Alexander Fleming and The Accidental Discovery of Penicillin

Even though antagonism between some bacteria and molds had been detected as far back as the 19th century, and even though a name had been given to this phenomenon—antibiosis—very little was made of these discoveries at the time.

A traditional practice that involved the use of mold in medicinal preparations was similarly disregarded. It wasn’t until 1945 that Alexander Fleming (1881–1955) was awarded the Nobel Prize in Physiology or Medicine for his discovery of penicillin, which was produced from the Penicillium notatum mold.

Fleming made the discovery in 1928. Fleming himself was unaware of the significance of his discovery; for the next ten years, he concentrated his attention on the possible applications of penicillin as a topical antiseptic for wounds and surface infections as well as a method for isolating specific bacteria in laboratory cultures.

It was left up to his colleagues, Nobel Prize winners Howard Florey and Ernst Chain, to establish in 1940 that penicillin could be employed as a medicinal drug to combat a wide variety of different bacterial infections.

Alexander Flemming and The Accidental Discovery of Penicillin
Alexander Flemming and The Accidental Discovery of Penicillin

Education and Early Life

Fleming was the seventh of his father’s eight children and the third of the farmer’s second wife’s four children. Fleming’s mother was a Scottish hill farmer. Growing up in the countryside of southwest Scotland honed his powers of observation and instilled in him a deep passion for the natural world from an impressionable age.

He started his education at Loudoun Moor, which was a smaller school, and then moved on to Darvel, which was a larger school, before enrolling at Kilmarnock Academy in the year 1894.

In 1895, he made the trip to London to live with his older brother Thomas, who was working as an oculist at the time. While in London, he finished his primary education at Regent Street Polytechnic.

Fleming’s Journey to St. Mary’s

Fleming moved to London at the age of 13 to join his stepbrother, who was already a practicing physician, after receiving a solid education at local schools. He attended courses at Regent Street Polytechnic, worked as a shipping clerk, and served in the army during the Boer War (1899–1902), but he did not participate in any real battle.

In 1901, he was awarded a scholarship at St. Mary’s Hospital Medical School in Paddington, London, where he remained for the rest of his career.

Combating Infectious Disease Approaches

St. Mary’s welcomed Fleming following his studies, and he joined the staff of the Inoculation Department in 1906 under the guidance of Sir Almroth Wright, who supervised Fleming.

The injection of chemical agents from outside the body—as advocated by chemotherapy—Wright saw vaccination treatment as a better way to boost the body’s own immune system. Salvarsan, a novel syphilis treatment developed by Paul Ehrlich and his colleagues, was given to Fleming as a sample by Ehrlich.

When Fleming administered the medicine to patients, he found that the results were positive and therefore began to provide Salvarsan to rich syphilis victims. Dr. Fleming worked in a special wound-research facility in Boulogne (France) run by Wright during the First World War.

At the university, he launched research in line with Wright’s ideas. Because of this, carbolic acid and other regularly used chemical antiseptics were shown to be ineffective in sterilizing jagged wounds.

An advertisement advertising penicillin's miracle cure
An old advertisement advertising penicillin’s miracle cure

On the other hand, he demonstrated that the body’s first line of defense—the white blood corpuscles (leukocytes)—is damaged by chemical antiseptic dilution that is safe for bacteria.

Even after the First World War, Fleming maintained his research on leukocytes and antisepsis. He identified in nasal mucus in 1921 a chemical that disintegrates germs.

Later, Fleming and a coworker found this protein in human blood serum and tears, saliva, milk, and a wide range of other fluids. He dubbed this substance lysozyme. Lysozyme appeared to be more efficient against non-pathogenic airborne bacteria than pathogenic bacteria in its natural condition.

There was little success in attempting to increase its antibacterial qualities by concentrating it.

Accidental Discovery of Penicillin Through Experimentation

It was in the midst of these cultural and political upheavals in 1928 when the accidental discovery of penicillin occurred. Staphylococci, a kind of Gram-positive bacteria with an unusual cell wall, was the subject of Alexander Fleming’s initial investigation.

The possibility that his own nasal mucus possessed antibacterial properties was also on Fleming’s radar. Fleming took a vacation in July 1928, abandoning his job in the laboratory. Before he left, he spread Staphylococcus bacterium on a culture plate and left it on his lab bench.

In late August or early September, he returned and discovered an intriguing event. Mold producing a yellow material was found on numerous culture plates, preventing the development of bacteria.

Fleming took a closer look at a random piece of food on the table. For some distance around the mold development, he saw that Staphylococcal colonies displayed lysis, the killing of bacterium cells.

Fleming had no idea that a spore of a rare mold type called Penicillium notatum had landed on the plate before he left for vacation. A chilly spell in London coincided with Fleming’s decision not to keep the plate in an incubator, which allowed the mold to grow.

Penicillin was discovered in 1928, marking the start of modern medicine
Penicillin was discovered in 1928, marking the start of modern medicine

Moldy contaminant-free portions of the plate remained unaffected by the rapid growth of Staphylococcus bacteria. “Eureka!” was Fleming’s reaction upon seeing this intriguing phenomenon.

