Unanswered questions about the 1918 influenza pandemic: origin, pathology, and the virus itself.

The influenza epidemic of 1918 represented the greatest failure of medical science in the 20th century. Fortunately, research throughout subsequent years has been making amends. Some studies have applied RT-PCR to the tissue samples from that time, whereas others have reconstructed the pathogen in its virulent state. But the resurrection of the 1918 influenza virus leaves questions unanswered: although more virulent than contemporary H1N1 epidemic viruses in animal models, this increased virulence of the 1918 influenza virus is not sufficient to have been the sole cause of the high mortality rates recorded in humans during the epidemic. Thus, other hypotheses have been investigated. The immune history of the different age groups exposed at the time to the pandemic virus could be a factor, and the notion of original antigenic sin provides an explanation for the unusual pattern of deaths. The presence, or absence, of a cytokine storm in the lungs of young adults might also be involved. The time and location that the 1918 influenza pandemic first emerged from its avian reservoir is contentious, with arguments for China, Europe, and the USA, at various dates. Novel vaccines were tested during 1918, which are the precursors of the universal influenza vaccines that might offer protection in a future pandemic.