Actions and medicinal use of spider venoms

ACTIONS AND MEDICINAL USE OF SPIDER VENOMS By OTTO LE~ISER, M.D., Phil.D.(Berlin) TH~ phylum Arthropoda includes--besides the insects, crustaceans, and others - - t h e class of Araehnida. This class comprises the scorpions, mites and ticks, harvestmen, and a few minor orders, and the order of Araneida or spiders. The Araneida are divided into five sub-orders, only two of which concern us here: (1) the Aranomorphae or Dipneumones, having one pair of lungs, and (2) the Mygalomorpha~ or Tetrapneumones, with two pairs of lungs. The Aranomorphae, or "true" spiders, comprise the vast majority of species. They are sometimes called Tarentulas. Thus "Tarentuta" nowadays designates neither a genus nor a family. W h a t our Pharmacopoeias have under the names of Tarentula hispanica and Tarentula cubensis needs re-identification. The former is Lycosa (Hogna) hispanica and belongs to the family of Lycosidae, "wolf-spiders" (sub-order Aranomorphae). There is no agreement between experts as to whether " H o g n a " is a true sub-genus of Lycosa. The old name Lycosa tarentula hispanica is still in use. Tarentula cubensi8 is Eurypelma spinicrus Latreille (1), and belongs to a family of the sub-order Mygalomorphae; thus the name Tarentula should be abandoned for this species. The Aranomorphae are called true spiders because most of them weave true webs. The woff-spiders (Lycosidae), however, are ground-dwellers, and line their burrows with silk-tubes similar to those of the Mygalomorphae. The Mygalomorphae, living mainly in holes, weave tubes provided with a trap-door, hence their name "trap-door spiders", or if they do not attach lids to their burrows, "funnel spiders". The craftsmanship of spinning and weaving, in m a n y species of spiders (for instance Aranea) developed-to a highly artistic instinct, could not fail to fascinate naturalist-man. The fine threads of viscid silk produced from the spinning apparatus at the end of the abdomen ("spinnerets") have been used as a vulnerarium in antiquity, as Dioscorides tells us (see Appendix I). I t m a y well be that the delicate strands could facilitate the formation of fibrin, and this primitive use is no more abstruse than the use made of cobweb-tincture by the eclectic school of the last century; the symptoms indicating to them "Tela aranearum" are strongly reminiscent of those known as actions of the whole spider; thus, it seems, "pars pro toto" has been taken. The subject is, however, now only of historical interest. The spinning and weaving of artful traps for their prey, mainly insects, is obviously a highly specialized heritage of spiders, peculiarly adapted to their way of living. The differences in the formations of these (a posteriori!) activities offer a useful criterion for their classification; more so even than the colour markings on the abdomen of m a n y species, as these undergo considerable changes in the course of the development of both male and female of the same species. The other direction in which spiders have become specialized, is related to their feeding habits (activities a priori!). The peculiar instruments for paralysing and killing their victims are the chelicerae, a pair of claws rather than jaws, for they form no part of the mouth, but are inserted around it; they are apparently transformed antennae. Each ends in a sharp chitinous hook or "fang". The chelicerae contain the ducts of the two venom glands in the eephalothorax of the spider. The gland ducts terminate in an orifice near the tip of the "fangs" so that the venom is instilled immediately with the wounding;

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strictly speaking it is neither a bite nor a sting; the venom glands are not salivary glands. The venom glands and ducts of the Aranomorphae are elongated and their "fangs" move horizontally in "pincer-fashion", the Mygalomorphae have short glands and ducts and their "fangs" move in a vertical plane. The habits of the various species in overpowering and killing their entrapped victims differ. Latrocdectus maetans, the "black widow", fetters its prey, which

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L A T R O D E G T U S M A G T A N S , .FEMAL E The Black Widow 3 t i m e s life size a p p r o x .

m a y be many times its own size and weight, in a very strong mantle of silk strands and then approaches and seeks a point at which it may insert the claws; then the spider retires and awaits the result; in a few minutes the struggles of the victim cease; the spider leisurely returns, completes enwrapping the body and hoists it to the desired position in the web. Fastening the mouth parts to some portion of the body the spider then proceeds to suck the body fluids. The abdomen of the spider after feeding may be twice its original size. Later the dry skeletal husk is cut out and dropped from the web (2). Other spiders proceed

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more rapidly: they jump at the entangled insect, "bite" into its neck near the cervical gangha, injecting at the same time the venom so that the victim is paralysed. The effects indicate a chiefly neurotropie character of the venom. I n some spider species it must be very potent; not only small snakes, hzards and birds, but even mammals like mice, sheep, goats, dogs and even men m a y succumb from the poisoning. However, the composition of the venoms apparently differs from species to species of spiders, as can be inferred from the diverse effects of the bites. When more of the chemical composition of the venoms becomes known, it m a y well prove a characteristic for each species. Judging from the sequelae of the bite of spiders in man, there are two main types of venom. A number of species, particularly South American ones, are known to cause local inflammation and more or less extensive necrosis, which m a y be followed b y an intermittent, septic feverish condition. Cutaneous arachnidism or "gangrenous spot of Chile", i.e. severe local necrotic and gangrenous lesions, but without direct systemic effects, are caused for instance by Loxosceles lzeta (3). Other species, whose bite shows prominently necrotic effects, are Lycosa raptoria, Araneus audax, Ctenus nigriventer and Eurypelma spinicrus. I t is assumed that their venoms contain a potent proteolytic enzyme similar in action to trypsin; h u m a n serum is able to antagonize it. These necrotizing agents are more readily inactivated b y heat and ultraviolet radiation t h a n the so-called neurotoxins are; thus the two proteinic (or protaminic?) constituents are distinct. A common constituent of spider (as of m a n y other animal) venoms seems to be the "spreading factor", the enzyme hyaluronidase. I n the body fluid of spiders, particularly of fertilized females and in their eggs, a complex poisonous substance different from the venom of the chelicerae glands, has been found, the so-called araneilysine (or aranolysine). This is said to have hmmolytic properties and further to contain thrombokinase. Apart from one assertion in respect of Aranea diademata (see v. Grauvogl) (12), there is, however, no evidence t h a t extracts of whole spiders interfere with blood coagulation in man. Differences betweenthe gland venoms and extracts of the whole crushed spiders are certain to exist and therefore the effects of bites can supply no more t h a n a partial toxicological basis for the actions of our preparations from whole animals. About the two species of Mygalomorphae which are rarely used in Homoeopathy, iittle needs to be said here. Eurypelma spinicrus (under the old name of "Tarentnla cubensis" or Myg~le cubensis) has not been subjected to provings. Its use for necrotic carbuncles, phlegmona and panaritium is based solely on the local tissue-effects of the bite. Evidence of its usefulness in these conditions is not available. I t has, therefore, no proper place in homceopathic materia medica yet. Avicularia avicularia (under the old names Mygale Lasiodora and Mygale avicularis) has had a very scanty proving by one lady (4). The symptoms from taking 10-20 drops (of the M. tincture?) for 3 days accord well with those from better-known spiders; they were: "Aversion to food, nausea with strong palpitation of the heart, dimness of sight, general weakness, great prostration, sadness, pain in the back extending to the front, tremulousness over the whole body in the evening, restless all night with ridiculous dreams." One case of a man bitten by "Mygale avicularis", too, reveals nothing t h a t is not better and more fully described for other spiders. Hence there is as yet no reason why this Mygale should have advantage over Tarentula hispanica in chorea or twitehings of facial muscles, etc. The other spiders with which we are concerned here, belong to the sub-order of Aranomorphae. They are species of the three families: Theridiidae, Lycosidae and Epeiridae.

