Griffith Searches for the Genetic Material
In 1928, a British medical officer named Frederick Griffith was trying to develop a
vaccine against pneumonia. He was studying Streptococcus pneumoniae, a bacterium
that causes pneumonia in mammals. Griffith had two strains (varieties) of the bacterium,
one pathogenic (disease-causing) and one nonpathogenic (harmless). He was surprised
to find that when he killed the pathogenic bacteria with heat and then mixed the cell
remains with living bacteria of the nonpathogenic strain, some of the living cells became
pathogenic. Furthermore, this newly acquired trait of pathogenicity was inherited by all
the descendants of the transformed bacteria. Apparently, some chemical component of
the dead pathogenic cells caused this heritable change, although the identity of the
substance was not known. Griffith called the phenomenon transformation, now defined
as a change in genotype and phenotype due to the assimilation of external DNA by a cell.
Avery’s Team Makes a Major Contribution
In the early 1940s, a team of scientists led by Oswald Avery tried to answer the question
raised by Griffith’s results. Avery, together with his colleagues Colin MacLeod and Maclyn
McCarty, inactivated various substances in the heat-killed S-strain bacteria. They then
mixed the heat-killed S-strain bacteria with the harmless R-strain bacteria. When
proteins and RNA were inactivated, the R-strain still transformed into the deadly S-strain.
This ruled out proteins and RNA as the genetic material. Why? Even without the S-strain
proteins or RNA, the R-strain was changed or transformed, into the deadly S-strain.
However, when the researchers inactivated DNA in the S-strain, the R-strain did not
transform. This led to the conclusion that DNA is the substance that controls the
characteristics of organisms. In other words, DNA is the genetic material.
Hershey and Chase Seal the Deal
The conclusion that DNA is the genetic material was not widely accepted at first. It had to
be confirmed by another research. In the 1950s, Alfred Hershey and Martha Chase did
experiments with viruses known as bacteriophages, a virus that infects bacteria, and
bacteria. Viruses are not made of cells. Bacteriophages are basically DNA inside a protein
coat. To reproduce, a virus must insert its own genetic material into a cell (such as a
bacterium). Then it uses the cell’s machinery to make more viruses. The researchers used
different radioactive elements to label the DNA and proteins in viruses. This allowed
them to identify which molecule the viruses inserted into bacteria. DNA was the molecule
they identified. This confirmed that DNA is the genetic material.
Further Evidence by Chargaff
Further evidence that DNA is the genetic material came from the laboratory of biochemist
Erwin Chargaff. Chargaff analyzed the base composition of DNA from a number of
different organisms. In 1950, he reported that the base composition of DNA varies from
one species to another. For example, he found that 32.8% of sea urchin DNA nucleotides
have the base A, whereas only 24.7% of those from the bacterium E. coli have an A. This
evidence of molecular diversity among species, which most scientists had presumed to
be absent from DNA, made DNA a more credible candidate for the genetic material.
Chargaff also noticed a peculiar regularity in the ratios of nucleotide bases. In the DNA of
each species he studied, the number of adenines approximately equaled the number of
thymines, and the number of guanines approximately equaled the number of cytosines.
In sea urchin DNA, for example, the four bases are present in these percentages: A =
32.8% and T = 32.1%; G = 17.7% and C = 17.3%. (The percentages are not exactly the
same because of limitations in Chargaff’s techniques.)