By BLOOMBERG NEWS
Published: January 18, 2007
Scientists infected monkeys with a virus that caused the 1918-19 influenza pandemic and said in the Jan. 18 issue of the journal Nature that it caused an illness like that suffered by patients with the bird flu now spreading in Asia.
Infection with a reconstructed version of the 1918 virus, known as the Spanish flu, incited a deadly chemical reaction in the laboratory animals, a group of scientists said in the magazine.
The group was led by Darwyn Kobasa, a researcher for the Public Health Agency of Canada in Winnipeg, Manitoba. Both the Spanish flu and H5N1 bird flu in Asia appear able to set off the reaction, the researchers said. Studying the Spanish flu virus’s interaction with monkeys may help health officials prepare for a possible pandemic caused by H5N1.
“We see responses that are similar between humans infected with H5N1 and nonhuman primates infected with the 1918 virus,” said Yoshihiro Kawaoka, a virologist at the University of Wisconsin in Madison. “By studying this model in detail, we may learn to cope with those immune responses.”
The 1918 flu may have killed as many as 50 million people, about 2 percent of those infected. Researchers say the outbreak started as a bird virus, until genetic changes enabled it to spread in people.
Similar mutations may allow H5N1 to set off a pandemic, researchers say. The bird flu has infected 267 people, mostly poultry workers or keepers in Asia, and killed 161 of them since late 2003, according to data compiled by the World Health Organization.
While the study points to an immune response as a probable cause for the destructiveness.. of the 1918 flu, researchers are still learning about the virus, said Michael Katze, a microbiologist at the National Primate Research Center at the University of Washington in Seattle.
“We know very little about why these viruses are so lethal,” Dr. Katze said.
Research has shown that H5N1 kills mice, causing the same kind of chemical reaction, called a cytokine storm, seen in the monkeys. Many other flu viruses are also fatal in mice, and the researchers said it was important to conduct studies in primates.
In 2005, Army scientists reported that they had reconstructed the Spanish flu virus by extracting genetic fragments from the bodies of victims exhumed from the Alaskan permafrost. American and Canadian researchers compared the effects of the virus on monkeys with those of seasonal flus.
The 1918 virus grew faster and spread more widely in the monkeys than the other viruses. While the immune reaction to the seasonal viruses abated after a few days, the response in monkeys with Spanish flu persisted, damaging tissues and impairing lung function, the study said.
http://www.nytimes.com/2007/01/18/health/18flu.html?ex=1326776400&en=4133fd36181a9c2a&ei=5088&partner=rssnyt&emc=rss
Scientists recreate 1918 flu virus, see parallels with H5N1
Robert Roos * News Editor
Oct 5, 2005 (CIDRAP News) – Scientists today reported findings that may help explain what made the 1918 pandemic influenza virus so deadly and that reveal similarities between that virus and the H5N1 avian influenza virus now circulating in Asia.
Scientists at the Centers for Disease Control and Prevention (CDC) reconstructed the virus and tested it in laboratory animals, which quickly died. The CDC says the work, to be reported in Science, will enhance preparedness for the next flu pandemic, a potential benefit believed to justify the risk of recreating the virus and publishing the information.
In the other study, researchers at the Armed Forces Institute of Pathology (AFIP) report that the close resemblance of the 1918 virus to avian flu viruses suggests that the 1918 virus was an avian strain that managed to adapt to humans without first acquiring any genes from existing human flu viruses. Further, the researchers found that several of the same mutations that differentiated the 1918 virus from avian flu viruses are found in the H5N1 virus, which has killed more than 60 people in Asia. The report appears in Nature.
The 1918 flu pandemic, regarded as the worst in history, killed as many as 100 million people. In recent years scientists have been able to learn the structure of the H1N1 virus that caused it by analyzing samples preserved from pandemic victims, including tissue from a frozen body exhumed in Alaska and material stored in the AFIP's warehouse of autopsy samples.
In a joint statement today, the directors of the CDC and the National Institute of Allergy and Infectious Disease (NIAID), Dr. Julie Gerberding and Dr. Anthony Fauci, said, "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 statement was released by the NIAID.
"The new studies could have an immediate impact by helping scientists focus on detecting changes in the evolving H5N1 virus that might make widespread transmission among humans more likely," the statement said.
Because of concern that terrorists could exploit the information, both articles were reviewed by the National Science Advisory Board for Biosecurity before publication, according to the NIAID statement. The board unanimously endorsed publishing them.
