Howard Walter Florey and The Creation of Penicillin

Throughout history, numerous world-changing drug discoveries have been made and they often left profound, long lasting impacts in the healthcare of the human population. Amongst many great drug discovery pioneers, Sir Howard Walter Florey (24 September 1898 – 21 February 1968), was responsible for the discovery of Penicillin, an antibiotic drug capable of killing a wide range of different bacterial species. The creation of Penicillin, in addition to saving countless lives in World War 2, lead to the onset of The Golden Age of Antibiotics, where many new innovations of antibiotic drugs were made available in the pharmaceutical industry. Florey’s contribution to the development of Penicillin was so significant to the world that the 12th Prime Minister of Australia, Sir Robert Menzies said, “In terms of well-being, Florey was the most important man ever born in Australia” (The University of Adelaide 2018). He was awarded the Nobel Prize in Physiology or Medicine in 1945 alongside Sir Ernst Chain and Sir Alexander Fleming for his contributions to the discovery of Penicillin (Science History Institute 2017). Florey was born to Joseph Florey, a boot manufacturer English immigrant and Bertha Mary, a native-born Australian in Adelaide, South Australia (Fenner 1996). He graduated from the University of Adelaide with a M. B. , B. S in 1921 and shortly after, was offered a Rhodes Scholarship by the University of Oxford where he completed his B. Sc. and M. A. degrees in 1924 (Fenner 1996). He then transferred to the University of Cambridge where he conducted research on natural antibacterial substances, particularly lysosome (discovered by Alexander Fleming to have antibacterial properties in 1922) and attained his Ph. D. in 1927 (Fenner 1996).

After attaining his Ph. D. degree, Florey would take on various positions as an academic, starting off with lecturing at Cambridge pathology department where he also conducted his thesis on the flow of blood and lymph (Fenner 1996). Following on, he was appointed as the professor of pathology at the University of Sheffield in 1931 before finally transferring to Sir William Dunn School of Pathology as a director in 1936 (Fenner 1996). Prior to his retirement from Sir William Dunn School in 1962, it was there where Florey would go on to make his legendary discovery of Penicillin (Fenner 1996). Nowadays bacterial infections are sometimes viewed as somewhat trivial or at the very least, not very concerning to the current generation. Prior to the discovery of Penicillin, the threat that a bacterial infection posed to a patient was of equivalence to the danger that cancer poses to a patient today. In 1929 Fleming published an article in the British Journal of Experimental Pathology which essentially summarised that Penicillium fungus mould inhibited the growth staphylococci on a staphylococcus culture plate (Eickhoff 2008). While Fleming was credited for uncovering the antibacterial properties of Penicillium mould, he was unable to develop it into an applicable antibiotic in the industry as he struggled with isolating and mass-producing Penicillin synthetically. Fleming’s ended his research on Penicillin in 1931 and many years later Florey along with Ernst Chain would break the code and find a way to isolate Penicillin (Eickhoff 2008). World War 2 particularly sparked awareness of the extreme dangers of bacterial infections and raised its demand into top priority – troops were dying by minor cuts and grazes on the battlefield. As such, the American War Production Board (WBP), were willing to fund huge sums of money into antibacterial drug research (Quinn 2013).

