Simulation: Meselson-Stahl experiment

Debate in the 1950s

After the DNA structure model had been proposed, one point was clear: before each cell division, genetic information has to be copied reliably so that both daughter cells receive complete DNA. What remained unclear was how the two strands of the double helix are distributed to the daughter DNA during replication. DNA was known to be the carrier of genetic information, but the copying process could not be observed directly with the methods available at the time.

In the 1950s, researchers therefore studied the structure and function of DNA more closely. Complementary base pairing was especially important: adenine pairs with thymine, guanine pairs with cytosine. This led to the idea that an old DNA strand could serve as a template for a new, complementary strand. However, it was still unclear what happens to the original double helix.

Several possible replication models were discussed. The old double helix might stay together, each daughter DNA might contain one old and one new strand, or old and new DNA sections might be mixed. To clarify this, scientists needed an experiment based on measurable properties such as labeling, density and generation. Enzymes were also important: replication is an enzyme-catalyzed process in which enzymes make and speed up the building of new DNA strands.

Experimental idea (labeling & density)

The bacteria first grow in a medium with heavy nitrogen (¹⁵N). This labels their DNA as “heavy”. They are then transferred to a medium with light nitrogen (¹⁴N) and continue to reproduce there. An isotope such as ¹⁵N or ¹⁴N is a variant of the same element. The atoms are slightly heavier or lighter because they have different numbers of neutrons in the nucleus. In the experiment, the bacteria are centrifuged every 20 minutes. These 20 minutes correspond approximately to one bacterial generation.

Principle of density-gradient centrifugation: During centrifugation, a density gradient forms in a concentrated salt solution. DNA molecules move through it until they reach the position where their buoyant density matches the density of the surrounding solution. Heavily labeled DNA (¹⁵N) has a higher density and forms a band farther down. Light DNA (¹⁴N) forms a band farther up. Hybrid DNA with one heavy and one light part appears in between.