||THE MYSTERY OF DNA REPLICATION 17 hairpins and locked the template strands together so that they never again could be separated. The resolution of the paradox was gradual and complex. It required a complete change in the approach to the enzymology of DNA replication and an acceptance by geneticists that the DNA molecule might be much more flexible than they had ever believed, that its integrity could be almost, but not quite, damaged. John Cairns and Reiji Okazaki played a remarkable role in this change of attitude. Both began with definite prejudices and both were willing to expend a major effort to establish their beliefs. Okazaki believed in polymerase I, more than he believed that the continuity of the double helix needed to be rigidly conserved. Therefore, he conceived of a way in which the helix could be replicated continuously on one side and discontinuously on the other. Thus, the new strand would be extended in one continuous elongation on the side in which the enzyme's polarity coincided with that demanded by the template. On the opposite side, it would work backwards synthesizing a series of small pieces, each of which would be joined to the growing chain. To defend this notion, he had to demonstrate that small pieces were made and that they were subsequently joined into long DNA. Moreover, he had to postulate the existence of a joining enzyme. In 1967 he demonstrated small pieces which were joined together shortly after their synthesis. Within a year, others had isolated a joining enzyme. It was Okazaki's faith in polymerase I which motivated him to search within the living cell for an explanation, and because Okazaki was a reputable biochemist in his own right, other enzym-ologists were more willing than usual to credit the results of in vivo experiments. Thus, his work did much to bridge a widening credibility gap between in vitro and in vivo work. Perhaps, if Cairns' experiments had preceded those of Okazaki, discontinuous synthesis would have remained hidden for a few more years. Cairns could not believe that the enzyme was the correct one, despite its near-perfect attributes. He felt that more than just the polarity paradox was wrong with polymerase I.