Between 1953 and 1957, before the Meselson-Stahl experiment verified semi-conservative replication of DNA, scientists debated how DNA replicated. In 1953, James Watson and Francis Crick proposed that DNA was composed of two helical strands that wound together in a coil. Their model suggested a replication mechanism, later termed semi-conservative replication, in which parental DNA strands separated and served as templates for the replication of new daughter strands. Many scientists, beginning with Max Delbrück, questioned Watson and Cricks’ model and suggested new theories for DNA replication. By 1957, three theories about DNA replication prevailed: semi-conservative, conservative, and dispersive replication. Then, Matthew Meselson and Franklin Stahl conducted the Meselson-Stahl experiment, which returned results that supported the semi-conservative theory of DNA replication. The collaboration among scientists that ultimately produced concrete evidence of the DNA replication mechanism furthered both theoretical and physical explanations of genetics and molecular biology, providing insight into how life develops, reproduces, and evolves.

Matthew Meselson, Franklin Stahl, and Jerome Vinograd, developed cesium chloride, or CsCl, density gradient centrifugation in the 1950s at the California Institute of Technology, or Caltech, in Pasadena, California. Density gradient centrifugation enables scientists to separate substances based on size, shape, and density. Meselson and Stahl invented a specific type of density gradient centrifugation, called isopycnic centrifugation that used a solution of cesium chloride to separate DNA molecules based on density alone. When Meselson and Stahl developed the technique in the mid-1950s, scientists had no other way to separate macromolecules that were of similar size but varied in density. Meselson and Stahl employed their method to determine how DNA replicates, became known as the Meselson-Stahl experiment. Density gradient centrifugation using cesium salts allowed scientists to isolate DNA and other macromolecules by density alone.

George Herbert Hitchings researched and developed medications that targeted specific parts of DNA replication processes to treat cancers and various illnesses in the US during the twentieth century. By studying DNA analogs, or manmade substances that resemble the structure of naturally occurring DNA components and are capable of inhibiting DNA replication, Hitchings promoted a novel approach to pharmaceutical research and drug development, known as rational drug design. Using that novel approach, Hitchings and his research team created acyclovir, one of the first medications to effectively treat herpes, a condition that can be sexually transmitted but can also be passed from mother to child, causing life-threatening illness in infants. Hitchings also contributed to the development of cancer treatments, immunosuppressant medications, anti-viral medications, and anti-malarial medications. Hitchings’s research on DNA analogs established rational drug design as a method to create new pharmaceutical drugs, some of which treat sexually transmitted illnesses.