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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