J R Coll Physicians Edinb 2007; 37:77–84 PAPER © 2007 Royal College of Physicians of Edinburgh Solanaceae IV: Atropa belladonna, Deadly Nightshade MR Lee Emeritus Professor of Clinical Pharmacology and Therapeutics, University of Edinburgh, Edinburgh, Scotland ABSTRACT The Deadly Nightshade, Atropa belladonna, is a plant surrounded by Published online March 2007 myth, fear and awe. In antiquity, the Greeks and the Romans knew that it contained a deadly poison. In medieval times, it was widely used by witches, Correspondence to MR Lee, 112 sorcerors and professional poisoners. Linnaeus later codified its remarkable Polwarth Terrace, Edinburgh, properties as the genus Atropa, the Fate that slits the thin spun life and the species EH11 1NN belladonna because of its power to dilate the pupils. In the 1830s, the pure tel. +44 (0)131 337 7386 alkaloid l-atropine was isolated from the plant. This proved to be a significant tool in the study of the autonomic nervous system leading to the identification of acetylcholine as an important neurotransmitter in mammals. When pure atropine became available, it caused a large number of deaths, whether by accident, suicide or homicide. KEYWORDS Acetylcholine,Atropa, belladonna, murder, poisoning, quinine DECLARATION OF INTERESTS No conflict of interests declared. In this, the final article of a short series on the Solanaceae, I describe the deadly nightshade (Atropa belladonna), a plant hallowed by long tradition as one of the classic poisons of antiquity. Extracted from the plant is the alkaloid atropine (dl-hyoscyamine) which was to prove a cornerstone in the study of autonomic pharmacology. The use of atropine as a homicidal poison seemed to have gradually faded away but then in the 1990s, Dr Agutter in Edinburgh attempted, in a spectacular fashion, to poison his wife with the pure alkaloid. This has become a landmark example, in so far as Agutter wove a tangled web of deceit in order to divert attention from his nefarious activities. Indeed the case ranks with that of Crippen (with hyoscine) or Armstrong (with arsenic) as benchmarks in the history of forensic medicine. Fortunately, no deaths occurred in the Agutter poisoning case, but this was more due to good luck than other factors. THE PLANT FIGURE 1 Deadly Nightshade. Atropa belladonna. Courtesy of The Atropa genus comprises a group of four species of the Library of the Royal College of Physicians of Edinburgh. erect perennial herbs (see Figure 1). They have simple typical alternate leaves and bell shaped five-lobed flowers. that the sorceress Circe administered to the sailors on The genus is widely distributed from Western Europe to Odysseus’ ship. This subsequently drove them mad and the Himalayas. The best known species is Atropa ‘turned them into swine’! Odysseus resisted the poison belladonna which has erect stems up to two metres in by taking the antidote ‘moli’ which was probably either height. The fruit is a purple-black berry. All parts of the the snowdrop (Galanthus nivalis) or the snowflake plant are poisonous (particularly the berries.)1 (Leucojum vernum).2 NIGHTSHADE IN MYTHOLOGY The Greeks realised the plant was extremely poisonous HISTORY and they therefore identified it with one of the three The plant was well known to the Ancient Greeks and Fates. Clotho spins the thread of human life; Lachesis indeed it is a strong candidate for the drug (or potion) measures it off and Atropa (the Inflexible) severs it. 77 MR Lee Hence the quotation ‘Comes the Blind Fury that slits the BELLADONNA thin spun life.’3 Interestingly, Lachesis, the Disposer (or Measurer) also gave her name later to the anticholinergic The species name for the deadly nightshade derives from drug lachesine (now rarely used). the dramatic effect that the plant has on the eye and its functions. The eye occupied a central place in traditional The plant Atropa later became associated with the Greek healing, being regarded as the window to the soul. cult of Dionysius (Bacchus to the Romans). Worshippers of these gods took wine and then dissolved in this liquid Matthiolus (Pietro Andrea Mattioli 1501–1577) was a ivy,Atropa and other drugs to make a magic potion. On distinguished physician practising in Sienna in Italy. taking this decoction the devotees passed into a trance in Amongst other things he wrote a great commentary on which they danced with abandon and committed lewd the botanical works of the Greek physician Dioscorides. and libidinous acts. Those initiated into the rite were He also described the custom of the ladies of Venice who promised eternal life and continued sexual potency! put Atropa into their eyes in order to dilate their pupils. These Bacchanalian orgies presage those which would be As a result tincture of Atropa became known as ‘bella- carried out by the medieval witches (see below). donna’ (or beautiful lady). When Linnaeus undertook his outstanding formal classification of the plant kingdom in One problem that the Greeks faced was that