Living with bird flu

Elspeth Garman sits on the floor holding a fluffy pink pig in one hand and a plastic duck in the other. It's a routine that I suspect that she may have rehearsed before, for those struggling to grasp the complexities of the H5N1 virus.

You might suppose the sight of a leading Oxford University biochemist waving around a large cuddly toy to be faintly comic. But that would be to ignore the gravity of her subject and Dr Garman's skill at explaining the source of the deadly virus that has come to strike fear in millions from Scotland to Indonesia.

Bird flu now occupies a place in all our minds with the dull anxiety with which we followed events in the Far East, now transformed into real dread as we witness the impact of a single dead swan on a coastal area of Fife.

But if avian flu has become part of our lives over months, it has played a major part in Dr Garman's for more than 13 years.

Back in 1997, as the world came to terms with the first documented outbreak of human H5N1 infection in the Far East, which saw six deaths and Hong Kong's entire poultry population destroyed, Dr Garman already knew about the potential threat of a major flu pandemic. Five years ago, she published research showing the desperate need to stockpile antiviral drugs, the paper ending with the starkest of warnings: "Supplies of these drugs, at the moment, are woefully inadequate."

Since then she has become a familiar and authoritative voice in the struggle to understand and contain bird flu as it has inexorably spread across Asia to the western extremes of Europe.

Always her advice about the immediate priority for governments and scientists has been the same. "What we need is a very fast diagnostic test," she says.

The good news is that in Tamiflu and Relenza we have drugs to combat flu viruses.

But even if vast stockpiling ensured supplies were adequate in the event of millions of people clamouring for them at the onset of a UK pandemic, Dr Garman continues to stress that they only work in the first 48 hours after symptoms have developed.

She believes that local pharmacists could yet play a key role in distributing the anti-virals in the event of a flu pandemic, if a way could be found for patients to undergo an on-the-spot diagnostic test inside a chemist's shop.

While her comments at press briefings have been making headlines around the world only in recent months, Dr Garman's opinions on flu are based on ongoing research. It is a subject that has continued to fascinate and frustrate her in almost equal measure, as it has other scientists over generations. And with good reason.

For increasingly crowded conditions and rapid transportation in the modern world had made the chance of a serious viral epidemic like the 1918 Spanish influenza, which killed 40 million people before disappearing as mysteriously as it appeared, increasingly likely even before the public had heard of bird flu.

Much of Dr Garman's work has focused on understanding the workings of the part of the flu virus that is blocked by Tamiflu and Relenza. Yet she developed her flu fascination by chance. In fact she caught it from a famous Australian scientist on a research trip to Russia in search of a slot on their space station.

Dr Garman began her working life as a teacher in a secondary school in Swaziland. After obtaining a B.Sc. in Physics at Durham University, she arrived at Oxford University in 1980 to study for a doctorate in experimental nuclear physics. Initially, it appeared that she was destined to become a nuclear physicist, after working as a research officer for seven years in Oxford University's Nuclear Physics Department.

In 1987, she moved a short distance across the university science area to the Laboratory of Molecular Biophysics, where she turned her attention to protein crystallography.

She is married to the Oxford scientist Dr John Barnett. Their Oxfordshire home contains the old mechanical telephone exchange from the Oxford Playhouse. They acquired it when the theatre was being renovated and it allowed the exceptionally busy couple to have bakelite telephones in every room.

Initially, she was involved in the UK's early scientific efforts to develop anti-HIV drugs and, in 1989, in a bid to overcome a major technical difficulty, she was sent to Moscow.

Her unusual mission was to ask the Russians if protein from Oxford could go into space on the Soviet space station. But the trip was to see her enter the intriguing orbit of the flu virus.

Dr Garman explained: "The team in Oxford, led by the well-known scientist David Stuart, had spent two years trying without success to grow crystals from HIV1, which cause Aids. We had been experiencing problems growing them and we decided to turn to the Russians for help.

