Friday, October 07, 2005

COM: The battle against poultry flu

Bird flu pandemic risk 'very high'
U.S. official tours Asia to coordinate plans for outbreak

BANGKOK, Thailand (AP) -- The likelihood of a human flu pandemic is very high, U.S. Health and Human Services Secretary Michael Leavitt said as he began a tour of Southeast Asia to coordinate plans to combat bird flu.

The H5N1 strain of bird flu has swept through poultry populations in many parts of Asia since 2003 and jumped to humans, killing 60 people, mostly through direct contact with sick fowl.

While there have been no known cases of person-to-person transmission, World Health Organization officials and other experts have been warning that the virus could mutate into a form that spreads easily among people. In a worst-case scenario, they say millions of people could die.

Three influenza pandemics have occurred over the last century and "the likelihood of another is very high, some say even certain," Leavitt said Monday after meeting with Thai health officials to review the country's preparations against the disease.

"Whether or not H5N1 is the virus that will ultimately trigger such a pandemic is unknown to us," he told a news conference.

"The probability is uncertain. But the warning signs are troubling. Hence we are responding in a robust way."

Leavitt, accompanied by the director of WHO and other top health professionals, also plans to visit Laos, Cambodia and Vietnam to prepare for the anticipated public health emergency.

His tour comes after U.S. President George W. Bush last month established the "International Partnership on Avian and Pandemic Influenza" to coordinate a global strategy against bird flu and other types of influenza. (Full story)

Leavitt said "containment" was the first line of defense against the illness, encouraging countries to step up development and production of vaccines and strengthen efforts to detect any cases of human-to-human transmission early.

"Anywhere, the sooner we know, the faster we can respond and the more lives that will be saved," he said.

Thai Public Health Minister Suchai Charoenratanakul said Thailand would contribute at least 5 percent of its antiviral drug supplies to a proposed Southeast Asian regional stockpile.

So far, 41 people have died of bird flu in Vietnam, 12 in Thailand, four in Cambodia and three in Indonesia. Leavitt said he would also visit Indonesia at a date to be announced.

World Heath Organization Director General Dr. Lee Jong-wook said preparation was the key to preventing a flu epidemic such as the one that struck in 1918, killing an estimated 40 million to 50 million people. (Full story)

"Now we know in advance what is happening and we have to prepare ourselves. That is our duty," he said.

Health Secretary to Emphasize Urgency of Avian Flu in Asia
By SETH MYDANS, International Herald Tribune, October 10, 2005

BANGKOK, Oct. 10 - The United States health and human services secretary, Michael O. Leavitt, began a four-nation tour of Southeast Asia today with a message of urgency in preparing for a possible pandemic of avian influenza.

"We in the United States do not have the capacity to manufacture vaccines for our own population," he said, urging regional leaders to increase their capacities for making antiviral vaccines.

"Most natural disasters have a geographic confinement to them," he said. "Most have a relatively short time period which they are active. An influenza pandemic could geographically expand in unlimited numbers of locations and sometimes grow as long as a year or a year and a half."

Mr. Leavitt said the goal of his trip was to increase international cooperation as the best defense against an outbreak.

"For all of us, the best defense is containment, to find it and find it soon and then work as an international community to contain it," he said. "That requires all of us to act in a way that is both transparent and cooperative."

His trip in the region, where 60 people reportedly have died of avian flu, began here in Thailand, where he said preparedness and cooperation were already at a high level. More than 40 million chickens and ducks have been killed in Thailand over the past two years and 12 human deaths have been confirmed.

Mr. Leavitt plans to travel to Laos and Cambodia, where the levels of public health and awareness are low relative to Thailand and where preventive action is hindered by lack of money and organization. Finally, he is scheduled to travel to Vietnam, where the World Health Organization has recorded 91 cases of avian flu, including 41 that have resulted in death. The secretary said he would make a separate trip to Indonesia, where the flu appears to be spreading rapidly and where the most recent four fatalities have been recorded.

The organization's director general, Jong Woo Lee, who is traveling with Mr. Leavitt, said the recent appearance of infected birds in Russia and Central Asia amounted to a worldwide warning. There were also reports of outbreaks in Turkey and Romania over the weekend.

