Antibiotics play a major role in the field of medicine today. Yet many do not know of how they got their start. Who could’ve imagined that something we use today on a regular basis in hospitals, clinics, and private offices was discovered by chance? The discovery of antibiotics was slow, but once it was really paid attention to on the affect it could have, antibiotics are now something the world could not do without. (Rosenberg, 2011)
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In September 1928 a man by the name of Alexander Fleming would make a discovery that would change medicine forever. Fleming had just returned from a vacation with his family and was going through stacks of Petri dishes. These petri dishes were experiments he had left before going on vacation. He was sifting through them to see which ones could still be used and which ones needed to be gotten rid of. While cleaning and getting rid of the contaminated dishes one in particular stuck out at him, it was growing mold but, the mold that was growing had killed off the Staphylococcus aureus that had been growing in the dish. It was then that he realized he had by chance discovered something very substantial. Research with the bacteria staphylococci was something he had been performing and had other discoveries in. At the time of his discoveries most of his research was revolved around finding a cure for scarlet fever, pneumonia, diphtheria, and typhoid fever. After his finding he published them in 1929 in the British Journal of Experimental Pathology. His publication gained little or no attention and he soon ran into another problem with the penicillin itself. He found it hard to cultivate and it proved to be even more of a problem to isolate the antibiotic agent. Because of these two things Fleming came to two assumptions, first that the penicillin would not be important in treating infection due to the fact that it seemed slow acting and there was the problem of producing a great enough quantity. Secondly, he assumed that the penicillin would not stay in the body for a long enough period of time to kill bacteria effectively. Fleming continued his work and many trials after that did show promise but in 1940 he finally abandoned his penicillin research, giving someone else the chance to possibly find a way to refine the penicillin. (Lloyd, 2009)
Not long after Fleming had abandoned his research two chemists by the names of Howard Florey and Ernst Chain soon took up the task of refining the penicillin. Something Fleming alone had not been able to do. Ernst Chain, a biochemist who had fled Nazi Germany in 1939 had come across Fleming’s earlier work on penicillin. Along with Howard Florey, an Australian pharmacologist and pathologist, who was also Chain’s supervisor at the time helped to isolate the antibiotic in a larger quantity. The first experiment that was conducted two with mice by injecting the penicillin into the mice which had been infected with bacterial disease. The mice recovered and they furthered their research by increasing their numbers from just two to fifty mice. Even though by doing these experiments the scientists still ran into a huge problem. They could hardly isolate enough of the antibiotic to help one person let alone possibly thousands, and World War II was soon approaching making their need for a solution of even more importance. Ernst took on most of the responsibility of isolating and testing the penicillin to make sure it was in fact safe for use on humans. Florey took on the task of how to get the penicillin mass produced by locating companies that would take on this daunting task. Several companies in the U.S. agreed to mass produce the antibiotic due to the fact that many others would be preparing for the upcoming war. (Lloyd, 2009)
World War II played a major part in getting the antibiotic mass produced. It pushed and challenged companies like Merck and Co. and Pfizer to find better ways of efficiently producing large enough quantities for many people. In March of 1942 the first patient was treated for streptococcal septicemia, which ended up using half of the total supply available on that one patient. By June in 1942 there was only enough left to help ten patients. Soon in 1943 another discovery was found by a woman in a Peoria, Illinois market. Her name was Mary Hunt, a lab worker and she brought a moldy cantaloupe which turned out to be infected with another strain of penicillin called, Penicillin chysogeum. This new species of penicillin would produce more than 200 times more than the strain Fleming had discovered and with some research and more experimenting with x-rays to mutate the strain, they were able to increase that number to 1000 times more. By 1944 they were able to produce 2.3 million doses of this antibiotic just in time before the invasion of Normandy. During the World War this drug proved to be very vital in curing infections of wounds and amputations. Large scale production was engineered by a woman named Margaret Hutchinson Rousseau, who created a fermentation deep-tank. A man by the name of G. Raymond Rettew had a great contribution during this time for coming up with techniques to produce commercial quantities of penicillin. During the war The National Health System was established in Britain. This system gave free health care to those who were in need because prior to this if you needed a shot of penicillin you would have had to pay for it. (Moberg & Cohn, 1990)
