Alexander Fleming
From Wikipedia, the free encyclopedia
For other uses, see Alexander Fleming (disambiguation). Sir Alexander Fleming
FRSE, FRS, FRCS(Eng) | | Born | 6 August 1881
Lochfield, Ayrshire, Scotland | Died | 11 March 1955 (aged 73)
London, England | Nationality | Scottish | Fields | Bacteriology, immunology | Alma mater | Royal Polytechnic Institution
St Mary's Hospital Medical School
Imperial College London | Known for | Discovery of penicillin | Notable awards | * FRS (1943)[1] * Nobel Prize (1945) * Knight Bachelor (1944) | Signature |
Sir Alexander Fleming, FRSE, FRS,[1] FRCS(Eng) (6 August 1881 – 11 March 1955) was a Scottish biologist, pharmacologist and botanist. He wrote many articles on bacteriology, immunology, and chemotherapy. His best-known discoveries are the enzyme lysozyme in 1923 and the antibiotic substance penicillin from the mould Penicillium notatum in 1928, for which he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Boris Chain.[2][3][4][5][6][7]
Contents
* 1 Early life and education * 2 Research * 2.1 Work before penicillin * 2.2 Accidental discovery * 2.3 Purification and stabilisation * 2.4 Antibiotics * 3 Myths * 4 Personal life * 5 Death * 6 Honours, awards and achievements * 7 See also * 8 Bibliography * 9 References * 10 External links
Early life and education
Fleming was born on 6 August 1881 at Lochfield farm near Darvel, in Ayrshire, Scotland. He was the third of the four children of farmer Hugh Fleming (1816–1888) from his second marriage to Grace Stirling Morton (1848–1928), the daughter of a neighbouring farmer. Hugh Fleming had four surviving children from his first marriage. He was 59 at the time of his second marriage, and died when Alexander (known as Alec) was seven.
Fleming went to Loudoun Moor School and Darvel School, and earned a two-year scholarship to Kilmarnock Academy before moving to London, where he attended the Royal Polytechnic Institution.[8] After working in a shipping office for four years, the twenty-year-old Fleming inherited some money from an uncle, John Fleming. His elder brother, Tom, was already a physician and suggested to his younger sibling that he should follow the same career, and so in 1903, the younger Alexander enrolled at St Mary's Hospital Medical School in Paddington; he qualified with an MBBS degree from the school with distinction in 1906.
Fleming had been a private in the London Scottish Regiment of the Volunteer Force since 1900,[2] and had been a member of the rifle club at the medical school. The captain of the club, wishing to retain Fleming in the team suggested that he join the research department at St Mary's, where he became assistant bacteriologist to Sir Almroth Wright, a pioneer in vaccine therapy and immunology. In 1908, he gained a BSc degree with Gold Medal in Bacteriology, and became a lecturer at St Mary's until 1914. Fleming served throughout World War I as a captain in the Royal Army Medical Corps, and was Mentioned in Dispatches. He and many of his colleagues worked in battlefield hospitals at the Western Front in France. In 1918 he returned to St Mary's Hospital, where he was elected Professor of Bacteriology of the University of London in 1928. In 1951 he was elected the Rector of the University of Edinburgh for a term of 3 years.
Research
Work before penicillin
Following World War I, Fleming actively searched for anti-bacterial agents, having witnessed the death of many soldiers from sepsis resulting from infected wounds. Antiseptics killed the patients' immunological defences more effectively than they killed the invading bacteria. In an article he submitted for the medical journal The Lancet during World War I, Fleming described an ingenious experiment, which he was able to conduct as a result of his own glass blowing skills, in which he explained why antiseptics were killing more soldiers than infection itself during World War I. Antiseptics worked well on the surface, but deep wounds tended to shelter anaerobic bacteria from the antiseptic agent, and antiseptics seemed to remove beneficial agents produced that protected the patients in these cases at least as well as they removed bacteria, and did nothing to remove the bacteria that were out of reach. Sir Almroth Wright strongly supported Fleming's findings, but despite this, most army physicians over the course of the war continued to use antiseptics even in cases where this worsened the condition of the patients.
In 1921, Fleming discovered "lysozyme", an enzyme that had an antibacterial effect.[9]
Accidental discovery

Miracle cure.
Main article: History of penicillin
"When I woke up just after dawn on September 28, 1928, I certainly didn't plan to revolutionise all medicine by discovering the world's first antibiotic, or bacteria killer," Fleming would later say, "But I suppose that was exactly what I did."[10]
By 1927, Fleming had been investigating the properties of staphylococci. He was already well-known from his earlier work, and had developed a reputation as a brilliant researcher, but his laboratory was often untidy. On 3 September 1928, Fleming returned to his laboratory having spent August on holiday with his family. Before leaving, he had stacked all his cultures of staphylococci on a bench in a corner of his laboratory. On returning, Fleming noticed that one culture was contaminated with a fungus, and that the colonies of staphylococci immediately surrounding the fungus had been destroyed, whereas other staphylococci colonies farther away were normal, famously remarking "That's funny".[11] Fleming showed the contaminated culture to his former assistant Merlin Price, who reminded him, "That's how you discovered lysozyme."[12] Fleming grew the mould in a pure culture and found that it produced a substance that killed a number of disease-causing bacteria. He identified the mould as being from the Penicillium genus, and, after some months of calling it "mould juice", named the substance it released penicillin on 7 March 1929.[13] The laboratory in which Fleming discovered and tested penicillin is preserved as the Alexander Fleming Laboratory Museum in St. Mary's Hospital, Paddington.
He investigated its positive anti-bacterial effect on many organisms, and noticed that it affected bacteria such as staphylococci and many other Gram-positive pathogens that cause scarlet fever, pneumonia, meningitis and diphtheria, but not typhoid fever or paratyphoid fever, which are caused by Gram-negative bacteria, for which he was seeking a cure at the time. It also affected Neisseria gonorrhoeae, which causes gonorrhoea although this bacterium is Gram-negative.
Fleming published his discovery in 1929, in the British Journal of Experimental Pathology,[14] but little attention was paid to his article. Fleming continued his investigations, but found that cultivating penicillium was quite difficult, and that after having grown the mould, it was even more difficult to isolate the antibiotic agent. Fleming's impression was that because of the problem of producing it in quantity, and because its action appeared to be rather slow, penicillin would not be important in treating infection. Fleming also became convinced that penicillin would not last long enough in the human body (in vivo) to kill bacteria effectively. Many clinical tests were inconclusive, probably because it had been used as a surface antiseptic. In the 1930s, Fleming’s trials occasionally showed more promise,[15] and he continued, until 1940, to try to interest a chemist skilled enough to further refine usable penicillin. Fleming finally abandoned penicillin, and not long after he did, Howard Florey and Ernst Boris Chain at the Radcliffe Infirmary in Oxford took up researching and mass-producing it, with funds from the U.S. and British governments. They started mass production after the bombing of Pearl Harbor. By D-Day in 1944, enough penicillin had been produced to treat all the wounded in the Allied forces.
Purification and stabilisation

3D-model of benzylpenicillin.
In Oxford, Ernst Boris Chain and Edward Abraham discovered how to isolate and concentrate penicillin. Abraham was the first to propose the correct structure of penicillin.[16][17] Shortly after the team published its first results in 1940, Fleming telephoned Howard Florey, Chain's head of department, to say that he would be visiting within the next few days. When Chain heard that he was coming, he remarked "Good God! I thought he was dead."
Norman Heatley suggested transferring the active ingredient of penicillin back into water by changing its acidity. This produced enough of the drug to begin testing on animals. There were many more people involved in the Oxford team, and at one point the entire Dunn School was involved in its production.
After the team had developed a method of purifying penicillin to an effective first stable form in 1940, several clinical trials ensued, and their amazing success inspired the team to develop methods for mass production and mass distribution in 1945.
Fleming was modest about his part in the development of penicillin, describing his fame as the "Fleming Myth" and he praised Florey and Chain for transforming the laboratory curiosity into a practical drug. Fleming was the first to discover the properties of the active substance, giving him the privilege of naming it: penicillin. He also kept, grew, and distributed the original mould for twelve years, and continued until 1940 to try to get help from any chemist who had enough skill to make penicillin. But Sir Henry Harris said in 1998: "Without Fleming, no Chain; without Chain, no Florey; without Florey, no Heatley; without Heatley, no penicillin."[18]
Antibiotics

