Described as the “Most Beautiful Experiment In Biology” (J. Cairns) the demonstration by Meselson and Stahl that DNA replicates semiconservatively is one of the major landmarks in the genesis of modern biology. And indeed it is most pleasing, both visually and cerebrally.
By semiconservative is meant that each strand of a DNA molecule retains its integrity during replication, an old “Watson strand” pairing with a newly made “Crick strand” and conversely. Simple as this may sound, the experiment required the development of a method that would allow to separate “new” from “old” strands. What M&S did was to label the DNA with N15 by growing cultures in the presence N15 ammonium chloride and then transferring them to a medium with N14. This way, they labeled the “old” strands with N15, the “new” ones with N14. They now subjected the DNA to cesium chloride gradient centrifugation.
This was a novel procedure whereby the relatively heavy cesium chloride “spins out” towards the bottom of the centrifuge cell. In time, this results in a spontaneously made density gradient where molecules would find the layer corresponding to their own density and accumulate at that position as a band. New and old strands, as well as intermediate ones, could now be visualized. The result proved that DNA replication was indeed semiconservative. And indeed, they did it with astounding simplicity and elegance.