A Rush to Judgment?

Stem cells from embryos might someday provide an endless supply of new tissues to replace those worn out by aging or disease, but many experts caution that miracle cures are still years away.

Fountain of youth? Hope for patients with hopeless diseases? Or a perilous step down the slippery slope toward a dystopian Brave New World with a body-parts superstore at the local strip mall? Embryonic stem (ES) cells have sparked more heated debate than any other scientific discovery in the past decade. The cells, which are derived from early embryos, retain the capacity to give rise to any tissue in the body. Their tantalizing potential has raised the hope that ES cells might lead to novel cures for a range of diseases that plague our aging population, including heart disease, Parkinson's disease, and stroke. Although some advocates claim that the first clinical trials using ES cells might be just a year or two away, others in the field caution that ES cells are not ready for prime time and that claims about speedy clinical trials will unfairly raise the hopes of patients.

ES cells are derived from week-old embryos, in which only the very first steps of development have taken place. At that early stage, the immature cells are still poised to become all the tissues in the body. During the past few years, scientists have learned how to keep these cells forever young, allowing them to hold on to their developmental plasticity as they continue to grow in a culture dish. Now researchers are racing to discover ways to harness that unlimited potential to create a cornucopia of tissue types in the lab: cardiac muscle cells to repair weakened hearts, nerve cells to mend damaged spinal cords, and even brain cells to replace those destroyed by Parkinson's disease or stroke.

But the source of the cells is troublesome. For those who believe that human life begins at conception, deliberately destroying an early embryo is wrong. Even some who take a more pragmatic view--that week-old embryos are barely differentiated balls of cells without nervous systems or the capacity for suffering--still feel that an embryo's potential for developing into a person makes its cells different from other cell types and that embryo research should be carefully regulated. Many opposed to embryo research argue that stem cells that are found in small numbers in some adult tissues could be used in place of ES cells. But the two types of stem cells most likely have different capabilities, so scientists urge that research go forward on both fronts. After months of public debate and deliberation, President George W. Bush declared that federally funded researchers could work only with ES cell cultures derived before 9 August 2001, the date he announced his policy. His goal was to discourage scientists from creating new ES cell cultures--which would require destroying more embryos.

Many scientists were not particularly happy with the compromise, and in recent weeks, the controversy over Bush's policy has erupted again. Senator Arlen Specter, a Republican from Pennsylvania and a strong supporter of ES cell research even before August 2001, wrote a letter to Bush asking him again to reconsider. Specter's latest salvo was prompted in part by recent comments from some researchers that they might soon be using tissues grown from ES cells to treat patients. Robert Klupacs, CEO of ES Cell International, a company in Singapore and Australia, says researchers at his company could start clinical trials using ES-cell-derived pancreas cells to treat diabetes patients as soon as 2005. And Tom Okarma, CEO of Geron Corp. in Menlo Park, California, has told reporters that his company might also be ready to launch clinical trials--possibly for diabetes or spinal cord injuries--in a year or two. These companies are free to derive and use new ES cell cultures as they are privately funded and thus are not affected by the federal regulations. But Specter is concerned that the limits on federally funded researchers will prevent some of the best researchers from working at the forefront of the field.

Others are more cautious about the possibility of hurrying to clinical trials. In preliminary studies, ES cells have cured several dozen rats and mice of diabetes, stroke, and spinal cord injury. But most experts say that they don't yet understand enough about the cells to put them safely into patients. "It doesn't surprise me that people want to rush to the clinic," says George Daley of the Whitehead Institute at the Massachusetts Institute of Technology in Cambridge, who works with both mouse and human ES cells. "But I still think we need to learn more about how to make the kinds of cells we want, and how they behave in animal models." More animal experiments--including some long-term studies in monkeys, which are more closely related to humans than are mice--are needed to show that the cells are safe and won't cause tumors or other dangerous side effects, he says. He predicts that the field is 5 to 10 years away from safely treating people. Daley, however, says he does want some of the restrictions lifted--not because clinical trials are just around the corner, but because the Bush's policy keeps many researchers in the United States from developing new ES cell cultures. Because each stem cell culture is derived from a single embryo, each is slightly different, he says. Having access to additional cultures would allow researchers to study these cells more fully and to learn how to exploit their capabilities.

Although making optimistic claims about the field's progress attracts the attention of politicians--and potential investors--it might be damaging in the long run. Researchers worry that such Pollyanna promises raise false hopes in sick patients who are desperate for a cure. Furthermore, starting clinical trials too soon could lead to serious setbacks. Researchers point to the troubles that have plagued gene therapy, which a decade ago was said to hold similar promise for curing untreatable diseases. In several cases, gene therapies have led to severe side effects that have shaken the field. In 1999, a relatively healthy teenager with a rare metabolic disease died after he was treated with a gene designed to produce an enzyme that his liver cells lacked. And late last year several children developed leukemia after they were administered gene-altered cells that were designed to correct their faulty immune systems.

Even if clinical trials are years away, stem cell biologist Ron McKay of the National Institute of Neurological Diseases and Stroke says he's optimistic. "The promise of the field doesn't simply rely on short-term clinical success. Obviously that would be great," he says. But even without touching a patient, scientists studying the biology of stem cells will learn more about how tissues develop naturally. The results could lead to therapies that would prompt damaged tissues to repair themselves--perhaps circumventing fears about future Brave New Worlds.

Gretchen Vogel is Berlin correspondent for Science magazine. She is waiting for researchers to discover how ES cells can help her speak perfect German.