A Mathematical Approach to Multilevel, Multiscale Health Interventions: Pharmaceutical Industry Decline and Policy Response

238 Pages·2013·16.202 MB·English

by  Rodrick Wallace, Deborah Wallace

A MATHEMATICAL APPROACH
TO MULTILEVEL, MULTISCALE
HEALTH INTERVENTIONS
Pharmaceutical Industry Decline and Policy Response
TThhiiss ppaaggee iinntteennttiioonnaallllyy lleefftt bbllaannkk
A MATHEMATICAL APPROACH
TO MULTILEVEL, MULTISCALE
HEALTH INTERVENTIONS
Pharmaceutical Industry Decline and Policy Response
Rodrick Wallace
Deborah Wallace
Columbia University, USA
Imperial College Press
ICP
Published by
Imperial College Press
57 Shelton Street
Covent Garden
London WC2H 9HE
Distributed by
World Scientific Publishing Co. Pte. Ltd.
5 Toh Tuck Link, Singapore 596224
USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601
UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
A MATHEMATICAL APPROACH TO MULTILEVEL, MULTISCALE
HEALTH INTERVENTIONS
Pharmaceutical Industry Decline and Policy Response
Copyright © 2013 by Imperial College Press
All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means,
electronic or mechanical, including photocopying, recording or any information storage and retrieval
system now known or to be invented, without written permission from the Publisher.
For photocopying of material in this volume, please pay a copying fee through the Copyright
Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to
photocopy is not required from the publisher.
ISBN 978-1-84816-996-8
Printed in Singapore.
Veronica - A Mathematical Approach.pmd 1 1/10/2013, 9:43 AM
January 10, 2013 9:26 P880 - Multiscale Health Interventions - 9in x 6in
Preface
Many physiological phenomena involve the transmission of information.
Even‘lowlevel’regulatoryprocesses,likegeneexpressionandtheoperation
of protein folding chaperones, can be interpreted as cognitive, in a formal
sense, and associated with a ‘dual’ information source. Calculation shows
thatisolationofsuchsourcesfromsignalcrosstalkbetweenthemconsumes
more metabolic free energy than does permitting correlation, allowing an
evolutionaryexaptationleadingtodynamicglobalbroadcastsofinteracting
physiological and larger cognitive modules at multiple scales and levels of
organization. This is similar to the well-studied exaptation of noise to
trigger stochastic resonance signal amplification.
Thelivingstateisthereforenotonlycharacterizedbycognitionatevery
scale and level, but by multiple, tunable, cooperative broadcasts that link
selected subsets of modules to address problems facing the organism. This
viewpointhasimplicationsforcurrenteffortsintranslationalmedicinethat
havefollowedthecollapseofpharmaceuticalindustrymagicbulletresearch.
The central focus of such work is to speed the application of results avail-
able from laboratory studies at the molecular and cellular levels to drug
development.
Itisincreasinglyclear,however,thatfailuretorespondtotheinherently
multilevel,multiscalenatureofhumanpathophysiologydoomstranslational
medicine: reductionist magic bullets are simply not enough. An essential
feature of the full dynamic is that the principal environment for humans
is other humans, their cultures, histories, and socioeconomic institutions –
a layered composition of larger scale, interpenetrating cognitive and other
structures and artifacts in which we all participate. Indeed, the evolution-
ary anthropologist Robert Boyd claims that culture is as much a part of
human biology as the enamel on our teeth.
v
January 10, 2013 9:26 P880 - Multiscale Health Interventions - 9in x 6in
vi MULTISCALE HEALTH INTERVENTIONS
It is, then, necessary to seek, rather than reductionist magic bullets,
carefully designed, synergistic, multilevel ‘magic strategies’ that will act
across the scales and levels of organization of the human cognome – the
overlapping assembly of cognitive modules within each human and the set
of those in which each human is embedded – to restore normal function for
individuals, populations, and even larger structures.
This book outlines a formal foundation for the design of such multi-
level, multiscale treatment strategies, based on statistical models derived
from the asymptotic limit theorems of information theory that provide a
toolset for data analysis and policy construction. This work synthesizes,
and significantly extends, a series of recently published papers, as listed
below.
