A is for Arsenic (8 page)

How neurotransmitters work. Signals are transmitted across the gap between nerves (or nerves and muscles) using chemicals called neurotransmitters. They are released from the nerve-ending of one and dock at receptors on the other, triggering a response.

Atropine – in small doses – can be used to dry up the secretions normally produced as a result of PN activity. In the past it was used to treat the symptoms of hay fever and colds by stopping the production of mucus, and atropine is still sometimes used today in cough syrup, where it has the added effect of relaxing the muscles used to cough. Atropine is also injected before operations to dry up bronchiole secretions in the lungs, which might otherwise block airways during surgery,
²⁹
and it is sometimes administered as a palliative to stop
the ‘death rattle' in dying patients that can be so distressing for the family; the ‘death rattle' is caused by an accumulation of saliva in the throat and upper chest, which the patient is no longer able to clear for themselves.

The PN stimulates digestion by increasing the production of gastric juices, and by activating muscles that move food through the gut. It also controls the excretion of waste from the bowel and bladder. Atropine is therefore sometimes prescribed in the treatment of irritable bowel syndrome, and in the past it was given to children to stop bed-wetting because it blocks signals to the muscles controlling the bladder.

Even when atropine is given in therapeutic doses (5–10mg) there can be worrying side effects in sensitive individuals, such as dilated pupils, blurring of vision and an increased heart rate. But these side effects can be utilised, in the treatment of eye conditions such as miosis,
³⁰
for example. Another condition treated with atropine is anterior uveitis, which causes inflammation of the iris. Atropine paralyses the muscles controlling the iris, causing the pupil to dilate and thereby relieving the pressure. Blurred vision will occur initially because the muscles that control the lens inside the eye are also temporarily paralysed, but these effects soon wear off. However, the effect on pupil-size can last for days. The dose is low, and application is localised (with drops administered directly to the eye) to minimise side effects, though some individuals have reported suffering hallucinations as a result of using these eyedrops.

The feelings of disorientation and even hallucinations from atropine use are due to its effects on the other main part of the nervous system, the central nervous system, or CNS. Hallucinations from the use of atropine are visual and realistic – the appearance of faces, trees and snakes are often
reported, as opposed to the psychedelic images and patterns often experienced by those under the influence of drugs such as LSD. People often describe their visions in terms of looking at the world through a sheer fabric or piece of tissue paper, which possibly reflects a combination of the effects of the drug on the lens in the eye as well as on the brain. In medical conditions, patients given a dose of atropine often appear as if they are daydreaming – it is difficult to get and maintain their attention. Initially patients are docile, but this may progress to paranoia as they realise that what they think they are seeing isn't really there; there are difficulties with the perception of time, and a sense of disorientation is common. The hallucinogenic effects of atropine can last for up to twelve hours.

Atropine has a short half-life in the body of around two hours. Most of the compound is excreted unchanged in urine, but a significant proportion is metabolised by enzymes in the liver. Even so, it takes a long time for all the atropine to disappear from the body, and the effects of the drug can persist for days. This also means that regular small doses can accumulate in the body, leading to chronic poisoning. At high doses atropine causes hot, dry, red skin (sometimes a rash appears, usually on the upper half of the body), dry mouth, a rapid pulse and breathing, urinary retention, muscular stiffness, fever, convulsions and coma, in addition to the disorientation, hallucinations and delirium seen at smaller doses. The most worrying effects are on the heart and on breathing.

The effect of atropine on the heart is caused by the presence of muscarinic receptors in that organ. The sympathetic nervous system acts to increase heart rate, while the PN slows it. By blocking muscarinic receptors in the heart, atropine serves to diminish the signals from the PN telling it to slow down; this means that atropine can be used as an antidote for overdoses of drugs that slow the heart (it will also help raise the blood pressure and pulse). However, if too much atropine is administered, atropine poisoning can result. Fortunately it is fairly easy to diagnose atropine poisoning, by following this mnemonic: ‘hot as a hare, blind as a bat, dry as a bone, red as a
beetroot and mad as a hatter'. A patient who survives for longer than 24 hours will probably recover.

Is there an antidote?

When low doses of atropine have been administered, simply removing the source of the poisoning is often enough for the victim to make a full recovery from the effects, though it may take a few days; atropine does not cause any permanent damage to the body. A poisoner might choose to take a more direct approach to dispatching their victim, though, by administering a single large dose of atropine, perhaps in some food or drink. Due to its bitter taste, atropine is easily detected by anyone consuming tainted food, so the poisoner must ensure that a lethal dose is ingested in the first mouthful. This was the approach taken by the murderer in the Miss Marple short story
The Thumb Mark of St Peter
.
³¹

Even if the victim has ingested a fatal dose there is still a chance of recovery, as a range of antidotes and treatments is available. In a rare moment of compassion for her victims, Dame Agatha tells us of one antidote for atropine poisoning, pilocarpine, in
The Thumb Mark of St Peter
; Geoffrey Denman calls out ‘pilocarpine' as he succumbs to the fatal effects of the atropine that had been added to a glass of water by his bedside. Christie was not kind enough to have Geoffrey Denman survive; witnesses at his death think he's delirious and talking about fish, with one witness saying it ‘sounded like “pile of carp”'. The short-sighted doctor attending Geoffrey misses the tell-tale signs of dilated pupils.