"The burning question is, will there be a human influenza pandemic," Mr. Leavitt said. "On behalf of the W.H.O., I can tell you that there will be. The only question is the virulence and rapidity of transmission from human to human."

The health organization has warned that a possible pandemic of avian influenza could kill as many as 7.4 million people. It has urged nations in the region to draw up preparedness plans and stockpile antiviral drugs that could be effective against an emerging strain.

"At present, there is no convincing evidence of sustained human-to-human transmission of the H5N1 virus," the organization said in a statement. "However, there have been incidents, in Thailand, Vietnam and Cambodia, where limited transmission between humans was suspected."

Mr. Leavitt met with Thai government officials, nongovernmental groups and officials from the health organization. "Three times in this century we have experienced pandemic influenza and they will come again," he said. "We must be ready."

He added, "Our preparations are not yet complete nor are they adequate."

What would a modern quarantine look like?
Experts: Isolating bird flu patients could be accomplished in several ways
The Associated Press, Updated: 5:34 p.m. ET Oct. 10, 2005

WASHINGTON - Quarantine — or some version of it — in a 21st-century flu pandemic would look very different from the medieval stereotype of diseased outcasts locked in a do-not-enter zone.

President Bush’s specter of a military-enforced mass quarantine is prompting debate of the Q-word as health officials update the nation’s plan for battling a pandemic — a plan expected to define who decides when and how to separate the contagious from everyone else.

“All the options need to be on the table,” said Dr. Marty Cetron, head of quarantine at the Centers for Disease Control and Prevention.

Bush’s comments recall how quarantines were enforced in parts of this country in the 1890s, when armed guards patrolled streets to keep victims of smallpox and other dread diseases confined to their homes.

'A whole range of options'
“The image that perhaps was inadvertently conveyed is really a setting in extreme that’s less likely,” Cetron cautioned. “There’s a whole range of options in the public-health toolbox for ways to achieve this goal of social distancing.”

For three years the CDC has been helping states plan how they would enact quarantines in case of a bioterrorism attack. The instructions stress using the least restrictive means necessary to stem an infection’s spread.

And public health officials expect a U.S. quarantine today to almost always be voluntary, with incentives to cooperate. In case of a horrific outbreak, quarantined areas would get first shipments of scarce medicines.

“I don’t think either the Tennessee National Guard or the U.S. Army and Marines will try to establish a cordon sanitaire around Nashville,” said Dr. William Schaffner of Vanderbilt University, an influenza expert who advises the federal government. “That’s not going to happen.”

Actually, “we practice in this country quarantine every day,” said Health and Human Services Secretary Mike Leavitt. “If a child gets the measles, their mothers are expected to keep them at home.”

Vaccination is the cornerstone of fighting a pandemic, and quarantine-like steps are supposed to be brief, “designed to buy time until we have an adequate supply of countermeasures,” CDC’s Cetron said.

Voluntary measures?
The SARS epidemic of 2003 illustrated that “the public will voluntarily comply with measures to both protect themselves and their loved ones” — if doctors make the case that the steps are for their own good, he added.

Legally, “isolation” is the term for separating people who already are sick from others. That happens routinely in hospitals, as they limit access to patients being treated for certain infections.

“Quarantine” means restricting the movement of still healthy people who may have been exposed to an infectious disease, in case they’re carrying it. It’s almost always for a brief time; during SARS, for instance, hospital workers exposed to suspect cases were asked to stay home from work during the respiratory disease’s 10-day incubation period.

States have the primary legal authority to enact quarantines during outbreaks within their borders. Federal quarantine authority involves preventing infectious diseases from entering the country and stopping interstate spread. Expanding that authority to encompass a military role might entail legislation, something lawmakers’ staffs have begun mulling as public health experts downplay the need.

With SARS, CDC used its existing authority to stop that virus from spreading here like it did in Asia: Over three months, CDC workers delayed on the tarmac 12,000 airplanes carrying 3 million passengers arriving from SARS-affected countries. Anyone with SARS symptoms was isolated. Anyone possibly exposed was told what symptoms to watch for in the next 10 days and how to seek help without exposing entire emergency rooms if symptoms arose.

