The young scientist, normally calm and measured, seemed edgy when he stopped by his boss's office.
"You are not going to believe this one," he told Ron Fouchier, a virologist at the Erasmus Medical Center in Rotterdam. "I think we have an airborne H5N1 virus."
The news, delivered one afternoon last July, was chilling. It meant that Dr. Fouchier's research group had taken one of the most dangerous flu viruses ever known and made it even more dangerous - by tweaking it genetically to make it more contagious.
What shocked the researchers was how easy it had been, Dr. Fouchier said. Just a few mutations was all it took to make the virus go airborne.
The discovery has led advisers to the United States government, which paid for the research, to urge that the details be kept secret and not published in scientific journals to prevent the work from being replicated by terrorists, hostile governments or rogue scientists.
Journal editors are taking the recommendation seriously, even though they normally resist any form of censorship. Scientists, too, usually insist on their freedom to share information, but fears of terrorism have led some to say this information is too dangerous to share.
Some biosecurity experts have even said that no scientist should have been allowed to create such a deadly germ in the first place, and they warn that not just the blueprints but the virus itself could somehow leak or be stolen from the laboratory.
Dr. Fouchier is cooperating with the request to withhold some data, but reluctantly. He thinks other scientists need the information.
The naturally occurring A(H5N1) virus is quite lethal without genetic tinkering. It already causes an exceptionally high death rate in humans, more than 50 percent. But the virus, a type of bird flu, does not often infect people, and when it does, they almost never transmit it to one another.
If, however, that were to change and bird flu were to develop the ability to spread from person to person, scientists fear that it could cause the deadliest flu pandemic in history.
The experiment in Rotterdam transformed the virus into the supergerm of virologists' nightmares, enabling it to spread from one animal to another through the air. The work was done in ferrets, which catch flu the same way people do and are considered the best model for studying it.
"This research should not have been done," said Richard H. Ebright, a chemistry professor and bioweapons expert at Rutgers University who has long opposed such research. He warned that germs that could be used as bioweapons had already been unintentionally released hundreds of times from labs in the United States and predicted that the same thing would happen with the new virus.
"It will inevitably escape, and within a decade," he said.
But Dr. Fouchier and many public health experts argue that the experiment had to be done.
If scientists can make the virus more transmissible in the lab, then it can also happen in nature, Dr. Fouchier said.
Knowing that the risk is real should drive countries where the virus is circulating in birds to take urgent steps to eradicate it, he said. And knowing which mutations lead to transmissibility should help scientists all over the world who monitor bird flu to recognize if and when a circulating strain starts to develop pandemic potential.
"There are highly respected virologists who thought until a few years ago that H5N1 could never become airborne between mammals," Dr. Fouchier said. "I wasn't convinced. To prove these guys wrong, we needed to make a virus that is transmissible."
Other virologists differ. Dr. W. Ian Lipkin of Columbia University questioned the need for the research and rejected Dr. Fouchier's contention that making a virus transmissible in the laboratory proves that it can or will happen in nature. But Richard J. Webby, a virologist at the St. Jude Children's Research Hospital in Memphis, said Dr. Fouchier's research was useful, with the potential to answer major questions about flu viruses, like what makes them transmissible and how some that appear to infect only animals can suddenly invade humans as well.
"I would certainly love to be able to see that information," Dr. Webby said, explaining that he has a freezer full of bird flu viruses from all over the world. "If I detect a virus in our activities that has some of these changes, it could change the direction of what we do."
Some scientists dismiss fears of bioterrorism via influenza, because flu viruses would not make practical weapons: they cannot be targeted, and they would also infect whoever deployed them.
Dr. Fouchier said it would be easier to weaponize other germs. Which ones? He would not answer.
"That should tell you something," he said. "I won't tell you what I as a virologist would use, but I would publish this work."
However, some experts argue that appeals to logic are useless.
"You can't know who might try to re-create H5N1," said Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.
The A(H5N1) bird flu was first recognized in Hong Kong in 1997, when chickens in poultry markets began dying and 18 people fell ill, 6 of them fatally. Hoping to stamp out the virus, the government in Hong Kong destroyed the country's entire poultry industry - killing more than a million birds - in just a few days. Buddhist monks and nuns in Hong Kong prayed for the souls of the slaughtered chickens, and world health officials praised Hong Kong for averting a potential pandemic.
But the virus persisted in other parts of Asia, and reached Europe and Africa; that worries scientists, because most bird flus emerge briefly and then vanish. Millions of infected birds have died, and many millions more have been slaughtered. Since 1997, about 600 humans have been infected, and more than half died.
