In 1869, a combination of nucleic acid and protein from pus was extracted by Swiss surgeon Friedrich Miescher. Then, he published a paper on the discovery of this substance and named it “nuclein” in 1871.
Five nitrogenous compounds from nuclein are isolated by German biochemist Albrecht Kossel in 1880: adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U).
Richard Altmann claimed in 1888 that he had obtained a "nuclein" that was completely free of protein. This acidic substance was named nucleic acid that was quickly accepted by scientist to replaced Nuclein.
Phoebus Aaron Theodore Levene was a Russian-American physician and chemist. He found that some saccharides in nucleic acids consisted of five carbon atoms in 1909. This saccharide was named "ribose" by Levene. In later years, deoxyribose that lacks an oxygen atom was found in yeast nucleic acid. Nucleotides are basic units of nucleic acids. They contain purine, pyrimidine, ribose or deoxyribose, and phosphate. Levine proposed the ridiculous tetranucleotide hypothesis according to wrong data, since the quantitative analysis techniques were not advanced and accurate enough at that time. Nucleic acids are made up of four types bases that are simply repeated. The quantity of every type is the same, so proteins are prioritized for genetic material research at that time. This false hypothesis was popular for decades and served as a hindrance to research. Someone denounced it as a scientific catastrophe in the field of DNA.
In 1928 Frederick Griffith identified that two forms of pneumoniae. The non-virulent R-type bacteria that did not have a polysaccharide shell were easily removed by immune system. Polysaccharide shell protected S-type bacteria from phagocytosis, so they cound survive and cause disease in mice or humans. He believed that S-type was transform into R-type with the help of some transforming factor.
In 1944 Oswald Avery crushed S-type pneumoniae and extracted saccharides, lipids, proteins and DNA in order to unveil the secret of transforming factor. Only R-type bacteria cultured with DNA from S-type could become S-type. If DNA was broken down by enzyme, transformation disappeared. He considered DNA as the genetic material. However, the tetranucleotide hypothesis made other researchers reluctant to believe his point. A little protein also made his conclusion doubtful.
In 1950 Erwin Chargaff measured nucleobase content accurately. There is a law of DNA composition or the Chargaff's rules: quantity of purines equals quantity of pyrimidines.
In 1952 Alfred Hershey experimented with phage, radioactive elements (³²P and ³⁵S) labeled E. coli to further confirm DNA as genetic material.