7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

1/29

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

2/29

ConvergenceofDisciplines

ObjectivesToreviewthecomplexityofhealthanddiseasewithemphasisonhealthdisparities

Tosuggestanewresearchmodel---Convergence---holdspromiseforaddressingtheproblem

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

3/29

ConvergenceofDisciplines

InRetrospect BiologicalRevolutionsFirstRevolution;MolecularandCellularBiologySecondRevolution:Genomics(drivetostudyan

organismentiregenomics)

ThirdRevolution:Convergence---Thepathforward

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

4/29

ConvergenceofDisciplines

ProgressinHealthImprovementLifeexpectancyroseagainto78.2yearsin2009from78ayearearlier

Improvedunderstandingofsmokingasariskfactorformultiplediseases

Survivalrateforcanceris66%,upfrom50%in1975CVDprevalencedeclinedfrom6.7%to6.0%-2006to2010

THEDOWNSIDE:Healthdisparitiespersist

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

5/29

ConvergenceofDisciplines

TheConvergenceoftheLifeSciences,PhysicalSciences,

andEngineering

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

6/29

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

7/29

ConvergenceofDisciplines

HealthDisparitiesAfricanAmericanWomenhigherrateofmortalityofbreastcancer

Littleisknownaboutenvironmentalriskforbreastcancer

Associationwithexposureto1)ionizing,2)weightgainaftermenopause,3)industrialchemicals,4)

shiftworkNoevidenceofriskofhairdyes,cellphones,microwaveovens

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

8/29

ConvergenceofDisciplines

HealthDisparitiesType2diabetespoorlyunderstoodFailuretounderstandthemechanism(biologicalprocesses)ofdiseasessuchastype2diabetesandobesity Frustrates

efforttodevelopimprovedtreatmentand

preventionstrategies

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

9/29

ConvergenceofDisciplines

HealthDisparitiesCardiovascularDiseaseDisproportionateburdenonminorities

MechanismunderlyingindividualdifferencesinpresentationandpathophysiologicalfeaturesPoorlyunderstood

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

10/29

ConvergenceofDisciplines

HealthDisparities CardiovascularDisease:EstablishedRiskFactorsAgeHypertensionDiabetesTobaccouse

Accountfor50/60%ofCases

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

11/29

ConvergenceofDisciplines

HealthDisparitiesCardiovascularDiseaseOtherRiskFactors:ParticulateAirPollution

qKeyfactors/characteristicsParticlesizeChemicalcompositionofparticlesOtherphysicalandbiologicalfactors

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

12/29

ConvergenceofDisciplines

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

13/29

ConvergenceofDisciplines

CardiovascularDiseaseQUESTION:WhichchemicalcomponentsofairpollutionparticlesisresponsibleforCVDandotherhealtheffects?

ANSWER:UnknownIMPLICATIONS:Notpossibletotargettheirsourceforcontrol

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

14/29

ConvergenceofDisciplines

ConcerningHealthdisparities(HD)Complex,butimportantindicatorsofcommunityhealth

Researchmusttranscendboundariesofasingledisciplines

Challengeswithfingerprintsofscienceintheircausesandintheirsolutions

Theremaybenosingleorsimpleexplanationfordisparitiesinlifeexpectancyandmortality

Therearereasontobelievethatmolecularetiologicforcesinindividualsmayofferanexplanation

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

15/29

ConvergenceofDisciplines

ComplexityofDisease,therationaleforconvergence

Cancerisoftentreatedwithacombinationofsurgery,chemotherapy,radiation

QUESTION:whydoesaparticulartreatmenthelpsonepersonwithcoloncancer.while

someoneelsewithsamecancergetsametreatment,succumbstothedisease

Whyarecancercellssodifficulttokill?

