Working as an amateur chemist and assisting his brother, Sir Humphry Davy (1778-1829), John Davy, M. D. (1790-1868), in 1812, synthesized a compound salt called zinc chloride (zincane or ZnCl2). In the passage below, Sir Humphry explains the process:
When zinc is burned in chlorine a solid substance is formed of a whitish gray colour, and semi-transparent. This is the only compound known of zinc and chlorine. It may likewise be made by heating together zinc filings and corrosive sublimate; it is as soft as wax, fuses at a temperature a little above 212 degrees, and rises in the gaseous form as heat much below the red heat. Its taste is acrid, and it corrodes the skin; it acts upon water and dissolves in it, producing much heat, and its solution decomposed by an alkali affords the white hydrated oxide of zinc. The compound of zinc and chlorine has been called butter of zinc and muriate of zinc; following the nomenclature already proposed its name will be zincane; from the experiments of my brother, Dr. John Davy, it consists of nearly equal parts of zinc and chlorine. [H. Davy: 214; J. Davy: 186]
Knowing that a number of substances had been routinely used in anatomy labs and in surgery, John Davy tested sulfuric acid as an anatomical preservative and corrosive sublimate (mercury chloride) as a disinfectant. Although his published papers do not contain explicit commentary on the applications of zincane (“An Account of Some Experiments,” 169-204; “On the Action of Corrosive Sublimate,” 279-89), his description of the obsolete state of Ceylonese medicine, observed during his Army service there (August 1816 to February, 1820), includes a passing reference to escharotic surgery, to which he contrasts the alternative: surgical cauterization with red-hot knives:
Surgery amongst them [the Ceylonese] is in an extremely rude state. The surgical operations they perform are chiefly those of cauterizing and cupping, and opening boils; . . . during the last 40 years, the only great operations performed in Kandy was the amputation of a leg, which was accomplished in the ancient manner, by means of a knife heated to dull redness. [An Account of the Interior of Ceylon, 249]
John Davy. c. 1825. Courtesy of the Wellcome Library, London. Click on image to enlarge it.
Davy, in his Account, neither elaborated on the subject nor clarified whether the escharotic procedure was part of indigenous medicine or a British importation. But it is clear from the fragmentary evidence that he was conversant with escharotic medicine generally; had recognized the place of caustics as surgical adjuvants; and that thermal disinfection with red-hot instruments was unsatisfactory.
The British pharmacopeia of 1810 had a wide-range of products, a list of 22 classes of medication, everything from Antacids to Tonics. But when it came to destroying neoplasms chemically, the choices were few and the side-effects great. According to John Murray’s 1810 edition of A System of Materia Medica and Pharmacy (1810), in the treatment of cancer, and particularly of scirrhous (hard tumors composed of dense connective tissue), a physician only had at his disposal Belladonna extract, hemlock, arsenic, and, a concoction of barium sulfate, sulfuric, and carbonic acid. These substances, which constituted the toxic, anticancer pharmacopeia of John Davy’s times, had no doubt been imported to Ceylon (“scirrhous,” OED. II, 2669; Murray , I: 173, 175-176, 23, 233, 235, 485; II: 23). Since excisions had terrible outcomes, and since these caustics were poisonous if used incorrectly, a breakthrough was needed.
From 1812 to 1830, although the pharmacology of zincane developed slowly, its chemistry was well known in Britain. David Brewster’s 1830 contribution to The Edinburgh Encyclopedia replicates Davy’s 1812 instructions: “Zinc only forms one compound with chlorine. It has received the name zincane. It may be obtained by evaporating to dryness the muriatic zinc, and fusing the residue in a glass tube. It is not volatile at a strong red heat in closed vessels. When exposed to the air it deliquesces. It is composed of 34.5 zinc + 34.4 chlorine” (66). In 1831, the British physician, Thomas Thomson, M. D., Regius Professor of Chemistry at the University of Glasgow, expressed interest in Davy’s discovery from a pharmaceutical standpoint. Serious experimentation on ZnCl2 as a caustic, however, would commence in the late 1830s (548).
