It is not that we do not know how to decipher the genome. This book is full of experiments that attempt to do just that. Such experiments usually entail engineering embryos – either by surgically adding or removing organs, or else by adding or removing genes. Of course, the embryos always belong to animals: newts, frogs, chickens and mice. They tell us a great deal about ourselves since, as it happens, the genetic grammars of all creatures are quite similar. But just as, over time, the vocabulary and grammatical rules of human languages diverge from one another in ways large and small, so too do the languages of genes. To learn from animals alone is to run the risk of an error rather like that made by Leonardo da Vinci when he sketched a human foetus attached to what is clearly the placenta of a cow. We need, ultimately, some direct way into the human genome and into the human body. Cleopatra, one source alleges, ordered the dissection of pregnant slave girls so that she could observe the progress of their embryos. While we may admire her curiosity and ability to fit laboratory work into a busy social schedule, we can hardly follow her lead. We must approach the human body more circumspectly. We must find mutants.
I
MUTANTS
[AN INTRODUCTION]
We had heard that a monster had been born at Ravenna, of which a drawing was sent here; it had a horn on its head, straight up like a sword, and instead of arms it had two wings like a bat’s, and the height of its breasts it had a fio [Y-shaped mark] on one side and a cross on the other, and lower down at the waist, two serpents, and it was a hermaphrodite, and on the right knee it had an eye, and its left foot was like an eagle. I saw it painted, and anyone who wished could see this painting in Florence.
IT WAS MARCH 1512, and a Florentine apothecary named Lucca Landucci was writing up his diary. He had much to write about. Northern Italy was engulfed by war. Maximillian of Germany and Louis XII of France were locked in combat with the Spanish, English and Pope Julius II for control of the Venetian Republic. City after city was ravaged as the armies traversed the campagna. Ravenna fell eighteen days after the monster’s birth. ‘It was evident,’ wrote Landucci, ‘what evil the monster had meant for them! It seems as if some great misfortune always befalls the city when such things are born.’
FRONTISPIECE TO FORTUNIO LICETI 1634 De monstrorum natura caussis et differentiis.
THE MONSTER OF RAVENNA (1512). FROM ULISSE ALDROVANDI 1642 Monstrorum historia.
Landucci had not actually seen the monster. It had been starved to death by order of Julius II, and Landucci’s account is of a drawing that was on public display in Florence. That image was among the first of many. Printed woodcuts and engravings spread the news of the monster throughout Europe, and as they spread, the monster acquired a new, posthumous, existence. When it left Ravenna it had two legs; by the time it arrived in Paris it had only one. In some prints it had bat wings, in others they were more like a bird’s; it had hermaphrodite genitalia or else a single large erection. It became mixed up with the images of another monster born in Florence in 1506, and then fused with a medieval icon of sinful humanity called ‘Frau Welt’ – a kind of bat-winged, single-legged Harpy who grasped the globe in her talons.
As the monster travelled and mutated, it also accreted ever more complex layers of meaning. Italians took it as a warning of the horrors of war. The French, making more analytical effort, interpreted its horn as pride, its wings as mental frivolity and inconstancy, its lack of arms as the absence of good works, its raptor’s foot as rapacity, and its deformed genitalia as sodomy – the usual Italian vices in other words. Some said that it was the child of a respectable married woman; others that it was the product of a union between a nun and a friar. All this allegorical freight makes it hard to know what the monster really was. But it seems likely that it was simply a child who was born with a severe, rare, but quite unmysterious genetic disorder. One can even hazard a guess at Roberts’s syndrome, a deformity found in children who are born with an especially destructive mutation. That, at least, would account for the limb and genital anomalies, if not the two serpents on its waist and the supernumerary eye on its knee.
ROBERTS'S SYNDROME. STILLBORN INFANT. FROM B.C. HIRST AND G.A. PIERSOL 1893 Human monstrosities.
