An Accidental Discovery | Alexander Fleming and Penicillin
“One sometimes finds what one is not looking for. When I woke up just after dawn on Sept. 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I guess that was exactly what I did.”
- Alexander Fleming on is discovery of a mold that killed bacteria
The room is hot and muggy. Streams of sunlight come in through the closed windows contrasting the dark, unlit corners. Particles of dust float in the still air. Stacks of books and papers line the walls. Across the room, long tables with laboratory equipment are askew and full of half-empty vials, cultures, and beakers. The smell in the room is almost acidic.
A rustle comes from the behind the entrance. A man fumbles his keys looking for the right one. When he enters, he walks directly to an adjacent table to put down his bag and supplies. He turns towards the table near the closed windows and walks to open one so he can let in some fresh air. As he walks, he sees in the shadows a stack of cultures he had created before leaving. His mind works quickly, calculating the time he was gone, and solving for the number of bacteria which should have grown.
He leaves the window and walks to the cultures. One is different than the others. He picks it up and holds it in the light.
Mold is growing in the culture. Around the mold, the bacteria are dead.
“That’s funny,” he says, and smiles to himself.
A World Without Penicillin
In 1924, Calvin Coolidge Jr. is playing tennis at the White House. The 16-year-old-son of President Calvin Coolidge, Calvin Jr. is a healthy young man and had gone out to play a quick game without his shoes. During the game, he develops a blister on the underside of his foot which he ignored for the better part of 24 hours until it became infected. In a few days, the infection spread to his blood, degenerating into sepsis and causing widespread blood poisoning. In under a week, he is dead.
In 1862, a man lays in a cot outside of the Antietam battlefield. The guns are silent. The battle is over, but not for him. He’s sweating, looking up at the roof of the tent in delirium as an infection from his injured leg ravages his body. Doctors come over to him and smelling the necrotic flesh, decide to take him to the table. He doesn’t realize what’s happening until the saw begins to mangle his body. He isn’t given opium to numb the pain, because they ran out of it two days before. Instead, he lets himself pass out as he screams into the night.
In 1625, a nobleman hears the bells in the distance as Charles I ascends the throne. The man has been sick for a week, and the doctors have called the barber for his blood-letting services. He remembers the red and white barber pole from the street. He had passed it many times, knowing what it meant but never thinking he would need such services. As the barber begins to cut his vein, he feels the blood flow out of his body, and he goes limp. As he passes out, he has time to think that this will be enough to heal him.
How is it possible that a simply infected blister caused the death of an otherwise healthy 16-year-old? How was infectious disease responsible for over 37,000 deaths in the Civil War? Why did doctors use antiquated methods to attempt to cure common infections?
These three stories illustrate what the world was like before antibiotics. Doctors and surgeons were restricted to methods and processes that were, as much as they could guess, effective against infection and disease. They relied on past pathologies of disease, the application of precedent for treatment, and the history of medicine that had been collected in the preceding centuries. Unfortunately, much of that history was predicated on assumptions about the human body that was inherently false. A new predicate was required.
The Discovery
Alexander Fleming started to study medicine in 1903 after inheriting some money from a deceased family member. He graduated with distinction from St Mary's Hospital Medical School in Paddington in 1906 and stayed as a lecturer until he went to war in fields of World War I. During his time in the war, he witnessed countless infections kill soldiers on the battlefield. Most notable was his attention to the dangers of antiseptic for deep wounds. To resolve this issue with field surgeons, Fleming wrote a paper during the war cautioning against antiseptic use. Despite this paper and the praise it received, field doctors and surgeons continued to use antiseptic even if it was to the detriment of their patients.
After the war, Fleming continued his study of bacteria, sepsis, and other blood-related infections at St Mary's Hospital. It was here that he discovered the natural inhibitory effect of nasal secretions on certain strands of bacteria. In his continued work, he found this effect to be present in other bodily secretions such as tears and salvia. He was able to identify the enzyme and called it lysozyme. Though this enzyme had beneficial effects against bacteria, it was not powerful enough against most strands he was studying at the time.
In 1928, after returning from an elongated family holiday, Fleming arrived back at his laboratory to find one of his bacterial cultures contaminated by mold. Fleming was known to keep an untidy lab, with many of his colleagues making jokes and comments about how messy he was in his work and experiments. But when Fleming looked at the contaminated culture and the mold growing around the petri dish, he noticed something. Surrounding each mold was a barren circle of dead bacteria. The strain of staphylococci bacteria was in a state of lysis around each mold. He did extensive testing and found that the substance was Penicillium fungi and that it was able to kill certain strands of bacteria even when diluted up to 800 times the original dose. After weeks of calling the substance “mold juice”, he settled on Penicillin.
