Homeotic genes come as clusters: groups of genes arrayed side by side on a single chromosome. The first few genes in the fly’s homeotic cluster are involved in giving the head segments of the fly their identities; the next few genes along do the same for the thoracic segments; and the last few do the same for the abdominal segments. There is, it seems, a uncanny correspondence between the order of genes on the chromosome and the order of the fly itself. So, too, mutatis mutandis, is it for us. We have four clusters of homeotic genes on four chromosomes against the fly’s one, but within each cluster the genes preserve the order along the chromosome that their cognates have in flies. Just as in flies, the first genes of each cluster are needed for our heads, the last for our tails, and the rest for the parts in between.
Why the homeotic genes should work in this way, and why they should have stayed doing so, is not clear. Nevertheless, they point to a system of building bodies that evolved perhaps as much as a thousand million years ago in some worm-like ancestor and that has been retained ever since. Indeed, the homeotic genes were merely the first indication that many of the molecular devices that make our bodies are ancient. Over the last ten years it has become plain that we are, in many ways, merely worms writ large. A gene called ems is needed to make a fruit fly’s minute brain. So vast is the evolutionary gulf, both in time and complexity, between a fly’s brain and the hundred-thousand-million-neuron edifice perched upon our own shoulders, that one could hardly expect that the same devices are used in both. Yet mutations in a human cognate of ems cause an inherited disorder that results in a brain abnormally riven with fissures (and so mental retardation and motor defects). Another fly gene called eyeless is needed to make a fly’s compound eyes. Flies devoid of eyeless are, well, eyeless. So, in effect, are humans who inherit mutations in the cognate gene. They are born without irises.
In the cyclical way of intellectual fashion, all this has been said before, albeit far more obliquely. More than 150 years ago, that eccentric genius Étienne Geoffroy Saint-Hilaire – Linnaeus of deformity, discoverer of the universal law of mutual attraction – sought to construct a scientific programme, a philosophic anatomique, that would demonstrate that the animal world, seemingly so vast and various, was in fact one.
His initial goal was modest enough. Geoffroy attempted to show that structures that appear in mammals were the same, only modified, as those that appeared in other vertebrates, such as fish, reptiles and amphibians. In other words, he attempted to identify what we now call homologues, arguing, for example, that the opercular bones of fish (which cover the gills) were essentially the same as the tiny bones that make up the middle ears of mammals (the malleus, stapes and incus).
But opercular bones were small beer for a truly synthetic thinker: Geoffroy went on to find homologies between the most wonderfully disparate structures in the most wildly different creatures. Confronted with the exoskeleton of an insect and the vertebrae of a fish, he proposed that they were one and the same. To be sure, insects have an exoskeleton (all their guts inside their hard parts) while fish have an endoskeleton (bones surrounded by soft parts), but where other anatomists saw this as ample reason to keep them distinct, Geoffroy explained with the simple confidence of the visionary that ‘every animal lives within or without its vertebral column’. Not content with this, he went on to show how the anatomy of the lobster was really very similar to that of a vertebrate – if only you flipped it on its back. Where lobsters carry their major nerve cord on their ventral sides (bellies) and their major blood vessels on their dorsal sides (backs), the reverse is true for vertebrates. And then there was the curious case of cephalopods: if one took a duck and folded it in half backwards so that its tail touched its head (an exercise performed, I believe, on paper alone), did its anatomy not resemble that of a cuttlefish?
It did not. Geoffroy’s speculations attracted the wrath of Cuvier, his powerful rival at the Museum. The result was a debate in front of the Académie Française in 1829 that Geoffroy lost – a duck doesn’t look like a cuttlefish no matter how you bend it; even homologies between fish opercula and the mammalian middle ear didn’t bear serious scrutiny. Yet if the particular homologies that he proposed sometimes seemed absurd, even in his day, his general method was not. Different organisms do have structures that are modified yet somehow similar. Indeed, the idea of homology is so commonplace in biology today (we speak of homology among genes as easily as among fore-limbs) that it is easy to read into Geoffroy’s claims an evolutionary meaning he did not intend. The homologies that he saw, or thought he saw, were, as far as he was concerned, placed there by the Creator. It was the age of what would be called Transcendental Anatomy.
