A case of genetic manipulation

This week marks the 50th anniversary of the discovery of DNA's double helix

This week marks the 50th anniversary of the discovery of DNA's double helix. Dick Ahlstrom, Science Editor looks at the finding's impact.

FOR: In learning the secrets of DNA, we are learning the secrets of life itself. With this knowledge come discoveries in medicine, agriculture and new drugs.

Fifty years ago this week a brief report in the science journal, Nature, announced to the world that DNA, our genetic blueprint, takes the form of a double helix. This momentous discovery has transformed our understanding of the processes that control life.

It has opened up completely new ways of diagnosing and treating diseases. From it has come the ability to harness the molecular machinery of yeasts and bacteria for the production of drugs. The double helix has made cloning and genetically modified plants possible. It also helped solve some of the greatest biological mysteries.

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Few scientific findings can claim such a profound influence as James Watson and Francis Crick's explanation of the chemistry behind DNA's helical shape. "The event itself was an epoch-making discovery," says Prof John Atkins, director of biotechnology at Science Foundation Ireland, a body that channels State support for research into biotechnol-ogy and computer technology. "In 1,000 years time it will be seen to be as important as the start of the industrial revolution or the switch in early humans from hunter gatherer to agriculture. DNA itself is important but it also represents a molecular understanding of life," he says.

"Crick said they had discovered the secret of life and he was right," says Prof David McConnell of the Smurfit Institute of Genetics at Trinity College Dublin. "Life is distinguished by the fact that organisms replicate. Organisms replicate because the molecule DNA has the capacity to replicate. Watson and Crick discovered the structure of DNA in 1953 and its structure showed them how it replicated."

Shape is everything for the chemical substances in our cells, with shape usually dictating function. In the case of DNA, the molecule that carries our genes, understanding its shape immediately made clear how cells divide and divide, over and over, so successfully with so few genetic errors.

DNA has a form like a ladder that has been twisted into a helix, a shape like the wire that holds the pages of a notebook together. Exact copies of DNA are made when the ladder splits into two halves down the centre of each step. The two halves seek to renew themselves, automatically reassembling using building elements provided by the cell, and with each half of the ladder providing a template that guarantees a perfect copy.

Knowing the shape "suggests the mechanism of DNA's replication and readout," says Atkins. "Because of its stability it is the repository of nearly all of the genetic information."

Watson and Crick's starting point has led to a revolution in biological science. It created a new technological field - biotechnology - which is transforming medicine and agriculture. "It is virtually impossible to do anything in biology these days without looking into DNA and genetics," says McConnell. "It has had a huge impact on medicine because it has allowed us to explain disease in molecular terms."

How this all works can be seen in action at the National Centre for Medical Genetics, Our Lady's Hospital, Crumlin, Dublin. "It has made a huge difference to the treatment and management of families with genetic disorders," says the centre's director and professor of medical genetics at University College Dublin, Prof Andrew Green.

Testing at the centre can confirm if symptoms are caused by an inherited disease. It can also inform the decisions taken by parents considering subsequent children.

Our genes also have a part to play in our susceptibility or response to disease conditions, Prof Green says. "There are genetic components to many types of diseases," for example heart disease. This could make it possible to screen for high risk individuals on the basis of their genetic makeup.

Application of the genetic technologies is also making it possible to design drugs that target genetic components of a disease mechanism. A successful new drug against a form of leukaemia tackles the disease "based on our genetic understanding of why a disease occurs", says Green.

Advances in genetic engineering have led to a switch from the use by diabetics of life- saving pig insulin to much safer insulin produced by genetically engineered yeast. It has opened up new opportunities for medical diagnostics with rapid tests confirming the presence of say viral or bacterial DNA, as in the new test announced only last week for the emerging illness, Severe Acute Respiratory Syndrome (SARS).

The human genome project involved describing each of the billions of ladder steps in our DNA, information that provides an unprecedented view of our genetic makeup. Researchers believe it will soon be possible to tailor a drug therapy to the genetic environment of the individual patient.

Discoveries in the genetic technologies are also apparent in cancer research, says Atkins. They have allowed researchers to tackle the molecular basis of cancer. "This is not the needle in the haystack," with researchers reaching into the darkness of ignorance, he says. "The needles have been found", and research teams are finding more every day, he adds. This emerging technology is also important for the good of the State, says Matt Moran, director of the Irish BioIndustry Association.

Support for biotechnology research via Science Foundation Ireland and the Higher Education Authority's Programme for Research in Third Level Institutions is a key aspect of Government policy backed up with funding from the National Development Plan.

The Government view is that discoveries in biotechnology "offer potential discoveries in medicine, drug development and agriculture", says Moran. "From an Irish standpoint, we took the view five or six years ago that we had such strong agricultural, therapeutic, medical and food sectors that the next wave was going to be genetics and biotechnology. If we wanted to try to remain competitive we needed to start fairly significant investment."

Biotechnology and the genetic technologies have a profound impact on key sectors for the Republic including the pharmaceutical and food industries, he says.

