September 28th marks the anniversary of a discovery that has saved 80 million lives. In 1928, the life expectancy in the US and Europe was around 55 years. Then, one fateful day in September, a 47-year-old bacteriologist named Alexander Fleming left for a vacation without tidying up his work bench. When he returned, he found a blue green mold had started to grow in one of his petri dishes also growing the staphylococcus bacteria. He could have easily tossed the moldy dish away, but instead he took a closer look and noticed a ring around the location of the mold where the bacteria wouldn’t grow. This simple act of curiosity ended up revolutionizing modern medicine. That mold was a strain of penicillium, and his discovery eventually led to the development of antibiotics, the reason you and I don’t have to fear death from simple scrapes and bruises. Before Fleming, as many as 80% of infections were fatal. There are hints that the ancient Egyptians were aware of the potential for antibiotics as they were known to put moldy bread on infected wounds. However, the world was truly changed by Fleming’s discovery. Fleming has stated that, “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.” So how did this growth of mold lead to the antibiotics we take today? How do antibiotics work? And what can we do about the rise of antibiotic resistance? The First Antibiotics Antibiotics, like the penicillin drug derived from the penicillium mold, are actually compounds produced by bacteria themselves with the intention of killing off or otherwise inhibiting other competing species. After Dr. Fleming of St Mary’s Hospital in London noted the ability of the penicillium mold to fight the staphylococcus bacteria and published his findings, the task of harnessing that power was picked up by Dr Howard Florey, Dr. Norman Heatley, and Dr. Ernst Chain of Oxford. These three gentlemen conducted extensive research to find and extract the active ingredient from the fluid in the mold culture, purify it, and then test just what infections it could fight. They quickly realized that their biggest problem would be volume. 2,000 liters of “mold juice” was necessary to make enough penicillin to treat just one person with sepsis. In 1941, Albert Alexander, an Oxford constable in his 40s, scratched his face while pruning his rose bushes. The scrape became infected with streptococci and staphylococci which quickly spread to his eyes, face, and lungs. Doctors treated him with the experimental penicillin drug out of Oxford, and Alexander made a quick but brief recovery until the supply of the drug ran out. He died a few days later. The researchers grew mold in everything they could find (bedpans, milk churns, bath tubs) but it just wasn’t enough. By 1941, the war had made resources tight in Great Britain, so the group traveled to the US where they teamed up with scientists at the Northern Regional Research Laboratory (NRRL) in Peoria, Illinois. There they tested a variety of ways to increase the yield of the medicine from their cultures, including different fermentation liquids, using submerged versus surface cultures, and later even ultraviolet radiation. The lab always had a surplus of corn-steep liquor, a byproduct of the corn milling process, and they discovered using that in the fermentation process increased the yield. Mary Hunt, a lab technician, further aided in identifying a more productive strain of penicillium by bringing in a cantaloupe with a peculiar gold mold she’d found in a Peoria market. The unique structure of the molecule was also later determined by X-ray crystallography thanks to the pioneering work of Dorothy Crowfoot Hodgkin. As the drug’s potential became clearer, eventually the war became less of a hindrance and more of an inspiration for the development of penicillin. In World War I, the death rate from bacterial pneumonia was 18%, but that fraction fell to < 1% in World War II, thanks to antibiotics. By 1945, production had increased to 10,000 gallon tanks producing a yield of 80-90%. How Do Antibiotics Work? In March 1942, Anne Miller became the first civilian whose life was saved by penicillin. She had contracted blood poisoning after suffering a miscarriage in a hospital in New Haven, CT. Penicillin works by effectively causing bacterial cell walls to burst. More specifically, peptidoglycan, a lattice-like structure made from amino sugars and peptides that surrounds the plasma membrane in bacteria acts to fortify its cell walls and keep fluid out. To multiply, small holes need to open up in the cell walls which are quickly filled in with new peptidoglycans but penicillin prevents this process, known as transpeptidation. Instead, water enters the cell, and the cell explodes. Penicillin has proven successful against many bacterial infections including chlamydia, strep throat, listeria, staph infections, a type of gangrene, gastritis, lyme disease, typhoid, pneumonia, gonorrhea … the list goes on. Antibiotic Resistance According to the CDC, each year at least 2 million people are infected with bacteria that are antibiotic resistant. Unfortunately, this story does not yet have a happy ending. In 1945, when Fleming was awarded the Nobel Prize in Physiology or Medicine along with Florey and Chain, he warned that the overuse of antibiotics could lead to bacterial resistance. According to the CDC, each year at least 2 million people are infected with bacteria that are antibiotic resistant and 23,000 people die annually from bacterial infections. The evolution of antibiotic-resistant bacteria, so-called super bugs, will occur naturally over time, but, through misuse of antibiotics, we are accelerating the process before we can develop new tools in the bacterial fight. Without antibiotics, we could return to an era when a small scratch from a rose could be fatal. A world without antibiotics also threatens our ability to conduct any procedures that require that we make ourselves vulnerable to infection, including organ transplants, cancer chemotherapy, diabetes management, and any major surgery, like C-sections. Drug resistance is already proving a challenge in fights against TB, HIV, gonorrhea, and malaria. The World Health Assembly has adopted a global action plan to address antimicrobial resistance and officials met to discuss the topic this month at the United Nations General Assembly. The World Health Organization further provides a list of recommendations for how you and I can play a role in the fight against super bugs as members of the general public: Prevent infections by regularly washing hands, practice good food hygiene, avoid close contact with sick people, and keep vaccinations up to date Only use antibiotics when prescribed by a certified health professional Always take the full prescription and never use left over antibiotics Never share antibiotics with others Source