"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," Gerberding and Fauci stated.
Resurrection of the 1918 virus
In the Science article, Terrence M. Tumpey and colleagues report that they generated a flu virus bearing all eight gene segments of the 1918 virus in order to study what made it so virulent. They exposed groups of mice to that virus and to other viruses in which some of the 1918 virus's genes were replaced by genes from recent flu viruses.
The 1918 virus turned out to be extremely virulent. Mice infected with it died in as little as 3 days, and mice that survived as long as 4 days had 39,000 times as many virus particles in their lungs as did mice infected with a control flu virus, a Texas strain of H1N1 from 1991. All the mice infected with the 1918 virus died, while those exposed to the Texas strain survived. Further, the 1918 virus was at least 100 times as lethal as an engineered virus that contained five 1918 genes and three genes from the Texas H1N1 strain.
The researchers found that the mice had severe inflammation in their lungs and bronchial passages—findin..gs very similar to those in people who died of the 1918 virus. However, the virus did not spread in the mice to the brain, heart, liver, or spleen.
The scientists also tested the virus's behavior in a laboratory culture of human lung cells. Within 24 hours, the lung cells released at least 50 times as much virus as did lung cells infected with the Texas H1N1 strain.
In comparing the 1918 virus with recombinant viruses containing only some of the 1918 genes, the researchers found that the 1918 hemagglutinin and polymerase genes were "essential for optimal virulence." The complete 1918 virus was more pathogenic for mice than any other human flu virus that has been tested, the report says.
Likeness between 1918 virus and avian strains
The Nature article, by Jeffery Taubenberger and colleagues from the AFIP, reports on an analysis of the three polymerase genes in the 1918 virus, the last three genes to be fully spelled out. The researchers found that these genes closely resembled their counterparts in avian flu viruses.
"The polymerase protein sequences from the 1918 human influenza virus differ from avian consensus sequences at only a small number of amino acids, consistent with the hypothesis that they were derived from an avian source shortly before the pandemic," the report states.
Accordingly, the researchers propose that the 1918 virus was not a "reassortant," like those that caused the smaller pandemics of 1957 and 1968. In those cases, avian flu viruses traded some genes with human-adapted flu viruses to spawn new hybrids. The 1918 virus was "an entirely avian-like virus" that somehow adapted to humans, they suggest.
The report says only 10 amino-acid changes in the polymerase genes consistently distinguish the 1918 virus and subsequent human flu viruses from the same genes in avian viruses. It adds, "A number of the same changes have been found in recently circulating, highly pathogenic H5N1 viruses that have caused illness and death in humans and are feared to be the precursors of a new influenza pandemic."
A news story accompanying the report in Nature says that all eight genes from the 1918 virus differ in important ways from other human flu genes, which suggests that none of the genes came from a flu strain that had previously infected people. "It is the most bird-like of all mammalian flu viruses," Taubenberger is quoted as saying.
According to the Nature news story, some scientists are questioning the wisdom of recreating the 1918 virus and publishing information on how it was done. Richard Ebright, a bacteriologist at Rutgers University in New Jersey, said Tumpey and colleagues "have constructed, and provided procedures for others to construct, a virus that represents perhaps the most effective bioweapons agent now known."
In a news release, the CDC said it used "stringent" precautions in the research. "The work was done in a high-..containment Biosafety Level 3 lab with enhancements that include special provisions to protect both laboratory workers and the public from exposure to the virus," the agency said.
Taubenberger JK, Reid AH, Lourens RM, et al. Characterizatio..n of the 1918 influenza virus polymerase genes. (Letter) Nature 2005 Oct 6;..437(..7060):889-892 [Full text]
Tumpey TM, Basler CF, Aguilar PV, et al. Characterizatio..n of the reconstructed 1918 Spanish influenza pandemic virus. Science 2005 Oct 7;..310(..5745):77-80 [Abstract]
See also:
Oct 5 NIAID Press release
http://www3.niaid.nih.gov/news/newsreleases/2005/0510state.htm
Of course the CDC scrubbed any record of this off their website,but other news outlets reported the story,so the info is still out there no matter how much they try to hide it.
http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/oct0505studies.html
October 5, 2005
STATEMENT
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 scientists 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 counterproducti..ve 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.
http://www3.niaid.nih.gov/news/newsreleases/2005/0510state.htm
