24 January 2004	Saturday	01 Zilhaj 1424

LONDON: Few revolutions happen without misplaced hopes - and the fledgling genetics revolution of the 1990s was no exception. If you believed the hype, as soon as scientists mastered how to handle genes , humanity would be able to take on nature at its own game.

The inevitable curses of untreatable disease and even ageing, could be tackled head on. And it would all be thanks to gene therapy, a technique that would replace your duff genes with good ones, making the damaged or decrepit all shiny and new.

Of course, it didn't quite turn out that way. More than a decade of gene therapy trials have so far failed to deliver. So what is going wrong? The first signs that gene therapy was going to be tougher than some scientists made out appeared shortly after trials in humans began.

In 1993, the US food and drug administration called a halt to one trial for patients with cystic fibrosis, a genetic disorder that leads to repeated and ultimately fatal lung infections. Rather than improve their condition, some of the patients developed inflamed lungs while on the trial. The setback was minor, though, compared with what was to come some years later.

In 1999, 18-year-old Jesse Gelsinger became the first person to die from gene therapy. Gelsinger suffered from a liver disorder that meant he was unable to break down ammonia, but the condition was hardly life-threatening - he was able to manage it by carefully controlling his diet.

The trial he signed up for at the University of Pennsylvania was designed to correct the disorder, but after receiving a high dose of the treatment, Gelsinger suffered a huge inflammatory reaction. His liver failed, followed swiftly by other organs.

Alarmingly, a subsequent investigation by the US national institutes of health, found that other researchers had failed to report complications in their own gene therapy trials. Gene therapy, which conceptually at least seemed an elegant and obvious way of treating conditions medicine had no other answer for, was in deep trouble.

It's unsurprising that gene therapy ran into immediate difficulties. At the time, most researchers used a technique that relied on a virus called an adenovirus to get copies of "good" genes into the cells where they were needed. The principle was simple: take a virus and strip out all the genetic material that makes it dangerous.

Then insert a gene or two that will fix the condition you are trying to treat. Next, inject a few million of these engineered virus particles into the body, where they do what viruses do best - invade your cells, hijack their genetic machinery and dupe them into churning out whatever proteins the virus's genetic material specifies. If all goes according to plan, the new proteins will cure the condition you are trying to treat.

So much for the principle. It turned out that adenoviruses were a bad choice. They are the cause of around a fifth of common colds. "We've spent millions of years evolving with these viruses and our immune systems are very good at spotting when we're infected with them," says gene therapy expert Steve Hyde of the University of Oxford in south-east England. It's no great mystery then that some patients on the trials suffered immune reactions.

The realization prompted scientists to change tack. Some looked for viruses that would not cause a significant immune reaction, while others opted for a different route altogether, wrapping genes in tiny parcels of fat that can attach to cells in the body and, with luck, force some of their genes into the cells.-Dawn/The Guardian News Service.