Around April 6, 1915, the Russian composer Alexander Scriabin noticed a pimple on his upper lip. Soon, the blemish had become infected, and Scriabin was bedridden and feverish. On April 11, he died in agony from septicemia, despite doctors’ best efforts to save him.i
In the era before antibiotics, Scriabin’s fate was all too common. The smallest of cuts, nicks or scrapes (not to mention battlefield wounds) could become a death sentence. Throughout the millennia, millions of people died, slowly and painfully, from infections.
Today, as researchers work to develop a Covid-19 vaccine, it’s worth examining how, 100 years ago, the British bacteriologist Alexander Fleming discovered his first antibiotic, and how that breakthrough, achieved without advanced computer technology or genetic and genomic science, paved the way for the discovery of penicillin.
‘Happy Accident’ or ALIEN Thinking?
Bob Ross, host of the popular “Joy of Painting” TV series, was fond of saying, “We don’t make mistakes. We have happy accidents.” For generations, the world’s schoolchildren have learned that a small mistake by Alexander Fleming produced one of the happiest accidents in human history.
But was penicillin’s discovery entirely attributable to luck?
We believe the discovery and development of this wonder drug had less to do with luck than with “ALIEN Thinking,” an innovation framework that stands for Attention, Levitation, Imagination, Experimentation and Navigation. We classify Fleming, and those who followed up on his discovery, as ALIEN thinkers. Because these people see the world differently and approach breakthrough solutions differently, they make their own luck.
• Attention: Knowing How to Look
Attention is about actively looking at the world to observe problems that need to be solved, opportunities worth addressing and solutions that can be dramatically improved.
On the famous day in September 1928 when Fleming returned to his untidy lab and noticed that one of his bacterial cultures had been contaminated with mold spores possessing antibiotic properties, he was actively looking for anti-microbial agents. In fact, he had already discovered one antibiotic agent in 1921 (lysozyme) – exactly 100 years ago – by Experimenting with nasal mucus and human tears. Professor Charles Pennet, a classmate and fellow worker, said that “with lysozyme, the first step in the discovery of penicillin had been accomplished.”ii
Although the contamination of the petri dish with what was later identified as Penicillin notatum was indeed a stroke of luck, Fleming’s observation of the mold and its effect on the surrounding bacteria, was the result of Attention.
• Levitation: From Observation to Insight
Levitation is the act of stepping back to make sense of what you’ve noticed. Having found what he was not looking for, Fleming adopted a “30,000-foot view” to expand and enrich his understanding of the observations. This caused him to realize that it wasn’t the mold itself, but a liquid produced by the mold, that had killed nearby bacteria. Even more important, Fleming decided to save the contaminated dish for further study. Such mishaps happen all the time, and most are routinely discarded.
As The New York Times later noted: “Fleming deserved every honor conferred on him just for saving that mold.”iii That single sample would seed the experiments of others for years to come.
Fleming’s first paper on penicillin, published in 1929, was greeted with indifference or dismissal by his colleagues, but Fleming continued his research.
• Imagination: Envisioning What Does Not (Yet) Exist
Imaginative breakthroughs often occur when an ALIEN thinker connects seemingly unrelated “dots” – insights and ideas from separate worlds.
Because of his field hospital experiences during World War I, Fleming cautioned against the routine use of antiseptics. Publishing in the Lancet in 1917, he argued that while antiseptics were a good treatment for surface wounds, they prevented deep wounds from healing by killing white blood corpuscles.
A decade later, Fleming connected the dots: what if penicillin could be harnessed as an alternative to antiseptics? This insight spurred his research for years to come. Unfortunately, Fleming had neither the lab resources nor the chemistry background needed to “take the next giant steps of isolating the active ingredient of the penicillium mold juice, purifying it, figuring out which germs it was effective against, and how to use it.”[iv]
In 1938, this challenge was taken up by an Oxford University team led by Howard Florey, along with Ernst Chain and Norman Heatley, after they uncovered Fleming’s 1929 paper (Attention). Ultimately, Florey’s team would shepherd penicillin through the testing, development and production phases.
• Experimentation: Let’s Test
Experimentation is the process of turning a promising idea into a workable solution to a real need.
Like many ALIEN thinkers, Fleming had a well-developed sense of play, sometimes describing his research as “having fun with bacteria.” This sense of humor led him to introduce unlikely substances, such as nasal mucus and human tears, into bacterial cultures. As it turned out, these substances have distinct antibiotic properties, and it was this experimentation that led to the discovery of lysozyme.
Later, the Oxford team set out to prove their hypotheses and, just as important, to also uncover new information. Their experiments with both mice and human subjects revealed penicillin’s efficacy against certain bacteria, as well as its limitations. The tests also exposed issues related to both treatment and manufacturing. For example: in two early human tests, patients initially recovered from their infections — only to die when the supply of penicillin ran out. This testing revealed that to treat a single case of sepsis, 2,000 liters of mold culture fluid was needed to obtain enough penicillin.[v]
• Navigation: Steering Past the Obstacles
Navigation is about maneuvering to gain traction for your potential solution. In existing innovation models, it’s often referred to as “implementation” or “execution,” but this does scant justice to the ingenuity and resourcefulness required.
Florey and Chain saw the potential in Fleming’s findings, but transforming penicillin into a medicine required a whole different approach and set of capabilities. As biochemists, rather than bacteriologists, they had access to the facilities and expertise needed for extracting the pure chemical.[vi] This allowed them to establish that penicillin was only stable when dry, to succeed in producing concentrated doses, and to develop processes for manufacturing it at scale.
And unlike Fleming, Florey was a master Navigator. He was adept at marshaling resources and leveraging connections in the scientific community and the U.S. chemical and pharmaceutical industries. Eventually, Florey enlisted the help of 21 chemical and drug companies, boosted by U.S. entry into World War II. Within a few years, penicillin was available at every corner pharmacy.
It was the Oxford team that changed the trajectory of antibiotic research, accomplishing the difficult task of turning penicillin into a life-saving drug. Thanks to their efforts, penicillin went from a cottage industry to a commodity in the span of four years. But none of this would have been possible without Alexander Fleming. As an ALIEN thinker, he provides an invaluable lesson in Attention and luck favoring the prepared mind.
A key takeaway is that “seeing with fresh eyes” is a challenge not just at the Attention phase, but throughout the innovation process, right through to Navigation.
The other key point is the distinction between Alien thinkers and Alien thinking. Fleming was clearly an Alien thinker. His contribution was clearly necessary, but not sufficient, to reach a breakthrough solution. Innovation success called for ALIEN thinking on the part of multiple contributors to develop and scale his invention. Fleming later remarked: “Penicillin started as a chance observation. My only merit is that I did not neglect the observation and that I pursued the subject as a bacteriologist.”[vii]
i. Melissa Lesnie, “The 13 strangest composer deaths in classical music.” Limelight, April 12, 2012.
ii. H. Berger, M.D., “Sir Alexander Fleming, 1881-1955.” Clinical Cardiology, 12, 1989.
iii. A version of this article appears in print on April 15, 1984, Section 7, Page 12 of the National edition with the headline: THE FORGETFUL FATHER OF PENICILLIN.
iv. “The real story behind penicillin.” Health, September 27, 2013.
vi. Pdf article by colleague
vii. From Alexander Fleming’s Nobel Prize acceptance speech.