All About Penicillin
Image is courtesy of Medical News Today.
Infectious diseases were a major cause of morbidity and mortality before the beginning of the twentieth century, according to an Annals of Ibadan Postgraduate Medicine article. Even in the industrialized world, the average life expectancy at birth was 47 years. Cholera, pneumonia, smallpox, typhoid fever, plague, tuberculosis, and other infectious diseases were common. A simple scratch or blister could result in infection and death. Penicillin, which was accidentally discovered, became an antibiotic that changed the world, heralding the start of the antibiotic era. Medical News Today states that penicillins are a group of antibiotics that fight a wide spectrum of bacteria, and were the first antibiotic that doctors used. Hailed as a miracle drug, many bacterial infections could be treated quickly, which could have otherwise killed millions of people.
The Discovery of Penicillin
Thanks to Alexander Fleming, a professor of bacteriology in London, penicillin was discovered in 1928, according to a Live Science article. When Fleming returned from vacation, he started cleaning up his messy lab and discovered that an uncovered petri dish containing Staphylococcus bacteria had been contaminated with mold spores as stated in a Singapore Med J article. He noticed that the bacteria around the mold colonies were dying. He then extracted an active agent from the mold, and discovered it was a Penicillium species, more specifically Penicillium notatum, which inhibited the normal growth of Gram-positive bacteria, including those that cause scarlet fever, gonorrhea, pneumonia, meningitis and diphtheria. His conclusion was that the bacteria had not been destroyed by the mold itself, but by the “juice” it produced and named the “mold juice” penicillin. “When I woke up just after dawn on September 28, 1928, I certainly didn't plan to revolutionize all medicine by discovering the world's first antibiotic, or bacteria killer. But I guess that was exactly what I did,” Fleming later wrote about his findings.
Image is courtesy of TIME.
Despite the fact that Fleming published his discovery of penicillin in the British Journal of Experimental Pathology in 1929, his work was first met with skepticism by the scientific world. Furthermore, Fleming struggled to isolate the “mould juice” in massive quantities. However, it wasn’t until 1940 that two scientists, Howard Florey and Ernst Chain, took interest in penicillin, just as Fleming was contemplating retirement. Before the first trial with a human, they and their colleagues were able to purify penicillin and assess its efficacy on animals at the Sir William Dunn School of Pathology at Oxford University. According to the American Chemical Society, Albert Alexander became the first person to use the Oxford penicillin on February 12, 1941. While pruning roses, he scratched the side of his mouth, developing a life-threatening infection with huge abscesses affecting his face, eyes, and lungs. He was given penicillin, and in just a few days, he made a spectacular recovery. Unfortunately, there was not enough drug supply, so he died before being completely healed.
A year later, they eventually had enough penicillin to be able to treat the next patient, Anne Miller, at New Haven Hospital in Connecticut successfully. She had a miscarriage and developed an infection, which resulted in blood poisoning. According to an article published in The Washington Post, doctors attempted every treatment possible during her stay, from sulfa medications to blood transfusion, while her temperature reached over 106 degrees at times. Miller’s infection was cured when she was given a tablespoon of penicillin, which was half the amount of antibiotic available in the United States in 1942. Because it was terribly difficult to extract the mold due to its tendency to dissolve during the extraction process, doctors had to collect her urine and extract the remaining penicillin from it at around 70% potency, and re-inject it to give her the complete treatment.
Penicillin was considerably more successful and safer in combating bacteria in animals than sulfa drugs, which were the treatment for infections at the time, because they had terrible side effects. The drug was later mass-produced in the United States and Britain in time for usage during World War Ⅱ. Infection, rather than battle injuries, has been the leading cause of death in wars throughout history. Eric Lax, author of “The Mold in Dr. Florey’s Coat,” said, “... of the 10 million soldiers killed in World War Ⅰ, about half died not from bombs or shrapnel or bullets or gas but rather from untreatable infections from often relatively minor wounds and injuries.” Amazingly, penicillin drastically lowered the death rate from bacterial pneumonia from 18% to 1%, according to Dr. Howard Markel's column for PBS NewsHour.
Function and Resistance
Medical News Today states that penicillin-class drugs function by breaking bacterial cell walls indirectly. They accomplish this by directly acting on peptidoglycans, which are structurally important in bacterial cells. Peptidoglycans form a mesh-like structure surrounding the plasma membrane of bacterial cells, increasing cell wall strength and preventing external fluids and particles from entering the cell. As a bacterium multiplies, tiny holes open up in its cell walls during cell division. These gaps are subsequently filled with newly-produced peptidoglycans, helping to rebuild the walls. Penicillins work by blocking the protein struts that connect peptidoglycans together. As a result, the bacteria is unable to close the holes in its cell walls. Since the water concentration of surrounding fluid is higher than inside the bacterium, water flows through the holes into the cell, causing the bacterium to burst. Different types of penicillin are used for different infections.
Bacteria have been on earth for billions of years, and they have withstood extreme conditions, becoming extremely adaptable and developing resistance to penicillins. In general, there are three ways for bacteria to gain penicillin resistance:
Penicillinase: Bacteria can create penicillinase, an enzyme that degrades penicillins. In a process known as conjugation, this ability may spread across the bacterial population via a tiny ring of DNA. Individual organisms transfer this new genetic information between them in this bacterial equivalent of asexual reproduction.
Altered bacterial structure: Some bacteria may modify the format of penicillin-binding proteins in their peptidoglycan wall, preventing penicillins from binding to it.
Penicillin removal: Other bacteria can develop mechanisms that allow them to export penicillin. Efflux pumps are used by the bacteria to discharge substances from the cell. Some of these pumps can be repurposed to help the cell get rid of penicillins.
An Annals of Ibadan Postgraduate Medicine article states that the antibiotic era began with the discovery of penicillin. Many new antibiotics were discovered during this era, and the period between the 1950s and 1970s was dubbed the golden era of novel antibiotic discovery. Since then, no new antibiotic classes have been identified, and the approach to discovering new medicines after that was to modify current antibiotics. This era revolutionized the treatment of infectious diseases, with lots of success in the developing world. For instance, in the United States, the leading cause of death has shifted from communicable diseases to non-communicable diseases (cardiovascular disease, cancer, and stroke), the average life expectancy at birth has increased to 78.8 years, and the older population has increased from 4% to 13% of the total US population. Ultimately, the accidental discovery of penicillin helped paved the way for new antibiotics, and it was truly one of the most significant scientific discoveries in history.
Article Author: Tanya Kor
Article Editors: Victoria Huang, Sherilyn Wen