“ IF THE ULTIMATE AIM OF SCIENCE IS TO CLARIFY MANKIND’S RELATIONSHIP TO THE UNIVERSE , THEN BIOLOGY MUST BE GIVEN A

1. “ IF THE ULTIMATE AIM OF SCIENCE IS TO CLARIFY MANKIND’S RELATIONSHIP TO THE UNIVERSE , THEN BIOLOGY MUST BE GIVEN A CENTRAL POSITION” Jacques Manod ,Nobel prize (allosteric transitions)

2. Scientific discovery inmolecular biology

3. MOLECULAR BIOLOGY MOLECULAR BIOLOGY BIOCHEMISTRY CELL BIOLOGY GENETICS

5. 1600s1800s 1850s 1900s 1950s 2000s 1632-1723 • Antony van Leeuwenhoek – shopkeeper, Dutch

6. 1600s1800s 1850s 1900s 1950s 2000s 1635-1703 • RobertHooke – physicist, London • Micrographia, published in 1665 . . . I could exceedingly plainly perceive it to be all perforated and porous, much like a Honey-comb, but that the pores of it were not regular. . . . these pores, or cells, . . . were indeed the first microscopical pores I ever saw, and perhaps, that were ever seen, for I had not met with any Writer or Person, that had made any mention of them before this. . .

7. 1600s 1800s 1850s 1900s 1950s 2000s 1800-1882 • Friedrich Wöhler - German chemist • synthesized a natural product - urea (1828) • Bridge between living/non-living

8. Urea Cycle • Urea - nitrogenous waste of mammals. • Comes from the breakdown of amino acids • Ammonia - extremely toxic base and its accumulation in the body would quickly be fatal. • The liver contains a system of carrier molecules and enzymes which converts the ammonia (and carbon dioxide) into urea.

9. Urea • Industrial use - the manufacture of plastics (specifically, urea-formaldehyde resin), a component of many fertilizers, providing a nitrogen source that is necessary for plants. • Laboratory use - a powerful protein denaturant. • Medical significance - high levels of urea in the blood indicate a problem with the removal, or more rarely with the over-production, of urea in the body.

11. 1600s1800s 1850s 1900s 1950s 2000s 1773 – 1858 • Robert Brown-Scottish botanist • Found nucleus (1825) • Brownian Movement

12. 1600s1800s 1850s 1900s 1950s 2000s 1804-1881 • Matthias Schleiden -German botanist 1810-1882 • Theodor Schwann - German cytologist , physiologist • Developed the cell theory in 1839, which identified cells as the fundamental particles of plants and animals

13. 1600s1800s1850s 1900s 1950s 2000s 1821-1902 • Rudolf Virchow - German pathologist "Omnis cellula e cellula" (where a cell arises, there a cell must previously have existed). (1858)

14. 1600s1800s1850s 1900s 1950s 2000s 1822-1895 • Louis Pasteur–French chemist • Solved the mysteries of rabies, anthrax, chicken cholera, and silkworm diseases, and contributed to the development of the first vaccines • Reason for fermentation (yeast)

15. 1600s1800s1850s 1900s 1950s 2000s 1823-1884 • Gregor Mendel – Czech monk • Fundamental laws of genetics (1865)

16. 1600s1800s1850s 1900s 1950s 2000s 1844-1895 • Friedrich Miescher - Swiss physician • isolated nucleic acid • became known as nucleic acid after 1874, when Miescher separated it into a protein and an acid molecule.

17. 1600s1800s1850s 1900s 1950s 2000s 1843-1905 • Walter Flemming - German scientist • 1870 Discovered chromosomes • 1871 Discovered mitosis • Linked mitosis to Mendel’s observations

18. 1600s1800s1850s 1900s 1950s 2000s 1860-1917 • Eduard & Hans Buchners– German brothers • Eduard Buchner Winner of the 1907 Nobel Prize in Chemistry • 1897 - Discovery of cell-free fermentation

19. 1600s1800s 1850s 1900s 1950s 2000s 1862 - 1915 • Theodor Boveri – German biologist 1877-1916 • Walter Sutton - graduate student in the Department of Zoology (1902) chromosome theory of Heredity

20. 1600s1800s 1850s 1900s 1950s 2000s 1920 • Nucleic Acids major component of chromosomes

21. 1600s1800s 1850s 1900s 1950s 2000s 1881 – 1955 • Sir Alexander Fleming • Nobel Prize in 1945. • "One sometimes finds what one is not looking for." • He published a report on penicillin 1929,but it raised little interest

23. 1600s1800s 1850s 1900s 1950s 2000s 1927 • James Sumner – American biochemist • Purified and crystallized the first protein enzyme (urease from bean) • 1946 - Nobel Prize for Chemistry

24. 1600s1800s 1850s 1900s 1950s 2000s 1881 - 1941 • FrederickGriffith -an English army medical officer •    in1928Discovered “Genetic Transformation”

25. Frederick Griffith’s 1920s Experiment

26. 1600s1800s 1850s 1900s 1950s 2000s 1877-1955 • Oswald Avery – American bacteriologist • 1943– proved that DNA carries genes S R DNA S

27. Discovery of DNA • the extracts of heat-killed S bacteria cells contained protein, RNA and DNA which of these substances were essential for transformation? • How did they figure out which substance was essential for transformation?

