One of my favorite detective stories is Agatha Christie's "The Crooked House." The plot revolves around an elderly tycoon who requires daily insulin shots. He also suffers from glaucoma for which he has been prescribed eyedrops. Everything is fine until someone in the "Crooked House" switches the eyedrops with the insulin. Murder most foul!
Does the chemistry make sense? Let's do a little detective work of our own. As clearly stated in the novel, the eyedrops contain physostigmine, a substance introduced in the late 1800's for the treatment of excess pressure in the eyeball, a symptom characteristic of glaucoma. Physostigmine, or "eserine" as it is also known, opens up the tiny ducts through which excess fluid is normally expelled from the eye. Could this drug really be lethal if injected into the bloodstream?
Physostigmine has a long and interesting history. It is the active ingredient in the "ordeal" bean, found in the Calabar region of Nigeria. Why the term "ordeal" bean? Because it was traditionally used by certain tribes as a test of guilt. Someone suspected of having committed a crime was forced to swallow a handful of beans. If he died, he was guilty. Unfortunately, he probably died even if he wasn't guilty. Physostigmine is known to enhance the activity of acetylcholine, a chemical essential for the proper functioning of our nervous system. It does this by inactivating an enzyme called cholinesterase that normally degrades acetylcholine after it has done its job. The result is a buildup of acetylcholine leading to paralysis of the respiratory muscles and death. Maybe if the accused were really confident of his innocence, he would eat the beans quickly, vomit and survive!
By the late 1800's, physostigmine had been isolated from the Calabar bean and was widely used in the form of eyedrops for the treatment of glaucoma. The amount needed on a daily basis was very little, but there certainly would have been enough active ingredient in a bottle to kill if directly injected with a syringe. Had a physician arrived soon enough, the effects probably could have been reversed. Atropine, found in the belladonna plant, can block the receptor sites on nerve cells which are normally activated by acetylcholine. This antidote was routinely carried by the doctors of the day, not necessarily to deal with physostigmine poisoning, but because atropine is a potent heart stimulant. But if the victim had lived, there would have been no murder, and no story. Who needs a story though, when real life poisonings may be stranger than fiction!
Just consider the celebrated murder trial in which the prosecution began its case with an unusual demonstration, one that would never be condoned today. But back in 1893, the judge agreed that a cat be brought into the court room and administered a lethal dose of morphine. As its life ebbed away, a few drops of belladonna extract were applied to its eyes. Why was such a cruel experiment necessary? Because the prosecutor wanted to demonstrate to the jury that the characteristic pin-pointing of the pupils of the eye caused by morphine could be reversed with atropine.
Dr. Robert Buchanan had been accused of murdering his wife after he had struck up a relationship with the wealthy proprietress of a brothel. In 1892 Mrs. Buchanan developed a sudden illness and died. The medical examiner concluded that the cause had been brain hemorrhage and refused to consider the possibility of murder even though one of the brothel owner鈥檚 former lovers insisted that the doctor had done away with his wife, probably with morphine. But the medical examiner maintained this was impossible because the victim had shown no signs of pinpoint pupils.
When the "New York World" newspaper began to question the treatment of the case, the coroner was forced to order an exhumation. The remains were found to contain enough morphine to have caused death, and Buchanan was put on trial for murder. His undoing was a conversation that was reported by a witness. The doctor, it seems, had railed against another accused morphine poisoner as an incompetent. His downfall had been the tell-tale pinpoint pupils of the victim's eyes. The fool, Buchanan had said, should have applied some belladonna! When this story emerged, another witness recalled Dr. Buchanan putting some sort of drops into his wife鈥檚 eyes before she died. The good doctor was convicted and executed in the same electric chair in which the 鈥渂ungler鈥� had met his end two years earlier.
