Innovation in genetics now racing far ahead of ethics

THE year is 2050, and the genetic technologies have wrought wonderful changes for humanity.

Cures for cancer and most inherited diseases have been achieved and heart, liver and kidney transplants are available on demand using organs grown in laboratories.

Almost uncontrolled population growth, however, has helped foster outbreaks of untreatable viral infections particularly in the Third World - which resist all forms of antibiotics. Some commentators blame accidental release of genetically engineered viruses for these new 21st-century plagues.

Crop production meanwhile has trebled in the First World with wheat, maize and vegetable yields boosted by genetic enhancement. Some genetic experiments have not gone so well, however. A genetically modified barley variety unexpectedly caused a gene transfer to a common wild grass, rendering it resistant to any known variety of weed killer. Up to 40 million hectares - of arable land worldwide have been rendered unusable and the weed continues to spread.

Novel bacteria were engineered, enabling them to clean up soils polluted by oil spills. They have mutated, however, and can now survive without oxygen deep underground. They have been detected in great numbers in oil-producing areas and now threaten dwindling world supplies of this precious commodity.

Even worse, an unauthorised laboratory conducting experiments on brown rats has caused a potential environmental catastrophe. The rats carried a range of modified genes giving them resistance to the current generation of poisons. The hybrids managed to escape into the sewers and may now be breeding with natural rat populations.

FICTION? Maybe, but are these examples as fanciful as they seem? Not on the basis of where scientists themselves believe the genetic technologies are taking us. The creation and use of genetically modified organisms (GMOs) are now routine in many industries.

Interferon, for example, a drug used in cancer treatment, is produced here at a plant which uses modified yeasts to provide this valuable product. Most insulin used by diabetics to keep their condition under control, is also produced in this way.

All genetic technologies are based on the manipulation of the genetic blueprint of an organism. This blueprint, known as DNA, is found in the nucleus of all living things from the simplest single celled amoeba or bacteria to humankind.

At this stage, many aspects of genetic technology are old hat, for example using bacteria or yeasts to produce insulin, penicillin or interferon. To oversimplify, researchers first locate a chemical of interest produced by an organism and then establish the DNA sequence that causes that chemical to be produced.

The sequence is sometimes copied by machine or can be "clipped" from original DNA. Next follows the tricky process of causing the receiving organism to "accept" the foreign DNA sequence as one of its own. But if the DNA element is successfully transplanted, the organism will begin to reproduce the chemical faithfully.

Add two decades of research into manipulation of plant, animal and human DNA and you reach Dolly the cloned sheep. Until Dolly, researchers were only recombining DNA elements by adding or taking away from an organism's genetic blueprint.

It had been theorised from the earliest days, however, that it should be possible to take the DNA from a complete, adult organism, extract the DNA from a single cell - which like all cells would have a complete DNA copy - and then use this to "grow" an exact replica of the original organism.

Cloning research using mice and frogs had failed, but the team from the Roslin Institute in Scotland made cloning a reality using three types of sheep cells including those from a six-year-old adult. And at a press conference earlier this week, one of the researchers, Dr Ian Wilmut, acknowledged - that it should be possible - again in theory - to clone any mammal, including humans,

From the earliest days GMO technology has always tended to gallop ahead faster than the ethical considerations of such experimentation or discussions on any legislation to control the research activity. The cloning success has again reminded policy makers that there are issues to be addressed which must be addressed soon. The future of genetic technology has already arrived with the birth of Dolly.

Ironically, most scientists who strongly support the importance and value of genetic technology research see little value in the cloning of organisms. "With cloning you close the genetic box," explains Dr Eamonn Kelly of the department of veterinary medicine at University College Dublin.

Clones become genetically outdated very quickly, he argues. "Natural methods will always win. Each time you would create the optimal animal, nature is working on the basis of mutation, creating new (genetic combinations) which can bring improvements."