Although ZnCl2 gradually made its way into the Western pharmacopeia, the escharotic or cauterization method, employing other agents (minerals, salts, acids, and botanicals) had been well established for centuries. The utilization of arsenic as a cancer caustic, for example, dates back to classical antiquity; and, as an adjuvant to the knife, to the French physician and surgeon, Guy de Chauliac, in 1368 (Stone 628-629; Watters 730-734). A resurgent interest in escharotic medicine can be found in medical texts, published from 1822 to 1832, which contain annotated catalogues of organic and inorganic compounds, designed to treat dermatological diseases. Nathaniel Chapman’s, “Of Caustics and Escharotics,” in the 1822 edition of the Elements of Therapeutics and Materia Medica, for example, identifies the types and properties of caustic substances. He points out that caustics and escharotics (substances that either erode or dissolve animal tissue) differ from each other in terms of their intensity or degree of “excessive action.” Agents in this class destroy tissue on contact and produce sloughs. Furthermore, the activity of a caustic can be either actual or potential: the actual kinds, having a long history, destroy tissue on contact through intense heat (fire or heated iron, as Davy had noted in regard to Ceylonese surgery). Surgery and ligature, fortunately, superseded both forms of cauterization but did not eliminate the potential mode which gradually dissolves or coagulates diseased tissue chemically. Chapman enumerates 12 such agents commonly found in medicine cabinets for dermatological application. Among these were potash (for indolent epidermal ulcers), Alum (for venereal ulcers); white oxide of arsenic (as a cancer escharotic); and tar ointment (for fungal infections) (130-139). In John Murray, the Younger’s, 1832 Materia Medica, zincane had still not made its way onto the standard list of escharotics. Murray, like Chapman, enumerates a dozen agents, with the noteworthy addition of botanical extracts (Savine and Asian Moxa leaves) (Murray , 347-353).
As the British pharmacopeia of the early nineteenth century was developing, on the continent zincane entered the pharmacy without delay. European physicians, Papenguth in St. Peterburg, Häncke in Breslau, and Canquoin in Paris, had taken the lead, introducing the compound to medicine between 1812 and 1819 (Peirera , 280-281). During this period, the surgeon, J. F. Papenguth, of St. Petersburg, diluted a solution of ZnCl2, either for topical use or as an injectable, for the treatment of ulcers and sores. As a caustic, he considered it superior to longstanding arsenical preparations (Pereira : 279; : 820-821; Dunglison : 689-690). In an 1819 paper on the treatment of scrofulous fistulas, Papenguth recollects that, for 32 years, he had searched, unsuccessfully, for a way to treat tubercular lesions, until he learned of ZnCl2 (“Traitement,” 112). He prescribed it, initially, for a desperately ill, twenty-five-year-old man who had debilitating tuberculosis; his knee was swollen and infected; and his arms, ulcerated (112). Papenguth had to act as his own apothecary, customizing a supply of ZnCl2 for his patient. Following the instructions of Humphry and Davy, he dissolved a quantity of zinc in hydrochloric acid, mixed the compound with eight ounces of water, and then applied one half-ounce of the lotion to the patient’s ulcerous upper arm (113). This “bath,” as he called it, was repeated three to four times per day on the affected arm, while saturated compresses were placed on the knee. After three weeks, four of the ulcers developed scars, while the discharges of the others became odorless. Papenguth applied an even more concentrated solution. He realized that, since tuberculosis affected the entire constitution, which was true for his patient, topical treatment, though palliative, could not do much against the internal infection. He decided to administer the fluid internally, prescribing 10 drops of the solution in an ounce of peppermint water, morning and evening. Because the patient vomited, Papenguth halved the oral dosage. Over a period of two months, he reported that the patient was fully recovered. Presumably the skin and joint lesions healed, but there was no hard evidence that the oral dosage had any constitutional benefit. When a scrofulous skin lesion reappeared, Papenguth systematically managed it with the muriatic zinc in the space of eight days, and the young man is said to have recovered his health completely. On similar occasions, Papenguth claims to have followed the same routine, with prompt and “radical healing” achieved in each instance.
