Lathyrism Historical Notes Stockman 1932

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181

HISTORICAL NOTES ON POISONING BY LEGUMINOUS FOODS


BY

RALPH STOCKMAN, M.D.,


Professor of Materia Medica and Therapeutics, University of Glasgow.

In a recently published research ') I have shown that the vetchlings Lathyrus sativus and L. cicera and the bitter-vetch (Ervum ervilia) owe their well-known poisonous actions on the nervous system of man and animals to the presence of an organic acid. Further investigation revealed the hitherto unsuspected fact that such commonly used pulses as lentils (Ervum Lens), the common cultivated pea (Pisum sativum), the soya bean (Soya hispida), the pigeon pea (Cajanus indicus) and tares (Vicia sativa) possess similar poisonous properties and that the active principle is probably the same in all of them. Feeding experiments with these pulses and hypodermic administration of the active substance caused in monkeys and other animals extensive degeneration of the central nervous system leading to paralysis and sometimes to death, results which are not due to dietetic causes or vitamin deficiency but to a poison present in the seeds '). That the excessive consumption of peas and beans ordinarily used by mankind as everyday articles of food may occasion paralysis is no new observation as it has been known since Hippocratic times. In the Epidemics the first historical outbreak of the kind is recorded briefly but very clearly : 'Ev Aivcc
UV%/O, y\eixi Kpveve, <rxwv x.pxTse ysvovTO, xctt xxi opootpoiysovTtq yovvotXyeev 2 ). 1) Journal of Hygiene, XXXI, 1931. 2) Bk. II, Sect. IV. 3 and Bk. VI, Sect. IV.

At Ainos all, both men and women who continuously ate pulses became impotent in the legs and remained so, but those who ate the bitter-vetch suffered from pains in the knees. Ainos was a town in Thrace at the mouth of the river Hebrus (now Maritza) close to Gallipoli and therefore not far from Cos. The Greek word oexpiov is a general term for pulses and includes beans, lentils, lathyrus, the bitter-vetch, lupines and other grains, but was often more specially applied to beans (Vicia Faba). Littr translates it as des lgumes", Clifton J) as leguminous food", Farr 2 ) as beans", but owing to the special mention of poog (Latin ervum, the bitter-vetch, Ervum ervilia L.) subsequent writers have not infrequently attributed the epidemic of paralysis to the consumption of this particular pulse. What happened at Ainos, however, was probably what has happened many times since in Southern Europe, North Africa and India, that owing to failure of the cereal and other crops the poorer people were forced to depend for their subsistence on many kinds of wild and cultivated legumes, which, while harmless as a moderate part of a mixed dietary, exerted their poisonous action when consumed as the whole or principal part. It is, however, remarkable that the cause of the epidemic of paralysis should have been so clearly and definitely recognised. 7he Bitter- Vetch. Ervum ervilia. Huber has suggested 3) that by pooc in the Hippocratic account Lathyrus cicera and (or) Ervum ervilia should be understood, but the bitter-vetch was anciently much used for fodder and to some extent for human food and therefore w;is not liable to be mistaken for any other plant. Dioscorides indeed describes it as well known to all" and lathyrus was probably included in the general term ovyrpiov. It grows well in poor soil and with little cultivation which makes it a cheap food for cattle, and owing
1) Hippocrates upon Air, Water and Situation : upon Epidemical Diseases, etc. London 1734. 2) The History of Epidemics by Hippocrates. London 1780. 3) Bltter f. gerichti. Med., XXXVII, 34. 1886.