Consequently, this allowed Florey, as the director of Sir William Dunn School of Pathology, to begin scouting for versatile scientists with strong knowledge in multiple disciplines of the field from all over the world. Amongst the team that Florey assembled, was Ernst Chain, a genius who specialised in the field of chemistry and physiology; he also happened to be one of the first scientist that was hired (Science History Institute 2017). Florey and his team began a research project on the crystallization of lysosome (an enzyme he had studied in the past which continues to spark his interest) and the characteristics of its substrate (Science History Institute 2017). Their research on lysosome ended in 1938 and this led to their next research project; production of antibacterial substances by certain microorganisms (Penicillin being one of them) and their biochemical and biological properties (Science History Institute 2017). During the research, Chain discovered a method to purify and concentrate Penicillin, which consisted of a few key points; the Penicillin broth had to be controlled within a certain pH range, the sample had to be chilled and the product had to be evaporated repeatedly (Science History Institute 2017). On May 1940, Florey conducted perhaps the most important experiment ever conducted, he injected Penicillin into four out of eight hemolytic streptococci infected mice with Penicillin and something extraordinary happened (Science History Institute 2017). Sixteen and a half hours passed and the four mice that were injected with Penicillin were still alive while the remaining four all died from the streptococci infection (Science History Institute 2017). This experiment was repeated numerous times for confirmation of the effectiveness of Penicillins antibacterial property and before long, Florey and Chain published an article on their findings on the Lancet in 1940 (Science History Institute 2017). By no surprise this left researchers from all over the globe in awe at Florey’s and his teams astounding discovery.

Naturally, Florey proceeded with human testing on January 1941 and in February 1941, an infected policeman became the first ever patient to be treated with Penicillin. During the early stages of the treatment, the drug appeared to be effective. However, there was an issue with a limited supply of Penicillin. Due to a lack of supply of Penicillin, the policeman eventually died. This motivated Florey to find a way to mass produce Penicillin (Science History Institute 2017). One of the first steps in the production of Penicillin was to surface-culture the Penicillium mould where it can be exposed to air and thus grow (Science History Institute 2017). In an urge to produce as much Penicillin as possible, all the institutions lab and neighbouring facilities at the Dunn School of Pathology were being occupied by ceramic pots and bedpans growing the Penicillium mould (Science History Institute 2017). Even despite going to this extent the reality was that they still weren’t producing anywhere near as much Penicillin as they need. Florey desperately contacted many British pharmaceutical companies requesting for assistance in Penicillin production, but every firm rejected him (due to priorities in manufacturing other drugs) except the Imperial Chemical Industry (although many of the companies that rejected his request would later cooperate). Florey’s alternative strategy was to seek help from America and thankfully, due to his connections he was able to receive assistance from his former laboratory director, A. N. Richards who was now the chair of the Committee on Medical Research in the Office of Scientific Research and Development (an organisation created by the Allies for military purposes).

Richards, who had a strong trust for Florey and saw the potential in Penicillin, accelerated the launched of a Penicillin production program which involved thousands of people and thirty-five institutions. Within the next few years, the program proved to be a huge success as 650 billion units of Penicillin were being made monthly in the US (Eickhoff 2008). Penicillin was used vastly in the WW2 as an antibiotic to prevent amputations and death of troops. It was also used as a treatment for an issue called Septicaemia which occurs when patients are operated on with equipment that has not been sterilized properly (Eickhoff 2008). Today, Penicillin is a highly accessible drugs with the ability to treat a wide range of different bacterial infections such as common flu, Syphilis, Gonorrhoea, Pneumonia etc. (Eickhoff 2008). The birth of Penicillin made a truly remarkable change in medicine and clinical practises, as mentioned instead of amputating a patient which would have been required before Penicillin to prevent death, patients could now simply ingest a drug to prevent amputation.

Furthermore, drugs such as antisera and sulphonamides which showed potential to treat some infectious diseases like as Pneumonia were completely abandoned simply because Penicillin’s effectiveness was on a different level in comparison (Eickhoff 2008). Then came the Golden Age of Antibiotics, where scientists began investigating all sorts of microorganisms (especially from soil environment) and observing if they too produced antibiotic substances. Several hundred of new antibiotics were discovered during this age, Amoxicillin being one of the notable examples (also Penicillium fungi derived) which is used to treat infection of the; ear, throat, larynx, lungs etc (Ogbru 2016). It is because of Florey that various bacterial infection diseases, which would have been classified as life threatening prior to Penicillin, are now considered as curable. Florey’s work on Penicillin will always be remembered as a legendary discovery and Florey himself will forever be remembered as one of the world greatest drug discovery pioneer.