biogen

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BC

1750TheSumeriansbrewbeer.

500TheChineumoldysoybeancurdsasanantibiotictotreatboils.

250TheGreekspracticecroprotationtomaximizesoilfertility.

100PowderedchrysanthemumisudinChinaasanincticide.

AD:Beforethe20thCentury

1590ThemicroscopeisinventedbyJansn.

1663CellsarefirstdescribedbyHooke.

1675Leeuwenhoekdiscoversprotozoaandbacteria.

1797Jennerinoculatesachildwithaviralvaccinetoprotecthimfromsmallpox.

1802Theword"biology"firstappears.

1824Dutrochetdiscoversthattissueiscompodoflivingcells.

1830Proteinsarediscovered.

1833Thecellnucleusisdiscovered.

Thefirstenzymesareisolated.

rbecomesamajorrearch,

development,andproductiontoolforbiotechnology.

Pasteurbeginsworkingwithyeast,eventuallyprovingtheyarelivingorganisms.

1863Mendel,inhisstudyofpeas,discoversthattraitsweretransmittedfromparentstoprogeny

bydiscrete,independentunits,ervationslaythegroundworkforthe

fieldofgenetics.

1869MiescherdiscoversDNAinthespermoftrout.

1877AtechniqueforstainingandidentifyingbacteriaisdevelopedbyKoch.

1878ThefirstcentrifugeisdevelopedbyLaval.

Theterm"microbe"isfirstud.

1879Flemmingdiscoverschromatin,therod-likestructuresinsidethecellnucleusthatlatercome

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tobecalled"chromosomes."

1883Thefirstrabiesvaccineisdeveloped.

1888ThechromosomeisdiscoveredbyWaldyer.

AD:FirstHalfofthe20thCentury

1902Theterm"immunology"firstappears.

1906Theterm"genetics"isintroduced.

1907Thefirstinvivocultureofanimalcellsisreported.

1909Genesarelinkedwithhereditarydisorders.

1911Thefirstcancer-causingvirusisdiscoveredbyRous.

1914BacteriaareudtotreatwageforthefirsttimeinManchester,England.

1915Phages,orbacterialvirus,arediscovered.

1919Theword"biotechnology"isfirstudbyaHungarianagriculturalengineer.

1920ThehumangrowthhormoneisdiscoveredbyEvansandLong.

1927MullerdiscoversthatX-rayscaumutation.

1928Flemingdiscoverspenicillin,thefirstantibiotic.

1938Theterm"molecularbiology"iscoined.

1941Theterm"geneticengineering"isfirstudbyaDanishmicrobiologist.

1942Theelectronmicroscopeisudtoidentifyandcharacterizeabacteriophage-avirusthat

infectsbacteria.

1943AverydemonstratesthatDNAisthe"transformingfactor"andisthematerialofgenes.

1944DNAisshowntobethematerialsubstanceofthegene.

1949Paulingshowsthatsicklecellanemiaisa"moleculardia"resultingfromamutation.

1950to1960

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1951McClintockdiscoverstransposableelements,or"jumpinggenes,"incorn.

1953WatsonandCrickrevealthethree-dimensionalstructureofDNA.

1954Cell-culturingtechniquesaredeveloped.

1955Anenzymeinvolvedinthesynthesisofanucleicacidisisolatedforthefirsttime.

1956ThefermentationprocessisperfectedinJapan.

KornbergdiscoverstheenzymeDNApolymeraI,leadingtoanunderstandingofhowDNAis

replicated.

1957Sicklecellanemiaisshowntooccurduetoachangeofasingleaminoacid.

1960Exploitingbapairing,hybridDNA-RNAmoleculesarecreated.

MesngerRNAisdiscovered.

1961Thegeneticcodeisunderstoodforthefirsttime.

1964Theexistenceofrevertranscripta(RT)ispredicted.

1967Thefirstautomaticproteinquencerisperfected.

1969Anenzymeissynthesizedinvitroforthefirsttime.

1970s

1970Specificrestrictionnucleasareidentified,openingthewayforgenecloning.

RTisdiscoveredindependentlyinmurineandavianretrovirus.

1971RTisshowntohaveribonucleaH(RnaH)activity.

