A is for Arsenic (5 page)

Arsenic trioxide, arsine gas and the arsenic pigments such as Scheele's green are all
arsenite
compounds rather than arsenates; they kill because of a different chemical interaction with the body. To describe how arsenite compounds do this I'll use the example of arsenic trioxide, as this has been the arsenite compound most commonly employed in murder over the centuries.

The first symptoms of arsenic poisoning – severe vomiting and abdominal pain – appear approximately thirty minutes after ingestion, and are triggered by the irritant effects on the tissues of the stomach. If the victim is lucky much of the poison will be eliminated from the body at this point, but the unlucky ones will have absorbed a fatal amount, approximately 100–150mg, into the bloodstream. Many victims of arsenic poisoning in the past survived for weeks, probably because they purged much of the poison in vomit and diarrhoea. Many nineteenth-century arsenic poisoners were very attentive nurses, ensuring that they were on hand to administer extra doses to achieve their desired result.

The inflammation of tissues in the stomach and intestine caused by arsenic trioxide may be visible to pathologists at post-mortem examination, but it is not the cause of death. The violent vomiting and profuse diarrhoea, however, can cause dehydration, and this may kill if the fluids cannot be replaced. However, it is arsenic trioxide's disruption of biochemical processes in the body that usually proves terminal for the victim.

Chemical reactions inside the body are carried out by proteins called enzymes. These are large molecules made from
strings of amino acids that wrap and twist into precise shapes that allow them to carry out their function. Enzymes are able to carry out specific chemical reactions, on compounds generically referred to as substrates, at a very fast rate. One analogy often used to describe their operation is the ‘lock and key' theory. The enzyme is the lock, the substrate is the key and the active site where reactions occur is the space where the key fits into the lock. Very few keys will open more than one lock because of the close match needed between the two complementary elements. The enzyme alters the substrate or ‘key' in a chemical reaction, changing its size and shape so it no longer fits in the ‘lock'. The substrate then dissociates from the enzyme, leaving it free for the next substrate to bind to.

Some of the amino acids that form proteins and enzymes contain sulfur atoms, and these atoms often form crucial chemical bonds that hold an enzyme in shape.
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Arsenic (in the form of arsenite) bonds very strongly to sulfur atoms, and this can distort the shape of the enzyme or ‘lock' and thereby stop it working. Once arsenic compounds have entered the bloodstream they can be distributed around the body and potentially affect any sulfur-containing enzymes or proteins that they encounter.

Because of the huge number of enzymes and their diverse roles in the body, arsenic poisoning can present many different symptoms. The amount of arsenic administered has a dramatic effect on the symptoms displayed, and the ultimate cause of death. Massive doses of arsenic, ten times the minimum lethal dose, will produce symptoms of violent gastroenteritis, vomiting and intense stomach pain, along with copious amounts of watery or bloody diarrhoea. Later the skin becomes cold and clammy, blood pressure drops and death comes from circulatory failure within hours. Convulsions and coma may be seen, and these signal that the individual is very close to death.

Some of the many enzymes that arsenite compounds can disrupt are those involved in the energy process within cells. Without a supply of energy a cell cannot function, and it rapidly dies. When large numbers of cells die this leads to organ failure. Some cells have higher energy demands than others; for example, heart and nerve cells require more energy than red blood cells do. Other enzyme-regulated metabolic processes within cells are also susceptible to arsenic interference; there are many ways arsenic can cause cell death. If the poisoned individual survives for a day or two they grow jaundiced, and urine output reduces or stops because of damage to the liver and kidneys, the organs normally involved in detoxifying and eliminating poisons from the body.

