Mutants

by Armand Marie Leroi

  The painting, commissioned by Cardinal Odoardo Farnese, was completed in 1599. It was only a trifle compared to the magnificent interiors of the Palazzo Farnese in Rome that the Carraccis had already done for him. Attached to this palace, which now houses the French Embassy, were a botanical garden and a small menagerie, almost certainly the source of the animals depicted in Agostino’s painting. The wild man, a gift from the Cardinal’s kinsman Ranucci Farnese, lived there as well. His cloak hints at his status and identity. It is a tamarco, the robe of the Guanches, who once inhabited Tenerife in the Canary Islands but who had been briskly subjugated and largely exterminated by the Spanish a hundred years before.

  HYPERTRICHOSIS LANUGINOSA. ARRIGO GONSALVUS, ROME 1599. DETAIL FROM AGOSTINO CARRACCI, ARRIGO PELOSO, PIETRO MATTO e AMON NANO.

  Arrigo Gonsalvus, to give the wild man his full name, was not himself a Guanche. He was, however, the son of one, and a rather unusual one at that. In 1556 Petrus Gonsalvus arrived at the court of Henri II of France, brought there possibly as a slave from Tenerife. He could not have been more than twelve, but already a thick pelt of facial hair obscured his features. He seems to have been treated kindly there and was even given some education. In 1559, after the King’s death, Gonsalvus appears at the court of Margaret, Duchess of Parma, despot of the Spanish Netherlands, where he married a young and rather pretty Dutchwoman who bore him at least four children of whom three were exceptionally hairy as well, among them Arrigo.

  Margaret of Parma returned to Italy in 1582, the hairy family trailing in her wake. They were wonders, marvels of nature, and the Hapsburgs and Farneses could not get enough of them. Frederick II, Archduke of Tyrol, commissioned a set of individual portraits for his Wunderkammer at Schloss Ambras near Innsbruck where they may still be seen, part of his collection of natural curiosities. A group portrait of the family by Georg Hoefnagel appears in the illuminated Bestiary of Rudolf II, Emperor of Austria and Frederick’s nephew, the only humans to do so. Perhaps the loveliest of the many portraits that depict this remarkable family is by the Bolognese painter Lavinia Fontana. It is of Arrigo’s younger sister, Tognina, and shows the little hairy girl dressed in silvery brocades, smiling sweetly as she holds a document recounting her history aloft, and looking much like a preternaturally intelligent, if amiable, cat.

  It may be thought that these portraits exaggerate the family’s hairiness, but this is certainly not so. The travels of the family Gonsalvus in northern Italy were noted by that assiduous encyclopaedist of nature Ulisse Aldrovandi, by then Professor of Natural History at the Papal University of Bologna. In his Monstrorum historia, he records meeting the family, describes them with care, and includes four woodcut portraits of them. Some scholars have suggested that Mad Peter, who stares so fixedly at the hairy man in Agostino Carracci’s painting, is a portrait of Aldrovandi himself. In support of this charming conceit, it is certainly true that the bearded figure resembles Aldrovandi, and artist and naturalist had known each other since their student days. But in 1599 Aldrovandi would have been in his seventies, whereas Mad Peter is clearly in his vigorous prime.

  HYPERTRICHOSIS LANUGINOSA. PETRUS GONSALVUS, AUSTRIA C. 1582. UNKNOWN PAINTER, GERMAN SCHOOL.

  Aldrovandi refers to Petrus Gonsalvus as the ‘man of the woods’ from the Canaries, and evidently believes that there were others like the Gonsalvus family there, a race of hairy people. There were not, of course. Petrus Gonsalvus was merely a man who happened to have been born with a mutation that caused a layer of hair to grow over parts of his face and body where in most people it does not. Nothing is known about the ultimate fate of Petrus, his wife, or his son. We do know that Petrus’ daughter Tognina eventually married and bore several children who were as hairy as she.

  Petrus Gonsalvus and his family were not the only hirsute people to have attracted royal curiosity. In 1826 John Crawfurd, British diplomat and naturalist, visited the Burmese capital of Ava to the north of Mandalay. On the throne was Bagydaw, scion of the Konbaungs, a family noted chiefly for the savagery of its dynastic struggles. (One of Bagydaw’s predecessors had celebrated his succession to the throne of Ava in 1782 by slaughtering his brothers, their families, and some hundreds of his subjects – most of whom he immolated on a single gigantic pyre.) The Kongbaungs were also expansionist, a policy that attracted the ire of the dominant regional power, the British government in India. After the First Anglo–Burmese war, a humiliating peace was imposed upon the Burmese. The treaty was carried to Ava by Crawfurd, who found in Bagydaw’s court a scene of medieval splendour complete with white elephants and human albinos. He also found Shwe-Maong.

