Table Of ContentRodrick Wallace · Deborah Wallace
Gene
Expression and
Its Discontents
The Social Production of Chronic
Disease
Second Edition
Gene Expression and Its Discontents
Rodrick Wallace • Deborah Wallace
Gene Expression and Its
Discontents
The Social Production of Chronic Disease
Second Edition
123
RodrickWallace DeborahWallace
DivisionofEpidemiology NewYork,NY,USA
TheNewYorkStatePsychiatricInstitute
atColumbiaUniversity
NewYork,NY,USA
ISBN978-3-319-48077-0 ISBN978-3-319-48078-7 (eBook)
DOI10.1007/978-3-319-48078-7
LibraryofCongressControlNumber:2016955556
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Preface
Within the United States, beginning in the late 1980s, several chronic conditions
began epidemic increases of both incidence and prevalence. These conditions
includedasthma,obesity,obesity-relateddiseasessuchasdiabetes,certaincancers,
andAlzheimer’sdisease(AD).Scientificpapersdulyreportedtheexistenceofgenes
that putatively made their carriers more vulnerable to these conditions than the
generalpublic.However,thegeneticcompositionofUSpopulationsdidnotchange
so rapidly as to be a basis for these rapid epidemics. HIV/AIDs and tuberculosis,
although infectious, are classed as chronic diseases and also became epidemic in
the United States during these years. Mental disorders also form an important set
ofpersistentchronicconditionshaving“environmental”correlationsthatchallenge
simplegeneticetiologies.
Furthermore, many of these epidemics had geographic foci at multiple levels
of organization: neighborhood, municipality, county, state, and country. Many
conditions formed “syndemics”—multiple epidemics with the same geography.
Poor neighborhoods of color showed heightened incidence and prevalence within
citiesandformedthecentersfromwhichtheepidemicsspread.Poorneighborhoods
thathadexperiencedresidentialupheavalsandinstabilitiesparticularlyshowedgreat
vulnerability. Cities with residential and economic instability showed higher inci-
dence/prevalence than others and formed the foci of spread between metropolitan
regionsofthecountry.ThestatesoftheSoutheast,characterizedbyextremesocial
andeconomicinequality,rigidsocioeconomichierarchyovertime,loweducational
attainment, and a culture-based ideology of individualism, showed the highest
incidence/prevalenceofobesity,obesity-relateddiseasesandmortalities,AIDS,and
ADmortality.
Maps of prevalence and incidence reflect complex cognitive processes. Socioe-
conomic and environmental signals impinge on populations and their individual
constituents,havingvaryingsensitivityandvulnerability.Sensitivityandvulnerabil-
ityaredeterminedbytheinterlinkedfactorsofculture,historicaltrajectory,material
resources,socialstructureandstability,and,mostcentrally,publicpoliciesthatcan
mitigateorexacerbatethesefactors.
v
vi Preface
Individualsandpopulationsarecognitive—abletochooseoneorafewresponses
fromalargersetofthosepossible—andactinamultilevellinkedprocessagainst,
or consonant with, these signals. Within individuals, the signals and responses
involve internal cognitive processes, for example, the “fight or flight” response
to a perceived threat, a response involving the brain, pituitary gland, adrenal
gland, circulatory system, and energy regulatory mechanisms. Epigenetic changes
triggered by the signals or the initial recognition of the signals induce cognitive
geneticprocessesaswell.
The strong influence of cognitive processes at levels of organization from the
nationdowntothemolecularbiologyofindividualsimpliesthatinformationtheory,
controltheory,andmathematicalmodelingbasedonthemcandescribeandpredict
patterns of chronic disease in cultural and socioeconomic contexts. In this book,
we develop statistical models of such processes that are akin in spirit to—but
differentfrom—ordinaryregressionmodelsandreportempiricaldataandanalyses
toillustratethisparadigm.
The first six chapters use the asymptotic limit theorems of information theory
tounderstandhowepigeneticcontextaffectsorganismaldevelopmentbyinvokinga
cognitiveparadigmforgeneexpression.Asimpleargumentsuggeststhatepigenetic
information sources act as analogs to a tunable catalyst, directing development to
differentcharacteristicpathwaysinamannersimilartoecosystemresilienceshifts.
Theresultshavesignificantimplicationsforepigeneticepidemiology,showinghow
environmentalstressors,inalargesense,caninduceaspectrumofchronicdisorders.
