Sunday, January 23, 2011

The Demon Under the Microscope

Somehow, despite my chemical background and years reviewing pharmaceutical documents, I managed to know next to nothing about sulfa drugs.  I knew they were precursors of a sort to antibiotics, and that they were often (always?) a powder sprinkled on wounds, but that was it.  Antibiotics were stronger, less toxic, and effective against a wider range of microbes, totally eclipsing the first family of magic bullets.

More soldiers died from infection and disease during WWI.  Epidemics swept through crowded, unsanitary trenches and shrapnel drove mud and filth into the bodies of men who sometimes laid for hours or days in pools of stagnant water.  Doctors did what they could, amputating obviously infected limbs and flushing bodies with antiseptics we now know should only be used externally, but patients died at an alarming rate.  A generation later, things had changed.  Thanks to sulfa drugs, infection killed no one after the attack on Pearl Harbor.  As infamous as that day was, it would have been much worse without the work of a German doctor and his chemist colleagues.

Gerhard Domagk enlisted in the German army in 1914 and was wounded shortly before Christmas.  While being treated, the army discovered that he had been a medical student and transferred him to the hospital staff where he saw the horrors of battlefield medicine and how little could be done for patients with infected wounds.  In France, Sir Almoth Wright encountered the same problem - an expert surgeon and believer in antiseptics, he and the doctors under him were operating in sterile conditions and flushing wounds internally with strong antiseptics and still patients died of gas gangrene.  

Domagk returned to medical school after the war, specializing in pathology.  Eventually he went to work for Bayer where, following the example of Paul Erlich and his dye-based syphilis cure Salvasan, he worked with a team of chemists adding functional groups to dyes until he found one which cured a handful of common bacterial infections with few side effects other than temporarily dying the patent's skin pink.   Once this miracle drug (named Prontosil) was released to the public, French and American scientist worked on improving the drug, eventually discovering that it was the functional group - the sulfa - that killed microbes and that the dye did nothing but temporarily stain the patients' cells.  Meanwhile, Leonard Colebrook, one of Sir Almoth's assistants, put sulfa drugs to practical use in maternity wards.  A combination of isolating infectious patients and the use of sulfa drugs made the formerly hazardous hospital births safe.

Sulfa drugs didn't just revolutionize wound care.  As Thomas Hager points out in the introduction, before sulfa drugs doctors had few effective drugs and most medicines were patent medicines - snake oil which were at best ineffective and often harmful.   After the discovery of sulfa drugs, the nascent pharmaceutical industry invested in research and made modern medicine possible.  Doctors, too, underwent a transformation, from men who could do little more than check symptoms and comfort patients to scientists who could cure many if not most diseases (although perhaps at the expense of bedside manner).  Sulfa drugs even played a supporting role in the regulation of drugs, after over a hundred people died from a patent sulfa medicine which used ethylene glycol as a solvent, and early reports of sulfa-resistant drugs sent a warning (which was largely ignored) about antibiotic resistance.  We owe a lot to sulfa drugs, especially when you consider how they were superseded by antibiotics barely a decade after their introduction.

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