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Avian (Chicken) Flu 'Epidemic' Expected
  Scientists resurrect 1918 flu, study deadliness
Wed Oct 5, 1:25 PM ET
WASHINGTON (Reuters) - Scientists who resurrected the 1918 "Spanish flu" virus that killed as many as 50 million people said on Wednesday they are beginning to understand why it caused such a deadly pandemic and say it could happen again.
They have begun comparing the genetic mutations in the 1918 flu to those being seen in the H5N1 avian flu virus killing tens of millions of poultry and some people in Asia, in the hope of being able to predict and perhaps even prevent a similar pandemic.
"We felt we had to recreate the virus and run these experiments to understand the biological properties that made the 1918 virus so exceptionally deadly," said Terrence Tumpey of the U.S. Centers for Disease Control and Prevention in Atlanta, who helped write the reports published jointly this week in the journals Nature and Science.
The experiment, in which the virus was recreated employing a process called reverse genetics using preserved samples of the 1918 virus, allowed the researchers to test it in the laboratory and in several animals.
It will help answer important questions, said Dr. Jeffery Taubenberger of the Armed Forces Institute of Pathology in Rockville, Maryland.
"How did the virus get into humans and how did the pandemic start? Second is to understand how this particular virus was so virulent," Taubenberger told reporters in a telephone briefing.
"What can we learn from the lessons of 1918 to prepare for and mitigate against a future influenza pandemic?" he asked.
Drugs and vaccines could be designed to target the mutations found in the research, Taubenberger said.
Taubenberger's team used pieces of virus taken from preserved samples from 1918 victims, as well as from the corpse of a victim dug up from a frozen grave in Alaska in 1998.
They used these pieces to make a replica of the 1918 virus, and brought it back to "life" -- viruses are not truly alive like other microbes -- by combining it with modern influenza virus pieces and growing it in bacteria.
"We now think that the best interpretation of the data available to us is that the 1918 virus was an entirely avian-like virus that adapted to humans," Taubenberger said.
This, he said, was different from the two other 20th century flu pandemics, in 1958 and 1967, in which different flu viruses actually swapped genes to become especially virulent. "It suggests that pandemics can form in more than one way," Taubenberger said.
There were several changes in each gene of the 1918 flu, Taubenberger said. The H5N1 flu is beginning to show some of the same changes, he said, but appears to be early on in the process.
The findings reinforce the fears of health officials about H5N1 avian flu, which now does not easily infect humans but which has killed more than 60 people in four Asian nations. It will take only a few mutations for a virus that has killed tens of millions of birds to become just as infectious and deadly in people.
But now the scientists are beginning to understand what the mutations are and perhaps start work on drugs and vaccines that can fight them.
"We identified a number of virus proteins that were essential for the development of severe pulmonary (lung) disease," Tumpey said.
In particular, he said, a protein called hemagglutinin -- the "H" in flu names -- was key. When the 1918 hemagglutinin was replaced with a modern influenza hemagglutinin, the resulting virus was not very deadly at all.
Also, another protein called neuraminidase was mutated in the 1918 virus in such a way that it could replicate itself under unusual conditions, perhaps deeper in the lung than other flu viruses. Neuraminidase is another key flu gene that makes up the "N" in flu designations.
The 1918 flu was an H1N1 flu and very different from H5N1, the researchers stress. They also said there was no danger to the public from their experiments, which are conducted in biosafety level 3 labs designed to contain the virus.
And today's human flu viruses are all descendants of the 1918 flu, which means people have some immunity to them, CDC director Dr. Julie Gerberding said. What is frightening about H5N1 is that people do not have any immunity to it.
If not H5N1, then some other influenza virus is certain to cause a pandemic that could be much worse than the 1918 flu, Gerberding said.
"Most experts agree it is not a question of if -- it is a question of when," she said.
"This important science creates new information and new clues that does help us prepare for the pandemic."
Researchers Reconstruct 1918 Pandemic Influenza Virus; Effort Designed To Advance Preparedness
October 5, 2005
Unmasking the 1918 Influenza Virus:
An Important Step Toward Pandemic Influenza Preparedness

Anthony S. Fauci, M.D., Director, National Institute of Allergy and Infectious Diseases National Institutes of Health and Julie L. Gerberding, M.D., M.P.H., Director, Centers for Disease Control and Prevention
The mysteries of the 1918-1919 influenza pandemic, that killed an estimated 50 million people across the globe, are finally beginning to be solved. Two scientific papers published this week provide insights into the virus that caused the most deadly influenza outbreak in modern history. This virus was unusual because it spread so quickly, was so deadly, and exacted its worst toll among the young and healthy. In just over one year, the virus infected one-third of the world's population with death rates approximately 50 times higher than those associated with regular seasonal influenza.
