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Stem Cell Pioneers

Despite federal opposition to embryonic stem cell research, the promise of medical benefits, academic freedom and profits in California is luring scientists to the field

But adult stem cells, versatile as they are, have more limited power than embryonic stem cells, which can turn into any type of cell in the body. In the late 1990s, two independent discoveries pushed embryonic stem cells to center stage.

First, scientists in Scotland rocked the world in February 1997 with the announcement that they had created a cloned lamb, Dolly. Ian Wilmut and his co-workers accomplished that feat by removing a cell from the body of a 6-year-old ewe and then fusing it with a sheep egg that the scientists had hollowed out to remove its genetic material. The egg functioned like a time machine. It somehow made a regular old body cell revert all the way back to its embryonic root and behave like a normal fertilized egg. The rejuvenated cell then developed into Dolly. Much as Dolly wowed the public, her existence raised the question of whether a human being could be created by cloning. The prospect sent shivers through scientific, political and religious communities.

The second breakthrough was announced in November 1998. Scientists led by James Thomson of the University of Wisconsin had grown human embryonic stem cells in a culture dish, a scientific first. They'd constructed embryonic stem cell "lines" that, like a yogurt or sourdough culture, could renew in perpetuity and be propagated in still more cell cultures. These cell lines, which a nonprofit subsidiary of the University of Wisconsin would soon sell to researchers around the world (two vials, $5,000), made minds race. Scientists could attempt to turn the embryonic cells into any tissue the body makes. Imagine: an endless supply of young neurons to fix damaged brains, cardiac cells to repair damaged hearts, or pancreatic cells to create insulin for people with diabetes. Maybe they could even regenerate whole organs.

To date, scientists worldwide have made more than 100 different human embryonic cell lines. Still, the existing lines have serious limitations. Most have been grown on a lattice of mouse embryonic skin cells for support. Consequently, the human embryonic cells are contaminated by mouse cells, and though they're still useful for research, Weissman says, they are "absolutely useless" to develop therapies. Even if they weren't contaminated, the existing lines probably could help only a patient who had a close genetic match to the embryonic stem cells, as the patient's immune system likely would destroy any cells that got transplanted. And cells kept in culture can change, acquiring mutations that could lead them to cause cancer or other diseases.

Combining the lessons of Dolly and embryonic stem cell lines, however, suggested a mind-blowing possibility. If a scientist took the nucleus from, say, a human patient's skin cell and put it into a scooped out human egg—the technique that created Dolly—it could become an embryo. One could convert its cells into a cell line—rather than allowing it to develop into a fetus by implanting it into a uterus—coax it into whatever type of cells the patient needs, and treat an ailment without fear of immune rejection. This process is called therapeutic cloning, as opposed to reproductive cloning, and even though it was partly inspired by Dolly, it has nothing to do with creating cloned animals or human babies.

Scientists also say that cloned embryonic stem cell lines could be a boon to the study of genetic diseases. Researchers could make embryonic stem cell lines from people with genetic diseases, then study exactly how a disease process works, including possibly pinpointing flawed genes that cause the disease. Such cells would allow scientists to assess whether experimental drugs were likely to harm or help people. "You're on a road that we can't even approach in modern medicine," says Weissman. "Every human genetic disease theoretically could be studied in this way. And there's no other way to do that."

Embryonic stem cell research is entangled with the issue of abortion in myriad ways, and indeed the Bush administration's position has roots in the 1973 Roe v. Wade decision that made abortion legal in the United States. Worried that scientists might use aborted embryos or fetuses for research, Congress in 1974 passed a "temporary moratorium"on the federal funding of any such work. Subsequent legislation extended this ban to the creation of embryos. With the breakthroughs in stem cell research in the late 1990s, Weissman and many other scientists urged Congressto reconsider this sweeping ban. Then, on August 9, 2001, President Bush gave a speech on national televisionfrom his Texas ranch that focused on stem cell research, describing a new policy that attempted to please people on both sides of the issue.

Bush declared that researchers who used federal funds could work on human embryonic stem cell lines that scientists had already created but could not make any new ones. Bush, who characterized the issue as "one of the most profound of our time," said that he was worried "about a culture that devalues life" and said that he had arrived at this compromise after "prayer and considerable reflection." About two dozen stem cell lines meet his criteria for federal funding.

Most embryonic stem cell lines, including the federally approved lines from Wisconsin, are derived from embryos donated by patients at in vitro fertilization clinics. Many couples undergoing IVF treatment, which fails about 70 percent of the time, create more embryos than can be implanted in a given treatment session, and they freeze the "excess" ones for possible future use. (A2003 study estimated that assisted reproduction clinics in the United States stored about 400,000 frozen embryos, an untold number of which will ultimately be destroyed.) Stem cell scientists working with donated embryos typically extract cells from the embryo when it is 3 to 5 days old and about the size of the period at the end of this sentence, and discard the rest. The researchers do not culture any cells that are programmed to turn into a placenta. That's one reason an embryonic stem cell line can't develop into a baby. Congress, with support from key Republicans such as Bill Frist and Orrin Hatch, appears likely to pass a bill next year that would allow researchers to create new lines with donated, excess embryos, but President Bush has vowed to veto it.

Critics say that the federal regulations on embryonic stem cell research have relegated the U.S. National Institutes of Health (NIH), which has bankrolled research on everything from cancer and heart disease to diabetes and AIDS, to bit-player status in the stem cell field. Singapore, the United Kingdom, Australia, Israel and China, they contend, have rushed to fill the vacuum by funding their own scientists. South Korean scientists, to the surprise of many, were the first to create human embryonic stem cell lines using cloning—the highly anticipated first step toward developing personalized stem cell therapies.

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