Microorganisms were an almost entirely unknown part of life before the invention of the microscope in the 17th century. There was some speculation about the existence of invisible beings causing disease, but this was not based in the scientific method. The first observation of (and use of the word) cells using a microscope was made by Robert Hooke, which he described in his book Micrographia. This allowed for the first entry into the field of microbiology with Antoni van Leeuwenhoek’s observation of microbes. He did not make the connection to the many processes that various microbes cause (fermentation, causing diseases, etc.), but the establishment of the existence of “invisible life” was groundbreaking. This establishment allowed Lazzaro Spallanzini and Louis Pasteur to both conduct experiments in which they sterilized a nutrient broth and tested whether microorganisms would grow. Spallanzini’s experiments proved that sterilization via boiling was possible and showed that microorganisms would only grow when the broth was exposed to air; Pasteur’s experiments expanded on and eventually proved the idea that spontaneous generation could not happen. Some organization within the field began to happen when Ferdinand Cohn classified bacteria into 4 basic shapes (categories that are still used today) and when Robert Koch established that microbes can cause disease and subsequently established Koch’s postulates. Koch’s postulates establish criteria to determine whether or not a specific bacteria is the cause of a disease. They state that:
The bacteria must be present in every case of the disease.
The bacteria must be isolated from the host and grown in a pure culture.
The same disease must be reproduced if a pure culture is inoculated into a healthy susceptible host.
The bacteria must be isolated from the experimentally infected host.
Naturally, Koch’s postulates are not applicable in every case. Some bacteria cannot be grown in pure culture or do not have an adequate animal model used for testing. Others are not pathogenic in every case. However, finding bacteria as a causal agent of disease was a massive, groundbreaking step. The logical next step was, of course, finding a way to treat and cure bacterial diseases. This first step was taken by Paul Ehrlich, who studied hundreds of derivatives of a highly toxic drug for syphilis, eventually discovering one that was effective and safe. Until the 1940s when it was replaced by penicillin, Ehrlich’s drug was the most commonly prescribed drug in the world. Soon after Ehrlich’s success, Alexander Fleming discovered the antibacterial properties of Penicillium mold by accidentally letting it grow in some cultures while he took a vacation. After this discovery, he spent a decade working to purify penicillin for clinical use, but largely failed. Interest in the antibiotic waned and studying it fell out of favor until 1939, when a team at Oxford were finally able to purify penicillin and test it on mice infected with a strain of Streptococcus. The results were striking, and after some clinical efficacy testing, the Oxford team traveled to the US to research strains of Penicillium mold that produce penicillin and to hand off production of the antibiotic to drug companies (which was promptly taken over by the US government when World War II began). Immunology as a field began before Pasteur, Koch, or Fleming with Edward Jenner’s invention of the first vaccine through intentional infection with cowpox as a protective measure against smallpox. However, Pasteur took this concept and expanded heavily on it. He initially found that strains of chicken cholera (an infection actually caused by bacteria in the genus Pasteurella) would become attenuated, or less pathogenic, over time. He took these attenuated strains and inoculated susceptible chickens, who were then immune to the pathogenic strains. He took this concept and focused on it for the rest of his career, applying it to multiple other diseases. He eventually created a vaccine for anthrax, used in farm animals, and a vaccine for rabies, used in humans. His rabies vaccine was, incidentally, a foray into the field of virology, though the existence of viruses was not yet known. The existence of viruses was first hinted at with the experiments of Adolf Mayer and Dmitri Ivanowsky, who both separately found that the sap of tobacco plants infected with tobacco mosaic disease could be passed through laboratory filters with pores too small for bacteria to pass through and still be infectious. Neither came to the conclusion that the disease was caused by a novel infectious agent; that connection was made by Martinus Beijerinck, who did the same experiment, but continued studying the disease, finding that it was infectious, but could not grow independently and required host cells to reproduce. Beijerinck thus established the existence of viruses, though this discovery would take almost twenty years to be widely accepted due to the ubiquity of Koch’s postulates. The field of microbiology is, at the moment, going through a convergence, almost entirely focusing on the novel coronavirus SARS-CoV-2. Given the near-complete lack of control of this virus in the US, the first priority right now is finding an effective treatment for the coronavirus. The next priority is finding a vaccine, a few of which are already in clinical testing. The treatments being tested are largely being adapted from existing medicines used for other viruses. These treatments typically do one of two things; they either directly interrupt the viral replication, or they aim to either boost the innate immune system’s reaction to the virus or mitigate damage done by an overactive immune system. Some of the treatments being tested for replication interruption include Remdesivir, Favipiravir, and Ivermectin. One interesting treatment designed to bolster the immune system is the addition of natural killer cells, cells which already occur in the body and are vital to the function of the immune system, to those with lowered immune function. On the other hand, antibodies from those who have already contracted and recovered from COVID-19 are being studied and developed for use in patients who have adverse effects from the cytokine storm caused by COVID-19. In the realm of vaccines, there are multiple types being developed and tested. An mRNA vaccine, which allows human cells to create antigens from the mRNA in the vaccine, is currently being tested in humans. Other vaccines, such as a recombinant protein vaccine, a live attenuated vaccine, and an inactivated virus vaccine are all in preclinical testing. Though the mRNA vaccine is the furthest in testing phases, it is also the newest and most experimental technology. However, if safe and effective, an mRNA vaccine would be significantly easier and cheaper to produce than the other types of vaccines being tested.