Sunday, January 15, 2006

News - Bird Flu: Death in the air

This is how the nightmare begins: a child plays with chickens in her yard and catches bird flu. She already has ordinary flu. The two mix inside her body, combining to produce a new virus that passes easily from human to human. It spreads fast. No existing vaccine is effective. Before long, millions of people are dead.

This is not a scare story. It is the scenario that three research scientists at a locked and sealed laboratory in north London expect to meet every day they go to work. Their high-security lab, hidden away in the unsuspecting suburb of Mill Hill, is suddenly on the front line of the global fight against bird flu.

Yesterday they were placed on high alert as it seemed the nightmare was about to become real. A Russian journalist had got off a flight from an infected area in Turkey and had gone straight to hospital with flu-like symptoms.

He was put in isolation; blood tests were taken and Mill Hill prepared for samples to arrive. Panic began to rise all over Europe. But then the Belgian health minister announced to a packed press conference that the test results had made doctors "100 per cent sure" their patient did not have bird flu after all. Panic over. For now.

If (or when, as the scientists say) the virus does make the change that would enable it to cause a pandemic and kill up to 150 million people worldwide, the British scientists will probably be the first to spot it. The faster they can do so, the more lives will be saved.
"We do have a great responsibility here," says their boss, Sir John Skehel. "Flu research requires that you accept that."

Alan Douglas is one of the scientists, a 54-year-old research associate who last week became the first person to isolate and grow the strain that had killed three children in a village in Turkey. He and his colleagues at the World Influenza Centre worked flat out on their samples for days. They knew people were dying, but that their results would tell doctors which drugs to use against the virus.

They were also looking for evidence of the big change that the world dreads. Two days ago the World Health Organisation announced that the H5N1 virus found in the body of a 14-year-old boy from a village in Turkey had mutated. The protein spikes on its surface had changed and it was now more attracted to people than birds. This was not the nightmare scenario, insisted Sir John Skehel, but it was "one step along the way".

He is director of the National Institute for Medical Research at Mill Hill, which contains the World Influenza Centre on its 50-acre site. The centre is one of four labs that receive samples from new victims of bird flu - but as the others are in America, Japan and Australia, it is London that will test the European outbreaks first. Few outsiders ever see the lab, but last week The Independent on Sunday was given unprecedented access.

The head of the centre, Dr Alan Hay, cut short a holiday when he heard the news of an outbreak in the Van region of Turkey. The other scientists cancelled days off as samples from the dead boy and his sister were flown to London, a week ago last Thursday. They were driven to Mill Hill from the airport in a car with Turkish diplomatic plates. As it swept through red and white security barriers the passenger, a woman from the Ministry of Health in Turkey, may just have felt she had seen the institute before. The main block is a tall building with a presence unsettling enough to have been used as an asylum in Batman Begins.

The samples were driven down the hill overlooking the parklands and big houses of Totteridge - "where the millionaires live", as one member of staff on government wages puts it - to Containment Four, the laboratory with the highest level of security. From the outside, the lab looks like the boiler house on a 1960s polytechnic campus, with pipes and ducts sprouting from the walls. Only four people have permission to enter the laboratory: the security manager and three scientists.

Before starting work, Alan Douglas showered and left his clothes in a decontamination room, then dressed in royal blue overalls very like a surgeon would wear in an operating theatre, with a white laboratory coat. He unlocked the door and entered the laboratory, the air in which passes through a complicated series of filters, each sterilised with formaldehyde. This is to stop unwelcome particles from ruining experiments, but it is also to stop viruses with which the scientists work from escaping into the atmosphere.

The air pressure inside the building is lower than outside, so that if an accident happens air will be sucked inside rather than out. Black polythene is taped up at the windows to prevent sunlight from getting in. All waste leaving the lab is sterilised.

