CHAPTER 6
GRIFFITH/HERSHEY/CHASE: DNA IS THE GENETIC MATERIAL
In 1928, Frederick Griffith was able to transform harmless bacteria into virulent pathogens with an extract
that Oswald Avery proved, in 1944, to be DNA. In 1952, Martha Chase and Alfred Hershey used
radioactively labeled virus DNA to infect bacteria, proving the same point. These important experiments
established that DNA is the genetic material.
IDENTIFICATION OF DNA
Deoxyribonucleic acid (DNA) was first described by Friedrich Miescher in 1869, only four years after
Mendel’s work was published. But it took over 80 years for its role as the genetic material of most
organisms to become firmly established. DNA was first characterized as acid-precipitable material from
the cell nuclei of pus and fish sperm. The proportion of nitrogen and phosphorus was very unusual
compared to other known organic substances, convincing Miescher he had discovered a new biological
substance. He called it nuclein, because it was associated exclusively with the nucleus. Further work
demonstrated that nuclein is a complex of protein and DNA.
DNA AND HEREDITY
Although clear experiments linking DNA to heredity were not performed until the mid 1940s, there was a
good deal of circumstantial evidence that this was the case. In higher organisms, DNA was found almost
exclusively in the chromosomes. The histone proteins and RNA, which chromosomes also contain, did not
seem likely candidates as genetic material; sperm contained almost no RNA, and the histones are replaced
in sperm by a different protein, protamine.
Unlike RNA and protein, every diploid cell of an organism has about the same amount of DNA. In the hen,
for example, the red blood cells contain 2.6 x 10-12g of DNA per cell, the kidney contains 2.3 x 10-12g per
cell, and the liver contains 2.6 x 10-12g per cell. Furthermore, the amount of DNA seems correlated with
chromosomal division; entering mitosis, the amount of cellular DNA doubles, while the haploid products of
meiosis have only half the normal amount (thus rooster sperm contains 1.3 x 10-12g of DNA). In polyploid
plants, which contain multiples of the diploid number of chromosomes, the quantity of DNA is also a
multiple of the diploid amount. Thus, the close association of DNA with chromosomes strongly implicates
DNA as the genetic material.
DNA CAN GENETICALLY TRANSFORM CELLS
The first unambiguous evidence that DNA was the hereditary material came from Frederick Griffith’s
studies in 1928. Griffith used chemical mutagens to isolate a nonvirulent form of the bacterium that causes
pneumonia, Diplococcus pneumoniae. Virulence required the presence of a polysaccharide capsule around
the bacterium. The nonvirulent mutants lacked this capsule. Colonies of nonvirulent capsuleless bacteria
appeared rough and were designated R. In contrast, the virulent form produced colonies that appeared
smooth, so it was designated S. Several virulent forms were known, each with a characteristic
polysaccharide capsule (called IS, IIS, IIIS, etc.), which is genetically inherited and is immunologically
distinct from other forms.
A smooth bacterium of a particular capsule type (say IIS) can mutate to a nonencapsulated, nonvirulent
form (IIR, because it derives from a type II cell). This happens at a very low frequency (in less than one in
