Lewin's Cells

Eighty years ago, the cellular world opened up. The electron microscope granted us, for the first time, a detailed perspective of basic cellular structures, and the ultracentrfuge allowed us to biochemically isolate and characterize fractions of cytoplasmic and nuclear material. Geneticists could investigate the relationship between the evershifting chromosomal structure and the molecular mechanisms of genetic inheritance—an effort that culminated with the triumphant revelation of the structures of DNA and RNA and a translation of the genetic code. But we have come a long way from there. We have perfected our understanding of genes themselves, adjusting our definition from “determinants of a genetic phenotype,” to “protein-encoding segments of DNA,” and now, more precisely, “units of genomic information required for the transcription of functional messenger RNA or noncoding RNA.” So far, the complete genomes of over 4,000 organisms have been published, revealing the sequences of over 100 million genetic loci. And we are still learning about the proteins these mRNAs produce. The RSCB Protein Data Bank (PDB) was established in 1971 as an international repository for structural data, but it did not truly begin to grow until the early 1990s. Now, in 2013, it holds more than 90,000 structures and is expanding at the rate of about 7,000 structures per year. For now, X-ray crystallography and nuclear magnetic resonance are the only techniques available for the determination of macromolecular structures at high resolution. Important advances in other methods, however—including visualization of fluorescently tagged proteins in living cells and new types of electron microscopy—are describing cellular structures and processes in ever-increasing detail.