Early Observations:
Prehistoric humans had a very limited understanding of the causes of disease, and various cultures developed different beliefs and explanations. While many believed that illness was punishment for angering the gods or was simply the result of fate, archaeological evidence suggests that prehistoric people attempted to treat illnesses and infections.
Several ancient civilizations appear to have had some understanding that disease could be transmitted by things they could not see. This is especially evident in historical attempts to contain the spread of disease.
The ancient Greeks attributed disease to bad air, mal'aria, which they called "miasmatic odors." They developed hygiene practices that built on this idea. The Romans also believed in the miasma hypothesis and created a complex sanitation infrastructure to deal with sewage.
The Greek philosopher and historian Thucydides (460 - 395 BC) is considered the father of scientific history because he advocated for evidence-based analysis of cause-and-effect reasoning. Among his most important contributions are his observations regarding the Athenian plague that killed one-third of the population of Athens between 430 and 410 BC. Having survived the epidemic himself, Thucydides made the important observation that survivors did not get re-infected with the disease, even when taking care of actively sick people. This observation shows an early understanding of the concept of immunity.
Even before the invention of the microscope, some doctors, philosophers, and scientists made great strides in understanding the invisible forces (what we now know as microbes) that can cause infection, disease, and death.
Hippocrates:
The Greek physician Hippocrates (460 - 370 BC) is considered the "father of Western medicine" and was a pupil of Democritus (who proposed the idea of the atoms). Unlike many of his ancestors and contemporaries, he dismissed the idea that disease was caused by supernatural forces. Instead, he posited that diseases had natural causes from within patients or their environments.
Hippocrates intorduced a new system of treatment; he began by making a careful study of the patient's body, and having diagnosed the complaint, set about curing it by giving directions to the sufferer as to his diet and the routine of his daily life, leaving nature largely to heal itself.
Birth Of Microbiology:
Marcus Terentius Varro (116 - 27 BC) was a prolific Roman writer who was one of the first people to propose the concept that things we cannot see (what we now call microorganisms) can cause disease. In Res Rusticae (On Farming), published in 36 BC, he said that “precautions must also be taken in neighborhood swamps... because certain minute creatures [animalia minuta] grow there which cannot be seen by the eye, which float in the air and enter the body through the mouth and nose and there cause serious diseases.
While the ancients may have suspected the existence of invisible "minute creatures," it wasn't until the invention of the microscope that their existence was definitively confirmed. While it is unclear who exactly invented the microscope, a Dutch cloth merchant named Antonie van Leeuwenhoek (1632 - 1723) was the first to develop a lens powerful enough to view microbes. In 1675, using a simple but powerful microscope, Leeuwenhoek was able to observe single-celled organisms, which he described as "animalcules" or "wee little beasties," swimming in a dropof rain water.