The material is presented at an advanced undergraduate mathemati-
cal level, assuming some knowledge of probability, abstract algebra, and
calculus. Specialized topics are summarized in a Mathematical Appendix.
The most direct reading would be Chapters 1–3, followed by 10–12,
withdetailsfilledinasneededfromintermediatechaptersthatincorporate
examples of the methodology.
The approach should be of compelling interest to the broad spectrum
of scientifically informed policymakers who are called upon to pay the bill
for increasingly expensive rearrangements of deck chairs on a reductionist
biomedical Titanic.
Sources
Wallace, R., 2007, Culture and inattentional blindness: a global
workspace perspective, Journal of Theoretical Biology, 245:378–390.
Wallace, R., 2008, Developmental disorders as pathological resilience
domains, Ecology and Society, 13:29.
Wallace, R., 2010, Protein folding disorders: toward a basic biological
paradigm, Journal of Theoretical Biology, 267:582–594.
Wallace, R., 2010, Expanding the modern synthesis, Comptes Rendus
Biologies, 333:701–709.
Wallace, R., 2011, Structure and dynamics of the ‘protein folding code’
inferred using Tlusty’s topological rate distortion approach, BioSystems,
103:18–26.
Wallace, R., 2011, Multifunction moonlighting and intrinsically disor-
dered proteins: information catalysis, non-rigid molecule symmetries and
the ‘logic gate’ spectrum, Comptes Rendus Chimie, 14:1117–1121.
January 10, 2013 9:26 P880 - Multiscale Health Interventions - 9in x 6in
PREFACE vii
Wallace, R., 2012, Extending Tlusty’s rate distortion index theorem
methodtotheglycome: Doeven‘lowlevel’biochemicalphenomenarequire
sophisticated cognitive paradigms? BioSystems, 107:145–152.
Wallace, R., 2012, Spontaneous symmetry breaking in a non-rigid
molecule approach to intrinsically disordered proteins, Molecular BioSys-
tems, 8:374–377.
Wallace, R., 2012, Consciousness, crosstalk, and the mereologi-
cal fallacy: an evolutionary perspective, Physics of Life Reviews, doi
10.1016/j.plrev.2012.08.002.
Wallace, R., 2012, Metabolic constraints on the evolution of genetic
codes: didmultiple‘preaerobic’ecosystemtransitionsentrainricherdialects
viaSerialEndosymbiosis? TransactionsonComputationalSystemsBiology
XIV, LNBI 7625:204–232.
Wallace, R., D. Wallace, 2008, Punctuated equilibrium in statistical
models of generalized coevolutionary resilience: how sudden ecosystem
transitionscanentrainbothphenotypeexpressionandDarwinianselection,
Transactions on Computational Systems Biology IX, LNBI 5121:23–85.
Wallace, R., D. Wallace, 2009, Code, context, and epigenetic catalysis
in gene expression, Transactions on Computational Systems Biology XI,
LNBI 5750, 283–334.
Wallace, R., D. Wallace, 2011, Cultural epigenetics: on the heritability
ofcomplexdiseases,TransactionsonComputationalSystemsBiologyXIII,
LNBI 6575:131–170.
Wallace, R.G., R. Wallace, 2009, Evolutionary radiation and the spec-
trum of consciousness, Consciousness and Cognition, 18:160–167.
TThhiiss ppaaggee iinntteennttiioonnaallllyy lleefftt bbllaannkk
January 10, 2013 9:26 P880 - Multiscale Health Interventions - 9in x 6in
Contents
Preface v
1. BEYOND MAGIC BULLETS 1
1.1 The Pharmaceutical Catastrophe . . . . . . . . . . . . . . 1
1.2 A New Perspective . . . . . . . . . . . . . . . . . . . . . . 6
1.3 Cognition as ‘Language’ . . . . . . . . . . . . . . . . . . . 8
1.4 The Human Cognome . . . . . . . . . . . . . . . . . . . . 11
2. EXPANDING THE THEORY 19
2.1 No Free Lunch . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2 Multiple Broadcasts, Punctuated Detection . . . . . . . . 22
2.3 Metabolic Constraints . . . . . . . . . . . . . . . . . . . . 25
2.4 Environmental Signals . . . . . . . . . . . . . . . . . . . . 27
3. DYNAMIC ‘REGRESSION’ MODELS 29
3.1 The Simplest Approach . . . . . . . . . . . . . . . . . . . 29
3.2 A Rate Distortion Reformulation . . . . . . . . . . . . . . 35
3.3 Multiple Time Scales . . . . . . . . . . . . . . . . . . . . . 38
3.4 Incoming Information . . . . . . . . . . . . . . . . . . . . 39
3.5 Pathologies . . . . . . . . . . . . . . . . . . . . . . . . . . 40
3.6 Refining the Model . . . . . . . . . . . . . . . . . . . . . . 42
4. AN EVOLUTIONARY EXCURSION 47
4.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . 47
4.2 Ecosystems as Information Sources . . . . . . . . . . . . . 50
4.3 Genetic Heritage . . . . . . . . . . . . . . . . . . . . . . . 53
ix