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on November 20, 2006
On behalf of most of the Moms I know, I will admit that I have taken a child to the doctor with a sore throat and said the following out loud, "Well, I kind of hope it's strep so they can just put him/her on an antibiotic and he/she will be able to go back to school in a day or so." Well, when our grandparents were small children...people DIED from strep! In large numbers! Something like 1 in 4 women who gave birth in certain hospitals died from something called "childbed fever". More people in WWI died from infection than from war wounds. In WW1, Gonorrhea (the clap) was second only to the flu as a cause of disability and absence from duty.

This was in a time when people had electricity, cars, telephones and movies...but they could not cure easily transmittable diseases from which people died!

The simple solution to these infections and diseases was a class of drugs using Sulfa as the active ingredient. The story of how these drugs were discovered, developed, tested and used spans several decades and countries and had far-reaching effects on our current system of drug research and testing. At the beginning of the Sulfa era, people were still buying "patent medicines" which were unproven at best and dangerous or fatal at worst. The country's food and drug laws had no teeth...a perfect example being when a drug was found to have killed almost 100 people, the company which produced it could not be tried for negligence or murder, but could be tried for mislabeling!

The story is fascinating. The "characters" involved are as complex, heroic and villainous as characters in fiction. And the narrative moves along at a clip that fiction readers can deal with.

The Demon Under the Microscope is meticulously researched without those annoying footnotes on every page. Hager instead adds a chapter entitled "Source Notes" which describes where he got the information on a chapter by chapter basis, followed by an extensive bibliography. As a non-technical reader of the book, this is much more helpful and keeps the book from being bogged down in details that would only be of interest to other researchers.

If you enjoy these kinds of historical NON-fiction The Demon Under the Microscope would definitely be a good addition to your library.
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Some dolt on a bicycle slammed into me yesterday. Fortunately I did not break any bones, but the bruises are giving me an uncomfortable time since then. After rinsing both knees with chlorhexidine and iodine, I was not concerned; if there was an infection, antibiotics would take care of it.

But it wouldn't have been that way seventy years ago, when the most you could do to prevent a wound from getting infected...was wait, and perhaps apply some crude remedies. That was how it had been for two hundred years. For all the progress we had made, bad bugs still mostly got the better of us. It is appalling that about fifty percent of deaths in WW1 were from infections that riddled shrapnel wounds, and not from explosives or gunfire themselves. Once infection set in and gas gangrene made its hideous appearance, all one could do was wait, and maybe hope that the suffering would end soon...until sulfa drugs appeared on the scene.

That era of sulfa drugs, and not the one of penicillin, was the first heroic age of antibiotics. Most of us, if asked to name the first wonder-drug antibiotic, would name penicillin. But long before penicillin, sulfa saved thousands of lives. Without sulfa around, Hoover's son died. With sulfa, FDR's son, and Winston Churchill, survived. Thomas Hager has done an excellent job in bringing this forgotten but extremely important story to life in "The Demon Under the Microscope". The former biographer of Linus Pauling has shown us how different it was to suddenly have a drug that cured infections that previously would have almost certainly killed you. The time until the 1930s was a scary time, with every kind of Strep and Staph waiting to kill you after entering your body through the slightest cut, and diseases whose names we don't even remember now were rampant and much feared. It was sulfa that first declared war on and largely eradicated all these infections.

At the center of the sulfa story is the remarkable doctor and biochemist Gerhard Domagk. Domagk was an officer in WW1 and saw thousands needlessly die around him in agony, all because nobody could prevent the infection that set in after they were hit. After the war, Domagk went through a succession of jobs and finally ended up at Bayer, where he had a trailblazing career in the discovery of new cures for old infections. Building upon Paul Ehrlich's convictions about azo dyes as bacteriocidal agents, he and his colleagues tested hundreds of analogs, until he hit on the right one. This was the beginning of SAR as we know it today. And here, we can see the chemist's tragedy. Domagk tested the compounds, but it were two chemists who actually made them. Yet, they were excluded from the prize that Domagk would gather. This was not his fault, but really the workings of the Swedish committee, which did not behave this way for the first and last time. Patriotic and yet conscientious, Domagk stayed put after Hitler came to power, losing himself in his work to distract himself from the injustice that was taking place around him. In 1939, he was awarded the Nobel prize, but the Nazis did not allow him to accept it. Bayer itself became connected with the notorious IG Farben, which designed hydrogen cyanide vials (Zyklon B) for the gas chambers.

There is much in the book that is eye-opening, and sulfa is only one chapter in a book that also deals with medical history and the social history of science. There were several things I was unaware of; one revelation was that the modern American university model is based on the German model. The Germans were the world leaders in both industry and academia, and the modern and highly successful trend of close collaboration between industry and academia was already widespread in Germany. For all their philosophical bent, the Germans never saw any contradiction between pure and applied research, and the university-industry collaboration and connection led to very fruitful research in engineering and medicine. The modern patent regime too was pioneered by German industry.

