n 1835, the formula for zinc-chloride paste, which Dr. Canquoin had been using in skin and breast cancer therapy, arrived in England. The Scottish surgeon, Alexander Ure, M.D. (1810-1866), proclaimed himself responsible for its importation. Dr. Alexandre Canquoin deserves the greatest credit for recognizing the need to share his method with the British medical community; after all, he was indebted to Dr. John Davy, who had discovered the compound in 1812. Controversy, however, marred the return of zinc chloride to its country of origin.
Ure studied medicine at Edinburgh University, became House Surgeon in the Royal Infirmary at Glasgow, and moved to London to practice at the Westminster General Dispensary and, later, at St. Mary’s Hospital. While at North London Medical School and St. Mary’s, he was a pathology and anatomy lecturer, a member of the Pharmaceutical Society, and, in 1857, President of the Harveian Society (Obituary, 673). In the 1835 Lancet paper, “Observations and Researches on a New Method of Curing Cancer,” Ure translated Canquoin’s memoirs and attempted to improve the formula (392). He conducted experiments, for example, to find a way to shorten Canquoin’s 8-12 week treatment plan without compromising its effectiveness. Related laboratory investigations would demonstrate how ZnCl2 (zincane) worked when in contact with living tissues.
Ure confirmed that zincane coagulated albumen, a protein abundant in blood plasma and serum, in muscle, milk, egg whites, and in animal and plant substances. This finding was consistent with those of Canquoin and of the French chemist, François Foy (1793-1867) (“Observations and Researches,” 303). Ure demonstrated that ZnCl2 had “great affinity for albumen,” while Foy calculated the albumen content in malignant tissues to be between 42% to 47%; it was logical, therefore, to conclude that the high albumen content accounted for the chloride’s capacity to devitalize diseased tissue so extensively (303). This information, in turn, provided practitioners with a way to calculate, precisely, the respective proportions of chloride to wheaten base required to treat a particular lesion. An escharotic layer of tissue, for instance, could be attained over a 7-to-8-hour period; and, though time-consuming, the process would proceed, layer by layer, until the entire neoplasm was destroyed and eventually peeled away. Ure was amazed to find that tumors could be coagulated chemically, while ZnCl2 retained its potency during each round of treatment. On superficial cancers, the effects were most dramatic: once the caustic had done its work, a renovated surface was left, no longer generating “morbid products” (303-04). Because cell biology and microscopy were in their infancy, the early nineteenth-century surgeon could not be sure that the paste had destroyed the abnormal tissue entirely. Ure’s albumen experiments, however, constituted an important early phase of the investigation (304).
In the second installment of “Observations and Researches,” Ure affirmed that ZnCl2 was superior to arsenic, mercury, and other commonly-used preparations. To improve the chloride’s effectiveness further, he concentrated on the inactive matrix. He argued that, since Canquoin’s base consisted of albumen-rich farina, it would absorb the zinc chloride too quickly, preventing it from diffusing through the base gradually (433). To make the chloride more efficient, he sought a less permeable and more potent matrix: “if some inert inorganic powder were substituted for the vegetable matter, capable of absorbing and retaining a sufficient quantity of moisture to form a paste . . . [in] a simple mechanical mixture, it would then be possible to turn to account the full escharotic powers of the chloride” (433). He began by using Canquoin’s No. 4-formula as a model: the antimony (stibnite) substituted for the farina in No. 4, had given the paste a soft-wax consistency, malleable enough to conform to irregular skin surfaces. Ure’s renovation was to substitute anhydrous Calcium sulfate of lime (CaSO4) for No. 4’s stibnite. In effect, he decided to combine zinc chloride with Plaster of Paris, a quick-setting paste. CaSO4, in the form of a pure, crystalized gypsum prepared at low heat, was ground down to a fine powder, mixed with ZnCl2 and water, and then kneaded into “a paste like putty.” A medium both plastic and porous, it theoretically would permit “the escharotic gradually to exude into the morbid texture” (Ure 433 & note). Because CaSO4 appeared to provide malleability, gradual permeability, and sustained potency--Ure considered it an upgrade over Canquoin’s stibnite permeant. Moreover, the renovated formula had reputedly accentuated the caustic’s effects and minimized discomfort, apparently without anesthetic (433). He outlined his rationale in a 10 December 1836 article:
The preparation of the chloride which I proposed and introduced into practice in this country, differs in a most important feature from that originally employed by M. Canquoin. The wheaten flour prescribed in the French formula is apt to envelop the chloride in a glutinous dough, which blunts its power, or at any rate tends to confine its action to the particles on the surface of the paste; but the anhydrous gypsum of my formula, while it can exercise no chemical action upon the chloride, forms a porous medium through which the whole particles of the deliquescent chloride may transude upon the morbid or [albuminoid] tissue, with the effect of decomposing or destroying it with certainty to any definite depth. This preparation of mine has been adopted in several of the London hospitals, and has found to be unfailing in its escharotic power. It was probably owing to the counteraction of the vegetable farina that Mr. Sauson, the distinguished surgeon of the Hôtel Dieu at Paris, failed last year [with] the paste . . . . [Ure, “Observations,” 440n.]
