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(Follow along on page 226 of your textbook.) First Isolation of DNA • In 1869, Friedrich Miescher isolated the first crude preparation of DNA from bandage pus and named it “nuclein.” • Along with most scientists, Miescher believed that proteins were the molecules of heredity. It would be years before the role of nucleic acids were recognized. • However, Miescher laid the groundwork for the molecular discoveries that followed. The year was 1928… Frederick Griffith, an army medical officer, was attempting to develop a vaccine against Streptococcus pneumoniae. Griffith never did develop a vaccine. But his work unexpectedly opened a door to the molecular world of heredity. Griffith’s Bacteria Griffith isolated and cultured two different strains of the bacterium. He noticed that colonies of one strain had a rough surface appearance, but those of the other strain appeared smooth. He designated the strains “S” and “R” and used them in a series of four experiments. Experiment #1 Laboratory mice were injected with living “S” cells. Experiment #1 The mice died. Blood samples taken from them teemed with live “S” cells. (The “S” strain was pathogenic.) Experiment #2 Laboratory mice were injected with living “R” cells. The mice did not develop pneumonia. Experiment #2 Laboratory mice were injected with living “R” cells. The mice did not develop pneumonia. (The “R” cells were harmless.) Experiment #3 “S” cells were killed by exposure to high temperatures. Mice injected with these cells did not die. Experiment #3 “S” cells were killed by exposure to high temperatures. Mice injected with these cells did not die. (The heat-killed “S” cells were harmless.) Experiment #4 Live “R” cells were mixed with heat-killed “S” cells and injected into mice. Experiment #4 The mice died. Blood samples taken from them teemed with live “S” cells. Summary “S” “R” What Happened? Maybe the heat-killed “S” cells in the mixture weren’t really killed. But what if that were true? What should have happened to the mice in Experiment #3? What Else Might Have Happened? Maybe the harmless “R” cells in the mixture mutated into a killer form. But what if that were true? What should have happened to the mice in Experiment #2? The Simplest Explanation: Heat did kill the “S” cells “R” but did not destroy their hereditary material, including the part that specified “how to cause infection.” Somehow, that material had been transferred from dead “S” cells to living “R” cells where it was put to use. “S” The Importance of Griffith’s Work Essentially, what Griffith had done was similar to putting a harmless live kitten and a stuffed toy tiger cub in a box and suddenly finding yourself with a live roaring tiger!!!! The Importance of Griffith’s Work Griffith called the process he had observed “transformation.” He had shown that something had been transferred from the heat-killed diseasecausing bacteria to the live harmless bacteria. Scientists soon began searching for this unknown material. Today, we know this material is: Oswald Avery, 1944 Erwin Chargaff, 1947 • Chargaff’s Rule: The number of adenines approximately equals the number of thymines, and the number of guanines approximately equals the number of cytosines. Alfred Hershey and Martha Chase, 1952 (see Online Activity 11.1) Watson and Crick, 1953 • James Watson and Francis Crick published the first accurate model of the DNA molecule in 1953. • Crick conjectured that the DNA strands must be antiparallel. • Based on Chargaff’s rule, Watson surmised that the bases must be paired in a specific way: adenine with thymine, and cytosine with guanine. Rosalind Franklin • Franklin, an X-ray crystallographer, made the photo that Watson and Crick used in deducing the double-helical structure of DNA. • Franklin died of cancer in 1958, when she was only 38. • Her colleague Maurice Wilkins received the Nobel Prize in 1962 along with Watson and Crick.