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BC
1750TheSumeriansbrewbeer.
500TheChineseusemoldysoybeancurdsasanantibiotictotreatboils.
250TheGreekspracticecroprotationtomaximizesoilfertility.
100PowderedchrysanthemumisusedinChinaasaninsecticide.AD:Beforethe20thCentury
1590ThemicroscopeisinventedbyJanssen.
1663CellsarefirstdescribedbyHooke.
1675Leeuwenhoekdiscoversprotozoaandbacteria.
1797Jennerinoculatesachildwithaviralvaccinetoprotecthimfromsmallpox.
1802Theword"biology"firstappears.
1824Dutrochetdiscoversthattissueisposedoflivingcells.
1830Proteinsarediscovered.
1833Thecellnucleusisdiscovered.Thefirstenzymesareisolated.
1855TheEscherichiacolibacteriumisdiscovered.Itlaterbeesamajorresearch,development,andproductiontoolforbiotechnology.Pasteurbeginsworkingwithyeast,eventuallyprovingtheyarelivingorganisms.
1863Mendel,inhisstudyofpeas,discoversthattraitsweretransmittedfromparentstoprogenybydiscrete,independentunits,latercalledgenes.Hisobservationslaythegroundworkforthefieldofgenetics.
1869MiescherdiscoversDNAinthespermoftrout.
1877AtechniqueforstainingandidentifyingbacteriaisdevelopedbyKoch.
1878ThefirstcentrifugeisdevelopedbyLaval.Theterm"microbe"isfirstused.
1879Flemmingdiscoverschromatin,therod-likestructuresinsidethecellnucleusthatlateretobecalled"chromosomes."
1883Thefirstrabiesvaccineisdeveloped.
1888ThechromosomeisdiscoveredbyWaldyer.AD:FirstHalfofthe20thCentury
1902Theterm"immunology"firstappears.
1906Theterm"genetics"isintroduced.
1907Thefirstinvivocultureofanimalcellsisreported.
1909Genesarelinkedwithhereditarydisorders.
1911Thefirstcancer-causingvirusisdiscoveredbyRous.
1914BacteriaareusedtotreatsewageforthefirsttimeinManchester,England.
1915Phages,orbacterialviruses,arediscovered.
1919Theword"biotechnology"isfirstusedbyaHungarianagriculturalengineer.
1920ThehumangrowthhormoneisdiscoveredbyEvansandLong.
1927MullerdiscoversthatX-rayscausemutation.
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1928Flemingdiscoverspenicillin,thefirstantibiotic.
1938Theterm"molecularbiology"iscoined.
1941Theterm"geneticengineering"isfirstusedbyaDanishmicrobiologist.
1942Theelectronmicroscopeisusedtoidentifyandcharacterizeabacteriophage-avirusthatinfectsbacteria.
1943AverydemonstratesthatDNAisthe"transformingfactor"andisthematerialofgenes.
1944DNAisshowntobethematerialsubstanceofthegene.
1949Paulingshowsthatsicklecellanemiaisa"moleculardisease"resultingfromamutation.
1950to1960
1951McClintockdiscoverstransposableelements,or"jumpinggenes,"incorn.
1953WatsonandCrickrevealthethree-dimensionalstructureofDNA.
1954Cell-culturingtechniquesaredeveloped.
1955Anenzymeinvolvedinthesynthesisofanucleicacidisisolatedforthefirsttime.
1956ThefermentationprocessisperfectedinJapan.
KornbergdiscoverstheenzymeDNApolymeraseI,leadingtoanunderstandingofhowDNAisreplicated.
1957Sicklecellanemiaisshowntooccurduetoachangeofasingleaminoacid.
1960Exploitingbasepairing,hybridDNA-RNAmoleculesarecreated.MessengerRNAisdiscovered.
1961Thegeneticcodeisunderstoodforthefirsttime.
1964Theexistenceofreversetranscriptase(RT)ispredicted.
1967Thefirstautomaticproteinsequencerisperfected.
