A History of the Use of Arsenicals in Man

The arsenicals (compounds which contain the heavy metal element arsenic, As) have a long history of use in man – with both benevolent and  malevolent intent. The name ‘arsenic’ is derived from the Greek word ‘arsenikon’ which means ‘potent'”. As early as 2000 BC, arsenic trioxide, obtained from smelting copper, was used as a drug and as a poison 2.

Hippocrates (460 to 377 BC) used orpiment (As2S3) and realgar (As2S2) as escharotics. Aristotle (384 to 322 BC) and Pliny the Elder (23 to 79 AD) also wrote about the medicinal properties of the arsenicals. Galen (130 to 200 AD) recommended a paste of arsenic sulphide for the treatment of ulcers. Paracelsus (1493 to 1541) used elemental arsenic extensively. He is quoted as saying ‘All substances are poisons … The right dose differentiates a poison and a remedy’ – an apt statement for the arsenicals 3.

In the eighteenth century, Fowler’s solution (1% potassium arsenite) was used for the relief of various ailments and remained very popular for over 150 years.  In the nineteenth century arsenicals were ingested, inhaled as vapours, injected intramuscularly and intravenously, and given in enemas. They caused cutaneous capillary dilatation – the fashionable ‘milk and roses’ complexion. Arsenicals were used to treat acne caused by iodides and bromides, and were later added to bromide containing mixtures to prevent bromide eruptions 4. By the early 1900s, physicians were using arsenicals
to treat pellagra and malaria. In 1912 arsenic was recognized as the best agent in the Pharmacopoeia’. At about the same time Ehrlich’s experiments yielded arsphenamine, and arsenicals remained the mainstay of treatment for syphilis for nearly 40 years until the advent of penicillin.

Arsenicals were also popular in treating vaginal discharge of any origin. They were supplied as vaginal inserts or powder for insufflation, and were apparently effective against trichomonas5. However, they were superseded by metronidazole – the first clinical reports of its efficacy appearing in 1959.

Today arsenicals are still used in the treatment of sleeping sickness. Some Indian women take arsenic containing medicines during the first trimester of pregnancy, believing that this increases their chance of having a son 4. In humans no nutritional role is known for arsenic, although it has a function in animal husbandry – organic arsenicals are added to animal feed to control disease and promote growth 4. However, small doses of inorganic arsenicals have long been felt to have a ‘tonic’ or ‘alternative’ property. Large quantities of arsenical ores were consumed by the ‘arsenic eaters’ of the Austrian mountains in the belief that they improved their stamina, appearance and sense of wellbeing. This may be just folklore, but it has been suggested that arsenic may be an unrecognized essential nutrient, in which Western diets are deficient’.

Chemistry

Arsenic (atomic number 33, atomic weight 75) is a member of the nitrogen group in the periodic table. It is classified as a transitional element or metalloid. Arsenic can exist in three different valency states: elemental arsenic (zero oxidation state); trivalent; or pentavalent arsenic. It forms alloys with metals and also readily reacts with carbon, oxygen and hydrogen, forming covalent bonds. The chemistry of arsenic is further mystified by the practice of often not specifying in published work the chemical nature of the arsenic-containing compound, but just referring to it as ‘arsenic’.

The toxicity of an arsenical varies with the valency state (trivalent are more toxic than pentavalent compounds), the physical state of the compound, and the rates of absorption and elimination. Elemental arsenic (the metalloid) is non-toxic even if eaten in substantial amounts 4. Of the inorganic compounds, those containing pentavalent arsenic (derivatives of arsenic acid, H3AsO4, the arsenates) are much less toxic than those containing trivalent arsenic. Inorganic compounds of trivalent arsenic are derivatives of arsenious acid, H2As203 (the arsenites) and include arsenic trioxide (As203, ‘the poison of poisons’). Arsine (AsH3, a gaseous hydride of arsenic trioxide) is the most toxic of all the arsenicals. Its toxic effects are distinct
because it is inhaled, rather than absorbed through the skin or gastrointestinal tract. Organic arsenicals contain arsenic (either trivalent or pentavalent) linked to a carbon atom by a covalent bond. In general, they are excreted more rapidly than inorganic compounds6. The most important trivalent organic arsenicals are the arsphenamines, which were used in the treatment of syphilis. Pentavalent organic compounds were used in the treatment of sleeping sickness.