28. Discovery of DNA • They decided to use the process of elimination • Extracts were treated with either • Proteases (to destroy protein) • RNase (to destroy RNA) • DNase (to destroy DNA) • Transformation was due exclusively to DNA

29. 1600s1800s 1850s 1900s 1950s 2000s • Alfred Hershy and Martha Chase 1952 • used bacteriophage to prove that DNA was the hereditary material • the bacteriophage was the ideal organism for settling the debate between protein and DNA.

30. What are viruses? • Viruses are organized associations of macromolecules:-nucleic acid contained within a protective shell of protein units . A virus is NOT alive. A virus is NOT made out of a cell.

31. DNA discovery Hersy-Chase 1952

32. DNA discovery Hersy-Chase 1952

33. 1600s1800s 1850s 1900s 1950s 2000s 1929-1992 • Erwin Chargaff – Austrian American biochemist • (1950) Discovered the base-pairing regularities or "complementarity relationships" of nucleic acids that provided one of the key steps in developing a structural model for DNA.

34. 1600s1800s 1850s 1900s 1950s 2000s 1920 – 1958 • Rosalind Franklin- English Chemist • the most beautiful X-ray photographs of any substance ever taken • (1952) crucial contributions to the solution of the structure of DNA

35. 1600s1800s 1850s 1900s 1950s 2000s 1953 • James Watson – American ornithologist • Francis Crick – British Physicist

36. 1600s1800s 1850s 1900s 1950s 2000s 1955 Fred Sanger- British Biochemist • The Nobel Prize in Chemistry 1958 • First complete sequence of the protein (insulin) • The Nobel Prize in Chemistry 1980 • "for their contributions concerning the determination of base sequences in nucleic acids" • Principle of the Chain-terminating (dideoxy Method for Sequencing DNA

37. 1600s1800s 1850s 1900s 1950s 2000s • Marshall W. Nirenberg • Heinrich Mathieu • protein synthesis poly-U experiments and the first clue to the genetic code • 1968 - Nobel Laureate in Medicine

38. 1600s1800s 1850s 1900s 1950s 2000s 1980 • Paul Berg, Walter Gilbert, Frederick Sanger • The Nobel Prize in Chemistry 1980 • "for their contributions concerning the determination of base sequences in nucleic acids"

39. 1600s1800s 1850s 1900s 1950s 2000s 1978 • David Botstein- California • Discovery of Restriction Enzymes

40. 1600s1800s 1850s 1900s 1950s 2000s 1977 • Bill Rutter and Howard Goodman • Isolated the gene for rat insulin 1978 • Harvard researchers used genetic engineering techniques to produce rat insulin

41. 1600s1800s 1850s 1900s 1980s 2000s Kary B. Mullis • 1980

42. 1600s1800s 1850s 1900s 1950s 2000s 1980 - Kary B. Mullis • Cetus Corporation in Berkeley, California, invented a technique for multiplying DNA sequences in vitro by, the polymerase chain reaction - PCR. PCR has been called the most revolutionary new technique in molecular biology in the 1980s. Cetus patented the process, and in the summer of 1991 sold the patent to Hoffman-La Roche, Inc. for $300 million

43. The idea was not the product of a painstaking laboratory discipline, but was conceived while cruising in a Honda Civic on Highway 128 from San Francisco to Mendocino. • "I do my best thinking while driving," the scientist with the tanned face and bleached hair once explained. For this brilliant idea born at the speed of 50 m.p.h., he received a $10,000 bonus from Cetus, with whom he eventually parted ways. (Cetus later sold the technolgy to LaRoche for $300,000,000.) He now lives in a small apartment across from Windansea Beach, a surfing spot made famous by Tom Wolfe's novel, "The Pump House Gang." A man interested in many things in life besides molecular biology and surfing, he has refused to team up with the biotechnology industry or academia. Currently, he consults and lectures around the world about biotechnology or the development of the scientific method, its successes and its failures.

44. 1600s1800s 1850s 1900s 1950s 2000s 1983 • Jay Levy's lab at University of California San Francisco and Pasteur Institute in Paris and at the NIH isolated theAIDS virus

45. 1600s1800s 1850s 1900s 1950s 2000s 1986 • A regiment of scientists and technicians at Caltech and Applied Biosystems, Inc., invented the automated DNA fluorescence sequencer

46. 1600s1800s 1850s 1900s 1950s 2000s 1990 • Mary Claire King, epidemiologist at UC-Berkeley • reported the discovery of the gene linked to breastcancer in families with a high degree of incidence before age 45.

47. 1600s1800s 1850s 1900s 1950s 2000s 1997 • Researchers at Scotland's Roslin Institute report that they have cloned a sheep--named Dolly- from the cell of an adult ewe. Polly the first sheep cloned by nuclear transfer technology bearing a human gene appears later.

48. 1600s1800s 1850s 1900s 1950s 2000s 1999 • “Celera genomics” – Rockville, Maryland • Drosophila genome http://www.fruitfly.org/

49. 1600s1800s 1850s 1900s 1950s 2000s 2000 • Complete Human Genome Project http://www.genome.gov/ 2002 • Mouse Genome Project http://www.informatics.jax.org/

50. Physicists developed the most powerful techniques used by biochemists: • Electron microscopy • X-ray diffraction • Nuclear Magnetic Resonance