Chapter 7 examines the US obesity epidemic from this viewpoint. Chapters 8
and9applytheperspectivetoheartdiseaseandcancerand,intheirlatersections,
introduce tools from control theory that illuminate the central role of “environ-
mental” context. Chapters 10–12 apply the general model to a number of diseases
broadly associated with obesity that are becoming pandemic, using US data at
different scales of observation. Chapters 13 and 14 study how “culture” and
“environment”affecttheonsetandprogressionofmentaldisorders.Chapters15–18
provide case histories involving low weight births, “Right-to-work” laws and AD,
diabetesandthyroidcancerinManhattan’sChinatown,andtheetiologyofviolence
andobesity.Chapter19exploresacompositemodelofpsychopathology,sleep,and
cultureinthecontextofenvironmentalinsult.
Thetheoryappears toworkverywellatindividual andsimpleaggregate levels
for anumber of chronic conditions instressedpopulations. Environments thatcan
be characterized as having regularities of “grammar” and “syntax” can interact
with organismal development via epigenetic catalysis to literally write distorted
images of themselves onto the human life course in a highly pleiotropic and
oftenpunctuatedmanner,producingtrajectoriestoarangeofseriousdysfunctions.
Communities, in which individuals respond collectively, however, display more
complicated patterns of chronic disease that may represent another example of a
“mesoscale resonance” in which the dynamics of ecological keystone structures
entrainphenomenaatotherscales.
One implication of this work is that pandemic chronic diseases at both the
individual, via pleiotropy, and the population scales, via collective modalities
Preface vii
of gene expression, are unlikely to respond to individual-level—i.e., medical—
interventionsinthefaceofserious,persistentindividualandcommunitystressand
may require large-scale changes in public policy and resource allocation for their
amelioration.Drugspowerfulenoughtoaffectdeleteriousepigeneticprogramming
are likely to trigger profound iatrogenic “side effects” that, over the life course,
wouldnotonlyobviatetheinterventionbutmostlikelyleadtoshortenedlifespans.
The book, a synthesis across a number of peer-reviewed publications and
additionalmaterialwrittenforthisvolume,canbereadatseverallevels.Chapters1
and 6–20 form a natural introductory unit that can be followed by the more
mathematicalsectionsasdesired.Mathematicaldetailsarecollectedinanappendix.
However,thecontroltheorymethodsintroducedinthelatterpartsofChaps.8and9
areusedextensivelyinChaps.14and19.
In sum, we provide something of a badly needed corrective to simplistic
“genetic”explanationsofchronicdiseasethat,politically,areinherentlyusefulfor
blamingthevictimandundercuttinginterventionstrategiesseenasdisruptivetothe
interestsofrulingelites.Wefocusinsteadonthegenerationofdiseasephenotypes
bysocialforcesthatcanbemitigatedoramplifiedbypublicpolicy.
NewYork,NY,USA RodrickWallace
DeborahWallace
Contents
1 Introduction ................................................................ 1
1.1 TowardNewTools.................................................. 1
1.2 EpigeneticEpidemiology........................................... 2
1.3 EcosystemResilience............................................... 6
1.3.1 ComorbidDisorders....................................... 7
1.3.2 SomeCognitiveModulesofHumanBiology............ 8
1.3.3 Cognitionas“Language”:anIntroduction............... 11
1.3.4 AMultiplicityofResilienceTopologies ................. 12
1.3.5 InSummary................................................ 14
1.4 AFirstSurveyoftheObesityPandemicintheUSA.............. 15
2 ModelsofDevelopment .................................................... 27
2.1 TheSpinglassModel ............................................... 27
2.2 ShiftingPerspective:CognitionasanInformationSource........ 30
3 GroupoidSymmetries...................................................... 35
3.1 TheFirstLevel...................................................... 36
3.2 TheSecondLevel................................................... 36
3.3 SpontaneousSymmetryBreaking.................................. 37
3.4 ABiologicalExample .............................................. 38
4 EpigeneticCatalysis........................................................ 43
4.1 TheBasicIdea ...................................................... 43
4.2 RateDistortionDynamics.......................................... 44
4.3 MoreTopology...................................................... 47
4.4 InheritedEpigeneticMemory ...................................... 48
4.5 MultipleProcesses.................................................. 49
4.6 “Coevolutionary”Development.................................... 50
4.7 MultipleModels .................................................... 51
4.8 EpigeneticFocus.................................................... 52
ix
x Contents
5 DevelopmentalDisorders.................................................. 55
5.1 NetworkInformationTheory....................................... 55
5.2 EmbeddingEcosystemsasInformationSources.................. 56
5.3 EcosystemsFarmDevelopment.................................... 56
5.4 ASimpleProbabilityArgument.................................... 59
5.5 DevelopmentalShadows............................................ 60
5.6 EpigeneticProgrammingofArtificialSystems
forBiotechnology................................................... 62
