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END O
AS WE KE
S-
Bruce S. McEwen
with Elizabeth Norton Lasley
T H E
l.~.~0M
P R E S S
Joseph Henry Press
Washington, D.C.
S,)
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Joseph Henry Press · 500 Fifth Street, N.W. · Washington, D.C. 20001
The Joseph Henry Press, an imprint of the National Academies Press, was created with the goal
of making books on science, technology, and health more widely available to professionals and
the public. Joseph Henry was one of the founders of the National Academy of Sciences and a
leader in early American science.
The Dana Press, a division of the Charles A. Dana Foundation, publishes health and popular
science books about the brain for the general reader. The Dana Foundation is a private philan-
thropic organization with particular interests in health and education.
Any opinions, findings, conclusions, or recommendations expressed in this volume are those of
the author and do not necessarily reflect the views of the National Academy of Sciences or its
affiliated institutions.
Library of Congress Cataloging-in-Publication Data
McEwen, Bruce S.
The end of stress as we know it / Bruce S. McEwen, with Elizabeth
Norton Lasley.
p. cm.
Includes bibliographical references and index.
ISBN 0-309-07640-4
1. Stress (Physiology) 2. Stress (Psychology) 3. Stress management.
I. Lasley, Elizabeth Norton. II. Title.
QP82.2.S8 M38 2002
155.9'042 dc21
2002014006
Cover design by Michele de la Menardiere. Cover photograph by Lars Klove/The Image Bank.
Author photograph by Ingbert Gruttner.
Illustrations on pages 22,71, 192, 194, 195, 197, and 198 by Kathryn Born.
Copyright 2002 by Bruce S. McEwen and Elizabeth Norton Lasley. All rights reserved.
Printed in the United States of America
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co
Foreword
Acknowledgments
~ A New Way to Look at Stress
2 The Stress Response—or How We Cope
3 Stress and the Emotional Connection
4 Allostatic Loads When Protection Gives Way
to Damage
5 Stress and the Cardiovascular System
6 Stress and the Immune System
v
· —
V11
X1
1
17
39
55
67
89
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vi / Contents
7 Stress and the Brain
8 How Not to Be Stressed Out
9 Positive Health
10 Where We Could Go from Here
107
135
154
173
Appendix: Chemical Messengers of Allostasis, Their
Receptors, and Their Protective and Damaging Effects 191
Notes
Index
203
225
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The 20th century was filled with ah sorts of brilliant, eccentric
physicists who came up with some pretty cryptic sound bites now and
then God not playing with dice, things of that sort. One of them,
Niels Bohr, had a great one: "Sometimes the opposite of a great truth
is a great falsehood. But sometimes the opposite of a great truth is
another great truth." This is relevant to the course of scientific progress.
There's a perception that science proceeds in a very directional, linear
manner, with an accepted knowledge base and people toiling to inch
the edifice away from great falsehoods toward The Great Truth. In
reality, though, what scientists often have to do is lurch knowledge to-
ward a great truth to counteract their field lurching too far, nearly cap-
sizing, with an enthusiasm for a different great truth.
Psychology, for example, spent the last century lurching. Early on
the field was dominated by William James, who emphasized the great
truth that the mind is the organ of philosophizing. This made psy-
chology an armchair sport of thinking about what's going on inside
that head. By midcentury, psychology was dominated by a different
. .
All
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viii / Foreword
great truth, one meant as a purgative of philosophical psychology. This
one, behaviorism, emphasized how the mind is the organ that produces
measurable behavior, behavior that is shaped by rates of positive and
negative reinforcement. And soon you had B. F. Skinner proclaiming
that a pigeon equals a rat equals a boy, doesn't matter, so long as you
can quantify the number of lever presses they make for a reward just
be able to measure the behavioral output and don't get gummed up
with that mumbo jumbo of what is going on in that black box called
"mind." And psychology has spent recent decades tacking back from
that woefully excessive truth.
.
Medicine has been doing its own zigzagging. One of the most
Important great truths that Western thinking has ever embraced is the
reductionist credo: If you want to understand something complex,
break it down into its small component parts. Understand those build-
ing blocks, fix the ones that are broken, put them back together, and
you're in business. It's a great strategy for fixing Guttenberg's printing
press should it have a mechanical problem. Or for fixing your com-
puter. And it has constituted one of the great truths of medicine for
the last century. If you want to fix a disease, you must understand the
itty bitty things that make you sick bacteria, viruses, or parasites or a
miniscule stretch of DNA containing a mutation.
Now this approach is great. It's gotten us vaccines for yellow fever,
smallpox, polio. Drugs that block the precise step in the replication of
a virus's DNA. It's gotten us the molecular explanation of genetic dis-
orders like sickle cell anemia and Huntington's disease. And it's gotten
us something approximating the sequence of the human genome, the
holy text of reductive medicine.
I'm serious that this really is great. Having been a ki(1 in the Jonas
Salk era, I'm mighty glad I got his vaccine (or maybe it was Sabin's-
let's not even go there). Reductive medical approaches have made stag-
gering inroads against infectious diseases, extending our life spans to
unprece(lente(1 lengths.
