Throwback: How Penicillin Saved the World

By: Ahmed Mahmood

Modern medicine seems like science fiction but the science behind modern medicine couldn’t be closer to reality. In the 1980’s, genetic engineering allowed scientists at Genentech to synthesize human insulin in E. coli bacteria which greatly improved the lives of diabetes patients. Studies conducted starting from 2005 to 2012 report that various kinds of tissue and organ damage can be easily repaired and regenerated through the use of stem cells. In 2010, Scientists at Organovo, an organ bioengineering company, harnessed the technology of 3D printing and literally printed organ scaffoldings for adult cells to grow on. The list of medical breakthroughs goes on. To truly appreciate today’s innovations in medicine, we must go back in time to one of the greatest medical discoveries: penicillin.

Before discovering penicillin, Alexander Fleming attended St. Mary’s Hospital Medical School at the University of London and became a bacteriologist. Later, he served in Royal Army Medical Corps in France during World War I and worked with antiseptics. Fleming conducted experiments with antiseptics that proved antiseptics were ineffective against bacterial infection and were actually damaging white blood cells. After the war, he returned to St. Mary’s to become the assistant director of the Inoculation Department in 1928. And so begins a legendary tale. Fleming left for a two-week vacation and unknowingly forgot to put a Petri dish containing a Staphylococcus culture in the incubator. When he came back, he noticed that the Petri dish had been contaminated with a Penicillium spore. Some accounts say that he discovered that the fungal colony caused the bacteria to lyse, or split open, and other accounts say he saw a “clearing” of bacteria surrounding the mold “juice.” Whatever the case, Fleming realized that the chemical inside this mold juice was killing off the bacteria. Even though he was unable to extract the chemical, he had already named it “penicillin” after the fungus from which it came.

Photo credit: Leo Reynolds / Foter / CC BY-NC-SA

Photo credit: Leo Reynolds / Foter / CC BY-NC-SA

Most people think the tale of penicillin stops here, but it doesn’t. Tom Volk, Mycologist and Professor of Biology at University of Wisconsin-La Crosse, has a Fungus of The Month article series that is dedicated to the unsung story of penicillin. Volk writes that the story continues with  Fleming and Ronald Hare, his colleague, trying to recreate those original conditions for Penicillum to thrive. They finally got the fungus to grow under cold conditions and noticed that not all strains of this fungus, Penicillium notatum (later changed to P. chrysogenum), produced penicillin. In 1929, Fleming published a paper that documented his experiments with Penicillium and observed that the fungus would only kill gram-positive bacteria. Gram-positive bacteria have a thick cell wall with peptidoglycans which are long chains of repeating units of sugar molecules mixed with amino acids. It was later discovered that penicillin breaks up those peptidoglycan chains and disrupts the cell wall of the bacteria, causing it to lyse. Gram-negative bacteria don’t have much peptidoglycan and have another layer on top of the peptidoglycan layer, so penicillin was noted to be virtually ineffective against them.

After publication, Fleming’s work was ignored for almost 10 years. It wasn’t until a team of University of Oxford scientists, including Howard Florey, E.P. Abraham, Boris Chain and Norman and Mary Heatley, believed that they could isolate penicillin from P. chrysogenum and combat infections brought upon by World War II that penicillin got its day in the spotlight.

During this time, Great Britain was under heavy bombing, so the scientists came to the U.S. to continue their work. The first strain they cultured only produced 4 units/mL of penicillin. Through tedious culture medium modification, the output of their strain became 40 units/mL, but that wasn’t nearly enough. Their strain could not grow in a submerged culture which is essential to increase penicillin output. To find another viable strain, they tasked young lab worker Mary Hunt, unfortunately nicknamed “Moldy Mary,” to go to local produce markets and look for moldy foods. She finally brought in a moldy cantaloupe which turned out to be the perfect sample. Mary’s sample yielded a strain that produced 70-80 units/mL, and then the scientists isolated a spore that resulted in a strain producing 250 units/mL of penicillin. The results were so astounding that the War Production Board, a U.S. government agency that was in charge of manufacturing and distribution of war assets during World War II, set up projects in other labs. Soon fungal lab strains were producing 900 units/mL and through UV radiation some strains produced over 2500 units/mL penicillin. Today, industrial strains of P. chrysogenum, distantly related to the original cantaloupe strain, produce 50,000 units/mL of penicillin (which is equivalent to 30 milligrams) and is extremely effective.

Alexander Fleming once said, “…I certainly didn’t plan to revolutionise all medicine by discovering the world’s first antibiotic…But I suppose that was exactly what I did.”

Yes, that is exactly what he did. Tom Volk states in his penicillin article, “We are grateful to veterans for fighting in wars, but veterans should likewise be grateful for Penicillium’s production of penicillin, as well as the scientists who made that possible.” According to Volk, only 25 percent of World War I soldiers healed from infection. Once penicillin was introduced, the number of World War II soldiers that healed from infection skyrocketed to 95 percent. In an interview, Dr. Ali S. Khan comments, “With penicillin…we were no longer talking about the prevention of infectious diseases, we started to talk about treatment…which gave us a brand new weapon to use on microbes.” Even though resistance to antibiotics is a threat, for once in human history, we are actually winning the war against microbes. Modern medicine is allowing our population to grow, our lifespan to be longer, and our quality of life to be much higher, and it all started with the accidental discovery of penicillin.