Mutants

From the walls of the Prado, the Louvre and the National Gallery they stare balefully at us. As depicted by Velazquez, Argenti, Bronzino, Carracci, Van Dyck and another dozen now forgotten painters, the court dwarfs stand clad in rich and elaborate dress, miniature daggers at their sides, surrounded by the other possessions of rich and powerful men. In one painting, a princeling stands next to a dwarf, the better to display the boy’s youthful elegance. In another, a dwarf is placed next to a glossy, pedigreed hound. The man’s shoulders are level with the dog’s withers.

‘Towards the end of the seventeenth century,’ wrote Isidore Geoffroy Saint-Hilaire, ‘it was necessary to dream up amusements of a special sort for the leisure of princes and it was to dwarfs that fell the sad privilege of serving as the toys of the world’s grandees.’ But the court dwarfs were older than that. Most of the paintings that depict them date from a century earlier. Catherine de Medici (1519–89) had set the fashion. In the hope of breeding a race of miniature humans she had arranged a marriage between a pair of dwarfs. A few years later, the Electress of Brandenburg tried the same thing, but both couples proved childless. Peter the Great took the amusement to its extreme. In 1701 he staged a wedding between two dwarfs to which he invited not only his courtiers, but also the ambassadors of all the foreign powers posted to his capital. He also ordered all dwarfs within two hundred miles to attend. A dozen small men and women rode into the capital on the back of a single horse, trailed by a jeering mob. At court some of the dwarfs, perceiving that they were there to be ridiculed, refused to take part in the fun. Peter made them serve the others.

Were all the court dwarfs unhappy, degraded creatures stripped of all human dignity? Geoffroy, writing in 1832, thought so. So had Buffon fifty years earlier. Joseph Boruwlaski, however, would not have agreed. For him, being small was a gift, an opportunity. It had lifted him out of obscurity. His Memoirs take up the tale:

The Boruwlaskis were poor. Joseph was only nine years old when his father died, leaving the family destitute. Eighteenth-century rural Poland was, however, a profoundly feudal society in which patronage counted for all; Boruwlaski’s mother had a patron, a young local noblewoman, the Staorina de Caorliz. Charmed by the young Joseph, she prevailed upon his mother to send the boy to live with her so that he could be educated. Boruwlaski thrived in his new home. By his early teens he was only 61 centimetres (two feet) tall, but he had acquired graces that would not have shamed the most noble of Polish youths. Things became a bit difficult for Boruwlaski when the Staorina got married and had a child, but even then he had an eye for a good thing. He became the protege of another, even wealthier, aristocratic woman, the Comtesse de Humiecka. It was the making of him. For the Comtesse was not one to linger in the obscurity of provincial Poland; she had a yen for travel and for society. Bundling Boruwlaski into a carriage, she set out to conquer the courts of Europe.

Vienna, 1754. ‘What,’ asked Marie-Theresa, ‘is the most remarkable thing in this room?’ Boruwlaski gazed about the rococo splendours of the Schönbrunn, but knew the answer. ‘The most remarkable thing in this room is the sight of a little man in the lap of a great woman.’ Her Imperial Majesty, Empress of all Austria and Hungary, was delighted. In Munich, Prince Kaunitz offered Boruwlaski a pension for life. In Lunéville the exiled Stanislaus, King of the Poles, professed himself delighted by his conversation – so much more interesting than that of his own court dwarf, an unhappy youth by the name of Bébé. The Comte de Treffan was also there, making notes for his article Nain in the Encyclopédic In Paris Boruwlaski stayed with the Duc d’Orléans; at The Hague he had an audience with the Prince Stadholder. At Versailles the teenage Marie Antoinette gave him a diamond ring from her very own finger.

Ten brilliant years passed in this manner. And then Boruwlaski fell in love. He paid his court to an actress. She rejected him with scorn. Years later he would write: ‘If I can upbraid nature with having refused me a body like that of other men, she has made me ample amends, by endowing me with a sensibility which, it is true, displayed itself rather late, but, even in my constitutional warmth, spread a taint of happiness, the remembrance of which I enjoy with gratitude and a feeling heart.’ But by then he could reflect on his youthful passion with calm. For he had long won the heart of another, a dark-eyed young noblewoman named Isalina Borboutin. She too had laughed at him, toyed with him, treated him like a child. But he persisted. He wrote to her, often and passionately. He petitioned the King of Poland for a pension so that he could support her. He was given one and a title as well: she relented.

Boruwlaski was a product of the French Enlightenment. In his Memoirs we hear the humane, rational, questing voice of the Encyclopédistes. ‘It was easy,’ he writes,

This is fascinating and rather strange. Most people stop growing some time between the ages of seventeen and twenty. But Boruwlaski, small though he was, continued to grow throughout his twenties. It also took him a while to discover the charms of women: ‘At age twenty-five I was like any lad of fifteen.’ He was evidently a late bloomer.

Joseph Boruwlaski died in his sleep on 5 December 1837 in the quiet English cathedral town of Durham. He had had a happy life, a rich life. Born into obscurity, he had achieved dizzying social heights. Famed for his conversation and his skill with the violin, he had known most of the crowned heads of Europe. Ennobled by the King of the Poles, he had also won the patronage of the Prince of Wales. He could call the Duke and Duchess of Devonshire his friends. He was an ornament of Durham; its council paid him merely to live there. He had married a noble beauty, raised a family and, when he died at the distinguished age of ninety-eight, had outlived nearly all his contemporaries. It was a graceful end to a remarkable life. For Joseph, le Comte de Boruwlaski, was not merely any Continental aristocrat exiled from his homeland. He was the last of the court dwarfs.

PERFECTION IN PROPORTION

Why was Boruwlaski so small? The delay in puberty points to a possible explanation. So do several portraits in oil, half a dozen engravings, and a full-sized bronze that stands even now in the foyer of Durham City Hall. They all show that le Comte was perfectly proportioned in his smallness. True, his proportions were not quite those of a full-sized adult; they are rather closer to those of a child of the same size. But there is no sign of bone disorders such as achondroplasia or pycnodysostosis that cause limbs to grow stubby or bent. It is a kind of smallness that speaks of a failure in one of the most powerful and far-reaching molecular devices that regulate the size we are.

