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184    Chapter 6    DNA Structure, Replication, and Recombination


              Figure 6.4  Transformation. (a) S bacteria are virulent and can cause lethal infections when injected into mice. (b) Injections of R
              mutants by themselves do not cause infections that kill mice. (c) Similarly, injections of heat-killed S bacteria do not cause lethal infections.
              (d) Lethal infection does result, however, from injections of live R bacteria mixed with heat-killed S strains; the blood of the dead host
              mouse contains living S-type bacteria.



              (a)





                      S                                   Inject                                            Dead

              (b)

                                 Mutates to

                      S                       R                                Inject                       Alive
              (c)





                                                       Cell
                      S                      Heat-killed  components            Inject                      Alive


              (d)



                                           Cell
                      S           Heat-killed  components  Combined                                      Tissue analyzed

                                                                    Inject                Dead


                                                                                                    Living S
                                           R                                                        recovered



                medium in the presence of components from dead S forms   Once purified, the transforming principle had to be
              (Fig. 6.5a). Avery then embarked on a quest that would   characterized. In 1944, Avery and two coworkers, Colin
              remain the focus of his work for almost 15 years: “Try to     MacLeod and Maclyn McCarty, published the cumulative
              find in that complex mixture, the active principle!” In other   findings of experiments designed to determine the transform-
              words, try to identify the heritable substance in the bacte-  ing principle’s chemical composition (Fig. 6.5c). In these
              rial extract that induces the transformation of harmless    experiments, the purified transforming principle was active
              R bacteria into pathogenic S bacteria. Avery dubbed the   at the extraordinarily high dilution of 1 part in 600 million.
              substance he was searching for the transforming principle   Although the preparation was almost pure DNA, the inves-
              and spent many years trying to purify it sufficiently to be   tigators nevertheless exposed it to various enzymes to see
              able to identify it unambiguously. He and his coworkers   if some molecule other than DNA might have caused the
              eventually prepared a tangible, active transforming principle.   transformation. Enzymes that degraded RNA, protein, or
              In the final part of their procedure, a long, whitish wisp   polysaccharide had no effect on the transforming principle,
              materialized  from  ice-cold  alcohol solution  and  wound   but an enzyme that degrades DNA completely destroyed its
              around the glass stirring rod to form a fibrous wad of nearly   activity. The tentative published conclusion was that the
              pure transforming principle (Fig. 6.5b).             transforming principle appeared to be DNA. In a personal
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