AFRICAINTHEAGEOFBIOLOGY WilmotJames HSRC Publishers SCI 5_Africa Biology 007 8/25/04, 11:22 AM1 Free download from www.hsrcpublishers.ac.za SocialCohesionandIntegrationResearchProgramme,AfricaHumanGenomeInitiativeOccasionalPaperSeriesNo.3 SeriesEditor:Prof.WilmotJames,ExecutiveDirector:SocialCohesionandIntegrationResearchProgrammeofthe HumanSciencesResearchCouncil PublishedbyHSRCPublishers PrivateBagX9182,CapeTown,8000,SouthAfrica www.hsrcpublishers.ac.za ©2004HumanSciencesResearchCouncil Firstpublished2004 Allrightsreserved.Nopartofthisbookmaybereprintedorreproducedorutilisedinanyformorbyanyelectronic, mechanical,orothermeans,includingphotocopyingandrecording,orinanyinformationstorageorretrievalsystem, withoutpermissioninwritingfromthepublishers. ISBN0796920737 ProductionbycomPress DistributedinAfricabyBlueWeaverMarketingandDistribution, POBox30370,Tokai,CapeTown,7966,SouthAfrica. Tel:+27+21-701-4477 Fax:+27+21-701-7302 email:orders@blueweaver.co.za Distributedworldwide,exceptAfrica,byIndependentPublishersGroup, 814NorthFranklinStreet,Chicago,IL60610,USA. www.ipgbook.com Toorder,calltoll-free:1-800-888-4741 Allotherinquiries,Tel:+1+312-337-0747 Fax:+1+312-337-5985 email:Frontdesk@ipgbook.com SCI 5_Africa Biology 007 8/25/04, 11:22 AM2 Free download from www.hsrcpublishers.ac.za Preface The Human Sciences Research Council (HSRC) has established an occasional paper series. The occasional papers are designed to be quick, convenient vehicles for making timely contributions to debates or for disseminating interim research findings,ortheymaybefinished,publication-readyworks.Authorsinvitecomments andsuggestionsfromreaders. ThispaperwaspresentedasthefirstannualJohnGerhartMemorialLectureat theconferenceoftheAfricaGenomeInitiativeheldinCairofromMarch26to29, 2004.ConsiderationsofEgyptianscienceandartsandtheirlastingimpactonAfrica areafittingtributetotheroundednessofJohnGerhart,himselfanartcollectorof somenote,agiftedstory-teller,anenthusiasticbirder,aneconomistbytrainingand ascientistbyinclination,aphilanthropistofgreatempathyandskill,andauniversity presidentwithvisionandleadership.OneofthelastthingsJohnGerhartdidbefore hediedwas tovisit thatbirder’sdream, theGalapagos Islands,oncedescribedin thetitleofabookasEvolution’sworkshop(Larson2001).ItwasherethatCharles Darwinspentagreatdealoftimeobservingthebehaviourofspeciesofbeingsthat hadevolvedoverhundredsofthousandsofyearsinisolationandintheabsenceof naturalpredators.Ifyouapproachedandtouchedthosebirds,theydidnotflyaway. LikeJohnGerhart,theylackedthebiochemistryoftrepidation. SCI 5_Africa Biology 007 8/25/04, 11:22 AM3 Free download from www.hsrcpublishers.ac.za 1 SCI 5_Africa Biology 007 8/25/04, 11:22 AM4 Free download from www.hsrcpublishers.ac.za 1 AfricaintheAgeofBiology Harvard University’s RichardLewontininhis book Human diversity explainsthe meaning ofwhatis known in theworldof mathematics asMarkovianproperties operatingaspartofthedynamicsofphysicalandnaturalsystems. The properties were named after the St Petersburg University trained Russian mathematician whofirststudied them.AndreiMarkov (n.d.) isbest remembered forhisstudyofsequencesofrandomvariableswherethefuturestateofavariableis determinedbyacurrentvariablebutisindependentofthewayinwhichthepresent statearosefromitspredecessors.So,forexample,indemography,informationabout thesizeof,say,theEgyptianpopulationin2004dependsonlyonhowmanypeople werealivein2003andonthebirthanddeathratesamongthevariousageandsex cohorts,withouthaving toknowforpurposes ofpredictionhowthey cametobe so. Lewontintalks aboutMarkovianproperties inreference toanunderstanding of speciesevolutionandparticularlythatofhominids,whereallweneedtoknowin