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to its special mention in the account of the Hippocratic epidemic and to its being known to cause poisoning among farm animals classical and mediaeval and modern authors have directed more attention to it than its importance might seem to demand. The peas are small and wedge-shaped and have a quite distinct but not very pronounced bitter taste which is imparted to water. Galen's account of it (second century) reads ; In our country and among many other peoples, cattle are fed on bitter vetches after they have been sweetened in water, but men abstain from the seeds for they are sour and of a bad flavour. When they have been washed twice and sweetened frequently in water they lose their unpleasantness and with their unpleasantness their cutting and cathartic power so that the earthy element of their bitterness becomes a dish of a certain parching quality" '). He alludes also to its mention in the Hippocratic writings as causing paralysis but states that it is eaten only under constraint of famine. Dioscorides (first century) says that boiled or well soaked in water it is used as fodder for cattle. Columella 2) (first century) enumerates it among the most valuable forage plants but does not mention it in a considerable list of those employed for human food. He adds that farmers say that a crop sown in March is harmful to cattle and renders them violent after eating it, and Palladius 3) (fourth century) advises that it should be sown in February for this reason. Pliny (first century) says of it 4 ): As a food is unsuitable, it causes vomiting and disturbs the bowels and is heavy on the head and stomach. It weakens the knees also. But soaked in water for several days it is very useful for oxen and draught animals." Ramazzini 5) mentions an epidemic in the Duchy of Modena in 1691, when paralysis of the legs occurred ob usum leguminum ac ervi praesertim" and identifies it with the Hippocratic description.

Valisnieri1 ) (1720) describes weakness of the legs as occurring in persons who ate bread made from the seeds and in horses after eating the plant, and Rossi2) (1762) states that the seeds poison pigs and hens but fatten cattle. Bourlier 3) (1882) relates that on a farm in Algiers fifty pigs were fed on the seeds in the evening and next morning thirtyseven of them were found dead, and similar occurrences have been recorded by others. In England Southall 4), having occasion to determine the cause of death in certain pigs which died after being fed on peas imported from Turkey, grew the seeds and identified the resulting plant as the bitter-vetch. Proust5) (1883) says it is still used as food by the Kabyles and is one of the plants responsible among them for causing lathyrism". We have thus a long and fairly continuous although somewhat scanty record of poisoning by the bitter-vetch, but only when it was eaten in immoderate quantity or over a long period. It seems never to have been popular as human food and probably was used as such only by the poor or in hard times. At the present day it must be scarcely used in any part of the world except as cattle fodder. It is interesting that from a very early period it has been recognised by farmers and recorded by writers that its poisonous properties could be got rid of by soaking it in water and this seems to have been the common practice among agriculturists and when it was used for human food. The Vetchlings. Lathyrus. Lathyrus sativus (the chickling vetch) is described as growing wild from the Southern Caucasus to Northern India but it has been cultivated in India, Southern Europe and North Africa from
1) Esperion/e cd osscrvaiione speltanti all' istoiia medica c naturalc. Venezia 1720. 2) De nonnullis plantis quae pro venenatis habentur observationes et experimenta.

1) %tpi Ttov ev T/ rpotyoci Svvxfiiuv. BK.I. 2) De re rustica, Lib. II, XI. Ibid VII. 3) De re rustica, Lib. Ill, Tit. Vil. 4) Lib. XXII, Cap. 73. 5) Conslkutio epidmica anni 1691. Modena.

Pisa 3) 4) 5)

