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1、2020/10/28,2003-2004,Steps on the Road to Biotechnology,SECTION 1,2020/10/28,8000 B.C.,Humans domesticate crops and livestock. Potatoes first cultivated for food.,2020/10/28,4000-2000 B.C.,Biotechnology first used to leaven bread and ferment beer, using yeast (Egypt). Production of cheese and fermen

2、tation of wine (Sumeria, China and Egypt). Babylonians control date palm breeding by selectively pollinating female trees with pollen from certain male trees.,2020/10/28,500 B.C.,First antibiotic(抗生素): moldy soybean curds(臭豆腐) used to treat boils (China).,2020/10/28,A.D. 100,First insecticide(生物杀虫剂)

3、: powdered chrysanthemums (China).,2020/10/28,1322 An Arab chieftain first uses artificial insemination to produce superior horses. 1590 Janssen invents the microscope.,2020/10/28,1663 Hooke discovers existence of the cell,2020/10/28,2020/10/28,1675 Leeuwenhoek discovers bacteria,2020/10/28,1761 Koe

4、lreuter reports successful crossbreeding of crop plants in different species. 1797 Jenner inoculates a child with a viral vaccine to protect him from smallpox.,2020/10/28,1830-Proteins discovered. 1833-First enzyme discovered and isolated. 1835-1855 Schleiden and Schwann propose that all organisms a

5、re composed of cells, and Virchow declares, Every cell arises from a cell.,2020/10/28,1857 Pasteur proposes microbes cause fermentation,Pasteur showed that microbes are responsible for fermentation. Fermentation is the conversation of sugar to alcohol to make beer and wine. Microbial growth is also

6、responsible for spoilage of food. Bacteria that use alcohol and produce acetic acid spoil wine by turning it to vinegar (acetic acid).,2020/10/28,On the Origin of Species,1859 Charles Darwin publishes On the Origin of Species, establishing the Theory of Evolution and its mechanism, natural selection

7、, and challenging both the accepted scientific and religious views of Western culture that had been taught for centuries.,The first edition sold out on the day it was published. Theologians quickly labeled Darwin the most dangerous man in England. Yet, after reading it, Darwins friend and colleague

8、T. H. Huxley had a different reaction: How extremely stupid not to have thought of that. Q,2020/10/28,1865 The age of genetics begins,When Gregor Mendel, studying inherited traits of pea plants, outlines the basic laws of heredity that still hold true today for all organisms. Mendels discoveries abo

9、ut heritable factors (genes) are not recognized by other scientists for over 35 years.,2020/10/28,1870-1890,Using Darwins theory, plant breeders crossbreed cotton, developing hundreds of varieties with superior qualities. Farmers first inoculate fields with nitrogen-fixing bacteria to improve yields

10、. William James Beal produces first experimental corn hybrid in the laboratory. 1877-A technique for staining and identifying bacteria is developed by Koch. 1878-The first centrifuge is developed by Laval. 1879-Fleming discovers chromatin, the rod-like structures inside the cell nucleus that later c

11、ame to be called chromosomes.,2020/10/28,1900 The rediscovery of Mendel,2020/10/28,1900 The rediscovery of Mendel,2020/10/28,1900 Drosophila (fruit flies) used in early studies of genes. 1902 The term immunology first appears. 1906 The term genetics is introduced.,2020/10/28,1910 Chromosomal theory

12、of inheritance proposed,Thomas Hunt Morgan establishes that genes are located on chromosomes by physically tracing a specific gene to a specific chromosome. Morgan wins the 1933 Nobel Prize in Medicine.,2020/10/28,1911 The first cancer-causing virus is discovered by Rous. 1914 Bacteria are used to t

13、reat sewage for the first time in Manchester, England. 1915 Phages, or bacterial viruses, are discovered.,2020/10/28,1919 First use of the word biotechnology in print. 1920 The human growth hormone is discovered by Evans and Long.,Penicillin discovered as an antibiotic: Alexander Fleming.,2020/10/28

14、,1928,A small-scale test of formulated Bacillus thuringiensis (Bt) for corn borer control begins in Europe. Commercial production of this biopesticide begins in France in 1938. Karpechenko crosses radishes and cabbages, creating fertile offspring between plants in different genera. Laibach first use

