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Fri Apr 29 04:05:17 PDT 2005

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 Stem Cell Reality

 By David A. Shaywitz

  This week the National Academies released new guidelines for research involving human embryonic stem cells, the latest milestone in what has been an unusually eventful time for investigators in this field. Last November the voters of California approved $3 billion in funding for stem cell research, and earlier this month Massachusetts lawmakers approved powerful new legislation that defines and defends this exciting new area of science. Yet, unless proponents of stem cell research learn to preach patience as well as promise, their celebration will be short-lived.

 Human embryonic stem cells were first identified less than a decade ago. They captured the attention of scientists because of two essential properties: They can duplicate themselves in a culture dish, and they can go on to form any cell type in the body. The therapeutic potential seems both apparent and unlimited: Convert these cells into neurons and treat Parkinson's disease, the reasoning goes; turn them into insulin cells and cure diabetes.

 That's the plan, anyway. In fact, the deliberate conversion of human embryonic stem cells into any other type of cell remains a formidable scientific challenge. Even growing these stubborn cells is notoriously difficult. And even if we could make replacement cells in a culture dish, we would still face the daunting task of introducing them into the body.

 The real question, however, isn't whether these problems will be solved, but when. And here, the unfortunate truth is that science -- good science -- can be maddeningly slow. While stem cell advocates have helped voters connect embryonic stem cell research with compelling images of patients who might one day benefit from treatment, such therapies are unlikely to emerge soon enough to benefit most current proponents -- although patients with Type 1  diabetes may represent an important exception.

 So  on the advocacy groups that have been so instrumental in supporting stem cell science will face mounting pressure to demonstrate that they have bet on the right technology. From the researchers, tremendous progress will be expected, and the science is unlikely to keep pace with the eager expectations.

 This scenario has a familiar ring. For years it was not stem cells but gene therapy -- the idea of fixing a disease by mending broken DNA -- that seemed to be the ultimate expression of molecular medicine. Cures, we were told, lay just around the corner. Unfortunately, success turned out to be much harder to achieve in people than to diagram on a chalkboard. The tragic death of clinical study volunteer Jesse Gelsinger, and the concurrent realization that the promised cures were years away, finally burst the bubble. Today a disappointingly small number of hardy investigators remain in what was once medicine's most highly anticipated new area of research.

 Is this going to be the fate of embryonic stem cell science in five or 10 years? I hope not, and yet it's also not very difficult to imagine this happening. Already newspapers are filled with extravagant claims of progress and cures. These reports belie the very slow rate of true scientific advancement. Add to this the explicit expectation of rapid clinical progress -- a key component of California's recently approved stem cell initiative, for example -- and you have a recipe for trouble. If embryonic stem cells are rushed into clinical trials before the solid science has been done, the resulting fiasco could easily doom the entire future of the field.

 How can we avoid this fate? For starters, scientists must do a better job of articulating the limitations of our existing knowledge, taking care to emphasize not only the ultimate therapeutic potential of these cells, but also how far we are from achieving such therapies. Advocacy groups must also level with their stakeholders and explain why treatments based on stem cells will take such a long time to materialize -- and why the wait is worth it. At the same time, these organizations must continue to push scientists to work harder and achieve results faster, encouraging investigators to keep in mind the patients in whose name the research is being conducted (and funded).

 Editors of scientific journals, as well as mainstream reporters, must shape up as well. Research articles of questionable quality shouldn't be accepted for publication, even if they are certain to garner significant media coverage. Similarly, journalists must resist the temptation to lavish attention on every published scientific article with the words "stem cell" in the title.

 Finally, we would all do well to keep in mind that in contrast to the tidy, syncopated tableau of television's "CSI," science in the real world is frequently tedious and almost always messy. But there are also moments of great clarity and wondrous insight -- moments I anticipate we will experience with increasing frequency in stem cell research. In the end, I suspect embryonic stem cells will evolve into a therapeutic tool even more useful than anything we can now envision. But the development of this entirely new area of science will take dedication, funding and, above all, time. "Genius is eternal patience," Michaelangelo observed. Let us hope that for those looking to stem cells for treatment, the wait will not be quite so long.

 The writer is an endocrinologist and stem cell researcher at Harvard University.

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