The Improbable Journey Of Fleming's Discovery of Penicillin

Now without further ado, we present to you a Microbigals production of Penicillin's Discovery: The Improbable Journey To Revolutionizing Modern Medicine. ENJOY!

The story of the discovery of penicillin in 1928 goes beyond just being bizarre; it’s a story of accidents, neglect, and improbable coincidences. Penicillin features a handful of zany characters that imitate a handful of stereotypical personas such as the materialistic Americans, the pompous German, the stoic Scot, and the polite Brit. It’s wrapped up in feuding countries as the allied forces held nearly covert operations to keep the discovery of antibiotics hidden from the militant Nazis. The story is riddled in secrecy and unknowns as some aspects of this story were hyperbolized by the media, while others were lost to history. Regardless, the story of the discovery of antibiotics is exciting, absurd, and filled with copious amounts of luck!

In my lab, we used to joke about the “science gods”. If the science gods were angry at you they would mess up your experiments or contaminate your lab. We'd joke saying we would pray to them to bless our experiment, to make it work when we couldn't figure out why it failed. When all else failed we banter about building a shrine in their honor, in hopes our experiment would finally work! I don’t think the Science Gods were ever looking out for me, but after this story, it's hard not to believe there isn’t some engaging force making it so. I think this story truly shows Science is not just intelligence, it's luck, timing, and following the right side projects.

As a primer, penicillin revolutionized modern medicine. It was the first of several antibiotics that would shift not only our knowledge of feuding microbial communities but would, for the first time in history, give humanity an actual chance against militant microbes. Antibiotics mean without life. These are substances produced by microbes to destroy other microbes. Like humans, microbes are constantly at war with each other. They create new weapons to destroy their competitors or to defend themselves from their foes. They are in a constant arms race for resources and space. When we learned to harness these microbial compounds, our entire world drastically changed.

You see, at the start of the 20th century, life expectancy in the US was only about 47 years (the giant dip in 1918 is of course the “Spanish Flu”). Things were a little rocky until about the 1940s where life expectancy really took off. Why is this?

The answer is: we entered the age of antibiotics! The discovery of antibiotics transformed medicine, changing the leading cause of death in the US from communicable (infectious diseases) to non-communicable (cancer, heart disease, etc.). Strep throat was no longer fatal and meningitis would no longer kill 90% of its victims, all due to the discovery of penicillin!

“Discovery” may be a strong word. Some people like to say “serendipitous”, but I find that to just be a fancy word that sounds better than part neglect, part accident, and a big heaping pile of pure dumb luck.

In reality, this discovery of antibiotics, which increased life expectancy, decreased childhood death, and revolutionized medicine, was nothing but an accident. Well, I’ll give a little more credit; a series of accidents that all had to occur at the precise time to produce marketable penicillin, making so many of our lives attributed to a series of fortuitous discoveries.

Accident 1: Fleming's Fortunate Fate To St. Mary’s

Alexander Fleming was the man who discovered penicillin, but he originally didn’t want to be a researcher; he really didn't seem to aspire to be anything. He working in a shipping office just to feed his family. It seemed like a dead-end job so when the opportunity arose to go study medicine and train to be a surgeon he took it. After all, it had to be less monotonous than the shipping office.

He now had the funds, so off he went to St. Mary’s, a place he would spend the majority of his career, although he never intended to. After a few years at St. Mary’s, Alexander was ready to go off to medical school, but the rifle club was unwilling to say goodbye to someone who was such a good shot, so the captain convinced him to stay and do research with a fellow club member, Sir Almroth Wright.

These are really two accidents: Alexander deciding to pursue med school and being convinced to stay at a school to remain on the rifle club. Regardless, we’ll call it one accident and Fleming's Fate to stay at St. Mary’s.

Accident 2: The Neglectful, Messy Scientist Who Made The Discovery of Antibiotics

Penicillin was an “Oops baby”, born from neglect and nearly lost to history.

Fast forwarding, we are now in September 1928, and our lucky scientist, Alexander Fleming is returning from a nice relaxing holiday.

But it was this mess, and neglect, that eventually got him a Nobel Prize in 1945. Alexander Fleming had left a petri dish of Staphylococcus bacteria on his desk, while he was away. Some say the lid was off, others say it was on. Some say it was left near an open window others say by an open door. Truth is no one, probably not even Alexander Fleming knows exactly what happened here.

But, when he came across that plate again, he noticed something peculiar. The plate was contaminated and there was a strange relationship forged by the two microbes during his absence. And this is where I will give Fleming some credit, he may have been lucky, but he was also observant. Many people would probably have come into the lab and quickly tossed the plates before their PI/boss saw them.

Instead of tossing the obviously contaminated plate immediately into the waste (as I often do), he took a look at it. There was a strange blue/green mold growing on one edge of the plate, while the bacteria were on the other side. He noticed there was a halo, or a clear ring around the mold, like a forcefield or a moat, clearly stating “You shall not pass!” with all its moldy powers!

Great, so Fleming found a microbe that produces something that inhibits/kills the growth of another microbe! This led to a new problem: could he harness this power?

Fleming did not have the strong chemistry background necessary to hone in on this microbial product. He could reproduce it in a petri dish, allowing the two microbes to duke it out on his desk, but he couldn’t isolate the compound or, more “specifically,” the mold juice, that prevented Staphylococcus from growing. And so, he published his results and waited for the scientific community to become ecstatic. However, there was little giddiness for the discovery among researchers, and they all went about their business.

