Mutants (32 page)

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 from 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.

BENEATH THE NAKED APE

Four centuries and two continents apart, Petrus Gonsalvus and Shwe-Maong are startlingly alike. Were Petrus to discard his richly sombre robes with their scarlet facings and knot a lungyi about his waist, the two men could be brothers. Nineteenth-century scientists such as Carl von Siebold and Alexander
Brandt were, however, more impressed by the resemblance of the hairy men to orangutans. Influenced by the new
Darwinismus
they suggested that hairiness was atavistic. This may seem like a version, albeit dressed up in scientific terminology, of the ancient equation between hairiness and bestiality. But the scientists were careful to note that though their subjects may have looked like apes, they were in fact quite human.

One can still, occasionally, come across claims that surplus-hair mutations reveal the fur beneath the naked ape. But there is reason to think that the atavism hypothesis is wrong – at least as applied to these two families. Both the hairy Burmese and Canary Islanders are described as having exceptionally fine, silken hair. This does not really resemble the robust pelt that covers adult apes – nor even human scalp or pubic hair. And hairy as great apes are, they are less so than the hairiest humans. Petrus and Shwe-Maong had noses, cheeks and ears that were covered in hair – exactly where great apes have rather little.

Where, then, does the surplus hair come from? One possible source is the foetus. Around five months after conception every human foetus grows a dense coat of hair. This ‘lanugo’ hair is fine, silky, less than a centimetre long, and enigmatically fleeting. Just weeks after it has grown it is shed again. Were it not for the occasional child born with lingering remnants of lanugo (often on the ears), we would hardly know that it was ever there. It seems likely that the mutation that afflicted the hairy families caused this lanugo to be retained. Instead of switching over to the normal pattern of juvenile, and then adult, hair production, their hair follicles were arrested in foetal mode.

And not just their hair follicles. In his description of Shwe-Maong, John Crawfurd notes that the hairy Burmese man had only nine teeth: four incisors and one canine in the upper jaw, four incisors in the lower, and no molars in either. Shwe-Maong’s daughter, Maphoon, had even fewer. Careful inquiries showed that they had not lost their missing teeth: they had never grown them. It was as if their teeth and hair had simply come to a halt somewhere around the sixth month of foetal development even as the rest of their bodies marched on.

Darwin himself knew of the Burmese hairy family. In
The descent of man and selection in relation to sex
(1859) he cites the bribe needed to secure Maphoon a husband as proof that hairiness in women is universally unattractive. Nowhere, however, does he suggest that hairiness is an atavism. He is, instead, interested in the connection between hair and teeth. A Mr Wedderburn had told him of a ‘Hindoo’ family in the Scinde – modern-day Pakistan – in which ten men from four generations were almost entirely toothless, but, far from being hairy, were rather bald – and had been so from birth. The bald, toothless Hindoos also lacked sweat glands; unable to perspire, they wilted in Hyderabad’s heat.

Hair, teeth, sweat glands and (though Darwin does not mention them) breasts, organs seemingly so various in their purpose and plan, are intimately connected. They are all places where skin has swollen or cavitated to make something new. The simple tube that is a hair follicle, the robust anvil of dentine and enamel that is a tooth, and the bulging burden of ducts that is a breast, are all variations on a constructional theme. A genetic
disorder – there are more than a hundred – that affects one of these organs will often affect another.

These organs do not merely share an origin in skin; they are also made in much the same way. Even as hair follicles are forming throughout the foetal epidermis, other epidermal cells are clumping and cavitating to form teeth or mammary glands. Like the hair follicle, each of these skin organs is a chimera: part ectoderm, part mesoderm.

The kinship between all these organs can be seen in the molecular signals that make them. The ‘Hindoos’ still live near Hyderabad, where, confusingly, they are known as ‘Bhudas’ but are in fact Muslim. By 1934, six generations of Bhudas had spread across eight families. Now there are many more. Their distinctive appearance means that they recognise each other as relations, but the name of their mutant forebear seems to be forgotten. Just as Darwin’s correspondent said, they have neither sweat glands nor teeth (except for the occasional molar), but they do have at least a little scalp hair. They carry a mutation in a gene that encodes a protein called ectodysplasin, named for the disorder its absence causes:
Ectodermal dysplasia
. A mutation in the same gene may also explain the Mexican hairless dog. Alias
El perro pelon
or the
Xoloitzcuintle
, the dog is said to have been bred by Aztecs in the fourteenth century, possibly for meat but more likely as a kind of bed-warmer. It, too, is bald, toothless and has dry and crinkly skin for want of sebaceous glands.

An even deeper organ-kinship is evident in an odd variety of aquarium fish. Since at least the start of the Tokugawa Shogunate in the early seventeenth century, Japanese fanciers
have bred the Medaka,
Oryzias latipes
, a small fish that normally lives in rice-paddies. A sort of poor man’s Koi, they can be bought from the night-stalls in Japanese cities where, among the varieties for sale – albino, spotted, long-fin – there are mutants that have no scales. The Medaka’s nudity, like the Bhudas’, is caused by a mutation that disables ectodysplasin signalling.

The use of a single molecule in the making of human teeth, hair follicles and sweat glands is a legacy of the evolutionary history that these organs share. This history is evidently also shared – at various removes – with the feathers of birds and the scales of fish and reptiles. All these organs have evolved from some simple skin organ possessed by some ancient, long-extinct ancestor of the vertebrates. No one knows exactly what this organ was. The best guess is that it resembled the tooth-like scales that give shark skin its roughness.