6000BC– Breadmaking (involving yeast fermentation)
3000BC– Moldy soybean curd used to treat skin infections in China.
2500BC-Malting of barley, fermentation of beer in Egypt.
1783-Spallanzani noted that meat was liquefied by gastric juice of hawks.
1790-Patent act provides no protection for plants and animals since they are considered to be products of nature
1787-Fabroni defined fermentation as a decomposition of one substance by another substance.
1810-Planche observed that extracts of plant roots turn guaiacum tincture blue. He called the thermolabile, soluble agent, cyanogen.
1814-Kirchhoff observed that a glutinous component of wheat is capable of converting starch to sugar and dextriin.
1830-Robiquet and Boutron, also Chalard discovered the hydrolysis of amygdalin by bitter almonds. Liebig and Whohler (1837) and Robiquet (1836) named the enzyme emulsin.
1831-Leuchs described the diastatic action of ptyalin.
1833-Payen and Persoz separated active amylase from malt.
1835-Faure described sinigrinase.
1836-Schwann described pepsin.
1837-Berzelius included fermentation under catalytic processes.
1838-Berzelius proposes the term catalysis, meaning a loosening down.
1856-Corvisart described trypsin.
1858-Pasteur noted that green mould fermented only dextro tartaric acid and did not attack levo tartaric acid.
1862-Danielewski separated pancreatic amylase from trypsin by adsorption.
1870-Liebig developed a purely chemical theory of enzyme action.
1871-Pasteur showed that living yeast was necessary for fermentation. A difference was made between organized ferments such as yeast and lactic acid-producing bacteria and unorganized ferments such as pepsin and diastase.
1877-Pasteur and Joubert discover that some bacteria can kill anthrax bacilli.
1878-Kuhne designated the latter class of substances as enzymes, which means in yeast.
1883-Duclaux introduced the custom designating an enzyme by the substrate on which its action was first observed and adding the suffix, -ase.
1894-Emil Fischer began investigations on which our ideas of enzyme specificity are based.
1896– Gosio discovers mycophenolic acid, an antibacterial substance produced by microbes; too toxic for use as antibiotic.
1898-Croft-Hill performed the first enzymatic synthesis, that of isomaltose.
1900-Catalysts of oxidation were considered as enzymes.
1902-Bacillus thuringiensis fi rst isolated from silkworm culture by Ishiwata
1908-Ikeda identifi es monosodium glutamate (MSG) as flavour enhancer in Konbu Invertase adsorbed onto charcoal i.e. first example of immobilized enzyme
1909-Ajinimoto (Japan) initiates commercial production of sodium glutamate from wheat gluten and soybean hydrolysates
1909-Sorensen pointed out the dependence of enzyme activity on pH.
1900–1920 Ethanol, glycerol, acetone andbutanol produced commercially by large-scale fermentation.
1922-Banting and best treat human diabetic patient with insulin extracted from dog pancreas.
1923-Citric acid fermentation plant using Aspergillus niger by Charles Pfizer.
1926-Sumner prepared cystalline urease.
1928-Alexander Fleming discovers penicillin from Penicillium notatum
1930-Plant Patent Act, which allows for patenting of asexually produced plants i.e. plants reproduced by, tissue culture or propagation of cuttings.
1930-Northrop crystallized pepsin.
1931-Northrop and Kunitz crystallized trypsin.
1943-Submerged culture of Penicillium chrysogenum opens way for large -scale production of penicillin.
1945-Production through fermentation process scaled up to make enough penicillin to treat 100,000 patients per year. Beginning of rapid development of antibiotic industry; during World War II, research driven by 85% tax on excess profits, encouraged investment in research and development for antibiotics
1953-DNA structure and function elucidated Xylose isomerase discovered
1957-Commercial production of natural ( l) amino acids via fermentation facilitated the discovery of Micrococcus glutamicus (later renamed Corynebacterium glutamicum) Glucose-isomerizing capability of xylose isomerase reported
1960-Lysine produced on a technical scale
1961-First commercial production of MSG via fermentation
1965-Corn bran and hull replaces xylose as inducer of glucose (xylose) isomerase in Streptomyces phaeochromogenus. Phenyl methyl ester of aspartic acid and phenylalanine (aspartame) synthesized at G. D. Searle Co.
1967-Clinton Corn Processing ships fi rst enzymatically produced fructose syrup
1970-Smith et al. report restriction endonuclease from Haemophilis infl uenzae that recognizes specifi c DNA target sequences.
1971 Cetus founded
1973 Cohen and Boyer report genetic engineering technique (EcoRI enzyme) (Cohen et al. 1973) Aspartase in immobilized E. coli cells catalyzes l-aspartic acid production from fumarate and ammonia.