In the sixteenth and seventeenth centuries, monsters were everywhere. Princes collected them; naturalists catalogued them; theologians turned them into religious propaganda. Scholars charted their occurrence and their significance in exquisitely illustrated books. In Germany, Conrad Lycosthenes produced his Prodigiorum ac ostentorum chronicon (1557, later translated as The Doome, calling all men to judgement); from France came Pierre Boaistuau’s Histoires prodigieuses (History of prodigies, 1560–82) and Ambroise Paré’s Des monstres et prodiges (Monsters and prodigies, 1573). A little later, the Italians weigh in with Fortunio Liceti’s De monstrorum natura caussis et differentiis (On the nature, causes and differences of monsters, 1616) and Ulisse Aldrovandi’s Monstrorum historia (History of monsters, 1642).
In an age in which religious feelings ran high, deformity was often taken as a mark of divine displeasure, or at least of a singularly bad time in the offing. Boaistuau’s Histoires prodigieuses, which is especially rich in demonic creatures, has a fine account not only of the unfortunate Monster of Ravenna but also of the Monster of Cracow – an inexplicably deformed child who apparently entered the world in 1540 with barking dogs’ heads mounted on its elbows, chest and knees and departed it four hours later declaiming ‘Watch, the Lord Cometh.’ Allegory was a sport at which Protestant scholars excelled. In 1523 Martin Luther and Philipp Melanchthon published a pamphlet in which they described a deformed ‘Monk-Calf born in Freiburg and another creature, possibly human, that had been fished out of the Tiber, and interpreted both, in vitriolic terms, as symbols of the Roman Church’s corruption. Catholics responded by identifying the calf as Luther.
By the late 1500s, a more scientific spirit sets in. In Des monstres, his engagingly eclectic compendium of nature’s marvels, the Parisian surgeon Ambroise Paré lists the possible causes of monsters. The first entry is ‘The Wrath of God’, but God’s wrath now seems largely confined to people who have sex with animals (and so produce human-horse/goat/dog/sheep hybrids) or during menstruation (Leviticus disapproved). Luther’s Monk-Calf also appears in Des monstres, but shorn of its anti-papal trappings. It is, instead, a monster of the ‘imagination’, that is, one caused by maternal impressions – the notion, prevalent in Paré’s day and still in the late nineteenth century, that a pregnant woman can, by looking at an unsightly thing, cause deformity in her child. Like most of the other causes of deformity that Paré proposes (too much or too little semen, narrow wombs, indecent posture), the theory of maternal impressions is simply wrong. But it is rational insofar that it does not appeal to supernatural agents, and Des monstres marks the presence of a new idea: that the causes of deformity must be sought in nature.
At the beginning of the seventeenth century, teratology – literally, the ‘science of monsters’ – begins to leave the world of the medieval wonder-books behind. When Aldrovandi’s Monstrorum historia was published posthumously in 1642, its mixture of the plausible (hairy people, giants, dwarfs and conjoined twins) and the fantastic (stories taken from Pliny of Cyclopes, Satyrs and Sciapodes) was already old-fashioned. Fortunio Liceti’s treatise, published in 1616, is mostly about children with clearly recognisable abnormalities – as can be seen from the frontispiece where they are assembled in heraldic poses. True, they include a calf born with a man’s head and, inevitably, the Monster of Ravenna. But even this most terrible of creatures is almost seraphic as it grasps the title-banner in its talons.
