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Frederick Miescher was the first scientist to isolate nucleic acids. While studying white blood cells from puss found in infections, he isolated a new molecule called nuclein, a protein associated with DNA. He spent his entire life researching these nucleic isolations and this specific protein found in a cell’s nucleus. Although he believed that proteins were the molecules of genetic information, his findings were the basis for coming molecular research.

Source: http://www.dnaftb.org/15/bio.html

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Frederick Griffith was a bacteriologist who conducted an experiment that helped discover and gave insight into the role of DNA as a genetic carrier. To find this, he led an experiment on two variants of the same bacterium. One of the strains was virulent (lethal) to mice the other was nonvirulent (harmless). He observed that mice exposed to either the heat-killed virulent bacteria or living nonvirulent bacteria remained free of infection. When exposed to both, it was proven to be fatal. The virulent strain somehow converted the non-virulent strain into an agent of disease. Known as bacterial transformation, an alive bacteria can pick up the genetic information from its surroundings, in this case, from the heat-killed virulent bacteria. A chemical “transforming principle” turned the bacteria’s phenotype from non-disease-causing to pathogenic. Something was passing down heritable information and had potential to go now generations of bacteria. This experiment inspired further research and led to the discovery of DNA.

Source: https://www.britannica.com/biography/Frederick-Griffith

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Oswald Avery is credited for proving that DNA is the substance responsible for heredity and the passing of genetic information. Avery conducted further research on the chemical nature of the substance that transformed the bacteria in Griffth’s experiment. With the help of colleagues, he reported that the genetic material carrier of the cell was DNA (deoxyribonucleic acid). His work was the basis for molecular genetics yet was highly regarded with skepticism.

Source: https://www.britannica.com/biography/Oswald-Avery

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Erwin Chargaff is a biochemist that researched DNA and nucleotide base pairing. He studied nucleic acids using chromatographic techniques, including DNA. The tetranucleotide hypothesis by Phoebus Levene was widely accepted at the time and predicted that adenine, thymine guanine, and cytosine were all of the equal measures in DNA. Therefore, genetic variation couldn’t have come from DNA, leading many to believe genetic information is in proteins. Chargaff discovered that the amounts of adenine were proportional to thymine and cytosine to guanine. These nucleotides complemented each other and varied in measures. Which explains the storage of genetic information and the genetic diversity DNA allows. Nucleotide base pairing was one of Chargaff's rules, the second, was that the composition of DNA varies from species to species, therefore the relative amounts of A, G, T, and C bases also varies. These findings helped lead to the discovery of the double helix structure of DNA.

Source: https://www.bionity.com/en/encyclopedia/Erwin_Chargaff.html

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Maurice Wilkins gave Rosalind Franklin the idea to use X-ray diffraction to produce the images which revealed the structure of DNA. Before Franklin came, Wilkins was isolating strands of DNA and gathering information about nucleic acids. Wilkins was the one who leaked Franklin’s unpublished findings on DNA’s double helix structure to James Watson and Francis Crick. Wilkins’s most notable contribution to DNA was his X-ray photographs that showed the crystalline symmetry in DNA. Unfortunately, Wilkins’s work was used as only supplementary evidence to prove that Watson and Crick’s work was correct.

Source:

https://www.yourgenome.org/stories/giants-in-genomics-maurice-wilkins

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Martha Chase and Alfred Hershey -  1952 

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Martha Chase and Alfred Hershey -  1952 

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Chase and Hershey conducted a series of experiments that verified genes were made of DNA. This well-known experiment resolved the debate on the composition of genes which were commonly known to have been proteins. Hershey and Chase analyzed how bacteriophages (viruses that infect bacteria) infected the host bacterium, by attaching themselves to the outside and releasing a replicating piece of phage inside. This experiment determines whether the replicating pieces were made from DNA. Since bacteriophages are made from both proteins and DNA, radioactive isotope labeling (DNA contains phosphorus, proteins contain sulfur) allows them to distinguish between DNA and proteins. Their final experiment, the Waring Blender experiment, showed that despite a protective protein coat being formed around the bacteriophage, only internal DNA was injected into the bacterium that infected it and allowed replication. Meaning, that genes were not composed of proteins, but rather DNA. These findings were concrete evidence and more widely accepted by scientists.

Source: https://embryo.asu.edu/pages/hershey-chase-experiments-1952-alfred-hershey-and-martha-chase

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Rosalind Franklin studied X-ray diffraction (also known as X-ray crystallography) and applied the method to study DNA. Using X- ray diffraction, Franklin took extremely clear pictures of DNA. She exposed the DNA to different humidities, such as wet and dry. The DNA appeared thicker in the dry atmosphere, and the X-ray pattern scattered and had many distinct points. The DNA appeared more stretched in a clear X-shape when exposed to a wetter atmosphere. The dry form of DNA is known as “A-DNA” and holds less water, while the wetter form of DNA is known as “B-DNA,” and water molecules cling to B-DNA. Since phosphates attract water, Franklin concluded that there must be phosphates on the outside of DNA. Her famous image of DNA is known as photo 51. Using photo 51, the double helical structure of DNA was uncovered. Franklin’s findings would be later stolen and used by James Watson and Francis Crick.

Source:

https://undsci.berkeley.edu/the-structure-of-dna-cooperation-and-competition/franklin-joins-the-fray/

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Linus Pauling incorrectly proposed that DNA has three nucleotides coming from three different chains, theorizing that DNA has triple helix structure. He thought that DNA has nitrogenous bases on the outside and phosphates on the inside. He said that the phosphate group of one strand would attach to a sugar of the same strand, and a phosphate group from the neighboring strand using hydrogen bonds. Pauling further justified his theory by stating how molecules can attach to DNA easily if the nitrogenous bases face the outside. Sodium ions stick to phosphates, but in Pauling’s triple helix structure there was no room for sodium ions. In addition, Pauling’s model had too many hydrogen bonds, and the phosphates were packed too tightly. However, Pauling correctly stated that DNA is made of a smaller unit called nucleotides. He wrote that nucleotides are made of a phosphate group, a sugar, and purine and pyrimidine bases.

Source:

https://embryo.asu.edu/pages/proposed-structure-nucleic-acids-1953-linus-pauling-and-robert-brainard-corey

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James Watson and Francis Crick used Rosalind Franklin’s leaked image (photo 51) of DNA to determine the structure of DNA. Watson and Crick relied on data from other scientists such as Alexander Todd and Erwin Chargaff to make their model of DNA. Their first few models were flawed, consisting of three polynucleotide strands, adenine pairing with adenine, etc. They realized that adenine should pair with thymine, and guanine with cytosine. This way, the bases were held together by hydrogen bonds and fit between the sugar-phosphate backbone. Watson and Crick’s idea of complementary base pairing led to the discovery of DNA replication. Crick stated that the sequence of bases in DNA is a genetic code in which information can be passed down. Without Rosalind Franklin’s photo 51, Watson and Crick would not have been able to confirm the sugar and phosphate groups facing the outside of DNA, leading to the double helical structure.

Source:

https://profiles.nlm.nih.gov/spotlight/sc/feature/doublehelix