"The Russians had previously sent protein from the flu virus up on the MIR space station for three months to see if they could get better crystals in zero gravity conditions than could be grown on Earth. So I went with my colleague, Dave Stammers, to see if some of our protein could go up to their space station."

One of the scientists she met in the Soviet Union was the Australian, Graeme Laver, who had important contacts in Russia. But he also happened to be one of the world's foremost authorities on flu, playing a key part in the major discovery that sea birds on the Great Barrier Reef are riddled with influenza viruses.

Over years, Dr Laver and his colleague, Robert Webster, had been telling scientists, politicians, regulatory agencies, the press and anyone else who would listen that it was only a matter of time before the world faced the next influenza pandemic. Later, despite widespread scepticism, they arranged a trip to a deserted coral island off the coast of Queensland and discovered birds that had flu virus antibodies.

While the Australian convinced her about the scale of the potential threat of a pandemic, as a scientist Dr Garman was also drawn by the challenge of taking on the flu virus itself.

The virus has the ability to dramatically change and appear in a completely new form. All the recent major shifts, which have occurred about every decade, have originated in China. In 1957, it was Asian flu, 1968 Hong Kong flu, 1977 Russian flu (which spread to the Soviet Union from China) and then, in 1997, as a highly lethal virus spread from chickens to people in Hong Kong. The antigens on the surface of the virus also continually change their structure, allowing it to easily outwit the human body's immune system. But until 1997 scientists had believed it to be impossible for flu to spread from bird to humans. They thought that bird and human flu viruses mixed in pigs to make new potentially lethal human strains.

Despite having just returned without sleep from an all-night experiment in Grenoble, she happily undertook to explain the virus's cunning with a variety of oddly-shaped building bricks to show its surface of protein spikes. The traditional approach to develop antiviral agents had been to test thousands of compounds chosen more or less at random. But the approach followed by flu researchers has been to study the detailed three-dimensional structure of the virus using X-ray crystallography and then design substances that will bind tightly to the active side of the flu enzyme.

Laver and Garman's work has contributed to the production of tailor-made drugs on which millions would depend in the event of a pandemic.

"The reason they are so good is that modern science has designed them to target viruses specifically. Tamiflu and Relenza stop the N part of the H5N1 virus from working."

She is soon explaining how N stands for neuraminidase and is shaped like a four-petalled flower on a stalk, which allow newly formed viruses to escape from infected cells to the rest of the body. Each petal apparently has a small pocket in the top and Tamiflu and Relenza are designed to snugly fit into the pocket to stop the neuraminidase doing its worse.

But time is everything and, because they stop the multiplication of the virus, to be most effective the drugs should be given in the first six to 12 hours after the symptoms develop, although they are still worth taking during the first 48 hours.

The UK has stockpiled enough Tamiflu for 15 million people, said Dr Garman. But the drugs are treatments, not vaccine, and although they can be used as prophylactics, are most useful to someone already infected. The big problem is to ensure supplies are not wasted on the 'worried well' and that drugs go to people with avian flu.

This explains Dr Garman's urgent desire to focus on finding a fast and easy diagnostic test available at the local chemists. She can already see it: "You could walk in and scrape your throat with a lollipop and it would turn bright green or bright red and the chemist could confirm whether or not you had flu."

With time running out, however, Dr Garman reports that the prize of such a high-tech lollipop is still beyond the grasp of scientists. While we are all focused on a dead swan in Scotland, it is a worrying fact that avian flu is unlikely to be defeated until it can be quickly diagnosed in people as well as birds.

Meanwhile, Dr Garman continues explaining the facts about Tamiful and Relenza to anyone prepared to listen.

A total of 35,000 chickens are being slaughtered this week in a farm in Norfolk after a strain of avian flu was discovered in the flock. The movement of all birds in and out of the farm has been stopped.

The strain is the less serious H7 type, though further tests are being carried out at Government laboratories.