SARS showed that tracking down patients and people they may have exposed — allowing individuals, not large areas, to be contained — can work, Cetron said.

Flu would spread more easily than SARS
At the same time, a super-flu would demand more intense measures because it would spread more easily, perhaps even before symptoms appeared. Drafts of the pandemic plan make clear that affected communities would probably close schools, shut down large gatherings and restrict travel.

Ramping up gradually is crucial to minimize social and economic fallout, Schaffner cautioned.

He offered his home city of Nashville as an example: Authorities first might urge people to watch the Titans play football on TV instead of at the stadium, and to avoid shopping malls. Then schools might close for a while. Then people might be told to postpone holidays or business trips to Nashville, all steps to stem transmission by minimizing contact — but well short of compulsory quarantine.

“We’re going to have to permit ourselves a graduated, intelligent response to the magnitude of the threat,” he concluded.

Resurrecting a Killer Flu
A scientist explains why he re-created the lethal virus that killed millions in 1918 and what it can teach us about today’s avian flu.
By Anne Underwood, Newsweek, Updated: 6:06 p.m. ET Oct. 7, 2005

Oct. 7, 2005 - Scientists have long puzzled over the exceptional lethality of the 1918 flu, which killed between 20 million and 50 million people worldwide. What features of the viral genome enabled it to become both highly transmissible and lethal at the same time? Some of those questions were answered this week, with the publication of twin papers in the journals Nature and Science. In Nature, Jeffery Taubenberger of the Pentagon's Armed Forces Institute of Pathology announced that he had completed sequencing the genome of the 1918 flu. At the same time, Terrence Tumpey, senior microbiologist at the Influenza Branch of the Centers for Disease Control and Prevention, reported in Science that he and his colleagues had used Taubenberger’s sequence to reconstruct the actual 1918 virus, a living copy of the germ that killed millions.

Fears that it could escape into the environment or be appropriated by bioterrorists made it a controversial move. But Tumpey says the risk was worth the trade off because of the information we stand to learn from the virus. What was particularly chilling about the last killer flu was that it appeared to come, with only minimal changes, from an avian virus--bringing a new urgency to the current flu sweeping Southeast Asia. Tumpey spoke with NEWSWEEK's Anne Underwood about his findings. Excerpts:

NEWSWEEK: What is the significance of these twin papers?
Terrence Tumpey: For the first time we have a truly avian pandemic influenza virus that we can study. Not only did we want to rescue the virus, but also characterize some of the important viral proteins that made it so exceptionally virulent.

And we know for sure now that this was a purely avian virus, not a hybrid. Was it really changes of just 25-30 amino acids out of 4,400 in the viral RNA that transformed the virus into a killer?
That’s Jeff Taubenberger’s work, but it appears that way. The dogma until [the current bird flu struck in] 1997 was that pandemics were caused by shuffling of genes between avian and mammalian viruses. But both the current bird flu outbreak and the 1918 virus appear not to be a human/avian reassortant virus, but an avian virus that made minimal changes to infect humans directly. Thankfully, bird flu virus hasn’t figured out how to spread yet. The 1918 virus did.

Does this confirm our worst fears about current bird flu?
It’s hard to know whether or not the current flu will emerge into the human population and spread efficiently. But it’s a good guess that with enough time, it will figure out how to transmit human to human. If so, it will fit the three criteria of a pandemic: a novel subtype, a subtype to which the population has no immunity and high transmissibility.

Why was it important to create a living virus from the sequence?
There is little information in the sequence itself that tells us why it would be so deadly. We see from the sequence that it is avianlike, but there are not any obvious molecular smoking-gun features that we can point to and say, "That is the reason why it killed so many people." Reconstructing the virus helps us do that and identify targets for vaccines and antiviral drugs. The knowledge we’re gaining to protect public health far outweighs the hypothetical risk of working with this strain or providing the information to the public.

