72 Penicillin & Pneumonia

introduction

In today’s world, we view pneumonia as a common and easily fought infection. In most cases, antibiotics are prescribed and the infection is gone in a matter of days. But how bad would this common infection be if we didn’t have the antibiotics we rely on and often take advantage of? Before Penicillin was discovered as a cure for Pneumonia, this disease was one of the most common causes of death. The discovery and mass production of Penicillin has allowed the medical field to defeat the once deadly disease of Pneumonia, which lead to a decreased mortality rate for people who had been affected by the disease.

Pneumonia and it’s Effect on Society 

Symptoms of pneumonia have been found in history dating all the way back to 460 BC. However, it wasn’t until the late 1880’s that the exact cause was found. Pneumonia is an infection that can be caused by viruses or bacteria. Viral Pneumonia typically goes away on its own, however bacterial Pneumonia must be treated.  The most common bacterium responsible for causing pneumonia is Streptococcuspneumoniae (S pneumoniae), which was first isolated by Pasteur and Sternberg in 1880. Pneumonia, a bacterial infection in the lungs, causes air sacs in the lungs to inflate and fill with fluid and pus. People who are infected with pneumonia experience shortness of breath, coughing, yellow mucus, fever, sweating and chills, rapid and shallow breath, sharp chest pain, low energy, loss of appetite, and nausea and vomiting Today, bacterial pneumonia is treated with antibiotics, however, these medical solutions have not always available (Pneumonia Symptoms and Diagnosis, 2019).

Pneumonia was coined as the “captain of the men of death” in the early 20thcentury when the fatality rate had increased to 30-40% (Osler, 1912, p. 75), Adam J., and Jeffrey N. Weiser). One of the most prominent major death events involving pneumonia was during the dust bowl that destroyed the southern plains in 1931-1939. High winds from the dust storms caused large amounts of dirt to pollute the air. The inhalation of dust lead to type of pneumonia that became commonly known as “dust pneumonia”. With no cure for pneumonia, over 7,000 people fell victim to the infectious disease (“When Deadly Dirt Devastated the Southern Plains.” , 2011). Succeeding this increase in fatality was a race to find the cure. Before penicillin was discovered, scientists were finding very little success in creating a cure. The infection was treated with several different processes including sulfonamide therapy and serum therapy. However, these treatments were expensive and showed very little promise in curing those inflicted with pneumonia (“When Deadly Dirt Devastated the Southern Plains.” , 2011).

Not only did Pneumonia have a massive impact on general society, it also greatly affected the war. Before the discovery of penicillin, one of the major causes of death in soldiers were caused by infections from wounds. This accounted for about 18% of deaths. After Penicillin was mass distributed to wounded soldiers during World War II, the death due to bacterial infections fell to less than 1% (Cressy, 1955).

Video detailing medicine used in WWII.

Royal College of Physicians of Edinburgh. (2018, June 26). Medicine in World War Two: Wounds, Shellshock and Penicillin. 

The Discovery and Mass production of Penicillin 

Before the discovery of antibiotics, common infections such as pneumonia, tuberculosis and blood poisoning had no cure and were extremely deadly. Antibiotics are antimicrobial agents created by microorganisms that are designed to target the growth and replication of a bacterium.

Antibiotics work by either killing or inhibiting the growth of the target bacterium. Some antibiotics can be specialized and target specific bacterium, while others are broad-spectrum and effect a wide range of bacteria, including ones that may be important in our bodies (Markel, 2013). In 1928 a scientist, Dr. Alexander Fleming stumbled upon the accidental discovery of Penicillin, the first antibiotic. At the time, Dr. Fleming was working in the lab studying the influenza virus. Fleming, who was known as being careless in the lab, left for a two week vacation while he was working with streptococcus in the lab. When he returned, he noticed his dishes that had been inoculated with streptococcus before he left, were covered with colonies. He also noticed a mold was growing on the plate and the area around the mold was clear of any colonies. He realized that the mold had secreted something that inhibited the growth of the bacteria streptococcus (Markel, 2013). “The staphylococcus colonies became transparent and were obviously undergoing lysis … the broth in which the mold had been grown at room temperature for one to two weeks had acquired marked inhibitory, bactericidal and bacteriolytic properties to many of the more common pathogenic bacteria.” (Fleming, A. 1929).Fleming called his discovery “mold juice”. He later found out that the “mold juice” that was secreted was a strand of Penicillin notatum (Markel, 2013). After performing more experiments, Fleming found that the “mold juice” killed or inhibited the growth of many harmful bacteria including streptococcus and meningococcus, the bacteria that causes meningitis. Fleming, along with his assistants, attempted to isolate the “mold juice” but were unsuccessful and ultimately published his findings in 1929 (Markel, 2013).