Accident 3: A Lucky Lap Through Long Lost Papers Sparks a Resurgence In Fleming’s Discovery of Penicillin

Some years later, Dr. Howard Florey (an opportunist) and Dr. Ernst Chain (a biochemist) happened upon Fleming’s research as they flipped through a stack of old papers in Oxford and saw the value in Fleming’s fungal strain. Fleming had shown his strain of Penicillium nonatum was capable of killing several human pathogens, he just didn’t isolate the compound. They wondered if they could, and if so, would it work in humans? Would it be safe? If yes, this would change medicine as they knew it, and so they begin the Penicillin Project.

Dr. Ernst Chain was a brilliant biochemist and made quick work of isolating the mold juice. Step 1 was complete, now on to step 2, efficacy and toxicity tests! Upon accomplishing this, he ran down to the vivarium and injected some mice with a lethal dose of Streptococcus.

Half of the mice were also injected with penicillin and then he watched. For 16 hours he watched as half of the mice grew sick, tired, and eventually died. To his delight, the other half he injected with the mold juice survived, the juice worked in vivo (in a living thing)! They were now one step closer to proving this would benefit humanity.

Next up were human trials, but which person? Back in the day, there weren’t so many rules and policies on experimenting on the sick and dying. So, in September 1940, Chain and Florey popped into Radcliffe Infirmary to find their first patient.

Albert Alexander was a police constable, 48. He got a nasty dual infection of Staphylococcus and Streptococcus across his eye from working in his rose garden. He was being treated for the infection, but the current treatment did not affect him, meaning he was going to die.

This was bad news for the constable but great news for Chain and Florey; it couldn’t do any harm to inject him with some mold juice and see what happens.

In the first few days they saw a startling improvement, Albert was seemingly going to pull through! He wasn’t dead yet, he was actually feeling better. Alas, the penicillin supply diminished, and as soon as they ran out and it was clear the Staphylococcus and Streptococcus were going to win the war of Albert Alexander. Sadly, they watched as their first patient died, after giving him hope of survival.

Accident #4: Bedpan Mold Factory Miraculously Avoids Contamination Catastrophe

Chain did it, not Alexander Fleming. Chain had discovered penicillin, or so he saw it in his eyes. Fleming may have stumbled upon it, but Ernst Chain had made it useful, but he had failed to make it manufacturable. Ernst Chain’s method took 2,000 liters of mold culture to produce enough penicillin to cure one person of sepsis, making it very difficult to actually treat patients with it.

Our devoted penicillin team lead by Florey had to build a mold factory and they had just the man to do it: Dr. Norman Heatley. He gathered every surface he could, from laboratory jars and ceramic cups to the hospital's bedpans, yes even bedpans, and began to grow all the penicillin they could. Amazingly, this worked and everything didn’t get contaminated.

Accident #5: Or Maybe Just Some Really Good Timing

Now, this is the WWII era, money and supplies are tight and infectious diseases are killing soldiers left and right, very similar to the first world war. It was important to the Brits to keep penicillin away from the Germans as this had the potential to cure soldiers and put men back on the battlefield. And so, Florey tapped into his American contacts. If there was an allied country that could figure out how to mass-produce something, it was the materialistic Americans.

In the summer of 1941, right before the US entered WWII, Florey and Heatly flew to America to work at the U.S. Department of Agriculture Lab in Peoria, Illinois to mass-produce this wonder drug. It was good timing.

Accident #6: The Moldy Melon That Massed Produced Penicillin

This brings us to another accident, led by our only female character in this saga, Mary Hunt, AKA Moldy Mary. Moldy Mary was charged with finding new molds or penicillins in hopes of finding one that was better at producing the golden juice.

One day, at the corner grocer’s, she found mold on a cantaloupe; this fungus was Penicillium chrysogenum. It produced 200x more penicillin than Fleming’s strain, and with a few zaps from the X-ray gun, new mutants arose from this original strain. Some of these mutants produced 1000x as much penicillin as the original. Now they had a weapon for mass production.

The Aftermath

In 1942, Anne Miller was on her deathbed, plagued with a terrible infection. She had tragically faced a miscarriage and, to add insult to injury, she developed a dreadful infection. The doctor’s deemed her a lost cause and thus she was a good candidate to test penicillin once more. This time, however, there would be enough penicillin. Anne became the first American patient to be successfully treated and cured. She may have lost her baby that day, but she did not lose her life.

Penicillin was immediately shipped to the front lines, saving countless lives. In the first 5 months of 1942, 400 million units of penicillin were produced. As an example, in WWI, pneumonia killed 18% of its victims. In WWII, with the discovery of penicillin, you had <1% of soldiers dying from the disease. By D-Day, there was enough penicillin to treat every soldier. At the end of the war, America was pumping out 650 billion units/month of the stuff and a million people had been treated with the wonder drug. It’s no wonder we got addicted to antibiotics.

To the great annoyance of Chain, in 1945 Fleming, Florey and Chain were awarded the Nobel Prize for collectively discovering, isolating, and manufacturing penicillin. I was unable to find out why Heatley, with his bedpan mold manufacturing commitment, was not awarded the Nobel Prize. He was, however, given an honorary doctorate of medicine at Oxford, so I guess that’s sort of the same as a Nobel Prize.

During his Nobel Prize acceptance speech, Fleming warned us of the dangers of the misuse of antibiotics. He knew it was not hard for microbes to evolve resistance against penicillin. This was a warning we should have taken more seriously, for today we are facing the next great medical catastrophe, widespread antibiotic resistance.

This is our story of penicillin; it's littered with coincidences and fate-defining moments. Accident after accident and one serendipitous moment after another; it's truly a superb story. Honestly, I’m both delighted and astonished we even have penicillin today.

What did you think of our story? Did we miss something or do you have an interesting fact about penicillin? Let us know by commenting below or email us, we'd love to hear it.