Modern antibiotics are tested using a method similar to Fleming's discovery
Fleming's accidental discovery and isolation of penicillin in September 1928 marks the start of modern antibiotics. Before that, several scientists had published or pointed out that mould or penicillium sp. were able to inhibit bacterial growth, and even to cure bacterial infections in animals. Ernest Duchesne in 1897 in his thesis "Contribution to the study of vital competition in micro-organisms: antagonism between moulds and microbes",[19] or also Clodomiro Picado Twight whose work at Institut Pasteur in 1923 on the inhibiting action of fungi of the "Penicillin sp" genre in the growth of staphylococci drew little interest from the direction of the Institut at the time. Fleming was the first to push these studies further by isolating the penicillin, and by being motivated enough to promote his discovery at a larger scale. Fleming also discovered very early that bacteria developed antibiotic resistance whenever too little penicillin was used or when it was used for too short a period. Almroth Wright had predicted antibiotic resistance even before it was noticed during experiments. Fleming cautioned about the use of penicillin in his many speeches around the world. He cautioned not to use penicillin unless there was a properly diagnosed reason for it to be used, and that if it were used, never to use too little, or for too short a period, since these are the circumstances under which bacterial resistance to antibiotics develops.
Myths
The popular story[20] of Winston Churchill's father paying for Fleming's education after Fleming's father saved young Winston from death is false. According to the biography, Penicillin Man: Alexander Fleming and the Antibiotic Revolution by Kevin Brown, Alexander Fleming, in a letter[21] to his friend and colleague Andre Gratia,[22] described this as "A wondrous fable." Nor did he save Winston Churchill himself during World War II. Churchill was saved by Lord Moran, using sulphonamides, since he had no experience with penicillin, when Churchill fell ill in Carthage in Tunisia in 1943. The Daily Telegraph and the Morning Post on 21 December 1943 wrote that he had been saved by penicillin. He was saved by the new sulphonamide drug, Sulphapyridine, known at the time under the research code M&B 693, discovered and produced by May & Baker Ltd, Dagenham, Essex – a subsidiary of the French group Rhône-Poulenc. In a subsequent radio broadcast, Churchill referred to the new drug as "This admirable M&B."[23] It is highly probable that the correct information about the sulphonamide did not reach the newspapers because, since the original sulphonamide antibacterial, Prontosil, had been a discovery by the German laboratory Bayer, and as Britain was at war with Germany at the time, it was thought better to raise British morale by associating Churchill's cure with the British discovery, penicillin.
Personal life
On 23 December 1915, Fleming married a trained nurse, Sarah Marion McElroy of Killala, County Mayo, Ireland. Their only child, Robert Fleming, (b. 1924) became a general medical practitioner. After Sarah's death in 1949, Fleming married Dr. Amalia Koutsouri-Vourekas, a Greek colleague at St. Mary's, on 9 April 1953; she died in 1986.[24]
Death
On 11 March 1955, Fleming died at his home in London of a heart attack. He was buried in St Paul's Cathedral.[25]
Honours, awards and achievements

Display of Fleming's awards, including his Nobel Prize. Also shows a sample of penicillin and an example of an early apparatus for preparing penicillin.

Fleming (centre) receiving the Nobel prize from King Gustaf V of Sweden (right) in 1945

Faroe Islands stamp commemorating Fleming
His discovery of penicillin had changed the world of modern medicine by introducing the age of useful antibiotics; penicillin has saved, and is still saving, millions of people around the world.[26]
The laboratory at St Mary's Hospital where Fleming discovered penicillin is home to the Fleming Museum, a popular London attraction. His alma mater, St Mary's Hospital Medical School, merged with Imperial College London in 1988. The Sir Alexander Fleming Building on the South Kensington campus was opened in 1998 and is now one of the main preclinical teaching sites of the Imperial College School of Medicine.
His other alma mater, the Royal Polytechnic Institution (now the University of Westminster) has named one of its student halls of residence Alexander Fleming House, which is near to Old Street. * Fleming, Florey and Chain jointly received the Nobel Prize in Medicine in 1945. According to the rules of the Nobel committee a maximum of three people may share the prize. Fleming's Nobel Prize medal was acquired by the National Museums of Scotland in 1989 and is on display after the museum re-opened in 2011.[27] * Fleming was a member of the Pontifical Academy of Sciences.[2] * Fleming was elected a Fellow of the Royal Society of London[1] * Fleming was awarded the Hunterian Professorship by the Royal College of Surgeons of England. * Fleming was knighted, as a Knight Bachelor, by king George VI in 1944.[28] * He was made a Knight Grand Cross of the Order of Alfonso X the Wise in 1948. * In 1999, Time magazine named Fleming one of the 100 Most Important People of the 20th century, stating:
It was a discovery that would change the course of history. The active ingredient in that mould, which Fleming named penicillin, turned out to be an infection-fighting agent of enormous potency. When it was finally recognized for what it was, the most efficacious life-saving drug in the world, penicillin would alter forever the treatment of bacterial infections. By the middle of the century, Fleming's discovery had spawned a huge pharmaceutical industry, churning out synthetic penicillins that would conquer some of mankind's most ancient scourges, including syphilis, gangrene and tuberculosis.[29] * When 2000 was approaching, at least three large Swedish magazines ranked penicillin as the most important discovery of the millennium. * In 2002, Fleming was named in the BBC's list of the 100 Greatest Britons following a nationwide vote.[30] * A statue of Alexander Fleming stands outside the main bullring in Madrid, Plaza de Toros de Las Ventas.[31] It was erected by subscription from grateful matadors, as penicillin greatly reduced the number of deaths in the bullring.[31] * Flemingovo náměstí is a square named after Fleming in the university area of the Dejvice community in Prague. * A secondary school is named after him in Sofia, Bulgaria. * In mid-2009, Fleming was commemorated on a new series of banknotes issued by the Clydesdale Bank; his image appears on the new issue of £5 notes.[32] * 91006 Fleming, an asteroid in the Asteroid Belt, is named after Fleming.
See also * Medicinal molds
Bibliography
* The Life Of Sir Alexander Fleming, Jonathan Cape, 1959. Maurois, André. * Nobel Lectures,the Physiology or Medicine 1942–1962, Elsevier Publishing Company, Amsterdam, 1964 * An Outline History of Medicine. London: Butterworths, 1985. Rhodes, Philip. * The Cambridge Illustrated History of Medicine. Cambridge, England: Cambridge University Press, 1996. Porter, Roy, ed. * Penicillin Man: Alexander Fleming and the Antibiotic Revolution, Stroud, Sutton, 2004. Brown, Kevin. * Alexander Fleming: The Man and the Myth, Oxford University Press, Oxford, 1984. Macfarlane, Gwyn * Fleming, Discoverer of Penicillin, Ludovici, Laurence J., 1952
References
Penicillin
From Wikipedia, the free encyclopedia
For the Japanese band, see Penicillin (band).

Penicillin core structure, where "R" is the variable group.
Penicillin (sometimes abbreviated PCN or pen) is a group of antibiotics derived from Penicillium fungi,[1] including penicillin G (intravenous use), penicillin V (oral use), procaine penicillin, and benzathine penicillin (intramuscular use).
Penicillin antibiotics were among the first drugs to be effective against many previously serious diseases, such as bacterial infections caused by staphylococci and streptococci. Penicillins are still widely used today, though misuse has now made many types of bacteria resistant. All penicillins are β-lactam antibiotics and are used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms.
Several enhanced penicillin families also exist, effective against additional bacteria: these include the antistaphylococcal penicillins, aminopenicillins and the more-powerful antipseudomonal penicillins.
Contents
* 1 Medical uses * 1.1 Susceptibility * 2 Adverse effects * 3 Mechanism of action * 4 Structure * 5 Biosynthesis * 6 Production * 7 History * 7.1 Discovery * 7.2 Medical application * 7.3 Mass production * 7.4 Structure determination and total synthesis * 7.5 Developments from penicillin * 8 See also * 9 Notes * 10 References * 11 External links
Medical uses
The term "penicillin" is often used generically to refer to benzylpenicillin (penicillin G), procaine benzylpenicillin (procaine penicillin), benzathine benzylpenicillin (benzathine penicillin), and phenoxymethylpenicillin (penicillin V). Procaine penicillin and benzathine penicillin have the same antibacterial activity as benzylpenicillin but act for a longer period of time. Phenoxymethylpenicillin is less active against gram-negative bacteria than benzylpenicillin.[2][3] Benzylpenicillin, procaine penicillin and benzathine penicillin are given by injection (parenterally), but phenoxymethylpenicillin is given orally.
Susceptibility
Despite the expanding number of penicillin resistant bacteria, penicillin can still be used to treat a wide range of infections caused by certain susceptible bacteria. Some of these bacteria include Streptococci, Staphylococci, Clostridium, and Listeria genera. The following list illustrates minimum inhibitory concentration susceptibility data for a few medically significant bacteria:[4][5] * Listeria monocytogenes: from less than or equal to 0.06 μg/ml to 0.25 μg/ml * Neisseria meningitidis: from less than or equal to 0.03 μg/ml to 0.5 μg/ml * Staphylococcus aureus: from less than or equal to 0.015 μg/ml to more than 32 μg/ml
Adverse effects
Main article: Penicillin drug reaction
Common adverse drug reactions (≥ 1% of patients) associated with use of the penicillins include diarrhoea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection (including candidiasis). Infrequent adverse effects (0.1–1% of patients) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in people with epilepsy), and pseudomembranous colitis.[6]
Mechanism of action | This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (January 2014) |
Main article: Beta-lactam antibiotic

Bacteria that attempt to grow and divide in the presence of penicillin fail to do so, and instead end up shedding their cell walls.