Arsenic trioxide: This inorganic compound of trivalent arsenic has been used extensively as a remedy and as a poison. In 1786 Thomas Fowler, an English physician, reported the use of a flavoured solution of arsenic trioxide in the cure of agues, remittent fevers, and periodic headaches. Fowler, with Hughes (an apothecary) had identified arsenic as the major constituent of the ‘ague drops’ patented by Thomas Wilson, a London chemist, in 1781 7. 288 Journal of the Royal Society of Medicine Volume 86 May 1993

Fowler’s solution (1% potassium arsenite, K AsO2) was used as a tonic for anaemia and rheumatism. It was used to treat psoriasis, eczematous eruptions, dermatitis herpetiformis, asthma, cholera and syphilis. In 1865, Fowler’s solution was the first chemotherapeutic agent used in the treatment of leukaemia (which was first described in 1845). It was chosen as it was known to produce smoother coats and improve digestion in horses! In human leukaemics it produced a transient improvement. In 1931 Forkner and Scott, at Boston City Hospital, ‘rediscovered’ Fowler’s solution for the treatment of chronic myeloid leukaemia, and arsenicals and irradiation remained the treatment of choice until busulphan was introduced in 1953 7.

Arsenic trioxide has an even longer history of use with malevolent intent. Its popularity as a poison was probably due to its availability, inexpensiveness, and lack of taste and odour. It has the appearance of sugar (it is also known as ‘white arsenic’) and does not destroy the appetite. It is the most toxic arsenical after arsine, but does not produce instantaneous death. In Arsenic and old lace, John Kesselring’s 1941 play, half a teaspoonful of strychnine and a pinch of cyanide were also added to the teaspoonful of ‘arsenic’ in a gallon of elderberry wine; the concoction which the old ladies used rapidly to dispatch their gentlemen callers.

One of the earliest documented cases of homicide caused by an arsenical occurred in 55 AD, when Nero poisoned Britannicus to secure his Roman throne.

The Borgias used arsenicals. In the Middle Ages the poisoner became a part of social and political life. White arsenic acquired a reputation, it was called ‘poudre de succession’ or ‘inheritance powder’. It was the favourite poison in nineteenth century France (phosphorus was the second most popular). However, its use rapidly declined towards the end of the century. This coincided with the development of a highly sensitive assay for arsenic 3. It continues to be used for suicidal purposes 8.

Organic arsenicals

In the early 1900s physicians began using the less toxic organic arsenicals3. About 32 000 organic arsenic-containing compounds have been made – more than any other trace element 1. Sodium cacodylate and sodium arsanilate were used for the treatment of pellagra, malaria and sleeping sickness.
Breinl and Thomas at the Liverpool School of Tropical Medicine had produced atoxyl (a pentavalent compound) which was used to treat sleeping sickness. However, its high arsenic content produced optic atrophy. This work inspired Paul Ehrlich. He instructed his workers to study the organic arsenicals to find ‘the silver bullet’ against the syphilis spirochaete (which was first identified in 1905) 9. The therapeutic problem was how to obtain maximum effect on the parasite with minimal effect on the body’s tissues. In 1907, the 606th preparation of an arsenobenzene compound (containing 32% arsenic) was synthesized. Its potential was overlooked for two years but later work, using syphilitic rabbits, convinced Ehrlich that arsphenamine was ‘the silver bullet’. It was first used to treat human syphilis in 1911. Hoechst eventually gained approval to market Salvarsan (also called ‘healing arsenic’ or ‘606’) and 65 000 free samples were sent to doctors all over the world. Arsphenamine was enthusiastically received by the international scientific periodicals, and was the subject of banner headlines in the newspapers. Ehrlich warned that the drug might be harmful, because of its potency, and urged caution with intravenous administration. The treatment of syphilis with arsenicals was a lengthy and unpleasant business: ‘two minutes with Venus, 2 years with mercury’ (aphorism, J Earle Moore). Arsphenamine was given by intravenous infusion, each treatment lasting an hour. Courses of arsenical treatments would be alternated with mercury rubs (which stained the patient’s underclothes and had a characteristic odour) or intramuscular mercuric succinamide. Later, 6-8 week courses of intravenous arsenical were alternated with 6-8 weeks of intramuscular bismuth. The minimum duration of treatment exceeded 18 months; 20 injections of arsphenamine and 30 to 40 injections of bismuth 10. The development of neoarsphenamine (Neosalvarsan or ‘909’), a less toxic derivative of arsphenamine which could be injected intravenously, enabled more rapid treatments, but was still associated with nausea and vomiting. Oxophenarsine hydrochloride (Mapharsen) could be injected rapidly and produced fewer reactions. In children sulpharsphenamine was given intramuscularly. It also produced nausea and vomiting, and occasionally a ‘nitratoid reaction’ – sweating, diarrhoea, hypotension and collapse. Silver arsphenamine was used for the treatment of central nervous system syphilis – a small amount being introduced into the cerebrospinal fluid via lumbar puncture. This was a very painful treatment which, in rare cases, caused serious spinal cord damage. Benefit may have resulted from the production of an aseptic meningitis or by altering the permeability of the blood brain barrier to intravenously administered drugs. In patients treated early, and those conscientious enough to complete the full course of treatment, arsenicals produced at least as good a cure rate as modern day syphilis therapy 10. They were used widely in Europe until the late 1940s and even later
in the Far East, where they were also used to treat yaws. Penicillin was first advocated as a treatment for syphilis in 1943 but was not generally available for several years. It had the great advantage that it could be given over a short period of time when the patient was most apprehensive and anxious for a cure. Today arsenicals are still used in man, in the treatment of African trypanosomiasis. This causes sleeping sickness which is always fatal without treatment. The original arsenical used was tryparsamide (containing 25% pentavalent arsenic in organic combination). This was associated with a high incidence of toxic reactions and could cause blindness. As the parasites’ resistance to it was increasing, it has been replaced by two other organic arsenicals – melarsoprol (Mel B), containing 18.8% trivalent arsenic, and melarsonyl (Mel-W). Both are given by intravenous injection and are toxic drugs. They may cause a potentially life threatening reactive arsenical encephalopathy.

