Silver FactsAn Indepth History of Silver: Historic Perspectives on Clinical Use and
Efficacy of Silver
by Eric J. Rentz, DO, MSc
Prior Civilizations
Since ancient times silver has been highly regarded
as a versatile healing tool. In ancient Greece, Rome, Phoenicia, and Macedonia,
silver was used extensively to control infections and spoilage. Hippocrates, the
“Father of Medicine,” taught that silver healed wounds and controlled disease.
Around 400 B.C. he listed as a singular treatment for ulcers “the flowers of
silver alone, in the finest powder.” Herodotus describes how the King of Persia
carried with him boiled water in silver flagons to prevent sickness. In 69 B.C.,
silver nitrate was described in the contemporary pharmacopoeia.
The popularity of medicinal silver especially arose
throughout the Middle East from 702 A.D. through 980 A.D. where it was widely
used and esteemed for blood purification, heart conditions, and used to control
halitosis.
Paracelsus (circa 1520) extensively used silver
medicinally, and later Caradanus, Pareus, and Sala also used it. For example,
Angelus Sala used silver nitrate to successfully treat chorea, tabes dorsalis
(syphilis), and, it is doubtable, epilepsy. These crude and inferior forms of
silver were reported by Sala to rarely cause the bluish-hue skin discoloration (argyria)
due to overuse. It is widely thought that during the Middle Ages silver utensils
and goblets contributed a bluish-hue to the skin-tone of the upper class,
resulting in the term “blue-bloods.” Plausibly, “born with a silver spoon in his
mouth” was coined during that time for the same reason, as an attribute for
describing the good fortune of being healthy more than being wealthy.
Blue-bloods were noted to have been afforded a measure of protection from the
rampant plagues common to Europe in those centuries.
During the wars with Napoleon, the armies of Tsar
Alexander used water casks lined with silver to clean drinking water from rivers
and streams. This practice by the Imperial Russian army was continued through
World War I and by some units in the Soviet Army in World War II.
Raulin recorded the first description of the water
cleansing effect by silver in 1869. He observed that Aspergillus niger
could not grow in silver vessels.
Modern Research using the Scientific Method
In 1861, Thomas Graham found that certain solutions
would pass through a membrane and others would not. He found a stable,
intermediate state of matter, and was able to describe it. Graham’s discovery
was that substances could enter a solution in such a manner that they exhibit
characteristics that are quite different from those of a true solution. He
applied the term “colloidal” (from kolla = glue) to this intermediate
state, as glue, gelatin, and related substances were the most obvious to him as
being in this unique state.
The Swiss botanist von Nageli recorded one of the
amazing discoveries of the nineteenth century in 1869. Von Nageli coined the
term “oligodynamic” to describe the microbiocidal properties of a metal hydrosol
(e.g. copper, silver and tin) at minute concentrations. , In 1884, Crede
introduced the use of 1% silver nitrate for the prevention of ophthalmia
neonatorum. By 1897, silver nitrate began to be used in America to prevent
blindness in newborns and is still used today. , By 1910, Henry Crookes had
documented that certain metals, when in a colloidal state, had strong germicidal
action, but were harmless to human beings. The oligodynamic concept has
motivated the development of many antimicrobial processes and products.
One of the water purification developments that
took place in 1928 was the development of katadyn silver, described as
a porous metallic, spongy mesh that attempts to maximize surface area. This
silver meshwork also contains a small quantity of gold or palladium. Katadyn
silver has been used inside flasks, storage containers and with water filters.
During the last century, advances in
pharmacological manufacturing methods sought to harness this time-valued
strategy expressed in nearly all silver formulations. Yet early manufacturing
methods rarely created high quality, homogenous oligodynamic Ag +. Nevertheless,
more than 96 different silver medicinals (many used intravenously) were in use
prior to 1939, as documented by The Council on Pharmacy and Chemistry of the
American Medical Association.
A project begun at the State University of New York
by Robert Becker and associates involved a silver nylon product in the early
1970’s. This project was originally instigated in order to find an
electromagnetic shield. Instead, it lead to the revolutionary discoveries by
Becker of silver’s unique antimicrobial properties, and his discovery that
silver ions could induce fibrocytes to dedifferentiate into stem cells and back
again. One of Becker’s research associates, A. Bart Flick, continued work in
this area for professional and commercial applications. As a result, Flick has
filed patents in 1994, 1996 and 2000 for silver-based wound dressings that are
far superior to anything that has ever been available before. He has also
obtained approval for these dressing from the US Food and Drug Administration.
