Over beer and coffee, in labs and at scientific conferences, the speculation has been intense for years: Who in the RNA interference (RNAi) field, biologists wondered, would win the Nobel Prize, and when? Science's ultimate accolade was considered increasingly inevitable as the gene-silencing method revolutionized genetics, spurred development of new medical treatments, and transformed our understanding of cellular behavior. But, under Nobel rules, the prize can go to no more than three people. Yet many had made seminal contributions to the discovery and understanding of RNAi.

Early Monday morning, several years earlier than many expected, the guessing game came to an end. Two Americans—Craig Mello of the University of Massachusetts (UMass) Medical School in Worcester and Andrew Fire of Stanford University in Palo Alto, California—learned that they had won this year's $1.37 million Nobel Prize in physiology or medicine. Like many Nobel winners before him, Fire, who was woken by a phone call from Sweden, wondered at first if he was dreaming, or the caller had the wrong number. Although many had predicted that he and Mello would be winners, Fire still felt a “certain amount of disbelief,” he said during a press conference.“We looked at this very, very complex jigsaw puzzle and put in a significant piece,” he said.