Conclusion

Throughout history arsenicals have been useful therapeutic agents for many of man’s ailments. Most have been superseded by less toxic drugs. Perhaps, in the future, there will be a substance amongst the many arsenic-containing compounds that will prove to be Journal of the Royal Society of Medicine Volume 86 May 1993 289 useful in treating some of the many lethal diseases of today.

References
1 Frost DV. The arsenic problems. Adv Exp Med Biol
1977;91:259-79
2 Frost DV. Arsenicals in biology – retrospect and prospect.
Fed Proc 1967;26:194-208
3 Gorby MS. Arsenic poisoning (clinical conference). West
J Med 1988;149:308-15
4 Winship KA. Toxicity of inorganic arsenic salts. Adverse
Drug React Acute Poisoning Rev 1984;3(3): 129-60
5 Forgan R. History of the treatment of trichomoniasis. Br
J Vener Dis 1972;48(6):522-4
6 Klaasen CD. Heavy metals and heavy-metal antagonists. In: Goodman LS, Gilman A, Rall TW, Murad F,
eds. The pharmacological basis oftherapeutics, 7th edn.
New York: Macmillan, 1985:1614-17
7 Sears DA. History of the treatment of chronic myelocytic
leukaemia. Am J Med Sci 1988;296(2):85-6
8 Jolliffe DM, Budd AJ, Gwilt DJ. Massive acute arsenic
poisoning. Anaesthesia 1991;46:288-90
9 Thorburn AL. Paul Ehrlich: pioneer of chemotherapy
and cure by arsenic (1854-1915). Br J Vener Dis
1983;59(6):404-5
10 Marlow FW Jr. Syphilis then and now. JAMA 1974;
230(9):1320-1

https://pubmed.ncbi.nlm.nih.gov/8505753/

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The Effect of Magnetic Fields on Wound Healing

The Effect of Magnetic Fields on Wound Healing Experimental Study and Review of the Literature

Steven L. Henry, MD, Matthew J. Concannon, MD, and Gloria J. Yee, MD Division of Plastic Surgery, University of Missouri Hospital & Clinics, Columbia, MO Published July 25, 2008

Objective: Magnets [...] Read more →

Pickled Eels

Vintage woodcut illustration of a Eel

 

This dish is a favorite in Northern Europe, from the British Isles to Sweden.

Clean and skin the eels and cut them into pieces about 3/4-inch thick. Wash and drain the pieces, then dredge in fine salt and allow to stand from 30 [...] Read more →

The Fowling Piece – Part I

THE FOWLING PIECE, from the Shooter’s Guide by B. Thomas – 1811.

