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6.1 Experimental Evidence for DNA as the Genetic Material   185


                       Figure 6.5  The transforming principle is DNA. (a) Bacterial transformation occurs in culture medium containing the remnants of
                       heat-killed S bacteria. Some transforming principle from the heat-killed S bacteria is taken up by the live R bacteria, converting (transforming)
                       them into virulent S strains. (b) Purified DNA extracted from human white blood cells. (c) Chemical fractionation of the transforming principle.
                       Treatment of purified DNA with a DNA-degrading enzyme destroys its ability to cause bacterial transformation, while treatment with enzymes
                       that destroy other kinds of macromolecules has no effect on the transforming principle.
                       b: © Phanie/Science Source
                           (a)                                                                  (b)





                                                                Time
                                     Living R form
                              Heat-killed
                              S components                                          Living S form
                              in medium

                                                           Protease           Protein      Introduce into      S cells
                                                                              destroyed    R cells          (Transformation)
                           (c)
                                                           RNase              RNA          Introduce into      S cells
                                                                              destroyed    R cells          (Transformation)
                                                           DNase              DNA          Introduce into      R cells
                                                                              destroyed    R cells         (No transformation)

                                                           Ultracentrifugation  Fats       Introduce into      S cells
                                                                              eliminated   R cells          (Transformation)

                                    Purified               Physical and        Indicates
                                  transforming            chemical            predominance
                                   principle              analysis            of DNA

                       letter to his brother, Avery went one step further and con-    machinery of their host cell to carry out growth and repli-
                       fided that the transforming principle “may be a gene.”  cation, they can be very small indeed and contain very few
                          Despite the paper’s abundance of concrete evidence,   genes. For many kinds of phages, each particle consists of
                       many within the scientific community still resisted the idea   roughly equal weights of protein and DNA (Fig. 6.6a).
                       that DNA is the molecule of heredity. They argued that   These phage particles can reproduce themselves only after
                       perhaps Avery’s results reflected the activity of contami-  infecting a bacterial cell. Thirty minutes after infection, the
                       nants; or perhaps genetic transformation was not happen-  cell bursts and hundreds of newly made phages spill out
                       ing at all, and instead, the purified material somehow   (Fig. 6.6b). The question is: What substance contains the
                       triggered a physiological switch that transformed bacterial   information used to produce the new phage particles—
                       phenotypes. Unconvinced for the moment, these scientists   DNA or protein?
                       remained attached to the idea that proteins were the prime   With the invention of the electron microscope in 1939,
                       candidates for the genetic material.                it became possible to see individual phages, and surpris-
                                                                           ingly, electron micrographs revealed that the entire phage
                                                                           does not enter the bacterium it infects. Instead, a viral
                       DNA, Not Protein, Contains the                      shell—called a ghost—remains attached to the outer sur-
                       Instructions for Virus Propagation                  face of the bacterial cell wall. Because the empty phage
                                                                           coat remains outside the bacterial cell, one investigator lik-
                       Not everyone shared this skepticism. Alfred Hershey and   ened phage particles to tiny syringes that bind to the cell
                       Martha Chase anticipated that they could assess the rela-  surface and inject the material containing the information
                       tive importance of DNA and protein in gene replication by   needed for viral replication into the host cell.
                       infecting bacterial cells with viruses called phages, short   In their famous Waring blender experiment of 1952,
                       for bacteriophages (literally bacteria eaters).     Alfred Hershey and Martha Chase tested the idea that the
                          Viruses are the simplest of organisms. By structure   ghost left on the cell wall is composed of protein, while the
                       and function, they fall somewhere between living cells   injected material consists of DNA (Fig. 6.7). A type of
                         capable of reproducing themselves and macromolecules   phage known as T2 served as their experimental system.
                       such as proteins. Because viruses hijack the molecular   Hershey and Chase grew two separate sets of T2 in bacteria
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