The sequencing of the Spanish influenza virus was considered a scientific breakthrough, but was highly controversial. Scientists, ethicists, and others argued that reconstituting a disease that infected a quarter of the world's population and caused more deaths than any other in history was both unnecessary and irresponsible.  When scientists reengineering the virus and infected mice, they found that the virus was still as lethal as it had been in 1918. So was the work worth the risk?

Humans today have antibodies that react to the H1N1 strain of the 1918 influenza virus. Ferrets who are given the vaccines that are developed yearly to combat seasonal flu also seem to show immunity against the 1918 Spanish flu. The evolutionary relationships between the 1918 influenza virus and subsequent classical swine viruses were highlighted with the unexpected emergence of the 2009 H1N1 pandemic. Because the 2009 pandemic H1N1 virus contains the HA gene derived from the classical swine H1N1 lineage, it is antigenically very similar not only to classical swine H1N1 viruses, but also to the 1918 virus, the likely ancestor of both human and classical swine H1N1 lineages. Consequently, seroepidemiologic studies demonstrated cross-protective immunity in the population, primarily in people >60 years. In a recent set of experiments, it was shown that mice vaccinated with the 2009 pandemic H1N1 vaccine were completely protected in a lethal challenge model with the 1918 influenza virus. These data suggest that either prior infection or vaccination with the 2009 pandemic H1N1 virus may protect the population from a possible future 1918 or 1918-like pandemic.

Studies on the reconstituted virus lead scientists to the conclusion that it emerged from an avian flu virus in birds, which is of use to epidemiologists watching for new virus outbreaks of H5N1 in bird populations today. The changes in the genes that have been identified in the 1918 virus may also help scientists discover how the 1918 virus was able to jump from birds to humans and pigs. Recreating the living virus helped researchers investigate why the Spanish flu was so highly virulent and what specific genetic factors were involved. This could lead to better vaccines and responses to pandemic influenza outbreaks.