A is for Arsenic (11 page)

There are many other sources of cyanide. As Agatha Christie mentions in
Sparkling Cyanide
, one legitimate reason for having cyanide compounds in the home, aside from those found within fruits and nuts, is for photography. The compounds involved are potassium ferricyanide (K
3
Fe(CN)
6
), an orange-red crystalline solid; and a compound we've already encountered, Prussian Blue, known in photographic circles as ferric ferricyanide([Fe
7
(CN)
18
]). These compounds are used to alter the tones of prints and to produce cyanotypes or blue-prints. Neither is particularly toxic, but both can generate hydrogen cyanide if mixed with acid.

Another form of cyanide compound, and a form commonly associated with murder and suicide, is a cyanide salt such as potassium (KCN) or sodium (NaCN) cyanide. Like table salt, these compounds dissolve easily in water to release the cyanide unit. The water molecules react with the cyanide salt to form hydrogen cyanide, in a process called hydrolysis. The bonds between cyanide and the rest of the molecule are broken easily; therefore potassium and sodium cyanide are both very toxic, with a lethal dose for an adult being around 200–300mg. These salts have applications in gold mining, as potassium cyanide reacts with gold to form soluble gold cyanide compounds that can be washed out of rocks and collected. The gold can then be easily extracted from its cyanide compound. Cyanide salts remain industrially important chemicals, and they can often be found in locked cupboards inside chemistry research labs. Today their sale is tightly regulated and use is restricted to those who know what they are doing.

Potassium and sodium cyanide were once commonly used as insecticides. In fact one suspect in
Sparkling Cyanide
is questioned about the contents of his gardener's shed, and another character discusses the high number of wasps' nests they had that summer. A small quantity of the cyanide salt was
shaken in a bottle of water or weak acid to release hydrogen cyanide, which would kill the wasps or other insects as well as anyone foolish enough to breathe in the gas. A similar process was used in the gas chambers inside US prisons, where convicted criminals were executed. The first execution by gas chamber was carried out in Nevada in 1921. It was supposed to be a quick death, but some prisoners held their breath and struggled. The prisoner was taken into an airtight room; after the door had been sealed, a lever was pulled that dropped sodium cyanide pellets into a bucket of sulfuric acid under the prisoner's chair. After the prisoner died – sometimes more than eight minutes after first exhibiting convulsions – the room was purged with air. The last execution by gas chamber was in 1999. Lethal injection is now the preferred method of execution in the United States.

The use of cyanide to murder people was perfected by the Nazis during the Second World War; cyanide compounds were used to kill millions in the Holocaust. Using the excuse of pest control, the Nazis manufactured and transported tonnes of Zyklon B (a trade name for a cyanide-based pesticide) to the concentration camps. Tins of Zyklon B contained hydrogen cyanide, a stabiliser and an odorant (ethyl bromoacetate), the latter presumably acting as a warning for the guards in case there was a leak. Hydrogen cyanide boils at 26⁰C and would quickly vaporise in the hot confines of the gas chambers. In large doses hydrogen cyanide is mercifully quick-acting and it can kill almost instantly. As the war drew to a close, many of the Nazi leaders, including Hitler himself, bit into cyanide capsules to kill themselves rather than face capture and trial.

How cyanide kills

Cyanide kills owing to its interaction with a specific enzyme, cytochrome c oxidase. Regardless of whether cyanide is introduced to the body in compounds such as amygdalin or in the form of cyanide salts, the result is the same. Enzymes in the gut interact with cyanogenic glucosides, and cyanide salts react with stomach acid; in both cases hydrogen cyanide is
produced. Hydrogen cyanide is rapidly absorbed into the bloodstream and transported to the places where it does the real damage.

In the bloodstream, cyanide attaches to haemoglobin, the protein that carries oxygen from the lungs to the rest of the body. Each haemoglobin protein contains four globular subunits, each containing a single atom of iron to which oxygen – or cyanide – binds. Cyanide binds more strongly to iron, so it can displace the oxygen molecules. Haemoglobin represents a highly efficient system for distributing oxygen around the body; this same efficiency allows cyanide to be rapidly delivered to the sites where it does the most damage – inside our cells.