Though this historic find was interesting, Fleming quickly realized that the fungi only affected gram-positive bacteria and had no effect on gram-negative. This limited its early applications and caused him to doubt the significance of his discovery. He published his findings in 1929 but got little attention, as he found cultivating penicillin to be extremely cumbersome and difficult for large-scale testing. Without such testing, his accidental discovery would never see wide-spread use.
He continued work on penicillin into the 1930s but largely abandoned it due to the set-backs in mass-production he encountered throughout his time with the fungi. In the end, he almost completely abandoned the experiments, but not before turning it over to a new team who would take the lead on deciphering the puzzle to its mass production.
The Crucible
Fleming turned over the discovery to scientists Howard Florey and Ernst Boris Chain to study it at Oxford. With funding from the US and British governments, the pair set to work on ways in which they could not only culture the fungi quickly but also if they could be modified to affect both gram-positive and negative bacteria.
The team’s first step was to construct a molecular model of the antibiotic. Once constructed, they published their results which prompted Fleming to return his attention to the work. Another member of the team, Norman Heatly, decided to add water to adjust the acidity of penicillin which made it viable for clinical trials with animals. The team at Oxford continued their work from 1940-1945, publishing their historic findings at each stage of their research. Attention to their work caught on, and funding was granted for mass production by 1941 just after the attack on Pearl Harbor.
The effect of penicillin on soldiers in World War II cannot be underestimated. In essence, it was the crucible for the historic drug. Infections from battlefield wounds and other diseases decreased exponentially with antibiotic treatments being credited with saving 12-15% of lives in both the European and Pacific theatres of the war. Doctors were able to perform more complex surgeries while repairing wounded limbs and organs without the same fear they had in the past for post-op infections. Antibiotics became so highly regarded and demanded that doctors all over the world began to ask for them, both at home and on the battlefield.
Once the war ended in 1945, more research was done regarding antibiotics and from 1950 – 1970 all known strains of the antibiotic were created. Today, there are five different groups of antibiotics of the penicillin class, all of which are responsible for saving over 200 million lives across the globe.
For his work in the discovery of penicillin and antibiotics, Alexander Fleming and the other researchers jointly received the Nobel Prize, knighthoods, and many other awards for their discovery. His findings were the basis for the development of more antibiotics and other medications used to fight disease. The team at Oxford who were responsible for its mass production were Ernest Chain, Howard Florey, and Norman Heatly. Though Fleming was humble about his part in finding the antibiotic, one of the Oxford team is quoted as saying, "Without Fleming, no Chain; without Chain, no Florey; without Florey, no Heatley; without Heatley, no penicillin."
Turning Point – A World with Penicillin
The discovery of antibiotics, though accidental, changed not only the way doctors treat the infection but the practice of medicine as a whole. According to the National Center for Biotechnology Information:
“The antibiotic era revolutionized the treatment of infectious diseases worldwide, although with much success in developed countries. In the US for example, the leading causes of death changed from communicable diseases to non-communicable diseases (cardiovascular disease, cancer, and stroke), the average life expectancy at birth rose to 78.8 years, and older population changed from 4% to 13% of the entire US population.”
Time Magazine highlighted the discovery when they named Fleming as one of the most influential people of the 20th Century in 1999.
“It was a discovery that would change the course of history. The active ingredient in that mold, which Fleming named penicillin, turned out to be an infection-fighting agent of enormous potency. When it was finally recognized for what it was, the most efficacious life-saving drug in the world, penicillin would alter forever the treatment of bacterial infections. By the middle of the century, Fleming's discovery had spawned a huge pharmaceutical industry, churning out synthetic penicillins that would conquer some of mankind's most ancient scourges, including syphilis, gangrene, and tuberculosis.”
Equally significant with the discovery of penicillin was the ability of bacteria to adapt to it. Fleming is noted as warning against the misuse of the antibiotics and stressed that if not monitored by trained physicians such use may be more harmful to the patient if the bacteria being treated developed resistance. While modern medicine has made great strides in not only improve the quality and potency of antibiotics, the threat of bacterial resistance is a constant one.
Without antibiotics, no modern surgeries would be possible. Scrapes and cuts would be just as deadly as they once were, and many of the infectious diseases which plagued mankind for centuries would be just as dangerous as ever. Most importantly, the false predicate that so many doctors used in the time before antibiotics would have continued for a longer time. Medicine is largely based on precedent, and with the creation of antibiotics the history of medicine – and human life- was forever altered and improved.