The Turkish samples came in plastic tubes, protected by bubble wrap, in a box containing carbon dioxide to keep them at the right temperature. One by one they were placed in an airtight chamber, then passed into a main cabinet. Mr Douglas and his colleagues work with their hands and arms thrust through a portal into gloves, or look into a microscope that extends out of the cabinet as a hood.
The best of the samples was a swab or slice from the lungs of Mehmet Kocyigit, a 14-year-old boy who had lived on a farm thousands of miles away in the village of Dogubayazit, in the mountains close to the border with Iran. He had died from the pneumonia-like symptoms of avian flu which have hospitalised 78 other people across Turkey. It is thought that Mehmet and his siblings had been playing with the severed heads of infected birds. His sisters Fatima and Hulya also died.

"I knew the boy offered our best chance of isolating and growing the virus," says Mr Douglas, who diluted the sample, and from part of it extracted the RNA, the genetic material that is the virus equivalent of DNA. This was then analysed.

The rest of the sample was shared out between dishes in which the virus might grow. Some contained chicken eggs, which are usually used for growing ordinary flu viruses; others contained tissue culture made from canine kidney cells.

"Four of us were working flat out," says Mr Douglas, 55, a research associate who was in the laboratory all last weekend. More people were being hospitalised in Turkey as he worked. "I came in on Sunday morning, checked the tissue culture under the microscope in the hood and took out fluids from all the eggs, and found out that the virus had grown."

He was thrilled. Nobody in Turkey had been able to grow, isolate and test the strain. Nobody else in the world had been asked to try. "On Monday morning I continued extracting, and I got the results that afternoon, then repeated the tests."

The World Health Organisation (WHO) let it be known that the virus had been isolated. American newspapers got hold of the story early and described Mill Hill as only one of the labs working on it. Mr Douglas and his colleagues were furious. "It was as if we were just another bunch of people working away in the background, but that's not true. We are the only ones in the world who have grown this virus. A lot of people are asking for it now, obviously. The Americans are going to be last on the list, I can tell you."

This is not merely a spat. The scientific world depends on patronage, which depends on kudos. The institute has been threatened with a move into central London and its workers do not want to go. They want the world to know about the work they are doing, and the Government to let them stay put. Another colleague shakes his head when asked about the Americans he perceives to be glory-grabbers: "Bastards," he sighs.

The World Influenza Centre used to spend most of its time tracking changes in human flu, but now it also has to keep pace with the avian virus that has so far infected 150 people and killed at least 78. People working with chickens in Hong Kong and South Korea were the first to die in the current outbreak, in 1997 and 2003. Since then there have been outbreaks and mass bird culls across South-east Asia. A South American parrot in a quarantine centre in Essex was said to have brought the virus to England in November, but the real carriers were 53 Taiwanese finches in the same compound. No humans were infected here.

Wild ducks can carry the virus without symptoms as they migrate, and give it to domestic poultry. British bird owners have been told to keep them away from lakes and waterways where the ducks might land during the migratory season. Once chickens are infected, humans can pick up the virus by touching the birds, their droppings or secretions, or inhaling faecal dust. Somebody with the virus might travel to another country before succumbing to the symptoms, as may have been the case with the suspected bird flu reported in Belgium yesterday. But so far humans cannot pass it to each other.

The tests at Mill Hill last week enabled the WHO to confirm that the anti-viral drugs Tamiflu and amantadine are effective against the Turkish strain. The British Government is one of many around the world stockpiling Tamiflu in case of an outbreak: the UK has four million doses now and expects to have another 10.6 million by the end of the year.

But the tests also showed that the H5N1 virus had changed in the boy's body. "Each virus contains eight RNA molecules carrying information for the proteins in the virus," says Sir John Skehel. "In one of the samples, one of the proteins had mutated in a way that would allow it to move from bird to human cells more effectively." That has been seen before, in Hong Kong in 2003 and Vietnam last year, but two more genetic changes will probably have to take place before the virus becomes infectious among humans, says Sir John.
In the meantime, the fewer people who become infected with avian flu now, the less likely one of them will be a host in which it mutates. "This is why all these chickens need to be killed," says Sir John. "It is not that they have done anything at all wrong; it is just that we cannot afford for them to infect large numbers of humans."