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LATRODECTUS MACTANS An extensive literature exists on Latrodectns mactans and the effects of its bite. This species is common in the Southern half of the U.S.A., where it is known under the name of "black widow", alluding to the matrimonial habit of the female of killing the smaller and weaker male soon after she has been fertilized; another name, "hour-glass-spider", refers to the red hour-glass-shaped marking on the black background of the ventral surface of the adult spider; another name, "shoe-button", to the shiny black of the globular abdomen. Lactrodectus mactans also seems to be the species found in South America. Other species of Latrodectus are: L. tridecimguttatns, the malmignatte of Southern Europe, L. lugubris, the " K a r a k u r t " of Russia, and L. Hasselti, the " K a t i p o " of New Zealand. From numerous case reports on persons bitten by Latrodectus mactans the acute local and systemic syndrome is well established. E. Bogen (5) gives a s u m m a r y of 400 cases of which more than a dozen were fatal, with references to several hundreds of papers on the subject. Clinical interest has centred on t h a t part of the syndrome which seems to emulate acute abdominal conditions by the board-like rigidity of the abdominal walls; but absence of local tenderness serves as differential sign and thus m a y prevent surgical intervention on a faulty diagnosis. Other syndromes which m a y be emulated are tabetic crises and angina pectoris. The course of events after the bite is best illustrated b y the experiment of A. W. Blair on himself (6). I n this instance the intense local inflammation of the bitten finger and ascending lymphangitis m a y be attributed to the fact t h a t Blair allowed the spider to bite for 10 seconds. I n the first stage of "lymphatic absorption" a slight numbness along the ulnar side of the hand appeared within 15 minutes, extending rapidly up the arm (others have observed burning sensations). Within 33 minutes after the bite Blair recorded slight aching pains over the precordium. The second stage which was called "vascular dissemination" by Blair, but m a y be considered as the first phase of the systemic actions of the venom, lasted approximately 2 hours. I t began with a dull, drowsy, lethargic feeling. The main features of this stage were increasing pains associated with spasms and rigidity of muscles, involving more and more regions of the trunk and then of the extremities, and further a shock-like condition. Aching in the epigastrium extended to the whole abdomen, where it rapidly grew to severe pains, the abdominal walls being tense and becoming more and more rigid, boardlike. Aching in the muscles of the neck spread to the lumbar region, to the chest with a feeling of constriction, speech was diJficult and jerky, respiration rapid and laboured. The pains became agonizing, it was "a torture to lie still on the back, while E.C.G.'s were made" (these were normal, but Bullman, U.S. Nay. Med. Bull., 47, 975, 1947, reported changes of the E.C.G. after Latr. mact. bite). The pain and rigidity spread to the legs and then to forearms and hands; "unable to straighten up and stand, rigid flexion of the legs, tremor, spasm of the flexor muscles of the forearms and the adductors of the thumb (accoucheur's hand)!'. A hot bath, and later hot water bottles, gave relief. Even the lips became tense and contracted so t h a t the mouth assumed an oval shape. The shock-like syndrome was marked by a fall of the blood pressure to 75/0 Hg., a lowering of the body temperature (1-2 degrees) and a pulse, first weak and slow, then becoming rapid, uncountable, weak and thready; extreme ashy pallor and cold clammy sweat; tingling sensation in hands and feet; slight dizziness and throbbing in the head. Profuse perspiration marked the end of this stage. The third stage of "elimination", as Blair calls it, shows the reactivity of the organism gradually getting the upper hand over the failing economy and circulation and reducing the hyperreflexia to normal, but at the same time some

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damage to the kidneys becomes manifest. The symptoms have been somewhat obscured probably by two injections of morphine. The blood pressure rose t o 154/92 Hg., the body temperature 1-2 degrees above normal, the leukocytes to 18,200 and 19,150, but the lymphangitis, starting from the inflamed finger, m a y account for that. The pulse became stronger. Eight hours after the bite t h e patient was very restless, had still severe pains in the abdomen, in the l u m b a r region and in the legs; sharp pains in the bitten finger; drank copiously, perspired freely; the eyes were red and watery, the face appeared swollen; abdomen still rigid; respiration shallow and somewhat laboured. The following night he was restless, sleepless, perspiring freely, troubled by muscular pains and chilly sensations. He got "so upset mentally t h a t he was afraid, ff firm control was not exercised, he would go insane". (It is to be regretted that no detailed description of this mental state has been given.) On the following morning the first signs o f renal damage were seen: trace of albumen, a few ]eukocytes, m a n y erythrocytes and epithelial cells, blood and granular casts; the casts (hyaline granular and leukocytic) were more numerous after two more days; on the sixth day of the experiment the urine was normal again. The urinary output was greatly reduced for the first 5 days, but the profuse sweating and liquid stools (after a dose o f magnesium sulphate!) may, at least partly, account for this. Outward signs o f the involvement of the kidneys were a swollen, puffy face for two days and a slight cedema of the ankles the first few days on moving about. Acute nephritis with anuria has been observed in a few severe cases after the bite of Latrodectus mactans, and it m a y well be that in these, like in Blair's experiment, the exceptionally intense inflammation was chiefly responsible for this sequel. N o peculiar affinity of the venom to the kidneys is established and for therapeutic purposes the occurrence of gross kidney lesions has thus hardly any selective value. I n the third stage, t h a t of enhanced reactivity of the organism, the painful tenseness of the muscles gradually diminished, but chilliness was more pronounce'd, a feature encountered in the symptomatology of so m a n y spider venoms that it can be regarded as characteristic. Sweating continued during this stage and weakness was notable; tremor of the hands m a y have been due partly to the chilly weakness, partly to muscular tenseness. During the recovery period generalized pruritus for some time and desquamation of the hands and feet for about three weeks were noted, but no further sequelae. The sensitization of the skin is of interest in connection with a papular eruption on the inner surface of the bitten finger and along the ulnar side of t h e hand noticed about 26 hours after the bite. Which component of the venom, whether a proteinase or hyaluronidase, m a y be responsible for upsetting t h e balance (of biogenic amines?) in the skin, and whether liberation of histamine plays a part, is at present an open question. As a reaction to antigenic proteins in general such symptoms are not distinctive for the actions of this particular venom. Blair's courageous experiment has brought out clearly the main features o f the actions of Latrodectus mactans on man. The m a n y case reports on patients bitten b y the spider have added or emphasized some traits in the picture. Vail (7) for instance describes a characteristic gait of the patients: bent forward with the hands held against the abdomen, motion of the legs m a y be accomplished slowly and with difficulty. He emphasizes more the precordial pains emulatincj angina pectoris and has observed extrasystolic irregularities; further, lachrymation and retention of urine in both his cases. As residual effects he noted: numbness, tingling, general weakness and transient muscle spasms for weeks or months, in one case; the skin over the lumbo-sacral region, hips and thighs extremely painfu~ to the slightest touch, caused her to cry out with pain.

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Greer (3) (1.c.) in his report on six cases also emphasizes a hypersensitivity of the skin; he thinks that a burning sensation of the soles of the feet might be pathognomonie. In his cases, besides the cramp-like pains in the abdominal walls, in the legs, arms and in the back, a general feeling of utter weakness, restlessness and extreme fear, often "hysteria", and further headache, dizziness, nausea: and vomiting were notable. Two of the patients experienced profound .shock, the blood pressure values were unobtainable; these two patients showed albuminuria. Greer mentions that in children bitten by the spider convulsions m a y occur which are difficult to control. Semple (8) has recorded a case in which the angina-like syndrome was most marked: "violent precordial pains extending to the axilla and down the left arm and forearm to fingers with numbness of the extremities and apnoea, the left arm ,almost paralysed, pulse 130, very feeble; skin cold as marble, countenance expressive of deep anxiety". I t is this syndrome which up to the present time has served as the main indication for the homceopathic use of Latrodectus mactans, for there have bee*~ no provings made so far with orally administered potencies. In a few severe cases of angina pectoris, suggesting myocardial infarction by the shock-like state, an icy coldness of the skin, especially of the extremities, great anxiety and fear of death from apncea, the author has used Latrodectus mactans 12x with apparent benefit. With an improved knowledge of the symptomatology the usefulness of this remedy is likely to go beyond this limited sphere. LATRODECTUS MACTANS--SuMMARY

Hyperreflexia Spasms, tenseness and rigidity of muscles with agonizing pains; abdomen board-like; constriction of chest, pains extending to left shoulder and arm; precordial pains, respiration rapid and laboured with great anxiety; icy cold extremities (angina pectoris, myocardial-infarction, pseudo-angina); cramps in muscles of neck, of the face; speech difficult; flexor-contractions of leg and arm muscles; pains followed by sensations of numbness, tingling and paralytic weakness; hypersensitivity to touch. Shock-like condition: Chilliness marked; first fall, later rise of blood pressure and body temperature;restlessness, deep anxiety and extreme fear, fear to go insane. Modalities: Spasms and pains relieved by hot bath. THERIDION CURASSA VICUM The orange spider of Curagao (and the West Indies generally), Theridion curassavicum, as C. Hering called it, is very closely related to Latrodectus mactans; according to W. Biicherl (personal communication) it is at most only a variety of Latr. mactans. The spider is said to live on orange-trees, Dividivitrees (Csesalpina eoriaria) and in maize fields; it is about the size of our cross spider, velvety black when young, with longitudinal lines composed of white dots; on the posterior body there are three orange-red spots, and on the belly a large square yellow SpOt. Though belonging to the family of Theridiidae, it is not a species of the genus Theridion, the members of which are supposed to be harmless. It is a species of the genus Latrodectus, whether identical with Latrodectus mactans or not; possibly what some authors call Latrodectus curacaviensis. In the West Indies it has a reputation of being very dangerous, and

