A is for Arsenic (21 page)

Alkaloids that can be extracted from
Aconitum
roots include mesaconitine, hypaconitine and jesaconitine, as well as aconitine. The concentration of alkaloids and the ratios of the different forms may vary enormously depending on the species of plant, the region and the season. Most of the poisonous compounds are found in the roots, but all parts of these plants can be lethal if ingested. This happens more often than you might expect, because the roots are often mistaken for horseradish. A tragic case from 2004 illustrates the confusion: Andre Noble, a young Canadian actor, went hiking with his aunt and ate
Aconitum
roots, mistaking them for radishes. He fell ill at his aunt's cabin, and died on the way to hospital.

How aconitine kills

As we've seen, aconitine is one of a number of alkaloids that occur in
Aconitum
plants; it was once used in medical applications, and was the poison used in
4.50 from Paddington
. Aconitine is poorly soluble in water but it readily dissolves in fats and oil; its solubility in fats increases its absorption across
the skin, which allowed the compound to be used in creams and salves for external application. It also means that toxic effects can be experienced by gardeners who handle the plant without wearing gloves.

When aconitine has been absorbed into the bloodstream it is distributed throughout the body, but it binds preferentially to sites that form part of sodium ion channels, found in the cell membranes of nerve and heart cells. Sodium channels allow sodium ions (Na
+
) to flow into a cell, triggering the release of potassium ions (K
+
) out of it. Switching the positions of the sodium and potassium ions is a process called depolarisation. Rapid depolarisation results in an electrical signal that is transmitted along the length of a nerve cell as a wave of sodium channels opens along its length. In heart cells the movement of sodium ions triggers the contraction of the cell, and the coordinated contraction of these cells results in a heartbeat (see page
here
). After each electrical signal or contraction the cell must reset itself to allow the process to be repeated, and molecular pumps move the sodium and potassium ions back to their original positions.

Aconitine is an agonist; it binds to a site on the sodium ion channel and activates it. The channel opens and sodium ions flood in, causing the nerve to fire or the heart cell to contract. But the aconitine causes the channel to stay open and the cell to remain depolarised. The cells cannot reset to their original arrangement because of the increased in-flow of sodium ions – like trying to empty a bath with the taps still running.

The result of aconitine's interactions with nerve and heart cells can be seen almost immediately; symptoms are rarely delayed for more than an hour. Aconitine affects sensory and movement responses as well as the heart, creating an irregular and rapid heartbeat. It produces a wide range of effects and sensations, a few of which appear to be unique to aconitine. A burning sensation is often experienced, which feels like a red-hot poker being drawn across the tongue. There is a sensation of numbness and tingling in the mouth and throat, and a feeling that the throat is swelling up. The individual may
also experience giddiness and a loss of muscular power. The pupils become dilated, the skin grows cold and the pulse feeble, with laboured breathing and ‘a dread of oncoming death'.
⁵⁷
Finally numbness and paralysis set in, rapidly followed by death in a few sudden gasps. Death, due to paralysis of the heart or breathing, usually occurs within two to six hours, but with very large doses death is almost instantaneous. A dose as low as 1–2mg can be fatal. This is a serious poison.

Non-lethal doses of aconitine can be excreted by the body, but the time taken can vary hugely between individuals. The half-life of aconitine is generally in the range of four to 24 hours. Excretion is mainly via the kidneys (though it can also occur via faeces). The rate at which it leaves the body depends on how efficiently the kidneys can filter the compound from the bloodstream and into the bladder. This filtration and excretion process can be affected by the efficiency of the heart; if aconitine is impairing its normal function, the rate of elimination will be slower. Aconitine may also affect the health of the kidneys, further slowing the rate of elimination from the body.

Is there an antidote?

There is no specific antidote available to treat aconitine poisoning, even today. The best care that can usually be offered is prevention of further absorption of the poison. This can be achieved by giving activated charcoal to absorb the poison, and using a pump to remove unabsorbed toxins from the stomach. Supportive care can then be given, such as artificial respiration to maintain breathing, and drug treatments to normalise the heart rhythm. If the patient survives the first 24 hours they can be expected to make a full recovery.

Some experimental antidotes for aconitine poisoning have been discovered, occasionally by accident, but none is a recognised or recommended method of treatment. One
involves giving the patient lidocaine, a local anaesthetic often used by dentists. The drug works by blocking the sodium ion channels in the nerves, thereby counteracting the effects of aconitine. This treatment was given to a Japanese man admitted to hospital with aconitine poisoning in 1992. He was suffering from premature ventricular contraction and ventricular tachycardia – heart problems that can prove fatal if not treated quickly. After administration of lidocaine the patient's heartbeat returned to normal. This drug was first synthesised in 1943 by Swedish chemist Nils Löfgren (1913–1967), and his colleague Bengt Lundqvist (1922–1953) performed the first anaesthesia experiments by injecting himself with it.

A more unusual treatment was discovered in 1992. A paper in the
Journal of Experimental Medicine
discussed the case of a 33-year-old woman who vomited and collapsed in the lobby of a Japanese hotel. An ambulance was called, but the woman fell unconscious during the journey to the hospital and died shortly after arrival. Her death was due to ventricular fibrillation, what is commonly thought of as a heart attack. A post-mortem analysis of her blood revealed the presence of aconitine, mesaconitine and hypaconitine, and it was determined that she had died of poisoning (through ingestion of an
Aconitum
plant, rather than the pure aconitine compound). Further analysis revealed that tetrodotoxin was also present in the woman's blood; this is a poison found in the skin, ovaries and liver of pufferfish. The raw fish, carefully prepared so as not to contaminate the flesh, is known as
fugu
, and it is a great gastronomic delicacy in Japan. Tetrodotoxin acts by inactivating sodium ion channels in nerve cells, and causes death by paralysis of the diaphragm. Tetrodotoxin binds to a different site in the channels to aconitine, and it can delay its action when the two substances are administered in a particular ratio. The symptoms and death of the woman in the Japanese hotel were delayed by the presence of this pufferfish poison.

