'older' in telomere terms than they would otherwise be. Tissues that are especially prone to cancer tend to be tissues that do a lot of cell division throughout life either for repair or for other reasons: skin, testis, breast, colon, stomach, white blood cells.
So we have a paradox. Shortened telomeres mean higher cancer risk, but telomerase, which keeps telomeres long, is necessary for a tumour. The resolution lies in the fact that the switching on of telomerase is one of the essential mutations that must occur if a cancer is to turn malignant. It is now fairly obvious why Geron's cloning of the telomerase gene caused its share price to rocket on the hopes of a general cure for cancer. Defeating telomerase would condemn tumours to suffer from the rapid advance of old age themselves.
C H R O M O S O M E 1 5
S e x
All women become like their mothers. That is their tragedy. No man does. That's his.
'La Monstrua vestida' and 'La Monstrua desnuda': the monster clothed and the monster naked. They show a grossly fat but very unmonstrous five-year-old girl called Eugenia Martinez Vallejo.
There is indeed clearly something wrong with her: she is obese, enormous for her age, has tiny hands and feet and strange-shaped eyes and mouth. She was probably exhibited as a freak at a circus.
With hindsight, it is plain that she shows all the classic signs of a rare inherited disease called Prader-Willi syndrome, in which children are born floppy and pale-skinned, refuse to suck at the breast but later eat till they almost burst, never apparently experiencing satiety, and so become obese. In one case, the parent of a Prader-Willi child found the child had consumed a pound of raw bacon in the back of a car while being driven back from the shop. People with this S E X 2 0 7
syndrome have small hands and feet, underdeveloped sex organs and they are also mildly mentally retarded. At times they throw spectacular temper tantrums, especially when refused food, but they also show what one doctor calls 'exceptional proficiency with jigsaw puzzles'.
Prader-Willi syndrome was first identified by Swiss doctors in 1956. It might have been just another rare genetic disease, of the kind I have repeatedly promised not to write about in this book because G E N E S A R E N O T T H E R E T O C A U S E D I S -
E A S E S . But there is something very odd about this particular gene.
In the 1980s doctors noticed that Prader-Willi syndrome sometimes occurs in the same families as a completely different, disease, a disease so different it might almost be called the opposite of Prader-Willi: Angelman's syndrome.
Harry Angelman was a doctor working in Warrington in Lanca-shire when he first realised that rare cases of what he called 'puppet children' were suffering from an inherited disease. In contrast to those with Prader-Willi syndrome, they are not floppy, but taut.
They are thin, hyperactive, insomniac, small-headed and long-jawed, and often stick out their large tongues. They move jerkily, like puppets, but have a happy disposition; they are perpetually smiling and are given to frequent paroxysms of laughter. But they never learn to speak and are severely mentally retarded. Angelman children are much rarer than Prader-Willi children, but they sometimes crop up in the same family tree.2
In both Prader-Willi and Angelman's syndrome it soon became clear that the same chunk of chromosome 15 was missing. The difference was that in Prader-Willi syndrome, the missing chunk was from the father's chromosome, whereas in Angelman's syndrome, the missing chunk was from the mother's chromosome.
Transmitted through a man, the disease manifests itself as Prader-Willi syndrome; transmitted through a woman it manifests itself as Angelman's syndrome.
These facts fly in the face of everything we have learnt about genes since Gregor Mendel. They seem to belie the digital nature 2 0 8 G E N O M E
of the genome and imply that a gene is not just a gene but carries with it some secret history of its origin. The gene 'remembers' which parent it came from because it is endowed at conception with a paternal or a maternal imprint — as if the gene from one parent were written in italic script. In every cell where the gene is active, the 'imprinted' version of the gene is switched on and the other version switched off. The body therefore expresses only the gene it inherited from the father (in the case of the Prader-Willi gene) or the mother (in the case of the Angelman gene). How this happens is still almost entirely obscure, though there is the beginning of an understanding. Why it happens is the subject of an extraordinary and daring evolutionary theory.
In the late 1980s, two groups of scientists, one in Philadelphia and one in Cambridge, made a surprising discovery. They tried to create a uniparental mouse — a mouse with only one parent. Since strict cloning from a body cell was then impossible in mice (post-Dolly, this is quickly changing), the Philadelphia team swapped the
'pronuclei' of two fertilised eggs. When an egg has been fertilised by a sperm, the sperm nucleus containing the chromosomes enters the egg but does not at first fuse with the egg nucleus: the two nuclei are known as 'pronuclei'. A clever scientist can sneak in with his pipette and suck out the sperm pronucleus, replacing it with the egg pronucleus from another egg — and vice versa. The result is two viable eggs, but one with, genetically speaking, two fathers and no mother and the other with two mothers and no father. The Cambridge team used a slightly different technique to reach the same result. But in both cases such embryos failed to develop properly and soon died in the womb.
In the two-mothers case, the embryo itself was properly organised, but it could not make a placenta with which to sustain itself. In the two-fathers case, the embryo grew a large and healthy placenta and most of the membranes that surround the foetus. But inside, where the embryo should be, there was a disorganised blob of cells with no discernible head.3
These results led to an extraordinary conclusion. Paternal genes, S E X 2 0 9
inherited from the father, are responsible for making the placenta; maternal genes, inherited from the mother, are responsible for making the greater part of the embryo, especially its head and brain.
Why should this be? Five years later, David Haig, then at Oxford, thought he knew the answer. He had begun to reinterpret the mammalian placenta, not as a maternal organ designed to give sustenance to the foetus, but more as a foetal organ designed to parasitise the maternal blood supply and brook no opposition in the process. He noted that the placenta literally bores its way into the mother's vessels, forcing them to dilate, and then proceeds to
