Nick Lane is Professor of Evolutionary Biochem istry in the Departmen t of Genet ics, Evolution, and Environment at University College London. His research is about how energy flow shapes the broad sweep of evolution, focusing on the origin of life and the improbable emergence of complex cells. Professo r Lane was a founding member of the UCL Consortium for Mitochondrial Research and is Co-Director of CLOE, UCL’s new Centre for Life’s Origins and Evolution. He has published four celebrated books, which have been translated into languages, and is a regular contributor to TV and radio as well as scientific and literary festivals. His book Life Ascendin g won the Royal Society Prize for Science Books in , while Bill Gates praised The Vital Question as “ a stunning inquiry into the origins of life” . Nick Lane’s work was recognize d by the Biochem ical Society Award for his outstanding contribution to the molecular biosciences, and the Royal Society Michael Faraday Prize, the UK’s premier award for excellence in communicating science.
Praise for Power, Sex, Suicide
‘The most interesting and significant addendum to Darwin’s theory I think I’ ve come across since Richard Dawkins explained how genes are the mechanism for evolution.’
Laurence Phelan, Independent on Sunday ‘An exhilarating visit to some frontiers of modern biology, by a writer who’s not afraid to think big and think hard.’
Frank Wilczek, Update Magazine, New York Academy of Sciences
‘Enthralling . . . The author has accomplished something quite breathtaking ...he brings the science alive . . . Every biologist should read this book.’
Philip John, Biologist
‘Impressive . . . readable, provocative and often persuasive. Although written for the general reader, it manages to cover its enormous range of topics in considerable depth, and the technical details are very well managed… Much of what is said is plausible, very well explained, and undoubtedly important. This is an exciting and unusual book.’
Jonathan Hodgkin, TLS
‘Lane argues with verve . . . A brave attempt to accomplish a feat that is becoming all too rare in contemporary science: to grasp the tangle of data from many disparate fields, and to weave them into a unifying pattern that makes sense of the way things are. ’
Franklin Harold, Microbe Magazine
‘A great read. I recommend wholeheartedly this book. It is superbly written.’
Barry Halliwell, Free Radical Research
‘I defy anyone to read this book and not come out amazed by the incredible subtly, complexity and downright unlikeliness of the mechanisms of biological construction. This book opens up the secrets with
an obvious delight from Lane that the readers are likely to share. Recommended.’
Popular Science
‘Lane writes with a fluent, easy-to-read style and discusses some major theories that are truly amazing and enlightening. ...I never thought that reading a lengthy book entirely about mitochondria could be so pleasurable. Lane excels at highlighting the importance and significance of this organelle, resulting in a text which is accessible and fascinating in equal measure.’
Lucy Moore, Sense about Science
‘An exhilarating ride through the geography and history of all life on earth ...I can ’t help being jealous of his audacity, ambition, breadth of knowledge, penetrating reasoning, and writing style.’
Guy Brown, Mitochondrial Physiology Society Review
‘You will be taken on an extraordinary journey, from the depths of time to the present and ultimately to where the Grim Reaper rules . . . Reading the book is a thought-provoking exercise that could invigorate mitochondrial research.’
Mark van der Giezen, EMBO Reports
‘A most thought-provoking book . . . His knowledge of the field is truly impressive, as he surveys major trends in evolutionary biology, cell biology, population biology and genetics, bioenergetics, power-law theory, and complexity, to name but a few of the fields covered and then follows the data to likely logical conclusions . . . Well worth reading.’
Eric A. Schon, Journal of Clinical Investigation
‘Presents an extraordinary account of how complex life arose, why we have to have sex to procreate, and even why our lives must lamentably end. A captivating and thought-provoking book, recommended to anyone intrigued by the wonder and bizarreness of life.’
Science a GoGo
3
Great Clarendon Street, Oxford, OXDP, United Kingdom
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. Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries
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, by licence 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 work in any other form and you must impose this same condition on any acquirer
Published in the United States of America by Oxford University Press
Madison Avenue, New York, NY , United States of America
British Library Cataloguing in Publication Data Data available
Library of Congress Control Number:
Printed and bound in Great Britain by Clays Ltd, Elcograf S.p.A.
