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Friedrich Miescher
Miescher began working with white blood cells coming from the pus of infections collected on bandages.
Using a salt solution and an alkaline solution, cell nuclei precipitated. -
Nuclein
Miescher, in his laboratory, isolated a substance named nuclein from cells nuclei. This was rich in phosphorus so he thought it was just a simple storehouse. -
Proteins
In the early 1900s, was discovered that nuclein was made of proteins and nucleic acids. Proteins are chains made of 20 different subunits called amino acids, which can be mixed in different ways; we can make millions of different combinations. -
Phoebus Levene
Levene believed proteins were the molecules of heredity, because they came in many different shapes and sizes.
He then started working on one specific nucleic acid, DNA. -
DNA structure
From Levene's studies, DNA has four different units called nucleotides, each one made of a phosphate group, deoxyribonucleic sugar and a nitrogenous base. There are four different nitrogenous bases: Adenine, Thymine, Cytosine and Guanine. These four nucleotides are linked by a phosphodiester bond between C3 and C5. With the Tetranucleotide Theory, he believed DNA was a polymer made of the same four nucleotides. -
Levene's idea
Because of the just 4 subunits of nucleotides, proteins were the better choice to be the nuclear heredity material, because they have an alphabet of 20 amino acids. -
Erwin Chargaff
Chargaff didn’t agree with Levene’s theory. Thanks to a specific experiment, using paper chromatography, he has been able to separate DNA molecule in the different nitrogenous bases and to determine the quantity of each one. The quantity of adenine and thymine was very close, and so did cytosine and guanine. -
Linus Pauling
Using X-ray crystallography he found the alpha-helix structure of proteins. It’s a technique used to find information about the structure and the shape of a crystallized molecule. If a stream of X-rays is direct at a crystallized substance, some rays are diffracted as they encounter the atoms. The scattered rays then interfere with each other and produce spots of different intensities. -
Rosalind Franklin and Maurice Wilkins
They made the two DNA X-ray diffraction patterns and worked on the famous Photo 51, one of the two diffraction patterns. -
New discoveries
Using the DNA “signature”, Franklin and Wilkins found out some new important information: the diameter of the helix, the height of one helical turn (34 Armstrong), the fact that there are 10 nucleotides per helical turn (3.4 Armstrong between stacked base pairs).
At the same time, Watson and Crick found out the double helix structure of DNA, with the phosphate groups on the outside and the bases on the inside. -
James Watson and Francis Crick
Gathering all the information from Franklin and Wilkins' discoveries, Watson started studying the weak hydrogen bonds between bases. He realized that adenine could pair with thymine with 2 hydrogen bonds and cytosine with guanine with 3; this complementary base pairing had the same length. Francis, instead, speculated that the two helices are antiparallel to one another, because of certain bond angles and the proximity of the base pairs. -
Tridimensional structure
Pauling thought that DNA had a triple helix structure, with the phosphate groups on the inside and the bases on the outside. It was obviously wrong: because of the negative charges, the structure couldn’t hold together, because they would’ve repelled one another. -
DNA model
Finally, James and Francis, built up a tridimensional model of DNA 6ft tall, with the complementary base pairing theory and the idea of antiparallel strands. Even Franklin and Wilkins agreed with their model. -
Nature
Watson and Crick wrote a 900-word paper in which explained the results of their studies. “It hasn’t escaped our notice that the specific pairing immediately suggests a possible copying mechanism for the genetic material”. -
Polymerase Chain Reaction (PCR)
Gene cloning, sequencing of complex genomes, DNA fingerprinting and DNA-based diagnostics are just some of the techniques that were either inefficient or plain impossible before PCR. Kary Mullis is generally credited with inventing PCR. Though the idea came in 1983, while he was driving, the process was ended in 1985. [https://bitesizebio.com/13505/the-invention-of-pcr/] -
Period: to
Human Genome Project: the world's largest collaborative biological project
The HGP was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying and mapping all of the genes of the human genome from both a physical and a functional standpoint. Planning started after the idea was picked up in 1984 by the US government, the project formally launched in 1990, and was declared complete on April 14, 2003.
[https://www.genome.gov/human-genome-project/Timeline-of-Events]
