Mutants (30 page)

Molecular devices are required to make a naive neural crest cell form a melanocyte rather than some other kind of cell, and also to guide the melanocytes to their final destinations. Mutations in at least five distinct genes cause piebaldism, and each of them disables one or more of these devices, so causing patches of skin that are devoid of melanocytes and therefore perfectly white. Some piebalds have only a white forelock, some have bodies covered in patches, and some have eyes of different colour. Yet others have more serious disorders. A few piebald infants have a debilitating intestinal condition known as ‘megacolon’ – a lower intestine that is swollen with massive constipation caused by the absence of gut nerves that drive defecation. These nerves too have their origin in the neural crest. Piebald children are also prone to deafness, for it seems that melanocytes serve some critical function in the inner ear.

DINKA VS. DUTCHMAN

Guinea pigs, dogs, cats and cattle may have been bred for variety of colour, but only humans come naturally in so many different shades. What gives us our skin colours? It is a curious thing, but for all that geneticists have learned about the causes of abnormal pigmentation, they have yet to give an account of the genes responsible for the difference in skin colour between, say, a Dinka and a Dutchman.

Why is this? In part it is due to the sheer difficulty of the problem. Geneticists agree that more than one gene makes the difference between naturally dark and fair skin (were it only one
gene, we would know it by now), but beyond that the guesses range between two and six, interacting in complex combinations to give any particular shade of pink, tan, brown or black. This makes things difficult. When many genes, each of which has many variants, combine to affect some property of the human body, the molecular identification of those genes becomes a challenging exercise in applied statistics. When the property in question is a disease – heart disease or non-insulin-dependent diabetes – geneticists have embraced the challenge with a will. They have been more cautious about studying skin colour.

This is understandable. Ever since Linnaeus divided the world’s people into four races –
Asiaticus, Americanus, Europaeus, Afer
– skin colour has been misused as a convenient mark of other human attributes. Linnaeus distinguished his four races not only by the colour of their skins but also their temperaments:
Asiaticus
was ‘stern, haughty, avaricious and ruled by opinions’;
Americanus
‘tenacious, contented, choleric and ruled by habit’;
Afer
, seemingly devoid of any redeeming virtue, was ‘cunning, slow, phlegmatic, careless and ruled by caprice’. What of his own race?
Europaeus
, Linnaeus thought, was ‘lively, light, inventive, and ruled by custom’. This was the beginning of an intellectual tradition that, via the writings of Arthur, Comte de Gobineau, the nineteenth-century theorist of Aryan supremacy, culminated in the most systematic chromatocracy that the world has ever known: apartheid South Africa.

For nearly half a century the architects of the South African
laager
held the world at bay and devoted much of that nation’s abundant resources towards the hopeless task of dividing the
racial seas. In the endless negotiations as to who could or could not sit on park benches marked
net blankes
(whites only) every policeman, magistrate, employer, practically every citizen, became an expert on racial identity. South African law was always deliberately vague as to what made someone
blank, swart
or a
kleurling
(‘coloured’ – in apartheid’s parlance, someone of mixed African and European descent). In part it was just who you knew, where you came from, what people thought you were. But mixed in with these social criteria was an elaborate array of pseudo-scientific tests that would, their proponents declared, infallibly betray African ancestry in someone trying to ‘pass for white’. Some placed their faith in the ‘pencil test’ – predicated on the notion that a pencil stuck in someone’s hair would only remain there if the subject was at least part black. Others held that the colour of the skin beneath the fingernails was critical, or else spoke of knowledgeably of eyelids and the Mongolian Spot. Yet others appealed to the colour of the genitals (‘the scrotum test’). In the segregation of schools, hospitals, jobs, indeed every aspect of public life in South Africa between 1948 and 1990, the destiny of a child could turn on the precise shade of almost any of his or her body parts.

In 1973 a forty-year-old Cape Town housewife named Rita Hoefling, who had until then enjoyed the privilege and security that came with being a white South African, began to turn black. She had been diagnosed with Cushing’s disease, a disorder caused by hyperactive adrenal glands. The glands were removed and for a while all seemed well, until she noticed that her skin was becoming rather dark. It wasn’t just a matter of a
tan, but rather a deep bronze, that altered her whole appearance – indeed, made her look like a
kleurling
.

