Penicillin discovered - Feb 14, 1929 - HISTORY.com Penicillin discovered Publisher A+E Networks Sir Alexander Fleming was a young bacteriologist when an accidental discovery led to one of the great developments of modern medicine on this day in 1929. Having left a plate of staphylococcus bacteria uncovered, Fleming noticed that a mold that had fallen on the culture had killed many of the bacteria. He identified the mold as penicillium notatum, similar to the kind found on bread. On February 14, 1929, Fleming introduced his mold by-product called penicillin to cure bacterial infections.

Related Videos This Day in History for February 14 – Penicillin Discovered and More - TSM Interactive This Day in History for February 14 – Penicillin Discovered and More By Shauna W February 13, 2012 11:00 PM Here’s a look at some interesting events that took place on this day in history: 1920 – The League of Women Voters is founded ( More info ) 1929 – Seven people, six of them gangster rivals of Al Capone’s gang, are murdered in Chicago in what would come to be known as the Saint Valentine’s Day massacre ( More info ) 1929 – Scottish scientist Alexander Fleming accidentally discovers penicillin ( More info ) 1939 – Hedda Hopper pens the first installment of what would become her tremendously influential gossip column in the Los Angeles Times ( More info ) 1989 – Iranian leader Ruhollah Khomeini issues a fatwa calling for the death of Salman Rushdie, author of the controversial book ‘The Satanic Verses’ ( More info ) TSM Welcome back to TSM Interactive It appears that you already have an account created within our VIP network of sites

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To keep your personal information safe, we need to verify that it's really you. To activate your account, please confirm your password. When you have confirmed your password, you will be able to log in through Facebook on both sites. Enter your password YES, Activate My Account Now! Welcome back to TSM Interactive It appears that you already have an account on this site associated with . To connect your existing account just click on the account activation button below. You will maintain your existing VIP profile. After you do this, you will be able to always log in to using your original account information. HERSHEY'S Valentines Day | Famous Events on Valentine's Day Back to Fun Stuff Famous Events on Valentine's Day While enjoying your Valentine's Day chocolates or choosing that perfect Valentine's Day gift basket, remember a few of the historical events that occurred on Valentine's Day. The holiday represents more than just Valentine's Day gifts and romance. Some of the most monumental events in United States history occurred on Valentine's Day, February 14th. Anna Howard Shaw, influential leader of the women's suffrage movement, was born. 1859 Oregon was admitted to the Union as the 33rd state.

1870 Esther Morris became the world's first female justice of the peace. 1903 Department of Commerce and Labor established. 1912 Arizona became the 48th state of the Union. 1919 The League of Women Voters was founded in Chicago. 1924 Thomas Watson founded International Business Machines Corporation (IBM). 1929 Seven rivals of mobster Al Capone are murdered, remembered as the "St. Valentine's Day Massacre."1929 Sir Alexander Fleming discovered Penicillin. 1946 The world's first all-electronic computer was unveiled at the University of Pennsylvania, ENIAC. 1948 First "micro on a chip" patented by Texas Instruments. Super Simple Advertisement Privacy Policy Legal Info Contact Us View All Brands What is Ad Alert? "Ad Alert" is our way of telling you that the website you're viewing may be trying to sell you something. If you are under the age of 18, always get permission from your parent or guardian before you make a purchase or even submit any information about yourself online. Thanks!

×Close You are leaving: Celebrate with HERSHEY'S You are about to leave for another site that may contain things for adults as well as kids. Do you want to leave or stay? 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). A Science Odyssey: People and Discoveries: Fleming discovers penicillin Fleming discovers penicillin 1928 - 1945 Photo: Alexander Fleming's photo of the dish with bacteria and Penicillin mold Alexander Fleming returned to his research laboratory at St. Mary's Hospital in London after World War I. His battlefront experience had shown him how serious a killer bacteria could be, much worse even than enemy artillery. He wanted to find a chemical that could stop bacterial infection. He discovered lysozyme, an enzyme occurring in many body fluids, such as tears. It had a natural antibacterial effect, but not against the strongest infectious agents. He kept looking. Fleming had so much going on in his lab that it was often in a jumble.

