First new antibiotic in 30 years discovered in major breakthrough Science First new antibiotic in 30 years discovered in major breakthrough The discovery of Teixobactin could pave the way for a new generation of antibiotics because of the way it was discovered. Sarah Knapton , Science Editor 7 January 2016 • 5:44pm The first new antibiotic to be discovered in nearly 30 years has been hailed as a ‘paradigm shift’ in the fight against the growing resistance to drugs. Teixobactin has been found to treat many common bacterial infections such as tuberculosis, septicaemia and C. diff, and could be available within five years. But more importantly it could pave the way for a new generation of antibiotics because of the way it was discovered. Scientists have always believed that the soil was teeming with new and potent antibiotics because bacteria have developed novel ways to fight off other microbes. But 99 per cent of microbes will not grow in laboratory conditions leaving researchers frustrated that they could not get to the life-saving natural drugs. Now a team from Northeastern University in Boston, Massachusetts, have discovered a way of using an electronic chip to grow the microbes in the soil and then isolate their antibiotic chemical compounds.

They discovered that one compound, Teixobactin, is highly effective against common bacterial infections Clostridium difficile, Mycobacterium tuberculous and Staphylococcus aureus. Professor Kim Lewis, Director of the Antimicrobial Discovery Centre said: “Apart from the immediate implementation, there is also I think a paradigm shift in our minds because we have been operating on the basis that resistance development is inevitable and that we have to focus on introducing drugs faster than resistance “Teixobactin shows how we can adopt an alternative strategy and develop compounds to which bacteria are not resistant.” The first antibiotic Penicillin, was discovered by Alexander Fleming in 1928 and more than 100 compounds have been found since, but no new class has been found since 1987. The lack of new drugs coupled with over-prescribing has led to bacteria becoming increasingly resistant to modern medicines. Dame Sally Davies, the government’s Chief Medical Officer, said antibiotic resistant was ‘as big a risk of terrorism; and warned that Britain faced returning to a 19th century world where the smallest infection or operation could kill.

The World Health Oganisation has also classified antimicrobial resistance as a "serious threat’ to every region of the world which ‘has the potential to affect anyone, of any age, in any country" However the new discovery offers hope that many new antibiotics could be found to fight bacterial infections. Crucially, the scientists believe that bacteria will not become resistant to Teixobactin for at least 30 years because of its multiple methods of attack. Testing on mice has already shown that the antibiotic works well at clearing infections, without side-effects. The team is now concentrating on upscaling production so that it could be tested in humans. “Right now we can deliver a dose that cures mice and a variety of models of infection and we can deliver 10 mg per kg so it correlates well with human usage,” added Professor Lewis. The breakthrough was heralded by scientists who said it could prove a ‘game-changer’ in the struggle against antimicrobial resistance.

Prof Laura Piddock, Professor of Microbiology at the University of Birmingham, said: “The screening tool developed by these researchers could be a ‘game changer’ for discovering new antibiotics as it allows compounds to be isolated from soil producing micro-organisms that do not grow under normal laboratory conditions.” Prof Mark Woolhouse, Professor of Infectious Disease Epidemiology, from the University of Edinburgh added: “Any report of a new antibiotic is auspicious, but what most excites me about the paper is the tantalising prospect that this discovery is just the tip of the iceberg. “Most antibiotics are natural products derived from microbes in the soil. The ones we have discovered so far come from a tiny subset of the rich diversity of microbes that live there. “Lewis et al. have found a way to look for antibiotics in other kinds of microbe, part of the so-called microbial “dark matter” that is very difficult to study.” Dr Angelika Gründling, Reader in Molecular Microbiology, Imperial College London said the discovery , ‘raises our hopes that new antibiotics can be brought to the clinics in the not too distant future.’ “The great hope is now that many more new antibiotics can be uncovered in a similar manner.” Public Health England also welcomed the breakthrough.

“The rise in antibiotic resistance is a threat to modern healthcare as we know it so this discovery could potentially help to bridge the ever increasing gap between infections and the medicines we have available to treat them,” said Prof Neil Woodford, Head of Public Health England’s Antimicrobial Resistance and Healthcare Associated Infections Reference Unit. The research was published in the journal Nature. Follow Telegraph Science & Tech Alexander Fleming Discovery and Development of Penicillin - Landmark - American Chemical Society Cite this Page Alexander Fleming’s Discovery of Penicillin Penicillin heralded the dawn of the antibiotic age. Before its introduction there was no effective treatment for infections such as pneumonia, gonorrhea or rheumatic fever. Hospitals were full of people with blood poisoning contracted from a cut or a scratch, and doctors could do little for them but wait and hope. Antibiotics are compounds produced by bacteria and fungi which are capable of killing, or inhibiting, competing microbial species. This phenomenon has long been known; it may explain why the ancient Egyptians had the practice of applying a poultice of moldy bread to infected wounds.

But it was not until 1928 that penicillin, the first true antibiotic, was discovered by Alexander Fleming, Professor of Bacteriology at St. Mary's Hospital in London. Returning from holiday on September 3, 1928, Fleming began to sort through petri dishes containing colonies of Staphylococcus, bacteria that cause boils, sore throats and abscesses. He noticed something unusual on one dish. It was dotted with colonies, save for one area where a blob of mold was growing. The zone immediately around the mold—later identified as a rare strain of Penicillium notatum—was clear, as if the mold had secreted something that inhibited bacterial growth. Fleming found that his "mold juice" was capable of killing a wide range of harmful bacteria, such as streptococcus, meningococcus and the diphtheria bacillus. He then set his assistants, Stuart Craddock and Frederick Ridley, the difficult task of isolating pure penicillin from the mold juice. It proved to be very unstable, and they were only able to prepare solutions of crude material to work with.

