Under the microscope, they look like luminous stars in a black-and-white galaxy. They are dazzling, mysterious, magical. They are human embryonic stem cells.
Hailed by some as a cure for deadly disease, derided by others as the destruction of human life, embryonic stem cells are at the center of a heated debate over science, religion and politics around the globe. These microscopic flecks have the extraordinary capacity to become any one of the more than 200 cell types that make up the human body, but to those who consider the fusion of sperm and egg sacred life--whether it takes place in the womb or a lab dish--they are morally off-limits for research. There are, however, less-controversial molecular building blocks: adult stem cells, derived from mature human beings. Several years ago research suggested that these cells were far more "plastic" than anyone dreamed, and embryonic opponents began praising them as the ethical answer to stem-cell science. But new studies are now challenging earlier data and raising questions about just how malleable and powerful adult stem cells really are. "People are starting to realize that the science of plasticity is not all there," says Harvard researcher Dr. Leonard Zon, president of the International Society for Stem Cell Research. In the minds of many scientists, embryonic stem cells are pulling ahead in the race toward a medical revolution.
Unlike embryonic stem cells, adult stem cells are wired to become a particular kind of tissue. Much like theatrical understudies, they stand quietly in the wings, rushing in only when cells need replenishment after injury or disease. Scientists know the most about adult stem cells of the blood, which have been used for decades in bone-marrow transplants for patients with cancer or blood diseases. That success prompted researchers to wonder: could adult blood stem cells have the same acrobatic ability as their embryonic counterparts? Initially Dr. Markus Grompe, of Oregon Health & Science University, thought yes. In 2000, he reported that adult blood stem cells were able to turn into liver cells in mice. Other studies reported that the cells could become neurons and heart muscle. But in 2002, several scientists put forth a new theory: adult bone-marrow cells weren't actually becoming new tissue types, they were fusing with existing cells. Those findings persuaded Grompe, a Roman Catholic who does not study embryonic stem cells on religious grounds, to reassess his data and revise his conclusion: the blood cells were indeed merging with liver cells--a case of biological identity theft rather than transformation.
New studies are now challenging earlier work on heart disease, as well. In 2001, news that bone-marrow stem cells turned into heart muscle after being injected into the damaged hearts of mice spurred great hope, even leading to human trials. Dr. Piero Anversa, of New York Medical College, worked on one of the original studies and stands by the research "1,000 percent." "What we're offering is a novel approach to the treatment of cardiac disease," he says. But other scientists were skeptical, and this spring, two groups reported that they could not reproduce the earlier findings, a critical step in the validation of science. "Our paper says it doesn't work," says Stanford University's Dr. Irv Weissman.
Scientists believe the greatest potential of adult stem cells may be in regenerating the organs they come from, and they are actively searching for stockpiles of the cells in different parts of the body. For years researchers hoped that adult stem cells in the pancreas could be coaxed into becoming insulin-producing beta cells, which people with type 1 diabetes lack. But last month Harvard biologist Doug Melton dashed the hopes of many when he reported that he could find no adult stem cells in the pancreas at all. While the study doesn't rule out their existence, the conclusion is clear to Melton: "If you want to make more beta cells, the place to look is embryonic stem cells."
Embryonic opponents are looking elsewhere--to a unique group of adult stem cells isolated by Dr. Catherine Verfaillie at the University of Minnesota. Verfaillie reports that the cells appear to have some of the transformative capacity of embryonic stem cells, converting into other tissue types, like muscle or liver. Scientists are watching closely. But the cells are exceedingly sensitive and difficult to grow, a challenge Verfaillie hopes to resolve as she continues to study their development. And the data need to be replicated by other labs before the cells' true powers can be confirmed. Even Verfaillie, clearly enthusiastic, says the cells' transformative ability as compared with embryonic stem cells remains to be seen. "It's way too early to tell," she says.
Too early, certainly, to make absolute statements about what works and what doesn't. Stem-cell science is constantly evolving: even with all the recent challenges to plasticity, new studies of adult stem cells continue to report intriguing successes. As a result, scientists say research must proceed down both pathways: adult and embryonic alike. The politicians, meanwhile, are still battling it out. Last week a spokesman for George W. Bush said the president would not relax his restrictions on embryonic research, but Massachusetts Sen. John Kerry, the Democratic presidential candidate, says he would overturn the current policy if elected in November. Other countries, like Ireland and Austria, have even stricter regulations. But elsewhere, in nations like South Korea, where scientists recently announced that they had extracted stem cells from cloned human embryos, and the United Kingdom, which last month opened the world's first stem-cell bank, more-liberal policies may lead to progress. And that, says Dr. Octavi Quintana, director of health research for the European Commission, will be all it takes to galvanize support for embryonic research around the globe. "The day the first clinical trial shows therapeutic benefits for a patient," he says, "the whole opposition will disappear." Just what the scientists--and millions of patients--want to hear.