A is for Arsenic (18 page)

Aristide had been taking eserine in the form of eyedrops to treat glaucoma. This is a group of eye conditions that cause the pressure in the eye to build to abnormally high levels. This compresses the optic nerve and can cause permanent nerve damage, resulting in loss of vision. Various treatments are available depending on the cause of the glaucoma, but in the case of acute glaucoma miotic drugs are used to contract the pupils.

There are two sets of muscles in the iris that control the size of the pupil. Radial muscles spread out from the pupils like spokes on a bicycle; their contraction causes the pupil to dilate. Circular muscles that form rings around the pupil contract to make the pupil smaller. The action of the radial muscles is controlled by the sympathetic nervous system, and the circular muscles by the parasympathetic nervous system (PN). As we've seen, eserine acts predominantly on the PN, and therefore causes the iris to stretch and the pupil to contract. By stretching the iris, it is pulled away from drainage channels in the eye, allowing fluid to drain out. Side effects of changes to pupil size include alterations to vision, problems with night vision and problems with focusing. These side effects can be minimised by using appropriate doses, and any inconvenience must be better than the potential loss of sight. Of course there could be other more dramatic and serious side effects caused by eserine's interaction with AChE in other parts of the body, such as the heart and muscles, but these are rare when using small doses applied directly to the eye.

In
Crooked House
, it is clear in the post-mortem examination that Aristide had been killed by an injection of eserine eyedrops, but would this have worked? Eserine can kill in relatively low doses if it is administered by injection because the drug is delivered directly into the bloodstream; if the drug is swallowed or absorbed through mucous membranes, the body has an opportunity to digest and break it down before it reaches the AChE enzymes and starts to cause problems.

Eserine eyedrops today are prescribed in solutions of 0.25 per cent w/v
⁵³
in 15ml bottles (equivalent to 15mg of eserine per bottle). From this bottle a patient puts a drop or two into each eye, between one and three times a day. The LD
50
(the amount required to kill 50 per cent of animals – in this case mice – in a test group) by injection is 0.6–1.0mg/kg. For a 70kg adult human this translates to 40–70mg, though the minimum lethal dose recorded is a mere 6mg. This means that a murderer would have to inject between three and five bottles of eserine eyedrops to kill a 70kg man – one would expect the victim to notice, and protest. It is true, however, that Aristide was an elderly man with a weakened heart, and he might have been expected to be killed by a dose at the lower end of the scale. To kill by ingestion, a poisoner would have had to increase the dose and administer approximately 14 bottles, or 210ml, to achieve the same end.

The volume of insulin injected into a diabetic patient varies, but it is generally around 1ml. If Aristide's insulin had been substituted with a modern prescription of eserine, he would have been injected with approximately 1mg of eserine, way below the minimum lethal dose; although Aristide's eserine medication may have been more concentrated than would be expected today, or his insulin injections may have been more dilute, requiring larger volumes to be injected. The time taken for Aristide to show symptoms of poisoning is also curious. He was apparently well for half an hour after his injection. This kind of time delay might be expected if he had ingested the poison, but an injection would have acted within a few minutes.

Eserine is certainly an unusual poison to choose for a murder mystery. It's certainly lethal in very small quantities; Agatha Christie's use of this alkaloid in the novel
Curtain
is highly realistic. However, the method she adopted for its use in
Crooked House
would have been unlikely to have killed Aristide, though it would probably have made him very ill. It is a rare example in Christie's work where the details don't quite add up, but this is quibbling, really;
Crooked House
is otherwise one of her best novels.

Notes

⁴⁹
The name most commonly used today is physostigmine, but eserine was the name Christie used in
Crooked House
, so for convenience I'll stick with that for the rest of this chapter.

⁵⁰
‘Cholinergic' means anything that mimics the action of acetylcholine.

⁵¹
Eserine was successfully used in several tetanus cases before vaccinations were available.

⁵²
Methanol extractions made from beans contain eserine, geneserine (at a quantity of 35 per cent that of eserine) and another alkaloid, norphysostigmine (at a quantity of 12 per cent that of eserine).

⁵³
w/v is shorthand for ‘weight by volume'. In this case, this is equivalent to 2.5g in one litre.

Five Little Pigs

My heart aches, and a drowsy numbness pains

My sense, as though of hemlock I had drunk …

John Keats, ‘Ode to a Nightingale'

HEMLOCK has been synonymous with poison and witchcraft since ancient times. This lethal plant famously brought about the death of Socrates in 399BC. It has been mentioned in poetry and prose throughout history – it was an ingredient in the witches' cauldron in
Macbeth
, for example, and has even been incorporated into the name of a
Sesame Street
character, the detective Sherlock Hemlock. Hemlock and extracts from it have been used in traditional remedies for millennia, and it was listed in the
British Pharmacopeia
until the early twentieth century. Considering the plant's notoriety it is surprising that, with the exception of Agatha Christie's writings, there have been no intentional hemlock poisonings since the time of
Socrates.
⁵⁴
However, there have been plenty of accidental cases, owing to the plant being mistaken for one of the edible varieties of the Apiaceae, commonly known as the carrot or parsley family, to which hemlock belongs; the leaves of hemlock have been mistaken for parsley, the roots for parsnips and the seeds for anise. In 1994, hemlock was reported as the third most frequent cause of plant poisoning. Anyone thinking of foraging for wild parsley or wild parsnips should make absolutely sure they have the correct species before they consume them (and if in doubt, don't eat it or feed it to anyone else).