1969Anenzymeissynthesizedinvitroforthefirsttime.1970s
1970Specificrestrictionnucleasesareidentified,openingthewayforgenecloning.RTisdiscoveredindependentlyinmurineandavianretroviruses.
1971RTisshowntohaveribonucleaseH(RnaseH)activity.
1972TheDNApositionofhumansisdiscoveredtobe99%similartothatofchimpanzeesandgorillas.
PurifiedRTisfirstusedtosynthesizecDNAfrompurifiedmRNAinvitro.
1973CohenandBoyerperformthefirstsuccessfulrebinantDNAexperiment,usingbacterialgenes.
1974TheNationalInstituteofHealthformsaRebinantDNAAdvisorymitteetooverseerebinantgeneticresearch.
1975ColonyhybridizationandSouthernblottingaredevelopedfordetectingspecificDNAsequences.
Thefirstmonoclonalantibodiesareproduced.
1976ThetoolsofrebinantDNAarefirstappliedtoahumaninheriteddisorder.Molecularhybridizationisusedfortheprenataldiagnosisofalphathalassemia.YeastgenesareexpressedinE.colibacteria.
1977Geneticallyengineeredbacteriaareusedtosynthesizehumangrowthprotein.
1978NorthCarolinascientistsHutchinsonandEdgellshowitispossibletointroducespecific
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mutationsatspecificsitesinaDNAmolecule.
1979Thefirstmonoclonalantibodiesareproduced.
1980s
1980TheU.S.SupremeCourt,inthelandmarkcaseDiamondv.Chakrabarty,approvestheprincipleofpatentinggeneticallyengineeredlifeforms.
TheU.S.patentforgenecloningisawardedtoCohenandBoyer.
1981TheNorthCarolinaBiotechnologyCenteriscreatedbythestate'sGeneralAssemblyasthenation'sfirststate-sponsoredinitiativetodevelopbiotechnology.Thirty-fiveotherstatesfollowwithbiotechnologycentersofvariouskinds.
Thefirstgene-synthesizingmachinesaredeveloped.
Thefirstgeneticallyengineeredplantisreported.
Micearesuccessfullycloned.
1982Humulin,Genentech'shumaninsulindrugproducedbygeneticallyengineeredbacteriaforthetreatmentofdiabetes,isthefirstbiotechdrugtobeapprovedbytheFoodandDrugAdministration.
1983ThePolymeraseChainReaction(PCR)techniqueisconceived.PCR,whichusesheatandenzymestomakeunlimitedcopiesofgenesandgenefragments,laterbeesamajortoolinbiotechresearchandproductdevelopmentworldwide.
ThefirstgenetictransformationofplantcellsbyTIplasmidsisperformed.
Thefirstartificialchromosomeissynthesized.
Thefirstgeneticmarkersforspecificinheriteddiseasesarefound.
Efficientmethodsaredevelopedtosynthesizedouble-strandedDNAfromfirst-strandcDNAinvolvingminimallossofsequenceinformation.
1984TheDNAfingerprintingtechniqueisdeveloped.
Thefirstgeneticallyengineeredvaccineisdeveloped.
ChironclonesandsequencestheentiregenomeoftheHIVvirus.
1985FullyactivemurineRTisclonedandoverexpressedinE.Coli.
1986Thefirstfieldtestsofgeneticallyengineeredplants(tobacco)areconducted.
OrthoBiotech'sOrthocloneOKT3,usedtofightkidneytransplantrejection,isapprovedasthefirstmonoclonalantibodytreatment.
Thefirstbiotech-derivedinterferondrugsforthetreatmentofcancer,Biogen'sIntronAandGenentech'sRoferonA,areapprovedbytheFDA.In1988,thedrugsareusedtotreatKaposi'ssara,aplicationofAIDS.
Thefirstgeneticallyengineeredhumanvaccine,Chiron'sRebivaxHB,isapprovedforthepreventionofhepatitisB.
1987Humatropeisdevelopedfortreatinghumangrowthhormonedeficiency.