In 1835, Ure’s claims of having introduced and renovated Canquoin’s system were challenged. Dr. A. M. Bureaud Riofrey (b. 1803-), co-claimant and colleague, revealed that, in January 1835, he, rather than Dr. Ure, had been the first British physician to learn of Canquoin’s work. At that time, Ure had agreed to care for the latter’s patients during Riofrey’s visit to Canquoin’s Paris clinic; the latter had personally invited Riofrey to Paris for several weeks to collaborate on the new escharotic regimen. Riofrey’s accusatory narrative follows: having permission to work in Riofrey’s personal library during his two-week absence, Ure had reputedly found Canquoin’s Mémoires among confidential papers, and clandestinely acquired, translated, and published the material in a British journal before Riofrey could have been credited with having imported Canquoin’s method to England. Riofrey stated his case, heatedly, in a 27 December 1836 article (“Dr. Bureaud’s Rejoinder,” 519; “Mr. Ure’s Refutation,” 544-46).
Ure responded that the escharotic formula in question had been circulating in the medical literature before Riofrey had informed him of the Paris invitation. Denying that he had purloined the Mémoires from his colleague’s library, Ure asserted that, because zinc-chloride fluid and powder had been around for a decade or more, he had learned about it independently, prior to any discussions with Riofrey. Ure cited the 1826 edition of Hufeland’s Journal where the caustic was described as a topical (lotion or powder) cancer remedy (“Mr. Ure’s Refutation,” 544). This claim was reinforced, in the 19 December 1835 “Observations,” by a reference to Dr. Häncke, of Breslau’s powdered ZnCl2 and adhesive plaster (Ure, “Observations and Researches,” 304). It is true that zinc chloride had been used clinically, from c. 1819 to the 1830s, as both lotion or powder, to treat a variety of skin disorders. But, since Canquoin’s original innovation—i.e., to use zinc chloride primarily as an enucleating paste, not as a lotion--had been publicized in 1835, Ure’s spirited defense dissolved. Canqouin had been the first to administer zinc chloride systematically as an ointment, and his formula had not been in the public domain prior to that date. Hence, barring another immediate source, Ure had to have learned about it through his association with Riofrey; furthermore, the aggrieved party could document his interactions with Canquoin prior to the appearance of Ure’s papers.
Asserting that his ethical and scientific obligation was to introduce the Canquoin-system to England, Riofrey dismissed as retrogressive Ure’s substitution of calcium sulfate of lime for stibnite in the No. 4 variant. Contrary to Ure, he argued that the calcium sulfate, unlike the granular stibnite, was excessively absorbent: the CaSO4 permitted the ZnCl2 to soak through the lime, “as though through a sponge,” preventing the caustic from reaching the tumor surface, at a pre-calculated rate conforming to its dimensions. Using CaSO4 in place of stibnite, therefore, was a blatant error. Hardening quickly, the gypsum also tended to break apart unexpectedly, rather than to remain consistently porous and adherent to the treated surface (New Treatment, 68-69; “Dr. Bureaud’s Rejoinder,” 521).
In the 1836 monograph, New Treatment of Malignant Diseases, and Cancer, Without Incision, Riofrey indicated that he planned to reform Canquoin’s method radically. First, to render the paste less painful for patients at St. Bartholomew’s Hospital, he prescribed 30 drops of laudanum, the highest strength. Second, he also opted for the No. 4 proportions (1:1, zincane + stibnite), at the very outset of treatment, rather than to progress slowly from weaker to stronger mixtures, as Canquoin had proposed. Retaining the stibnite base (farina was used for Nos. 1-3), Riofrey desired to achieve “deeper eschars” in less time and with fewer applications: accordingly, in two preparatory steps, he mixed a paste “in a reverse proportion to MR. CANQUOIN” (New Treatment, 67-68 ).
