The Griffith Experiment
Frederick Griffith (1879-1941) was a British microbiologist, who performed a very clever experiment that began to open up the field of molecular biology. He was able to demonstrate the presence of an inheritable material, that we now know as DNA, that could be transfered between microorganisms and conferred new phenotypes on the recipients. Followup work by Oswald Avery and his co-workers showed that this transforming factor was in fact deoxyribonucleic acid (DNA), and it was the essential but poorly acknowledged contributions of Rosalind Franklin that allowed Watson and Crick to piece together the structure of the DNA molecule. From those beginnings we go to today, where biotechnology has entered every aspect of our lives.
So what was the Griffith experiment all about? Lecture this week is focusing on a series of Gram positive pathogens, the diseases that they cause, and the virulence factors that these pathogens possess. Frederick Griffith was interested in one of these pathogens, Streptococcus pneumoniae, which causes a virulent form of bacterial pneumonia. Please keep in mind that pneumonia is a diagnosis, not a disease, and is caused by a variety of pathogens, including fungi, viruses, and a host of bacteria, and probably some protozoans too.
Now, Griffith noticed that some isolates of S. pneumonia were more virulent than others; that is, specimens isolated from patients with very severe forms of pneumonia caused then caused severe to lethal disease in mice (Koch’s Postulates working here) and isolates from mild cases caused mild disease in mice. He also noticed that after culturing some of these isolates in the lab that they became avirulent, or completely unable to cause disease when introduced into mice. When the virulent and avirulent isolates were examined under the microscope, they appeared identical, except the virulent strains had a capsule and the avirulent strains lacked the capsule.
Griffith then extended these observations. He took the virulent strain (with the capsule) and killed it by exposing it to heat. When the heat-killed virulent bacterium was put into a mouse, no disease occurred. When the live avirulent bacterium was put into a mouse, no disease occurred. When he mixed heat-killed virulent bacteria with live avirulent bacteria, the mice developed pneumonia and succumbed to the disease, and the organisms that were recovered from the mouse (remember Koch’s Fourth Postulate!!!!) all were of the virulent form and were encapsulated, and not of the avirulent form that lacked the capsule.
Griffith concluded from this experiment in 1928 that a “transforming principle” was present and released from the dead virulent bacteria, which was taken up by the avirulent bacteria, caused a change in their phenotype, and allowed them to become virulent. The work was received to mixed reviews for over a decade, but replication and refinement of the experiment gradually was able to purify and characterize Griffith’s “transforming principle” and show that it was DNA. BIO150 (Bio I) students at YCP do a variation of Griffith’s experiement to observe the transformation of E. coli, and acquisition of a novel phenotype.
What should our take home message be from this work? Virulence is a complicated phenomenon, and the relative virulence of a pathogen is ultimately due to the contribution of a number of virulence factors that the pathogen possesses. However, the work of Griffith began to demonstrate that the basis of these virulence factors is based on a DNA sequence, and that this DNA sequence can be transferred between pathogens! Microorganisms are not static and unchanging; they gain and lose characteristics that help or hinder their reproductive success, and because microorganisms reproduce very quickly, we can observe these changes in populations of pathogens as their ability to cause disease changes. Furthermore, unlike humans, bacterial DNA exchange can occur between members of different species, allowing transforming principles encoding virulence factors and antimicrobial resistance to be swapped between disparate species.