ourendeavourtopredictourfuturebiologicaltrajectoryisthepresentstateofour genes.Ourgenesare,nodoubt,asLewontinputit,‘aconsequenceoftheirhistory’, buthealsosaysthat‘thegenescurrentlypossessedbythespeciesareallthatmatters for itsevolutionary future, irrespectiveof howitacquired thosegenes’(Lewontin 1995:147). ProcessesofbiologicalevolutionworklikeMarkov’smathematicalchains,where memoryisinterestingbutirrelevant;forthereis,asLewontinputsit,no‘memoryin biology,onlyinbooks’(Lewontin1995:148).Afterthesequencingofthehuman genome,hemightnotbequitesocategoricalabouttheapparentlyahistoricalquality of genetic material, as molecular geneticists would certainly attribute ‘time’ to SCI 5_Africa Biology 007 8/25/04, 11:22 AM1 Free download from www.hsrcpublishers.ac.za WilmotJames 2 AfricaintheAgeofBiology 3 mutationaleventsthatarerecordedthereasjunkorrubbishortherealthing;but thenagainthismattersnot,foritisaboutwhatoneneedstoknowinordertopredict thefuture.History,howeveronemaywishtoconceiveofit,doesnotcountinthe caseofMarkovianproperties. By contrast, cultural systems such as modes of production, counting systems, language,writing,buildings,art,andsoon,alldependvitallyonanaccumulation of memory and well-functioning means of their transmission from generation to generation. Indeed,humanprogressinourstylesofmaterialandculturalmannerofliferelies onourabilitytostoreandpassonmemory.Herethelibrary,thearchitecturalstore ofwrittenhumanmemory,inbooksprincipally,orscrollsatthattimemorelikely, playedacentral,indisputablerole. And it is in illustrating the non-Markovian principle of muchofourcultural- historicalprocessesthatLewontintalksaboutthelibrariesofAlexandria:‘[T]helow stateofEuropeanculture,’hewrites,‘thatcontinuedlongafterthedisintegration ofRomewasinpartaconsequenceoftheimmenselossfromthefundoftechnical andhumanisticknowledgethatoccurredatthefinaldestructionofthelibrariesof Alexandriain391.’Hethenadds:‘Incontrast,Muslimculturegrewataprodigious ratebeginningintheseventhcenturypartlybecausetheknowledgeofclassicaltimes – knowledge then unavailable to the Latin and Greek scholars of Europe – was preservedinArabicmanuscripts’(Lewontin1995:148). ThereisnoquestionthatthelibrariesofAlexandriawerecentraltothecityand thebroadregionincludingwhattodayistheMiddle-East,NorthAfricaandmuchof CentralandWesternEurope;thattheywerenottheonlyonestoexistbutwerepart ofalargersetofinstitutionstoemergefromtheconcatenationsofcultural,scholarly andotherareasoflearningandapplicationofwhatwerethentheadvancedsocieties ofthispartoftheworld. Theagencyoftheirruinisnotsocertain,neitherisitclearwhatitwasinvolume andsubstance thatthelibrariesactually contained.Theinstitutionwascreatedby PtolemyISoterfirstasamuseumtowhichhissonPtolemyPhiladelphusaddeda library.ItwasJuliusCaesar,someclaimed,whodestroyedthelibrary,othersputthe blameonChristianmobs,andyetotherspeddlethestorythatitwas‘[o]ntheorders ofOmar,Caliph ofBaghdad,[that]theentirecollection ofbooks(exceptforthe worksofAristotle)storedattheLibraryofAlexandriawereremovedandusedasfuel toheatwaterforthecity’spublicbaths’(Librariesn.d.Accessed2004a+2004b). Theevidenceforwhathappenedisthin,andJamesHannan’sassessment,balanced itwouldseem,isthat‘CaesarwasmostprobablyresponsibleforthelossoftheRoyal SCI 5_Africa Biology 007 8/25/04, 11:22 AM2 Free download from www.hsrcpublishers.ac.za WilmotJames 2 AfricaintheAgeofBiology 3 Library’;asecondlibrarycalledtheSerapeum‘ceasedtobewhenaChristianmob tore it down to the foundations under the leadership of the orthodox patriarch TheophilusafterhehadreceivedwordfromtheEmperorTheodosius’(Librariesn.d. Accessed2004b).ThestoryaboutArabdestruction,bytheCaliphofBaghdad,isa myth,withoutanyevidenceitwouldseem.And,ofcourse,itisnotthefirsttime