During this period, using a lotion and a powder, Dr. Johann W. Häncke, of Breslau, routinely treated syphilis, fungal infections, and phagedenic facial ulcers, possibly forms of skin cancer. By 1826, ZnCl2 powder was, indeed, being used against malignant disease. As reported in Hufeland’s Journal, it reduced tumors to eschars that eventually detached and fell off in eight days (cited by A. Ure in, “Refutation,” 544). In a seminal paper, Dr. Häncke maintains that clinical observations, recorded over some years, had demonstrated the chloride’s benefit as a caustic; and he found it to be preferable to other popularly-used compounds. These included corrosive sublimate, silver nitrate, red-oxide of mercury, and arsenic. Zinc chloride, in contrast, was most helpful and provided the greatest advantage in the treatment of indolent syphilitic ulcers, along with malignant and fungoid lesions.
Improvising the mode of ZnCl2 delivery, Häncke applied it as either a lotion or as a powder. In the latter form, it could be sprinkled on the surface of a lesion and would penetrate it to the desired depth. Once the area had been covered with powder, the operator then placed an adhesive plaster on it. The caustic would work in 6-8 hours to produce a white or grey scar having a tough, elastic consistency. The coagulated tissue, from the sixth to eighth day, would peel away from the surface, revealing a fresh scar; in some cases, to achieve a “perfect cure,” one had to repeat the procedure. From an empirical perspective, Häncke was convinced that the caustic was curative. He employed zinc-chloride solutions at varying concentrations in water, alcohol, ether, or as a pomade combined with fat.
Experimenting with ZnCl2 as an internal remedy, Dr. Häncke made the questionable assertion that, if taken internally in diluted form, it could offer improvement to those suffering from epilepsy, chorea, and facial neuralgia; however, the neurological benefits he claimed to have achieved were derived from anecdotal evidence. The most suitable mixture of active ingredients in solution included one grain of ZnCl2 and two of muriatic ether, yielding 5 drops in 15 minutes. The chloride-ether was mixed in “a little sugar water.” It appears that he had adjusted dosages according to a patient’s overt reactions, without considering the possibility of insidious side-effects. Experience had taught him that too strong an internal dosage could cause severe pain, stomach inflammation, nausea, vomiting, anxiety, difficulty breathing, a sinking feeling, rapid pulse, cold sweats, fainting, and convulsions. On the basis of these side-effects, he recommends that the greatest caution be taken in the internal use of this medicine and that one should always start with “a very small dose.” Zinc chloride’s toxicity had become dramatically apparent to Häncke, and accidental overdose would become a serious health problem in the decades that followed.
Between 1824 and 1838, Alexandre Canquoin (1785-1881), a Parisian physician, applied zincane to cancer patients as a caustic paste (Mémoire, 23). Of the 600 case-studies he published, he claimed to have had a 62% rate of “cure,” in contrast to the abysmal 10%-cure rate attributed to the surgical excision of tumors (MacGregor 374). The term “cure,” in this period, tended to be used ambiguously to signify the success of an initial procedure, as distinguished from a prognosis of non-recurrence.
Preparing the paste required skill, but it was neither a novel nor difficult task. Although a pioneer in chemical surgery, Canquoin was not the first to have administered an anticancer agent as a paste. One innovator was Dr. John Obadiah Justamond (1737-1786). An Anglo-French surgeon practicing in London, Justamond, had devised a dermal “soft plaster,” composed of arsenic, sulfur, antimony, and powdered opium in an egg-yolk base (ìOn the Treatment of Schirrous Tumours,” 377). Spreading the mixture on a pad, he applied it to the uneven tumor surface. He then scarified the eschar, filling the crevices with powdered compound. Applying a succession of fresh dressings, he was able to coagulate tumors in two months, and the dead tissue naturally separated from the body and fell off (377-79).