Today it is scarcely possible to study the development of any creature without comparing it to another. This is because animals, no matter how different they look, seem to share a common set of molecular devices that are the legacy of a common evolutionary history, that are used again and again, sometimes to different ends, but which remain recognisably the same wherever one looks. Indeed, the results of the genome sequencing projects suggest as much. Humans may have thirty thousand genes, but flies have thirteen thousand – a difference in number that is far smaller than one would expect given the seemingly enormous difference in size and complexity between the two species. Another creature much loved by developmental biologists, the nematode worm Caenorhabditis elegans, has nineteen thousand genes – even though the adult worms are only 1.2 millimetres long and have bodies composed of only 959 cells.
Some of Geoffroy’s specific ideas are even being revived. One of these is his notion – on the face of it utterly absurd – that a vertebrate on its four feet is really just a lobster on its back. In the previous chapter I spoke of the signalling molecules that oppose each other to form the front and the back of vertebrate embryos. These same molecules – more precisely, their cognates or homologues – also distinguish back from belly in fruit flies; but with a twist. Where in a vertebrate embryo a BMP4 signal instructs cells to form belly, in flies the cognate molecule instructs cells to form back. And where in vertebrate embryos chordin instructs cells to form back, in flies the cognate molecule instructs cells to form belly. Somewhere in the evolutionary gulf that separates flies and mice there has, it seems, been an inversion in the very molecules that form the geometry of embryos, one that looks uncomfortably like the kind of twist that Geoffroy postulated. Absurd? Perhaps not. It is the sort of uncanny correspondence that one comes to expect in an age of Transcendental Genetics.
IV
CLEPPIES
[ON ARMS AND LEGS]
OF ALL THE DOCTRINES THAT HAVE BEEN OCCASIONED by human deformity, none is more dismal than the belief that it is due to some moral failing. We can call this idea ‘the fallacy of the mark of Cain’. For killing his brother, so Judeo-Christian tradition has it, God marked Cain and all his descendants. An apocryphal text from Armenia gives Cain a pair of horns; a Middle Irish history gives him lumps on his forehead, cheeks, hands and feet, while the author of Beowulf makes him the ancestor of the monstrous Grendel. None of this can actually be found in Genesis, which is, by comparison, a dull read. There Cain’s punishment is exile, the mark is for his own protection, and its nature is left obscure. But then, the link between moral and physical deformity has never really required biblical authority. It does not even require iniquitous parents. In 1999 the coach of the English national football team opined to an interviewer: ‘You and I have been physically given two hands and two legs and a half-decent brain. Some people have not been born like that for a reason. The karma is working from another life. What you sow, you have to reap.’ He took his cue from a Buddhist faith healer.
PHOCOMELIA. SKELETON OF MARC CAZOTTE, A.K.A. PEPIN (1757–1801). FROM WILLEM VROLIK 1844–49 TABULAE AD ILLUSTRANDAM EMBRYOGENESIN HOMINIS ET MAMMALIUM TAM NATURALEM QUAM ABNORMEM.
The fallacy of the mark of Cain flourished in Britain – football coaches aside – as recently as the seventeenth century. In 1685, in the remo
te and bleak Galloway village of Wigtown, two religious dissenters, Margaret McLaughlin and Margaret Wilson, were tried and convicted for crimes against the state. The infamy of their case comes from the cruelty of the method by which they were condemned to die. Both women were tied to stakes in the mouth of the River Bladnoch and left to the rising tide. Various accounts, none immediately contemporary, tell how they died. McLaughlin, an elderly widow, was the first to go; Wilson, who was eighteen years old, survived a little longer. A sheriff’s officer, thinking that the widow’s death-throes might concentrate the younger woman’s mind, urged her to recant: ‘Will you not say: God bless King Charlie and get this rope from off your neck?’
He underestimated the girl. Some accounts give her reply as a long and pious speech; others say she sang the 25th Psalm and recited Chapter 8 of Romans; all agree that her last words were pure defiance: ‘God bless King Charlie, if He will.’ The officer’s response was to give vent to his talent for vernacular wit. ‘Clep down among the partens and be drowned!’ he cried. And then he grasped his halberd and drowned her.
