Herbs in History: Foxglove

Foxglove

Digitalis purpurea L.


CONTENTS

By Alain Touwaide & Emanuela Appetiti | May 2023

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The Making of a Medicinal Plant

Foxglove (Digitalis purpurea L.)

Illustration 1: Foxglove (Digitalis purpurea L.)
 

The history of Foxglove (Digitalis purpurea L. [Plantaginaceae]) (Illustration 1) is well known at first glance. In 1785, the British physician William Withering (1741-1799) published An account of the foxglove and some of its medical uses; with practical remarks on the dropsy, and some other diseases (Birmingham: Swinney) (Illustration 2). As the story goes, Withering knew of a healer who successfully treated cases of dropsy by administering an herbal tea to her patients. He went to know the plants that were used to prepare tea and discovered later that the major active ingredient was Digitalis. Thanks to its cardio-tonic action, Foxglove was increasing cardiac activity and, as a consequence, drained the body.
 

Title page of William Withering

Illustration 2: Title page of William Withering, An account of the foxglove and some of its medical uses; with practical remarks on the dropsy, and some other diseases. Birmingham: Swinney, 1785
 

Beginnings

Though attested by documentation and exact, this story hides more than it tells about Foxglove and its medicinal uses through time. Native to western and southwestern Europe, western and central Asia, and northwestern Africa, Foxglove does not appear in the medical literature of the ancient Mediterranean World that provided the basis for research on so many other medicinal plants through history.
 
According to current literature, its first attestation appears in the famous 1542 Historia Stirpium (Research on plants, p. 892) by the German botano-therapist and physician Leonhart Fuchs (1501-1566). All the elements of his account are of interest, starting with the place of the chapter on Digitalis in the work. As per his own statement, Fuchs added this chapter at the very end of the work, since the whole material had been compiled and was ready to go into print: he preferred to publish it there, even out of order, rather than not mentioning it at all. The fact is that he was mostly following the classical texts in matter of medicinal plants. And, as he noted, Digitalis was not known at his time by either a Greek or a Latin name. Fuchs deduced that this was because Digitalis was unknown to the ancients. He pursued stating that, being seduced by the beauty of the plant, he could not accept it to be anonymous. He thus created a name, digitalis, on the basis of its German name Fingerhut, which does refer to finger, digitus in Latin. He modestly proposed this neologism until, as he wrote, a better name could be found.
 

Digitalis purpurea L.

 Illustration 3: Digitalis purpurea L. in Leonhart Fuchs, Historia Stirpium. Basel: Officina Isingriniana, 1542, p. 893
 

Digitalis lutea L.

Illustration 4: Digitalis lutea L. in Leonhart Fuchs, Historia Stirpium. Basel: Officina Isingriniana, 1542, p. 894
 

Again, based on the then traditional German usage, Fuchs identified two species: purpurea (purple, identified as brown in the German caption = Digitalis purpurea L.) (Illustration 3), and lutea (yellow, D. lutea L.), (Illustration 4). He then briefly described them, noting that, apart from the colour, they do not differ. They are characterized by leaves like those of Plantain (Plantago spp.), with a long and large seed, and a thin, hairy root. They grow in the mountains, in shady, rocky terrains, and bloom in July.
 
Fuchs went on defining the organoleptic qualities of Digitalis, which he identified as bitter, just like Gentian (Gentiana lutea L.), being hot and dry. Based on these qualities, Fuchs considered that Foxglove is pretty useful in cases when physicians need to reduce, cleanse and eliminate “obstructing matters” out of the body. He immediately made this general consideration more concrete, referring to menstruation, elimination of pus from the chest and the lungs, and all the conditions in which Gentian is efficacious.
 
Whereas Fuchs clearly reported traditional uses of his time instead of referring to earlier literature (the Greek and Latin classics) as he did for almost all the other plants in the work, he nevertheless referred to Galen (129-after [?] 216 CE). This might be the most interesting point of his chapter. In so doing, he cited Galen’s most significant treatise in matter of materia medica, De simplicium medicamentorum temperamentis et facultatibus (On the composition and properties of simple medicines), Book 4, Chapter 16, according to which bitter flavors dry, clear out, eliminate, and reduce thickness in the veins. Fuchs knew well his classics and was able to transpose their principles to materia medica that had not been analyzed in the classical texts. The effort is remarkable. Strangely enough, however, this affirmation about “thickness in the veins”, which is not otherwise explained, remained unobserved in subsequent literature whereas it might have been an early identification of the action of Digitalis on the vascular system discovered much later by Withering.

