"Combating a disease of unknown cause is a daunting task. One hundred years ago, a pandemic of poorly understood etiology and transmissibility spread worldwide, causing an estimated 50 million deaths. Initially attributed to Haemophilus influenzae, it was not until the 1930s that an H1 subtype was identified as the causative strain. Subsequent influenza pandemics in 1957, 1968, and 2009 did not approach levels of morbidity and mortality comparable to those of the 1918 “Spanish flu,” leaving unanswered for almost a century questions regarding the extraordinary virulence and transmissibility of this unique strain."