Wednesday, August 11, 2010

Genetic modification: glow-in-the-dark lifesavers or mutant freaks?

genetic-modified-piglets-glow
The genetically modified piglet glows in the dark as the result of jellyfish genes introduced into its cells at the University of Missouri. Photograph: Rex Features

At first glance, the creation of a chicken that glows in the dark seems a disturbing and unnecessary one. With a jellyfish gene inserted into its DNA, a hen modified this way acquires the power to fluoresce in a bright green hue when illuminated with blue light – an unsettling ability, to say the least. After all, who needs poultry that can shine a light on itself? More important, why go to the trouble of mixing the DNA of two such dissimilar creatures in the first place?

It is an important question that has recently been reflected in headlines that followed the release of Home Office figures which show there was a dramatic rise in the creation of genetically modified animals in laboratories in 2009. In total, 1.5m experiments on GM animals were carried out, a rise of 143,000 from the previous year. At the same time, there was a corresponding decrease in experiments on "natural" animals.

In other words, more and more scientists are now relying on the use of GM animals, as opposed to unmodified ones, for their research. But what gives the insertion of a piece of DNA from one living being into another such an advantage for scientists? After all, inserting invertebrate genes into mammals, and vice versa, is not easy. It also makes the public uncomfortable and raises the hackles of animal rights organisations. Yet it has become the standard route for researchers. Why?

Consider that glowing poultry. Fluorescent chickens were developed by scientists at Edinburgh University's Roslin Institute, the zoological research organisation responsible for the creation of Dolly the sheep. As we have noted, the technique involves putting jellyfish genes into the DNA of a chick so that it makes a green, fluorescent protein. "The protein itself does not affect the chicken in any way but it is a very useful tool for looking at the very early embryos," says Roslin researcher Professor Helen Sang.

The crucial point is that chicks are extremely useful for studying embryo development because their growth takes place inside an egg which can be kept in an incubator and studied fairly easily. By contrast, a mammal foetus gestates inside the uterus of its mother, making it far harder for researchers to monitor physiological changes. Thus the chick provides us with a key model for understanding the development of early embryos for all vertebrates, including humans. But the technique had been pushed to its limits by scientists – until the arrival of the GM mutant. This allows scientists to tinker with the way in which an embryo develops and so reveal processes that were previously obscured.

"You can take a sample of cells from a green embryo and then put them into a normal embryo," says Sang. "You can then watch and see what organ that group of cells develops into because that tissue will have a green fluorescence. For example, if this part of the chick embryo develops into stem cells, that tells us whether other animals, including humans, have stem cells in that part of their embryos and will therefore provide us with important basic biological insights." In other words, stem-cell science can get a boost from the glowing green chicken.

In fact, the chicken turns out to be a popular target for modification. Roslin scientists are also working on a strain that can express therapeutic proteins in the whites of eggs. In particular, they are working on whites in which the hen expresses antibodies that can block viruses which cause enteric – ie gut – diseases. Thus it may be possible one day to cook omelettes that could prevent us succumbing to disease, though most scientists envisage a slightly different route in which GM egg whites are dried out before their antibodies are removed and administered separately.

But what geneticists have not developed, insists Sang, is the featherless chicken, illustrated on the right. This animal is often held up as the ultimate GM horror, created so that farmers will be saved the effort of having to pluck feathers before poultry are sold to supermarkets. In fact, the partly featherless chicken is a species containing a natural mutation called naked neck which is becoming popular in hot countries, such as Israel, where the animals can be kept cool without a full feather covering .

Nevertheless, there are other criticisms of the use of GM animals, as the watchdog group GeneWatch has pointed out. Its director Helen Wallace says the rise in the use of GM animals reveals a disturbing trend: the "genetification" of biology. "There are undoubtedly some legitimate uses of GM animals but this blanket rise is worrying and bears little relation to reality," she says. Wallace points to the widespread creation of animals – mice in particular – that have been genetically altered so they succumb to human conditions such as obesity and cancer. These mutants are then used to test drugs that could counter these ailments in humans.

"The trouble with this approach is that it stresses the use of medical intervention for ailments that also have clear environmental causes," says Wallace. "Too much food and exposure to pollutants are also clear causes of cancer and obesity, but these are being ignored because of our obsession with genetics. In fact, in many conditions, genes have only a small role to play in the causation of the disease, yet we have become fixated on trying to tackle them, to the detriment of other, more fruitful approaches."

This point is acknowledged – partially – by genetic engineers. "We do concentrate a lot on genetic approaches to disease, but that is because we geneticists are only now catching up with other sciences," says Luke Alphey, head of Oxitec, an Oxford University spin-off genetics company. "For the first time, we have got the tools to do this sort of thing. And in any case, a disease is generally a combination of genetic and environmental causes. So the more we learn about genetic influences the more we will know about their environmental influences as well."

Alphey and his colleagues are working on techniques to prevent mosquitoes from spreading dengue fever, a severe, sometimes fatal viral illness that affects between 50 to 100 million people a year. "We have created a strain of genetically modified male mosquitoes of the Aedes aegypti species, the one responsible for spreading dengue fever," he says. "These males produce offspring that do not develop fully. So they block the appearance of new A. aegypti mosquitoes. Released into the wild, which we hope to do in a few years, these GM mosquitoes should eradicate A. aegypti populations and halt new dengue fever cases. If the technique works, we will have demonstrated just how powerful and useful this technology can be."

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