Because of the success of these silver dressings, many other medical product
manufacturers have filed for their own parallel products.
In the early 1970’s silver topical salves, such as
silver sulfadiazine, provided superior control and prophylaxis in severe burn
cases. Today, multiple drug resistant (MDR) microbes are challenging this
formulation’s effectiveness, but we shall review how state-of-the-art silver
protocols and formulations offer superior protection against microbial
strategies for acquiring resistance.
To date, absolute microbial resistance to medicinal
silver has not been scientifically established. Several studies indicated that
some bacterial species have physiological mechanisms that circumnavigate
silver’s toxicity. Although it is clear that some pathogens have mechanisms to
survive exposure to silver, these mechanisms are limited when compared to higher
life forms. Herein lie all the clues necessary to identify strategic silver
therapeusis that pathogens are unlikely to survive.
It is probable that pathogens lack sufficient
defense mechanisms to circumvent the toxic effects of silver ions when
oligodynamic silver is delivered in sufficient, physiologically compatible
quantities. In fact, the “apparent” resistance of microbes to silver was
mistakenly made by many who failed to notice and identify: (a) insufficient
oligodynamic Ag + particle concentrations, (b) inadequate protocols, or (c)
improper procedures. Reports that multiple-drug-resistant (MDR) pathogens (i.e.,
MRSA and Acinetobacter spp.) were truly resistant to silver proved to be
erroneous. Grier stated, “Some so-called Ag + resistant microorganisms may
result from an apparent neutralization of the metal’s inhibitory action or other
assay artifacts. These include the presence of chelators such as serial amino
acids, constituents of hard water, different buffers, light, incubation
temperature, and particularly, soluble components of trypticase soy agar (TSA)
and tryptose glucose extract agar (TGE).”
With the advent of antibiotic therapy, medicinal
silver products fell largely into disuse (circa 1940 -1945), with the notable
exceptions of topical silver salves and neonatal eye drop preparations. These
salves advanced the science of “silver salt-derived” Ag + delivery and
effectiveness in the mid 1960’s. Then, during the mid 1970’s, several papers
were published that utilized electrically activated silver probes as delivery
systems for targeted oligodynamic Ag + strategies. The interest in such
strategies continues to grow to the present, with high efficacy being obtained
for viral vectors such as HIV, and resistant bone and dental infection.
Sufficient defense capacity to mitigate morbidity
clearly exists in higher organisms, including humans (with the exception of
medically benign argyria). Zhao and Stevens state that, “With the rise of
antibiotic-resistant bacteria, silver is re-emerging as a modern medicine
because all pathogenic organisms have failed to develop an immunity to it (Ag
+).”
In vitro Studies
The medical literature of the early 20 th century
regarding silver provides an important cautionary lesson from the past. Previous
scientists, who were either supporters or detractors of silver medicinals,
typically expressed equivocal knowledge and misapplied context because they
failed to recognize silver speciation. This fault undermined their
definitive knowledge about silver. Correct and in-context discernment of
silver’s Therapeutic Threshold remains illusive to most investigators even
today. This “box” perception about silver will continue to lose its limitations
as technology continues to prove itself outside of that box in the coming
decades.
Clinical reports on silver medicinals began to
flood into the various medical journals worldwide at the start of the last
century. Initially, the Journal of the American Medical Association took a
negative position. But within 11 years, a true revolution in medical practice
with silver medicinals occurred that did not subside until the U.S. government’s
purchase of the patent rights to penicillin (circa 1940). Throughout this time
period (1920 through 1942), JAMA articles were replete with oral (per
os) and intravenous clinical reports of the efficacy and side effects of silver
medicinals. In tandem with research in America, Great Britain published
prominently in such respected journals as The Lancet and the
British Medical Journal.
Perhaps the first definitive attempt to
comprehensively evaluate the efficacy and variety of silver medicinals was
published by the Department of Pharmacology of the Medical School of Western
Reserve University, Cleveland, circa 1923. In terms of efficacy, this landmark
study arguably established “silver nitrate” as the benchmark for all silver
medicinals. Unfortunately, the excitement this study produced simultaneously
placed at risk subgroups of patients susceptible to symptoms of argyria. Had the
technology then existed to create vast surface areas with “pure hydrosols of
oligodynamic Ag +” not only would such products have revealed their greater
potency over that of silver nitrate; but also, argyric thresholds would have
been nearly impossible to attain during any course of therapy. Oligodynamic
(picoscale) surface area enables maximal exposure of silver particles in the
least amount of volume, thus achieving potency several orders of magnitude over
suspensions of much higher ppm- silver speciations (which necessarily manifest
inferior surface area exposures). In other words, technology today can produce
smaller quantities of silver that are vastly more potent than was ever
historically possible. The result is a dramatic elucidation of the Therapeutic
Index, resulting in unprecedented safety, efficacy, and dimension to protocol
parameters.