The most important fact which I was not aware of was the pivotal albeit unfortunate role that sulfa played in revitalizing the FDA and granting it powers to implement laws that made it mandatory for manufacturers to display warnings and ingredients labels on their products. Before that, almost anyone could set up shop and sell metals, elixirs, and liquids that promised cures for everything from syphilis to baldness, a practice that went back two hundred years. But in the 1930s, through a series of unfortunate events, a concoction of sulfa in, of all the things, ethylene glycol, was sold extensively in many states. Today, we would be horrified at such large-scale use of an industrial solvent for mixing a drug. But at the time, there were almost no laws that required manufacturers to list such petty things as solvents on their bottles. The FDA was a skimpy and ineffectual agency at the time, with a few dozen agents scuttling around to mainly keep a check on excessive profit making. After the sulfa-ethylene glycol concoction was sold, a wave of death began that did not stop until several hundred people died, and public outrage changed the face of the FDA- and the way in which drugs are developed, manufactured and sold in the US- forever. After the tragedy, the FDA acquired new powers that it could have only dreamt of before. Of course, it took the thalidomide tragedy to have the kind of strict FDA regime that we have today, but the sulfa tragedy started it all, and made drugs substantially safer for the public.

An amusing and ironic chemical fact also accompanies the discovery of sulfa. Even though it were the Germans who pioneered its development, it was a French group that discovered the most important fact about the drug; that it was not the azo chemical linkage, but the benzene sulfonamide group that was key to the action of the drug. Once they discovered this fact, all bets were off for the Germans, because the potent part of sulfa turned out to be benzene sulfonamide, a cheap bulk chemical that could not be patented! Even if the Germans tried to quickly get past this handicap by synthesizing new derivatives at a terrific pace to outnumber their French colleagues, the cat was out of the bag, and they could never top their initial success.

Gradually, sulfa made it everywhere, and into the United States through the perspicacity and interest of two Johns Hopkins researchers. It began to be marketed in every form and colour and flavour, as every derivative and analog. In the 1930s, it became the drug of choice for treating every imaginable kind of Strep or Staph infection, most of which it effectively tackled. Cure by sulfa was touted as a miracle cure, with its relentless and wondrous effect on cases that only ten years ago would have been totally hopeless. But as a drug, sulfa had already fallen behind. Penicillin had arived on the scene. In due course, resistance would develop to both drugs, albeit relatively gradually to sulfa.

Domagk spent the last days of his life in gloomy peace, distraught by his country's destruction, and somewhat validated by the thousands of lives he had saved. Sulfa is still used for topical purposes.

We now know that sulfa competes with PABA (para-amino benzoic acid) for the synthesis of dihydrofolate, an essential hub in the synthesis of folic acid. Sulfa and further related research led to, among other things, Methotrexate, a widely used current drug in cancer therapy. But in the end, what befell sulfa has befallen other antibiotics. The bugs have become resistant. When sulfa and penicillin were discovered, they were regarded as miracles. Perhaps we need another miracle for bad bugs today, and the age of fervent antibiotic research might be coming back to haunt us. But it should not be forgotten that sulfa was the first miracle drug, before penicillin.
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on November 23, 2006
In a time when Bird Flu, AIDS, Ebola, Marburg and God-only-knows what other viruses threaten life today, its easy to forget that not too long ago bacteria posed an even greater menace. Anyone with as little as a cut or a scrape, nevermind battlefield wound, could fall victim to infection any variety of which could become life ending.
Medical Science at the time was, in the author's words, no more effective than "a medicine man with a mask and bone rattle." This book is the fascinating, and little known story of those who changed all of this. Thomas Hager
has so painstakingly researched every minute detail of the story and assembled a richly informing narrative. Yet, the story he tells moves like a well writen novel, keeping the reader fastened to the end. My only regret is that the publisher did not see fit to include photographs of places and persons mentioned. Nevertheless, for anyone like myself, who enjoys reading science and history at its best, you won't be dissapointed.
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Everyone knows how penicillin revolutionized medical treatment of infections, most know about how Alexander Fleming discovered it, and some even know how Howard Florey and Ernst Chain took the discovery and made it something that could be used practically. Everyone knows that penicillin was a miracle drug, but almost everyone has forgotten that it was not the first miracle drug. The sulfa drugs came a decade before, producing unprecedented cures that physicians and patients thought of as miraculous; and then the penicillin-type antibiotics surpassed them. The history of the sulfa drugs is told in _The Demon Under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor's Heroic Search for the World's First Miracle Drug_ (Harmony Books) by Thomas Hager. It is clear that sulfa deserves much more attention in the history of medicine than it has gotten. By some definitions, since they are not made by living organisms, sulfa drugs are not really antibiotics, but they certainly fought microbial infections in their time, and got medicine beyond the limits of mere antisepsis or disinfecting. They also proved a model for scientific evaluation of drug effectiveness.