1762. Gaz. md. de l'Algrie, XVII, 139, 1882. Pharmaceut. Journ. 1879, X, 481. Bull. Acad. Md. XII. 829, 1883.

the cited work by Bourlier does not have any comment about V. ervilia and pigs

184 time immemorial partly and largely for human food and partly for fodder. Its peas along with those of L. cicera (the flat-podded vetch) and L. clymenum (Spanish vetch) have long had an unenviable reputation as apt to cause paralysis in man and all kinds of farm animals. Today as found in commerce the peas differ a good deal in size and appearance. Careful cultivation and selection in Europe have produced in L. sativus large white fleshy seeds, wedge-shaped and having a distinct resemblance to dogs' teeth (the dog-tooth pea). In India it occurs in two sizes, one about half the size of the European pea, with a brown seedcoat and wedge-shaped, the other much smaller, darker and meaner looking. Those grown in Algiers resemble the Indian variety. L. cicera peas grown in France are hardly distinguishable from the larger Indian kind of L. sativus while those of L. clymenum are smaller. All seem to be equally poisonous. The Greek name for vetchlings was Xxupo and Galen says of them In their substance the vetchlings are like pulse (xpoi) and kidney beans {(pxvyXoi) and countrymen in our part of Asia chiefly use them and most of all the men in Mysia and Phrygia, not only in the fashion in which the inhabitants of Alexandria and many other cities use pulse and kidney beans but also by preparing them like bruised lentils." The Roman name was cicera (L. cicera) and cicrcula (L. sativus). Columella says they were highly prized in Hispania Baetica (Andalusia) as fodder for cattle and that they are not useless for human food nor unpleasant to the taste. Dioscorides does not mention lathyrus but possibly he did not distinguish it from certain other peas. In the early days of botany and for long afterwards the classification of plants rested on very uncertain and variable features, hence the species and varieties of peas were very indefinitely differentiated both by botanists and medical writers. The current popular names were applied very loosely and often to different peas, so that it is sometimes difficult and even impossible to determine which is meant, a difficulty which has continued to this day (in France). Theophrastus l) (fourth century B. C.) in discussing the differences between pulses
1) Enquiry into Plants. The Loeb Classical Library 1916. Trans, by Horst. VIII, V, 1.

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says: In pulses we cannot find such differences whether for want of careful enquiry or because there is less diversity in these plants. For apart from chick pea (psivooc), lentil (cpctKog), and to a certain extent bean (KVX(OC) and vetch (pooc) in so far as in these we find differences of colour and taste, among the rest no distinct forms are recognised." Galen also says that Arachos has a seed very similar to that of vetchlings and that it is considered by many to be in no way different from them. In later times the bitter-vetch, lathyrus (sativus and cicera) and the chick pea (cicer) continued to be confused with each other. Eliny speaks of cicrcula when he evidently means cicer, while in the sixteenth century Matthiolus accuses and convicts Brasauolus ') and the celebrated botanist Fuchs 2 ) of somewhat similar irregularities. Fuchs, for instance, regarded L. sativus as the cultivated form of the bittervetch. An enquiry carried out in France by Lunier 3 ) in 1883 revealed that neither botanists nor the country people were agreed as to the popular names of these peas, nor as to the exact relationship of popular and botanical nomenclature. It was found that the names gesse, jarosse, jarat, besides other more local terms, were used indiscriminately for L. cicera, L. sativus, Ervum ervilia, and sometimes for tares and other vetches, and that they were often applied to different plants in districts quite close to each other. And the most eminent modern French botanists differ as much as the country people 4). The whole matter is not of much importance from the toxicological point of view as these plants have now been shown to possess similar poisonous properties. The earliest authentic account of a pandemic of paralysis due solely to lathyrus we owe to Joh. Nie. Binninger 3) (1673) who
1) Examen omnium simplicium medicamentorum quorum in officinis usus est. Lugduni 1543. 2) De historia stirpium. Lugduni 1549. 3) Bull. Acad. Md. XII, 910, 1883. 4) Conf. Billon, Diction, de Botanique 1886: Moquin-Tandon, Elements de Botanique Mdicale, Paris 1861 : Le Maout et Decaisne, Trait gn. de Bot., Paris 1868: Lamarck & Decandolle. Flore Franaise IV, 1815: Diet, encyclop. Se. Md. Article Gesse. 5) Observationum et curationum medicinalium Centuriae Quinqu. Montisbeligard 1673. Obs. 70, p. 571.

