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Page 1 of 212WHY ZEBRAS DON'T GET ULCERS BY ROBERT M. SAPOLSKY
WHY ZEBRAS DON'T GET ULCERS
Third Edition
ROBERT M. SAPOLSKY
Copyright © 1994,1998 by W. H. Freeman, and 2004 by Robert M. Sapolsky
ISBN:9780805073690
For Lisa, my best friend, who has made my life complete
CONTENTS
Preface xi 1 Why Don't Zebras Get Ulcers? 1 2 Glands, Gooseflesh, and Hormones 19 3 Stroke,
Heart Attacks, and Voodoo Death 37 4 Stress, Metabolism, and Liquidating Your Assets 57 5
Ulcers, the Runs, and Hot Fudge Sundaes 71 6 Dwarfism and the Importance of Mothers 92
7 Sex and Reproduction 120
8 Immunity, Stress, and Disease 144
9 Stress and Pain 186
10 Stress and Memory 202
11 Stress and a Good Night's Sleep 226
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12 Aging and Death 239
13 Why Is Psychological Stress Stressful? 252
14 Stress and Depression 271
15 Personality, Temperament, and
Their Stress-Related Consequences 309
16 Junkies, Adrenaline Junkies, and Pleasure 335
17 The View from the Bottom 353
18 Managing Stress 384
Notes 419
Illustration Credits 517
Index 521
PREFACE
Perhaps you're reading this while browsing in a bookstore. If so, glance over at the guy down the aisle when he's not
looking, the one pretending to be engrossed in the Stephen Hawking book. Take a good look at him. He's probably not
missing fingers from leprosy, or covered with smallpox scars, or shivering with malaria. Instead, he probably appears
perfectly healthy, which is to say he has the same diseases that most of us have—cholesterol levels that are high for an
ape, hearing that has become far less acute than in a hunter-gatherer of his age, a tendency to dampen his tension with
Valium. We in our Western society now tend to get different diseases than we used to. But what's more important, we
tend to get different kinds of diseases now, with very different causes and consequences. A millennium ago, a young
hunter-gatherer inadvertently would eat a reedbuck riddled with anthrax and the consequences are clear—she's dead a
few days later. Now, a young lawyer unthinkingly decides that red meat, fried foods, and a couple of beers per dinner
constitute a desirable diet, and the consequences are anything but clear—a half-century later, maybe he's crippled with
cardiovascular disease, or maybe he's taking bike trips with his grandkids. Which outcome occurs depends on some
obvious nuts-and-bolts factors, like what his liver does with cholesterol, what levels of certain enzymes are in his fat
cells, whether he has any congenital weaknesses in the walls of his blood vessels. But the outcome will also depend
heavily on such surprising factors as his personality, the amount of emotional stress he experiences over the years,
whether he has someone's shoulder to cry on when those stressors occur.
There has been a revolution in medicine concerning how we think about the diseases that now afflict us. It involves
recognizing the
interactions between the body and the mind, the ways in which emotions and personality can have a tremendous
impact on the functioning and health of virtually every cell in the body. It is about the role of stress in making some of
us more vulnerable to disease, the ways in which some of us cope with stressors, and the critical notion that you
cannot really understand a disease in vacuo, but rather only in the context of the person suffering from that disease.
This is the subject of my book. I begin by trying to clarify the meaning of the nebulous concept of stress and to teach,
with a minimum of pain, how various hormones and parts of the brain are mobilized in response to stress. I then focus
on the links between stress and increased risk for certain types of disease, going, chapter by chapter, through the
effects of stress on the circulatory system, on energy storage, on growth, reproduction, the immune system, and so on.
Next I describe how the aging process may be influenced by the amount of stress experienced over a lifetime. I then
examine the link between stress and the most common and arguably most crippling of psychiatric disorders, major
depression. As part of updating the material for this third edition, I have added two new chapters: one on the
interactions between stress and sleep, and one on what stress has to do with addiction. In addition, of the chapters that
appeared in the previous edition, I rewrote about a third to half of the material.
Some of the news in this book is grim—sustained or repeated stress can disrupt our bodies in seemingly endless ways.
Yet most of us are not incapacitated by stress-related disease. Instead, we cope, both physiologically and
psychologically, and some of us are spectacularly successful at it. For the reader who has held on until the end, the
final chapter reviews what is known about stress management and how some of its principles can be applied to our
everyday lives. There is much to be optimistic about.