1973–1974-Oil price increase (Yom Kippur war).
1975-Kohler and Milstein report monoclonal antibodies. Basic patent coverage for xylose (glucose) isomerase lost in lawsuit Opens up development of new HFCS processes.
1978-Biogen formed; develops interferons Eli Lilly licenses recombinant insulin technology from Genentech 3.5 billion lb HFCS produced in USA.
1979–1980-Energy-saving method for drying ethanol using corn (starch) and cellulose-based adsorbents reported.
1977–1982 Fermentation ethanol processes adapted by wet millers for fuel –grade ethanol
1980-Amgen founded. US Supreme Court rules that life forms are patentable
1981-HIV/AIDS cases identified and reported in San Francisco. Aspartame approved for food use by FDA. Chiron founded. Gene-synthesizing machines developed
1982-FDA approves Humalin (human insulin) made by Lilly. First transgenic mouse; rat gene transferred to mouse.
1983-Aspartame comes on market sold by G. D. Searle as Nutrasweet. First product sales of recombinant insulin. HIV virus identified as cause of AIDS.
1986-Phaseout of lead as octane booster in gasoline in USA creates demand for ethanol as a nonleaded octane booster for liquid fuels. Ethanol production at 500 million gal/year for use as octane booster.
1987-Merck licenses Chiron’s recombinant hepatitis B vaccine. Human growth hormone (Protropin) introduced by Genentech. Interleukin (IL-2), a protein used to treat cancer, by Cetus undergoes clinical trials.
1988-Ethanol production at 800 million gal/year. Cetus requested approval for IL -2 to treat advanced kidney cancer. Tissue plasminogen activator (TPA) introduced by Genentech.
1989-Human Genome Project started. Amgen introduces erythropoietin (EPO), a protein that stimulates red blood cell formation.
1990-FDA rejects IL -2 application of Cetus. Bristol Myers and Squibb merge. Beecham and SmithKline Beckman merge. Genentech’s tissue plasminogen activator (TPA), for dissolving blockages that cause heart attacks. Protropin (human growth hormone) earns $157 million. Amgen’s EPO sales at $300 million/year in USA; licensed by Kilag (Johnson & Johnson in Europe) and Kirin (Japan).
1991-First attempt at human gene therapy. Amgen EPO sales exceed $293 million by August 1991. Genetics Institute suit against Amgen for American rights to EPO. American Home Products buys $666 million (60%) share in Genetics. Institute; Chiron purchases Cetus for $650 million.
1992-IL-2 (now owned by Chiron) approved for further testing by FDA. TPA (from Genentech) under competitive pressure from less expensive product by Swedish Kabi. Policy guidelines for the agricultural biotechnology established.
1993-Chiron introduces Betaseron (a β-interferon) for treatment of multiple sclerosis. Healthcare reform proposals create uncertainty in biotechnology industry. Merck acquires Medco containment services.
1994-American Home Products Buys American Cyanimid
•SmithKline Beecham merges with Diversifi ed Pharmaceutical Services
•Eli Lilly acquires PCS Health Systems for $4.1 billion
•Bayer purchases Sterling Winthrop NA for $1.0 billion
•Process based on corn adsorbent dries half of fermentation ethanol in USA (750 million gallons/year)
1995-UpJohn and Pharmacia merge to form Pharmacia -UpJohn in a $6 billion stock swap Hoescht/Marion Merrell Dow merges for $7.1 billion.
1996-Monsanto purchases Ecogen for $25 million, Dekalb Genetics for $160 million; Agracetus for $150 million; and 49.9% of Calgene. Biogen introduces Avonex, to compete with Berlex ’s Betaseron for MS sufferers $27 billion merger of Ciba -Geigy AG and Sandoz AG to form Norvatis approved; estimated annual sales of $27.3 billion; US Federal Trade.
1997-SmithKline Beecham forms joint venture with Incyte to enter genetic –diagnostics business
•Schering-Plough Corporation Acquires Mallinckrodt Animal –Health Unit for $405 million
•Merck, Rh ône-Poulenc form animal healthcare 50/50 joint venture (Merial Animal Health)
•Dupont purchases Protein Technologies (division of Ralston Purina) for $1.5 billion as part of business plan to develop soy protein foods
•American Home Products discusses $60 billion merger with SmithKline Beecham PLC
•Monsanto spins off chemicals unit and becomes Monsanto Life Sciences
1998-SmithKline Beecham breaks off talks with American Home Products. Glaxo enters merger discussions with SmithKline. Beecham in a deal valued at $65–70 billion; merger discussions driven by successful hunt for human genes and opportunities for exploiting these findings for development of new pharmaceuticals; leads to formation of Glaxo SmithKline.