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~hat was apparently the reason why Hering made a proving of this spider in 1832 (9). As the proving has been done with the 30th potency only, there m a y be ~loubts as to its value, but the symptomatology, concordant with that of other ~pider venoms, would suggest that ttering included symptoms known to him from the bite of the spider. The anginoid syndrome of Latrodectus mactans is there: "Anxiety about the heart, sharp pains radiate to the arm a n d left shoulder; violent lancinations in the upper part of the chest under the left shoulder, must take a deep breath and sigh". The lancinations, however, m a y not be of cardiac origin but due to a k i n d of "radiculitis" of the upper spine as suggested by the symptoms: " A great sensitiveness between the vertebrae, sits sideways in a chair to avoid pressure against spine." The "sensitive spine" is a feature of other spider syndromes, too. We have so far no evidence of a direct action on the heart muscle. The cardio-vascular symptoms indicate rather a reflectory, shock-like 9ction via autonomous centres. I n common with other spider venoms a sensation of coldness, a tremulous chill, is noted; a general aggravation from cold and amelioration from warmth correspond to this. An icy-cold sweat over the body accompanies the more acute shock-like syndrome, syncope, hypothermia, vertigo and nausea. The involvement of the sensorium and the hyper~esthesia, also a common feature of spider venoms, has for Theridion curass, some characteristics which have proved useful in clinical application. Vertigo with nausea even to vomiting, worse on stooping and from the slightest movement and from noises, and particularly worse on closing the eyes has become a leading indication for Theridion curass. I n the author's experience simply "vertigo worse on closing the eyes" has led in a few cases to a successful use of Theridion ]2x. The hyper~esthesia of the senses appears pronounced in the vestibularacoustic sphere: "shrill sounds and reverberations penetrate the whole body; they are sensed especially in the teeth"; the aggravation of vertigo and nausea from the least noise point in the same direction. Hypersensitiveness to light is also mentioned. Disturbances of vision, flickering, obscuration and impaired accommodation, followed b y violent frontal headaches, pulsating towards the occiput, or band-like around the head would indicate Theridion in eases of migraine, where the modalities mentioned present themselves; but verifying reports are not available. The peculiar s y m p t o m "increased desire to smoke tobacco" ought to be mentioned in view of its occurrence in the proving of Aranea diadema and in the recent proving of Aranea ixoloba. One is tempted to think of the affinity to the sensorium, common to Tabacum and the spider venoms. THERIDION CURA$SAVICUM--SuMMARY (similar to Latrodectus mactans, but muscular spasms not apparent and cardiac syndrome chnically not yet verified). Hyper~esthesia, especially to shrill sounds; Spine sensitive between vertebrae (radiculitis). Hypothermia, tremulous chilliness. Sensorium: Vertigo worse on closing the eyes, from movements, stooping. Headaches with visual disturbances (migraine). Increased desire to smoke tobacco. Modalities: worse from cold generaUy. Vertigo worse on closing the eyes, movement, stooping. TARENTULA HISPANICA I n homceopathic practice, Tarentula hispanica is still the most important of the spiders, thanks to the excellent monograph of J. Nufiez (10). The good

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illustrations of the female Lycosa tarentula hispanlca in Nufiez's book leave no doubt about the species; only about the name the zoologists are not agreed. Lycosa (Hogna) hispanica is suggested, but "Lycosa Tarentula hispanica" m a y be retained. To do justice to Nufiez's book one would have to translate most of it, especially the part on the historical aspect of tarentulism and "tarantism", the provings by 10 doctors and 8 others (in 1846) and the clinical cases recorded therein (see Appendix II). Here a general survey of the drug picture must suffice. Characteristic of the actions of this spider venom on the organism is its interference with the motor and sensory functions. "Stung by a tarentula" is a popular phrase to denote peculiarly bizarre motor restlessness. Such unmotivated and uncontrolled agitation, strongly reminiscent of chorea, has indeed been recorded in the provings. Ten cases of chorea successfully treated are reported in Nufiez's book. I must confess, though, t h a t in two severe cases of chorea minor in our children's ward Tarentula hispanica in various potencies has failed to cure. The experience cured me of the reflex: Chorea-Tarentula. There is, however, no doubt t h a t certain agitated children are often benefited b y Tarentula

hispanica. I n the sensory sphere, an excessive sensitiveness and excitability of all the perceptive senses are marked. Light and glaring colours irritate and aggravate (though certain colours are said to have a quietening influence). Noises frighten and aggravate, too. Much has been written about the peculiar influence of music and especially the musical rhythms of the dance called Tarantella. Nufiez gives a full account of the strange experiences and usages among Mediterranean people in respect of Tarantism and Tarantella. Those bitten b y a Tarentula are said to be startled from an apathetic and drowsy state by these musical rhythms, played on guitars, violins, or other instruments; they become excited, start dancing, the dances become wilder and wilder, until the afflicted person is exhausted from profuse perspiration. Whether the subsequent improvement should be attributed to the animation or the sweating and exertion seems a moot point. Yet, not every kind of music has the said effect. The provings record as well that music caused uneasiness, annoyance and agitation with contraction of the fingers and impulse to move them automatically (rolling something between the fingers, etc.). Music thus seems to stimulate one set of reactions to the toxins of Tarentula. The peculiar point is the observation t h a t only the rhythms of the Tarantella or similar dance tunes (fandango, minuet) are apt to rouse persons severely stricken by the bite of Tarentula; and conversely the medieval outbreaks of endemic dancing-mania in I t a l y are alleged to have had their origin in tarentulism; the bizarre behaviour of the afflicted (or those pretending to have been bitten?) appears to have been contagious among highly suggestible people. Evidently music has a remarkable influence on the symptoms of Tarentula, but whether it is soothing, animating, exciting or annoying, whether ameliorating or aggravating, will depend on the kind of musical rhythms and on the emotional and imaginative condition of the patient; and this condition m a y be roused to extremes, verging on insanity, and m a y undergo abrupt changes. The point to be noted is that the Tarentula patient is highly impressionable to musical rhythms and in a similar way to colours. Tactile hyper~esthesia and aggravation of symptoms by touch are also asserted, the spine is said to be specially sensitive to pressure (cf. Theridion) so as to provoke muscular spasms. This is, however, hardly substantiated b y the provings, but seems to have been inferred from clinical observations. I n connection with the disordered sensory-motor functions the vertigo attested b y the provings of Tarentula hispanica has to be considered. I t comes on i~ sudden attacks and is so violent that it causes falling to the ground, but without

