The advent of penicillin forever changed the world of medicine at its discovery with its ability to treat diseases, deadly at the time, that are now considered commonplace and easily treatable. Penicillin was one of the greatest discoveries of the twentieth century, as antibiotics are one of the most highly prescribed drugs in the world today. Although its discovery is often described as serendipitous, the process by which it was cultivated was quite meticulous, and continued attention has been paid to penicillin’s further development. It is because penicillin and its derivatives have played such a vital role in everyday medicine that it is such an important topic.
Penicillin works by virtue of its beta-lactam ring that specifically binds to microbial enzymes in bacterial cell walls, and keeps the cell membrane structures from linking up. Eventually, if the bacterium keeps dividing, the cell membrane will become increasingly weaker and lyse. The beta-lactam ring is very simple in and of itself, but its ability to remain potent with several different functional groups attached to it makes it spectacular in its applications.
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As was noted earlier, the discovery of penicillin by Alexander Fleming was not as spontaneous as it might originally appear. The antibacterial effects of many molds had been observed numerous times before, and Fleming was doing testing in this area and in the area of lysozymes throughout the 1920s. When he first noticed the antibacterial effects of the penicillium strain of bacteria in 1928, he thought it unremarkable, though further testing revealed that he was onto something special. However, the bacterial strain Fleming was able to culture was unstable and difficult to produce in quantities large enough for testing or practical application. During this time, however, Fleming did meet with Howard Florey, who would later take on a vital role in the development of penicillin. By the mid 1930s, the advent of sulfa-drugs essentially ended all of Fleming’s research on penicillin. However, during this time period, Howard Florey had begun research on lysozymes, and took special interest in antibiotics in 1938 after reading Fleming’s original paper. Ernst Chain, working in Florey’s lab, carried out many of the initial experiments in lab mice, all highly successful in treating infections of streptococcus bacterium. Human tests soon thereafter, also proved penicillin to be highly effective, even in cases in which sulfa-drugs had failed. However, production of the drug was still a problem, and trials could not be conducted on a large scale. By this time it was 1941, and although penicillin’s benefits had proven, culture mediums were still only yielding one part-per-million penicillin. With Word War II raging, and resources becoming scarce, Florey negotiated with the Rockefeller Foundation of the United States to move himself and a colleague to the United States in order for him to continue his research. This project would gain added momentum when the United States entered the war, with the development of penicillin becoming a war project. Shortly thereafter, it was determined that Fleming’s original strain would not be able to produce the amount of bacterium necessary for medicinal application. New strains were sought out, with Penicillium chryogeum finally winning out. This new variety would produce two hundred times the amount of penicillin as the original Penicillium notatum. However, this amount was still inadequate. The bacteria was then bombarded with ultraviolet and X-rays in a successful attempt to induce mutations, which ultimately yielded one-thousand times the amount of penicillin as the original. In conjunction with this, new methods for culturing penicillin were discovered, increasing efficiency of production. By the time the war ended, scientists had gone from having to recycle patient’s urine in order to conserve penicillin to producing enough to treat seven million patients per year. In 1945, Fleming, Florey, and Chain were all awarded the Nobel Prize for Physiology and Medicine, so the discovery of penicillin was quite a drawn-out process when taken into consideration the amount of time it took to produce a practical form of the drug. This set off a search in medicine for more antibiotics, however, scientists would have to look away from the natural world this time.
Although selective breeding and radiation therapy already give penicillin a storied history in biotechnology, the advent of new genetic engineering techniques that allow for designer drugs to be produced have kept penicillin on the forefront of antibiotic treatment. Often,
The mechanism of action is still the same as far as the chemical structure is concerned. However, the means of production are much more efficient in terms of cost and evaluating new strains of bacteria. These two qualities are highly desirable in the field since bacteria have the ability to quickly mutate and render standard antibiotics ineffective.
Bibliography
class notes, Biotechnology in Society, Dr. McClure, Jan-May 2000
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