Question

Describe the series of experiments conducted by Frederick Griffith. Comment on the significance of the result obtained.
State the contribution of Avery, MacLeod and McCarty.

Hint:

Remember that Griffith discovered what transformation does (introducing the concept of a transforming principle), but Avery, MacLeod, and McCarty discovered how it works chemically by using targeted digestive enzymes to prove that DNA is the genetic material.

Answer 1

Step 1: Understanding the Question:
This question asks for a detailed description of Frederick Griffith's transforming experiments (1928) using Streptococcus pneumoniae and an explanation of the significance of his findings. It also requires stating how Avery, MacLeod, and McCarty chemically identified the transforming principle.

Step 2: Key Formula or Approach:
Griffith's Framework: Uses two distinct bacterial strains—the virulent, smooth (S) strain containing a polysaccharide capsule, and the non-virulent, rough (R) strain which lacks a capsule.
Biochemical Characterization: Uses selective enzymatic digestion (Protease, RNase, and DNase) to identify the specific macromolecule that transfers genetic traits.

Step 3: Detailed Explanation:
(i) Griffith's Transforming Principle Experiments: Griffith worked with Streptococcus pneumoniae, a bacterium that causes pneumonia in mammals, and observed two distinct phenotypic strains:
1. Smooth (S) Strain: Produces smooth, shiny colonies because the cells synthesize an outer polysaccharide capsule. When injected into mice, they develop pneumonia and die (virulent strain).
2. Rough (R) Strain: Produces rough colonies because they lack this protective capsule. When injected into mice, the host's immune system clears the bacteria, and the mice survive (non-virulent strain).
3. Heat-Killed S Strain: Griffith heated the virulent S strain to kill the cells. When injected into mice, the mice survive, showing that the dead bacteria cannot cause disease.
4. Mixture of Heat-Killed S + Live R Strains: Griffith mixed the harmless heat-killed S bacteria with harmless living R bacteria and injected the mixture into healthy mice. Surprisingly, the mice developed pneumonia and died. Furthermore, he isolated living, fully capsuled S-strain bacteria from the blood of these dead mice.
Significance of the Result: Griffith concluded that the living R-strain bacteria had absorbed a hereditary material from the dead, heat-killed S-strain cells. This material permanently transformed the R strain, enabling it to synthesize a smooth polysaccharide coat and become virulent. He named this active chemical component the "Transforming Principle," which provided the first experimental proof that cells contain a transferable genetic material.
(ii) Contribution of Avery, MacLeod, and McCarty (1933-44): Griffith's work did not reveal the chemical identity of the transforming principle. Avery, MacLeod, and McCarty purified major macromolecules (proteins, RNA, carbohydrates, and DNA) from heat-killed S-strain cells to see which fraction could transform live R cells:
They treated the purified fractions with protein-digesting enzymes (proteases) or RNA-digesting enzymes (RNases) and found that transformation still occurred normally. This proved that neither proteins nor RNA carried the transforming information.
However, when they treated the mixture with a DNA-digesting enzyme (DNase), transformation stopped completely, and no live S-strain bacteria were formed.
This rigorous biochemical experiment proved that DNA is the transforming principle and provided the first definitive proof that DNA is the genetic material of living organisms.

Step 4: Final Answer:
(i) Griffith demonstrated that heat-killed S-strain bacteria can transfer a "transforming principle" to living R-strain bacteria, permanently changing them into virulent S-strain cells.
(ii) Avery, MacLeod, and McCarty discovered that this transforming principle is pure DNA by showing that DNA-digesting enzymes (DNase) completely halt the transformation process.