Founders and Contributors of Bacteriology

As Thanksgiving approaches, we at Macromoltek would like to express our appreciation for some of the founding scientists of modern medicine. Without their commitment to the discipline, it would not be where it is today. There are many iconic figures in the field — some of which we’ve talked about previously in our bioinformatics and antibody posts — but here we’ll focus on a few of the most important contributors to our area of study.

Louis Pasteur

Louis Pasteur was a French scientist known mostly today as the namesake of the process of pasteurization, but he made several other vital discoveries in his career, including the principles of vaccination and microbial fermentation. His work on understanding the causes and prevention of diseases, led to the creation of the first rabies and anthrax vaccines.

Louis Pasteur vaccinating a rabbit

Although Pasteur was not the first to propose the germ theory, it was his work that convinced most of the western world. He performed experiments which showed that microorganisms would develop in open sterilized flasks, but would not develop if those flasks remained closed. The dominant theory of the time was that microorganisms would spontaneously generate in a given medium, but these experiments showed that without contamination, microorganisms could not develop.

Louis Pasteur is known as the “father of microbiology,” and together with Ferdinand Cohn and Robert Koch, is regarded as one of the three main founders of bacteriology.

Robert Koch

Another of these founding fathers, German medical bacteriologist Robert Koch, was a longtime Pasteur rival. Despite the enmity between the two, their contributions to medical science are both important to this day. His study of of tuberculosis revealed that the disease is caused by the bacterial pathogen Mycobacterium tuberculosis, and, along with Pasteur, his work is part of the foundation of modern bacteriology.

Koch produced a medicine for tuberculosis called tuberculin, which spectacularly and scandalously failed when applied in practice. Despite its failure as a cure for tuberculosis, tuberculin was still, in a sense, a huge success. It still finds widespread use today for tuberculosis skin testing, and is on the WHO Model List of Essential Medicines. For his “investigations and discoveries in relation to tuberculosis”, Koch was awarded the Nobel Prize in Physiology or Medicine in 1905.

Paul Ehrlich

Koch was a longtime mentor to Paul Ehrlich, another important biologist of the 19th century. Ehrlich received his doctorate of medicine for his dissertation explaining the theory and practice of staining animal tissues with aniline dyes. His publication of his methods in 1882 led to his postdoctoral work with Koch and interest in immunization.

Later in his career, Ehrlich performed immunization experiments in his private lab by exposing lab mice to small yet increasing dosages of ricin. These mice became accustomed to ricin and retained their resistance to the poison regardless of intervals between doses. However, they were sensitive to the poison abrin and would not become resistant to it even after being immunized against ricin. This was one of the first experiments to reveal the antigen-specific nature of immunizations.

The offspring of these ricin-immune mice, he realized, also exhibited an acquired immunity to ricin for several months after birth. Ehrlich swapped offspring of immunized and non-immunized mothers, and discovered that the acquired immunity persisted — the children of non-immunized mothers gained immunity through nursing!

Ehrlich simultaneously began formulating his “side-chain theory” — the idea that antibody-antigen binding was accomplished via specific side chains using a lock-and-key mechanism — due to his combined understanding of dye-binding and immunity (see What is an Antibody). At the time, Ehrlich reasoned that if a compound could be made which selectively targeted a disease-causing organism, then a toxin for that organism could be delivered by way of the agent of that selectivity. This concept has been realized in the development of antibody-drug conjugates which enable cytotoxic drugs to be delivered to their targets directly, while minimizing the destruction of surrounding tissues!

Kitasato Shibasaburō and Emil Behring

Robert Koch (top second from left) and Kitasato Shibasaburō (top left) became very good friends during their time together in Berlin. Koch later visited Shibasaburō and his family in Japan.

In addition to mentoring Erlich, Robert Koch was also responsible for bringing Kitasato Shibasaburō to Germany. Shibasaburō had been educated at Tokyo Imperial University and worked with Koch at the Friedrich Wilhelms University in Berlin where he was the first to grow the tetanus bacillus in pure culture. It was at the behest of Koch that Shibasaburō remain to work with Emil Behring on a treatment for diphtheria and tetanus. During their experiments, they observed unexplained inconsistencies in the levels of immunity of their lab animals. Koch suggested that they and Ehrlich work together because of his previous experiments with immunization in lab mice.

Ehrlich was able to solve the problems with the inconsistencies and improve the levels of immunity. Their success led to clinical trials in humans for diphtheria treatment. Ehrlich always acknowledged serum therapy was developed by Behring and Shibasaburō, but maintained that he was the first to develop a serum viable in humans. His contributions were not recognized by the Nobel committee, however, and Von Behring was the only recipient of the first Nobel Prize in Medicine in 1901 for research on diphtheria. Seven years later, Ehrlich was finally awarded the Nobel Prize for Physiology or Medicine for his work on serum valency.

Thank You

The tireless efforts of these scientists have provided us with a crucial understanding of many infectious diseases and have led to a society free of many of them. Macromoltek appreciates their work and recognizes that, without them, our further advancements would never be possible.

Links and Citations
All pictures for this blog were provided by the Wellcome Collection: https://wellcomecollection.org/

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