When you tested the reconstructed 1918 virus in mice, chicken embryos and human lung cells, what did you find was different about it?
We demonstrated in mice that the hemagglutinin (HA) protein on the viral coat was essential for development of severe pulmonary disease. The 1918 HA seemed to target deeper areas of the lungs than standard viruses. It targeted the alveoli--delicate tissues where the exchange of oxygen and carbon dioxide takes place. In animals, we saw lots of inflammation deep in the lungs, blocking the airways. When you remove the HA protein from 1918 and replace it with the HA from a contemporary virus, you don’t see the virus target deeper areas of lung. That appears to be a unique function of the 1918 virus.

What’s more, it can propagate in culture without the enzyme trypsin. Normally, with garden-variety influenza, in order to grow the virus in culture, you have to add the enzyme, which enables the hemagglutinin to function properly. These enzymes are found in lung tissue, too, or else influenza wouldn’t grow in our lungs.

What does the trypsin do?
It cleaves the HA, breaking it into two pieces. One of the pieces is used to get inside cells [for the virus to replicate]. If the virus doesn’t cleave, it binds to the cell surface, but can’t get inside. But the 1918 virus doesn’t require trypsin. We demonstrated that the other protein on the viral coat, referred to as neuraminidase, was able to mediate that function by cleaving the hemagglutinin, although it’s not clear yet how it does that.

Targeting the alveoli and functioning without trypsin would help explain why the virus was so lethal. What accounted for its ease of transmission among humans?
We don’t have a clue about transmissibility of the 1918 virus. But we showed in the paper that the polymerase genes of the 1918 flu were essential for maximal replication of the virus. Polymerase is one of the most important genes of the virus. Think of polymerase as the engine of the virus, driving the replication machinery. A good polymerase makes more and more copies. A bad one won’t. The polymerase described in the Nature paper is almost all avian, with minimal changes. The current bird flu also appears to have a very good polymerase.

What kind of precautions do you have to take to work with the virus in the lab?
Before we even began this work, we had to undergo multiple safety approvals in order to protect ourselves and public. The 1918 virus was reconstructed in a high-containment, BSL-3-enhanced [biosafety-level-3-enhanced] laboratory. Of the different biosafety levels, the highest is 4. That’s for agents such as Marburg and Ebola that have no treatment at all and are deadly. The next level down is our level--BSL-3-enhanced--which is used for agents that are susceptible to current FDA-approved antiviral drugs and for which the public has some cross-immunity from other viruses.

The population already has some immunity against the 1918 flu?
Yes. H1N1 subtype viruses still exist, although they’re declining. Older individuals especially have good cross reactivity to the 1918 virus.

What other precautions do you take?
All viruses are handled inside a biosafety cabinet. In addition, we have a half-body suit with a respirator, so all the air is filtered before it reaches the head piece. We have to wear double gloves and shower out when we’re finished. And there are heightened security requirements mandated by the select agent program [to make sure the virus doesn’t fall into the wrong hands]. Fingerprinting pads are used for entering the high-containment lab. And to open the locked freezers, we use retina scanning for identification.

Once the sequence is out there, what’s to stop someone from whipping up a batch?
It takes a lot of skilled work by microbiologists. It can’t be done overnight in a less than ideal lab. And there are other complicated issues. You can’t grow it by conventional means because the 1918 flu kills eggs. Standard flu does not.

How did this project get started?
In 1995, Jeff Taubenberger started systematically going through the eight viral genes and sequencing them individually. The initial genetic material he used came from the Armed Forces Institute of Pathology, which was started as an Army medical museum in 1862 by Abraham Lincoln to help fight diseases of the battlefield. Jeff found tissues from two soldiers who had succumbed to infection in 1918. But they were just little tissue blocks the size of a nickel or a postage stamp. He didn’t have enough to sequence the whole virus.

Then a retired pathologist named Johan Hultin saw Jeff’s work and offered to help him get more tissue from victims whose bodies were preserved in permafrost. This pathologist, as part of his graduate studies in 1952, had gone to an Alaskan burial site to exhume bodies, after receiving permission from the city council. The poor village probably got the virus in the fall of 1918 from the mailman, who delivered the mail by dogsled. He delivered the mail and the 1918 flu. In November, 72 people died--about 85 percent of the adult population there. All were buried in this mass grave, below the permafrost layer. Hultin got permission from the town of Brevig Mission, and got lung tissue from a female that had died. He sent it to Jeff, who had enough genetic material then to work with.

