Immunity: the evolution of an idea 1st

Edition Alfred I. Tauber

Visit to download the full and correct content document:
https://textbookfull.com/product/immunity-the-evolution-of-an-idea-1st-edition-alfred-i-t
auber/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

To Conserve Unimpaired The Evolution of the National

Park Idea 1st Edition Prof. Robert B. Keiter K (Auth.)

https://textbookfull.com/product/to-conserve-unimpaired-the-
evolution-of-the-national-park-idea-1st-edition-prof-robert-b-
keiter-k-auth/

Salafi-Jihadism: The History Of An Idea Shiraz Maher

https://textbookfull.com/product/salafi-jihadism-the-history-of-
an-idea-shiraz-maher/

An Egyptian hieroglyphic dictionary Part I 2nd Edition

Budge E A Wallis Ernest Alfred Wallis Sir 1857 1934

https://textbookfull.com/product/an-egyptian-hieroglyphic-
dictionary-part-i-2nd-edition-budge-e-a-wallis-ernest-alfred-
wallis-sir-1857-1934/

An Introduction to Mathematics Alfred North Whitehead

https://textbookfull.com/product/an-introduction-to-mathematics-
alfred-north-whitehead/
The Digital Evolution of an American Identity 1st
Edition C. Waite

https://textbookfull.com/product/the-digital-evolution-of-an-
american-identity-1st-edition-c-waite/

Civil Society Second Edition The Critical History of an

Idea John R. Ehrenberg

https://textbookfull.com/product/civil-society-second-edition-
the-critical-history-of-an-idea-john-r-ehrenberg/

The Education of Children Alfred Adler

https://textbookfull.com/product/the-education-of-children-
alfred-adler/

A Genealogy Of Terrorism: Colonial Law And The Origins

Of An Idea Joseph Mcquade

https://textbookfull.com/product/a-genealogy-of-terrorism-
colonial-law-and-the-origins-of-an-idea-joseph-mcquade/

The Public Relations of Everything The Ancient Modern

and Postmodern Dramatic History of an Idea 1st Edition
Robert E. Brown

https://textbookfull.com/product/the-public-relations-of-
everything-the-ancient-modern-and-postmodern-dramatic-history-of-
an-idea-1st-edition-robert-e-brown/
Immunity
 Immunity
The Evolution of an Idea

A L F R E D I . TA U B E R

1
1
Oxford University Press is a department of the University of Oxford. It furthers
the University’s objective of excellence in research, scholarship, and education
by publishing worldwide. Oxford is a registered trade mark of Oxford University
Press in the UK and certain other countries.

Published in the United States of America by Oxford University Press

198 Madison Avenue, New York, NY 10016, United States of America.

© Oxford University Press 2017

All rights reserved. No part of this publication may be reproduced, stored in

a retrieval system, or transmitted, in any form or by any means, without the
prior permission in writing of Oxford University Press, or as expressly permitted
by law, by license, or under terms agreed with the appropriate reproduction
rights organization. Inquiries concerning reproduction outside the scope of the
above should be sent to the Rights Department, Oxford University Press, at the
address above.

You must not circulate this work in any other form

and you must impose this same condition on any acquirer.

Library of Congress Cataloging-​in-​Publication Data

Names: Tauber, Alfred I.
Title: Immunity : the evolution of an idea / Alfred I. Tauber.
Description: New York, NY : Oxford University Press, 2017.
Identifiers: LCCN 2016024105 | ISBN 9780190651244 (hardback : acid-free paper) |
ISBN 9780190651268 (ebook) | ISBN 9780190651275 (online resource)
Subjects: LCSH: Immunology—Philosophy. | BISAC: SCIENCE / Philosophy &
Social Aspects. | MEDICAL / Immunology.
Classification: LCC QR181 .T37 2017 | DDC 616.07/9—dc23 LC record available at
https://lccn.loc.gov/2016024105

9 8 7 6 5 4 3 2 1
Printed by Sheridan Books, Inc., United States of America
In memory of Lynn Margulis
Immunology has always seemed to me more a problem in philos-
ophy than a practical science.
Burnet (1965, p. 17)

In its historical development, the conceptualization of the immune

self has always suffered an “ontological obsession.”
Grignolio et al. (2014, p. 1)

Our imperative need for cause and effect is satisfied when each
process has one demonstrable cause. In reality, outside us this is
hardly so; each event seems to be over-​determined and turns out
to be the effect of several converging causes. Intimidated by the
countless complications of events research takes the part of one
chain of events against another, stipulates contrasts that do not
exist and that are created merely through tearing apart more com-
prehensive relations. … I do not mean to say that the world is so
complicated that every assertion must hit the truth somewhere.
No, our thinking has preserved the liberty of inventing dependen-
cies and connections that have no equivalent in reality. It obvi-
ously prizes this gift very highly, since it makes such ample use of
it—​inside as well as outside of science.
Freud (Moses and Monotheism 1939, p. 137)
 CONTENTS

Preface╇ ix
Acknowledgments╇ xvii

Introduction╇ 1

1. A History of the Immune Self╇ 23

2. Whither Immune Identity?╇ 57

3. Individuality Revised╇ 89

4. Immune Cognition╇ 129

5. Eco-╉immunology╇ 163

6. A New Biology?╇ 191

Epilogue╇ 219

Notes╇ 229
References╇ 255
Index╇ 295
 PREFACE

This book is about how ideas structure and orient the practice and the-
ory of a science. Such foundational ideas for the most part remain hid-
den, or at least implicit to the immediate goals of research. Indeed, the
most evident task of science is a practical enterprise; nevertheless, the tacit
dimension of intellectual (and often ideological) commitments is always
at play, guiding interpretations of data and the assembling of facts into
models and then theory. So, although Frank Macfarlane Burnet used a
bit of hyperbole when observing that immunology was “more a problem
in philosophy than a practical science” (Burnet 1965, p. 17), I fully con-
cur with his basic insight: Much of immunology fascinates because of its
intellectual challenges, the vibrancy of its key ideas, and the scope of phil-
osophical issues the study of immunology might address.
Immunology, from its earliest inception, has been concerned with
biological identity—​ its establishment and maintenance. Three key
characteristics—​ individuality, immunity, and identification—​ together
define immune identity, and as one notion changes meaning, so do the
others. Individuality framed immune theory from its inception, for the
attack of pathogens on a vulnerable patient (individual) defined the task
of immunity, namely to defend a self pitted against alien others. In this
scenario, distinct borders confer guarded individuality, and immunity
is the response to the violation of those boundaries. Simply, the individ-
ual is “self-​contained.” Contemporary immunology now recognizes the
fluidity of borders in the dialectical exchange of the organism with its
x Preface

environment, where the beneficial is absorbed through the active toler-

ance of the immune system. So beyond a defense of an insular individual,
the ecological context of the organism has changed the definition of indi-
viduality and the processes responsible for such differentiation. Moreover,
the concept of the organism as a holobiont, characterized by multiple
species living together in complex immune relationships, has further
deconstructed older versions of biological individuality. Add the growing
appreciation of the prevalence of symbiosis and the concept of an “indi-
vidual” has radically been altered.
In response to this ecologically informed conception of the individual,
the idea of immunity correspondingly widens. Accommodating the relaxed
criteria of “self ” and “other” requires appreciation of how the immune sys-
tem permits beneficial exchanges to occur. The shift from the almost exclu-
sive focus on aggressive immune responses to the study of the balance of
reactivities on an immune activation gradient has altered the basic notions
of what immunity is. Instead of immunity regarded exclusively as a defen-
sive state, it becomes an ongoing process of establishing and maintaining
organismal identity—​processes that require a group of physiological activ-
ities with protean functions. This reassessment includes the normal house-
keeping sentinel activities that monitor the host organism, where, again,
the self/​other distinction is replaced with a spectrum of immune responses
along a functional gradient.
Finally, in conceptually reconfiguring immunity, the immune system’s
identification processes are understood as determined not by recognition
of toxicity per se but, rather, by the context of the encounter in which the
potential danger is recognized. The classification of friend or foe is deter-
mined by multiple factors that together create the setting for the immune
response. Thus, in terms of understanding the nature of the immunity, this
contextual orientation has displaced the earlier understanding of immune
specificity as arising from some simple mechanical lock and key matching
between selected antibodies binding to simple antigens to one character-
ized by a collective response of diverse elements that together determine
the extent of the immune response. Here, two corollaries follow. First, a
simple “cue ball” mechanical model (a linear stimulus sequence) cannot
Preface xi

capture the dynamic modes of causation that characterize immune func-

tions, and from this understanding, a simple self/​nonself discriminatory
schema fails to account for immunity. So on this view, immune identity
is dynamic, and thus the notion of the immune self (an entity that lacks
singular definitional criteria, in any case) fails to ground immune theory.
Another account is required, and here an outline of such a revision is
offered.
Amending immunology’s governing precepts along these lines poses
philosophical evaluation of five major questions, each of which refracts
the underlying challenge of defining biological identity: (1) What is
immunity? (2) What are the defining characteristics of individuality as
determined by immunity? (3) What are the epistemological standing of
immune selfhood and the rhetorical uses of agency in its various forms
(literal, metaphoric, and idiomatic)? (4) How has the cognitive meta-
phor framed immune processes as an information processing system?
and (5) How to model biological causation of the immune system stud-
ied as a whole? Each of these issues directly pertains to philosophical
considerations about the character of the organism, the relationships of
parts to the whole, principles of biological organization and regulation,
and the ability of models to capture complex organic functions. The lit-
erature pertinent to addressing these issues is legion, but in regard to the
study of immunology, relatively little direct philosophical comment has
been made. Plainly, immunology is a rich philosophical mine yet to be
explored.