Penicillin and other β-lactam antibiotics act by inhibiting penicillin-binding proteins, which normally catalyze cross-linking of bacterial cell walls.
Bacteria constantly remodel their peptidoglycan cell walls, simultaneously building and breaking down portions of the cell wall as they grow and divide. β-Lactam antibiotics inhibit the formation of peptidoglycan cross-links in the bacterial cell wall; this is achieved through binding of the four-membered β-lactam ring of penicillin to the enzyme DD-transpeptidase. As a consequence, DD-transpeptidase cannot catalyze formation of these cross-links, and an imbalance between cell wall production and degradation develops, causing the cell to rapidly die.
The enzymes that hydrolyze the peptidoglycan cross-links continue to function, even while those that form such cross-links do not. This weakens the cell wall of the bacterium, and osmotic pressure becomes increasingly uncompensated—eventually causing cell death (cytolysis). In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases and autolysins, which further digest the cell wall's peptidoglycans. The small size of the penicillins increases their potency, by allowing them to penetrate the entire depth of the cell wall. This is in contrast to the glycopeptide antibiotics vancomycin and teicoplanin, which are both much larger than the penicillins.[7]
Gram-positive bacteria are called protoplasts when they lose their cell walls. Gram-negative bacteria do not lose their cell walls completely and are called spheroplasts after treatment with penicillin.
Penicillin shows a synergistic effect with aminoglycosides, since the inhibition of peptidoglycan synthesis allows aminoglycosides to penetrate the bacterial cell wall more easily, allowing their disruption of bacterial protein synthesis within the cell. This results in a lowered MBC for susceptible organisms.
Penicillins, like other β-lactam antibiotics, block not only the division of bacteria, including cyanobacteria, but also the division of cyanelles, the photosynthetic organelles of the glaucophytes, and the division of chloroplasts of bryophytes. In contrast, they have no effect on the plastids of the highly developed vascular plants. This supports the endosymbiotic theory of the evolution of plastid division in land plants.[8]
The chemical structure of penicillin is triggered with a very precise, pH-dependent directed mechanism, effected by a unique spatial assembly of molecular components, which can activate by protonation. It can travel through bodily fluids, targeting and inactivating enzymes responsible for cell-wall synthesis in gram-positive bacteria, meanwhile avoiding the surrounding non-targets. Penicillin can protect itself from spontaneous hydrolysis in the body in its anionic form, while storing its potential as a strong acylating agent, activated only upon approach to the target transpeptidase enzyme and protonated in the active centre. This targeted protonation neutralizes the carboxylic acid moiety, which is weakening of the β-lactam ring N–C(=O) bond, resulting in a self-activation. Specific structural requirements are equated to constructing the perfect mouse trap for catching targeted prey.[9]
Structure

Chemical structure of Penicillin G. The sulfur and nitrogen of the five-membered thiazolidine ring are shown in yellow and blue respectively. The image shows that the thiazolidine ring and fused four-membered β-lactam are not in the same plane.
The term "penam" is used to describe the common core skeleton of a member of the penicillins. This core has the molecular formula R-C9H11N2O4S, where R is the variable side chain that differentiates the penicillins from one another. The penam core has a molecular weight of 243 g/mol, with larger penicillins having molecular weights near 450—for example, cloxacillin has a molecular weight of 436 g/mol. The key structural feature of the penicillins is the four-membered β-lactam ring; this structural moiety is essential for penicillin's antibacterial activity. The β-lactam ring is itself fused to a five-membered thiazolidine ring. The fusion of these two rings causes the β-lactam ring to be more reactive than monocyclic β-lactams because the two fused rings distort the β-lactam amide bond and therefore remove the resonance stabilisation normally found in these chemical bonds.[10]
Biosynthesis

Penicillin G biosynthesis
Overall, there are three main and important steps to the biosynthesis of penicillin G (benzylpenicillin). * The first step is the condensation of three amino acids—L-α-aminoadipic acid, L-cysteine, L-valine into a tripeptide.[11][12][13] Before condensing into the tripeptide, the amino acid L-valine must undergo epimerization to become D-valine.[14][15] The condensed tripeptide is named δ-(L-α-aminoadipyl)-L-cysteine-D-valine (ACV). The condensation reaction and epimerization are both catalyzed by the enzyme δ-(L-α-aminoadipyl)-L-cysteine-D-valine synthetase (ACVS), a nonribosomal peptide synthetase or NRPS. * The second step in the biosynthesis of penicillin G is the oxidative conversion of linear ACV into the bicyclic intermediate isopenicillin N by isopenicillin N synthase (IPNS), which is encoded by the gene pcbC.[11][12] Isopenicillin N is a very weak intermediate, because it does not show strong antibiotic activity.[14] * The final step is a transamidation by isopenicillin N N-acyltransferase, in which the α-aminoadipyl side-chain of isopenicillin N is removed and exchanged for a phenylacetyl side-chain. This reaction is encoded by the gene penDE, which is unique in the process of obtaining penicillins.[11]
Production
Penicillin is a secondary metabolite of certain species of Penicillium and is produced when growth of the fungus is inhibited by stress. It is not produced during active growth. Production is also limited by feedback in the synthesis pathway of penicillin. α-ketoglutarate + AcCoA → homocitrate → L-α-aminoadipic acid → L-lysine + β-lactam
The by-product, l-lysine, inhibits the production of homocitrate, so the presence of exogenous lysine should be avoided in penicillin production.
The Penicillium cells are grown using a technique called fed-batch culture, in which the cells are constantly subject to stress, which is required for induction of penicillin production. The available carbon sources are also important: Glucose inhibits penicillin production, whereas lactose does not. The pH and the levels of nitrogen, lysine, phosphate, and oxygen of the batches must also be carefully controlled.
The biotechnological method of directed evolution has been applied to produce by mutation a large number of Penicillium strains. These techniques include error-prone PCR, DNA shuffling, ITCHY, and strand-overlap PCR.
Semisynthetic penicillins are prepared starting from the penicillin nucleus 6-APA.
History
Discovery
Main article: History of penicillin

Alexander Fleming, who is credited with discovering penicillin in 1928.
Sample of penicillium mould presented by Alexander Fleming to Douglas Macleod, 1935
In 1897 a French physician, Ernest Duchesne at École du Service de Santé Militaire in Lyons, published a medical thesis entitled Contribution à l’étude de la concurrence vitale chez les micro-organismes : antagonisme entre les moisissures et les microbes (Contribution to the study in vital competition in microorganisms: antagonism between molds and microbes) in which he specifically studied the interaction between Escherichia coli and Penicillium glaucum. He independently discovered healing properties of P. glaucum, even curing infected guinea pigs from typhoid. His dissertation[16] was ignored by the Institut Pasteur. Although he is the precursor to antibiotic-mediated therapy and penicillin in particular, his works were subsequently forgotten.[17]
The discovery of penicillin is attributed to Scottish scientist and Nobel laureate Alexander Fleming in 1928.[18] He showed that, if Penicillium rubens[19] were grown in the appropriate substrate, it would exude a substance with antibiotic properties, which he dubbed penicillin. This serendipitous observation began the modern era of antibiotic discovery. The development of penicillin for use as a medicine is attributed to the Australian Nobel laureate Howard Walter Florey, together with the German Nobel laureate Ernst Chain and the English biochemist Norman Heatley.[20]
Fleming recounted that the date of his discovery of penicillin was on the morning of Friday, September 28, 1928.[21] The traditional version of this story describes the discovery as a fortuitous accident: in his laboratory in the basement of St Mary's Hospital in London (now part of Imperial College), Fleming noticed a Petri dish containing Staphylococcus that had been mistakenly left open, was contaminated by blue-green mould from an open window, which formed a visible growth.[22] There was a halo of inhibited bacterial growth around the mould. Fleming concluded that the mould released a substance that repressed the growth and caused lysing of the bacteria.[20]
Scientists now suspect that Fleming’s story of the initial discovery of the antibacterial properties of the penicillium mould is inaccurate. With a modern understanding of how the bacteria and the mould interact, scientists know that if bacteria were already present on the petri dish they would have inhibited the growth of the mould and Fleming would not have noticed any mould on the plate at all. A more likely story is that a spore from a laboratory one floor below, run by C. J. La Touche, was transferred to Fleming's petri dish before the bacteria were added. At the time of the initial discovery La Touche was working with the same mould found in Fleming's petri dish.[22]
Once Fleming made his discovery he grew a pure culture and discovered it was a Penicillium mould, now known to be Penicillium notatum. Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the Penicillium mould. Fleming asked C. J. La Touche to help identify the mould, which he incorrectly identified as Penicillium rubrum (later corrected by Charles Thom). He expressed initial optimism that penicillin would be a useful disinfectant, because of its high potency and minimal toxicity in comparison to antiseptics of the day, and noted its laboratory value in the isolation of Bacillus influenzae (now called Haemophilus influenzae).[23][22]
Fleming was a famously poor communicator and orator, which meant his findings were not initially given much attention.[22] He was unable to convince a true chemist to help him extract and stabilize the antibacterial compound found in the broth filtrate. Despite the lack of a true chemist, he remained interested in the potential use of penicillin and presented a paper entitled "A Medium for the Isolation of Pfeiffer’s Bacillus" to the medical research club of London, which was met with little interest and even less enthusiasm by his peers. Had Fleming been more successful at making other scientists interested in his work, penicillin for medicinal use would possibly have been developed years earlier.[22]
Despite the lack of interest of his fellow scientists, he did conduct several experiments on the antibiotic substance he discovered. The most important result proved it was nontoxic in humans by first performing toxicity tests in animals and then on humans. His following experiments on penicillin's response to heat and pH allowed Fleming to increase the stability of the compound.[23] The one test that modern scientists would find missing from his work was not testing penicillin on an infected animal, the results of which would likely have sparked great interest in penicillin and sped its development by almost a decade.[22]
Medical application