At the base of our brains, in a cavity of the skull, lies a gland called the pituitary. As big as a pea, it is immensely powerful. The pituitary secretes six hormones that collectively regulate the development of breasts in pubescent girls and the secretion of milk in mothers; the production of sperm in men and the maturation of ova in women; our allergic responses and the way we cope with stress.

But much of the pituitary is devoted to making growth hormone: it makes about a thousand times more of this one molecule than any of the other five. Secreted into the bloodstream, growth hormone circulates throughout the body. Its message to the body’s cells is a simple one: ‘grow and divide’. Growth hormone is not, of course, the only molecule that can do this. Every organ has its own molecular devices for regulating its size and shape, but the ability of growth hormone to spread throughout the body from a single source means that it simultaneously affects the growth of all tissues. It is the multiplier of our flesh and bones.

Joseph Boruwlaski has all the signatures of growth-hormone failure: a body the size and proportions of a four-year-old’s, delayed puberty, and a briskly adult intellect. It is impossible to identify the molecular fault with any precision. A mutation in any one of half a dozen genes that control the regulation of growth hormone may have been responsible for Boruwlaski’s smallness. Alternatively, he may have had lots of growth hormone, but no receptor for it to bind to. In the foothills of the Ecuadorean Andes there is an entire community of more than fifty people who have mutated receptors; when fully grown, the men are only 124 centimetres (four feet) tall. They live in just two villages and are rather inbred. Although Catholic, many of them have Jewish names; they are thought to descend from conversos who came to the New World in flight from the Inquisition. It is likely that they brought the dwarfism mutation with them, since exactly the same mutation has also been found in a Moroccan Jew. The Ecuador dwarfs are bright; as children they have a knack for winning prizes at school. But as they get older they tire of being teased by schoolmates and tend to drop out, and in the most recent generation not one of the adults has married.

In 1782 Joseph Boruwlaski met his physical opposite.

Boruwlaski does not tell us the name of this man, but contemporary prints record the meeting of a dapperly dressed dwarf and a man called O’Brien who billed himself as ‘the Irish Giant’. This hardly clarifies matters, since there were at least four ‘Irish Giants’ circulating about Georgian London, two of whom called themselves O’Brien. Both O’Briens were born in Ireland around 1760 and claimed lineal descent from Brian Boru, an Irish monarch of mythically gigantic dimensions. Both came to London in the early 1780s; one exhibited himself in Piccadilly, the other in St James’s. Both claimed they were over eight feet tall, but neither was more than 235 centimetres (seven feet eight inches).

We know this because their skeletons have been measured. One of these men, Patrick Cotter, was buried in Bristol; his casket was found in 1906 and his skeleton examined before re-interment. The skeleton of the other, Charles Byrne, hangs in the Hunterian Museum of the Royal College of Surgeons and Physicians in Lincoln’s Inn Fields, London. He is known there as Charlie, and he is an imposing sight, conveying an impression of oaken massivity. This is partly due to the brown tint of the bones, caused, it is said, by the speed and secrecy of their preparation. His jaw, chin and postorbital ridges are of a strength that must have given him a forbidding appearance in life. Towards his death, which was probably due to drink, he developed the morbid fear that anatomists would seize his bones. He was right to be worried, for a contemporary newspaper describes how ‘the whole tribe of surgeons put in a claim for the poor departed Irishman and surrounded his house, just as harpooners would an enormous whale’. In the event the anatomist and surgeon John Hunter got him, boiled him, and hung him where he can be seen today.

Charles Byrne had a pituitary tumor. In 1911 Sir Arthur Keith, Curator of the Hunterian, opened Charlie’s skull. The indentation that had once contained the pituitary was cavernous; the gland itself must have been more the size of a small tomato than a pea. Pituitary tumors secrete vast amounts of growth hormone. They cause the cells in the growth plates of a child’s limbs to divide abnormally fast, which in turn makes for super-charged growth. Childhood pituitary tumors are no less common now than when Irish giants stalked London’s West End, but these days they are quickly detected and surgically removed. In May 1941, when the Hunterian suffered a direct hit from German incendiary bombs, John Hunter’s giant fossil armadillo was destroyed, as were his stuffed crocodiles and many of the exquisite anatomical preparations to which he had devoted his life. Charlie, however, survived, so to speak.

PYGMIES

An old photograph shows a triptych of skeletons that used to stand in the public galleries of the Natural History Museum in London. The central skeleton once belonged to a European man. On his left stood the hunched skeleton of a lowland gorilla; on his right, the gracefully erect one of a pygmy woman. A label, barely discernible, credits the pygmy skeleton to Emin Pasha, African explorer and Ottoman administrator. His 1883 expedition diary records that it had been unusually expensive, an outbreak of cannibalism having inflated the price of human remains in Monbuttu-land. Yet he had paid the asking price without a murmur. Pygmy skeletons were highly desirable and every museum in Europe wanted one. It had only been thirteen years since an African pygmy had first stepped out of myth and into the modern world.

The writer’s name was George August Schweinfurth, a Riga-born botanist and traveller; the pygmy’s name was Akadimoo. They met in 1870 on the banks of the Uele River in what is now the northernmost province of the Democratic Republic of Congo.

Akadimoo should not have existed. By the time Schweinfurth came across him the notion that there was, buried somewhere in the dark heart of Africa, a race of very small people had long been dismissed as the fancies of Greek mythographers. ‘The Trojans filled the air with clamour, like the cranes that fly from the onset of winter and sudden rains and make for the Ocean Stream with raucous cries to bring sudden death to the Pigmies,’ wrote Homer. Later authors wrote about a pygmy queen named Genara who had, for her beauty and her vanity, been transformed into a crane by a jealous goddess and set against her own people.

The war of the pygmies, the Geranomachia as the Greeks called it, is an engaging story, and one that endured for millennia. Pliny repeats and embroiders it; he places the pygmies in Thrace, Asia Minor, India, Ethiopia and at the source of the Nile, and cannot resist adding that they rode into battle on the backs of goats and were only seventy-three centimetres (two feet four inches) tall. Puzzled medieval scholastics wondered if people so small could be human, and concluded that they could not. As late as 1716 Joseph Addison wrote twenty-three Latin verses entitled The Battle of the Pygmies and the Cranes. Along with them he published two other Latin poems in praise of the barometer and the bowling ball. In his essay on Addison, Dr Johnson comments that some subjects are best not written about in English.