Fleming published his findings in the British Journal of Experimental Pathology in June 1929, with only a passing reference to penicillin's potential therapeutic benefits. At this stage it looked as if its main application would be in isolating penicillin-insensitive bacteria from penicillin-sensitive bacteria in a mixed culture. This at least was of practical benefit to bacteriologists, and kept interest in penicillin going. Others, including Harold Raistrick, Professor of Biochemistry at the London School of Hygiene and Tropical Medicine, tried to purify penicillin but failed. Back to top Penicillin Research at Oxford University It was Howard Florey, Ernst Chain and their colleagues at the Sir William Dunn School of Pathology at Oxford University who turned penicillin from a laboratory curiosity into a life-saving drug. Their work on the purification and chemistry of penicillin began in earnest in 1939, just when wartime conditions were beginning to make research especially difficult. To carry out a program of animal experiments and clinical trials the team needed to process up to 500 liters a week of mold filtrate.

They began growing it in a strange array of culture vessels such as baths, bedpans, milk churns and food tins. Later, a customized fermentation vessel was designed for ease of removing and, to save space, renewing the broth beneath the surface of the mold. A team of "penicillin girls" was employed, at £2 a week, to inoculate and generally look after the fermentation. In effect, the Oxford laboratory was being turned into a penicillin factory. Meanwhile, biochemist Norman Heatley extracted penicillin from huge volumes of filtrate coming off the production line by extracting it into amyl acetate and then back into water, using a countercurrent system. Edward Abraham, another biochemist who was employed to help step up production, then used the newly discovered technique of alumina column chromatography to remove impurities from the penicillin prior to clinical trials. In 1940, Florey carried out vital experiments, showing that penicillin could protect mice against infection from deadly Streptococci. Then, on February 12, 1941, a 43-year old policeman, Albert Alexander, became the first recipient of the Oxford penicillin.

He had scratched the side of his mouth while pruning roses, and had developed a life-threatening infection with huge abscesses affecting his eyes, face, and lungs. Penicillin was injected and within days he made a remarkable recovery. But supplies of the drug ran out and he died a few days later. Better results followed with other patients though and soon there were plans to make penicillin available for British troops on the battlefield. War-time conditions made industrial production of penicillin difficult. A number of British companies, including Glaxo (now GlaxoSmithKline) and Kemball Bishop, a London firm later bought by Pfizer, took up the challenge. Back to top Penicillin Production in the United States during WWII Substantial amounts of penicillin would be needed for the extensive clinical trials required to confirm the promise of the early results and to provide adequate supplies of the drug for therapeutic use if it did live up to its potential. Florey recognized that large-scale production of penicillin was probably out of the question in Britain, where the chemical industry was fully absorbed in the war effort.

With the support of the Rockefeller Foundation, Florey and his colleague Norman Heatley traveled to the United States in the summer of 1941 to see if they could interest the American pharmaceutical industry in the effort to produce penicillin on a large scale. Yale physiologist John Fulton helped to put his British colleagues in touch with individuals who might be able to assist them in their goal. They were referred to Robert Thom of the Department of Agriculture, a foremost mycologist and authority on the Penicillium mold, and eventually to the Department's Northern Regional Research Laboratory (NRRL) in Peoria, Illinois, because of the expertise of its Fermentation Division. This contact proved to be crucial to the success of the project, as the NRRL was a key contributor of innovations that made large-scale production of penicillin possible. Back to top Increasing the Yield of Penicillin Orville May, Director of the NRRL, agreed to have the Laboratory undertake a vigorous program to increase penicillin yields under the direction of Robert Coghill, Chief of the Fermentation Division. It was agreed that Heatley would remain in Peoria to share his expertise with his American colleagues.

Within a few weeks, Andrew Moyer found that he could significantly increase the yield of penicillin by substituting lactose for the sucrose used by the Oxford team in their culture medium. Shortly thereafter, Moyer made the even more important discovery that the addition of corn-steep liquor to the fermentation medium produced a ten-fold increase in yield. Corn-steep liquor was a by-product of the corn wetmilling process, and the NRRL, in an attempt to find a use for it, tried it in essentially all of its fermentation work. Later, the Peoria laboratory increased the yield of penicillin still further by the addition of penicillin precursors, such as phenylacetic acid, to the fermentation medium. It was recognized that the Oxford group's method of growing the mold on the surface of a nutrient medium was inefficient, and that growth in submerged culture would be a superior process. In submerged culture fermentation, the mold is grown in large tanks in a constantly agitated and aerated mixture, rather than just on the surface of the medium. Florey's Penicillium culture, however, produced only traces of penicillin when grown in submerged culture.

Under the direction of Kenneth Raper, staff at the NRRL screened various Penicillium strains and found one that produced acceptable yields of penicillin in submerged culture. Soon a global search was underway for better penicillin producing strains, with soil samples being sent to the NRRL from around the world. Ironically, the most productive strain came from a moldy cantaloupe from a Peoria fruit market. A more productive mutant of the so-called cantaloupe strain was produced with the use of X-rays at the Carnegie Institution. When this strain was exposed to ultraviolet radiation at the University of Wisconsin, its productivity was increased still further. Back to top U.S. Pharmaceutical Companies Support Production While Norman Heatley remained in Peoria helping the NRRL staff to get the penicillin work started, Howard Florey visited various pharmaceutical companies to try to interest them in the drug. Although Florey was disappointed in the immediate results of his trip, three of the companies (Merck, Squibb and Lilly) had actually conducted some penicillin research before Florey's arrival and Pfizer seemed on the verge of investigating the drug as well.

