In 1979, Susan B. Horwitz’s publication on the true intermoleculear features of taxol, including the mitotic inhibition caused by the molecule upon injection, created a new interest in the molecule. The 80’s produced the first phases of efforts to analyze the affects of paclitaxel as a cancer treatment, which began preliminary trials in 1984. By 1988, phase II trials were underway, meaning an inceases in the amount of pacific yew tree bark needed to synthesize the molecule.
Pacliatxel, developed initially from the Taxus brevifolia or Pacific yew tree in 1967, underwent many stages of development prior to reaching the level it is used today. Arthur S. Barclay’s work in collecting and discovering the taxol molecule from the bark of the yew tree on the Pacific coast of Washington set in motion many stages of synthesis and debate over the molecule.
Paclitaxel, a derivative of the pacific yew tree Taxus brevifolia, is a remarkably effective but controversial cancer treatmenting drug. The history associated with paclitaxel is one of a tremendous battle between three groups: environmentalists, who lobby for an alternate way of creating the drug; scientists, who feel the drug is particuarily effective on breast and ovarian cancers; and congressmen, who juggle the two sides in a perpetual game of ethics. Removing paclitaxel from external politics and ethics, the drug is effective because it is a mitotic inhibitor, that stops the growth of the cancer cell through hyper-stabilization of the cell. The paclitaxel injection strongly affects rapidly reproducing cancer cells because the drug is particuarily effective at disrupting the cell division in both the cytoskeleton of the cell and by docking at the specific protein responsible for cell building. Paclitaxel’s effectiveness, though controversial in its development, is key to the history of cancer treatment over the past 50 years and is a drug of remarkable dimensions, both histroically and biochemically.
Florey, H.W. Chain, E. (1949).Antibiotics: A Survey of Penicillin, Streptomycin, And Other Antimicrobial Substances From Fungi, Actinomycetes, Bacteria, and Plants.London: OxfordUniversity Press.
Hare, R. (1970). The Birth of Penicillin and Disarming of Microbes.London: George Allen and Unwin.
Klein, J.O. (1994). Otitis externa, otitis media, mastoiditis. In G.L. Mandell, J.E. Bennett, and R. Dolin 9eds). Mandell, Douglas and Bennett’s Principles and Practices of Infectious Diseases. New York: Churchill Livengstone.
Le Couteur P. & Burreson J. (2003). Napoleon’s Buttons. 17 Molecules that Changed History.New York: Penguin.
McGowan, J.E.J. (1983). Antimicrobial Resistance in Hospital Organisms and its Relation to Antibiotic Use. Reviews of Infectious Diseases 5 (6): 1033-1048.
Schlessinger, D. (1993). Biological Basis for Antibacterial action. Mechanisms of Microbial Disease, 230, 77, 95.
Tyndall, J. (1876). The Optical Deportment of the Atmosphere in Relation to the Phenomena of Putrefaction. Philosophical Transactions of the Royal Society, 166, 20-55.
U.S. Congress Office of Technology Assessment. (1995). Impacts of Antibiotic- Resistant Bacteria. WashingtonDC: U.S. Government Printing Office.
Wilson, D. (1976). In Search of Penicillin. New York: Alfred A. Knopf.
The discovery of penicillin controlled many life-threatening diseases, reduced the tolls of death and illnesses, and increased the life expectancy worldwide (Schlessinger, 1993, p.90). However, many cases were reported later in which penicillin or any antibiotic had any effect in curing or reducing the danger of the infectious disease. Antibiotic-resistant bacteria complicated treatment of illnesses starting with simple infections such as ear infection to deadly infections such as pneumonia and tuberculosis. The problem with anti-biotic resistance is that it is random. Any use of antibiotics whether “appropriate” or “inappropriate,” can lead to the emergence and spread of anti-biotic resistance. The appropriate use of antibiotics is the use that helps the patient by killing the bacteria that caused the infection and stop its spread in the body. Inappropriate use of antibiotic is the use that does not help the patient or stop the infectious disease. On the opposite, it increases the risk of promoting the spread of anti-biotic resistant bacteria (U.S. Congress, office of technology assessment, 1995, p. 50).
Many studies have proved that there is a direct relationship between the use of antibiotics and the spread of antibiotic resistant bacteria (McGowan, 1983, p. 1035). Accordingly, the reducing the inappropriate use of antibiotic may lower the spread of antibiotic-resistant bacteria. Sometimes, resistant microbes emerge even when antibiotics are used properly. However, the effect of these resistant microbes will not be as obvious as it is when the antibiotics are used inappropriately. Resistant strains can “infect other individuals and spread within a community or institution. They cal also transfer the genetic information for resistance to other bacteria” (U.S. Congress, office of technology assessment, 1995, p. 50-51).
