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.