BC1750TheSumeriansbrewbeer.500TheChineseusemoldysoybeancurdsasanantibiotictotreatboils.250TheGreekspracticecroprotationtomaximizesoilfertility.100PowderedchrysanthemumisusedinChinaasaninsecticide.AD:Beforethe20thCentury1590ThemicroscopeisinventedbyJanssen.1663CellsarefirstdescribedbyHooke.1675Leeuwenhoekdiscoversprotozoaandbacteria.1797Jennerinoculatesachildwithaviralvaccinetoprotecthimfromsmallpox.1802Thewordbiologyfirstappears.1824Dutrochetdiscoversthattissueiscomposedoflivingcells.1830Proteinsarediscovered.1833Thecellnucleusisdiscovered.Thefirstenzymesareisolated.1855TheEscherichiacolibacteriumisdiscovered.Itlaterbecomesamajorresearch,development,andproductiontoolforbiotechnology.Pasteurbeginsworkingwithyeast,eventuallyprovingtheyarelivingorganisms.1863Mendel,inhisstudyofpeas,discoversthattraitsweretransmittedfromparentstoprogenybydiscrete,independentunits,latercalledgenes.Hisobservationslaythegroundworkforthefieldofgenetics.1869MiescherdiscoversDNAinthespermoftrout.1877AtechniqueforstainingandidentifyingbacteriaisdevelopedbyKoch.1878ThefirstcentrifugeisdevelopedbyLaval.Thetermmicrobeisfirstused.1879Flemmingdiscoverschromatin,therod-likestructuresinsidethecellnucleusthatlatercometobecalledchromosomes.1883Thefirstrabiesvaccineisdeveloped.1888ThechromosomeisdiscoveredbyWaldyer.AD:FirstHalfofthe20thCentury1902Thetermimmunologyfirstappears.1906Thetermgeneticsisintroduced.1907Thefirstinvivocultureofanimalcellsisreported.1909Genesarelinkedwithhereditarydisorders.1911Thefirstcancer-causingvirusisdiscoveredbyRous.1914BacteriaareusedtotreatsewageforthefirsttimeinManchester,England.1915Phages,orbacterialviruses,arediscovered.1919ThewordbiotechnologyisfirstusedbyaHungarianagriculturalengineer.1920ThehumangrowthhormoneisdiscoveredbyEvansandLong.1927MullerdiscoversthatX-rayscausemutation.1928Flemingdiscoverspenicillin,thefirstantibiotic.1938Thetermmolecularbiologyiscoined.1941ThetermgeneticengineeringisfirstusedbyaDanishmicrobiologist.1942Theelectronmicroscopeisusedtoidentifyandcharacterizeabacteriophage-avirusthatinfectsbacteria.1943AverydemonstratesthatDNAisthetransformingfactorandisthematerialofgenes.1944DNAisshowntobethematerialsubstanceofthegene.1949Paulingshowsthatsicklecellanemiaisamoleculardiseaseresultingfromamutation.1950to19601951McClintockdiscoverstransposableelements,orjumpinggenes,incorn.1953WatsonandCrickrevealthethree-dimensionalstructureofDNA.1954Cell-culturingtechniquesaredeveloped.1955Anenzymeinvolvedinthesynthesisofanucleicacidisisolatedforthefirsttime.1956ThefermentationprocessisperfectedinJapan.KornbergdiscoverstheenzymeDNApolymeraseI,leadingtoanunderstandingofhowDNAisreplicated.1957Sicklecellanemiaisshowntooccurduetoachangeofasingleaminoacid.1960Exploitingbasepairing,hybridDNA-RNAmoleculesarecreated.MessengerRNAisdiscovered.1961Thegeneticcodeisunderstoodforthefirsttime.1964Theexistenceofreversetranscriptase(RT)ispredicted.1967Thefirstautomaticproteinsequencerisperfected.1969Anenzymeissynthesizedinvitroforthefirsttime.1970s1970Specificrestrictionnucleasesareidentified,openingthewayforgenecloning.RTisdiscoveredindependentlyinmurineandavianretroviruses.1971RTisshowntohaveribonucleaseH(RnaseH)activity.1972TheDNAcompositionofhumansisdiscoveredtobe99%similartothatofchimpanzeesandgorillas.PurifiedRTisfirstusedtosynthesizecDNAfrompurifiedmRNAinvitro.1973CohenandBoyerperformthefirstsuccessfulrecombinantDNAexperiment,usingbacterialgenes.1974TheNationalInstituteofHealthformsaRecombinantDNAAdvisoryCommitteetooverseerecombinantgeneticresearch.1975ColonyhybridizationandSouthernblottingaredevelopedfordetectingspecificDNAsequences.Thefirstmonoclonalantibodiesareproduced.1976ThetoolsofrecombinantDNAarefirstappliedtoahumaninheriteddisorder.Molecularhybridizationisusedfortheprenataldiagnosisofalphathalassemia.YeastgenesareexpressedinE.colibacteria.1977Geneticallyengineeredbacteriaareusedtosynthesizehumangrowthprotein.1978NorthCarolinascientistsHutchinsonandEdgellshowitispossibletointroducespecificmutationsatspecificsitesinaDNAmolecule.1979Thefirstmonoclonalantibodiesareproduced.1980s1980TheU.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.Thefirstartifici