186 calls it a new and unheard of disease". It occurred in the neighbourhood of Montbliard, a town in the department of Doubs on the Swiss frontier of France, but at that time part of the dominions of the House of Wrttemberg. Probably he was no great botanist and misled by consulting Matthiolus he calls the plant Ervuw. His description of the peas, however, leaves no doubt that it was lathyrus, and Duvernoy who described a similar outbreak in the same district a hundred years later shows Binninger to have been mistaken and adds that the bitter vetch is not grown in this region. The plant had been introduced ten years previously by a local farmer and owing to its luxuriant growth his neighbours had also cultivated it extensively and used it to feed their cattle and horses and to make bread for themselves. Only the country people were affected, the towndwellers escaped, and with admirable acumen Binninger traced the disease to the bread. His strikingly graphic and accurate description of the symptoms and gait along with his identification of it as a disease of the nervous system stamp him as an outstanding clinician. He gives a list of his patients of whom none were relieved, none cured, none died." Horses fed on the whole plant suffered from paralysis and tremors and it required this to convince the inhabitants that Binninger's explanation of the cause of their own misfortunes was the correct one. Its culture was prohibited by solemn ducal edict in 1672 but as the edict was renewed in 1705 and again in 1714 it is unlikely that it was effective. Duvernoy ') (1770) devotes much space and attention to the botany of lathyrus and in his clinical account notes for the first time that women are much less often affected than men, wives than their husbands, although living on the same food. Horses fed on it became weak in the legs, and pigs affected in the same way lay down a great deal and were apt to become very fat. This, he adds, is hard to understand as cattle in certain parts of Switzerland devour it and are not injured. In 1784 in consequence of a failure of the crops in Tuscany
i) Dissertatio inauguralis medica de Lathyri quadam venenata specie in Comitatu Montbelgardensi culta. Basileae 1770.

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peas were imported from Tunis to make bread and as a result many cases of paralysis of the legs occurred. This outbreak has been described by Targioni Tozzetti ') who grew the peas and identified the plant as L. sativus. Matthiolus (sixteenth century) says that L. sativus (cicrcula) was largely eaten in Italy in his time and there is little doubt that the same was true of France and Spain and the Mediterranean countries generally. L. cicera was also grown extensively and used as food, and under such names as crurum exsolutio, crurum imbecillitas, crurum impotentia the disease which was later called lathyrism by Cantani (Naples, 1873) seems to have been very familiar to the physicians of those days. During the nineteenth and twentieth centuries much interest has been taken in the subject both by governments (India, France) and by individual investigators, and many outbreaks have been carefully studied and recorded in India, France, Italy and Algeria. Since 1820 when the Veterinary School at Alfort (Paris) published a warning to horse-owners against the use of L. cicera as a feedingstuff there has accumulated an extensive veterinary literature regarding poisoning in horses, cattle, pigs, sheep and poultry. Many agriculturists have stated as their own personal experience that they have never seen any ill-effects from feeding stock on lathyrus either the whole plant or peas but the evidence on the other side is overwhelming and Cornevin gives a most interesting and conclusive account of it 2). The explanation is, as I have shown elsewhere, that different samples of lathyrus peas vary greatly in their content of the toxic substance. Proust says that in Algeria a crop sown in March (instead of April) is believed to be especially poisonous and the influence of soil and weather has to taken into account as factors determining the degree or toxicity at different times and places. But in all cases in which poisoning has occurred the amount consumed must be regarded as having been excessive 3).
1) Memoric sullc Cicherchie. Firenze 1793. 2) Plantes vnneuses. Paris 1887. ./ 3) The literature of lathyrism is fully given by Schuchardt, Deutsch. Archiv, klin. j 1 Med., XL, 312, 1887 & Stockman, Edin. Med. Journ., Nov. 1917 & Journ. of j Pharmac. & Exper. Therap. XXXVII, 1929. l'[

i88

189 produce sexual power so that for this reason it is given to stallions to eat". Paul of Aegineta says: Cicera instant, abstergunt, gnitale semen augent, venerem stimulant, calculum terent." It is a very considerable article of food in India, Spain and other countries and in India (Anglo-Indian gram) is the chief grain used for feeding horses. No experimental examination of its action on animals has ever been made and there is no indication in the literature of any deleterious effects when used as a food either for man or horses. From the foregoing account it is evident that during the long ages that leguminous plants have been used by mankind for food only a very insignificant number of them have aroused any suspicion that they might be poisonous. This is due to the circumstance that their consumption has usually been kept within the limits of safety and in consequence there have been no harmful effects which might have attracted attention. Very few of them have hitherto been subjected to careful pharmacological investigation but now that a beginning has been made ') it will probably be found that others, and probably all of them, contain a poisonous substance capable of damaging the nervous system and that their shortcomings as foods are due to this and not to deficiency of vitamins or amino-acids as has been sometimes assumed.
l) Jour. Hygiene loc. cit.

