It may come as a surprise that less than a century ago, even the most educated members of the scientific community were unaware that DNA was a hereditary material. Frederick Griffith conducted a series of experiments with Streptococcus pneumonia bacteria and mice in 1928 and concluded that the R-strain bacteria must have picked up a "transforming principle" from the heat-killed S bacteria, allowing them to "transform" into smooth-coated bacteria and become virulent.
In this article, we'll look at one of the classic experiments that led to the discovery of DNA as a genetic information carrier.
The "Griffith's Experiment," carried out by English bacteriologist Frederick Griffith in 1928, described the transformation of a non-pathogenic pneumococcal bacteria into a virulent strain.
Griffith combined living non-virulent bacteria with a heat-inactivated virulent form in this experiment.
He was the first to discover the "transforming principle," which led to the discovery of DNA as a carrier of genetic information.
He suggested that bacteria can transfer genetic information via a process known as transformation.
Griffith's goal was not to identify the genetic material but to create a vaccine against pneumonia. In his experiments, Griffith used two related strains of bacteria known as R and S.
Griffith's work was expanded by Avery, MacLeod, and McCarty.
Streptococcus pneumonia comes in several types or strains. Griffith chose two different strains for his experiment.
One strain of bacteria has smooth surfaces and is known as the smooth strain (S strain), while the other has rough surfaces and is known as the rough strain (R strain).
Bacteria of the S strain have smooth surfaces because they produce a polysaccharide protective coating that forms the outermost layer.
Apart from the morphological differences, Griffith discovered another significant difference between the S and R strains of bacteria, i.e., the S strain is the "virulent" strain capable of causing death in mice, whereas the R strain is the "nonvirulent" strain that will not cause death in mice.
Griffith observed that when he injected these bacteria into mice, the mice infected with the virulent S strain died from pneumonia, whereas the mice infected with the nonvirulent R strain survived.
R Strain and S Strain of Streptococcus Pneumonia
Griffith was researching the possibility of developing a pneumonia vaccine.
He used two strains of pneumococcus (Streptococcus pneumonia) bacteria that infect mice – a virulent (causing disease) S (smooth) strain and a non-virulent type R (rough) strain.
The S strain produced a polysaccharide capsule that protected itself from the host's immune system, resulting in the host's death, whereas the R strain lacked that protective capsule and was defeated by the host's immune system.
Griffith attempted to inject mice with heat-killed S bacteria as a part of his research (i.e., S bacteria that had been heated to high temperatures, causing the cells to die). The heat-killed S bacteria, but unsurprisingly, did not cause disease in the mouse.
When harmless R bacteria were combined with harmless heat-killed S bacteria and injected into a mouse, the experiments took an unexpected turn.
Not only did the mouse develop pneumonia and die, but Griffith discovered living S bacteria in a blood sample taken from the dead mouse.
He concluded that some factor or biomolecule from the heat-killed S bacteria had entered the living R bacteria, allowing them to synthesise a polysaccharide coating and become virulent. As a result, this factor "transformed" the R bacteria into S bacteria.
Griffith called this factor the "transforming principle," concluding that it carried some genetic material from the S bacteria to the R bacteria.
This process is now known as bacterial transformation and is used in a variety of significant genetic engineering applications.
Griffith Experiment Diagram
One of the characteristics of hereditary material is a changing phenotype. Griffith referred to the phenotypic-changing factor as the transforming principle.
His work on the transforming principle received the most attention, but only after a group of Canadian and American scientists set out to investigate the chemical nature of the transforming principle in Oswald Avery's laboratory.
Avery's group concluded in their studies that deoxyribonucleic acid was the molecule identified by Griffith as the transforming principle after conducting numerous experiments.
The implications of this discovery are farfetched because it was made at a time when scientists considered protein molecules to be genetic material.
DNA, or deoxyribonucleic acid, is now recognised as the molecule that encodes all cell functions and transmits genetic information from parent to offspring in almost every living species.
In the 1940s, however, DNA was thought to be a less qualified candidate for genetic material. Avery and colleagues' research on Griffith's experiment provided the first solid evidence that DNA could be the genetic material.
Griffith's ultimate goal was to find a way to cure pneumonia. Griffith inoculated mice with various strains of pneumococci to see if they would infect and eventually kill the mice. Griffith concluded that heat-killed virulent bacteria transformed living, non-virulent bacteria into virulent bacteria. He performed his experiment on the two strains of Streptococcus pneumonia, which differ from each other due to the presence of a polysaccharide coat.
Griffith's findings were published in the Journal of Hygiene. In 1928, his experiments with mice led to his major discovery of bacterial transformation. Griffith's experiment discovered that bacteria can transfer genetic information through transformation.
1. Explain the Oswald Avery Experiment.
Avery and his colleagues conducted additional research on the virulent S strain of Streptococcus pneumonia. They were aware that the potential carriers of genetic material were proteins, RNA, or DNA. When the mixtures were treated with protein-digesting or RNA-digesting enzymes, the DNA remained intact and was capable of transforming R bacteria into S bacteria. However, when the DNA in these mixtures was broken down with DNase, the genetic material could not be passed from the heat-killed S bacteria to the live R bacteria, preventing transformation. As a result, Avery and his colleagues concluded that the transforming principle described by Griffith had to be DNA.
2. What are the characteristics of genetic material?
Any substance that forms the genetic material must fulfil some essential requirements:
It must be stable.
It should be able to carry and transcribe information which is required to control the processes.
It should be able to replicate itself and remain unchanged while passing down from one generation to another.
It must be able to mutate itself to provide variations.
A genetic material must be able to store the information, transmit it, replicate it and provide variation.
DNA fulfils all the above-mentioned requirements and hence acts as genetic material.
3. Define Horizontal Gene Transfer.
Horizontal gene transfer (HGT) is the exchange of genetic information between organisms, which includes the spread of antibiotic resistance genes among bacteria (except those passed down from parent to offspring), thereby, fueling pathogen evolution.
Bacterial horizontal gene transfer occurs via three mechanisms: transformation, transduction, and conjugation. Conjugation is the primary mechanism for the spread of antibiotic resistance in bacteria, and it is critical in the evolution of the bacteria that degrade novel compounds such as pesticides created by humans, as well as in the evolution, maintenance, and transmission of virulence.