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I believe that everyone can benefit from some of these ideas and can be excited by the science on which they are
based. Science provides us with some of the most elegant, stimulating puzzles that life has to offer. It throws some of
the most provocative ideas into our arenas of moral debate. Occasionally, it improves our lives. I love science, and it
pains me to think that so many are terrified of the subject or feel that choosing science means that you cannot also
choose compassion, or the arts, or be awed by nature. Science is not meant to cure us of mystery, but to reinvent and
reinvigorate it.
Thus I think that any science book for nonscientists should attempt to convey that excitement, to make the subject
interesting and accessible even to those who would normally not be caught dead near the
subject. That has been a particular goal of mine in this book. Often, it has meant simplifying complex ideas, and as a
counterbalance to this, I include copious references at the end of the book, often with annotations concerning
controversies and subtleties about material presented in the main text. These references are an excellent entree for
those readers who want something more detailed on the subject.
Many sections of this book contain material about which I am far from expert, and over the course of the writing, a
large number of savants have been called for advice, clarification, and verification of facts. I thank them all for their
generosity with their time and expertise: Nancy Adler, John Angier, Robert Axelrod, Alan Baldrich, Marcia Barinaga,
Alan Basbaum, Andrew Baum, Justo Bautisto, Tom Belva, Anat Biegon, Vic Boff (whose brand of vitamins graces
the cupboards of my parents' home), Carlos Camargo, Matt Cartmill, M. Linette Casey, Richard Chapman, Cynthia
Clinkingbeard, Felix Conte, George Daniels, Regio DeSilva, Irven DeVore, Klaus Dinkel, James Doherty, John
Dolph, Leroi DuBeck, Richard Estes, Michael Fanselow, David Feldman, Caleb Tuck Finch, Paul Fitzgerald, Gerry
Friedland, Meyer Friedman, Rose Frisch, Roger Gosden, Bob Grossfield, Kenneth Haw-ley, Ray Hintz, Allan
Hobson, Robert Kessler, Bruce Knauft, Mary Jeanne Kreek, Stephen Laberge, Emmit Lam, Jim Latcher, Richard
Lazarus, Helen Leroy, Jon Levine, Seymour Levine, John Liebeskind, Ted Macolvena, Jodi Maxmin, Michael Miller,
Peter Milner, Gary Moberg, Anne Moyer, Terry Muilenburg, Ronald Myers, Carol Otis, Daniel Pearl, Ciran Phibbs,
Jenny Pierce, Ted Pincus, Virginia Price, Gerald Reaven, Sam Ridgeway, Carolyn Ristau, Jeffrey Ritterman, Paul
Rosch, Ron Rosenfeld, Aryeh Routtenberg, Paul Saenger, Saul Schanburg, Kurt Schmidt-Nielson, Carol Shively, J.
David Singer, Bart Sparagon, David Speigel, Ed Spielman, Dennis Styne, Steve Suomi, Jerry Tally, Carl Thoresen,
Peter Tyak, David Wake, Michelle Warren, Jay Weiss, Owen Wolkowitz, Carol Worthman, and Richard Wurtman.
I am particularly grateful to the handful of people—friends, collaborators, colleagues, and ex-teachers—who took
time out of their immensely busy schedules to read chapters. I shudder to think of the errors and distortions that would
have remained had they not tactfully told me I didn't know what I was writing about. I thank them all sincerely:
Robert Ader of the University of Rochester; Stephen Bezruchka of the University of Washington; Marvin Brown of
the University of California, San Diego; Laurence Frank at the University of California, Berkeley; Craig Heller of
Stanford University; Jay Kaplan of Bowman Gray Medical School; Ichiro Kawachi of Harvard University; George
Knob of the Scripps Clinic; Charles Nemeroff of Emory University;
Seymour Reichlin of Tufts/New England Medical Center; Robert Rose of the MacArthur Foundation; Tim Meier of
Stanford University; Wylie Vale of the Salk Institute; Jay Weiss of Emory University; and Redford Williams of Duke
University
A number of people were instrumental in getting this book off the ground and into its final shape. Much of the
material in these pages was developed in continuing medical education lectures. These were presented under the
auspices of the Institute for Cortext Research and Development, and its director, Will Gordon, who gave me much
freedom and support in exploring this material. Bruce Goldman of the Portable Stanford series first planted the idea
for this book in my head, and Kirk Jensen recruited me for W H. Freeman and Company; both helped in the initial
shaping of the book. Finally, my secretaries, Patsy Gardner and Lisa Pereira, have been of tremendous help in all the
logistical aspects of pulling this book together. I thank you all, and look forward to working with you in the future.
