Atropine Molecule of murder In an exclusive article adapted from his new book, John Emsley explores the hallucinogen, medicine, deadly poison and antidote that is atropine HAMISH KIDD / SCOTT OLLINGTON SCOTT / KIDD HAMISH

64 | Chemistry World | August 2008 www.chemistryworld.org The drama and mystery of forensics retained one bottle to which he had artificial ventilation, and give is attracting young people back to added 103mg, but then put the rest ‘She drank diazepam to control convulsions. The chemistry. And while the CSI back on the supermarket shelf. As only half of poison will be eliminated from the drama series is fictional, much as half a litre drunk from any body in about 72 hours. Antidotes like many real life of the other bottles would not the poisoned physostigmine are available but rarely cases have been a fatal dose. drink before needed. Atropine takes its name from one Bitter poison collapsing’ of the three Fates of Greek legend, The following Saturday Atropos, who determined when evening Agutter’s wife a person would die. It is a white, was relaxing with a gin odourless, crystalline powder first and tonic poured by her isolated from the roots of deadly husband. Fortunately nightshade (Atropa belladonna) by for her, because it tasted a German apothecary, Wein, in 1831 so bitter, she drank only and was first synthesised 70 years half of it. Within just a later by Richard Willstätter (Nobel few minutes she began to laureate 1915). Atropine is racemic suffer hallucinations. Then she hyoscyamine and it is still extracted collapsed. from plants which actually produce are just A similar event was to be played out only l-hyoscyamine – the deadly as intriguing. at the home of Geoffrey Sharwood- isomer – but work-up results in a None more so than the Smith whose wife Elizabeth racemic mixture. Such is the demand attempted murder of Alexandra Sharwood-Smith, and 18-year-old son for atropine that Atropa belladonna Agutter by her husband Paul in 1994. Andrew, displayed similar symptoms. genetically modified to give increased He used atropine – choosing a readily They were rushed to hospital where yields is now grown. The plant grows available poison that was difficult to doctors were informed by Sharwood- to about 1.5m with dark green leaves, detect in bodily fluids and tissues. Smith, himself an anaesthetist at the violet flowers, and luscious looking It would be almost impossible, Royal Infirmary of Edinburgh, that he berries. he concluded, to link him to the suspected they were suffering from Atropine itself is not very soluble intricate plan he had devised to hide atropine poisoning. in water but this can be overcome his crime. Soon other cases of atropine by forming atropine sulfate, Agutter knew atropine had poisoning were being admitted to which has several trade names a major drawback as a murder the infirmary. Sharwood-Smith was including Atrophate and Atropisol. weapon: it has a very bitter taste, familiar with the drug because it was Alternatively, and also to reduce its detectable at concentrations as low sometimes given prior to surgery. toxicity, a second methyl group can as 100 parts per million (0.001 per Indeed atropine is to be found in be added to the nitrogen atom to form cent). He thought he could mask many medical and surgical wards, Atropine is isolated atropine methyl nitrate (trade names this by adding it to the already bitter operating theatres, and even on from the roots of deadly include Atrodote and Eumydrin). The tonic his wife had with her gin. Her resuscitation trolleys. nightshade (Atropa sulfate is remarkably soluble – 100ml unexpected death would eventually Treatment for atropine poisoning belladonna) of water will dissolve more than 100g be explained as atropine poisoning, is to wash out the stomach, apply of the salt. so he also needed someone else to blame. His answer was to construct an elaborate scheme to make it appear as though a fictional poisoner had maliciously spiked several bottles of tonic water. But his intention was that his wife would be the only one to die. He would then gain control of the family home, and would be free to marry the new love of his life, a mature student at the university where he worked. Agutter was familiar with atropine. He was a biologist at Napier University in Edinburgh, UK, and a member of the university’s highly- rated biomedicine research group whose speciality was toxicology. His poison of choice was available in the department – he had used it as part of an experiment a few years previously. In August 1994 he removed some from an opened bottle of atropine sulfate. He then went to the nearby Safeway supermarket and purchased a dozen litre bottles of tonic water to which he added small amounts of the poison – between 11 and 74mg. He SHEILA TERRY / SCIENCE PHOTO LIBRARY PHOTO SCIENCE / TERRY SHEILA www.chemistryworld.org Chemistry World | August 2008 | 65 Atropine