True to form, Fleming correctly concluded that the mold had secreted a chemical that inhibits the development of bacteria. Penicillin is the name given to the mold’s active component by Fleming.

During his discovery of penicillin, Fleming employed a few aspects of the Scientific Method. Because Fleming discovered penicillin by chance, he didn’t bother asking any questions or putting out any hypotheses about it.

The experiment with the culture plates, however, was his idea. In addition, he gathered and analyzed data, creating tables and graphs from it. In order to understand the facts, Fleming came up with reasonable interpretations.

He hypothesized that a mold would prevent germs from growing. In contrast, he didn’t come up with a hypothesis for the penicillin experiment since he was attempting to test a different antibacterial theory using mucus from his own nasal passages when he started the experiment.

Also, Fleming published a paper and gave lectures to other scientists in order to disseminate his results. Consequently, Fleming used certain aspects of the Scientific Method in his research.

Materials And Methods Used By Fleming

When it came to testing for inhibitory power, there was a straightforward way. To begin, a hole was cut into an agar plate, and a solution of equal parts agar and mold broth was poured into it.

Cultures of diverse microbes were streaked from the furrows to the plate’s edges at right angles after this solidified. Staphylococcus was an appropriate organism for testing the broth in this incident because it was robust, survived well in cultures, grew quickly, and was extremely susceptible to penicillin.

In the agar, the inhibitory material spread swiftly. A centimeter before the observable development of microbes, the inhibitory component spread out in sufficient quantity to prevent the growth of a sensitive bacterium.

Alexander Flemings mould samples sold at auction
Alexander Fleming’s mould samples sold at auction

The closer the fungus was to the culture, the more transparent the culture became. Most of the microbes were dissolved in this section of the culture, which was analyzed.

This indicated that the anti-bacterial chemical was still able to kill bacteria by diffusing into the agar. The mold culture’s antibacterial and antibacteriolytic capabilities were therefore shown using this technique.

There was a method for determining the concentration of the drug that had the highest ability to inhibit. There were several repetitions of serial dilutions of penicillin in a fresh nutritional broth. Then, all of the tubes that had been injected with the same volume of bacterial suspension were incubated for the same period of time.

The opacity (cloudiness) of the broth served as a measure for inhibition. There would be fewer microorganisms present if the environment was more opaque. Thus, penicillin had a higher inhibitory impact.

Outcomes of Penicillin Discovery

The penicillin study had nine significant outcomes. Initially, a Penicillium species developed an antibiotic compound in cultivation. When cultured for seven days at a temperature of 20°C (68°F), the culture’s antibacterial potency peaked. After ten days, the antibacterial effectiveness reduced until it had nearly vanished in four weeks.

Second, the optimal medium for the creation of the antibacterial material was the nutrient broth. In the third place, the active ingredient was filterable, and the term penicillin was given to filtrates of broth cultures and molds. It was also shown that after boiling for five minutes, the active ingredient was not destroyed.

Boiling for an hour diminished the power, but autoclaving for 20 minutes at 115°C (239°F) completely destroyed it in an alkaline solution.

Both ether and chloroform were unable to dissolve the substance. Sixthly, the drug proved effective against pyogenic and diphtheria bacilli.

Enterococcus, influenza-bacillus, and colityphoid bacteria were all resistant to the chemical. Finally, penicillin was found to be safe for animals even when administered in high dosages.

It had no more of an impact on leucocytic function than regular broth at the dosages tested. Penicillin was found to be an effective antiseptic when applied topically or intravenously to affected regions, which was the study’s eighth finding.

Using penicillin on culture plates resulted in various bacterial inhibitions not seen in standard cultures, which was an interesting finding. Penicillin’s usefulness in aiding in the isolation of B. influenza, a virus, has also been shown.

End Results

In Fleming’s experiments, he discovered that Penicillium species create a potent antibiotic chemical that inhibits the growth of many different bacteria. These bacteria are the least susceptible to antibiotics, with Gram-negative bacilli being the most vulnerable. Microbes appear to be the primary target of the inhibition.

A small dilution with fresh, nourishing material is seldom enough to overcome the inhibitory chemicals’ strength. Penicillin, on the other hand, does not interfere with the original Penicillium that was used to make it.

It is vital that the concentration of penicillin in the body be maintained at a particular level in order for it to be effective. In addition, penicillin appears to offer benefits over antiseptics in the treatment of infections caused by sensitive microbes.

Unlike carbolic acid, penicillin is non-irritating and non-toxic. Therefore it may be administered directly to affected areas.

One in eight hundred dilutions of penicillin will completely suppress Streptococcus pyogenes, Staphylococci, and pneumococcus. As a result, penicillin may still be applied to a dressing even if it is diluted eight hundred times.

Conclusion

Penicillin was discovered by Alexander Fleming, a Scottish physician, and scientist. Fleming shared the 1945 Nobel Prize in Physiology or Medicine with Howard Florey and Ernst Chain for the discovery and widespread use of penicillin, an antibiotic that has saved millions of lives since its invention. It was indeed a great discovery, doesn’t matter if that was accidental.

Grave of Sir Alexander Fleming in the crypt of St Pauls Cathedral, London.
Grave of Sir Alexander Fleming in the crypt of St Paul’s Cathedral, London

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