Even with all these great advancements with the antibiotic though, the drug was still extremely limited. It actually became very common to collect penicillin from urine, which had been seen to be excreted from the body with a very high renal clearance rate. Penicillin was then isolated and reused. This was definitely not something the scientists or doctors wished to do but due to the era and importance of the medicine they did what was necessary. They wanted to find a molecule that could slow down the excretion rate from the body. Soon an agent called probenecid proved to be a suitable agent for this task. When probenecid and penicillin are administered together it not only slows the rate at which penicillin leaves the body but it also increases its concentration. Mass production on a grand scale began after the bombing of Pearl Harbor and they soon had enough of the antibiotic made to treat the allied forces by D-Day. By the end of the war U.S. companies were making 650 billion units of this antibiotic every month. In 1945 Fleming, Chain, and Florey all received Nobel Prize honors for their discoveries and achievement in the advancement of penicillin. By this time several more strains of the penicillium mold had been discovered. (Moberg & Cohn, 1990)
Antibiotics that have been found through the advancement of penicillin are ampicillin, flucloxacillin, dicloxacillin, and methicillin. Unfortunately these antibiotics are not effective against methicillin-resistant strains of Staphylococcus aureus. Another development of antibiotics includes mecillinams, carbapenams, and one of these most important cephalosporins. (Moberg & Cohn, 1990)
The main companies that played a major role in getting the penicillin mass produced were Merck, Squibb, Lilly, and Pfizer. At the time they were introduced to the idea though all information on penicillin was based on clinical trials. In June of 1941, Florey contacted a few old friends who then helped the research gain the attention it needed and urged the companies to take on the task. They were informed that they would be doing it to serve the nation’s best interest and that they could receive backing from the federal government. Soon after a meeting was held, in attendance were the directors, Randolph T. Major of Merck, Jasper Kane of Pfizer, George A. Harrop of the Squibb Institute for Medical Research, and Y. SubbaRow or Lederle. In 1942 Merck and Squibb were joined by Pfizer collaborating on their own with their own contracts with each other. Pharmaceutical companies had their own battles and advances in trying to produce the penicillin on a large scale. The mold proved to be very unstable along with the isolation process being difficult. One problem was penicillin needed air to grow and in fermentation tanks that was not possible. They had attempted to use sterile air pushed up through the tanks, but this caused severe foaming. Squibb scientists soon came up with a solution with a chemical called, glyceryl monoricinolate as an anti-foaming agent. They also designed new cooling systems that would allow them to be able to stir the penicillin mix more effectively. The Lilly Company succeeded in helping create new types of penicillin. Because of the instability of these new strains they had to be removed at low temperatures. In response to this new issue, Pfizer devised the idea to create a cooling system out of an old ice cream freezer this was mainly due to shortages on materials because of the war. On March 1, 1944, Pfizer opened the first commercial plant used for large scale production of penicillin located in Brooklyn, NY. It was then at this time that penicillin was recognized as the primary treatment of diseases in the armed forces of the United States and Britain. Due to these great advancements it opened the door for pharmaceuticals, which are now very lucrative businesses. Two companies heard of quite frequently are Merck and Co. and Pfizer. Merck and Pfizer both can easily spend up to 2 billion a year on research and development for new medications. One of Merck’s biggest selling drugs to date is Vasotec which banked 6.6 billion in 1988 alone. Pfizer today is one of the largest pharmaceutical companies today that researches and develops drugs for distribution. To date an estimated 12 billion dollars can be spent on advertising alone when a new drug becomes available to the public. This industry will be one to continually grow and expand due to the fact that there are always new medications being made or discovered and new illnesses needing a cure. (ACS Chemistry for Life, 2011)
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Penicillins were the world’s first antibiotics discovered and produced from the bacteria penicillium. Today there are at least 20 different types of penicillin being used to treat all kinds of diseases, infections, and wounds. Over the years, there have been many more antibiotics discovered but, penicillin is still the antibiotic of choice when dealing with bacterial infections. Penicillins are most often used to treat anything from a simple ear infection to a sexually transmitted disease. Without Sir Alexander Fleming, who was knighted along with Howard Florey in 1944, and his “accident” the medical world as we know it today would prove to be much different. (Rosenberg, 2011)
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