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Authors: Kathryn Harkup

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What exactly constitutes a lethal dose of nicotine for a human is a point of some debate. It is generally agreed that between 0.5 and 1mg/kg would constitute a lethal dose by injection or inhalation. This corresponds to a dose of between 40 and 70mg for a 70kg adult (one or two drops). A much higher dose would be needed to kill by absorption through the skin or by ingestion. A recent estimate of the lethal oral dose is between 500 and 1000mg (approximately ten to twenty drops).

Is there an antidote?

As is usual in an Agatha Christie novel, little was done to help the victims in
Three Act Tragedy,
though medical support might have saved them. The first thing to do is to remove the source of poisoning by washing the skin or enforced vomiting (emesis), depending on how the nicotine got into the body. It is likely that the patient will be vomiting anyway, and can remove much of the poison themselves. If the patient is not vomiting, activated charcoal can be given to absorb nicotine in the stomach, and a stomach-pump will remove more of it. Artificial respiration should be given as required.

There is, however, a specific antidote for nicotine – atropine (see page
here
), which can be administered by injection. Atropine activates the nerves of the sympathetic nervous system, while
nicotine, at high concentrations, will depress their activity. Additional measures can be taken to control the symptoms of nicotine poisoning as necessary; for example, anticonvulsants to control seizures.

Some real-life cases

Agatha Christie was quite right in
Three Act Tragedy
when she pointed out that nicotine was rarely used for the purposes of murder, and much of her knowledge of it must have been drawn from cases of accidental poisoning. But there is one famous case of murder by nicotine, dating from 1850. It is important, not only because it is an unusual choice of murder method, but also because it is the first case where scientific evidence was used to prove the presence of a plant-based poison in a corpse.

In a courtroom in France a few years before the murder in question, a prosecuting lawyer who was unsuccessfully trying to prove a case of murder by morphine declared thus: ‘Henceforth, let us tell would-be poisoners … use plant poisons. Fear nothing; your crime will go unpunished. There is no
corpus delecti
[physical evidence], for it cannot be found.' The fact that at the time nicotine was undetectable in a corpse may have been the reason why Count Hippolyte Visart de Bocarmé chose it as his poison, but it was probably his arrogance that made him believe he would never be convicted.

Count Bocarmé had an extraordinary life to match his extraordinary name. He was born during a thunderstorm in 1818 on board a ship bound for Java, where his father had been appointed Governor. The Count spent his early years in Java before returning to Europe with his family. He was a badly behaved young man, known to be a swindler and womaniser. When he was 24 his father died, and Hippolyte inherited his father's title and the family estate, Château de Bitremont near Bury, Belgium.

The inheritance was soon gone and, desperately short of money, the Count married Lydie Fougnies, the daughter of a retired grocer, believing her to be rich. Although she brought
with her a small annual income, which more than doubled a few years later when her father died, it was nowhere near enough to support the excessive lifestyle the couple were leading. In order to fund the wild parties, extravagant hunts and their family of four children as well as a large household staff, they started selling off land. When this supply of cash ran out they started to look at Lydie's brother, Gustave Fougnies, in a new light. Gustave was unmarried, and had inherited the bulk of his father's fortune. He also suffered from poor health.
63
In his will Gustave considerately left everything to his sister upon his death. The Count and his wife assumed that they wouldn't have long to wait until they inherited the cash, so they continued with their expensive lifestyle, and mortgaged everything they could to fund it.

When Gustave announced he was getting married, the Count feared that his brother-in-law would change his will in favour of his new wife. He decided action was required before he lost the inheritance he felt he was due. By the beginning of 1850 Count Bocarmé had developed an intense interest in chemistry, and started a correspondence with a professor of chemistry, using a false name. With the knowledge he gained from the professor the Count was successfully able to distil a quantity of pure nicotine from a large amount of tobacco leaves that he had purchased during the summer of 1850.

On 20 November 1850, Gustave accepted an invitation to dinner at Château de Bitremont, during which he died. Only three people were present in the room at the time – Gustave, the Count and the Countess. The Count and Countess asserted the cause of death was ‘apoplexy' (i.e. a haemorrhage) but the presence of bruising and scratches on Gustave's face indicated otherwise. Something had been forced into Gustave's mouth, and whatever it was had run down from the corner of his mouth, causing blistering to the skin.

