What makes us human?
The unfortunate 'rat people' of Pakistan could provide the answer. Armand Leroi investigates
Travel the Grand Trunk Road between Lahore and Islamabad, and you come to the city of Gujrat. Awash in the smog and sewage produced by its million-odd inhabitants, it is an unlovely place best known for the manufacture of electrical fans. It is also the location of a shrine to a 17th-century Sufi Saint by the name of Shua Dulah. For at least 100 years, but perhaps for centuries, it has been, though is no longer, a depository for children with microcephaly.
The word "microcephaly" comes from the Greek, "small head". But in Pakistan, such children are known as chuas or "rat people". The name is uncharitable but apt, for their sloping foreheads and narrow faces do, indeed, have a rodent quality. When I visited the shrine earlier this year, I found only one chua, a 30-year-old woman called Nazia. Mentally disabled - I would judge her intelligence to be about that of a one- or two-year-old child - her nominal function is to guard the shoes that worshippers leave at its entrance, but that work seems to be mostly done by her companion, a charming hypopituitary dwarf called Nazir.
These days, most chuas are intinerant beggars. Travelling up and down the Grand Trunk Road, following a seasonal calender of religious festivals. Each chua is owned, or perhaps leased, by a minder, often a raffish, gypsy-like figure. The Chua-master looks after, and profits from, his chua rather as a peasant might a donkey; together, they may earn as much as 400 rupees per day, about £4. Most people I asked supposed that there are about 1,000 chuas in the Punjab, but no one really knows.
Where do they come from? There is, inevitably, a local myth to account for origins of the chuas. Infertile women, the story runs, come to the shrine to ask the saint to intercede on their behalf, to give them children. This he does, but only at a price: the first-born child would be a chua. That child has to be given back to the shrine where it would be raised, and live, as an acolyte. Should she fail to do so, all future children will be born chuas as well.
Nazia aside, the Pakistan government has banned microcephalics from the shrine. Yet women still go there to petition the saint. At least some of them still believe the myth. Educated Pakistanis know better. Dismissing the Curse of Shua Dulah as mere superstition, they have a better theory: that chuas aren't born, but made. Priests, chua-masters, or perhaps even parents, they say, purposefully deform healthy infants by placing pots or metal clamps on the heads of healthy infants and so retard the growth of the brain.
The Bonsai theory of microcephaly is at least 100 years old. In colonial times, British health officials fulminated against "this barbaric practice". Their concern has modern echoes. Every few years, some globetrotting reporter or public health official learns of the chuas and calls for their manufacture to be stamped out. While the sentiment may be admirable, its premise is almost certainly false.
There are several reasons for believing that microcephaly in the Punjab is not caused by clamping. The first is simply that no one, or at least no one I spoke to, seems to have actually seen it. The source of the allegation always seems to be an untraceable relation in an unreachable village. The second is that it is probably biologically impossible. The brain of an infant grows for the first nine years of life and the skull has gaps - sutures - to accommodate that growth. Should these sutures seal prematurely, as they do in certain rare genetic conditions, the result is not microcephaly but rather death, as the brain is forced through the hole at the base of the skull, so compressing the spinal cord.
But the strongest reason for dismissing the Bonsai account of microcephaly is that the disorder occurs among British Pakistanis as well. And they, it is quite clear, are not clamping their children.
In 1967, Pakistan dammed the Jhelum River that forms the frontier between Punjab and Kashmir. The resulting reservoir displaced thousands of peasants who were farming the river's flood plains. They emigrated: some went as far as Bradford and Leeds, where they formed the nucleus of one of Britain's largest Asian communities.
Microcephaly is a rare disorder in Britain. No one seems to know precisely how common it is in the Asian community of north England, but it was common enough to attract the attention of Geoff Woods, a geneticist working at Leeds University. He found that it ran in families. That implied that its cause was genetic; it was caused by a mutation. Or, more precisely, several. By the late 1990s, the disorder had been mapped to deficiencies in at least six different genes.
In the last few years, Woods and his collaborators have identified several of them. All seem to encode proteins that are needed if neuroblasts - the cells that give rise to the brain's neurons - are to divide and prosper. Should a child be born with an insufficiency of one of these proteins, the neuroblasts fail to divide. Or perhaps they divide slowly or die prematurely - the precise cellular defect is still obscure. In any event, the result is a brain that, in the extreme, grows to only one third of its normal size.