So what’s the next step for you?
We are planning on looking at the other four of the 1918 influenza genes that were not addressed in the current work. Now that we know the full virulence of the pandemic virus, we can replace individual genes with genes from contemporary viruses and determine their importance in replication and virulence.

First deadly bird flu cases suspected in Europe
H591 virus may have caused deaths of ducks in Romania, officials say
Reuters, Updated: 8:14 p.m. ET Oct. 7, 2005

Three domestic ducks have died of bird flu in eastern Romania, but authorities said Friday they had not confirmed whether the birds were infected by the H5N1 strain that experts are tracking for fear it could mutate and spawn a human flu pandemic.

There are several strains of bird flu but only a few are deadly. Agriculture officials said they strongly suspected that tests now under way in Britain would confirm the birds were infected with H5N1.

If so, it would be the first time the virus strain has been detected in Europe.

Authorities worldwide are on alert for confirmed cases of fowl infected with H5N1 now circulating in parts of Asia.

H5N1 has infected 116 people in Asia, killing 60 — but experts are more worried the virus could mutate into a form that passes easily between people. That could trigger a human flu pandemic.

The best defense against a pandemic is to stamp out any outbreak in birds before the virus has a chance to change.

The dead birds were first noticed in the remote eastern village of Ceamurlia de Jos near the Black Sea in late September, Agriculture Minister Gheorghe Flutur said. Samples were sent to a lab in Bucharest, where scientists found antibodies to bird flu.

However, that lab did not have the capability to determine the exact strain of the virus, and sent the samples to Britain. Results were expected in the next few days.

World leaders meet in effort to contain poultry flu
Officials from 80 nations gather in Washington to devise plans to halt virus
Reuters, Updated: 8:09 p.m. ET Oct. 7, 2005

WASHINGTON - President Bush asked vaccine makers to do their utmost to boost flu vaccine production on Friday, while officials from 80 countries and the United Nations met to start setting up ways to fight a feared influenza pandemic.

Neither meeting provided any immediate solutions, but U.S. officials said they served to raise the profile of the potential crisis and start setting up the networks needed to deal with outbreaks.

“I think what this is, is ratcheting this up,” said Dr. Bruce Gellin, vaccine coordinator at the U.S. Department of Heath and Human Services and coordinator of the federal influenza preparedness plan.

Experts have been warning since 2003 that the H5N1 avian influenza is the biggest current health threat to the world but policy efforts to battle it have only reached a peak in recent weeks.

The virus has killed millions of birds across Asia and infected more than 100 people, killing more than 60 of them in four Asian nations.

If it acquires the ability to pass easily from person to person, it could kill millions in the space of a few months, experts say. The world does not have enough vaccine to fight off annual flu, let alone a pandemic of avian flu, and part of the problem is that very few companies make the vaccine.

Calls for more vaccine
Last year there was a shortage of annual flu vaccine. Congress and HHS agencies have been working to find ways to lure companies back into the business of making it.

So Bush met with the chief executive officers of some of the top corporate makers of vaccines.

They included Richard Clark, president and CEO of Merck & Co. Inc., Robert Essner, chairman, president and CEO of Wyeth, Jean-Pierre Garnier, CEO of GlaxoSmithKline, David Mott, president and CEO of MedImmune, Howard Pien, chairman, president and CEO of Chiron Corp., and David Williams, CEO of Sanofi Pasteur, the vaccine unit of Sanofi-Aventis.

“It was primarily for the president to express directly to them the importance he places on this issue and to thank them for their willingness to step up and to cooperate with us on the development of a pandemic plan, both for the short-term and the long-term,” Health and Human Services Secretary Mike Leavitt, who attended the meeting, told reporters.

“We talked about what’s necessary to get to the goal of having enough vaccine in the shortest possible amount of time.”

International meeting
Only a few blocks away, the U.S. State Department wrapped up a meeting of diplomats and United Nations experts.

“That’s a very good indication of the importance countries around the world place on this issue, said Kang Kyoung-wha, director general of the South Korean Foreign Ministry’s international organizations bureau.

“This initiative on the part of the United States government has solidly placed the avian influenza and the very real threat of a pandemic very high on the global agenda,” Kang told Reuters.