If the marks on the body were not enough to arouse suspicion, then the behaviour of the Count and Countess immediately after the death certainly was. The Count tipped glass after glass of vinegar into Gustave's mouth. The body was also washed with vinegar, and Gustave's clothes were removed and taken to the laundry along with those of the Count and Countess from that evening. The Countess then busied herself with washing the floor in the dining room. Later, the Count applied himself to scraping the wooden floor of the dining room with a knife. The cleansing and tidying up continued until the afternoon of the following day, when the Count and Countess went to bed exhausted. Not surprisingly, the servants were very suspicious, and decided to call the authorities.

When a magistrate arrived the Count was reluctant to show him Gustave's body, and refused to pull the curtains back to allow him to see properly. He tried to shield Gustave's face with his hand but to no avail. It was apparent from the cuts and bruises that Gustave had not died a natural death.

Further investigations revealed inflammation in Gustave's throat and stomach, and it was concluded that he had been forced to drink some kind of corrosive substance, such as sulfuric acid, and that had been what killed him. Tissue samples from Gustave's body were bottled in alcohol and hastily taken to the laboratory of Jean Stas (1813–1891), with the request that he try to identify what had been used to kill Gustave. Stas was the most famous chemist in Belgium, and world-renowned for his work on atomic weights; he had converted his whole house into a working laboratory for his experiments.

A quick examination of the inflamed tissues in Gustave's mouth and throat convinced Stas that sulfuric acid had
not
been used. The damage from an acid would have been quite different. Like many other chemists at the time Stas made use of his senses of taste and smell in his experiments. He noted a taste of acetic acid in the remains, and the police explained how Bocarmé had doused the body in vinegar (the principal component of which is acetic acid), and poured many glasses
of the stuff down Gustave's throat. Acetic acid alone would not kill a man, so Stas suspected the vinegar had been used to disguise the presence of another poison.

The eminent chemist worked night and day to extract whatever it might have been that killed Gustave. He added more alcohol to a portion of the remains, filtered it, added water and filtered it again. After evaporating off all the alcohol and water Stas was left with a sticky residue, to which he added caustic potash (potassium hydroxide, KOH). For the briefest moment, Stas smelled the distinctive aroma of nicotine.

Stas then spent three months developing a reliable method of extracting plant alkaloids from human tissue. The first step was to digest the tissues to release the alkaloid. This was done using acetic acid and alcohol. Gustave's murderer had already helped this process along by washing the body with vinegar, and the investigating authorities had helped Stas further by preserving the tissue samples in alcohol. The poison, now released from the tissues, would be dissolved in the alcohol. Stas reasoned that compounds within the body might be soluble in water or alcohol or neither, but not both. Nicotine (and other plant alkaloids), on the other hand, was soluble in both water and alcohol. By using a series of extractions with both these liquids, nicotine could be separated from the compounds normally found in the body. The final step was to wash the alcohol layer with portions of ether, and allow the ether to evaporate in a dish. What was left in the dish was a brownish residue with the unmistakable smell of nicotine.

Next, Stas carried out an extensive series of chemical tests to prove beyond doubt that the substance he had isolated was nicotine. He then contacted the police and suggested they look for evidence that Bocarmé had extracted nicotine from tobacco leaves. A thorough search was conducted at Château de Bitremont, and the chemical glassware that the Count had used was found hidden behind some wooden panelling, while in the garden they found the bodies of cats and other animals that Bocarmé had tested his tobacco extracts on. The gardener
also remembered that the Count had purchased a large quantity of tobacco leaves the previous summer; he had told the gardener he was making perfume.

While the search of the château was going on Stas had continued his experiments, and he had extracted enough nicotine from Gustave's liver and tongue ‘to kill several persons'. He also analysed clothing and wood shavings from the floor at Château de Bitremont to determine the presence of nicotine. In another experiment, Stas killed two dogs by administering nicotine by mouth. One dog then had quantities of vinegar poured down its throat, while the other dog received no treatment. Blackish burns appeared in the mouth of the dog that received no treatment but the acetic acid in the vinegar successfully neutralised the corrosive effects of nicotine in the other, and no signs of chemical injury appeared. Clearly the Count had learnt a lot about the chemistry of nicotine, and when Gustave put up a struggle, causing the nicotine to be splashed around, the Count did his best to conceal the evidence using vinegar.