AdvancedGeneticSciences'Frostban,ageneticallyalteredbacteriumthatinhibitsfrostformationoncropplants,isfieldtestedonstrawberryandpotatoplantsinCalifornia,thefirstauthorizedoutdoortestsofanengineeredbacterium.
Genentech'stissueplasminogenactivator(tPA),soldasActivase,isapprovedasatreatmentforheartattacks.
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ReversetranscriptionandPCRarebinedtoamplifymRNAsequences.
ClonedmurineRTisengineeredtomaintainpolymeraseandeliminateRnaseHactivity.
1988CongressfundstheHumanGenomeProject,amassiveefforttomapandsequencethehumangeneticcodeaswellasthegenomesofotherspecies.
1989Amgen'sEpogenisapprovedforthetreatmentofrenaldiseaseanemia.
MicroorganismsareusedtocleanuptheExxonValdezoilspill.Thegeneresponsibleforcysticfibrosisisdiscovered.
1990s
1990Thefirstfederallyapprovedgenetherapytreatmentisperformedsuccessfullyona4-yearoldgirlsufferingfromanimmunedisorder.
1991AmgendevelopsNeupogen,thefirstofanewclassofdrugscalledcolonystimulatingfactors,forthetreatmentoflowwhitebloodcellsinchemotherapypatients.
Immunex'sLeukine,usedtoreplenishwhitebloodcountsafterbonemarrowtransplants,isapproved.
Genzyme'sCeredaseisapprovedforthetreatmentofGaucher'sdisease.
1992Thethree-dimensionalstructureofHIVRTiselucidated.Rebinate,developedbyGeneticsInstituteandusedinthetreatmentofhemophiliaA,beesthefirstgeneticallyengineeredbloodclottingfactorapprovedintheU.S.Chiron'sProleukinisapprovedforthetreatmentofrenalcellcancer.
1993Chiron'sBetaseronisapprovedasthefirsttreatmentformultiplesclerosisin20years.TheFDAdeclaresthatgeneticallyengineeredfoodsare"notinherentlydangerous"anddonotrequirespecialregulation.
TheBiotechnologyIndustryOrganization(BIO)iscreatedbymergingtwosmallertradeassociations.
1994Genentech'sNutropinisapprovedforthetreatmentofgrowthhormonedeficiency.Thefirstbreastcancergeneisdiscovered.
Calgene'sFlavrSavrtomato,engineeredtoresistrotting,isapprovedforsale.
1995Thefirstbaboon-to-humanbonemarrowtransplantisperformedonanAIDSpatient.ThefirstfullgenesequenceofalivingorganismotherthanavirusispletedforthebacteriumHemophilusinfluenzae.
Thethree-dimensionalstructureofacatalyticallyactivefragmentofmurineRTiselucidated.1996Biogen'sAvonexisapprovedforthetreatmentofmultiplesclerosis.Thepanybuildsa$50millionplantinResearchTrianglePark,N.C.,tomanufacturetherebinantinterferondrug.Scottishscientistscloneidenticallambsfromearlyembryonicsheep.
1997Scottishscientistsreportcloningasheep,usingDNAfromadultsheepcells.AgroupofOregonresearchersclaimstohaveclonedtwoRhesusmonkeys.AnewDNAtechniquebinesPCR,DNAchips,andaputerprogram,providinganewtoolinthesearchfordisease-causinggenes.
1998UniversityofHawaiiscientistsclonethreegenerationsofmicefromnucleiofadultovarian
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cumuluscells.Humanskinisproducedinvitro.Embryonicstemcellsareusedtoregeneratetissueandcreatedisordersmimickingdiseases.Thefirstpleteanimalgenomefortheeleganswormissequenced.Aroughdraftofthehumangenomemapisproduced,showingthelocationsofmorethan30,000genes.ClonedvainRTwithfullyactivepolymeraseandminimizedRnaseHactivityisengineered.TheBiotechnologyInstituteisfoundedbyBIOasanindependentnational,501(c)(3)educationorganizationwithanindependentBoardofTrustees.
1999Thepletegeneticcodeofthehumanchromosome
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