For example, beginning in 1970 at the University of
Wisconsin, under contract from NASA to determine the biocidal effects of silver,
researchers were able to determine that lethal effects of silver ions could be
reliably reproduced at concentrations of only 250-ppb when exposed to infectious
agents over two hours or less in vitro. These researchers even found
that even 50-ppb over four hours or less achieved a significant biocidal effect.
The University study with laboratory-produced silver ions worked extremely well,
although the extinction times were long. Follow-on investigations of these early
silver medicinals failed to exert adequate lethal effects upon antibiotic
resistant infectious organisms. However, as technology advanced, these highly
resistant organisms were again found to succumb to the lethal effects of new
silver medicinals. Additionally, extinction times proved to be dramatically
lessening.
In vivo Studies
At the height of its popularity (from 1900 through
1940), a fair estimate of humans given intravenous silver medicinals worldwide
exceeded several million. The shear scale of its utilization defined and
confirmed silver medicinals as effective anti-microbials.
During my training as a medical student, I had an
opportunity to witness several of my elder attending physicians using various
silver formulas in their clinical practice. It was fascinating to me that silver
medicinals were widely used by one generation of clinicians, yet this
therapeutic approach simply ended by my generation. Why? In terms of safety and
efficacy, was there a justification for abandonment of this approach?
One recent and noteworthy in vivo study
published in the Journal of Clinical Ultrasound (2000) reported on a protocol
involving puncture, aspiration, injection, and re-aspiration (PAIR) with silver
nitrate directly into hepatic hydatid cysts with beneficial long-term results.
Other preliminary evidence in vivo suggests that both hepatitis-C virus
(HCV) and HIV , and other viral vectors, as well as in vitro studies on
herpes, and the worst bacterial scourges (i.e., antibiotic resistant disease
vectors) may become events of the past via the judicious and strategic use of a
state-of-the-art silver medicinal and delivery system.
Antimicrobial coatings for the inside and outside
of medical catheters using silver have been developed for latex, polyurethane
and Teflon devices. These silver coatings are very effective at blocking
bacteria, such as E coli and S aureus, from entering the body along a catheter
pathway.
At the present time, in vivo studies
concerning the efficacy of oral (per os) and intravenous use of
state-of-the-art picoscale oligodynamic Ag + are just beginning. Given the high
technology formulated silver product now available, this promises to be an
exciting time. Concerning inferior grade silver [salt] medicinals, or “large
particle size (i.e., 0.1 microns or larger)” colloidal silver preparations, it
may be said that unless educational initiatives are undertaken, history is apt
to repeat itself -- needless iatrogenic events with such products will gestate a
new wave of preventable argyric cases.
Thomas Graham was a physical chemist honored as the
founder of colloid chemistry. He is known for contributions to diffusion
phenomena in liquids leading to the colloidal state; he coined the terms
“colloid” and “dialysis.” Graham also contributed to the understanding of gas
diffusion, including the law that the velocities of gases are inversely
proportional to the square roots of their densities.
Since a colloidal solution is not a true solution,
it is preferably termed a sol.
More information is available from the US
FDA on Silverlon® or the company that manufactures this dressing product.
See the following section heading – In
vitro Studies.
Bechhold, H,
Colloids in Biology and Medicine, NY, D. van Nostrand, 1919; p. 364-76.
Thompson, NR,
Comprehensive Inorganic Chemistry, Pergamon Press, Elmsford, NY, 1973; Vol. 5,
Chapter 28.
Hippocrates, “On
Ulcers,” 400 B.C.E.; translated by Francis Adams, © 1994-2000: http://classics.mit.edu/Browse/browse-Hippocrates.html
Blakeney, EH, [ed]
The History of Herodotus, translated by Rawlinson, G; London.
Cumston, CG, History
of Medicine, A.A. Knoff Co., NY, 1926; p. 216.
Charcot and Ball,
Dictionaire Encyclopedique des Sciences Medicals, P. Asselin, Sr. de Labes, V.