The case went to trial. The Count and Countess did their best to accuse each other of the crime, but the evidence was damning. Somewhat inexplicably, Countess Lydie Bocarmé was found not guilty. Count Bocarmé was sentenced to death by guillotine.

Agatha and nicotine

In Agatha Christie's
Three Act Tragedy
, all three murders are committed by the ingestion of nicotine. The first takes place at the house of Sir Charles Carmichael, a stage actor. Sir Charles invites a group of friends and acquaintances to dinner at his house, including Hercule Poirot. Cocktails are handed round and the local vicar, the Reverend Babbington, sips at his before pulling a face, clearly indicating that he does not like the flavour. But being every inch the polite English vicar, he does not wish to offend his host or appear unsophisticated in his tastes, and he drinks down the whole glass. Within minutes Babbington's face is convulsed; he rises to his feet, sways a bit
and collapses. Two minutes later he is dead, long before a doctor can arrive to treat him.

The death is initially treated as suspicious because of Babbington's clear distaste for the cocktail. There must have been something in it, something so strongly flavoured that it could not be masked by gin and vermouth. Also, there was the sudden seizure he experienced shortly after drinking the cocktail. ‘Seizure' is a vague term that doesn't really indicate any particular illness or poison. Such a general term can refer to any number of symptoms and causes. Only strychnine or tetanus produces characteristic seizures that could be used as a diagnosis. The cocktail glass Babbington drank from is taken for analysis, but tests reveal that it contains nothing but gin and vermouth. Wild theories are put forward about hypodermics of untraceable arrow poisons from South America being injected into the unfortunate clergyman. With no evidence of poison in his cocktail glass, and no idea of a motive for doing away with a rather dull vicar, the death is attributed to natural causes. But suspicion lingers, because although Babbington was advanced in years he was in good health.

Weeks later, there is another dinner party, this time hosted by Sir Charles's friend, Sir Bartholomew Strange, at his home in Yorkshire. Most of the guests had also been present at the previous party, when the Reverend Babbington died. After the meal port is served, and Sir Bartholomew is soon taken ill. He dies within minutes, showing similar symptoms to those of Babbington. Sir Bartholomew Strange was in the prime of his life, and a heart attack or stroke seems an unlikely cause of death. He was in good spirits on the night of his death, so suicide is also eliminated. A post-mortem is carried out on Sir Bartholomew's body, and his port glass is sent for analysis. No trace of poison is found in the glass of port, but the post-mortem reveals that Sir Bartholomew died of nicotine poisoning.

There may be very little physical evidence of nicotine poisoning post-mortem. As we have seen pure nicotine is corrosive, so with large doses there may be signs of burning in the mouth and throat. However, even if there are no physical
signs, nicotine can still be identified, as it can be extracted from human tissue. The method eventually figured out by Jean Stas (see pages
here
–
here
) remains little changed, even today, though modern scientists can use a variety of subtle chromatographic techniques to isolate and identify nicotine, and find out how much of it is present. Chromatography methods were still fairly basic when Agatha Christie was writing
Three Act Tragedy
, and pathologists would have had to rely on chemical reactions to detect the presence of nicotine. There was a variety of tests available, using compounds such as gold chloride (Au
2
Cl
6
) or picric acid (C
6
H
2
(NO
2
)
3
OH).
64
Nicotine reacts with these chemicals to produce crystals such as nicotine picrate (after reaction with picric acid). The most sensitive test in the 1920s used silicotungstic acid (H
4
[W
12
SiO
40
]) and dilute hydrochloric acid, and could detect nicotine in quantities as tiny as one part in 300,000. If nicotine was present the reaction mixture clouded almost immediately, and crystals appeared when the mixture was left to stand. The crystals could be collected, washed and weighed to determine the amount of nicotine present in the sample.

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