2.2 Applications and skills

2.2.6 Nature of science: Watson, Crick, Meselson, Stahl

The examples on this page illustrate the following points about the nature of science:

  • Models, based on theoretical understanding, are used to explain processes that may not be observable.
  • Improved instrumentation and knowledge in one field can drive discovery in another field.
  • Evidence is used to develop theories, generalise, and form hypotheses that can be tested.

Using models to represent the real world: DNA

  • DNA was isolated for the first time in 1944 but its structure remained unknown for almost ten years.
  • Watson and Crick were two of many scientists involved in the ‘race’ to discover DNA structure.
  • Maurice Wilkins and Rosalind Franklin were two physical chemists who helped Watson and Crick by providing crucial evidence.

Figure 2.2.6a – An X-ray diffraction pattern for a DNA molecule.Figure 2.2.6a – An X-ray diffraction pattern for a DNA molecule.

  • From the X-ray diffraction patterns, the physical chemists were able to deduce the dimensions of DNA molecules. Click on the image to discover what Wilkins and Franklin contributed.
  • Earlier, the chemist Erwin Chargaff isolated bases from DNA and discovered that the amounts of pyrimidine (C,T) and purine (A,G) bases were approximately equal.
  • Watson and Crick used the physical evidence and Chargaff’s ratios to begin to build models of DNA structure.
  • While modelling, they learned that hydrogen bond lengths between complementary bases (A with T, and C with G) were constant. This suggested that there were two strands of nucleic acids bonded together in one molecule of DNA.

Figure 2.2.6b – Watson and Crick used templates of bases to understand bond geometry. (retrieved from sciencemuseum.org.uk)Figure 2.2.6b – Watson and Crick used templates of bases to understand bond geometry. (retrieved from sciencemuseum.org.uk)

  • The final key to their model was turning one of the backbone strands upside down so that the two strands were anti-parallel. It was the only way to make the bond angles and lengths ‘fit’ the known dimensions.
  • In 1953, Watson and Crick published a paper outlining the ‘double helix’ structure we recognise today.

Obtaining evidence for theories: semi-conservative replication

  • At the end of their paper, Watson and Crick hypothesised that DNA replication was semi-conservative, and most scientists intuitively agreed. However, an alternative was also possible – see Figure 2.2.6c.

Figure 2.2.6c – Alternative patterns for DNA replication: semi-conservative and conservativeFigure 2.2.6c – Alternative patterns for DNA replication: semi-conservative and conservative

  • Matthew Meselson and Franklin Stahl provided the first evidence for the semi-conservative nature of DNA replication in 1958. 

Figure 2.2.6d – The Meselson-Stahl experimental designFigure 2.2.6d – The Meselson-Stahl experimental design

  1. E. coli bacteria are cultured in a medium rich in 15N, a heavy isotope of nitrogen. As the colony grows and replication occurs, new DNA incorporates the heavy isotope.
  2. After many generations, the colonies are transferred to a medium containing only 14N, a lighter isotope, and allowed to grow and replicate DNA.
  3. At specific time intervals, bacterial DNA is extracted from the culture, placed in solution with cesium chloride (CsCl), and spun in an ultracentrifuge.
  4. Once removed from the centrifuge, the vials are placed under UV lights in order to observe bands of DNA.

Figure 2.2.6e – Results of the Meselson-Stahl experimentFigure 2.2.6e – Results of the Meselson-Stahl experiment

  • After one generation in 14N medium, all DNA is concentrated at an intermediate depth. This suggests that half of the nucleotides are made of 15N and the other half of 14N.
  • If replication were conservative, we would expect there to be one band at each location indicated by the dotted lines after one generation.

Skill: Analysis of Messelson and Stahl’s results

Figure 2.2.6f – DNA banding patternsFigure 2.2.6f – DNA banding patterns

  1. State the number of generations represented by the data.
  2. Locate on the graph the beginning of each new generation.
  3. Explain the banding pattern at t = 30 minutes.
  4. Calculate the ratio of 15N to 14N in the DNA sample at t = 60 minutes.

Figure 2.2.6g – Double helixFigure 2.2.6g – Double helix
Discovering the structure of DNA took cooperation and competition.

Figure 2.2.6h – Oswald AveryFigure 2.2.6h – Oswald Avery
Owald Avery (1877–1955) was a physician and medical researcher who reported in 1944 that DNA was the molecule of heredity.

Figure 2.2.6i – Linus PaulingFigure 2.2.6i – Linus Pauling
The chemist Linus Pauling (1901–94) used models to help him discover the alpha helix structure of proteins in 1933. He was also working to find the structure of DNA.

Did you know?

Molecular biology, and the reductionist approach, was the most important paradigm in biological research in the 20th century.


The DNA story illustrates the cooperation and collaboration among scientists that exists alongside competition between research groups. To what extent is hoarding results ‘anti-scientific’? What is the relationship between shared and personal knowledge in the natural sciences?

Figure 2.2.6 – Rosalind FranklinFigure 2.2.6j – Rosalind Franklin
Rosalind Franklin (1920–58), a physical chemist, did not receive a Nobel Prize for the discovery of DNA structure, though Watson, Crick and Wilkins did.

Try it!

How do the discoveries of DNA structure, and semi-conservative replication illustrate themes in the nature of science?