15、s embryo rescue to obtain hybrids from wide crosses in crop plants-known today as hybridization.,2020/10/28,1930 U.S. Congress passes the Plant Patent Act, enabling the products of plant breeding to be patented. 1933 Hybrid corn, developed by Henry Wallace in the 1920s, is commercialized. Growing hy

16、brid corn eliminates the option of saving seeds. The remarkable yields outweigh the increased costs of annual seed purchases, and by 1945, hybrid corn accounts for 78 percent of U.S.-grown corn.,2020/10/28,1938 The term molecular biology is coined. 1941 The term genetic engineering is first used by

17、Danish microbiologist A. Jost in a lecture on reproduction in yeast at the technical institute in Lwow, Poland.,2020/10/28,1941 One gene, one enzyme,George Beadle and Edward Tatum establish that one gene makes one enzyme or protein, and share the 1958 Nobel Prize in Medicine.,2020/10/28,1942,The ele

18、ctron microscope is used to identify and characterize a bacteriophage-a virus that infects bacteria.,Penicillin mass-produced in microbes,2020/10/28,1944,DNA is proven to carry genetic information - Avery et al. Waksman isolates streptomycin(链霉素), an effective antibiotic for tuberculosis(肺结核).,2020/

19、10/28,1946,Discovery that genetic material from different viruses can be combined to form a new type of virus, an example of genetic recombination. Recognizing the threat posed by loss of genetic diversity, the U.S. Congress provides funds for systematic and extensive plant collection, preservation

20、and introduction.,2020/10/28,1947 McClintock discovers transposable elements, or jumping genes, in corn. 1949 Pauling shows that sickle cell anemia is a molecular disease resulting from a mutation in the protein molecule hemoglobin. 1951 Artificial insemination of livestock using frozen semen is suc

21、cessfully accomplished.,2020/10/28,1952 The Waring Blender Experiment:,Martha Chase and Alfred Hershey use the common kitchen appliance to separate the protein coats of viruses from their DNA to demonstrate that DNA is the substance that transmits inherited characteristics from one generation to the

22、 next. Hershey wins the 1969 Nobel Prize.,2020/10/28,2020/10/28,2020/10/28,1953 Unraveling the double helix,James Watson and Francis Crick deduce the structure of the DNA molecule - a double helix - without ever doing a single experiment at the bench.,In a classic race to the finish, Watson and Cric

23、k submit a one-page paper to the journal Nature, starting with We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.), and ending with the subtle understatement: It has not escaped our notice that the specific pairing that we have postulated immediately suggests a possible

24、copying mechanism for the genetic material. Their work is recognized with the 1962 Nobel Prize, shared with Maurice Wilkins,2020/10/28,2020/10/28,1955 An enzyme involved in the synthesis of a nucleic acid is isolated for the first time. 1956 Kornberg discovers the enzyme DNA polymerase I, leading to

25、 an understanding of how DNA is replicated. 1958 Sickle cell anemia is shown to occur due to a change of a single amino acid. 1958 DNA is made in a test tube for the first time. 1959 Systemic fungicides are developed. The steps in protein biosynthesis are delineated. Also in the 1950s Discovery of i

26、nterferons. First synthetic antibiotic.,2020/10/28,1960 Exploiting base pairing, hybrid DNA-RNA molecules are created. 1960 Messenger RNA is discovered. 1961 USDA registers first biopesticide: Bacillus thuringiensis, or Bt. 1963 New wheat varieties developed by Norman Borlaug increase yields by 70 p

27、ercent. 1964 The International Rice Research Institute in the Philippines starts the Green Revolution with new strains of rice that double the yield of previous strains if given sufficient fertilizer.,2020/10/28,1965 Harris and Watkins successfully fuse mouse and human cells. 1966 The genetic code i

28、s cracked, demonstrating that a sequence of three nucleotide bases (a codon) determines each of 20 amino acids. 1967 Cracking the the genetic code Har Khorana, Robert Holley, and Marshall Nirenberg decipher(译解) the mechanism that enables DNA to be translated into proteins. Nirenberg, Khorana, and Ho

29、lley share the 1968 Nobel Prize. 1967 The first automatic protein sequencer is perfected.,2020/10/28,Established the chemical structure of tRNA,Established the in vitro system for revealing the genetic codes,Devised methods to synthesize RNAs with defined sequences,2020/10/28,1968 Stanley Cohen,Stud

30、ying bacterial disease at Stanford, determines that bacteria carry genes for antibiotic resistance on plasmids, extrachromosomal circles of DNA. Cohen learns how to purify plasmids and reinsert them into other bacterial cells, transferring antibiotic resistance in the process.,2020/10/28,1969,An enz