The leader of the World Influenza Centre, Dr Alan Hay, flew to Turkey last week to advise doctors and scientists there. "A flu pandemic really is inevitable," he said last year. "We don't know when it will arrive, but we are anticipating it."

There on a hill in north London, hidden in a lab that looks like a boiler house, his team will be ready to tell the world if the nightmare comes true.

THE HUMAN MIXING BOWL

How avian flu could mutate and cause a pandemic

1. WILD DUCKS

Migrating wildfowl may carry the H5N1 virus without symptoms as they fly thousands of miles to another continent

2. CHICKENS

Domestic poultry become infected with the virus if they have contact with the nasal secretions or faeces of migrating wildfowl

3. HUMANS

People working closely with chickens inhale faeces dust or touch secretions and droppings carrying the H5N1 virus

4. MUTATION

If avian flu infects a patient who also has human flu the body may act as a mixing bowl for the two. They will combine to form a new avian/human flu virus with a new genetic make-up. The protein spikes on its surface are a new shape, making the virus resistant to all known vaccines. The victim could travel to another country before succumbing to the symptoms

5. PERSON TO PERSON

The new virus may be so different that humans have little or no immunity. This would allow it to spread across the world very quickly, carried through the air like old-fashioned flu by droplets from coughs and sneezes. Experts say it could kill as many as 150 million people
1997 was when the current outbreak of avian flu first killed a human being

6 people died in Hong Kong that year and 18 were infected

72 more people have been killed by the virus since that time

158 have needed treatment in countries spreading from Thailand to Turkey

14.6m shots of the Tamiflu anti-viral drug ordered by the British government

150m people could die across the world if the virus mutates and causes a pandemic

This is how the nightmare begins: a child plays with chickens in her yard and catches bird flu. She already has ordinary flu. The two mix inside her body, combining to produce a new virus that passes easily from human to human. It spreads fast. No existing vaccine is effective. Before long, millions of people are dead.

This is not a scare story. It is the scenario that three research scientists at a locked and sealed laboratory in north London expect to meet every day they go to work. Their high-security lab, hidden away in the unsuspecting suburb of Mill Hill, is suddenly on the front line of the global fight against bird flu.

Yesterday they were placed on high alert as it seemed the nightmare was about to become real. A Russian journalist had got off a flight from an infected area in Turkey and had gone straight to hospital with flu-like symptoms.

He was put in isolation; blood tests were taken and Mill Hill prepared for samples to arrive. Panic began to rise all over Europe. But then the Belgian health minister announced to a packed press conference that the test results had made doctors "100 per cent sure" their patient did not have bird flu after all. Panic over. For now.

If (or when, as the scientists say) the virus does make the change that would enable it to cause a pandemic and kill up to 150 million people worldwide, the British scientists will probably be the first to spot it. The faster they can do so, the more lives will be saved.
"We do have a great responsibility here," says their boss, Sir John Skehel. "Flu research requires that you accept that."

Alan Douglas is one of the scientists, a 54-year-old research associate who last week became the first person to isolate and grow the strain that had killed three children in a village in Turkey. He and his colleagues at the World Influenza Centre worked flat out on their samples for days. They knew people were dying, but that their results would tell doctors which drugs to use against the virus.

They were also looking for evidence of the big change that the world dreads. Two days ago the World Health Organisation announced that the H5N1 virus found in the body of a 14-year-old boy from a village in Turkey had mutated. The protein spikes on its surface had changed and it was now more attracted to people than birds. This was not the nightmare scenario, insisted Sir John Skehel, but it was "one step along the way".