The basic position developed here is that the idea of immunity is insep-
arable from how immune identity is construed because (1) differing
constructions of identity yield different notions of immunity and, recip-
rocally, (2) different modalities of immunity confer distinctive con-
ceptions of agency. The story of this mutual dependence begins at the
origins of immunology. With the discovery of infectious diseases, the vio-
lated organism, regarded as an autonomous entity, required protection.
However, the insularity characterizing such an animal proved unstable,
and so when we peer at immunology’s development, the striking ways
xii Preface

in which the meanings of immune agency have shifted mark the disci-
pline’s history. The science is now expanding beyond an exclusive focus
on defense to a broadened ecological orientation in which immunity
becomes a mediator of environmental exchange of both the dangerous
and the benign. This broadened bidirectionality—​attack balanced against
(active) tolerance—​is radically altering the science’s organizing principles
and its corresponding research agenda. In short, moving from a defensive
posture to a fully ecological alignment heralds a major shift in immunol-
ogy’s governing theory and a correction of its understanding of immune
selfhood at the heart of the discipline’s conceptual history. Note that I do
not envision immunology devoid of its semantic and theoretical depen-
dence on notions of agency, but simple dichotomies characterizing cur-
rent models fail to capture the dynamic forces at play.
This study presents a scientific, linguistic, and philosophical analysis
of immune identity along two thematic lines. The historically dominant
model asserts that the immune system protects a self, a conception that
incorporates the following three cardinal features: (1) A “self ” exists;
(2) this entity has certain identifying characteristics, of which immune
tolerance distinguishes that which is “self ” from “the other” (or non-
self); and (3) identity arises as a developmental process, which may be
modulated throughout life but essentially represents a protected “space”
of immune silence (nonreactivity). This account of demarcation derives
from a prominent Western anthropocentric extrapolation, one that may
be directly traced to the original clinical orientation in which immunol-
ogy emerged—​a threatened self. As previously mentioned, this theoretical
scenario has been challenged by what I call the “ecological imperative,”
which works by an altogether different construction, one that displaces
immunology as the science of self-​defense for one in which organismal
identity emerges in dialogue with both internal and external environ-
ments. According to this alternate point of view, a biology that ignores the
larger context in which immune mechanisms operate will fail to explain
immunity’s full functional panoply.
To compose a more comprehensive design, I argue that immunity is
fundamentally an information-​processing faculty, and like the nervous
Preface xiii

system, the immune system perceives and then mediates environmen-

tal information (organic and inorganic; internal and external). That role
has evolved under pressures to maximize the organism’s fitness in an
environment composed of both friend and foe. On this ecological view,
immune reactivity (rejection or tolerance) is a second-​order response to
the immune system’s primary cognitive functions. This dynamic orienta-
tion, in acknowledgment of the organism’s flexible borders and changing
parameters of individuality, dispenses with any characterizing essences—​
genetic, molecular, or immune. Study of this commerce leads to models
of the various interactions among organisms that capture how individuals
exist in their complex ecology, in terms of both defensive and cooperative
relationships. To remain restricted within an analysis that only assumes
a protective posture limits the understanding of how animals live in
exchange with others. Thus, when the immune system is conceived in its
more basic perceptive role, “defense” becomes only one of several subordi-
nated physiological functions. In short, immunity is more than immunity
as originally construed.
Such an understanding commits immunology to holistic constructs
and a widened research agenda. That effort requires the reconceptualiza-
tion of selfhood, one that breaks the formal alterity of “the other” and
thus denies a rigid subject–​object dichotomy. This view is hardly radical.
Immunologists have long appreciated that the original theories outlin-
ing self/​nonself discrimination severely limit the comprehension of those
multifaceted immune-​mediated interchanges, which characterize biologi-
cal organization and regulation (Vaz 2016). Indeed, from an ecological
perspective, there can be no circumscribed, self-​defined entity that is des-
ignated the self because not only can such an entity not be defined but also
immunity itself is highly dependent on extraneous factors. For instance,
immune identity changes as a result of previous immune encounters, the
context of the organism’s placement in the environment, the immune sta-
tus of the animal, and other factors that contribute to the final adjudica-
tion of the immune response. Some essential core of immune identity is
no longer the operative foundation of immunity but, rather, the process
of information transfer—​both within the borders of the organism and in
xiv Preface

dialogue with the external environment—​becomes the dominant issue in

understanding immune regulation.
This alternate orientation opposes a long (and accomplished) record of
research success directed at discerning the particular mechanisms of host
defense, which has been the study of immunity in its fully activated state.
However, when immunity is regarded as mediating normal exchanges
with the environment, such intercourse requires active “acceptance” of
“the other.” Note that tolerance invokes a different modality of immune
cognizance—​ regulated quiescence as opposed to triggered assault.
Consequently, “immunity” modulates its original meaning as a state of
defense to include those processes directed at establishing identity and
maintaining the organism’s balanced placement in the environment. With
that conceptual turn, an ecological orientation attains equal partnership
with an older organism-​centered biology (Nicholson 2014).
Such an approach will likely push immunology toward a major revision
in its underlying theory, where defense of autonomous entities is replaced
with more comprehensive models describing the organism’s interactions
in a community of others—​for good and ill. This enlarged vision of immu-
nity places immunobiology fully within the organism’s environment,
and by characterizing the ecological economy in which the organism
lives, immunology assumes a central role among the ecological sciences.
Immunity: The Evolution of an Idea is organized around this ecological ori-
entation, one informed by the larger influence of placing immunity in its
evolutionary context as the mediator of environmental interactions. My
appreciation of how immunology is both framed by this understanding
and contributes to it begins with Lynn Margulis (1938–​2011), to whose
memory this study is dedicated.
I first met Lynn when we were colleagues at Boston University in the
late 1980s. Little did I understand at the time how influential Lynn’s pro-
motion of serial endosymbiosis theory (SET) in explaining evolution
would be on my own intellectual development. Now, 25 years later, I rec-
ognize that influence. According to SET, the evolution of eukaryotic cells
arose from both classical Darwinian natural selection and symbiotic
mergers of prokaryotic organisms. In 1967, Lynn presented the hypothesis
Preface xv

that symbiosis of eubacteria and archaebacteria into early cells gave rise
to intracellular organelles: Mitochondria were descended from parasitoid
bacteria, and chloroplasts arose from once free-​living photosynthetic bac-
teria. Robert Schwartz and Margaret Dayhoff proved the symbiogenesis
hypothesis in 1978 by showing that mitochondria and chloroplasts pos-
sess their own genes and their own translation machinery (reviewed in
Lang, Gray, and Burger 1999).
The evolutionary role of symbioses had been repeatedly postulated
throughout the twentieth century, but it was dismissed and ridiculed
insomuch as it conflicted with the main tenets of classical biology. In
promoting the ubiquity of symbiosis, Lynn radically shifted the “thought
collective” (Fleck 1979). Given the lineal heterogeneity of all organisms,
Lynn not only challenged the gradualism of Darwinian evolution but also
further envisioned a dynamic biology that broke the bounds of previous
thinking about the classification of life. She upset the entrenched dogma,
which divided the organic world into plants and animals, by proposing
a modification of Robert Whittaker’s five kingdoms taxonomy (Margulis
and Chapman 2009). This perspective, namely a view framed by efforts to
explain the evolution of microbiota, contrasted with the prevalent orien-
tation of neo-​Darwinist evolutionary biologists trained in the tradition of
zoology. She asserted that the focus on animal evolution ignored nearly
90% of the evolution of life on Earth, including the most fundamental
evolutionary innovation. In short, by championing symbiosis, Margulis
effectively challenged the modern synthesis that had dominated evolu-
tionary biology for a more complex theory that included neutral fixation
by random drift, horizontal gene transfer, punctuated equilibrium, and
gene duplication (Koonin 2012).
Lynn holds a legitimate claim as “the master architect for re-​thinking
biology in terms of interacting consortia” (Gilbert, Sapp, and Tauber
2012, p. 336). Drawing upon genetics, cell biology, protistology, earth sys-
tems science, and taxonomy, she reconceived notions of atomistic organ-
isms that characterized a biology she sought radically to revise. As she
stated, “Each of us is a colossus of nanobeasts, a coordinated bestiary”
(Margulis 2004, p. 80), a formulation in which such associations create
xvi Preface