The harsh reality of the 1918 pandemic is never far from the minds of scientists and public health officials who are monitoring the current influenza outbreak occurring in Asia. Since December 2003, a strain of influenza virus that usually infects only birds has sickened at least 116 people and killed 60 in Thailand, Vietnam, Cambodia, and Indonesia. This virus, known as H5N1 avian influenza A virus, has killed or forced the culling of more than 100 million chickens in 13 countries, has infected ducks and other migratory birds, and has been transmitted to tigers, cats, and pigs. So far the virus is not easily passed from birds to humans, and thankfully, is not efficiently spread from one person to another when it does cross species. However, influenza viruses are notoriously capable of changing, and should the avian virus develop the ability to spread easily among people, a worldwide influenza pandemic could ensue, potentially rivaling in impact the 1918-1919 pandemic.
Understanding why and how influenza virus can reach global proportions and cause so many deaths is now an urgent imperative. The new research findings, published in the journals Science and Nature, provide critical clues to the genesis of the 1918 pandemic and why it was so lethal. The findings reveal essential information to help us speed our preparation for-and potentially thwart-the next influenza pandemic. For the first time, researchers have deciphered the entire gene sequence of the 1918 virus and have used sophisticated techniques to assemble viruses that bear some or all of these genes so their effects can be understood. Importantly, they have identified gene sequences that may predict when an influenza virus strain is likely to spread among humans. They also have determined in the test tube and in mice which genes are most likely to account for the lethal effects of the 1918 virus.
The new studies could have an immediate impact by helping scientist focus on detecting changes in the evolving H5N1 virus that might make widespread transmission among humans more likely. For example, on the basis of these studies we know that the H5N1 virus currently circulating in Asia has acquired five of the 10 gene sequence changes associated with human-to-human transmission in the 1918 virus. In addition, the findings also may lead to identification of new targets for drugs and vaccines to treat and prevent influenza, now and in the future.
The techniques described in these reports are not new and are already accessible to anyone with the will and means to conduct similar experiments. Nevertheless, some have understandably questioned whether these research findings should be reported in scientific journals because of concern that this knowledge could be used by those with nefarious intent. Prior to publication, these scientific papers were reviewed by the National Science Advisory Board for Biosecurity (NSABB), an advisory committee to the U.S. Secretary of Health and Human Services and to the heads of all federal departments and agencies that conduct or support life science research. The Board was established to provide advice on ways to minimize the possibility that knowledge and technologies emanating from vitally important biological research will be misused to threaten public health or national security. The Board is comprised of members with a broad range of expertise in molecular biology, infectious diseases, biosafety, public health, veterinary medicine, plant health, national security, biodefense, law enforcement, scientific publishing and related fields. The Board unanimously endorsed publication of the manuscripts and recommended "making such information widely available to the scientific community for the purpose of validating the research findings, building upon the research, and advancing the development of diagnostic assays, treatments, and preventative measures."
The rationale for publishing the results and making them widely available to the scientific community is to encourage additional research at a time when we desperately need to engage the scientific community and accelerate our ability to prevent pandemic influenza. It would be impossible and counterproductive to attempt to enforce a worldwide ban on conducting research on the 1918 influenza virus or similar viruses because of fear of the misuse of such knowledge. Likewise, the dissemination of information emanating from this research should not be suppressed; rather, we must foster a culture of responsibility among the scientific community such that research is conducted under the safest possible conditions and research results are presented openly and responsibly for the purpose of improving human health.
We concur fully with the recommendations of the NSABB. Moving forward with research conducted by the world's top scientists and openly disseminating their research results remain our best defense against H5N1 avian influenza virus and other dangerous pathogens that may emerge or re-emerge, naturally or deliberately. With better tools for detection and more effective countermeasures, the threat posed by such dangerous pathogens can be greatly reduced. We feel that the certain benefits to be obtained by a robust and responsible research agenda aimed at developing the means to detect, prevent and treat these threats far outweigh any theoretical risks associated with such research.
Media inquires can be directed to the NIAID OCPL media group at 301-402-1663.
NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.
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