I received tremendous help with organizing and editing the first edition of the book, and for that I thank Audrey
Herbst, Tina Hastings, Amy Johnson, Meredyth Rawlins, and, above all, my editor, Jonathan Cobb, who was a
wonderful teacher and friend in this process. Help in the second edition came from John Michel, Amy Trask, Georgia
Lee Hadler, Victoria Tomaselli, Bill O'Neal, Kathy Bendo, Paul Rohloff, Jennifer MacMillan, and Sheridan Sellers.
Liz Meryman, who selects the art for Natural History magazine, helping to merge the cultures of art and science in
that beautiful publication, graciously consented to read the manuscript and gave splendid advice on appropriate
artwork. In addition, I thank Alice Fernandes-Brown, who was responsible for making my idea for the cover such a
pleasing reality. In this new edition help came from Rita Quintas, Denise Cronin, Janice O'Quinn, Jessica Firger, and
Richard Rhorer at Henry Holt.
This book has been, for the most part, a pleasure to write and I think it reflects one of the things in my life for which I
am most grateful—that I take so much joy in the science that is both my vocation and avocation. I thank the mentors
who taught me to do science and, even more so, taught me to enjoy science: the late Howard Klar, Howard
Eichenbaum, Mel Konner, Lewis Krey, Bruce McEwen, Paul Plotsky, and Wylie Vale.
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A band of research assistants have been indispensable to the writing of this book. Steve Bait, Roger Chan, Mick
Markham, Kelley Parker, Michelle Pearl, Serena Spudich, and Paul Stasi have wandered the basements of archival
libraries, called strangers all over the world with questions, distilled arcane articles into coherency. In the
line of
duty, they have sought out drawings of opera castrati, the daily menu at Japanese-American internment camps, the
causes of voodoo death, and the history of firing squads. All of their research was done with spectacular competence,
speed, and humor. I am fairly certain this book could not have been completed without their help and am absolutely
certain its writing would have been much less enjoyable. And finally, I thank my agent, Katinka Matson, and my
editor, Robin Dennis, who have been just terrific to work with. I look forward to many more years of collaborations
ahead.
Parts of the book describe work carried out in my own laboratory, and these studies have been made possible by
funding from the National Institutes of Health, the National Institute of Mental Health, the National Science
Foundation, the Sloan Foundation, the Klingen-stein Fund, the Alzheimer's Association, and the Adler Foundation.
The African fieldwork described herein has been made possible by the long-standing generosity of the Harry Frank
Guggenheim Foundation. Finally, I heartily thank the MacArthur Foundation for supporting all aspects of my work.
Finally, as will be obvious, this book cites the work of a tremendous number of scientists. Contemporary lab science
is typically carried out by large teams of people. Throughout the book, I refer to the work of "Jane Doe" or "John
Smith" for the sake of brevity—it is almost always the case that such work was carried out by Doe or Smith along
with a band of junior colleagues.
There is a tradition among stress physiologists who dedicate their books to their spouses or significant others, an
unwritten rule that you are supposed to incorporate something cutesy about stress in the dedication. So, to Madge,
who attenuates my stressors; for Arturo, the source of my eustress; for my wife who, over the course of the last
umpteen years, has put up with my stress-induced hypertension, ulcerative colitis, loss of libido, and displaced
aggression. I will forgo that style in the actual dedication of this book to my wife, as I have something simpler to say.
1
WHY DON'T ZEBRAS GET ULCERS?
It's two o'clock in the morning and you're lying in bed. You have something immensely important and challenging to
that next day—a critical meeting, a presentation, an exam. You have to get a decent night's rest, but you're
still wide awake. You try different strategies for relaxing— take deep, slow breaths, try to imagine restful mountain
scenery—but instead you keep thinking that unless you fall asleep in the next minute, your career is finished. Thus
you lie there, more tense by the second.
If you do this on a regular basis, somewhere around two-thirty, when you're really getting clammy, an entirely new,
disruptive chain of thought will no doubt intrude. Suddenly, amid all your other worries, you begin to contemplate
that nonspecific pain you've been having in your side, that sense of exhaustion lately, that frequent headache. The
realization hits you—I'm sick, fatally sick! Oh, why didn't I recognize the symptoms, why did I have to deny it, why
didn't I go to the doctor?
When it's two-thirty on those mornings, I always have a brain tumor. These are very useful for that sort of terror,
because you can attribute every conceivable nonspecific symptom to a brain tumor and justify your panic. Perhaps
you do, too; or maybe you lie there thinking that you have cancer, or an ulcer, or that you've just had a stroke.
Even though I don't know you, I feel confident in predicting that you don't lie there thinking, "I just know it; I have
leprosy." True? You are exceedingly unlikely to obsess about getting a serious case of dysentery if it starts pouring.
And few of us lie there feeling convinced that our bodies are teeming with intestinal parasites or liver flukes.
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