The Meselson-Stahl experiment was an experiment by Matthew Meselson and Franklin Stahl to prove that DNA replication was semiconservative. Semiconservative replication means that when the double stranded DNA helix was replicated, each of the two double stranded DNA helices consisted of one strand coming from the original helix and one newly synthesized.

Nitrogen is a major constituent of DNA, the genetic material of all cells. It is commonly found in the ¹⁴N isotope, but it can also be found in the heavier ¹⁵N isotope.

E. coli were grown for several generations in a medium with ¹⁵N. The DNA of the resulting cells had a higher density (was heavier). After that, E. coli cells with only ¹⁵N in their DNA were put back into a ¹⁴N medium and were allowed to divide only once. DNA was then extracted from a cell and was compared to DNA from ¹⁴N DNA and ¹⁵N DNA. It was found to have exactly an intermediate density. This supported the idea of semiconservative replication.

The DNA was intermediate in density because it had an all ¹⁵N DNA strand and an all ¹⁴N DNA strand. The all ¹⁵N strand was one of the original strands in the original cell. The all ¹⁴N strand was a newly synthesized strand.

Trivia: Richard Feynman served on the committee during Meselson's PhD thesis defense (the chair was Linus Pauling), although he had not previously read the dissertation [1]. Feynman quotes this experiment as one of his reasons for staying at Caltech. Feynman had just gotten an offer from the East coast and was seriously debating going there when Meselson approached him with the results of this experiment. Feynman thought, "there is no way this can happen anywhere else," so he decided to stay.