The argument over whether US government funding can be used for human embryonic stem cell research has intensified, on paper at least, and looks likely to enter its most critical period in the next three months.

Although the Department of Health and Human Services (HHS) gave the green light to federal funding for such research in January, 70 members of Congress have since contested the agency's legal reasoning in a letter to HHS Secretary Donna Shalala. And last month, 33 Nobel laureates wrote to Congress urging federal funding for human stem cell research.

All eyes are now on guidelines for this research being drawn up by the National Bioethics Advisory Commission (NBAC) at the request of Harold Varmus, director of the National Institutes of Health (NIH). Once the guidelines have been established, the NIH will begin accepting and reviewing grant applications for such studies.

The issue central to the legal debate is the distinction between the derivation and use of the cells. In their letter of objection, the Congressmen, most of whom are Republicans, assert that "any NIH action to initiate funding of such research would violate both the letter and spirit of the federal law." They are referring to wording in the 1996 appropriations bill, which includes a rider prohibiting "research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death..." Congressional aides say that new legislation banning stem cell research has not been ruled out by the letter's signatories.

Proponents of stem cell research counter that since the cells have already been isolated and cultured as immortal lines, subsequent work on them would not entail destroying embryos, so this research could be funded by the NIH.

John Fletcher, University of Virginia, a member of NBAC, insists that the possible medical benefits of stem cell research make a legislative ban unlikely. "There are certainly more votes [in favor of funding] because of advances in research," says Fletcher, adding that he believes the appropriations committee is leaning towards lifting the current restrictions on embryo research rather than strengthening them.

The letter from the Nobel laureates, written under the aegis of the American Society for Cell Biology, points to the "serious negative consequences" of not funding federal research programs: "The net effect will be to bar the majority of the Nation's most prominent researchers who are supported by the National Institutes of Health and the National Science Foundation at universities and non-profit institutions throughout the country [those most qualified to make dramatic advances towards using stem cells for the treatment of disease] from engaging in this critical research." The letter goes on to say that "any new scientific understanding that emerges would not flow into the public domain and may be restricted to the commercial sector."

At NBACs meeting last month, preliminary discussion seemed to be leaning towards permitting both the use and derivation of human stem cells in federally funded studies, according to NBAC's executive director, Eric Meslin. NBAC's recommendations for research guidelines will be released in June.