A is for Arsenic (7 page)

The belladonna story

Atropa belladonna,
more commonly known as deadly nightshade, is one of the most poisonous plants growing wild in Britain. Both the scientific and common names highlight the plant's deadly characteristics. The name
Atropa
is from Atropos, the third sister of the three Fates in Greek mythology; Clotho spun the thread of human life, Lachesis measured the thread, and Atropos cut it.
Atropa
is also the origin of the name of belladonna's most toxic component – atropine. ‘Belladonna' is
Italian for ‘beautiful lady', and the plant is so named because the berries of the plant were used by Renaissance women to make themselves more attractive. The juice would be squeezed from the berries and applied directly to the eye using a feather. Atropine in the berry juice would cause the pupil to dilate.
²⁵
Belladonna extract could dilate the pupils for up to three days but could also cause blurred vision, and extensive use could result in blindness. A more beneficial modern use of belladonna extracts is in ophthalmic applications, since dilating the pupils allows a better examination of the interior of the eye.

Agatha Christie made use of belladonna's effect on the pupils in a few of her stories, as a means of disguise. The idea was that very wide pupils would make the eyes appear darker, though it would have no effect on the colour of the iris. In
The Big Four
Hercule Poirot uses belladonna in his eyes and sacrifices his moustache to disguise himself as his fictional brother. This somewhat implausible trick seems to fool the villains. A similar ploy is used in
Three Act Tragedy
.
²⁶

Belladonna is a member of the family Solanaceae, which includes other notorious species such as mandrake and datura. All these plants have their place in witchcraft, medicine and myth. Other members of the family are considerably less terrifying – potatoes and tomatoes, for example. Even so, when tomatoes were first introduced into Britain people recognised their similarity to deadly nightshade and refused to eat them, thinking the fruits were poisonous. Displays of tomato-eating were arranged to reassure the public.

Perhaps the most famous of the poisonous Solanaceae is the mandrake. This plant is mentioned in the Bible and in several Shakespeare plays, and was even grown in the greenhouses at Harry Potter's school, Hogwarts. It was once believed that the mandrake was the living link between plants and animals
because underneath the green foliage its bifurcated root looks like a pair of legs. Close examination of the roots may tell you whether a particular plant is a mandrake or a ladydrake, and some roots were cut and carved to emphasize the distinction. Mandrakes contain several toxic compounds, which are present in all parts of the plant except the fruit. In the past the roots were sold for medical uses such as easing childbirth, inducing sleep and numbing pain before surgery. Compounds within the mandrake would have been effective in these applications, though by using only crude extracts of the plant, there would have been little control over potency or side effects. Mandrake roots were also sold as charms to increase fertility, and as an aphrodisiac, which would not have been effective at all. Mandrake harvesters ran a considerable risk in obtaining these roots. Legend has it that the plant gives a deadly shriek when it is uprooted, so painful and piercing it could kill a man. Anyone wishing to uproot the plant was advised to block their ears and tie a piece of rope from the plant to a starving dog. The dog would then be lured away with some appetising morsel, pulling up the mandrake behind it.

Agatha Christie mentions belladonna in several of her novels, but not mandrakes. She seemed to favour another member of the Solanaceae, datura, to inspire particularly villainous poison plots. Datura's poisonous compounds are found primarily in the flowers and seeds. The plant has a variety of common names, including thorn apple, because of the appearance of the fruit, and moonflower, because it flowers at night. One species of datura,
Datura strammonium
, known as jimsonweed (‘James-Town weed'), was responsible for a mass poisoning of soldiers in Jamestown, Virginia.

The James-Town Weed (which resembles the Thorny Apple of Peru, and I take to be the plant so call'd) is supposed to be one of the greatest coolers in the world. This being an early plant, was gather'd very young for a boil'd salad, by some of the soldiers sent thither to quell the rebellion of Bacon (1676); and some of them ate plentifully of it, the effect of which was a very pleasant comedy, for they
turned natural fools upon it for several days: one would blow up a feather in the air; another would dart straws at it with much fury; and another, stark naked, was sitting up in a corner like a monkey, grinning and making mows
[grimaces]
at them; a fourth would fondly kiss and paw his companions, and sneer in their faces with a countenance more antic than any in a Dutch droll.

In this frantic condition they were confined, lest they should, in their folly, destroy themselves – though it was observed that all their actions were full of innocence and good nature. Indeed, they were not very cleanly; for they would have wallowed in their own excrements if they had not been prevented. A thousand such simple tricks they played, and after eleven days returned
[to]
themselves again, not remembering anything that had passed.

(from Robert Beverly's
The History and Present State of Virginia
,
1705)

In Haiti datura is known as the zombie cucumber, because of its use in zombie powders. Making a Haitian zombie is a two-stage process. Stage one uses a powder whose principal component is pufferfish. The poison found in pufferfish, tetrodotoxin, relaxes muscles by blocking the action of the nerves that stimulate them. The muscles for breathing can become paralysed, making the victim appear dead, even though their heart may continue to beat very faintly and they are fully conscious. There is no antidote to tetrodotoxin, but poison victims can recover if their breathing is supported artificially. Stage two of the zombie-making process uses a second powder, administered after the victim revives from the effects of the first. The principal component of the second powder is datura. The hallucinogenic properties of compounds in datura can make an individual susceptible to suggestions, and thereby controllable. By careful dosing and maintenance of a controlled diet an individual can be sustained indefinitely in a stumbling, stupefied state.

