Part I: Some of Nature’s Deadly Chemicals: From Medicine to Murder CHAPTER 1 Ricin and the Rolled Umbrella A word shown in bold indicates that further information will be found in the Glossary 1.1 Waterloo Sunset An umbrella is not the most obvious way of delivering a fatal dose of poison, but that was the weapon chosen by the Bulgarian secret service in 1978. Its targets were 26-year-old Vladimir Kostov and 49-year-old Georgi Markov, dissidents who had defected to the West and were embarrassing the corrupt communist dictatorship of President Todor Zhivkov by broadcasting on the US propaganda station Radio Free Europe. Kostov survived, but Markov died. On 7 September 1978 Markov parked his car near Waterloo Sta- tion and was waiting for a bus to take him over the River Thames to Bush House, where he worked for the BBC World Service. Suddenly he felt a sharp pain in his leg, and turned to find a man behind him with an umbrella which he had dropped on to the pavement. Al- though Markov did not know it, the umbrella had fired a tiny metal pellet no bigger than a pin-head into his thigh. By the time Markov reached his home in Balham that evening he was already feeling very ill. He began vomiting and was running a high fever. Markov was unaware that beneath the skin of his leg was a minute pellet containing one of the deadliest of all poisons. He died in agony four days later despite being in intensive care. The following week I was drawn into the story, when I was rung up by The Guardian Molecules of Murder: Criminal Molecules and Classic Cases By John Emsley r John Emsley, 2008 3 4 Chapter 1 newspaper to be told about the pellet that had killed him. Could I speculate about the type of toxic chemical which it might have contained? I guessed a spider or snake venom, but I was wrong. It was something far more deadly, and originating from a plant; it was almost certainly ricin. 1.2 Toxicology and Chemistry Ricin is produced by the castor bean plant, Ricinus communis. It makes this toxic protein molecule in its seeds, presumably to deter predators. Once the seed has germinated the toxin is no longer needed and it disappears. Until this happens the ricin is indeed a very effective deterrent, deadlier even than the most powerful of the nerve gases. The toxicity of a poison can be judged by its LD50.Forricinit is 0.1 micrograms per kilogram (mg/kg)ofbodyweight,whereasthe figure for the most lethal nerve gas known, coded VX, is as high as 20 mg/kg. Although these measurements were made using rodents, if they were to apply to a human they would suggest that for someone of average weight, say 70 kg, a dose of a mere 7 mg of ricin would pose a serious threat to life. This is a conservative estimate, as the route of exposure and the person’s immune status would also play a role. The ricin molecule consists of two long chains, A and B, neither of which in itself constitutes a dangerous toxin—indeed other plants such as barley make chain A, without a noticeable effect on those who eat it. Chain B is the key to the toxicity. This binds to a par- ticular carbohydrate component on the outside of a cell membrane and lies in wait. Eventually the membrane allows chain A to pass through, but once inside the cell it seeks out the site where the es- sential enzymes the cell needs are made and blocks it. Without its supply of enzymes the cell dies. A single ricin molecule is sufficient to kill a living cell, so in theory a mere 3 mg of ricin, with its ten trillion molecules, would be enough to poison every cell of the human body. It has been estimated that it would take about 10 castor beans to kill a human, and the same is true for other domestic animals. On the other hand, hens and ducks seem to be relatively unaffected when they eat this number of crushed seeds, in fact it takes ten times as many beans to kill them, and one bird, the tambourine dove, happily consumes the seeds of the castor plant without harm. Humans are particularly sensitive to the toxin, and it has been said that a single bean contains enough ricin to kill a young child, Ricin and the Rolled Umbrella 5 although this is an extremely rare event, and certainly in the UK it is almost unknown for a child to be poisoned by swallowing a castor bean. Even when this has happened, the child invariably survives the ordeal. What protects a child from the toxin is the seed coating of the castor bean, which is so hard that provided it remains unbroken it can pass through the intestine undigested and emerge intact. The fatal dose of ricin for an adult is calculated to be as little as 70 mg, ten times the amount estimated from its LD50. In practice a higher dose than this is needed to kill, because the immune system begins to produce antibodies which destroy the ricin invader, and it also depends on the route by which ricin has entered the body, e.g. whether by injection, digestion or inhalation. In fact between 200 and 500 mg of ricin is needed to kill an adult, but this is still a minute amount and several such doses would fit on the head of a pin. A larger dose is needed to kill if the ricin is swallowed rather than inhaled or injected. 1.3 Ricin in Chemical Warfare There is no antidote for ricin, but there are vaccines available to people who are likely to encounter the toxin. These have been de- veloped because ricin has potential as a chemical warfare agent, and indeed may have been used as such in the Iran–Iraq war of the 1980s. That the Iraqis possessed this capability was confirmed in 1995 when they admitted to UN inspectors that 10 litres of con- centrated ricin solution had been produced. They also admitted that it had been tested as an offensive weapon in the form of artillery shells which would explode and disperse it. There was also evidence that they had continued to stockpile ricin, and in 1998 the RAF and USAF attacked a castor oil production plant in Fallujah, Iraq, which was suspected of producing it. That there was a continuing threat from ricin seemed to be confirmed when quantities of it were found in al-Qaeda caves in Afghanistan. It had been known for many years that ricin could be a possible weapon and work on it by the US Army began in World War I. Eventually they concluded that it offered no advantages over the traditional chemical warfare agents, chlorine and mustard gas, which were then in use. Nevertheless it was developed further in World War II when cluster bomblets were tested as a way of dis- persing a cloud of ricin dust over an enemy, but again the 6 Chapter 1 conclusion was reached that it was not very effective. The dust was meant to contaminate clothing and surroundings so that even after the attack it would be possible for a person to ingest a fatal dose merely by breathing it in. It would remain a threat for quite some time until the bond between chains A and B was severed by chemical reaction with components of the atmosphere, such as ozone and nitrogen dioxide. Once A and B become separate entities then the potency is lost. The difficulties with ricin as a weapon were, firstly, the need to protect one’s own troops from exposure to it and, secondly, the inability to treat them if ever this happened. Today, protection against ricin is possible but it has to be given before exposure to the toxin, in other words as a vaccine. There is still no antidote, nor is there ever likely to be. In 2003 the defence division of the US company, BioPharma, was licensed in the USA to test a genetically modified vaccine incorporating chain B, which induces the body’s immune system to produce antibodies against the whole ricin molecule. 1.4 Production and Applications Ricin is produced naturally by a number of plants but in such tiny amounts that it poses no threat, whereas the castor plant makes it in relative abundance. This plant is grownasacropforitsoil,whichis extracted by heating the beans to 140 1C for around 20 minutes to denature the ricin proteins, and then crushing and pressing the beans to extract the 50% or so of oil which they contain. More than a million tonnes of castor oil are produced every year, mainly from beans grown in Brazil, India and China. Castor oil consists almost wholly of just one relatively rare fatty acid, ricinoleic acid.Indeedthe presence of this fatty acid in a blend of edible oils can be used to detect whether any castor oil is present. Castor oil is used for pre- serving wood and leather, and as a raw material for the production of sebacicacid,whichisusedinbrakefluidsandasanengineeringoil. In ancient times castor oil was burned in lamps or applied as an ointment to the skin. It was used in these ways in India as long ago as 2000 BC, and its laxative properties were also recognised. A spoonful of castor oil was prescribed as a cure for stubborn constipation, which it did indeed cure.