In 1869, the Swiss surgeon Friedrich Miescher first extracted from pus a combination of nucleic acid and protein, which was called nuclein, and in 1871 he published the first paper on nucleic acids.
In 1880, the German biochemist Albrecht Kossel isolated five nitrogenous compounds from nucleic acids: adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U). These are the compounds known in modern biology as nucleobase.
In 1889, the German pathologist Richard Altmann obtained from yeast tissue fluid the acidic nucleus without proteins and coined the term nucleic acid which replaced Nuclein.
In 1909, a Russian-American physician and chemist, Phoebus Aaron Theodore Levene, discovered that the sugar contained in nucleic acids consisted of five carbon atoms and named this sugar "ribose". In later years, he discovered that the sugar in yeast nucleic acid lacks an oxygen atom and named this sugar "deoxyribose". He also discovered that nucleic acids could be broken down into fragments containing purine, pyrimidine, ribose or deoxyribose and phosphate and their combination are called nucleotide. Since the quantitative analysis of nucleobase was not precise enough at that time, the tetranucleotide hypothesis was proposed by Levin: nucleic acids contain approximately equal amount of adenine (A), cytosine (C), guanine (G), thymine (T), and the nucleic acids structure is just a simple repetition of them. This made a mismatch between nucleic acid and complex genetic material, so protein became the first choice for the study of genetic material at that time. This false hypothesis was popular for decades and served as a hindrance to scientific research, which someone called a scientific catastrophe.
In 1928 Frederick Griffith discovered that two forms of pneumoniae, S form (with polysaccharide coat) and R form (without polysaccharide coat) could transform each other. He believed that some kind of transforming factor was at work.
In 1944 Oswald Theodore Avery crushed S-type pneumoniae and extracted sugars, lipids, proteins and DNA in order to study the composition of this transforming factor. He found that only R-type pneumoniae cultured with DNA could be transformed into S-type bacteria. If DNA was broken down by DNAase, no transformation occurred. He considered DNA as the genetic material. However, the dominance of the tetranucleotide hypothesis and a little protein made his conclusion doubtful.
In 1952 Alfred Hershey experimented with phage, radioactive elements (³²P and ³⁵S) labeled E. coli to further confirm DNA as genetic material.
In 1950 Erwin Chargaff accurately measured the nucleobase content in DNA. He discovered the law of DNA composition or the Chargaff's rules: the number of purines equals the number of pyrimidines. This means A is paired with T and C is paired with G.
Wilkins and Rosalind Franklin used X-ray crystallography to study the structure of DNA. In 1952, they produced the now-famous "Photo 51," which was a high-quality X-ray diffraction image of DNA. This image provided key information about DNA structure.
Watson and Crick proposed the double helix structure of DNA in 1953. They were awarded the 1962 Nobel Prize with Wilkins.