Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century Read Online Free PDF Page B

followed by studies in animals, first to determine what doses could be tolerated and then their effects against infections; finally clinical tests in humans would be considered. He quickly concentrated on azo dyes, compounds in which two nitrogen atoms were linked by a double bond. First developed in 1909, these dyes were very resistant to fading from washing and light since they bond so effectively with the proteins in wool and silk. Might these agents react as well with the proteins of a bacterial cell?
    Domagk was utterly single-minded in his approach. He soon focused his interest on a single bacterium, the streptococcus. Domagk was elegantly economical in his choice, aiming to treat a host of diseases due to one germ. Streptococcus was the cause of devastating infections that were both acutely life-threatening and chronically debilitating with frequent lethal effects. It was the cause of severe tonsillitis, infected glands in the neck, bacterial infections of the large joints (septic arthritis), puerperal fever, epidemics of scarlet fever, and rheumatic fever, which damaged heart valves and resulted in chronic kidney damage. Infection of the middle ear (otitis media) could result inpermanent deafness. Physicians also dreaded its skin manifestations when it spread into the tissues from an infected site: the scarlet wave of erysipelas (streptococcal cellulitis) and the sharp red lines indicating lymphatic spread. In such cases, amputation of an infected limb was often the only recourse. Most ominous was its tendency to cause blood poisoning, or streptococcal sepsis, which, along with its toxic products, could infect almost any site in the body. This invariably constituted a death warrant.
    In 1932 Domagk was looking at a new brick-red azo dye that had a sulfonamide group attached to its molecule. It was being used to dye leather and was commercially marketed as Prontosil Rubrum. Tests in the laboratory showed it to be virtually inactive against bacteria in a Petri dish. Undaunted, Domagk went on to test it against streptococcal infections in laboratory mice. 2 The results astonished him. Despite having been injected with a deadly species of streptococcus, every mouse inoculated with this new crystalline chemical was alive and frisky, running about in its cage. All those in the control group given that same bacterium but no red dye were dead.
    Domagk was an intense researcher who was driven by an independence of thought. His close-shaven head and pale blue eyes gave him the appearance of an unemotional man. But witnessing those results in the laboratory cages, five days before Christmas, moved him to exaltation: “We stood there astounded at a whole new field of vision, as if we had suffered an electric shock.” 3 IG Farben wasted no time in claiming its priority. On Christmas Day, it submitted an application for a German patent on Prontosil.
    Over the next two years, as Domagk quietly investigated the new compound with the help of selected local physicians treating patients with streptococcal infections, several dramatic cures in humans testified to the new drug's effectiveness. The first patient was a ten-month-old infant severely ill with staphylococcal septicemia (blood poisoning), a condition from which no one had ever been known to recover. Treating the baby with Prontosil was a daring gamble on Domagk's part. If the child had not survived, it would not have been clear whether the drug or the disease had killed him. The child's skin turned red, and hisphysicians were able to calm his excited nurse only by explaining that the drug was basically a dye. Within days, the child miraculously recovered. Prontosil was distributed for clinical trial in 1933.
    In a dramatic twist of fate, a few months later Domagk was forced to use Prontosil to cure his own six-year-old daughter, Hildegard, who was facing a similar life-threatening infection. She had pricked her hand with an embroidery needle in the web of tissue between her