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

16/29

ConvergenceofDisciplines

Investmentsinhealthdisparitieshasprovidedawealthofinformation Notsufficienttobetranslatedintointervention

designedtoclosethegapbetweenblack-whitemorbidity

WHY?Epidemiologist/otherscientistsestablishassociationswhichseemplausible

Theyarevalidatedwhenscientistsdemonstratesarobustbiologicalmechanism

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

17/29

ConvergenceofDisciplines

BiologicalMechanismoftheDiseaseThecellistheunitstructureinlivingorganismHence,itisinthecellwheretheeffectsorriskfactorsunfold;

Theproblemiscomplicatedatthecellularlevel.Examples:complexnetworksthatareinteracting

andconstantlychanging

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

18/29

ConvergenceofDisciplines

BiologicalMechanismsofDisease.

IN1970Researchersconcluded:theycouldtrulyunderstanddiseaseONLYiftheyunderstooditatthe

molecularlevelinsidethecell

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

19/29

ConvergenceofDisciplines

BiologicalMechanismsofDiseaseComplexity

Highcholesterollevelsareassociatedwithheartdisease

Someindividualswithhighcholesterolleveldonotdevelopheartdisease

Metastasisofagiventypeoftumoroccurwithfrighteningspeeds,butnotatallinothers.(geneticmakeupandenvironmentalhistory

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

20/29

ConvergenceofDisciplines

BiologicalMechanismofDiseaseComplexity

Question:Whatistherelationshipofanindividualsgeneticmakeupandenvironmentalhistoryto:

IndividualhealthriskSusceptibilitytodisease

Responsetotreatment

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

21/29

ConvergenceofDisciplinesBiologicalMechanismsofDisease

AnotherimportantConsiderationMechanismsmusttakeintoaccountnotonlyourhumangenomebutalsogenomeswithin thetrillionsofmicroorganisms(microbiome)thatareassociatedwitheachhumanbeing

Microbiome implicatedinavarietyofdisorders(i.e.metabolicsyndrome)

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

22/29

ConvergenceofDisciplines

InSummary

Aricherunderstandingofmechanisms:

ProvidesabasisforincreasedconfidencethatanygivenAssociationisjustifiablylabeledcausal.

Enhanceseffortstoidentifysubpopulationofindividualsatsubstantiallydifferentdegreesofrisk(i.e.geneticvariationsorsomaticvariations)

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

23/29

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

24/29

ConvergenceofDisciplines

WhatistheConvergenceofDisciplinesThemergingofnewtechnologies,processingdisciplines,ordevicesintoaunifiedwhole

Itinvolvethecomingtogetherofdifferentfieldofstudy

Combiningmolecularandcellularbiologywithgenomics,engineeringandknowledgeofthephysicalsciences

Convergencemodelrequirenotsimplycollaborationbetweendisciplinesbuttruedisciplinaryintegration

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

25/29

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

26/29

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

27/29

ConvergenceofDisciplines

Convergence:ExampleqConvergenceofengineeringwithlifesciencesEngineeringofferawayofthinkingthatcancontributesubstantivelytounravelingtheinherently

complexityofbiologicalscienceEngineersseektocreatesystemsthatcanoperatereliably

Engineeringdesignisalmostalwaysundertakenwithincompleteinformation

Bringinganengineeringmindsettobearonbiologicalquestionsisalreadyunderway

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

28/29

ConvergenceofDisciplines

Convergence:IssuesFragmentationwithinandacrossinstitutionalboundariesposesabarrier

Researchuniversitiesarestructuredarounddepartmentalstructure----analogoustoseparategovernmentalagents

Scientist:1)attendseparateprofessionalmeeting,2)belongtoseparateprofessionalsocieties,3)readseparatejournals,4)haveseparatevocabularies

7/31/2019 Convergence of Disciplines April 25,2012 10AMK[1]

29/29

Amajorscientificchallengeovertheforthcomingyearswillbetoputmechanistfleshon

thebarebonesoftheseassociations.

StephenORahilly

ConvergenceofDisciplines