For Ana And for Eneko
Born, appropri ately enough, in Part
CONTEN TS
List of Illustrations
Acknowledgements
Preface
Introduction. Mitochondria: Clandestine Rulers of the World
. The Deepest Evolutionary Chasm
. Quest for a Progenitor
. The Hydrogen Hypothesis
. The Meaning of Respiration
. Proton Power
. The Origin of Life
. Why Bacteria are Simple
. Why Mitochondria Make Complexity Possible
. The Power Laws of Biology
. The Warm-Blooded Revolution
. Con flict in the Body
. Foundations of the Individ ual
. The Asymmetry of Sex
. What Human Pre history Says About the Sexes
. Why There Are Two Sexes
. The Mitochondrial Theory of Ageing
. Demise of the Self-Corre cting Machine
. A Cure for Old Age?
Epilogue
Glossary
Further Reading
Index
LIST OF ILLUSTRATIONS
. Schematic structure of a mitochond rion, showin g cristae and membranes
. Schematic illustrations of a bacterial cell compared with a eukaryotic cell
. Hydroge nosomes interacting with methanogens
Courtesy of Professor Bland J. Finlay, FRS, Queen Mary University of London, The River Laboratory, Dorset
. Schematic showing the steps of the hydrogen hypothesis
Adapted from Martin et al., ‘An overview of endosymbiotic models for the origins of eukaryotes, their ATP-producing organelles (mitochondria and hydrogenosomes), and their heterotrophic lifestyle’ . Biological Chemistry
. The respiratory chain, showing complex es
. The ‘elementary particles of life’—ATPas e in the mitochon drial membrane
From Gogol, E. P., Aggeler, R., Sagerman, M., & Capaldi, R. A., ‘Cyroelectron microscopy of Escherichia coli F adenosine triphosphatase decorated with monoclonal antibodies to individual subunits of the complex’ . Biochemistry
. The respiratory chain, showing the pumping of protons
. Primordial ‘cells’ with iron-sulphur membranes
From Martin, W., and Russell, M. J., ‘On the origins of cells: a hypothesis for the evolutionary transitions from abiotic geochemistry to chemoautotrophic prokaryotes, and from prokaryotes to nucleated cells’ . Philosophical Transactions of the Royal Society B, , (), –, by permission of the Royal Society
. Merez hkovskii’s inverted tree of life, showin g fusion of branches
From Mereschkowsky, C., ‘Theorie der zwei Plasmaarten als Grundlage der Symbiogenesis, einer neuen Lehre von der Entstehung der Organismen’ . Biol. Centralbl. (), –
,
. Internal membranes of Nitrosomon as, giving it a ‘eukaryotic’ look
. The respiratory chain, showin g the coding of subunits
. Graph showin g the scaling of resting metabo lic rate versus body mass
From ‘Scaling: why is animal size so important?’ by Knut Schmidt-Nielsen (). By permission of Cambridge University Press. After: Benedict, Francis G. (). Vital Energetics: A Study in Comparative Basal Metabolism. Carnegie Institution of Washington
. Mitochondrial network within a cell
From Griparic, L. & van der Bliek, A. M., ‘The many shapes of mitochondrial membranes’ . Traffic () (), –. By permission of John Wiley and Sons
The publishers apologize for any errors or omissions in the above list. If contacted they will be pleased to rectify these at the earliest opportunity.
ACKNOWLEDGEMENTS
Writing a book sometimes feels like a lonely journey into the infinite, but that is not for lack of support, at least not in my case. I am privileged to have received the help of numerous people, from academi c specialists, whom I contact ed out of the blue by email, to friends and family, who read chapters, or indeed the whole book, or helped sustain sanity at critical moments.
A number of specialists have read various chapters of the book and provided detailed comments and suggested revisions. Three in particular have read large parts of the manuscri pt, and their enthusiastic responses have kept me going through the more difficult times. Bill Martin, Profes sor of Botany at the Heinrich Heine University in Düsseldorf, has had some extraordinary insight s into evolution that are matched only by his abounding enthusiasm. Talking with Bill is the scientific equivalent of being hit by a bus. I can only hope that I have done his ideas some justice. Frank Harold, emeritus Professor of Microbiology at Colorado State University, is a veteran of the Ox Phos wars. He was one of the first to grasp the full meaning and implications of Peter Mitchell’s chemi-osmotic hypothesis, and his own experiment al and (beautifu lly) written contributions are well known in the field. I know of nobody who can match his insight into the spatial organiz ation of the cell, and the limits of an overly genetic approach to biology. Last but not least, I want to thank John Hancock, Reader in Molecular Biology at the University of the West of England. John has a wonderfully wide-rangin g, eclectic knowledge of biology , and his comments often took me by surprise. They made me rethink the workability
of some of the ideas I put forward, and having done so to his satisfaction (I think) I am now more confident that mitochondria really do hold within them the meaning of life.
Other specialists have read chapters relating to their own field of expertise, and it is a pleasure to record my thanks. When ranging so widely over different fields, it is hard to be sure about one ’s grasp of significant detail, and without their generous response to my emails, nagging doubts would still beset me. As it is, I am hopeful that the looming questions reflect not just my own ignoran ce, but also that of whole fields, for they are the questions that drive a scientist’s curiosity. In this regard, I want to thank: John Allen, Professor of Biochemistry, Queen Mary College, University of London; Gustavo Barja, Professo r of Animal Physiology, Complutense University, Madrid; Albert Bennett, Professo r of Evolutionary Physiology at the University of Califo rnia, Irvine; Dr Neil Blackstone, Associat e Professor of Evolutionary Biology at Northern Illinois University; Dr Martin Brand, MRC Dunn Human Nutrition Unit, Cambridg e; Dr Jim Cummins, Associate Professor of Anat omy, Murdoch University; Chris Leaver, Professor of Plant Sciences, Oxford University; Gottf ried Schatz, Professo r of Biochemist ry, University of Basel; Aloysius Tielens, Profes sor of Biochem istry, University of Utrecht; Dr Jon Turney, Science Comm unication Group, Imperial College, London; Dr Tibor Vellai, Institute of Zoology, Fribo urg University; and Alan Wright, Professo r of Genet ics, MRC Human Genetics Unit, Edinburgh University.
I am very grateful to Dr Michael Rodgers, formerly of OUP, who commissioned this book as one of his final acts before retiring. I am honoured that he retained an active interest in progress, and he cast his eagle eye over the first-draft manuscript, providing extremely helpful critical comment s. The book is much improved as a result. In the same breath I must thank
Latha Menon, Senior Comm issioning Editor at OUP, who inherited the book from Michael, and invested it with her legendary enthusiasm and appreciation of detail as well as the larger picture. Many thanks too to Dr Mark Ridley at Oxford, author of Mendel’sDemon, who read the entire manuscript and provided invaluable comments. I can ’t think of anyone better able to evaluate so many disparate aspects of evolutionary biology, with such a generous mind. I’ m proud he found it a stimulating read.
A number of friends and family members have also read chapters and given me a good indication of what the general reader is prepared to tolerate. I want to thank in particular Allyson Jones, whose unfeigned enthusiasm and helpful comments have periodical ly sent my spirits soaring; Mike Carter, who has been friend enough to tell me frankly that some early drafts were too difficult (and that later ones were much better); Paul Asbury, who is full of thoughts and absorbing conversation, especially in wild corners of the country where talk is unconstrained; Ian Ambrose, always willing to listen and advise, especially over a pint; Dr John Emsley, full of guidance and inspiration; Professo r Barry Fuller, best of colleagues, always ready to talk over ideas in the lab, the pub, or even the squash court; and my father, Tom Lane, who has read most of the book and been generous in his praise and gentle in pointing out my stylistic infelicities, while working to tight deadlines on his own books. My mother Jean and brother Max have been unstinting in their support, as indeed have my Spanish family, and I thank them all.
The frontispiece illustrations are by Dr Ina Schuppe-Koistinen, a researcher in biomedi cal sciences in Stockholm and noted watercolorist, who is making a name in scientific art. The series was specially commissioned for this book, and inspired by the themes of the chapters. I’ m very grateful to her, as I think they
bring to life the mystery of our microscopic universe, and give the book a unique flavour.
Special thanks to Ana, my wife, who has lived this book with me, through times best described as testing. She has been my constant sparring companion, bounci ng ideas back and forth, contributing more than a few, and reading every word, well, more than once. She has been the ultimate arbiter of style, ideas, and meaning. My debt to her is beyond words.
Finally, a note to Eneko: he is antithetical to writing books, preferring to eat them, but is a bundle of joy, and an education in himself.
PREFACE
In the Hitchhik er ’ s Guide to the Galaxy, Ford Prefect spends
years researching his revision to the Guide’ s entry on the Earth, which originally read ‘Harmless’ . His long essay on the subject is edited down by the Guide to read ‘Mostly harmless’ . I suspect that too many new editions suffer a similar fate, if not through absurd editing decisions, at least through a lack of meaningful change in content. As it happens, nearly years have passed since the st edition of Power, Sex, Suicide was published, and I am resisting the temptation to make any lame revisions. Some say that even Darwin lessened the power of his arguments in the Origin of Species through his multiple revisions, in which he dealt with criticisms and sometimes shifted his views in the wrong direction. I prefer my original to speak for itself, even if it turns out to be wrong. Let me give one example why.
This book is about mitochondria, the tiny ‘powerhouses’ of our cells that provide essentially all the energy and many of the molecular building blocks needed for us to remain alive. They derive from bacteria that took up residence inside a host cell some . to two billion years ago, and retain a tiny but vitally important genome of their own. This mitochondrial genome is inherited from our mothers alone, in her egg cells; the father’s mitochond rial genome, in the sperm, is destroyed. That sexual asymmetry is nearly universal across complex life, and is one of the deepest distinctions between the sexes females pass on their mitochon dria, males do not, even in microscopic, singlecelled organisms where there is no other visible difference between sexes.
What is less certain is exactly why. In Part of this book, I discuss work suggesting that having two sexes enables natural selection to choose the best mitochondrial genes isolating a single type of mitochon drial DNA, from a single parent, allows it to be ‘test-driven’ to see how well it works with the rest of the genes in the nucleus of the new individual. But I also noted that there is a potenti al problem here, because we inherit two sets of nuclear genes, one set from each of our parents. So what happens if one of these sets of nuclear genes works well with our mitochondrial genes, but the other set doesn’t? I suggested that some of the father’s nuclear genes those that interact directly with mitochondria might be switched off (or ‘imprinted ’), allowing optimisation of mitochon drial function. But since writing the book I learned that this is not true there is not a jot of evidence for imprinti ng of any paternal genes in this case.
These things rankle. Since then I have spent seven years working on this question with a good colleague at University College London, Andrew Pomiankowski, and drawn in several highly gifted students. I thought we had figured out the answer we realised that ‘sex’ and ‘two sexes’ serve two different purposes. Sex is all about generating differences between individuals in their nuclear genes, making each of us genetically unique. If we were all clones, we could all be wiped out by the same virulent disease, perhaps contracted from a dirty telephone; as it is, the innumerable differences between individuals mean that we each present a subtly different face to the changing environment, for better or worse. Some of us will survive to die another day.
But having sex does not demand that there should be two sexes; in many respects that is the worst of all possible worlds. From an evolutionary point of view, it would be better if everybody were the same sex, or if (mechan ical issues aside) there were lots of different sexes then individuals could procreate
with more or less everyone, not merely half the population. So why do most species have two sexes? After a lot of modelling (using the equations of population genetics) we realised that the answer is that two sexes generate differences between individuals in their mitochondrial genes. It’s so simple! We each have two genomes, mitochon drial and nuclear. Sex enables natural selection to operate on genes in the nucleus; two sexes allows selection to act on mitochondrial genes. QED.
And then I came across recent work from Antonio Enriquez, a molecular biologist working in Madrid. Enriquez , too, notes that having two sets of nuclear genes that both interact with the mitochond rial genome could cause problems. He, too, agrees there is no evidence to suggest that paternal genes interacting with mitochon dria are switched off. Instead, he calls on a slightly different phenomenon known as ‘monoal lelic expression’,in which only one of the two nuclear copies is switched on, but the copy that is turned on or off is rando m, and may differ from one cell to the next. That is harder to detect, and requires sophisticated methods to sequence the transcripts of genes in single cells. Lots of single cells. Luckily, Enriquez has this power to hand in his lab, and in a few years’ time we should know the answer.
In the meantime, I’ m back to square one. Nearly years ago, I wrote that one of the two nuclear copies of genes interacting directly with mitochon dria might be switched off; that’s still true. Now, I must alter the word ‘imprinting’ to ‘mono-allelic expression ’—‘harmless’ to ‘mostly harmless’ . But if I had revised this book a year ago, I would have made it less correct than it had previously been. It’s a mug ’s game.
That’s not to say there haven’t been any exciting developments since ; there have been plenty. It’s just that most carry some measure of uncertainty, and were touched on at least
as an idea back then. Let me run through a few of my favourite examples, and give you a sense of how things have changed since .
More than anything else, this book is about the origins of complex life. To be honest, the full force of this theme only hit me when I was writing the book it is nominally about a tiny compartment of the cell, after all and I have been revolving around these same questions ever since. The reason for this confabulation relates to the acquisition of mitochon dria what sort of cell originally played host to the bacteria that eventually became our mitochondria? In the book, I advocate a powerful, counter-intuitive hypothesis proposed by the pioneering biochemists Bill Martin and Miklos Müller, known as the hydrogen hypothesis. The idea is counter-productiv e because it rejects the apparently central role of oxygen in the evolution of complex ity (as I had previously assumed, having written an earlier book on oxygen), instead placing the nub of the deal on hydrogen gas.
That matters less for what it is than what it is not according to Bill Martin, the host cell was not a complex phagocyte (a cell that engulfed other cells for a living) but a morph ologically simple, self-sufficient (autotrophic) cell that grew from gases alone. It lacked the complexity of our own ‘eukaryotic’ cells (from the Greek for true nucleus). The idea was controversial then and is no less controversial now; and the evidence for or against remains equivocal. But the essence of the idea that the host was a simple cell, lacking ‘eukaryotic’ complexity now looks more secure with the discovery of a group of cells known as the Lokiarchaeota, or Loki for short. Loki shares so many similarities in its genes with complex eukaryot ic cells that there can be little doubt that the host cell that acquired mitochondria was closely related to it. Loki is as close to a smoking gun as we
are likely to get for an episode that happened close to two billion years ago.
Yet Loki is also utterly tantalising . It was detected in the muds around Loki’s Castle, a submarine hydrot hermal system located between Norway and Greenland. I say ‘detected’ , not ‘discovered’ , because we still don’t know what Loki looks like everything we know about it comes from gene sequences pieced together laboriously into full (or nearly full) genomes. Various related cells have been detected since then, which are now all grouped together into the Asgard superph ylum, after the home of the Norse gods. Yet the same mystique applies to them all: none has been isolated or cultured or viewed with certainty under a microscope they exist only as cryptic gene sequences, encoding . . . what exactly? We don’t know what they are, or how they live. From what little we do know, though, it seems likely that they are small cells, simple in their morphology, as predicted by the hydrogen hypothesis. There’s even a suggestion that they can grow using hydrogen.
Why does that matter? It matters because, if true, it implies that all eukaryotic complexity arose in the aftermath of an intimate relationship between two simple cells (or more precisely, populat ions of simple cells). One of those cells went on to become the mitochondria, the other was ultimately transformed into a complex host cell, the likes of which the world had never seen before; nor has such cellular complexity ever arisen again. The origin of complex life on Earth was a singular event. The discovery of Loki is exciting, and will no doubt teach us much; but in broad terms, Loki chimes with the themes elaborated here. It emphasizes them. They are more, not less, likely to be true.
Another exciting recent development that emphasizes a theme explored in this book relates to the temperature at
which mitochon dria operate. Just a few months ago, as I write, Pierre Rustin and colleagues published an extraordinary paper that seems to show that mitochon dria are maintained at nearly °C, around °C hotter than the rest of the body. These findings look scarcely credible, and are challenged by some physicists, who doubt that such extreme temperature gradients could be maintained across such short distances. Yet there is no doubt but that the science is well done.
The question revolves around the nanoscale engineering of fluorescent probes that can be targeted to the inner sanctum of mitochondria, the ‘matrix’ , where the intensity of fluorescence reports back on the local temperature. Or at least it is supposed to. We don’t know for sure if temperature is the only thing that these probes report on. Nor do we know what ‘temperature’ really means in a small con fined space crammed full of gyrating protein machinery. One marvellous molecular machine, the ATP synthase, is a rotating protein motor that spins at revolutions per second. There are tens of thousands of them in each mitochon drion. Surely they must agitate nearby water molecules, stirring up molecular motion that might be detected as heat (also a form of molecular motion) by the dye. In any case, even if the dye is not strictly accurate, it seems likely that mitochondria are hotter than we had thought.
I’d like to think that this will draw attention back to some older questions in biology that I discuss in this book, notably the origins of endothermy (warm-blooded ness). We already knew that most heat derives from the mitochon dria, and that much of the temperature difference between reptiles and mammals or birds relates to the number of mitochon dria mammals tend to have about five times as many mitochondria as equivalent reptiles. Why? One possibilit y is that having more mitochondria increases stamina and supports much more sustained activity.
But there has always been a puzzling disconnect between maximal metabo lic rates (supported by the cardiovascular system and skeletal muscles) and the resting metabol ic rate, which reflects the activity of visceral organs such as liver or intestines. There is no obvious reason why evolving a high maximal metabo lic rate should force up the resting metabol ic rate the two could theoretically be disconnected, and there are argument s about whether therapod dinosaurs did indeed disconnect the two.
