The Pathological Protein: Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases

289 Pages·2003·1.746 MB·English

by  Philip Yam (auth.)

The Pathological Protein
The
Pathological
Protein
Mad Cow, Chronic Wasting,
and Other Deadly Prion Diseases
Philip Yam
copernicus books
An Imprint of Springer-Verlag
© 2003 Philip Yam
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, electronic,
mechanical, photocopying, recording, or otherwise, without the prior written
permission of the publisher.
Published in the United States by Copernicus Books,
an imprint of Springer-Verlag New York, Inc.
Amember of BertelsmannSpringer Science+Business Media GmbH
Copernicus Books
37 East 7th Street
New York, NY10003
www.copernicusbooks.com
Book design and line art by Jordan Rosenblum.
Library of Congress Cataloging-in-Publication Data
Yam, Philip.
The pathological protein: mad cow, chronic wasting, and other deadly prion
diseases / Philip Yam.
p. cm.
Includes bibliographical references and index.
ISBN 0-387-95508-9 (alk. paper)
1. Prion diseases—Popular works. I. Title.
RA644.P93 Y35 2003
616.8’3—dc21 2002042730
Manufactured in the United States of America.
Printed on acid-free paper.
9 8 7 6 5 4 3 2 1
ISBN 0-387-95508-9 SPIN 10880347
To my father, Peter, and my mother in memoriam, Wanda
CONTENTS
Acknowledgments xi
Introduction xii
CHAPTER 1 A Death in Devizes 1
An unusual death in the U.K. marks the arrival
of a harrowing new brain disease.
A Boundless Future 2
Troubling Signs 4
“You Don’t Die of Depression” 8
No Answers 9
CHAPTER 2 One in a Million 13
A rare disease only gradually becomes recognized
as the most common human spongiform encephalopathy.
The Unlucky Few 16
Diagnosing CJD 17
Stephen’s Case: CJD? 20
CHAPTER 3 The Cannibals’ Laughing Death 23
On a South Pacific island, two pioneering researchers begin
to unlock the mysterious epidemic of kuru.
Epidemic in the Bush 26
A Real-Life M*A*S*HDoctor 28
A Lifelong Pursuit Begins 30
Brain Clues 34
CHAPTER 4 Connecting the Holes 37
Linking kuru to a disease of sheep enables researchers to
experiment with a brain-destroying agent.
An Uncanny Resemblance 38
Studying Scrapie 41
Trying Transmissions 43
Georgette’s Sacrifice 45
The Kuru–CJD Link 47
An End to an Epidemic 48
Nobel Worthy 49
CHAPTER 5 The Birth of the Prion 51
The unusual mode of attack and biochemical durability
of the TSE agent leads to an heretical idea.
A Tough Invader 56
The Elusive Agent 58
TSEs’ New Player 59
Prion Proposal 62
Fatal Filaments 64
The Normal and the Diabolical 66
CHAPTER 6 Family Curses 69
Two rare hereditary diseases add support to the prion
hypothesis—and challenge it, too.
Coding for Disease 71
The Family That Couldn’t Sleep 74
One Codon, Two Diseases 79
The Strains Puzzle 81
Explaining Strains with Prions 84
CHAPTER 7 On the Prion Proving Grounds 87
Research in yeast and other studies show how prions can
possess hereditary information and change their shapes.
Prions of Yeast 89
From Helix to Sheet 92
Cofactors or Cold Fusion? 98
The Copper Connection 102
Double Trouble 104
CHAPTER 8 Consuming Fears 107
Modern agriculture enables prions to adapt to a new host,
creating the dread mad cow disease.
Tracking the Source 110
Forced Cannibalism 112
Tackling an Epidemic 117
Mad Max 121
The Watcher 124
Approaching the Watershed 127
CHAPTER 9 Mad Cow’s Human Toll 137
Figuring out how many people will succumb to variant
Creutzfeldt-Jakob disease isn’t easy—especially now that
BSE has spread around the world.
Calculating Mortality 138
Mad Sheep Disease? 144
Spreading the Madness 145
CHAPTER 10 Keeping the Madness Out 153
Several measures help ensure that animal prion diseases do
not contaminate the U.S. food supply—but there are gaps.
Cows in the Crosshairs 154
Bovine Barricades 157
Breaks in the Firewall 160
American Madness? 163
In Case of Emergency . . . 166
Pigs and Sheep 168
CHAPTER 11 Scourge of the Cervids 171
Chronic wasting disease of deer and elk, once confined
to a patch in the Rockies, spreads across the nation.
Out and About 176
Venison and Beyond 178
CHAPTER 12 Misadventures in Medicine 183
Prion diseases spread to humans through medical mishaps.