31、yme is synthesized in vitro for the first time.,2020/10/28,1970 Restriction enzymes discovered,UCSF scientist Herb Boyer, working with bacteriophages(抗菌素), discovers that certain bacteria preferentially fought off (or restricted) certain phages by producing enzymes that chopped up the phages DNA, le

32、aving sticky ends on the cut strands. Boyer isolates the Big Daddy of restriction enzymes, EcoR1. In the ensuing years, hundreds of different restriction endonucleases are found that cleave DNA at specific sites. Earlier investigators studying restriction enzymes win the1978 Nobel Prize in Medicine.

33、,2020/10/28,1971 First complete synthesis of a gene. 1972 The DNA composition of humans is discovered to be 99 percent similar to that of chimpanzees and gorillas. 1972 Initial work with embryo transfer.,2020/10/28,1972 Recombinant DNA technology begins,Stanford biochemist Paul Berg splices together

34、 two blunt-ended fragments of DNA from the SV40 virus and E. coli, creating recombinant DNA. Berg shares the 1980 Nobel Prize in Chemistry with Walter Gilbert and Fred Sanger,2020/10/28,1972 From Corned Beef to Cloning,In November, at a scientific meeting in Hawaii, Cohen hears Boyer describe his wo

35、rk with EcoR1 and his findings that the sticky ends of DNA can be linked together or spliced with DNA ligases. Cohen and Boyer meet at a Waikiki Beach Deli, where they discuss ways to combine plasmid isolation with DNA splicing. They form the idea of inserting desired DNA into bacterial plasmds that

36、 would then churn out specific proteins - the basis of the biotechnology industry,2020/10/28,1973 Stanley Cohen and Herbert Boyer perfect techniques to cut and paste DNA (using restriction enzymes and ligases) and reproduce the new DNA in bacteria. 1974 The National Institutes of Health forms a Reco

37、mbinant DNA Advisory Committee to oversee recombinant genetic research.,2020/10/28,1975 Asilomar Conference,Pacific Grove CA: Paul Berg organizes an international conference on recombinant DNA technology with over 100 other scientists to discuss what they knew (and didnt know) about recombinant DNA

38、and to draw up guidelines that would let the science proceed without undue risk. The scientists agree to suspend research involving recombinant DNA technology research until potential risks can be evaluated, a milestone of self-regulation in science. Although recombinant DNA technology turned out to

39、 be much more harmless than many had suspected, Asilomar remains an important scientific landmark, a rare instance of scientists independently questioning and successfully regulating their own work,2020/10/28,1975 DNA sequencing developed,Walter Gilbert and Allan Maxam of Harvard University and Fred

40、 Sanger of Cambridge University simultaneously come up with two techniques for determining the exact sequence of bases that make up a gene. Gilbert and Sanger share the 1980 Nobel Prize (also with Paul Berg).,2020/10/28,1975 Cesar Milstein,Georges Kohler and Niels Jeme develop monoclonal antibody(单克

41、隆抗体) technology by fusing immortal tumor cells with antibody-producing B lymphocyte(淋巴) cells to produce “hybridomas(杂种细胞), that continuously synthesize identical (or monoclonal) antibodies. Milstein, Kohler and Jeme are awarded the 1984 Nobel Prize in Medicine.,2020/10/28,1976 Big bucks for Biotech

42、,The commercial potential of using cells as factories for hormones and proteins to produce biopharmaceuticals is not lost on the business world. Robert Swanson, a 29-year-old Silicon Valley venture capitalist, and Herb Boyer team up to form Genentech, Inc. (for GENetic ENgineering TECHnology) with t

43、he goal of cloning human insulin. Genentech goes public on Oct. 14, 1980, offering one million shares of stock for $35 a share - and makes $35 million in an afternoon. By the end of the day, Genentechs stock makes market history by hitting a high of $89, a record for an initial public offering,2020/

44、10/28,1976,The tools of recombinant DNA are first applied to a human inherited disorder. Molecular hybridization is used for the prenatal diagnosis of alpha thalassemia. Yeast genes are expressed in E. coli bacteria. First time the sequence of base pairs for a specific gene is determined (A, C, T, G