Addison’s poem was the last flourish of the Homeric tradition. By the late 1600s, the hardheaded men of the Royal Society were testing legend against empirical evidence and finding it wanting. In 1699 Edward Tyson wrote a pamphlet to prove that a putative pygmy corpse he had dissected was not human. He was right, as it happens, for his pygmy was a chimpanzee. Tyson then went on to write a scathing commentary in which he pointed out that though the inhabited world was well known, no race of little men had been found; the pygmies, as well as the cynocephali (dog-headed men) and satyrs of the Greeks, were merely garbled stories about African apes.

Tyson’s reasoning was clear and his intentions admirable, but he overestimated the extent of the world that was actually known. He also failed to consider that Homer’s lovely simile might have been concrete knowledge transmuted. Homer certainly knew that the storks that can still be seen nesting in Greek villages in late summer, winter each year in Africa. The inference that his pygmies must live there too is plain. He was also probably remembering something distantly learned from the Egyptians. Almost a thousand years before Homer lived, Pepy II of the sixth dynasty had written to one of his generals urging him to look after a pygmy found in an expedition to the Southern Forests.

Akadimoo, the first modern pygmy, belonged to a people called the ‘Aka’ – a name by which they are still known. The Aka are only one of a rather heterogeneous collection of shortish peoples who live in the African forest between the parallels 4° North and South. If a pygmy is defined as any member of a group with an average adult male height of less than 150 centimetres (four feet ten inches), then Africa has about a hundred thousand of them. The shortest are the Efe of the Ituri forest; their men are only 142 centimetres (four feet eight inches), their women 135 centimetres (four feet five inches). They are thought to have been there long before the invasion of the taller Bantu from the north-west about two thousand years ago.

The French anthropologist Armand de Quatrefages thought that African pygmies are the remnants of a small, dark, frizzy-haired and steatopygous people who once occupied much of the globe. This is not a ridiculous idea. In the islands of the Indian Ocean and the South China Sea there are groups of people who are almost physically indistinguishable from African pygmies. These are the ‘negritos’ who have been a shadowy presence in anthropology ever since the Spanish first encountered them when settling the interior of Luzon Island in the Philippines archipelago. Recent genetic studies suggest that the negritos are ancient: that they were the first Palaeolithic colonists of Asia. Like the rest of humanity, they came from Africa, but they are not especially closely related to Africans, much less African pygmies. They may have evolved smallness quite independently.

Theories about the cause of pygmy shortness long antedate sure knowledge of their existence. The Geranomachia was a favourite theme of Attic artists, who knew only two things about pygmies: that they were short and that they did not like cranes. A red-figure rhyton from the Classical period therefore shows an achondroplastic dwarf clubbing a bird. The diagnosis of achondroplasia is unambiguous – the limbs of the bird’s assailant are short and bowed, yet his torso, head and genitals are of normal size. Pompeii has yielded a fresco, now in the Naples Museum, in which bands of pygmies hunt crocodiles while others are consumed by hippos, and yet others copulate energetically on the banks of the Nile. These Roman pygmies are not deformed, but rather have the large heads and spindly limbs of emaciated three- or four-year-old children. The oddness of these images is perfectly excusable, since none of the artists had ever seen a pygmy; they were depicting the fabulous by appealing to the familiar. More surprisingly, as recently as 1960 a leading anthropologist and expert on pygmies asserted that they are small because of an achondroplastic mutation. Little is known about what makes pygmies short, but this is certainly wrong.

That pygmy proportions are not the result of any known pathology is clear from the skeleton collected by Emin Pasha. It shows that pygmies have limbs that are beautifully proportioned, but that differ from those of taller people in subtle ways. The action of natural selection over the course of tens of thousands of years has made a form more gently sculpted than the dramatic mutations familiar to the clinical geneticist. Studies of children fathered by tall African farmers on pygmy women suggest that pygmy smallness is probably not due to a single mutation, since the children have a height intermediate to that of the parents. So several genes are probably responsible for pygmy shortness. We do not know what these genes are, but we do have some idea of what they do. Careful measurements of pygmies (and thousands of them have been measured) show that compared to taller people, pygmies have relatively short legs but relatively long arms. They also have heads and teeth that are relatively large for their torsos. They have, in fact, not only the height, but also the linear proportions of an eleven-year-old British child.

By ‘linear proportions’ I mean the relative lengths of torso, arms and legs. Pygmy men have the broad chest and shoulders of adult men anywhere, and pygmy women have fully adult breasts and hips. But the juvenile linear proportions of pygmies immediately suggest two devices by which they should come to be so small. Perhaps they simply stop growing at age eleven. Alternatively, perhaps they grow for as long as taller people do (until age eighteen or so), but very slowly.

In principle it should be easy to distinguish between these two ways of being small – it is just a matter of measuring many pygmy children of known age to see when they stop growing. But pygmies do not know how old they are. They have no calendar and so no interest in birthdays. Occasionally, however, pygmy children have been measured. Schweinfurth traded a dog for an Aka called Nsévoué and attempted to bring him back to Europe, but they did not get far before the child succumbed to dysentery. In 1873 another attempt was made, but this time it was the explorer who died. Giovanni Mani, an Italian following Schweinfurth’s trail, traded a dog and a calf for two Aka children, Thibaut and Chair-Allah, and headed north only to expire from the rigours of his journey. The children, however, went on and arrived in Rome in June 1874, where they were presented to King Victor Emmanuel II and then bequeathed, along with Mani’s diaries, to the Geographical Society of Italy.

The geographers, entranced by their acquisition but puzzled what to do with it, passed the children on to Count Miniscalchi-Errizo, a Veronese nobleman. Redubbed Francesco and Luigi, they flourished under the good Count’s care and were soon speaking, reading and writing Italian with panache. Thibaut-Francesco taught himself piano and would pick out delicate airs though his fingers spanned less than an octave. Schweinfurth visited the boys in 1876 and recorded with delight the sight of them sauntering down the streets of ancient Verona with local friends.

The intellectual progress of the two boys was much commented on in the scholarly journals of the day, not least because it refuted the belief that pygmies might not be too bright. That this notion existed at all was partly Schweinfurth’s fault. Although he had evidently been fond of Nsévoué, the published account of his travels, The heart of Africa, gives a rather damning estimate of his friend’s ability and character. But the learned men who streamed through the Palazzo Miniscalchi to view Chair-Allah-Luigi and Thibaut-Francesco were less interested in the boys’ conversation than in simply standing them against a wall and measuring them. Before they had even left Africa, Chair-Allah-Luigi and Thibaut-Francesco had been measured by at least seven scientists, and the pace picked up in Rome. The age of the boys remains in some doubt, but they were thought to be eight and twelve when they arrived in Italy, and they lived there for nearly six years. As they grew, a curious thing was noticed. They didn’t have a pubertal growth spurt.

