tissue in the body, researchers hope they will lead to cures for many major afflictions, including diabetes, Parkinson's disease and paralysis.
But the field is highly controversial, primarily because the cells are usually derived by destroying days-old embryos, which some consider the equivalent of killing a person.
Since the cells were isolated in 1998, researchers have been trying to create stem cells that could be used to generate replacement body parts that would contain the genes of the patients getting them, avoiding rejection by a recipient's immune system.
This process, sometimes known as "therapeutic cloning," is done using the same techniques that cloned Dolly the sheep. Genes from an adult are transferred into an egg that has had its genetic material plucked out. Scientists then stimulate the egg with its new genes to begin developing into an embryo so they can harvest stem cells.
Previous attempts to produce human embryonic stem cells this way, however, have either failed or been marred by disputed or fraudulent claims. One obstacle has been difficulty getting enough women to donate their eggs to give scientists adequate raw material to work from.
The New York scientists took advantage of the state's 2009 decision to become the first to allow researchers to pay women for eggs for embryonic-stem-cell research. Although women are commonly compensated for donating eggs to infertile couples, it has been generally considered unethical to do so for stem-cell research.
Women who had volunteered to donate eggs to couples at Columbia University's infertility clinic got the option of instead letting their eggs be used for stem-cell research for the same $8,000 payment. Sixteen women agreed, providing 270 eggs.
Like other researchers, Egli and his colleagues first tried removing the nucleus of the eggs containing the donor's genes and replacing it with the chromosome-containing nucleus from skins cells from patients with type 1 diabetes and healthy volunteers. But, like previous attempts, development arrested before generating any stem cells.
The researchers then tried putting the genes from the skin cells of diabetics and healthy volunteers into eggs without removing the original genes. Those eggs developed into 13 early embryos from which the researchers obtained two colonies of cells. Detailed analysis found that the cells were indistinguishable from embryonic stem cells, with no traces of the adult cell from which they were derived.
The cells, however, contained an extra set of gene-carrying chromosomes - one set of 23 chromosomes from the egg and the usual two sets of 46 chromosomes from the diabetics who provided their genes. That makes them useless for treating anyone.
Nevertheless, the scientists and other leading experts said the advance was important because the cells can now be studied to decipher how eggs reprogram genes.
"It will make people perk up their ears," said George Daley, a prominent Harvard stem-cell researcher who wrote one of several articles published with the research. "It says, technologically, we can get there."
Egli called the extra DNA in the cells a technical hurdle that he was confident scientists could overcome.
In the meantime, scientists have begun studying the cells in the hopes of identifying how eggs can reprogram an adult cell's genes.
"We have a number of things on our to-do list," Egli said. "We definitely think this is going to work."
by Rob Stein Washington Post Oct. 6, 2011 12:00 AM
Pivotal advance made in stem-cell research
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