Ingenious Genetics ... New Ways To Create Medically Promising Stem Cells May Raise Fewer Moral and Religious
Objections.

By Faye Flam - Inquirer Staff Writer

Posted on Mon, May. 03, 2004

While society remains stalemated over the use of human embryos and cloning for medical research, the grounds for debate
are shifting like desert sand as scientists keep redefining what it means to be a potential human life.

No longer is conception - the union of a sperm and an egg - the only way to start life for mammals. First scientists
created animals through cloning, then last month a group in Japan produced baby mice by mixing DNA from two females,
leaving the males out of the picture. And researchers at the University of Pennsylvania veterinary school have
suggested a way to leave females out of the equation by showing that male mice might be able to produce eggs.

Such new ways to manipulate the building blocks of life could eventually allow scientists to avoid many of the ethical
and religious objections surrounding research involving human embryos, said Penn's Hans Schöler. He and other
researchers are hoping to deliver on the unique medical promise of embryonic stem cells without having to destroy
anything that many people regard as a potential human life.

Schöler, 51, a soft-spoken reproductive biologist, overturned a basic assumption about life a year ago when he found he
could make that quintessentially female cell - the egg - without a female. Instead he made mouse eggs using embryonic
stem cells - cells cultured from those that start dividing after a sperm fertilizes an egg. These incredibly versatile
cells, which give rise to all the parts of the body, can also be made by cloning - replacing an egg's nucleus with
genetic material from a male or a female.

Schöler did the work in mice, but his technique nevertheless prompted commentators around the world to agonize over the
possibility that two men could combine their genetic heritage in a baby - one man supplying sperm and the other the
egg.

The talk of male couples having babies is just so much cocktail party chatter, Schöler said recently, at his desk at
Penn's bucolic New Bolton veterinary center in Kennett Square. For him, there is method in the seemingly mad science.

Part of his goal is simply to understand the still-mysterious workings of life. How can something as simple as an egg
cell grow into a complete animal or human being?

"The eggs are the most exciting cells in the body," Schöler said - more interesting than sperm because they reset the
genetic clock. If you transfer DNA from an ordinary adult cell to an egg, the egg reprograms the DNA, making it forget
where in the body it came from. The new "cloned" cell becomes a blank slate capable of giving rise to any other kind of
cell or, in the right circumstance, a baby animal such as Dolly the sheep.

In cloning, "you're borrowing the machinery of the egg to turn the cell back in time," said biologist Jose Cibelli of
Michigan State University, who investigated creating human embryos through cloning while working for the company
Advanced Cell Technology near Boston.

The other part of Schöler's quest is to harness the power of egg cells for medicine. If fertilized or altered through
cloning, egg cells can be made into embryonic stem cells, much touted for their medical promise because they can divide
to become all sorts of other cells: newborn skin cells that might someday treat burns, neurons that might be used for
Parkinson's patients, or pancreatic cells that could revolutionize the treatment of diabetes. Scientists are working
toward those goals, but so far there are no workable treatments.

In so-called therapeutic cloning, doctors would transfer DNA from a patient to an egg and produce embryonic stem cells
that might differentiate into replacement tissues or cells with the patient's genetic code - a perfect, rejection-proof
match.

In a quest for such cells, scientists in South Korea announced this year that they had cloned an early human embryo
using eggs women had donated. The work raised objections not only because it advanced the prospect of cloning as a way
to produce children, but because the research produced and destroyed clusters of cells that at one stage, in theory,
could have developed into babies if they were implanted in a woman's uterus.

Legislators in the United States are still debating several cloning bills that might outlaw such an experiment here.
And three years ago, the Bush administration put restrictions on the type of embryonic stem cell research that can be
done with federal funding.

Some people argue that microscopic, unstructured embryos, no matter how they are created, are human beings, while
others see them as just cells.

Roman Catholic Church and evangelical Christians are holding fast to the position that if a cell or group of cells
could potentially become a human life, then it is deserving of human dignity, said Ted Peters, professor of theology at
Pacific Lutheran Theological Seminary in Berkeley, Calif.

Peters said he had tried to encourage a compromise in which the Catholic Church would not grant human status to cells
until after they attach to the womb. But nobody is budging, he said.

If Schöler's experiment making mouse eggs would work in humans, it would mean that researchers such as those in South
Korea could develop the cells necessary for therapeutic cloning without putting women through the invasive process of
donating eggs. Making the eggs in a petri dish would also distance the procedure for therapeutic cloning from anything
resembling baby-making, Schöler said.

"It would be wonderful if we could get the eggs directly from the shelf," said Michigan's Cibelli.

Schöler didn't so much make the egg cells as discover them. Before his finding, scientists had demonstrated that
embryonic stem cells could generate any cell type except for sperm and egg. Schöler thought perhaps a few of the mouse
stem cells he studied were turning into eggs but no one could spot them. He devised a scheme to pinpoint them by
infusing embryonic stem cells with genes that, when activated, trigger the production of a protein that glows green.
The genes are only supposed to be activated in egg cells, he said, so when he saw cells glowing, he knew he'd found
them.

Once Schöler identified the eggs, he said, he began trying to fertilize them with mouse sperm to create baby mice. So
far it hasn't worked. Eggs are finicky about when they are ready to make a baby, he said. Catch them too early or too
late and nothing happens. Sperm are more versatile - you can inject them into eggs at various stages and they will
still work.

George Daley, a Harvard University scientist, also had been trying to make egg cells last year when he learned he was
scooped by Schöler. But soon after he succeeded in making mouse sperm from stem cells and using them to fertilize mouse
eggs.

Some of Schöler's mouse egg cells may have the unnatural property of carrying the male Y chromosome. Eggs normally
carry only the female X chromosome, while sperm can carry either an X or a Y, thus determining the sex of the
offspring. To survive, animals need at least one X chromosome, but Schöler said that perhaps the Y eggs could develop
into male offspring if fertilized with X sperm.

Schöler, who has been at Penn since 1999, is in the process of moving back to his native Germany, where he will
continue his work at the Max Planck Institute for Molecular Biomedicine.

The more progress scientists make in the lab, the more ethical options will be available, he said. Use of cloning to
make embryonic stem cells, he said, is far preferable to the chilling prospect of paying a woman to incubate cloned
cells until they grow into a fetus, at which point it might be aborted and used for replacement tissue.

"That's the most horrible vision," Schöler said. "It's really generating life to use it."
Contact staff writer Faye Flam at 215-854-4977 or [log in to unmask]

SOURCE: Wilkes Barre Times-Leader, PA
http://www.timesleader.com/mld/timesleader/living/health/8575439.htm

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