In 1953, using x-ray diffraction data collected by Rosalind Franklin, James D. Watsonand Francis Crick proposed the double helix structure of deoxyribonucleic acid (DNA). Their paper, “Molecular Structure of Nucleic Acids: A Structure of Deoxyribonucleic Acid”, proposed a simple and elegant solution to the then unknown chemical structure of DNA. It also provided an insight into how genetic instructions are stored inside organisms and passed from one generation to the next. This discovery was the end of a story that began a century earlier with an unknown 25-year-old Swiss physician, named Johannes Friedrich Miescher.
In 1868, working at the University of Tübingen, Miescher performed experiments on the chemical composition of leukocytes, using puss from discarded surgical bandages. He discovered a new type of cellular material that was not a protein and contained large amounts of phosphorous. Since he had isolated it from the cell nuclei, he named it nuclein (now nucleic acids). He discovered that this substance was not only found in puss cells, but in cells from yeasts, liver and kidney, and then went on to prove that nucleic acids were a characteristic component of all cell nuclei.
A German professor of physiology named Albrecht Kossel was one of the first to discover that nucleic acids contained both protein and non-protein parts. He was further able to show that the nucleic acids, when broken down, produced carbohydrates as well as nitrogen-bearing compounds: two bicyclic purines, guanine (G) and adenine (A); and the monocylic pyrimidines, thymine (T), cytosine (C) and uracil (U). He then went on to show that nucleic acids exists in two forms, and that thymus nucleic acid contained the four nitrogen compounds adenine; cytosine; guanine and thymine, whereas yeast nucleic acids differed, containing uracil instead of thymine. He was awarded the Nobel Prize in 1910 for his work on cells and proteins. The picture below shows guanine, adenine, thymine and cytosine respectively. Uracil differs from thymine only by the absence of a methyl group.
A Russian-American biochemist called Phoebus Levene, who was appointed as head of the biochemical research at the Rockefeller Institute of Medical Research, spent most of his career trying to identify the components of DNA. In 1909 he found that the carbohydrate present in yeast nucleic acids is the pentose sugar ribose, but it was not until 1929 that he successfully identified the carbohydrate in thymus nucleic acids. It was also a pentose sugar, but lacks one oxygen atom of ribose at the 5’ position, and was therefore called deoxyribose. All this information enabled Leven to suggest the correct structure of the sugars and their linkages in 1935.
As well as working on the structure of DNA, scientists were also trying to discover its function and trying to find where genetic information is stored. Frederick Griffithdiscovered in 1928 that the bacteria Streptococcus pneumonia could mysteriously transform form one harmless strain into a different deadly strain (Griffith’s experiment). What Frederick was observing was DNA from the deadly strain being taken up by the harmless strain. This DNA contained the genes for forming a protective polysaccharide capsule, protecting the bacteria from a host’s immune system by turning the bacteria into the deadly strain and killing the host. It was not known at the time that DNA was responsible for this transformation and it was thought that genetic information was contained in cell protein. This was until a team lead by Oswald Avery, who were continuing Frederick’s work, proved that it was in fact DNA that was the carrier of genes in 1944.