On April 25th 1953, the article describing the DNA double helix by James Watson and Francis Crick was published in Nature.
The discovery of DNA
The history of DNA had begun about one century earlier by the Swiss chemist Friedrich Miescher, who, in 1869, discovered a substance within the nuclei of white blood cells, and he called it nuclein.
In 1919, Russian Biochemist, Phoebus Levene discovered that this molecule, renamed nucleic acid, was composed of repeated units that he called nucleotides.
Each nucleotide is made of:
- a nitrogenous base between adenine (A), thymine (T), cytosine (C) or guanine (G)
- a sugar molecule
- a phosphate group (PO43-).
Levene characterised two different forms of nucleic acids: RNA, which has ribose as sugar, and DNA, which has deoxyribose instead.
The race to discover the structure of DNA
Levene’s discoveries paved the way to further research on the structure of DNA. Levene himself suggested a model in which the four bases were always repeated in the same order. With time, it became clear that DNA has a regular tridimensional shape, and many scientists tried to unveil it: in February 1953, Linus Pauling almost got there, suggesting a structure made of three intertwined helices.
On April 25th 1953, three papers about the structure of DNA were published in the same issue of Nature. The paper by Watson and Crick was the most complete among them, and the two scientists had already announced two months earlier, in the Eagle Pub in Cambridge, that they had discovered “the secret of life”.
Rosalind Franklin and Maurice Wilkins, authors of the other two papers, had played important roles in Watson and Crick’s theory elaboration, as I mentioned in another post.
DNA and RNA
DNA is made of two identical strands of nucleotides running in opposite directions (antiparallel) that assemble in a double helix. The way the two strands match is not random, but follows the Watson-Crick base-pairing rules: if on one strand there is an A it will only match with a T on the opposite strand, while a C will only pair with a G. Nevertheless, the order of the bases on a strand (the sequence) is extremely variable, and a huge number of combinations is possible.
On the other hand, RNA is a single helix, and it presents with a different base, uracil (U), in the place of thymidine.
From DNA to proteins: the genetic code
The DNA carries all the instructions to build the cells, in the form of genes, which are sequences of nucleotide. Such information is transferred (transcribed) on an RNA strand called messenger (mRNA) following the Watson-Crick rules, with the difference that a U is inserted every time the DNA strand carries an A. The mRNA travels from the nucleus of the cell to little organelles called ribosomes, that translate these instructions into proteins.
The proteins are sequences of 20 different units called amino acids. The scientists faced the challenge of understanding how a 4-letter alphabet (the 4 bases of the nucleic acids) could be translated into a 20-letter alphabet (the 20 amino acids of the proteins). Once again, the work of many researchers was necessary to unravel the mystery: the studies of Severo Ochoa, Francis Crick, Marshall Niremberg, and Har Gobind Khorana among others, allowed to decipher the genetic code, in which specific blocks of three bases correspond to one specific amino acid.
The mechanism reading and performing the instructions carried in the genes is known as the central dogma of molecular biology.
Beyond DNA: the human genome
With the discovery of the DNA structure, numerous other findings and the advancement of techniques became possible, such as determining the full sequence of human DNA, the human genome. The Human Genome Project (started in 1990 and completed in 2003) had the aim of determining the sequence and function of all the human genes, and their relative position in the DNA, and to build maps to follow the inheritance of genetic traits through generations, with a particular focus on genetic diseases.
This knowledge, combined with modern biotechnology, led to new forms of medicine such as gene therapy and cellular therapy.
Bibliography
Discovery of DNA structure and function: Watson and Crick. Pray, L. Nature Education 1(1):100, 2008 https://www.nature.com/scitable/topicpage/discovery-of-dna-structure-and-function-watson-397/
The structure of yeast nucleic acid: IV. Ammonia hydrolysis. Levene P., J. Biol. Chem. 40: 415-. 1919 https://www.jbc.org/content/40/2/415.full.pdf
A Proposed Structure For The Nucleic Acids. Pauling L. and Corey R., Proc Natl Acad Sci U S A, Feb; 39(2): 84–97,1953. https://doi.org/10.1073/pnas.39.2.84
A structure for deoxyribose nucleic acid. Watson, J. D., & Crick, F. H. C., Nature 171, 737–738, 1953 https://doi.org/10.1038/171737a0
Molecular Structure of Deoxypentose Nucleic Acids., Wilkins M. et al., Nature 171, 738-740, 1953 https://doi.org/10.1038/171738a0
Molecular Configuration in Sodium Thymonucleate, Franklin R. and Gosling R., Nature 171, 740-741, 1953 https://doi.org/10.1038/171740a0
General nature of the genetic code for proteins. Crick, F. H. C., et al., Nature 192, 1227–1232, 1961 https://doi.org/10.1038/1921227a0
RNA codewords and protein synthesis, VII. On the general nature of the RNA code. Niremberg M. et al, Proc Natl Acad Sci U S A. 53(5): 1161–1168, 1965 https://doi.org/10.1073/pnas.53.5.1161
The Human Genome Project: https://www.genome.gov/human-genome-project
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