There is a moment in time, a few decades around the civil war that racked seventeenth-century England, when the discovery of the natural world has a freshness and clarity that it seems to have lost since. When vigorous prose could sweep away the intellectual wreckage of antiquity and simple experiments could reveal beautiful new truths about nature. In Norfolk, the physician and polymath Sir T
homas Browne published his Pseudodoxia epidemica, or, enquiries into very many received tenents and commonly presumed truths (1646). In this strange and recondite book he investigated a host of popular superstitions: that the feathers of a dead kingfisher always indicate which way the wind is blowing, that the legs of badgers are shorter on one side than the other, that blacks were black because they were cursed, that there truly were no rainbows before the Flood – and concludes, in each case, that it isn’t so. In another work, his Religio medici of 1642, he touches on monsters. There is, he writes, ‘no deformity but in Monstrosity; wherein notwithstanding, there is a kind of Beauty. Nature so ingeniously contriving the irregular parts, as they become sometimes more remarkable than the principal Fabrick.’ This is not precisely a statement of scientific naturalism, for Browne sees the works of nature – all of them, even the most deformed – as the works of God, and if they are the work of God then they cannot be repugnant. It is, in a few beautiful periods, a statement of tolerance in an intolerant age.
At Oxford, William Harvey, having triumphantly demonstrated the circulation of the blood, was attempting to solve the problem of the generation of animals. In 1642, having declared for the King, Harvey retreated from the turmoil of civil war by studying the progress of chick embryos using the eggs of a hen that lived in Trinity College. The Italians Aldrovandi and Fabricius had already carried out similar studies, the former being the first to do so since Aristotle. But Harvey had greater ambitions. Charles I delighted in hunting the red deer that roamed, and still roam, the Royal Parks of England, and he allowed Harvey to dissect his victims. Harvey followed the progress of the deer embryo month by month, and left one of the loveliest descriptions of a mammalian foetus ever written. ‘I saw long since a foetus,’ he writes, ‘the magnitude of a peascod cut out of the uterus of a doe, which was complete in all its members & I showed this pretty spectacle to our late King and Queen. It did swim, trim and perfect, in such a kind of white, most transparent and crystalline moysture (as if it had been treasured up in some most clear glassie receptacle) about the bignesse of a pigeon’s egge, and was invested with its proper coat.’ The King apparently followed Harvey’s investigations with great interest, and it is a poignant thought that when Charles I was executed, England lost a monarch with a taste for experimental embryology, a thing not likely to occur again soon.
The frontispiece of Harvey’s embryological treatise, De generatione animalium (1651), shows mighty Zeus seated upon an eagle, holding an egg in his hand from which all life emerges. The egg bears the slogan Ex Ovo Omnia – from the egg, all – and it is for this claim, that the generation of mammals and chickens and everything else is fundamentally alike, that the work is today mostly remembered, even though Harvey neither used the slogan himself nor proved its truth. Harvey has some things to say about monstrous births. He revives, and queries, Aristotle’s claim that monstrous chickens are produced from eggs with two yolks. This may not seem to amount to much, but it was the expression of an idea, dormant for two millennia, that the causes of monstrosity are not just a matter for idle speculation of the sort that Paré and Liceti dealt in, but are instead an experimentally tractable problem.
It was, however, a contemporary of Harvey’s who stated the true use of deformity to science – and did so with unflinching clarity. This was Francis Bacon. Sometime Lord Chancellor of England, Bacon comes down to us with a reputation as the chilliest of intellectuals. His ambition was to establish the principles by which the scientific inquiry of the natural world was to be conducted. In his Novum organum of 1620 Bacon begins by classifying natural history. There are, he says, three types of natural history: that which ‘deals either with the Freedom of nature or with the Errors of nature or with the Bonds of nature; so that a good division we might make would be a history of Births, a history of Prodigious Births, and a history of Arts; the last of which we have also often called the Mechanical and the Experimental Art’. In other words, natural history can be divided into the study of normal nature, aberrant nature and nature manipulated by man. He then goes on to tell us how to proceed with the second part of this programme. ‘We must make a collection or particular natural history of all the monsters and prodigious products of nature, of every novelty, rarity or abnormality.’ Of course, Bacon is interested in collecting aberrant objects not for their own sake, but in order to understand the causes of their peculiarities. He does not say how to get at the causes – he simply trusts that science will one day provide the means.
