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Science: When is a leg not a wing?

Experiments have identified genes that confer `legness', and it is very exciting

Lewis Wolpert
Thursday 17 June 1999 23:02 BST
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"THE ULTIMATE Frankenstein bird has been created in the laboratory". So crowed the Daily Express recently beneath the headline: "Now scientists serve up the 3-legged hen", reporting hostility to the experiment from animal welfare campaigners, who said the research was an adult version of a child pulling the wings off insects.

Such articles give undue prominence to pressure groups and do little to advance the relationship between scientists and public. But then, that is not the aim of the tabloids - they know that genetic pornography that titillates and shocks, sells papers. You can imagine their headline 60 years ago - "Dracula doctors do their bloody worst" - when blood transfusion was at last being successfully carried out. Does not taking blood from one person and putting it into another amount to playing God in a truly dangerous manner?

The limb experiment is unlikely to make a contribution to human health on the scale that blood transfusion has, but it tries to understand some basic biology, namely how we develop from a single cell, the fertilised egg.

There are undoubtedly those among the pressure groups hostile to science who think that this is both unnecessary and dangerous. But those who wish to censor and stop such activities should come out and say so, and not shriek from behind a wall of high moral virtue from which they attack scientific advances with spurious arguments.

The vertebrate limb has long been a good model for studying pattern formation in the developing embryo. While the embryo generates lots of different cell types, such as blood, nerves and bone, it is how these are organised in space that makes us human beings, rather than hippopotamuses or chimpanzees. The limb has the advantage that its pattern is quite simple to observe in the early stages, the main feature being cartilaginous elements such as the humerus and the digits. Moreover, in the early chick embryo it is possible to manipulate the limb's development and see the effects long before the time of hatching - at least a week.

One of the ways pattern can be specified is by the cells knowing where they are in the limb and then developing in the right way; they have positional information, plus a set of instructions in the genes on how to interpret their position in terms of cell behaviours. The cells acquire positional identity as the limb grows out, and it has been found that the signals that give the cells their positional information as the limb develops are the same in the arm/ wing, as they are in the leg. So why is the wing so different from the leg?

The recent experiments have identified genes that confer "legness", and this is very exciting for all those working in this general area. One of these genes goes by the unhelpful name of Pitx (it was originally discovered in relation to the development of the pituitary gland). Using a special virus as a carrier, workers at Harvard expressed Pitx in the developing wing. The result was striking - instead of wing digits, structures much more like toes developed. It is an important step in our understanding of how organs develop, though there is still a long way to go. But since as many as 5 per cent of children are born with some sort of abnormality, it could play a significant role.

And why is Pitx on in the leg and not the wing? That is another story, for another time.

The writer is professor of biology as applied to medicine at University College London

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