Pufferfish poisoning has been known of for centuries. Captain Cook recorded the first known case in 1774, when some of his crew ate pufferfish and the leftovers were given to
the pigs. The crew suffered from shortness of breath; the pigs died. The active ingredient of pufferfish poison was first isolated in 1909 by Yoshizumi Tahara, and it has been used since the 1930s in Japan to manage pain in terminal cancer and for migraines.

Some real-life cases

Murders involving the use of aconitine or
Aconitum
plants are very rare, though there has been a relatively recent case. In 2009, Lakhvir Kaur Singh attempted to kill her ex-lover, Lakhvinder ‘Lucky' Cheema, and his fiancée, Gurjeet Choong, using curry laced with poison. The announcement of the couple's engagement was too much for Singh, who apparently bought her poison – probably a crude extract from
Aconitum ferox
, a species known as Indian aconite, and one of the most poisonous plants in the world – especially for the purpose of poisoning the two. After eating the curry, Lucky and Gurjeet complained of feelings of numbness, pains in the stomach, failing sight and dizziness. An ambulance was called but doctors at the hospital were unable to save Lucky's life. Gurjeet recovered after being placed in a coma for two days while the poison was identified and treatment administered. The murderer received a sentence of a minimum of 23 years' imprisonment.

The best-known case of aconitine poisoning, one that Agatha Christie was almost certainly aware of, occurred in 1881. There are several similarities between the real-life case and the fictional poisoning written about later by Christie. Dr George Henry Lamson was a medical doctor who volunteered as an army surgeon in Romania and Serbia. When he returned to England he set up a medical practice in Bournemouth, but he had acquired a morphine habit, perhaps as a result of his experiences of war. Initially Lamson prospered, but as his morphine addiction took over his life his practice floundered, and debts started to build up.

Financial relief came in 1879 in the form of an inheritance. Lamson's wife, Kate, was one of four siblings who had equal shares of the inheritance from their parents. When Lamson's brother-in-law Herbert John died, his portion of the inheritance was redistributed amongst the three remaining siblings.
⁵⁸
However, Lamson's financial relief was short-lived, and his debts continued to grow.

Lamson decided that the only way out of his financial difficulties was another inheritance, and he set his sights on Percy John, Kate's 18-year-old crippled brother. Percy had a curvature of the spine that had paralysed him from the waist down, though he had full use of his upper limbs and was in otherwise good health. Lamson made his first attempt on the boy's life in the summer of 1881. While on holiday on the Isle of Wight, Lamson gave Percy a pill that he dutifully swallowed. Soon afterwards he became very ill, but he made a complete recovery and returned to his boarding school in Wimbledon for the autumn term. Lamson's money worries were becoming acute, and he went to America to try to make his fortune but returned with his situation unimproved. While he was there, Lamson made a significant purchase; a type of gelatin capsule designed for taking powdered medication.

On 24 November 1881, Lamson made another important shopping trip. He bought two grains of aconitine (approximately 130mg) from a pharmacist in London. Lamson was unknown to the pharmacist, but because he was a medical doctor he was able to purchase poisons without having to answer any awkward questions – the pharmacist simply asked for Dr Lamson's name and checked in the register of medical professionals. Finding everything in order he sold the aconitine to Lamson for 2s 9d.
⁵⁹

On 3 December, Lamson paid a visit to Percy at his school in Wimbledon. When he arrived he sat down to talk with
Percy and the headmaster. Sherry was served, to which Lamson added a spoonful of sugar, claiming that it counteracted the effect of the alcohol. At some point during the visit Lamson produced a Dundee cake with three slices already cut and he proceeded to offer them to Percy and the headmaster. He took the last slice for himself. Conversation turned to Lamson's recent trip to America, and he produced some of the capsules he had bought there. He recommended the capsules to the headmaster as a means of giving bitter medications to the pupils so they wouldn't have to taste them. To demonstrate, he filled one of the capsules with sugar, from the same bowl he had used for his sherry, then pushed the two halves together. He gave the capsule to Percy, complimented him on being a champion pill-taker, and asked him to show the headmaster how easy it was to swallow these special pills. Percy did as he was told. Lamson then promptly made his excuses and left, saying he did not want to miss his train to catch the boat to France. In fact he had just missed one train and the next would not be for 30 minutes or so; the station was just a few minutes' walk away, but Lamson would not stay.

Within ten minutes of Lamson leaving, Percy became ill. He vomited and complained of stomach pains. He was carried up the stairs to his room by his friends. He said he felt the way he had after taking the pill Lamson had given him on holiday. His condition worsened, with his whole body convulsing so he had to be forcibly held down. Two doctors attended the boy. Both were baffled by Percy's symptoms, though there was no doubt he was in considerable pain. His mouth and throat were burning; he said it felt as if his skin was being pulled from him. Not surprisingly, Percy was writhing in agony. The doctors administered two doses of morphine in an effort to relieve the pain, but they were at a loss as to how to help the boy. The doctors later admitted in court that they knew nothing about the action of a fatal dose of aconitine on the human body. Percy died that night, after suffering four hours of torment.

The doctors believed that the boy had been poisoned with some kind of vegetable alkaloid. Suspicion fell on Lamson
almost immediately, and the police began to search for him. Though he had successfully made it to France, Lamson voluntarily returned to England, and walked into a police station to help with their enquiries. He was promptly arrested for murder.