At this time, however, the promise of penicillin was still based on only limited clinical trials. Florey next visited his old friend Alfred Newton Richards, then vice president for medical affairs at the University of Pennsylvania. More importantly, Richards was chair of the Committee on Medical Research (CMR) of the Office of Scientific Research and Development (OSRD). The OSRD had been created in June, 1941, to assure that adequate attention was given to research on scientific and medical problems relating to national defense. Richards had great respect for Florey and trusted his judgment about the potential value of penicillin. He approached the four drug firms that Florey indicated had shown some interest in the drug (Merck, Squibb, Lilly and Pfizer) and informed them that they would be serving the national interest if they undertook penicillin production and that there might be support from the federal government. Richards convened a meeting in Washington, D.C., on October 8, 1941, to exchange information on company and government research and to plan a collaborative research program to expedite penicillin production. In addition to representatives of the CMR, the National Research Council and the U.S.

Department of Agriculture, participants included research directors Randolph T. Major of Merck; George A. Harrop of the Squibb Institute for Medical Research; Jasper Kane of Pfizer; and Y. SubbaRow of Lederle. The next CMR penicillin conference, held in New York in December, ten days after Pearl Harbor and U.S. entry into the Second World War, was more decisive. At this meeting, which was attended by the heads of Merck, Squibb, Pfizer and Lederle, as well as the company research directors, Robert Coghill's report on the success at the NRRL with corn steep liquor was encouraging to the industry leaders present. As Coghill later recalled, George W. Merck, who had been pessimistic about the possibility of producing adequate quantities of penicillin given the constraints of available fermentation techniques and yields,"...immediately spoke up, saying that if these results could be confirmed in their laboratories, it was possible to produce the kilo of material for Florey, and industry would do it!".

It was agreed that although the companies would pursue their research activities independently, they would keep the CMR informed of developments, and the Committee could make the information more widely available (with the permission of the company involved) if that were deemed in the public interest. Although there was some concern that investments in fermentation processes might be wasted if a commercially-viable synthesis of penicillin were developed, other companies also began to show an interest in the drug. Some firms worked out collaborative agreements of their own (e.g., Merck and Squibb in February 1942, joined by Pfizer in September). Merck's pilot plant continued to produce several hundred liters of penicillin culture per week using both flasks and tray, and in December, Heatley joined the Merck research staff for several months, where he introduced the Oxford cup plate method of penicillin assay, which soon became a standard method industry-wide. By March 1942 enough penicillin had been produced under OSRD auspices to treat the first patient (Mrs. Ann Miller, in New Haven, Connecticut); a further ten cases were treated by June 1942, all with penicillin supplied by Merck & Co., Inc.

"The discovery and development of penicillin 1928-1945” commemorative booklet produced by the National Historic Chemical Landmarks program of the American Chemical Society in 1999 (PDF). Scaling-up Penicillin Production Pharmaceutical and chemical companies played an especially important role in solving the problems inherent in scaling up submerged fermentation from a pilot plant to a manufacturing scale. As the scale of production increased, the scientists at Merck, Pfizer, Squibb and other companies faced new engineering challenges. Pfizer's John L. Smith captured the complexity and uncertainty facing these companies during the scale-up process: "The mold is as temperamental as an opera singer, the yields are low, the isolation is difficult, the extraction is murder, the purification invites disaster, and the assay is unsatisfactory." Because penicillin needs air to grow, aerating the fermentation mixture in deep tanks presented a problem. When corn steep liquor was used as the culture medium, bubbling sterile air through the mixture caused severe foaming. Squibb solved this problem by introducing glyceryl monoricinolate as an anti-foaming agent.

Submerged fermentation also required the design of new cooling systems for the vats and new mixing technology to stir the penicillin mash efficiently. Lilly was particularly successful in making the mold synthesize new types of penicillin by feeding precursors of different structure. Once the fermentation was complete, recovery was also difficult; as much as two-thirds of the penicillin present could be lost during purification because of its instability and heat sensitivity. Extraction was done at low temperatures. Methods of freeze-drying under vacuum eventually gave the best results in purifying the penicillin to a stable, sterile, and usable final form. The steps of fermentation, recovery and purification and packaging quickly yielded to the cooperative efforts of the chemical scientists and engineers working on pilot production of penicillin. On March 1, 1944, Pfizer opened the first commercial plant for large-scale production of penicillin by submerged culture in Brooklyn, New York. Meanwhile, clinical studies in the military and civilian sectors were confirming the therapeutic promise of penicillin. The drug was shown to be effective in the treatment of a wide variety of infections, including streptococcal, staphylococcal and gonococcal infections.