Before the 1940s, medicine was unable to do anything against bacterial infections. When diagnosed early, infections could be lanced or surgically opened and cleaned, and locally acting antiseptics could be used to “sterilize the area.” however, too little could be done once the infection had become “systemic” and in the blood stream. In World War I, once an infection from even a minor wound developed into dreaded gangrene which is “an infection caused by Clostridium bacteria related to the bacteria that caused botulism” (U.S. Congress, office of technology assessment, 1995, p. 37). Unfortunately, there was no treatment for this infection except for amputation of the wounded limb and prayer that the infection had not reached a soldier’s vital organs.
Military personnel were more susceptible to serious infections than other people because of their living conditions. In wartime, soldiers lived in close quarters, did not have access to healthy food or clean water. Furthermore, they had few opportunities to exercise good personal hygiene. Even in peacetime soldiers were trained in crowded and confined quarters, which facilitated transmission of infectious diseases. Historians recorded the existence and widely spread respiratory diseases among soldiers in peacetime. Soldiers suffered from streptococcal pneumonia, rheumatic fever and other respiratory diseases that were incurable at that time. So, the losses among soldiers were huge even in peacetime. The soldiers’ mothers or relatives had but little hope that their son would come back again when his military training during peacetime was over. Only few people had a little hope that their son would come back from the war because most soldiers underwent an amputation procedure of a wounded limb. However, after the discovery of penicillin, the rates of respiratory diseases among soldiers significantly decreased. Also, there was no more need for a surgical opening of the wound or even an amputation of a limb because penicillin could treat infections without any necessary surgical procedure. Thus, soldiers were able to go back home when the war finished healthy as they were when they left it before the war (U.S. Congress, office of technology assessment, 1995, p. 37).
It is incorrect to say that all kinds of bacteria are dangerous to people. Some bacteria play an essential role in keeping people healthy. According to the office of technology assessment of the U.S. congress (1995), “more than one thousand different species of bacteria normally live benignly in and on the human body.” Some bacteria that live in the human body provide a protection to the body against the bacteria that cause disease. For example, intestinal bacteria account for about thirty percent of the bulk of human faces, generate essential vitamins that are absorbed by the body and provide a barrier against other kinds of bacteria becoming established in the intestine. Accordingly, ” a person can ingest a small numbers of pathogenic salmonella bacteria but not get sick because the salmonella is prevented from growing to large numbers by the presence of commensal bacteria in the intestine” (U.S. Congress, office of technology assessment, 1995, p. 35). Even though human body relies to a great extent on bacteria for health, bacteria are far better known as causes for disease. In 1830, infectious diseases caused by bacteria and other microorganisms were a major cause of death, and most shockingly, only fifty percent of the population lived past the age of twenty five (Schlessinger, 1993, p. 90). The bacterial cell resembles to an extent an animal cell. They both have nearly similar cellular structures. Penicillin interacts with the wall of the bacteria cell with the presence of a certain enzyme. Thus, penicillin destroys the bacteria cell and prevents it from spreading in the body. Animal cells do not have walls, they rather have cell membrane. Penicillin does not interact with the cell membrane that is why penicillin does not have a destructive effect on our cells (Le Couteur and Burrenson, 2003, p. 196-7).
Alexander Fleming was not the first one to discover penicillin. In 1875 an English distinguished physician named John Tyndall was busily engaged in his study about germs and Bacteria. He was trying to find if there was a systematic dispersion of bacteria in the atmosphere i.e. whether or not bacteria aggregated and evenly distributed in ‘clouds.’In order to do this, Tyndall sat up a number of open test tubes containing broth. Depending on his theory about bacteria, he believed that all of the tubes should become thick and muddy because of the growth of bacteria falling into them from the air.
Tyndall prepared one hundred tubes of broth, placed them comparatively close to each other. He kept the tubes open in order to be exposed to the air for twenty four hours. The next day, Tyndall noticed that the broth in some tubes remained clear which proved that no bacteria had fallen into these tubes despite the fact that all the tubes were kept open. This also indicated that Tyndall’s theory about the even distribution of bacteria in the atmosphere was wrong.
Tyndall also observed that on the surface of other tubes there was a penicillium. Tyndall thought that the penicillium was “exquisitely beautiful.” Tyndall believed that there was a battle between the bacteria and the mold, and “in every case where the mold was thick and coherent, the bacteria died or became dormant and fell to the bottom as a sediment”
(J. Tyndall, 1876).
Tyndall only marked and studied the physical properties of penicillium, or what we now know as (Penicillium notatum). He observed that penicillium was able to destroy bacteria falling into the tubes from the air, but he did not know at that time that bacteria could cause disease (Friedman, 1998, p. 169).
Around 1896, doctors and physicians were unable to help patients suffering from a serious infection. The only thing they could do was to amputate a leg, remove an appendix. In case of other serious infections, the doctors waited and depended only on the patients’ immune system to fight the infection (Friedman, 1998, p. 169). However, many patients died while waiting for their bodies to fight bacteria.