But it's time for many branches of medicine to lurch away from
the great truth of reductive medicine to another great truth: You can't
understand a disease outside the context of the person with the dis-
ease something that might be called a holistic approach (a term that
most me(lical scientists loathe for purely visceral reasons).
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Foreword / ix
Think about the following: gazillions are spent by pharmaceutical
companies to invent new drugs targeting reductive steps in disease.
But a huge problem is figuring out why people so often stop taking
their medicine the second they feel better, guaranteeing that they'll have
to do it all over again and that the medicine won't be as effective the
next time. Or that there already exist mountains of very good science
about what constitutes a healthy lifestyle, but still our leading cause of
death is I'll Do It Starting Tomorrow people continuing to eat poorly,
smoke, not exercise, drink in excess.
Other facets of our current picture of health and disease also show
just how little of it has to do with reductive science. Consider that a
major predictor of your risk for a bunch of diseases is your socio-
economic status. Even after controlling for an array of risk factors and
protective factors. Even in countries where there's universal health care,
where no one's poor. Even for diseases that have nothing to do with
how often you go to the doctor. Or that an even better predictor of
health than your socioeconomic status is what you perceive your socio-
economic status to be. Go find a pill to cure the adverse effects of that
on health.
Or how about that public health prognosticators predict that by
2025 the second leading cause of medical disability on earth will be
clinical depression? You're never going to be able to vaccinate people
against life in a way that would provide a reductive cure for that dis-
ease. Or that if you want to save millions of lives annually in the (level-
oping worI(l, forget reductive medicine and get people some clean
water. Or that Americans now spend roughly a quarter of their health
dollars on alternative medicine, in large part because its practitioners
actually do something as retro as talk to their patients, spend more
than 8.3 minutes with them. Or that being isolated, anonymous, lonely
is (lemonstrably (lamaging to your health.
We've entered the gil(le(1 genomics era just in time to have to a(l-
mit that most of our ills have to do with extraordinarily ungenomic
things like your psychological makeup and patterns of social relations,
your social status and the society in which you have that status, your
lifestyle. And at the center of this nexus is stress what stressors we
are expose(1 to and how we cope. Most of us will live long enough and
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x / Foreword
well enough to get seriously ill with a stress-related disease. And given
that most of us would rather have this happen later than sooner, it is
well worth learning about the links between stress and disease. To that
end, you have in your hands a superb introduction to this subject.
There is no one better situated to have written such a book than Bruce
McEwen.
His own scientific history is interesting. Despite being intrigued
with psychology back in high school, he started his research career as a
graduate student in the early 1960s as a cell biologist doing that re-
ductive science stuff. And McEwen has continued making seminal con-
tributions in that reductive realm since then, in showing the effects of
stress on the brain and the immune system. This has earned him a
trunk-full of accolades: an endowed professorship at one of the most
prestigious research institutes in the world, presidency of the interna-
tional Society for Neuroscience, election to the National Academy of
Sciences, the highest honor for an American scientist.
But along the way McEwen also branched off into that more inte-
grative realm of this subject, involving himself in the markedly
unreductive issues of what emotions, coping, socioeconomic status,
and so on have to do with health. And in that path he has pioneered
some extraordinarily important research showing what "allostatic
loa(l" what might be called the cumulative wear and tear of life, a
topic covered at length in this book has to do with disease. What
these parallel branches of investigation have produced is the leading
living scholar of stress. This book represents a wonderful distillation of
that knowledge clear, readable, as scientifically authoritative as you
can find. It is a decidedly unreductive fact that reading the right book
can improve your health; this is one such book.
Robert Sapolsky
Stanford, California
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Ackn'
ents
I wish to thank my current and former students and postdoctoral
fellows who taught me at least as much as I taught them. A lot of their
hard work and some of their names are referred to in the pages of this
book. I also thank many professional colleagues, particularly Don Pfaff,
Fernando Nottebohm, Paul Greengard, and Torsten Wiesel at the
Rockefeller University, and a host of other neuroscientists throughout
the world who have inspired me and provided important insights along
with their collaborative energies. I am particularly indebted to col-
leagues, past and present, of the MacArthur Research Network on So-
cioeconomic Status and Health (Nancy Adler, University of California,
San Francisco, Chair), and particularly Teresa Seeman at UCLA and
Burton Singer at Princeton University, for their efforts in
operationalizing the concept of allostatic load. I want to acknowledge
my mentors: the late Alfred Mirsky, Vincent AlIfrey, the late Holger
Hyden, the late Neal Miller, and the late Eliot Stellar, who helped to
shape my scientific thinking and my concept of the responsiblities of a
scientist toward society.
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xii /Ackr~owledgmer~ts
Special thanks to the scientists who gave of their time to review
and comment on the manuscript, including John Mason, most recently
of Yale University, Car] Sheck of Oregon State University, Stephen
Porges of the University of Illinois at Chicago, and Firdaus Dhabhar of
Ohio State University.
Finally, the work involved in writing this book was made much
easier by the administrative and clerical efforts of Adelaide Acquaviva,
Halina Korsun, and Maryse Aubourg, and by the tireless efforts of the
editorial team. Heartfelt thanks to Stephen Mautner at the Joseph
Henry Press and to Jane Nevins at the Dana Press for their vision, criti-
cism, and enthusiasm.
Bruce McEwen
New York City
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