Chapter 1
Imagine that ā¦
Alexander Fleming cleans up his dishes ⦠and penicillin is washed down the drain
Following a month-long family holiday, Alexander Fleming returned to St Maryās Hospital on the morning of 3 September 1928. The Scot found his laboratory even more cluttered than usual. He had hastily swept his petri dishes to one side before his trip, to clear room for his lab partner Stuart R. Craddock, and the dishes were now piled high. His first task of the day was to sort them. Unsurprisingly, after stewing in the laboratory for a month, the majority of the cultures growing in the dishes had been swamped by mould. Fleming took a large tray of Lysol disinfectant and began placing the contaminated samples within. Normally this would have been a job for a lab assistant but, eager to get back to work, he undertook the task himself. A pivotal distraction soon arrived in the form of D Merlin Pryce, Flemingās ex-lab assistant, stopping by to welcome him back from holiday.
Six years earlier Fleming had made a key scientific discovery which had drastically impacted upon his work in medicine. At the time, he was monitoring the condition of a patient who was suffering heavily from a head cold, collecting mucus and applying it to samples of bacteria on a daily basis. After a few days of no reaction, the mucus suddenly began to fight the bacteria on day four, successfully killing off large patches and weakening the rest. This had never been seen before. He soon discovered that he was observing the effects of Lysozyme, a naturally occurring bacteria-fighting agent present in tears and mucus.
Newly aware that it was possible to fight bacteria safely and successfully, Fleming spent the following years attempting to devise a drug that would do exactly that. He had been growing cultures of a bacterium called Staphylococcus aureus (Staph aureus) prior to his holiday, a strain responsible for a number of diseases and infections. Staph aureus was just the latest target in a long line of tests.
As he discussed his ongoing research with Pryce, the pair pored over the mouldy dishes. The Lysol tray was now overflowing with contaminated samples and only a handful of dishes at the bottom were fully disinfected. Fleming pulled one of the unwanted samples from the tray to show to his former colleague. Pryce instantly noticed something highly unusual. Where the spores of mould had formed, no bacteria surrounded them ā the same phenomenon that Fleming had observed in the Lysozyme. This could mean only one thing: the key to the cure lay in the mould.
He enlisted the help of his lab assistants and partners and set about studying the mould in greater detail. After growing the mould in a pure form they identified the substance as a derivation of a genus of fungi named Penicillium and so penicillin was born. This provided a much needed update from its previous moniker of āMould Juiceā. The team soon found that it could combat far more than just Staphylococcus. More importantly, their studies showed penicillin to be non-toxic. In 1888, a German scientist named E. de Freudenreich had managed to isolate an antibacterial substance named Pyocyanase, but faced one small problem. Pyocyanase was highly toxic to humans. Flemingās work on both Lysozyme and penicillin had proven that non-toxic antibiotics were a possibility. Work began on creating exactly that.
Fleming and his team lacked the required expertise to do this though, so they handed over the research. It was picked up by a team of pharmacologists based at Oxford University, led by Howard Florey (left) and Ernst Chain. It would take a decade and a horde of tireless biochemists the world over to transform the raw penicillin into the worldās first antibiotic. After a number of yearsā worth of successful trials had been carried out on mice, the first āpositiveā human trial ended in tragedy.
In February of 1941, Reserve Constable Albert Alexander of the County of Oxford Police Department sustained an injury to the inside of his mouth while pruning roses in his garden. He was rushed to hospital having contracted an aggressive infection which caused large abscesses to form both internally and on the surface of his body. With a host of trial data supporting the drug, it was finally time to try penicillin out on a human. The doctors were given the go-ahead and Constable Alexanderās course of treatment began. The early signs were hugely encouraging and, what with the abscesses clearing and his overall condition improving greatly, he looked like he would make a full recovery.
The medical team were still learning about penicillin, however, and, with no prior practical experience, mistakes were always a possibility in the maiden test. The doctors fell short of the required dosage and when supplies ran out they were unable to produce more due to the wartime restrictions placed upon the laboratory. Without penicillin to aid him, Constable Alexander suffered a relapse and eventually died on 15 March 1941. It was a personal tragedy but a medical triumph. The patientās initial response left the team in no doubt as to the drugās healing capabilities. Numerous successful trials followed and penicillin began to make its way into the hands of doctors.
Serving in World War I, Fleming had seen first-hand the damning effects of bacteria in warzones, with even the most innocuous looking grazes rendered fatal. It was a harsh reality that had long troubled him and was the driving force behind his successful research. His hopes were realised in 1941, thanks to Howard Florey. With the US entering into the war, Florey managed to persuade American pharmaceutical companies to mass produce the drug. No fewer than 39 laboratories were set up across the United States with the specific intention of synthesising inorganic penicillin for mass production. In 1943 British companies followed suit.
By 1944 there were sufficient supplies of penicillin to cover the Allied armies, providing a much needed boost at a crucial stage of the conflicts. The new antibiotic meant that patients needing surgery could be sustained for longer, keeping infections at bay so that many received life-saving surgery and treatment that would otherwise have been futile. It was the perfect drug for the army, since it did not require refrigeration like many other medicines that had been developed up until then. As a result, large quantities could be stored easily, which was a necessity when caring for entire army camps. Death and amputation rates soon dropped.
The worldwide effort to develop this āwonder drugā meant that there need not be a repeat of the sad case of Constable Alexander: by the end of World War I, penicillin was 20 times more potent than the pre-war trial version. Small scratches were no longer potentially fatal, even in undeveloped nations. Doctors were now able to save children from scarlet fever and stomach infections. It was not just the potency that had increased either. By the 1950s, more than 250,000 patients a month were being prescribed penicillin for their ailments. Never before had pharmacists possessed a drug that was in such ...