Antibiotic | Research & Encyclopedia Articles

Antibiotic

Antibiotics are drugs such as penicillin, streptomycin, and erythromycin that are administered orally or by injection to rid the body of harmful bacteria that cause disease. Some microscopic bacteria that enter the human body through an opening or a wound quickly find abundant food and reproduce in great numbers, releasing toxins as they grow or when they die. The toxins can destroy human cells or interfere with cell function, causing diseases like pneumonia or tuberculosis. Antibiotic drugs are derived from natural compounds that are antagonistic or harmful to bacteria. In nature, some organisms such as fungi and certain bacteria have evolved ways of defending themselves against harmful bacteria by producing their own toxins that destroy bacterial cells. Molds, such as those in the Penicillium family or Streptomyces griseus, have become a source of drugs for human use. These anti -(against) biotic (life) compounds usually work by either damaging the bacterial cell membrane or interfering with an important life function of bacteria.

The story of how antibiotic drugs came to be as accessible as the nearest pharmacy has a long history. The phenomenon of bacterial antagonism as it is known was observed as long ago as 1871, when the surgeon Joseph Lister first made note of it. In 1877, the French scientist Louis Pasteur, working with Jules François Jobert, discovered that when there were more common germs present first, something inhibited the growth of bacteria that caused anthrax, a fatal disease in farm animals. In the 1880s German researchers found that rabbits gained protection against anthrax if they were administered bacteria from the streptococcus family. But research into bacterial antagonism as a cure for anthrax did not proceed because Pasteur had already developed a successful anthrax vaccine to prevent the disease.

A decade later, an Italian scientist, Dr. B. Gosio was investigating cases of pellagra, thought at the time to be caused by infected corn, but now known to be a deficiency disease. He studied microorganisms that attack corn, several of which belonged to the penicillium group. He cultured penicillium mold and found that the culture stopped the growth of anthrax germs in a test tube. However, Gosio did not have the resources to continue with this line of research. Several British scientists took up where Gosio had left off, producing a substance they called penicillic acid, which killed some bacteria--but it also killed experimental mice.

In 1928 Alexander Fleming, a Scottish doctor, made an important discovery that eventually led to the development of penicillin. In his crowded hospital laboratory, Fleming was examining the colorful patches of bacteria in each covered dish and noticed that a green mold had gotten into one dish. Fleming had seen molds growing in a laboratory dish before, knowing that mold spores travel through the air and can easily land in a dish when left uncovered. Fleming noticed that the bacteria closest to the mold seemed to have disappeared or dissolved. He looked carefully at the mold with a trained eye and even photographed it. Fleming's colleague identified it as Penicillium notatum. Curious about how the bacteria in this dish were killed, Fleming used the greenish "fluff" on the dish to make a mixture that his laboratory workers called "mold juice." Fleming named the juice penicillin and gave it to some laboratory mice. He found that the penicillin killed only the bacteria and not the cells in the mice, making Fleming's "mold juice" safer than any other known bacteria-killing substances. It was an incredible discovery. If this mold mixture could be made into a drug then someone with an infection could be cured of disease without harm.

Using penicillin as a drug sounded like a great idea, but Fleming found that when he grew mold in a dish it would kill bacteria for a while, then would lose its potency. He found also that the mold juice would not dissolve in common solutions, making it difficult to use. So although Fleming discovered penicillin and knew the value of it, he could not produce anything useful to doctors. He continued to use the mold in his laboratory all the time to keep unwanted bacteria out of his culture dishes, and in 1929 Fleming wrote a report about his discovery. Other scientists read it, but it did not generate much excitement at the time.

Several years later one of Fleming's own students, Dr. C. G. Paine, cured several children of eye infections using a mixture like Fleming's mold juice. Dr. Paine found the mixture very hard to work with and very few people heard about how Fleming's penicillin could cure disease. In the mid-1930s Grieg Smith, an Australian bacteriologist, discovered that a group of soil organisms showed antibacterial activity. His paper was read with interest by scientists in the United States, steering research in a new direction.

In 1939 René Jules Dubos, a French-American microbiologist

whose research interest was soil microbiology, made another important discovery. Working at the Rockefeller Institute for Medical Research in New York, Dubos isolated an antibacterial substance in the bacterium Bacillus brevis. He named the substance tyrothricin. With chemical analysis, he found tyrothricin to be a mixture of proteins consisting of relatively short amino acid chains. The compounds themselves did not prove to be effective agents against bacteria. However, Dubos's reports helped to revive interest in Fleming's earlier work on penicillin.

In 1939 Dubos's teacher at Rutgers University in New Jersey, Dr. Selman Abraham Waksman, began looking closely at the antibacterial properties of soil organisms. Waksman, also a soil microbiologist, had a large collection of streptomycetes fungi at his disposal at his Rutgers laboratory. He isolated antibacterial agents from the streptomycetes but found them all to be toxic to human cells. It was Waksman who coined the term antibiotic to describe the compound that would be harmful to bacteria without being toxic to human cells.

In 1940, two scientists, Howard Florey (1898-1968), a professor of pathology originally from Australia, and Ernst Chain (1906-1979), a German biochemist who had fled Hitler's Germany, began to experiment with penicillin at England's Oxford University. After many experiments, they found a way to get penicillin in its pure form and began toxicity tests on mice. Finding that the drug could be tolerated by mice with few side effects, they began testing it on humans. By this time World War II had begun and the wounded were crowding into hospital, and Florey and Chain's team of workers rushed to finds ways of developing a useful form of penicillin to fight bacterial infection.

