A is for Arsenic (33 page)

Most of us will recognise castor oil as a safe and relatively mild laxative, sold as an over-the-counter remedy, but castor oil and its derivatives have a wide range of uses as lubricants, in paints and dyes, in plastics, pharmaceuticals and many more; it is ricinoleic acid, a fatty acid found within castor oil, that is of particular interest industrially because of its chemical properties.
The plants are grown widely as a crop to satisfy the considerable demand for castor oil and ricinoleic acid. The oil is pressed from the seeds, and the remaining husks, or mash, can contain up to 5 per cent ricin. The mash can be used as a fertiliser but not as cattle feed, as is often the case with husks of other seeds from which oil is extracted, because it would poison the animals. Ricin is water-soluble but will not dissolve in fats, so little is found in the oil after it is pressed from the seed, but to ensure no ricin makes it into the castor oil it is heated to more than 80°C as it is extracted; this denatures the protein, so inactivating it.

Harvesting castor oil seeds can be hazardous to those who come into contact with the seeds, though not necessarily because of the presence of ricin – the tough outer shell of the castor seeds prevents the ricin from being released. Swallowing the seed whole without chewing is unlikely to prove fatal, as the seed coat is tough enough to survive the digestive process intact. However, the plants have allergenic compounds on their surfaces, which can cause permanent nerve damage to those who work with the plants. For reasons such as these there is great interest in finding alternative sources of ricinoleic acid, or in genetically modifying castor oil plants so that they do not produce ricin or these allergenic compounds.

How ricin kills

Ricin is a toxalbumin, a poisonous protein formed from two chains, A and B, which are linked by a single bond between two atoms of sulfur. All cells have a cell membrane that controls which substances are allowed to pass in and out of the cell. Chain B of ricin attaches to the surface of a cell, allowing the whole ricin protein to cross the cell membrane and enter the cell body. Inside the cell the two chains break apart,
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releasing chain A, which is the part that does the damage.

Ricin is classed as a ribosome-inhibiting protein, which is abbreviated to RIP.
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When separated from chain B, chain A can permanently disable the ribosomes, structures within cells that build new proteins and enable cells to function and replicate. Chain A breaks a crucial bond in the ribosome structure, inactivating it. Since ribosomes are essential for metabolism, growth and repair in the body, this is very bad news; the body can no longer carry out basic processes, or repair itself. If enough ribosomes are inactivated a cell will die, and if enough cells die in an organ, haemorrhage occurs and the organ fails. In addition, a single molecule of chain A is not restricted to damaging just one ribosome – it can roam around the cell, disabling up to 1,500 individual ribosomes per minute without being damaged or destroyed itself.
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The ability of one molecule to do so much damage means that ricin is lethal in extremely small doses. Less than 1mg injected under the skin is enough to kill an adult human; inhaling ricin dust can be just as deadly. Ingestion of ricin is slightly less dangerous, because the gastrointestinal tract treats ricin like any other protein we eat and breaks it up into its constituent amino acids for use in the body, thereby inactivating it. A murderer would need at least 100 times more ricin in order to kill by ingestion; however, this does still equate to just 100mg to kill an adult.

The symptoms of ricin poisoning appear approximately six hours after ingestion, and only slightly quicker if the poison is administered by injection or inhalation. There is a sensation of burning in the mouth, followed by nausea, vomiting, cramps, drowsiness, cyanosis (blue colour in the skin), stupor, circulatory
collapse, blood in the urine, convulsions, coma and death. Haemolysis (the breakdown of red blood cells) occurs even at extreme dilutions of ricin, resulting in severe haemorrhaging. Death occurs between three and five days after poisoning.

Ricin has no approved therapeutic uses, but there have been suggestions that it could be modified into an effective treatment for cancer, because of its ability to disrupt cell function. Another potential use would be to use chain B to deliver pharmaceutical drugs into a cell interior (since without chain A, chain B would have no damaging effects).

Despite the fact that castor oil plants can be grown legally, researchers working with ricin must be registered if they are storing more than 100mg in their lab. Outside of registered laboratories, anyone trying to isolate ricin or with pure ricin in their possession would certainly require a very convincing argument for the authorities. The high toxicity of ricin and its relative availability means it has been looked at closely as a potential biological weapon. Trials were conducted by the United States Army during the First World War; it was concluded that ricin was no more effective than phosgene or the other chemical-warfare agents that were then in use, the major problem being that methods of deploying ricin created sufficient heat to denature the protein. In the years leading up to the Second World War and during the conflict itself, more research was conducted independently by the Allies. The French thought ricin too dangerous for research until an antitoxin had been developed, so their plans were abandoned at an early stage. The British got further in their research and developed bomblets that were designed to spread clouds of inhalable ricin dust. The US Army's research was even more advanced; it developed the means to produce large quantities of ricin powder, or ‘Agent W', using a novel chilled-air grinder to prevent the heat from the friction of grinding from denaturing the protein.

Field trials of ‘Agent W' exposed another downside of ricin as a biological weapon. Any area exposed to ricin dust remained dangerous for a long time (until the bond between chain A and chain B had been broken – this could be two or three days). The dust would also attach to clothing and could subsequently be inhaled, proving fatal to friend and foe alike. The delayed action of the poison and ethical concerns over its use meant that ricin was never used in combat. The protein is less stable than anthrax and less toxic than botulinum toxin (which was also developed, as ‘Agent X'), so a much higher quantity must be produced to guarantee the same killer effect.

Is there an antidote?

There have been attempts to develop antidotes for ricin poisoning because of the poison's potential use as a biological weapon, but nothing is commercially available to date. Supportive care is the best that can be offered to anyone unfortunate enough to be exposed to ricin.