Dr. Donald A. Henderson, a leader in the eradication of smallpox and now a biosecurity expert at the University of Pittsburgh, noted that even the notorious flu pandemic of 1918 killed only 2 percent of patients.
"This is running at 50 percent or more," Dr. Henderson said. "This would be the ultimate organism as far as destruction of population is concerned."
Dr. Fouchier was working on AIDS when the first bird flu outbreak occurred. He immediately became fascinated by the new disease and gave up AIDS to study it. He has worked on bird flu for more than a decade.
The medical center in Rotterdam built a special 1,000-square-foot virus lab for this work, a locked-down place where people work in spacesuits in sealed chambers with filtered air and multiple precautions to keep germs in and intruders out and to protect the scientists from infection. Dr. Fouchier said that even more security measures had been added recently because of the publicity about his work.
The Dutch government and the United States Centers for Disease Control and Prevention approved the laboratory, and the National Institutes of Health gave the Erasmus center a seven-year contract for flu research.
Because a government advisory panel has recommended that the full recipe for mutating the bird flu virus not be published, Dr. Fouchier declined to explain much about how it was done.
But he previously described the work at a public meeting, and various publications have reported that the experiment involved creating mutations in the virus and then squirting it into the respiratory tracts of ferrets. When the ferrets got sick, the researchers would collect their nasal secretions and expose other ferrets to the virus. After repetitions of this process, a strain of virus emerged from sick ferrets last summer that could infect animals in nearby cages without being squirted into them - just by traveling through the air.
The published reports say five mutations were all it took to transform the virus. Dr. Fouchier declined to confirm or deny that, and would say only that it took "a handful" of mutations.
Looking back on that day in July with Sander Herfst, the member of his team who told him the virus had gone airborne, Dr. Fouchier said, "We both needed a beer to recover from the shock."
Then they planned their next step, repeating the experiment to make sure the results were reliable. There was one major obstacle: they had run out of ferrets. They ordered a new shipment from Scandinavia. So they had to wait several weeks to find out whether their discovery was real. Dr. Herfst took a vacation, timed to end the day the ferrets arrived.
They ran the tests again. Once more, A(H5N1) went airborne.
"You are not going to believe this one," he told Ron Fouchier, a virologist at the Erasmus Medical Center in Rotterdam. "I think we have an airborne H5N1 virus."
The news, delivered one afternoon last July, was chilling. It meant that Dr. Fouchier's research group had taken one of the most dangerous flu viruses ever known and made it even more dangerous - by tweaking it genetically to make it more contagious.
What shocked the researchers was how easy it had been, Dr. Fouchier said. Just a few mutations was all it took to make the virus go airborne.
The discovery has led advisers to the United States government, which paid for the research, to urge that the details be kept secret and not published in scientific journals to prevent the work from being replicated by terrorists, hostile governments or rogue scientists.
Journal editors are taking the recommendation seriously, even though they normally resist any form of censorship. Scientists, too, usually insist on their freedom to share information, but fears of terrorism have led some to say this information is too dangerous to share.
Some biosecurity experts have even said that no scientist should have been allowed to create such a deadly germ in the first place, and they warn that not just the blueprints but the virus itself could somehow leak or be stolen from the laboratory.
Dr. Fouchier is cooperating with the request to withhold some data, but reluctantly. He thinks other scientists need the information.
The naturally occurring A(H5N1) virus is quite lethal without genetic tinkering. It already causes an exceptionally high death rate in humans, more than 50 percent. But the virus, a type of bird flu, does not often infect people, and when it does, they almost never transmit it to one another.
If, however, that were to change and bird flu were to develop the ability to spread from person to person, scientists fear that it could cause the deadliest flu pandemic in history.
The experiment in Rotterdam transformed the virus into the supergerm of virologists' nightmares, enabling it to spread from one animal to another through the air. The work was done in ferrets, which catch flu the same way people do and are considered the best model for studying it.
"This research should not have been done," said Richard H. Ebright, a chemistry professor and bioweapons expert at Rutgers University who has long opposed such research. He warned that germs that could be used as bioweapons had already been unintentionally released hundreds of times from labs in the United States and predicted that the same thing would happen with the new virus.
"It will inevitably escape, and within a decade," he said.
But Dr. Fouchier and many public health experts argue that the experiment had to be done.
If scientists can make the virus more transmissible in the lab, then it can also happen in nature, Dr. Fouchier said.
