Thalassaemia: The Biography

258 Pages·2010·1.662 MB·English

by  David Weatherall

thalassaemia
This page intentionally left blank
thalassaemia
The Biography
R
David Weatherall
3
3
Great Clarendon Street, Oxford ox26dp
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 in
Oxford New York
Auckland Cape Town Dar es Salaam Hong Kong Karachi
Kuala Lumpur Madrid Melbourne Mexico City Nairobi
New Delhi Shanghai Taipei Toronto
With offi ces in
Argentina Austria Brazil Chile Czech Republic France Greece
Guatemala Hungary Italy Japan Poland Portugal Singapore
South Korea Switzerland Thailand Turkey Ukraine Vietnam
Oxford is a registered trade mark of Oxford University Press
in the UK and in certain other countries
Published in the United States
by Oxford University Press Inc., New York
© David Weatherall 2010
The moral rights of the author have been asserted
Database right Oxford University Press (maker)
First published 2010
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, or under terms agreed with the appropriate
reprographics rights organization. Enquiries 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 book in any other binding or cover
and you must impose the same condition on any acquirer
British Library Cataloguing in Publication Data
Data available
Library of Congress Cataloging in Publication Data
Library of Congress Control Number: 2010930323
Typeset by SPI Publisher Services, Pondicherry, India
Printed in Great Britain
on acid-free paper by
Clays Ltd., St Ives Plc
ISBN 978–0–19–956560–3
1 3 5 7 9 10 8 6 4 2
preface
The thalassaemias are among the most common genetic
diseases and affect thousands of children throughout the
world. This short account of the history of this disorder and
how the elucidation of its underlying causes helped to lead the
way towards the era of molecular medicine is based in part on
a more extensive account in an earlier book, The Thalassaemia
Syndromes, and several other essays and reviews on the same
theme. For readers who wish to explore aspects of this fi eld in
more detail, or its extensive literature, there is a short bibliog-
raphy to point them in the right direction. For those who are
unfamiliar with current genetics, there is also a short glossary.
In tracing this complex story I have had the help of many
colleagues over the years, notably Maxwell Wintrobe, Ida
Bianco, Robin Bannerman, Vernon Ingram, and John Clegg.
I would also like to acknowledge the help of Jeanne Packer
and Liz Rose in preparing this manuscript, Lady Brabourne
for giving permission to reproduce the picture of Lady
Mountbatten and Jaspir Thapa, Wolf Zeulzer for the photo-
graph of Thomas Cooley, Elizabeth Letsky for the photograph
of the thalassaemic child, and Blackwell/Wiley for permission
to reproduce other fi gures from The Thalassaemia Syndromes.
v
This page intentionally left blank
contents
List of Illustrations ix
Prologue 1
1 The First Descriptions of Thalassaemia 6
2 Thalassaemia as a Genetic Disease 24
3 Thalassaemia as a Genetic Disorder of
Haemoglobin Production 35
4 The Diversity and Pathology of the Thalassaemias 59
5 Early Improvements in the Management of
Children with Thalassaemia 89
6 Thalassaemia and the Dawn of Molecular
Medicine 111
7 The Control and Management of Thalassaemia
in the Cellular and Molecular Era 146
8 The Commonest Genetic Diseases:
Was Haldane Right? 175
9 Epilogue: Thalassaemia and Molecular Medicine 194
Glossary 207
Bibliography and Further Reading 213
General Index 237
vii
This page intentionally left blank
list of illustrations
1. Lady Mountbatten with Jaspir Thapa, February 1960.
Courtesy of Lady Brabourne 4
2. Letter from Lord Mountbatten to the author,
May 1979 5
3. Thomas B. Cooley. Courtesy of Wolf Zeulzer 11
4. A child with severe thalassaemia. Courtesy of
Elizabeth Letsky 12
5. A skull X-ray from a child with severe thalassaemia 13
6. Peripheral blood fi lm of a child with thalassaemia 14
7. Haemoglobin electrophoresis on starch gel 40
8. The haemoglobin patterns in the sickle-cell trait
and sickle-cell b thalassaemia 47
9. Haemoglobin changes in the sickle-cell trait 48
10. Ragged inclusion bodies in the red-cell
precursors in the bone marrow of a patient
with b thalassaemia 75
11. Globin synthesis in normal and b thalassaemic
red cells 80
12. The effects of the development of prenatal
diagnosis on the expected number of births
with thalassaemia 109
ix