The word ‘datura' is Hindi in origin. In India the plant is associated with both poisons and aphrodisiacs. It is used in the Indian traditional medicine system, Ayurveda, and in rituals and prayers to Lord Shiva. Datura has also been used in India
for less beneficial applications, including deliberate self-poisoning. Exact numbers are difficult to obtain but they run into the thousands (more than 2,700 in a 15-year period). Fortunately, the majority of these attempts are unsuccessful, but around one in ten poisoning cases results in death. It was the stories of datura's use in India that inspired Agatha Christie and her fictional poisoners in
A Caribbean Mystery
and
The Labours of Hercules.
There are several compounds within datura and other deadly Solanaceae that can affect the human body, but the dominant toxic compound in belladonna is atropine.

Atropine

Atropine is classed as a plant alkaloid. These compounds, when dissolved in water, generally produce alkaline solutions. They also tend to have a bitter taste. Many plant alkaloids have significant effects on the human body, and have found their way into medicine. Atropine is described as a tropane alkaloid because it contains the tropane chemical group (see Appendix 2). Tropane-based compounds are found in a wide range of plants, and their effects on the human body differ hugely.

Members of the Solanaceae family contain atropine and another closely related tropane compound, scopolamine, also known as hyoscine. Scopolamine was allegedly used by Dr Hawley Crippen to murder his wife Cora (see page
here
), and by Agatha Christie to dispose of Sir Claude in her first play
Black Coffee
. The chemical differences between scopolamine and atropine are minor, and their effects on the body tend to be very similar.

The two chiral forms of hyoscamine, which together make up atropine.

Atropine was first isolated from belladonna in 1831 by Heinrich F. G. Mein (1799–1864) and this plant, along with jimsonweed, remains the source of atropine for medical use today. Atropine is actually a mixture of two different forms of a chemical called hyoscyamine. These are called
l-
hyoscyamine and
d-
hyoscyamine; the two forms are mirror images of each other. Compounds such as these are described as ‘chiral', and they are like a left hand and a right hand. Hands have identical components (fingers, thumb, palms and so on) but they are arranged slightly differently on each hand, forming mirror images that cannot be superimposed onto each other (hence the labelling in chiral compounds:
l-
for
laevo
, ‘left' in Latin, and
d-
for
dextro
, ‘right'). The two forms are chemically identical and have the same physical properties, such as melting point and solubility in water, but they differ in their interactions with other chiral molecules. Think of the difference between putting a left-handed glove on your left hand and putting the same glove on your right hand.

Biology is very good at producing just one hand of a chiral compound rather than the other, and our bodies are full of ‘handed' molecules. The effects of drug molecules are caused by their interaction with other chemicals in the body; consequently, left- and right-handed forms of drug compounds can have very different effects in the body. In the case of
l-
and
d-
hyoscyamine most of the biological activity at low doses is thought to come from the
l-
version. At lethal doses, both forms appear to have equal potency. Individual sensitivity to atropine varies widely; some victims have died as a result of a dose of 10mg while others have survived 1,000mg, but it is generally agreed that toxic symptoms start to appear at doses of 5–10mg and a lethal dose is around 100mg.

How atropine kills

Atropine can enter the bloodstream by injection, ingestion or absorption through the skin and mucous membranes. In its pure form atropine is not very soluble in water, but it is soluble in fats and oils, so this form is more easily absorbed through the skin. Atropine in medication, in the form of eyedrops or
for injections, is normally administered as a salt to improve its solubility in water.
²⁷
Converting atropine into a salt does not alter its effect as a drug, just the ease with which it can be absorbed. For medical applications atropine is normally converted to its sulfate salt, which is readily absorbed through the gastrointestinal tract and mucous membranes but which tends not to pass through the skin.

Once absorbed into the bloodstream, atropine is quickly distributed through the body. It interacts with one of the two branches of the autonomic nervous system.
²⁸
One of its branches, the sympathetic nervous system, is responsible for the body's ‘fight or flight' responses to perceived danger; the other, the parasympathetic nervous system or PN, enables the body to ‘rest and digest', and regulates the production of fluids such as tears, saliva and bronchial mucus. The PN does this by sending a chemical messenger (or neurotransmitter) called acetylcholine from its nerve cells to the target organs.

Acetylcholine is released from nerve endings that dock at specific receptors on adjoining organs or nerves. They work a little like a child's shape-selector toy – a neurotransmitter such as acetylcholine fits into a receptor and triggers a response in the target organ or nerve. In our analogy, pushing the correct shape into the hole would result in a light coming on. Other chemicals or ‘shapes' can also fit into the receptors. A chemical that binds and activates a receptor is known as an
agonist
. However, some shapes may get jammed in the hole, so that the light won't come on and the hole is now blocked. A molecule that binds but does not produce a response is known as an
antagonist
.

The different types of neurotransmitter receptor are often named after compounds that interact with them. Muscarinic receptors, which are found throughout the body, can be
activated by muscarine, a toxic substance found in several kinds of mushroom. Molecules of muscarine will compete with acetylcholine to bind to and activate these receptors. Atropine also competes with acetylcholine to bind to muscarinic receptors. However, it
doesn't
activate the receptor and is therefore an
antagonist
. By blocking the effects of acetylcholine, atropine hinders the actions of the parasympathetic nervous system (the PN, the ‘rest and digest' mechanism).