From Poison Arrows to Prozac. Stanley Feldman

he arranged for the demonstration before the members of the Royal Society in London in 1812.

      In this experiment it is reported that he brought a ‘she ass’ into the lecture theatre. He showed that the arrow poison, which on this occasion he termed ‘woorari’, killed its victim. It is recorded in the minutes of the society that, shortly after the injection of a small dose of woorari into the leg of an ass, it caused the animal to become paralysed and to stop breathing.

      He performed an immediate tracheostomy, an operation with which every surgeon was well practised in the days of diphtheria, and inserted a domestic bellows into the animal’s windpipe. This allowed him to maintain the animal’s life by inflating its lungs with air (in this he was 140 years ahead of his time, for it was only during the polio epidemic of the 1950s that positive-pressure artificial ventilation was used to overcome respiratory paralysis). The minutes of the society state that ‘he restored the life to a she ass poisoned by woorari by rhythmically pumping air into the animal’s lungs for two hours’. It is also recorded that the animal survived the experience and lived content for several years after the experiment.

      It was by means of this demonstration that Brodie showed how curare killed its victim. Unlike other more common poisons, it did not kill by poisoning the brain or the heart but by causing paralysis of the muscles of respiration, resulting in death from asphyxia.

      Although there is good evidence that Charles Waterton also performed a similar experiment on an ass he called ‘Wouralia’ with a similarly successful outcome at about the same time, he failed to convince the scientific community of the importance of his observation. This may have been due to the lack of public awareness of his experiment, but is more likely to have been due to scientific scepticism concerning his work. Although there is some uncertainty as to whether Brodie or Waterton was the first to demonstrate that artificial ventilation was capable of maintaining life in animals poisoned with curare, Brodie’s presentation at the end of 1812 was undoubtedly more scientifically significant than the anecdotal account of Waterton’s experiment.

      What is the arrow poison?

      One of the problems that dogged the early experiments with the South American arrow poison was the variation that occurred in the amounts of the different ingredients that went into the samples used and the question of whether it deteriorated with age. Benjamin Brodie recognised this and commented that his woorari was similar to that supplied to the Abbé Fontana for his experiments.

      The poison certainly varied according to the region in which it was produced. Specimens collected from the Orinoco basin by the Schomburgks were largely composed of the bark and root of the creeper Strychnos nux. (Fig 7) Indeed, they called the poison Strychnos toxifera. As a result of its strychnine content, the immediate convulsive effects predominated, concealing the onset of the paralysis produced by the curare. This was probably why the German physiologist Albert von Bezold, using a preparation given to him by the Schombergs, believed the drug killed its victims by inducing convulsions. The poisons prepared from the more western jungles of Ecuador and the Peru were principally composed of an extract of the bark of vicuñas, and particularly that of the creeper, Chondrodendron tomentosum. (Fig 8) These contained high concentrations of curare and were similar to those collected by Waterton and those used by Brodie to demonstrate the paralytic properties possessed by their toxins. In an attempt to reduce the confusion, Dr Rudolph Boehm, in 1886, suggested classifying the curares according to their mode of preparation in the belief that the means used to store the poison indicated the region from which it came. He separated the curares into pot curare, tube curare, and calabash or gourd curare. This classification reduced the confusion, but it was not until 1935 – when Harold King, working in the Burroughs Wellcome laboratories in England, isolated and identified the chemical structure of curare – that pure specimens of the drug became available for study.

      By the middle of the nineteenth century supplies of crude tube and calabash curare, of a reasonably consistent quality, were available in Europe thanks to the work of Wilhelm Peyer, who prepared a crystalline salt of the poison. Although this was later shown to contain potassium carbonate and phosphate as impurities, it was much better than the crude preparations previously available.

      By this time it was appreciated that curare caused death by paralysing the muscles of ventilation, and that, provided artificial ventilation was maintained, it did not cause any long-lasting ill effect on the body. The riddle of how and why it produced paralysis was to wait until the simple, elegant experiments of Claude Bernard in France, the intuition of the physiologist Otto Loewi and the experiments of the Henry (later Sir Henry) Dale and his team of fellow pharmacologists at University College, London.