1. From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug The Demon Under the Microscope By Thomas Hager

2. Courtesy Professor at the University of Oregon Raised in Portland Oregon Has earned masters degrees in medical microbiology, immunology, and journalism Started his career as a communications intern at the National Cancer Institute Has 100+ articles on medicine and science published in various journals including Reader’s Digest, the Wall Street Journal, and many others. Has given public talks before many meetings and associations such as the American Association for the Advancement of Science Thomas Hager

3. Gas Gangrene Often a problem in military medical facilities, forced surgeons to aggressively amputate parts of the body Bacteria such as Clostridium perfringensand Staphylococcus aureuscan cause this type of infection Eventually lead to blood infection in most cases, causing sepsis and death Puerperal Fever, “Childbed Fever” Most often afflicted new mothers and children Extreme stomach pain, a cough, and high fever were common New mothers experienced a hardening of the uterus, distended stomachs, occasionally black tongues, and excruciating pain from contact to the skin Problematic Diseases Before Antibiotics

4. More Diseases Caused by Bacteria Erysipelas, “St. Anthony’s Fire” Thought to be caused by miasma (corrupted air) or the devil Caused weakness, prodding pain in the back of the head, putrefaction of innards, swelled the eyes shut, painful red rashes, darkening of the blood, and extreme sensitivity of the skin (often referred to as “burning”) Pneumonia, meningitis, gonorrhea, cellulitis, septicemia, many others… All caused by bacteria, or can be caused by bacteria Simple disinfectants were not enough to contain bacterial diseases – the medical staff themselves could carry the bacteria from patient to patient

5. Before antibiotics were discovered, many wars were fought where military hospitals were deadlier than the battlefield In particularly swampy areas, disease spread quickly Wounds incurred on the battlefield often had shrapnel, pieces of clothing, and bacteria-laden soil embedded in them, making infection of the wound near certain Military surgeons tried washing wounds extensively with copious amounts of painful chemicals to wash away the bacteria, but because the residue was often buried deep within the wound this rarely worked to ward off infection Military Problems

6. Streptococcus was a highly variable and common bacteria Various strains of these bacteria caused a wide variety of diseases as they traveled through the body including… Erysipelas (St. Anthony’s Fire) Cellulitis (Infection of the subcutaneous tissue) Septicemia (Infection of the bloodstream) Meningitis (Infection of the spinal fluid) Puerperal Fever (“Childbed Fever”) Pneumonia Many more. “Strep was responsible, they said, for half of the white hairs on every physician’s head.” –Hager Staphylococcus would often cause similar diseases to Streptococcus, and in turn also be somewhat susceptible to some, but not all, Streptococcus treatments Streptococcus and Staphylococcus

7. Started out as a German medic; after seeing the horrors of gas gangrene on the battlefield, he was determined to find a way to protect patients from their invisible killers, bacteria. Worked in labs and universities throughout his lifetime such as the University of Greifswald, University of Münster, and finally the labs at the Bayer (part of the IG Farben conglomerate) Company in Germany Ended up receiving the Noble Prize in Medicine but was forced to decline because the Nazi rulers at the time forbade any German nationals from accepting the prize Was imprisoned for a week by the Gestapo because his letter declining the honor to the Nobel Prize Committee was “too friendly” Often known as the person who first discovered an antibiotic, even though the process would not have been possible without the large team at the Bayer research labs, in particular the chemists Joseph Klarer and Fritz Mietzch Gerhard Domagk

8. Because of its relations with the IG Farben conglomerate (a company infamous for its support of the Nazi ambition), Bayer Labs were under pressure to clear their employee roster of their prize Jewish scientists during the Nazi regime The Bayer branch in the United States today is the result of the original founding branch in Germany which expanded rapidly as a result of the sulfa discovery At the time of Domagk’s research, Bayer was well known for its best-selling drug, aspirin, which it is still known for today The Bayer Company

9. Based off of an azo dye commonly produced in Germany at the time, Domagk and his chemists discovered a red dye that could kill bacteria When taken by patients, the bright red drug would temporarily turn their skin red and marvelously cure many diseases, almost all of which were caused by Streptococcus The only notable side effects of Prontosil was that it could damage the kidneys and temporarily discolor the skin, which in Domagk’s time was thought to be relatively harmless considering the alternatives The Revelation of Prontosil

10. For whichever reason, Bayer’s German research labs avoided or missed the opportunity to test colorless (not based off of azo dye) Sulfa. Different theories exist about why the Germans did not continue on to discover colorless Sulfa themselves. A French researcher named Ernest Fourneau obtained samples of Prontosil and directed his lab towards testing variations of it. Within a few weeks, they discovered by chance that the dye was not the active part of the medicine – the sulfa was. Tension between the German scientists at Bayer and the French scientists at the Pasteur Institute (Fourneau’s place of study) rose because of the inability for the Germans to patent a drug as simple as sulfa for sales worldwide The French Discovery

11. Pure Sulfa was equally as effective as Prontosil but without the extraneous azo dye attached Prontosil worked because the azo dye was detached from the sulfa inside the body, allowing the sulfa to fight infection and causing the dye to be visible in the skin Such a simple compound was unpatentable, limiting the profits any one company could make from its discovery. Companies found ways around this by making novel Sulfa molecules which were different enough to be patentable The Germans may not have continued research towards Pure Sulfa for a number of reasons: It was not patentable and therefore not profitable German mentality respected the dye industry and did not consider that the answer was possible without it Understanding of bodily functions was perhaps not advanced enough to assume that the metabolite, sulfa, was the effective part of Prontosil rather than the dye Pure Sulfanilamide

12. Note the difference in structure between Prontosil and Pure Sulfa: Prontosil Pure Sulfa The bacteria Sulfa was effective against depended on a particular chemical referred to as PABA to stay healthy. PABA and Sulfa have similar structures; when sulfa binds to PABA binding sites, it blocks the bacterial enzymes from performing their jobs and the bacteria dies. Why Did Sulfa Work?

13. Sulfa also sparked a “revolution” in the drug regulation industry. Because Sulfa was not patented by any one company, companies all over the world began making their own “home remedies” containing the trusted Sulfa drug In American south, over 100 people died from kidney failure due to the sales of an Elixir Sulfa; a then-weak FDA is given the ability for the first time to remove a pharmaceutical from the market It turned out that the other ingredient in the Elixir, Diethylene glycol, was the toxic substance. For a short while after consumers were afraid to take Sulfa. In response to the Elixir Sulfa disaster, new laws were passed requiring drug companies to perform safety tests on their products. The FDA was also given more control over the safety of drugs. Eventually, sulfa became a prescription drug as a result of the tighter regulations on pharmaceuticals Elixir Sulfa and the FDA

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