Matthew Meselson and Franklin Stahl performed the following experiment in 1958. They grew E. coli in a medium containing ¹⁵NH₄Cl (¹⁵N is the heavy isotope of nitrogen) as the only nitrogen source for many generations. The result was that ¹⁵N was incorporated into newly synthesised DNA (as well as other nitrogen containing compounds).

This heavy DNA molecule could be .distinguished from the normal DNA by centrifugation in a cesium chloride (CsCl) density gradient ¹⁵N is not a radioactive isotope, and it can be separated from ¹⁴N only based on densities).