Three weeks have passed, as this issue of Nature Methods goes to press, since a federal judge ruled that US government funding of human embryonic stem cell (ESC) research violates the Dickey-Wicker amendment and granted a preliminary injunction preventing the implementation of the 2009 National Institutes of Health guidelines on human ESC research.

In the meantime, an appeal by the US government has resulted in a temporary stay of the injunction, but this could be lifted within the next days. If it does, and if legislation counteracting the ruling has not been successfully enacted by then, many federally funded US scientists working on human ESCs will have to restrict or even entirely stop their work.

This is far from an optimal way to conduct research and could, in the long run, weaken the role of US scientists in a field that has much medical promise. The Dickey-Wicker amendment, which states that federal funds cannot be used for research that harms human embryos, was instated before human ESCs had even been isolated. What is more, human ESC research has been funded by three US administrations with various levels of restriction for more than a decade. To now severely curtail and potentially stop this work, which has already been substantially funded by American taxpayers and holds great potential for alleviating human suffering, is a mistake.

One indirect outcome of human ESC research is the discovery in recent years of an alternative way to confer pluripotency on other human cells. The resulting induced pluripotent stem cells (iPSCs), made by expressing a set of transcription factors in somatic cells, have generated huge excitement, not least because iPSCs are not as vulnerable as human ESCs to ideological attacks. In fact, earlier this year we selected iPSCs as Method of the Year 2009 for their potential as tools for understanding basic and disease biology. But for iPSCs to be good alternatives to ESCs either for basic research or in the clinic, they must be very similar to ESCs; at the very least, any differences between these cell types must be systematically studied and understood.

Reports published over the past years suggest that iPSCs and ESCs, although very similar, are not identical. For instance, expression patterns of genes and of microRNAs have been reported to differ between human iPSCs and ESCs. Recent work in the mouse has shown that iPSCs retain at least transient epigenetic memory of their tissue of origin, which most probably influences their propensity to differentiate along one or another developmental lineage. For human cells also, differentiation of iPSCs along some lineages is reported to be less efficient and more variable than that of ESCs.

But such experimental comparisons are not straightforward to carry out. There is variability within sets of iPSC and ESC lines, and confounding effects of genetic background, reprogramming methods and the culture or laboratory environment must be taken into account. The field has not as yet reached a consensus on methods either to generate iPSCs or to functionally test human pluripotent cells. Patterns of gene expression and epigenetic marks, although potentially very informative, do not fully tell us how well ESCs or iPSCs, or their derivatives, function. Much work remains to be done.

Indeed, as stated by the director of the National Institutes of Health in his declaration accompanying the government's request for a stay, among the projects that will be directly disrupted by the court's injunction are precisely such systematic comparisons of human iPSCs and ESCs. This type of work is an essential prerequisite to an understanding of whether or not iPSCs are viable alternatives or useful complements to ESCs for research or therapy. Loss of US funding will inevitably slow down progress in this direction.

Comparative studies and the clinical success stories of adult stem cells aside, the value of ongoing research on human ESCs can hardly be overstated. These cells are, at present, the best understood pluripotent human cells. Unlike adult stem cells, ESCs can, in principle, give rise to every type of cell in the human body and could be a source of treatment for many devastating diseases—some of which are already moving into clinical translation.

For all its tremendous promise, research on human ESCs and iPSCs is still young. If the US is to play a central role in harnessing the full potential of these cells, there must be a positive legislative resolution that resolves the current regulatory ambiguity once and for all.