“new individuals” with “more inclusive levels of organization” and myr-

iad cooperative functions (Margulis 1998, p. 9). And the holobiont, with
its integrated community of species, must be considered a unit of natu-
ral selection, whose evolutionary dynamics suggest complexity hitherto
largely unexplored. Indeed, when species, understood in terms of lineal
descent, is replaced with the dynamics of cooperative symbiotic interac-
tions, evolutionary biology melds into ecology. Driven by her vision of
biology’s unity and earth’s biota as a planetary phenomenon, she pro-
moted the Gaia hypothesis as a self-​regulated ecosystem. She thus helped
bring such communal thinking into its fullest expression, which, beyond
its importance for biology, has had a lasting cultural impact on environ-
mental consciousness.
Lynn was a valued interlocutor and a source of seemingly endless
ideas and opinions. So whether we were conversing about the geneal-
ogy of shrimp larvae, the role of spirochetes in the etiology of AIDS, or
Emily Dickenson’s sex life, I always departed invigorated by her sparking
intellect. Simply, it was a privilege to be counted one of her friends and
comrades-​in-​arms. I sorely miss her.
Alfred I. Tauber
Avaloch Farm
Boscawen, New Hampshire
 ACKNOWLEDGMENTS

Immunity: The Evolution of an Idea is both the synthesis and the capstone
of work published during the past 17 years. Although the key insights
presented in these earlier studies have not fundamentally changed, I have
modified certain views and, I hope, deepened my own understanding of
the conceptual structure of immunology’s theory and the various func-
tions of immunity. To acknowledge all those who have guided, provoked,
and aided me during this period is simply beyond my memory. I trust
all recognize my gratitude, and to any who feel slighted, I apologize.
However, a special acknowledgment is due to several colleagues: Eshel
ben Jacob (of blessed memory), Irun Cohen, and Nelson Vaz. Each gener-
ously explored with me questions of mutual interest concerning cognition
and information. They enlightened my own knowledge and perspectives
in varied and important ways about the basic mechanisms of immune reg-
ulation and how we might conceive the structure of the immune system.
Ilana Löwy introduced me to Ludwig Fleck’s critical appraisal of organism
as a ‘construction’ and thus anticipated much of the current philosophical
discussion about identity and individuality, which comprise the intellec-
tual scaffolding for my own work (Fleck 1979). The notion of organism
remains problematic because of the prevalence of symbiosis (thus obscur-
ing boundaries) and the deeper conceptual directives at work that define
individuals according to particular research interests. Ilana’s seminal
paper, long dormant in the literature, deserves special recognition for sow-
ing the early seeds of what finally emerged as key elements of Immunity’s
xviii Acknowledgments

theme and argument (Löwy 1991). Eileen Crist prodded me to rethink my

interpretations of early immunology and urged me to adopt a more plu-
ralistic attitude about the use of selfhood in this science. Elling Ulvestad’s
Defending Life (2007) qualifies as the most comprehensive treatment to
date of the ecological alignment described here, and therefore to him
I owe a large intellectual debt. Three more intellectual companions reside
in a special niche. Aside from Lynn Margulis, whose influence I describe
in the Preface (and to whom this book is dedicated), I cite Richard (Dick)
Lewontin and Scott Gilbert as deserving special acknowledgement.
Dick’s vision of a dialectical biology (shared and developed with
Richard Levins) provided the conceptual template for this book. When
I first read The Dialectical Biologist (Levins and Lewontin 1985) in the late
1980s, I immediately recognized the importance of its arguments against
the reductionism I found restrictive and even inimical to my own views.
The misgivings I held about the laboratory science I practiced originated
in my training as a physician, where an integrated, holistic approach to the
patient was taught and practiced in the face of an ever-​growing influence
of scientific medicine (Tauber 2006a). In my search for a more balanced
view, Dick’s writings were salutary. On a personal note, he encouraged me
to pursue my intellectual interests independently. His endorsement of my
project, in the face of disciplinary boundaries and the idiosyncratic char-
acter of my scholarship, buoyed me in many ways. Happily, I vividly recall
his answer to my query about suitable mentors to help guide the reinven-
tion of my professional persona: “No one. Do it yourself.” The “it” has been
most gratifying.
Scott Gilbert completes my list of fellow travelers. We began our schol-
arly dialogue 25 years ago, and over the years we have worked together on
several joint projects, but since 2008 our intellectual relationship has deep-
ened. That year, I published my first papers on immunology’s ecological
turn (Tauber 2008a; 2008b), and Scott was finishing a textbook devoted
to the synthetic view of development situated in its broader ecological
context (Gilbert and Epel 2008). These works displayed our shared outlook
about biology’s transition into what I would call a “unified field theory.”
That New Re-​synthesis assembles those studying evolution, development,
Acknowledgments xix

ecology, and immunology into a joint effort to characterize the holobiont.

And, conversely, unraveling the complex relationships of the holobiont
has reorganized the basic problems of each domain of the life sciences.
Scott has helped me to traverse this largely uncharted territory. To him,
then, I am particularly appreciative of our long-​standing comradeship.
This text includes modified excerpts from previously published papers.
As I have integrated and thus adapted those materials for the larger themes
presented here, significant revisions and expansions were required.
Chapter 1’s discussion of Metchnikoff is in part excerpted from Crist, E.,
and Tauber, A. I. (2001). The phagocyte, the antibody and agency in immu-
nity: Contending turn-​of-​the-​century approaches. In A. M. Moulin and
A. Cambrosio (eds.), Singular Selves: Historical Issues and Contemporary
Debates in Immunology. Amsterdam: Elsevier, 2001, pp. 115–​139, and is
adapted here with permission of the publisher and Prof. Eileen Crist. The
discussion of Burnet in Chapters 1 and 5 is based on Crist, E., and Tauber,
A. I. (1999). Selfhood, immunity, and the biological imagination: The
thought of Frank Macfarlane Burnet. Biology and Philosophy 15:509–​533,
and is adapted here with permission of the publisher and Prof. Eileen
Crist. Materials describing Jerne’s network theory in Chapter 2 are drawn
from Tauber, A. I. (2004). Immunology and the enigma of selfhood. In
M. N. Norton Wise (ed.), Growing Explanations: Historical Perspectives
on Recent Science. Durham NC: Duke University Press, pp. 201–​221, and
is adapted here with permission of the publisher. A portion of Chapter 3
on symbiosis is excerpted and adapted from Gilbert, S. H., Sapp, J., and
Tauber, A. I. (2012). A symbiotic view of life: We have never been indi-
viduals. Quarterly Review of Biology 87:325–​341, and is republished here
with permission of the publisher and Profs. Gilbert and Sapp; materials
on autoimmunity first appeared in Tauber, A. I. (2015). Reconceiving
autoimmunity: An overview. Journal of Theoretical Biology 375:52–​60,
and are republished here with permission of the publisher. Chapter 3
contains material adapted from Tauber, A. I. (2010). Reframing develop-
mental biology and building evolutionary theory’s new synthesis: Essay
review: Ecological Developmental Biology: Integrating Epigenetics,
Medicine, and Evolution by Scott F. Gilbert and David Epel. Sunderland,
xx Acknowledgments