From 1824 to 1835, Canquoin recorded his treatment regimen and read his Mémoires before the French Academy of Medicine. The first, delivered on 24 November 1834, introduced his aims and methods. In the second one (1835), delivered before the same body, he tried to persuade his listeners that ZnCl2, though a powerful caustic, was neither dangerous nor difficult to use, and that its effects were predictable (Munro 410-414). The eschar it produced fell away in as little as 8-to-12 days. From 1829 to 1835, he claimed to have extirpated tumors successfully in the majority of cases treated (Mémoire , 2).
Canquoin provided detailed directions on how the regimen was made. The paste required careful preparation and systematic application, especially when treatment could not be combined with surgery. According to the 1838 monograph, after having tested 16 escharotic compounds beginning in 1824, he identified zinc chloride as the most effective, the safest, and the least painful regimen; it far surpassed arsenic in terms of overall effectiveness, and its risk of toxicity was low (Traitement du Cancer, 61-65, 75-80). The preparation, according to his experience, had numerous advantages over the 16 most common then in use: ZnCl2 had a long shelf-life; its effects did not extend beyond the area of application; the area and depth of its caustic activity could be calibrated; it was minimally painful; and, to a degree, it was hemostatic. The most important positive effect was that it rapidly enucleated tumors, reducing them to eschars. Causing no bleeding, the caustic left a clear area resembling what one would find after a successful excision and healing.
To improve the deliverability of the compound, Canquoin experimented with inert materials, such as sulfate of lime, resin, and farina. Farina became the base of choice because it allowed the zincane to adhere evenly to the tumor surface. The regimen could be applied in precise dosages, corresponding to the size and depth of the lesion; and the farina, a permeable matrix, allowed the ZnCl2, if correctly administered, to penetrate to pre-determined depths on a flat lesion: for example, from .122 to as much as 58.8 mm. (62). Canquoin developed four water-diluted strengths: No. 1, in weight the most concentrated, consisted of 1 part of ZnCl2 to 1 part of farina; the ratio of No. 2, a weaker mixture, was 1 part of ZnCl2 to 2 parts of farina; that of No. 3, an even weaker mixture, at 1 part ZnCl2 to 3 parts of farina. No. 4, a variant of No. 1, had been specially formulated to have a thick, waxy texture to cover the uneven surface of some tumors; it combined the potency of No. 1 (equal parts of ZnCl2 and farina) and the thickening property of stibnite, a metalloid, white crystalline element. The waxy consistency allowed Canquoin to distribute the paste thoroughly over an uneven, tumor surface (Traitement du Cancer, 64-65). The escharotic could be prepared to meet the needs of each patient, and the operator could dilute each formula, as needed, by simply adding 24-30 drops of water per ounce of ZnCl2. Canquoin’s chemist reduced the ZnCl2 to a powder with the exact measure of farina, to ensure that the prescription was correct. The particulate in the paste matrix was then ground down with a spatula to a fine, homogenized consistency. Using a roller, the chemist flattened the paste into layers of graduated thickness, ranging from .122 mm to 101.6 mm lines, that could be further diluted with water.
Canquoin concluded, on the basis of clinical examination and experiment, that of all the caustics then in use, chloride of zinc offered the greatest promise for the management and possible cure of these disorders. Skeptics, however, challenged Canquoin’s inflated cure rates. Without modern clinical trials and randomized studies, the value of Canquoin’s regimen could not be definitively assessed. However, Canquoin’s published findings, in 1835, alerted the British medical community that a new treatment for cancer might, at last, be available.
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Last modified 6 May 2021