Surgical Spread 184
Deadly Eyes 188
Hazardous Hormones 188
Patch Full of Prions 191
Blood Safety 193
Dental Danger 197
Beyond Beef 199
Mystery Pills 202
CHAPTER 13 Searching for Cures 205
New hope that the death sentence of prion diseases might
someday be lifted.
New Use for Old Drugs 206
Rational Thinking 211
Diagnosing Prion Diseases 215
CHAPTER 14 Laying Odds 223
Are prion diseases more prevalent than we thought?
Revisiting Sporadic CJD 223
A Case for Undercounting 227
Maverick Mayhem 232
Menu Choices 234
Man-Made Madness 235
Notes 239
Glossary 257
For Further Information 265
Index 269
Acknowledgments
This book is really a story of many career-long struggles to understand a
rare family of neurodegenerative diseases, and I could not have told it
without the time and attention that so many researchers granted me.
Their contributions should be clear in these pages. My gratitude also
goes to David and Dorothy Churchill, who allowed me into their home
and re-lived their loss for my sake.
Friends and colleagues pitched in in many ways that made the book
writing possible. John Rennie, Ricki Rusting, Gary Stix, and Molly
Frances at Scientific Americangave support, provided notes, reviewed
drafts, and watched over my magazine duties while I worked on this
project. I thank Bridget Gerety and Ed Bell for their help on the photo-
graphs, David Labrador for his fine-toothed fact-checking, and Julia
Karow for her skilled translations of technical articles from old
German journals. I am particularly indebted to Steve Mirsky, whose
research assistance and draft comments were indispensable, and to
Karen Hopkin, who helped get me started on this project and gave
expert insight, guidance, and input in several areas of molecular biology.
Additional valuable feedback came from Michael Yam and Lucy Chou,
who also cheerfully did the driving on the opposite side of the road
while we were in the U.K.
I thank my agent, Jennifer Gates of the Zachary Shuster Harmsworth
Agency, editors Tim Yohn and Lyman Lyons, and designers Jordan
Rosenblum and Stephanie Blumenthal. At Copernicus Books, thanks to
Anna Painter, Mareike Paessler, and especially Paul Farrell, whose com-
mitment and belief in the project saw it through some trying times.
Philip Yam
March 2003
xi
Introduction
As I reclined in the patient chair in my dentist’s Midtown Manhattan
office last February, waiting for a lead apron and the film for bitewing x-
rays, I noticed the stainless steel instruments glistening under the hard
light of the examination lamp. Sharp hooks and pointed probes were
carefully laid out on the tray. Some were still in their plastic wrapping,
indicating that they had been sterilized. Soon, the dentist would push
these tools between my teeth, under my gums, down the little pits in
my enamel. One of the instruments might even draw a bit of blood—
not an uncommon occurrence when the gums are inflamed by plaque
buildup and sharp bits of metal are involved.
Then a thought occurred to me. “Do you have British patients?”
“Oh sure. I had two from Europe the other day,” my dental hygienist
replied as she circled behind the chair to clasp a paper bib around my
neck. Alot of transatlantic traffic comes through this New York City
office, she added. Some Europeans, she guessed, prefer the American
approach of preventive dental care.
And that’s when I realized that my risk of catching the human form
of mad cow disease from these instruments was not zero.
You might wonder: How could this be? Are the instruments not steril-
ized? The answer is yes—and no. Many surgical and dental tools are
steam-heated for 15 to 30 minutes at some 121˚ C (250˚ F). These scorch-
ing temperatures are more than a match for the bacterium that causes
tuberculosis and the viruses that cause AIDS and hepatitis. In fact, you
name it, and time and temperature in the autoclave will take care of it.
Yet such extreme conditions cannot completely destroy the “mad cow”
agent that, over time, peppers the brain with microscopic holes, caus-
ing clumsiness, dementia, and eventually death. Even formaldehyde,
xii