slides--my talk 2/94 These spectacular discoveries in biochemistry ran far ahead of the genetic study of the pneumococcus transformation, which relied on the capsule as a sole genetic marker. Until this study was broadened about 1951 with experiments on drug resistance and other markers (8, 9), a variety of opinions were forwarded (mostly on a purely speculative level) on the biological interpretation of Griffith's finding. They included the following versions of the transforming substance: 1. It was a specific mutagen with a special ability to direct a particular gene to mutate in a definite direction. 2. It was a polysaccharide autocatalyst (perhaps as a complex with DNA) that primed an enzymatic reaction for polysaccharide synthesis. 3. It was a bacterial virus, which on infecting the bacteria provoked capsular synthesis as a host reaction. 4. It was an autonomous cytoplasmic gene or a morphogenetic inducer. 5. It might be acting at a distance without penetrating the bacterium. 6. It was a fragment of the genetic make-up of the bacterium, the only one to have been tested to that time. 7. It was an element sui generis for which no general conception should be adduced. Lederberg 1956.