For thousands of years, millions of people died from invisible enemies, germs, and disease-causing bacteria. Many diseases such as typhoid fever, sepsis, tuberculosis, dysentery, and pneumonia, which are now successfully treated, have recently been considered almost incurable. Numerous cases of wound infections can also be added to this list. In the XVI century, the average human lifespan was 30 years (Zuchora-Walske 2014). In the early XX century, a little scratch could result in death (Zuchora-Walske 2014). The situation greatly changed with the discovery of antibiotics. In the XX century, physicians received an excellent tool that could fight purulent and infectious diseases, pneumonia, tuberculosis, otitis, sinusitis, abscess, and cellulitis (Zuchora-Walske 2014). However, scientists later discovered numerous disadvantages of antibiotics including side-effects and resistance. The beginning of the XX century was marked by a number of new discoveries that gave the world great opportunities. The discovery of antibiotics has made a real revolution in medicine and the world in general. The purpose of the paper is to explore the discovery of antibiotics and detailed research into their negative effects.
Antibiotics are a group of natural and semi-synthetic organic compounds capable of destroying microbes or suppressing their reproduction. “Antimicrobial drugs or antibiotics are biologically active molecules against microorganisms” (Gualerzi et al. 2013, p. 28). They are obtained by the extraction from the colonies of fungi, bacteria, as well as plant or animal tissues. In some cases, the original molecule is subjected to further chemical modifications to improve certain properties of the antibiotic. These are semi-synthetic antibiotics. However, in medicine, only several groups of antibiotics are used (Dougherty & Pucci 2011). Due to high toxicity, the other antibiotics cannot be used for treating infectious diseases in humans. A great variety of antibiotics served as a reason for the creation of the classification and division into classes. Thus, a certain group of antibiotics contains preparations of a similar chemical structure, which are derived from the same raw material molecules, and action. Currently, scientists know many types of antibiotics endowed with different properties. Knowledge of these properties is the basis of the correct antibiotic treatment. Individual qualities and effects of the antibiotic mainly depend on its chemical structure.
People have used antibiotics since ancient times. “The history of antibiotics goes back to mercury and bismuth, heavy metals which are toxic to people, but in correct doses, were more toxic to the organism that causes syphilis” (Levy 2013, p. 9). In folk medicine, people used extracts of lichen for treating wounds and tuberculosis. Subsequently, doctors began to add extracts of bacteria Pseudomonas aeruginosa to ointments to treat superficial wounds. However, no one knew the action of these bacteria. At that time, the phenomenon of antibiosis was unknown. Despite that fact, some of the first scientists-microbiologists were able to detect and describe antibiosis (Dougherty & Pucci 2011). They called the state of some preparations the inhibition of the growth of organisms by other ones. The fact is that the antagonistic relations between different microorganisms are shown in their growth in mixed culture. Prior to the development of methods of pure cultivation, different bacteria and mold had grown together in optimal conditions for the manifestation of antibiosis. In 1877, Louis Pasteur described antibiosis between soil bacteria and pathogenic bacteria, which are causative agents of anthrax (Dougherty & Pucci 2011). The scientist even suggested that antibiosis might be the basis of treatment.
In the book Antibiotics: A Multidisciplinary Approach, the authors note that before the 1930’s, there had been no drug that could fight bacterial infections (Gallo, Lancini & Parenti 2013). Doctors only focused on preventive measures. However, they made active attempts to find the ultimate weapon against infections. The first antibiotics had been extracted even before they became known for their ability to oppress the growth of microorganisms. Thus, in 1860, scientists obtained the blue pigment pyocyanin in a crystalline form. It produced small movable rod-shaped bacteria of the genus Pseudomonas. However, its antibiotic properties were discovered only after many years. In 1896, scientists managed to crystallize another chemical kind from the mold called mycophenolic acid (Dougherty & Pucci 2011). Gradually, it became clear that antibiosis has the chemical nature and is possible owing to the production of specific chemical compounds. In 1929, Alexander Fleming discovered penicillin while watching antagonism of Penicillium notatum and staphylococcus in a mixed culture (Dougherty & Pucci 2011). “Fleming published his work on penicillin in 1929 reporting that the extracts of the mold were able to kill a number of gram-positive pathogens in addition to staphylococci and even the gram-negative pathogen responsible for gonorrhea” (Dougherty & Pucci 2011, p. 10). He suggested the possibility of its use for medicinal purposes. During the war, this medicine saved thousands of seriously ill patients from septic complications. After the discovery of penicillin, the process began to gain momentum and new types of antibiotics started to appear almost every year. “During the golden age of antibiotics discovery, between the 1940s and 1960s, almost all currently known classes of antibiotics were discovered” (Gualerzi et al. 2013, p. 28). This fact gave doctors tremendous opportunities. They were able to cure syphilis, gonorrhea, pneumonia, tuberculosis, and rheumatic fever. Many skin diseases were treated very easily.