  ‘We had heard much,’ wrote Crawfurd,

  of a person said to be covered all over with hair, and who, it was insisted upon more resembled an ape than a human being; a description, however, which I am glad to say was by no means realised in his appearance…The whole forehead, the cheeks, the eyelids, the nose, including a portion of the inside, the chin – in short, the whole face, with the exception of the red portion of the lips, were covered with fine hair. On the forehead and cheeks this was about eight inches long; and on the nose and chin it was about four inches. In colour it was of a silvery grey; its texture was silky, lank, and straight. The posterior and interior surfaces of the ears, with the inside of the external ear, were completely covered with hair of the same description as that on the face, and about eight inches long: it was this chiefly which contributed to give his whole appearance at first sight an unnatural and almost inhuman aspect.

  Shwe-Maong was a Lao, a hills-man who as a five-year-old had been sent as tribute to Bagydaw’s court by a local chieftain. Slightly built with mild brown eyes, he lived precariously, weaving baskets and playing the buffoon; as a boy he had been taught to imitate the monkeys that lived in the teak forests of the Burmese hinterland. When Shwe-Maong was in his early twenties, Bagydaw gave him a court beauty in marriage by whom he fathered four children, one of whom, a ‘stout and very fine’ girl named Maphoon, was also hairy. Born with hairy ears, by the time she was six months old the rest of her body was covered in fine grey down. When Crawfurd saw her she was two or three years old and her face was no longer visible. Thirty years after Crawfurd’s account Maphoon appears again in the record of another diplomatic mission to Ava sent to deal with the ever-fractious Kongbaungs. By then she was a mature woman who looked much like her father, long since dead. Silky hair flowed over her face, leaving only her eyes and lips exposed; her neck, breasts and arms were covered with a fine down, and she also had her father’s gentle manners. She had married – Bagydaw’s successor, perhaps out of intellectual curiosity, had offered a reward to any man who would have her – and was the mother of two boys, both of whom were hairy as well. One of them later married, and a photograph that dates from perhaps 1875 shows three generations of the family – Maphoon, her son, and his daughter – all identically hairy.

  In 1885 the British finally conquered Upper Burma in the Third Anglo–Burmese War, and the palace at Ava was destroyed. Maphoon and her family fled into the forests where, some weeks later, they were found by an Italian army officer who persuaded them to travel to Europe. And it is there, in the summer of 1886, that we last hear of Shwe-Maong’s family, exhibiting themselves at the Egyptian Hall in Piccadilly and in Paris at the Folies Bergère.

  THE TOPOGRAPHY OF HAIR

  We are born with about five million hair follicles, and that is all we will ever have. The hair follicles are arranged in rows, adjacent follicles intercalated between each other in strict order. How does this regularity come about? If hair follicles were simply scattered randomly upon our scalps, each of us would have at least a few gaps in the thatch. The problem of how follicles come to be arranged with such precision is deep and difficult. It is the problem of how to make a regular pattern out of nothing.

  The difficulty lies in the word ‘regular’. It is fairly easy to imagine how an organism can make unique parts – five different fingers, for example. It is merely a
matter of having preprogrammed cells respond to a single gradient in the concentration of some molecule. Our fingers are, indeed, specified in just this way. But what if, instead of a hand with five unique fingers, one wished to make a hand with only two alternating finger-types, say, ring fingers and index fingers? A strange variety of hand that looked something like this: ring-index-ring-index-ring? No such hand has ever existed. But this, in essence, is the problem that our skins present. Out of bland embryonic uniformity the skin must somehow order itself into a lattice of regularly spaced hair follicles separated by bits of skin. Clearly, some subtle device is needed.

  HYPERTRICHOSIS LANUGINOSA. MAPHOON, BURMA C. 1856.

  The exact form of that device is still quite obscure, but the logic of its workings is not. What is needed is a way of making hair follicles, but of not making them everywhere. A foetus begins to develop the first of its follicles around three months after conception. Five million hair follicles do not appear all at once: instead, they début on our brows, then spread like a rash, first to the rest of the head and face, then down the neck, throat and torso, across the hips and shoulders, and finally down arms and legs.

