Stem cells are a wonderful potential source of cells for scientists looking to clone animals-but the clones produced from those stem cells are not as alike as clones should be.

In the July 6, 2001, issue of Science, Professors Rudolph Jaenisch and Ryuzo Yanagimachi reported on their successful cloning of a population of mice from stem cells. They were able to produce a population of mice from stem cells that were, as expected, genetically identical. And indeed, the mice looked exactly alike. But the mice harbored a number of different genetic abnormalities. Which genes were turned on and active and which were dormant differed from mouse to mouse, or clone to clone.

The scientists looked carefully at the clones and at the stem cells from which they had arisen. They discovered that stem cells that should theoretically have been identical already showed variability in terms of what genes were turned off. In other words, they were already demonstrating the differentiation, at least on a molecular level, that the offspring of those stem cells would show. Put another way, these results suggest that mice stem cells do not stay pluripotent, or able to produce a mouse cell of any type, for as long as scientists have believed. This has serious implications for research into human stem cells and their potential.

If human stem cells are as unstable as mouse stem cells, then the potential of human stem cell research might not be as encouraging as scientists have hoped. President Bush's decision to permit stem cell research on existing cell lines, but not to permit new lines to be developed might be far more limiting than was realized. If the 64 cell lines described in the President's decision (and there are scientists who dispute that number, worrying it is too optimistic) are like the mouse cell lines, and already committed to becoming one type of cell, their potential is less than had been believed. Scientists may need to start multiple other stem cell lines in order to produce the sort of cells they hope to use, such as healthy heart, nerve or blood cells.

If the embryonic human stem cells in existing lines approved by the President are unstable, scientists may ask that the President and Congress revisit the issue. Alternatively, they might focus on adult stem cells, and hope that these cells show the therapeutic promise that embryonic stem cells seem to show.