ALEXANDER FLEMING: BIOGRAPHY AND CONTRIBUTIONS - SCIENCE - 2024

Alexander Fleming (1881-1955) was a Scottish bacteriologist and pharmacologist, winner of the Nobel Prize in Medicine in 1945 along with his colleagues Howard Florey and Ernst Boris Chain, for the discovery of penicillin.

Fleming observed that many soldiers died during World War I from sepsis that affected infected wounds. The antiseptics that were used at the time to treat these wounds made the wounds worse, a fact that Fleming described in an article for the medical journal The Lancet.

Fleming in his laboratory.

Despite this discovery, most doctors continued to use these antiseptics throughout the war, even though they actually made the wounded worse.

Fleming continued his research on antibacterial substances at St. Mary's Hospital and found that nasal mucus had an inhibitory effect on bacterial growth, which led to the discovery of lysozyme.

Biography

Alexander Fleming was born on August 6, 1881 in Scotland, specifically in the town of Ayr. Fleming's family was of peasant origin; He had three siblings, all born from his father's second marriage, Hugh Fleming.

When Alexander was seven years old his father died. As a consequence of this, the farm where they lived was left in charge of Hugh Fleming's widow, named Grace Stirling Morton.

Fleming's early studies were somewhat precarious, given the family's financial situation. This training lasted until 1894, when Alexander was thirteen years old.

At this time Fleming moved to London, a city where a stepbrother doctor worked. While there, Fleming enrolled at the Royal Polytechnic Institute, located on Regent Street. After this he worked in a shipping company, within which he worked in different offices.

In the midst of this context, in 1900 Fleming decided to enlist in the London Scottish Regiment, since he wanted to participate in the Boer War, however, the war ended before he had the opportunity to even embark in the direction of the conflict.

Fleming was characterized by being a man interested and attracted by war and its elements, for which he remained an active member of the regiment in which he enrolled long ago and participated in the First World War; in fact, he was an officer in the Royal Army Medical Corps on French territory.

University studies

In his early twenties, Alexander Fleming received a modest inheritance from his uncle John Fleming.

Thanks to this, Fleming was able to begin his studies at St. Mary's Hospital Medical School, which was part of the University of London. It was his doctor brother who motivated him to enroll in that institution.

He entered there in 1901 and in 1906 he became part of the working group of Almroth Wright, a bacteriologist and an important figure in the field of epidemiology in general and vaccines. This working relationship between Fleming and Wright lasted about 40 years.

Fleming graduated as a physician with honors in 1908, obtaining the gold medal awarded by the University of London.

Teaching stage

After obtaining his medical degree, Fleming was a professor of bacteriology at St. Mary's Hospital Medical School until 1914. A year later, he married Sarah Marion McElroy, who was a nurse originally from Ireland and with whom he had a son named Robert Fleming.

In the midst of this context, Fleming's participation in the First World War took place. His work focused on the western part of France, on field hospitals.

Fleming carried out this work until 1918, when he returned to St. Mary's Hospital Medical School and, in addition, obtained the appointment of professor of bacteriology at the University of London.

This was in 1928 and in that same year Fleming was appointed director of the Wright-Fleming Institute of Microbiology, which was founded in recognition of Fleming and Almroth Wright. Fleming was in charge of this institute until 1954.

He continued teaching at the University of London until 1948, when he was appointed Emeritus Professor of this house of studies.

Most important discoveries

Between 1922 and 1928, Fleming made his two most relevant discoveries: lysozyme, in 1922, and penicillin, in 1928.

Both findings were very relevant and transcendental for humanity, and in 1945 he received the Nobel Prize in Physiology and Medicine, shared with Ernst Boris Chain and Howard Walter Florey, North American scientists who also contributed their knowledge to the development of penicillin.

Second nuptials and death

Four years after receiving the Nobel Prize, his wife Sarah Marion McElroy died. In 1953 Fleming remarried Amalia Koutsouri-Vourekas, who was also a physician and worked at St. Mary's Hospital Medical School.

Two years later, on September 11, 1955, Alexander Fleming passed away. He suffered a heart attack while at home; At this time, Fleming was 74 years old.

Discovery of penicillin

It is said that Alexander Fleming came to the discovery of penicillin almost by chance (serendipity), derived from an oversight caused by the scientist himself within his laboratory. Don't detract from it, however, as Fleming was a hard-working and dedicated worker.

The exact date associated with the discovery of penicillin is September 15, 1928. In the summer of that year, Fleming took a two-week vacation, leaving his laboratory at St. Mary's Hospital for a few days. Medical School.

