Back to basics

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    Abstract

    Nucleic acids and the people and proteins that love them have been honored with awards this year. In so doing, the prize committees have reaffirmed the importance of basic research.

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    The 2006 Albert Lasker Award for Basic Medical Research was shared by Elizabeth Blackburn (University of California, San Francisco), Carol Greider (Johns Hopkins University) and Jack Szostak (Massachusetts General Hospital) “for the prediction and discovery of telomerase, a remarkable RNA-containing enzyme that synthesizes the ends of chromosomes, protecting them and maintaining the integrity of the genome.” The Nobel Prize in Physiology or Medicine went to Andy Fire (Stanford University) and Craig Mello (University of Massachusetts Medical School) “for their discovery of RNA interference—gene silencing by double-stranded RNA.” And the Nobel Prize in Chemistry was awarded to Roger Kornberg (Stanford University Medical School) “for his studies of the molecular basis of eukaryotic transcription.” These honorees and their achievements epitomize the importance of basic, non-applied research and the fact that it is impossible to predict which advances from basic research will in time benefit society, and in what ways.

    The Nobel committee said that it was honoring Kornberg's fundamental work over 20 years on how the information stored in genes is copied. Kornberg's long-term studies on RNA polymerase II would not have been possible without the financial support, since 1979, of the US National Institutes of Health (NIH) for basic biomedical research.

    The structure of a multi-component RNA polymerase, though sought after for many years by many different labs, was still elusive when Patrick Cramer (Ludwig-Maximilians-University of Munich) joined the pursuit. He describes his journey and the colleagues who made it possible in one of three Essays in this issue. The papers highlighted by the Nobel committee showed RNA polymerase caught in the act of transcription, making it possible for the first time to design elegant structure-function studies that would answer basic questions about the mechanism of transcription.

    The Fire-Mello award honors a discovery that opened an entire field of study and explained otherwise confusing and contradictory results with antisense and sense RNAs, as well as providing a fundamental tool for all biomedical research. As Mary Montgomery (Macalester College) explains in the second Essay in this issue, at the time she joined the Fire lab, simple antisense-based inhibition was used as a way to interfere with gene expression. In their landmark paper, Fire and Mello found that double-stranded RNA was more effective at producing interference than either of the two RNA strands alone. Their study noted that interference could spread between cells, could be inherited and was an apparently catalytic process. RNAi is now known to be an ancient mechanism of sequence-specific, post-transcriptional gene silencing that is found in plants and animals.

    Finally, the discovery of telomerase, which is now considered a medically important enzyme, arose from work seeking to understand a very basic biological problem: the molecular nature of chromosome ends. Studying the ends of linear ribosomal DNA molecules from Tetrahymena thermophila, a pond-dwelling ciliate, Blackburn found tandem copies of the sequence TTGGGG. Szostak and Blackburn collaborated on what they both admit was a crazy experiment—to see whether Tetrahymena telomeres might function in yeast. Sure enough, they did. Not only that, yeast added its own telomeric DNA sequence to the ends of chromosomes in what seemed to be an untemplated reaction. Szostak and Blackburn suggested that a terminal transferase-like enzyme might be adding the repeats to chromosome ends. To find such an activity, Blackburn, joined by Carol Greider, took a biochemical approach and Szostak and Vicki Lundblad (Salk Institute) used “the awesome power of yeast genetics.” In the first of the three Essays in this issue, Lundblad relates what it was like to be there during that time of discovery.

    Although Blackburn and Greider have received many awards for the discovery of telomerase, this is the first time that Jack Szostak has been honored along with them. In an essay by Titia de Lange (Rockefeller University; Cell 126, 1017–1020, 2006) and in Joe Goldstein's (University of Texas Southwestern Medical Center) presentation of the award, Szostak's important contributions are described together with those of Blackburn and Greider. The telomerase tale is also told by the three awardees themselves in a recent Commentary (Nature Medicine 12, 1133–1138, 2006).

    The collaboration between Blackburn and Szostak, Mello and Fire's persistence in trying to fully understand a puzzling phenomenon, and Kornberg's relentless pursuit of the RNA polymerase II structure all underscore the importance of doing basic, curiosity-driven research. There is no way of knowing a priori where certain lines of research will lead, and so the need for basic research is paramount. The applications will come only once the foundations are laid down.

    This seems especially pertinent in light of the past three years of flat or declining NIH budgets. If the funding situation does not improve quickly and dramatically, it is likely that a new generation of scientists will be dissuaded from entering science in the first place or will be denied funding. So while we celebrate these remarkable achievements and the winners themselves, we should take every opportunity to advocate for the continued strong support of basic research.

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