The Mesel­son-Stahl Ex­per­i­ment

Pic­tures Con­sid­ered #17

by Elio

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.

For fur­ther elab­o­ra­tion on this ex­per­i­ment, see an ar­ti­cle by T.H. Davis and one by P. C. Hanawalt.