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In this article we will discuss about the history of bacteriophages.
In 1896, for the first time, Ernest Hankin (a British bacteriologist) reported for the presence of antibacterial activity (against Vibrio cholerae) in the waters of the Ganges and Yamuna rivers in India. He suggested that an unidentified substance (which passed through fine porcelain filters and was heat labile) was responsible for this phenomenon and for checking the spread of cholera epidemics.
In 1898, Gamaleya (a Russian bacteriologist) observed a similar phenomenon while working with Bacillus subtilis. In the mean time, several other investigators also reported such phenomenon. In 1915, Frederick William Twort (a medical bacteriologist of England) reported a similar phenomenon and advanced the hypothesis that it may have been due to the presence of a virus.
In 1910, Felix d’Herelle (a French-Canadian microbiologist at the Pasteur, Institute Paris) first observed the bacteriophage phenomenon while studying microbiologic means of controlling an epizootic of locusts in Mexico. In 1915, there was an outbreak of severe hemorrhagic dysentery among French troops stationed in Paris. Several soldiers were hospitalized and d’Herelle was assigned to conduct an investigation of the outbreak.
D’Herelle conducted experiments and observed the appearance of small and clear areas on agar cultures to which he initially called taches and later the plaques. In 1917, d’Herelle’s findings were presented during the meeting of the Academy of Sciences.
He had little doubt about the nature of the phenomenon. He proposed that it was caused by a virus which was capable of parasitizing bacteria. D’Herelle also proposed the name ‘bacteriophage’ (Greek, Backerion means bacteria and Phagein means to eat).
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D’Herelle was made aware of the prior discovery of Twort but maintained that the phenomenon described by Twort was distinct from his discovery. Many scientists accepted the independent discovery of bacteriophages made by Twort and d’Herelle and referred to it as the ‘Twort-d’Herelle phenomenon’, and later the ‘bacteriophage phenomenon’.
Frederick Twort:
P.M. Twort (1877-1950) was an English bacteriologist who discovered the bacteriophages. During the early of 20th century leprosy bacillus was found un-culturable. Twort incorporated the dead tubercle bacilli in the growth medium and succeeded in culturing leprosy bacillus. The essential substance supplied by the tubercle bacillus that was missing from the media turned out to be vitamin K.
In 1914, Twort identified the ‘essential substance’ that would allow vaccinia virus to grow in vitro. Smallpox vaccines made for the skin of calves were always contaminated with Staphylococcus. Twort speculated that the contaminating bacteria might be the source of the ‘essential substance’ needed by vaccinia to survive.
He plated some of the smallpox vaccines on nutrient agar slants and obtained large bacterial colonies. He found minute glassy areas not growing after sub-culturing due to the destruction of the bacterial cells. He picked up some of these areas and transmitted smallpox from one Staphylococcus colony to another.
He found that the agent could pass through porcelain filters and required bacteria for growth. Twort had discovered most of the essential features of bacteriophages. He published these results in the Lancet in 1915 and called the contagion as the bacteriolytic agent. Unfortunately, his discovery was ignored. Felix d’Herelle discovered phage independently, and Twort’s work may have been lost to time, but for Jules Bordet and Andre Gratia rediscovered it.
One prominent scientist in the field was Salvador E. Luria (1912-1991), an Italian-American biologist especially interested in how X-rays cause mutations in bacteriophages. Luria was also the first scientist to get clear images of a bacteriophage using an electron microscope. Luria emigrated from Italy to the United States and met Max Delbrack (1906-1981), a German-American molecular biologist.
In the 1940s, Delbruck worked out the lytic mechanism by which some bacteriophages replicate. Luria, Delbruck and their group studied the genetic changes that occur when viruses infect bacteria. Until 1952, it was unknown which part of the virus, the protein or the DNA, carried the information for viral replication.
The scientists performed a series of experiments using bacteriophages. These experiments proved DNA to be the molecule that transmits the genetic information. For their discoveries concerning the structure and replication of viruses, Luria, Delbruck and Hershey shared the Nobel Prize for physiology or medicine in 1969.
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In 1952, two American biologists, Norton Zinder and Joshua Lederberg at the University of Wisconsin, discovered that a phage can incorporate its genes into the bacterial chromosome. The phage genes are then transmitted from one generation to the other. In 1980, the English biochemist, Frederick Sanger, was awarded a Nobel Prize for determining the nucleotide sequence in DNA using bacteriophages.