Officials have used SARS as an example of how countries must quickly share information.

Severe Acute Respiratory Syndrome first started affecting people in China’s Guangdong province in late 2002, but it was not reported until months later. By June 2003 it had swept to several cities around the world, infecting close to 8,000 people and killing about 800 before it was stopped.

China was accused of failing to share information and ask for help quickly enough.

“I think they’ve learned from their SARS experience that transparency is important from the earliest stages,” Kang said.

Leavitt: Bird flu 'demands our attention'
International representatives in U.S. to discuss preparations

WASHINGTON (AP) -- The Bush administration's top health official said Thursday that "no one in the world is ready" for a potentially catastrophic outbreak of Avian bird flu.

But Health and Human Services Secretary Mike Leavitt also said that U.S. officials and their counterparts around the globe recognize that a pandemic is possible and are working hard on ways to protect people from it.

"The good news is, we do have a vaccine," Leavitt said on CBS's "The Early Show." But he cautioned that officials do not currently have an ability to mass produce it or get it to people quickly.

"It's enough of a possibility that it demands our attention," he said. "We have to be prepared all the time ... for that type of problem and we need to improve."

Outlining the pandemic plan in an interview Wednesday with The Associated Press, Leavitt said U.S. health officials would rush overseas to wherever a bird flu outbreak occurred and work with local officials to try to contain it.

"If you can get there fast enough and apply good public health techniques of isolating and quarantining and medicating and vaccinating the people in that area, you can ... squelch it or you can delay it," Leavitt said in an interview with The Associated Press.

Leavitt is traveling to Asia to shore up international cooperation should bird flu mutate to easily infect people.

To further that goal, more than 65 countries and international organizations were to participate in discussions Thursday at the State Department about preparations for the possibility of worsening bird flu.

Next week, Leavitt plans to meet with leaders of the Southeast Asia countries that are the epicenter of the virus.

There have been three flu pandemics in the last century; the worst, in 1918, killed as many as 50 million people worldwide.

Scientists say it is only a matter of time before the next worldwide influenza outbreak. Concern is rising that it could be triggered by the avian flu called H5N1.

That virus has killed or led to the slaughter of millions of birds, mostly in Asia, but also in parts of Europe. It has killed about 60 people, mostly poultry workers, because so far the virus does not spread easily from person to person.

The fear is that it will mutate to spread easily, a catastrophe because H5N1 is so different from annual flu strains that people have no natural immunity.

"The probability that the H5N1 virus will create a pandemic is uncertain. The signs are worrisome," Leavitt said. He added that the updated pandemic plan, due this month, envisions other super-strains of flu, too.

Role-playing different outbreak possibilities over the past few months led federal health officials to broaden their focus on how to detect a bird-flu mutation in another country and quickly send overseas help.

If that fails, the pandemic plans' first draft last year called for closing schools, restricting travel and other old-fashioned quarantine steps, depending on how fast the super-strain was spreading and its virulence. Those steps are getting renewed attention after President Bush's comments Tuesday that troops might have to be dispatched to enforce a mass quarantine.

Typically, state and local authorities deal with quarantine decisions -- isolating the sick and closing large gatherings where diseases might spread.

"They have to be prepared, and frankly they're not," Leavitt said.

The updated plan will outline when federal health officials will take over for the locals, something that will depend on how the flu is spreading, he said. For instance, mass quarantines were needed in 1918, but not during the pandemics of 1957 and 1968, he said.

As for treatment, HHS last month began spending $100 million for the first large-scale production of a bird flu vaccine. But the department has been criticized for only stockpiling enough of the anti-flu drug Tamiflu for several million people. The Senate last week passed legislation that would increase those purchases by $3 billion.

A bigger gap is how to create quickly a vaccine to match whatever pandemic flu strain erupts, Leavitt said. That currently takes months. The new plan will focus on rejuvenating vaccine production to speed the process, he said.

Researchers reconstruct 1918 virus
Scientists seek better understanding of bird flu

ATLANTA, Georgia (AP) -- Scientists have made from scratch the Spanish flu virus that killed as many as 50 million people in 1918, the first time an infectious agent behind a historic pandemic has ever been reconstructed.

