Penicillin when was it first used

The first patient was successfully treated for streptococcal septicemia in the United States in However, supply was limited and demand was high in the early days of penicillin. Penicillin helped reduce the number of deaths and amputations of troops during World War II. According to records, there were only million units of penicillin available during the first five months of ; by the time World War II ended, U.

To date, penicillin has become the most widely used antibiotic in the world. Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. British Journal of Experimental Pathology. Haven KF. Marvels of Science: 50 Fascinating 5-Minute Reads. Connecticut: Libraries Unlimited; Healio News Endocrinology.

Issue: August By Katie Kalvaitis. Perspective from Theodore C. Eickhoff, MD. View Issue. Source: Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation ofB.

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 , 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. Their work on the purification and chemistry of penicillin began in earnest in , 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 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. 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 , Florey carried out vital experiments, showing that penicillin could protect mice against infection from deadly Streptococci. Then, on February 12, , a 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. 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 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.

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. 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. 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.

The OSRD had been created in June, , 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. Department of Agriculture, participants included research directors Randolph T. Major of Merck; George A. SubbaRow of Lederle.

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," A method for mass production was devised by Howard Florey and Ernst Chain in , and it was first mass produced in , with half of that total supply used for one patient being treated for streptococcal septicaemia.

In , 2. And it was then that the miracle of penicillin became clear. Soldiers who had previously died from septicaemia were surviving. Expectations rose. If penicillin could cure septicaemia, what about other serious infections like meningitis, pneumonia and kidney infections?

Of course, we should use it for these, too. And what about nasty chest infections and troublesome sinusitis? Or inconvenient sore throats which could affect wedding days or job interviews — should these be treated with penicillin?

It seems and for good reason that we all wanted to be part of the 20th-century miracle that was penicillin. So antibiotic use grew and grew — and grew. Today, tens of millions of prescriptions are written in the UK every year, mostly by GPs and nurses in primary care.

But all is not well. Fleming was aware of the problem as soon as he discovered penicillin. Most bacteria were killed by the medicine, but others were immune, somehow able to resist the miracle.