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Scientists report possibly crucial advance in human embryonic stem cell research

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Scientists reported Wednesday that for the first time they had used cloning techniques to generate embryonic stem cells containing the genes of specific patients.

The step marks a possibly pivotal advance toward the long-sought goal of creating stem cells that could be used to treat many major diseases because they would not be rejected by patients’ immune systems.

The experiments, which produced genetically abnormal cells useful only for research, have raised new concerns in a field rife with ethical, moral and political quandaries.

For the first time, scientists paid women for their eggs to use for human embryonic stem cell research, stirring worries about women being exploited and putting their health at risk. And they made the stem cells by producing and then destroying mutant embryos. Because of their genetic abnormalities, those embryos could not have survived. Their moral status immediately became the subject of debate.

“They have created human embryos. They are abnormal, but they are still human embryos,” said Daniel P. Sulmasy, a professor of medicine and ethics at the University of Chicago. “Anyone who is opposed to the deliberate creation and destruction of human embryos, as I am, would be opposed to this research.”

Many other bioethicists, researchers and advocates, however, hailed the work as meticulously done and an important scientific advance that is ethically justifiable.

“I think it will teach us a lot of how to control the generation of all the different cell types that we would like to study and use for therapy,” said Lawrence Goldstein, who directs the stem cell research program at the University of California at San Diego. “I think it’s a really exciting development.”

Supporters of human embryonic stem cell research consider the field one of the most promising in biomedical research. Because it is thought that the cells are able to morph into virtually any tissue in the body, researchers hope they will lead to cures for many afflictions, including diabetes, Alzheimer’s disease and paralysis. But the field is highly controversial, primarily because the cells are usually derived by destroying embryos, which some consider equivalent to killing a person.

Since the cells were isolated in 1998, researchers have been trying to create stem cells that could be used to generate cells, tissue or replacement body parts that would contain the genes of the patients who would receive them, avoiding rejection by a recipient’s immune system.

This process, sometimes known as “therapeutic cloning,” uses the same techniques that cloned Dolly the sheep in 1996. 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.

Although researchers have done that for many species, attempts in people have been repeatedly stymied or marred by questionable or fraudulent claims of success. In 2004, a South Korean scientist claimed to have produced a stem cell line derived from a cloned human embryo. The announcement excited scientists and potential patients but raised fears that the techniques used in non-humans might be used to create embryos that could be placed into a woman’s womb to develop. It turned out to be a fraud.

One obstacle has been getting women to donate their eggs to give scientists adequate material to work with. The New York scientists who conducted the research 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 for use by 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 had 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, Dieter Egli of the New York Stem Cell Foundation and his colleagues first tried removing the nucleus from each egg containing the donor’s genes and replacing it with genes from adult skin cells, in this case either from patients with type 1 diabetes or from healthy volunteers. The hope was that the eggs would develop into embryos containing stem cells with a diabetic’s genes, which could be transformed into insulin-producing cells. But development arrested before generating any stem cells.

The privately funded researchers then tried putting the genes from adult skin cells into eggs without removing the original genes. Those eggs developed into 13 early embryos, from which the researchers obtained two colonies of cells — one containing the genes of a diabetic and the other a healthy volunteer’s DNA, the researchers reported in the journal Nature.

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 researchers said they eventually were able to produce one colony per egg donor.

“This work for the first time demonstrates that the human egg has the ability to turn a specialized cell into a stem cell,” Egli said.

The embryos and cells, however, contained an extra set of gene-carrying chromosomes — one set of 23 from the egg and the usual two sets of 46 from the diabetic and healthy volunteer. That makes the embryos non-viable, sidestepping concerns that the approach could be used for human cloning, but also making the cells useless for treating anyone.

Nevertheless, the scientists and other leading experts said the advance is important because the cells can now be studied to decipher how eggs reprogram genes.

“It will make people perk up their ears,” said George Q. Daley, a Harvard stem cell researcher who wrote one of several articles published with the research. “It says, technologically, we can get there.”

Scientists are now trying to produce cells with a normal number of chromosomes or find a way to remove the excess genes. Other cells, for example, may work better than skin as a starting point, Egli said.

“We have a number of things on our to-do list,” he added. “We definitely think this is going to work.”

Some researchers, however, questioned the usefulness of the research.

“These are grotesquely abnormal cells, so they have no clinical applications. Even scientifically they are of questionable value,” said Maureen L. Condic, an associate professor of neurobiology and anatomy at the University of Utah.

A political cross section of scientists, women’s health advocates and bioethicists also expressed concern about paying women for the millions of eggs that would be demanded if the work ever led to treatments for common diseases. Egg donation requires risky hormone injections.

“I do have some very serious concerns about such wholesale solicitation of young women for their eggs at such very attractive prices,” said Judy Norsigian, executive director of Our Bodies Ourselves, a women’s health guide.

The research was published with an editorial putting the results in historical context, along with a pair of commentaries evaluating the scientific importance and ethics of the research and a letter calling for more uniform regulation of the field.

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