ORDEAL BY POISON

Te Awamutu Courier, Volume 53, Issue 3822, 16 October 1936, Page 3

ORDEAL BY POISON

A SCIENTIFIC ROMANCE. A romance of research from the discovery of Calabar bean in darkest Africa to the synthesis of a new and potent therapeutic agent a few years ago. This story begins on the West African coast—Old Calabar, in 1846, Here it was first noted that the crushed seeds of an aquatic plant , were made into a potion with water to be taken by persons accused of a capital offence. If the subject was fortunate enough to vomit, he survived, and at the same time established his innocence. If not, then death was rapid, and as certain ns his guilt was adjudged to be! The scene shifts from Old Calabar to Edinburgh in the great days of that famous medical school, when, after having studied the effects of the bean upon animals, and then upon himself, Professor Christison <frank his shaving water to save his life by emesis. Thomas Fraser, Christison’s assistant, and later the famous professor of medicine of that school, followed up the study of Calabar bean, and accurately described its action and the antidote effect of belladonna in his M.D. thesis in 1863. Before this, however, Argyll Robertson, whose name is almost synonymous with opthalmology, had acted upon the evidence of its action upon the pupil of the eye, and tried it upon himself. He found that deadly nightshade counteracted the effect, and introduced it into opthalmology, where it has retained a valuable place to this day. DAYS OF GREAT POSSIBILITIES. The scientific name, too, was given by the, professor of botany at Edinburgh, J. H. Balfour—Physostigma viiienosum—and the active principle came to be termed Physostigmine. To become properly orientated with these names and dated one need only remember that they are the times of “Darkest Africa,” of Livingstone, Speke, Bruce,, and other explorers. Dr Kirk, botanist with Livingstone, brought back some arrow poison from the Zambesi to Fraser in 1862, and from’ that date medicine came to know and 'to use. strophantin. From Australia, too, the poisonous narcotic chewed by the aborigines went back to Fraser, whose judgment concerning its 'constitution has only recently been affirmed by work done in the University of Adelaide, after 60 years of conflicting opinion. r . They were the spacious days of great possibilities, and Edinburgh happened to have the men. Out of their hands, then, came Physostigmine. It had the valuable property of constricting the pupil of the eye, and in addition was known to act as a powerful motivator of the intestine, while it also slowed the heart. In fact, this latter effect, if severe, caused death. Our next interest centred naturally in the constitution of this powerful poison, and that brings us to 1893, from which date until 1924 Polonovski published eleven papers upon his researches in this field, his last paper being in collaboration with his son. Upon this foundation, Barger, also of Edinburgh, built further, and estaßlished a formula for the substance in 1925, which in 1933-35 was con-

firmed by its synthesis by Robinson of Oxford. Such is the nature of the long and laborious chemical work underlying therapeutic advance. From the moment of publication by Barger of the probable formula of Physostigmine it became possible to examine the physiological properties of the substance in terms of its structure, and to this the great firm of Hoffmann la Roche, in Basle, bent the energies of some of its best research chemists. To Aeschlimann, a British chemist upon their staff, fell the honour of synthesising, after numerous compounds had been constructed, the now widely known substance Prostigmine. The object aimed at was to secure, if possible, the effective action upon the intestine without at the same time, poisoning the heart, and the object was achieved in his new preparation which now places in the physician’s hands a new and valuable therapeutic agent. NEW INVESTIGATION. It has been shown by chemical trial to be an effective substance for certain post-operative motor disturbances of the intestine, but its effect in Myasthenia Gr,avis has been perhaps the most spectacular, though the condition fortunately is quite rare. In this disease muscular weakness passing into paralysis is the chief phenomenon, and although Physostigmine was shown to remove the weakness, its effect upon the heart and intestine was inconvenient. Prostigmine can be used without these side effects being troublesome, and has enabled physicians to investigate this disease from which, except in cases of spontaneous reinission, there was no recovery. The physiological action of Physostigmine, and now of Prostigmine, has opened a new avenue of investigation along which rapid movement has taken place in the past year. It now seems to be established beyond doubt that, when a nerve to amuscle transmits an impulse, causing it tp contract, the final stimulus to the muscle has been a chemical one. To establish this, Physostigmine has been the essential weapon, for it prevents the otherwise rapid destruction of the chemical transmitter (acetylcholine), which was previously discussed in these columns. The object in mentioning this, however, is to show that the period intervening between Old Calabar in the “earlies” and Europe in the post-war period has seen, among many things, the laborious unfolding of the story of Physostigmine, and with it the means for unlocking the secret of nervemuscle action. We may now hope to see increasing knowledge of many paralytic conditions which hitherto have resisted investigation. C.S.H. in Melbourne Age.