Fire and Mello win Nobel Prize
Researchers are honored for discovering the mechanism of RNA interference
Andrew Z. Fire
, a professor in Stanford University School of Medicine's Department of Pathology and Genetics, and Craig C. Mello
, professor of Molecular Medicine at the University of Massachusetts Medical School, have won this year's Nobel Prize in Physiology or Medicine for uncovering the mechanism of RNA interference, a discovery that "heralded the start of a new research field," according to the Nobel Academy.
"They started a revolution with the discovery of RNA interference," Nobel Laureate Philip Sharp
, who won the prize in 1993 and studies the interference role of microRNA at the Massachusetts Institute of Technology, told The Scientist.
Sharp said Fire, Mello, and their colleagues' landmark Nature study
in 1998 -- which has been cited in more than 2,500 papers, according to Web of Science (Thomson Scientific) -- not only launched a new field
in RNA research, but also has had "profound impacts" on the understanding of gene regulation and function.
This year's prize represents "one of the quickest recognitions of a discovery," said Nick Hastie, Director of the Medical Research Council Human Genetics Unit in Edinburgh, in a statement. "To find this in 1998 and get a Nobel Prize in 2006 is remarkable."
Fire and Mello made their discoveries in the nematode, Caenorhabditis elegans. Richard Jorgensen, associate professor at the University of Arizona Tucson, had noted
the powerful co-suppression of petunia pigmentation genes using RNA constructs in the early 1990s. Antisense effects couldn't account for the extreme knockdowns in expression that researchers saw.
In 1998, Fire and Mello investigated whether in fact double-stranded RNAs might be the trigger, and thus opened a new facet of RNAs' many duties in the cell. They found that just a few molecules were sufficient for wiping out gene expression, and in a modest prediction, the authors concluded, "The use of dsRNA injection adds to the tools available for studying gene function in C. elegans."
RNAi has grown into an extremely powerful tool. In the years since Fire and Mello's discovery, RNAi
has been applied not only to uncovering gene function in many other organisms, but also to understanding and potentially treating human diseases.
The revolution has created a new sector in the biotechnology industry. Alnylam Pharmaceuticals
, based in Cambridge, MA, is one of a number of companies using RNAi to develop therapeutics and has one product already in clinical development. CEO John Maraganore said he believes the award of the prize to Fire and Mello is a reflection of the fact that RNAi "has such enormous implications for basic biology and the promise for the discovery of new medicines."
Maraganore estimates the market capitalization of therapeutic RNAi companies is well over one billion dollars. He expects RNAi can be applied to numerous diseases, including respiratory syncytial virus, Parkinson's disease, and influenza.
"It is extremely gratifying to see RNAi applied so broadly in labs around the globe," Mello said in a statement. "Our work was just one piece of a puzzle but I think it is opening a door to a whole new frontier from which we can learn so much more about our bodies' own protective mechanisms."
Sharp says Fire and Mello's impact on the study of RNAi still reverberates. "This discovery is still unfolding. This summer there was a whole other class of RNAs uncovered call
. There is a whole RNA world in our cells that has (yet to be explored)."
Links within this article:
Andrew Z. Fire
Craig C. Mello
Fire, et al. 1998 Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806-811.
"Small Worms, Small RNAs, Big Questions," The Scientist, July 2002
Napoli, et al. 1990. Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous genes in trans. Plant Cell
"Shhhh: Silencing Genes with RNA Interference," The Scientist, April 2003).
Lau et al. 2006. Characterization of the piRNA complex from rat testes. Science 313:363-367.