The phenomenon was first reported in 1954 by Hazel D. Barner and Seymour S. Cohen in
Escherichia coli when thymine-requiring mutants of the bacteria lost viability when grown in a medium lacking
thymine but containing other essential nutrients. Subsequently, this discovery led to the development of theories to explain the mechanism of action of several
pyrimidine analogs that targeted thymine metabolism in bacteria and tumor cells. The phenomenon was commonly attributed to "unbalanced growth" wherein cells continued fundamental processes of
RNA transcription,
protein synthesis and
metabolism in the absence of DNA replication. However, nutrient starvation does not generally kill cells to the extent observed in cells that lack thymine. The molecular mechanism of thymineless death remains unknown; Possible pathways involved with the killing mechanism include: replication initiation, breakage of ongoing replication forks, and an addiction module. == References ==