Wednesday, June 18, 2008

A genetic gamble?

Be it for medical or industrial ends, advances in DNA therapy have taken age-old principles of selective breeding into new, controversial territories
Filipino children eat rice, a staple crop that is under pressure across the developing world

"Golden rice" is genetically engineered to contain extra beta carotene, which the body needs to make vitamin A. Photograph: Romeo Gacad/AFP/Getty Images

Humans have been unwittingly altering the genetic makeup of animals and plants for thousands of years through selective breeding. But this process, which involves the natural exchange of thousands of genes in each crossing, is very slow and can only occur within a single species.

Genetic engineering allows this process to be accelerated by adding genetic material, very often from another species, directly into an organism's genome. A range of techniques are used to do this, which together are called recombinant DNA technology.

The first genetically modified organism (GMO), an E coli bug containing a salmonella gene, was created in 1973. GM technology is used to introduce pest, disease or herbicide resistance into crops or to make them better suited to harsh environments. The most common modifications seen in plants are those that make them tolerant to the herbicide glyphosate or ones that contain Bt toxin, an insecticide. A wide range of plants have been modified, including cotton, oilseed rape and tobacco.

Other modifications are used to increase the shelf life or food value of a plant. For instance, "golden rice" has additional betacarotene content, which the body needs to manufacture vitamin A. Researchers are currently developing GM bananas that would include a dose of hepatitis B vaccine, meaning that people in developing countries could be vaccinated without needles or the need for cold storage of vaccines.

The use of GMOs has been highly controversial. Concerns centre around four areas: ethical opposition to GM technology on principle, because it is seen as "playing God"; concern that there may be adverse, long-term consequences to environmental or human health; worries that GM technology rests in the hands of a few multinational companies; and, finally, issues of equity, with the cost of modified crops being beyond the reach of those who most need them. This latter concern has been heightened by the industrial development of a technology called Terminator. Yet to be commercialised, this technology effectively allows the production of GM crops that only yield sterile seed, thereby forcing the farmer to return to the company to buy more seed.

Labelling and proper separation of GM and non GM foods is a further difficulty.

In medicine, genetically modified bacteria are used to produce insulin. GMOs produce a wide range of pharmaceutical products, such as enzymes, hormones and vaccines, and GM is a basic tool in biological research. Transgenic animals, principally mice, are used to study responses to disease.

Gene therapy

Gene therapy uses genetically modified viruses to treat human disease. Viruses operate by inserting their own genetic material into that of their host. In gene therapy, this process is hijacked. Viruses, typically ones called adenoviruses, retroviruses or herpes simplex viruses are modified to carry the corrected gene of a faulty human one. Target cells, such as a patient's liver or lungs, are infected by the virus, which then unloads its genetic material (carrying the altered human gene) into the target cells. The cells that carry the altered genes then work normally.

The first recipient of gene therapy was a four-year-old girl, Ashanthi DeSilva, who had a rare immune disorder called SCID - known as the "bubble boy disease". Although this therapy was successful, the subsequent history of gene therapy has been fraught with difficulty and controversy.

Gene therapy came to a virtual halt in 1999, following the death of 18-year-old Jesse Gelsinger, who had a severe immune response to the virus carrier (the vector). In 2003, two of 10 children treated with gene therapy for SCID with a retrovirus vector developed a leukaemia-like condition.

Despite initial excitement, this technique has not yet delivered the goods. There are many problems, including trouble with the vectors themselves, the response of the recipient's immune system and the short-lived nature of the treatment, which means patients have to undergo multiple treatments.

But there have been successes. Recently doctors at Moorfields Eye Hospital

were able to treat a type of inherited childhood blindness caused by a single abnormal gene, restoring vision.

A totally new approach involves zinc finger proteins, which are proteins that bind with DNA. They can carry the DNA equivalent of scissors, which gives them the potential to detect and alter individual gene mutations.

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