THE first rumours of a macabre ritual practised in the south-eastern corner of Nigeria reached Britain around 1840. Missionaries reported that those suspected of witchcraft, murder and other terrible crimes were forced to swallow a bean that contained a deadly poison. If they died, which was more than likely, they were pronounced guilty. If they vomited the bean up and survived, they were innocent. Waverers who showed ill-effects without expiring were sold into slavery.
So fervently did local people believe in the divinatory powers of esere, that the wrongly accused would often demand to be put to the test. Less than half a bean could kill, but the beans varied in their potency according to their ripeness, and those in power knew how to select weak or strong to achieve the verdict they wanted. Esere was also a popular choice of weapon in duels. Adversaries would carefully divide a bean, swallow half each, and more often than not, watch each other die. Not surprisingly, European missionaries regarded esere as a great social evil. But for many of them, that only fuelled their desire to lay their hands on it.
In the 1840s, collecting botanical specimens was all the rage. Explorers, missionaries, amateur and not-so-amateur scientists scoured the globe for plants, which they transported back to the botanic gardens at Kew or Edinburgh. These exotic plants weren鈥檛 just novelties for the garden but were the source of new drugs, poisons and other useful chemicals. Travellers brought coffee beans from Africa, the bark of cinchona trees from Peru, the seeds of the East Indian tree Strychnos nux vomica, from which chemists isolated caffeine, quinine and strychnine. But for 20 years the vital ingredient of esere eluded them.
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The biggest obstacle was identifying the plant that produced the bean. It was some sort of vine with purplish flowers but, try as they might, nobody could lay their hands on more than a few miserable leaves. Eventually, the Reverend Waddell discovered that the local king had ordered the wholesale destruction of the vine so that he could maintain a monopoly on the few plants that remained and control the administration of justice.
In 1855, Waddell smuggled out a few seeds and sent them to the great toxicologist Robert Christison in Edinburgh. Christison passed some of the seeds to the city鈥檚 botanic garden. The beans sprouted and grew vigorously. But they produced no flowers. It was another 4 years before another missionary sent home a flowering specimen preserved in alcohol, and the plant was finally given a name, Physostigma venenosum.
In the meantime, Christison had decided to observe the physiological effects of esere. He had a simple technique which he had tried before with arsenic, opium and hemlock. He swallowed some. Just a quarter of a bean was enough to slow down his heart, and he speculated that the bean probably killed by paralysing the heart. 鈥淭he absolute absence of pain in his personal experience suggested to him that the drug might be humanely employed in the execution of criminals condemned to death,鈥� wrote John Uri Lloyd, an American pharmacologist, in 1897. But it never came to that.
Like the African judges before them, British doctors realised that the effect of the ordeal poison depended critically on its dose, and in small amounts it could be put to good use in healing. Chemists isolated two active ingredients, of which the most important is the alkaloid physostigmine. Just a few milligrams could counteract the effects of another potentially lethal poison, belladonna or atropine. The usual victims of this type of poisoning were children who had swallowed the berries of deadly nightshade, and many were saved by swift treatment with physostigmine.
Ophthalmologists also found it handy. Atropine and physostigmine have opposite effects on the autonomic nervous system, which controls involuntary actions such as the dilation of pupils. While ladies used to drop belladonna into their eyes to dilate their pupils and enhance their beauty, it soon became common practice among ophthalmologists to apply physostigmine drops during eye examinations to make pupils contract.
The autonomic nervous system also controls another reflex, ejaculation, and in the past few years physostigmine has found a novel application helping paralysed men who want children. Unable to respond to the signals of sexual arousal, these men had been considered infertile. But by triggering the reflex, injections of physostigmine enabled them to become fathers.
And that鈥檚 not all. The ordeal bean may have an important role in modern warfare 鈥� not as a weapon but as a means of protecting troops from nerve agents. In 1934, Mary Walker, an assistant medical officer at St Alfege鈥檚 Hospital in London, made a surprise discovery. Walker was searching for a cure for the progressive muscle-wasting disease, myasthenia gravis. We now know that this is an autoimmune disease in which the body produces antibodies against receptors for the neurotransmitter acetylcholine, which makes muscles contract. The antibodies lock onto the receptors in place of acetylcholine, preventing contraction.
Walker didn鈥檛 know what was going on, but she did notice that the symptoms were similar to those of curare poisoning. By this time physostigmine was a recognised antidote for curare as well as atropine, and Walker speculated that it might also reverse her patients鈥� weakness, at least temporarily. One patient, Miss C, was unable to raise herself up in bed or lift a teacup. But according to Walker鈥檚 medical notes, 15 minutes after an injection of physostigmine, Miss C was up and about and vigorously 鈥渦sing a heavy floor-polishing brush鈥�.
Later studies showed that physostigmine binds to the enzyme that normally soaks up free acetylcholine, preventing the enzyme from doing its job and thereby prolonging the action of acetylcholine. The nerve agent sarin, which was released by terrorists on the Tokyo subway in March 1995, killing 12 people and injuring thousands, also binds to this enzyme. The difference is, sarin binds permanently, sending the muscles into spasm and causing long-term nerve damage, while physostigmine releases the enzyme after a short interval. Given at the right time, physostigmine can block the worst effects of agents like sarin without causing any lasting damage.
British and American troops going into conflict are already given a related drug called pyridostigmine to protect them against attack by nerve gas. But scientists experimenting with physostigmine at the British government鈥檚 Defence Science and Technology Laboratory (DSTL) at Porton Down, Wiltshire, are finding that it affords better protection. In wars of the future, soldiers could be taking the main ingredient of esere into battle with them.
But as the Swiss physician Paracelsus said: 鈥淭he right dose differentiates a poison and a remedy鈥�. And lest we forget that the first recorded use of physostigmine was as a lethal poison, the odd historical accident serves as a reminder. First in 1864 and again seven years later, two cases of mass physostigmine poisoning were reported in Liverpool. Despite the African king鈥檚 decree, the odd bean had found its way onto British merchant ships trading with West Africa, and gangs of children roaming over the city鈥檚 docks picked up the discarded beans and ate them. Thanks to prompt treatment with atropine, only 1 of the 57 poisoned children died.