Scientist vs. Scientist #7 - Alexander Fleming and Louis Pasteur

In this episode, we will discuss Alexander Fleming and Louis Pasteur. First, we will discuss Alexander Fleming. Alexander Fleming was born on the 6th of August, 1881, in Darval, a town in Ayrshire, Scotland, to Hugh Fleming and Grace Morton, both of whom were farmers from local families. Alexander had seven siblings, four of whom were from his father's previous marriage. Alexander's father died when Alexander was only seven years old, leaving the family short on money and requiring Alexander to help out on the farm. Alexander's work on the farm, and his upbringing surrounded by nature, improved his skill in the observation of the natural world, an ability that would later contribute significantly to his scientific career. Fleming attended the Laudan Moor School and the Darval School in his youth, and at the age of 12 earned a scholarship which allowed him to attend Kilmarnock Academy. In 1895, Alexander moved to London to live with his brother Thomas. In London, Alexander received his basic education at the Royal Polytechnic Institution and worked as a shipping clerk for four years. After his position in the shipping office, Fleming entered St. Mary's Medical School in London University, with some money provided to him by his uncle John Fleming and some from a scholarship. Alexander's brother Thomas, who was also in the field of medicine, was the primary reason for Fleming's decision to attend medical school. Fleming was a distinguished student at St. Mary's Medical School, passing the qualifying examination of the conjoint board with distinction in 1906. The examination allowed Fleming to become a surgeon. However, he started work in the pathology department, which provided a source of income. In 1908, Fleming passed the London MBBS with gold medal, and soon after also passed the final exam for the fellowship of the Royal College of Surgeons. Fleming also became a lecturer at the medical school, a position which he would occupy until the beginning of World War I. The captain of Fleming's rifle club at the medical school recommended that Fleming join the research department at St. Mary's, and Fleming became a research assistant to Sir Almroth Wright, a renowned British bacteriologist responsible for developing an inoculation for typhoid fever. Wright's influence on Fleming was pivotal in the latter's path in the field of bacteriology. Prior to his apprenticeship with Wright, Fleming had wanted to become a surgeon. Aside from assisting Wright with his research, Fleming began his own private venereology practice which helped supplement the modest salary he received as apprentice. With the beginning of the First World War in 1914, Fleming was enlisted to serve in the Royal Army Medical Corps, and deployed to treat troops returning from the Western Front. While tending to wounded soldiers, Fleming noticed that many soldiers were dying of infections of typhoid, cases of gangrene, and sepsis. Although antiseptics were available to treat certain diseases, they often worsened the infections. Specifically, wounds that were near the surface of the skin would often be aided by the application of antiseptics, whereas deeper wounds would be exacerbated by the application of antiseptics. Fleming proposed that the antiseptics were having an adverse effect on the body's natural antibodies, and could not reach deeper beneath the wound to treat the infections. Instead of applying antiseptics, Fleming and his colleagues recommended cleaning and drying the wounds, but army physicians largely disregarded his suggestion. During the war, Fleming also studied species of streptococci, bacteria responsible for certain common infections, in great detail. Fleming found that only those species of streptococcus that caused the rupture of red blood cells were likely to lead to severe infection. Such streptococci were only found in a fifth of wounds at time of infection, but only a week after the wound was inflicted, the hemolytic streptococcus strains were found in 90% of wounds. The explanation for this drastic increase in strep bacteria was the transfer of bacteria from infected patients to uninfected patients while in the treatment wards, a phenomenon now known as hospital infection. Upon their return to St. Mary's in early 1919, Fleming and his fellow physicians found themselves in a hard situation regarding funding. The University Grants Committee had decided that the medical school would receive an annual budget of £30,000, not enough to upgrade facilities or cover salaries. Sir Charles Wilson took over control of affairs at St. Mary's and immediately set about making grand changes to the school. He appointed new professors, set new standards for admitted students and actively worked to gather