The first humiliations were small ones, the stuff of ‘petty’ apartheid. Thrown off a ‘whites only’ bus by a zealous conductor, she was forced to carry a card that explained and excused her dark skin. But in apartheid South Africa any citizen could be a self-appointed Race Commissioner, and it was not long before Rita felt compelled to move to another area – only to have her new neighbours issue a petition of protest as well. All this in Cape Town, even then South Africa’s most cosmopolitan and racially tolerant city. The strain eventually told on her family. When her father died, Rita was not allowed to attend his funeral: ‘I do not want,’ said her mother, ‘to be embarrassed by your black body at Daddy’s grave.’

Driven from the white community, Rita Hoefling was befriended and sustained by blacks. They welcomed her into their homes in the segregated townships, and kept her sane. She became fluent in Xhosa. And then, one day in 1978, Rita spontaneously turned white again. She attempted to return to her old life, but by then her husband – a former Royal Navy officer – and her children had left her. For the last ten years of her life she lived on charity and a small pension and moved between grimy bedsits in Cape Town’s slums. It was in such a bedsit that in 1988, aged fifty-five, she died of bronchial pneumonia.

Rita Hoefling had a disorder called ‘Nelson’s syndrome’ which occurs in about a third of patients who have adrenodectomies. One of the critical tasks that the adrenal gland does (rather like the thyroid) is keep the pituitary gland in check. In
the absence of her adrenals, Rita’s pituitary began to grow, became tumorous, and produced a surplus of pituitary hormone that caused her skin to darken.

Charlie Byrne, the Irish Giant, also had a pituitary tumor. It may seem surprising that a tumor in a single organ can manifest itself in such different ways, but the pituitary is a remarkably versatile organ. Not so much a hormonal factory as an industrial park, each of the half-dozen-odd hormones that it secretes is the product of a group of specialist cells. This means that tumors that start in different pituitary cell types can have very different consequences. Most pituitary tumors start in cells devoted to producing growth hormone and so cause either gigantism or acromegaly. More rarely the tumor starts in cells devoted to the production of a group of hormones called melanotropins.

Like growth hormone, melanotropins circulate throughout the body; however, where growth hormone affects nearly all of the body’s cells, melanotropins tend to be more discriminating. Among the cells they affect most spectacularly are the melanocytes. When the hormone binds to its receptor on the melanocyte, the cell begins to produce eumelanin, the pigment that gives us the dark shades in our skin, hair and eyes. Just as too much pituitary growth hormone causes the over-multiplication of flesh and bone, an excess of melanotropin causes our skin to bronze – at least it does in fair-skinned people. But melanotropins do not simply turn eumelanin production on. Children who have no melanotropins are not blonds, but redheads. And they are fat.

They are fat because one of the melanotropins, a molecule called a-melanocyte-stimulating hormone (?-MSH), does more
than its name suggests. On melanocytes it binds to, and activates, a molecule called melanocyte-stimulating hormone receptor-1 or MC1R. In the brain, however, it binds to another receptor called MC4R that is encoded by a different gene. The brain receptor controls appetite. When ?-MSH activates MC4R a neuronal signal tells us to stop eating. Children who lack α-MSH are obese because they simply do not know when to say to say ‘when’.

Yet not all redheads are fat. Indeed, casual recollection suggests that rather few are. Why is this? The answer appears to be that most redheads do not owe their fiery locks and translucent skins to a lack of any hormone but to unusual receptors. When MC1R is active, melanocytes make eumelanin – brown and black pigments; inactive, they make phaeomelanin – red pigments. Red-haired Celts have receptors that are more or less permanently inactive – something they share with red setters, red foxes, and red-haired Highland cattle.

Note the weasel-word – ‘unusual’. Throughout this book, I have used the language of clinical genetics. I have spoken of ‘mutations’ that ‘disable’ proteins or else render them ‘defective’. But there are so many redheads around that it seems a bit harsh to speak of their genes in this invidious fashion. And yet the question niggles: are redheads mutants?

