This page intentionally left blank The Fetal Matrix: Evolution, Development and Disease New discoveries reveal how crucial interactions that determine our destiny occur before birth, when our genes interact with their environment as the embryo and fetus develop. These processes – in the matrix of the womb – are evolutionary echoes of mechanisms that allowed our hunter–gatherer ancestors to survive. These exciting insights into predictive adaptive responses suggest new ways of protecting the health of the fetus, infant and adult. If inappropriate they can trigger obesity, diabetes and heart disease, formerly thought to result solely from adult lifestyle. The new concepts in this book are crucial to understanding the daunting public health burden in societies undergoing rapid transition from poverty to affluence. They add an important new dimension to evolutionary theory. Synthesising developmental biology, evolutionary history, medical science, public health and social policy, this is a ground-breaking and fascinating account by two of the world’s leading pioneers in this important emerging field. Professor Peter D. Gluckman is Professor of Paediatric and Perinatal Biology, Director of the Liggins Institute (for Medical Research) and Director of the National Research Centre for Growth and Development, at the University of Auckland. Professor Mark A. Hanson is Director of the Developmental Origins of Health and Disease Research Division at the University of Southampton Medical School, and British Heart Foundation Professor of Cardiovascular Science. The Fetal Matrix: Evolution, Development and Disease PeterGluckman University of Auckland, New Zealand Mark Hanson University of Southampton, UK CAMBRIDGE UNIVERSITY PRESS Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo Cambridge University Press The Edinburgh Building, Cambridge CB2 8RU, UK First published in print format ISBN-13 978-0-521-83457-5 ISBN-13 978-0-521-54235-7 ISBN-13 978-0-511-33701-7 © P. Gluckman and M. Hanson 2005 2004 Information on this title: www.cambridge.org/9780521834575 This publication is in copyright. Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written p ermission of Cambrid g e University Press. ISBN-10 0-511-33701-9 ISBN-10 0-521-83457-0 ISBN-10 0-521-54235-9 Cambridge University Press has no responsibility for the persistence or accuracy of urls for external or third-party internet websites referred to in this publication, and does not g uarantee that any content on such websites is, or will remain, accurate or a pp ro p riate. Published in the United States of America by Cambridge University Press, New York www.cambridge.org hardback paperback paperback eBook (EBL) eBook (EBL) hardback Time present and time past Areboth perhaps present in time future Andtime future contained in time past. T. S. Eliot, ‘Burnt Norton’ m ¯ at’rix,n.(pl. –ices)womb; place in which thing is developed; formative part of animal organ; mass of rock etc. enclosing gems etc.; (biol.) substance between cells; mould in which type etc. is cast or shaped. [L, f. mater mother] Oxford English Dictionary Contents Preface page ix 1 Shaping our destiny: genes, environment and their interactions 1 2Mother and fetus 25 3Fetal choices 59 4Predictive adaptive responses and human disease 78 5Obesity, diabetes and other diseases 103 6The biology of predictive adaptive responses 118 7Predictive adaptive responses – critical processes in evolution 144 8Evolutionary echoes and the human camel 173 9Improving human health 190 10 Fetal futures 206 Further reading and references 216 Index 240 vii [...]... embryonic and fetal development, and what might be the life-long consequences of the effects of those influences In chapters 4, 5 and 6 we give a description of how events in early fetal life can impact on later life and, in particular, lead to a greater risk of diseases such as heart disease and diabetes The implications of this for both the developed and developing worlds are discussed in chapters 9 and 10 ... prevention of disease and to understanding the ecology of disease across the planet It has significant implications for those involved in public health policy Three major themes are covered: developmental biology and fetal and perinatal physiology; clinical epidemiology; and evolutionary biology In chapters 1 and 2 we provide a description of how the early phases of life progress in humans and other mammals,... PDG MAH Auckland, Southampton and places in between August 2003 2 Genes, environment and their interactions In the early chapters of the book we examine how genes and environment interact to control our development. 2 We look at the relative roles of genes and environment, and we start to ask the questions of when and why these interactions occur, and what are the consequences – not just the immediate... to the sub-tropical southern islands such as Okinawa When the Japanese army invaded the tropics in 19 41 they discovered that heat stroke was more common amongst those soldiers who had been born in the northern islands than in those born in the south Heat stroke occurred more often because these soldiers could not effectively use one of their key means to reduce body heat – that is sweating – and they... led to the discovery that the number of active sweat glands is set soon after birth and does not change through life But the ability to determine the number of active sweat glands is a once -and- for-all choice in development – once determined it is irreversible and one has to cope with that number of active glands throughout life It was the number of functional sweat glands that differed between the different... a powerful microscope, without harming either, and they are then transplanted back into the donor mother, when each then fully develops into a calf 10 Genes, environment and their interactions So while there is understandably much interest in the role of genes in determining our fate (and the fate of the cow) it is obvious that genes cannot provide an understanding of everything in life – this is a... makes the pigment yellow, but y is an inactive gene that makes no colour If Y is a dominant gene then the presence of one Y gene will make the pea yellow So peas with the genetic make up YY or yY or Yy will all be yellow and the yy will be green If, however, the Y gene is recessive and therefore needs two copies to be fully active and visible, then the YY peas are yellow and the yy peas are green, and the. .. and their interactions Fig 1. 1 Within a species, variations in phenotype can confer a survival advantage in a given environment, or in the face of an environmental change The beaks of one species of finch in the Galapagos Islands are a good example They were instrumental in the development of the theory of natural selection by Darwin Redrawn from F J Sulloway Journal of The History of Biology 15 (19 85),... gland activation, has life-long consequences Clearly the number of active sweat glands is not genetically determined Indeed, examination of the total number of sweat glands in the skin shows that all Japanese have similar numbers – the difference is that some become activated and some do not This is determined by the degree of innervation of the sweat glands by the sympathetic nervous system It is the. .. on the work and ideas of both ourselves and others About 15 years ago, it was first suggested that some adult diseases had their origins partly in fetal life A raft of experimental work and epidemiological and clinical observation has followed that has led us to a reasonable understanding of the biological processes underpinning this link But as we have considered comparative perspectives and as developmental . University Press The Edinburgh Building, Cambridge CB2 8RU, UK First published in print format ISBN -1 3 97 8-0 -5 2 1- 8 345 7-5 ISBN -1 3 97 8-0 -5 2 1- 5 423 5-7 ISBN -1 3 97 8-0 - 51 1-3 370 1- 7 © P. Gluckman and M. Hanson. without the written p ermission of Cambrid g e University Press. ISBN -1 0 0-5 1 1-3 370 1- 9 ISBN -1 0 0-5 2 1- 8 345 7-0 ISBN -1 0 0-5 2 1- 5 423 5-9 Cambridge University Press has no responsibility for the persistence. ix 1 Shaping our destiny: genes, environment and their interactions 1 2Mother and fetus 25 3Fetal choices 59 4Predictive adaptive responses and human disease 78 5Obesity, diabetes and other diseases