smallpox prophylaxis, is treatment with unattenuated variola virus taken from a pustule or scab of a smallpox patient into the superficial layers of the skin, commonly the upper arm. Variolation was often done 'arm-to-arm' or, less effectively, 'scab-to-arm', and often caused the patient to become infected with smallpox, which in some cases resulted in severe disease. Vaccinations began in the late 18th century with the work of Edward Jenner and the smallpox vaccine. Preventing disease versus preventing infection Some vaccines, like the smallpox vaccine, prevent infection. Their use results in sterilizing immunity and can help eradicate a disease if there is no animal reserve. Other vaccines, including those for , help to (temporarily) lower the chance of severe disease for individuals, without necessarily reducing the probability of becoming infected. Safety Vaccine development and approval Just like any medication or procedure, no vaccine can be 100% safe or effective for everyone because each person's body can react differently. While minor side effects, such as soreness or low grade fever, are relatively common, serious side effects are very rare and occur in about 1 out of every 100,000 vaccinations and typically involve allergic reactions that can cause hives or difficulty breathing. However, vaccines are the safest they ever have been in history and each vaccine undergoes rigorous clinical trials to ensure their safety and efficacy before approval by authorities such as the US Food and Drug Administration (FDA). Prior to human testing, vaccines are tested on cell cultures and the results modelled to assess how they will interact with the immune system. During the next round of testing, researchers study vaccines in animals, including mice, rabbits, guinea pigs, and monkeys. Vaccines that pass each of these stages of testing are then approved by the public health safety authority (FDA in the United States) to start a three-phase series of human testing, advancing to higher phases only if they are deemed safe and effective at the previous phase. The people in these trials participate voluntarily and are required to prove they understand the purpose of the study and the potential risks. During phase I trials, a vaccine is tested in a group of about 20 people with the primary goal of assessing the vaccine's safety. Phase II trials expand the testing to include 50 to several hundred people. During this stage, the vaccine's safety continues to be evaluated and researchers also gather data