Arsenic doesn't only kill by acute poisoning, as described above. It is also lethal following the slow accumulation of small amounts administered over a long period of time; this is known as chronic poisoning. At these lower doses, arsenic causes nausea and vomiting but also headaches, dizziness, cramp and variable paralysis that may progress over a period of several weeks. In addition, heart arrhythmias may occur. Death in chronic cases is due to multi-system organ failure; in such cases there can also be damage to the nerve cells of the central nervous system, specifically to the axons, the long parts of a motor neuron (a nerve cell that controls movement) that stretches from the spinal cord to the extremities, carrying messages. Symptoms that result from this damage include numbness or burning sensations in the hands and feet. Chronic poisoning may also damage the liver, kidneys and circulatory system. Regular doses of arsenic accumulate in areas of the body with high sulfur content, such as in the protein keratin, which makes up hair and nails and is also present in the skin. Over time the skin of an arsenic-eater, for example, would lose its ‘peaches and cream' quality and become darkened (a process called hyperpigmentation), with horny or scaly patches on the palms of the hands and feet. Characteristic transverse white lines across the nails, known as Mees lines, would also appear. There is likely to be weight loss and, if the
person survives all of this, arsenic can go on to cause cancer of the skin, lungs and liver.
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The increased risk of cancer from exposure to arsenic has been known about for more than a century. Sir Jonathan Hutchinson (1828–1913), a physician and an expert in dermatology, amongst other things, noticed an unusually high number of skin cancers in patients who had been prescribed arsenical medication for various illnesses. It is thought that arsenic disrupts the body's ability to repair DNA damage, though several mechanisms may be involved.

The consequences of long-term exposure to arsenic are amply demonstrated in places such as the Ganges Delta, where wells built by well-intentioned aid agencies were bored through arsenic-containing rocks. This led to mass low-level poisoning. The wells were built to prevent the spread of water-borne diseases such as cholera that were common in areas where surface waters were poorly maintained. The wells have saved lives through lowering incidents of cholera, but tens of millions are now at risk of arsenic exposure.

The body does excrete arsenic, but slowly. As long as arsenic is not ingested at a higher rate than it can be excreted all is well, and this is the case for most of us, most of the time. Arsenic is present in our environment, in the soil and in water, and thereby gets into our food supply, but it's generally in very small quantities that our bodies can manage.

The half-life (time taken for half the amount to disappear) of arsenic trioxide in humans is approximately ten hours. Arsenic trioxide is either excreted unchanged in urine or metabolised into other arsenic compounds. Methyl groups (–CH
3
) are sequentially added to the arsenic molecule; it was once thought that this process detoxified the arsenic. In fact
many of the methylated arsenic compounds are just as toxic as arsenic trioxide, if not more so. The methylated compounds may result in a garlicky odour to the breath, similar to the odour of trimethylarsine produced by the mould growing on Victorian wallpaper. Methylated arsenic compounds have a half-life of around thirty hours. Therefore, excretion of 50 per cent of ingested arsenic can take between one and three days.

Is there an antidote?

A treatment for acute arsenic poisoning was first demonstrated in 1813 at the French Academy of Sciences, when chemist Michel Bertrand (1774–1857) ingested 5g of arsenic (around 40 times the lethal dose) along with some charcoal. He survived and showed none of the usual symptoms of arsenic poisoning, proving that the charcoal had somehow inactivated the arsenic. In fact the arsenic became trapped in tiny cavities within the charcoal, preventing it from being absorbed into the body. Studies have shown that charcoal is effective in absorbing many other poisons and it is still used as the first line of treatment in suspected poisoning cases, though it is only really effective if it is used relatively soon after ingestion.
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Charcoal can be processed further to make it ‘activated charcoal' by treating it with steam, carbon dioxide, oxygen, zinc chloride and sulfuric acid at high temperatures (260–480°C); this increases the number of pores (and therefore it can absorb more poison).

Once arsenic has been absorbed into the body charcoal cannot remove it, and alternative methods must be used. These were developed in response to the invention of Lewisite gas, an arsenic-based poison, in the First World War. British Anti-Lewisite (BAL), or dimercaprol, is known as a ‘chelating' compound; a chelate wraps around a metal ion, such as arsenic, binding to it at several points to form a tightly bound metal-chelate complex. Once BAL has scavenged the arsenic from
the body, the resulting arsenic-chelate can be excreted. Other chelating agents have been developed since then that can extract arsenic more efficiently; these are more specific for toxic heavy metals, and so have fewer side effects. Unfortunately, chelating agents aren't effective for
chronic
arsenic poisoning. The most effective treatment in these circumstances is simply to reduce exposure.