initially the 1700s, he incorporated both ideas: the generic name Atropa was confused with the mandrake (Mandragora).4 Atropa (the cutting or deadly Fate) and the species name Indeed they are closely related members of the belladonna (an interesting conjunction). Solanaceae family. Subsequently, Dioscorides recognised that Atropa was, in fact, a distinct plant and should not be THE ADVENT OF THE HERBALISTS used in preference to the mandrake because it was much more poisonous than the latter. Throughout the medieval period the deadly nightshade was largely confined to the hidden world of witches, WITCHES AND ATROPA wizards and folkhealers. Then in the sixteenth and seventeenth centuries herbalists and apothecaries arrived The deadly nightshade was an important plant in the on the scene and they embarked upon a systematic study witches’ pharmacopoeia. The hags also used mandrake; of useful and dangerous plants. The major figures in henbane and hemlock. (The reader is referred to Britain were Gerard, Culpepper and Parkinson. earlier articles in this series.3a) Atropa was pre- eminent because it was regarded as one of the Devil’s Gerard called the plant the lethal Solanum or Sleepy favourite plants. The story goes that he sprinkled the Nightshade.7 He recounts three cases of poisoning with plant with his own blood every night of the year and the berries and instructs the readers of his Herball to regularly took cuttings for his malign purposes. On banish these pernicious plants from their gardens. only one night did he neglect his duties. That was Otherwise, he said, women and children will lust after the Walpurgis night (the 30th of April) when he had other shining black berries which are so beautiful. He concludes far more important things to do in taking part in the however that they are ‘vile and filthie’. Black Mass celebrations.5 Eventually the plant came to be included in Witches (and wizards), recognising that the plant had pharmacopoieas and dispensatories. One of the classic found favour in the eyes of the devil, would use it as a descriptions is that by Andrew Duncan in the Edinburgh constituent of their flying ointments. These were also Dispensatory of 1803.8 He says that Atropa can be used known as the ‘sorcerors pomade’. The usual with benefit in the following disorders: combination employed in a flying ointment was nightshade, hemlock, mandrake and henbane pounded 1 Several febrile illnesses, particularly the plague. into an ointment with bear’s grease.6 This was then 2 In nervous diseases such as palsy, apoplexy, epilepsy, rubbed into the skin, genitals and vagina. The witch chincough (whooping cough), hydrophobia, would then experience delusions; hallucinations and melancholy and mania. sometimes sensations of levitation or flying. Sexual arousal could also ensue together with orgasm! Duncan advises that the powdered leaves (or root) Witches also took, on a regular basis, small amounts of should be used first and if these fail then an infusion in nightshade by mouth in order to practise divination warm water can be tried. The dose of all these (fortune telling). This was generally recognised as being preparations should be gradually increased on a day by potentially dangerous. Conversely the peasants had a day basis until ‘tension in the throat’ developes. It would popular superstition that if a sprig of deadly (or woody) then be imprudent to increase the dose further! In other HISTORY nightshade was kept in the house, then this would ward words the toxic threshold had been passed. Duncan also off evil spirits, preventing fiends from attacking their mentions that Professor Reimarus, a Continental eye families, homes or livestock. specialist, had used the infusion of Atropa to dilate the 78 J R Coll Physicians Edinb 2007; 37:77–84 © 2007 RCPE Solanaceae IV: Atropa belladonna, Deadly Nightshade FIGURE 2 The chemical structures of the closely related anticholinergic alkaloids atropine and hyoscine. The only difference between the molecules is the extra oxygen atom in the tropane ring of hyoscine. FIGURE 3 Belladonna porous plaster British Pharmaceutical Codex.About 1950, from a specimen in the author’s collection. pupil in order to facilitate the removal of cataracts. This example was the plaster that also included an extract episode marks the beginning of the use of mydriatic drugs of the monkshood (Aconitum napellus). This plant in intraocular surgery. produces the deadly alkaloid, aconitine, which can cause cardiac and respiratory failure. Murderers were SOLVING THE CHEMICAL CONUNDRUM known to purchase this deadly plaster. They would then steep off the two alkaloids, aconitine and atropine At around the time that Duncan was compiling his in order to use the resulting poisonous liquid for their dispensatory in Edinburgh, in the early 1800s, chemistry deadly activities. began its great leap forward with the work of Sir Humphrey Davy in London, and the activities of the ATROPINE POISONING French and German chemists.