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 1800s 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 res- piratory 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 1800s, 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 of the 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 that 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 pros- ecution began its case with an unusual demonstration, one that would never be condoned today. But back in 1893, the judge agreed for a cat to be brought into the courtroom, and for it to be given 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 having struck up a relationship with the wealthy propri- etress 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 possi- bility of murder, even though one of the brothel owner’s former lovers insisted that the doctor had done away with his wife, probably with morphine. But the medical examiner main- tained 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 telltale pinpoint pupils of the victim’s eyes. The fool, Buchanan had said, should have applied some belladonna! When this story came out, another witness recalled having seen Dr. Buchanan put some sort of drops into his wife’s eyes before she died. The good doctor was convicted and executed in the same electric chair in which the “bungler” had met his end two years earlier.
Now let’s fast-forward about 100 years and get acquainted with Dr. Paul Agutter, who probably would have appreciated Buchanan’s efforts. A well-known biochemistry professor in Edinburgh, Scotland, he, like Buchanan, tried to do away with his wife in a chemical fashion. He figured a high dose of atropine would do the job, and put some into the tonic water she always had with her gin. This was a good choice, because the bitter tonic disguised the taste of the atropine. To throw the police off his trail, he also adulterated some bottles of tonic water in the
local supermarket with small doses of atropine to suggest that a mass poisoner was on the loose. But Dr. Paul Agutter was unlucky. One of these bottles happened to be purchased by the wife of an anesthetist. When she and her son became ill, he recognized the symptoms as atropine poisoning! Within the next few days, five other locals were diagnosed with the same condition. All survived after they were appropriately treated. The police tested their tonic water and found atropine, but not as much as was in the bottle belonging to Mrs. Agutter. Paul Agutter finally confessed to attempted murder and was sen- tenced to twelve years in prison. Why did he want to murder his wife? It was the age-old reason. He wanted to inherit her fam- ily fortune and then marry his mistress. He probably would have gotten away with it, too, had one of the bottles not ended up in the household of an alert anesthetist.