Swiss microbial geneticist, Werner Arber shared the 1978 Nobel Prize in Physiology or Medicine with Hamilton Smith and Daniel Nathans for their discovery of restriction endonucleases. Arber was interested in electron microscopy, in which he studied transduction in E. coli bacteriophage lambda. Encountering limitations with electron microscopy as a tool, he began using microbial genetics as a methodology for his studies. Arber found that the virus would not efficiently propagate. Recalling research done seven years earlier by Joe Bertani and Jean Weigle on "host-controlled restriction-modification", he realized there must be a host-controlled modification of the invading DNA, and sought to identify the mechanism. Based on Grete Kallengerger's work that demonstrated degradation of both irradiated and non-irradiated phage lambda following injection in a host, Arber and his graduate student, Daisy Dussoix further investigated the fate of DNA, and found that restriction and modification (later determined to be postreplicative nuclotide methylation) directly affected DNA, but did not cause mutations.
Arber and Daisy Dussoix also found that theses were properties of the bacterial strains, and that both viral and cellular DNA were degraded. Together, Arber and Dussoix reported their findings to scientific community in 1961 at the First International Biophysics Congress in Stockholm. Aber also presented the research to the Science Faculty of University of Geneva in 1962, earning the Plantamour-Prevost prize. Based on his work and the work of others, he hypothesized that an enzyme in the host bacterium cut DNA into smaller pieces at specific sites, and methylase modified the host DNA to protect it from the digestive enzyme. These theories were later confirmed by Urs Kuhnlein, who found that mutation of specific sites rendered the phage resistant to cleavage; Hamilton smith, who identified Type II endonuclease HindII; and Daniel Nathans, who used HindII to break the SV40 virus into 11 fragments, allowing him to determine its method of replication. Since the discovery of restriction endonucleases, researchers have used them as tools to study the functions of genes of all types of organisms.
1953 was a historical year for biology, as it marked the birth of the DNA helix, but also a report by Bertani and Weigle on ‘a barrier to infection’ of bacteriophage λ in its natural host, Escherichia coli K12, that could be lifted by ‘host-controlled variation’ of the virus. This paper lay dormant till Nobel laureate Arber and PhD student Dussoix showed that the λ DNA was rejected and degraded upon infection of different bacterial hosts.
Arber,W. and Dussoix,D. (1962) Host specificity of DNA produced by Escherichia coli. I. Host controlled modification of bacteriophage lambda. J. Mol. Biol., 5, 18-36.
Dussoix,D. and Arber,W. (1962) Host specificity of DNA produced by Escherichia coli. II. Control over acceptance of DNA from infecting phage lambda. J. Mol. Biol., 5, 37-49.