By 1942 penicillin was being made in large amounts by British companies. Many soldiers were saved from the infections that developed after they were wounded in battle. People called penicillin the new " wonder drug" for the thousands of cures it made possible, usurping the title for the sulfonamide drugs that had been developed a decade earlier. Penicillin cut the death rate from bacterial pneumonia from 60 to 80 percent down to 1 to 5 percent. Fleming received the 1945 Nobel Prize in Medicine as a result of the numerous uses found for penicillin.

Despite the effectiveness of penicillin, it was soon found that the drug worked only against Gram-positive bacteria. During the early 1940s Selman Waksman had been concentrating on Gram-negative bacteria. After numerous failures, Waksman succeeded in finding a nontoxic compound derived from Streptomycetes griseus mold which he named streptomycin. By January of 1944 he announced that this antibiotic could work against both Gram-positive and Gram-negative bacteria and was particularly effective against tuberculosis.

At the end of World War II, it became clear that the chemical structures of antibiotic compounds could be discovered. However, Ernst Chain, who figured prominently in the development of penicillin did not believe that the drug could ever be synthesized--that is, made in a factory without using molds or bacteria. But the great researcher was wrong. In post-war United States, drug companies hastily moved toward research in these areas. In fact, entering the race to produce antibiotics was the way many infant drug companies got their start, with researchers looking in nooks and crannies for all sorts of molds that could be potential drug sources. John Ehrlich and Quentin Bartz isolated another soil microbe in 1947, which the chemists of Parke Davis and Company found they could synthesize into an antibiotic. Thus the drug chloramphenicol, the first antibiotic that was antagonist toward a wide spectrum of bacteria, became the first of many synthetic drugs. Johnson and others developed bacitracin in 1945. Also in 1945, Benjamin Dugger, Y. Subbarow, and A. Dornbush discovered aureomycin, the first of the class of antibiotics known as tetracyclines. By 1948, Lederle Laboratories was producing aureomycin commercially. Working with Lechavalier, Waksman developed neomycin in 1949. A. C. Finlay and Gladys Lounsbury Hobby (who had also worked on penicillin) discovered another antibiotic, then marketed by Pfizer Drugs as terramycin in 1950. Some of these antibiotics, such as the cephalosporins and of course penicillin were developed from molds. Other antibiotics were developed from bacteria-- chloramphenicol, erythromycin, and the tetracyclines such as aureomycin.

This enormous array of life-saving drugs can be classified into groups based on their chemistry. Included in the penicillin group are penicillin G, the most commonly used penicillin, ampicillin and amoxicillin. Penicillins are used to treat pneumonia, meningitis, strep infections, and sexually transmitted diseases. The cephalosporins, such as cephalothin and cephalexin, share many of their uses with penicillin. The aminoglycosides group includes streptomycin, used chiefly for Gram-negative bacterial infections like tuberculosis, and neomycin, which at one time was used to fight systemic infections and has now been replaced in many instances by kanamycin and gentamicin. The tetracylines, including tetracycline and chlortetracycline are broad-spectrum antibiotics that often cause side effects and thus are used in fewer cases. The macrolides include erythromycin, a drug that fights gram-positive bacteria and is often administered to patients that are allergic to penicillin. Bacitracin, an antibiotic often used topically as an ointment, belongs to the polypeptide group that is generally effective against Gram-negative bacteria. Sulfonamide drugs, such as sulfadiazine, are synthetic drugs used primarily in urinary tract infections often in conjunction with penicillin.

Today's antibiotics may be given as an injection with a needle, or in a pill that can be swallowed by the patient. Each antibiotic does something that prevents bacterial cells from growing or dividing normally. For example, penicillin works by preventing the cell wall of each new bacterial cell from forming. The antibiotic compound mimics similar compounds in the bacterial cell wall. If the antibiotic becomes part of the bacterial cell wall, it leaves a gap and thus the bacterium no longer has its cell contents encased and protected. The contents spill out and the cell dies. That is why Fleming saw bacterial cells that looked like they had dissolved.

Tiny, ubiquitous, and invisible to the eye, bacteria are capable of reproducing every 20 minutes. An antibiotic may be very effective in halting the reproduction of bacteria at first. However, there are always some bacteria which are naturally resistant to the drug. Soon the resistant strain is able to catch up and reproduce in strong numbers. The first observation of antibiotic resistance was noticed as early as the 1940s. Since that time, some authorities believe that antibiotics are often overused when they should be used only when necessary. Today in many quarters, antibiotics are routinely administered to farm animals to keep them from getting sick. Unfortunately, the antibiotics are then in the meat that people eat. It is also possible that antibiotic resistant bacteria can be consumed when eating meat. Excessive use of antibiotics in humans as well as in animals speeds up the development of antibiotic resistant bacteria.

Antibiotics had an enormous impact on the safety and quality of human life in the twentieth century. In 1924 President Calvin Coolidge 's younger son had been playing tennis and got a blister. The blister became infected and the resulting blood poisoning killed him. At that time such small accidents could cause death. With a dose of an antibiotic he most probably would have been cured. Antibiotics do not work against viruses, only bacteria--and only some bacteria at that. Although antibiotics are not perfect, they changed forever how people are cured of disease and have lived up to their name, "wonder drugs."

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