Ten years later in 1939, a team at Oxford University, including Howard Florey, Ernst Chain and their colleagues, set out to successfully isolate penicillin. In order to successfully isolate and test penicillin, their experiments required them to produce hundreds of liters of the mold filtrate each week. They extracted the penicillin bacteria from the mold filtrate, removed impurities from the Penicillin and then performed experiments. They found that bacteria were successful in treating various infections on mice and eventually they gave the first injection to a man named Albert Alexander (Kalvaitis, 2008). Alexander, who suffered from an infection due to a cut on his face, eventually died when the supplies of penicillin ran out. After several other patients were treated with Penicillin with positive results, Penicillin’s potential was finally realized (Kalvaitis, 2008).

When Foley and his fellow scientists at Oxford University first began experimenting with Penicillin in 1939, World War II was in full effect. While this made research more difficult for the scientists, it also allowed Penicillin to be mass distributed in an exceptionally fast manner. Once the magnitude of Penicillin’s ability to fights infections was realized, plans were immediately put into place to mass produce the drug and send it to the soldiers injured from war. However, this task proved difficult in Britain, so in 1941, Foley traveled to the United States to work with scientists in Peoria, Illinois on a means of mass production (Sowards, 2015). These scientists eventually found a strand of Penicillin that yielded a much larger amount of the bacteria than the species discovered by Fleming. After this discovery, mass production was able to begin and within the first six months of 1942, 400 million units of penicillin were created (Sowards, 2015).

Video of how Penicillin was mass produced and distributed during WWII.

 (n.d.). Retrieved November 12, 2019

Women Revolutionizing Penicillin 

It is as if there is a notion that males are the leaders in science and discovery of new inventions, yet this should not be. This does have truth to it, as seen with this chapter that Dr. Alexander Fleming discovered penicillin; and how Howard Florey, Ernest Chain, and their colleagues set out to successfully isolate penicillin. As mentioned previously, Florey, Chain, and others first began experimenting in 1939, then in 1942 discovered how penicillin could be mass-produced and distributed to fighting soldiers injured and unwell during the eruption and chaos of World War II. However, there are implications in that Howard Florey and his team’s discoveries led solely to the understanding of how penicillin could be mass-produced. Dorothy Crowfoot Hodgkin and Gladys Lounsbury Hobby were the”women” behind the curtain who allowed Florey and his team to manufacture dozens of thousands of this medication.

Dorothy Crowfoot Hodgkin was fascinated by minerals and geometric shapes of crystalline structures beginning at a young age. She carried this passion into her career and ultimately made a breakthrough on the antibiotic discovered by Sir Alexander Fleming, penicillin. Hodgkin obtained her chemistry degree at Oxford University and then acquired her Ph.D. at Cambridge University. Proceeding her education in 1934, she returned to Oxford to begin her scientific career. Then in 1945, she and her team of researchers were able to determine the structure of penicillin using a technique called X-ray crystallography. X-ray crystallography simply consists of making an X-ray image of a mineral. After an X-ray image of penicillin was taken and a characteristic pattern appeared, Hodgkin was able to perform a detailed mathematical analysis of the patterns and then deduce the crystalline structure of penicillin. From this scientific research and discovery, knowing the three-dimensional molecular structure of penicillin allowed researchers to optimize the manufacturing of this drug and improve upon it (Doménech, 2019).

Taking the scientific discovery made by Dorothy Crowfoot Hodgkin, Gladys Lounsbury Hobby was able to build upon it. Hobby was undoubtedly an influential person who was part of an extensive network of individuals that brought penicillin from the laboratory to the clinic. As part of a research team at the Columbia Medical School, from 1934 to 1943, Hobby labored away tirelessly trying to perfect penicillin, specifically for the use of curing several infectious diseases (Gale, 2000). In addition to her research at Columbia, in the early 1940s, Hobby and a team of other scientists researched and explored efforts to discover an approach to manufacture substantial amounts of penicillin. After many trials and errors, Hobby and her team eventually learned how to mass-produce safe penicillin in clinics. The plan was then implemented and successful (Saxon, 1993).