Alexander Fleming accidentally rediscovered penicillin when he was engaged in studying different kinds of bacteria and molds in his laboratory. He once opened one of his Petri dishes for a few seconds to smear it with a strain of staphylococcus which is a bacterium that typically occurs in clusters resembling grapes.Fleming noticed a halo of inhibition of bacterial growth around a contaminant blue-green mold staphylococcus plate culture. Fleming concluded that the mold was releasing a substance that was inhibiting bacterial growth and lysing the bacteria. He grew a pure culture of the mold and discovered that it was a penisillium mold, now known to be penicillium notatum. This was surprising because it was too short a time for a penicillium spore or two to find the dish. Tyndall waited 24 hours before he observed the existence of penicillium in some of his test tubes containing broth, whereas Fleming only left his dish exposed to the air for a few seconds and he observed a strain of staphylococcus being attacked by penicillium. On Fleming’s occasion, probably billions of penicillium spores happened to be floating in the atmosphere of Fleming’s laboratory. An expert on mold was growing penicillium notatum just one floor below Fleming’s laboratory. Because at that time there was no sufficient method to prevent spores from floating away, the light spores, ascended the elevator shaft and the staircase to Fleming’s laboratory door, which he habitually kept open (Hare, 1970, p. 199).
Fleming was interested in what he saw on his Petri dish. Unlike Tyndall who was only interested in the physical properties of penicillium, Fleming wanted to know the functional properties of penicillium. He wanted to find out the strange ability of penicillium to stop the growth of staphylococci. Fleming applied a simple screening method in order to observe the functional properties of penicillin.
Without doubt, this was a great discovery that would help the physicians to cure dangerous infections. However, there was a problem in applying Fleming’s discovery in the real life because some distinguished physicians in addition to Fleming’s colleagues believed that “antibacterial drugs are a delusion” (Wilson, 1976, p. 147).Despite this common belief, Fleming took a big step when he injected the penicillium broth filtrate into a rabbit and a mouse. He then observed that there was no ill results were present after the injection. Fleming further tried penicillin on human being when he irrigated an infected human eye, an inflamed maxillary sinus, and the infected surface of an amputated leg with a penicillin solution. None of these three cases showed any toxic effects of penicillin. However, only the first two tissues lost their infections and were totally cured. The infected tissue on the amputated leg did not show any sign of positive change or healing. This was the only applicable experiment of Fleming on penicillin.
The development of penicillin for the medical use is attributed to an Australian nobleman called Howard Walter Florey who worked with a team at Oxford University Florey’s team wanted to investigate the biochemical and biological properties of antibacterial substances that microorganisms might possess. The team eventually discovered that penicillin was a molecule and not an enzyme as physicians used to consider it. The team also discovered that penicillin was very unstable unlike other simple molecules. Florey’s team members were able to produce stable penicillin by “reducing the temperature of a water solution of penicillin by freeze drying it (Freidman, 1998, p. 179). Then, Florey experimented penicillin on animals, especially white mice, before he applied it on human beings.
He was a poor Scottish farmer. His name was Fleming. One day, while trying to make living for his family, he heard a cry for help coming from a nearby bog. He dropped his tools and ran to the bog. He found a terrified boy mired to his waste with black muck. Farmer Fleming helped the boy and saved him from what could be an inevitable death. The next day, a fancy carriage appeared at the door of Fleming. An elegantly dressed gentle man stepped out and introduced himself to Fleming as the father of the boy whom Fleming saved yesterday. “I want to repay you,” said the gentleman. “You saved my son’s life.” “No, I can’t accept payment for what I did,” the Scottish farmer replied waving off the offer. At that moment, the farmer’s own son came to the door. “Is that your son?” asked the gentleman. “Yes” the farmer replied proudly. “I’ll make you a deal. Let me provide him with the level of education my son will enjoy. If the lad is anything like his father, he will no doubt grow up to be a man we both will be proud of.” The Scottish farmer accepted this offer because he was poor and was not able to provide his son with a respectful education.
Farmer Fleming’s son who was born in Lochfield, Scotland in 1881 and died in 1955, attended the best schools at that time, graduated from the University of London, and worked in St. Mary’s Hospital became to be known throughout the world as the noted Sir Alexander Fleming, the discoverer of penicillin. The name of the nobleman who offered Alexander Fleming all these opportunities was Lord Randolph Churchill, the Father of Sir Winston Churchill.
Penicillin was mistakenly considered an enzyme before physicians and chemists were able to prove that it is a molecule. Penicillin went through a long history before physicians were able to benefit from its crucial medical properties. Its discovery help cure the most dangerous and sometimes the deadliest infections. Thus, penicillin was taken from small laboratories to huge medical factories and eventually became one of the most famous antibiotics in the medical industry. Penicillin does not only play an essential role in changing history, history changes penicillin to a great extent also.
