If Rip van Winkle had just awoken from a slumber that started five or six years ago, the current political debate over human embryonic stem cell research would seem bewildering. Both sides make passionate rhetorical claims about the potential—or lack thereof—for this line of research to cure major diseases. Ideological opponents dismiss the medical potential, claiming embryonic stem cells have negligible promise compared to adult stem cells. Proponents point to the massive human suffering that could be alleviated by cures waiting just around the corner—if only restrictions could be loosened and more resources made available for research. However, few scientists believe that those cures actually are imminent. In such a charged climate, disabusing supporters of such ideas may seem like giving ground to the opposition, but allowing a mismatch between expectation and reality to flourish may be even more dangerous in the long run.

Here we will not debate the morality of embryonic stem cell research, but instead will discuss the scientific value and realistic gains to be expected of this young field. The promise of cell replacement therapy using stem cells is clear. Most scientists accept that embryonic stem cells, which have the unique ability to turn into any kind of cell, have enormous promise for replacing neurons lost to neurodegenerative disease. Opponents argue that adult stem cells have already proven to be just as useful as embryonic cells, but it remains controversial whether non-neural adult stem cells can turn into real neurons. In contrast, normal brain development leaves no doubt that embryonic cells can become neurons in the appropriate context.

In Parkinson disease, and to a lesser extent, Huntington disease, clinical trials of fetal tissue transplantation have provided a proof of principle that cell replacement can work. Dopaminergic neurons from human fetal tissue survive in patients' brains, and take over the function of neurons lost to disease. Some patients show encouraging reduction of symptoms, and the grafted neurons have survived as long as ten years. These clinical improvements have been accomplished with tissue derived from aborted fetuses, which is often obtained under non-optimal scientific circumstances. Neurons derived under controlled circumstances would undeniably accelerate these efforts, but Anders Björklund of Lund University cautions that supply is only one immediate problem. Once the cells become available, he stresses, systematic research would still be needed to ensure a safe, effective treatment. “Even if the cells were to become available tomorrow, we would not have a therapy immediately. The field would simply enter a new phase of research.”

In both these diseases, a clearly localized population of neurons is degenerating, and so targeted replacement is a straightforward solution. For other neurodegenerative disorders, such as Alzheimer disease, in which the affected population of neurons is less well defined, or amyotrophic lateral sclerosis, in which the new motor neurons would have to navigate very long distances to their eventual targets, an effective cell replacement therapy is likely to be further in the future.

Our understanding of the developmental biology of human embryonic stem cells is increasing steadily. Scientists are able to stimulate human embryonic cells in vitro into taking on the chemical, structural and even electrophysiological characteristics of neurons. More importantly, when injected into developing mice, these cells appear to become neurons and glia. These are promising findings, and clearly show the potential of human embryonic stem cells. But scientists caution that outside the human embryo, these newly born neurons lack the environmental cues that enable them to mature normally, and it will probably take years of research before embryonic cells will be ready to be injected into adult humans.

Stem cell research also has wide potential beyond cell replacement that seems often to go under the radar of the public and many scientists. Stem cell cultures provide a unique opportunity for scientists to study almost every aspect of human biology, from development to gene function. Cells can be genetically modified or infected to create models for studying disease mechanisms or for drug screening. This potential should not be ignored.

Given the great possibilities of this field, it must be encouraged to mature under supportive but responsible conditions. In the United States, the government funding situation is anything but. Three years ago President Bush made a decision to restrict government research funding to certain cell lines created before September 2001, and the administration assured the public that this would provide an ample supply of cells. Despite initial claims that over 70 lines would be eligible, most have turned out to be unsuitable or have died, and the National Institutes of Health website now lists just 12 cell lines available for purchase. Further hampering research, all the lines eligible for federal funding are grown on mouse cells, which some scientists feel seriously compromises their utility in clinical applications.

With no guaranteed relief from these restrictions in sight, we applaud the efforts of those in the United States who are pushing the research ahead without federal funding. This November, voters in California will decide on Proposition 71, a $3 billion initiative for stem cell research. New Jersey recently passed a law permitting stem cell research and has already raised $11 million in start-up funds for a new stem cell research center. Several universities have raised donations to fund their own stem cell institutes, including the University of Wisconsin at Madison, Rockefeller and Harvard, where this journal's former editor Charles Jennings is now executive director. Clearly, there are many in the public who are willing to invest in this scientific effort.

These are exciting times, but as scientists around the world solicit public support, both political and financial, for embryonic stem cell research, we encourage moderation in promising rapid clinical cures. In the current politically charged atmosphere, rash promises will ultimately be detrimental. Small scientific setbacks are used by ideological opponents as ammunition, and they run the risk of disillusioning supporters whose hopes were falsely raised. The realistic scientific potential of embryonic stem cells should be argument enough for pushing this line of research forward.