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Two new stem cell options presented

The panel of experts that advises President Bush on bioethical issues heard descriptions yesterday of two new laboratory techniques that may give scientists a way to get large numbers of medically promising stem cells without creating or killing human embryos.
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The panel of experts that advises President Bush on bioethical issues heard descriptions yesterday of two new laboratory techniques that may give scientists a way to get large numbers of medically promising stem cells without creating or killing human embryos.

The two proposals were greeted enthusiastically, with several panel members saying the techniques, still in the experimental stage, may hold the promise of solving one of the most contentious bioethical dilemmas of the past decade.

"If this pans out scientifically, it will be a major step forward. It may provide an opportunity to get through the political impasse," said Leon R. Kass, the physician who chairs the President's Council on Bioethics.

In one technique, scientists would harvest viable cells from embryos created to treat infertility but which have stopped developing and are functionally dead. Taking the cells — which can grow into stem cells — would be analogous to removing organs of brain-dead accident victims for transplant.

In the second technique, scientists would intentionally sabotage a cloning process called "nuclear transfer" so that the resulting bundle of cells is not an embryo but still has stem cell precursors. They could then be removed and used.

The purported advantage of both techniques is that neither involves an embryo with the potential for growth. In the first, the embryo has already died; in the second, it never existed.

Conventional methods for obtaining stem cells involve the destruction of a viable embryo, which opponents, including President Bush, consider unethical.

'Almost too good to be true'
The two new strategies have been under development for at least two years by researchers in several labs but only recently became widely known. They would need more refinement in animals before they could be tried with human cells.

Kass said the ideas raise the possibility that "the partisans of scientific progress and the defenders of the dignity of nascent human life can go forward in partnership without anyone having to violate things they hold dear."

Panel member Diana Schaub, a political scientist at Loyola College in Maryland, said, "It seems to me almost too good to be true — that scientific advance would solve a moral dilemma."

Stem cells are cells that have the capacity to develop into many types of tissue, and theoretically even whole organs. Many biologists believe they could yield a universe of therapies for diseases in which a person's organs or tissues fail. People whose insulin-producing part of the pancreas is destroyed by Type 1 diabetes, for example, might be able to replace it with tissue grown from stem cells.

Complicated political issue
The federal government currently funds embryonic stem cell research only on embryos created before 9 p.m. Aug. 9, 2001. Twenty-two colonies of stem cells (called "lines") fitting that restriction are available. Non-government funding — by universities, charities or private donors — can pay for research on other cell lines, but some scientists argue that the lack of federal funds is slowing research.

That view was apparently shared by many California voters, who in the recent election passed a bond issue that will provide as much as $3 billion over 10 years to pay for research on "non-qualifying" stem cell lines and on cloning of human embryos for therapeutic purposes.

The bioethics panel has not taken a stand on whether the federal restrictions on the financing of stem cell research should be loosened. The 17-member group is roughly divided on the matter.

The first technique was described last month in the Journal of Clinical Investigation by two Columbia University researchers, Donald W. Landry and Howard A. Zucker, who spoke to the panel yesterday. They argued that a certain percentage of embryos created, frozen and later thawed for potential use in assisted-reproduction procedures are similar to brain-dead adults. The embryos no longer have the capacity for human life.

Cells have stopped dividing in those embryos, which in some cases account for about 60 percent of ones made in infertility treatments. Most such embryos die because of biological accidents that occur in the crucial first days after fertilization. The embryos cannot be put back on the path to normal development into a fetus and infant. They are, in Zucker and Landry's term, "organismically dead."

Studies have shown, however, that some of those "dead" embryos contain cells that are entirely normal and, if removed, capable of developing normally into stem cells. Removing them and using them, the scientists argued, would be like removing organs for transplantation from a brain-dead adult kept alive on a mechanical ventilator — an act accepted by society.

"We would like to extend this idea to the developing human," Landry told the panel.

To do that, biologists would need to learn to identify with certainty which thawed embryos are "organismically dead." That will be done by observing many of them for days and determining whether there are biological "markers" — something that can be tested for in a lab — shared by all embryos that have stopped growing.

The second technique was described by William B. Hurlbut, a physician from Stanford University who is a member of the panel. Although he helped develop the concept, Hurlbut does not have the expertise to undertake the procedure himself or do research on it.

Hurlbut called his idea "altered nuclear transfer" — a cloning procedure with one crucial alteration.

One or more genes essential for normal embryonic development would be temporarily canceled or inactivated at the start. The cluster of growing and dividing cells that would be produced would have no capacity ever to develop into a human fetus. Consequently, it would not have the status of a person by anyone's definition, he argued.

Agglomerations of cells such as this, known as teratomas, sometimes arise spontaneously as tumors from human egg or sperm cells. The teratomas contain partially or fully developed tissue, sometimes even teeth. But they are structurally disorganized and nonviable.

In Hurlbut's concept, the cells could be removed and then have their inactivated genes restored, making them functionally normal and presumably capable of developing into usable stem cells.

"If we could biologically mimic what goes on in teratomas, that would be what I'm after," he said.

Enthusiasm for the two ideas was not universal.

Paul R. McHugh, a psychiatrist from Johns Hopkins University, told Hurlbut: "What you propose, really, is to build a weird genetic hybrid. ... Is that right?"

He added that he had not "finished my thoughts on this. But a few red flags come up."