new students. Meanwhile, Sir Almaroth Wright remained in the position he had been appointed to during the war, and his deputy was appointed to his old spot. This led to Fleming's promotion to Assistant Director of St. Mary's Inoculation Department, a considerable promotion due to the new responsibilities and projects that Fleming would have to take care of. In addition to managing commercial activities, Fleming was also responsible for scientific research and was in line to inherit the position Sir Almaroth Wright had previously occupied. Fleming carried out the tasks he was in charge of in an efficient and disciplined manner. In November of 1921, Fleming was attempting to find an antibiotic that could be effective against bacteria found in soldiers' wounds, particularly streptococcal bacteria. At the time, Fleming had a slight cold, and while preparing plates of cultured bacteria, a drop of mucus from Fleming's nose fell onto a plate. Considering that the mucus might have an antibacterial effect due to its function in the human body, Fleming left the plate to stand. After a few weeks, Fleming noticed that bacteria had grown around the area, but where the droplet had hit, the plate was clear of growth. After further examination, Fleming determined that a specific enzyme, lysozyme, was responsible for the lack of bacteria. Lysozyme is an enzyme found naturally within the immune systems of animals and can be isolated from, as Fleming correctly described, tissues and secretions of animals. Lysozymes break down the cell walls of certain bacteria by hydrolyzing glycosidic bonds in peptidoglycans, weakening the bacterial cell's walls and ultimately leading to their rupture. Due to the biological nature of lysozymes, they are effective against gram-positive bacteria, but significantly less effective against gram-negative bacteria, which have a thinner peptidoglycan cell wall. Although most of the bacteria of interest to Fleming were gram-negative, Fleming did not disregard the discovery of lysozyme. He published a scientific paper on the subject in 1922 and later remarked that his discovery of lysozyme was the best scientific achievement of his career. In the fields of observation, chance favors only the prepared mind. A famous quote from Louis Pasteur certainly applied to Alexander Fleming on the morning of September 3rd, 1928. Having returned from a vacation with his family, Fleming was cleaning his laboratory when he noticed that a culture plate he had left out looked different from the other plates. A mold had apparently contaminated this particular plate and the colonies of Staphylococcus aureus near this mold had been eliminated. Fleming and his assistant suspected that this mold could produce an agent responsible for the absence of bacterial colonies in the vicinity of the mold. Initially, Fleming believed that the mold produced an enzyme with antibacterial properties. Upon culturing the mold itself on a separate plate and conducting further investigation, he determined that the substance from the mold was an antibiotic. Fleming tested the effects of the substance on many bacteria with interesting results. The substance was effective against most gram-positive bacteria as well as some gram-negative bacteria. However, it was not effective against typhoid or paratyphoid fever, both of which were of interest to Fleming. The mold was later identified as Penicillium notatum and Fleming thus named the antibiotic substance penicillin, following scientific guidelines. At the time, Fleming did not accurately predict how potent penicillin was against bacteria, at least in part due to his failure to purify the antibiotic and in part due to its rather slow activity. Nonetheless, Fleming did understand that penicillin would be a useful substance and published a paper on penicillin in the British Journal of Experimental Pathology in May of 1929. Fleming continued to work with penicillin for another decade but made no more great breakthroughs. In 1940, Ernest Chain and Howard Florey, two pathologists working in Oxford, isolated penicillin and conducted the first clinical trials to demonstrate its effectiveness. Fleming's discovery and Florey and Chain's consequent development of penicillin has saved over 200 million lives to date and earned the three scientists the Nobel Prize in Physiology in 1945. Alexander Fleming died on the 11th of March in 1955, at the age of 73, from a heart attack. Fleming's discovery of penicillin revolutionized medicine and his other discoveries and experiments paved the way for further exploration into the field. Fleming has received many posthumous awards and honors for his work in medicine. Now we will discuss Louis Pasteur. Louis Pasteur was born on the 27th of December, 1822, in the town of Dole, in France, to Jean-Joseph