Laboratory in disorder

In this laboratory, Fleming had several cultures of bacteria that he was analyzing; These bacteria were growing in plates that the scientist had arranged for it and that were in an area near a window.

After two weeks of vacation, Fleming returned to his laboratory and noticed that several of the plates had mold, an element that had grown in his absence.

This resulted in the fact that Fleming's experiment had been damaged. Then, Fleming took the plates and dipped them in a disinfectant with the intention of killing the bacteria that had been generated.

Of all the plates, Fleming was interested in one in particular, in which he had the bacterium Staphylococcus aureus: it turned out that the mold that grew there, which was a blue-green color, had killed this bacterium.

This mold that grew there turned out to be Penicillium notatum fungi, and Fleming realized at the time that this substance was capable of killing Staphylococcus aureus bacteria.

Cultivation of the fungus and more discoveries

After this Fleming sought to cultivate the fungus separately, under controlled conditions, and the results he obtained only made him even more convinced of the harmful effect it had on this bacterium.

Fleming did not stop at this discovery, but began to make other microorganisms interact with the fungus that he discovered at first almost by chance, and he realized that there were other bacteria that were also killed by the mold in question.

Chance involved

Some consider that the discovery of penicillin was full of random elements, beyond the carelessness of the scientist himself in his previous experiment.

For example, it was discovered that precisely in the summer of 1928 London experienced more abrupt and more intense temperature changes than usual: at the beginning of August temperatures between 16 and 20 ° C were experienced, and later the temperatures rose to about 30 ° C.

This was relevant because this oscillation generated the perfect scenario for two elements to develop that need very different temperatures to generate. Penicillium notatum grows at a temperature of approximately 15-20 ° C, unlike staphylococcus, which needs a temperature of 30-31 ° C.

This scenario generated by chance allowed two elements to develop on the same surface, which together managed to demonstrate the effect that one had on the other.

Of course, chance would not have been decisive had it not been for the critical eye and curiosity of Alexander Fleming, who decided not to discard the result obtained, but to analyze it.

Publication of the finding and first doubts

In 1929 Alexander Fleming published his research and conclusions in the British Journal of Experimental Pathology, a widely recognized publication in the field of medicine.

Despite the importance that Fleming saw from the beginning of its discovery, in the scientific community this finding did not have a major impact.

Even Fleming noted that other scientists had published works similar to his, in that they had also identified certain fungi that prevented certain bacteria from being generated, and those works had not been of much importance either.

Failed attempts

Fleming continued to try to focus on the development of penicillin, and during the 1930s he conducted various investigations with the intention of purifying and stabilizing the compound. In his research he realized that it was not easy to isolate the active compound from the fungus that was working.

This made him think that it was very likely that, even if he did manage to isolate said antibiotic compound, the production of the drug would be very complex, and it would be practically impossible to mass-produce the drug, in a way that was available to everyone.

In addition, the experiments that he had carried out up to that moment made him think that the effect generated by penicillin was temporary, and that the antibiotic could not be active long enough to generate a notable improvement in patients.

However, this notion was discarded by himself when he began to consider a non-superficial application of the drug. He continued testing and researching until 1940, when he gave up the project because he could not purify the compound and he did not find another scientist who would be interested in this research.

Verification

This was only the beginning of the process, as Alexander Fleming subsequently had to perform various checks to verify how safe the drug was to use in humans, and how effective it could be once inside the body.

As seen above, Fleming did not get scientists to support him, in addition to the fact that the British context of the time did not allow a very high investment in his research, given that Great Britain was involved in World War II, and all his efforts were directed towards that front.

However, the publications of the findings made by Fleming crossed the British horizons and reached the ears of two North American scientists, who through the Rockfeller Foundation began to investigate and experiment to achieve the development of penicillin in a massive way.

These two scientists, with whom Fleming shared the Nobel Prize he won in 1945, were Ernst Boris Chain and Howard Walter Florey.

American collaboration

Since Alexander Fleming was not a chemist, he was unsuccessful in his attempts to stabilize penicillin. It was only 10 years after their first experiments that the biochemist Chain and the doctor Florey showed interest in this compound, specifically because of its bactericidal characteristics.

Both scientists worked at the Oxford Institute of Pathology and there they formed a team through which they sought to analyze the components of penicillin and purify it, so that it could be stabilized and used on a small scale in experiments with mice that had been previously infected.

These experiments were positive, since it was found that the mice without treatment died as a consequence of the infection; In contrast, the mice that had been given the antidote created from penicillin, managed to heal and live.

This was the last check that determined decisively that the Staphylococcus aureus infection was cured.

Utilization

These discoveries occurred in the pre-World War II era, and it was precisely this scenario in which penicillin was used the most, in such a way that it was even named as "the wonder drug."

