In 1958, Meselson and Stahl investigated the mechanism of DNA replication using E. coli. Bacteria were grown for many generations in a medium containing heavy nitrogen (
15N), ensuring all DNA was fully labelled. They were then transferred to a medium containing light nitrogen (
14N) and allowed to replicate. After each round of replication, DNA was extracted and its density analysed by caesium chloride density gradient centrifugation.