Chances are that you have never even heard the name of the doctor whose work is the backbone for this story, Gerhard Domagk. Domagk makes a tenacious but unspectacular hero, working day after day through clinical trials, mostly with mice, but he was inspired by his harrowing experiences as a medic in the First World War to fight against the infections he had seen there caused by the strep germ, a feared killer, one that killed in many different ways, infecting tissue, blood, or spinal fluid. For five years, there were no results of his labwork, until he was sent a molecule with sulfonamide attached to it. Sulfa worked in mice; did it work in humans? It is quite amazing to read about how the drug was tested for human use, because it is nothing like the trials of any new drug today. The tests did not involve, for instance, assigning patients randomly to drug versus placebo groups, or doing double blind testing. The drug was simply leaked to hospitals who had serious cases, patients who had gotten all the usual treatments and were simply going to die if nothing out of the ordinary was tried. Domagk was awarded the Nobel Prize in 1939, and was thrilled to be following his heroes Koch and Ehrlich. But because four years previously, the Peace Prize had been awarded to a German pacifist, Hitler had forbidden any German citizen to accept any further Nobel. Not only could Domagk not claim his award, he was put in jail for being "too polite to the Swedes" who awarded the prize. After the Nazi blight was cleared away, Domagk was able to claim his prize in 1947, when sulfa was old news. When he gave his speech of acceptance, he alluded to the emergence of resistant strains of bacteria, a prescient warning which could not have been fully appreciated by his audience at the time.

The main reason the sulfa revolution has been forgotten, of course, is that the first miracle drugs were followed by more broadly powerful antibiotics starting with penicillin. Researchers testing the new medicines used many of the laboratory procedures Domagk's team had initiated, and also did not have to face the previous pessimism that taught that chemicals would never be able to fight infection. It might be that sulfa's greatest contribution to medical history was a needed increase in medical confidence. Hager's fine history highlights sulfa's role in industrial, medical, social, and military changes of the time; sulfa did far more than just kill strep germs.
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on February 11, 2013
As a physician, I had heard the story of Fleming's discovery of penicillin often, but the development of the first clinically available antibiotic, sulfa, is a fascinating story that is not widely known. Instead of the inspired alchemy of a brilliant scientist that one assumes goes into the discovery of a brand new class of medications, the discovery of sulfa is a much more methodical affair of a driven science team funded by the deep pockets of a huge corporation. Interwoven with the events of two world wars and German industrialism, the story touches of both the scientific and personal challenges of a years-long drug development effort.

My only complaint is that the book title implies a look into the development of antibiotics in general, where in reality, it only recounts the development of sulfa alone. There is only passing reference to Fleming and penicillin.

All in all, a fascinating book that should be required reading for all medical students as well as physicians and anyone interested in how we arrived in the modern medical era we are in today.
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VINE VOICEon November 4, 2014
Excellent book on the battle to conquer strept. We don't think a whole lot about strept now. When our kids get sick with this bug/microbe it usually causes a sore throat. This is what doctors test for. But in my grandmother's time, streptococcus of any kind could kill you. Streptococcus infections caused sepsis, wound infections, and if it traveled from the throat to the heart, it could cause rheumatic fever. I know about this because my grandmother ended up with it.

The Germans were the first to find something that would work on streptococcus. Before antibiotics existed sulfa drugs were used. This is the story of the research done by Bayer and other companies in Germany to find something that would prevent the many deaths seen during war time from disease. For the most part, during both the Civil War and World War 1 (and the other small wars in between these years) more men died from disease, including gangrene and wound infections, than died from bullets. So the race was on among all countries including Great Britain, France, and Germany to find something that could cure men of disease, and get them back to the fronts. This of course, was of more concern than civilian deaths. Streptococcus was also known to cause puerperal fever in women who were delivering children. This was another huge concern for many doctors.

This race to find a drug that would help prevent infections led to some of the typical fiascos seen in the science community. These men are very competitive, especially when other countries are known to be searching for the same thing. These competitions mean that mistakes will be made, usually someone's feelings will get hurt due to being ignored when awards are given, jealousy runs rampant, etc. All of those things happened here in this story.

What's interesting isn't just the research done, and the men involved, but how short the use of sulfa drugs actually was. We still use some sulfa drugs, such as sulfonamide, but it is known that many of the antibiotics we currently use are causing resistance among bacteria. So it might come to the point we will need to use more sulfa drugs again in the future.

