Charles Hilton Fagge 2026-10-31
English physician who investigated physiological tests for digitalin. External portrait catalogue: Wellcome Collection, photograph reference 15134i.
The principal period groups were digitalis preparations, squill, broom, juniper oil, buchu, nitrous ether spirit, and several soluble potassium salts. They were grouped by observed promotion of urine flow, rather than by one common mechanism. The following are historical adult quantities per administration, expressed in the contemporary units; they are not present-day prescriptions.
- Digitalis preparations: powdered leaves, ½–2 grains; Infusum Digitalis, 2–4 fluid drachms; Tinctura Digitalis, 5–40 minims; digitalin, 1/40–1/10 grain in the period table. Historical digitalin was not simply a modern pure digoxin product.
- Squill: powder, 1–2 grains; Pilula Scillae Composita, 5–10 grains; Tinctura Scillae, 10–20 minims; Syrupus Scillae, ½–1½ fluid drachms.
- Broom: Decoctum Scoparii, 1–3 fluid ounces; Succus Scoparii, 1–4 fluid drachms.
- Buchu: powdered leaves, 20–40 grains; Infusum Bucco, 1–2 fluid ounces; Tinctura Bucco, 1–2 fluid drachms.
- Juniper oil: Spiritus Juniperi, 10–30 minims in the 1864 commentary. This unusually concentrated spirit contains one volume of juniper oil in ten; its dose must not be borrowed from a later, weaker formula.
- Nitrous ether spirit, Spiritus Aetheris Nitrosi: 30 minims to 2 fluid drachms.
- Potassium acetate: 10–20 grains; potassium citrate: 20–60 grains; potassium nitrate: 5–20 grains; potassium tartrate: 10–60 grains; potassium hydrogen tartrate: 20–60 grains.
- Ammonium acetate solution, Liquor Ammoniae Acetatis: 10–40 minims of the concentrated British preparation, diluted for administration.
[ref]
The Essentials of Materia Medica and Therapeutics by Alfred Baring Garrod (1865). Posological table: Digitalis, Infusum Digitalis, Scoparius preparations, Bucco preparations, Spiritus Aetheris Nitrosi, potassium salts and Liquor Ammoniae Acetatis; Liliaceae: squill preparations
[ref]The Prescriber's Analysis of the British Pharmacopoeia by John Birkbeck Nevins (1864). p. 61, Spiritus Juniperi, 1 in 10 and 10–30 minims
Other recognised period agents included dandelion and copaiba. The dandelion decoction was given in quantities of 1–2 fluid ounces, its soft extract in quantities of 10–30 grains, and its preserved juice in quantities of ½–2 fluid drachms. Copaiba was given in quantities of 15–30 minims, and copaiba oil in quantities of 5–20 minims. Their historical inclusion does not establish that they are suitable substitutes for current diuretic therapy. [ref]
The Essentials of Materia Medica and Therapeutics by Alfred Baring Garrod (1865). Posological table, Taraxacum preparations, Copaiba and Copaibae Oleum
The distinction between preparations matters more than a single “dose of the plant”: an infusion, tincture, juice and powder have different concentrations. Likewise, a salt's small historical diuretic dose is not its larger purgative dose. A modern explanation also separates a direct effect on renal tubules from improved cardiac output in appropriate heart failure: digitalis preparations cannot be understood simply as agents that make every kidney excrete more water. Modern digoxin is used for selected cardiac indications, rather than as a general treatment for low urine output. [ref]
Digoxin by MedlinePlus. Why is this medication prescribed?
Retain the original material, examine separate portions for arsenic and digitalin, and require corroboration beyond a single colour or deposit. One is an inorganic element; the other is a historical pharmaceutical preparation of organic cardiac poisons. A procedure suited to one can destroy or lose the other.
Record the receipt, container, quantity and condition of the stomach contents. Preserve a sealed portion unchanged. Mix the remainder sufficiently to obtain representative aliquots, retaining solid particles as well as liquid. Record the portions consumed by each test and retain the resulting preparations. Test the reagents separately and include an unpoisoned comparison material where available. An analyst must distinguish poison originally present from contamination introduced by apparatus, acids or metals.