A newborn infant grows about eighteen centimetres (seven inches) in its first year. This extraordinary rate is not maintained; rather it drops smoothly, year by year, to about five centimetres (two inches) per year. At around the age of twelve for boys, ten for girls, this decline is reversed and growth rate leaps up, albeit only temporarily. Although familiar to any adolescent, the pubertal growth spurt is a rather difficult thing to measure. In 1759 the French aristocrat and friend of Buffon, Philibert Guéneau de Montbeillard (yet another count), began measuring his newly born son, and continued to do so at six-monthly intervals until the boy’s eighteenth birthday. This same boy was eventually guillotined by Robespierre, but the record of his growth remains one of the most perfect of its kind. Though de Montbeillard – or rather Buffon, who wrote up the results – failed to realise it, the data show a beautiful pubertal growth spurt. At the age of thirteen, de Montbeillard’s son’s growth rate spiked at twelve centimetres (nearly five inches) per year. This is a very human thing. Male chimpanzees and gorillas pack on muscle at adolescence and baboons’ snouts elongate, but no other primate shows this sort of skyward leap.

The pubertal spurt is driven by a burst of growth hormone. Pygmies might, then, be expected to have growth hormone levels much lower than those of taller people; but curiously, they don’t. Their shortness seems to be due to a relative lack of another growth-promoting molecule called insulin-like growth factor-1, or IGF-1. As implied by its name, IGF-1 is structurally rather similar to insulin – the hormone of sugar metabolism. Growth hormone regulates the IGF gene so that levels of the two hormones in the bloodstream tend to rise and fall in synchrony. But each hormone makes a unique contribution to growth.

The proof of this is the mini-mouse. A normal laboratory mouse weighs around thirty grams when fully grown. This is rather larger than Mus musculus in its natural habitat (cellars, attics, barns); generations of la dolce vita in the world’s laboratories have made the geneticist’s mouse tame, slow, and slightly corpulent. Be that as it may, if a defective growth-hormone receptor gene is engineered into a laboratory mouse (rather as occurs naturally in Ecuadorean dwarfs), it grows up to be only half the size of a normal mouse. If a defective IGF gene is engineered into another mouse it grows up to about one third the normal size. If these two miniature mice are crossed, the result is the mini-mouse in which both genes are defective and that weighs, when fully grown, only five grams.

This, for a mammal, is minute. It is almost as small as the smallest of all mammals, the bumblebee bat of Thailand, which weighs around two grams. A British five-pence piece weighs 3.2 grams; a euro-cent 2.4 grams; a dime two grams. An adult human that was the same relative size as a mini-mouse would weigh as much as a fourteen-month-old child – a result that suggests that neither the pygmies of the Congo, nor the dwarfs of Ecuador, nor even Joseph Boruwlaski, small as they are, even begin to approach the limits of human smallness.

CRETINS

Schweinfurth’s discovery set off a global hunt for other pygmies. Little people had always cropped up in explorers’ logs and local myths in this or that part of the globe. Such tales had never received much credence, but in the 1890s they were assiduously collected and analysed. Suddenly there seemed to be pygmies in Guatemala, the Yucatan, the Cascade Range of British Columbia, the Atlas Mountains of Morocco, Sicily and the Val de Ribas of Spain. An archaeologist claimed the existence of a race of Neolithic pygmies in Switzerland. Perhaps all these little people were related; perhaps they were the remnants of an earlier, shorter, version of humanity.

The fossil record shows otherwise. Our direct ancestor, Homo erectus, was about 160 centimetres (five feet two inches) tall; Homo neanderthalensis was about 170 centimetres (five feet six inches) tall; and early anatomically modern humans (‘Cro-Magnon man’) were only a little shorter. To be sure, there are short people in various parts of the world. Adult men of the Yanomamo tribe who live at the headwaters of the Orinoco and Amazon rivers have an average height of only 153 centimetres (five feet). The Papua New Guinean highlanders who live on Mount Goliath are also small. The enormous differences among people from around the globe show that the size we are is very malleable. We cannot be sure that smallness evolved independently in African pygmies and Asian negritos, but elsewhere in the world, smallness has evolved again and again.

I say evolved, but a note of caution is required. Most small people live in remote and impoverished parts of the world. It is difficult to know just how tall they would be if fed a protein-and calorie-rich supermarket diet. No one believes that African pygmies would grow much taller if transported en masse to California, but we would do well to remember that the children of Mayan refugees who moved to Los Angeles in the 1970s gained an additional 5.5 centimetres (about two inches) over their relations who stayed in Guatemala.

It is even possible that the most recent, and probably the last, pygmy tribe to be discovered will prove not to be pygmies at all, but rather people with a severe and rather specific nutritional deficiency. In 1954 a Burmese soldier marching through the montane forests near the joint frontiers of Burma, India, Tibet and China came across a village of small people. He was not quite the first to do so. Before Burma’s independence, a series of British explorers – lean, lone Indian Army officers – had traversed back and forth across the region where the four great rivers of Asia, the Irrawaddy, Salween, Mekong and Yangtse, descend from the Tibetan Plateau. Their reports are scanty, but consistent. They record the existence of an ethnically distinct group of ‘dwarfs’ who seemed to have their centre in the upper reaches of the valley of the Taron, a remote tributary of the Irrawaddy. The dwarfs were variously called Darus, Nungs, Naingvaws, Hkunungs or Kiutzu. They were elusive and no one had studied them at any length, yet most accounts agreed that they were a cheerful and hardy, if notably dirty, people who tattooed their faces, lived in tree houses, and were often enslaved by the taller hill-tribes such as the Lisu. A Captain B.E.A. Pritchard measured some Nungs and found they had an average height of 158 centimetres (five feet two inches). He later drowned while trying to ford the Taron after the Nungs cut the bridge that spanned it.