  I like the simile of a rash, for it suggests the spread of some infectious change in the skin cells, a change that expands outwards from a small beginning. This change transforms the cells of the skin from a quiescent state to one capable of producing follicles. It probably happens cell by cell. Perhaps it begins with just one cell somewhere on the forehead which induces the same change in its neighbours, which then transform their neighbours, and so on and so on. No one knows what the nature of the change is, but it is possible to make some guesses.

  Each hair follicle is a chimera, a hybrid, of two different tissues. So is skin itself. The skin that we see, that we touch, and that weathers the elements, is the epidermis, a stratified layer of cells that originate in the outermost germ layer of the embryo, the ectoderm. Underneath the epidermis is another, thicker, layer, the dermis, which comes from the mesoderm. Dermis and epidermis are intimate collaborators in the making of a hair follicle. Their relationship is of the nature of talkers holding a conversation, a molecular dialogue of signal and counter-signal.

  There is a simple, if slightly eccentric, experiment that shows this. In 1999, trading on a shared devotion to each other and to science, a married pair of scientists used each other as guinea pigs. They excised a piece of dermis from his scalp and then transplanted it to the hairless region underneath her arm. It may seem surprising that she didn’t reject (in the immunological sense) her spouse’s tissue, but it appears that hair follicles are somehow protected from immune-system surveillance. In the event, shortly after the wound healed she started growing long scalp hairs in the area that had received the transplant. The experiment showed that the dermis has a voice, one that tells the epidermis: ‘make follicles here’. Indeed, the change that spreads like a rash across the foetus as it develops hair follicles is the dermal cells acquiring that voice in succession – a volubility that spreads to dermal cells everywhere bar those in the fingertips, palms, soles, lips and genitals, which for some reason remain silent.

  If, in the conversation of the skin, the dermis’s instructions are the opening gambit, it is one to which the epidermis has immediate right of reply. As dermal cells spring to life, urging the epidermis to make follicles, it must, with regularity and firmness, reply ‘no’. Were it not to do so, the foetus’s skin would become a single giant hair follicle, or perhaps a tumorous mass of malformed follicles and hairs. The way in which the epidermis counters the dermis is what gives hair follicles their precise spacing. Each newly formed hair follicle issues instructions that prevent the epidermal cells around it from also becoming hair follicles. Not only does each newly formed follicle prevent surrounding cells from hearing the dermis’s insistent demands, it probably shuts them off at source.

  The words in this conversation seem to be signalling molecules of the sort that we have come across before. Bone morphogenetic proteins are good candidates for the epidermal inhibitor. Bird feathers are distantly homologous to mammal hair, and if a bead soaked with BMP is placed on a chicken embryo’s skin, the infected patch will not form feathers. If the same experiment is done with fibroblast growth factor, extra (albeit weirdly distorted) feathers will form – perhaps it is the original follicle-inducing signal. These molecules are thought to work in the same way in our hair follicles. But the signals around the developing follicle are so various, abundant and dynamic that it is difficult to know what they all do. We do know that mice engineered with defective hair-follicle signals are often bald.

  GRASSLESS FIELDS

  The one thing that many of us would dearly like to know about hair is why we lose it. Just how many men suffer from ‘androgenetic alopecia’ or ‘male pattern balding’ is a matter of definition, but claims that it can be detected in 20 per cent of American men in their twenties, 50 per cent of thirty-to-fifty-year-olds, and 80 per cent of seventy-to-eighty-year-olds seem about right. Balding is truly a white man’s burden: Africans, East Asians and Amerindians (Native Americans) all have lifetime probabilities of balding lower than 25 per cent. Medically innocuous, it is a dispiriting disorder. When Ovid wrote in Ars amatoria: ‘A field without grass is an eyesore/so is a tree without leaves/so is a head without hair,’ he spoke for legions. For at least a century Americans have shown a marked aversion to electing bald men to their nation’s highest office. Excluding Gerald Ford (1974–77), who was bald but not elected, the last bald president was Dwight D. Eisenhower (1953–61). Europeans have been more sympathetic to the bare-headed politico (Churchill, Papandreou, Simitis, Giscard d’Estaing, Mitterrand, Chirac, Craxi, Mussolini), but even they lagged behind the Soviets, who inexplicably installed, if not exactly elected, bald and hirsute leaders in strict alternation: Lenin (bald), Stalin (hairy), Khrushchev (bald), Brezhnev (hairy), Andropov (bald), Chernenko (hairy), Gorbachev (bald) – a tradition that has been maintained in the Russian Republic with Yeltsin (hairy) and Putin (comb-over).