He is director of the National Institute for Medical Research at Mill Hill, which contains the World Influenza Centre on its 50-acre site. The centre is one of four labs that receive samples from new victims of bird flu - but as the others are in America, Japan and Australia, it is London that will test the European outbreaks first. Few outsiders ever see the lab, but last week The Independent on Sunday was given unprecedented access.

The head of the centre, Dr Alan Hay, cut short a holiday when he heard the news of an outbreak in the Van region of Turkey. The other scientists cancelled days off as samples from the dead boy and his sister were flown to London, a week ago last Thursday. They were driven to Mill Hill from the airport in a car with Turkish diplomatic plates. As it swept through red and white security barriers the passenger, a woman from the Ministry of Health in Turkey, may just have felt she had seen the institute before. The main block is a tall building with a presence unsettling enough to have been used as an asylum in Batman Begins.

The samples were driven down the hill overlooking the parklands and big houses of Totteridge - "where the millionaires live", as one member of staff on government wages puts it - to Containment Four, the laboratory with the highest level of security. From the outside, the lab looks like the boiler house on a 1960s polytechnic campus, with pipes and ducts sprouting from the walls. Only four people have permission to enter the laboratory: the security manager and three scientists.

Before starting work, Alan Douglas showered and left his clothes in a decontamination room, then dressed in royal blue overalls very like a surgeon would wear in an operating theatre, with a white laboratory coat. He unlocked the door and entered the laboratory, the air in which passes through a complicated series of filters, each sterilised with formaldehyde. This is to stop unwelcome particles from ruining experiments, but it is also to stop viruses with which the scientists work from escaping into the atmosphere.

The air pressure inside the building is lower than outside, so that if an accident happens air will be sucked inside rather than out. Black polythene is taped up at the windows to prevent sunlight from getting in. All waste leaving the lab is sterilised.

The Turkish samples came in plastic tubes, protected by bubble wrap, in a box containing carbon dioxide to keep them at the right temperature. One by one they were placed in an airtight chamber, then passed into a main cabinet. Mr Douglas and his colleagues work with their hands and arms thrust through a portal into gloves, or look into a microscope that extends out of the cabinet as a hood.
The best of the samples was a swab or slice from the lungs of Mehmet Kocyigit, a 14-year-old boy who had lived on a farm thousands of miles away in the village of Dogubayazit, in the mountains close to the border with Iran. He had died from the pneumonia-like symptoms of avian flu which have hospitalised 78 other people across Turkey. It is thought that Mehmet and his siblings had been playing with the severed heads of infected birds. His sisters Fatima and Hulya also died.

"I knew the boy offered our best chance of isolating and growing the virus," says Mr Douglas, who diluted the sample, and from part of it extracted the RNA, the genetic material that is the virus equivalent of DNA. This was then analysed.

The rest of the sample was shared out between dishes in which the virus might grow. Some contained chicken eggs, which are usually used for growing ordinary flu viruses; others contained tissue culture made from canine kidney cells.

"Four of us were working flat out," says Mr Douglas, 55, a research associate who was in the laboratory all last weekend. More people were being hospitalised in Turkey as he worked. "I came in on Sunday morning, checked the tissue culture under the microscope in the hood and took out fluids from all the eggs, and found out that the virus had grown."

He was thrilled. Nobody in Turkey had been able to grow, isolate and test the strain. Nobody else in the world had been asked to try. "On Monday morning I continued extracting, and I got the results that afternoon, then repeated the tests."

The World Health Organisation (WHO) let it be known that the virus had been isolated. American newspapers got hold of the story early and described Mill Hill as only one of the labs working on it. Mr Douglas and his colleagues were furious. "It was as if we were just another bunch of people working away in the background, but that's not true. We are the only ones in the world who have grown this virus. A lot of people are asking for it now, obviously. The Americans are going to be last on the list, I can tell you."