The United States Army established the value of penicillin in the treatment of surgical and wound infections. Clinical studies also demonstrated its effectiveness against syphilis, and by 1944, it was the primary treatment for this disease in the armed forces of Britain and the United States. Back to top Penicillin, WWII and Commercial Production The increasingly obvious value of penicillin in the war effort led the War Production Board (WPB) in 1943 to take responsibility for increased production of the drug. The WPB investigated more than 175 companies before selecting 21 to participate in a penicillin program under the direction of Albert Elder; in addition to Lederle, Merck, Pfizer and Squibb, Abbott Laboratories (which had also been among the major producers of clinical supplies of penicillin to mid-1943) was one of the first companies to begin large-scale production. These firms received top priority on construction materials and other supplies necessary to meet the production goals. The WPB controlled the disposition of all of the penicillin produced. One of the major goals was to have an adequate supply of the drug on hand for the proposed D-Day invasion of Europe.

Feelings of wartime patriotism greatly stimulated work on penicillin in the United Kingdom and the United States. For example, Albert Elder wrote to manufacturers in 1943: "You are urged to impress upon every worker in your plant that penicillin produced today will be saving the life of someone in a few days or curing the disease of someone now incapacitated. Put up slogans in your plant! Place notices in pay envelopes! Create an enthusiasm for the job down to the lowest worker in your plant." As publicity concerning this new "miracle drug" began to reach the public, the demand for penicillin increased. But supplies at first were limited, and priority was given to military use. Dr. Chester Keefer of Boston, Chairman of the National Research Council's Committee on Chemotherapy, had the unenviable task of rationing supplies of the drug for civilian use. Keefer had to restrict the use of the drug to cases where other methods of treatment had failed. Part of his job was also to collect detailed clinical information about the use of the drug so that a fuller understanding of its potential and limitations could be developed. Not surprisingly, Keefer was besieged with pleas for penicillin.

A newspaper account in the New York Herald Tribune for October 17, 1943, stated: "Many laymen - husbands, wives, parents, brothers, sisters, friends - beg Dr. Keefer for penicillin. In every case the petitioner is told to arrange that a full dossier on the patient's condition be sent by the doctor in charge. When this is received, the decision is made on a medical, not an emotional basis." Fortunately, penicillin production began to increase dramatically by early 1944. Production of the drug in the United States jumped from 21 billion units in 1943, to 1,663 billion units in 1944, to more than 6.8 trillion units in 1945, and manufacturing techniques had changed in scale and sophistication from one-liter flasks with less than 1% yield to 10,000-gallon tanks at 80-90% yield.

The American government was eventually able to remove all restrictions on its availability, and as of March 15, 1945, penicillin was distributed through the usual channels and was available to the consumer in his or her corner pharmacy. By 1949, the annual production of penicillin in the United States was 133,229 billion units, and the price had dropped from twenty dollars per 100,000 units in 1943 to less than ten cents. Most British companies moved over to the deep tank fermentation production of penicillin, pioneered in the United States, after the end of the war to meet civilian needs. In the United Kingdom, penicillin first went on sale to the general public, as a prescription only drug, on June 1, 1946. In Britain, Chain and Abraham continued to work on the structure of the penicillin molecule, aided by the X-ray crystallographic work of Dorothy Hodgkin, also at Oxford. The unique feature of the structure, which was finally established in 1945, is the four-membered highly labile beta-lactam ring, fused to a thiazolidine ring.

In the same year Alexander Fleming, Howard Florey, and Ernst Chain were awarded the Nobel Prize for their penicillin research. The co-operative efforts of American chemists, chemical engineers, microbiologists, mycologists, government agencies, and chemical and pharmaceutical manufacturers were equal to the challenge posed by Howard Florey and Norman Heatley in 1941. As Florey observed in 1949, "too high a tribute cannot be paid to the enterprise and energy with which the American manufacturing firms tackled the large-scale production of the drug. Had it not been for their efforts there would certainly not have been sufficient penicillin by D-Day in Normandy in 1944 to treat all severe casualties, both British and American." Landmark Designation and Acknowledgments Landmark Designation The American Chemical Society and Royal Society of Chemistry designated the Discovery and Development of Penicillin an International Historic Chemical Landmark on November 19, 1999, at the Alexander Fleming Laboratory Museum in London, UK. The plaque commemorating the event reads: In 1928, at St. Mary's Hospital, London, Alexander Fleming discovered penicillin.

This discovery led to the introduction of antibiotics that greatly reduced the number of deaths from infection. Howard W. Florey, at the University of Oxford working with Ernst B. Chain, Norman G. Heatley and Edward P. Abraham, successfully took penicillin from the laboratory to the clinic as a medical treatment in 1941. The large-scale development of penicillin was undertaken in the United States of America during the 1939-1945 World War, led by scientists and engineers at the Northern Regional Research Laboratory of the US Department of Agriculture, Abbott Laboratories, Lederle Laboratories, Merck & Co., Inc., Chas. Pfizer & Co. Inc., and E.R. Squibb & Sons. The discovery and development of penicillin was a milestone in twentieth century pharmaceutical chemistry. Plaques were also given to commemorate the contributions of the U.S. Department of Agriculture National Center for Agricultural Utilization Research and five American pharmaceutical companies including Abbott Laboratories, Lederle Laboratories (now Pfizer, Inc.), Merck & Co., Inc., Chas. Pfizer & Co. Inc. (now Pfizer, Inc.) and E.R.