This disorder proved very fortunate. In 1928, he was straightening up a pile of Petri dishes where he had been growing bacteria, but which had been piled in the sink. He opened each one and examined it before tossing it into the cleaning solution. One made him stop and say, "That's funny." Some mold was growing on one of the dishes... not too unusual, but all around the mold, the staph bacteria had been killed... very unusual. He took a sample of the mold. He found that it was from the penicillium family, later specified as Penicillium notatum. Fleming presented his findings in 1929, but they raised little interest. He published a report on penicillin and its potential uses in the British Journal of Experimental Pathology. Fleming worked with the mold for some time, but refining and growing it was a difficult process better suited to a chemist. The work was taken over by a team of chemists and mold specialists, but was cut short when several of them died or relocated. In 1935, Australian Howard Florey was appointed professor of pathology at Oxford University where he headed up a laboratory.

This was a daunting task in an economically depressed time, and seeking funding for the researchers and work he hoped to do took much of his time. One researcher he hired soon after his arrival was Ernst Chain . Chain was paid to do cancer research, and work that spilled over into Florey's own interest and work on lysozyme. Chain became quite enthusiastic about the search for antibacterial chemicals. In looking back at old articles written about lysozyme, including those by Fleming in the 1920s, he happened across Fleming's paper on penicillin. "I had come across this paper early in 1938 and on reading it I immediately became interested," he wrote. The Oxford team, as Florey's researchers have become known, began experimenting with the penicillin mold. They took it one step further than Fleming did: they did not just try it topically or in a petri dish, but injected it in live mice. With controlled experimentation, they found it cured mice with bacterial infections. They went on to try it on a few human subjects and saw amazing results. By now it was 1941, and England was at war.

As Fleming first foresaw, the wartime need for an antibacterial was great, but resources were tight and penicillin still very experimental. Florey had connections at the Rockefeller Foundation in the United States, however, and it funded further research. The biggest problem was producing enough penicillin. This was hard and expensive to accomplish. Florey and another researcher traveled to the U.S. to talk to chemical manufacturers and ended up in Peoria, Illinois. An agricultural research center there had developed excellent techniques of fermentation, a process needed for penicillin growth. The agriculture of Illinois proved useful, too. The nutrient base for the penicillin grown there was corn (maize), which was not commonly grown in Britain. The penicillin loved it, and yielded almost 500 times as much as it had before. More vigorous and productive strains of the mold were sought, and one of the best came from a rotting canteloupe from a Peoria market! By this point, the United States had entered World War II as well. Penicillin's benefits was now known, and the government pushed industry into producing penicillin, recruiting more than 21 chemical companies into production.

From January to May 1943, only 400 million units of penicillin had been made; by the time the war ended, U.S. companies were making 650 billion units a month. Related Features History of Penicillin Smith Collection/ Iconica/ Getty Images Updated October 05, 2015. Penicillin is one of the earliest discovered and widely used antibiotic agents, derived from the Penicillium mold. Antibiotics are natural substances that are released by bacteria and fungi into the their environment, as a means of inhibiting other organisms - it is chemical warfare on a microscopic scale. Born August 6, 1881 in Darvel, Scotland Died March 11, 1955 in London, England In 1928, Sir Alexander Fleming observed that colonies of the bacterium Staphylococcus aureus could be destroyed by the mold Penicillium notatum, proving that there was an antibacterial agent there in principle. This principle later lead to medicines that could kill certain types of disease-causing bacteria inside the body.

continue reading below our video 5 Ways to Improve Your Credit Score At the time, however, the importance of Alexander Fleming's discovery was not known. Use of penicillin did not begin until the 1940s when Howard Florey and Ernst Chain isolated the active ingredient and developed a powdery form of the medicine. History of Penicillin Originally noticed by a French medical student, Ernest Duchesne, in 1896. Penicillin was re-discovered by bacteriologist Alexander Fleming working at St. Mary's Hospital in London in 1928. He observed that a plate culture of Staphylococcus had been contaminated by a blue-green mold and that colonies of bacteria adjacent to the mold were being dissolved. Curious, Alexander Fleming grew the mold in a pure culture and found that it produced a substance that killed a number of disease-causing bacteria. Naming the substance penicillin, Dr. Fleming in 1929 published the results of his investigations, noting that his discovery might have therapeutic value if it could be produced in quantity. Hodgkin used x-rays to find the structural layouts of atoms and the overall molecular shape of over 100 molecules including penicillin.

Dorothy's discovery of the molecular layout of penicillin helped lead scientists to develop other antibiotics. Dr. Howard Florey It was not until 1939 that Dr. Howard Florey, a future Nobel Laureate, and three colleagues at Oxford University began intensive research and were able to demonstrate penicillin's ability to kill infectious bacteria. As the war with Germany continued to drain industrial and government resources, the British scientists could not produce the quantities of penicillin needed for clinical trials on humans and turned to the United States for help. They were quickly referred to the Peoria Lab where scientists were already working on fermentation methods to increase the growth rate of fungal cultures. One July 9, 1941, Howard Florey and Norman Heatley, Oxford University Scientists came to the U.S. with a small but valuable package containing a small amount of penicillin to begin work. Pumping air into deep vats containing corn steep liquor (a non-alcoholic by-product of the wet milling process) and the addition of other key ingredients was shown to produce faster growth and larger amounts of penicillin than the previous surface-growth method.