Some real-life cases

Agatha Christie referred to many real-life arsenic-poisoners in her novels, and used poisoning cases as inspiration for her plots. One poisoner she mentioned by name was Frederick Seddon, a particularly avaricious landlord who was found guilty of killing one of his tenants. Miss Eliza Mary Barrow, a wealthy spinster, died after Seddon had persuaded her to make over all her money to him. Suspicion was only aroused by Barrow's relatives, who were surprised to hear that not only had Eliza died, but that she had already been buried. Seddon even haggled over the price of the funeral. When the relatives enquired about the money they knew Eliza possessed, they were told by Seddon that there had been very little. In court the prosecution was able to show that arsenic was present in Barrow's body. Seddon claimed that Barrow must have got up and drunk from the dishes of arsenical fly-papers that had been placed in her room.

Another possible arsenic murderer, Madeleine Smith, also gets a mention in several Agatha Christie stories. In 1855, aged 20, the Glasgow socialite embarked on an affair with Pierre Emile L'Angelier. Smith had promised to marry L'Angelier, but her parents, unaware of her attachment, had found another eligible bachelor, William Harper Minnoch, and arranged a formal engagement with their daughter. Madeleine attempted to end the relationship with L'Angelier and asked him to return her love letters. He instead threatened to send them to her parents so her engagement to Minnoch would be broken and she would be forced to marry L'Angelier. Soon afterwards L'Angelier wrote in his diary that he felt unwell, often after
seeing Madeleine. It was claimed she gave him cocoa to drink. He told his friends that he thought Madeleine was poisoning him, and around this time Madeleine was seen buying arsenic in a pharmacy. By March 1857 L'Angelier's illness had grown so severe that a doctor was called, and morphine was administered to alleviate his pain. This was to no avail – by the following morning he was dead. An autopsy revealed an enormous amount of arsenic in his stomach, more than 87 grains (approximately 5g). At the time no other case of murder had seen such large quantities present in the body (although suicide cases had). Such a large amount might be expected to be difficult to administer without the victim noticing but, as was discussed in the trial, up to 6g (20 to 60 times the lethal dose) of fine arsenic powder, mixed with two teaspoons of cocoa, plus milk or boiling water in a teacup, cannot be detected by appearance or smell. However, on cooling, the arsenic sedimented out of the cocoa, and curdled the milk.

Though Madeleine had a motive to kill her lover and was known to have purchased arsenic, the case was far from clear-cut. Madeleine claimed that the arsenic was for her complexion but, in accordance with the law, the arsenic she had purchased from the pharmacist was coloured with indigo dye. Madeleine must have known of a way of removing the dye from the arsenic before applying it to her skin (washing the arsenic in cold water would have done the trick). The arsenic found in L'Angelier's stomach was white arsenic with no trace of dye. The defence barrister prevented L'Angelier's diary from being entered as evidence in the trial, and the prosecution had failed to keep Madeleine's 200 undated love letters in their original envelopes. It became impossible to prove conclusively when the two had met, or that Madeleine had had the opportunity to administer the poison.

The scandal of pre-marital sex and murder ensured huge publicity for the trial, and even after the case against Smith was found ‘not proven', speculation continued. On one side many believed that Madeleine had murdered her lover, but the prosecution was simply unable to prove when. Others believed
that L'Angelier had committed suicide. After the trial Smith went to live in England under an assumed name and married an artist, George Wardle. Two children were born but after many years of marriage the couple separated. Madeleine moved to New York where she changed her name once more, and finally died in 1928.

Agatha and arsenic

The title of Agatha Christie's 1939 novel,
Murder is Easy
, is appropriate. It charts seven murders in a tiny English village in the course of just over a year. The methods used were varied, and chosen to look like accidents or natural diseases. The first victim, Mrs Horton, seemed to have died of acute gastritis after a long illness. Her death was all the more tragic as she had seemed to be getting better before a sudden and dramatic relapse. Even the doctor attending her had been surprised at the suddenness of her death but at the time there was no suspicion of foul play. Only a year later, when the village churchyard is filling up a little too rapidly, does anyone take a closer look at the circumstances of Mrs Horton's illness and death.