Florey (pictured), Fleming and Chain shared a Nobel Prize in 1945 for their work on penicillin.
In 1930, Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, attempted to use penicillin to treat sycosis barbae, eruptions in beard follicles, but was unsuccessful. Moving on to ophthalmia neonatorum, a gonococcal infection in infants, he achieved the first recorded cure with penicillin, on November 25, 1930. He then cured four additional patients (one adult and three infants) of eye infections, and failed to cure a fifth.[24][25][26]
In 1939, Australian scientist Howard Florey (later Baron Florey) and a team of researchers (Ernst Boris Chain, Arthur Duncan Gardner, Norman Heatley, M. Jennings, J. Orr-Ewing and G. Sanders) at the Sir William Dunn School of Pathology, University of Oxford made progress in showing the in vivo bactericidal action of penicillin. In 1940 they showed that penicillin effectively cured bacterial infection in mice.[27][28] In 1941 they treated a policeman with a severe face infection; the patient improved, but then supplies of penicillin ran out and he died. Subsequently, several other patients were treated successfully.[29]
Mass production
A technician preparing penicillin in 1943
By late 1940, the Oxford team under Howard Florey had devised a method of mass-producing the drug, but yields remained low.[29] In 1941, Florey and Heatley traveled to the U.S. in order to interest pharmaceutical companies in producing the drug and inform them about their process.[29]
Florey and Chain shared the 1945 Nobel Prize in Medicine with Fleming for their work.
The challenge of mass-producing this drug was daunting. On March 14, 1942, the first patient was treated for streptococcal septicemia with US-made penicillin produced by Merck & Co.[30] Half of the total supply produced at the time was used on that one patient. By June 1942, just enough US penicillin was available to treat ten patients.[31] In July 1943, the War Production Board drew up a plan for the mass distribution of penicillin stocks to Allied troops fighting in Europe.[32] The results of fermentation research on corn steep liquor at the Northern Regional Research Laboratory at Peoria, Illinois, allowed the United States to produce 2.3 million doses in time for the invasion of Normandy in the spring of 1944. After a worldwide search in 1943, a mouldy cantaloupe in a Peoria, Illinois market was found to contain the best strain of penicillin for production using the corn steep liquor process.[33] Large-scale production resulted from the development of deep-tank fermentation by chemical engineer Margaret Hutchinson Rousseau.[34] As a direct result of the war and the War Production Board, by June 1945, over 646 billion units per year were being produced.[32]

Penicillin was being mass-produced in 1944.
G. Raymond Rettew made a significant contribution to the American war effort by his techniques to produce commercial quantities of penicillin.[35] During World War II, penicillin made a major difference in the number of deaths and amputations caused by infected wounds among Allied forces, saving an estimated 12%–15% of lives.[citation needed] Availability was severely limited, however, by the difficulty of manufacturing large quantities of penicillin and by the rapid renal clearance of the drug, necessitating frequent dosing. Methods for mass production of penicillin were patented by Andrew Jackson Moyer in 1945.[36][37][38] Florey had not patented penicillin, having been advised by Sir Henry Dale that doing so would be unethical.[29]
Penicillin is actively excreted, and about 80% of a penicillin dose is cleared from the body within three to four hours of administration. Indeed, during the early penicillin era, the drug was so scarce and so highly valued that it became common to collect the urine from patients being treated, so that the penicillin in the urine could be isolated and reused.[39] This was not a satisfactory solution, so researchers looked for a way to slow penicillin excretion. They hoped to find a molecule that could compete with penicillin for the organic acid transporter responsible for excretion, such that the transporter would preferentially excrete the competing molecule and the penicillin would be retained. The uricosuric agent probenecid proved to be suitable. When probenecid and penicillin are administered together, probenecid competitively inhibits the excretion of penicillin, increasing penicillin's concentration and prolonging its activity. Eventually, the advent of mass-production techniques and semi-synthetic penicillins resolved the supply issues, so this use of probenecid declined.[39] Probenecid is still useful, however, for certain infections requiring particularly high concentrations of penicillins.[6]
After World War II, Australia was the first country to make the drug available for civilian use. In the U.S., penicillin was made available to the general public on March 15, 1945.[40]

