Mismatch.Pdf

Mismatch This page intentionally left blank mismatch Why our World No Longer Fits our Bodies PETER GLUCKMAN AND MARK HANSON 1 3 Great Clarendon Street, Oxford ox2 6dp 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 offices 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 © Peter Gluckman and Mark Hanson Foreword © Robert Winston, 2006 The moral rights of the authors have been asserted Database right Oxford University Press (maker) First published 2006 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 this same condition on any acquirer British Library Cataloguing in Publication Data Data available Library of Congress Cataloging in Publication Data Gluckman, Peter D. Mismatch : Why our bodies no longer fit our world Peter Gluckman and Mark Hanson. p. cm. Includes bibliographical references and index. ISBN-13: 978-0-19-280683-3 (alk. paper) ISBN-10: 0-19-280683-1 (alk. paper) 1. Ecological genetics. 2. Evolution (Biology). 3. Genotype—environment interaction. I. Hanson, Mark. II. Title. QH456.G58 2006 576.5′8—dc22 2006019107 Typeset by RefineCatch Limited, Bungay, Suffolk Printed in Great Britain on acid-free paper by Clays Ltd., St Ives plc ISBN 0–19–280683–1 978–0–19–280683–3 13579108642 Foreword At the end of the first chapter of The Life and Opinions of Tristram Shandy, Mrs Shandy asks ‘Pray, my dear, have you not forgot to wind up the clock?’ to which Tristram’s distracted father responds: ‘Good G—! Did ever woman, since the creation of the world, interrupt a man with such a silly question?’ And once he is born, Tristram is trapped thereafter in a time-warp, his whole life (and the book about him) muddled by time. As he says, ‘I wish either my father or my mother, or indeed both of them, as they were in duty both equally bound to it, had minded what they were about when they begot me; had they duly considered how much depended upon what they were then doing.’ Lawrence Sterne was writing in 1759. But this idea—that events at the time of conception, or during gestation, influence not only the outcome of a pregnancy but also the developing character of the child—has prevailed since earliest written records. There is evidence for this in cuneiform tablets from Sumer and in papyri from ancient Egypt. The Biblical account in Genesis when Jacob encourages the birth of speckled sheep (probably a genetically recessive characteristic) in Laban’s flock of pure whites, by showing them black and white whittled sticks at the moment of conception, suggests that this notion has been widely prevalent for a very long time indeed. The discoveries of Gregor Mendel, the gardening monk from Brno who died in 1884, led to a more ‘rational’ understanding of inheritance. But the implications of his work were not fully accepted until well after his death, more than forty years after his original observations. His detailed experi- ments with around 28,000 pea plants eventually gave birth to the idea of the gene being the unit of inheritance, with the Laws of Inheritance named after him. That insight, and the rising importance of the theory of evolution promulgated by Charles Darwin, who died just two years before Mendel (and who may have just possibly known of his controversial work), led to a radical change in our ideas of inherited characteristics. These ideas were not universally accepted very quickly. It took until the v FOREWORD 1920’s when it became widely agreed that the genetic variation in popula- tions occurred because of mutations, or changes, in genes. Phenotypic changes, i.e. changes in the constitution or appearance of an organism, were seen to be gradual as a response to the pressures of natural selection which selected those inherited characteristics that better matched the organism with its environment. Subsequently the modern science of molecular biology showed how the structure of the DNA with its base-pair sequences influences the phenotype by producing specific changes in the RNA and the manufacture of various proteins. And it also became clearer how the mater- nal and paternal chromosomes, carrying the genes were passed to their offspring. But this knowledge, once accepted, led to rather determinist notions about human genetics. It was very easy to think of a gene consistently producing just one aspect of the phenotype, but this is far from the complete story. Genes can produce their influence in ways that are much more subtle than was widely understood. So it is only quite recently that the con- ventional, deterministic view of genetic inheritance has had to be re- evaluated. In the last fifteen years or so there has been increasing evidence that the environment can have a much greater effect on the way genes work than was realized in Mendel’s original concept. There is startling evidence, too, that the environment that prevails during an individual’s early development can radically affect later life. These early influences may be particularly important when the individual is still inside the uterus. There is strong evidence that many of these effects may be caused by chemical changes in genes and may immediately alter the characteristics of succeed- ing generations. One compelling, recent discovery was that disease in middle or old age could have its origins in events before birth. David Barker, from the Uni- versity of Southampton, meticulously trawled through a huge number of records of the births of children delivered in Hertfordshire just before, during, and after the First World War. Most of the mothers of these children had normal pregnancies. But inevitably, there were some hospital records of women with complicated pregnancies. Some of their babies experienced a deficient environment while in the uterus and were not well nourished, being born well below normal birth weight in consequence. In general, the babies who were born much smaller than average particularly those who were really small, around two kilograms in weight—turned out to be at vi FOREWORD increased risk of ill health in later life. A far greater proportion of the adults who started life as very small babies died from coronary heart disease before the age of 65 years. The beginning of their life had been spent in a sub- optimal milieu and the effort of attempting to compensate for this left them with constitutional scars which had grave effects decades later. These babies were, in effect, mismatched to their early environment and had tried to adapt to survive. David Barker and his colleagues subsequently showed that heart disease was not the only risk. They were also more likely to suffer the related diseases of stroke, high blood pressure, and diabetes by the time they reached middle age. Even more remarkable are observations that the environment during early development can produce striking effects in later generations. In 2001, Lars Bygren and his colleagues in Sweden published studies showing how some boys born in 1905 seemed adversely affected by their grandparents’ diet. In particular, their grandfathers’ access to copious food, or lack of it, affected the longevity of these boys. In an isolated, remote part of northern Sweden there had been regular crop failures and bumper harvests in different years between 1799 and 1880, and these had been very well documented in public records. If the paternal grandfather had had access to copious food from a bumper crop during the time when he went through puberty, his grandchild —if male—was more likely to die at a younger than average age. No cause and effect has been firmly established. Yet the higher incidence of diabetes in these grandsons argues that a plentiful diet produced some chemical changes in the genes on the Y chromosome of their grandparents’ germ cells during a critical stage of early development. These changes could have affected how the genes in their sperm expressed when they produced their children. So the environment of the grandparent had a deleterious effect on the boys (who carried that Y chromosome) two generations later. This book is in part about these intriguing influences arising during development, which so far have received too little attention. It places these within the context of how humans evolved, because we now live in a very different world from that which our species first inhabited. The book breaks new ground in our understanding and will be essential reading for anybody interested in the fascinating complexities of human biology. It is a privilege to write the foreword to this book by Peter Gluckman and Mark Hanson, two eminent researchers who have managed to describe their ideas in an accessible and entertaining manner.

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