This is not merely a spat. The scientific world depends on patronage, which depends on kudos. The institute has been threatened with a move into central London and its workers do not want to go. They want the world to know about the work they are doing, and the Government to let them stay put. Another colleague shakes his head when asked about the Americans he perceives to be glory-grabbers: "Bastards," he sighs.

The World Influenza Centre used to spend most of its time tracking changes in human flu, but now it also has to keep pace with the avian virus that has so far infected 150 people and killed at least 78. People working with chickens in Hong Kong and South Korea were the first to die in the current outbreak, in 1997 and 2003. Since then there have been outbreaks and mass bird culls across South-east Asia. A South American parrot in a quarantine centre in Essex was said to have brought the virus to England in November, but the real carriers were 53 Taiwanese finches in the same compound. No humans were infected here.
Wild ducks can carry the virus without symptoms as they migrate, and give it to domestic poultry. British bird owners have been told to keep them away from lakes and waterways where the ducks might land during the migratory season. Once chickens are infected, humans can pick up the virus by touching the birds, their droppings or secretions, or inhaling faecal dust. Somebody with the virus might travel to another country before succumbing to the symptoms, as may have been the case with the suspected bird flu reported in Belgium yesterday. But so far humans cannot pass it to each other.
The tests at Mill Hill last week enabled the WHO to confirm that the anti-viral drugs Tamiflu and amantadine are effective against the Turkish strain. The British Government is one of many around the world stockpiling Tamiflu in case of an outbreak: the UK has four million doses now and expects to have another 10.6 million by the end of the year.
But the tests also showed that the H5N1 virus had changed in the boy's body. "Each virus contains eight RNA molecules carrying information for the proteins in the virus," says Sir John Skehel. "In one of the samples, one of the proteins had mutated in a way that would allow it to move from bird to human cells more effectively." That has been seen before, in Hong Kong in 2003 and Vietnam last year, but two more genetic changes will probably have to take place before the virus becomes infectious among humans, says Sir John.
In the meantime, the fewer people who become infected with avian flu now, the less likely one of them will be a host in which it mutates. "This is why all these chickens need to be killed," says Sir John. "It is not that they have done anything at all wrong; it is just that we cannot afford for them to infect large numbers of humans."
The leader of the World Influenza Centre, Dr Alan Hay, flew to Turkey last week to advise doctors and scientists there. "A flu pandemic really is inevitable," he said last year. "We don't know when it will arrive, but we are anticipating it."
There on a hill in north London, hidden in a lab that looks like a boiler house, his team will be ready to tell the world if the nightmare comes true.
THE HUMAN MIXING BOWL
How avian flu could mutate and cause a pandemic
1. WILD DUCKS
Migrating wildfowl may carry the H5N1 virus without symptoms as they fly thousands of miles to another continent
2. CHICKENS
Domestic poultry become infected with the virus if they have contact with the nasal secretions or faeces of migrating wildfowl
3. HUMANS
People working closely with chickens inhale faeces dust or touch secretions and droppings carrying the H5N1 virus
4. MUTATION
If avian flu infects a patient who also has human flu the body may act as a mixing bowl for the two. They will combine to form a new avian/human flu virus with a new genetic make-up. The protein spikes on its surface are a new shape, making the virus resistant to all known vaccines. The victim could travel to another country before succumbing to the symptoms
5. PERSON TO PERSON
The new virus may be so different that humans have little or no immunity. This would allow it to spread across the world very quickly, carried through the air like old-fashioned flu by droplets from coughs and sneezes. Experts say it could kill as many as 150 million people
1997 was when the current outbreak of avian flu first killed a human being
6 people died in Hong Kong that year and 18 were infected
72 more people have been killed by the virus since that time
158 have needed treatment in countries spreading from Thailand to Turkey
14.6m shots of the Tamiflu anti-viral drug ordered by the British government
150m people could die across the world if the virus mutates and causes a pandemic

Independent Online Edition > Science & Technology

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