It is easy to see why peculiar theories of the origins of microcephaly have proliferated in Pakistan. To the untrained eye, the occurrence of the disorder is hard to explain. Healthy parents may have microcephalic children; microcephalic parents - there are a few - may have healthy children. To a geneticist, however, this merely speaks of recessive mutations. A child will only have microcephaly if it has inherited two copies of the mutant gene, one from each parent who are its carriers. Disorders caused by recessive mutations are normally rather rare. But not in Lahore; nor in Leeds. That's because of the Pakistani way of marriage. Most of us marry people quite distantly related to ourselves and, as we travel ever further, our mates become ever more genetically remote. In Pakistan, however, some 60 per cent of marriages are between first cousins; the frequency in Bradford and Leeds is thought to be comparable. The result is that clinical genetics units serving the British Pakistani community see a range and frequency of genetic disorders unknown elsewhere in the country.
The discovery of the microcephaly genes was important. It instantly told us something about how the human brain grows. But the true beauty of this work is that it has told something even more profound: how the human brain has evolved.
In the last three million or so years, the human brain has approximately trebled in size. This change, remarkable in its extent and speed, must have been caused by mutations - advantageous mutations - that swept through the populations of our ancestors as they wandered, generation after generation, across the African veldt. That such mutations must exist has long been obvious. The problem has been how to find them.
One way to do this is to compare our genome with that of our nearest relative, the chimpanzee. That's now easily done. The chimp genome was sequenced in 2005. To find the genes that matter to human evolution (the genes that make us different from an ape, that make us human) it should be just a matter of lining the two genomes up side-by-side and looking for the differences.
But genomes are vast. Chimps and humans each have about three billion nucleotides in their genomes - 99 per cent of those may be identical, but that still leaves about 30 million differences. Most of those are unimportant, the background noise of genomic evolution. But some matter: which?
Therein lies the importance of microcephaly. The discovery of genes that control the growth of the brain immediately suggested that these genes might also have changed in the last six million years since we last shared an ancestor with chimps. And so it proved: of the four microcephaly genes that have been found, three bear the hallmarks of rapid evolution. To be sure, chimps have versions of these genes, but the human version is different. So different, in fact, that their evolution must have been driven by natural selection.
It is hard to understate the beauty of this result. Ever since Aristotle, philosophers have wondered: what makes us different from the beasts? What makes us human? The answers that they have supplied: that man is a political animal, a thinking animal, a naked animal, a tool-making, tool-using animal - answers that, for all the aphoristic pleasure they provide, are essentially meaningless if not blatantly false, can now be discarded.
Now, when we ask: "What makes us human?" we can answer: this gene and that one... and that one. We can write the recipe for making a human being. Or, at least, we can begin to.
There is bittersweet irony in the discovery that the genes underlying a disorder as disabling as microcephaly should have also been responsible for the thing that we, as a species, are most proud of: our brains. Yet for all intellectual fascination of these discoveries, we should not neglect one more thing that they have given us: a way to meliorate the disease that pointed to their discovery.
Microcephaly cannot be cured. But it can now be prevented. Now that some of the mutations have been found, parents from families with a history of the disorder can have their newly conceived embryos tested. If the embryo has two copies of the mutation, it can be aborted.
Some will find this application of genetics, now routinely used in Britain to prevent many inherited disorders, repugnant. I am not among them. In Lahore, I met a middle-class family with two microcephalic children. Their mother, a woman who loved her disabled children passionately, spoke of her joy when just such a genetic test - the first in Pakistan - enabled her to give birth to a healthy girl.
It is easy to see why. The care that Pakistan provides for the mentally disabled is negligible. "What," said Rubina, speaking of her microcephalic children, "will happen to them when I am gone?" "Who will look after them?" "They will become" - she could barely say the word - "chuas". She wept; we filmed her; I did not know what to say. Dr Armand Leroi, of Imperial College London, examines 'What Makes Us Human?' on Channel 4 (Aug. 12 and 19, 8pm).