Squibb & Sons (now Bristol-Myers Squibb Company). Acknowledgments: Adapted for the internet from "The discovery and development of penicillin 1928-1945," produced by the American Chemical Society and the Royal Society of Chemistry in 1999. Cite this Page American Chemical Society International Historic Chemical Landmarks. Discovery and Development of Penicillin. (accessed Month Day, Year). The real story behind penicillin | PBS NewsHour The real story behind penicillin EMAIL BY Dr. Howard Markel September 27, 2013 at 2:06 PM EST In a monthly column for PBS NewsHour, Dr. Howard Markel revisits moments that changed the course of modern medicine on their anniversaries, like the development of penicillin on Sept. 28, 1928. Above: Jean-Claude Fide is treated with penicillin by his mother in 1948.

Photo by Bert Hardy/Picture Post The discovery of penicillin, one of the world’s first antibiotics, marks a true turning point in human history — when doctors finally had a tool that could completely cure their patients of deadly infectious diseases. Many school children can recite the basics. Penicillin was discovered in London in September of 1928. As the story goes, Dr. Alexander Fleming, the bacteriologist on duty at St. Mary’s Hospital, returned from a summer vacation in Scotland to find a messy lab bench and a good deal more. Upon examining some colonies of Staphylococcus aureus, Dr. Fleming noted that a mold called Penicillium notatum had contaminated his Petri dishes. After carefully placing the dishes under his microscope, he was amazed to find that the mold prevented the normal growth of the staphylococci. Sir Alexander Fleming (1881 – 1955), studying a test tube culture with a hand lens. Photo by Chris Ware/Getty Images. It took Fleming a few more weeks to grow enough of the persnickety mold so that he was able to confirm his findings.

His conclusions turned out to be phenomenal: there was some factor in the Penicillium mold that not only inhibited the growth of the bacteria but, more important, might be harnessed to combat infectious diseases. As Dr. Fleming famously wrote about that red-letter date: “When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I guess that was exactly what I did.” Fourteen years later, in March 1942, Anne Miller became the first civilian patient to be successfully treated with penicillin, lying near death at New Haven Hospital in Connecticut, after miscarrying and developing an infection that led to blood poisoning. But there is much more to this historic sequence of events. Actually, Fleming had neither the laboratory resources at St. Mary’s nor the chemistry background to take the next giant steps of isolating the active ingredient of the penicillium mold juice, purifying it, figuring out which germs it was effective against, and how to use it. That task fell to Dr.

Howard Florey, a professor of pathology who was director of the Sir William Dunn School of Pathology at Oxford University. He was a master at extracting research grants from tight-fisted bureaucrats and an absolute wizard at administering a large laboratory filled with talented but quirky scientists. This landmark work began in 1938 when Florey, who had long been interested in the ways that bacteria and mold naturally kill each other, came across Fleming’s paper on the penicillium mold while leafing through some back issues of The British Journal of Experimental Pathology. Soon after, Florey and his colleagues assembled in his well-stocked laboratory. They decided to unravel the science beneath what Fleming called penicillium’s ”antibacterial action.” A petri-dish of penicillin showing its inhibitory effect on some bacteria but not on others. Photo by Keystone Features/Getty Images. One of Florey’s brightest employees was a biochemist, Dr. Ernst Chain, a Jewish German émigré. Chain was an abrupt, abrasive and acutely sensitive man who fought constantly with Florey over who deserved credit for developing penicillin. Despite their battles, they produced a series of crude penicillium-mold culture fluid extracts.

During the summer of 1940, their experiments centered on a group of 50 mice that they had infected with deadly streptococcus. Half the mice died miserable deaths from overwhelming sepsis. The others, which received penicillin injections, survived. It was at that point that Florey realized that he had enough promising information to test the drug on people. But the problem remained: how to produce enough pure penicillin to treat people. In spite of efforts to increase the yield from the mold cultures, it took 2,000 liters of mold culture fluid to obtain enough pure penicillin to treat a single case of sepsis in a person. In September 1940, an Oxford police constable, Albert Alexander, 48, provided the first test case. Alexander nicked his face working in his rose garden. The scratch, infected with streptococci and staphylococci, spread to his eyes and scalp. Although Alexander was admitted to the Radcliffe Infirmary and treated with doses of sulfa drugs, the infection worsened and resulted in smoldering abscesses in the eye, lungs and shoulder.

Florey and Chain heard about the horrible case at high table one evening and, immediately, asked the Radcliffe physicians if they could try their ”purified” penicillin. After five days of injections, Alexander began to recover. But Chain and Florey did not have enough pure penicillin to eradicate the infection, and Alexander ultimately died. A laboratory technician examining flasks of penicillin culture, taken by James Jarche for Illustrated magazine in 1943. Another vital figure in the lab was a biochemist, Dr. Norman Heatley, who used every available container, bottle and bedpan to grow vats of the penicillin mold, suction off the fluid and develop ways to purify the antibiotic. The makeshift mold factory he put together was about as far removed as one could get from the enormous fermentation tanks and sophisticated chemical engineering that characterize modern antibiotic production today. In the summer of 1941, shortly before the United States entered World War II, Florey and Heatley flew to the United States, where they worked with American scientists in Peoria, Ill., to develop a means of mass producing what became known as the wonder drug.

Aware that the fungus Penicillium notatum would never yield enough penicillin to treat people reliably, Florey and Heatley searched for a more productive species. One hot summer day, a laboratory assistant, Mary Hunt, arrived with a cantaloupe that she had picked up at the market and that was covered with a ”pretty, golden mold.” Serendipitously, the mold turned out to be the fungus Penicillium chrysogeum, and it yielded 200 times the amount of penicillin as the species that Fleming had described. Yet even that species required enhancing with mutation-causing X-rays and filtration, ultimately producing 1,000 times as much penicillin as the first batches from Penicillium notatum. In the war, penicillin proved its mettle. Throughout history, the major killer in wars had been infection rather than battle injuries. In World War I, the death rate from bacterial pneumonia was 18 percent; in World War II, it fell, to less than 1 percent. This is the penicillin table in a U.S. evacuation hospital in Luxembourg in 1945. Photo by Photo12/UIG.