If the entire mass had been permeated and reduced to dead tissue over a 6-to-11-day period, Riofrey believed that the destruction of visible tumor had been achieved (New Treatment, 70). The caustic applications were renewed if visible tumor remained and were continued until healthy tissues was reached. Aware of the intensity of the pain, he never applied the paste for more than 24 hours. The use of concentrated No. 4 achieved Canquoin’s results in less time, and laudanum, if needed, served as an anesthetic. Even though discomfort could not be completely eliminated, Riofrey argued that ZnCl2 was comparatively less painful than pastes containing arsenic or sulfate of copper (70).
The great advantage of the Canquoin-Riofrey system was that, in most cases, eschars separated as early as the sixth day, without bleeding, infection, absorption of the chloride, or toxicity (72). A contemporary, Dr. Alfred Velpeau (1795-1867), who was a Parisian anatomist and surgeon, used the formula in his practice successfully, preferred it over other escharotics, notwithstanding the pain, and he endorsed Riofrey’s more energetic formula (Velpeau 245; New Treatment, 68; Parker 15). In 1856, Velpeau wrote a detailed account corroborating Canquoin’s results, including precise metrics: for instance, two-millimeter thickness of paste produces, in depth, a four-millimeter eschar; and a one-centimeter eschar requires “a plate of caustic five or six millimeters thick” (245).
Although Riofrey was convinced that the ZnCl2 paste was “one of the greatest improvements in the treatment and cure of Cancers,” he did not entertain the idea that every cancer could be cured by caustic alone (New Treatment, viii). Nor did the escharotic method, as he understood it, justify “the indiscriminate application of this agent.” Rather, it called for the “judicious employment of all the means sanctioned by experience” (viii).
From 1837 to 1850, medical scientists continued to experiment with the escharotic formula, for its place in medicine was as-yet undefined. Other substances were added to the basic zinc chloride and water formula, and variants regularly appeared. As the ZnCl2 formula gained popularity, its limitations were also manifested; and its critics became more voluble (Dunglison, “CLXXIII Zinci Chloridum” New Remedies, 690). Dr. Edward William Tuson (1802-1865), a surgeon at Middlesex Hospital, used it successfully as a topical lotion and as a tonic (a grain of chloride every morning in caraway water) (Dunglison, “CLXXIII Zinci Chloridum New Remedies, 691); but, in 1846, he determined that the chloride paste, rather than being curative, was “only of use in arresting the progress of [cancer]” (Tuson,The Structure and Functions, 399). For Tuson, Canquoin’s formula offered remission but did not guarantee non-recurrence: “we are flattered by vain anticipations of curing the disorder, buoyed up with hope which is fallacious and disappointing, whilst cancerous disease continues slowly in its progress, daily growing an ascendancy upon the constitution, until death alone checks its malignant propensity” (The Structure and Functions, 401). Nevertheless, positive outcomes, at least in the short-term, were reported in urology and in orthopedics (Guthrie in 1840) (Dunglison, New Remedies, 691-692). Ure’s Plaster of Paris matrix still had advocates, one of whom, Dr. W. P. Brooks, in the 1848 paper “On Scirrhus of the Lips,” describes promising results in the treatment of skin cancer on a patient’s lower lip after three applications of two parts ZnCl2 and (using Ure’s base) three parts gypsum.
During the late 1840s and early 1850s, physicians in the tradition of Papenguth and Canquoin—more than one dozen are on record--used zinc chloride routinely as lotion, powder, or paste against skin diseases. In 1848, the chemical solution would become widely accepted as a disinfectant under the brand name, Burnett’s Disinfecting Fluid, only to fall into disrepute, by 1905, as an antimicrobial (Dunglison, “CLXXIII Zinci Chloridum” New Remedies, 689).
Brooks, W. P. “On Scirrhus of the Lips.” Medical Times. 19.475 (4 Nov. 1848): 196. Google Books. 9 Jan. 2016.
Canquoin, Alexandre. Mémoire sur un Nouveau Mode de Traitement des Affections cancéreuses adresse à l’Académie royale de médecine . Paris: l’auteur, 1835.