The executioner’s words are interesting. In the old Scottish dialect to ‘clep’ is to call; ‘partens’ are crabs. Thus: ‘Call down among the crabs and be drowned.’ In another version of the story, the officer was asked (by someone who had evidently missed the fun) how the women had behaved as the waters rose around them. ‘Oo,’ he replied in high humour, ‘they just clepped roun’ the stobs like partens, and prayed.’ Either way, it is here that the story slides from martyrology into myth. For it seems that shortly after the officer – a man named Bell – had done his cruel work, his wife gave birth to a child who bore the ineradicable mark of its father’s guilt: instead of fingers, its hands bore claws like those of a crab. ‘The bairn is clepped!’ cried the midwife. The mark of Bell’s judicial crime would be visited on his descendants, many of whom would bear the deformity; they would be known as the ‘Cleppie Bells’.
The spot at which the women are supposed to have died was marked by a stone monument in the form of a stake; today it stands in a reed-bed far from the water’s edge, the Bladnoch having shifted course in the intervening three centuries. Another, far more imposing, monument to the martyrs stands on a hill above the town, and their graves, with carefully kept headstones, may be found in the local churchyard. Here, as elsewhere, the Scots nurse the wounds of history with relish.
There are are other modern echoes of the event as well. As recently as 1900, a family bearing the names Bell or Agnew, and possessing hands moulded from birth into a claw-like deformity, lived in the south-east of Scotland and were said to be descendants of the Cleppie Bells. We know nothing more about them; they may be there yet. We do know that in 1908 a large, unnamed family, living in London but of Scottish descent, were the subject of one of the first genetic studies of a human disorder of bodily form. Their deformity, known at the time as ‘lobster-claw’ syndrome, is certainly the same malformation that the Cleppie Bells had, though these days clinical geneticists eschew talk of ‘lobster claws’ and speak of ‘split-hand-split-foot syndrome’ or ‘ectrodactyly’, a term rendered palatable only by the obscurity of Greek, in which it reads as ‘monstrous fingers’. This second Scots family may have been related to the Cleppie Bells, but it is quite possible that they were not and that the deformity arose independently in the two families. At one end of this story there is the historical trial and death of Margarets Wilson and McLaughlin, at the other there are the Cleppie Bells and a clinical literature. The mythical element, of course, lies in the causal connection between the two. Nothing that officer Bell ever did could have caused his descendants to be born with only two digits on each hand, widely spaced apart. If the Bells were clepped, it was because some of them carried a dominant mutation that affected the growth of their limb-buds while they were still in the womb: it certainly had nothing to do with the partens.
SPLIT-HAND-SPLIT-FOOT, OR ECTRODACYTLY, OR LOBSTER-CLAW SYNDROME. GIRL WITH RADIOGRAPH OF MOTHER’S FOOT, ENGLAND. FROM KARL PEARSON 1908 ‘ON THE INHERITANCE OF THE DEFORMITY KNOWN AS SPLIT-FOOT OR LOBSTER CLAW’.
THE USE OF LIMBS
The fragments of myth, folklore and tradition that remain to us from a pre-scientific age are like the marks left in sand by retreating waves: void of power and meaning, yet still possessed of some order. Muddied by time and confused causality, they still bear the imprint of the regularities of the natural world. It is surely significant that in such lore – no matter what its origin – few parts of the human body are as vulnerable to deformity as the limbs. Greek mythology has only one deformed Olympian, crook-foot Hephaestus who, abandoned by Hera (his mother), betrayed by Aphrodite (his wife), and spurned by Athena (his obsession), nevertheless taught humanity the mysteries of working metal and so is the god of craftsmen and smiths. Depicted on black-and-red-ware he is usually given congenital bilateral talipes equinovarus, or two club-feet. Oedipus, perhaps the most famous deformed mortal, wore his swollen foot in his name.
