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BC
1750TheSumeriansbrewbeer.
500TheChineseusemoldysoybeancurdsasanantibiotictotreatboils.
250TheGreekspracticecroprotationtomaximizesoilfertility.
100PowderedchrysanthemumisusedinChinaasaninsecticide.
AD:Beforethe20thCentury
1590ThemicroscopeisinventedbyJanssen.
1663CellsarefirstdescribedbyHooke.
1675Leeuwenhoekdiscoversprotozoaandbacteria.
1797Jennerinoculatesachildwithaviralvaccinetoprotecthimfromsmallpox.
1802Theword"biology"firstappears.
1824Dutrochetdiscoversthattissueiscomposedoflivingcells.
1830Proteinsarediscovered.
1833Thecellnucleusisdiscovered.
Thefirstenzymesareisolated.
1855TheEscherichiacolibacteriumisdiscovered.Itlaterbecomesamajorresearch,development,andproductiontoolforbiotechnology.
Pasteurbeginsworkingwithyeast,eventuallyprovingtheyarelivingorganisms.
1863Mendel,inhisstudyofpeas,discoversthattraitsweretransmittedfromparentstoprogenybydiscrete,independentunits,latercalledgenes.Hisobservationslaythegroundworkforthefieldofgenetics.
1869MiescherdiscoversDNAinthespermoftrout.
1877AtechniqueforstainingandidentifyingbacteriaisdevelopedbyKoch.
1878ThefirstcentrifugeisdevelopedbyLaval.
Theterm"microbe"isfirstused.
1879Flemmingdiscoverschromatin,therod-likestructuresinsidethecellnucleusthatlatercometobecalled"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.
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.
1972TheDNAcompositionofhumansisdiscoveredtobe99%similartothatofchimpanzeesandgorillas.
PurifiedRTisfirstusedtosynthesizecDNAfrompurifiedmRNAinvitro.
1973CohenandBoyerperformthefirstsuccessfulrecombinantDNAexperiment,usingbacterialgenes.
1974TheNationalInstituteofHealthformsaRecombinantDNAAdvisoryCommitteetooverseerecombinantgeneticresearch.
1975ColonyhybridizationandSouthernblottingaredevelopedfordetectingspecificDNAsequences.
Thefirstmonoclonalantibodiesareproduced.
1976ThetoolsofrecombinantDNAarefirstappliedtoahumaninheriteddisorder.
Molecularhybridizationisusedfortheprenataldiagnosisofalphathalassemia.
YeastgenesareexpressedinE.colibacteria.
1977Geneticallyengineeredbacteriaareusedtosynthesizehumangrowthprotein.
1978NorthCarolinascientistsHutchinsonandEdgellshowitispossibletointroducespecificmutationsatspecificsitesinaDNAmolecule.
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,laterbecomesamajortoolinbiotechresearchandproductdevelopmentworldwide.
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'ssarcoma,acomplicationofAIDS.
Thefirstgeneticallyengineeredhumanvaccine,Chiron'sRecombivaxHB,isapprovedforthepreventionofhepatitisB.
1987Humatropeisdevelopedfortreatinghumangrowthhormonedeficiency.
AdvancedGeneticSciences'Frostban,ageneticallyalteredbacteriumthatinhibitsfrostformationoncropplants,isfieldtestedonstrawberryandpotatoplantsinCalifornia,thefirstauthorizedoutdoortestsofanengineeredbacterium.
Genentech'stissueplasminogenactivator(tPA),soldasActivase,isapprovedasatreatmentforheartattacks.
ReversetranscriptionandPCRarecombinedtoamplifymRNAsequences.
ClonedmurineRTisengineeredtomaintainpolymeraseandeliminateRnaseHactivity.
1988CongressfundstheHumanGenomeProject,amassiveefforttomapandsequencethehumangeneticcodeaswellasthegenomesofotherspecies.
1989Amgen'sEpogenisapprovedforthetreatmentofrenaldiseaseanemia.
MicroorganismsareusedtocleanuptheExxonValdezoilspill.
Thegeneresponsibleforcysticfibrosisisdiscovered.
1990s
1990Thefirstfederallyapprovedgenetherapytreatmentisperformedsuccessfullyona4-yearoldgirlsufferingfromanimmunedisorder.
1991AmgendevelopsNeupogen,thefirstofanewclassofdrugscalledcolonystimulatingfactors,forthetreatmentoflowwhitebloodcellsinchemotherapypatients.
Immunex'sLeukine,usedtoreplenishwhitebloodcountsafterbonemarrowtransplants,isapproved.
Genzyme'sCeredaseisapprovedforthetreatmentofGaucher'sdisease.
1992Thethree-dimensionalstructureofHIVRTiselucidated.
Recombinate,developedbyGeneticsInstituteandusedinthetreatmentofhemophiliaA,becomesthefirstgeneticallyengineeredbloodclottingfactorapprovedintheU.S.Chiron'sProleukinisapprovedforthetreatmentofrenalcellcancer.
1993Chiron'sBetaseronisapprovedasthefirsttreatmentformultiplesclerosisin20years.
TheFDAdeclaresthatgeneticallyengineeredfoodsare"notinherentlydangerous"anddonotrequirespecialregulation.
TheBiotechnologyIndustryOrganization(BIO)iscreatedbymergingtwosmallertradeassociations.
1994Genentech'sNutropinisapprovedforthetreatmentofgrowthhormonedeficiency.
Thefirstbreastcancergeneisdiscovered.
Calgene'sFlavrSavrtomato,engineeredtoresistrotting,isapprovedforsale.
1995Thefirstbaboon-to-humanbonemarrowtransplantisperformedonanAIDSpatient.
ThefirstfullgenesequenceofalivingorganismotherthanavirusiscompletedforthebacteriumHemophilusinfluenzae.
Thethree-dimensionalstructureofacatalyticallyactivefragmentofmurineRTiselucidated.
1996Biogen'sAvonexisapprovedforthetreatmentofmultiplesclerosis.Thecompanybuildsa$50millionplantinResearchTrianglePark,N.C.,tomanufacturetherecombinantinterferondrug.
Scottishscientistscloneidenticallambsfromearlyembryonicsheep.
1997Scottishscientistsreportcloningasheep,usingDNAfromadultsheepcells.
AgroupofOregonresearchersclaimstohaveclonedtwoRhesusmonkeys.
AnewDNAtechniquecombinesPCR,DNAchips,andacomputerprogram,providinganewtoolinthesearchfordisease-causinggenes.
1998UniversityofHawaiiscientistsclonethreegenerationsofmicefromnucleiofadultovariancumuluscells.
Humanskinisproducedinvitro.
Embryonicstemcellsareusedtoregeneratetissueandcreatedisordersmimickingdiseases.
Thefirstcompleteanimalgenomefortheeleganswormissequenced.
Aroughdraftofthehumangenomemapisproduced,showingthelocationsofmorethan30,000genes.
ClonedvainRTwithfullyactivepolymeraseandminimizedRnaseHactivityisengineered.
TheBiotechnologyInstituteisfoundedbyBIOasanindependentnational,501(c)(3)educationorganizationwithanindependentBoardofTrustees.
1999Thecompletegeneticcodeof
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