1 The Treasure Under the Right Stone

Abstract

When the reverse transcriptase was first discovered back in 1970, the Central Dogma of DNA→RNA→protein so completely dominated thinking that the notion of RNA-dependent DNA synthesis came as a great surprise. That surprise grew out of consideration of how RNA tumor viruses are able to transform cells stably. It was the general feeling then, and time has reinforced it, that RNA is a transient molecule in cells. There were already known and well-understood classes of lytic viruses that used RNA as their genetic material, but the stability of their heredity was not a contradiction to RNA’s lability because they grew only transiently in any one cell and continually required new cells for their propagation. These viruses stayed one step ahead of the grim reaper. The existence of a group of RNA-containing viruses that could permanently alter the heredity of cells —a situation that was particularly obvious because these viruses made the cells tumorigenic — required either that they make a uniquely stable RNA, one that can equal the permanence of DNA, or that they transmute their information into a stable condition. Howard Temin had long argued that the likely solution was that they encode a DNA able to integrate itself into the cell’s chromosomes, a provirus, but the community of molecular biologists found this hard to accept given the sway of the Central Dogma. Looked at in retrospect, it was a comfortably conservative viewpoint because the chemistry was so easy to imagine. DNA→RNA or RNA→DNA makes very little chemical difference, and...