In 1962 the Burmese government decided to find out more. A caravan of military men and physicians walked for two weeks across razor-backed ridges and rope-bridged ravines to the Taron Valley. Their study was published in one of the world’s most obscure journals, the Proceedings of the Burma Medical Research Society, but it is clear and comprehensive. The Burmese found ninety-six people living in two villages. Disappointingly, there were no tree houses and no tattoos, but the men had an average height of only 144 centimetres (four feet eight inches). This was as short as the shortest African pygmies. Yet these people, who called themselves Taron after the river on which they lived, were clearly of Tibeto-Burman stock, and spoke a Tibeto-Burman language. Subsistence farmers of a meagre sort, they lived in conditions of abject poverty and squalor. Three generations previously, the Taron said, they had crossed over from Yunnan; a landslide had blocked the pass through which they had come and they had been in Burma ever since.

Who were they? The Burmese weighed up the evidence and decided that the Taron were probably identical to the Nungs of earlier reports, and therefore a race of genetically short people. How many more of them there were, and their precise origins, were questions left unanswered. The hypothesis that they were true pygmies appeared to be supported by the fact that they lived in close proximity to taller people whose diets seemed no worse than theirs. Yet there were disquieting aspects to the Taron. Of the ninety-six living in the two villages, nineteen were mentally defective. This is a high proportion, even allowing for the fact that they were inbred (pedigrees showed many first-cousins marriages). Several had severe motor-neuron disorders and were unable to walk. And the Taron themselves claimed that when they had come from China they had been of normal size; only in Burma had they become small. That is all we know of the Taron, and we are not likely to know more soon – foreigners have not been allowed into Upper Burma for decades. But it is possible that the Taron are not so much pygmies, or even dwarfs, but rather simply cretins.

It is not a pretty word, but it is the correct one. Cretins are people who are afflicted from birth by a mix of neurological and growth disorders. Traditionally, they have been classified into two types: ‘neurological’ cretins who are mentally defective, have severe motor-neuron problems and tend to be deaf-mute; and ‘myxedematous’ cretins who have severely stunted growth, dry skin, an absence of eyelashes and eyebrows and a delay in sexual maturity. A peculiarly vicious form of myxedematous cretinism, in which growth and sexual development simply stop at about age nine, is found in the Northern Congo. These Congo cretins may be in their twenties and still show no sign of breasts or pubic hair, menstruation or ejaculation, and they never grow taller than 100 centimetres (three feet three inches). This is an extreme. The Taron may have a milder form of the same disease.

Cretinism is a global scourge. In 1810 Napoleon Bonaparte ordered a survey of the inhabitants of the Swiss canton of Valais; his scientists found four thousand cretins among the canton’s seventy thousand inhabitants. The location is telling. As the Taron Valley lies in the foothills of the Himalayas, so Valais lies at the base of the Alps. Swiss cretins have not been spotted since the 1940s, but a belt of cretinism still tracks most of the world’s other great mountain ranges: the Andes, the Atlas, the New Guinea highlands, the Himalayas. What these areas have in common is a lack of iodine in the soil. People and animals alike rely on their food for a ready supply of iodine, but in many parts of the world, especially at high altitude, glaciation and rainfall have leached most of the iodine out of the soil so that the very plants are deprived. Cretinism is caused by a diet that contains too little iodine. Globally, about one billion people are at risk of iodine deficiency; six million are cretins.

In the Gothic cathedral of Aosta, ten kilometres south-east of Mont Blanc, the choir stalls are decorated with portraits of cretins. They were carved to keep their fifteenth-century viewers mindful of the unpleasantness of Eternal Torment: a local version of the fabulous creatures and demonic creatures of misericords elsewhere. Many of the cretins have a curious feature: their necks are bulging and misshapen; one even has a bi-lobed sack of flesh hanging from his throat large enough to grasp with both hands. Just over a hundred years after Aosta Cathedral was built, Shakespeare would write in The Tempest: ‘When we were boys/Who would believe that there were mountaineers/Dew-lapp’d like bulls, whose throats had hanging at them/Wallets of flesh?’

The Aosta cretins and Shakespeare’s mountaineers were goitrous. Goitre is an external manifestation of an engorged thyroid, a butterfly-shaped organ located just above the clavicles. Like cretinism, it is a sure sign of iodine deficiency. When first discovered in 1611, the thyroid was thought to be a kind of support for the throat, a cosmetic device to make it more shapely. In fact it is a gland that makes and secretes a hormone called thyroxine. The thyroid needs iodine to make this hormone, and should iodine become scarce, the thyroid attempts to restore order by the rather drastic device of growing larger. The result is at first a swollen neck, then a bulging neck, and finally, in elderly people who have lacked iodine all their lives, an enormous bag of tissue that spreads from beneath the chin onto the chest, and that contains vast numbers of thyroid tissue nodules, some of which are multiplying, others of which are dying, yet others of which are altogether spent. In England this is called ‘Derbyshire neck’.

A goitre is an ugly but useful thing to have, particularly for a pregnant woman. Thyroxine is yet another hormone, albeit not a protein, that promotes cell proliferation in the bones of foetuses and growing children. It also controls the number of cells that migrate down the growth plate to swell and die before forming bone. A foetus gets the thyroxine it needs from its mother; should it not get enough it is born cretinous. Lack of dietary iodine during childhood can also cause cretinism. And cretinism can also be, albeit rarely, a genetic disease. Many human mutations are known that disrupt the production of thyroxine, its storage, its transport around the body, or its ability to dock to its receptor.

There is also a class of mutations more vicious by far than those that simply cause thyroid malfunction. These mutations affect the pituitary. Among the hormones that the pituitary produces is one that controls the thyroid. This hormone, thyrotropin, regulates the way that the thyroid absorbs iodine, the rate at which it manufactures thyroid hormone, and the way it grows and shrinks according to need. The pituitary is the thyroid’s check and its balance. Goitre is a witness to its workings. The pituitary monitors the level of thyroid hormone that circulates around the body and, should it perceive a want, begins producing thyrotropin, which then spurs the thyroid to greater efforts – in the extreme, spurs it to make a goitre. Children who have defective pituitaries are dwarfed for want of growth hormone and cretinous for want of thyroxine.