45、). First guidelines for recombinant DNA experiments released: National Institutes of Health-Recombinant DNA Advisory Committee.,2020/10/28,1977,First expression of human gene in bacteria. Procedures developed for rapidly sequencing long sections of DNA using electrophoresis.,2020/10/28,1978 Human in

46、sulin cloned into E. coli by Genentech sciensists.,Genentech licenses the human insulin technology to Eli Lilly. In 1982, human insulin, or Humulin, becomes the first recombinant DNA drug approved by FDA.,2020/10/28,1978,High-level structure of virus first identified. Recombinant human insulin first

47、 produced. North Carolina scientists show it is possible to introduce specific mutations at specific sites in a DNA molecule. 1979 Human growth hormone first synthesized.,2020/10/28,Also in the 1970s,First commercial company founded to develop genetically engineered products. Discovery of polymerase

48、s. Techniques for rapid sequencing of nucleotides perfected. Gene targeting. RNA splicing.,2020/10/28,1980,The U.S. Supreme Court, in the landmark case Diamond v. Chakrabarty, approves the principle of patenting recombinant life forms, which allows the Exxon oil company to patent an oil-eating micro

49、organism. The U.S. patent for gene cloning is awarded to Cohen and Boyer. The first gene-synthesizing machines are developed. Researchers successfully introduce a human gene-one that codes for the protein interferon-into a bacterium. Nobel Prize in Chemistry awarded for creation of the first recombi

50、nant molecule: Berg, Gilbert, Sanger.,2020/10/28,1981,Scientists at Ohio University produce the first transgenic animals by transferring genes from other animals into mice. Chinese scientist becomes the first to clone a fish-a golden carp.,2020/10/28,1982,Applied Biosystems, Inc., introduces the fir

51、st commercial gas phase protein sequencer, dramatically reducing the amount of protein sample needed for sequencing. First recombinant DNA vaccine for livestock developed. First biotech drug approved by FDA: human insulin produced in genetically modified bacteria. First genetic transformation of a p

52、lant cell: petunia(矮牵牛花).,2020/10/28,1983,The polymerase chain reaction (PCR) technique is conceived. PCR, which uses heat and enzymes to make unlimited copies of genes and gene fragments, later becomes a major tool in biotech research and product development worldwide. The first genetic transformat

53、ion of plant cells by TI plasmids is performed. The first artificial chromosome is synthesized. The first genetic markers for specific inherited diseases are found. First whole plant grown from biotechnology: petunia. First proof that modified plants pass their new traits to offspring: petunia.,2020

54、/10/28,1984,The DNA fingerprinting technique is developed. The entire genome of the human immunodeficiency virus is cloned and sequenced.,2020/10/28,1985,Genetic markers found for kidney disease and cystic fibrosis. Genetic fingerprinting entered as evidence in a courtroom. Transgenic plants resista

55、nt to insects, viruses and bacteria are field-tested for the first time. The NIH approves guidelines for performing gene-therapy experiments in humans.,2020/10/28,1985 Genentech,Becomes the first biotechnology company to launch its own biopharmaceutical product in 1985, ProTropin - growth hormone fo

56、r children with growth hormone deficiency,2020/10/28,1986 The Polymerase Chain Reaction (PCR),is conceived by Kary Mullis and revolutionizes molecular biology. PCR uses a thermostable DNA polymerase to amplify any given DNA segment billions of times in a few hours. Taq polymerase is chosen as the 19

57、89 Molecule of the Year by the journal Science. Kary Mullis, having parted ways with his employer (Cetus) as well as alienated himself from the scientific establishment, is not even mentioned in the Science article. However, Mullis IS awarded the 1993 Nobel Prize in Chemistry and goes on to become a

58、 best-selling novelist. A long, bitter David vs. Goliath patent struggle between Hoffman-LaRoche and Promega Biotech over ownership of PCR technology and the key enzyme,Taq polymerase, was at last resolved in 1999.,2020/10/28,2020/10/28,1986,First recombinant vaccine for humans: hepatitis(肝炎) B. Fir

59、st anti-cancer drug produced through biotech: interferon. The U.S. government publishes the Coordinated Framework for Regulation of Biotechnology, establishing more stringent regulations for rDNA organisms than for those produced with traditional genetic modification techniques. A University of California-Berkeley chemist describes how to combine antibodies and enzymes to create pharmaceuticals(药品). The first field tests of transgenic plants (tobacco) are conducted. The Environmental Protection Agency approves the release of the first transgenic crop-gene-altered tob

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