If it were not for Dorothy Crowfoot Hodgkin or Gladys Lounsbury Hobby, the drug penicillin would not have advanced in the way it did and influenced other drugs created. The research done by Hodgkins disbelieved the norms of what the penicillin structure was thought to be at that time. She proved that penicillin’s molecular structure contains a beta-lactam ring. This ring is influential since it is a fundamental component of several other families of pharmaceutical drugs (Doménech, 2019). Since discovering this fact, it promoted the development of new medicines. The exploration and analysis were done by Gladys Hobby, allowing for penicillin to be manufactured in substantial quantities greatly aided the wounded soldiers fighting in the war (Gale, 2000). This discovery was at its peak since World War II was occurring and many soldiers were injured. Through Hobby and her team’s efforts, finding a way to mass-produce penicillin safely, manufacturers were able to accomplish this, and clinicians could distribute the drugs to wounded soldiers. These endeavors were indispensable and saved the lives of many soldiers during this time. 

Penicillin on Pneumonia

The effects of penicillin on Pneumonia were astounding. Once penicillin was discovered, the fear of pneumonia in the medical world faded away. In the late 1800’s, before discovering penicillin, Gram was performing experiments on S. pneumoniae, the bacteria that causes Pneumonia, and established a staining technique, known as Gram staining. Gram staining classifies bacterium into two categories, Gram positive and Gram negative. The two different cell types stain differently based on the structure of their cell wall. When working with S. pneumoniae, Gram found that it was a Gram positive bacterium. The cell walls of Gram positive bacteria are made up of 90% peptidoglycan, a rigid polysaccharide. Peptidoglycan consists of two sugar molecules, N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM), that are connected via amino acids to form the back layer of the molecule. The layers of NAM and NAG are connected by peptide bonds between the amino acids. When gram positive cells are growing, the cell punches holes in their cell wall to expand and allow for a newly constructed piece to be inserted and the amino acids in peptidoglycan in the cell walls will link up. Penicillin works by preventing the amino acids in the peptidoglycan to link up. The new pieces of the cell wall won’t connect and will fall out, leaving large holes in the cell wall and the cell will eventually die (Society, Microbiology). This is how penicillin words to effectively kill the bacteria that cause pneumonia, and the inflicted patient will begin to feel better in a few days (Pneumonia Symptoms and Diagnosis, 2019).

Pneumonia and individuals ALLERGIC to the cure

This chapter centers its attention on how penicillin was discovered and how it is crucial for treating pneumonia. As mentioned throughout, penicillin is the most prevalent antibiotic used to heal pneumonia; however, some individuals are allergic to penicillin, so how are these individuals cured? There are alternative antibiotics that do not fall under the penicillin family that is used to fight pneumonia, such as carbapenems and fluoroquinolones.

The penicillin allergy is the body’s immune system reacting to the antibiotic drug. Usually, the body will respond through hives, rashes, and itching. On the other end of the spectrum, severe reactions include anaphylaxis, which is a life-threatening condition that affects various systems within the body (Mayo Clinic Staff, 2021).

It is doubtful that individuals allergic to the penicillin antibiotic who have contracted pneumonia also would like to agonize with the signs and symptoms of the penicillin allergy, so the overwhelming question to ask is, “How are individuals who are allergic to penicillin treated for pneumonia?”

Thankfully because of scientific research and advancements in technology, researchers, scientists, and a handful of other individuals have generated alternative antibiotics that can treat pneumonia and that are not categorized as penicillin or fall into penicillin’s family of antibiotics. Such alternative antibiotic medicines include carbapenems and fluoroquinolones. These two alternative antibiotics are unrelated to penicillins and are safe to use for treating pneumonia in penicillin allergic patients who’ve contracted this illness (Mancini, et. al, 2021).

If carbapenems and/or fluoroquinolones were not invented then penicillin allergic individuals who have contracted pneumonia would still be facing adversity and even possibly death. Due to scientific research and technology that can produce these alternative antibiotics, a portion of society is greatly helped and have the same opportunities as those individuals who are able to ingest penicillin without any side effects.

Conclusion

Since the discovery of penicillin, scientists have not directly been concerned with pneumonia, but rather, prevention through vaccines and the treatment of more deadly infections caused by pneumonia such as sepsis and septic shock. Since the discovery of Penicillin, the medical field has been able to defeat a once devastating disease, pneumonia. This has lead to a decrease in mortality rate for people affected by the disease.