From January to May in 1942, 400 million units of pure penicillin were manufactured. By the end of the war, American pharmaceutical companies were producing 650 billion units a month. Ironically, Fleming did little work on penicillin after his initial observations in 1928. Beginning in 1941, after news reporters began to cover the early trials of the antibiotic on people, the unprepossessing and gentle Fleming was lionized as the discoverer of penicillin. And much to the quiet consternation of Florey, the Oxford group’s contributions were virtually ignored. That problem was partially corrected in 1945, when Fleming, Florey, and Chain — but not Heatley — were awarded the Nobel Prize in Physiology or Medicine. In his acceptance speech, Fleming presciently warned that the overuse of penicillin might lead to bacterial resistance. In 1990, Oxford made up for the Nobel committee’s oversight by awarding Heatley the first honorary doctorate of medicine in its 800-year history.

Maybe this September 28, as we celebrate Alexander Fleming’s great accomplishment, we will recall that penicillin also required the midwifery of Florey, Chain and Heatley, as well as an army of laboratory workers. Dr. Howard Markel writes a monthly column for the PBS NewsHour website, highlighting the anniversary of a momentous event that continues to shape modern medicine. He is the director of the Center for the History of Medicine and the George E. Wantz Distinguished Professor of the History of Medicine at the University of Michigan. He is the author or editor of 10 books, including “Quarantine! East European Jewish Immigrants and the New York City Epidemics of 1892,” “When Germs Travel: Six Major Epidemics That Have Invaded America Since 1900 and the Fears They Have Unleashed” and “An Anatomy of Addiction: Sigmund Freud, William Halsted, and the Miracle Drug Cocaine.” Related Content History of Antibiotics History of Antibiotics Sign Up for Our Free Newsletters Thanks, You're in! Health Tip of the Day Sign up There was an error. Please try again. Please select a newsletter. Please enter a valid email address.

Did you mean ? < Continued from page 1 Updated October 05, 2015. (Gr. anti, "against"; bios, "life") An antibiotic is a chemical substance produced by one organism that is destructive to another. The word antibiotic came from the word antibiosis a term coined in 1889 by Louis Pasteur's pupil Paul Vuillemin which means a process by which life could be used to destroy life. Ancient History The ancient Egyptians, the Chinese, and Indians of central America all used molds to treat infected wounds. However, they did not understand the connection of the antibacterial properties of mold and the treatment of diseases. Late 1800s The search for antibiotics began in the late 1800s, with the growing acceptance of the germ theory of disease , a theory which linked bacteria and other microbes to the causation of a variety of ailments. continue reading below our video 5 Ways to Improve Your Credit Score As a result, scientists began to devote time to searching for drugs that would kill these disease-causing bacteria. 1871 The surgeon Joseph Lister , began researching the phenomenon that urine contaminated with mold would not allow the successful growth of bacteria.

1890s German doctors, Rudolf Emmerich and Oscar Low were the first to make an effective medication that they called pyocyanase from microbes. It was the first antibiotic to be used in hospitals. However, the drug often did not work. 1928 Sir Alexander Fleming observed that colonies of the bacterium Staphylococcus aureus could be destroyed by the mold Penicillium notatum, demonstrating antibacterial properties. 1935 Prontosil, the first sulfa drug, was discovered in 1935 by German chemist Gerhard Domagk (1895–1964). 1942 The manufacturing process for Penicillin G Procaine was invented by Howard Florey (1898–1968) and Ernst Chain (1906–1979). Penicillin could now be sold as a drug. Fleming, Florey, and Chain shared the 1945 Nobel Prize for medicine for their work on penicillin .

1943 In 1943, American microbiologist Selman Waksman (1888–1973) made the drug streptomycin from soil bacteria, the first of a new class of drugs called aminoglycosides. Streptomycin could treat diseases like tuberculosis, however, the side effects were often too severe. 1955 Tetracycline was patented by Lloyd Conover, which became the most prescribed broad spectrum antibiotic in the United States . 1957 Nystatin was patented and used to cure many disfiguring and disabling fungal infections. 1981 SmithKline Beecham patented Amoxicillin or amoxicillin/clavulanate potassium tablets, and first sold the antibiotic in 1998 under the tradenames of Amoxicillin, Amoxil, and Trimox. Amoxicillin is a semisynthetic antibiotic. How were antibiotics discovered? - Antibiotic - Sharecare How were antibiotics discovered? Topics | Pharmacology | Anti-Infective Agent | Antibiotic | How were antibiotics discovered? A Answers (1) A Dr.

Mehmet Oz, MD , Cardiology (Cardiovascular Disease), answered It is unlikely that anyone alive today can remember what life was like before antibiotics. It was a pivotal point in the history of medicine and probably the whole of mankind. If it weren't for the ingenious speculation of men like Alexander Fleming that not all bacteria live in harmony with other bacteria, we may never have discovered penicillin, the first antibiotic to treat bacterial disease in humans. The Penicillium fungus, a type of mold often seen growing on bread, exudes a chemical that causes the cell wall of certain bacteria to rupture and die. Since then, researchers have studied the various ways bacteria are antagonized to develop new antibiotics. History of Antibiotics - The Discovery by Alexander Fleming History of Antibiotics Share this page on your website: <a href="">History of Antibiotics</a> History of antibiotics can be described in two segments early history and modern history. Most important is the discovery of pencillin by Alexander Fleming.

