Influenza
Researchers Reconstruct 1918 Pandemic Influenza Virus
By Centers for Disease Control and Prevention
Oct 6, 2005, 21:26

Influenza pandemics occur when a new strain emerges to which people have little or no immunity. Most experts believe another pandemic will occur, but it is impossible to predict which strain will emerge as the next pandemic strain, when it will occur or how severe it will be.

Scientists at the Centers for Disease Control and Prevention have successfully reconstructed the influenza virus strain responsible for the 1918 pandemic, a project that greatly advances preparedness efforts for the next pandemic.

�This groundbreaking research helps unlock the mystery of the 1918 flu pandemic and is critically important in our efforts to prepare for pandemic influenza,� said CDC Director Dr. Julie Gerberding. �We need to know much more about pandemic influenza viruses. Research such as this helps us understand what makes some influenza viruses more harmful than others. It also provides us information that may help us identify, early on, influenza viruses that could cause a pandemic.�

The work, done in collaboration with Mount Sinai School of Medicine, the Armed Forces Institute of Pathology and Southeast Poultry Research Laboratory, determined the set of genes in the 1918 virus that made it so harmful. This week�s issue of Nature also includes a related article entitled �Characterization of the 1918 influenza virus polymerase genes� which describes the final three gene sequences of the 1918 influenza virus. The 1918 pandemic killed an estimated 20-50 million people worldwide, including 675,000 in the United States. The pandemic�s most striking feature was its unusually high death rate among otherwise healthy people aged 15-34. During normal seasonal flu outbreaks, severe complications and death are most common among the elderly and young children.

The Spanish Flu Pandemic, also known as the Great Influenza Pandemic, the 1918 Flu Epidemic, and La Grippe, was an unusually severe and deadly strain of influenza, a viral infectious disease, that killed some 25 million to 50 million people worldwide in 1918 and 1919. It is thought to have been one of the most deadly pandemics so far in human history.

�Influenza viruses are constantly evolving, and that means our science needs to evolve if we want to protect as many people as possible from pandemic influenza.�

In reconstructing the 1918 influenza virus, researchers learned which genes were responsible for making the virus so harmful.

In September 2000, Noymer and Garenne published a study that poses an �tiological theory explaining the unusual W-shaped mortality age profile of the virus. This profile is characterized by a mode in the 25�34-year age group. Usually, influenza has a U-shaped profile, being most deadly to the young and the old. Additionally, after the pandemic the difference in life expectancy between men and women decreased (women had a historically longer life expectancy). Noymer and Garenne have causally linked these two anomalies with the predominantly-male mortality of tuberculosis.

In October 2002, the Armed Forces Institute of Pathology teamed up with a microbiologist from the Mount Sinai School of Medicine in New York. Together, they started to reconstruct the Spanish Flu. In an experiment, published in October 2002, they were successful in creating a virus with two 1918 genes. This virus was much more deadly to mice than other constructs containing genes from contemporary influenza virus. The experiments were conducted under high biosafety conditions at a laboratory of the US Department of Agriculture in Athens, Georgia.

In the February 6, 2004, edition of Science magazine it was reported that two teams of researchers, one led by Sir John Skehel, director of the National Institute for Medical Research in London and another by Professor Ian Wilson of the Scripps Research Institute in San Diego had managed to synthesize the hemagglutinin protein responsible for the 1918 outbreak of Spanish Flu by piecing together DNA procured from a lung sample taken from the body of an Inuit woman buried in the Alaskan tundra and a number of preserved samples taken from American soldiers of the First World War. The two teams had analyzed the structure of the gene and discovered how subtle alterations to the shape of a protein molecule had allowed it to move from birds to humans with such devastating effects.

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