Howard Walter Florey and The Creation of Penicillin

Introduction

Throughout history, numerous world-changing drug discoveries have been made and they often left profound, long-lasting impacts on the healthcare of the human population. Among 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 during World War II, led to the onset of The Golden Age of Antibiotics, where many new innovations in 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 and English immigrant, and Bertha Mary, a native-born Australian, in Adelaide, South Australia (Fenner, 1996). He graduated from the University of Adelaide with an 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).

Howard Walter Florey and The Creation of Penicillin

After attaining his Ph.D. degree, Florey took on various positions as an academic, starting off with lecturing at the Cambridge pathology department where he also conducted his thesis on the flow of blood and lymph (Fenner, 1996). Following this, 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 went 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 equivalent 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 summarized that Penicillium fungus mold inhibited the growth of staphylococci on a staphylococcus culture plate (Eickhoff, 2008). While Fleming was credited for uncovering the antibacterial properties of Penicillium mold, he was unable to develop it into an applicable antibiotic in the industry as he struggled with isolating and mass-producing Penicillin synthetically. Fleming 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 II particularly sparked awareness of the extreme dangers of bacterial infections and raised its demand to top priority – troops were dying from minor cuts and grazes on the battlefield. As such, the American War Production Board (WBP) was willing to fund huge sums of money into antibacterial drug research (Quinn, 2013).

The Breakthrough

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 specialized in the field of chemistry and physiology; he also happened to be one of the first scientists 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 continued 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; the 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 Penicillin's antibacterial property and before long, Florey and Chain published an article on their findings in 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 team’s astounding discovery.

Human Trials and Mass Production

Naturally, Florey proceeded with human testing in 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, 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 mold where it could be exposed to air and thus grow (Science History Institute, 2017). In an urge to produce as much Penicillin as possible, all the institution’s labs and neighboring facilities at the Dunn School of Pathology were being occupied by ceramic pots and bedpans growing the Penicillium mold (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 needed. Florey desperately contacted many British pharmaceutical companies requesting 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 organization created by the Allies for military purposes).

The Impact and Legacy

Richards, who had a strong trust in Florey and saw the potential in Penicillin, accelerated the launch 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 World War II as an antibiotic to prevent amputations and death of troops. It was also used as a treatment for an issue called Septicemia which occurs when patients are operated on with equipment that has not been sterilized properly (Eickhoff, 2008). Today, Penicillin is a highly accessible drug with the ability to treat a wide range of different bacterial infections such as the common flu, Syphilis, Gonorrhea, Pneumonia, etc. (Eickhoff, 2008). The birth of Penicillin made a truly remarkable change in medicine and clinical practices, 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.

The Golden Age of Antibiotics

Furthermore, drugs such as antisera and sulphonamides which showed potential to treat some infectious diseases like 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 environments) and observing if they too produced antibiotic substances. Several hundred new antibiotics were discovered during this age, Amoxicillin being one of the notable examples (also Penicillium fungi derived) which is used to treat infections 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 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's greatest drug discovery pioneers.

References

• Eickhoff, T. C. (2008). The Emergence of Antibiotics: A Historical Perspective. Clinical Microbiology and Infection, 14(1), 1-8.
• Fenner, F. (1996). Sir Howard Florey: A Biography. Oxford University Press.
• Ogbru, O. (2016). Amoxicillin. RxList. Retrieved from https://www.rxlist.com/consumer_amoxicillin/drugs-condition.htm
• Quinn, R. (2013). Rethinking Antibiotic Research and Development: World War II and the Penicillin Collaborative. American Journal of Public Health, 103(3), 426-434.
• Science History Institute. (2017). Howard Florey and the Development of Penicillin. Retrieved from https://www.sciencehistory.org/historical-profile/howard-florey
• The University of Adelaide. (2018). Howard Florey: The Man Who Made Penicillin Available to the World. Retrieved from https://www.adelaide.edu.au/library/special/exhibitions/florey/