Smallpox The culprit responsible for causing smallpox is the variola virus. The reason it is such a dangerous biological weapon is because it has only existed in military laboratories since the late 1960s. Consequently, we have a whole generation of human beings who have never received a vaccine. The threat looms large because some of the few frozen vials that exist are in the hands of certain individuals with hostile intentions. Smallpox has an insidious onset. During the first two to four days, this disease resembles the flu, with fever and joint and muscle aches. Then the victim breaks out in a rash over the entire body, including the hands and the soles of the feet. One to two weeks later, the rash turns to multiple scabs. The variola is an airborne virus and spreads from person to person via large and small respiratory droplets. Cross-contamination through direct contact can also occur. People with smallpox become contagious at the onset of the rash and remain so for about three weeks until the scabs start to slough.