 

Fits and Starts

Fuchs’ chapter was nevertheless foundational. Fuchs’ nearly contemporary and homologue medico-botanist Rembert Dodoens (1516/17-1585) took up, indeed, where Fuchs left. All details are significant, particularly the differences from the 1583 to the 1616 edition.
 
Dodoens did adopt Fuchs’name for the plant (1583 edition, p. 169), even though he also listed the names in German, Flemish, French and English, stressing, about French, that the plant is called Gants notre Dame (Our Lady’s Gloves) by some, implying in a certain way that Fuchs did follow a traditional usage.
 
In the botanical description, Dodoens differed from Fuchs by distinguishing more than two species, up to four, which he distinguished not only by the colour of the flower as Fuchs did, but also by the shape and colour of the leaves. The first such species is the purple one of Fuchs, which Dodoens described with greater precision, including nevertheless the habitat identified as per Fuchs, that is, the mountains, shadowy places and rocky soil. Adding that it grows abundantly in Germany and Belgium, Dodoens also noted that it can be introduced in gardens. Although he described three other species in quite great detail, he provided only the illustration of his first species, Digitalis purpurea (Illustration 5).
 

Digitalis purpurea in Rembert Dodoens

Illustration 5: Digitalis purpurea in Rembert Dodoens, Stirpium Historiae Pemptades Sex, sive Libri XXX. Antverpiae: Ex officina Christophori Plantini, 1583, p. 169
 

Though indirectly, Dodoens introduced some sense of taxonomy through the position of his chapter in the whole work. He did not leave it out of order as did Fuchs, but included it between Campanula Autumnalis (p. 168) and Lychnis coronaria (p. 170). Even though he did not provide any explicit statement about this classification, the representations of all three plants and their sequence (Campanula, Digitalis, Lychnis) make it clear that the flower justified the grouping due to its apparent similarity in all three species.
 
This botanical section of Dodoens’ chapter is followed by the following brief paragraph, which substantially differs from Fuchs’ chapter:
 

Because they are bitter, the leaves of Digitalis result in a hot and dry property, associated with a certain power of elimination. Whatever, they are of no use and are not either administered in medicines. Only the flower pleases, but only for its beauty and shape, which are a delight.

 
This was a substantial step back. Dodoens clearly knew Fuchs’ chapter and made the same considerations about the properties of the plant. Nevertheless, even though he specifically considered the leaf whereas Fuchs mentioned only the herb in a very generic way, he did not recommend it for any use, even negating that it might have any.
 
However radical it might seem, this statement finds an explanation in the 1616 edition, where Dodoens describes experiments that can properly be qualified as pharmacognostic. The text is really interesting (1616 edition, p. 170):
 

There are some people who claim that its leaves have a nocive and venomous property. This is manifestly known through an experiment. If yolk eggs are prepared with leaves of this and other plants, all those who have tasted and eaten them are reported to have soon been unwell and prone to vomiting.

 
This clearly refers to trials made to test a plant for which there was no previous literature. It might explain why, in the 1583 edition, Dodoens negated that Digitalis had medicinal applications.
 
There is more in this. The test briefly described in the 1616 edition exactly recalls a similar experiment reported by Galen about the way to determine the lethal dosage of a plant. As he reported it, indeed, Galen prepared small balls of bread in which he mixed the plant the toxicity of which he wanted to assess, and he threw these bread balls to hens. After the first dosage simply killed the animals, Galen gradually reduced the amount of the toxic plant until he found the exact dosage of tolerance.
 
Returning to Dodoens, the remarkable point is that he remembered Galen’s experiment and he transferred it to a plant that was previously unknown to assess its lethality in a truly experimental way.
 
Interestingly, in the 1616 edition, Dodoens maintained the statement of the 1583 edition about the lack of therapeutic applications of Digitalis. After the experiment reported in the 1616 edition, he was probably more cautious than ever about recommending any therapeutic use of Digitalis.
 