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loss of consciousness; or, sudden giddiness in the open air, or when going downstairs. These phenomena could have a vestibular or cerebellar origin. Other records point to dizziness associated with headache and gastric symptoms, thus more to the vasomotor type. There seem to be no clinical reports from which the significance of the vertigo-syndrome within the picture of Tarentula could be judged. Some of these spells of giddiness are probably connected with the migraine-syndrome to which so m a n y symptoms of Tarentula point; but this indication, too, has not yet been adequately followed up by chnical observations. The great number and variety of headaches (Nufiez registers some 90 kinds) would indeed require a special analysis. I t appears arbitrary to single out. for instance, "pain in the occiput as if struck by a hammer", which is neither distinctive nor does it seem to have been verified. Other accounts of headaches are more in line with the trend of symptoms of Tarentula and other spider venoms; for instance "headache aggravated by touch which causes a very disagreeable sensation" indicating the hypersesthesia to touch; or "painful sensation as ff cold water were poured on to the head over the body" which accords with the predominance of coldness and chilliness in the drug picture of most spider venoms. Such observations as "headache with giddiness when focusing the eyes on any object" and "pain deep in the head with restlessness and agitation which do not let him rest in the same place, with an uneasiness and inner anxiety like that at the onset of a grave disease; the pain extends to the front at one time and to the occiput at another, with photophobia, the light instantly evoking complaints and screaming" need no further comment after what has been said before. A study of the numerous symptoms of mental aberrations under the influence of Tarentula-venom would be most rewarding. One should not dismiss them as "hysterical" or "bordering on insanity". They illustrate excesses of perceptual images, of imagination and of emotional drives over intellect, memory, adaptation to the reahty of the environment and social restraint. Visual impressions and images can attain an intensity so that they appear to the "normal", rational surroundings as illusions and hallucinations. "Visions of ghostly shades, shapes, flashes, faces, frightening monsters, of insects, of strangers in the house, etc." The stirred imagination is reflected in most vivid dreams. Like the voluntary movements and the perceptual impressions, the emotions and drives get out of the usual control. Extreme sexual excitement m a y manifest itself as lasciviousness, obscenity, nymphomania or even exhibitionism. (Cfi other animal venoms like Murex and Bufo.) The mood changes abruptly, without apparent motivation, from excessive gaiety with fits of laughing, singing, dancing and screaming to deep depression with sombre fantasies, thoughts of death or an indifference and taciturnity bordering on stupor. Aggressive drives m a y give vent to sudden impulses to destroy objects, to beat oneself or others (reminiscent of the flagellants in the Middle Ages). In some instances the undisciplined, irrational behaviour appeared strongly suspect of acting and simulating, but to diagnose it as hysteria does not lead very far. I n Nufiez's books several cases are cited where Ignatia had been given without, or with little effect, but Tarentula cured. Numerous and multifarious pains are recorded which indicate t h a t the peripheral nerves are involved b y the action of Tarentula. I t appears wholly uniustified to interpret them as "rheumatic" or even "arthritic", as has been done. I n connection with the hyperreflexia, the rigidity and cramps of muscles, extreme weakness, numbness, trembling and even paresis of the legs, also frequently recorded for Tarentula, evidence points rather to the spinal cord being affected. The recommendation of Tarentula hispanica as an euthanasiacum in certain cases, where it is desirable to calm the twitchings and convulsions of the dying, should be kept in mind.

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Of Tarentula as of other spiders and of some snakes it is often asserted t h a t symptoms from the bite recur annually. From this and from (not very well substantiated) observations that feverish attacks come on every day towards evening, a periodicity has been claimed for Tarentula, but this is hardly borne out by case reports. It would be futile and merely confusing to dwell upon the multitude o f symptoms from all the organ-systems potentially affected by the action o f Tarentula on the autonomous nervous controls. By themselves they are not distinctive of this particular drug. From the many cardio-vascular symptoms, for instance, an anginoid syndrome similar to that of Latrodectus could easily be, abstracted. Precordial anxiety, great oppression in the left side of the chest. impairing respiration, palpitations, lancinating pains at the heart and arteries of the left side into the left arm, all can be found, even coldness of the lower extremities with cramps in association with pain at. the heart, oppression and sighing. The analogy with Latrodectus is, however, up to now merely of theoretical interest for want of clinical utilization and confirmation. Of the modalities, those arising from hyper~esthesia, especially visual and tactile, are evident. Rest and particularly rest in bed aggravate the symptoms manifesting the intrinsic agitation and inco-ordination ~of the actions o f Tarentula. Aggravation by strong and sudden emotions, fright, etc., is also readily understood. Cold and particularly cold water aggravate most symptoms of the predominantly chilly patient. To the general improvement in the open air the opposite influence on vertigo seems to make an exception. Movement relieves some pains, for instance, headaches, but aggravates certain neuralgias. Periodicity is a doubtful modality. Tarentula hispanica has been commonly used in 6x, 12x and 30th potencies. TARENTULA H I S t ' A N I O A - - S u M M A R Y

Motor restlessness, purposeless agitation, choreiform movements (Chorea). Hyper~esthesia, highly impressionable, especially by musical rhythms; very sensitive to light, to glaring colours, to touch; noises frighten; spine sensitive, especially to pressure; headaches with photophobia, aggravated by touch; headache with giddiness when focusing the eyes on any object; vertigo, sudden attacks, coming on in open air and when descending stairs. Abrupt changes of mood, emotionally upset; sudden impulses to destroy objects, to beat oneself or others; extreme sexual excitement; illusions and hallucinations. Modalities: Worse from strong sensory impressions; causative: strong and sudden emotions; worse while resting; worse from cold, especially cold water; Better generally in open air, but vertigo worse. ARANEA DIADEMATA Aranea diademata is the common cross spider of the family Epeiridae. The older name is Epeira diademata. For its actions we rely mainly on the proving~ of two doctors with the tincture (ll), and on v. Grauvogl's report (12). V. 9Grauvogl seems to have made frequent use Of Aranea 2x and at least part of his indications are ab usu in morbis. The source of his remark that in some cases Aranea has caused strong h~emorrhages (1.c. (12), p. 302), especially h~emoptysis,

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cannot be traced; but it is interesting in view of the fact now known t h a t t h e araneilysin of the female spider is said to contain a h~emolytic agent and thrombokinase. V. Grauvogl based his use of Aranea mainly on two modalities which to him characterize the "hydrogenoid" constitution: sensitiveness to and aggravation from cold and dampness of any kind, for instance, bathing, damp dwellings, staying near a lake, etc.; and, secondly, a periodic recurrence of symptoms. The first modality, aggravation from cold dampness, is not substantiated by the provings. The periodicity is inferred from v. Grauvogl's observation: sudden violent pains in the teeth of the whole upper and lower jaw, at night, immediately after lying down; but more clearly from the earlier proving stating: sensation of heaviness in the thighs, so that they can hardly be carried forward, with confusion in the head; returns the next day, like intermittent fever, at the same time; lasts half an hour; and "sensitive, cold sensation in the right lower incisors, especially on drawing in air; came on again the next day at the same hour, like intermittent fever". One is reminded of the ancient tales recorded b y Dioscorides; but taken together with t h e - - a d m i t t e d l y scanty--evidence from other spider venoms, there is at least some basis for this modMity. I t seems t o apply also to the "chills mostly coming on toward evening", but the clinical indication "periodically recurrent complaints following malaria accompanied b y enlargement of the spleen" would appear to require more than the one case given b y v. Grauvogl (I.e. (12), p. 303f) for confirmation. Chilliness is a feature Aranea has in common with other spider venoms; in this instance it has been somewhat dramatized by describing it thus: "chilly as if the bones were made of ice, even in summer", or "coldness felt painfully in the long bones, not to be alleviated by anything, prevents sleep". Besides neuralgias, already referred to in respect of teeth and jaws, parmsthesias are described in v. Grauvogl's short proving of a lady: "On the fourth and fifth fingers of both hands a sensation as if they had gone to sleep and of formication," thus involving both nn. ulnares. More peculiar and significant is a syndrome recorded in the earlier provings: "Restless sleep from which he awakens repeatedly and always with the sensation as if the hands and forearms were greatly swollen, twice the size, as it were, of their normal condition; they seemed so heavy that he thought he could not lift theme" This looks like the familiar syndrome of brachialgia par~esthetica nocturna. We find it frequently caused by pressure on the roots of the plexus brachialis in the cervical intervertebral joints. The syndrome appears to be due to a so-called radiculitis which we have reason to presume for the actions of other spider venoms as well. (It does by no means follow that Aranea is the remedy for this syndrome; the condition is mostly due to arthritis and such remedies as Rhus rex. and Pulsatilla have proved helpful in the author's experience.) In view of what has been said about Theridion curassavicum (and what will be said presently about Aranea ixoloba) the very peculiar modality stated three times b y one prover (1832) deserves attention: "Headache and confusion of the head, both relieved by smoking." The headaches are apparently of migraine type, for they are associated with an unpleasant flickering in the forehead and eyes, are worse from reading and writing and better in open air. On v. Grauvogl's authority Aranea has usually been given in low potency (2x). The author's very limited experience with Aranea does not bear out v. Grauvogl's opinion that the remedy is suited to "hydrogenoid constitutions". ARANa~A DIADEMATA--SUMMARu Periodicity, especially chills towards evening? Chilliness, icy coldness painfully felt in the bones, even in summer, prevents sleep.

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Sensation as if the hands and forearms were greatly swollen and heavy, o n awakening from restless sleep (brachialgia para~sthetica nocturna?). Headache and confusion, both relieved b y smoking. Headache with flickering in the eyes, worse from reading and writing; better in open air.

