In whose interest?

Scientists are moving inexorably to human cloning. Colin Tudge fears we are ill-prepared
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The Independent Online
EDINBURGH scientists have produced a clone of sheep identical down to the last gene - only two young ewes, so far, but with promise of battalions to follow: as many as anyone cares to order. Talk of monsters, the creation of a caste of slaves and the redundancy of the male sex - all mooted in national newspapers this past few days - does seem a touch over-imaginative. But this is heady stuff and we have to ask: "Is this good or is it bad?"

Leaving aside all talk of blasphemy and hubris (which apply in principle to all serious biological interventions) the answer is: "It depends what the research is used for." We can certainly envisage some good uses, for work as fundamental as this must spill over into all aspects of cell biology, which effectively means all medicine. It will also help us to produce genetically engineered ("transformed") animals more easily, and some such transformations are worthwhile. But the people most likely to finance such work in the long run, and to benefit from it, will be motivated simply by cash, producing meat and milk for rich societies that have too much already and, we can be sure, without regard for the welfare of the animals. In a few decades, too, extrapolations from this line of work will enable the richest among us to re-create facsimiles of themselves, for no better reason than their own self-importance. As so often, then: the science is wonderful, the potential is great, but it's a shame about the reality.

Cloning per se dates from the 1980s, when it proved possible to divide the embryos of sheep at the two, four, or even the eight-celled stage and grow an entire new animal from each of the daughter cells - each genetically identical to all the others and all collectively forming a clone. But, for two reasons, the size of clones produced in this way was strictly limited.

First, as the cells divide they lose the quality of totipotency - the ability to give rise to all the different tissues needed to produce an entire organism. For as the embryo cells divide they also start to differentiate, which means they begin to "decide" whether they are to become skin or muscle or gut or whatever: and as differentiation progresses so groups of genes are switched off, permanently, limiting the cell's versatility. Cells that are fully differentiated - like the skin, muscle, or gut cells of a mature animal - cannot be persuaded to form an entire individual. They still contain copies of all the genes that were initially present in the one-cell embryo; but once they have differentiated, most of the genes needed in development are irrevocably suppressed.

Then again, embryos that are split and split again quickly run out of steam. The first cell divisions occur before the embryo starts to grow, so the individual daughter cells become smaller and smaller. At least, the daughter nuclei, which contain the DNA of the genes, stay the same size in each succeeding generation; but the cytoplasm that surrounds each nucleus becomes more and more meagre.

The cells in an eight-cell sheep embryo retain their totipotency - each could still become a whole foetus. But they barely have enough cytoplasm to carry them through, however well they are nurtured. So although it is theoretically possible to produce identical sheep octuplets just by splitting the embryo, no one in practice has got above quins.

The new work, by Keith Campbell and his colleagues at the Roslin Institute, addresses both these problems, and opens whole new possibilities. First, the Edinburgh scientists have been able to maintain sheep embryo cells in culture, and induce them to multiply, without sacrificing their totipotency. Thus, in principle, they can produce not just eight but hundreds, or thousands, or a billion identical and still totipotent cells.

But such culturing alone is not enough. For cytoplasm is not just a nourishing jelly. It is highly organised, active stuff in perpetual dialogue with the nucleus. In the very young embryo the cytoplasm takes the lead, orchestrating the first cell divisions. When the new embryo is implanted in the womb the cytoplasm signals to the mother that all is well; that this hopeful ball of cells is not a speck of dust to be extruded.

But after culturing, the cytoplasm is no longer able to carry out all the functions appropriate to an early embryo. To make them acceptable to a foster mother and exploit their totipotency, nuclei from the cultured cells have to be fitted with new cytoplasm. This, too, has been done at Edinburgh; each cultured nucleus is introduced into a sheep ovum, whose own nucleus has been removed. The result behaves like an embryo and can be implanted into a foster mother. So far only two live lambs have been produced. But the remaining technical problems will surely be overcome. In principle, the identical twins produced from cultured embryonic cells might be a flock of any size.

So how will this research be applied? The work is brilliant, for it deals with issues at the core of modern biology. How are cells switched on and off? Is the suppression that accompanies differentiation really irrevocable? After all, many cells in many creatures do seem able to regenerate whole ranges of tissues after they seem differentiated. Lizards replace severed tails; whole plants may be generated from single cells. Why do their cells differ from ours? What is the nature of the signals that pass between nucleus and cytoplasm? There can hardly be a field of medicine or of any theoretical biology that could not benefit from such explorations.

More immediately, such cloning makes it possible to produce entire regiments of creatures that have been transformed by genetic engineering. Sheep fitted with human genes that produce the "factors" which promote blood clotting express those factors in their milk, and so provide a safe (notably HIV-free) agent for treating haemophiliacs. The initial engineering is difficult, however, and it would be a great advantage to do this just once, and then clone the most successfully transformed animal.

The problem is that we live in an age when science is applied according to the "customer-consumer" principle. What happens is what the rich and powerful want to happen. And animals are not transformed solely to solve the urgent problems of medicine. Cattle are being fitted with extra genes for growth hormone so they will provide more milk. Sober, highly paid executives talk of producing chickens with nerveless beaks, so their beaks can be painlessly cut off and they can no longer peck their cage-mates when packed in batteries. Many farm animals suffer already from over-breeding: too much flesh held up by too little bone; far more milk than any creature can produce without suffering. It is easy to see how genetic transformations on the grand scale could make this worse, and much less easy to see how they could make them better.

There is a political dimension, too. In both the rich world and the poor, farmers are increasingly obliged to grow only what big business demands, for this is the logic of "vertical integration". The more hi-tech the crops and the livestock become, the harder it is for anyone to break free.

There are still more fundamental implications. The Edinburgh work is nibbling at the edges of totipotency; producing whole organisms from sets of genes that have already taken some steps towards differentiation. Why, with further development, should we not produce whole organisms from adult flesh? As Davor Solter of the Max Planck Institute in Freiburg comments in Nature: "Cloning animals from adult cells ... can no longer be considered impossible."

Does this matter? Well, the Catholic church already objects to the waste of embryos occasioned by in vitro fertilisation, and it will be interesting to see what it says when any farm-worker's severed finger could populate an entire continent. More to the point, however, is that whatever becomes possible is liable, sooner or later, to be done. Tom Wilkie pointed out in Thursday's Independent that "cloning humans is illegal in Britain" - but so what? Not every doctor in the world feels the sense of vocation still common in Britain. Many elsewhere are in it simply for the money; and we can easily envisage medical entrepreneurs offering to provide tycoons and tyrants and faded femmes fatales precise facsimiles of themselves - or a half a dozen - in exchange for, say, pounds 1m. Just a quick, painless biopsy and no questions asked; a little work in a fairly ordinary lab; an infection-free Colombian girl to take the foetus to term for, say, pounds 1,000 (though pounds 50 might do the trick in some countries). And Bob's your uncle: Horace B Bonegrinder or Glanda Dolores Mammal live again.

But that is only the start: after that you can let your imagination roll. Is this scaremongering? Not in an age when scientists are encouraged to seek funds from whoever is able to pay; or in an age when the highest of technologies rapidly become available as off-the-shelf kits. Does it matter? Well, doesn't it?

The writer is a Visiting Research Fellow at the Centre for Philosophy of the London School of Economics.

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