Ironically, after a worldwide search, it was a strain of penicillin from a moldy cantaloupe in a Peoria market that was found and improved to produce the largest amount of penicillin when grown in the deep vat, submerged conditions. Andrew J. Moyer By November 26, 1941, Andrew J. Moyer, the lab's expert on the nutrition of molds, had succeeded, with the assistance of Dr. Heatley, in increasing the yields of penicillin 10 times. In 1943, the required clinical trials were performed and penicillin was shown to be the most effective antibacterial agent to date. Penicillin production was quickly scaled up and available in quantity to treat Allied soldiers wounded on D-Day. As production was increased, the price dropped from nearly priceless in 1940, to $20 per dose in July 1943, to $0.55 per dose by 1946. As a result of their work, two members of the British group were awarded the Nobel Prize. Dr. Andrew J.

Moyer from the Peoria Lab was inducted into the Inventors Hall of Fame and both the British and Peoria Laboratories were designated as International Historic Chemical Landmarks. Andrew J Moyer Patent On May 25, 1948, Andrew J Moyer was granted a patent for a method of the mass production of penicillin. Resistance to Penicillin Four years after drug companies began mass-producing penicillin in 1943, microbes began appearing that could resist it. The first bug to battle penicillin was Staphylococcus aureus. This bacterium is often a harmless passenger in the human body, but it can cause illness, such as pneumonia or toxic shock syndrome, when it overgrows or produces a toxin. Penicillin: the first miracle drug Penicillin: the first miracle drug Early penicillin culture facility at the Sir William Dunn School of Pathology, Oxford, England. © Museum of the History of Science, Oxford Many of you are here only because penicillin saved your life, or the life of one of your parents or grandparents.

Penicillin's ability to cure people of many once-fatal bacterial infections has saved so many lives that it is easy to understand why it was once called a "miracle drug". Antibiotics are chemicals, effective at very low concentrations, created as part of the life process of one organism, which can kill or stop the growth of a disease-causing microbe--a germ. In 1929, Alexander Fleming, a doctor and researcher at St. Mary's Hospital in London, England, published a paper on a chemical he called "penicillin", which he had isolated from from a mold, Penicillium notatum. Penicillin, Fleming wrote, had prevented the growth of a neighboring colony of germs in the same petri dish. Dr. Fleming was never able to purify his samples of penicillin, but he became the first person to publish the news of its germ-killing power. Howard Florey, Ernst Chain and Norman Heatley expanded on Fleming's work in 1938, at Oxford University. They and their staff developed methods for growing, extracting and purifying enough penicillin to prove its value as a drug.

World War II (1939-1945) had begun by the time their research was showing results. The main research and production was moved to the United States in 1941, to protect it from the bombs pounding England. Work began on how to grow the mold efficiently to make penicillin in the large quantities that would be needed for thousands of soldiers. As the destruction of the war grew, so did interest in penicillin in laboratories, universities and drug companies on both sides of the Atlantic. The scientists knew they were in a race against death, because an infection was as likely to kill a wounded soldier as his wound. Photograph courtesy Chains of conidia (spores) produced by hyphal branch from mycelium Photograph courtesy of Associated Press Sir Alexander Fleming, 1952 Creating the right environment for growth was the first step in producing enough penicillin to be used as a drug. In Oxford, experiments showed that Penicillium notatum grew best in small shallow containers on a broth of nutrients. Penicillium need lots of air. In the United States, it was discovered that huge "deep fermentation" tanks could be used if sterilized air was pumped continually through the tanks.

Production increased even more when corn steep liquor, a thick, sticky by-product of corn processing, was added to the tanks. Corn steep liquor contained concentrated nutrients that increased the yield 12-20 times. Formerly considered a waste material, corn steep liquor became a crucial ingredient in the large-scale production of penicillin. Scientists were also determined to find another strain of Penicillium that might grow better in the huge deep fermentation tanks. Army pilots sent back soil samples from all over the world to be tested for molds. Residents of Peoria, Illinois, were encouraged to bring moldy household objects to the local U.S. Department of Agriculture laboratory, where penicillin research was being conducted. Laboratory staff members also kept an eye out for promising molds while grocery shopping or cleaning out their refrigerators. Photograph courtesy of Merck Archives, ©Merck & Co. Inc. Refrigeration equipment for large fermentation unit at Cherokee Plant, Danville, PA. Photograph courtesy of Merck Archives, ©Merck & Co. Inc. Fermentation unit used in purifying penicillin in 1945. Photograph courtesy of Merck Archives, ©Merck & Co. Inc.

