The Pharmaceutical Journal Vol 265 No 7128 p933-934
December 23/30, 2000 Christmas miscellany

Alfred Barnes, Argyrol and art

Arthur Williams, FRPharmS

Arthur Williams, FRPharmS, relates the tale of how the successful exploitation of a single pharmaceutical product resulted in the assembly of one of the world’s finest art collections

Behind this rather mundane prescription (and many like it) written over 50 years ago in Manchester lies a truly remarkable story of the highly successful commercial exploitation of a single pharmaceutical product by a brilliantly successful and ruthless American physician and businessman, Dr Albert Coombs Barnes (1872-1951). His legacy is not pharmaceutical but is the finest collection in the world of impressionist and post-impressionist paintings (and other masterpieces) housed in the Barnes Foundation in Merion, west of Philadelphia, United States. Dr Barnes was able to fund his highly discerning appreciation of the arts by virtue of the great fortune he made on profits from the sale of Argyrol. Argyrol is a compound of silver and protein used as an antimicrobial agent. Although it is little used today, the product dominated the topical ophthalmic antimicrobial market for almost the whole first half of the 20th century.
To understand how the profits from one product could produce a vast fortune it is necessary to consider aspects of topical drug therapy in the pre-antibiotic era. Prior to the introduction of antibiotics and other sophisticated antimicrobial compounds, relatively simple inorganic and organic compounds were used to treat localised infections. (Options for the treatment of systemic infections were even more limited.) Compounds available for the treatment of localised infections included mercury compounds, silver salts, boric acid, flavines, chlorine-containing compounds and phenol solutions. These were often used in dilute aqueous solutions in a range of concentrations depending on the clinical circumstances. Many of these compounds were far too toxic and irritant for application to mucous membranes and the eye. Silver compounds (nitrate, acetate or lactate) were found to be suitable for application to the eye and mucous membranes. However, these compounds had significant local toxicity which limited their use. The interaction of the silver ion with body tissues and physiological secretions resulted in loss of activity, tissue damage and argyria — a permanent grey staining of the conjunctiva and/or skin due to prolonged exposure to silver compounds (usually the nitrate). As a result of these problems, concentrations of silver compounds used in topical solutions had to be low, usually 1/2,000–1/4,000. In an attempt to produce a compound with the antimicrobial activity of silver compounds without the associated toxicity, chemists developed a number of fairly complex organic compounds of silver. Squire’s companion to the 1916 British Pharmacopoeia describes a number of interesting compounds, some of which are briefly outlined in Table 1.

Table 1: Some organic compounds of silver described in Squires’ Companion to the BP (19th ed, 1916)
Product	Other names/notes/silver content
Albargin	Gelatose silver or silver glutin used as bowel wash. Silver content 15 per cent
Argentamin	Silver phosphate dissolved in ethylene-diamine solution. Contains silver corresponding to a 10 per cent solution of nitrate.
Argonin L	A compound of silver nitrate and casein-soda, which is more soluble than Argonin. Contains 10 per cent silver.
Argyrol	A compound of silver with a protein extracted from wheat. Wide range of indications especially in ophthalmic practice, although danger of argyria emphasised. Contains 30 per cent silver.
Collargol	A colloidal form of silver used as a solution and in an ointment, mainly for ophthalmic indications.
Ichthargan	Silver ichthyolate, mainly used in infections of the genitourinary tract. Contains 30 per cent silver.
Largin	Silver albuminate used in treatment of gonorrhoea. Contains 11 per cent silver.
Protargol	Silver protein, claimed to be more effective than Collargol and Argyrol when used to treat chronic inflammation of the conjunctiva. Contains 8 per cent silver.

