Biotechnology Raj Mutharasan



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Biotechnology




Applications



Applications II



History – Early Developments

  • 1953 Watson and Crick determined DNA structure

  • 1970 First restriction endonuclease isolated

  • 1973 Boyer and Cohen establish recombinant DNA methodology

  • 1975 Kohler and Milstein describe production of monoclonal antibodies

  • 1978 Genentech produced human insulin in E. Coli

  • 1978 John Baxter reported cloning the gene for human growth hormone

  • 1980 Kary Mullis(Cetus Corp.) conducted in vitro, the polymerase chain reaction (PCR).

  • 1981 Genentech, Inc. cloned interferon gamma. Bill Rutter and Pablo Valenzuela identify hepatitis B surface antigen. Scientists at Ohio University produced the first transgenic animal.

  • 1983 Syntex received FDA approval for a monoclonal antibody based diagnostic test for Chlamydia trachomatis.

  • 1984 Chiron Corp. announced the first cloning and sequencing of the entire human immunodeficiency virus (HIV) genome



History – Middle Developments

  • 1986 Orthoclone OKT3® (Muromonab CD3) approved for reversal of acute kidney transplant rejection. Automated DNA fluorescence sequencer invented. First recombinant vaccine (for hepatitis) to Chiron Corp approved. First genetically engineered crop, gene altered tobacco plant approved.

  • 1987 Genentech received FDA approval to market rtPA (genetically engineered tissue plasminogen activator) to treat heart attacks. Recombivax HB® (recombinant hepatitis B vaccine) approved.

  • 1989 Epogen® (Epoetin alfa) a genetically engineered protein introduced.

  • 1990 Approval for human somatic cell gene therapy trial. GenPharm International, Inc. created the first transgenic dairy cow. The Human Genome Project launched. Estimated cost: $13 billion.

  • 1993 Chiron's Betaseron is approved for multiple sclerosis. Researchers clone human embryos and successfully nurture them in a Petri dish for several days.

  • 1994 The BRCA1 gene reported to cause of non-inherited breast cancers. Vpr, a gene governing reproduction of the HIV virus.



History – Recent Developments

  • 1994 The enzyme telomerase reported as responsible for the unchecked growth of cells seen in human cancers.

  • 1995 Gene therapy, immune system modulation and genetically engineered antibodies enter clinical trials.

  • 1996 Biogen's recombinant interferon drug. Avonex® approved for multiple sclerosis.

  • 1997 Researchers at Roslin Institute report cloning 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. A new DNA technique combines PCR , DNA chips, and computer programming providing a a new tool in the search for disease causing genes.

  • 1998 Favorable results with a new antibody therapy against breast cancer, HER2neu (Herceptin), herald a new era of treatment based on molecular targeting of tumor cells.

  • 2000 A near complete draft of the human genome map is produced, showing the locations of more than 30,000 genes.



An Overview



Market Values



Early Success



Cloning Challenges



Regulatory Challenges



Business Challenges



Industry Summary - 1999



Jobs in Biotechnology



Structure of Bacteria



Bacteria – SEM view



Structure of an Animal Cell



Biochemicals of Life



Pairing of Nucleotides



Central Dogma



Genetic Code



Essential Cloning Steps



Essential Cloning Steps



Amino Acids – Back bone of Proteins



Amino Acids – II



Process Overview



What are cells made of?



Concept : Growth Reaction



Concept : Cell Yield



Cell Yield – Formal Definition



Cell Growth in Batch Culture



Cell Growth - Kinetics



Typical Growth Rates



Nature of Specific Growth



Metabolic Quotients



Metabolic Quotients - II



Factors Affecting Growth Rate - Temperature



Factors Affecting Growth Rate - pH



Factors Affecting Growth Rate - DO



Growth Associated Product Formation



Non-Growth Associated Product Formation



Oxygen Transfer in Bioreactors



Oxygen Transfer in Bioreactors-II



Oxygen Transfer Coefficient



A Design Example



Biotechnology – The next steps





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