A is for Arsenic (38 page)

Ringworm is a fungal infection of the skin, and to treat it effectively it is best to remove the hair from the affected area. By the 1920s the standard treatment was 8mg per kilogram body weight of thallium acetate, given in a single dose. By around 15 days later all the hair on the head would have fallen out, exposing the area affected by ringworm. Sulfur drugs were then administered daily to treat the fungus. This method was considered safe, despite a growing appreciation of the toxic effects of larger doses of thallium salts. Around 40 per cent of those treated for ringworm reported mild side effects, and 25 per cent suffered more severe problems, with pains in the legs and stomach upsets. The alternative method of treatment was to use X-rays to make the hair fall out; by comparison, thallium was probably the lesser of two evils.

Later, it was realised that the patient didn't have to swallow the thallium acetate, as it could be applied as an ointment to the affected area. Thallium would then be absorbed through the skin with the same effect, but only a localised patch of hair would fall out. By the 1930s thallium acetate had become such a standard in the treatment of ringworm that it was sold without prescription in over-the-counter remedies called Celio and Koremlou. A 10g tube of one of these typically contained 700mg of thallium acetate.
⁹⁷

In 1930s pharmacies, alongside creams for ringworm, another thallium salt would have been on sale, only this one was a pesticide; somehow, no one thought it odd that thallium compounds were considered completely safe for humans, yet deadly to other animals. Thallium sulfate was added to a sugary syrup that was particularly attractive and effective for rats, cockroaches and ants. Accidents, suicides and even murders using thallium pesticides led to it being banned in the United States in 1972, with many other countries rapidly following suit.

Alternative methods of treating ringworm are now available, and pesticides contain compounds that are more toxic to the target pest than to humans, so you won't find thallium salts for sale in pharmacies today. But there is one medical application of thallium still in use: the thallium stress-test. A radioactive form of thallium, known as thallium-210, is injected in sub-lethal doses (as the chloride salt). The radioactivity emitted by the thallium-210 is detectable from outside the body, and is used to monitor the health of the heart when the patient does moderate exercise. This technique allows specialists to monitor blood flow in the hearts of patients with coronary heart disease, as the thallium-210
is only taken up by healthy parts of the heart muscle, where there is a good blood flow.

How thallium kills

Precisely how thallium interacts with the human body is not fully known. It has no natural biological role, but because of its similarity to potassium it is readily absorbed into the body. Potassium is very abundant in the human body; there is approximately 120g of potassium in the average 70kg man, and it performs a variety of roles. Thallium can replace potassium at all sites in the body, but it will not perform the same functions, leading to a degeneration of all the processes that normally involve potassium. The symptoms of thallium poisoning are a direct result of potassium-based process malfunction.

One of the most important potassium roles is in nerve function. Uptake of thallium in nerve cells is high, because of the abundance of potassium needed by them to generate an electrical signal. Once inside the cell thallium causes significant damage (especially to the long part of the cell, the axon).

Other biological functions of potassium include the release of adenosine triphosphate (ATP), the body's source of energy. Cells with high energy demands, such as nerves, heart and hair follicles (the latter due to their being replaced at a high rate) are therefore particularly badly affected when thallium replaces potassium. There are more problems inside the cell: potassium is important for stabilising ribosomes, structures that build proteins that enable the body to grow, repair itself and carry out chemical reactions. Another important potassium role lies in the production of thiamine, a B vitamin; thallium poisoning can resemble a deficiency of this vitamin.

Thallium has a particular affinity for sulfhydryl groups (–SH), which are common in proteins. It binds to these groups, and disrupts the protein's function. Thallium doesn't target any one protein or enzyme in particular, which explains the wide range of symptoms observed in poison victims. The strength of the interaction between thallium and the sulfhydryl group is not strong enough to trap the thallium permanently at a specific site, so it can dissociate and move on to other proteins or structures in the body, causing further chaos.

The majority of these effects are reversible once thallium has been excreted from the body. It can be excreted in urine, faeces, saliva and sweat, and can also be lost through breast milk and tears. Opinion on how long it takes to excrete thallium via these bodily functions varies, but the size of the initial dose is important. At low doses the half-life of excretion may be between one and three days; larger doses can take a month or more for half the amount of thallium to be lost. Because thallium does not perform the same chemical reactions as potassium, despite its ions being a similar size and identical in charge, cells can recognise the difference, and the body will attempt to excrete thallium, passing it into the gastrointestinal tract. The problem is that as the thallium travels further along the tract it is reabsorbed, because of this likeness to potassium. In this way the same dose of thallium can keep re-poisoning and damaging the body in a cycle of excretion and reabsorption across the walls of the whole gastrointestinal tract.

Owing to its long half-life in the body, levels of thallium can accumulate rapidly through regular small doses until a lethal level is attained. This process causes chronic symptoms over the period of poisoning. No effects may be seen for up to 24 hours, but there may then be symptoms similar to those of mild flu. Thallium salts are irritants, so these initial effects include nausea, vomiting and diarrhoea, but these subside, to be replaced by severe abdominal pains. As the days go by and the doses of thallium accumulate, the symptoms grow progressively worse. There may be muscle weakness and atrophy, a tingling and numbness in the extremities; damage to the peripheral nervous system, and painful legs, with the feet feeling as if they are on fire; the body becomes very sensitive to touch. There can be psychological effects, too, with mood swings, sleeplessness, periods of confusion and even hallucinations.