Dorothy Hodgkin determined the chemical structure of penicillin.
Structure determination and total synthesis
In 1945 the chemical structure of penicillin was determined using X-ray crystallography by Dorothy Crowfoot Hodgkin, who was also working at Oxford.[41] She later received the Nobel prize for this and other structure determinations.
Chemist John C. Sheehan at the Massachusetts Institute of Technology (MIT) completed the first chemical synthesis of penicillin in 1957.[42][43][44] Sheehan had started his studies into penicillin synthesis in 1948, and during these investigations developed new methods for the synthesis of peptides, as well as new protecting groups—groups that mask the reactivity of certain functional groups.[44][45] Although the initial synthesis developed by Sheehan was not appropriate for mass production of penicillins, one of the intermediate compounds in Sheehan's synthesis was 6-aminopenicillanic acid (6-APA), the nucleus of penicillin.[44][46][47][page needed] Attaching different groups to the 6-APA 'nucleus' of penicillin allowed the creation of new forms of penicillin.
Developments from penicillin
The narrow range of treatable diseases or "spectrum of activity" of the penicillins, along with the poor activity of the orally active phenoxymethylpenicillin, led to the search for derivatives of penicillin that could treat a wider range of infections. The isolation of 6-APA, the nucleus of penicillin, allowed for the preparation of semisynthetic penicillins, with various improvements over benzylpenicillin (bioavailability, spectrum, stability, tolerance).
The first major development was ampicillin in 1961. It offered a broader spectrum of activity than either of the original penicillins. Further development yielded β-lactamase-resistant penicillins, including flucloxacillin, dicloxacillin, and methicillin. These were significant for their activity against β-lactamase-producing bacterial species, but were ineffective against the methicillin-resistant Staphylococcus aureus (MRSA) strains that subsequently emerged.
Another development of the line of true penicillins was the antipseudomonal penicillins, such as carbenicillin, ticarcillin, and piperacillin, useful for their activity against Gram-negative bacteria. However, the usefulness of the β-lactam ring was such that related antibiotics, including the mecillinams, the carbapenems and, most important, the cephalosporins, still retain it at the center of their structures.[48]
Alexander Fleming was a great Scottish biologist and pharmacologist who made way for antibiotic medicines with his discovery of penicillin from the mould “Penicillium notatum”. Fleming’s discoveries brought new hope to mankind in battling certain diseases and treating bacterial infections. Fleming’s various works are recorded in his articles on bacteriology, immunology, and chemotherapy. He won his Nobel Prize in Physiology or Medicine for his outstanding contributions and path breaking discoveries in medicines. Such is the impact of the great man that his name had even featured in the list of 100 Most Important People of the 20th Century as recently as in 1999. Present day penicillin upgrades carried put by the medicine world stand on one man’s quest and that is none other than Fleming. By discovering synthetic penicillin Fleming paved the way for preventing and fighting serious illnesses like syphilis, gangrene and tuberculosis which were never imagined of being treated before Fleming’s discoveries.
Alexander Fleming Childhood
Alexander Fleming was born on 6 August 1881 at Lochfield, a farm located near Darvel in Ayrshire, Scotland. Fleming was third among 4 children born to father Hugh Fleming and Grace Stirling Morton. Alexander lost his father at the age of 7. Education
Fleming received his formal education from Loudoun Moor School and Darvel School. He worked his way in earning a scholarship for 2 years to pursue his studies at Kilmarnock Academy. Soon after completing his primary education Fleming shifted his base to London enrolling himself in the Royal Polytechnic Institution. Fleming was recruited in a shipping office for 4 years before inheriting some money from his uncle John Fleming. Alexander’s elder brother Tom was a physicist who suggested Alexander to take up the same career. This brotherly suggestion made Alexander enrol himself at St Mary's Hospital, Paddington, London in 1903 where he earned a distinction in 1906 which qualified him to become a surgeon. Career in the Military
Alexander had been a prominent member of the rifle club. Since 1900 Alexander had actively remained a member of the Volunteer Force which was formed by citizen army group practicing part-time rifle, artillery and engineer corps. This group became very popular in the mid 19th century and many volunteer units were recruited by the British Army. The captain of the rifle club wanted Fleming to stay with the team which made Fleming join the research department at St Mary's and later become an assistant bacteriologist to Sir Almroth Wright who was a pioneer in vaccine therapy and immunology. Fleming soon gained his rightly earned positions, earning his M.B. and later a B.Sc. with Gold Medal in 1908. Fleming was appointed as a lecturer at St. Mary's where he remained till 1914. Fleming was called to serve at the World War I where he was a captain in the Royal Army Medical Corps and was awarded MID (Mentioned in Dispatches). Fleming played his part all through the war. Fleming, along with many of his colleagues, served in several battlefield hospitals at the Western Front in France. It was only in 1918 that Fleming could return to St. Mary's Hospital, which turned into a teaching hospital. Fleming was chosen as the Professor of Bacteriology in 1928. Research Works on Penicillin
The war had a great impact on Fleming’s scientific mind. Having witnessed deaths of so many soldiers, Fleming frantically searched for anti bacterial agents in order to create medicines that could treat infections and wounds. Fleming was not keen to create antiseptics which did nothing to kill the fast increasing bacteria instead they reduced the sufferer’s immunological defences. Fleming had greatly explained the unworthy nature of antiseptics in one of his article written for the medical journal ‘The Lancet’ during World War I where he had discussed about an experiment he had conducted showing the reasons why antiseptics were killing more soldiers than infection itself during World War. Fleming showed the world that antiseptics actually did not work well in treating deep wounds but were great on surface wounds. Fleming’s serious researches on uselessness of antiseptics for deep wounds were greatly supported by Sir Almroth Wright. In spite of Fleming’s findings several physicians continued using antiseptics on wounded patients during the war thus worsening their conditions. Fleming became famous for his research works. By 1928 Fleming had started off his research on the properties of ‘staphylococci’ bacteria. By this time Fleming had earned a high name as a great researcher. Fleming was known to keep his laboratory untidy. It was on 3 September 1928 when Fleming returned to his laboratory from an August holiday to find one of his staphylococci cultures (which he had stacked on a corner of a bench in his laboratory before leaving for his holiday) contaminated with a fungus. Fleming intently noted that the colonies of staphylococci that had immediately surrounded the affected culture were destroyed while other colonies kept far away remained normal. Fleming took the contaminated culture to his former assistant Merlin Price for consultation. Merlin said that Fleming had chanced upon the discovery of lysozome. So Fleming decided to grow the mould in a pure culture and discovered that it was able to produce an element which killed a number of disease-causing bacteria. Fleming discovered the mould to be of the Penicillium genus. Soon after a few months he named the substance it released as ‘penicillin’ on 7 March 1929. Fleming extensively researched on the positive qualities (anti bacterial effect) of the element and found that it affected several bacteria such as staphylococci and many other Gram-positive pathogens that cause scarlet fever, pneumonia, meningitis and diphtheria. In 1929 Fleming brought his discovery in the British Journal of Experimental Pathology which did not attract much attention. Fleming found it very difficult to extract and collect penicillium as there was much difficulty in isolating the antibiotic agent. Fleming continued with his quest for penicillin but started having the impression that its actions were slow and that it would not find importance in treating infections. Fleming started believing that penicillin would not have a lasting impact on the human body in killing the bacteria effectively. Several tests performed by him remained incomplete. However, Fleming’s researches on penicillin started finding firm shape in the 1930s. He strived till 1940 to arouse chemists’ interest in further refining usable penicillin. After several years Fleming decided to give up his quest for penicillin. Soon after this, Florey and Chain, at the Radcliffe Infirmary in Oxford, started researching and successfully produced penicillin with the U.S. and British governments’ funds. The Pearl Harbour bombing on 7 December 1941 resulted in the Infirmary producing penicillin hugely which served in treating all the wounded allied forces. Personal Life
On 23 December 1915, Fleming married a trained nurse, Sarah Marion McElroy. She died in 1949 leaving Fleming with their only child, Robert Fleming who later became a general medical practitioner. On 9 April 1953 Fleming married his second wife Dr. Amalia Koutsouri-Vourekas, a Greek colleague at St. Mary's Hospital where Fleming had been attached throughout his life. Awards and Honours
Fleming’s chance but firm discovery of penicillin changed the medicine world entirely. The inception of antibiotics and modern day medicines shaped the future for treating millions of people around the world. Fleming shared his knighthood along with Florey in 1944. In 1945 Fleming won his Nobel Prize in Medicine sharing the award with Florey and Chain. Fleming was honoured with the Hunterian Professorship by the Royal College of Surgeons of England. Death
Fleming died of a heart attack in 1955 at his London residence. One week after his death, Fleming was cremated and his ashes were interred in St Paul's Cathedral.
ALEXANDER FLEMING TIMELINE
1881:
– Fleming was born on 6 August
1900:
Alexander had actively remained a member of the Volunteer Force
1903:
Alexander enrolled himself at St Mary's Hospital, Paddington, London
1906:
He earned a distinction which qualified him to become a surgeon
1908:
He earned his M.B. and later a B.Sc. with Gold Medal
1914:
Fleming was appointed as a lecturer at St. Mary's where he remained till 1914
1915:
– On 23 December Fleming got married to a trained nurse, Sarah Marion
1918:
Fleming could return to St. Mary's Hospital
1928:
Fleming was chosen as the Professor of Bacteriology
1928:
Fleming had started off on his research of investigating the properties of ‘staphylococci’ bacteria
1928:
– On 3 September Fleming chanced upon the discovery of penicillin
1929:
Fleming brought his discovery in the British Journal of Experimental Pathology
1929:
He named the substance it released penicillin on 7 March
1930 :
Fleming’s researches on penicillin started finding firm shape in the 1930s
1940:
– Fleming strived hard to arouse a chemist’s interest in further refining usable penicillin
1941:
The Pearl Harbour bombing on 7 December resulted in the Infirmary (Florey and Chain at the Radcliffe Infirmary in Oxford) producing penicillin hugely which served in treating all the wounded allied forces
1944:
Fleming shared his knighthood along with Florey
1945:
Fleming won his Nobel Prize in Medicine sharing the award with Florey and Chain
1949:
Sarah Marion died leaving Fleming with their only child Robert Fleming who later became a general medical practitioner
1953:
– On 9 April Fleming married his second wife Dr. Amalia Koutsouri-Vourekas
1955 :
– Fleming died on 11 March after suffering from a heart attack

Read more at http://www.thefamouspeople.com/profiles/alexander-fleming-151.php#7iq11XMJ7lMTQTBT.99
Penicillin-Then & Now

By swcricket98, Williamson, GA

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Image Credit: Elizabeth B., Wichita Falls, TX
The author's comments:
Wrote this in 7th grade for a research project.
Known as the 'miracle drug' by millions, penicillin is an antibiotic that has saved many lives. It is so effective that, as Britannica and Wikipedia state, in 1999, Time Magazine named Scottish biologist and pharmacist Alexander Fleming one of the 100 Most Important People of the 20th Century for his discovery of penicillin. It is also said that penicillin was one of the most important discoveries of the millineum. It is estimated that penicillin has saved over 200 million lives. Compared to other drugs that originated from an accident, this is amazing.

The discovery of penicillin was one of the most important advances in the history of medical science, and it all began with mistake. According to de la Bedoyere, in September of 1928, Alexander Fleming was researching bacteria – the cause of multiple diseases. After a vacation that lasted no more than a few days, he was cleaning up some of his lab dishes that held the bacteria he had been studying. Throughout some thorough examinations of these plates, he realized a peculiar mold that was stopping bacteria from forming cell walls so they couldn't divide and multiply. This mold - known scientifically as Pencillium notatum – contained a substance that killed bacteria. As noted by Wikipedia, Fleming called this fungus 'penicillin'.

When penicillin was first discovered, it was not supported by the public. It took many years until penicillin was proven effective and safe. After many different scientists studied the 'miracle drug' and accepted its usefulness, it began mass producing around 1944. While the scientists were approving the drug, most of the penicillin went to to the Armed Forces in Europe and Asia. During World War 2, penicillin saved an estimation of 12-15% of people in the military's lives. (de la Bedoyere and Wikipedia)

“Once a clue has been obtained, teamwork may be absolutely necessary to bring the discovery to full advantage.” -Alexander Fleming in The Discovery of Penicillin. This is true as you observe the fascinating evolution of penicillin. Throughout the years of its mass production, multiple scientists studied and analyzed penicillin. As Sir Henry quoted in 1998 - “Without Fleming, no Chain; without Chain, no Florey; without Florey, no Heatley; without Heatley, no penicillin.” These are some of the names of the most famous and well-known biologists working toward the development of this antibiotic. Said by Woodall, “Over the years, penicillin has become medically improved by doctors, scientists, and other medical professionals.”