MA: Sinauer Associates, 2009. Perspectives in Biology and Medicine 53:257–​

270; adapted here with permission of the publisher. Chapter 4 includes
material adapted from Tauber, A. I. (2013). Immunology’s theories of
cognition. History and Philosophy of the Life Sciences 35:239–​264, and is
included here with permission of the publisher. Chapter 5, dealing with
the ecological perspective, is based on a book review essay, Tauber, A. I.
(2008b). Expanding immunology: Defensive versus ecological perspec-
tives: Essay review: Defending Life. The Nature of Host–​Parasite Relations
by Elling Ulvestad, Dordrecht: Springer, 2007. Perspectives in Biology and
Medicine 51:270–​284, and is adapted here with permission of the pub-
lisher. In addition, excerpts from Tauber, A. I. (2008a). The immune sys-
tem and its ecology. Philosophy of Science 75:224–​245, are adapted here
with permission of the publisher. Portions of Chapter 6’s discussion of
systems biology appeared in Tauber, A. I. (2009). The biological notion
of self and non-​self. In E. N. Zalta (ed.), Stanford Encyclopedia of Science,
http://​plato.stanford.edu/​archives/​sum2009/​entries/​biology-​self.
Finally, I am most appreciative of the efforts made by Lucy Randall,
Damian Penfold, and the Oxford University Press staff, who brought this
project to a successful completion. I published my first book, Metchnikoff
and the Origins of Immunology, with Oxford University Press 25 years ago,
and it seems most fitting that my “immunology quartet” has been com-
pleted in this most hospitable publishing house.
 Introduction

What is immunity? The commonsensical answer holds that a host ani-

mal possesses mechanisms by which to defend itself against pathogens,
and the completion of that process results in immunity, a protected state.
But then how to conceive of all of those other activities conducted by the
same cells and mediators directed toward other functions—​for example,
surveillance for malignancies; processing of effete, damaged, or dead cells;
mediation of oral intake; monitoring gaseous exchange; active toleration
of what is not destroyed? As evident from this (incomplete) list, immu-
nity not only serves as a noun designating the outcome of a particular
defensive function but is also a verb that captures the ongoing processes
that maintain the identity of the organism whether from invasive insult or
internal decay. So, although the immune system has largely been defined
as those cells and mediators comprising the immune response to invad-
ing microbes, that ensemble in fact has diverse roles in the body’s cease-
less economy of internal cellular turnover and external exchanges with the
environment. To account for all of the functions within a single concep-
tual scheme of immunity is the key challenge of this study.
The strength of the “host defense” orientation resides in a long and
prominent clinical history. Indeed, the dominant formulation originates
with the identification of the etiological agents of infectious diseases dur-
ing the 1870s and 1880s. That such microorganisms must be combatted—​
neutralized or killed—​defined a biology of competition in the war of
survival. In this scenario, three implicit ideas organized the nascent
2 I m m u n it y: T h e E v o l u ti o n o f a n I d e a

science: Immunity was constituted by the requirements of (1) protecting,

(2) an autonomous, (3) individual. These features—​protection, autonomy,
and individuality—​thus served as the foundations of what would become
in due course a fully developed theory of immunity. Note that this para-
digm emerged directly from the original clinical orientation of the science
and its early therapeutic successes (i.e., passive immunized serum therapy
for diphtheria [Linton 2005; Silverstein 2009]). And by the mid-​twentieth
century, the research and therapeutic program was well established, sup-
ported by compelling investigative successes that showed how immune
mechanisms evolved in tandem with the evolutionary pressures induced
by the threat of deleterious microbes (Frank 2002).
As immunology developed, the self/​nonself dichotomy became the
central theoretical scaffolding of the discipline. All immune functions, it
was thought, are organized around this central idea, namely the immune
system ignores the “self ” and attacks the “other.” And given the commit-
ments of the science to clinical medicine, this defensive posture assumed
dominance. Note that the “self/​nonself model” is not a model in the usual
sense but, rather, serves as a guiding paradigm or a basic presupposition
of the science that begins with this differentiation of identity. Accordingly,
“the self ” orders immune phenomena and, as will be discussed in detail,
serves as shorthand to represent immune silence or nonreactivity. In other
words, virtually all models of immune function build in the basic premise
of self/​nonself discrimination.1
This explicit differentiation evolved during the 1940s when transplan-
tation biology became a focus of intense interest as a result of attempts to
transplant skin into severely burned patients (Silverstein 2009). Shortly
following those studies, pathological autoimmunity was recognized as a
window into immune function that heretofore had not been fully appreci-
ated. With these developments, Frank Macfarlane Burnet hypothesized a
model of immune regulation that would eventually define immunology.
He argued that during embryonic development, immune cells recognize
“self ” elements, and once recognized, the “self-​recognizers” are purged
from the immune library. The expunged thus leaves a “hole” in the reactive
profile of the immune system corresponding to host constituents (Burnet
Introduction 3

and Fenner 1949). This “hole” (or “negative space”) is the “immune self.”
The implicit presence of the self emerged with the formalized self/​nonself
distinction, which has been widely designated as immunology’s govern-
ing paradigm (Golub and Green 1991, p. 15) and consistently defended by
those committed to the self/​nonself discrimination as the basis of immune
function (Cohn 2015; Bretscher 2016).
The modern historiography of immunology has followed the Burnet-​
authored framework and has accepted the centrality of self/​nonself dis-
crimination as its fundamental theme. But adopting this version of
immunology’s history omits the deeper perplexities of the science that
remain largely unstated and thus ignored. An alternate history begins
with Elie Metchnikoff ’s theory of immunity (Chernyak and Tauber 1990;
Tauber and Chernyak 1991; Tauber 1991a, 1994a, 2003). Unlike Burnet’s
proposal of a firm demarcation between self and nonself, Metchnikoff
regarded immune processes as mediating the organism’s identity through
a continuous, lifelong developmental process. Accordingly, immunity is
that function which supervises the integrity of the organism in its inter-
nal economy of repair, cell turnover, and surveillance. On this view, host
defense becomes a subordinate aspect of a more general identification
process. Thus, the notion of a self, transcendentally cohesive and fixed,
was displaced by a conception of the organism with a dynamic identity,
whose boundaries and structure evolved in the face of internal and exter-
nal challenges (Tauber 1994a, 1994c, 2003). My revisionist theme is based
on this insight.
Whereas immunology as a science has been defined as the “science of
self/​nonself discrimination,” from a philosophical point of view, follow-
ing Metchnikoff, immunology is the science concerned with establish-
ing and maintaining the immune identity of the organism. This more
expansive designation allows for conceiving immune processes in their
broadest biological context, namely in addition to defensive and restor-
ative processes, the immune system also may be understood as engaged
in information processing and cognition, exchange with the environment
to allow for benign intercourse, and tolerance for symbiotic relationships
constitutive of an organism conceived as a complex holobiont. Placing the
4 I m m u n it y: T h e E v o l u ti o n o f a n I d e a

organism in its full ecological context displaces the defensive insular con-
ception of a host (a “self ”)—╉originally defined as requiring protection—╉
to one in which the immune system arbitrates the organism’s dialectical
exchanges with its environment. “Dialectical”—╉the conceptual basis of an
ecological orientation—╉refers broadly to immunity as enacting the organ-
ism’s capacities to control its environment and in turn be determined by
it. Immunity establishes the balance between these two engagements by
addressing both defensive and benign interactive functions. And upon
that platform, philosophical issues pertaining to identity, individuality,
cognition, information, biological causation, mechanism, model, and
metaphor assume more complex meanings than those used in a dichoto-
mous self/╉other framework. Here, the significance of these differing con-
ceptions of immune identity for philosophy of biology is reviewed.

THE ECOLOGICAL IMPERATIVE

Metchnikoff ’s view of organismic identity undergirds the ecological per-

spective adopted here, in which a dynamic view of the organism requires
the exercise of dialectical exchanges and evolving relationships that effec-
tively balance the active intercourse of the organism with its environment.
His concept of immunity has continued relevance inasmuch as a precise
definition of the immune self, which carries many meanings and func-
tions in diverse ways, has not been attained. The underlying reason for
this “failure” resides within a larger framework in which a conceptual
ambiguity reflects a deeper issue: Immunity itself has several applications,
and correspondingly selfhood has contested meanings. The traditional
notion of defense reflects immunology’s original clinical orientation, but
much of what has been called “autoimmunity” in fact includes both toler-
ant sentinel functions of host tissue and incorporation of substances at
the interface of host and its external environment. These “resting” func-
tions comprise normal physiological immunity now oriented by “toler-
ance.” And once the economy between organism and its environment is
regarded as more than one of conflict and competition, but also includes
Introduction 5

beneficial exchanges as well, the horizon of immunity widens. Indeed, tol-

erance, immune acceptance of the same as well as the foreign, balances the
original paradigm of host defense with an ecological perspective that must
account for all of the relationships and encounters the organism faces in
its life cycle. This balanced orientation organizes Immunity: The Evolution
of an Idea, and as we will see, this perspective markedly alters immunolo-
gy’s governing theory, its notions of agency, and the modeling of immune
cognition that follows.