Upper part of fermentors (tanks) used to produce penicillin and vitamin B12. In 1943, laboratory worker Mary Hunt brought in an ordinary supermarket cantaloupe infected with a mold that had "a pretty, golden look." This Penicillium species, Penicillium chrysogenum grew so well in a tank that it more than doubled the amount of penicillin produced. The deep fermentation method, the use of corn steep liquor and the discovery of P. chrysogenumby Mary Hunt made the commercial production of penicillin possible. Researchers continued to find higher-yielding Penicillium molds, and also produced higher yielding strains by exposing molds to x-rays or ultraviolet light. Penicillin kills by preventing some bacteria from forming new cell walls. One by one, the bacteria die because they cannot complete the process of division that produces two new "daughter" bacteria from a single "parent" bacterium. The new cell wall that needs to be made to separate the "daughters" is never formed. Some bacteria are able to resist the action of antibiotic drugs, including penicillin.

Antibiotic resistance occurs because not all bacteria of the same species are alike, just as people in your own family are not exactly alike. Eventually, the small differences among the bacteria often mean that some will be able to resist the attack of an antibiotic. If the sick person's own defenses can not kill off these resistant bacteria, they will multiply. This antibiotic-resistant form of a disease can re-infect the patient, or be passed on to another person. Taking antibiotics for viral illnesses like colds can also cause antibiotic resistant bacteria to develop. Antibiotics have no effect on viruses, but it will kill off harmless and even the beneficial bacteria living in the patient's body. The surviving resistant bacteria, free from competition, will live and multiply and may eventually cause disease. Patients with bacterial infections, who don't finish their antibiotic prescriptions completely, also allow resistant bacteria to develop. This happens because a small number of semi-resistant bacteria, which needed the full course of antibiotics to kill them, survive. Instead of being a small part of the bacteria causing an infection, the more resistant bacteria take over when sensitive bacteria are killed by the antibiotic.

Today, in the United States, deaths by infectious bacterial diseases are only one-twentieth of what they were in 1900, before any antibiotic chemicals had been discovered. The main causes of death today are what are referred to as "the diseases of old age": heart disease, kidney disease and cancer. We would be shocked to hear of someone dying from an infection that started in a scratch, but, before antibiotics like penicillin, it was common for people to die from such infections. Humans can slow the creation of antibiotic resistant diseases by understanding the uses and limits of antibiotics. Take all of an antibiotic, and only take them when prescribed by a doctor. Research to develop new antibiotics to treat resistant bacteria continues, but research takes time. Time is running out because the world's biodiversity is decreasing--the source of half of our disease-fighting chemicals. An example of the importance of preserving the world's biodiversity occurred in 1996, in New York state. Students at Cornell University collected a fungus that finally made it possible to identify the two very different life stages of the mold that produces the drug cyclosporin. Cyclosporin prevents the rejection of transplanted organs. Without it, transplant operations would be impossible.

Knowing the full life history of the cyclosporin-producing fungus may make it easier to find related molds. Even people who see no special beauty or value in the world's biodiversity may one day benefit from the currently unknown and powerful substances, produced by fungi and other microbes, that are waiting for discovery in familiar places. WEB RESOURCES: Lewis, Ricki. "The Rise of Antibiotic-Resistant Infections". FDA Consumer Magazine, 1995, and U. S. Food and Drug Administration web site. ( The Penicillin Memorial and Rose Garden [with text], The Oxford Virtual Science Walk, Museum of the History of Science, Oxford, England. The partial image of the memorial was taken by Sophie Huxley, © Huxley Scientific Press. She notes that further down on the memorial, after a brief description of the Oxford group's work, are the words "All Mankind Is In Their Debt." ( READING: These books are currently out-of-print, but your local library may be able to borrow them for you by interlibrary loan. Gray, William D. The Relation of Fungi to Human Affairs. New York: Henry Holt and Company, Inc., 1959. Jacobs, Francine.

Breakthrough: The True Story of Penicillin. New York: Dodd, Mead & Company, 1985. (ISBN 0-396-08579-2)

Question: Who discovered penicillin on Valentine's Day in 1929?
Answer: Sir Alexander Fleming