A R A N E A IXOLOBA The unsatisfactory state of our knowledge on the actions of Aranea diademata was one reason why in 1952, at the post-graduate courses of the Robert Bosch I-Iospital in Stuttgart, a new proving was undertaken. Another reason was that J . Mezger, who conducted the provings and recently published the results (13), had the opportunity of obtaining the separate venom from the glands of the chelicerae of Aranea ixoloba, thanks to the work of G. Pooch. At that time we read reports from the U.S.A., saying t h a t cross-spider venom had been given intravenously with good results in angina pectoris; coronary insufficiency and vascular spasms (14). Aranea ixoloba is described as a species slightly bigger than Aranea diademata. I t seemed desirable to subject to provings the venom separated from t h e admixture of araneilysine and possibly other active substances of whole spider preparations. One would expect the effects of the venom of the gland to correspond more closely to those of the bite. Thirty-two doctors (25 men, 7 women) took part in the provings. Of these, 21 had the venom (1 :],000,000 saline solution) injected subcutaneously every day or every second day, 5-13 injections in a first series. (A second series of subcutaneous injections after an interval of 3-5 weeks was on the whole not very informative; this is not surprising, as in the meantime antibodies to the proteinic principle must have been formed. From the immunological point of view, it is of interest, that one prover. in the second series of injections, noted: at each injection the site became red for 24 hours; thus a slight Arthus phenomenon!) Eleven provers took 12x dil. (three times a day, 5 drops) for 2-3 weeks, then, after an interval of 2-3 weeks (with varying placebo-periods in between) seven provers received 6x trit. and two others again 12x dfl. for 1-2 weeks. When the extensive records of a new proving are sifted so as to find the characteristic symptoms and modalities, it is inevitable that the first reviewers differ in arrangement, emphasis and interpretation of the data. Experience accumulating from future use of that drug will in time settle such differences of opinion. Meanwhile the factual material of this proving is to be surveyed in our present context. Eight provers described in varying detail the restlessness they experienced, for instance, "great restlessness, an inner inquietude, faculty of concentration greatly impaired, constraint to move about, better in open air" (from 12x), or "after a completely sleepless night, no tiredness, but inner inquietude and hastiness; could not do anything quickly enough, time went too slowly" (6x), or "intense inner inquietude and restlessness could not be mastered by autogenic training which formerly used to work in such a condition " (inj.), or "during the first days harassed dreams, not known before. Increased inner restlessness and trembling of hands" (inj.). And from still another prover: "inquietude and sleeplessness. The inner restlessness increased during the following days, sensation as if under an electric current, or feeling of inner trembling. Concentration was markedly impaired, mental work was very fatiguing and aggravated the restlessness and nervosity" (inj.). Peculiar was the strong craving for tobacco smoking reported by two provers, possibly from a desire to calm the nervousness. Six provers reacted to the injections first with euphoria,

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as for instance a feeling of lightness of the body, increased animation, talkativeness and bantering, but five of them went later into a depressive and irritable phase, weary mood, bad temper and impairment of mental activities. Six other provers recorded depression and irritability without a preceding phase of euphoria. I t would be arbitrary to assume that in the latter cases, too, there was a "stimulative" phase, though too cursory to be noticed. Indeed, the favourite usage of opposing stimulative to inhibitive effects is but an e m p t y abstraction, if it is not clearly stated to which function it applies. W h a t appears to be mental hyperactivity under the influence of a drug m a y well be the result of inhibition of the ordinary restraining control b y the higher nervous centres, and reversely any subdued or impaired activity m a y result from stimulation of just these centres, gomceopathic teaching avoids the pitfall of thinking in terms of stimulation versus inhibition and contents itself with describing the symptoms; they show the deviations from the normal fluctuations in activities of a person in his particular situation, in the present instance as manifested in the mental and emotional sphere under the influence of the spider venom. Judging from these provings of Aranea ixoloba, the mental and emotional symptoms are pronounced, but do not go to such neurotic extremes and are not so peculiar as those seen from Tarentula hispanica. I n the provings of Aranea ixoloba the frequent disturbances of the sleep with exceptionally vivid, mostly disagreeable dreams m a y be attributed to an increased irritability and stirred imagination. Sixteen provers reported such experiences. One of them noted, for instance, "Since the second day of the proving disturbances of sleep have manifested themselves, sleep is very restless and every night terrible and disquieting dreams have occurred. (Normally I never dream.) In the daytime tiredness and a partly angry-irritated, partly depressed and unstable mood and great forgetfulness are noted" (inj.). Another one mentions in addition: "sensitiveness to noises with superficial sleep" (inj.). Olfactory hypersensitivity goes to illusion in one instance: "Oversensitive to smells and illusion of smells, thinks there is a smell like in a post-mortem room; smell not noticed by others". Impairment of accommodation, "focusing of remote objects appears to be difficult", was noticed by one prover (12x). Giddiness and confusion occurred several times. O n e observation (though considered as doubtful b y Mezger and left out in his summary) seems worth recording: "During the seventh d a y (of after-observation, when "placebo" was given) an attack of disturbance of the equilibrium occurred, worse in the dark, after mental work. Some letters and syllables get confused. I m p a i r m e n t of concentration; have to read a sentence twice or three times in order to understand it. Moreover nausea comes on, I have to discontinue working and go to bed. The ceiling of the room seems to swing to and fro and to turn round. The following morning the vertigo has gone." I n view of a similar action of other spider venoms on the sensorium, such observations should not be dismissed off-hand. I t is as disingenuous as it obscures the point at issue, if the medley of sensations and pains located in muscles, joints and along peripheral nerves are summarily designated as "rheumatic". I n this respect the records of the provers of Aranea ixoloba deserve and reward a more discriminative analysis. Eighteen of the 32 provers have described such sensations. Some clearly point to a state of neuro-muscular hyperreflexia. Knowing the syndrome from the early provings of Aranea diademata, one can hardly consider as fortuitous the record of one obviously good observer (prover No. 9): "Heaviness in the limbs, particularly in the arms. Sensation as if the right hand were much heavier than the left one, also as if the right hand were much larger and clumsier than the left one." J u s t because the syndrome is peculiar, this corroboration is valuable. Another.syndrome of the same prover points to hyperreflexia in the muscular $

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response, and t h a t in regions preferably affected b y spider venoms: "Stiffness of the neck, of sudden onset, radiating over the mm. trapezil to the shoulders. Backache over the lower thoracic spine". Another prover, receiving daily injections, reports: " F r o m the seventh day of the proving increasing rheumatic symptoms appeared, mainly in the neck, in both shoulders and arms, also in the sacral region; after discontinuation of the injections these symptoms disappear only gradually." The term "rheumatic" has obviously been used in this context not in a diagnostic, but merely a vaguely descriptive sense. Nor would it be justified to interpret as muscular rheumatism what another prover describes thus: "On the eleventh day (of taking 12x, 5 drops three times daily) I awoke in the morning with a lumbago in the sacral region so intense that I was unable to work for some days. These pains radiated to the shoulders and the thighs; at times I was unable to move." As a spasmodic condition of the long muscles of the back this would well fit in the picture of actions known from spider venoms. Many sensations and pains as reported by the provers point at peripheral sensory nerves being involved, especially when, as in two instances, numbness in certain parts of the extremities was noticed. Practically all the pertinent symptoms in this sphere can be readily understood as an interference with the reflexes controlled by the spinal cord, and none appear characteristic of an inflammatory process in the mesenchymal tissue which could be called "rheumatic". The influence of rest or movement on these sensations was not uniform. In conformity with the trend to "chilliness" in the symptomatology of this as of other spider venoms, the neuromuscular symptoms were generally aggravated by cold and partly better from warmth. Chilliness has been well brought out as a feature of the effects of this Araneavenom. Of the 6 provers who testified to this effect, 3 m a y be quoted: "Constantly feeling cold and chilly. Two hours after injection a sensation of warm affinx in the left arm and left leg, independently of the site of the injection, whether at the right or the left side. Sensation of warmth around the mouth. On one of the days free of injection the right arm felt warmer than the left one, respectively the left arm cooler than the right one." Another prover: "Marked sensation of chilliness, with backache, persistent over the whole d a y " (inj.). A third: "Chilliness, like at the onset of a cold, though no catarrhal symptoms. Chilliness, though in a warm room, cold feet that failed to get warm even from m o v e m e n t " (inj.). This interference with the autonomous control of vegetative functions shows primarily a parasympathetic tendency, the occasional flushes in parts of the surface are quite consistent with this interpretation, and so are the reports of 4 other provers on perspiring in parts, or over the whole surface of the body. The changes of the white blood cell count of one prover under 12x point in the same direction: a marked lymphocytic tendency and decrease, both relative and absolute, of polynuclear leukocytes. The changes in the blood cell counts of all the other provers were not significant, l~egrettably the bloodpressure has not been recorded in the course of these provings. I n the vasomotor and cardiovascular sphere 13 provers noted headaches of varying kind and localization, but in the main of congestive character, with relief in open air; two or three suggest the migraine type, one ended with the excretion of 189 litres of bright-yeflow urine in the morning, when, in spite of frequent urging, a remarkably small amount of urine was voided while the headache lasted. On the whole, the headaches showed no peculiar and distinctive modalities. Seven provers had sensations related to the heart and carotids; the descriptions of two m a y be quoted: "Most noticeable were the sensations from the heart, like intense palpitation with slight oppression. The palpitation extends to the carotids and into the upper abdomen. I t occurred mostly at mid-day