But the vast majority of the world’s cases of cretinism are caused by a simple lack of dietary iodine. The tragedy of six million cretins is that the cure and the prevention of the disease is known, and costs next to nothing: it is simply iodised salt. It was the legislated spread of iodised salt in the early twentieth century that eliminated European goitre and cretinism within a generation, so that today these diseases are little more than folk-memories. Indeed, iodine deficiencies are so utterly forgotten in the developed world that outside medical and scientific circles the term ‘cretin’ exists only as a casual term of abuse. What is more, ‘cretin’ survives where comparable epithets have been justly banished from decent conversation. The word simply has no constituency, no defenders. Are the Taron of Upper Burma cretins? Is their smallness part of the vast and glorious tapestry of human genetic diversity, or are they merely victims of a peculiar form of high-altitude poverty? Were we to hear that there are no longer tribes of little people in the vertiginous gorges of the upper Irrawaddy, should we cheer or lament?

IL COLTELLO

Nearly fifteen hundred years ago, while working on a remote Aegean island, Aristotle made an observation that was at once banal, beautiful and chilling. ‘All animals,’ he wrote, ‘if operated on when they are young, become bigger and better looking than their unmutilated fellows; if they be mutilated when full grown, they do not take on any increase of size…As a general rule, mutilated animals grow to a greater length than the unmutilated.’

By ‘mutilation’ Aristotle meant castration. Hence the banality of his observation that merely repeated facts as well known to any fourth-century Greek farmer as to any modern one. What makes the observation beautiful is that Aristotle thought to write it down. He has taken a barnyard commonplace, that gelded rams, stallions and cockerels are larger than intact animals, and made a scientific generalisation of it – one, moreover, that still stands. What makes these facts so chilling is that when he spoke of animals, Aristotle also meant men.

Boys who are castrated before puberty grow up to be tall, unusually so. It is a fact that is largely lost to us now, but that would have been everyday knowledge in fourth-century Athens, a city pullulating with slaves culled from all corners of the Mediterranean, among them many eunuchs. It would also have been known to any fashionable eighteenth-century Italian. The monarchs of the great opera theatres such as La Scala were not, as now, the tenors, but rather the castrati. Feted for the range, power and unearthly quality of their voices, some castrati became rich, famous and influential. Farinelli sang for Phillip V of Spain and was given the title Caballero; Cafarelli became a duke and built a palazzo in Naples; Domenico Mustapha became a papal knight and Perpetual Director of the Pontifical Choir. Rossini, Monteverdi, Handel, Gluck, Mozart and Meyerbeer all wrote for them. When they sang, audiences cried ‘Eviva il coltello!’ – ‘Long live the knife!’– and swooned in the stalls.

The Italian castrati seem never to have been measured, so we do not know exactly how tall they were. But a wealth of anecdotes and images suggests that they were taller than their contemporaries, and somewhat oddly shaped. An engraving attributed to Hogarth shows a castrato performing a piece by Handel. Mouth ajar in soaring bel canto, ungainly limbs akimbo, he towers above his audience. It is a caricature, and a cruel one; all the more so as the castrati suffered from much more than physical inelegance. Beyond the direct consequences of the invariably brutal surgery and the bar to marriage and fatherhood, old age frequently brought severe kyphosis, the broken-back posture that is symptomatic of osteoporosis, otherwise mostly a disease of elderly women. Many castrati also developed large and pendulous breasts. True, they never went bald, and never got prostate cancer, but these were small compensations. In eighteenth-century Italy, some four thousand boys per year lost their testicles for the sake of their golden voices. Few can ever have found the rewards that might have justified the sacrifice.

Why were the castrati so tall? Italian castrati fell from fashion and were banned by Pope Pius X in 1920; the last Vatican castrato, Alessandro Moreschi, died in 1922. But elsewhere hundreds, if not thousands, of men who had been castrated as boys survived well into the twentieth century. These were the court eunuchs, and there were many of them. At its demise, the Chinese Imperial family, last of the Qings, employed upwards of two thousand eunuchs in the Forbidden City at Peking. The last Chinese court eunuch, Sun Yaoting, was buried only in 1996 – along with his testicles, which had been carefully preserved in a jar. About two hundred eunuchs lived at the Topkapi palace in Istanbul until 1924, when the Sultan whom they had served was sent into exile, and many more must have been scattered about the vast territories once controlled by the Sublime Porte. In the 1920s some of these Istanbul eunuchs were carefully examined by a group of German physicians. What they found was distinctly odd. These elderly men, the last in a chain of eunuchs who had successively served Roman, Byzantine and Ottoman masters, had the bones of adolescents.

As children approach late adolescence, the growth plates, source of the cells that drive the growth of bones, gradually become sealed over, and it is this that finally causes growth to stop. Radiography can show how far this process has gone, and can even be used to judge the ‘bone age’ of a child. Where an eight-year-old has wide growth plates at each end of his long bones, those of a fourteen-year-old are narrower, while those of an eighteen-year-old are nearly, if not entirely, occluded. A handful of radiographs showed that the Istanbul eunuchs had unsealed growth plates. The inference was clear, if slightly startling: for want of their testicles, they had never stopped growing.

Testes, then, are not only the source of hormonal signals that regulate gender; they are also the source of at least one hormone that in late adolescence instructs bones to seal their growth plates and so cease growth. The nature of that hormone became apparent in 1994, when a Cincinnati clinician diagnosed a man who showed classical eunuchoid features – those disproportionately long limbs – despite having two perfectly intact and apparently healthy testes. Twenty-eight years old and 204 centimetres (six feet eight inches) in height, he was tall, but not remarkably so. What was peculiar is that, according to his driver’s licence, at the age of sixteen he had been only 178 centimetres (five feet ten inches) tall. Somewhere in the intervening twelve years he had gained nearly ten inches. The molecular fault, when traced, proved to be a surprise: a mutation in the estrogen receptor.

We think of the estrogens – estradiol and estrone – as being quintessentially female hormones, and so they are. They are the hormones of breasts, periods, pregnancy and menopause. But men produce estrogens as well, and in large quantities; it is the stuff from which testosterone is made. Not all male estrogen is converted, and what remains appears to be critical in stopping the growth of bones. Two other men have been found in recent years – one in Japan, the other in New York – who cannot produce estrogens at all for want of an enzyme. They too were in their twenties and still growing fast. Conversely, children who produce an excess of estrogen tend to go through puberty very early. They grow fast but stop soon and remain short all their lives.