By the turn of the millennium, immunology’s conceptual foundations

began to shift under pressure from the “ecological imperative.” Multiple
disciplines joined the growing consensus that biological functions must
be considered within the full environmental context in which they are
examined. Three levels of ecological organization demand attention: The
first, and most traditional, is the dynamics of competitive struggle. This
Darwinian orientation, as mentioned previously, has dominated immune
theory; however, the full calculation of environmental factors also includes
cooperative exchanges as well. So a second level of study enlarges the eco-
logical perspective to include all of the organism’s interactions—​that is,
both dangerous and salutary.
Note that the “environment” is not only the external space in which the
organism lives but also includes the complex assembly of the organism’s
own constituents that live together harmoniously within conventional
anatomic confines. Thus, a third level of analysis commands attention,
namely the internal physiology of the animal, in which tolerated resi-
dent organisms live in symbiotic arrangements. Accordingly, organisms
traditionally conceived as independent entities now must be regarded
as complex cooperative collectives. The idea of the “holobiont”—​a con-
glomerate of diverse organisms living in cooperative relationships within
the organism—​holds that all organisms are in fact complex consortia
(Rosenberg et al. 2007). Accordingly, a larger ecological context not only
includes traditional studies of the organism placed in its external envi-
ronment but also examines how the holobiont constitutes the site of an
integrated internal ecosystem.2
6 I m m u n it y: T h e E v o l u ti o n o f a n I d e a

The pervasiveness of symbionts affects every domain of biology—​

evolution, development, anatomy, and physiology, including immunology—
and challenges classical definitions of individuality. A symbiotic
​
perspective opens important areas of research and offers fundamentally
new conceptions of the organism, for if “we have never been individuals,”
immunology moves from its dominant concern with discerning the pro-
tective mechanisms of autonomous individuals to the science of under-
standing the cooperative assemblies of organisms (Gilbert, Sapp, and
Tauber 2012). Indeed, making symbiosis the rule and not the exception
of organization, alters the governing precepts of biology. A different set
of scientific questions becomes paramount as our view of life shifts from
exclusive attention to competitive struggle to one that includes the inti-
mate cooperation between species as a fundamental feature of evolution.
On such a revision, individual selection assumes a very different cast if all
organisms are regarded as chimeras as opposed to monogenetic individu-
als.3 And so instead of the focus on competition, we set our sights on the
cooperative and complex nature of the tangled web of life; immunology
finds itself at the nexus of both concerns. In consideration of this wider
agenda, a new field, eco-​immunology, has emerged that studies these rela-
tionships in their full complexity (Demas and Nelson 2011; Maligoli and
Ottaviani 2014).
Beginning in the 1990s, efforts to describe the natural variation in
immune functions were undertaken to assess the cost/​benefit ratios of
mounting immune responses to parasites (Sheldon and Verhulst 1996).
This research initiated an important disciplinary re-​orientation, inas-
much as immunity became a measure of virulence not solely in terms of
parasite eradication but in regards to trade-​offs that sought an adjusted
equilibrium between host organism and infection that determine selec-
tion and population dynamics. Then the agenda widened to include the
benefits of immune-​mediate cooperative relationships as well. Infection
is more complex than a straightforward disease-​causing phenomenon.
The boundaries between interpenetrating organisms are pliable, and thus
the lines between parasitism, tolerance, and symbiosis are variable and
dynamic.
Introduction 7

In assuming this broad agenda, immunity is being studied as an integral

part of organismal biology in regard to examining the regulatory mecha-
nisms that “maximize fitness in the context of costs, constraints, and com-
plex interactions” (Brock, Murdock, and Marin 2014). Also referred to
as “ecological immunology,” “disease ecology,” and “integrative biology,”
eco-​immunology endeavors to describe and explain natural variation in
immune functions and thus addresses questions at multiple levels of bio-
logical organization (e.g., comparative evolution, short-​term physiologi-
cal adjustments, and comparative endocrinology) and thereby impacts
diverse research fields. This interdisciplinary effort is a recent develop-
ment. Only within the past two decades have serious attempts been made
to integrate immunology and ecology, and the early studies suggest rich
harvests (Demas and Nelson 2011; Gewin 2011; Martin, Hawley, and
Ardia 2011). For example, behavioral ecologists showed that immunity
varies with the environmental characteristics of the habitats occupied by
hosts, their life history strategy and stage, and a diversity of other factors
(Brock et al. 2014). Perhaps the most promising findings concern immune
interactions with the neuroendocrine system in regard to stress responses,
reproductive physiology, and social behavior (ibid.). Already key insights
about the dynamics and plasticity of immune identity have emerged, for

the magnitude of variation in immunity between individuals,

groups, and species is far greater than was implicitly predicted by
traditional immunology. In spite of strong selection against disease,
most organisms maintain a degree of genetic and physiological vul-
nerability to infection. This key insight would not have been possible
using a small number of model species in the controlled laboratory
setting of traditional immunology. (Pedersen and Babayan 2011,
quoted in Brock et al. 2014, p. 354)

To explain this variation and its consequences, several research programs

are at play: (1) an adaptationist approach to investigate the costs and ben-
efits of investment in immune activity; (2) the potential role of patho-
gens in shaping life history variation; (3) the genetics and evolutionary
8 I m m u n it y: T h e E v o l u ti o n o f a n I d e a

mechanisms that operate to establish genomes determined by environ-

mental factors; (4) the direct contributions of nutritional, pathogenic,
reproductive, and psychosocial factors to human immune functions; and
(5) the relevance of cultural and ecological factors to the development
and function of the immune system (Lochmiller and Deerenberg 2000;
McDade 2005; Schulenburg et al. 2009; Pedersen and Babayan 2011).4
Once such factors are incorporated into the study of immunity, the cur-
rent precepts of immune theory relying on the immune self placed within
more narrow considerations must be reconceptualized. Here our analysis
begins.

REVISING IMMUNE THEORY

The ecological orientation described here commits immunologists not

only to examine the internal systems of immunity as traditionally con-
ceived but also to address the challenge of defining the immune system
in the full context of its environment and the commune of individu-
als comprising the species. Herd immunity represents an important
parameter of the ecological context—╉in this instance, the ecology of
the population of the species. 5 However, the more general proper-
ties with which we are concerned refer to the greater ecology of the
immune system, where the borders function as sieves to allow material
exchange. Note that the larger context includes both the internal and
the external environments sensed and acted upon. On this understand-
ing, the immune system is endowed with a high degree of communica-
tive abilities for sensing danger (in the form of pathogens, allergens,
toxins, etc.) but also, and just as important, allowing the free exchange
of even a larger universe of substances and organisms engaged for
the organism’s benefit. Accordingly, the immune system mediates the
ongoing negotiation of various interactions between the organism and
its environment. To remain restricted within an analysis that already
assumes only a defensive posture limits understanding how animals
live in intercourse with others. In short, with this widened conception
Another random document with
no related content on Scribd:
the system inaugurated by David, and treats this edifying topic at
some length.

²And Hezekiah appointed the courses of the

priests and the Levites after their courses,
every man according to his service, both the
priests and the Levites, for burnt offerings and
for peace offerings, to minister, and to give
thanks, and to praise in the gates of the camp
of the Lord.
2. the courses] Compare 1 Chronicles xxiv. 1 ff.

to minister, and to give thanks, and to praise in the gates] Better,

as LXX., altering the order, to give thanks and to praise and to
minister in the gates. “To minister in the gates,” i.e. to be
doorkeepers, compare 1 Chronicles xxvi. 1.

the camp of the Lord] i.e. (in the language of Deuteronomy) “the
place which the Lord chose,” Jerusalem or, more exactly, the Temple
area. Compare 1 Chronicles ix. 18, note.

³He appointed also the king’s portion of his

substance for the burnt offerings, to wit, for the
morning and evening burnt offerings, and the
burnt offerings for the sabbaths, and for the
new moons, and for the set feasts, as it is
written in the law of the Lord. ⁴Moreover he
commanded the people that dwelt in
Jerusalem to give the portion of the priests
and the Levites, that they might give
themselves ¹ to the law of the Lord.
 ¹ Hebrew be strong in.

