It was noticed that Milk Maidens did not contract smallpox and that started the investigation. They discovered almost all had cowpox at one time and thus came the smallpox vaccine. I didn't know that about the Milk Maidens. That is amazing.
That is like John Snow observing that cholera was occurring near a specific water pump at Broad Street in the Soho district of the City of Westminster, London, England.
Also hand washing and general cleanliness of surgical aparatus traces to a Hungarian physician working in a maternity ward at a hospital in Vienna in the 1840s. He noticed that women who had their babies delivered by male doctors often got infections and died. Women who had their babies delivered by female midwives generally didn't. He further noted that the doctors often worked on other patients and even dissected cadavers prior to doing a child delivery and they never washed their hands, the midwives didn't treat sick people or corpses. He postulated that the doctors were somehow carrying illness from other patients on their hands and ordered them to wash. Death rates in the ward went from something like 18% to below 1%.
And still doctors refused to do it for a long time and rejected his findings. He ended up committed to a mental hospital and died in his 40s. But eventually the medical community caught on.