Why did they do it? Researchers say it may help them better understand -- and develop defenses against -- the threat of a future worldwide epidemic from bird flu.

Like the 1918 virus, the current avian flu in Southeast Asia occurs naturally in birds. In 1918, the virus mutated, infected people and then spread among them. So far, the current Asian virus has killed at least 65 people but has rarely spread person-to-person.

But viruses mutate rapidly and it could soon develop infectious properties like those seen in the 1918 bug, said Dr. Jeffery Taubenberger of the U.S. Armed Forces Institute of Pathology.

"The effort to understand what happened in 1918 has taken on a new urgency," said Taubenberger, who led the gene-sequencing team.

The public health risk of resurrecting the virus is minimal, U.S. health officials said. People around the world developed immunity to the deadly 1918 virus after the pandemic, and a certain degree of immunity is believed to persist today. Also, in previous research, scientists concluded that modern antiviral medicines are effective against Spanish flu-like viruses.

The virus recreation, announced Wednesday, is detailed in the journal Science. The completion of that gene sequencing was announced in the journal Nature.

The virus was made from scratch, but based on a blueprint from Alaska.

Taubenberger's team sequenced genome information recovered from a female flu victim buried in the Alaskan permafrost in 1918. Then, they shared the data with researchers at New York's Mount Sinai School of Medicine. Using a technique called reverse genetics, the Mount Sinai researchers used the genetic coding to create microscopic, virus-like strings of genes, called plasmids.

The plasmids then were sent to the federal Centers for Disease Control and Prevention in Atlanta, where they were inserted into human kidney cells for the final step in the virus reconstruction.

"Once you get the plasmids inside the cell, the virus assembles itself," said Terrence Tumpey, the CDC research scientist who assembled the virus. "It only takes a couple of days."

About 10 vials of virus were created, each containing about 10 million infectious virus particles, Tumpey said in an interview with The Associated Press. More may be created, he said, to accommodate researchers' future needs.

The virus particles are being stored at the CDC, and there are no plans to send samples off campus, said Dr. Julie Gerberding, the agency's director.

However, the genetic information sequenced by Taubenberger is being placed in GenBank, a public genetic sequence database operated by the National Institutes of Health.

Scientists need access to the research as they try to develop vaccines and antiviral medications against potential future pandemic agents, said Donald Kennedy, editor-in-chief of Science.

"We carefully considered the implications of publishing this research and concluded that the knowledge we're gaining to potentially protect public health far outweighs the risk of working with the virus," Kennedy said.

The Spanish flu of 1918 was a terrible pandemic. In a few months, it killed more people than any other illness in recorded world history -- an estimated 20 million to 50 million worldwide, including roughly 550,000 in the United States.

In severe cases, victims' lungs filled with fluid and they essentially drowned in a disease process that took less than a week. It was known for being particularly dangerous to young adults, a group usually less susceptible to flu complications than younger and older people.

A flu virus has eight gene segments. Taubenberger and other researchers previously had published the sequences of five of them, but they accounted for less than half of the virus's total sequence. The new work completes it.

The three new segments appear to be crucial in explaining how the bird-based virus became adapted to humans, Taubenberger said.

Tumpey also confirmed the 1918 virus's avian-like characteristics by injecting it in fertilized bird eggs. It killed the eggs, just like the Asian bird flu does. Other modern-day flu strains that are human-based don't kill fertilized bird eggs, he noted.

The researchers also refined their focus on one gene, the HA gene, that encodes the hemagglutinin surface protein that help the virus attach to cells and multiply. The 1918 virus is deadly with the HA gene, but when the gene was replaced, it was not virulent, Tumpey said.

The virus's genetic properties may explain why it was able to settle deeper in the lungs than most current flu strains, causing the drowning condition, he said.

Virologist Yoshihiro Kawaoka of the University of Wisconsin-Madison and the University of Tokyo called the work important.

"We need to understand why this virus was so pathogenic," he said.

He also noted that Tumpey's work had to go through a variety of scientific reviews and approvals -- a process Tumpey said took about three years.

"If there was any concern about safety, the experiment would not have been approved," Kawaoka said.