I AM perfectly aware that a large volume might be written on this subject; but, as my intention is to give only such information and instruction as is necessary for the sportsman, I shall forbear introducing any extraneous [...] Read more →

Fly Casting Instructions

It is a pity that the traditions and literature in praise of fly fishing have unconsciously hampered instead of expanded this graceful, effective sport. Many a sportsman has been anxious to share its joys, but appalled by the rapture of expression in describing its countless thrills and niceties he has been literally [...] Read more →

King Arthur Legends, Myths, and Maidens

King Arthur, Legends, Myths & Maidens is a massive book of Arthurian legends. This limited edition paperback was just released on Barnes and Noble at a price of $139.00. Although is may seem a bit on the high side, it may prove to be well worth its price as there are only [...] Read more →

Art Fraud

A la Russie, aux ânes et aux autres – by Chagall – 1911

Marc Chagall is one of the most forged artists on the planet. Mark Rothko fakes also abound. According to available news reports, the art market is littered with forgeries of their work. Some are even thought to be [...] Read more →

Vitruvius Ten Books on Architecture

VITRUVIUS

The Ten Books on Architecture

TRANSLATED By MORRIS HICKY MORGAN, PH.D., LL.D. LATE PROFESSOR OF CLASSICAL PHILOLOGY

IN HARVARD UNIVERSITY WITH ILLUSTRATIONS AND ORIGINAL DESINGS PREPARED UNDER THE DIRECTION OF HERBERT LANGFORD WARREN, A.M.

NELSON ROBINSON JR. PROFESSOR OF ARCHITECTURE IN HARVARD [...] Read more →

Beef Jerky

BEEF JERKY

Preparation.

Slice 5 pounds lean beef (flank steak or similar cut) into strips 1/8 to 1/4 inch thick, 1 to 2 inches wide, and 4 to 12 inches long. Cut with grain of meat; remove the fat. Lay out in a single layer on a smooth clean surface (use [...] Read more →

Snipe Shooting

Snipe shooting-Epistle on snipe shooting, from Ned Copper Cap, Esq., to George Trigger-George Trigger’s reply to Ned Copper Cap-Black partridge.

——

“Si sine amore jocisque Nil est jucundum, vivas in &more jooisque.” -Horace. “If nothing appears to you delightful without love and sports, then live in sporta and [...] Read more →

Chinese 9 Course Dinner

The following recipes form the most popular items in a nine-course dinner program:

BIRD’S NEST SOUP

Soak one pound bird’s nest in cold water overnight. Drain the cold water and cook in boiling water. Drain again. Do this twice. Clean the bird’s nest. Be sure [...] Read more →

Origin of the Apothecary

ORIGIN OF THE APOTHECARY.

The origin of the apothecary in England dates much further back than one would suppose from what your correspondent, “A Barrister-at-Law,” says about it. It is true he speaks only of apothecaries as a distinct branch of the medical profession, but long before Henry VIII’s time [...] Read more →

The Character of a Happy Life

How happy is he born and taught. That serveth not another’s will; Whose armour is his honest thought, And simple truth his utmost skill

Whose passions not his masters are; Whose soul is still prepared for death, Untied unto the world by care Of public fame or private breath;

Who envies none that chance [...] Read more →

Cleaner for Gilt Picture Frames

Cleaner for Gilt Frames.

Calcium hypochlorite…………..7 oz. Sodium bicarbonate……………7 oz. Sodium chloride………………. 2 oz. Distilled water…………………12 oz.

 

Home Top of Pg. Read more →

Palermo Wine

Take to every quart of water one pound of Malaga raisins, rub and cut the raisins small, and put them to the water, and let them stand ten days, stirring once or twice a day. You may boil the water an hour before you put it to the raisins, and let it [...] Read more →

Ought King Leopold to be Hanged?

King Leopold Butcher of the Congo

For the somewhat startling suggestion in the heading of this interview, the missionary interviewed is in no way responsible. The credit of it, or, if you like, the discredit, belongs entirely to the editor of the Review, who, without dogmatism, wishes to pose the question as [...] Read more →

The Kalmar War

Wojna Kalmarska – 1611

The Kalmar War

From The Historian’s History of the World (In 25 Volumes) by Henry Smith William L.L.D. – Vol. XVI.(Scandinavia) Pg. 308-310

The northern part of the Scandinavian peninsula, as already noticed, had been peopled from the remotest times by nomadic tribes called Finns or Cwenas by [...] Read more →

Of Decorated Furniture

DECORATED or “sumptuous” furniture is not merely furniture that is expensive to buy, but that which has been elaborated with much thought, knowledge, and skill. Such furniture cannot be cheap, certainly, but the real cost of it is sometimes borne by the artist who produces rather than by the man who may [...] Read more →

Indian Mode of Hunting – Beaver

Jul. 30, 1898 Forest and Stream Pg. 87

Indian Mode of Hunting.