Pasteur and Jean-Étienne Roquet. Pasteur was the third child in the family and had four siblings. Although Pasteur's father had no formal education, he had a strong work ethic and a passion for knowledge, which his son inherited. During Pasteur's youth, the family moved homes twice, settling in the town of Arbois in 1827. In 1831, Pasteur entered primary school, where he stood out as an exceptional artist due to his propensity for sketching everything around him. While Pasteur had a talent for drawing, he was a mediocre student in other respects, as his interests lay elsewhere. In 1838, Pasteur left for Paris to enroll in a preparatory school for higher levels of education, but became homesick and returned to Arbois within a year. In 1839, he enrolled in the Royal College at Besançon, determined to pass the entrance tests to the École Normale Supérieure. During his time at the Royal College, Pasteur earned his Bachelor of Letters degree and was appointed Assistant Mathematics Master. At the time, Pasteur's academic performance was still mediocre. Pasteur managed to earn a bachelor's degree in science from the Royal College with a poor grade in chemistry. Despite this, Pasteur was intent on entering the École Normale Supérieure. In 1842, Pasteur took the entrance examinations for the École Normale Supérieure. His results, good enough to enter the school, were not to his satisfaction, and Pasteur decided to retake the examinations next year. During this interim period, Pasteur continued his education, taking classes and attending lectures at the Lycée Saint-Louis. One particular lecturer, Jean-Baptiste Dumas, a French pioneer in organic chemistry, fascinated Pasteur and inspired him to pursue a career in the field. Pasteur successfully passed the entrance examinations to the École Normale Supérieure in 1843 Due to his dedication, Pasteur became Jean-Baptiste Dumas' teaching assistant. His entrance to the École Normale Supérieure allowed Pasteur's aptitude for scientific thinking to fully develop. In 1845, Pasteur obtained his Master of Science degree and, two years later, submitted two doctoral theses. Pasteur also started his research work under the supervision of the professor Anton-Jérôme Ballard, another influential French chemist. Soon after joining Ballard as graduate laboratory assistant, Pasteur left the École Normale Supérieure to become a professor at the Dijon Lycée, but soon left this role as well and accepted the position of professor of chemistry at the University of Strasbourg, taking his research with him. Pasteur had begun research into crystallography while at the École Normale Supérieure, specifically the ability of certain organic molecules to rotate the plane of polarized light. This phenomenon had been observed in many organic molecules and an even more fascinating phenomenon had been observed in molecules occurring naturally in wine, known as tartrates. Despite the widely held belief that the molecules of tartrates and peritartrates were identical and chemical testing seeming to indicate that the molecules had the same chemical properties, scientists had been unable to explain why tartrates rotated polarized light while peritartrates did not. Pasteur was convinced that, in spite of the ardent belief of other scientists, he could find a difference between the molecules. He thus began by studying the physical structure of both crystals. Pasteur found that peritartrates were actually an equal mix of two tartrate crystals that were mirror images of each other and, after separating these crystals, Pasteur found that both rotated polarized light, but in opposite directions. This would explain why peritartrates did not rotate light. The effects of both crystals cancelled out. Pasteur's work on these molecules was the first demonstration of molecular chirality and laid the foundation for stereochemistry. Pasteur continued this work for ten years, until roughly 1854. While working at the University of Lille, Pasteur was asked to solve problems related to the fermentation process of wine. Even though the presence of microorganisms in alcoholic fermentation had been known since ancient times, their role in the process was severely misunderstood. The dominant view of fermentation at the time was that yeast acted merely as a catalyst and that the process was purely chemical. Pasteur, however, could not come to terms with this explanation because he himself had had first-hand experience with wine fermentation and had noticed the organic, optically active molecules in the wine after fermentation. His prior research on optically active molecules led Pasteur to believe that these molecules were the result of a living process during the fermentation of wine and likely the fermentation of many other substances. Pasteur was invited