However, there are preventative measures that can be taken before exposure, in the form of a vaccine. This is developed from an inactive form of chain A, and it has been shown to be effective for several months – though you need a little bit of time for the body to develop its own antibodies. Because ricin is quickly cleared from the blood (owing to its entering the cells), treatment with antibodies after exposure is ineffective – this would be like giving someone a measles vaccine after they have already come out in spots.

Some real-life cases

Most incidents of ricin poisoning are due to the accidental ingestion of castor oil seeds;
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the survival rate is an excellent 95 per cent because the seeds can generally be removed from the
stomach before much of the ricin has been absorbed. The first ricin murder in Britain took place in 1978, after Agatha Christie's death, but it is one of the most famous cases of assassination.

Georgi Markov was a Bulgarian dissident, writer and journalist working for the BBC and Radio Free Europe. He made many broadcasts about the regime in Bulgaria and the privileged lives of those in power in that country, and was particularly scathing in his comments about the president, Todor Zhivkov. On 7 September 1978, as Markov waited at a bus stop on Waterloo Bridge, he felt a sharp pain in his thigh, like an insect sting. Turning around, he saw a man bending over to pick up his umbrella; the man apologised and quickly crossed the road to get into a taxi, which drove away. Markov later told one of his colleagues at work about the incident, and showed him the tiny mark on the back of his thigh. Markov recorded his broadcast, and went home a couple of hours later.

That night Markov developed a fever and started vomiting. The next day he was still feeling very unwell, and he stayed at home. His doctor came to see him and called for an ambulance. At the hospital, Markov showed the house physician the wound on the back of his leg. The doctor examined the area, which was now inflamed, with a tiny pin-prick at the centre. He did not think this was the cause of Markov's illness, but the thigh was X-rayed just in case. Nothing showed up.

Markov's condition continued to deteriorate. Doctors suspected his symptoms were caused by severe septicaemia. He had a rapid pulse, very low blood pressure and an elevated white blood cell count, indicating an infection of some kind; he was not passing urine, because his kidneys were damaged, and he was still vomiting blood. Fluid started to collect on his lungs, and on 11 September his heart stopped. Three days after the incident on the bridge, Markov was dead.

Because of Georgi Markov's unusual symptoms and his sudden death, a post-mortem was carried out. This showed damage to the lungs, liver, intestines, lymph glands, pancreas and testicles, and there were haemorrhages to several organs.
Markov had died of acute blood poisoning, but the cause of the poisoning was not known. Examination of the wound on Markov's leg, however, revealed a tiny metal pellet inside the flesh (checking the X-ray again, what was thought to have been a blemish on the film was now revealed to be the pellet). Measuring only 1.7mm in diameter, the pellet had minute holes drilled into it. It was suggested that the minuscule reservoir formed where the holes met had contained the poison that had killed Markov, but there was no poison remaining in the pellet. The cavity in the pellet was much too small for a lethal dose of arsenic or cyanide; something far more potent had been used. The cumulative evidence from the post-mortem and the symptoms Markov displayed during his final illness suggested ricin, and this was the verdict given at the inquest. Further testing was carried out at Porton Down, a government-run military scientific research facility near Salisbury, England, to confirm this.

By measuring the space inside the pellet, Porton Down scientists were able to calculate the volume of poison it would have contained. They found that a mere 0.5mg of material would have filled the cavity. Ricin is one of the few poisons potent enough to kill in the quantities that could fit inside the pellet.

An identical amount of ricin was given to a pig, and the symptoms the animal developed matched the symptoms displayed by Markov. Pigs are often used as proxies for humans as they are of a similar size, they are hairless, their guts contain similar bacteria and their organs are of a comparable size, so injury and decay processes are also comparable. A post-mortem on the pig revealed similar damage to the internal organs; in fact the similarities were close enough to exclude all other possibilities. Ricin was confirmed as the poison that was used to kill Georgi Markov. The capsule could have been coated in wax, which would have melted at body temperature to release the poison, or in sugars that would have dissolved inside the body.

A similar assassination attempt in Paris, involving another Bulgarian defector, Vladimir Kostov, allowed the British authorities to make further comparisons. Ten days before the attack on Markov, Kostov had been standing on an escalator of the Paris Metro when a pellet was fired into the small of his back. He felt a sting just above the belt of his trousers. A small wound on his back appeared and swelled slightly. The following day Kostov felt unwell; he developed a fever, and went to his doctor. The doctor said there was nothing to worry about, and after a few days his temperature was almost back to normal. After Markov's death Kostov allowed the wound on his back to be examined, and a pellet, identical to Markov's, was removed, along with a sample of tissue for examination. The pellet still had some of the original coating attached, and most of the ricin was still within the pellet. The small amount that had leaked into the surrounding tissue had caused Kostov's symptoms, but it also allowed his body to develop antibodies to the toxin. These antibodies were detected in the tissue samples.

From all the evidence it was hypothesised that an agent of the Bulgarian secret service had fired a pellet into Markov's leg that contained a lethal dose of ricin. The pellet was fired either from an ordinary air pistol, and an umbrella was dropped at the same time as a distraction, or from a specially adapted umbrella designed and built with the collaboration of the Russian secret service. After the fall of the communist regime in Bulgaria it was hoped that the mysteries surrounding Markov's assassination would be cleared up. Documents relating to Markov and the incident were kept in the Bulgarian secret service archives, but many are missing or destroyed. There are still many questions to be answered; no one has ever stood trial for Georgi Markov's murder, or even been seriously accused of committing the crime.