Bacon’s recommendation that ‘monsters and prodigious products’ should be collected would not have startled any of his contemporaries. Princes such as Rudolf II and Frederick II of Austria had been assembling collections of marvels since the mid-1500s. Naturalists were at it too: Ulisse Aldrovandi had assembled no fewer than eighteen thousand specimens in his musem at Bologna. Bacon’s proposal that the causes of oddities should be investigated was equally conventional. The depth of his thinking is, however, apparent when he turns to why we should concern ourselves with the causes of deformity. Bacon is not merely a physician with a physician’s narrow interests. He is a philosopher with a philosopher’s desire to know the nature of things. The critical passage is trenchant and lucid. We should, he says, study deviant instances ‘For once a nature has been observed in its variations, and the reason for it has been made clear, it will be an easy matter to bring that nature by art to the point it reached by chance.’ Centuries ahead of his time Bacon recognised that the pursuit of the causes of error is not an end in itself, but rather just a means. The monstrous, the strange, the deviant, or merely the different, he is saying, reveal the laws of nature. And once we know those laws, we can reconstruct the world as we wish.
In a sense this book is an interim report on Bacon’s project. It is not only about the human body as we might wish it to be, but as it is – replete with variety and error. Some of these varieties are the commonplace differences that give each of us our unique combinations of features and, as such, are a source of delight. Others are mere inconveniences that occupy the inter-tidal between the normal and the pathological. Yet others are the result of frank errors of development, that impair, sometimes grievously, the lives of those who have them, or simply kill them in early infancy. At the most extreme are deformities so acute that it is hardly possible to recognise those who bear them as being human at all.
Bacon’s recommendation, that we should collect what he called ‘prodigious births’, may seem distasteful. Our ostensible, often ostentatious, love of human diversity tends to run dry when diversity shades into deformity. To seek out, look at, much less speak about deformity brings us uncomfortably close to naive, gaping wonder (or, to put it less charitably, prurience), callous derision, or at best a taste for thoughtless acquisition. It suggests the menageries of princes, the circuses of P.T. Barnum, Tod Browning’s film Freaks (1932), or simply the basements of museums in which exhibits designed for our forebears’ apparently coarser sensibilities now languish.
Yet the activity must not be confused with its objective. What were to Bacon ‘monsters’ and ‘prodigious births’ are to us just part of the spectrum of human form. In the last twenty years this spectrum has been sampled and studied as never before. Throughout the world, people with physiologies or physiognomies that are in some way or other unusual have been catalogued, photographed and pedigreed. They have been found in Botswana and Brazil, Baltimore and Berlin. Blood has been tapped from their veins and sent to laboratories for analysis. Their biographies, anonymous and reduced to the biological facts, fill scientific journals. They are, though they scarcely know it, the raw material for a vast biomedical enterprise, perhaps the greatest of our age, one in which tens of thousands of scientists are collectively engaged, and which has as its objective nothing less than the elucidation of the laws that make the human body.
Most of these people have mutations – that is, deficiencies in particular genes. Mutations arise from errors made by the machinery that copies or rep
airs DNA. At the time of writing mutations that cause some of us to look, feel, or behave differently from almost everyone else have been found in more than a thousand genes. Some of these mutations delete or add entire stretches of chromosome. Others affect only a single nucleotide, a single building block of DNA. The physical nature and extent of the mutation is not, however, as important as its consequences. Inherited disorders are caused by mutations that alter the gene’s DNA sequence so that the protein it encodes takes a different, usually defective form, or simply isn’t produced at all. Mutations alter the meaning of the genes.
Changing the meaning of a single gene can have extraordinarily far-flung effects on the genetic grammar of the body. There is a mutation that gives you red hair and also makes you fat. Another causes partial albinism, deafness, and fatal constipation. Yet another gives you short fingers and toes, and malformed genitals. In altering the meanings of genes, mutations give us a hint of what those genes meant to the body in the first place. They are collectively a Rosetta Stone that enables us to translate the hidden meanings of genes; they are virtual scalpels that slice through the genetic grammar and lay its logic bare.
Mutants Page 2