John Gerard, Herball or General historie of plants.

Illustration 6: John Gerard, Herball or General historie of plants. London: Norton, 1597, p. 646 
 

A British Tradition?

After Dodoens’ caution based on experiments, John Gerard (1545-1612) offered a more complete analysis. His Herball or General historie of plants first published in 1597 largely relied on Dodoens’ work, which, however, it completed on a great many points on the basis of both literature and personal experience. This was particularly the case with Digitalis, about which Gerard provides a very different set of information (1597 edition, pp. 646-647) (Illustration 6).
 
Gerard thus describes several species, mostly the purpurea one for which he provides abundant details. Of the other species, which differ only by their color, he adds that he grows the yellow one in his garden, as well as the species that he defines as ferruginea, with the color of “rustie iron”.
 
He then identifies the type of soil and places where Digitalis grows, open, and sandy soils, and “almost every where” under hedges. And, according to him, they are spontaneous in “Landesdale, and Craven, in a field called Cragge close, in the north of England; likewise in Colchester in Essex; neere Excerster in the west parts, and in some fewe other places. The other two are stangers in England, neverthelesse they do grow with the others in my garden”.
 
As for their properties and medicinal uses, Gerard repeated earlier literature, stating that Digitalis is bitter, hot and dry “with a certaine kinde of cleansing quality”. Following Dodoens, he concluded that “yet they are of no use, neither have they any place among medicines, according to the auncients”.
 
After such a statement, Gerard could very well have concluded the chapter there. In this case, such chapter would have been mostly of horticultural value, including the plant distribution. Gerard did not stop there, however, adding a section entitled “The vertues” in which he reported formulae for medicines with their applications:
 

“... boiled with water or wine and drunk, [this medicine] cuts and reduces thick phlegme and bad humors [of the body]; it opens obstructions of the liver, spleen, gallbladder, and other internal parts of the body ...”
 
“... taken in the same way or boiled with honey or sugar, it cleans the chest and brings thick, bad humors to mturation, allowing for their elimination ...”
 

John Gerard, Herball or General historie of plants.

Illustration 7: John Gerard, Herball or General historie of plants. London: Norton and Whitakers, 1636, p. 790
 

We do not know whether these therapeutic applications come from Fuchs, as they are similar, or from popular traditions from which both Fuchs and Gerard took their material. Nevertheless, Fuchs does not provide formulae for medicines and refers to uses of Digitalis as a herb, without specifying any part. Furthermore, Gerard does not reproduce Fuchs’ usage about “thickness in the veins”. We need to remember that, whereas the core of Gerard’s Herball was made of a translation of Dodoens, the text was completed with material from other sources, personal experience, and usages of that time. This is probably the case here, with the apparent contradiction between the data from literature (Dodoens and his statement about the lack of therapeutic applications) and the formulae reported here. In that case, both Fuchs and Gerard seem to have reproduced common practice of their time.
 
After this original part, Gerard returns to classical literature and he compares the uses of Digitalis to those of Gentian, claiming that Galen already did so. This false claim is corrected in the 1636 edition, which specifies that reference should have been made to Fuchs and not to Galen in addition to providing representations of two more species, alba and ferruginea (1636 edition, p. 790) (Illustration 7).
 
At this point, the history seemed complete. It illustrates the gradual making of a medicinal plant previously unknown in literature and shows the efforts made to describe and analyze this plant, among others by using the model of the classical tradition and later assimilating data from contemporary practice. All this in almost fifty years and thanks to some experiments duly organized. This would already change quite substantially the traditional narrative of Digitalis and its discovery by Withering. But there is more, hinting at deeper traditions all too often overlooked, if not unknown, which open new perspectives.
 

Digging Deeper in Time

If Foxglove does not appear in the medico-botanical literature of the ancient Mediterranean World, it cannot be found either in the many manuals of therapeutic of the Middle Ages, be they the famous Qanun of ibn Sina better known as Avicenna (980-1037) or the later Latin Tractatus de herbis (Treatise on Medicinal Plants) possibly of Southern-Italian origin, of the 13th century.
 
