Featured in Episode 07: In Search of a Cure of The Health Files Podcast
Returning from holiday on September 3, 1928, Dr. Alexander Fleming began to sort through petri dishes he left in his office in London, each containing bacteria called Staphylococcus. Looking at the results of his experiment he noticed something unusual on one dish. The entire surface of it was covered with little colonies of bacterial growth, all except for one area where just a blob of mold was growing. The blob itself wasn't that interesting, though, it was the area around the blob: it was clear, as if, Dr. Fleming thought, the mold had secreted something that stopped the bacteria from growing.
Fleming was curious enough to run a few more experiments using this "mold juice, and he found that it was capable of killing a wide range of harmful bacteria. He then set his assistants the difficult task of isolating the pure compound from the mold juice that contained these bacteria fighting properties. Anybody currently pursuing their Ph.D. and having to be a teaching or research assistant just to make ends meet probably understands how they felt having been handed this task. The mold juice proved to be very unstable.
The pharmaceutical giant Pfizer's chairman John L. Smith later describes it as being: "as temperamental as an opera singer, the yields are low, the isolation is difficult, the extraction is murder, the purification invites disaster, and the testing is unsatisfactory."
Because of all of these things, Fleming's two assistants were only able to prepare small solutions of crude material to work with. Nevertheless, they had enough to run some cool little experiments and Dr. Fleming published his findings in the British Journal of Experimental Pathology in June 1929, citing the vast applications of his discovery: its main application would be in separating different types of bacteria in a mixed bacteria culture.
And it very well could have stayed there, unknown and forgotten, as a curiosity. If not for Oxford researchers Howard Florey, Ernst Chain and Charles Fletcher you may not have ever heard of this strange compound. Luckily, they saw a much more important use for it.
In 1939, just when WW2 conditions were beginning to make research especially difficult, they decided to carry out a program of animal experiments to test out the hunch that there was more to this compound than bacteria sorting. But again, they were faced with the same problem of production. In order to get enough mold juice to run their studies, the team needed to process up to 500 liters a week of mold. They began growing it in a strange array of culture vessels such as baths, milk jugs and food tins, which I assume is what we call Tupperware here in 2017. Florey, Chain and Fletcher, and most likely a team of underpaid research assistants carried out vital experiments, showing that this mold juice had much more widespread uses: it could protect mice against infection from deadly Streptococci bacteria family, which can take credit for causing not only strep throat, but also pink eye, meningitis, bacterial pneumonia, and 'flesh-eating' bacterial infections.
Seeing good results in mice, and at that time not really having a strict review or approval process for medical research, they immediately moved on to human trials.
They found a 50 year old woman who had advanced stage breast cancer and had not very long to live, and asked her to volunteer to take a dose of the new potential drug. Not because it could help her, but as a test as to its toxicity. She, apparently, agreed. The drug was injected into her vein, and the researchers waited.
Luckily, except for a slight fever, there seemed no serious side effects and the search for more volunteers was on. The second person to try out the drug - and the first person who could actually potentially benefits from its properties, was a 43-year old policeman, Albert Alexander. Despite being a policeman, the story of why he was in the hospital may surprise you: he had scratched the side of his mouth while pruning roses in his garden, and had developed a life-threatening infection with huge abscesses - an inflamed area n the body tissues that is filled with pus - affecting his eyes, face, and lungs. As described in the official accounts of the trial: "he was desperately and pathetically ill". There was all to gain and nothing to lose for him during this trial. The policeman received injections of the drug and within days he was showing remarkable improvement. Unfortunately, due to the crude way the mold juice drug was being developed, and the need for constant injections the researchers soon found their supplies dwindling. They got creative. As the official account from one of the researchers states:
"All the patients urine was collected and each morning I was took it to the Dunn Laboratory on my bicycle so that the excreted drug could be extracted to be used again."
Now that is what I call recycling...
Despite being injected the "recycled" drug, the policeman was showing a striking improvement, and after only five days he was eating well, and a visible reduction in the abscesses on his face. But when the supplies of the drug finally ran out, he regressed and died a few days later. Though a tragic story, this case was monumentally important. For the first time showed the remarkable effects of this new drug, proved its safety in continuous use in humans, and set it on a path to become one of the greatest inventions of all time.
The drug, of course, was called penicillin, and it is still one of the most widely used antibiotics in the world today, treating everything from acne to STDs, to pneumonia and sepsis.
Discovery and Development of Penicillin
Fletcher, Charles. "First clinical use of penicillin." British medical journal (Clinical research ed.) 289.6460 (1984): 1721.
Bhatt, Arun. "Evolution of clinical research: a history before and beyond James Lind." Perspectives in clinical research 1.1 (2010): 6.