References

Cressy, Norman L.  (1955) “The Pneumonias.” Chapter 12 in United States. Army Medical Department. Historical Unit, & United States. Surgeon-General’s Office. (Vol. 4). Department of Defense, Department of the Army, Office of the Surgeon General. https://history.amedd.army.mil/booksdocs/wwii/PM4/CH12.Pneumonia.htm.

Doménech, F. (2019, May 16). Dorothy Hodgkin, the Woman who saw Penicillin. OpenMind. Retrieved December 2, 2021, from https://www.bbvaopenmind.com/en/science/leading-figures/dorothy-hodgkin-the-woman-who-saw-penicillin/.

Fleming, A. (1929). ON THE ANTIBACTERIAL ACTION OF CULTURES OF A PENICILLIUM, WITH SPECIAL REFERENCE TO THEIR USE IN THE ISOLATION OF B. INFLUENZA. LaboratoriesoftheInoculationDepartment, St Mary’sHospital, London., 226–230. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2048009/pdf/brjexppathol00255-0037.pdf

Gladys Hobby. (2000). In Notable Women Scientists. Gale. https://link.gale.com/apps/doc/K1668000180/UHIC?u=clemsonu_main&sid=bookmark-UHIC&xid=23580ea7

Kalvaitis, K. (2008, August) “Penicillin: An Accidental Discovery Changed the Course of Medicine.” Endocrine Today on Healio. https://www.healio.com/endocrinology/news/print/endocrine-today/{15afd2a1-2084-4ca6-a4e6-7185f5c4cfb0}/penicillin-an-accidental-discovery-changed-the-course-of-medicine.

Mancini, C. M., Wimmer, M., Schulz, L. T., Zhang, Y., Fu, X., Postelnick, M., Bhowmick, T., Lee, F., & Blumenthal, K. G. (2021). Association of Penicillin or cephalosporin allergy documentation and antibiotic use in hospitalized patients with pneumonia. The Journal of Allergy and Clinical Immunology: In Practice, 9(8). https://doi.org/10.1016/j.jaip.2021.04.071

Markel, H. (2013, September 27) The Real Story behind Penicillin. Public Broadcasting Service (PBS). https://www.pbs.org/newshour/health/the-real-story-behind-the-worlds-first-antibiotic.

Mayo Clinic Staff. (2021, September 29). Penicillin allergy. Mayo Clinic. Retrieved December 2, 2021, from https://www.mayoclinic.org/diseases-conditions/penicillin-allergy/symptoms-causes/syc-20376222.

Osler, W. (1912). The principles and practice of medicine. D. Appleton and Company. https://books.google.com/books?hl=en&lr=&id=cJ5DlgAIkI4C&oi=fnd&pg=PR24&ots=UtIaPqPxvs&sig=Ba4tb6YuqPSEF6NtErqlFjaFJpU

“Pneumonia Symptoms and Diagnosis.” (2019, September 30). Retrieved from https://www.lung.org/lung-health-and-diseases/lung-disease-lookup/pneumonia/symptoms-and-diagnosis.html.

Sowards, W. (2015, August 20). Pneumonia: History and Prevention of the ‘Winter Fever’, Passport Health, 20 Aug. 2015, https://www.passporthealthusa.com/2015/08/pneumonia-history-and-prevention-of-the-winter-fever/.

Saxon, W. (1993, July 9). Gladys Hobby, 82, Pioneer in Bringing Penicillin to Public. The New York Times. Retrieved December 2, 2021, from https://www.nytimes.com/1993/07/09/obituaries/gladys-hobby-82-pioneer-in-bringing-penicillin-to-public.html.

“When Deadly Dirt Devastated the Southern Plains.” (2011, May 12) The Denver Post, https://www.denverpost.com/2011/05/12/when-deadly-dirt-devastated-the-southern-plains/.

Figures & Videos:

Medicine in World War Two: Wounds, Shellshock and Penicillin. (2018, June 26). Royal College of Physicians of Edinburgh.   Retrieved from https://www.youtube.com/watch?v=pMhfnMhLly4

“First page of Alexander Fleming’s paper on penicillin” by Welcome Images is licensed under CC BY 4.0

“How Penicillin was Mass Produced in WWII” (n.d.). Retrieved November 12, 2019, from https://www.youtube.com/watch?v=UJ6KTKVxkcM&feature=youtu.be.