Interestingly, however, we do find Digitalis in a Middle English herbal possibly of the late 14th century, the treatise traditionally identified as Agnus Castus from the name of the first plant it describes, Vitex agnus-castus L., Chaste tree. This manual is made of a series of monographic entries identified by the name of the plant they deal with and listed in the alphabetical order of these names.
 
The entry of interest here is Erpina, a name to which we will return shortly. This name is immediately followed by a synonym that allows for identification: foxglove, that is, the current English name of Digitalis. The plant is then briefly described in a way that does not leave space to doubt about the identification of Erpina:
 

This herb is like gentian, but it is not so clear-coloured and has a long stalk and a flower much like gloves and it grows much in the woods.

 
Though brief, the description provides enough characteristic diagnostic signs to allow for identification: Erpina seems to be our Digitalis. The comparison with Gentian is significant—with, however, the difference in the colour—, all the more because it reminds the organoleptic characterization by Fuchs.
 
Strangely, no therapeutic uses are listed, contrary to what happens for many of the other plants in the treatise. However, the very name of the plant here—Erpina—might provide a key from this viewpoint. It has been interpreted, indeed, as a derivative of the Greek name herpes, which refers to several skin affections. If so, this name hints at a dermatological usage that has not been reported in any other ancient source, which was probably common knowledge at the time of the manual Agnus Castus, inviting new investigations.
 
As this history of Digitalis shows, the making of a medicinal plant is much more than its discovery in recent pharmacognosy; it is a long process going back in time that relies on many sources, including traditions now lost that can be traced, however, in ancient texts still to be explored.


Literature

Flora Europaea 3 (1972): 239-241 for the genus, 239-240 for the species.

Articles

Whayne Th. F. Jr 2018. Clinical Use of Digitalis: A State of the Art Review. American journal of cardiovascular drugs: drugs, devices, and other interventions 18(6) (2018): 427-440. https://doi.org/10.1007/s40256-018-0292
 
Kreis W. 2017. The Foxgloves (Digitalis) Revisited. Planta Medica 83 (2017): 962-976.
doi: https://doi.org/10.1055/s-0043-111240
 
Wagner, C. S., J. De Gezelle, M. Robertson, K., Robertson, M. Wilson, S. Komarnytsky. 2017. Antibacterial activity of medicinal plants from The Physicians of Myddvai, a 14th century Welsh medical manuscript. Journal of ethnopharmacology 203 (2017): 171-181. https://doi.org/10.1016/j.jep.2017.03.039
 
Fornaciari G., V. Giuffra, F. Bortolotti, R. Gottardo, S. Marvelli, M. Marchesini, S.Marinozzi, A. Fornaciari, G. Brocco, F. Tagliaro. 2015. A medieval case of digitalis poisoning: the sudden death of Cangrande della Scala, lord of Verona (1291–1329). Journal of Archaeological Science 54 (February 2015): 162-167.
https://doi.org/10.1016/j.jas.2014.12.005
 
Norn S., P. R. Kruse. 2004. Hjerteglykosider: Fra oldtiden over Witherings digitalis til endogen glykosider [Cardiac glycosides: From ancient history through Withering's foxglove to endogeneous cardiac glycosides]. Dansk medicinhistorisk arbog 2004: 119-132.
 
Groves M.J., N.G. Bisset. 1991.A note on the use of topical Digitalis prior to William Withering.  Journal of Ethnopharmacology 35(2) (December 1991): 99-103.
https://doi.org/10.1016/0378-8741(91)90061-H
 
Wade O. L. 1986. Digoxin 1785-1985. I. Two hundred years of digitalis. Journal of clinical and hospital pharmacy11(1) (1986): 3-9.
https://doi.org/10.1111/j.1365-2710.1986.tb00822.x
 
Burchell H.B. 1983. Digitalis poisoning: Historical and forensic aspects. Journal of the American College of Cardiology 1(2, Part 1) (February 1983): 506-516.
https://doi.org/10.1016/S0735-1097(83)80080-1
 
Maurice S. Jacobs, “The History of Digitalis Therapy”, read before the Section of Medical History, College of Physicians, Philadelphia, April 13, 1936. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939868/pdf/annmedhist155570-0022.pdf

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