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and then mainly when lying down (no previous overloading of the stomach). Slight pressure in the left chest, better on rubbing. The said heart symptoms were absent while walking fast or ascending stairs. On the 17th day (5 days after the 7th injection), after having felt quite well for ten days, once more pressure at the heart with strong pulsation up to the neck, mainly at rest, more so when lying, better when moving about. Sensation of heaviness in the left side of the chest, slightly anginoid. On the 18th day, forenoon and midday, feeling o f constriction at the throat, intense pulsations like flushes to the head, but without redness. The same on 19th day, pulse rate 90 instead of 70." Another prover, under 6x: "At night, especially before falling asleep, oppression in the chest with feeling of anxiety and at times stabbing at the heart region. Increase of the pulse rate from 70 to 90." (An attack of tachycardia and extrasystoles of another prover have to be regarded as an exacerbation of symptoms following a myocarditis 2 years previous to the proving, 12x). None of the provers recorded those constrictive and radiating pains that one associates with coronary spasm or occlusion. At the most, a decrease in the coronary blood flow could be inferred from the symptoms, indicating a parasympathetic trend. Most of the symptoms from the respiratory tract (of 8 provers) and from the gastro-intestinal tract including gall-ducts (25 provers) lend themselves readily to the same interpretation: a shift in the autonomous equilibrium towards parasympathetic preponderance. I t is true, we have to assume that the drug stimulus acts primarily on the controlling centres and not on the effectual peripheral tissues and organs. Yet, even if all the relevant symptoms were amenable to such an explanation, it would be no help in recognizing and choosing the particular agent. On the other hand, "catarrhal" syndromes of the upper respiratory tract or symptoms of indigestion, meteorism, etc., are by themselves not distinctive, however frequent they m a y occur among the provers. Peculiar symptoms and modalities, characteristic of the action of a particular drug, are by the same token rare, and the more so among the symptoms from specialized tissues, organs or organ-systems, the so-called "particulars". I t is thus of little significance when one prover reports: "Asthmoid oppression behind the sternum, in a stove-heated room," because this had been experienced occasionally before, though less frequently than during the proving, and the modality is an ordinary one for such a symptom. Somewhat more significant, provided confirmation is forthcoming in the future, is the record of another prover: "The coughing increased rapidly in intensity, was worse in bed, on lying down, at night and on transition from cold to warmth and reversely." The aggravation in bed, on lying down, accords with that mentioned for heart symptoms and m a y point to the influence of the change in the pulmonary circulation in that position. The second modality in respect of cough is reminiscent of Phosphorus and would thus require, in a given case, further discriminative comparison between that polychrest and the newcomer Aranea ixoloba. The abdominal symptoms were chiefly meteoric and spasmodic. The most striking feature was that ten provers located the sensations of fullness, pressure and stabbing in the right hypochondrinm or related them direct to the gallbladder. I n three cases there were definite signs of the gall-secretion being involved: subicterus or clay-like stools; but in one of them only an exacerbation by the injections can be assumed, as some "biliousness" had persisted since a hepatitis 8 years previously, and in another case the aggravation of dyspeptic symptoms, so that the gall-flow became impaired, was apparently due to a very unsuitable meal. Nearly all of the manifold gastro-intestinal symptoms of 25 provers can be interpreted as an increase of tone and peristaltic motility of the smooth muscle-ducts; this again a parasympathetic predominance. In one instance this was emphasized by an aggravation between 3-5 o'clock in the

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early morning, the parasympathetic acme. Several times relief from stretching and bending backwards was noted, but the reverse, relief from doubling up or drawing the legs up against the abdomen, was also reported. The other modalities were much as one would expect in such meteoric and spasmodic conditions. Three of the 7 female provers had the period 1-2 weeks before the normal time, but one of them was known to be under emotional stress. This and only this prover showed signs of an enlarged thyroid (during post-observation after 12x). I t would be rash indeed to ascribe this occurrence to A ranea. Seven provers noted various skin symptoms, such as acneiform efflorescences, flea-bite-like erythema, r h a g a d e s on lips and fingers, increased failing-out of hair and dandruff; but in view of what has been said under Latrodectus, the observation of one prover appears worth mentioning: "Skin desquamating on both hands, as after scarlatina, and on the nose where it is more seborrhceic". This prover was oversensitive to woollen clothes; it is remarkable that his predisposed skin should be sensitized b y 12x of the venom. No therapeutic indications, however, ought to be inferred from such occurrences. Altogether this proving of Aranea ixoloba does not support the earlier assertions regarding Aranea diademata, namely periodicity of feverish symptoms and aggravation from damp environment. Whether the single observation of one prover: "Sensorium somewhat impaired, especially on warm-humid days and under the influence of 'Fcehn', " has any significance or not, this is not the same as what v. Grauvogl claimed to be a modality of Aranea diademata. ARANEA IXOLOBA--SuMMARY (abstracted from provings only) Restlessness: Sleep with exceptionally vivid, mostly disagreeable dreams. Transient euphoria, followed by a depressive and irritable phase. Concentration impaired. Giddiness and confusion. Attack of vertigo with nausea. Craving for tobacco smoking (cf. Aranea diad., Theridion cur.). Hypersensitive to noises and to smells. Illusion of smells. Heaviness and sensation o f distension in the arms (cf. Aran. diad.). Sensation of numbness in p a r t s . Stiffness and tension in muscles of neck, back and extremities. Chilliness, though in a warm room, coldness of feet not relieved b y movement. Oppression in heart region and palpitations, worse lying down. Constriction at the throat. Coughing worse in bed, and on transition from cold to warmth and reversely. Meteorism with fullness and pain especially in right hypochondrium. Gall secretion impaired. Menses too early. Our knowledge on the pharmacodynamics of spider venoms is still very limited. Yet, a survey of the available data reveals fairly well the common trend in the potential actions on man of this natural group, Any recognition or diagnosis is the result of comparing symptoms and signs, and comparison always presents two aspects, neither of which must be neglected: discrimination and unification, differentiation and integration must complement each other. BIBLIOGRAPHY (1) I am indebted to Prof. W. Biicherl, of the Butant~m Institute, S~o Paulo, Brazil, for his competent advice on taxonomical questions.

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(2) A. W. Blair, "Life History of Latrodeetns mactans", Arch. Internal. Med., 54, 844, 1937. (3) Macchiavello, Puerto Rico J. Publ. Health, 22, 425, 1947, cir. Greer, "Arachnidism", NeW Egland J. of Med., 240, 5, 1949. (4) gouard, Hahn. Monthly, 5, 8, 1869. (5) E. Bogen, Arch. Internal Med., 38, 623, 1926! and 61, 375, 1932. (6) A. W. Blair, Arch. Internal Med., 54, 831, 1934. (7) Vail, J. Miss. St. Med. Ass., 36, 330, 1939. (8) Semple, Virginia Med. Monthly, 1875. (9) H e . g , Ar~,h,~. ho~. Heilku~de, Vol. 14, part 1, p. 157. (10) J. Nufiez, Etude m6dicale sur le venin de la Tarentule" (from the Spanish text, translated into French by J. Perry, Balli4re et ills, Paris, 1866). (11) Allg. Hom. Ztg., l, 122, 1832. (12) v. Grauvogl, Lehrbueh d. Hom., pt. 2, p. 303, Niirnberg, 1866. (13) J. Mezger, "Arzneimittelpriifung des Chelizerengfftes der Kreuzspinne Aranea Ixoloba", Beiheft zur Deutsch. Horn. Monatssehr., l, 1958. (14) H. Morrison and Baranell, New York, 1947.

