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Formation of the bacterial cell wall, during the process of cell division. When the bacterial cell is dividing, it needs to cross-link strings of polymers involving sugars and peptide chains of amino acids. In order for this to happen, it introduces an enzyme called transpeptidase. Penicillin is now known to block the action of transpeptidase during bacterial cell division. It does this by lodging on the enzyme where peptide strings would otherwise be gathered. The penicillin mould developed a clear biochemical structure, involving a beta-lactam ring and side chains, that enable this inhibiting action to be accomplished. The mould produces the penicillin as a means of inhibiting the growth of bacteria that would compete with it for food sources. Howard Florey was determined to find an important and effective means of combating bacterial infection utilizing substances produced for that purpose by nature. Prior to the discovery and use of penicillin as an antibiotic, a simple scratch could lead to deadly infection.
In 1928, Alexander Fleming noticed a mould growing on a discarded culture dish in his London laboratory. On closer examination, he saw that either the mould of something in it was stopping bacteria from growing anywhere near it. He later found out that the mould: Penicillium notatum was killing the bacteria around it. Fleming began to make a broth of the mould to test its antibacterial qualities but stopped investigating when his first results were disappointing, yet the mould was actually producing penicillin.
Historical Development
The innovation of penicillin was established when the Australian medical researcher Howard Florey teamed up with German biochemist Ernst Chain at oxford university in England, researching the bacteria-killing secretion of a mould, Penicillium notatum, first founded by Alexander Fleming. Florey lead and established a large research team to work with at a time when most scientists worked alone. Other Australians working on Floreys team included chemists John Cornforth and Rita Harredence, who were involved in working out the atomic structure of penicillin, Ethel Florey, who closely supervised the early clinical trials in Britain, and Hugh Cairns, who supervised trials on war wounds in Africa.
The innovation of penicillin was around the time of the discovery of sulfonamides and their little toxicity, which meant the end of the earlier attitude against toxic magic bullets . Florey was interested in how staphylococci was sensitive to the Penicillium mould but also unaffected by sulfonamides and lysozyme. Chain was intrigued by the failure of Fleming to identify the active ingredient in the penicillin mould-broth . Florey and Chain purified the penicillin from a section of Flemings mould that they developed, where they were able to demonstrate how penicillin could fight bacterial infection in mice and humans. Once they had found that the mould produced a bacterial emission, Florey and his multidisciplinary team isolated and identified the chemical agent responsible, where they found its effects in a purified form. To ensure that their work was not destroyed in an air raid, Florey and Chain rubbed bacteria of the mould inside their pant pockets when they left the lab at night.
In 1938, while attempting to find the active ingredient in the penicillin mould broth , Florey began testing on mice, where he successfully isolated Penicillium notatums antibacterial activity. He injected eight mice with lethal doses of Streptococcus pyogenes, two were given a single dose of penicillin (10mg), two were given 5mg of penicillin, plus three additional doses of 5mg at 3, 5, 7, and 11 hours after infection, and four were served as controls where they received no penicillin. After 17 hours, the four mice that did not receive penicillin had all died, while the mice that had received a penicillin dose survived. This observation provided substantial data that penicillin had the potential as a life-saving drug. Florey was then able to persuade breweries to ferment the mould for the beginning of trials on the battlefields of North Africa. Florey and his colleagues began by setting up their own ceramic culture vessel, where at the end of 1940, they received vessels, where they infected them with the fungus on December 25th. By the start of February 1941, the oxford team had purified abundant penicillin for clinical trials in humans.
Florey began working with American colleagues who helped established The Penicillin Project . There were three main streams that were included in the project. The first was focused on improving the purification of penicillin, the second intended to discover more effective efforts of Penicillium where Dr Norman Heatley worked closely with the US Department of Agriculture to portray these efforts, and the third was dedicated to finding pharmaceutical companies which would conduct the mass manufacture of penicillin.
Creativity
Mathematical creativity ensures the development of mathematics as an entire. It was found that imagery, social interaction, intuition, heuristics, and proof were the common features of mathematical creativity. Modern representations of creativity from psychology were studied and used to understand the characteristics of mathematical creativity. The discovery of penicillin is seen as to of happened purely to chance, not the result of conscious decision, emphasising how mathematical creativity does not need to be based on deliberate choices but can happen unintentionally.
Factors Affecting Innovation
Florey and his co-worker Dr Norman Heatley (who had worked out how to extract penicillin in a stable form utilizing a solvent extraction process) travelled to the USA in June 1941, where they were given a great reception, first at the Rockefeller Foundation, and then in further meetings in Washington involving officials from the National Research Council and the Bureau of Plant Industry (making a link with the mould as the basis of penicillin production).
A critical breakthrough came almost at once with the realization that the people who would most probably understand how to scale up the production of penicillin were not medical experts or biochemists, but agricultural and veterinary scientists.
