Colchic and Colchicotherapy

  

COLCHIC AND COLCHICOTHERAPY

André J. Fabre                     Octobre 2012                       j

This humble flower of the wet meadows holds a major place in the History of Medicine.

First comes to attention the multiplicity of the names given, through ages and countries, to the Colchicum autumnalis (Liliaceae) of the botanists. In Greek, all is simple, the name refers to the land of Colchis, supposed place of birth of the plant.

Many other names were given by the Ancients : hermodactylus (“finger of Hermes”), ephemeron, bulbus and spalax (Greek name of a tiny mole). In Orient, colchic was names as "surungam", all over Europe the strangest qualifiers have been used : "naked lady", "naked boy" in England, "herbstzeitlose" in Germany, "desmonia" and "paternostar" in Italy as in France, "dogs killer" was another reminder of the frightening reputation of the colchic.

On top of all, were flourishing wrong botanical appellations : "meadow saffron", "bastard saffron", "water lily" , "crocus", "lily" or "iris".

Antiquity

Tradition traces the origins of colchic back in the country of Colchis, on the Eastern strands of the Black Sea, where a river, Phasis comes to separates Europe from Asia.  

Very early, in Greece, appeared a botanical knowledge from the works of Theophrast of Eresos (372- 287 A.J.C.) who gave to the colchic a name due to last for many centuries "Hermodactylus". There is no mention of the plant in Hippocrates (460-377 A.J.C.) nor in Celsus (14 A.J.C.-37), Caelius Aurelianus (towards 450?) or Serenus Sammonicus (end of IId century).

 However, in the IVth century, a therapeutic use of colchic was clearly proposed in a text, work of Actuarius of Byzance (see the original texts in appendix) mentioning in De Med. Compositione "hermodactylus" as an "antidote" against pod Agra and other joint diseases".

 Thereafter, History of colchic had been, for centuries, a long succession of ambiguities and confusions among species ("colchic ","iris", "crocus") and names ("hermodactylus", " ephemèron" and "colchicum").

 The worst was that the specific therapeutic properties of colchic remained so long time unknown.

 Colchitherapy, as we intend, was due to take birth in Byzance, capital of Easter Roman Empire with the works of Alexander of Tralles (525-605) and Paul of Aegina (livelily around 650)

 Direct heirs to Byzantine Medecine in this field were some great names of Arab medecine : Rhazès (Xth century) recommended the use of "suringam" in gout and Avicenne (in XIth century), also from Persian origin (he came from the same city as Rhazès), mentioned a personal experience of a drug coming from the lndus.

Middle Ages

 In fact, the first to promote colchic under its current name appears to be lbn el-Baytar, who taught medecine in Cairo during the XIIIth century

 In Italy, at the very start of XVI century, Pietro-Andrea Mattioli (1500-1577) son of a Venetian physician and physician himself, proposed a good description, without any ambiguities of the colchic from a study of samples brought back from Constantinople by the ambassador of Ferdinand I, brother of the most famous of all gout sufferers, Emperor Charles Quint.

 Great progresses could thus be acquired although without any hint that colchic was by no means exotic plant. After the Middle Ages, however, it became obvious that suringam imported with so large expenses from Orient was not different from the colchic so common in the meadows of Occident but, for a long time, colchic was only regarded as a purgative medication...

 Without any doubt, Gilbertus Anglicus (1170-1180?) was the first author in Europe, to mention colchic but, in 1764, was issued, in the Gentleman's Magazine (1764, XXXIV, 426-9) the first publication reporting, from the "baron Anthony Storck, adviser aulic and chief-physician of the Impress", under the title "Some Account of the Use and Effects of the Root of Meadow Saffron", a medicinal use of colchic but . It should be noted that the paper mentioned colchitherapy as a treatment of hydrops but at the same time, colchic began to be administered to famous gut sufferers as George IV of England who reigned from 1820 to 1830, and supposedly, king Louis XVIII of France during his exile in England.

 There is also some belief that Franklin, other notorious "gouty", had discovered in Paris where he was ambassador in 1779, the beneficial effects of colchic and then brought it back to the United States. The truth is somewhat different : Franklin had composed during its Parisian stay a lampoon on gout sufferers without direct reference to colchic in his pamphlet. However, there is some suggestions, in Franklin's correspondence, that he was well aware of an miracle "English medicine".

