1. Discovering DNA By early 20th century
DNA composed of deoxy, P, A, C, T, G,
Proteins thought to be the key to the gen

2. 1931 Griffith Discovers Transformation
Bacteriologist F. Griffith discovers a variation in pneumonia bacteria: 1 • ‘rough’ PM; not coated doesn’t kill mice 2 • smooth variant has a polysaccharide coated PM; (unique protein) kills mice
after prolonged cultivation on artificial medium, some cells lose the ability to form the capsule, and the surface of their colonies is wrinkled and rough ("R"). With the loss of their capsule, the bacteria also lose their virulence. Injection of a single S pneumococcus into a mouse will kill the mouse in 24 hours or so. But an injection of over 100 million (100 x 106) R cells is entirely harmless. The reason? The capsule prevents the pneumococci from being engulfed and destroyed by scavenging cells.
DNA can be taken up by cells in a variety of ways – through plasmids, for example.

3. Genetic Transformation
trial 3
trial 4
Griffith uses heat to kill smooth bacteria
(heat destroys proteins)
mice live
Heat-killed smooth & rough strains of bacteria mixed together…
mice die!
In 1928, Fred Griffith performed the first experiment which suggested that protein was not the genetic material. His experiment was actually fairly simple. He first injected mice with a live strain of virulent (deadly) bacteria, and not to anyone's surprise, all of those mice died. Then, he killed the virulent bacteria cells by heating them. Mice injected with these heat-killed virulent bacteria did not die. In another set of mice, Griffith injected a live non-virulent strain of bacteria, and these mice did not die, the result which Griffith expected.
The surprise came when Griffith injected a group of mice with both live non-virulent bacteria and heat-killed virulent bacteria. In that group, some of the mice died. When Griffith examined those mice, he found live virulent bacteria in their blood. Griffith drew the conclusion that the genetic information in the heat-killed virulent bacteria survived the heating process and was somehow incorporated into the genetic material of the non-virulent strain to cause them to become virulent. But Griffith knew that heat denatures protein, so he suggested that the genetic material must be something else. However, his results did not specifically point to DNA as a possibility.
unexpected!

4. Conclusions
info from smooth bacteria passed into non-virulent bacteria; genetic code is changed; transformation
Bacteria cultures (‘offspring’) successfully kill mice – the change is heritable between generations
info is not likely a protein, since it is expressed despite heating
DNA can be taken up by cells in a variety of ways – through plasmids, or here, fragments, for example.

5. Avery, McCarty, and MacLeod conclude it’s DNA that is transformed
Walk through animation
Used same bacteria strains as Griffith:
heat-killed smooth non-pathogenic rough
1. Mix bacteria strains, plus an enzyme that destroys one macromolecule type +
4. Only destroying DNA prevents transformation of pathogen info;
Code is DNA
no RNA
no carbs
Oswald Avery followed up on Griffith's experiment in the following decade. Like Griffith, Avery first used heat to kill virulent bacteria. He then extracted RNA (ribonucleic acid), DNA, carbohydrates, lipids, and proteins from these dead cells, all of which were considered to be possible candidates for the carriers of genetic information. Next, he added each type of molecule to a culture of live non-virulent bacteria to determine which was responsible for changing them into virulent bacteria as Griffith had observed. Only the non-virulent cells which were given DNA from the dead virulent strain became virulent, so Avery concluded that DNA must be the genetic material.
no lipids
no proteins
no DNA x
3. mouse lives!
2. mouse dies in all cases

6. The Hershey-Chase Experiment : viral DNA (not the protein coat) carries the genetic info
Attached radioactive labels to the DNA & protein coat of a bacteriophage
These viruses invades bacteria, injecting its DNA, & leaving it’s protein coat behind
DNA

7. The Race to Discover DNA Structure
Key discoveries
Linus Pauling
1940s
Discovered the alpha-helical structure of proteins.

8. Key discoveries
Chargaff’s Rule : the amount of adenine always equals the amount of thymine; same with cytosine and guanine

9. Franklin’s x-ray image of DNA (looking down on the molecule) gave Watson & Crick the last piece of the structural puzzle Franklin’s photo published in same issue of Nature
Key discoveries
Wilkins lab
Franklin’s work
1951
Franklins colleague, Wilkins, was also awarded the Nobel, but since Franklin was dead and the Nobel is not awarded post-humously she did not.
Photo 51

10. Watson & Crick Nobel Prize, 1962
25 year old post-doc!

11. Structure deduced DNA is a double-helix A sugar-phosphate backbone
4 nucleotides, in 2 pairs:
Adenine + Thymine
Guanine + Cytosine