  What causes balding? Samuel Johnson’s views on the matter – ‘The cause of baldness in man is dryness of the brain, and its shrinking from the skull’ – may be safely discounted, as can the theory, popular around 1900, that it was due to the wearing of hats. But dermatologists are hard pressed to offer more convincing explanations. Baldness obviously runs in families, but claims that it is due to a single recessive mutation or else ‘inherited from the mother’s side’ (recessive X-linked) are wrong. Male pattern balding is caused by several genes, none of which has been yet identified. Whatever they are, they must affect the life-cycle of the hair follicle.

  Hair follicles have the peculiar habit of periodically destroying and then reconstructing themselves. Most of the time they simply produce hair. A single scalp follicle can work on lengthening a hair for anywhere between two and eight years; the longer it does so, the longer the hair becomes. Mouse follicles work on a given hair for only two weeks, which explains why their fur is so short. When the follicle comes to the end of its growth period it begins to retreat within the skin and die, and the hair falls out. Halfway down the follicle, however, there is a bulge of epidermal cells – ‘stem cells’ – that have two remarkable properties: they are immortal, and they can become all the other types of epidermal cells of which the follicle is made. They are the stuff from which the follicle rebuilds itself.

  But not in bald men. Instead of rejuvenating into a fully productive follicle, all that is produced is a pale and feeble imitation of the real thing; a follicular epigone capable only of making tiny hairs. Why this happens remains a mystery. One fact is, however, known: to go bald you need testosterone, and plenty of it. In the passage of Historia animalium in which Aristotle tells us that eunuchs are tall, he also says that they do not go bald, an observation confirmed in 1913 by a study of the last of the Ottoman eunuchs. The first rigorous demonstration that testosterone, rather than any other testicular hormone such as estrogen, is the culprit came f
rom a 1942 study by the American physician James Hamilton. Some of the fifty-four eunuchs he studied were born without testes; some had been castrated as boys out of medical necessity (inguinal hernias, for example). Hamilton does not reveal where he found the rest of his experimental subjects, but one of his later papers suggests that they were mentally retarded men who had been castrated as boys in Kansas mental institutions, a legacy of eugenic programmes that ran in the United States until the 1960s (and even later elsewhere). Consistent with Aristotle’s claim, none of the men who had been castrated before their late teens developed any sort of baldness, not even the relatively high foreheads that nearly all mature men have. This wasn’t because they all happened to come from families with good hair – several had balding male relatives. Proof that the eunuchs’ boyish hairlines were due to their lack of testosterone came when Hamilton gave them male hormone supplements and some of them began to lose their hair. When he stopped the treatment, it promptly grew back.

  The need for balding men to have their testicles is the likely origin of the idea that prematurely bald men are unusually virile. It is a claim that has the ring of wistful propaganda about it. (Even Julius Caesar, it is said, rejoiced in the title ‘the bald adulterer’.) To be sure, there is a sad irony in the fact that the very hormone that gives men their beards in puberty denudes their scalps a few years later, but there is no evidence that prematurely bald men either have more testosterone than their hairier contemporaries or father more children. On the other hand, it is probably a lack of testosterone that prevents women from going bald. Women who acquire, for whatever reason, abnormally high levels of testosterone not only grow beards but tend to go bald as their baldness genes, hitherto silent, manifest themselves.

  Is there any hope for the bald? Contrary to the folklore of depilation, shaving does not make hair grow faster, thicker, or darker – so there’s no point removing what little you have left except on aesthetic grounds. More usefully, at least one of the baldness therapies currently marketed, said to be quite effective, is an inhibitor of dihydroxytestosterone (DHT), the more potent version of testosterone. If this doesn’t appeal (and only a few users suffer impotence as a side-effect), then other therapies may soon be available. The resting hair follicles of a young mouse can be made to produce hair if dosed with a virus expressing high levels of sonic hedgehog. The surplus sonic probably forces the proliferation of the stem cells in the bulge of the hair follicle; if it could do the same for the crippled follicles on bald scalps, then a cure for baldness would surely be at hand. But maybe the hair follicles of bald scalps cannot be rejuvenated; if so, it will be necessary to make new ones. This may well be possible. Mice that have been engineered to overproduce a special form of the protein ?-catenin make entirely new hair follicles at an age when normal mice don’t. Unfortunately, both sonic hedgehog and ?-catenin are extremely potent molecules. Excess amounts of either tend to produce hair-follicle tumors – the product of all those extra stem cells. It may be easy to spur skin to make new hair; rather harder to tame it.