But there must be more to stopping growth than estrogen. Testicular estrogen may instruct adolescent bones to fuse their growth plates and so cease growing, but men without estrogen or its receptor do not grow at a rate of nearly an inch per year for their entire lives. The eunuchs who guarded Ottoman harems, regulated the affairs of the Celestial Empire and bestrode the stage of La Scala may have been imposing figures, but they were not nine feet tall. This is probably because after adolescence, bloodstream levels of IGF-1 decline, causing a general slowdown in rates of cell division throughout the body. That it does so is probably just as well.

ON BEING THE RIGHT SIZE

Growth hormone and IGF are extremely powerful growth-promoting molecules. Vital if a child is to grow to the size that it should, they must also be continually kept in check. If they are not, growth spins out of control, and the result is growth without growth’s checks and balances, or, as it more commonly known, cancer.

Among the body’s devices that curb IGF-1’s propensity to make cells proliferate is a protein called PTEN. Infants who are born with a single defective copy of the PTEN gene show, initially, little sign that anything is wrong with them; they have, at worst, slightly larger skulls than normal. The problems come later when, as inevitably happens, the second copy of the gene mutates in a few cells of the growing child. In these cells, and their descendants, a want of PTEN protein causes cell division to spin out of control; the result is an exotic array of tumors in the mucosal lining of the mouth, lower colon, breast, ovaries and thyroid and, oddly enough, hair follicles.

These cancers are often fatal. But inheriting a defective copy of PTEN can have far more devastating consequences than this. Should the second mutation happen to occur in the first cells of the embryo (instead of in late childhood), a large fraction, perhaps even a half, of the infant’s body will be completely devoid of PTEN. The afflicted fraction of the body becomes, in effect, a single, enormous and inexorably spreading tumor.

The condition is known as Proteus syndrome, named for the most versatile of Greek gods. ‘Some have the gift to change and change again in many forms,/Like Proteus, creature of the encircling sea/Who sometimes seemed a lad, sometimes a lion/Sometimes a snake men feared to touch, sometimes/A charging boar, or else a sharp-horned bull,’ wrote Ovid, who elsewhere calls the sea-god ‘ambiguous’. The syndrome is very rare, known from no more than sixty people worldwide. Children with Proteus syndrome appear normal at birth, but their faces and limbs become increasingly distorted with age as chaotic outgrowths of bone and soft connective tissue expand over their bodies, often just on one side. They have large tracts of creased and crenulated skin, particularly on the soles of their feet, and they usually die before the age of five. In some, the cerebral hemispheres of their brains grow lopsided and they die of neural seizures; others cannot breathe because of overgrown ribs; yet others die when one of the many odd tumors to which they are prone becomes malignant. It is now believed that James Merrick, the so-called ‘Elephant Man’ who died in 1890 at the age of twenty-eight, had Proteus. If he did, then in one sense he was lucky to have lived for as long as he did.

The intimate relationship between growth and cancer is shown by dogs. A Great Dane puppy has far more IGF circulating in its bloodstream than a Chihuahua puppy does, and grows nearly eight times faster to ten times the size. It pays a cost for doing so. Great Danes, Newfoundlands, St Bernards and many other giant breeds of dogs have a risk factor of osteosarcoma or bone cancer eighty times greater than do smaller breeds. The cancer nearly always begins in one leg, and usually only amputation will prevent its spread.

Osteosarcoma is also one of the most common cancers in children. As in dogs, it usually begins in the leg bones, and then during the pubertal growth spurt when the cells of the growth plate are dividing most vigorously. In the Hunterian Museum, not too far from Charles Byrne’s skeleton, is a display cabinet containing a desiccated ribcage and larynx taken from a young man who died of advanced osteosarcoma. These macabre specimens have the added horror of being covered in hard, grey nodules resembling lumps of coal. They are secondary tumors, clumps of bone-producing cells that had metastasised from the primary leg tumor – which Hunter had attempted to cure by radical amputation. In children, as in dogs, size is a risk factor for osteosarcoma. More than 50 per cent of cases are found in children who are in the seventy-fifth centile for height at any given age.

Big dogs and tall children may be more susceptible to cancers simply because they have more cells than smaller dogs and shorter children. More likely, however, it is probably not large size per se that is dangerous, but rather the high levels of growth hormone and IGF that big dogs and children tend to have. Pituitary tumors, of the sort that the giant Charles Byrne must have had as a child, occasionally appear in adults as well. As in Byrne’s case, they produce vast amounts of growth hormone, but this doesn’t cause an increase in height, since the long-bone growth plates have fused. Instead, only the bones of the jaws, hands and feet grow, a condition known as ‘acromegaly’. Often the first sign that an adult has a pituitary tumor is the need for ever-larger shoes. A pituitary tumor is a moderately dangerous and unpleasant thing in itself. But it also has a nasty indirect effect, causing elevated rates of colon, breast and blood cancers (leukaemias). These cancers are not caused by metastasis of the pituitary tumor, which is benign, but rather by something it does: namely, stimulate the entire growth-hormone-IGF system.

Why this should cause high levels of cancer is not exactly clear, but one idea is that IGF stops sick cells from dying. Cells that are stricken with a potentially carcinogenic mutation often suicide. IGF overrides this altruistic impulse and so acromegalics, big dogs and tall children are relatively prone to cancers. It is as well to be clear about the magnitude of these risks. Of all the spectres that might assail a parent, childhood cancer is the least substantial. Osteosarcoma, though a pernicious and aggressive disease, is very rare: it afflicts only 1 in 300,000 children. The parents of tall teenagers should not worry; the owners of large dogs should.

The bad news for big dogs does not end there. Many people buy health insurance for their pets so that their faithful companions do not bankrupt them as, in their dotage, the dogs require heart bypass surgery. Insurance companies, seeking as ever to minimise their risk, have collected vast databases on the health and mortality rates of their clients (the dogs, not the premium-paying humans) which show quite clearly that, independent of the risk of osteosarcoma, big dogs age faster than smaller dogs. Great Danes, Newfoundlands, and St Bernards have average lifespans of four to five years; Chihuahuas and toy poodles live about ten years longer. There are about four hundred distinct breeds of dogs: for every kilogram that one of these breeds is heavier than another, it loses eighteen days of life.

