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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 * * * ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn