On 12 February 2001, an international team of scientists announced that they had substantially deciphered the human genome – the genetic instructions for creating and maintaining a human being, and our evolutionary birthright. The event was reported in the New York Times as an achievement representing a pinnacle of human self-knowledge. The effort to sequence the human genome has been compared with the Apollo programme to put astronauts on the Moon, so the scientists were surely entitled to a certain amount of self-congratulation.
To describe the sequencing of the genome as a technical feat – like sending astronauts to the Moon, or even crossing the Himalayas on a unicycle – is to miss the point. To be sure, it is fun to learn that if each one of the three billion DNA bases that make up the genome were magnified to the size of a letter on this page, the genome itself would stretch across the continental United States and back again. But such facts stupefy rather than edify. The genome is important not because of what it is made of, but because of what it does: it is the agency that creates and maintains an organism, urging an endless variety of exquisite life forms from formless eggs. As such, it transcends the particularities of its substance and becomes a motif that has been central to biological thought since antiquity, making the achievement of 2001 all the more profound and exciting.
If any discovery represents a pinnacle of human self-knowledge, it does so only by virtue of the support of the mountain on which that pinnacle is raised. For thousands of years, people have wondered about the identity of the mysterious and marvellous entity that makes babies, shapes our evolutionary history and populates the world with living things of almost unimaginable variety – in short, the thing that teases form from the void. The history of biology can be retold as the story of the search for this agency, the genome. My aim in this book is to tell that story. Or rather, three stories.
The first, and the most direct, is an account of the intricate development of a human embryo from an egg. A pea-sized embryo recognizable as human develops from a fertilized egg in just four weeks, often before the mother even realizes she is pregnant. In this first strand can be seen the initial impetus for this book, which grew out of a desire to express the wonder that every new parent feels on confronting birth, an event which is both intimate and timeless.
The development of a human embryo is at the same time an expression of unique individuality and universal heritage. At this point the first story gives way to the second: how the course of individual development mirrors the history of human evolution itself, back to the dawn of life. Put another way, the human genome directs the development of every single embryo, but is itself a product of evolution and a reservoir of evolutionary memory.
The third story – and the one around which the book as a whole has been constructed – is the tale of discovery, of how people over many centuries have come to understand the development of individuals in terms of the variation, diversity and evolution of species.
As I researched the book, I found to my surprise that the story can be traced back to antiquity and extends more or less seamlessly down to the present. From a fully historical perspective, modern scientific research shows clear evidence of its ancient roots. For example, every scientist takes for granted that the genome in any particular individual, while unique to that individual, is at the same time the vehicle for our heritage. This is not a modern view, but stems directly from a theory which is now all but forgotten – the theory of ‘preformationism’. This idea, which formed the mainstream of biological thought in the late seventeenth and for much of the eighteenth century, holds that the germ of each individual is not made anew with each conception, but was created in all its essentials at the beginning of time. In other words, conception does not start a new life from scratch, but simply activates a programme that was already in existence, and which has existed since the beginning of time. The modern idea of the genome as the eternal encapsulation of the instructions to produce a human being owes much to preformationism. Watson and Crick’s classic paper from 1953 on the structure of DNA, containing the now famous line ‘It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material’,1 is pure preformationism.
To take another example: all modern evolutionary biologists are conscious of a link between the events in the development of any particular embryo and the shape of the history of the species to which that embryo belongs, and indeed the history of all life. Scientists now take for granted that there is a deep connection between embryology and evolution; and that the shapes of living organisms are not random, but display very clear patterns which are indicative of a shared evolutionary relationship. This insight emerged during the era of romanticism at the turn of the nineteenth century, and found scientific expression in a movement known as ‘nature-philosophy’, which saw human development as an expression – indeed a culmination – of a universal tendency towards perfection: the ‘microcosm’ that measured the ‘macrocosm’. Nature-philosophy was very much associated with the thought of the great German savant Goethe, and survives today in its purest form in ‘anthroposophy’ – the view of life developed by the Austrian philosopher Rudolph Steiner. It also turns up, more or less disguised, in various ‘alternative’ points of view, from homeopathy to ecological activism. Given this heritage, many scientists would be intrigued, even horrified, to learn (if they did not already know) that modern developmental biology grew directly from the work of nineteenth-century German embryologists who had been schooled in the prevailing atmosphere of nature-philosophy. Indeed, after long dormancy, it is now almost possible for a serious biologist to whisper the name of Goethe in a lecture without raising sniggers at the back.
A slightly more recent and telling example of ancient roots traceable in modern thinking concerns the founder of the science of genetics, William Bateson. He realized, in the 1890s, that the nature of genetic variation was completely unknown – a serious problem, given that Darwin’s theory of natural selection had been based on variation. This, Bateson saw, was the source of the general dissatisfaction with Darwinism being shown in the last decades of the nineteenth century. His solution was to produce a catalogue of every case of biological variation he could find, in the hope of discerning general laws. The result, Materials for the Study of Variation (1894), was fundamental, and in more ways than one. As well as trying to address variation from first principles, Materials harked back to an archaic tradition in scientific thought, that of the ‘bestiary’ – the medieval catalogue of natural freaks and monsters, a genre which early scientists such as Francis Bacon recommended as a useful exercise in understanding the extent of natural variation. But Materials is far more than a dry catalogue – it is a work wrought in passion by a scientist determined to uncover the roots of variation and inheritance. Less than a decade after Materials was published, Bateson coined the name for a new science – genetics. Through him, therefore, the modern science of the genome has deep connections with the earliest stirrings of biological thought, if not the fumes and smoke of alchemy.
Why, then, should I have been surprised that our modern understanding of the genome has such clearly visible if ancient roots? After all, I did not have to consult ancient grimoires, scrawled in forgotten dialects, locked in the dusty libraries of remote and haunted castles: my investigations led me no further than a small number of reasonably well-known and available texts that can be read with ease while strap-hanging on the London Underground.
I believe that our view of the long history of biology has been clouded and distorted by the titanic presence of Charles Darwin and his book On the Origin of Species by Means of Natural Selection, Or the Preservation of Favoured Races in the Struggle for Life, published in 1859. No one who considers themselves open to the facts (and I presume to include myself here) can doubt the pre-eminence of this book in the history of biological thought, and the explanatory power of the theory of evolution that has grown from Darwin’s simple mechanism of natural selection. What is less appreciated, I believe, is the extent to which Darwin and his theories were very much products of their time, and that the reputation of both have waxed and waned since 1859. The contemporary Darwin industry has bred a strain of popular science from which it would be easy to conclude that nobody knew anything about anything until Darwin arrived in 1859, as if on a fiery chariot from heaven, and gave the world his graven tablets – after which the scales fell from the eyes of all, and nothing remained to be discovered. I sometimes wonder whether Darwin – a practical man yet given to crippling insecurities, forever worried about the health of his family and his share portfolio as much as matters of science – would have recognized himself in the grotesque monster that is his contemporary hagiography.
This somewhat cartoonish view of history engenders a similarly simplistic view of the history of science more generally, in which we are seen as progressing steadily, as if on a unified front from the past into the future, forever shining brighter lights of discovery into an ever-shrinking puddle of ignorance. As a consequence, if we hear anything at all of biology before Darwin, it is brought up only to be belittled. If the nature-philosophers are depicted as hopeless romantics, the preformationists will be seen as periwigged buffoons who drew little men in the heads of spermatozoa and believed it truth; and the contributions of the alchemists, self-locked in crepuscular dungeons of horror, are to be viewed as entirely undeserving of serious consideration. One of my tasks in this book is to set Darwin in context and show how these earlier sources influenced both Darwin and later scientists, down to our own age. I feel very strongly that this rehabilitation is not only desirable but necessary, as we shall require the fullest and most dispassionate appreciation of the entire historical perspective of biology if we are to face the coming decades, in which our knowledge of the human genome might be applied to alter the Earth – and human beings – beyond recognition.
That time has not yet come. It is evident, however, that the standard of debate surrounding related issues of our own day – abortion, in vitro fertilization, the genetic modification of crops, and so on – is hardly adequate to address even these problems, and yet the prospect of the modification of genomes makes those concerns trivial indeed. The time has arrived when we must address – seriously – the relationship between our biology and our humanity. But before we can do that we must understand how we got to where we are now, and it is to this end that I offer this modest contribution.
The genesis of this book was as involved as that of any living creature. It started some years ago with a conversation I had with my agent, Jill Grinberg, in the lobby of the Kitano Hotel on Fifth Avenue, New York City. I thank Jill for her continuing support; I should also like to thank Carl Zimmer for sharing the earliest pangs of this book when I lodged at his apartment in Queens. I thank Peter Robinson and Sam Copeland at Curtis Brown, Christopher Potter, Leo Hollis, Catherine Blyth and Sophie King at Fourth Estate, and Angela Von Der Lippe at Norton, for their guidance and encouragement. I thank the librarian, staff and fellowship of the Linnean Society of London for housing me for part of the time I was sketching the draft, and for finding a number of important sources I would certainly otherwise have missed.
I would never have got anywhere without the indulgence of my colleagues at Nature, especially Christopher Surridge and Rory Howlett, who kindly commented on various parts of the draft; and Michael Kenward of the Association of British Science Writers, without whom I would not have discovered Clara Pinto-Correia’s book The Ovary of Eve until it was too late. Joanne Webber handled the administration with her customary elegance.
A number of others were kind enough to read and comment on earlier versions of this book, either in part or as a whole, at various stages of its gestation. They were Wallace Arthur, Ted Chiang, Jack Cohen, Craig Davidson, David and Shirley Forbes and family, Walter Gratzer, David and Fiona Hulbert and family, and Charles Middleburgh. My wife Penny hefted the draft across London from east to west and back at unsocial hours. I am grateful to Philip Ball for suggestions and materials related to Paracelsus and Goethe; and to Paul Carline for being an articulate exponent of an entirely different view of life from my own, and whose opinions resulted in many reconsiderations and some radical transformations. I thank John Woodruff for an expert edit. I owe a particular debt to Tony Kerstein, who, in his role as The Man on the Ilford Omnibus, read and commented on almost every draft as it emerged. Tony, the drinks are on me.
Not all these kind people enjoyed the book, and any errors and opinions are my own unless noted otherwise.
In addition, I thank the following for permission to use copyright material: Francis Crick, Macmillan Magazines Ltd, North Atlantic Publications, Oxford University Press, Princeton University Press, Random House UK, The University of Chicago Press and James D. Watson.
Needless to say, all this would have been impossible without the unstinting support of my family – Penny, Phoebe, Rachel, Marmite and Fred. The Cranley is gone, but not forgotten.
Henry Gee
Ilford, September 2003
1 Watson, J. D. and Crick, F. H. C, ‘A structure for deoxyribose nucleic acids’, Nature, vol. 171 (1953), pp. 737-8.