Masson & Sons, 1867; 6:68-74.
Gettler, AO, Rhoads, CP,
Weiss, S, “A Contribution to the Pathology of Generalized Argyria with a
Discussion on the Fate of Silver in the Human Body,” Am J Pathol, 1927;
3:63151.
Hill, WR, Pillsbury, MA,
Argyria: The Pharmacology of Silver, The Williams & Wilkins Company,
Baltimore, 1939; p. 2.
Raulin, J, Sci
Nature 11 (1869):93, Berk (3) Abstract 1.
Berk, RG, “Abstracts of
articles on oligodynamic sterilization.” The Engineer Board, US Army Corps of
Engineers [Project WS 768], Fort Belvoir, Virginia.
Von Nageli, KW,
Denschr Schweiz Naturforsch Ges 33 (1893):174, Berk (3) Abstract 5.
Crede, KSF, Ber Klin
Wochenschr, 1901; 38:941.
Zhao, G, Stevens, SE,
“Multiple Parameters for the Comprehensive Evaluation of the Susceptibility of
Escherichia coli to the Silver Ion,” BioMetals, 1998; 11:27.
Sykes, G, “Disinfection
and Sterilization” 2 nd Ed, (1965) Spon, London.
Tobler, T, Schweiz
Med Wchnschr, 1922; 52:774.
Hill, WR, Pillsbury, DM,
Argyria: The Pharmacology of Silver, The Williams & Wilkins Co.,
Baltimore, 1939; p. 169.
Voigt, J, Ztschr f d
ges exper Med, 1926; 52:33-40.
Hall, RE, Bender, G,
Marquis, RE, “Inhibitory and Cidal Antimicrobial Actions of Electrically
Generated Silver Ions,” J Oral Maxillofac Surg, 1987; 45:783.
McHugh, GL, et al.,
“Salmonella typhymurium Resistant to Silver Nitrate, Chloramphenicol and
Ampicillin,” Lancet, 1975; 1:235.
Summers, AO, et al.,
“Metal Cation and Osyanion Resistances in Plasmids of Gram Negative Bacteria,”
In: Schlessinger, edit. Microbiology, Am Soc Microbiol, Washington, DC,
1978.
Bridges, K, et al.,
“Gentamicin and Silver Resistant Pseudomonas in a Burn Unit,” Br Med J,
1979; 1:446.
Hamilton-Miller, JM,
Shah, S, Smith, C, “Silver Sulfadiazine: A Comprehensive in vitro
Reassessment,” Chemotherapy, 1993; 39:405-9.
Grier, N, “Silver and
Its Compounds,” In: Disinfection, Sterilization and Preservation, S.
Block, edit. Lea & Febiger, Philadelphia, PA, 1983, p. 385.
Fox, CL, “Silver
Sulfadiazine – A New Topical Agent,” Arch Surg, 1968; 96:184-8.
Becker, RO, Spadaro, JA,
“Treatment of Orthopaedic Infections with Electrically Generated Silver Ions,”
J Bone Jt Surg, 1978; 60:871-81.
Etris, S, “Clinical
Experiments Show Silver Compound Can Help AIDS Patients: Researchers Say Silver
Oxide Offsets AIDS Loss of Immune Response,” In: The Silver Institute’s
Silver News – February-March 1998; www.silverinstitute.org
Kim, TN, et al.,
“Antimicrobial Effects of Metal Ions (Ag +, Cu 2+, Zn 2+) in Hydroxyapatite,”
J Mater Sci Mater Med, 1998; 9:129-34.
Berger, TJ, et al.,
“Electrically Generated Silver Ions: Quantitative Effects on Bacterial and
Mammalian Cells,” Anti Microb Agents, 1976; 9(2): 357-8.
Zhao, G, Stevens, SE,
“Multiple Parameters for the Comprehensive Evaluation of the Susceptibility of
Escherichia coli to the Silver Ion,” BioMetals, 1998; 11:28.
Hill, WR, Pillsbury, DM,
Argyria: The Pharmacology of Silver, The Williams & Wilkins Co.,
Baltimore, 1939; p. 169.
Duhamel, BG, “Electro
Metallic Colloids, Etc.,” The Lancet, January 13 th, 1912.
Simpson, WJ, Hewlett,
RT, “Experiments on the Germicidal Action of Colloidal Silver,” The Lancet,
December 12 th, 1914; p. 359.