Pigeon Pea. Cajanns indicus. The pigeon pea is largely eaten in the East and West Indies. The Indian names are arhar, urhur, toar. Kinloch Kirk ') says it causes chronic poisoning, the symptoms being urticaria, heat in the stomach, redness of the oral mucosa, discoloration and cracks of the skin, a burning feeling in the hands and feet, rheumatic pains and thickening of the periosteum. It is also said that the physical powers and moral sense deteriorate and that women become barren 2). This description is reminiscent of what is seen in pellagra, but such effects seem to be unknown to medical men either native or British with experience of Indian practice. Kirk however had a very expert knowledge of leguminous foods and was a reliable observer. The peas of Dolichos pilosus, a dal known as oordh or maash, are also said by Kirk to have similar effects. Vicia sativa var. angustifolia Vernacular, akta, akri. Anderson, Howard and Simonsen 3) have described a series of experiments on animals which shows that the seeds of this vetch have an action similar to that of lathyrus. It is a weed which grows very plentifully in the fields in India and is not used for human food. I have found that the seeds of the cultivated Vicia sativa (tares) grown in Europe and largely used as feeding-stuff produce similar poisonous effects 4). Chickpea. Cicer arietinum, Galen's account of it is that it is largely used as a food made into soup, boiled with milk, boiled and eaten with salt, or sprinkled with powdered cheese. It is also eaten green. He continues: It is believed to kindle sexual desire and at the same time to
1) Indian Annals of Med. Science, VII, 144, 1861. 2) Journal of Trop. Med., I, 1899. 3) Ind. Journ. Med. Research XII, 613, 18245. McCombie Young, Inp. Journ. Med. Research, XV, 453, 1927 & Transact, of the F.E.A.T.M., Vol. Ill, 444, Calcutta 1929. Acton & Chopra. Ibid. 4) Jour, of Hygiene XXXI, 1931.

Archives internationales pour l'Histoire de la Mdecins et la Gographie Mdicale.


(Organe de la Socit historique nerlandaise des Sciences mdicales, exactes et naturelles. )

JANUS
RDACTEURS.

Dr. AOYAMA, Prof., Tokyo; Dr. D. A. FERNANDEZ-CARO

Y NOUVILAS, Madrid; Dr. A. CAL-

METTE, Dir. de l'Iust. Pasteur, Lille; Dr. ERNST COHEN, Prof., Utrecht; Dr. Cn. CUEICTON, Londres; Dr. A. CORSINI, Prof., Florence; Dr. A. DAVIDSON, Prof., Edinbourg; Dr. P. DOKVEAUX, Bibliothcaire, Paris; Dr. F. M. G. DE FEYFER, Geldermalsen-, Dr. A. FON AHN, Kristiania; Dr. J. HEMMETER, Prof., Baltimore; Dr. A. JOHANNESSEN, Prof., Christiania; Dr. J.KERMOKGANT, Insp. du serv. md. des colonies franaises, Paris; Dr. KITASATO, Prof., Tokyo; Dr. J. P. KLEIWKO DE ZVVAAN, Prof., Amsterdam; Prof. Dr. A. B. LUCIIHARDT, Chicago; Dr. J. E. MONJAKAS, Saint-Louis-Potosi, Mexique; Dr. VAN SCHEVENSTEEN, Anvers; Dr. C. SINOER, Prof., London; Dr. K. SUDHOFF, Prof., Leipzig; Dr. C. J. S. THOMPSON, Stanmore ;Dr. G. F. TREIM.K, Insp. K. II. du Serv. Md. des Colonies, Vichy; Dr. E. WICKERSHEIMER Strasbourg.

Trente et Sixime Anne.

LEYDE. E. J . BRILL, S. A.c.

1932.

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