Almost every cell in our body contains structures called mitochondria, which function as the ‘engines' of the cell by carrying out respiration. Respiration is the process whereby oxygen from the lungs, delivered by haemoglobin, reacts with glucose in a series of controlled steps to release energy in the form of adenosine triphosphate (ATP). Cells with high energy demands have large numbers of mitrochondria. Liver cells can contain more than 2,000 mitochondria (while red blood cells have none). Mitochondria are particularly important in heart and nerve cells owing to their high energy demands. Each step in the complex process of energy release and ATP production is controlled by a specific enzyme. The cytochrome c oxidase enzyme is the final step in the cascade of reactions of respiration. An atom of iron lies at the active site of cytochrome c oxidase, and it is here that an oxygen molecule normally binds. As in haemoglobin, cyanide readily takes the place of oxygen; it binds to the iron atom irreversibly, stopping the flow of chemical reactions in their tracks. With the source of its energy blocked, the cell rapidly ceases to function, and cell death occurs quickly.

Swallowing large doses of cyanide can kill in minutes owing to massive, widespread cell death; though some individuals may survive longer, death usually occurs within four hours. The symptoms shown by cyanide victims in the short window of
time before they die can include dizziness, rapid breathing, vomiting, flushing, drowsiness, a rapid pulse and unconsciousness.

Is there an antidote?

Any emergency treatment has to be given quickly, to prevent the cyanide reaching the cytochrome c oxidase enzyme. The problem with any antidote, though, is the speed at which cyanide acts. Even today, with a range of antidotes available, 95 per cent of accidental cyanide poisonings are fatal. Mouth-to-mouth resuscitation is not advisable when dealing with cyanide poisoning, as the rescuer is likely to inhale hydrogen cyanide from the stomach or lungs and be poisoned themselves. Today, people working with cyanide compounds as part of their job will usually have a cyanide antidote kit to hand in case the worst happens.

The first known effective antidote was amyl nitrite, a compound that was first synthesised in 1857. Its effect on the human body was soon noticed, and by 1859 the compound had been shown to relax smooth muscle and was being used to treat heart pain and angina. Around the turn of the century its effectiveness in the treatment of cyanide poisoning was also noted; the results of a study carried out in the United States and published in 1933 confirmed this. If UK doctors had read the paper and adopted its recommendations this treatment might have been available to George and Rosemary Barton in
Sparkling Cyanide
.

Amyl nitrate is a clear, colourless liquid that boils at 21°C. Glass vials would be popped open so the vaporised liquid could be inhaled, hence the name ‘poppers' for modern recreational use of the drug. One of the actions of the compound is the conversion of haemoglobin to a similar compound, methaemoglobin; cyanide binds preferentially to the iron in the methaemoglobin rather than the iron in cytochrome c oxidase. The resulting compound is not toxic and is safely excreted in urine, leaving the cytochrome c oxidase uncontaminated and the patient able to process oxygen normally. This treatment is still used for cyanide poisoning today, but it does have a downside.
Methaemoglobin is unable to bind with oxygen, so the body suffers a reduced oxygen capacity. This can lead to symptoms including headaches and convulsions. Another chemical, methylene blue, is needed to convert the methaemoglobin back to haemoglobin, so it can function normally again.

Today there are many antidotes for cyanide poisoning, but none of them is completely free from complications. Many work in a similar way to amyl nitrite by providing an alternative site for the cyanide to bind to, so it doesn't affect cytochrome c oxidase. One example of this is the use of hydroxocobalamin, a form of vitamin B12. It acts in a similar way to methaemoglobin, and the resulting cyano-complex is non-toxic and excreted in the urine. This antidote has the added benefit of leaving all the body's haemoglobin untouched so no further treatment is required. Unfortunately, hydroxocobalamin is expensive, and not universally available. A cheaper alternative is dicobalt-EDTA, sold as Kelocyanor. Cyanide binds to cobalt just as well as it does to iron, but cobalt compounds are themselves toxic. A patient given Kelocyanor when they have not been poisoned by cyanide may die of the cure.

