Until 1998, geneticists had a frustrating vacancy in their molecular toolbox. They had abundant tools for adding new genes to cells but no simple way to find out what would happen if they took a gene away. That left one side of genetic research more or less unexplored.

Then came a Nature paper by Andrew Fire, PhD, at the Carnegie Institution’s embryology research center in Baltimore, and Craig Mello, PhD, of the University of Massachusetts Medical School in Worcester. This paper showed for the first time that the well-known molecule RNA could slip into a cell, seek out a gene’s “make a protein” message and then destroy it. They called this process RNA interference or RNAi.

Since that paper was published, thousands of researchers have caught the RNAi bug. Fire and Mello had revealed RNAi in their laboratory animal of choice, the nearly microscopic roundworm. But others soon found that it also operates in flies, mice, plants and human cells. So far the only laboratory organism in which RNAi fails to operate is the lowly yeast. In 2002, the journal Science heralded the technology “Breakthrough of the Year.” RNAi research has taken off, particularly at hotbeds at Cold Spring Harbor Laboratory in New York; the Massachusetts Institute of Technology; the University of Massachusetts, Amherst; and now Stanford.

With their new tool in hand, researchers can dream up previously impossible experiments. Eliminate the protein made by a gene and look for cellular changes? Develop gene therapies that quiet disease-causing genes? Knock out all gene products in a cell one by one to look for a particular effect? None of these was possible before Fire and Mello sussed out RNA’s double life. Now they’re practically routine.

Since arriving at Stanford in the fall of 2003 and joining the pathology department, Fire has rallied RNAi researchers from across the medical school and the university, starting a weekly journal club to discuss RNAi research. This meeting might be the only place at Stanford where people studying gene therapy, cell division, viral RNA replication, tumor formation and plant development all enthuse over the same scientific questions. The biggest of those is how best to harness RNA’s gene-disabling identity now that it has been revealed.

By Amy Adams

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