APPENDIX I Petri Andreae Matthioli Commentarii in libros sex Pedacii Dioscoridis de Medica Materia, Venetiis, 1554 (in librum secundum, Cap. 57, Arachne, Araneus) Araneus which they call holcus or lycos, that is wolf, mixed with splenium (probably the fern Asplenium ceterach L.) and spread on a linen cloth, cures tertian intermittent fevers when applied to both temples or the forehead. Its web, when laid on to wounds, stops bleeding: it clears wounds of the skinsurface of inflammatory damage. There is also another genus of araneus which spins a white, thin and dense web; this spider, when sewn in a bag and attached to the upper arm, is said to cure quartan intermittent fevers. As a decoction with rosaceum (oleum rosaceum?), and as an infusion it helps in pains of the ear. (In his commentary on the above chapter of Dioscorides' materia medica, Matthiolus first discusses the classification of spiders according to Aristoteles, Plinius and Aetius and avers that all the genera mentioned by these authors can be found in Italy, though Plinius asserted that poisonous spiders, which he called phalangia, did not exist in Italy.) Then Matthiolus continues thus: "Besides the genera mentioned one finds here and there also another genus and that the most pernicious of all, called Tarantula after the city of Tarantum in Apulia where they, in great numbers, rove the fields during the whole summer. People stung by them are indeed variably and differently tormented; while some continuously go on singing, some laugh, some cry, some shout, .some sleep, some are afflicted with sleeplessness, many suffer from vomits, certain others dance, some perspire, some tremble, there are some obsessed by fright or suffer from other complaints and appear like insanes, panic-stricken and maniacs. And these symptoms, so varying and different, come, it must b e assumed, either from variations of the poison of these animals or from the constitution of the bitten persons. For in those tending to melancholy (black gall) we have seen all this owing to their constitution; there are, however, others who believe that the poison of Tarantula changes daily and even hourly and that this is the reason why people stung by the spider suffer from so varying symptoms. Tarantulae are frequent also on our Senensian shore b y t h e Tyrrhenian sea and in the Roman countryside, though not so numerous as in Apulia. They are hidden among the corn in holes in t h e ground, from which they emerge occasionally and often sting the reapers who, unaware of the danger, don't have their legs protected by leggings. I have seen people who had been stung, sometimes lying in yards or in inns and being tormented b y the said afflictions. But it is miraculous how easily the force of this poison is mitigated by music; since indeed those stung

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b y Tarantula, as I myself can testify, on hearing string instruments or the sounds of flutes, at once, on the first impact, come out of their languors and begin to stamp and dance to the fore, and as long as they carry on with it, they seem healthy and no more troubled with any pain. When it should happen t h a t the flute-players are silent for a moment and pause, they very soon fall to the ground and revert to their previous state of languor; if not, while they dance and stamp the ground to the continuing tune, the virus of the venom has escaped and been dispersed, in part imperceptibly by the pores of the skin, in part by sweating. I t is for this reason that the flautists are hired for a fee and are changed in relays, so t h a t the bitten persons m a y dance until they quieten down completely cured. Yet there m a y be some who, while this goes on, would support them with antidotes, indeed with theriac, mitridate and others t h a t act against bite-poisonings." APPENDIX II Translated from J. Nufiez, Etude m6d. sur le venin de la Tarentule. Baglivi, De anatome, morsu et effectibus tarentulae (end of 17th century), "The bite of a tarantula causes the same sensation as that of an ant or a bee; sometimes the part which has been bitten becomes painful, at other times it feels numb and is the seat of a certain insensitivity; in general it becomes discoloured purple, black, or yellow. I t m a y swell up and produce a painful swelling which disappears with the other symptoms. "Few hours after the bite there is violent pain near the heart and great sadness; but before this there is extreme difficulty in breathing; the patients complain in a doleful voice and when they are asked where the seat of their pain is, they do not answer, or point with their hand to their chest, or the precordial region. These symptoms m a y often be present in the beginning of the malaise, they are, however, neither constant nor of the same intensity in every case; they v a r y according to temperament, to atmospheric conditions, and according to the variety of Tarantula, for it has been found that those from the North of Apulia are more poisonous and t h a t the effects of their bites are much more serious. The patients show a certain pleasure when t h e y see certain colours such as red, green, or sky-blue, on the other hand they are really horrified by other colours, so much so t h a t they maltreat those who exhibit them. Moreover, the bite of the whitish tarantula produces a slight pain with pruritus, tearing in the stomach, and diarrhoea; the tarantula with a star-like pattern causes a more acute pain, heaviness of the head, and stupor, irritation of the whole body, etc. The black one develops all these symptoms, as well as severe swelling of the bitten part, spasms, rigidity, cold sweat all over, loss of voice, tendency to vomit, distension of the abdomen, and other s y m p t o m s . . . " Baglivi then discusses the way in which the poison of the tarentula works in the body. He compares the disease which it produces to more or less similar ones, assures us t h a t it recurs every year towards the month of July, and that ff one does not use the only known remedy which is effective, music, grave disorders ensue through the whole of the body. The skin becomes yellow, anxiety-states develop, lack of appetite, and a low fever which never disappears completely. Symptoms of those who have been bitten and who are being subjected to the influence of music: "The patients begin by moving their hands, their feet, and all their limbs; gradually these movements increase, the patients get up and begin to dance and to jump without losing control, and without becoming tired; on the

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contrary, they feel much more relaxed and stronger the longer they are dancing, even if it is for 12 hours on a stretch. I f there should be a false note the patients stop, sigh deeply, and complain of pain around the heart, and their discomfort only passes when the music again becomes harmonious and they start dancing again. Strangely enough, in that condition the most uneducated peasant or otherwise very stupid people notice the slightest flaw in the music. There is no time limit to the cure effected b y this exercise; some need it until they get rid of all their symptoms which on the average is about 3-4 days. On the whole all the patients sigh during the dance, complain, and are not master of their senses, like people who are drunk. They cannot distinguish between their next of kin and strangers, they cannot remember their past, they are fond of water, brilliant objects, of green leaves, cloths of exciting colours, etc. Not all the patients bitten by a tarantula are induced to dance by the same sounds of the same instruments, nor by the same melodies. W h a t is essential is a very quick rhythm, similar to the one which is known as the Tarantella, which served at the time to distinguish between true 'tarantism' and the simulated form. For it happened quite often that women who were looking for entertainment pretended to be stung by the spider in order to have an opportunity to dance to whatever music there was, which never happens with those who are afflicted by the bite of tarantula." Don Francisco X. Cid published in 1787 his " T a r a n t i s m as observed in Spain", which confirms t h a t of Apulia. Cid's description of Tarentula hispanica: "The male is smaller than the female, more hairy and pale in colour, or ashen. Its 8 eyes, the same number as in the female, are closer together and seem differently arranged. The four back ones are more to the side and are definitely bigger than the four in front. These one can hardly recognize unless one has very good sight, or with the help of a microscope. They are in both sexes black, shiny and prominent, especially the four lateral ones. The abdomen of the female is much more developed. Otherwise the sexes are similar, having 8 eyes, 8 legs, each with three joints, two feelers or antennae (palpae), and each of them two others in the middle, with darts which are very sharp and with which the Tarantula stings or bites (for she does the one as well as the other, at the same time), and injects her poison." M. Mestre's description: "The Spanish Tarantula has a greyish chest, an abdomen of a dark blue, the back is marked by black spots arranged in twos, with fine transversal lines which are black toward the posterior extremities, at the abdomen bluish black, the legs slightly bent backwards, and marked by big white and black spots." According to Dufour the Spanish tarantula (Lycosa Tarentula hispanica) is 10-14 lines long, of a greyish thorax, a fawn coloured abdomen, marked on the back b y six separate stripes which run in pairs, and towards the posterior end various fine rays which run across and are black. The exterior eyes of the anterior row are bigger than the interior ones. The abdomen is a velvety black throughout. The anal region is ochre-coloured as in the Egyptian tarantula. The legs have white and grey spots at their end. CASE REPORTS

Intermittent fever with choreiform attacks. (Dr. Firmat, of Montellano). (1) A young girl, aged 11, thin, delicate, and highly strung after having been scolded when she left the dinner table, became shivery, felt cold, vomited, and showed slight convulsive movements which disappeared after about 1~ hours, under mild perspiration.