A different approach makes use of the body's own defence against cyanide, the enzyme rhodenase, which evolved over the millennia to deal with cyanide in our diet. The enzyme uses thiosulfate (S
2
O
3
2
-
) to convert cyanide (–CN) to thiocyanate (–SCN) but it works slowly, too slowly to be effective against a sudden large dose of cyanide. By supplying the body with extra thiosulfate, the enzyme can react with more cyanide. This treatment is slow-acting so it is often given along with amyl nitrite to speed things up. So far this method of treatment is based only on animal experiments, with few case studies. Giving oxygen is another treatment that can support life while the body metabolises the cyanide naturally, but it is not an antidote in itself.

Some real-life cases

Agatha Christie did her research on cyanide poisoning, but, excluding the use of hydrogen cyanide in the Holocaust, she
had quite a few real-life murder cases to draw on. Perhaps one of the best-known cyanide poisonings is a failed but famous attempt from 1916.

Confidant of the Tsarina of Russia, Grigori Yefimovich Rasputin, known as the ‘mad monk', had more than a few enemies. Some of them – Prince Felix Yusupov, the Grand Duke Dmitri Pavlovich, and the right-wing politician Vladimir Purishkevich – apparently lured Rasputin to the Yusupovs' Moika Palace for cake and Madeira wine. The cake and wine were said to be laced with enough cyanide to kill ‘a monastery of monks' but it left Rasputin unaffected. He was then shot, at least twice, but was still alive and fighting back against his would-be assassins. At this point he was beaten into submission, tied up in a carpet and dropped into the frozen Neva river. His body was recovered two days later, and a post-mortem revealed that he had died from drowning.

There are a number of theories that might explain what happened that day:

1. His assassins were terrible poisoners and did not put enough cyanide in the food to kill him, or mistook an innocuous substance for cyanide salts.

2. Rasputin suffered from alcoholic gastritis.

3. Suspecting someone might try and poison him, Rasputin dosed himself regularly with small amounts of poison to build up an immunity to a larger, normally lethal, dose.

4. The sugary cakes and wine acted as an antidote to the cyanide.

5. The story is made up and Rasputin was killed by a single shot to the head fired by a British secret service agent.

The first theory is now impossible to prove or disprove. The cake and wine were not analysed, and those involved changed their stories several times, making their testimony rather unreliable.

The second theory is certainly reasonable and based on good science. Alcoholic gastritis could offer some protection against cyanide poisoning because it causes a thickening or inflammation of the stomach lining, and a decrease in production of stomach acid. With less stomach acid about, less of the potassium cyanide would have been converted into lethal hydrogen cyanide. However, we do not know if Rasputin suffered from this condition; his sister reportedly claimed he suffered from an
excess
of stomach acid, and was therefore unlikely to eat cakes and wine in the first place.

The third theory is also worth closer scrutiny, as stories of Mithridatism, as it is properly known, have been around for at least 2,000 years. The King of Pontus, Mithridates, fearful of poisoners, apparently built up an immunity to poison by regularly administering sub-lethal doses over a long period of time. The concoction he developed included more than 50 ingredients and was said to protect against every known poison. When the King was captured, and wished to kill himself by poisoning, the attempt failed (obviously) and he had to ask a guard to run him through with a sword.

Much of Mithridates' life is the stuff of legend, but could someone develop an immunity to poison using this method, or an adapted version of it? The answer is yes – and no. It is possible to develop immunity to some animal venom by administering sub-lethal doses. This is used successfully by people who work closely with venomous animals, zoo-keepers for example. But animal venom is very different from cyanide; your body will not build up an immunity by eating small amounts of cyanide salts. It will process the cyanide into thiocyanate and get rid of it, or you will be poisoned and quite possibly die.

The fourth theory, the possibility of a glucose antidote, is also promising. Research on rats has revealed that glucose offers some protection against the effects of cyanide poisoning, though the mechanism is not known. One theory is that the cyanide reacts with glucose to form non-toxic compounds that can be excreted, but more work is needed to establish the
exact method; glucose is not officially recognised as an antidote to cyanide poisoning.

The fifth Rasputin theory is, of course, the most likely explanation.