Welcome back. In this session, let's talk about Antibiotics. Antibiotics are the foundation of modern medicine. Antibiotics are chemicals that kill or inhibit the growth of bacteria. Some antibiotics like penicillin are naturally occurring and some are synthetic. Antibiotics facilitated the development of modern medicine. So many of the treatments that we take for granted, like elective surgeries, cancer, chemotherapies, immunosuppressive therapies for auto immune diseases would simply become too risky to do because the chance for infection would become too high. Antibiotics have been used since ancient times. For example, human skeletal remains have been found to have traces of tetracycline. It's believed that these traces of tetracycline were from food such as beer, and that was used in ancient Egypt and Jordan. The red soils in Jordan had antibiotic-like properties and were used for skin infections. Actinomycete bacteria were found in the soils and they do indeed produce antibiotics. This lotus cup pictured here very likely contained beer that did have some antibiotic properties. Antibiotics were also used in ancient China. For example, ancient Chinese herbalist use the plant Artemisia annua for thousands of years for treatment of fever and other illnesses. In the 1970s, the drug qinghao was isolated from the plant and discovered to have potent anti-malarial activity. Here's a picture of the plant. Ancient Chinese medicine used other herbs which are being investigated for antimicrobial properties as well. In South America, antibiotics were used from the Cinchona trees to treat fevers. During the colonial period, the Spanish Countess of Cinchon was visiting Peru, came down with a fever and was treated with the bark from these trees. She was successfully treated and returned to Spain with samples from the bark. This bark yielded quinine, an important anti-malarial compound. Before the formal antibiotic era of the 20th century, Civil War medicine usually relied on amputation. In other words, cutting off the infection rather than treating it. Otherwise, the patient would die, and indeed more patients died from infections than they did from the injuries they incurred from the battles that they fought. The discovery of microbes causing disease was a major breakthrough in the history of medicine and public health. You heard Dr. Louis Pasteur discovering the germ theory of disease when he did a number of experiments using flasks filled with water. Dr. Robert Cook, a German physician, also discovered the germ theory of disease. He did this work independently of Dr. Pasteur, and he developed the Cook's postulates, which showed that the microorganism must be grown from the diseased animal, inserted or injected into another animal and proven to have cause the disease. Dr. Joseph Lister, a British surgeon, applied Louis Pasteur's Germ Theory of Disease to surgery. He insisted on conducting his surgery as sterilely as possible and would use carbolic acid and other compounds to clean surgical instruments and to clean wounds. His work led to a dramatic reduction in postoperative infections. For his work, he's considered the "Father of modern surgery." The treatment of syphilis was rather barbaric for many centuries. The strategy was to cause purging of bodily fluids. So patients were given mercury and other toxins. Dr. Ehrlich developed Salvarsan, the first modern antimicrobial. For his work, he won the Nobel Prize. Penicillin was discovered by Dr. Alexander Fleming in the late 1920s. He had gone off on vacation and came back and found one of his Petri dishes contaminated with a mold. But he discovered something very interesting about this mold. He discovered that the mold appeared to prevent or inhibit the growth of the bacteria surrounding it. He published an article describing his findings. But unfortunately, the penicillin was chemically unstable and he was unable to concentrate it and develop it into an antibiotic. Dr. Gerhard Domagk was a German bacteriologist who developed the sulfonamides. He treated his own daughter with the drug and saved her from having to lose her arm. Now, he was also awarded the Nobel Prize, but the Nazis forced him to give it up because of previous winners denouncing the regime. Sulfonamides was less effective and more toxic than penicillin, which is why they were generally not used quite as much. In order to develop penicillin as a drug, it had to be become more stable and be able to be concentrated for mass production. The key people for this work were Dr. Howard Florey, a pharmacologist, and Dr. Ernst Chain who was a biochemist. Both doctors, Flory and Chain, shared the Nobel Prize with Dr. Fleming for their discovery and subsequent development and production of penicillin as an antibiotic. They tested this new drug in mice and had amazing results, but they needed enough of the drug to use it as a treatment in humans. So the first person who was saved by penicillin was 33-year-old Anne Sheafe Miller, who was dying from a streptococcal infection in March 1942. She had been hospitalized for a month with high fevers, chills, slipping in and out of consciousness. All efforts, including surgeries, sulfa drugs, and other treatments failed to save her. A small quantity of penicillin was injected into her and yielded amazing results. Her successful treatment inspired the American Pharmaceutical Industry to ramp up production of penicillin. During World War II, countless servicemen and civilians were saved by penicillin. Ms. Miller lived a full life and died at the ripe old age of 90. Most of the modern antibiotics have been developed over the course of the 20th century. But the pipeline largely dried up in the late 1980s, early 1990s, and there's been a discovery void. However, the concern of rising antimicrobial resistance has resulted in many physicians and public health professionals to clamor for new antibiotics, and there have been some government efforts to inspire the pharmaceutical industry with financial incentives to produce new drugs. Antibiotics have a variety of mechanisms of action. They can inhibit cell wall synthesis, nucleic acid synthesis, or even protein synthesis. As I said in the previous slide, there's been a dwindling pipeline of new antibiotics. The development of these drugs requires investments in the hundreds of millions of dollars and require decades of research. Big pharmaceutical companies lost interest in developing antibiotics because they're usually used for a relatively short period of time and then the people are cured, in contrast to drugs for chronic diseases such as hypertension or diabetes, where people take these drugs usually for the rest of their lives. The low-hanging fruit of antibiotics have already been discovered. Most of the antibiotics come from soil bacteria, and many of those have been discovered, such as penicillin. Discovering new antibiotics is going to require a lot of research and development. In addition, there have been some regulatory hurdles that demand clinical study protocols, high standards proving safety and efficacy, and harmonizing across different governments, all making the development of new antibiotics a particularly challenging. However, as of 2018, according to the Pew Charitable Trusts, 42 new antibiotics have been in phase 1, 2, or 3 clinical trials. A clinical trial uses volunteers to test the safety and the efficacy of the drug. Phase 1 is tested in healthy volunteers to ensure safety. Phase 2 is tested in small groups of patients to ensure safety and effectiveness. Phase 3 is tested in large groups of patients, usually over a 1,000 people for additional information on safety, efficacy, benefits, and risks. Despite all this effort, though, fewer than one in four of the new antibiotics represent a true new class of drug or mechanism of action. Now, while antibiotics have been critical for modern medicine and have saved millions of lives from deadly infections, there have been challenges with them. Advances in science and technology have yielded surprising findings. We've discovered that the microbes that live in us and on us are important to our health and well-being as any organ, such as a heart or the kidneys. What happens with antibiotics is when they're broad spectrum, it means that they kill off the good and the bad bacteria. Ideally, you would have narrow spectrum antibiotics that would only affect the bacteria-causing disease. Dr. Martin Blaser, an infectious disease expert, wrote the book, The Missing Microbes. In his book, he found strong suggestions of a link between the use of antibiotics and the rise of chronic diseases including food allergies, asthma, celiac disease, obesity, and even certain cancers. So antibiotic use while it's been very important and saving lives, has also caused some serious problems that must be addressed. So the questions for this session then are, what is an antibiotic? Why are antibiotics essential for the practice of modern medicine? Give two examples of antibiotics used by ancient peoples. What was the typical treatment for infections during the pre-antibiotic era? Why is Joseph Lister considered the "Father of modern surgery?" Finally, what are some of the problems associated with antibiotic use? With that, I'd like to thank you for your time and attention.