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She was quite normal until the following afternoon when I saw her for the first time. Shortly after her meal she shivered again, s o o n afterwards she vomited and brought up her meal and then bile, and started to h a v e choreiform convulsions which I witnessed. The girl, who was supported b y her mother, leaned against her bed; she was unable to lie down and she made continual involuntary incoordinate movements which affected her limbs, her abdomen, her chest, and her face; they were worse on the left side, especially at the shoulder. The child could not say a word because the muscles of the tongue and of the pharynx were involved. Her pulse was increased to 130 and her temperature was raised. The attack lasted about 8 minutes, after which she could talk and go to bed. She only complained of pain in the region of the spleen. H e r intellectual faculties were unimpaired; she was thirsty, but the tongue was moist. Considering t h e cause of her symptoms, she got Ignatia 12 in a tablespoon of water every hour. I n spite of it the child contirmed to have violent attacks until 2 o'clock in the morning, when she began to perspire freely, and afterwards slept peacefully. On waking she had another, milder attack which did not prevent her from resting in bed; no increase in temperature, and the pulse remained 80; no headache, nor pain at the site of the spleen, no thirst either. This condition lasted until 4 p.m., when another attack started without her having had a meal. The return of the symptoms after a free interval showed the intermittent nature of the disease. I therefore prescribed Tarentula, as Ignatia had had no effect. Tarentula seemed indicated because of the periodic nature of the attacks and of their choreiform character. I gave 6 globules of the 12th, in 8 tablespoons of water, one tablespoon of this every three hours from the time when the sweating would begin. The next day I was told that shortly after the first spoonful, given at 2 a.m., she had a rather violent convulsion, though less severe than the six previous ones which the child had had during the feverish attack, and that this last one, like the one preceding it, ended with copious sweating and a peaceful sleep. The day after this the child had neither a t e m p e r a t u r e nor convulsions in the evening. She had slept well and was in good condition. However, I thought it better to give her Tarentula 200 for three more days. Chorea (Dr. F. Firmat). (2) A young woman of 36, thin, looking liverish and nervy, irritable, and who had very scanty menstrual periods, suffered from the age of 18 from attacks of chorea which recurred so frequently that she had hardly a day without one, in spite of the multitude Of allopathic medicines prescribed for her. Six years before she was seen by me she started on Homceopathy and she definitely improved, for she had no attacks for up to three months. The attacks were as followS: Involuntary movements, which were incoordinated, irregular, confined either to the left arm or leg, or to one limb only, rarely involving the left arm and the right leg at the same time, and accompanied by grimaces. Nux yore., Belladonna, Stram., which were the remedies most frequently prescribed, sometimes stopped the attacks with remarkable promptitude, and prevented their return, but only for some months. But after her last attack, at which I administered Tarentula to her, she had no more convulsive movements; her temper improved greatly and her menstruations became more copious.: The dose was Tar. 12, eight globules dissolved in six tablespoons of water,

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of which the patient took a tablespoon every 6 hours; and after t h a t 200, every fortnight for two months. Chorea (Dr. Gaudy, Bruxelles) (3) A young woman of 25, who was rather placid and in good general health, suffered for some years from attacks of chorea which returned at the end of summer. The attacks were characterized by ineoordinated, irregular movements of feet and hands. They were so violent t h a t she dropped whatever object she carried in her hands. I n November, she was seen for the first time and she got Tarentula 6 dil., every 3 or 4 days, or even at longer intervals, according to how she felt. After the first doses she felt considerably better and took the remedy at fairly long intervals. At the end of December there was no longer any trace of convulsive movements and they have not returned since. (4) A boy was brought to me who was suffering from nocturnal chorea for six months. He was of a lymphatic type. Several allopathie doctors had been treating him without success. One of them who thought he might have worms (asearides) submitted him to vermifuges for a month. When the mother brought the child to me she told me t h a t as soon as he went to sleep he started with convulsive, irregular movements of all the voluntary muscles. Arms and legs were thrown about in all directions, his eyelids alternated between being spasmodically contracted and then immobile for several minutes; at other times the eyeballs rolled round in their sockets. This condition lasted all night until daybreak, when it stopped entirely. During the day the child felt very well and nobody who saw him would have believed t h a t he suffered from such attacks. However, he was sad, restless, and often sighed deeply. I gave him Tarentula 6, three globules to be taken in the afternoon. After three days he slept peacefully and since then the convulsive movements did not recur. (5) A boy of 15 had chorea for more t h a n six months. He had been under treatment at the Bruxelles hospitals. When he was first seen only the right arm and leg were affected. The arm was never kept still, it was constantly and violently thrown about, mostly sideways or backwards, rarely forwards. To this was added a movement of rotation of the arm itself, and a lifting of the shoulder. The foot movements were less forceful and less frequent, but they were forward movements which repeatedly made the patient fall down. All the other functions were normal. He got Tarentula 6, three globules to be taken in the afternoon. After seven days there was an obvious improvement, after two weeks the arm was perfectly steady. He got another dose of Tar. 15, to be taken as the previous one. After a month he was cured and remained so. Chorea (Dr. Garcia Lopez) (6) A weak, lymphatic child of 9 years of age had been suffering from chorea for a year. The disease affected all the voluntary muscles, mainly however the face, the right arm, and the left leg. The child was in continual agitation. There were m a n y and multiform gestures and bizarre contortions and he could only walk with difficulty. He had to be supported by holding his arm, otherwise he would have fallen. On the other hand, he could easily run, without fear of falling down whilst he was running. His speech was difficult and the words unintelligible. He was best in bed, because then the convulsions ceased almost completely. He had had all sorts of allopathie treatment for a long time, among others valerian, quinine, iron, and anthelmintics. After having s t a r t e d on Homceopathy he received Bellad., Cina, Sulphur, with only very short-lived ameliorations. He was then given Tarentula 12,

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16 globules dissolved in eight spoonfuls of water, three times a day. After 8 days the general agitation and movements of the muscles had stopped. There still remained some grimaces and he had speech difficulties. He got Tar. 200, one dose every day for three days. Two weeks later, that is from the beginning of his taking Tarentula, he was cured. However, the arm and the leg which had been mainly affected showed signs of paralytic weakness which caused the child to limp and prevented him from carrying anything heavy in his right hand. He complained of weakness in his shoulder joint and in the hip. China and Rhus made the last vestiges of the disease disappear. After three months he was his old self again. Chorea (Dr. A. Gonzalez) (7) A child suffered for about 30 days from irregular and uncoordinated movements which she could not suppress. They were limited to the left foot and hand. She was treated with anti-spasmodic medicines and cold water apphcations. A dose of Tarentula 200 was sent to her. After three days the involuntary movements diminished, and after six days they ceased altogether. The foot was as strong as before and the hand, which had been discoloured and had a brownish tinge, became normal again. Chorea (Dr. Dewilde, Tirlemont) (8) On 23rd June a child of 7 entered the hospital for violent chorea. All the voluntary muscles were affected. She could not walk and she had to be held down in bed. One even had to put her into a straight-jacket. She had to be fed and at moments she had difficulty in swallowing. Her way of speaking was so inarticulate that one could hardly understand her. On the morning o f the 24th I made her swallow one globule of Tarentula 6, dissolved in water. The same dose was repeated on the 25th, 26th, and 28th. On the 28th the nursing sister noticed a little improvement. She made her get up and let her walk for a few minutes in the ward, supporting her with care. On the 29th I found a considerable improvement in the upper limbs. On the 30th the right arm could be controlled for a few moments and the child could make the sign of the cross. She walked on her own and her speech became more distinct. From the 1st to the 4th of July she made obvious progress on the right side, and on the 5th she talked quite comprehensibly; she also could feed herself. On the 7th she was eating without help, walked alone in the ward, and altogether her movements were less irregular. On the l l t h I gave the child a tablespoonful of water in which Tarentula 6 was dissolved, and from then onwards her progress was rapid and on the 25th she could leave the hospital cured. (9) A girl of 15, who had not yet menstruated, blonde and tall, had been ill for three weeks: Her mother came with her and thought that she was bewitched. The right arm and leg of the young person showed bizarre and irregular movements. She got Tarentula 6 during three days before breakfast. A week later iher mother told me with great joy that her daughter was almost cured and at the end of six more days she was completely in order. ~(10) A father came to consult me about his daughter aged 13. For four months she had continual choreatic movements of both legs. I gave Tarentula 6, to be taken during three days. Six days later the father came and was very distressed, telling me that the disease had taken on quite extraordinary proportions. I was convinced that this was an aggravation due to the remedy; I gave him some Sac. lac. Seven days later there was a distinct improvement and another dose of Tarentula 6 was given. A week later the father came to tell ~ne that the child was completely cured.