Mad as a hatter atropine together with obidoxime The symptoms of atropine poisoning or pralidoxime. Atropine blocks the were once summarised as: hot as a receptors that the ACh is targeting, hare, blind as a bat, dry as a bone, red while the oxime goes to work to as a beetroot, and mad as a hatter. destroy the sarin molecules and free Hot because the temperature soars; up the cholinesterase. Soldiers in

SCOTSMAN PUBLICATIONS LTD PUBLICATIONS SCOTSMAN blind because the iris of the eye is war zones carry syringes containing so dilated that everything appears the antidotes with which to inject blurred; dry due to suppression of the themselves in the event of a nerve salivary glands; red due to dilation gas attack. Allied soldiers in the Gulf of the blood vessels of the skin; mad War of 1991 were issued with these because of hallucinations. Atropine after it was discovered that the Iraqi affects the central nervous system government had placed large orders and the autonomic nerves, which for atropine. Of course this carried govern the heart, lungs, and gut. It the risk of soldiers who injected interferes with the neurotransmitter themselves unnecessarily suffering acetylcholine (ACh), blocking the atropine poisoning. receptors this is meant to activate. It particularly inhibits the release of Deadly delay salivary and bronchial secretions and A similar demise was planned for it does so at very low doses, which is Agutter’s wife. On the evening of why it is given before surgery. the attempted murder Agutter rang Atropine has been prescribed as a not for an ambulance but for their treatment for the spasms associated local doctor, who was not at home, with certain conditions such as although he left a message on his Parkinson’s disease, and it improves answering machine making it sound walking, sitting, and the speech of urgent. He knew that the more he those affected. could delay medical help the more It is also stockpiled for military was professor of pharmacology at Paul Agutter was found likely it was that his wife would die. reasons; not to be used as an offensive the University of Edinburgh and guilty of attempting to But the message was picked up by weapon but as an antidote for the whose research is seen as one of the murder his wife with the locum practitioner who sent an organophosphorus nerve agents, landmarks in the development of atropine ambulance round to the Agutters’ such as sarin. pharmacology. The antidote action home straight away. Sarin is a powerful and deadly centres on ACh, which acts as a The paramedic took possession nerve agent. It was used by the Iraqi messenger molecule in the nervous of the bottle of tonic, and poured the government against the Kurds, who system. When ACh has completed remains of the tainted drink into an did not have atropine to combat its task of passing a chemical signal empty jam jar to be analysed. Agutter the effects. It was also used by the across a synapse gap to receptors had added extra atropine directly Aum Shinri Kyo doomsday sect in the body’s tissues, it needs to be to his wife’s glass, and analysis against commuters on the Tokyo removed quickly. The body does this uncovered the discrepancy. The underground, who were treated by breaking it down with enzymes concentration of atropine in her drink with the drug. That attack occurred known as cholinesterases. These was three times that of the bottle. during the morning rush hour on 19 enzymes can be put out of action by Eventually the police also took April 1995 and, while 12 people died, nerve gases, which block them so Agutter’s car away for analysis and a 5000 others recovered thanks to effectively that less than one mg is minute trace of atropine was found atropine. fatal. The victim dies of excess ACh, on a cassette case, a triumph for In fact atropine has long been which builds up and repeatedly forensic analysis at the time. Agutter known to be the antidote for another triggers the same receptors, causing was arrested and brought to trial on toxin, physostigmine, which attacks the organs stimulated by the 24 January 1995. the same enzymes as nerve gases. receptors to malfunction by going Atropine and pralidoxime During the trial, the forensic The action of atropine as an antidote into spasm and paralysis. are used together as a scientist Howard Okley gave to physostigmine was discovered Sarin poisoning can be treated by rapid antidote to nerve evidence about the atropine poisoned by Thomas Fraser (1841–1920), who the rapid injection of two antidotes: gases bottles. He deduced that Agutter’s wife had probably drunk about 150ml of the poisoned drink and imbibed around 50mg, half a fatal

GETTY IMAGES GETTY dose. Agutter was found guilty on 21 February, and sentenced to 12 years in prison, of which he served seven.

John Emsley is a science writer based at the University of Cambridge, UK. His new book Molecules of Murder was published by the RSC in July

Further reading M R Lee, J. Roy. Coll. Physician Edinb., 2007, 37, 77 R S Holzman, Anaesthesiology, 1998, 89, 241

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