October 22, 2004

Warren Triennial Prize honors innovators of RNA interference

The latest installment of a tradition going back more than a century took place last week with the presentation of the Warren Triennial Prize, established in 1871 in honor of MGH co-founder John Collins Warren. The 2004 recipients Ð Andrew Fire, PhD, of Stanford University, and Craig Mello, PhD, of UMass Medical Center and the Howard Hughes Medical Institute — are the pioneers of RNA interference (RNAi) a powerful new technique for understanding and controlling the activity of genes.

Long thought merely a messenger molecule that helps convert the information encoded in DNA into proteins, RNA was shown to have an unexpected function by Fire and Mello. Their 1998 study described how tiny fragments of a double-stranded version of RNA, which is usually a single strand of nucleic acids, could actually turn off the associated gene. The finding has opened a new field of molecular research devoted to both understanding how this process works naturally and investigating how it might be used to treat cancer or other conditions.

In his address, Fire described how his group, Mello's and other research teams discovered why introducing RNA into cells often decreased production of the associated protein, rather than increasing production as originally expected. He compared the way tiny RNA fragments identify their target messenger RNA molecules and mark them for destruction to the specific recognition ability of the immune system. Mello addressed how his team has been using RNAi to understand the development of the c. elegans worm, a common research model. By looking for mutant worms that resist RNAi, they are learning more about how essential the process is to normal development.

"Fire and Mello achieved a real breakthrough in determining that the mechanism of some unusual immune properties originally observed in plants was double-stranded RNA," says Daniel K. Podolsky, MD, chief of the MGH Gastrointestinal Unit and chair of the MGH Executive Committee on Research. "RNA interference now is bringing an entirely new dimension to our understanding of the regulation of cell function and opening the possibility of new cell-specific therapies."