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The discovery of the transforming principle The first clue that DNA was the carrier of hereditary information came with the demonstration that DNA was responsible for a phenomenon called transformation. The phenomenon was first observed in 1928 by Fred Griffith, an English physician whose special interest was the bacterium that causes pneumonia, Streptococcus pneumonia. Griffith had succeeded in isolating several different strains of S. pneumonia (type I, II, III, and so forth). In the virulent (disease-causing) forms of a strain, each bacterium is surrounded by a polysaccharide coat, which makes the bacterial colony appear smooth when grown on an agar plate; these forms are referred to as S, for smooth. Griffith found that these virulent forms occasionally mutated to nonvirulent forms, which lack a polysaccharide coat and produce a rough-appearing colony on an agar plate; these forms are referred to as R, for rough.

Griffith was interested in the origins of the different strains of S. pneumonia and why some types were virulent, whereas others were not. He observed that small amounts of living type IIIS bacteria injected into mice caused the mice to develop pneumonia and die; on autopsy, he found large amounts of type IIIS bacteria in the blood of the mice (Figure 10.2a). When Griffith injected type IIR bacteria into mice, the mice lived, and no bacteria were recovered from their blood (I FIGURE 10.2b). Griffith knew that boiling killed all the bacteria and destroyed their virulence; when he injected large amounts of heat-killed type IIIS bacteria into mice, the mice lived and no type IIIS bacteria were recovered from their blood ( FIGURE 10.2c).

The results of these experiments were not unusual. However, Griffith got a surprise when he infected his mice with a small amount of living type IIR bacteria, along with a large amount of heat-killed type IIIS bacteria. Because both the type IIR bacteria and the heat-killed type IIIS bacteria were nonvirulent, he expected these mice to live. Surprisingly, 5 days after the injections, the mice became infected with pneumonia and died ( FIGURE 10.2d). When Griffith examined blood from the hearts of these mice, he observed live type IIIS bacteria. Furthermore, these bacteria retained their type IIIS characteristics through several generations; so the infectivity was heritable.

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