thatBaghdadhasbeenblamedforsomethingitdidnotdoornotblamedforwhat itdiddo. Thispaperstartswiththisstoryinpartbecausesome,ifnotmost,ofAristotle’s workwashousedintheAlexandrialibrary;andthisgreatfigure,principallyknownfor hisphilosophicalscholarship,wasalso,asthingstendedtobethen,oneoftheworld’s firstembryologistsanddevelopmentalbiologists.ThissameAristotle,whocollected and dissected embryos, and observed them closely, got the sex determination of humanbeings,wenowknow,terriblywrong.Heclaimedthatthesexofapersonwas determinedbytheheatofthemalepartnerduringintercourse.Themoreheatedthe passion,thegreatertheprobabilityofmaleoffspring.Hehadcounselledelderlymen toconceiveinthesummeriftheywishedtohavemaleheirs.ScottGilbertinhistext DevelopmentalbiologysaysaboutAristotlethathe‘promulgatedaverystraightforward hypothesisofsexdetermination.Womenweremenwhosedevelopmentwasarrested too early’(Gilbert 2000:523).With nosenseat allofthe microbiological,never mindthemolecularbiological,Aristotleandmanysincethenhadnotaclueabout theroleofXandYchromosomes,geneticheredityandtheboosttohumansurvival ofsexualasopposedtoasexualreproduction. Still,Aristotlewascrucialinthehistoryofbiologyandmedicineforhispainstaking observations,hismethod ofpursuing somekey questionsabouthumanity andits evolution,andhisunusualpreoccupationwithembryology,eventhoughhecould notrecognisethatsexualasopposedtoasexualreproductionwasnature’smasterful secrettohumanvarietyandsurvival. Egyptanditshistoryarewhatlieattheheartoftheearlyhistoryofmedicalbiology, engineering,physics,mathematics,architecture,artandliterature.Althoughscholars todaytendto thinkonly ofearly Egyptians’knowledgeofthemedicalbiology of mummificationandtheirunderstandingofanatomy,thebiochemistryofsoftand hard tissue,decay and preservation,it is clearas Sameh Arab,AssociateProfessor of Cardiology atAlexandriaUniversity writes, that ‘[s]omekindofmedicine was alreadypracticedinEgyptintheearliestprehistoricdays’.HereferstotheKahung gynaecology papyrus dating to 1825 BC which ‘describes methods of diagnosing pregnancyandthesexofthefetus,toothacheduringpregnancy,diseasesofwomen, aswellasfemininedrugs’andtotheEdwinSmithpapyrusof1600BC,whichcanbe SCI 5_Africa Biology 007 8/25/04, 11:22 AM3 Free download from www.hsrcpublishers.ac.za WilmotJames 4 AfricaintheAgeofBiology 5 describedasareferenceworkoninternalmedicine,dealingasitdoeswith‘diseasesof theeye,skin,extremities,gynecologyandsomesurgicaldiseases’(Arabn.d.).There is,ofcourse,muchmoretobesaidaboutancientEgyptianmedicineanditslinkwith modernbiology,butthatwillhavetobeleftforanothertime,anotherplace. ... Among some recentlyfoundfossils left in the StillBayarea along South Africa’s southernmostcoastlineby whatmust havebeen ancestralKhoi orSan peopleis a pieceofdecoratedochre,aformofironore.ItisnamedinAfrikaanstheblombos (flower-bush)ochreafterthecavewherethefossildiscoverieswerefound.Thename isanoddlinguisticconstruction,beingpartofthevocabularyusedtodescribethe indigenousfaunavarietyofthesouth-westernCapeknownasfynbos(fine-bush),to befoundonlythereinallofitssplendidvarietyandage. ChristopherHenshilwoodoftheStateUniversityofNewYork,thearchaeologist diggingatthissite,describestheredochreas‘measuringtwoandthreeincheslong’, ‘firstscrapedandgroundsmoothtocreateflatsurfaces’,and‘thenmarkedwithcross hatchesandlinestocreateaconsistentcomplexgeometricmotif’(Highfieldn.d.). Whatthesemarkingsmeanisopentodebate.Onemorecautiousinterpretationis that theyare‘tally marks’,‘makingthem the oldestform ofrecorded countingever found’[BlombosCaven.d.].Thereisnoindependentsourceofproofastowhatitis theseancestorswerecounting.Itcouldhavehadsomethingtodowiththeordinary material habits of hunters and gatherers, and