We are now aware of the function of DNA as the genetic material. However, it involved the observations made by several scientists to make this discovery.

Many scientists had put forward their ideas about hereditary. Eventually in 1860s, Mendel postulated that each trait is determined by a pair of inherited factors (now known as genes). After around 50 years, in 1910, Thomas Hunt Morgan showed that chromosomes were the carriers of genes. However, it was not clear if the molecules responsible for the inheritance were proteins or the DNA, in the chromosomes. At this time, experiments conducted by Frederick Griffith on Streptococcus pneumoniae in mice took the scientific community a step further towards the fact the DNA was the genetic material. Though his experiment itself did not concluded this, it led to the other scientists of carry out various experiments, finally leading to the conclusion.

Let’s look into the experiment carried out by Frederick Griffith in this post.

Fig 1: Frederick Griffith (1879–1941; Image source: Wikipedia).

Frederick Griffith (fig 1) was an English army doctor, who was working to make vaccine against Streptococcus pneumoniae. In his work published in 1928 (Griffith, 1928), he has actually written about the examination of sputum samples from patients of lobar pneumonia. He found that the causative bacteria were of two types; R strain and the S strain.

(Just for info: Have a look at the original paper of Frederick Griffith published in 1928).

The main differences between the two strains were as follows:

1) R strain:

It produced typical colonies with well-defined edges but a rough appearance (fig 2A).

The bacteria belonging to this strain where non-encapsulated or did not produce polysaccharide capsules.

This strain was non-virulent. It did not lead to death of the mice when injected alone.

Fig 2: Colony morphology of various S. pneumoniae strains grown on blood agar. (A) Smooth strain (D39); (B) Rough strain (R6). (Image Source: Belanger, 2005).

2) S strain:
This strain produced colonies with smooth appearance (fig 2B).

The S bacteria were encapsulated. Infact, the smooth edge was considered to be due to the ability to produce polysaccharides capsule (fig 3), which the R strain lacked.

S strain was virulent and could kill the mice. The polysaccharide capsule shields the bacteria from the host immune system and helps in the establishment of the colonization within the mice.

Fig 3: Electron micrograph of Streptococcus pneumoniae and the associated pneumococcal capsular polysaccharide ( Image adapted from: Jones, 2005)

It was observed that the two types of strains could be converted from one form to another. The bacteria belonging to the R strains were thought to preserve the capacity to produce the polysaccharide capsule. In order to know more, Griffith carried out a series of experiments.
The four main experiments and the respective observations are mentioned below:

Experiment 1:

When the live R bacteria were injected into the mice, the mice did not cause disease and were alive (fig 4).

Experiment 2:

When the live S bacteria were injected into the mice, the mice developed pneumonia and died (fig 4).

Fig 4: The Griffith’s Experiments.

Experiment 3:

Griffith first killed the mice by heating them to a high temperature. When the heat-killed S bacteria were injected into the mice, the mice did not get the disease and the mice were alive (fig 4).

Experiment 4:

In another experiment, Griffith mixed the heat-killed S bacteria (could not cause disease alone) and live R bacteria (could not cause disease alone) and injected this mixture into the mice. Surprisingly the mice developed the disease and died. He found that the bacteria from the dead mice had the characteristic of S bacteria (fig 4).

From the set of observations, Griffith drew the conclusion that the S bacteria, even the dead ones, could transform the live R bacteria into S bacteria. Hence, he concluded that some component from the S bacteria, which he called as the “transforming principle’, could cause the transformation of the R bacteria to the S bacteria.

We now know that, this process is called Transformation and that the transforming particle was DNA. However it was not clear at that time whether it was DNA or proteins from the chromosomes that brought about the transformation.

Further experiments conducted by Oswald Avery and his colleagues and Alfred Hershey and Martha Chase showed that the ‘transforming principle’ was actually DNA.

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Morgan (1944) Transformation of Pneumococcal Types. Nature 153: 763–764.

Griffith (1928). The Significance of Pneumococcal Types. Journal of Hygiene 27(2): 113-159.

Petsko (2006) Transformation. Genome Biol. 7(10): 117.

Jones (2005). Vaccines based on the cell surface carbohydrates of pathogenic bacteria. Anais da Academia Brasileira de Ciências. 77: 293-324.

Belanger et al (2005). Pyruvate Oxidase Is a Determinant of Avery’s Rough Morphology. Journal of bacteriology. 186: 8164-71.