The impacts of penicillin have been tremendous over the past fifty years. Although penicillin could not kill all bacteria, it opened the door to a new field of pharmaceutical research. As a result of the narrow range of treatable diseases of penicillin, scientists had to discover new drugs that could treat a wider range of infections, such as ampicillin, flucloxacillin, dicloxacillin, and methicillin. (Wikipedia) Because it is possible to to change the characteristics of the antibiotic, these different variations of penicillin were created for different therapeutic purposes. (Britannica) Alexander Fleming received a Nobel prize for medicine in 1945.

The discovery of penicillin was one of the most widely known and frequently dicussed scientific events of the twentieth century, says Slinn. Penicillin has changed history, and is known as one of the best medical discoveries of all time. Due to the medical and technological advances of the 20th century, penicillin is no longer a 'wonder drug', but it is, and most likely will, continue to be useful.

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Penicillins
Gale Encyclopedia of Children's Health: Infancy through Adolescence | 2006 | Ross-Flanigan, Nancy; Uretsky, Samuel | Copyright
Penicillins
Definition
Penicillins are a group of closely related antibiotics that kill bacteria.
Description
There are several types of penicillins, each used to treat different kinds of infections, such as skin infections, dental infections, ear infections, respiratory tract infections, urinary tract infections, gonorrhea, and other infections caused by bacteria. These drugs will not work for olds, flu, and other infections caused by viruses.
Examples of penicillins are penicillin V (Beepen-VK, Pen-Vee K, V-cillin K, Veetids) and amoxicillin (Amoxil, Polymox, Trimox, Wymox). Penicillins are sometimes combined with other ingredients called beta-lactamase inhibitors, which protect the penicillin from bacterial enzymes that may destroy it before it can do its work. The drug Augmentin, for example, contains a combination of amoxicillin and a beta-lactamase inhibitor, clavulanic acid. Penicillins are available only with a prescription.
The original form of penicillin is called penicillin G. It is a narrow-spectrum antibiotic, which can be destroyed by stomach acid, but it is still useful against anaerobic bacteria (bacteria that can live in the absence of air). Newer penicillins are resistant to stomach acid, such as penicillin V, or have a broader spectrum, such as ampicillin and amoxicillin.
General use
Penicillins are useful against infections in many parts of the body, including the mouth and throat, skin and soft tissue, tonsils, heart, lungs, and ears. However, since many bacteria are resistant to penicillin, it is often wise to do a culture and sensitivity test before using penicillins. In some cases, there are only a few types of bacteria that are likely to be a problem, and so it is appropriate to use a penicillin without testing. For example, dentists often prescribe penicillin to prevent infections after dental surgery.
Precautions
Penicillins are usually very safe. The greatest risk is an allergic reaction, which can be severe. People who have been allergic to cephalosporins are likely to be allergic to penicillins. Moreover, people with certain medical conditions or who are taking certain other medicines can have problems if they take penicillins. Before taking these drugs, patients should be sure to let the physician know about any of the following conditions.
Low-sodium diet
Some penicillin medicines contain large enough amounts of sodium to cause problems for people on low-sodium diets. Parents of children on on such a diet should make sure that the physician treating the infection knows about the special diet.
Diabetes
Penicillins may cause false positive results on urine sugar tests for diabetes. People with diabetes should check with their physicians to see if they need to change their diet or the doses of their diabetes medicine.
Phenylketonuria
Some formulations of Augmentin contain phenylalanine. People with phenylketonuria (PKU) should consult a physician before taking this medicine.
Side effects
The most common side effect of penicillin is diarrhea . Nausea , vomiting , and upset stomach are also common. With some penicillins, particularly the broad spectrum products, there is a risk of increased growth of organisms that are not affected by penicillin. This situation can lead to candidal infections of the mouth and vagina.
Most side effects of penicillin cannot be prevented. Amoxicillin has a lower incidence of diarrhea than ampicillin and is the preferred drug in most cases.
Interactions
Birth control pills may not work properly when taken at the same time as penicillin. Penicillins may also interact with many other medicines. When this happens, the effects of one or both of the drugs may change or the risk of side effects may be greater. People who take penicillin should let their physician know all other medicines they are taking. Among the drugs that may interact with penicillins are the following: * acetaminophen (Tylenol) and other medicines that relieve pain and inflammation * medicine for overactive thyroid * other antibiotics * blood thinners * antiseizure medicines such as Depakote and Depakene * blood pressure drugs such as Capoten, Monopril, and Lotensin
The list above does not include every drug that may interact with penicillins. A physician or pharmacist should be consulted before a patient combines penicillins with any other prescription or nonprescription (over-the-counter) medicine.
Parental concerns
Parents should verify that their children have an infection requiring antibiotic therapy. Unnecessary use of antibiotics leads to development of bacterial resistance, while it subjects the child to some needless risk of adverse effects and wastes money.
Liquid forms of penicillin should be refrigerated after reconstitution. These preparations must be shaken well before use and measured with a medicinal teaspoon, not a household teaspoon.
Any adverse effects should be discussed with the prescriber. Penicillin should not be used in patients allergic to the drug; however, an incorrect report of an allergy to penicillin may cause prescribers to select a different drug which may cause even more severe side effects.
Penicillins should be administered exactly as directed. Users should never give larger, smaller, more frequent, or less frequent doses. To make sure the infection clears up completely, patients should take the medicine for as long as it has been prescribed. They should not stop taking the drug just because symptoms begin to improve. This point is important with all types of infections, but it is especially important with strep infections, which can lead to serious heart problems if they are not cleared up completely.
This medicine should be used only for the infection for which it was prescribed. Different kinds of penicillins cannot be substituted for one another. Do not save some of the medicine to use on future infections. It may not be the right treatment for other kinds of infections, even if the symptoms are the same.
KEY TERMS
Anaerobic —An organism that grows and thrives in an oxygen-free environment.
Beta-lactamase —An enzyme produced by some bacteria that destroys penicillins.
Broad spectrum —A term applied to antibiotics to indicate that they are effective against many different types of bacteria.
Enzyme —A protein that catalyzes a biochemical reaction without changing its own structure or function.
Microorganism —An organism that is too small to be seen with the naked eye, such as a bacterium, virus, or fungus.
Mononucleosis —An infection, caused by the Epstein-Barr virus, that causes swelling of lymph nodes, spleen, and liver, usually accompanied by extremely sore throat, fever, headache, and intense long-lasting fatigue. Also called infectious mononucleosis.
Resources
BOOKS
Beers, Mark. H., and Robert Berkow, eds. The Merck Manual, 2nd home ed. West Point, PA: Merck & Co., 2004.
Mcevoy, Gerald K., et al. AHFS Drug Information 2004. Bethesda, MD: American Society of Healthsystems Pharmacists, 2004.
Siberry, George K., and Robert Iannone, eds. The Harriet Lane Handbook, 15th ed. Philadelphia, PA: Mosby Publishing, 2000.
PERIODICALS
Apter Andrea J., et al. "Represcription of penicillin after allergic-like events." Journal of Allergy and Clinical Immunology 113, no. 4 (April 2004): 764–770.
ORGANIZATIONS
American Academy of Pediatrics. 141 Northwest Point Boulevard, Elk Grove Village, IL 60007–1098. Web site: <www.aap.org>.
Centers for Disease Control. 200 Independence Avenue, SW, Washington, DC, 20201. Web site: <www.cdc.gov>.
WEB SITES
"Penicillins (Systemic)." Available online at <www.nlm.nih.gov/medlineplus/druginfo/uspdi/202446.html> (accessed September 29, 2004).
"Treat Sore Throat without Penicillin." Available online at <www.medicinenet.com/script/main/art.asp?articlekey=25627> (accessed September 29, 2004).
Nancy Ross-Flanigan Samuel Uretsky, PharmD
Cite this article
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Ross-Flanigan, Nancy; Uretsky, Samuel. "Penicillins." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Encyclopedia.com. 19 Jan. 2015 <http://www.encyclopedia.com>.
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ANNOTATED BIBLIOGRAPHY

Primary

Early Sample of Flemings Mould. 1935. Artifact. Science Museum UK, London. This source is an artifact. It is a early sample of Alexander Fleming's mold. Alexander Fleming gave a mold of his, that had penicillin on it, to a friend to prove it was important. The mold was put on display. This helped me see what it physically looked like as a visual instead of described in words like most sources do.