6 AnInterimPerspective..................................................... 63
7 TheObesityPandemicintheUSA........................................ 67
7.1 Introduction ......................................................... 67
7.2 StressandtheHPAAxis............................................ 68
7.3 HPAAxisCognition................................................ 69
7.4 InteractingInformationSources.................................... 69
7.5 AHPAAxisModel................................................. 71
7.6 PsychosocialStress,OccupationalControl,andWeightGain.... 74
7.7 ObesityasaDevelopmentalDisorder.............................. 74
7.8 RecentTrajectoriesofStructuredStressintheUSA.............. 75
7.9 ConfrontingtheObesityEpidemic................................. 82
8 HeartDisease................................................................ 87
8.1 CoronaryHeartDiseaseintheUSA ............................... 87
8.1.1 Cognition,ImmuneCognition,andCulture ............. 90
8.1.2 PunctuatedInterpenetration:Adaptingto
PathogenicHierarchy ..................................... 93
8.1.3 ImplicationsforIntervention ............................. 94
8.2 Thrombogenesis..................................................... 97
8.2.1 ControlTheory:TheDataRateTheorem................ 98
8.2.2 TheInformationCostofHemostaticRegulation........ 99
8.2.3 ControlFailureDynamics ................................ 101
8.2.4 CognitiveSymmetryBreaking ........................... 102
8.2.5 Onsetof“Turbulent”ClotGrowth ....................... 103
8.2.6 ImplicationsforIntervention ............................. 104
9 Cancer ....................................................................... 107
9.1 ADevelopmentalModel............................................ 107
9.2 EnvironmentalInsultandRegulatoryFailure ..................... 114
10 AutoimmuneDisorders .................................................... 121
10.1 Introduction ......................................................... 121
10.2 NonorthogonalEigenmodesofImmuneCognition............... 124
10.3 CircadianandOtherCycles ........................................ 126
10.4 TheRetinaoftheImmuneResponse .............................. 129
10.5 Circadian-HormonalCycleSynergism ............................ 130
10.6 TheCognitiveHPAAxis ........................................... 131
Contents xi
10.7 PhaseTransitionsofInteractingInformationSystems............ 132
10.8 AutoimmuneDisease............................................... 133
10.9 AnApplicationtoAsthma.......................................... 135
10.10 ImagesofPathogenicSocialHierarchy............................ 136
11 DemoralizationandObesityinUpperManhattan...................... 141
11.1 Introduction ......................................................... 141
11.2 Methods ............................................................. 142
11.2.1 RecruitmentoftheMothers............................... 142
11.2.2 PrenatalQuestionnaire.................................... 142
11.2.3 SocioeconomicData ...................................... 144
11.2.4 ChronicCommunityStressIndex........................ 144
11.3 DataAnalysis ....................................................... 147
11.4 ModelingDemoralizationandChronicStress..................... 147
11.5 Results............................................................... 148
11.5.1 DemoralizationandChronicStress ...................... 148
11.5.2 SignalTransductionModeling............................ 150
11.5.3 BodyMassIndex.......................................... 151
11.5.4 HouseholdDeprivation ................................... 152
11.6 Discussion........................................................... 154
11.6.1 TheAsymmetricInverted“U”Curve .................... 154
11.6.2 TheBodymassIndex..................................... 155
11.7 Conclusion .......................................................... 157
12 Death at an Early Age: AIDS and Related Mortality
inNewYorkCity ........................................................... 161
12.1 Introduction ......................................................... 161
12.2 DataandAnalysis................................................... 163
12.3 Results............................................................... 165
12.4 Discussion........................................................... 170
13 WesternAtomismandItsCulture-BoundSyndromes ................. 181
13.1 Introduction ......................................................... 181
13.2 WesternAtomisticEconomics ..................................... 183
13.3 CognitionasanInformationSource ............................... 185
13.4 EnvironmentasanInformationSource............................ 187
13.5 InteractingInformationSources.................................... 188
13.6 CrosstalkTopologies................................................ 189
13.7 PunctuatedCriticalPhenomena.................................... 190
13.8 Implications......................................................... 192
14 EnvironmentalInductionofNeurodevelopmentalDisorders.......... 195
14.1 Introduction ......................................................... 195
14.2 StabilizingGeneExpression ....................................... 197
14.3 TheCostofRegulation............................................. 198
14.4 Parsing(cid:2)............................................................. 198
14.5 TheDynamicsofControlFailure.................................. 199