3. the burnt offerings] Compare viii. 12, 13.

⁵And as soon as the commandment came

abroad, the children of Israel gave in
abundance the firstfruits of corn, wine, and oil,
and honey, and of all the increase of the field;
and the tithe of all things brought they in
abundantly.
5. and honey] Honey (Hebrew dĕbhash) is not elsewhere
mentioned as subject to tithe; perhaps grape syrup (modern Arabic
dibs) is meant here, as in Genesis xliii. 11 and Ezekiel xxvii. 17
(according to some commentators). Honey (like leaven) was
forbidden for sacrificial use (Leviticus ii. 11).

⁶And the children of Israel and Judah, that

dwelt in the cities of Judah, they also brought
in the tithe of oxen and sheep, and the tithe of
dedicated things which were consecrated unto
the Lord their God, and laid them by heaps.
6. And the children of Israel] Compare xi. 16.

the tithe of dedicated things] a strange phrase without parallel.

Read probably the dedicated things.

⁷In the third month they began to lay the

foundation of the heaps, and finished them in
the seventh month. ⁸And when Hezekiah and
the princes came and saw the heaps, they
 blessed the Lord, and his people Israel.
⁹Then Hezekiah questioned with the priests
and the Levites concerning the heaps.
7. the third month] The Feast of Harvest took place at the
beginning of this month and seven weeks later the Feast of
Ingathering followed.

¹⁰And Azariah the chief priest, of the house of

Zadok, answered him and said, Since the
people began to bring the oblations into the
house of the Lord, we have eaten and had
enough, and have left plenty: for the Lord
hath blessed his people; and that which is left
is this great store.
10. Azariah the chief priest] Not mentioned in connection with
Hezekiah’s previous arrangements.

of the house of Zadok] Compare 1 Chronicles xxiv. 1‒4. Tradition

spoke of two main families of priests, (1) the descendants of Eleazar
the third son of Aaron, whose chief representative in David’s day
was Zadok (hence they are here called “the house of Zadok”), (2) the
descendants of Ithamar the fourth son of Aaron, represented in
David’s time by Ahimelech (Saul’s victim) or by Abiathar (David’s
protégé). The Chronicler prefers to name the descendants of Ithamar
after Ahimelech (1 Chronicles xxiv. 3, where see note).

the oblations] “The Hebrew word, tĕrūmāh, denotes properly

what is ‘taken off’ from a larger mass and so separated from it for
sacred purposes.” The word is sometimes rendered heave offering,
but this is due to a mistaken impression that a rite of elevation was
involved (see the full note in Driver, Exodus, p. 263).
 hath blessed his people] Compare Malachi iii. 10.

and that which is left is this great store] The Hebrew requires
some correction. Read as the LXX., καὶ κατελίπομεν ἐπὶ τὸ πλῆθος
τοῦτο, “we leave (‘have left’) this great store and more.”

11‒13. The offerings mentioned in verses 5‒10 were placed in

charge of Conaniah, Shimei and their subordinates for storage in the
Temple treasuries.

¹¹Then Hezekiah commanded to prepare

chambers in the house of the Lord; and they
prepared them.
11. chambers] compare 1 Chronicles ix. 26, note.

¹²And they brought in the oblations and the

tithes and the dedicated things faithfully: and
over them Conaniah the Levite was ruler, and
Shimei his brother was second.
12. the dedicated things] Compare xxix. 33 (note on the
consecrated things).

¹³And Jehiel, and Azaziah, and Nahath, and

Asahel, and Jerimoth, and Jozabad, and Eliel,
and Ismachiah, and Mahath, and Benaiah,
were overseers under the hand of Conaniah
and Shimei his brother, by the appointment of
Hezekiah the king, and Azariah the ruler of the
house of God.
 13. the ruler of the house of God] Compare 1 Chronicles ix. 11,
note.

14‒19. Distribution of the stores referred to in verses 11‒13 was

the duty of Kore and his subordinates. The exact meaning and
sequence of these verses is hard to follow, and probably the
obscurity is due to faults in the Hebrew text. The simplest view is as
follows: verse 15 states that the distribution was to be made to
priestly and levitical persons resident in the priestly cities but (verse
16) not to those who were for the time being on duty at the Temple,
since these no doubt would receive their share at the Temple itself.
Then verses 17‒19 seem to refer to the manner of the registration of
priests and Levites respectively for the purpose of the distribution;
but it must be confessed that the precise sense and connection are
uncertain, particularly as regards verse 19.

¹⁴And Kore the son of Imnah the Levite, the

porter at the east gate, was over the freewill
offerings of God, to distribute the oblations of
the Lord, and the most holy things.
14. the most holy things] To this class belonged the shewbread
(Leviticus xxiv. 9), the meal offering (Leviticus ii. 2, 3, vi. 14‒18 [7‒
11, Hebrew]), the sin offering (Leviticus vi. 25‒30), and the trespass
offering (Leviticus vii. 1‒7). These could be eaten by the priests only
and in the holy place only.

¹⁵And under him were Eden, and Miniamin,

and Jeshua, and Shemaiah, Amariah, and
Shecaniah, in the cities of the priests, in their
set office ¹, to give to their brethren by courses,
as well to the great as to the small:
¹ Or, trust.
 15. in the cities] The priestly cities are given 1 Chronicles vi. 54‒
60.

to the great as to the small] i.e. to old and to young alike.

¹⁶beside them that were reckoned by

genealogy of males, from three years old and
upward, even every one that entered into the
house of the Lord, as the duty of every day
required ¹, for their service in their charges
according to their courses;
¹ Or, for his daily portion.

16. beside] i.e. with the exception of.

as the duty of every day required] Or, as margin, for his daily
portion.

¹⁷and them that were reckoned by genealogy

of the priests by their fathers’ houses, and the
Levites from twenty years old and upward, in
their charges by their courses;
17. and them that] Render probably and as for the registration
of the priests it was made by their families....

¹⁸and them ¹ that were reckoned by genealogy

of all their little ones, their wives, and their
sons, and their daughters, through all the
congregation: for in their set office ² they
sanctified themselves in holiness:
 ¹ Or, even to give to them &c. ² Or, trust.

18. and them that] Render, and the registration included all
their little ones, etc. The connection of the last part of the verse is
very obscure.

their set office] Or, as margin, their trust (so also above verse
15).

they sanctified themselves in holiness] Or, they busied

themselves with the distribution of the sanctified things. No reliance
can be placed on the soundness of the text.

¹⁹also for the sons of Aaron the priests, which

were in the fields of the suburbs of their cities,
in every several city, there were men that were
expressed by name, to give portions to all the
males among the priests, and to all that were
reckoned by genealogy among the Levites.
²⁰And thus did Hezekiah throughout all Judah;
and he wrought that which was good and right
and faithful ¹ before the Lord his God. ²¹And in
every work that he began in the service of the
house of God, and in the law, and in the
commandments, to seek his God, he did it
with all his heart, and prospered.
¹ Hebrew faithfulness.

19. Again a most obscure verse, apparently meaning that the

priests had certain special officers, other than Kore and his
subordinates, who were charged with superintending the distribution
in the outlying districts. Text and interpretation are alike uncertain.
Kittel regards verses 17‒19 as a late addition.

the suburbs] compare 1 Chronicles v. 16 (margin “pasture

lands”), vi. 55, 57 [40, 42, Hebrew].

Chapter XXXII.
1‒8 (compare 2 Kings xviii. 13‒16).
Sennacherib’s threatened Invasion. Hezekiah’s Precautions.

The Chronicler introduces us somewhat abruptly to the Assyrian

crisis. From 2 Kings we learn that Hezekiah renounced the
suzerainty of Assyria (xviii. 7), which his father Ahaz had
acknowledged (2 Kings xvi. 7). Thereupon Sennacherib invaded
Judah, and Hezekiah was obliged to acknowledge with a heavy
payment of tribute his dependence on the Assyrian king (2 Kings
xviii. 13‒16). Sennacherib having discovered the weakness of
Judah, next demanded an unconditional surrender, intending to
transport the Jews to another country (2 Kings xviii. 31, 32). This
demand Hezekiah resisted, being strengthened thereto by Isaiah.
The Chronicler does not refer to the earlier invasion or to the tribute
—such a humiliation of the pious and devoted king being in his belief
unthinkable. That any invasion should have taken place “after these
things and this faithfulness” was sufficiently astonishing, until the
issue showed that the anxiety and distress were only for the greater
glory of Israel’s God and for the further proof of Hezekiah’s trust in
Him.

