The Griffith Experiment: How Frederick Griffith Discovered the Transfer of Genes Between Two Strains of Bacteria

Quick Take

Frederick Griffith was searching for a vaccine against Spanish flu and was using two strains of Streptococcus pneumoniae bacteria. During the process he discovered that gene transfer took place between two different bacterial strains.

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Bacteria Microbiology

Frederick Griffith’s experiment showed that bacteria were capable of transferring their genetic information by a process that he called transformation. Frederick Griffith was an English army doctor and his experiment, which consisted of testing the effects of killed bacteria on live cells, was actually intended to help develop a vaccine against a future outbreak of “Spanish flu,” the pandemic that killed millions of people after world War I.

For his experiment, which was conducted in 1928, Griffith used two of the three strains of Pneumococcus bacteria that had been discovered by the German bacteriologist Fred Neufeld. These bacteria infect and cause pneumonia in mice -

The virulent Type III-S strain - Type III-S has a smooth polysaccharide capsule covering that protects it from attacks from the host’s immune system.
The non-virulent Type II-R strain - Type II-R does not have a polysaccharide capsule covering, has a rough appearance and it can be destroyed by the host’s immune system.

Bacterial Transformation

Here’s what Griffith did and what he observed -

He injected mice with the Type II-R strain and the mice survived.
He injected mice with the Type III-S strain and the mice died.
He heat killed the Type III-S strain and then injected the mice with the dead bacteria and the mice lived.
He injected dead Type III-S strain and live Type II-R strain into the mice and the mice died. He then detected the presence of live Type III-S strain bacteria with live Type II-R strain bacteria in the blood of the dead mice.

This experiment led Griffith to conclude that the dead the Type II-R bacteria had been transformed by the Type III-S bacteria enabling it to develop a polysaccharide cover and take on its virulent properties.

This meant that the bacterial strains did not have fixed and non-interchangeable properties, which was the thinking at the time. They were capable of transformation and this clearly indicated gene transfer. Frederick Griffith was not, however, able to discover how this transformation took place; he knew about chromosomes and about nuclein (DNA and RNA) that Frederick Miescher had detected in 1869, but no one knew for sure if the genetic information was contained in nucleic acids or proteins.

Bacterial Transformation - What Really Happened?

What actually happened in Griffith’s experiment was that, after the Type III-S bacteria was heat killed, its DNA survived and was taken up by the II-R bacteria strain. The Type III-S DNA enabled the II-R bacteria to grow a protective capsule, gain virulent properties and defeat the host’s immune system.

However it was much later, in 1944, that three researchers from the Rockefeller Institute - Maclyn McCarty, Oswald Avery and Colin MacLeod - followed up on Griffith’s research and discovered that gene transfer from the Type III-S bacteria to the Type II-R bacteria was responsible for the transformation process.

Resources -

https://education.llnl.gov/bep/science/10/tLect.html

https://www.newton.dep.anl.gov/askasci/bio99/bio99074.htm

https://io.uwinnipeg.ca/~simmons/DNA/sld003.htm

https://juliantrubin.com/bigten/dnaexperiments.html

https://jem.rupress.org/cgi/reprint/179/2/379.pdf

https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=7968924

https://profiles.nlm.nih.gov/CC/A/A/O/F/ _/ccaaof.pdf

https://profiles.nlm.nih.gov/CC/A/A/A/M/ _/ccaaam.pdf

https://profiles.nlm.nih.gov/CC/

https://202.114.65.51/fzjx/wsw/newindex/wswfzjs/pdf/24avery.pdf

https://www.cuhk.edu.hk/bio/course _homepage/BIO2310/lecture/gen03DNARep%5B1%5D.pdf