1972TheDNAcompositionofhumansisdiscoveredtobe99%similartothatofchimpanzees

andgorillas.

PurifiedRTisfirstudtosynthesizecDNAfrompurifiedmRNAinvitro.

1973CohenandBoyerperformthefirstsuccessfulrecombinantDNAexperiment,usingbacterial

genes.

1974TheNationalInstituteofHealthformsaRecombinantDNAAdvisoryCommitteetoovere

recombinantgeneticrearch.

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1975ColonyhybridizationandSouthernblottingaredevelopedfordetectingspecificDNA

quences.

Thefirstmonoclonalantibodiesareproduced.

1976ThetoolsofrecombinantDNAarefirstappliedtoahumaninheriteddisorder.

Molecularhybridizationisudfortheprenataldiagnosisofalphathalasmia.

cteria.

1977Geneticallyengineeredbacteriaareudtosynthesizehumangrowthprotein.

1978NorthCarolinascientistsHutchinsonandEdgellshowitispossibletointroducespecific

mutationsatspecificsitesinaDNAmolecule.

1979Thefirstmonoclonalantibodiesareproduced.

1980s

eCourt,barty,approvesthe

principleofpatentinggeneticallyengineeredlifeforms.

forgenecloningisawardedtoCohenandBoyer.

1981TheNorthCarolinaBiotechnologyCenteriscreatedbythestate'sGeneralAsmblyasthe

nation'-fiveotherstatesfollow

withbiotechnologycentersofvariouskinds.

Thefirstgene-synthesizingmachinesaredeveloped.

Thefirstgeneticallyengineeredplantisreported.

Micearesuccessfullycloned.

1982Humulin,Genentech'shumaninsulindrugproducedbygeneticallyengineeredbacteriafor

thetreatmentofdiabetes,isthefirstbiotechdrugtobeapprovedbytheFoodandDrug

Administration.

1983ThePolymeraChainReaction(PCR),whichusheatand

enzymestomakeunlimitedcopiesofgenesandgenefragments,laterbecomesamajortoolin

biotechrearchandproductdevelopmentworldwide.

ThefirstgenetictransformationofplantcellsbyTIplasmidsisperformed.

Thefirstartificialchromosomeissynthesized.

Thefirstgeneticmarkersforspecificinheriteddiasarefound.

Efficientmethodsaredevelopedtosynthesizedouble-strandedDNAfromfirst-strandcDNA

involvingminimallossofquenceinformation.

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1984TheDNAfingerprintingtechniqueisdeveloped.

Thefirstgeneticallyengineeredvaccineisdeveloped.

ChironclonesandquencestheentiregenomeoftheHIVvirus.

.

1986Thefirstfieldtestsofgeneticallyengineeredplants(tobacco)areconducted.

OrthoBiotech'sOrthocloneOKT3,udtofightkidneytransplantrejection,isapprovedasthe

firstmonoclonalantibodytreatment.

Thefirstbiotech-derivedinterferondrugsforthetreatmentofcancer,Biogen'sIntronAand

Genentech'sRoferonA,1988,thedrugsareudtotreatKaposi's

sarcoma,acomplicationofAIDS.

Thefirstgeneticallyengineeredhumanvaccine,Chiron'sRecombivaxHB,isapprovedforthe

preventionofhepatitisB.

1987Humatropeisdevelopedfortreatinghumangrowthhormonedeficiency.

AdvancedGeneticSciences'Frostban,ageneticallyalteredbacteriumthatinhibitsfrostformation

oncropplants,isfieldtestedonstrawberryandpotatoplantsinCalifornia,thefirstauthorized

outdoortestsofanengineeredbacterium.

Genentech'stissueplasminogenactivator(tPA),soldasActiva,isapprovedasatreatmentfor

heartattacks.

RevertranscriptionandPCRarecombinedtoamplifymRNAquences.

ClonedmurineRTingineeredtomaintainpolymeraandeliminateRnaHactivity.

1988CongressfundstheHumanGenomeProject,amassiveefforttomapandquencethe

humangeneticcodeaswellasthegenomesofotherspecies.

1989Amgen'sEpogenisapprovedforthetreatmentofrenaldiaanemia.

MicroorganismsareudtocleanuptheExxonValdezoilspill.