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The antagonistic relations between pathogenic microbes for plants and nonpathogenic soil microorganisms identified in mixed cultures interested phytopathologists, who tried to use this phenomenon to control plant diseases. It is known that in the soil, there is a certain fungus, which reduces damping-off of grafts. In 1936, scientists extracted the antibiotic from this fungus (Dougherty & Pucci 2011). It was called gliotoksin. This discovery confirmed the value of antibiotics as a means of disease prevention.
Rene Jul Dubo was among the first researchers engaged in the purposeful search for antibiotics (Dougherty & Pucci 2011). The experiments, conducted by him and his staff, led to the discovery of antibiotics produced by certain soil bacteria, their extraction in pure form, and usage in clinical practice. In 1939, Dubo received tyrothricin – a complex of antibiotics consisting of gramicidin and tyrocidine (Dougherty & Pucci 2011). It was an incentive for other researchers who discovered even more important antibiotics for the clinic. In 1942, Howard Walter Florey, together with colleagues from Oxford University, re-examined penicillin and proved the possibility of its clinical use as a non-toxic treatment for many acute infections (Dougherty & Pucci 2011). At the same time, doctors and researchers started calling these substances antibiotics. Selman Waksman and his students at Rutgers University, USA, studied actinomycetes such as streptomyces (Dougherty & Pucci 2011). In 1944, they discovered streptomycin, which was effective in treating tuberculosis and other diseases (Dougherty & Pucci 2011). After 1940, scientists received a great number of clinically important antibiotics including bacitracin, chloramphenicol, chlortetracycline, oxytetracycline, amphotericin B, cycloserine etc (Dougherty & Pucci 2011). Throughout the world, there was a real boom in the usage of antibiotics. In the mid-1980s, in the United States, antibiotics were prescribed more often than any other medicines except for sedatives and tranquilizers (Dougherty & Pucci 2011). However, the rapid progress in this area ended soon. Over the 1940-1970 period, ten different classes of antibiotics were produced in the world, each of which with a unique mechanism of action (Dougherty & Pucci 2011). Since 1998, the United States has allowed to use only four new antibiotics with unique mechanisms of action (Dougherty & Pucci 2011). Breakthroughs in the creation of new antibiotics have temporarily stopped.
At first, antibiotics coped with their role. The scope of their activity was the bacterial infection of vital organs and rapidly progressing infections (Shlaes 2010). They are still essential for tuberculosis, flu, pneumonia, sepsis, and many others diseases. To prevent infections, they are often prescribed after surgeries. As a rule, a dentist recommends taking antibiotics after tooth extraction (Shlaes 2010). Only with the help of antibiotics such infections as mycoplasma infection, chlamydia infection, and some other diseases of the genitourinary system can be treated.
However, with time, doctors and scientists started noticing terrible side-effects of antibiotics (Shlaes 2010). In Latin, Anti bios means against life (Shlaes 2010). Therefore, it is possible to state that antibiotics are drugs against life. Nevertheless, the effect of antibiotics is not directed against a person but against microorganisms that penetrate the body. However, due to incorrect intake, they can cause numerous side-effects. The danger is that most of the antibiotics kill not only a pathogen of a disease but the whole groups of microbes (Shlaes 2010). Microbes are not only harmful bacteria but also those that are necessary for normal functioning of the body.
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It is known that the human intestine contains about two kilograms of microbes that are responsible for the normal bowel function. Beneficial bacteria are also present on the skin, in the mouth, and the vagina – in all places, where there may be the contact of the body with the external environment. Different groups of bacteria coexist in balance with each other and with other microorganisms, in particular, fungi. The imbalance leads to the excessive growth of antagonists, which are the same fungus. Consequently, dysbiosis or an imbalance in microorganisms in the human body develops. Scientists have discovered that dysbacteriosis is one of the most common negative effects of antibiotics. A particular manifestation of it is a fungal infection, a bright representative of which is oral moniliasis. Any antibiotic suppresses the growth of beneficial microbes and this adversely affects the homeostasis.