These results seem to tell us that large size is generally unhealthy, but it is just a correlation. Dog breeds differ from each other in so many ways that it is difficult to attribute differences in longevity among them to differences in size alone. Ten thousand years of dog breeding is a magnificent natural experiment, but like all natural experiments, it isn’t really an experiment at all – at least not in the sense of being a controlled manipulation. Fortunately, a real experiment is at hand: dwarf and giant mice. The mutant mice that are so small for want of growth hormone also live up to 40 per cent longer than their normal-sized brothers and sisters. Conversely, mice that are genetically engineered to be giant age fast and die soon. Whatever the causes of the inverse association between body size and ageing, it seems to be found in all mammals.

I am fascinated by these findings. If dogs and mice, why not people? Could it be that small people are genetically predisposed to live longer than taller people? Some scientists think so. They point to a family with defective pituitaries who live on the Adriatic island of Kruk and who seem to be (despite being both dwarfed and cretinous) rather longer-lived than the average Croatian. Or else to studies that show that the shortest American baseball players outlive taller ones by eight years. Maybe so, but the sample sizes in these studies are small, and large national surveys in Norway, Finland and Great Britain have consistently shown the opposite trend. This is hardly surprising. Socioeconomic factors account for most of a population’s variation in both height and health.

To be poor is to be both short and at higher risk of nearly any disease you care to name. This effect simply overwhelms any genetic tendency for the opposite trend, if such a tendency indeed exists. Will the poor always be short? Perhaps not. Young Dutchmen are, on average, 184 centimetres (six feet) tall. This makes the Dutch the tallest people in the world, taller even than Dinka goatherds or Masai morani. And they are getting taller: by 2012 their men will be 186 centimetres (nearly six feet one inch) tall, their women 172 centimetres (five feet seven inches). Recently, tall activists have even managed to persuade the Dutch government to raise – by twenty centimetres – the ceiling levels specified in that nation’s building codes.

This supremacy in centimetres is partly because Holland is a northern country rich in cows. Being northern, it has a population that tends to be genetically rather taller than, say, their southern neighbours the Belgians, who are in turn taller than their southern neighbours, the French. Dutch children also have a high consumption of animal protein – the product of all those placid black-and-white milk cows that give the Dutch landscape its characteristic look, and the Dutch atmosphere its characteristic tang. But Holland’s geographic peculiarities are probably not enough to explain the genial blond giants that can be seen in such numbers on its university campuses; for many years it has had a medical system that is excellent, efficient and egalitarian, if hard on its taxpayers’ wallets, and this must surely also contribute to the general stature of its young citizens. Most remarkably, it is no longer possible to judge the socio-economic background of Dutch children from their height. Decades of social engineering have eliminated the differences that have existed there (and everywhere else) for millennia. Égalité has begun to reach our very bones.

But not in most countries. Elsewhere, the rich remain tall and the poor short. Young Englishmen are, on average, 176 centimetres tall, a full eight centimetres shorter than young Dutchmen. England is also an exception to the rule that northern peoples are taller than southern ones. The inhabitants of Holland may be taller than the French, and the farmers of Schezwan taller than the Cantonese, but Yorkshire man is shorter than Essex man, and the average Scot is shorter yet. Celtic vs. Saxon genes may make a difference, but most public health experts point to the relative poverty of northern Britain. Notoriously, the inhabitants of some especially forsaken Glasgow council estates can travel for five kilometres in any direction without finding so much as a cabbage for sale.

The poverty and short stature of the north of England’s people is long-standing. More than 150 years ago, the northern cities of Leeds and Manchester became the site of the first serious investigation into the growth of British children when the social reformer Edwin Chadwick investigated the conditions of children working in the cotton mills. By modern standards, the factory children were remarkably small. Age-for-age, they were shorter than the shortest 3 per cent of modern British children, and the difference persisted, the average eighteen-year-old factory worker being only 160 centimetres (five feet three inches) tall. In 1833, the year that Chadwick published his report, the British Parliament passed a Bill against the employment of children under the age of nine.

It is precisely the antiquity of the positive association between health and height that probably accounts for the pervasive attractions of height. From George Washington to George Walker Bush there have been forty-three US presidents, and forty of them have been taller than the average American male. James Madison was famously only 164 centimetres (five feet four inches), but then he was also the architect of his nation’s constitution. Presidential candidates are not taller than the people they aspire to govern simply because they are wealthier. Voters actively choose height as well: forty of the forty-three election-winners have been taller than their closest rivals. Women of all cultures seem to prefer men who are on average five centimetres (about two inches) taller than themselves. Professors, who may be expected to value the intellect above all things, behave in the same way. Full professors in American universities are on average three quarters of an inch taller than lowly assistant professors, and department chairmen are taller yet. When asked what height they should like to be, American men of even average height invariably wish themselves taller. And who can blame them?

The pervasive attractions of height present us with a dilemma. As we learn more about the molecular mechanisms that control height, we will be able to manipulate with ever greater subtlety the size that we, or rather our children, grow to be. But what size should we be? The boundary between normal and pathological height is never distinct: it is a grey zone, dictated by clinical possibility, or even convenience. There are, it is true, many diseases, genetic or otherwise, of which shortness is symptomatic. But shortness, even when genetic in origin, is not always, or even most of the time, a disease. In the United States, some thirty thousand short children are currently being given recombinant growth-hormone supplements to make them grow. Most of these children are growth-hormone deficient, and for these the treatment is quite appropriate. But about a third of them have what is called ‘idiopathic short stature’. That is, they are not short because they are malnourished, or because they are abused, or because they have anything identifiably, clinically, wrong with them – they are merely short. They are given growth hormone because their parents would like them to be taller.

I wonder if this is right. Giant dogs and dwarf mice suggest that growth hormone affects bodies in ways that we do not yet fully understand. Given this, it is surely neither radical nor Luddite to suggest that we should not manipulate our children’s height when there is no good medical reason to do so. It is not just a matter of growth hormone either. As we learn more about the molecular devices that make us the size we are, the temptation to apply them will become ever greater. The boundary between the normal and the pathological is not only indistinct; it is mobile, ever shifting, ever driven by technology. In a way this is just as it should be. The transformation of biological happenstance into definable, curable disease is little less than the history of medicine. Should it be also this way for height? Tallness may be correlated with all sorts of desirable things, and few short men may have become President of the United States, but these are not really terribly interesting observations. Studies of short children have shown what we might have guessed: that of all the things that might affect a child’s chances for happiness and success in life, height is among the least important, far less important than intelligence, health, or the quality of care the child gets from its parents. And as we mark, with pride or anxiety, the progress of our children on doorframes, it is this that we should remember.