General Genetics/The Discovery of the DNA Molecule
In 1869, the Swiss biochemist Friedrich Miescher collected white blood cells from the pus on the nearby surgical clinic's used bandages. He was the first to separate the nuclei from the rest of the cell, which he accomplished by rinsing the cells many times with dilute (1:1000) hydrochloric acid at extremely cold temperatures. He later improved upon this protocol, using a solution of pepsin (a proteolytic enzyme present in stomach juices) and alcohol to degrade cytoplasmic proteins and lipids. He treated the isolated nuclei with an extremely dilute (1:100,000) sodium carbonate solution followed by hydrochloric or acetic acid to precipitate a novel substance he termed "nuclein." Upon the discovery of another nucleic acid (then termed "yeast nucleic acid") in 1909, nuclein's name was changed to "thymus nucleic acid." Eventually, thymus nucleic acid became known as deoxyribonucleic acid: DNA.
However, the working hypothesis in the scientific community was that proteins were the molecules responsible for the transmission of genetic information. After all, proteins are comprised of 20 different monomers (amino acids), whereas DNA is only comprised of 4 monomers (nucleotides). Therefore, proteins were seen as capable of conveying more complex information than nucleic acids.
In 1952, Alfred Hershey and Martha Chase used radioactive elemental isotopes to label T2 bacteriophages: one group was labelled with radioactive sulfur (35S) and the other with radioactive phosphorus (32P). Because protein (but not DNA) contains sulfur and DNA (but not protein) contains phosphorus, the 35S isotope marked the phages' proteins and the 32P marked only the phages' DNA. After allowing the labelled bacteriophages to infect E. coli cultures, Hershey and Chase found that the radioactive phosphorus was present inside of the bacteria -- but the sulfur was not. This indicated that genetic information in T2 was transmitted by DNA, not protein.
The next year, in 1953, James Watson and Francis Crick published a plausible double-helix configuration for DNA in the journal Nature, This theory relied on X-ray crystallography images of DNA taken by the physical chemist Rosalind Franklin.
Sam Kean (2011) The Disappearing Spoon