Recently Andy Clarke, now retired from the British Antarct ic Survey, pointed out that the maximal metabolic rate is a red herring what matters is not maximal performance, but ticking over: not a gallop but a canter. Of course, maximal metabol ic rate is subject to selection too, but that does not drive the evolution of endothermy directly. To sustain steady activity in the ‘field’ , as animals forage or hunt or compete for mates, demands continuous metabo lic activity and the processing of waste, which in turn requires more mitochon dria in visceral organs. That means the resting metabo lic rate is necessarily linked with the ‘field’ metaboli c rate because both draw on the same set of mitochondria in the visceral organs . Selection for more visceral mitochondria increases both stamina and heat, making our costly / lifestyle possible. If Clark e is right (and I think he is) then there must be very tight controls over the number of mitochondria in our organs, and there might well be unexpected costs or bene fits to any therapies that alter this number. I discuss some of these in the book, and those arguments become more pointed if mitochon dria really do generate a lot more heat that we had appreci ated. One fact to conjure with is this: selection for greater stamina over several generations in mice leads to longer lifespan and better health. As I sit at my keyboard, I’ m thinking ‘keep moving!’
In the final part of this book, I discuss mitochondrial diseases and their relationship with ageing and death. Mitochondrial diseases number amongst the most devastating conditions imaginable, for the simple reason that mitochondria are so central to the life and death of organisms, providing almost all the energy needed to live, but also triggering the death programme (apoptosis) in cells that can ’t make ends meet. The reason behind these terrible conditions may be simple; the reality is complex beyond measure. These diseases can be caused by mutations in mitochondrial genes or those in the nucleus that encode proteins targeted to the mitochondria. They can even be unmasked by apparently trivial incompatibilities between mitochondrial and nuclear genes trivial in the sense that there is nothing ‘ wrong ’ with either genome, they just don’t work well together. There are also differences between men and women in susceptibility to mitochondrial diseases, with some conditions being five times more common in males an aching tragedy known as ‘Mother’s curse’ , as mitochondria are inherited from the mother only.
The perplexing complexity of mitochondrial diseases is magnified by the number of mitochon dria. We each inherit hundreds of thousands of copies of mitochondrial DNA in the egg cell. A particular mutation may occur in just a few copies, or in hundreds, thousands, or tens of thousands of copies. These mutation s often segregate unexpectedly into different tissues, and even interfere with each other in ways that can cause heart disease, muscular degenerat ion and learning difficulties in mice. Mitochondrial conditions may kill in early childhood, or with little warning in middle age, or might gradually undermine health in ‘normal’ ageing. Mitochondrial dysfunction undoubtedly contributes to common conditions including cancer, Alzheimer’sdisease, and diabetes. What might have been slightly tenuous claims in now probably reflect the mainstream view.
One of the most important and controversial breakthroughs of the past few years is mitochondrial therapy. In the book, I discuss a discredited fertility treatment called ‘ooplasmic transfer’ , in which mitochondria are transferred into an oocyte (the egg cell) of the woman seeking treatment. While some apparently healthy children were born using this technique, it necessarily produces a mixture of mitochon dria (heteroplasmy ). The consequen ces of heteroplasmy were uncertain at the time, but are now known to be hazardous in mice; the technique was prudently banned by the US Food and Drug Administration (FDA) in the noughties . Far more promising as a treatment for mitochond rial disease is pronuclear (or spindle) transfer, which involves the transfer of the nucleus from a zygote (or fertilized egg cell) into a recipient egg cell that contains mitochon dria from a healthy donor. In principle, this method does not produce mixtures of mitochon dria in practice it may do anyway, as a few mitochondria can cling to the nucleus and may be amplified during embryonic development but the method has attracted press attention because it forms ‘three-parent embryos’ . The nuclear DNA of the would-be parents is supplemented by the mitochondrial DNA of the donor. While there is potential for complications through inadvertent heteroplasmy, or incompatibilities between the donor mitochon dria and the nucleus, the scope for good seems to me to far outweigh the potent ial for harm, which in a worst-case scenario would be essentially the same mitochondrial disease that the procedure aims to cure.
Some people understandably harbour ethical concerns over ‘genetic engineering’ in humans, but in the UK these issues have been addressed over two decades through public and legal consultations, steered with enormous sensitivity, dedication and skill by Douglas Turnbull in Newcastle. The claim that mitochon dria
