3/31/2017 Let Us Now Praise the Invention of the Microscope | Science | Smithsonian

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LetUsNowPraisetheInventionoftheMicroscope
Earlyscientistswieldedthisrevolutionarytooltostudytheinvisibleworldofmicrobes,andeventheirown
semen

Theimageshowsa6mmlong,12.5dayoldmouseembryoobtainedwiththeMesolens.Theinsetshowsablowupoftheeyeregionrevealingtheindividual
cellnuclei.Itispossibletoidentifyfinestructuresthroughouttheembryosuchasthedevelopingheartmusclefibersandfinedetailsintheeyesuchasthe
cornealendotheliumusingtheMesolens.(JohannaTrgrdh,UniversityofStrathclyde)

ByLauraPoppick
smithsonian.com
March30,20172:09PM

BradAmoshasspentmostofhislifethinkingaboutandlookingintotinyworlds.Now71yearsold,heworksasavisitingprofessoratUniversityofStrathclydein
Scotlandwhereheleadsateamofresearchersdesigninganextremelylargenewmicroscopelensaboutthelengthandwidthofahumanarm.NamedoneofPhysics
WorldsTopTenBreakthroughsof2016,thesocalledMesolensissopowerfulthatitcanimageentiretumorsormouseembryosinonefieldofviewwhile
simultaneouslyimagingtheinsidesofcells.

Ithasthelargecoverageofaphotographiccameralensandthefineresolutionofthemicroscopeobjective,soithastheadvantagesofthetwoapproaches,saysAmos.
Theimagesareextremelyuseful.

Today,microscopistslikeAmosareworkingaroundtheworldtoinnovatenewtechnologieswithwidespreadapplicationsinmedicineandhumanhealth.Butthese
cuttingedgeadvancementsalltracebacktotheveryfirstmicroscopesbuiltinthe16thand17thcenturies.Whilecuttingedgeforthetime,theywouldntimpressyou
muchthatwerentmuchstrongerthanahandheldmagnifyingglass.

Amoshasbeenobsessedwitheventhesesimplestofmicroscopeseversincehegotoneforabirthdayasakid.Hisintrigueinmicroscopicworldsbecameinsatiableashe
exploredanythinghecouldfind,fromtheforcewithintiny,poppingbubblestothewaypiecesofcoppermoldedunderthepokeofaneedle.Itslikeplaydough,itcan
beverysoft,Amossaysofcopper.Hedescribeshisaweatthephenomenahediscoveredunderthescopethathecouldntseewithhisbareeyes:Youarestudyinga
worldwhichdoesntevenobeythesamerulesofperception.

Thistypeofcuriosityinthegoingonsoftinyworldspropelledmicroscopyfromitsinception.ADutchfathersonteamnamedHansandZachariasJansseninventedthe
firstsocalledcompoundmicroscopeinthelate16thcenturywhentheydiscoveredthat,iftheyputalensatthetopandbottomofatubeandlookedthroughit,objectson
theotherendbecamemagnified.Thedevicelaidcriticalgroundworkforfuturebreakthroughs,butonlymagnifiedbybetween3xand9x.

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3/31/2017 Let Us Now Praise the Invention of the Microscope | Science | Smithsonian
Thequalityoftheimagewasmediocreatbest,saysStevenRuzin,amicroscopistandcuratoroftheGolubMicroscopeCollectionattheUniversityofCaliforniaat
Berkeley.Ihaveimagedthroughthemandtheyarereallyquiteawful,saysRuzin.Thehandlensesweremuchbetter.

Althoughtheyprovidedmagnification,thesefirstcompoundmicroscopescouldntincreaseresolution,somagnifiedimagesappearedblurryandobscured.Asaresult,no
significantscientificbreakthroughscamefromthemforabout100years,saysRuzin.

Butbythelate1600s,improvementstothelensesincreasedthequalityoftheimageandthemagnifyingpowertoupto270x,pavingthewayformajordiscoveries.In
1667,EnglishnaturalscientistRobertHookefamouslypublishedhisbookMicrographiawithintricatedrawingsofhundredsofspecimensheobserved,includingdistinct
sectionswithinthebranchofaherbaceousplant.Hecalledthesectionscellsbecausetheyremindedhimofcellsinamonasteryandthusbecamethefatherofcellular
biology.

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3/31/2017 Let Us Now Praise the Invention of the Microscope | Science | Smithsonian

DrawingsfromRobertHookesMicrographia,wherehedrawthefirstplantcelleverdiscoveredinthispinebranch.(RobertHooke,Micrographia/WikimediaCommons)

In1676,DutchclothmerchantturnedscientistAntonyvanLeeuwenhoekfurtherimprovedthecompoundmicroscopewiththeintentoflookingatthecloththathesold,
butinadvertentlymadethegroundbreakingdiscoverythatbacteriaexist.Hisaccidentalfindingopenedupthefieldofmicrobiologyandthebasisofmodernmedicine
nearly200yearslater,FrenchscientistLouisPasteurwoulddeterminethatbacteriawerethecausebehindmanyillnesses(beforethat,manyscientistsbelievedinthe
miasmatheorythatrottenairandbadodorsmadeussick).