Interesting story...
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on May 5, 2007
It's not mentioned in the book, but it is marketed as AVC Cream, most commonly placed on gauze and packed into the [...] after hysterectomy. Other dosage forms are long obsolete, but this one is still in use and probably always will be.

We hear all the time about antibiotic resistance, but most of us don't even think about what life was like before the drugs even existed. This is why home births really were safer prior to World War II, due to all the germs floating around in hospitals and NOTHING that could be done if infection struck. People, especially children like Hildegard Domagk, died from diseases we hardly bat an eye at now, and the drug got the ball rolling. I'm guessing we don't hear about it like we do with penicillin because it's not in general use any more.

This book is mostly the history of sulfanilamide, the first really effective systemic antibacterial drug. The drug had some really weird side effects, so it probably wouldn't be considered safe by modern standards. It also addresses political and business issues surrounding the drug and is a mini-bio of its discoverer, Dr. Gerhard Domagk. Who's Hildegard? His daughter, who got a deadly infection after being poked with a needle and was one of the first people who life was saved by this drug. Last I heard, she was still living and would be in her late 70s.

I purchased the book because of the chapter on the Elixir Sulfanilamide disaster of 1937, a very dark chapter in American medical history that has largely been forgotten to the point where I have never conversed with a fellow pharmacist who has ever heard of it. We associate the Massengill corporation with douches (LOL) but yes, that's who made it, and no, nobody tested the concoction to see if it was safe for human consumption before sending it out on the market, where it could be sold without a prescription. Sulfanilamide does not dissolve readily in alcohol or water, but it does dissolve in diethylene glycol (antifreeze) so that's what was used, causing the deaths of 107 of the 353 people known to have taken it. The History Channel did a program on this a few years ago called "Elixir of Death"; the author who was working on a book of this title who was prominently featured in the program died in a car accident shortly before it aired in 2003.

I also had the privilege of seeing Thomas Hager read from his book on C-Span II's Book TV. This was quite interesting to hear perspectives straight from the author.
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on June 16, 2016
I opened up this book at random and the first words I read were "an AUSTRALIAN researcher named Alexander Fleming"…………"BRITISH researchers Howard Florey and Ernst Chain" (p.296). Three mistakes, right off the bat…….perhaps it really doesn't MATTER very much that Alexander Fleming was a Scot, or that Howard Florey was from Australia while Ernst Chain was a German Jew naturalized before the war, but neither does it fill a reader with confidence to find such sloppy "scholarship" at the very first glance. I wouldn't place much confidence on the rest of the book, considering these really obvious errors. And that's too bad because the subject does fascinate me.
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on December 21, 2015
I read this book for a book club. The discussion during our meeting reflected the issue with this book. The doctors enjoyed it The rest of us were not sure. Portions of the book told a great story. The problem was that so much was very technical. It was difficult to understand what was going on. The biographical description of the scientists were interesting. On the other hand, I had a hard time figuring out what exactly was being done. Also there were pages describing illnesses that were a digression.

In short it was not a book for a general audience.
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VINE VOICEon March 26, 2010
It's sometimes surprising, when you look back into history, how often people died from disease. Even during wars, more were usually killed by illness and infection than in battle. I've looked into my own family history and it's not uncommon to find ancestors who died young by today's standards, or whose families could have been much larger if not for the children who died soon after birth (and mothers as well) or while still young. Today, we take it for granted that medicines and doctors can cure ailments that 60 or 70 years ago would have struck deathly fear in the hearts of those who lived and died with them.

During World War I many died from relatively minor wounds because of bacterial infections - primarily strep (the same that causes strep throat), staph, and gas gangrene. It wasn't until the early 1930s, however, that German researchers like Josef Klarer, Fritz Meitzsch, and Gerhard Domagk (who was awarded the Nobel Prize), and Frenchman Ernest Fourneau discovered and refined the amazing healing properties of a relatively common chemical: sulfonamide - frequently known as sulpha (I remember hearing it mentioned regularly on the television series M*A*S*H). Sulpha's reign as miracle drug didn't last long - penicillin replaced it by the mid to late 1940s - but it was a revolutionary drug that ushered in the age of antibiotics.

I enjoy medical histories that illuminate what life was like for ordinary people, not just the extraordinary leaders and events that stand out. I've read several medical histories that have been as riveting as a good war history and looked forward to this one. And I think I may have enjoyed it more had I read the book instead of listening to the audio book. Not that the narrator doesn't do an excellent job, but the material was harder (for me) to absorb through listening. Medical histories run a risk of being dry and technical, and Thomas Hager does a very good job of telling the bigger picture and fleshing out the important characters and events in the history of sulpha, but I think reading the book would have been easier to follow and more enjoyable. Still, a good read for those like me who enjoy such books.
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