Genetic engineering: way forward for medical science or sinister threat to all our futures?

THE phrase, a chip off the old block, takes on fresh meaning following the announcement this week that scientists in Scotland…

THE phrase, a chip off the old block, takes on fresh meaning following the announcement this week that scientists in Scotland have managed to clone a lamb. Some commentators warn however that it pushes scientific research into dangerous new territory.

British physicist and Nobel laureate Joseph Rotblat warned that the technology represented a threat to mankind's future. He campaigned for years against nuclear weapons and argued on BBC yesterday that developments in science had the power to "determine the whole fate of mankind".

"My worry is that other advances in science may result in other means of mass destruction, maybe more readily available even than nuclear weapons. Genetic engineering is quite a possible area because of these dreadful developments that are taking place there," he said.

Yet the research team at the Roslin Institute near Edinburgh where the groundbreaking work was accomplished have repeatedly pointed out the potential of the technology: the creation of animals that can produce lifesaving human blood products, that can be used to study genetic disorders and that can provide agents to fight disease.

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Like nuclear power, the technology has the potential to serve or to punish, depending on how it is applied. As one Dublin researcher who asked not to be named, pointed out: "A definite barrier has been crossed and society will have to look at it. I think a lot of our thinking will have to be reassessed."

What Dr Ian Wilmut and his colleagues at Roslin achieved is remarkable science by any standard. They managed to bring not one but eight live lambs into the world, cloned from three different cell types and without the contribution of a father.

Cloning is not as nature intended. Most plants and animals use sexual reproduction to produce offspring. In this case mother and father have an equal share in the genetic make-up of the progeny, each contributing half of the genetic blueprint contained in its DNA. Subtle variations in the way the DNA combines cause variations in resultant siblings, which although related may look quite different.

With cloning, an exact duplicate of the DNA taken from the donor is used to produce the "offspring", and so it will be a genetic carbon copy.

It should grow to look exactly like the "parent", although some variation might be expected because it won't have eaten the same food, experienced the same weather or lived through a duplicate life experience of the donor.

While cloning is now commonplace in plant research, where a single leaf can be processed into thousands of genetic duplicates, it had never been achieved in animals. Researchers had managed to grow tadpole clones in earlier experiments but they failed to produce viable adults. This is why the delivery of the lamb Dolly caused such a sensation.

The Roslin group used tissue taken from the udder of a six-year-old sheep, growing the tissues in culture in the lab. They then took the nucleus - which contains a full copy of the sheep's DNA blueprint - out of a single udder cell.

Separately, they had taken a single unfertilised egg cell from another sheep. They removed the nucleus from this cell, replacing it with the nucleus from the udder cell.

This new combination was then allowed to grow and divide before being placed in a third surrogate sheep which would carry the developing foetus to full term. The result was Dolly.

THIS simple explanation belies the enormous complexity of what the Roslin group achieved. They found that the egg cell and its foreign nucleus would grow only if the two cells were harvested at just the right time. Their technique involved cell and embryo culture - the keeping of cells alive in the test tube before return to the surrogate mother.

Most remarkable in a technical sense was what took place within the modified egg cell itself. The udder cell has only one purpose, to be an udder cell. Even though its nucleus contains a complete copy of the sheep's entire DNA blueprint, it uses only what it needs to live life as an udder cell. Cells which exhibit only their intended purpose, for example as skin or liver or udder tissues, are said to be differentiated.

But when the differentiated cell was placed within the egg it lost its differentiation and became what the researchers called "quiescent". It stopped being an udder cell and yielded up its DNA blueprint, allowing the cell to begin dividing and growing as if from a sexual conception.

This proved one key theory in genetics - that the DNA in differentiated cells is not irreversibly modified as the sheep grows. Theorists were uncertain whether the DNA changed during embryonic growth and development - which would have meant that the cloning of a creature as complex as a sheep could probably not be achieved.

Dolly has fellow clones living in Scotland but no actual copies. The Roslin group in separate experiments used cells taken from a nine-day-old sheep embryo and a 26-day-old foetus. Only 62 per cent of foetuses survived, three from embryo and four from foetal tissues. Only Dolly, of 13 udder tissue pregnancies, survived to birth and one of the eight cloned lambs died soon after birth. All others survived.

Is it something scientists will rush to apply in a human context? Most definitely No, according to most commentators.

"NOW we are even more certain it can't be done in humans," stated Prof David McConnell, head of the genetics department at Trinity College. "The general view of scientists and doctors is this should not be expanded to humans. There is no reason scientifically to do it in humans," he said.

It was no surprise that the work was accomplished at Roslin, he said, because it combines animal and genetic research and receives significant state funding. "It is a great credit to the people there. It shows what can be done if a research facility is set up and properly maintained."

He believes that while human cloning is pointless, the new technology would have great potential in the preparation of human drugs and blood products derived from genetically modified and cloned animals. The blood clotting component Factor 8, for example, has been expressed in sheep's milk, and other human proteins such as a protein that encourages red blood cell growth, could be produced in cloned animals.

Dr Jim Ryan, chief executive of BioResearch Ireland, which supports research in biotechnology, agreed it should have no direct application in human research and believes it is too expensive and complicated for use in animal breeding. "There is no particular advantage in reproducing animals using this complicated technology when you can use conventional breeding," he said. The only exception might be in cloning "elite" high value animals such as genetically modified animals used to produce human pharmaceuticals.

Dick Ahlstrom

Dick Ahlstrom

Dick Ahlstrom, a contributor to The Irish Times, is the newspaper's former Science Editor.