It has been a privilege to watch the growth of RNA interference technology over the last ten years. Starting with a mixture of curiosity and chagrin, the field has grown into a substantial enterprise which impacts (and utilizes resources from) virtually every field of biomedical research. Research in RNAi derives from a set of apparently unconnected observations: strange pigment patterns in plants, unexpected failures and successes in antisense and overexpression studies, small regulatory RNAs in bacteria. If there is an underlying and recurring scientific lesson, it has been: “Pursue the unexpected.” Basic and applied research each advance as a consequence of this pursuit; certainly this has been no better illustrated than in the last ten years of RNAi.

The work of hundreds of researchers in different fields that is reported in this book should provide the reader with both solid information (needed for experimental design and evaluation) and a lively and hopeful scientific story (needed to keep us all going through the long haul of scientific research). Our knowledge of the realm of genetic regulation by small RNAs has grown with remarkable speed. Starting in 1981 with a single known example of a modulatory short RNA (regulating copy number of the ColE1 plasmid), small RNAs are now known to regulate genetic activity at virtually every level: DNA and chromosome structure, transcription, RNA structure and stability, translation, and protein stability. Likewise, our ability to experimentally alter cells using this system has advanced at an unprecedented rate.