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The Medical Metals of Yesterday

SeeArrOh stumbles upon a book that’s something of a chemistry time capsule when it comes to metals and disease. SeeArrOh is a Ph.D. chemist working in industry.

“That which does not kill us makes us stronger” – Nietzsche

“The dose makes the poison” – Paracelsus

When we look back at ancient medicine, we view the treatments once espoused as cures to be near-barbaric: bloodletting, bodily humours, exorcism, even red-hot coins on the skin. Luckily, the advent of the 20th Century brought pharmaceutical companies, sanitation, and well-managed hospital facilities, escapes from the painful and potentially fatal cures of long ago. Modern medicine would never lead us down the path to poison, would it?

Purchasing stamp from The Story of Chemistry, USC-Los Angeles

Maybe we didn’t leave everything from that time behind. While browsing our company bookshelves, I happened across a book entitled The Story of Chemistry with a burlap-brown cover and a thick coat of dust. Published in 1929 by a Mr. Floyd L. Darrow, it pre-dates Chemical Reviews, covering most of the 1920s in medical, agricultural, and synthetic chemistry. To calibrate you to the time period, remember that WWII had not yet occurred, so WWI is referred to as “the Great War”, and the language of science writing waxed a bit poetic, such that the author draws comparisons between “fields of endeavor” and “[the] waters of the Niagara.”

I won’t try to cover all 528 pages, but I was drawn in by Chapter VII, called “Chemistry and Disease.” The author details all of the stunning advances of the late ‘20s, including the isolation of the 4(!) major Vitamins (A-D, with no extra “B-#s”, or E, or K), thyroxine, and steroids, though few chemists knew enough about the structure of these compounds to try rational drug design. (Three of the Vitamins (B1, C, D) would be synthesized in the 1930s. Poor Vitamin A had to wait until 1947.)

Enter Paul Ehrlich, who won the 1908 Nobel Prize in Medicine for his “magic bullet” theory of disease treatment and the first preparation of “specifics,” or chemicals used to kill a single microorganism from among many. Salvarsan, his pioneering treatment for syphilis, was originally called arsphenamine, and contained a diarsenic core. (This was shown in 2005 to be a cyclic analogue of 5 arsenic atoms.) Back then, organoarsenics were not generally recognized as toxic to humans, and scientists would go on to synthesize several other modified versions until more tolerable therapies, such as the sulfa drugs in the 1930s, could be produced.

Just two pages past Ehrlich, the author dives into more on the “specifics” of the day, including some high praise for mercurochrome. Originally derived from one of the coal tar dyes developed in Germany and England in the late 1800s, mercurochrome was first synthesized at Johns Hopkins by scientists studying the excretion of dyes from the kidneys. By 1929, the compound had found “wide use in the treatment of…the mucous membranes of the eye, the bladder, the pelvis, and the kidney.” In fact, in an interview for the book, the Johns Hopkins scientists proudly proclaimed that they had reversed two cases of blood poisoning by direct injection of mercurochrome into the bloodstream!  Amazingly, this compound, which is cheap and readily available in many countries, was not banned from the US shelves until 1998. (The FDA, concerned over health effects of mercury compounds in young children, commissioned several human health studies in the late nineties, and eventually de-listed mercurochrome and other organomercurates from the GRAS, or generally recognized as safe, list.)

The most shocking example, though, was saved for the end of the chapter. Cancer, the “most dreaded of human scourges” was treated in 1929 with the three best tools available: radium, high-voltage X-rays, and excision (removal by surgery).  What’s the chemotherapy du jour? Colloidal lead. First administered by direct injection by Dr. Blair-Bell of Liverpool, England, the treatment claimed to transform terminal cancer patients into “well and happy people,” with a cautious caveat towards the end that it was up to future chemists to somehow find a way to ameliorate the lead toxicity while still retaining the beneficial tumor-killing properties. Luckily, skepticism over the colloidal lead method led to seminal studies in the US, which discouraged its use in later cancer therapies.

Only 82 years have passed since these arsenic, mercury, and lead-based therapies were the front line against disease. One has to wonder what the future will bring.

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