The Discovery of DNA

Friedrich Miescher Began working with white blood cells in 1869. White blood cells are a major component of pus in infections. As a result, Miescher collected a lot of pus from bandages at a local hospital. Added a weak alkaline solution to the white blood cells– when he did the cells decomposed and caused the nuclei to move out of the solution. From the nuclei, Miescher isolated a substance known as “nuclein” After chemical analysis, nuclein was later renamed as DNA.

Frederick Griffith In the 1920s he was trying to develop a vaccine for pneumonia. Began to wonder if a strain of bacteria could transform into another strain. He took two strands of pneumococcus bacteria (deadly strain [III-S] and non-deadly strain [II-R]) and injected them into healthy mice. Firstly, he found that when injected with the deadly strain (III-S) the mice died, and when injected with the non-deadly strain (II-R), the mice survived.

Frederick Griffith Secondly, he heated up the deadly strain (III-S) to kill the bacteria and when injected into the mice, they did not die. Lastly, he co-injected the heated deadly strain (III-S) with the non-deadly strain (II-R) and when injected into the mice, they died. He concluded that some “principle” transformed the non-deadly strain (II-R) into a deadly strain (III-S). He called this the “transforming principle”

“Transforming Principle” Rough strain: II-R (non-deadly strain) Smooth strain: III-S (deadly strain) Third Experiment First Experiment Second Experiment

Joachim Hammerling .. In the 1930s, began experimenting with Acetabularia, a form of green algae. Cap He found that when you removed the cap, it grew back, but if you removed the foot, it would not grow back. Stalk This showed that the instructions for making the cap were in the foot (which was where the nucleus was). He concluded that the nucleus contained DNA, and was responsible for development. Foot

Oswald Avery, Maclyn McCarty and Colin McLeod (1944) Was interested in the work that Frederick Griffith did. What was the “principle” that transformed the non-deadly strain (II-R) into a deadly strain (III-S). They discovered that it was DNA, not protein that was responsible for transformation.

Erwin Chargaff In 1949, he began experimenting with DNA. He isolated DNA from different organisms and measured the levels of adenine, guanine, thymine and cytosine. These were his results: DNA Source Adenine Thymine Guanine Cytosine Calf Thymus 1.7 1.6 1.2 1.0 Beef Spleen 1.5 1.3 Yeast 1.8 1.9 Tubercle Bacillus 1.1 2.6 2.4

Chargaff’s Rule Levene’s tetranucleotide theory stated that adenine, guanine, cytosine, and thymine would equal each other. However, Chargaff concluded that the nucleotides must be arranged in a way that adenine and thymine are equal and that cytosine and guanine are equal (A=T/C=G). DNA Source Adenine Thymine Guanine Cytosine Calf Thymus 1.7 1.6 1.2 1.0 Beef Spleen 1.5 1.3 Yeast 1.8 1.9 Tubercle Bacillus 1.1 2.6 2.4

DNA Structure Was Discovered Through the work of Miescher, Griffith, Hammerling, Avery, McCarty, McLeod and Chargaff, the structure of the nucleotide was discovered. The structure of the nucleotide included: pentose sugar attached to a phosphate group at carbon 5 and a nitrogenous base at carbon 1.

Alfred Hershey and Martha Chase Conducted an experiment in 1952 on bacteriophage (viruses that attack and infect bacteria). Using radioactive isotopes, Hershey and Chase traced the movement of DNA and protein during phage infection. They showed that DNA, not protein entered the bacterial cell during phage reproduction and that only DNA was passed on to phage offspring. This concluded that DNA, not protein carries the genetic material of the cell.

Rosalind Franklin Began researching the structure of DNA in the early 1950s. Franklin used X-ray diffraction (a technique used to examine the shape and structure of a molecule) to take a picture of a DNA molecule. The picture showed the double helical structure of DNA. However, the picture shows the DNA molecule from the end, not the side.

James Watson, Francis Crick and Maurice Wilkins (1953) Wilkins passed on the photo that Franklin had taken to Watson and Crick. Using Franklin’s photo and Chargaff’s rule, Watson and Crick were able to explain and prove the double helical structure of DNA. Using Chargaff’s data, they were able to come up with the “complementary base pairing” in DNA where a purine (A/G) always binds with a pyrimidine (T/C).

James Watson, Francis Crick and Maurice Wilkins (1953) They proposed that the helix in DNA turned clockwise and was a right handed helix. They concluded that the helix would make a complete turn every 10 nucleotides, which is a distance of 3.4nm, so the space between nucleotides is 0.34nm. Also they discovered that DNA strands run anti-parallel to each other (one strand runs in a 5’ to 3’ direction and the other strand runs 3’ to 5’.)

James Watson, Francis Crick and Maurice Wilkins (1953) For all their research, Watson, Crick and Wilkins won the Noble Peace Prize in 1962. Rosalind Franklin was never given any credit for her discovery, and died in 1958.