 As early as XVIth century, colchic had been used in France as a treatment of the gout : Ambroise Pare (1509-1590) gives clearly reference to colchic in his "Traite de Medecine" .It should also be mentioned that, as early as the Middle Ages, a French chronicler, Villehardouin (1148-1213), had related a joint disease occurring among crusaders which could be cured by "local medicines".

XVIIIth century

 In more recent times, in 1703 in Paris, a book was published under the title "On the treatment of the gout by a drug from Turkey by the sior of Bisance" and, in 1765, of the Treaty of Mr. Murger devoted to an "Observation of the internal use of the bulb of colchic of autumn gives in the form of oxymel in hydrops".

 In 1783, Nicolas Husson who was military officer and not physician, obtained with the sales of colchic, a success so wide that police forces had to be called out. The secret of the miracle drug had been jealously kept until the beginning of XIXth century when an English pharmacist, Want, could demonstrate that "medicinal water" was, in fact, a suspension of colchic.

 In the XIXth century were issued in France the first scientific researches on colchic : two pharmacists, Pelletier and Caventou, reported in 1820 a method for isolation of the active ingredients in colchic and In 1884, Houde could obtain a crystallized preparation of colchicin . Still in our times, Colchicum autumnale remains the main source of colchicin.

 Several centuries had thus be necessary to solve the mysteries of colchic and its medicinal properties. Many factors can be discussed here, and in first the difficulties encountered to obtain from remote countries well preserved bulbs of colchic.

  It should also be taken into account the large number, at least about thirty, of botanical species. In retrospect, most important has been a total absence of international communications between scientists. An example can be given : in the famous Encyclopaedia of Diderot, there is no mention of colchic in the article on "gout" whereas hermodact, in its heading, is mentioned as a "panacea" for the treatment of "goutteux"...

Modern times

 In modern times, colchic has remained the "imperial" drug of gut sufferers but, the in the last decades, appeared a wide array of surprising new indications for the drug.

 A major indication for colchitherapy is Behcet disease, associating recurrent stomatitis, chronic polyvisceral vascularitis and ocular or cutaneous complications. Oncology is also part of the "colchic story" : at he end of XIXth century, Pernice, an Italian physician from Palermo reported that significant anomalies of cellular mitosis could be observed on animals having received large amounts of colchic. In spite of the significance of such findings, the report remained ignored until 1949.

 At the present time, oncologic use for colchic is still under discussion but the fact that colchicin is a potent inhibitor of cellular metaphase, in the same group that vincristin and the nocodazole, has been widely substantiated.

Gout, colchic, periodic disease and Coclchis

 Last but not least comes the discovery of a specific indication for colchic in the treatment of "periodic disease". This very peculiar (and largely enigmatic) disease was first reported by Siegal in 1945 on patients originating from the Middle East.

 The are often polymorphic associating abdominal pains, diarrhoea and fever in four to six days bouts recurring on five to six weeks cycles. The hallmark is a combination of polyseritis (peritoneal or pleural), mono-articular arthritis and persistent splenomegaly. Recent studies on the so-called "Mediterranean fever",  which seems to be a variant of the disease, have shown a genetic transmission, autosomic recessive type, with a gene localised in the short arm of chromosome 16.

 he most surprising finding came in 1972 when Goldfinger demonstrated a specific action of the colchic on the course of periodic disease...

 Obviously, many questions could arise from Ancient texts : could the many reported cases of "chronic fever, associated with splenomegaly and cured by "iris" or "crocus" have been variants of "periodic disease"? should we see a link between the well-demonstrated ethnic predisposition for the disease (most of the patients are originated from Armeny or Near-Orient; close to the borders of the Black Sea) and, in final, how should we interpret the legends of Colchis : myth or reality ???

 As a conclusion, can be stated that no other drug than colchic, except opium, has been so widely used, so early, in so many indications and in so many countries.

 This is the surprising fate given to the plant immortalized by Guillaume Apollinaire as the "eye shadowy flower of the meadows"...  

a.fabre.fl@gmail.com

 

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