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How a glowing monkey will help cure disease

Science Editor,Steve Connor
Friday 12 January 2001 01:00 GMT
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Andi, the first genetically modified monkey, was introduced to the world yesterday. Scientists said the GM primate could herald a revolution in the understanding and treatment of hitherto incurable human diseases.

Andi, the first genetically modified monkey, was introduced to the world yesterday. Scientists said the GM primate could herald a revolution in the understanding and treatment of hitherto incurable human diseases.

Andi, a rhesus macaque, was born last October after cutting-edge research successfully manipulated hisgenetic material to include a gene for a green fluorescent dye.

Scientists used the green dye gene, extracted from a jellyfish, as a marker to show "proof of principle" that monkeys can be genetically modified. They now intend to produce GM monkeys with genes added or taken away so they can emulate human diseases, such as breast cancer, Parkinson's or diabetes.

But the breakthrough has raised fresh ethical concerns about the direction of genetic research, with some leading scientists calling for further experiments to be subject to strict controls.

"Although medical benefits may result from producing GM monkeys, this sort of work must be subject to stringent monitoring of any harmful effects on the animals' welfare," said Professor Patrick Bateson, chairman of the Royal Society's working group on GM animals

Andi was the result of 224 separate attempts to modify the genes of unfertilised macaque eggs. The research produced 40 embryos and five pregnancies, but only one of the three live births was a GM baby. A set of GM macaque twins was stillborn.

In addition to understanding human diseases, GM monkeys could provide valuable insights into how human embryos grow in the womb and what can go wrong during this crucial stage of development.

Although many different species of animals, from rats and mice to sheep and goats, have been genetically modified, this is the first time that man's closest living relatives - the so-called non-human primates - have had their DNA successfully manipulated.

"Andi is frisky and plays normally with his two room mates," said Gerald Shatten, who led the research team from the Oregon Regional Primate Research Center in Beaverton, Oregon.

The extra green dye gene was added using an emasculated virus, designed to be non-infectious but still capable of inserting DNA into an unfertilised egg cell, says the research report published in the journal Science.

Professor Shatten says the same technique could be used to generate other laboratory animals carrying genes associated with medical conditions affecting humans.

"We could just as easily introduce, for example, an Alzheimer's gene to accelerate the development of a vaccine for that disease," Professor Shatten said.

"In this way we hope to bridge the scientific gap between transgenic mice and humans. We could also get better answers from fewer animals, while accelerating the discovery of cures through molecular medicine."

But some scientific ethicists have drawn the line at using primates for generating animal models of human diseases. "It's going a step to far," said Donald Bruce, director of the Church of Scotland's society, religion and technology project.

"Primates are closer to humans, have a higher degrees of sentience and consciousness and I think that justifies a higher degree of concern and respect for them," he added.

Andi - named after the reverse of Inserted DNA - has no visible effects of being genetically modified. But whenhe gets older his body might begin to produce the characteristic green fluorescent dye that was detected in the toenails and hair shafts of the stillborn twins.

His birth was an important step in proving that it is possible for man's closest living relatives to survive genetic manipulation prior to fertilisation. Further refinements of the technique might one day lead to calls for the genetic manipulation of human eggs, although few scientists believe there are sound medical reasons for allowing this.

Genetic modification of human eggs and sperm - so called "germline gene therapy" - is prohibited in Britain because of ethical concerns over the possible dangers to thefuture health of a baby andbecause of fears that it could lead to "designer babies".

John Clark, head of the genetics division at the Roslin Institute near Edinburgh, who pioneered the genetic modification of farmyard animals for medical research, said that although the birth of Andi made it technically more feasible to manipulate the DNA of human eggs or sperm, there was no justification for doing so.

"You can never say never but my views have not changed on this for 15 years," Dr Clark said. "But I wouldn't rule out it being done in another country, although it would be awful if it was done."

The Roslin Institute has pioneered the technique known as "pharming", where valuable human proteins used in medicine are produced in the milk of GM sheep or cows.

Several "pharmed" drugs are in the final stages of clinical trials, including a medicine for treating lung disease and cystic fibrosis produced in the milk of GM ewes. "GM has been an extremely powerful and incredibly rewarding technology for understanding basic science as well as for important medical applications," Dr Clark said. "But as you advance up the tree of sentient animals, you have to apply more stringent ethical and moral codes, especially when using primates," he added.

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