likely the tallying of animal kills. Or, perhaps,itrelatedtotradingwithneighbours,or,moreonadeeplyexistentiallevel, observingtheastronomical,with,asGeorgesIfrahputsitsobeautifullyintheUniversal historyofnumbers,afascinationwiththeregularityof‘thephasesofthemoon,theeternal returnofdayandnight,thecycleoftheseasons’or,wemightadd,giventhecontext,the ellipticalphasesofthetidesofgreatandmarvellousoceans(Ifrah2000:xvi). Inthehistoryofcounting,theSanandKhoiperhapsjoinedotherhumanbeingsand, inobservingthatbirdshavetwowings,animalsfourlegs,andtheytenfingerstotheir handsandtentoestotheirfeet,developedanumberingsystemusingtheirfingersortoes asthebaseten,themostcommontypeofcountingfoundamongearlierpeoples. OrperhapstheyjoinedtheMayans,Aztecs,CeltsandBasqueswholookeddown attheirfeetandrealisedthattheirtoescouldbecountedlikefingersandchosethe muchmoreunusualarithmeticbaseof20. SCI 5_Africa Biology 007 8/25/04, 11:22 AM4 Free download from www.hsrcpublishers.ac.za WilmotJames 4 AfricaintheAgeofBiology 5 Or again, perhaps, they joined the SumeriansandBabylonians,whochosefor reasonsunknowntoustodayabaseof60,whichweuseinrespectofmeasuringtime, withanhourbeing60minutesandaminutebeing60seconds;orthemeasurement ofacircleinto360degrees,eachof60minutesdividedinto60seconds. Countingis,ofcourse,thecrucialfirststep;butitisnotarithmeticanditcertainly does not approach mathematics: the earliest known evidence for the arithmetic foundationsofmodernmathematicswasfoundinElamandMesopotamia,Sumeria, AncientEgypt,Crete,GreeceandRome. The mathematics of Ancient Egypt were quite obviously remarkable in their sophistication –proofof this are theremainsof one of thegreatwonders of the world: the pyramids, which were engineeredwithextraordinaryprecision and on ascalethatstretchesthemind.And,inconfirmationofthetestofallconstruction tests,theystillstandtoday,strippedperhaps,vandalisedyes,lootedcertainly,butstill thereinalloftheirbeautyandgrace. Buildingthepyramidspresumedexpertiseinstonecutting,engineering,mathematics andphysics,nottomentionunderstandingandmasteringthebasicsofthephysicsof levers, navigation and water behaviour in moving these monstrous blocks of stone downthegreatriverNile.Theyare,intheirpracticalityandcomplexity,stunningto us;lookingaswedoinadmiration,backwardsathistory. This venture into biology and Africa is by way of counting and arithmetic then; becauseitisaninterestingdigressionintotheepistemologicallineageofmathematicsand, forreasonsthatwillbecomeclear,becausethereisacriticalmathematicalsidetohuman geneticswhichalsoindicateswhereAfricastandsinrelationtomodernbiologytoday. Themassmediahasover thelast fewyears beenreplete withnews andfeature storiesaboutdeoxyribonucleicacidorDNAandwhatitmeansandmightmeanfor medicine,forensics,humanoriginsandpopulationancestry.Inpart,themediahas beencelebratingbecauseofthe50yearsofprogressthathavepassedsinceDNAwas firstdiscoveredashavinga double-helicalarchitecture, andin partbecause ofthe sometimesover-dramatisedadvancesinunderstandingandtreatinginheriteddisease regimesmadepossiblebythesequencingofthehumangenome,thefullrepertoireof ourbiologicalinstructions. Threebillionbase-pairnucleotidesmakeupthehumangenomeandtheseaddup toanunknownnumberofgenesintheregion,itissaid,ofabout32000.Nucleotide informationisdigital,inthattwoelementscombineinamannerfollowingtheruleof A(foradenine)combiningwithT(forthymine)andG(forguanine)andwithC(for cytosine),makingupachain–thefullextentofwhichwehavestilltounderstand fullyfromthepointofviewoffunctionandpurpose;butwedo,ofcourse,knowthe SCI 5_Africa Biology 007 8/25/04, 11:22 AM5 Free download from www.hsrcpublishers.ac.za WilmotJames 6 AfricaintheAgeofBiology 7 exactsequenceofallthegeneticlettersofthenucleotidealphabet.Indeed,genomes