Enabling technologies in discovery: the 2009 Nobel Prize and its implications in antibiotic design

Abstract

Every year in early October the announcement of the winners of the Nobel Prize in different disciplines, including those awarded the Nobel Prize in Chemistry, is greeted with expectation and often surprise by the scientific community. Despite its many detractors claiming unjust and even political choices of the awardees, the Nobel Prize still carries an aura of scientific glamour that no other prized award in science or medicine does. The 2009 Nobel Prize in Chemistry recognized three researchers for elucidation of the structure and function of the ribosome, the protein production machinery that translates the DNA blueprint of life into life itself. The laureates, Venkatraman Ramakrishnan (MRC Laboratory of Molecular Biology, Cambridge, UK), Thomas A. Steitz (Yale University, CT, USA), and Ada E. Yonath (Weizmann Institute of Science, Rehovot, Israel) exemplify the spirit of scientific devotion that has long resulted in breakthrough discoveries. The road leading to the atomic resolution structure of the ribosome was a long journey. Ribosomes are large RNA-protein complexes. Obtaining the ribosomes at high purity and in large enough amounts to perform meaningful studies was, in itself, already a formidable task. The pinnacle of many years of tenacious work by Yonath and colleagues was the crystallization of the ribosomal 50S subunit from the thermophilic bacterium Geobacill stearothermophilus [1]; this was the first true breakthrough leading to the elucidation of the structure of the ribosomes. In the next two years a few other ribosomal subunits were crystallized, but most of them did not render enough diffraction resolution (i.e., only 10 A) to build a structure model with high fidelity. It took Yonath and colleagues ten full years to reach the second milestone in the revelation of ribosome structure when they finally obtained crystals from the 50S subunit from H. marismortui with a diffraction resolution of 3 A [2]. Strikingly, while it took almost two decades to advance from the first crystal to the low resolution structure, it took merely three years to move the resolution of the 50S subunit structure from low [3], via intermediate [4–7], to high [8–11]. This fast progress is largely because of improvement of other analytical methods that aided in the task, such as the employment of CCD area-detectors for precise and automated analysis of X-ray diffraction patterns.