- Feb 13, 2021
Louis Pasteur's first vaccine discovery was in 1879, with a disease called chicken cholera. After accidentally exposing chickens to the attenuated form of a culture, he demonstrated that they became resistant to the actual virus -- Louis Pasteur, the father of immunology --
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- Louis Pasteur is traditionally considered as the progenitor of modern immunology because of his studies in the late nineteenth century that popularized the germ theory of disease, and that introduced the hope that all infectious diseases could be prevented by prophylactic vaccination, as well as also treated by therapeutic vaccination, if applied soon enough after infection. However, Pasteur was working at the dawn of the appreciation of the microbial world, at a time when the notion of such a thing as an immune system did not exist, certainly not as we know it today, more than 130 years later. Accordingly, why was Pasteur such a genius as to discern how the immune system functions to protect us against invasion by the microbial world when no one had even made the distinction between fungi, bacteria, or viruses, and no one had formulated any theories of immunity. A careful reading of Pasteur’s presentations to the Academy of Sciences reveals that Pasteur was entirely mistaken as to how immunity occurs, in that he reasoned, as a good microbiologist would, that appropriately attenuated microbes would deplete the host of vital trace nutrients absolutely required for their viability and growth, and not an active response on the part of the host. Even so, he focused attention on immunity, preparing the ground for others who followed. This review chronicles Pasteur’s remarkable metamorphosis from organic chemist to microbiologist to immunologist, and from basic science to medicine.
IntroductionLouis Pasteur was really the father of immunology, despite Edward Jenner’s pioneering introduction of vaccination to prevent smallpox in 1798 . Edward Jenner is considered the founder of vaccinology in the West in 1796, after he inoculated a 13 year-old-boy with vaccinia virus (cowpox), and demonstrated immunity to smallpox. In 1798, the first smallpox vaccine was developed . Although successful, Jenner’s experiments led to no understanding as to how immunity develops. By comparison, in addition to his many contributions to microbiology, Pasteur introduced the concept that vaccination could be applied to any microbial disease, and he reported methods as to how the virulence of microbes could attenuated so that live microbes could be used to make prophylactic vaccines that could be made in the laboratory and manufactured in unlimited quantities for use worldwide. As if that were not enough, Pasteur also introduced the concept of therapeutic vaccines with his studies of rabies. Thus, he showed that what we now call post-infection prophylaxis could be used to treat individuals who were exposed to a virulent organism, and if applied soon enough after infection, clinical disease and death could be averted. Thus, he offered the hope that infectious microbial diseases could be both prevented and treated via immunology.
Of course, Pasteur was working at the dawn of microbiology, and using careful quantitative methods, he had already shown that microbes such as yeasts caused fermentation of sugar to produce alcohol, and as well, microbes are responsible for putrefaction, or the decay of tissues. Also, over 20 years, he extended his experiments to show that spoilage associated with the dairy, beer, wine, vinegar, and silk industries was explicable by contamination with bacteria. He is credited with the introduction of “pasteurization,” a process of heating to a sub-boiling point for a brief time, followed by rapid cooling, to kill most microbes.
Toward the end of his career, Pasteur moved from microbiology to the study of vaccines, a natural extension, to try to prevent infectious diseases in domestic animals. This change in scientific emphasis necessitated him to gain expertise in handling both small and large animals. To help him in this new experimental direction, Pasteur employed a young physician, Emil Roux. Pasteur’s pioneering vaccine work, especially the idea that it was important to use live attenuated microbes to generate immunity. Between the 1880s and the mid twentieth century, no one had reproduced Pasteur’s work, attenuating bacteria to make vaccines. One vaccine had been generated using Pasteur’s principles, the live attenuated Yellow Fever Virus vaccine, which was created in the 1930s . However, reading about this work now, I realized that the attenuated Yellow Fever Virus vaccine was made possible by a single random mutation, so that luck had a great deal to do with this vaccine. At the time of Pasteur’s work, the term virus, derived from the Latin, meaning “poison,” was used generally to describe any agent that was found to cause an infectious disease. In the latter half of the nineteenth century techniques introduced by Pasteur, Robert Koch, and others to cultivate these “viruses,” ultimately led to the discovery and identification of a myriad of bacteria. At the time, due to Pasteur’s work, microbes could be discriminated by the use of very fine filters. Those microbes that could be removed by filtration were relatively large and could be cultivated outside the body and observed to form colonies observable by the naked eye. These microbes were subsequently classified as belonging to the Kingdom of Bacteria. Other poisons were smaller and passed through the filters into the filtrate. These became know as viruses, and a filterable agent was the working definition of a virus until the 1940s and 1950s, when the electron microscope allowed a magnification of 10 million times, powerful enough to enable their visualization.
PASTEUR EXPERIMENTAL background, how he attenuated the microbes that he used for his live vaccines, especially the attenuation of bacteria. From experiments beginning in the 1950s, it became known that viruses, such as poliovirus, could be attenuated by prolonged passage in tissue culture, but exactly how this worked in many instances remained unknown until recently. Now, we know that prolonged passaging of viruses in tissue culture cells allows for the accumulation of many spontaneous random mutations throughout the genome. However, exactly which of the mutations cause the loss of virulence of a particular organism usually remains obscure, even today. Therefore, how was Pasteur so brilliant that he could have accomplished this feat with bacteria more than 100 years ago? We still cannot attenuate bacteria easily. We now know that bacteria contain >4000 genes, while viruses contain ∼10–100 genes. Moreover, bacteria have their own viruses that can introduce virulence encoding genes. Consequently, unless one knows which of the >4000 genes are responsible for the virulence of a particular bacterium, it is impossible to attenuate its virulence simply by passaging it many times in vitro. Now, most of our vaccines against bacterial diseases are not live attenuated organisms. Instead, they consist of parts of the microbe, and are called subunit vaccines, and by definition, they are not living. And how could he have attenuated the rabies microbe, which is now known to be a virus and not a bacterium? And why did his therapeutic vaccine for rabies work so well? LOUIS PASTEUR THE FATHER OF THE VACCINE IS LIFE STORY HERE THE LINK https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)61355-0/pdf