Itwashuge,saysKevinEliceiri,amicroscopistattheUniversityofWisconsinMadison,oftheinitialdiscoveryofbacteria.Therewasalotofconfusionaboutwhat
madeyousick.Theideathattherearebacteriaandthingsinthewaterwasoneofthegreatestdiscoveriesever.

Thenextyear,in1677,Leeuwenhoekmadeanotherhallmarkdiscoverywhenheidentifiedhumanspermforthefirsttime.Amedicalstudenthadbroughthimthe
ejaculateofagonorrheapatienttostudyunderhismicroscope.Leeuwenhoekobliged,discoveredtinytailedanimals,andwentontofindthesamewriggling
animalculesinhisownsemensample.Hepublishedthesegroundbreakingfindingsbut,aswasthecaseforbacteria,200yearspassedbeforescientistsunderstoodthe
truesignificanceofthediscovery.

Bythelate1800s,aGermanscientistnamedWaltherFlemmingdiscoveredcelldivisionwhich,decadeslater,helpedclarifyhowcancergrowsafindingthatwould
havebeenimpossiblewithoutmicroscopes.

Ifyouwanttobeabletotargetpartofcellmembraneoratumor,youhavetowatchit,saysEliceiri.

WhiletheoriginalmicroscopesthatHookeandLeeuwenhoekusedmayhavehadtheirlimitations,theirbasicstructureoftwolensesconnectedbyatubesremained
relevantforcenturies,saysEliceiri.Inthepast15years,advancementsinimaginghavemovedintonewrealms.In2014,ateamofGermanandAmericanresearchers
wontheNobelPrizeinChemistryforamethodcalledsuperresolutionfluorescencemicroscopy,sopowerfulwecannowtracksingleproteinsastheydevelopwithin
cells.Thisevolvingmethod,madepossiblethroughaninnovativetechniquethatmakesgenesgloworfluoresce,haspotentialapplicationsincombattingdiseasessuch
asParkinsonsandAlzheimers.

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3/31/2017 Let Us Now Praise the Invention of the Microscope | Science | Smithsonian
AnItalianmicroscopemadeofivoryinthemid1600s,partofthe
GolubCollectionatUCBerkeley.(GolubCollectionatUCBerkeley.
)

RuzinheadstheBiologicalImagingFacilityattheUniversityofCaliforniaatBerkeley,whereresearchersusethetechnologytoexploreeverythingfrommicrostructures
withintheGiardiaparasiteandarrangementsofproteinswithinbacteria.Tohelpbringmodernmicroscopyresearchintocontext,hemakesapointofsharingsomeofthe
oldestitemsfromtheGolubCollectiononeofthelargestpubliclydisplayedcollectionsintheworld,containing164antiquemicroscopesdatingbacktothe15th
centurywithhisundergraduatestudents.Heevenletsthemhandlesomeoftheoldestinthecollection,includinganItalianonemadeofivoryaround1660.

Isaydontfocusitbecauseitwillbreak,butIletstudentslookthroughit,anditkindsofbringsithome,saysRuzin.

Still,despitethepowerofsuperresolutionmicroscopy,itdoesposenewchallenges.Forexample,anytimeaspecimenmovesunderhighresolution,theimageblurs,
saysRuzin.Ifacellvibratesjustbythermalmotion,bouncingaroundbywatermoleculeshittingitbecausetheyarewarm,thiswillkillsuperresolutionbecauseittakes
time,saysRuzin.(Forthisreason,researchersdontgenerallyusesuperresolutionmicroscopytostudylivesamples.)

ButtechnologylikeAmosMesolenswithamuchlowermagnificationofjust4xbutamuchwiderfieldofviewcapableofcapturingupto5mm,oraboutthewidthof
apinkyfingernailcanimagelivespecimen.Thismeanstheycanwatchamouseembryodevelopinrealtime,followinggenesassociatedwithvasculardiseasein
newbornsastheybecomeincorporatedintheembryo.Priortothis,scientistswoulduseXraystostudyvasculardiseaseinembryos,butwouldntgetdetaildowntothe
cellularlevelastheydowiththeMesolens,Amossays.

Itsalmostunheardofforanyonetodesignanewobjectivelensforlightmicroscopyandwehavedonethistotrytoaccommodatethenewtypesofspecimensthat
biologistswanttostudy,saysAmoscolleagueGailMcConnellatUniversityofStrathclydeGlasgow,explainingthatscientistsareinterestedinstudyingintact
organismsbutdontwanttocompromisetheamountofdetailtheycansee.

Sofar,thedatastorageindustryhasexpressedinterestinusingtheMesolenstostudysemiconductormaterials,andmembersoftheoilindustryhavebeeninterestedin
usingittoimagematerialsfromprospectivedrillingsites.Thelensdesignpicksuplightparticularlywell,allowingresearcherstowatchintricatedetailsunfoldsuchas
cellsinametastasizingtumormigratingoutward.Butthetruepotentialofthesenewtechniquesremainstobeseen.

Ifyoudevelopanobjectivedifferentthananythingthathasbeenmadeforthepast100years,itopensupallkindsofunknownpossibilities,saysAmos.Wearejust
beginningtogetatwhatthosepossibilitiesare.

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