areencyclopaediasofgeneticmaterialscollectedquitemechanically,nottoprovea setofhypothesesbutsimplytodocumentwhatthereis–thehypothesescoming,as itwere,later.Andtheynowcomethickandfast. Mathematicswas required to countthe DNA.Mathematicalmolecular biology, calledbioinformatics,isrequiredtomakesenseoftheDNA,identifyanddiscoverthe candidategenesthataretheparticularstringsorchainsofDNAandbegintoascertain theirfunction.DescribedoncebytheSouthAfricanbornNobelLaureate,Sydney Brenner,intypicallysardonicandintellectuallydismissivemannerasanewbrandof libraryscience,bioinformaticsispartoftheessentialequipmentofeverygenehunter. Heorsheisthepersonwhocanmasterthesoftwareanddatamanagementassociated withmillionsandbillionsofbitsofdigitisedinformationthatadduptogenesand combinations of genes that programme the various parts of the human body, its maintenance, the death of cells and eventually the demise ofthe entire organism. Itisquiteabusiness,madepossiblebytheexponentialgrowthofcomputerisation, andinparticulartheworkofapersonafterwhomthewriter’svisitingprofessorship attheCaliforniaInstituteofTechnologyisnamed,GordonMoore.GordonMoore, founderofIntel,predictedthatthenumberoftransistorsthatcouldbeplacedona computerchipwoulddoubleevery18months,andsoithasbeenforover30years. Butpeopleshould notbemisledby SydneyBrenner’slovely,dolorous senseof humour:theinformationdemandsingenomicsarestaggering.Thegenomecontains twokindsofdigitalinformation,onethatencodestheproteinandRNA‘molecular machinesoflife’,andtheotherbeingtheregulatorynetworksthatspecifyhowthese genesareexpressedintime,spaceandamplitude. DNAinformationislayeredandarrangedinahierarchy,startingwiththegene, then the RNA, then the protein, then the protein interactions, then the protein complexes,thenthenetworksof proteincomplexes ina cell,then thetissues and organs,thentheindividualorganism,followedbypopulationsandtheecosystemsin whichtheylive.Inthiskindofdiscoveryscience,masteringsuchvastquantitiesof informationtoanswerimportantquestionsisaskillandanart. Andthehardware?Thefirstautomatedsequencingmachinetookaday,in1986, tosequence250ofthethreebillionbasepairs.Ittookthehumangenomeproject tenyearstosequencethehumangenome,twoyearsshorterthanpredicted;andthe privatecompanyCelerawithitsso-calledshotgunapproachtooklessthanthepublic consortium’s ten, using a warehouse of computers to do so. ‘With single-DNA- molecule sequencing, we foresee a time’ say the inventors of the first sequencing machine‘whentheentiregenomeofanindividualcouldbesequencedinasingle SCI 5_Africa Biology 007 8/25/04, 11:22 AM6 Free download from www.hsrcpublishers.ac.za . sense of humour: the informationdemands in genomicsarestaggering. The genomecontains twokinds of digitalinformation,onethatencodes the proteinandRNA‘molecular machines of life’,and the otherbeing the regulatorynetworksthatspecifyhowthese genesareexpressed in time,spaceandamplitude. DNAinformationislayeredandarranged in ahierarchy,startingwith the gene, then the RNA, then the protein, then the protein interactions, then the protein complexes,then the networks of . andnotonly in Africa, wherethereisastandingaccusation fromcertainquartersthatAfricaninstitutionsaremereplatformsfor the interests of the multinationalpharmaceuticalcompaniesanddonorcountryinterestsseekingless restrictiveplacestobio-prospect,testandmarketnewbiotechnologyproducts. Asatest of the integrity of whatitiswedo,weshouldaskhowbiotechnological research in Africa feedsbackinto the teaching of modern biology atitsuniversities, the training of the nextgeneration of researchscientists,and the establishmentand maintenance of qualityresearchlaboratories–ararecommodityonthiscontinent. We