Whether a given genetic sequence is a mutation rather than a polymorphism hinges on two issues: its global frequency and its usefulness – mutations being rare and harmful, polymorphisms being generally neither. As far as frequency goes, redheads may be common in northern Europe (6 per cent in Aberdeen), but globally they are rare. Worse, a count of heads overestimates the
frequency of the ‘redhead gene’. This is because each redhead is unusual in his or her own way. MC1R comes in at least thirty different versions, and many of them are found in Ireland. Six, but perhaps as many as ten, of these human MC1R versions, in a multiplicity of combinations, cause red hair – be it auburn, deep red, orange or strawberry blond. Africans, by contrast, all have just one kind of MC1R.

Globally, any single red hair version of the MC1R gene is so vanishingly rare that we must, it seems, call it a mutation rather than a polymorphism. But perhaps an argument can be made for utility? Some have speculated that northeners need lighter skins in order to garner sunlight for the manufacture of vitamin D, without which they would suffer rickets, a bone deformity. Darwin thought that the variety of human colour was due to sexual selection – generations upon generations of perfectly arbitrary choice for beautiful mates. This is a pleasing but difficult-to-prove hypothesis – at least if we discount Henri Toulouse-Lautrec’s belief that redheads give off an especially erotic odour.

On the other hand, it is easy to make a case against the usefulness of red hair. The uniformity of MC1R in Africa tells us that dark skin is needed in the tropics – there is no doubt that it protects against skin cancer. Removed from soft northern light, redheads are easily ravaged by the sun. Their MC1R genes give them delicate complexions that refuse to tan but only burn. Many Australian children are descended from Scottish and Irish immigrants, and Australian law ensures that they all wear hats and long sleeves in their schoolyards. None of these arguments
is conclusive. But the evidence tends to suggest that, delightful though it may be to look at, red hair is not good for anything at all. MC1R in northern Europeans may simply be a gene that is decaying because it is no longer needed, rather as eyes decay in blind cave-fish.

THE STORY OF PETRUS GONSALVUS AND SHWE-MAON

Pale, and proud of it, nineteenth-century European anthropologists typically ordered humanity by skin colour. Perhaps unsurprisingly, scholars from elsewhere have often seen matters differently. Upon returning from a European tour, the Chinese
savant
Zhang Deyi (1847–1919) informed his compatriots that many Frenchwomen had long beards and moustaches. Eschewing the skin-colour geographies of their European counterparts, Chinese anthropologists made maps showing which of the world’s people were or were not hairy. They were fascinated by the Ainu, a relatively hirsute northern Japanese people whom they depicted as a race of dwarfish ape-men. The Ainu are, of course, nothing of the sort. True, Ainu men take a traditional pride in the length of their locks and beards (neither of which they trim), yet they have no more body hair than most Europeans. But then, learned Qing commentators also compared European visitors to macaques, a pleasant tradition that persists in Singapore, where foreigners are still called
angmo
or
angmogao
, Hokkein for ‘red-haired ape’.

It is perhaps not quite fair to single out the Chinese for their
preoccupation with hair (it was, after all, almost certainly a white South African who invented the ‘pencil test’). And Europeans may be hairy, but this has never made them especially sympathetic to people who are hairier yet. Several genetic disorders called hypertrichoses cause infants to develop lush growths of hair on their noses, foreheads, cheeks and ears, limbs and torsos – parts that are, in most babies, only modestly clad. Grown up they have been the wild men,
Waldmenschen
and
femmes sauvages
of early travellers; the
hommes primitifs
and
Homo hirsutus
of taxonomists, and the dog-bear-lion-ape-people of fairground hucksters.

In the collection of the Capodimonte Museum in Naples there is a painting by Agostino Carracci, elder of the Bolognese artist brothers. Two figures frame the scene: a humorous dwarf and a bearded man of middle age whose teeth are bared in a grimace. Their attention is fixed upon a third figure, young, handsomely proportioned and serene, who sits between them. He is, it seems, a wild man, a man of the woods. Apart from a rude cloak he is naked, and his face is covered in hair – not just a beard, but locks that grow high on his cheeks and low on his forehead. The background foliage is lush, and a parrot, two monkeys and two dogs complete the bucolic scene. The whole thing could be an allegory of Nature were it not for the title,
Arrigo Peloso, Pietro Matto e Amon Nano
– Hairy Harry, Mad Peter and Tiny Amon – which tells us that it is really the inventory of a zoo.