This article is a part of the guide: Select from one of the other courses available: Discover 11 more articles on this topic Don't miss these related articles: Antibiotics - An Introduction Infections are very common and responsible for a large number diseases adversely affecting human health. Most of the infectious diseases are caused by bacteria. Infections caused by bacteria can be prevented, managed and treated through anti-bacterial group of compounds known as antibiotics. . . Definition Antibiotics can be loosely defined as the variety of substances derived from bacterial sources (microorganisms) that control the growth of or kill other bacteria. However, Synthetic antibiotics, usually chemically related to natural antibiotics, have since been produced that accomplish comparable tasks. Classifications A common scheme of classifications for antibiotics is drawn below: Antibiotics can also be classified based on their chemical structure. A similar level of effectiveness, toxicity and side-effects is rendered by the antibiotics of same structural group. Broad spectrum antibiotics are effective against a broad range of microorganisms in comparison to narrow spectrum antibiotics. Bactericidal antibiotics kill the bacteria whereas bacteriostatic antibiotics halt the growth of bacteria. . History of antibiotics can be described in two segments as under: Early History Greeks and Indians used moulds and other plants to treat infections.

In Greece and Serbia, mouldy bread was traditionally used to treat wounds and infections. Warm soil was used in Russia by peasants to cure infected wounds. Sumerian doctors gave patients beer soup mixed with turtle shells and snake skins. Babylonian doctors healed the eyes using a mixture of frog bile and sour milk. Sri Lankan army used oil cake (sweetmeat) to server both as desiccant and antibacterial. MODERN HISTORY Germany Gerhard Domagk discovered Sulfonamidochrysoidine (Prontosil ) During 1940's and 50's streptomycin, chloramphenicol, and tetracycline were discovered and Selman Waksman used the term "antibiotics" to describe them (1942) Sir Alexander Fleming Sir Alexander Fleming, a Scottish biologist, defined new horizons for modern antibiotics with his discoveries of enzyme lysozyme (1921) and the antibiotic substance penicillin (1928). The discovery of penicillin from the fungus Penicillium notatum perfected the treatment of bacterial infections such as, syphilis, gangrene and tuberculosis.

He also contributed immensely towards medical sciences with his writings on the subjects of bacteriology, immunology and chemotherapy. Alexander Fleming was born in Loudon, Scotland on 6 August, 1881 in a farming family. He carried on his schooling at Regent Street Polytechnic after his family moved to London in 1895. He joined St. Mary's Medical School and became research assistant to renowned Sir Almroth Wright after he qualified with distinction in 1906. He completed his degree (M.B.B.S.) with gold medal in 1908 from the University of London and lectured at St. Mart till 1914. He served as Captain during the World War I and worked in battlefield hospitals in France. After the war he returned to St. Mary in 1918 and got elected Professor of Bacteriology in 1928. The Discovery of Antibiotics "One sometimes finds what one is not looking for" (Sir Alexander Fleming) His research and study during his military career inspired him to discover naturally antiseptic enzyme in 1921, which he named lysozyme.

This substance existed in tissues and secretions like mucus, tears and egg-white but it did not have much effect on the strongly harmful bacteria. Six years later; as a result of some intelligent serendipity, he stumbled on discovering penicillin. It was in 1928 when he observed while experimenting on influenza virus that a common fungus, Penicillium notatum had destroyed bacteria in a staphylococcus culture plate. Upon subsequent investigation, he found out that mould juice had developed a bacteria-free zone which inhibited the growth of staphylococci. This newly discovered active substance was effective even when diluted up to 800 times. He named it penicillin. He was knighted in 1944 and was given the Nobel Prize in Physiology or Medicine in 1945 for his extraordinary achievements which revolutionized the medical sciences. How Do Antibiotics Work? Various types of antibiotics work in either of the following two ways: A Bactericidal antibiotic kills the bacteria generally by either interfering with the formation of the bacterium's cell wall or its cell contents.

Penicillin, daptomycin, fluoroquinolones, metronidazole, nitrofurantoin and co-trimoxazole are some example of Bactericidal antibiotics. A Bacteriostatic antibiotic stops bacteria from multiplying by interfering with bacterial protein production, DNA replication, or other aspects of bacterial cellular metabolism. Some Bacteriostatic antibiotics are tetracyclines, sulphonamides, spectinomycin, trimethoprim, chloramphenicol, macrolides and lincosamides. . Antibiotics 1928 - 2000 Before the Miracle Think back to the last time you cut or grazed yourself. Can you imagine that cut becoming infected with bacteria - so seriously infected that you couldn�t fight it? Before the discovery of antibiotics , there was nothing much anybody could do. Streptococcus pyogenes caused half of all post-birth deaths and was a major cause of death from burns. Staphylococcus aureus was fatal in 80 percent of infected wounds and the tuberculosis and pneumonia bacteria were famous killers. All this changed with the development of antibiotics. Who�d have thought a mouldy plate would lead to this?