"Explore 100 Famous Scientist Quotes Pages." Penicillin Quotes. N.p., n.d. Web. 21 Feb. 2013 <http://todayinsci.com/QuotationsCategories/P_Cat/Penicillin-Quotations.htm>. This source was full of quotes. It helped me put together my project with different points of views.

Laurence, William L. "More Penicillin- America Speeds Production Of This Bacteria Killer." The New York Times [New York] 1 Aug. 1943: E7. ProQuest Historical Newspapers. Web. 9 Jan. 2012. This source was a newspaper article written in 1943 in the New York Times. It focused on how America production rise. This article was intended for Americans, partnered with Florey and Chain to make penicillin who did not have a good idea of what penicillin was, to read. So it helped me picture what I would be thinking if I was back in 1943 reading the paper.

Maren, Thomas H. "Moulds That Heal." New York Times 9 Apr. 1950: BR4. ProQuest Historical Newspapers. Web. 9 Jan. 2013. This primary source had details about other people who also helped in the making of penicillin. It had a conversation Alexander Fleming had with a different scientist. The conversation quotes showed me how Fleming thought. It showed a reference between penicillin and sulfonamide drugs.

"Medicine: Penicillin's Progress." Time Magazine 7 June 1943: n. pag. Time Magazine. 7 June 1943. Web. 19 Dec. 2012. This source was primary from a magazine article in 1943. It showed me how hard they really were working on perfecting penicillin and what new findings were found along the way.

Ratcliff, J. D. "Here's Medical Magic!" Los Angeles Times 16 May 1943: 12+. ProQuest Historical Newspapers. Web. 9 Jan. 2013. This was a newspaper article that was titled "Here's Medical Magic!" It was written when penicillin was first announced to the world. It had details showing readers what penicillin is and what it does. It told the story of how it was located. It gave me a interesting idea of how things came to be. It also had a great title picture that I will use on my website.

Schwarz, Daniel. "The Mold That Fights For The Life of Man." New York Times 2 Jan. 1944: 8+. ProQuest Historical Newspapers. Web. 9 Jan. 2013. This source is a newspaper article that is telling readers that penicillin is a very great drug and can be used to treat multiple illnesses. It can be counted on to always do the job. This source shows how little penicillin is needed for a big difference. I learned how they get the penicillin from the mold to the powder.

"Sir Alexander Fleming Quotes." Sir Alexander Fleming Quotes. N.p., n.d. Web. 03 Jan. 2013. This website had tons of quotes. I got quotes from a couple different people talking about penicillin. But I also got a couple quotes from Alexander Fleming himself. This gave me good ideas about what they thought at that time.

Woolf, S. J. "Sir Alexander Fleming-- Man of Science and of Pencillin." American Scientist. No. 4 ed. Vol. 33. N.p.: Sigma Xi, The Scientific Reseatch Society, 1945. 242+. JSTOR. Web. 9 Jan. 2013. This was a very interesting point of view for a source. It was written as the author was close friends to Alexander Fleming so there was a bunch of thoughts and quotes that Fleming said that were in their. It was as if the author followed Fleming everywhere he went and wrote down what happened and everything Fleming did. But it was a fun source to read that was packed with good information.

YouTube. Perf. Alexander Fleming. YouTube. YouTube, 10 Feb. 2010. Web. 19 Dec. 2012. This is a video source. It tells the entire story of penicillin in a matter of minutes. It has tons of good detailed information and pictures. It helped me realize what life was like at that time in the world and how much everyone really needed it.

Secondary

Bellis, Mary. "The History Of Penicillin." About.com Inventors. N.p., n.d. Web. 07 Dec. 2012. This source was bursting with numbers. It had different dates that important findings were found on. It had prices of penicillin at different times per dose. It had the number of molecules Hodgkin took x-ray photos of. It gave me a better idea of when everything was happening and for what reason.

"The Discovery and Development of Penicillin." The Discovery and Development of Penicillin. N.p., n.d. Web. 19 Dec. 2012. This source gave me tons of information about things that most sources don't mention like people who tried to purify penicillin and failed. It had some details about how important penicillin was from the view of pharmaceutical companies and how they helped in the invention. It talked about penicillin and the war effort.

"The Discovery and Importance of Penicillin and the Development of Sulfa Drugs." Science and Its Times. Ed. Neil Schlager and Josh Lauer. Vol. 6. Detroit: Gale, 2001. Gale Student Resources In Context. Web. 7 Dec. 2012. This source had a lot of backround information. It talks about what medicine was before penicillin. It also gave a great argue of the impact penicillin made on the world.

"Duchesne, Ernest (1874-1912)." Duchesne, Ernest (1874-1912). N.p., 15 Oct. 2010. Web. 19 Dec. 2012. This source had a lot of information on Ernest Duchesne, who first discovered penicillin. This was one of the few sources that even talked about him. It gave great details about him.

Dunavan, Claire PA. "The Drug That Helped Win the War; The Mold in Dr. Florey's Coat The Story of the Penicillin Miracle Eric Lax John Macrae/Henry Holt." Los Angeles Times 11 Apr. 2004: n. pag. ProQuest Newsstand. Web. 7 Dec. 2012. This was a source from ProQuest Newsstand. It was written in 2004. So it was not primary but had some very good secondary information. This article described how penicillin was discovered by Alexander Fleming.

Gantz, Nelson M. "Penicillin." World Book Advanced. World Book, 2012. Web. 18 Dec. 2012. This World Book Database source told about what penicillin was and what it was made of. It gave up to date facts about what penicillin can be used to treat. It also had a good picture of what the penicillium mold looked like.

Goodrich Pharmacy, Jenny. "Penicillin Interview." Personal interview. Nov. 2012. This source was an actual interview I had with Jenny, from Goodrich Pharmacy in Elk River. She told me a lot about how penicillin was disovered and why it is important. She helped me get a starting base of what happened so I could find other notes to help build on top of that.

Jacobs, Francine. Breakthrough: The True Story of Penicillin. New York: Dodd, Mead, 1985. Print. This source was a book found at the Salk Media Center. The entire book had great details about the timeline and story of penicillin. It had many thoughts about the after effects of the drug.

Parshall, Gerald. "Medicine's Accidental Hero." U.S. News & World Report 125.7 (1998): 58. MAS Ultra - School Edition. Web. 12 Jan. 2013. This was and EBSCO secondary source titled "Medicine's accidental hero." It focused on Alexander Fleming and how he was the hero. It included events with Florey and Chain but stated Fleming as the true hero. It didn't completely meet my expectations because it had mostly the same information as all the other sources. But there was a couple facts I never knew before.

"Penicillin, The Wonder Drug." Penicillin, The Wonder Drug. N.p., n.d. Web. 07 Dec. 2012. "Penicillin, the Wonder Drug," was a fantastic source. It had the entire story of how Fleming found the penicillin and how Florey and Chain accomplished the isolating of the drug. It had different points of view which gave me a look at penicillin from a different angle. It also had a section with the motive for Chain working with penicillin, written by Ernst Chain himself. This was one of the most interesting source that I learned the most off of.

"Penicillin." U*X*L Encyclopedia of U.S. History. Sonia Benson, Daniel E. Brannen, Jr., and Rebecca Valentine. Ed. Lawrence W. Baker and Sarah Hermsen. Vol. 6. Detroit: UXL, 2009. 1207-1209. Gale Student Resources In Context. Web. 7 Dec. 2012. This source had a mini biography of the life of Sir Alexander Fleming. I learned what Fleming was doing before the accidental discovery and what he did afterwards. It also proved the importance of the life saving drug.

Reddy, Vinay N. "Antibiotics, Bacteria and (usually Not) Viruses." Antibiotics, Bacteria and (not) Viruses. N.p., 24 Feb. 1997. Web. 01 Jan. 2013. This secondary source "Antibiotics, Bacteria and (usually not) Viruses" is a greats reference source. It gives explanations of what different words mean and what they are. It helped me clarify what the job was for antibiotics and what sulfas were.

Rosenberg, Jennifer. "Alexander Fleming Discovers Penicillin." About.com 20th Century History. N.p., n.d. Web. 07 Dec. 2012. This source was a great overview of how Alexander Fleming discovered penicillin and the different things he found. It had a great connection in how important it was for World War 2.

Strathman, Paul. "The Start of the Modern Era." Medicine from Hippocrates to Gene Therapy. New York: Carrol & Graf, 2005. N. pag. Print. This source was great on the background information. It had lots of facts on what Fleming was doing before he discovered penicillin. It had details most sources don't include.

Torok, Simon. "Howard Florey - Maker of the Miracle Mould." Howard Florey - Maker of the Miracle Mould. N.p., n.d. Web. 19 Dec. 2012. "Maker of the Miracle Mould" was a very high detailed source that told the entire story of penicillin from how it started to now days. It included testing on patients, and important dates like when they performed a experiment on mice in May of 1940. This source gave me a great understanding of penicillin and its discoverers.