by a local winemaker to find out why his wine was turning sour. Conducting chemical analysis, Pasteur determined that the wine was souring due to the production of some lactic acid during the fermentation process. Pasteur hypothesized that, much like some bacteria was responsible for the fermentation of alcohol, other bacteria were responsible for the production of lactic acid. After conducting thorough experiments, Pasteur found the bacteria responsible for both alcohol and lactic acid fermentation in wine. Pasteur also demonstrated that the existing theory regarding fermentation was wrong. Rather than decomposition, yeast consumed sugar and produced alcohol, and lactic yeast produced lactic acid from sugar, processes which involved numerous intermediate reactions. Pasteur showed that exposing fermenting wine to air decreased the amount of sugar fermented and deduced that the bacteria responsible for fermentation were anaerobic. To find a solution to the souring of wine, Pasteur knew that he would have to eliminate the bacteria responsible for lactic acid fermentation. He initially attempted to kill the bacteria with chemicals, which had a negative impact on the wine's taste. It was then that Pasteur created the process of pasteurization. He heated the wine to above 60°C for a few hours and sealed the wine immediately afterwards. This process worked not only for wine, but for many other foods, and is used to this day. One implication of Pasteur's research on fermentation was that bacteria could not spontaneously appear in a medium and instead had to come from another source. This was in opposition to the hypothesis of spontaneous generation widely held at the time. Pasteur convincingly demonstrated that bacteria could not spontaneously appear with his famous Swan Neck Bottle experiment, eventually convincing all of his colleagues and all of Europe. Pasteur then turned his attention to a different problem, the silkworm crisis affecting most of Europe and, in particular, France. In the 1850s, a disease had begun spreading through silkworm nurseries across France, and by the time Pasteur started looking into the problem in 1865, the silk industry was nearing collapse. Pasteur began by learning about silkworm breeding, a smart decision since it allowed him to see that microbes were attacking the silkworm eggs. He determined that there were two organisms responsible for the widespread disease, pebrine and flashery. Affected silkworm eggs could either be affected by one or both of the diseases. In 1868, Pasteur suffered a partial paralysis of the left side of his body, but, nonetheless, continued his research into silkworms and, by 1870, was able to create a method of preserving healthy silkworm eggs. The method, known as graining, involved observing the moth pulp for signs of disease and destroying the diseased moth's eggs, a technique still widely used today. Continuing to work with diseases, Pasteur began studying diseases that affected larger animals, namely chickens, sheep, and humans. His first work on immunology focused on chicken cholera, and his work on this disease laid the foundation for his further work on many other diseases. Pasteur was provided cultures of chicken cholera by a fellow scientist, and, while cultivating the cultures, some of the bacteria spoiled. When Pasteur attempted to disease chickens with this bacteria, the bacteria failed to induce disease, and, when Pasteur again attempted to disease the chickens with new bacteria, he found that the bacteria now had no effect. Pasteur correctly predicted that the bacteria, having been attenuated, caused immunity to the strain of bacteria in the affected animal. Pasteur applied this knowledge to anthrax, a disease primarily affecting farm animals, and studied the bacteria responsible for the disease. After determining what conditions would weaken the bacteria, Pasteur prepared attenuated samples of bacteria and vaccinated 70 sheep in a public demonstration. The vaccinations were all successful, and, despite criticism from other scientists, Pasteur's methods were ultimately put to use in most modern vaccines. In addition to anthrax, Pasteur found a vaccination for rabies and conducted trials in 1885, which were also successful and led to the manufacture of rabies vaccines, turning rabies from a death sentence to a treatable malady. Louis Pasteur died on the 28th of September in 1895, at the age of 72, due to a stroke he suffered in 1894. Pasteur's numerous discoveries and scientific techniques helped save countless lives, revolutionized the many fields he conducted research in, and lay the groundwork for numerous other advancements in chemistry and biology. Thank you for watching this episode of Scientist vs. Scientist. 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