生物技术历史

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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