In 1928, Alexander Fleming, a bacteriologist at London�s St. Mary's Hospital, found that a mould on a discarded culture plate had an antibacterial action. The bacteria were staphylococci, a source of serious and often deadly human infection and the mould was �penicillin�. Penicillin kills bacteria by interfering with cell wall growth (image courtesy of Cellsalive ). But he didn�t realise what he�d discovered - he didn't have an inkling. His findings, written up in 1929, presented penicillin as a possible antiseptic. It was left for Australian-born Howard Florey and Ernst Chain, a Jewish refugee from Hitler's Berlin, to analyse the biochemistry, prove its efficacy and deliver penicillin to humanity. The Golden Age of antibiotics The first antibiotics were prescribed in the late 1930s, beginning a great era in discovery, development and prescription. Bacterial infection, as a cause of death, plummeted. Between 1944 and 1972 human life expectancy jumped by eight years - an increase largely credited to the introduction of antibiotics. Many experts were confident the tide had turned in the war against bacterial infections.

Indeed, in 1969, the then US Surgeon General, William Stewart, boldly told the US Congress it was time to "�close the books on infectious diseases." Some experts, however, were uncomfortable with these predictions including Alexander Fleming: "The greatest possibility of evil in self-medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out which can be passed to other individuals and from them to others until they reach someone who gets a septicaemia or pneumonia which penicillin cannot save." (New York Times June 26, 1945) The emergence of resistant bacteria By the 1950s, when antibiotics were still new, there was ample evidence of the emergence of resistance. In fact, within four years of penicillin being introduced onto the market, resistant infections were being reported. However, in the 1950s and 1960s, resistant bacterial strains seemed to matter very little. There was always a new antibiotic being developed to combat them.

But, by the end of the 1960s, new classes of antibiotics were no longer being developed. Instead, most work involved slightly altering existing antibiotics to reduce toxicity and to revive drugs rendered ineffective by the emergence of resistance. Drug companies had turned their attention elsewhere, to other areas such as viral infections. By the 1970s penicillin resistant strains of one of the most common causes of pneumonia, Streptococcus pneumoniae, as well as many venereal diseases, spread around the world. A completely new class of antibiotic wasn�t developed for another 30 years. In late 1999 the development of a drug called Zyvox was finally announced. It�s in a new class of antibiotics called the Oxazolidinones. It�s claimed to be effective against multi-resistant strains of bacteria. Resistance to antibiotics by 2000 Around the world, resistance is rapidly increasing to commonly used antibiotics. A 1999 assessment from Australia�s top experts is daunting: "Resistance has emerged for all known antibiotics in use.

For most antibiotics, and classes of antibiotics, antibiotic resistant genes have also entered the bacterial population in the domains where antibiotics are used (for example in hospitals, farms and aqua-culture ponds)." Who discovered the first anti-biotic and what was it? | eNotes Who discovered the first anti-biotic and what was it? besure77 | Middle School Teacher | (Level 1) Senior Educator Posted on April 10, 2010 at 12:36 PM Alexander Fleming discovered bacteria in a very fascinating way. He had a contaminated bacteria culture and thought it looked strange. He decided to take a closer look at it and what he found was startling. He noticed the that a colony of bacteria had a patch of mold growing close to it. The bacteria close to this patch of mold was not growing so he hypothesized that the mold produced something that inhibited bacteria growth. After many experiments he found that this substance did prohibit bacteria growth an he gave it the name penicillin. Technology at this time made it impossible to produce large amounts of penicillin. It was not until after World War II that technology was advanced enough to make mass quantities of this antibiotic.

like 1 dislike 0 April 11, 2010 at 2:16 AM The first antibacterial substance that can be considered as a limited-spectrum antibiotic was Salvarsan and it was discovered in 1910, by the German physician and chemist Paul Ehrlich (1854-1915). Salvarsan was a medicine meant to cure syphilis, which was very prevalent at that time. Salvarsan was followed, in 1928, by the epochal discovery of Penicillin, by Alexander Fleming, who noted that secretion of green mold "Penicillium notatum (Penicillium chrysogenum) destroys bacteria colony from the laboratory. Another finding which is worth mentioning is the discovery in 1935 of sulphonamides, by Gerhard Domagk, who is not an antibiotic, being not bactericidal but only bacteriostatic. It follows the discovery of a series of antibiotics as streptomycin, tetracycline, etc.

like 1 dislike 0 April 10, 2010 at 8:55 AM Sir Alexander Fleming a Scottish Biologist is attributed as having discovered the first antibiotic and it was penicillin. It was derived from the mold Penicillium chrysogenum which could be found on food and even waste. His discovery happened in 1928. Fleming was also a renowned writer in the scientific field and well known for presenting on various medical topics. In 1999 Time Magazine included Fleming as one of the most important men of the 21st century. His contribution of anti-biotics helped to save many lives and led the way for the advancement in the study of antibiotics. April 10, 2010 at 11:41 PM Antibiotics are microorganisms used as drugs that act on the principle of being selectively toxic to certain type of cells. Thus antibiotics attack and kill only the certain of pathogenic cells. These include disease causing organisms and cancerous cells. Different types of antibiotic drugs have been developed to treat different diseases. People have used antibiotic substances such as moulds to treat skin infections for thousands of years.

However, the first modern antibiotic drug named penicillin was first identified in1928 by a British scientist Sir Alexander Flemming (1881-1955). However the took some time to isolate penicillin and produce drug from it. This was first achieved in 1941.

Question: Which was the first antibiotic to be discovered?
Answer: Penicillin