Bush pushes for mass-produced bird flu vaccine
President urges drug manufacturers to expand production capacity
The Associated Press, Updated: 9:06 p.m. ET Oct. 6, 2005

WASHINGTON - President Bush summoned vaccine manufacturers to a White House meeting Friday, hoping to personally boost the rickety industry amid increasing fears of a worldwide outbreak of bird flu. It’s the latest in a flurry of preparations for a possible pandemic after criticism of the government’s response to Hurricane Katrina.

This month, vaccine maker Sanofi-Pasteur begins the first mass production of a new vaccine that promises to protect against bird flu, producing $100 million worth of inoculations for a government stockpile.

But it would take months to create a new vaccine from scratch if a different strain of bird flu than today’s known as H5N1 emerges. Even if the vaccine works, Sanofi is producing enough to protect anywhere from 2 million to 20 million people — depending on how much must be put into each dose — and it’s not clear when or where similar large stockpiles could be made.

The nation has only three main manufacturers of vaccine against the regular flu that circulates each winter.

Bush called together the heads of major vaccine companies “to press ahead to expand our manufacturing capacity for a vaccine to address this risk,” White House spokesman Scott McClellan said Thursday.

Obstacles to increased production
On the agenda for Friday’s meeting is liability, McClellan said. If healthy people suffer side effects from a vaccine, manufacturers can face huge lawsuits, one reason many companies have left the business in the last two decades.

Another reason is that vaccines simply aren’t very profitable, especially flu vaccine, which must be made fresh every winter to keep up with newly circulating strains. The irony: Although there have been three shortages since 2000 and supplies are strained again this year, in most years manufacturers throw away millions of unused flu shots.

“We cannot handle the threats we face today with a broken flu vaccine system,” said Sen. Hillary Rodham Clinton, D-N.Y.., who with Sen. Pat Roberts, R-Kan., introduced legislation Thursday that would, among other things, financially guarantee a market in return for more vaccine production.

A spokeswoman for one manufacturer who plans to attend Friday’s White House meeting said a pandemic will transcend those issues.

“When you’re actually in a pandemic situation, it’s all hands to the wheel,” said Nancy Pekarek, spokeswoman for GlaxoSmithKline, which hopes to begin testing its experimental bird flu vaccine in people next year. “It’s got to be many, many people producing what they can.”

Later this month, the Bush administration will issue updated plans to deal with a pandemic, and a key part will be “how to revitalize that industry in a way to have the capacity not just that it meets H5N1 but any potential pandemic virus,” Health and Human Services Secretary Mike Leavitt told The Associated Press.

'A Category 5 viral hurricane'
Scientists have been warning for two years that bird flu in Southeast Asia is growing more ominous and the nation must prepare.

“If the avian flu were to hit here, it would be like having a Category 5 viral hurricane hit every single state simultaneously. We’re not ready for that,” said Shelley Hearne, director of the nonprofit Trust for America’s Health, which backed the vaccine legislation.

“The lawmakers in the last few months have been paying attention,” said Hearne, who cites Hurricane Katrina as a key reason.

The Bush administration has been criticized for not getting help fast enough to devastated Gulf Coast states after the storm.

Bush has pushed the focus now on bird flu, by suggesting Tuesday that the military might be needed to enforce mass quarantines and by repeatedly raising the specter of a pandemic.

In the flurry of activity, the Senate last week passed legislation authorizing $4 billion for additional purchases of anti-flu medication. The vast majority is to buy Tamiflu, a pill to both treat and possibly prevent bird flu but that is in short supply. Leavitt has called for a Tamiflu stockpile to treat 20 million people, but the government has enough for just 4.3 million so far.

Influenza pandemics erupt every few decades — the worst was the 1918 Spanish flu that killed some 50 million people worldwide — when the virus mutates into a uniquely different strain. The world is overdue; the last pandemic was in 1968.

Even the ordinary flu kills 36,000 Americans every year. The bird flu so far has killed only about 60 people, mostly poultry workers, even as it has killed or led to the slaughter of millions of birds. But if it changes so it can spread easily from person to person, it would be catastrophic because people have no natural immunity to it.