The Lock and Key of Medicine: Monoclonal Antibodies and the Transformation of Healthcare

345 Pages·2015·3.44 MB·English

by  Lara V. Marks

the lock and key of medicine
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l ara v. marks
The Lock and Key
of Medicine
Monoclonal Antibodies and the
Transformation of Healthcare
n e w h av e n a n d l o n d o n
Copyright © 2015 by Lara V. Marks
All rights reserved.
This book may not be reproduced, in w hole or in part, including illustrations, in any form
(beyond that copying permitted by Sections 107 and 108 of the U.S. Copyright Law and
except by reviewers for the public press), without written permission from the publishers.
Yale University Press books may be purchased in quantity for educational, business, or
promotional use. For information, please e-m ail
To my two children, Daniel and Anna, and to the memory of César
Milstein, Hubert Schoemaker, and Michael Neuberger, each of whom
played a vital part in the development of Mabs, and to the memory of
my mentor Irvine Loudon
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contents
List of Illustrations ix
Preface xi
Ack nowl edgm ents xxi
List of Abbreviations xxv
1 Hunting for the Elusive “Magic Bullet” 1
2 A Hesitant Start: Patents, Politics, and Proc ess 25
3 Breakthroughs at the Bench 47
4 The First Medical Applications 69
5 Joy, Disappointment, Determination: Early
Clinical Tests 88
6 The Wild West of Antibody Commercialization 110
7 The Challenge of Monoclonal Antibody Drugs 139
8 Antibody Engineering: A Ren aiss ance for
Mab Therapeutics 159
9 Blockbuster Mab Drugs 184
10 A Quiet Revolution: The Legacy of Monoclonal
Antibodies 218
v i i i contents
Notes 237
Glossary 293
Bibliography 301
Index 307
illustrations
figures
1.1. P aul Ehrlich, ca. 1908, with his depiction of his side-c hain
theory of immunity 5
1.2. B asic structure of an antibody 15
1.3. M icroscope photo of hybridoma cell secreting
monoclonal antibodies 21
1.4. P etri dishes with fi rst Mabs grown by Milstein and Köhler 22
1.5. C ésar Milstein and Georges Köhler, 1984 23
2.1. C ésar Milstein with fl ask of Mabs growing in a fl uid 26
2.2. H ilary Koprowski 29
2.3. E quipment for the continuous growth of myeloma cells 35
2.4. B asic protocol developed by Georges Köhler and
César Milstein for making Mabs 41
3.1. C ésar Milstein and Claudio Cuello, ca. 1975 50
4.1. C ésar Milstein and David Secher, ca. 1980 72
4.2. D istinctive clumping of blood group A with anti-A Mab 80
5.1. R on Levy 97
5.2. H erman Waldmann, ca. 1970 100
6.1. D avid Murray celebrating Thames TV Business
Award, 1978 113
6.2. A erial photo of Sera-L ab, 1 986 117
6.3. S era-L ab’s portable cabins, early 1980s 117
6.4. A dvertisement for Mabs in Sera-L ab catal og, 1978 119
6.5. E arly Centocor founde rs, ca. 1979 126
6.6. H ubert Schoemaker, ca. 1987 127
6.7. J enny Murray, 1980s 136
8.1. C ésar Milstein, Michael Neuberger, and Gregory W inter 164
8.2. N ils Lonberg 171
8.3. D iff erent generations of Mabs showing murine and
h uman protein components 175
8.4. T imeline for Mab engineering techniques from
fi rst p ublication to fi rst drug approval 178