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The Birth of Modern Chemistry Was the Birth of Barbiturates

From pee to goofballs.

The death of vitalism was the birth of sedation.

In 1828 the German chemist Friedrich Wöhler synthesized urea, an organic molecule otherwise found in urine that primarily serves to remove nitrogen produced in metabolic reactions from the body. This synthesis from the inorganic ammonium cyanate should have been impossible given a key scientific hypothesis of the time that predicted the existence of an elusive lifeforce or "vital spark" within living creatures thought neccessary for the creation of organic molecules (and life itself).

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This belief was/is known as vitalism. It argues that the fundamental difference between living and nonliving entities can be found in an unseen aether-like substance permeating all living material that allows for bodily functionality and the synthesis of organic molecules. The basic idea of a soul or metaphysical inhabitant of the bag of mush that is the human body is of course ancient—Aristotle thought there were three distinct souls—but it found its way into emerging biological sciences in the 16th century and, within science, the assumption of mind-body dualism persisted thereafter.

"There is a vast difference between the mind and the body," Descartes would write in 1641 in his Meditations on First Philosophy, "in that the body is always divisible, while the mind is completely indivisible."

Mind-body dualism is a great fudge because it can sub in for most any sort of missing knowledge. It's still used as a great (and profitable) fudge in alt-medicine (acupuncture, reiki, homeopathy, chiropractic medicine) wherein all manner of bullshit might be supported by whatever form of invisible energy.

Then, in 1828, Wöhler did the impossible by creating something organic sans magic. It wasn't the broad takedown of vitalism that it's often made out to be (see: the Wöhler Myth), but clearly the lifeforce concept guiding biology through its pre- and early-history wasn't quite as neccessary as had been assumed. Following Wöhler's production of urea via a method that became known as the Wöhler synthesis, urea and its functions within the body and potential functions in industrial applications became very interesting to chemists, including another German, Adolf von Baeyer.

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Circa 1869, von Baeyer's chief interest was in uric acid, another nitrogenous waste product likewise excreted in animal urine. From uric acid, he created alloxan, a toxic glucose analog used in the production of purple dye, and parabanic acid. His goal was to create uric acid from urea, which he never quite accomplished. But, in 1864, he did hit on something interesting and quite different: barbituric acid.

It's unclear what von Baeyer thought might come of barbituric acid, and the longest academic bio of the chemist I could find makes only a passing reference to it. But, as the lore goes, he at least thought it was something worth celebrating, and von Baeyer and his pals made their way to a beer hall, where a soldier commented that they should name the new compound after Saint Barbara. December 4, the day of the discovery, happened to coincide with a feast celebrating the patron saint of military engineering.

Von Baeyer went on to synthesize indigo, for which he would win the Nobel Prize in Chemistry in 1905. His former lab assistant Emil Fischer, however, would continue pursuing barbituric acid, which itself had no pharmacological effects. He was joined by the pharmacologist Josef Freiherr von Mering and together they observed that a number of the mild proto-downers developed in the later 1800s were compounds featuring acetylurea, a molecule that might be swapped out in favor of barbituric acid.

What they came up with, diethyl-barbituric acid (or just barbital), was vastly more potent a sedative than anything thus far produced. On July 9, 1904, von Mering and Fischer received a patient for the new compound and the first barbiturate would hit the market as Veronal. The name was derived from the Latin word for "true," as Fischer felt that he had created the first-ever true hypnotic compound. The 20th century would produce no less than 2,500 barbiturate derivatives, 25 of which would actually reach the market.

Needless to say, barbiturates were a total hit (until they weren't), but the following decades will have to wait for a second post.