This was around the time of the discovery of sulfonamides and their minimal toxicity. To Florey, as to many others, this meant the end of the earlier mindset against toxic magic bullets . He was interested in the fact that staphylococci, while resistant to sulfonamides and lysozyme, were apparently sensitive to the Penicillium mould
After further intensive research and trials, the antibiotic went into mass production in 1944, just in time for the Allies World War 2 Normandy landing. For military surgeons, penicillin seemed miraculous, enabling dramatically faster treatment and recovery by virtually eliminating infection. It saved countless thousands of soldiers lives and undoubtedly helped influence the wars outcome.
Available and Emerging Technologies
During the innovation of Penicillin, there was a range of different available and emerging technologies presented. The use of corn steep liquor as a medium to grow the Penicillium mould was one of the main advances achieved during the innovation of Penicillin. The liquor was a result of the industrial processes used to produce starch from corn. Instead of using the culture vessel of a liquid in a bottle which Florey had developed at Oxford, by developing a submerged fermentation using a liquid medium of corn steep liquor doubled the amount of penicillin almost instantly. Within a few years, the first major technical breakthrough of the new biotechnology era occurred as the deep fermentation method revolutionised the production of penicillin.
Before 1942, the basic manufacturing process in pharmaceutical manufacturing developments in the United States produced vaccines only in small scale.
Outside Agencies
During the process of innovating Penicillin, Florey and Chain worked with many outside agencies to ensure the success of the drug. They began by making their own ceramic vessels where the Penicillium mould could grow and develop and in 1940, Florey and his colleagues arranged for their vessels to be mass-produced by a pottery firm 100m away from Oxford. Later that year they received the vessels and Heatley infected them with fungus on December 25th.
In 1941, Great Britain couldnt afford to manufacture Penicillin, so Florey turned to the USA where the mass production of Penicillin was made part of the war effort. In the USA the use of Penicillin was limited to treating war wounds and for life-or-death civilian cases. In 1944, Australia became the first country to manufacture penicillin for the domestic market at the Commonwealth Serum Laboratories in Melbourne. Clinical trials took place across the US to further prove the effectiveness of the drug, where up to 15 drug companies in both the UK and US worked on penicillin production.
The government, industry and British and American scientists efficiently collaborated efforts that led to sufficient supplies of penicillin being manufactured by 1944, when Allied troops landed in France. After the war, by 1946, penicillin was widely available for prescription.
Entrepreneurial Activities
An entrepreneur is a person who can efficiently and effectively organise and manage enterprise. They make decisions and bear risks with the view of making a profit. Floreys role as an entrepreneur enabled him to make decisions, manage finance and manage intellectual property of the innovation. Florey and his colleagues viewed patents as unethical for such a life-saving drug. Penicillin challenged the basic notion of a patent, considering it was a natural product produced by another living microorganism.
Ethical Issues
At the time of the innovation, the production of penicillin did not have many ethical issues, although nowadays there would be ethic issues in how it was produced. During the innovation of penicillin, eight mice were injected by Florey with lethal doses of group A streptococcus, where 4 mice received doses of penicillin, and the other four were considered controls where they received no penicillin. After 17 hours, the four mice that did not receive penicillin died, while the group that had received a penicillin dose survived. The use of animals to test the drug was not unethical when penicillin was developed, although nowadays animal testing is considered unethical as experimenting on them cause pain and reduce their quality of life in other ways. Animal research has had a vital role in many scientific and medical advanced in the past that have increased our understanding of many diseases. Animal experimentation is seen as cruel and unnecessary, regardless of its purpose or benefit.
Environmental Considerations
In producing penicillin, the fermentation process requires large quantities of water and yields as primary liquid waste. Penicillin is produced by soil fungi in small quantities, where an overuse of the antibiotic is thought to damage the environmental microbiome. The waste from penicillin is able to reach the environment not only by the direct use of preservatives for plants, but also through urine and stools excreted by antibiotic-treated animals. Environmental non-pathogenic or opportunistic species could be exposed to antibiotics and act as a reservoir of resistance genes. Extensive agricultural use of penicillin, primary as growth promoters and to prevent infection in livestock, is linked to consumption of infected poultry in many parts of the world as it travels through the food chain.
Contribution to Australian Society
The development of penicillin led to the discovery of a number of new types of antibiotics, most of which are still used today to treat a variety of common illnesses. Without penicillin, the development of many modern medical practices, including organ transplants and skin drafts, would not have been. Possible. The innovation of Penicillin lead to the revolutionary manufacturing process for the entire pharmaceutical industry, where difficulties were solved for the industrial-scale aerobic fermentation and sterile product refinement. The shift from chemistry to microbiology as the basis of pharmaceutical manufacturing laid the groundwork for the commercialisation of the multitude of. Future drugs. Penicillin was released through the early post-war period where companies were able to use penicillin technologies to discover and produce other antibiotics such as streptomycin, tetracycline, erythromycin, vancomycin, and an excess of semisynthetic antibiotics. The penicillin production methods were also not limited to a single kind of drug. The same scientific engineering and infrastructure enabled the mass production of steroid hormones such as cortisone and complex vitamins such as B12. Microbiology also led to the discovery and production of a diverse array of compounds produced by microorganisms such as antineoplastic agents immunosuppressives, and individual compounds that lower lipid, iron and glucose levels.
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