For arsenic detection, a useful period screen is deposition on clean copper warmed in an acidified portion of the material. A dark coating is only presumptive: other substances, including antimony, can interfere. Wash and dry the coated copper, then heat it in a small glass tube, examining the cooler portion for a sublimate of arsenic trioxide and its characteristic crystals under a microscope. A separately prepared clear extract allows corroborating reactions, such as the yellow arsenic trisulfide precipitate and the appropriate silver reaction. An 1844 primary account already stressed both reagent purity and the danger of confusing arsenic with other metals.[ref]
On Arsenic as a Poison; Its Tests and Antidote by E. J. Shearman. 1844, pp.3–4: reagent controls, copper deposition, sublimation and confirmatory tests; the author's speculative reaction mechanism is not adopted here
A second classical approach converts the suspected arsenic into volatile arsine in a hydrogen-generating apparatus and decomposes it in a heated glass tube, producing a metallic mirror. This separates a volatile product from much of the original organic material. A mirror alone is insufficient, since antimony can give a similar deposit; establish the deposit's identity by further chemistry. The initial blank must include the very zinc and acid used in the examination. The apparatus produces extremely poisonous gas: this is an explanation of historical laboratory evidence, not a procedure for an uncontained demonstration. The original method of James Marsh explains the value of separating the poison in gaseous form; later confirmation must still distinguish arsenic from interfering material.[ref]
Separation of Arsenic by James Marsh. Opening pages and apparatus description: hydrogen-based separation from animal and vegetable material
For digitalin, work on a fresh aliquot without mineralizing it. Use an alcoholic extraction, filter away coarse material, concentrate gently, and retain rather than discard fractions until their behaviour has been checked against a reference preparation. “Digitalin” did not denote one uniform pure compound: a contemporary 1864 report distinguished preparations with markedly different solubilities. Accordingly, a negative result after one solvent partition is inconclusive; it would be particularly misleading to assume that the substance must follow the acid–base extraction behaviour of a simple alkaloid.[ref]
Chemical News volume 10 (1864). 27 August, pp.99–100, “On Digitaline”: different pharmaceutical preparations and solubilities
Colour reactions could support the examination of a cleaned extract. Contemporary work described a brown or reddish colour with sulfuric acid, changed to violet by bromine vapour; the hydrochloric-acid green colour was already acknowledged to lack specificity. Compare a reference and a blank under the same conditions. Colour in a dirty stomach extract is not an identification, and tasting an unknown extract is not an acceptable analytical test.[ref]
Chemical News volume 10 (1864). “On Digitaline”, report of the sulfuric-acid and bromine reaction and the limitations of the hydrochloric-acid colour
A particularly relevant development available before this examination was the physiological test investigated by Charles Hilton Fagge and Thomas Stevenson in 1865. An extracted fraction was compared with known digitalin using the response of a frog's heart. The informative effect was irregular beating followed by arrest with the cardiac ventricle pale and firmly contracted, rather than mere illness or death. Crucially, their experiments also showed that ordinary human stomach contents could injure frogs, and other cardiac poisons could resemble digitalin. A solvent blank, a comparable unpoisoned extract and a reference poison therefore matter. These are historical experiments, not a proposal to repeat animal testing for this solution.[ref]
On the Application of Physiological Tests for Certain Organic Poisons, and Especially Digitaline by Charles Hilton Fagge and Thomas Stevenson. Royal Society archive AP/47/2, 1865: experiments with reference solutions and extracts
[ref]On Tests for Aconite and Digitaline in The British and Foreign Medico-Chirurgical Review (1866). pp.454–455: contracted pale ventricle, related cardiac poisons, and toxicity of ordinary gastric contents
The defensible conclusion combines extraction behaviour, chemical reactions, physiological specificity and the clinical circumstances, acknowledging uncertainty if these disagree. A modern laboratory would instead seek specific validated instrumental identification, for example chromatography coupled to mass spectrometry for an identified cardiac glycoside, with reference material and controls. That later capability must not be credited to an 1866 examiner.[ref]
Standard for Identification Criteria in Forensic Toxicology. Identification criteria: reliability requires appropriate analytical characteristics rather than one nonspecific response
Thomas Stevenson 2026-10-31
A physician and toxicologist who investigated physiological tests for digitalin. External portrait: National Portrait Gallery, portrait NPG D44989.