In Search of the Genetic Material

Long before anyone knew genes were made of DNA, cytologists were already watching the physical objects that would turn out to carry them. As early as 1848 the German botanist Wilhelm Hofmeister observed that, during mitosis, the material inside a cell's nucleus condenses into small, rod-shaped bodies, which were later named chromosomes. In 1869 the Swiss physician Friedrich Miescher isolated an unfamiliar substance from the nuclei of white blood cells and named it 'nuclein'; this substance was renamed nucleic acid by Richard Altmann in 1889, and we now know it as DNA. By around 1920 it was established that chromosomes are built from two kinds of molecule, protein and DNA, but it was not yet clear which of the two actually stored hereditary information, so a great deal of experimental work followed to identify the true carrier. Frederick Griffith's bacterial transformation experiments (covered in detail in Class XI) gave the first hint: when a harmless, non-virulent strain of bacteria was exposed to material from a heat-killed virulent strain, the harmless bacteria permanently acquired the virulent strain's disease-causing ability, a phenomenon called transformation. Griffith could not, however, say which chemical component of the dead cells was responsible. That question was answered by Oswald Avery, Colin MacLeod and Maclyn McCarty in 1944, who repeated Griffith's experiment outside a living animal (in vitro) and selectively destroyed each candidate molecule in turn -- protein, RNA or DNA -- before testing whether transformation could still occur; only destroying DNA abolished transformation, pointing squarely at DNA as the genetic material. Two related hypotheses that grew out of this era of gene-function research are also introduced here: George Beadle and Edward Tatum's work on the mould Neurospora crassa in the early 1940s led to the one-gene-o …