I.—Beaver.

Wa-sa-Kejic came over to the post early one October, and said his boy had cut his foot, and that he had no one to steer his canoe on a proposed beaver hunt. Now [...] Read more →

The English Tradition of Woodworking

THE sense of a consecutive tradition has so completely faded out of English art that it has become difficult to realise the meaning of tradition, or the possibility of its ever again reviving; and this state of things is not improved by the fact that it is due to uncertainty of purpose, [...] Read more →

Historic authenticity of the Spanish SAN FELIPE of 1690

San Felipe Model

Reprinted from FineModelShips.com with the kind permission of Dr. Michael Czytko

The SAN FELIPE is one of the most favoured ships among the ship model builders. The model is elegant, very beautifully designed, and makes a decorative piece of art to be displayed at home or in the [...] Read more →

The Hoochie Coochie Hex

From Dr. Marvel’s 1929 book entitled Hoodoo for the Common Man, we find his infamous Hoochie Coochie Hex.

What follows is a verbatim transcription of the text:

The Hoochie Coochie Hex should not be used in conjunction with any other Hexes. This can lead to [...] Read more →

Catholic Religious Orders

Saint Francis of Assisi, founder of the mendicant Order of Friars Minor, as painted by El Greco.

Catholic religious order

Catholic religious orders are one of two types of religious institutes (‘Religious Institutes’, cf. canons 573–746), the major form of consecrated life in the Roman Catholic Church. They are organizations of laity [...] Read more →

Horn Measurement

Jul. 23, 1898 Forest and Stream, Pg. 65

Horn Measurements.

Editor Forest and Stream: “Record head.” How shamefully this term is being abused, especially in the past three years; or since the giant moose from Alaska made his appearance in public and placed all former records (so far as [...] Read more →

Cup of Tea? To be or not to be

Twinings London – photo by Elisa.rolle

Is the tea in your cup genuine?

The fact is, had one been living in the early 19th Century, one might occasionally encounter a counterfeit cup of tea. Food adulterations to include added poisonings and suspect substitutions were a common problem in Europe at [...] Read more →

Country House Christmas Pudding

Country House Christmas Pudding

Ingredients

1 cup Christian Bros Brandy ½ cup Myer’s Dark Rum ½ cup Jim Beam Whiskey 1 cup currants 1 cup sultana raisins 1 cup pitted prunes finely chopped 1 med. apple peeled and grated ½ cup chopped dried apricots ½ cup candied orange peel finely chopped 1 ¼ cup [...] Read more →

Glimpses from the Chase

From Fores’s Sporting Notes and Sketches, A Quarterly Magazine Descriptive of British, Indian, Colonial, and Foreign Sport with Thirty Two Full Page Illustrations Volume 10 1893, London; Mssrs. Fores Piccadilly W. 1893, All Rights Reserved.

GLIMPSES OF THE CHASE, Ireland a Hundred Years Ago. By ‘Triviator.’

FOX-HUNTING has, like Racing, [...] Read more →

The Apparatus of the Stock Market

Sucker

The components of any given market place include both physical structures set up to accommodate trading, and participants to include buyers, sellers, brokers, agents, barkers, pushers, auctioneers, agencies, and propaganda outlets, and banking or transaction exchange facilities.

Markets are generally set up by sellers as it is in their [...] Read more →

Tuna and Tarpon

July, 16, l898 Forest and Stream Pg. 48

Tuna and Tarpon.

New York, July 1.—Editor Forest and Stream: If any angler still denies the justice of my claim, as made in my article in your issue of July 2, that “the tuna is the grandest game [...] Read more →

Carpenters’ Furniture

IT requires a far search to gather up examples of furniture really representative in this kind, and thus to gain a point of view for a prospect into the more ideal where furniture no longer is bought to look expensively useless in a boudoir, but serves everyday and commonplace need, such as [...] Read more →