Another disadvantage of antibiotics that was discovered soon after doctors had begun to prescribe them is their resistance. “Despite the widespread belief that antibiotics are always effective, resistance has become an increasingly common event” (Li & Corey 2013, p. 389). The principal difference of antibiotics from other classes of medications is that they act not only on the receptors of human cells but also on microorganisms. Therefore, each antibiotic kills all bacteria sensitive to it or inhibits their growth and reproduction regardless of whether they are responsible for disease in a patient or not. Consequently, the formation and improvement of the diverse and effective mechanisms of resistance to antibiotics have become the only condition for the survival of microorganisms in the changed environment. The emergence and spread of antibiotic resistance among causative agents of the disease have led to the loss of the clinical relevance of certain antibiotics and stimulated the search for ways to overcome the difficulties. Finally, the change of the prevalence and severity of resistance to certain drugs and classes of antibiotics causes necessity for the periodic review of the standards of the clinical use. The extent of the use of antibiotics increases annually. In 1954, the United States produced about 908 tons of antibiotics and in 2000, the country increased the production to almost 23 thousand tons. Every year, American doctors prescribe more than 100 million courses of antibiotics. In many cases, antibiotics are used incorrectly, for example, as a result of misdiagnosis. Data of the World Health Organization indicate that a number of pathogens, resistant to existing drugs, increases (Podolsky 2015). The fact that more pathogens become resistant to multiple types of antibiotics is especially disturbing. Antimicrobial resistance is a natural biological phenomenon. However, these days, it threatens humanity.
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Nowadays, it is little known about the fact that scientists began to warn about the possible occurrence of this problem shortly after the invention of penicillin. As a result, until the end of the 1940s, in most European countries and North America where antibiotics had been applied in large numbers, it had been forbidden to sell these drugs in the free market (Li & Corey 2013, p. 389). In the United States, this restriction exists to this day (Li & Corey 2013, p. 389). In the 1950s, the first cases of the appearance of resistance to antibiotics were observed by doctors (Li & Corey 2013, p. 389). People all over the world suffered from staphylococcus resistant to available antibiotics. In the United States, Britain, and France, scientists conducted studies that yielded a surprising result (Podolsky 2015). Among other things, a belief in the power of antibiotics was so high that the medical personnel began to neglect the safety rules hoping that any disease could be easily treated (Podolsky 2015). Stuart Levy, the author of The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle notes that one of the consequences of this crisis was the efforts to create new types of antibiotics, to which a new type of staphylococcus could not resist (Levy 2013). One of the results was the development of vancomycin (Levy 2013). The manufacturing company declined to release it into circulation preparing stocks of vancomycin in case a new type of drug-resistant pathogenic bacteria appeared. At that time, the production of synthetic antibiotic began, to which, as expected, the bacteria could not develop resistance. One of the consequences of this was the emergence of the drug called Cipro that was able to fight anthrax. This drug was fully synthetic.
However, the true extent of antibiotic resistance became apparent only in the late 1990s (Podolsky 2015). According to the Centers for Disease Control and Prevention, the list of causative agents of dangerous diseases, which resistance is developing extremely rapidly, includes the agents of pneumonia, meningitis, infections of the skin, lungs, blood vessels, gonorrhea, malaria, tuberculosis, and AIDS (Podolsky 2015). For example, each year, streptococcal infections become a cause of three thousand cases of meningitis, 150 thousand cases of pneumonia ending with hospitalizations, and more than 7 million of other diseases (Podolsky 2015). Currently, physicians state that in about a third of cases, these pathogens are resistant to existing antibiotics (Podolsky 2015). This phenomenon was observed even in the 1970s.
The production of antibiotics is one of the most advanced methods of competition between organisms in nature. Antibiotics are special agents of a biological origin that can suppress the growth of viruses, bacteria, and microorganisms or completely destroy them. Alexander Fleming was among the first scientists who received antibiotic in its pure form and called it penicillin. This substance acquired its name from the species of fungus, from the colonies of which, this antibiotic was obtained. However, it was only the beginning of the era of antibiotics. After the war, scientists continued research in this area and Fleming’s followers discovered a number of substances with the properties of penicillin. Ultimately, parallel studies in the field of microbiology, biochemistry, and pharmacology led to the invention of many antibiotics effective in treating a wide variety of infections caused by bacteria. Antibiotics changed the lives of people. Moreover, antibiotics dramatically changed medicine. They allowed doctors to fight many dangerous infections successfully. Thereby, they significantly decreased mortality and increased life expectancy. However, subsequently, researchers have discovered numerous side-effects of antibiotics that can cause great damage to the organism. One of the consequences of the large-scale use of antibiotics is the emergence of pathogens resistant to them.
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