Why was the 1918–1919 flu pandemic worse than any before or since?

Many different strains of influenza virus circulate among human populations and other vertebrate hosts each year, but only a few of those strains survive and produce descendants. One of the ways in which influenza strains differ is in the configuration of proteins on their surface. These surface proteins are the targets of recognition by the host immune system. When changes occur in the surface proteins of an influenza virus, the host immune system may no longer recognize the invading virus, so that virus is more likely to replicate successfully. Those virus strains with the greatest number of changes to their surface proteins are most likely to escape detection by the host immune system, and are therefore most likely to spread among the host population and result in future flu epidemics. In other words, there is positive selection for change in the surface proteins of influenza viruses.

As demonstrated by data presented in Investigating Life: Why Was the 1918–1919 Influenza Pandemic So Severe?, the 1918–1919 flu epidemic occurred shortly after the cross-species transfer of an avian flu virus into human populations. For humans, this was a new virus, different than any influenza viruses that had circulated before in human populations. As human immune systems had no previous exposure to this virus, they had not yet developed effective immune defenses. The virus overstimulated human immune systems, which led to secondary complications and death. Today, investigators carefully monitor influenza viruses circulating in human populations around the world. Early detection of new cross-species transmissions from birds or pigs into human populations is the key to their elimination before they can result in new global human influenza pandemics.

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Future directions

By comparing the survival and proliferation rates of influenza virus strains that have different gene sequences coding for surface proteins, biologists can study the adaptation of the viruses over time. If biologists can predict which of the currently circulating flu virus strains are most likely to escape host detection, they can then identify the strains that are most likely to be involved in upcoming influenza epidemics and can target those strains for vaccine production.

How can biologists make such predictions? By determining the ratio of synonymous to nonsynonymous substitutions in genes that encode viral surface proteins, biologists can detect which codon changes (i.e., mutations) are under positive selection. They can then assess which of the currently circulating flu strains show the greatest number of changes in these positively selected codons. It is these flu strains that are most likely to survive, proliferate, and lead to the flu epidemics of the future, so they are the logical targets for new vaccines. This practical application of evolutionary theory leads to more effective flu vaccines—and thus fewer illnesses and influenza-related deaths each year.