Dolly might also become old before her time, he says. It is known that the ageing process involves the loss of certain DNA elements which simply disappear from the "genome", or complete DNA sequence. Dolly's DNA was taken from a six-year-old animal, so is she six months old (her physical age) or six years old (her genetic age)?

While controlled natural breeding will remain central to the improvement of livestock, Dr Kelly can foresee a time when a designer animal might be put together as a mosaic of useful traits in an "assembly line genotype".

In the future, researchers will map the genome of, say, a valuable bull. This map will tell them where to find desirable traits. It should then be possible to patch together genome elements to produce the "ultimate" bull.

THE notion of growing human organs is not entirely fanciful, suggests Prof Marlin Clynes, director of the National Cell and Tissue Culture Centre at Dublin City University. It may be possible to extend current cell culture techniques into the growth of "artificial" organs, he says, possibly grown on from donations taken from the patient.

Even if full organs cannot be grown it may be possible to grow cell cultures that can perform - at least in part - like the organs they imitate. For example, a culture of pancreatic cells might be able to produce at least some of the insulin needed by a diabetic.

Dr Dan Bradley of the department of genetics at Trinity College is using DNA in an entirely different way, to profile populations in a form of "genetic anthropology". He and colleagues published ground-breaking work after genetically "fingerprinting" cattle to establish their genetic history, establishing kinship between types of cattle by comparing similarity of DNA.

The group offered compelling evidence that there were probably two distinct and geographically separated domestications of cattle by prehistoric humans. And similar work could be applied to human population studies to establish, for example, the origins of the "native" Irish.

The Irish describe themselves as a Celtic nation, but archaeological evidence shows that there was an extensive farming community here long before the Celts arrived. Such a study might in the future tell us where these people came from and - whether Irish DNA today is more like these ancient peoples or more like fellow Cells in Brittany, Wales and Scotland.

Prof Michael Ryan, head of UCD's department of pharmacology, predicts many important advances in human health arising from the genetic technologies. Much will flow from the world-wide co-operative effort to map the human genomc, a project which should be completed within a decade.

The vast "map" would actually exist on computer, and researchers could use powerful future systems to search through the 2,000 million ladder rungs of our DNA for small specific sequences.

Genetic technology is being used to develop highly sensitive tests for diseases at the National Diagnostic Centre at University College Galway. Its manager, Dr Terry Smith, predicts the use of rapid tests to detect disease long before symptoms appear.

Such a test would look for traces of foreign DNA indicating the presence of an infectious agent. They would also require very small samples, reducing the invasiveness of diagnosis.

THE ethical issues associated with plant genetics are far less complicated, so much research is under way in this area. Plants could be used to produce human vaccines, and are already being used in this way to vaccinate mink against a common virus.

DNA to produce the vaccine has been transplanted into a bean variety by a research group in Denmark, so in the future simply eating your greens might mean protection against common ailments.

Researchers are using genetics to develop plants that do not need artificial fertilisers or pesticides to keep them healthy, Dr Barry Kiely, general manager at the National Food Biotechnology Centre at University College Cork explained.

Environmentalists see no brave new world coming from these technologies. Ms Paula Giles, agriculture and food spokeswoman for the Green Party, points to the possibility that genetic diversity will be lost by overdeveloping plant varieties. She also warns of unexpected effects following release of genetically manipulated plants.

Will human cloning be a technology for the future? Current thinking across the board suggests it will not. But if it was pursued, what would be the result? Would it be appropriate to clone ourselves at birth in order to have a supply of spare parts should disease or accident bring about the need?

The closest equivalent we have to clones is identical twins. Anyone who knows a set of twins will immediately attest to the differences between them, either slight variations in appearance or differences in personality. One is usually more forward than the other.

We still know too little about the human genome to understand why these variations occur, but we know that they do. A human clone would have identical DNA but it would be impossible to achieve an identical life, environment and response to external influences. What if one caught colds and the other didn't? Would it have an effect 10 years on?

At the end of the day, a person wanting to have a clone on hand for spare body parts might come under scrutiny from the clone. What if it was the clone that wanted the liver or heart transplant?