New myths arise even now. In the mid-1960s a Rhodesian Native Affairs administrator claimed that he knew of a tribe of two-toed people in the darker reaches of the Zambezi river valley. In tones reminiscent of Pliny the Elder’s accounts of fabulous races in Aethiopia or the Indies they were, he said, variously called the Wadoma, Vadoma, Doma, Vanyai, Talunda or, most excitingly, the ‘Ostrich-Footed People’ – a primitive and reclusive group of hunter-gatherers who, by virtue of their odd feet, could run as swiftly as gazelles. Veracity was assured by a photograph of a Wadoma displaying his remarkable feet. In 1969 this same photograph appeared in the Thunderbolt, a newsletter published by the American National States Rights Party, illustrating an article which argued that since some Africans had ‘animal feet’ they were obviously a separate species (‘Negro is related to Apes – Not White People’). American academics, rightly outraged, denounced the photograph as a forgery. Wrongly so, for when geneticists investigated the matter, they found that the Wadoma certainly existed, although far from being a whole tribe of ‘ostrich-footed’ people, there was only a single family afflicted with an apparently novel variety of ectrodactyly. But it is impossible to keep a good myth down. In the mid-1980s two South African journalists claimed they had stumbled across a whole tribe of two-toed people in the darker reaches of the Zambezi. Now, websites assert that the Wadoma worship a large metal sphere buried in the jungle and are, in fact, extraterrestrials.
Limbs have an extraordinary knack for going wrong. There are more named congenital disorders that affect our limbs than almost any other part of our bodies. Is it that limbs are particularly delicate, and so prone to register every insult that heredity or the environment imprints upon them? Or is it that they are especially complex? Delicate and complex they are, to be sure, but the more likely reason for the exuberant abundance of their imperfections is simply that they are not needed, at least not for life itself. Children may grow in the womb and be born with extra fingers, a missing tibia, or missing a limb entirely, and yet be otherwise quite healthy. They survive, and we see the damage.
One of the strange things about limbs is how easy it is to compensate for their absence, either partial or entire. As the patriarch of one ectrodactylous family replied to a geneticist: ‘Bless ‘e, sir, the kids don’t mind it. They never had the use o’ fingers and toes, and so they never misses ‘em.’ Indeed, why should they? They could hold their own at school in writing, drawing and even needlework. Among the adults, one was a bootmaker, one drove a cab, and another had a party trick in which he picked up pins from the floor using his two opposable toes.
The neural and physical versatility of limbs is even more striking in people who lack upper limbs altogether. Among the most engagingly feisty of all armless artists was Hermann Unthan, ‘The Armless Fiddler’. Born in 1848 in a small German town, he narrowly escaped smothering by an infanticidal midwife, and was raised by his strict but loving parents on a diet of self-reliance that now seems positively heartless. Within days of his birth,
his father ordered that his son was never to be pitied, never to be helped, and was not to be given any shoes or socks. By 1868 the young Hermann was giving violin recitals to delighted Viennese audiences as the younger Johann Strauss conducted. In the course of his long and varied life he travelled widely, finally coming to rest in the United States, which he loved. At the age of eighty he wrote his autobiography, aptly titled The armless fiddler: a pediscript, with his toes and an electric typewriter. This sort of neural flexibility is common in mammals. Among the anatomical wonders of the 1940s was a little Dutch goat that, born without fore-limbs, managed to get about bipedally, rather in the manner of a kangaroo.
THE NEAR TO THE FAR
The ability of animals to survive without their limbs has long proved useful to biologists. Limbs can be counted, dissected and manipulated on a living creature without the need to open the body. They are naked to the biologist’s gaze. This visibility means that, of all the devices that make the body, those that make limbs are now exceptionally well understood. Much is known, for example, about their most salient characteristic: the fact that they stick out from our bodies.
At day 26 after conception, the first signs of a foetus’s arms appear: two small bumps, one on each flank, just behind the neck. By analogy to the precursors of leaves or flowers, these bumps are called limb-buds. A day or so later, another pair of limb-buds forms further down the torso; they will become legs. Like any of the bumps on the surface of an embryo, limb-buds are at first just a bag of ectoderm filled with mesodermal cells. There are as yet no bones, muscles, tendons or blood vessels. The limb-bud remains in this amorphous state for about five weeks, at which time faint outlines of bones – the first signs of structure – begin to form. Even before that, however, the limb-bud has not been quiescent, because from nothing more than a small bump it has grown into an appendage about 2 millimetres long. On day 50 after conception, the embryo crouches and holds its newly formed hands over its heart. On day 56, it touches its nose.
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