Knowing that the risk is real should drive countries where the virus is circulating in birds to take urgent steps to eradicate it, he said. And knowing which mutations lead to transmissibility should help scientists all over the world who monitor bird flu to recognize if and when a circulating strain starts to develop pandemic potential.
"There are highly respected virologists who thought until a few years ago that H5N1 could never become airborne between mammals," Dr. Fouchier said. "I wasn't convinced. To prove these guys wrong, we needed to make a virus that is transmissible."
Other virologists differ. Dr. W. Ian Lipkin of Columbia University questioned the need for the research and rejected Dr. Fouchier's contention that making a virus transmissible in the laboratory proves that it can or will happen in nature. But Richard J. Webby, a virologist at the St. Jude Children's Research Hospital in Memphis, said Dr. Fouchier's research was useful, with the potential to answer major questions about flu viruses, like what makes them transmissible and how some that appear to infect only animals can suddenly invade humans as well.
"I would certainly love to be able to see that information," Dr. Webby said, explaining that he has a freezer full of bird flu viruses from all over the world. "If I detect a virus in our activities that has some of these changes, it could change the direction of what we do."
Some scientists dismiss fears of bioterrorism via influenza, because flu viruses would not make practical weapons: they cannot be targeted, and they would also infect whoever deployed them.
Dr. Fouchier said it would be easier to weaponize other germs. Which ones? He would not answer.
"That should tell you something," he said. "I won't tell you what I as a virologist would use, but I would publish this work."
However, some experts argue that appeals to logic are useless.
"You can't know who might try to re-create H5N1," said Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.
The A(H5N1) bird flu was first recognized in Hong Kong in 1997, when chickens in poultry markets began dying and 18 people fell ill, 6 of them fatally. Hoping to stamp out the virus, the government in Hong Kong destroyed the country's entire poultry industry - killing more than a million birds - in just a few days. Buddhist monks and nuns in Hong Kong prayed for the souls of the slaughtered chickens, and world health officials praised Hong Kong for averting a potential pandemic.
But the virus persisted in other parts of Asia, and reached Europe and Africa; that worries scientists, because most bird flus emerge briefly and then vanish. Millions of infected birds have died, and many millions more have been slaughtered. Since 1997, about 600 humans have been infected, and more than half died.
Dr. Donald A. Henderson, a leader in the eradication of smallpox and now a biosecurity expert at the University of Pittsburgh, noted that even the notorious flu pandemic of 1918 killed only 2 percent of patients.
"This is running at 50 percent or more," Dr. Henderson said. "This would be the ultimate organism as far as destruction of population is concerned."
Dr. Fouchier was working on AIDS when the first bird flu outbreak occurred. He immediately became fascinated by the new disease and gave up AIDS to study it. He has worked on bird flu for more than a decade.
The medical center in Rotterdam built a special 1,000-square-foot virus lab for this work, a locked-down place where people work in spacesuits in sealed chambers with filtered air and multiple precautions to keep germs in and intruders out and to protect the scientists from infection. Dr. Fouchier said that even more security measures had been added recently because of the publicity about his work.
The Dutch government and the United States Centers for Disease Control and Prevention approved the laboratory, and the National Institutes of Health gave the Erasmus center a seven-year contract for flu research.
Because a government advisory panel has recommended that the full recipe for mutating the bird flu virus not be published, Dr. Fouchier declined to explain much about how it was done.
But he previously described the work at a public meeting, and various publications have reported that the experiment involved creating mutations in the virus and then squirting it into the respiratory tracts of ferrets. When the ferrets got sick, the researchers would collect their nasal secretions and expose other ferrets to the virus. After repetitions of this process, a strain of virus emerged from sick ferrets last summer that could infect animals in nearby cages without being squirted into them - just by traveling through the air.
The published reports say five mutations were all it took to transform the virus. Dr. Fouchier declined to confirm or deny that, and would say only that it took "a handful" of mutations.
Looking back on that day in July with Sander Herfst, the member of his team who told him the virus had gone airborne, Dr. Fouchier said, "We both needed a beer to recover from the shock."
Then they planned their next step, repeating the experiment to make sure the results were reliable. There was one major obstacle: they had run out of ferrets. They ordered a new shipment from Scandinavia. So they had to wait several weeks to find out whether their discovery was real. Dr. Herfst took a vacation, timed to end the day the ferrets arrived.
They ran the tests again. Once more, A(H5N1) went airborne.
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