Agatha Christie's "The Crooked House" is a great story. 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 which normally degrades acetylcholine after it has done its job. The result is a buildup of acetylcholine which can lead 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 phytostigmine 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!