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ObjectivesToreviewthecomplexityofhealthanddiseasewithemphasisonhealthdisparities
Tosuggestanewresearchmodel---Convergence---holdspromiseforaddressingtheproblem
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InRetrospect BiologicalRevolutionsFirstRevolution;MolecularandCellularBiologySecondRevolution:Genomics(drivetostudyan
organismentiregenomics)
ThirdRevolution:Convergence---Thepathforward
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ProgressinHealthImprovementLifeexpectancyroseagainto78.2yearsin2009from78ayearearlier
Improvedunderstandingofsmokingasariskfactorformultiplediseases
Survivalrateforcanceris66%,upfrom50%in1975CVDprevalencedeclinedfrom6.7%to6.0%-2006to2010
THEDOWNSIDE:Healthdisparitiespersist
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TheConvergenceoftheLifeSciences,PhysicalSciences,
andEngineering
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HealthDisparitiesAfricanAmericanWomenhigherrateofmortalityofbreastcancer
Littleisknownaboutenvironmentalriskforbreastcancer
Associationwithexposureto1)ionizing,2)weightgainaftermenopause,3)industrialchemicals,4)
shiftworkNoevidenceofriskofhairdyes,cellphones,microwaveovens
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HealthDisparitiesType2diabetespoorlyunderstoodFailuretounderstandthemechanism(biologicalprocesses)ofdiseasessuchastype2diabetesandobesity Frustrates
efforttodevelopimprovedtreatmentand
preventionstrategies
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HealthDisparitiesCardiovascularDiseaseDisproportionateburdenonminorities
MechanismunderlyingindividualdifferencesinpresentationandpathophysiologicalfeaturesPoorlyunderstood
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HealthDisparities CardiovascularDisease:EstablishedRiskFactorsAgeHypertensionDiabetesTobaccouse
Accountfor50/60%ofCases
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HealthDisparitiesCardiovascularDiseaseOtherRiskFactors:ParticulateAirPollution
qKeyfactors/characteristicsParticlesizeChemicalcompositionofparticlesOtherphysicalandbiologicalfactors
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CardiovascularDiseaseQUESTION:WhichchemicalcomponentsofairpollutionparticlesisresponsibleforCVDandotherhealtheffects?
ANSWER:UnknownIMPLICATIONS:Notpossibletotargettheirsourceforcontrol
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ConcerningHealthdisparities(HD)Complex,butimportantindicatorsofcommunityhealth
Researchmusttranscendboundariesofasingledisciplines
Challengeswithfingerprintsofscienceintheircausesandintheirsolutions
Theremaybenosingleorsimpleexplanationfordisparitiesinlifeexpectancyandmortality
Therearereasontobelievethatmolecularetiologicforcesinindividualsmayofferanexplanation
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ComplexityofDisease,therationaleforconvergence
Cancerisoftentreatedwithacombinationofsurgery,chemotherapy,radiation
QUESTION:whydoesaparticulartreatmenthelpsonepersonwithcoloncancer.while
someoneelsewithsamecancergetsametreatment,succumbstothedisease
Whyarecancercellssodifficulttokill?
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Investmentsinhealthdisparitieshasprovidedawealthofinformation Notsufficienttobetranslatedintointervention
designedtoclosethegapbetweenblack-whitemorbidity
WHY?Epidemiologist/otherscientistsestablishassociationswhichseemplausible
Theyarevalidatedwhenscientistsdemonstratesarobustbiologicalmechanism
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BiologicalMechanismoftheDiseaseThecellistheunitstructureinlivingorganismHence,itisinthecellwheretheeffectsorriskfactorsunfold;
Theproblemiscomplicatedatthecellularlevel.Examples:complexnetworksthatareinteracting
andconstantlychanging
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BiologicalMechanismsofDisease.
IN1970Researchersconcluded:theycouldtrulyunderstanddiseaseONLYiftheyunderstooditatthe
molecularlevelinsidethecell
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BiologicalMechanismsofDiseaseComplexity
Highcholesterollevelsareassociatedwithheartdisease
Someindividualswithhighcholesterolleveldonotdevelopheartdisease
Metastasisofagiventypeoftumoroccurwithfrighteningspeeds,butnotatallinothers.(geneticmakeupandenvironmentalhistory
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BiologicalMechanismofDiseaseComplexity
Question:Whatistherelationshipofanindividualsgeneticmakeupandenvironmentalhistoryto:
IndividualhealthriskSusceptibilitytodisease
Responsetotreatment
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ConvergenceofDisciplinesBiologicalMechanismsofDisease
AnotherimportantConsiderationMechanismsmusttakeintoaccountnotonlyourhumangenomebutalsogenomeswithin thetrillionsofmicroorganisms(microbiome)thatareassociatedwitheachhumanbeing
Microbiome implicatedinavarietyofdisorders(i.e.metabolicsyndrome)
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InSummary
Aricherunderstandingofmechanisms:
ProvidesabasisforincreasedconfidencethatanygivenAssociationisjustifiablylabeledcausal.
Enhanceseffortstoidentifysubpopulationofindividualsatsubstantiallydifferentdegreesofrisk(i.e.geneticvariationsorsomaticvariations)
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WhatistheConvergenceofDisciplinesThemergingofnewtechnologies,processingdisciplines,ordevicesintoaunifiedwhole
Itinvolvethecomingtogetherofdifferentfieldofstudy
Combiningmolecularandcellularbiologywithgenomics,engineeringandknowledgeofthephysicalsciences
Convergencemodelrequirenotsimplycollaborationbetweendisciplinesbuttruedisciplinaryintegration
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Convergence:ExampleqConvergenceofengineeringwithlifesciencesEngineeringofferawayofthinkingthatcancontributesubstantivelytounravelingtheinherently
complexityofbiologicalscienceEngineersseektocreatesystemsthatcanoperatereliably
Engineeringdesignisalmostalwaysundertakenwithincompleteinformation
Bringinganengineeringmindsettobearonbiologicalquestionsisalreadyunderway
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Convergence:IssuesFragmentationwithinandacrossinstitutionalboundariesposesabarrier
Researchuniversitiesarestructuredarounddepartmentalstructure----analogoustoseparategovernmentalagents
Scientist:1)attendseparateprofessionalmeeting,2)belongtoseparateprofessionalsocieties,3)readseparatejournals,4)haveseparatevocabularies
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Amajorscientificchallengeovertheforthcomingyearswillbetoputmechanistfleshon
thebarebonesoftheseassociations.
StephenORahilly
ConvergenceofDisciplines