About two weeks after first ingesting thallium salts, the hair starts to fall out – a classic signal of thallium poisoning, one that can leave the victim completely bald. There may also be skin-pigmentation changes and irritation, particularly around the roots of the hair, due to the effects of the poison on sweat
glands. Around three weeks later Mees lines – white horizontal lines – appear on the fingernails and toenails. These lines are also seen in arsenic poisoning (see page
here
), but they are less marked with that poison than in thallium poisoning. Unlike in arsenic poisoning, thallium is not reliably retained in the hair,
⁹⁸
despite its affinity for sulfhydryl units (which are abundant in hair and nails).

An alternative murder method to gradually poisoning the victim is to give them a single fatal dose. For humans this is 12–15mg for every kilogram of body weight; approximately 1g would constitute a fatal dose for an adult. The symptoms of acute thallium poisoning appear rapidly, with vomiting and diarrhoea occurring within hours, and severe neurological symptoms appearing between two and five days later. These symptoms can include abdominal pain, nausea, vomiting and diarrhoea, dramatic weight loss (owing to the vomiting the body cannot absorb enough nutrients to maintain body weight), delirium, slower breathing, and in a short space of time seizures, coma and death, which can occur any time between hours and weeks after the thallium is administered, depending on the dose and what, if any, treatment is given.

Is there an antidote?

When
The Pale Horse
was written in 1961, there was no standard treatment for thallium poisoning other than supportive care until the body could excrete the poison of its own accord, with luck. If thallium poisoning was suspected (which it rarely was), the suggested method of treatment was as follows: 1) removal of ingested thallium by stomach-pump, followed by treatment with activated charcoal; 2) promotion of urinary
excretion by abundant intake of fluids, followed by the administration of potassium chloride. If the thallium had been absorbed through the skin, then only the second part of the treatment was liable to be of any use.

A few years after the publication of
The Pale Horse
, research began on finding an antidote for thallium poisoning. Initial attempts used dimercaprol, or British Anti-Lewisite, a chemical developed during the First World War as an antidote to Lewisite, an arsenic-based chemical weapon. Dimercaprol contains sulfhydryl groups for which some metals, especially arsenic, have a high affinity. The compound binds to arsenic and other toxic metals, allowing them to be excreted safely. Unfortunately, dimercaprol has almost no effect on thallium. Even though the metal has affinity to sulfhydryl groups, it does not bind with sufficient strength to make dimercaprol an effective treatment for thallium poisoning.

A more successful antidote was dithizone, which significantly increased the amount of thallium excreted in urine but was not without its problems. Dithizone, though better than dimercaprol, still does not bind strongly enough to thallium to prevent some of it being re-released into the body; dithizone and other chemicals that work in this way (known as chelating agents) can therefore take thallium from areas where it has been sequestered and is causing few problems, and reintroduce it into a more active and dangerous role within the body. In other words, chelating agents can make poisoning symptoms worse, even while the patient is being treated.

Thallium can also be removed from the blood using dialysis, a process that forces thallium to diffuse out of the blood through a membrane. This process needs to be repeated again and again as more thallium leaches out of tissues and organs into the bloodstream. The leaching process can be speeded up by giving the patient potassium chloride. This helps displace thallium from around the body. However, Prussian Blue – a compound we have met a number of times (see pages
here
and
here
) – is nowadays the treatment of choice for thallium poisoning because it binds to the metal more effectively than other agents,
and has no known hazards associated with it. Doses of 250mg per kilogram of body weight are administered orally to trap the thallium, and to prevent its absorption into the body. The thallium-bound Prussian Blue is then excreted via the bowels, often turning the faeces blue. This treatment was established in the early 1970s – too late for the victims in
The Pale Horse
.

Some real-life cases

The first known case of murder by thallium poisoning in Britain occurred in 1962, only months after
The Pale Horse
was published. A coincidence? Many thought not, but then many things are more obvious in hindsight. The murder in question was of Molly Young by her 15-year-old stepson, Graham. Graham Young had been obsessed by the macabre, and poisons in particular, since he was a small boy, but the turning point in his career as a prolific poisoner was when his father gave him a chemistry set as a reward for passing his school exams, when he was 11. He purchased his first bottle of poison, 25g of sodium antimony tartrate, from a local pharmacist when aged 13½, even though sales of scheduled poisons were prohibited to those under 17. The pharmacist was duped into thinking Young was much older owing to his extensive chemical knowledge. Before this point Young had only studied the underlying theories of chemistry, and particularly of poisons, but in early 1961 he started putting his theories into practice. His victims were his father Fred, his sister Winifred, a school friend, Chris Williams, and Molly, his stepmother, who was singled out for particular attention because he disliked her.

Young chose his victims because it was easy to poison them, rather than because he had any particular grudge. He tampered with food in the family house, dropping antimony compounds into tea and coffee or sometimes into jars of sauce or chutney. The effects were dramatic. Antimony compounds have been used for centuries as emetics; their ingestion results in copious and violent vomiting. In this respect antimony is its own antidote; much of the poison is expelled shortly after ingestion. Unfortunately the small amount that remains in the body stays
for a long time, and repeated doses of antimony salts have a cumulative effect. A lethal dose for an adult is around 1g.

Young's antimony-based poisonings continued over several months, but despite the victims consulting numerous doctors and specialists, poisons, and indeed Graham, were never suspected. One morning Young's sister Winifred was drinking her usual cup of tea, but she complained that it tasted bitter. She didn't finish the tea, and went off to work as normal. On the way she started to feel dizzy, and she had to be helped off the bus. Somehow she got to work, where she found she could not focus her eyes properly. Her co-workers were worried, and one of them took her to a nearby hospital where she was diagnosed, and treated for atropine poisoning. This time Young was immediately suspected, and there was a huge row when Winifred arrived home. Graham flatly denied poisoning his sister, and became so upset that Winifred eventually apologised to him. Later he confessed to adding 50mg of atropine to her tea (the lethal dose is approximately 100mg).