_____. Mémoire Complementaire . . . sur le Traitement des Affections Cancéreuses la Pate Phagédénique que et sur les Modifications que Quelques Circumstonces Rendent Nécessaires . Paris: l’auteur, 1835.
_____. Traitement du Cancer, Excluant Toute Opération par L’Instrument Tranchant, suivi des Modifications qu’il à Apportées dans le Traitement Ordinaire des Ulcères de L’Utérus, et d’un Très-grand Nombre D’Observations . 2nd edition. Paris: l’auteur, 1838.
_____. Des Caustiques en général et de leur Emploi en Chirurgie . Paris: Labé, 1855.
Dunglison, Robley. “Zinc Chloride.” Medical Lexicon: A New Dictionary of Medical Science . 3rd edition. Philadelphia: Lea & Blanchard, 1842. Google Books. 6 January 2016.
_____. “Disinfectants.” Vol. 2 of General Therapeutics and Materia Medica, Adapted for a Medical Text-Book. 2 vols. Philadelphia: Lea and Blanchard, 1846. Hathi Digital Library. 22 November 2015.
Dunglison, Robley. “CLXXIII Zinci Chloridum.” New Remedies with Formulae for Their Preparation and Administration. Philadelphia: Blanchard & Lea, 1856. Pp. 689-695. Google Books. 26 May 2016.
Häncke, Johann W.. “De l’usage interne et externe du Chlorure de zinc.” Journal de Pharmacie et des Sciences Accessoires . Eds. P.-J. Bouillon-La Grange, L.-A. Planche, P.-F.-G. Boullay, et al.; and Bulletin de la Societé de Pharmacie de Paris. Eds. M. Robiquet and Special Commission. Vol. IX (16). Paris: Louis Colas and Sons Library, September 1830. Pp. 550-551. Google Books. 8 November 2016.
Hufeland, C. W., and E. Osann. Hufeland’s Journal der Practischen Heilkunde. Berlin: G. Reimar, 1826.
Parker, Samuel William Langston. The Modern Treatment of Cancerous Diseases by Caustics or Enucleation; An Inquiry into the Effects of Many New Remedies in Arresting the Progress of Cancer. London: John Churchill and Sons, 1867.
Riofrey, A. M. Bureaud. “Dr. Bureaud’s Claim to the Introduction of the Chloride of Zinc into Use in England, and His Rejoinder to Mr. Ure.” The London Medical Journal 17 (19 December 1835): 518-22. London: Longman, Rees, Orme, Brown, Green, and Longman, 1836. Google Books. 19 December 2015.
_____. New Treatment of Malignant Diseases, and Cancer, Without Incision. London: Longman, Rees, Orme, Brown, Green & Longman, 1836. Wellcome Library. 11 January 2017.
Tuson, Edward William. “On the Effects of Chloride of Zinc, and the Chloride of Lead, in the Treatment of Cancer.” The Lancet. 41.1063 (13 January 1844): 502-506.
Tuson, Edward William. The Structure and Functions of the Female Breast: As They Relate to Its Health, Derangement, and Disease. London: John Churchill, 1846. Google Books. 19 January 2016.
Ure, Alexander. “Observations and Researches on a New Method of Curing Cancer.” The London Medical Journal. Vol. 17 (19 December 1835): 301-304, 432-436. London: Longman, Rees, Orme, Brown, Green, & Longman, 1836. Google Books. 19 December 2015.
_____. “Observations on the Nature and Treatment of Lupus.” London Medical and Surgical Journal. 2.15 (10 December 1836): 438-448. Google Books. 23 June 2016.
_____. “On Cancer and Noli Me Tangere.” London Medical Journal. Vol. 18 (21 May 1836): 289-292.
_____. “Mr. Ure’s Refutation of Dr. Bureaud’s Rejoinder.” The London Medical and Surgical Journal. 2.18 (31 December 1836): 544-546. Google Books. 24 November 2015.
“Ure, Alexander.” Obituary. The Lancet. 87.2233 (16 June 1866): 673.
Ure, Alexander (1810-1866).” Plarr’s Lives of the Fellows Online. Royal College of Surgeons. Plarr’s Lives Online. 3 February 2016.
Velpeau, Alfred. A Treatise on Cancer of the Breast and the Mammary Region . Trans. William Marsden. London: Henry Renshaw, 1856. Google Books. 1 June 2016.
Last modified 19 January 2017