Thegeneresponsibleforcysticfibrosisisdiscovered.

1990s

1990Thefirstfederallyapprovedgenetherapytreatmentisperformedsuccessfullyona4-yearold

girlsufferingfromanimmunedisorder.

1991AmgendevelopsNeupogen,thefirstofanewclassofdrugscalledcolonystimulating

factors,forthetreatmentoflowwhitebloodcellsinchemotherapypatients.

Immunex'sLeukine,udtoreplenishwhitebloodcountsafterbonemarrowtransplants,is

approved.

Genzyme'sCeredaisapprovedforthetreatmentofGaucher'sdia.

1992Thethree-dimensionalstructureofHIVRTilucidated.

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Recombinate,developedbyGeneticsInstituteandudinthetreatmentofhemophiliaA,becomes

'sProleukinis

approvedforthetreatmentofrenalcellcancer.

1993Chiron'sBetaronisapprovedasthefirsttreatmentformultiplesclerosisin20years.

TheFDAdeclaresthatgeneticallyengineeredfoodsare"notinherentlydangerous"anddonot

requirespecialregulation.

TheBiotechnologyIndustryOrganization(BIO)iscreatedbymergingtwosmallertrade

associations.

1994Genentech'sNutropinisapprovedforthetreatmentofgrowthhormonedeficiency.

Thefirstbreastcancergeneisdiscovered.

Calgene'sFlavrSavrtomato,engineeredtoresistrotting,isapprovedforsale.

1995Thefirstbaboon-to-humanbonemarrowtransplantisperformedonanAIDSpatient.

Thefirstfullgenequenceofalivingorganismotherthanavirusiscompletedforthebacterium

Hemophilusinfluenzae.

Thethree-dimensionalstructureofacatalyticallyactivefragmentofmurineRTilucidated.

1996Biogen'panybuildsa

$50millionplantinRearchTrianglePark,N.C.,tomanufacturetherecombinantinterferondrug.

Scottishscientistscloneidenticallambsfromearlyembryonicsheep.

1997Scottishscientistsreportcloningasheep,usingDNAfromadultsheepcells.

AgroupofOregonrearchersclaimstohaveclonedtwoRhesusmonkeys.

AnewDNAtechniquecombinesPCR,DNAchips,andacomputerprogram,providinganewtool

inthearchfordia-causinggenes.

1998UniversityofHawaiiscientistsclonethreegenerationsofmicefromnucleiofadultovarian

cumuluscells.

Humanskinisproducedinvitro.

Embryonicstemcellsareudtoregeneratetissueandcreatedisordersmimickingdias.

Thefirstcompleteanimalgenomefortheeleganswormisquenced.

Aroughdraftofthehumangenomemapisproduced,showingthelocationsofmorethan30,000

genes.

ClonedvainRTwithfullyactivepolymeraandminimizedRnaHactivityingineered.

TheBiotechnologyInstituteisfoundedbyBIOasanindependentnational,501(c)(3)education

organizationwithanindependentBoardofTrustees.

1999Thecompletegeneticcodeofthehumanchromosomeisfirstdeciphered.

TherisingtideofpublicopinioninEuropebringsbiotechfoodintothespotlight.

2000andBeyond

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2000AroughdraftofthehumangenomeiscompletedbyCeleraGenomicsandtheHuman

GenomeProject.

Pigsarethenextanimalclonedbyrearchers,hopefullytohelpproduceorgansforhuman

transplant.

"GoldenRice,"modifiedtomakevitaminA,promistohelpthird-worldcountriesalleviate

blindness.

The2.18millionbapairsofthecommonestcauofbacterialmeningitis,Neisriameningitidis,

areidentified.

2001ThequenceofthehumangenomeispublishedinScienceandNature,makingitpossible

forrearchersallovertheworldtobegindevelopingtreatments.

2002Scientistscompletethedraftquenceofthemostimportantpathogenofrice,afungusthat

ininganunderstandingofthe

genomesofthefungusandrice,scientistswillelucidatethemolecularbasisoftheinteractions

betweentheplantandpathogen.

2003Dolly,theclonedsheepthatmadeheadlinesin1997,iuthanizedafterdeveloping

asthefirstsuccessfulcloneofamammal.