Name: The Demon Under the Microscope
ISBN: 9781400082131

The Demon Under the Microscope

The Nazis discovered it. The Allies won the war with it. It conquered diseases, changed laws, and single-handedly launched the era of antibiotics. This incredible discovery was sulfa, the first antibiotic. InThe Demon Under the Microscope, Thomas Hager chronicles the dramatic history of the drug that shaped modern medicine. Sulfa saved millions of lives--among them those of Winston Churchill and Franklin Delano Roosevelt Jr.--but its real effects are even more far reaching. Sulfa changed the way new drugs were developed, approved, and sold; transformed the way doctors treated patients; and ushered in the era of modern medicine. The very concept that chemicals created in a lab could cure disease revolutionized medicine, taking it from the treatment of symptoms and discomfort to the eradication of the root cause of illness. A strange and colorful story,The Demon Under the Microscopeilluminates the vivid characters, corporate strategy, individual idealism, careful planning, lucky breaks, cynicism, heroism, greed, hard work, and the central (though mistaken) idea that brought sulfa to the world. This is a fascinating scientific tale with all the excitement and intrigue of a great suspense novel. For thousands of years, humans had sought medicines with which they could defeat contagion, and they had slowly, painstakingly, won a few battles: some vaccines to ward off disease, a handful of antitoxins.

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photochemsynMay 2025

This approach is very interesting, and one attention-catching datum is that their proposed compound, ripasudil, is now largely out-of-patent with some caveats, via Google Patents and ChatGPT 03:

> 1999 - D. Western Therapeutics Institute (DWTI) finishes the discovery screen that produced K-115 = ripasudil and files the first PCT on 4-F-isoquinoline diazepane sulfonamides. (Earliest composition-of-matter priority. A 20-year term from a 1999 JP priority date takes you to 2019 (before any extensions).

> 2005 - Kowa (the licensee) files a follow-up patent covering the use of ripasudil for lowering intra-ocular pressure. U.S. counterpart US 8 193 193 issued 2012; nominal expiry 11 July 2026. (A method-of-use patent – can block generics in the U.S. even after the base substance expires).

Scanning the vast library of out-of-patent pharmaceuticals for novel uses has great potential for curing disease and reducing human suffering, but the for-profit pipeline in academic/corporate partnerships is notoriously uninterested in such research because they want exclusive patents that justify profits well beyond a simple %-of-manufacturing cost margin. Indeed they'd probably try to make random patentable derivatives of the compound in the hope that the activity of the public domain substance was preserved and market that instead (see the Prontosil/sulfanilimide story of the 1930s, well-related in Thomas Hager's 2006 book "The Demon Under The Microscope).

I suppose the user of these tools could restrict them to in-patent compounds, but that's ludicrously anti-scientific in outlook. In general it seems the more constraints are applied, the worse the performance.

Another issue is this is a heavily studied area and the result is more incremental than novel. I'd like to see it tackle a question with much less background data - propose a novel, cheap, easily manufactured industrial catalyst for the conversion of CO2 to methanol.

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rudyfinkJul 2023

Huh, I did not know they were related to sulfonamides like that. If you (or someone else) might like a book that goes into the history of sulfonamides, I'd recommend "The Demon Under The Microscope" by Hager (https://www.amazon.com/Demon-Under-Microscope-Battlefield-Ho...). It was an interesting read.

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photochemsynSep 2022

The whole story of the development of the sulfa drugs is pretty eye-opening, and is well-told in this popsci history book by Thomas Hager (2006), which also covers this toxic poisoning episode:

https://en.wikipedia.org/wiki/The_Demon_Under_the_Microscope

One fascinating aspect of this is that Bayer originally tried to convince the world that their patented derivative of sulfonamide, Prontosil (note nitrogenous ring additive) was the one that worked.

https://en.wikipedia.org/wiki/Prontosil

It turned out that the non-patentable sulfanilamide was the actual active species, which Bayer probably knew but kept secret because, well, patents and market share and so on:

https://en.wikipedia.org/wiki/Sulfanilamide

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rudyfinkDec 2021

From "The Demon Under the Microscope" by Hager--an interesting read on the history of Sulfonamides (the drug that kicks off the "golden age of antibiotics on the chart)--usage was entirely uncontrolled and people did not complete drug regimes. Generally (and I'll probably get this very wrong), that antibiotic worked by blocking uptake of external energy sources.

The drug was tremendously effective and widespread. The book made it sound like all of the strains that did not evolve a solution to that antibiotic were completely wiped out by the evolutionary pressure of the antibiotic.

I'd imagine (just guessing) that even if the antibiotic was stopped, the organisms would not have anything like the evolutionary pressure to change back (and the consequence of getting wiped out by the drug if they did). They probably get along "good enough" or the drift back is slow. In other words, the pressure to change was one of, essentially, absolute survival, while the change back is one of risky convenience.

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doublewaffleJan 2019

1. The Demon Under the Microscope... (T.Hager) 2. The Unpleasant Profession of Jonathan Hoag (Heinlein) 3. Masters of Doom... (D.Kushner) 4. Paycheck (P.Dick) 5. Dealers of Lightning (M.Hiltzik)

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nvahalikFeb 2018

Thomas Hager wrote that book along with “The Demon under the Microscope”. Excellent works.

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