A post-mortem examination of Denman's body fails to reveal the presence of atropine, though detection can be difficult if the post-mortem is delayed. Atropine leaves no obvious indications post-mortem; even the dilated pupils so characteristic of atropine use are an unreliable pointer after death, since the pupils naturally dilate as the muscles relax. In
cases of suspected poisoning it would be normal to take samples from the stomach contents and body tissue to analyse for toxic compounds. Toxic metals are relatively easy to extract in such cases, as the surrounding tissue can be destroyed by the heat of chemical action, leaving the metal behind. Organic compounds such as atropine are generally destroyed by such processes, though, so they must be extracted and isolated intact before they can be identified. A method for the extraction of plant alkaloids has been available since 1850, when one was devised by Jean Stas (see page
here
). A modified form of Stas's methodology is still in use today.

Once a plant poison has been isolated from human remains it has to be identified. In the past identification was often carried out by taste,
³²
or by administering some of the extracted compound to a test animal such as a mouse or a frog to watch what symptoms the animal developed. If the symptoms of the animal matched the symptoms shown by the human victim the poisonous element had successfully been isolated. The symptoms of poisoning could then be used to identify what the chemical was.

Today a range of analytical techniques is available to confirm the presence and identity of a poison, if poisoning is suspected. Chromatography (‘colour-writing') is a method for separating out components of a mixture. First developed in 1855, this method was initially used to separate out plant pigments. You may remember as a child putting dots of food colouring or coloured inks on pieces of paper and dipping the ends in water. The water slowly rises up the paper by capillary action, carrying the ink along with it. The varying solubility of the dyes and inks in water means they travel at different speeds up the paper, and the result is a series of differently coloured dots in a vertical line on the paper. The distances between the starting point and the point where the dots of ink stop are
characteristic for each ink. Scientists today use a variety of subtly different chromatography techniques and materials, but the principles are essentially the same. Samples extracted from tissues can be separated out by their differing solubilities in different solvents. Compounds that are very soluble are swept along in the solvent as it moves through the apparatus, while less soluble compounds lag behind. The rate of travel of compounds in an unknown sample is compared to known, pure samples. Identical rates under identical conditions indicate that the substances in the known and unknown samples are the same. This technique can also be used to determine how much of a plant alkaloid is present.

When Agatha Christie wrote
The Thirteen Problems
in 1932 chromatographic techniques were in their infancy, and commercial systems would not appear until after the Second World War. Chemical tests may have been available, and reactions between certain compounds carried out under certain conditions can produce characteristic colours, but these are unreliable (see page
here
). Despite the problems faced by 1930s pathologists, it should have been possible to identify atropine in Geoffrey Denman's remains had they known to look for it. Miss Marple, however, had no need to rely on toxicology reports; she identified the poison from the slightly obscure ‘pilocarpine' clue.

Pilocarpine is another plant alkaloid, isolated from the leaves of jaborandi,
Pilocarpus pinnatifolius
. It binds to the same receptors as atropine but acts as an agonist, activating them to cause increased sweating and salivation, and slowing the heartbeat. Pilocarpine has medical uses in sweat tests, to measure the amount of chloride and sodium excreted in sweat, and to treat dry mouth, a condition often experienced after radiation therapy for head and neck cancers. It has also been used, in the form of eyedrops, to treat glaucoma. Because the effects of atropine and pilocarpine are opposite they can act as antidotes to each other.

Pilocarpine has been used in a real-life poisoning case, and atropine was administered by doctors who treated the victims. Unfortunately two of the victims, residents at a long-stay psychiatric establishment, West Park Hospital, did not survive. On 14 August 1985, some of the patients on the Exford ward at West Park were taken ill after their evening meal. There were bouts of coughing and excessive salivation, five of the 24 patients on the ward had difficulty breathing, and three had to be taken to the nearby Epsom District Hospital for treatment. Two women, 82-year-old Nora Swift and 99-year-old Florence Reeves, died despite the best efforts of the hospital staff. Urine samples taken from the women were analysed and showed the presence of pilocarpine and atropine. The atropine had been administered by the hospital to treat the symptoms displayed by the patients; it was the pilocarpine that had poisoned them.