Various infections were cured quickly and effectively, which was decisive in the midst of this war conflict.

There was an unfavorable element, and that is that the production of the drug was very expensive and very complex to obtain it in the massive way in which it was necessary. Years later, this problem would find a solution thanks to the work of English-born chemist Dorothy Hodgkin, who managed to discover the structure of penicillin through X-rays.

This made it possible for synthetic penicillin to be produced, which allowed for much less expensive and faster production. Along with synthetic penicillin, Hodgkin's experiment also allowed the production of various antibiotics based on cephalosporins.

Main contributions

War wound healing

Between 1914 and 1918, Fleming was working together with his mentor, Sir Almroth Wright, in a military hospital in Bolougne, France.

The Great War left terrible consequences among the allied troops, and both were looking for ways to achieve the recovery of the greatest number of men in an age where a simple wound could lead to death.

Fleming focused on the performance of the antiseptics used at that time. His research was able to show that these products worsened the conditions of the deepest wounds, damaging the cells responsible for defending the body against the bacteria that cause gangrene and tetanus.

Although the study was controversial and widely questioned, it made a crucial contribution to the treatment of patients in subsequent wars.

Lysozyme as an antibacterial enzyme

In 1920, Fleming was observing the reaction of a culture of bacteria to which a drop of nasal discharge had fallen, that is: mucus.

The event, although hilarious, made him see that these bacteria had died right in the place where the drop fell.

Two years later he would publish the formal research, where he discovered the uses of lysozyme to fight certain types of bacteria, without damaging human cells.

Today lysozyme is used in the treatment of oropharyngeal infections and certain viral diseases, as well as to stimulate some reactions in the body and to contribute to the action of antibiotics or chemotherapy.

Although it is found in human fluids such as tears, mucus, hair, and nails, it is currently artificially extracted from egg whites.

Penicillin: the most important antibiotic in history

One of the most famous fables in the history of science originated when Alexander Fleming discovered penicillin in 1927. He had returned from a long vacation with his family to find his laboratory rather messy.

A staph culture was full of mold, but Fleming instead of discarding it wanted to look at it under his microscope. Surprisingly, the mold had killed all the bacteria in its path.

A more thorough investigation allowed him to find the substance that he himself called penicillin. This powerful element would become one of the first effective antibiotics against diseases that at the time could be fatal, such as scarlet fever, pneumonia, meningitis and gonorrhea.

Their work was published in 1929 in the British Journal of Experimental Pathology.

Penicillin improvement

Although Fleming had all the answers, he was unable to isolate the most important component, penicillin, from mold cultures, much less produce it in high concentrations.

It was not until 1940 that a team of biochemical experts at Oxford managed to find the correct molecular structure for penicillin: Ernst Boris Chain and Edward Abraham, under the tutelage of Howard Florey.

Later, another scientist named Norman Heatey proposed the technique that would allow to purify and produce the substance in mass.

After many clinical and manufacturing trials, penicillin became commercially distributed in 1945.

Fleming was always modest in his role in this story, giving more credit to fellow Nobel Prize winners Chain and Florey; however, its immense contribution to research is more than clear.

Antibiotic resistance

Long before any other scientist, Alexander Fleming had come up with the idea that the incorrect use of antibiotics has counterproductive effects on the body, causing bacteria to become increasingly resistant to the medication.

After the commercialization of penicillin, the microbiologist dedicated himself to emphasizing in multiple speeches and conferences that the antibiotic should not be consumed unless it is really necessary, and that if it is, the dose should not be too light, nor should it be taken in too short a period.

This misuse of the drug only allows the disease-causing bacteria to grow stronger, worsening the condition of patients and hindering their recovery.

Fleming couldn't be more right, and in fact, today this is still one of the lessons that doctors tend to emphasize the most.

References

1. Biography.com Editors. (2017). Alexander Fleming Biography.com.: A&E Television Networks. Recovered from biography.com
2. Unknown author. (2009). Alexander Fleming (1881-1955). Edinburgh, Scotland.: National Library of Scotland. Recovered from digital.nls.uk
3. IQB writing team. (2010). LYSOZYME. Buenos Aires, Argentina.: Collaborating center of the National Administration of Medicines, Food and Medical Technology -ANMAT-. Recovered from iqb.es
4. The Doc. (2015). Alexander Fleming.: Famous Scientists. Recovered from famousscientists.org
5. Alexander Fleming. (Without date). On Wikipedia. Retrieved on December 10, 2017 from en.wikipedia.org
6. Alexander Fleming (1881-1955): A noble life in science. (No date) In British Library. Retrieved on December 10, 2017 from bl.uk