Agatha Christie made use of hemlock in only one of her novels,
Five Little Pigs
,
⁵⁵
which was written in 1942. The novel concerns the murder of Amyas Crale, a talented but temperamental artist. His body was found sprawled in front of what was to be his last work, a portrait of the beautiful Elsa Greer. He had drunk from a glass of beer that had been poisoned with hemlock; his wife Caroline was found guilty and hanged. Many years later, their daughter Carla asks Hercule Poirot to reinvestigate the case, as she believes her mother was innocent. To find out what really happened, Poirot interviews ‘five little pigs', the five suspects present on the day of Amyas's death. The characteristics of hemlock poisoning provide Poirot with vital clues that allow him to solve the case.

The hemlock story

There are actually several species of plant that are collectively referred to as hemlock; these include four
Cicuta
species of water hemlocks, which grow throughout Europe and North America, and the closely related spotted hemlock,
Conium maculatum
. The plants are similar in appearance and are all highly toxic, but they contain very different poisons. These plants are also similar in appearance to less toxic species such as
Aethusa cynapium
, the poison parsley, which contains
compounds with similar toxic effects to
Conium
if ingested. The compounds in
Aethusa
cynapium
are less potent, however, and less likely to cause a fatality, though this is not a recommendation to try it in a salad. All of these plants are part of a family that includes edible species such as carrots, parsnips and parsley.

Socrates was found guilty of corrupting the minds of the youth of Athens, and of impiety. His punishment was to drink from a poisoned cup. In his dialogue
Phaedo
, Plato describes how Socrates was encouraged to walk around until his legs felt heavy, and then to lie down. He was also told not to speak, as talking was apt to ‘raise the heat' and interfere with the action of the poison. Those who excited themselves were sometimes obliged to take a second or third dose, as the jailer only prepared as much poison as he deemed sufficient. Socrates appears to have been indignant regarding the requirement to stop talking, and he told the jailer that he should be prepared to give him poison two or three times.

The death proceeded as the jailer predicted. Socrates walked until his legs began to fail. Numbness spread from his feet to his legs and through the rest of his body. He explained to his friends and pupils, who had gathered around him, that when the poison reached his heart he would die. Socrates was conscious and coherent to the very end. He talked to his pupils and requested that they settle his debts after he had died. There was a slight movement, then his eyes became fixed. His friend Crito then closed his eyes and his mouth.

Confusion over the naming of hemlock plants led many to believe that Socrates had been given a concoction made from
Cicuta
plants, which contain cicutoxin, a stimulant of the central nervous system that causes choking and violent convulsions. However, the symptoms of Socrates' poisoning are inconsistent with this; they simply do not tally with the peaceful death described in
Phaedo
, and many doubted Plato's account. Only in the nineteenth century was the matter cleared
up by Scottish pathologist John Hughes Bennett (1812–1875), after a terrible mistake. In 1845 Duncan Gow, a poor tailor living in Edinburgh, was brought a parsley sandwich by his children. Unfortunately the children had picked hemlock instead of parsley, and Gow was poisoned. Gow's symptoms were a slow, progressive paralysis followed by death. There was no choking and no convulsions, with Gow remaining lucid almost to the end. Bennett performed the post-mortem examination, and had the plant material identified. Gow, and Socrates, had been poisoned with
Conium maculatum
, the spotted hemlock.

Plato had sanitised the description of the symptoms, perhaps for the benefit of his readers and probably also out of respect for Socrates. From Plato's description the process appears almost painless, but this may not be the case. The slight movement reported at the very end may have been convulsions, and he would have gasped for his final breaths as he asphyxiated. Plato also fails to mention any increased salivation and slurring of words, probably because it was felt to be undignified, but the poisoner may have added other compounds to the drink to counteract these effects. One suggestion is that opium would have been added to the mixture, to relieve any pain and hasten death. Other plants such as belladonna (see page
here
) would have dried up any secretions, and these properties would certainly have been known to the ancient Greeks. The exact composition of the poisoned drink has not been passed on to us, but we know hemlock was involved.

Hemlock has also been implicated in the death of Alexander the Great, though many poisons have been suggested as the cause of his death, including arsenic and strychnine. Alexander died after eleven days of fever, aphasia (a disturbance of expression and comprehension of speech) and weakness in his limbs – classic symptoms of poisoning by
Conium maculatum
. Further circumstantial evidence comes from Pliny who claimed that a letter, written by a physician to Alexander, recommended that he drink wine as an antidote to
Conium maculatum
. Alexander died in 323BC and it seems unlikely that
we will ever be able to uncover the truth about his death after such a long time.