Photo Credits

1941 PENICILLIN DISCOVERY Antibiotics Penicillium Fungi for Disease in Newspaper. N.d. Photograph. Web. 21 Feb. 2013. This source is a photo of a newspaper. The title shows me that penicillin was very important and famous at that time and still today.

Alexander Fleming. N.d. Photograph. Web. 21 Feb. 2013. <http://www.biography.com/people/alexander-fleming-9296894>. This is a photo source of Alexander Fleming. I am using this photo when Fleming is first introduced.

Alexander Fleming. N.d. Photograph. Web. 21 Feb. 2013. This is another photo of Alexander Fleming and his penicillin. I think the pictures of him and in his lab will make my website even better. It helps the reader get an idea of where this was happening.

Alexander Fleming. N.d. Photograph. Web. 22 Feb. 2013. <http://www.art-prints-on-demand.com/a/englishphotographer/alexanderfleming1881-1955.html>. This is a photo of Alexander Fleming holding a petri dish. I think this a very good picture for when my project tells information about Penicillium mold in the petri dish.

Amoxicillin. N.d. Photograph. Web. 22 Feb. 2013. <http://en.wikipedia.org/wiki/File:Amoxicillin.JPG>. This source is a photo of Amoxicillin. I am using it to show there are many types of penicillin other than the original Penicillin G.

Ampicillin. N.d. Photograph. Web. 22 Feb. 2013. <http://stayuplating.com/>. This source is a photo of Ampicillin. This is to be included with the other photos of types of penicillins.

Bacteria In Test Tube. N.d. Photograph. Web. 22 Feb. 2013. <http://www.allposters.com/-sp/Bacteria-in-a-Sealed-Test-Tube-Re-Penicillin-Research-Posters_i8508994_.htm>. This is a photo of a tube filled with bacteria. It is cool to see what bacteria looks like especially in a test tube, which is the kind of thing Alexander Fleming would work with.

Better than Moldy Bread on an Axe Wound: Science Pub Visits the New Antibiotics. N.d. Photograph. Web. 21 Feb. 2013. This source is a photo of a small article. It was when penicillin was being introduced to the world.

Cephalosporins. N.d. Photograph. Web. 22 Feb. 2013. <http://www.cephalosporin.net/>. This is a photo of Cephalosporins which is a medicine found soon after penicillin. This was found from knowing the structure of penicillin.

Civilian Penicillin Production. N.d. Photograph. Web. 22 Feb. 2013. <http://www.exploringsurreyspast.org.uk/themes/subjects/50_objects/more_gallery/civilian_penicillin/>. This source is a picture of a sign from a pharmacy. It was the first pharmacy to produce penicillni filtrate.

Closeup of Penicillin Mold in the Bottom of a Flask. N.d. Photograph. Web. 22 Feb. 2013. <http://www.agefotostock.com/en/Stock-Images/Rights-Managed/ERE-SBDPENI-CS001-H>. This is a photo of penicillium mold in a flask. I am using it to show how penicillin was made.

Early Sample of Flemings Mould. 1940. Photograph. Science Museum, South Kensington, London. Science Museum. Web. 7 Feb. 2013. This photo was a great source. It was a display of penicillin in the petri dish. It was the actual mold Fleming made and gave to his friend. It had a description paragraph that went along with it. It was very interesting.

Ernest Duchesne. N.d. Photograph. Web. 22 Feb. 2013. <http://en.wikipedia.org/wiki/Ernest_Duchesne>. This source is a photo of Ernest Duchesne. I will use this in my background to show a picture of who found penicillin before Fleming.

Florey, Fleming, Chain Win Nobel Prize. N.d. Photograph. Web. 21 Feb. 2013. <http://www.xtimeline.com/evt/view.aspx?id=35870>. This source is a photo of all 3 inventors, Fleming, Florey, and Chain. I think this is very cool to have a photo of all three of them together because I couldn't find any others.

A Happy Accident: Flemings Idea. N.d. Photograph. Web. 22 Feb. 2013. <http://blog.europeana.eu/2012/08/a-happy-accident-flemings-penicillin/>. This source has 4 good photos of penicillium mold, production, Alexander Fleming and a paper Fleming wrote. I used these photos to help with a visual for parts of my project.

The History of Penicillin. N.d. Photograph. Web. 22 Feb. 2013. <http://indianapublicmedia.org/amomentofscience/history-penicillin/>. This is a photo of a sign on the building penicillin was found in. I used it at the end of my project as a type of memorial for Alexander Fleming.

History of Swine Flu. N.d. Photograph. Web. 22 Feb. 2013. <http://homepage.usask.ca/~vim458/virology/studpages2009/H1N1/History.html>. This is a photo during the time of world war II. It is a room full of sick people, I used this to show how many people needed penicillin.

Howard Florey. N.d. Photograph. Web. 22 Feb. 2013. <http://www.scribd.com/doc/80513868/Howard-Florey>. This is a document/photos of the nobel prize winners of 1945, Fleming, Florey, and Chain. I used this to tell the story of how they got that award.

Lord Howard Florey. N.d. Photograph. Web. 22 Feb. 2013. <http://www.adelaide.edu.au/adelaidean/image16684/medicine_02.jpg.html>. This is a photo of Howard Florey. I used this to show what Florey looked like.

Lysozyme. N.d. Photograph. Web. 22 Feb. 2013. This photo is a diagram of the lysozyme and the different parts. I used it to show what a lysozyme was.

Penicillin V. N.d. Photograph. Web. 22 Feb. 2013. This is a photo of Penicillin V. I added it to the group of different types of penicillin medicines.

Penicillin G. N.d. Photograph. Web. 22 Feb. 2013. <http://www.mexicanpharmacy.com.mx/buy-antibiotics/penicillin-g-24000000-injectable-vial/>. This is a image of the original kind of penicillin. I am using it to show how penicillin is given to patients.

Penicillin in Stock. N.d. Photograph. Web. 22 Feb. 2013. <http://www.nature.com/news/human-experiments-first-do-harm-1.9980>. This source is a photo of a pharmacist hanging a sign reading that penicillin is offered at that pharmacy.

Penicillin in World War II. N.d. Photograph. Web. 21 Feb. 2013. <http://pubs.acs.org/cen/coverstory/83/8325/8325penicillin.html>. This source is a photo of some doctors injecting penicillin into a dying soldiers arm. I will use it in my impact to show how penicillin was used to save many lives.

Penicillin Mold. N.d. Photograph. Web. 22 Feb. 2013. <http://kids.britannica.com/elementary/art-87585/Penicillium-mold-is-the-source-of-penicillin>. This source is a very detailed photo of the penicillium mold. I think this is very interesting to see what the mold looks like close up.

Penicillin. N.d. Photograph. Smithsonian. Web. 20 Feb. 2013. This image was of penicillin as a mold. It was cool to see where the penicillin was compared to all the bacteria. I am using this as my home page photo. I think it will be very cool to have everyone else see what penicillin looks like before it is made into a medicine.

Penicillin. N.d. Photograph. Web. 21 Feb. 2013. <http://altrapoint.com/2011/09/top-10-scientific-discoveries/>. This is another image close up of penicillium mold. But this photo shows the mold in the petri dish instead of just the mold.

Penicillin: The Miracle Drug of War. N.d. Photograph. Web. 21 Feb. 2013. This photo is a source showing how important penicillin really is to war. I will use this in my impact.

Preparation of Penicillin. N.d. Photograph. Learn NC. Web. 20 Feb. 2013. I thought this picture was really great! It has a table of penicillin in bottles and a girl taking the penicillin out of the bottles. I thought this was a good connection of how they did it back in the 1950-1970s compared to how they do it now.

Sir Alexander Fleming. N.d. Photograph. Science Direct. Web. 20 Feb. 2013. This photo is of Sir Alexander Fleming himself. It has him holding a petri dish with penicillin in it. I really liked this photo because I never really knew what Fleming looked like as I was doing my project, but now that I see him, I can picture the whole story of penicillin.

Soybeans. the Magical Fruit. N.d. Photograph. Web. 22 Feb. 2013. This source is a photo of soybeans. I used it as part of the background because soy beans were used to help skin infections.

Tales for Poster. N.d. Photograph. Web. 22 Feb. 2013. <http://talesofthings.com/totem/totem_view/6209/>. This source is a photo of a poster to show what was going on at the time of World War II. I will use this in the section that tells about how penicillin producution was done.

Thanks to Penicillin, He Will Come Home! N.d. Photograph. Online Textbook of Bacteriology. Web. 14 Feb. 2013. This source was a advertisement/photo from back when penicillin was just made and we were still in war. I found it cool to see what ads looked like back then. They look completely different than how they do now. From reading the title, I gathered that they were pretty confident in penicillin.

Mold Penicillin. N.d. Photograph. Web. 22 Feb. 2013. <http://spydersden.wordpress.com/2011/08/31/everyday-products-that-were-discovered-by-accident/>. This source is a photo of a short phrase. It was used as a ending image on the process paper.