¹After these things, and this faithfulness,

Sennacherib king of Assyria came, and
entered into Judah, and encamped against the
 fenced cities, and thought to win them ¹ for
himself. ²And when Hezekiah saw that
Sennacherib was come, and that he was
purposed ² to fight against Jerusalem,
¹ Hebrew to break them up.

² Hebrew his face was to fight.

1. After these things, and this faithfulness] The phrase is a

hendiadys and stands for, “After these faithful dealings.”

Sennacherib] This king (Sanḥērib in Hebrew, Sin-aḥi-irib [-irba] in

Assyrian, the Σαναχάριβος of Herod. II. 141) reigned 705‒681 b.c. He
was the son of Sargon (Isaiah xx. 1), father of Esar-haddon (2 Kings
xix. 37; Ezra iv. 3), and grandfather of Asshur-bani-pal, the well-
known Σαρδανάπαλλος of Herod. II. 150, who is commonly identified
with Osnappar (compare Ezra iv. 10). Under this dynasty Assyria
reached the height of its power. The empire included Babylonia
(which, however, was frequently in revolt), Assyria proper, Syria as
far north as Cilicia (inclusive), and (under Esar-haddon and Asshur-
bani-pal) Egypt. After Asshur-bani-pal’s death (about 626 b.c.) the
Assyrian power was speedily destroyed. The form Sennacherib is
derived from the LXX. through the Vulgate.

to win them] Literally to make breaches in them. According to 2

Kings xviii. 13 Sennacherib took these cites; and the Assyrian
account on the “Prism Inscription” of Sennacherib which is preserved
in the British Museum states that they were forty-six in number
(compare Driver in Hogarth, Authority and Archaeology, pp. 104‒
107; or Handcock, Latest Light on Bible Lands, pp. 153 ff.).

³he took counsel with his princes and his

mighty men to stop the waters of the fountains
 which were without the city; and they helped
him.
3. to stop the waters] Compare 2 Kings xx. 20 “[Hezekiah] made
the pool and the conduit and brought water into the city,” and Isaiah
xxii. 9, 11.

At the present day there is an underground tunnel cut through the

rock leading from St Mary’s Well down to the Lower Pool of Siloam
(Bädeker, Palestine⁵, pp. 25, 83). It is rudely constructed and owing
to its windings is 586 yards long, though the distance in a straight
line is only 368 yards. As therefore the Lower Pool was probably
within the ancient walls, while St Mary’s Well was outside, this tunnel
may be Hezekiah’s conduit. If the well were stopped, the besiegers
would lose the water, which would collect in the Pool for the use of
the besieged. An inscription in ancient Hebrew characters (“The
Siloam Inscription”) discovered in situ describes briefly the digging of
the tunnel, but does not enable us to fix the date of it with certainty.
For the original text and an English translation see G. A. Smith,
Jerusalem, I. 95 f., or Driver, Notes on Hebrew Text of Samuel, viii.
ff.

⁴So there was gathered much people together,

and they stopped all the fountains, and the
brook that flowed through the midst of the
land, saying, Why should the kings of Assyria
come, and find much water?
4. the brook that flowed] The Hebrew verb means “flow with
strong stream” (as a flood). We naturally look for such a brook either
east of Jerusalem in the valley of Kidron or south in the valley of the
son of Hinnom, but no perennial stream runs in either valley now.
Possibly (owing to physical changes in the configuration of the
country) the waters which fed such a brook in the Chronicler’s day
now lose themselves in the soil.
 ⁵And he took courage, and built up all the wall
that was broken down, and raised it up to the
towers ¹, and the other ² wall without, and
strengthened Millo in the city of David, and
made weapons and shields in abundance.
¹ Or, heightened the towers Or, went up upon the towers The
Vulgate has, built towers thereon.

² Or, another.

5. broken dozen] Compare xxv. 23 (note).

raised it up to the towers] Hebrew vayya‘al ‘al. Read and he

heightened the towers, i.e. omitting the second ’al as a dittography.

the other wall] In Isaiah xxii. 9‒11 the preparations to meet the
Assyrian attack are described by the prophet who speaks of a “ditch”
(Revised Version “reservoir”) made at this time between “the two
walls.” In Excavations at Jerusalem, 1894‒1897, Dr Bliss describes
a buttressed wall (pp. 96 ff.) built without lime (see his frontispiece
for an illustration of it) and enclosing the pool of Siloam on the south-
east, which, he says, “may date back as far as Hezekiah” (pp. 325
f.). Dr Bliss also, following up a clue given by earlier explorers, found
a second wall (running at an angle to the first) enclosing the pool on
the west. This second wall was probably due to Herod, but Dr Bliss
suggests that the line it follows may have been defended by a wall
as early as Hezekiah’s day (p. 326). For further discussion see G. A.
Smith, Jerusalem, I. 182, 207.

Millo] compare 1 Chronicles xi. 8, note.

weapons and shields] Properly, darts and shields. These were

meant, not for such trained soldiers as Hezekiah could collect, but
for the levy en masse with which the king proposed to man the walls.
A dart to throw and a shield to protect the thrower as he threw were
all that the citizen-soldier needed. The Hebrew word (shelaḥ) means
“dart, missile”; the more general rendering “weapons” obscures the
precise nature of Hezekiah’s preparations.

⁶And he set captains of war over the people,

and gathered them together to him in the
broad place at the gate of the city, and spake
comfortably to them, saying, ⁷Be strong and of
a good courage, be not afraid nor dismayed
for the king of Assyria, nor for all the multitude
that is with him: for there is a greater ¹ with us
than with him:
¹ Or, there be more.

6. in the broad place at the gate] Compare xxix. 4; Nehemiah viii.

16. There is nothing here to show which of the two broad places
mentioned in Nehemiah is meant, or whether some third place is
intended.

⁸with him is an arm of flesh; but with us is the

Lord our God to help us, and to fight our
battles. And the people rested themselves
upon the words of Hezekiah king of Judah.
8. an arm of flesh] Compare Jeremiah xvii. 5. Contrast the
frequent phrase “a mighty hand and a stretched out arm” (of
Jehovah). An “arm” is an ally or helper.

with us is the Lord] Compare xv. 2, xx. 17; Isaiah viii. 10.
 9‒19 (compare 2 Kings xviii. 17‒35).
Sennacherib’s Threatening Messages.

In this section Chronicles briefly and freely summarises 2 Kings.

⁹After this did Sennacherib king of Assyria

send his servants to Jerusalem, (now he was
before Lachish, and all his power with him,)
unto Hezekiah king of Judah, and unto all
Judah that were at Jerusalem, saying,
9. his servants] Three of these are specified in 2 Kings by their
titles, viz. the Tartan (“Commander-in-chief”), the Rabsaris (perhaps
“Chief of the Princes”), and the Rabshakeh (“Chief of the officers or
cup-bearers”).

now he was before Lachish] The capture of Lachish by

Sennacherib and its spoliation are shown on an Assyrian relief now
in the British Museum. The king himself besieged Lachish because it
was of more importance for the main object of the campaign than
Jerusalem. Sennacherib’s objective was Egypt (Herodotus II. 141),
and Lachish (Tell el-Ḥesi, Bädeker, Palestine⁵, p. 118) lay directly in
his path (compare Handcock, Latest Light on Bible Lands, p. 151).

¹⁰Thus saith Sennacherib king of Assyria,

Whereon do ye trust, that ye abide the siege ¹
in Jerusalem?
¹ Or, in the strong hold.

10. in Jerusalem] Isaiah promised deliverance in Jerusalem; e.g.

in Isaiah xxix. 8, xxx. 19.
 ¹¹Doth not Hezekiah persuade you, to give you
over to die by famine and by thirst, saying,
The Lord our God shall deliver us out of the
hand of the king of Assyria?
11. persuade] Or “entice”; compare 1 Chronicles xxi. 1
(“provoked” for the same Hebrew word).