"I think it is very important. Even if you take just pharmachem and food, that represents half our total exports," he says.

AGAINST: Many people have grave misgivings about our ability to tinker with the fundamental processes of life and fear the potential for hidden dangers.

Genetic engineering is not universally acclaimed as a way to cure disease and end world hunger. Many people fear there are risks that can't be foreseen and rightly point to the enormous ethical issues that have yet to be addressed with this technology.

Those expressing these concerns cannot all be dismissed as Luddites and religious conservatives. Some clearly are conscientious objectors, opposed to any application of genetic technology no matter what benefits might arise from safer drugs or improved crop yields. There are others who weigh up the issues carefully and still have doubts about the technology. They raise valid issues that require responses both from Government and from the scientific community.

One such opponent is Father Sean McDonagh, a theologian, anthropologist and author who spent 23 years as a missionary. His concerns about the genetic technologies were sharpened while serving as chairman of Greenpeace Ireland. He remains a member of VOICE, the group Greenpeace here later became.

He raises moral and ethical questions about a technology that gives us the potential to manipulate the genetic blueprint of any organism. "Does one species have the right to interfere with the genetic integrity of another species?" he asks. "There are ethical boundaries around species."

Many of his greatest worries relate to the potential for hidden risks that cannot be recognised andwhich could have dangerous consequences in the future. Genetically engineered foods or drugs may represent "a risk to human health which might not be known for a time". There is also the potential for risks to the environment given uncertainties about the use of this technology.

The proper response to this, he says, is the application of the "precautionary principle", which holds that no new technology should be applied outside the laboratory until it can be shown that the technology is safe. "If you don't know then don't do it," he says.

Scientists will argue that one can't prove a negative and those opposed to the technology will never be satisfied it is safe. Father McDonagh gives other reasons aside from health threats, however, about why he is unhappy with the technology.

A company involved in scientific research usually patents discoveries to protect profits. In the genetic technologies however, this means companies can patent life. "Genetically engineered plants are always patented," he says. "Fundamentally that gives control of food sources to six or seven trans-global corporations. I have grave problems with that. I am not against people making a profit, but I don't want to see private monopolies either."

He believes rapid application of engineered crops will severely reduce biodiversity, the range of the world's plant species. More than 80,000 rice species were grown in the past, but this is now down to 20 to 25 key species, he says. A superior rice engineered to survive drought, improve nutritional content or yield would reduce planted species still further, increasing the dangers inherent in monoculture such as disease attack.

Companies are also attempting to "steal" biodiversity from developing countries, hoping to patent useful discoveries for crops or drug development without recompense to the country where the plant was found. Such discoveries, he argues, are "the common heritage of all humankind" and should not belong to any one company. It also thwarts the aims of researchers, he adds. "This has a deleterious impact on scientific discovery."

He does not oppose patenting but patent procedures being applied to genetic discoveries were not designed for this use. "All I am against is bringing in patenting under a system that was designed for watches and machines."

Green Party MEP for Leinster, Nuala Ahern, echoes Father McDonagh's worries about human health and environmental risks. "We don't know to what extent modified foods or genetically engineered foods are safe," she says, and the rigorous testing used to prove a drug is safe for human use is not applied to modified foods.

"Drugs are carefully controlled, food isn't. You wouldn't know if there was an effect or not because you are not isolating people who have eaten the foods," she says. Leaving aside these questions, the application of genetically modified plant species represents a competitive loss for the State, she believes. "For Ireland this particular issue is key because we could be a GM free zone. It could be very retrograde in marketing quality food."

She also has problems with companies being able to claim rights over genetic discoveries. If a piece of DNA is used to develop a medical diagnostic test then the originating company has rights over this, but this may also prevent say a hospital laboratory from using a test because of costs.

An example of this is a breast cancer test created by US biotech company, Myriad. The test costs about $3,000 in the US but human rights and medical societies in several European countries and Canada are challenging Myriad's patent claims, which are based on its discovery of the BRCA1 gene's association with cancer.

Sen Mary Henry is a practising doctor and is broadly supportive of research into the genetic technologies because of the great promise it holds for medical diagnosis and new treatments. "It is going to mean we can look at diseases at a molecular level," she says. But, there are many areas of concern she says. "You can't be either all for or against it because some things are a marvellous breakthrough and others are less certain."

Testing for genetic disorders is one example, she believes. While it could be of great benefit for prospective parents to know if they could pass on inherited diseases to children, what should you do with the information? She cites Tay-Sachs disease, an invariably fatal disorder. "What is difficult about this is the child has a really difficult death two years after its birth," Sen Henry says. If the presence of the disease can be shown to exist in a developing embryo, what options should be available to the parents?

Experiments with stem cells from umbillical cords or embryos to cure diseases is another example. "Cord blood is absolutely excellent but I have my doubts about stem cells from human embryos," she says. "Society has a role in all of this. Our experimenters need someone to say, 'hold on'."