-
While studying white blood cells in pus from surgical bandages, Miescher isolated a new substance in cell nuclei. He observed that it had acidic properties and named it nuclein, although its function was unknown. This was the first discovery of DNA as a molecule. -
He identified the building blocks of DNA as the four nitrogenous bases: adenine (A), thymine (T), cytosine (C), and guanine (G).
The sugar deoxyribose.
The phosphate group.
He defined the nucleotide as being made up of sugar + phosphate + base.
He proposed the tetranucleotide model, according to which DNA was formed by a simple repetition of the four bases.
Because of this theory, it was thought for decades that DNA was too simple to carry genetic information. -
Studying pneumococci, he could transform a non-virulent strain into a virulent one.
His experiment used:
Strain S, with a capsule, virulent.
Strain R, without a capsule, non-virulent.
When he mixed the live R strain with the heat-inactivated S strain, the mice he was experimenting with died.
He concluded that there was a transforming substance that transmitted the characteristics of one bacterium to another, but he did not identify which molecule was responsible. -
They isolated different components from the dead bacteria, such as proteins, RNA, and DNA. They used specific enzymes:
Protease: eliminated proteins.
RNAse: eliminated RNA.
DNase: eliminated DNA. They discovered that the transformation only stopped when they destroyed the DNA.
Conclusion that DNA, not proteins, was the hereditary material. In 1944, they published Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types. -
Using chromatography and spectroscopy, Chargaff analysed the DNA composition of several species and discovered that the base ratios were not equal, as previously thought. He formulated Chargaff's Rules:
Adenine = Thymine (A = T).
Cytosine = Guanine (C = G). This revealed that DNA was not repetitive and simple, but rather contained a specific pattern in its bases. -
James Watson and Francis Crick published an early model of DNA, in which they proposed a double helix with the bases facing outward and the sugar-phosphate in the centre. However, this model was quickly shown to make no chemical sense. -
Rosalind Franklin, using X-ray diffraction techniques, obtained the clearest image of the structure of DNA.
She took her famous photograph in '51, which showed the pattern of a DNA helix. But her data was shared without her consent by Maurice Wilkins with James Watson and Francis Crick. -
Alfred Hershey and Martha Chase worked with bacteriophages, a virus that infects bacteria. They labelled DNA with phosphorus-32 (³²P) and proteins with sulfur-35 (³⁵S). After infecting bacteria, they observed that only DNA entered the cell and was responsible for generating new viruses.
The conclusion of the experiment was that DNA is the universal genetic material. -
They proposed that DNA has three spiral strands with phosphates in the center.
However, this model soon proved to be incorrect because it would cause electrical instability in the molecule. -
With indirect help from data from Rosalind Franklin and Maurice Wilkins, they constructed the correct model of DNA. And on April 25, 1953, they published their article in Nature along with two others, one by Franklin and one by Wilkins. The final structure of DNA is:
Double helix.
External sugar-phosphate backbone.
Nitrogenous bases inside, linked by hydrogen bonds (A with T, C with G). This discovery marked the beginning of modern molecular biology.