The considerable range of silver compounds available gives some indication of the importance attracted to the need for a safe and effective silver compound. The story of the development of Argyrol is complex and involves the difficult personal relationships between Dr Barnes and a German scientist, Dr Hermann Hille. Following his graduation as MD and a period practising medicine, Barnes decided to develop his expertise as a chemist. Overcoming considerable financial difficulties Barnes went to Berlin in 1896 to further his studies. In 1898 he returned to the US and took an appointment with a pharmaceutical company (H. K. Mulford). The company supported Barnes in further studies in Heidelberg, where he met Dr Hille, a brilliant research chemist. Barnes returned to Philadelphia and was joined there by Hille in September, 1900. Hille became a colleague of Barnes at Mulfords and they worked together on a number of pharmaceutical projects in their spare time. Barnes was ambitious and was keen to develop a product that would be capable of rapid commercial exploitation. After a number of false starts Barnes came up with the idea of developing a safe and effective compound of silver for use as a topical antimicrobial agent. In 1902 a suitable compound (Argyrol) had been prepared and clinically tested. Claims for its effectiveness were supported by various specialists in major hospitals. Encouraged by the reception of Argyrol by surgeons and other specialists, the company of Barnes&Hille was formed in 1902. The company grew rapidly and Barnes showed himself to be an enlightened employer who was concerned about the well being of his employees. Hille provided the technical expertise and Barnes proved himself to be a superb salesman. Their success was rapid and profits reflected this. Sadly the partners did not achieve good personal relationships. Amid some acrimony the partnership was terminated and Barnes achieved sole control of the company, and the very considerable profits. Over the years disputes continued between the two men as to the true discoverer of Argyrol. The Barnes company flourished and Hille achieved success via his own Chicago-based company.
Just as in modern therapeutics one product often emerges from a range of similar compounds to dominate a market sector, the reasons for the dominance of Argyrol are of considerable interest since they help to gain an insight into the character and personal qualities of Dr Barnes. Some idea of the widespread use of Argyrol in the United Kingdom can be obtained by an examination of formularies, pharmacopoeias and prescribing records (See Table 2).

An examination of some promotional literature produced by the company of Barnes&Hille (1902) shows that no fewer than 37 eminent specialists (from several countries) endorsed the valuable properties of Argyrol. Professors of surgery, pharmacology, clinical chemistry, genitourinary medicine, otorhinolaryngology and ophthalmology, together with other specialists in similar fields, expressed their positive views on the efficacy and safety of Argyrol. The contemporary promotional material examined emphasises the clinical value of Argyrol by particular reference to the amount of silver it contains, the high degree of solubility, stability in solution and lack of interaction with body tissues and fluids. Lack of local toxicity was also seen as a major advantage. A heavy emphasis was placed on the versatility of the product coupled with an effective bactericidal action on a large range of organisms commonly associated with infections of the eye and genitourinary tract. Comparisons (favourable to Argyrol) were made in the promotional literature with other organic compounds of silver available at that time (see Table 1). Argyrol was even recommended for internal administration for its anti- inflammatory effects in "ulcerative enteritis". Suppositories containing 10–25 per cent Argyrol were advocated for a range of local rectal conditions. To reduce handling costs, the product was originally supplied only in one-ounce bottles at $1.50. Samples were not supplied under any circumstances. Pharmaceutical company executives of today can only dream about making such a success of a single, unformulated product. Although the name Argyrol was protected in law the process for making Argyrol was not patented. Sales of Argyrol in 1904 were worth $100,000; by 1907 annual sales reached $250,000 producing a profit of $186,188. Barnes was a millionaire in 1907 at the age of 35.

Barnes and the Barnes Foundation

Since he had amassed a considerable fortune in a fairly short time, and because by 1910 his successful company no longer absorbed all his energies, Barnes decided to develop his early interest in art. Realistic as ever, Barnes knew he could never succeed as a painter and decided to become a collector. With the generous help of a former classmate (a well known art expert W. J. Glackens) Barnes rapidly gained knowledge and expertise. The work of the modern impressionists and post-impressionists was not widely appreciated at this time, collectors perhaps preferring "safer"works. With the continuing help of Glackens, Barnes began to build his art collection. Using his scientific training he painstakingly assessed paintings and came to understand the true genius of painters such as Renoir and Cézanne. As his knowledge and contacts grew Barnes travelled widely in Europe acquiring important paintings. His collection grew at an amazing pace. By 1923 he owned 50 Cézannes. Aided by his business acumen he found out how to source the work of artists he admired. The amazing story of Barnes’s collecting powers has been well described by Greenfield,¹ who also gives an account of Barnes’s passion for education through his foundation. Despite these enthusiasms, Barnes was protective of his art collection, allowing only restricted access even to recognised scholars of the day.
Today access to the Barnes Foundation is still restricted. But the foundation does give the public the opportunity to see a unique collection of paintings including 175 Renoirs, 65 Matisses, 66 Cézannes and many other masterpieces together with a range of domestic artefacts still arranged in the idiosyncratic manner decided by Dr Barnes. Although he was a controversial figure in many ways, Dr Barnes’s legacy of art is unrivalled even though the basis of its foundation, Argyrol is now largely forgotten. ACKNOWLEDGMENT Special thanks are due to Mrs Alison McLeod for preparing the manuscript