We’ve come a long way since Jenner’s primitive cowpox vaccine for smallpox. In the 1700s there was no concept of the microbial world and the pathogens that abound there. The nature of infectious diseases and how our bodies respond to protect us from these invisible marauders was a complete mystery. Yet curious men and women were beginning to make careful observations and develop rational explanations for the causes of illnesses. From these rudimentary attempts to understand disease grew the foundations of the scientific method: observe, hypothesize, test, and repeat. During the 1800s, advances in light microscopy and culture media fully revealed the microscopic world and allowed bacteria to be seen and grown by investigators. By the end of the 1800s, the brilliance of Pasteur, Koch, and their contemporaries disproved primitive ideas about infectious illnesses and established the causal relationship between specific microbes and diseases. The paradigm that each infectious disease was caused by a unique microbe was both revolutionary and transformative. No longer could sickness be ascribed to elusive and unsubstantial ill winds or bad humors. Instead, having a distinct, physical entity as the causative agent meant that pathogens could be isolated and studied to reveal their secrets. There was hope that understanding a microbe would lead to cures or preventative measures to combat its disease, and progress on this goal was being made on important illnesses such as anthrax, cholera, and rabies. It was a golden era of early microbiology as numerous bacteria were isolated, characterized, and named, giving order and structure to the previously unknown microscopic realm. But there was one final conundrum of that century, the filterable agents.