¹²Hath not the same Hezekiah taken away his

high places and his altars, and commanded
Judah and Jerusalem, saying, Ye shall
worship before one altar, and upon it shall ye
burn incense?
12. Hath not the same Hezekiah taken away] Besides this appeal
to the religious prejudices of the people, Sennacherib’s servants
employed two other arguments, according to 2 Kings—(1) the
paucity of Hezekiah’s soldiers (2 Kings xviii. 23) and (2) possible
reliance on Egyptian help (2 Kings xviii. 21, 25). These two
arguments are passed over by the Chronicler doubtless because
they seemed inconsistent both with the power and the character of a
king so God-fearing as Hezekiah.

his high places] compare 2 Kings xviii. 4. The “high places”

(bāmōth) were properly sanctuaries of Jehovah, and not necessarily
idolatrous in themselves. But since originally all, or almost all, of
these bāmōth had been sacred places of the Canaanite gods, old
idolatrous symbols (e.g. the ashērah) and old idolatrous ideas and
rites persisted in the worship there offered. When finally the Jews
restricted sacrificial worship to Jerusalem, the odium attaching to
these “high places” became greater than ever, and hostility towards
them came to be regarded as the mark of any pious monarch.
Hezekiah removed the bāmōth throughout the country.
 ¹³Know ye not what I and my fathers have
done unto all the peoples of the lands? Were
the gods of the nations of the lands any ways
able to deliver their land out of mine hand?
¹⁴Who was there among all the gods of those
nations which my fathers utterly destroyed ¹,
that could deliver his people out of mine hand,
that your God should be able to deliver you
out of mine hand? ¹⁵Now therefore let not
Hezekiah deceive you, nor persuade you on
this manner, neither believe ye him: for no god
of any nation or kingdom was able to deliver
his people out of mine hand, and out of the
hand of my fathers: how much less shall your
God ² deliver you out of mine hand? ¹⁶And his
servants spake yet more against the Lord
God, and against his servant Hezekiah.
¹ Hebrew devoted. ² Or, gods.

13. the peoples of the lands] In 2 Kings xviii. 34 the lands are
specified and include Samaria.

¹⁷He wrote also letters ¹, to rail on the Lord,

the God of Israel, and to speak against him,
saying, As the gods of the nations of the
lands, which have not delivered their people
out of mine hand, so shall not the God of
Hezekiah deliver his people out of mine hand.
 ¹ Or, a letter.

17. to rail on] Or, to defy (the same Hebrew word as in 2 Kings
xix. 4, 16, 22, 33, and there rendered “reproach”).

¹⁸And they cried with a loud voice in the Jews’

language unto the people of Jerusalem that
were on the wall, to affright them, and to
trouble them; that they might take the city.
18. in the Jews’ language] i.e. in Hebrew. From the parallel
passage, 2 Kings xviii. 26 ff., it is evident that the language of
diplomacy at this time in Western Asia was Aramaic (“Syrian,” 2
Kings); and that, whilst understood by the Jewish leaders and
officials, it was not yet intelligible to the common people. In the
negotiations the Rabshakeh showed clearly that his object was not
to treat with Hezekiah, but to excite a revolt among the Jews against
Hezekiah and so gain possession of the city.

¹⁹And they spake of the God of Jerusalem, as

of the gods of the peoples of the earth, which
are the work of men’s hands.
19. the God of Jerusalem] For this designation compare Psalms
cxxxv. 21.

20‒23 (compare 2 Kings xix. 1‒4, 14‒19, 35‒37).

Hezekiah and Isaiah pray. The Deliverance.

This section is a very brief summary of 2 Kings xix.

²⁰And Hezekiah the king, and Isaiah the

prophet the son of Amoz, prayed because of
this, and cried to heaven.
 20. And Hezekiah ... and Isaiah ... prayed] According to Kings,
Hezekiah prayed, and was answered by God through the medium of
a message delivered by Isaiah the prophet (2 Kings xix. 20‒34).

heaven] Here used reverently for “God”; compare xxviii. 9; Daniel

iv. 26; Luke xv. 21.

²¹And the Lord sent an angel, which cut off all

the mighty men of valour, and the leaders and
captains, in the camp of the king of Assyria.
So he returned with shame of face to his own
land. And when he was come into the house
of his god, they that came forth of his own
bowels slew him ¹ there with the sword.
¹ Hebrew caused him to fall.

21. all the mighty men] In number 185,000 according to 2 Kings

xix. 35 and Isaiah xxxvii. 36. The agency was probably the plague,
which is pictured as a destroying angel in 2 Samuel xxiv. 16.

And when he was come] The murder of Sennacherib did not

occur till some 20 years after his Judean expedition (circa 701 b.c.),
i.e. not till 681 b.c.

they that came forth] The Chronicler no doubt follows Isaiah

xxxvii. 38, “Adrammelech and Sharezer his sons smote him”; but the
accuracy of the present text of this passage of Isaiah is doubtful, for
in the parallel passage (2 Kings xix. 37, Kethīb) the words his sons
are missing. The only notice of Sennacherib’s death known to us at
present from the inscriptions reads “Sennacherib king of Assyria was
slain by his son (singular) in a revolt.” No name is given to this son.
(Driver in Hogarth, Authority and Archaeology, p. 109.)
 ²²Thus the Lord saved Hezekiah and the
inhabitants of Jerusalem from the hand of
Sennacherib the king of Assyria, and from the
hand of all other, and guided them on every
side.
22. guided them on every side] Read, as the LXX., gave them
rest on every side; compare xx. 30.

²³And many brought gifts unto the Lord to

Jerusalem, and precious things to Hezekiah
king of Judah: so that he was exalted in the
sight of all nations from thenceforth.
23. brought gifts] Compare Psalms lxviii. 29; Isaiah xviii. 7;
Haggai ii. 7, 8.

24‒33 (compare 2 Kings xx.; Isaiah xxxviii., xxxix.).

Hezekiah’s Sickness. The Ambassadors from Babylon.
Hezekiah’s Death.

²⁴In those days Hezekiah was sick even

unto death: and he prayed unto the Lord; and
he spake unto him, and gave him a sign ¹.
¹ Or, wonder.

24. Remark that this single verse epitomises 2 Kings xx. 1‒11.

In those days] The phrase is taken over from 2 Kings xx. 1, and it
cannot be determined what date is intended, though we may
conclude from 2 Kings xx. 6 that it was a time at which the Assyrian
danger was not yet past, and that it was about the fourteenth year of
Hezekiah (compare Barnes on 2 Kings xx. 1).

he spake] The Hebrew word means, in certain connections, “to

promise,” and the idea of “promise” is present here, the sense being
“God made him a promise and confirmed it by a wonder”; compare 2
Kings xx. 5, 6, 8‒11.

a sign] Rather, a wonder (margin), as in verse 31.

²⁵But Hezekiah rendered not again according

to the benefit done unto him; for his heart was
lifted up: therefore there was wrath upon him,
and upon Judah and Jerusalem.
25. his heart was lifted up] Compare verse 31; 2 Kings xx. 12‒15.

wrath] Hebrew ḳeṣeph, a visitation of Divine wrath; compare xix.

2, 10, xxiv. 18, xxix. 8.

²⁶Notwithstanding Hezekiah humbled himself

for the pride ¹ of his heart, both he and the
inhabitants of Jerusalem, so that the wrath of
the Lord came not upon them in the days of
Hezekiah.
¹ Hebrew the lifting up.

26. humbled himself] Compare 2 Kings xx. 19.

²⁷And Hezekiah had exceeding much riches

and honour: and he provided him treasuries
for silver, and for gold, and for precious
 stones, and for spices, and for shields, and for
all manner of goodly vessels;
27. riches and honour] Compare 2 Kings xx. 13 (= Isaiah xxxix.
2).

shields] Hebrew māginnōth, i.e. small round shields. Perhaps,

like Solomon’s (ix. 15, 16), they were overlaid with gold or silver.
Barnes suggested the reading migdānōth, “precious things” (as in
verse 23), instead of māginnōth. LXX. ὁπλοθήκας, i.e. “armouries”;
Peshitṭa (text being doubtful here) “shields” or “pearls” or “precious
gifts.”

²⁸storehouses also for the increase of corn

and wine and oil; and stalls for all manner of
beasts, and flocks in folds.
28. flocks in folds] The “folds” were enclosures with high stone
walls as a defence against robbers and wild beasts. The text is
probably faulty; Peshitṭa omits the clause.

²⁹Moreover he provided him cities, and

possessions of flocks and herds in
abundance: for God had given him very much
substance.
29. cities] The context suggests that these cities were meant
chiefly as places of refuge for the flocks and herds in time of war; but
again it is probable that the text is corrupt, and that this word should
be omitted.

³⁰This same Hezekiah also stopped the upper

spring of the waters of Gihon, and brought
them straight down on the west side of the city