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S. Koreans enhance cloning of stem cells

Research is called boost for studying of diseases

A team of South Korean scientists announced yesterday that they have discovered a highly efficient way to clone human cells, an advance that could alter the scientific and political debate over the procedure.

The researchers said they have created 11 new lines of cloned human embryonic stem cells, including, for the first time, two that are genetically matched to patients with a disease. This is the first step necessary for therapeutic cloning, a procedure in which patients might one day be treated with healthy nerve, blood, or other cells cloned from their own skin. The two disease-carrying cell lines, cloned from patients with juvenile diabetes and an inherited blood disorder, will offer researchers new ways of studying those maladies.

But the most immediate impact of the work, scientists said, was to establish the cloning of human cells as a robust, surprisingly reliable procedure. The team, led by Woo Suk Hwang at Seoul National University, for the first time cloned skin cells from men and from patients with a wide range of ages, from 2 to 56. The South Koreans announced the first successful cloning of human cells last year, but it required 242 egg cells, which are used to make microscopic embryos, to create a single batch, or ''line," of cells. By refining its laboratory techniques, the team made 11 new lines of embryonic stem cells using only 185 egg cells, more than a 10-fold improvement in efficiency.

''This is a very important paper," said Douglas Melton, a Harvard University biologist who is preparing an effort to clone human cells. ''I am very impressed by the speed with which they have done this."

Critics of cloning research have argued that treating patients will require large numbers of women to donate eggs, and egg donation carries some risk. The paper, published online yesterday by the journal Science, may dampen this concern, because the new research shows it is often possible to create a line of cloned embryonic stem cells using only the eggs gathered from a single cycle of fertility treatment in one woman. But the advances are likely to intensify another concern about the science: That the United States is falling increasingly behind.

''We are going to be playing catch-up," said Kevin Eggan, a Harvard scientist who works with Melton and who recently visited the South Korean team. ''They are the masters."

Embryonic stem cell research in the United States has been slowed by a political fight with roots in the abortion debate. Some critics of the research charge that destroying a human embryo, which researchers do to create embryonic stem cells, means taking a human life. On Aug. 9, 2001, President Bush announced that the government would not fund research using human embryonic stem cells created after that date, because he did not want the government to encourage embryo destruction. The new cell lines in South Korea, which were created with money from the government there, fall under that ban, but American scientists could study them using private funds or, in some places, state money.

Dissatisfaction with the president's policy has been mounting in Congress, fueled in part by announcements like yesterday's. The US House of Representatives is scheduled to vote next week on a measure that would allow scientists to work with newer lines of embryonic stem cells, though not stem cells created by cloning. That measure, sponsored by Representative Michael N. Castle, Republican of Delaware, and Representative Diana DeGette, Democrat of Colorado, has bipartisan support. DeGette said that more than the 218 members of Congress needed to pass it have told her privately that they support it.

The South Korean announcement ''underscores the urgent need to pass legislation in the United States that will both open up the research and also put ethical controls in place," said DeGette.

In the past, human embryonic stem cells have typically been created using frozen embryos left over from fertility treatments. But when the South Koreans announced last year that they had created stem cells via cloning, it intensified the ethical arguments over embryonic stem cells. Some critics, including Massachusetts Governor Mitt Romney, object to the creation of embryos specifically for research, an inherent part of the process.

Critics said that yesterday's announcement highlighted their concern that the science was proceeding without regard to the deep ethical issues it raises, and that the future potential of the work cannot justify destroying human lives.

''The core issue has to be human life," said Dr. David Stevens, executive director of the Christian Medical Association.

Another fear is that someone might use the technology to create cloned children, known as ''reproductive cloning." The paper, scientists said, will probably renew the calls for bans on reproductive cloning, which is legal in the United States because of a larger battle in Congress over stem cell policy. In their paper, the South Korean team repudiated any attempt at reproductive cloning as ''dangerous" and ''reckless" -- sentiments shared by virtually all scientists.

In an unusual move, the journal Science also published a paper by two ethicists, analyzing the impact of the work. The success of the South Korean team will probably draw more scientists into the field, and that will require scientists and society to take a more careful look at the issues raised, according to David Magnus and Mildred K. Cho, both of the Stanford Center for Biomedical Ethics. They cautioned against misleading patients, or the public, into thinking that treatments are close.

The two also emphasized that there has not been enough attention paid to the issues surrounding egg donors. Eggs are needed to perform cloning, but the procedure carries some risks. Egg donors are given drugs to stimulate their ovaries to produce many eggs, and this can lead to side effects -- serious ones in rare cases, and even death. And unlike some analogous situations, like kidney donation, there is no proof that the procedure will benefit anyone's health, the two wrote.

Around the world, scientists have been establishing major efforts to create and study human embryonic stem cells, which can become any cell in the body. These efforts are aimed at answering a wide range of questions about how the body develops, and how this knowledge might be used to fight diseases.

What the South Korean team has been able to do is create human embryonic stem cells with the genetic material of particular patients. With cloning, also called nuclear transfer, the scientists take a cell from a patient, remove the cell's nucleus containing the genetic material, and place this nucleus in an egg cell that has had its own nucleus removed. This hybrid cell is then stimulated to grow for several days, until it becomes a nearly featureless ball of about 200 cells, a type of embryo known as a blastocyst.

The first application of this technology is the creation of cells to study diseases. The South Koreans created a human embryonic stem cell with the DNA of a 6-year-old girl who suffers from juvenile diabetes. Now scientists can observe how these cells develop into more specialized cells and compare this with the development of embryonic stem cells that do not have the genes that contribute to juvenile diabetes. This could show them where the first problems arise that lead to the disease.

The other principal application, a more distant prospect, is therapeutic. In the Science paper, the team reports creating nine embryonic stem cell lines from patients who have suffered spinal cord injuries. In theory, the embryonic stem cells from one of the patients might one day be coaxed into becoming a more specialized nervous system cell and then be given back to the original patient, repairing damage. Because these cells were cloned from the patient, it is thought that the risk of rejection would be minimal, though that is not certain.

The scientists said that the improvements in efficiency came from a combination of technical changes, including a better way of growing the embryonic stem cells, using human cells to support them -- and, more simply, a lot of practice.

Gareth Cook can be reached at

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