Sanderson-Wells, TH, “A
Case of Puerperal Septicemia Successfully Treated with Intravenous Injections of
Collosol Argentum,” The Lancet, February 16 th, 1916; p. 258.
Fuller, AW, “Epidemic
Encephalitis of Severe Type,” The Lancet, July 24 th, 1926; 2:172.
“Colloidal Solutions and
Artificial Enzymes,” Brit Med J, February 3 rd, 1912; 6:252-4.
Marshall , CR, Killoh,
GB, “The Bactericidal Action of Collosols of Silver and Mercury,” Brit Med
J, January 16 th, 1915; 1:102-3.
Roe, AL, “Collosol
Argentum and its Ophthalmic Uses,” Brit Med J, January 16 th, 1915;
3:104.
Morris, M, “The
Therapeutic Effects of Colloidal Preparations,” Brit Med J, May 12 th,
1917; 1:617.
Pilcher, JD, Sollmann,
T, “Organic, Protein and Colloidal Silver Compounds: Their Antiseptic Efficiency
and Silver-Ion Content as a Basis for Their Classification,” The Journal of
Laboratory and Clinical Medicine, 1923; p. 301-10.
Cliver, DO, et al.,
“Biocidal Effects of Silver: Contract NAS 9-9300 Final Technical Report,”
University of Wisconsin, February 1970; p. 5.
In vitro
investigations published on letterheads from Departments of Microbiology,
Pathology, Infectious Diseases, Immunology, and Biology. Etc… from such
universities as: Johns Hopkins, Northwestern Univ. Medical School, Queen’s
University, University of Arkansas for Medical Sciences, Georgetown University
Medical Center, NYU Medical Center, University of Nebraska, University of
Massachusetts, etc…circa 1996-1998.
Ibid.
Odev, K et al.,
“Sonographically Guided Percutaneous Treatment of Hepatic Hydatid Cysts:
Long-Term Results,” J Clin Ultrasound, Nov-Dec 2000; 28(9): 469-78.
Etris, S, “Clinical
Experiments Show Silver Compound Can help AIDS Patients: Researchers Say Silver
Oxide Offsets AIDS Loss of Immune Response,” In: The Silver Institute’s
Silver News – February-March 1998; www.silverinstitute.org
Dean, W, et al.,
“Reduction of Viral Load in AIDS Patients with Intravenous Mild Silver Protein –
Three Case Reports,” Clinical Practice of Alternative Medicine, Spring,
2001.
Tokumaru, T, Shimizu, CL
For, “Antiviral Activities of Silver Sulfadiazine in Ocular Infections, “
Res Com Chem Pathol Pharmacol, 1974; 8(1): 151.
Chang, TW, L Weinstein,
“In vitro Activity of Silver Sulfadiazine Against Herpesvirus hominis,”
J Infect Dis, Jul 1975; 132(1): 79-81.
Becker, RO, Spadaro JA,
“Treatment of Orthopedic Infections with Electrically Generated Silver Ions,”
J Bone Jt Surg, 1978; 60-A: 871.
Chu, CC, et al., “Newly
Made Antibacterial Braided Nylon Sutures. 1. In vitro Qualitative and
in vivo Preliminary Biocompatibility Study,” J Biomed Mater Res,
1987; 21:1281.
Dietch, EA, et al.,
“Silver-Nylon Cloth: In vitro and in vivo Evaluation of
Antimicrobial Activity,” J Trauma, 1987; 27:301.
Haeger, K, “Preoperative
Treatment of Leg Ulcers with Silver Spray and Aluminum Foil,” Acta Chir
Scand, 1963; 125:32.
Marchant, RE, Miller,
KM, Anderson, JM, “In vivo Leukocyte Interactions with Biomer,” J
Biomed Mater Res, 1984; 18:1169.
Modak, SM, Sampath, L,
Fox, CL, “Combined Use of Silver Sulfadiazine and Antibiotics as a Possible
Solution to Bacterial Resistance in Burn Wounds,” J Burn Care,
July/August, 1988; 9(4): 359.
Spadaro, JA, Becker, RO,
“Some Specific Cellular Effects of Electrically Injected Silver and Gold Ions,”
Bioelectrechem Bioenergetics, 1976; 3:49.
Webster, DA, et al.,
“Silver Anode Treatment of Chronic Osteomyelitis,” Clin Orthop, 1981;
1961:105.
Shvets, I, DeLaurentis,
M, Beard, RB, Pourreyzaei, K, Trans 20 th Annual Meeting – Society for
Biomaterials, Boston (1994).
DeLaurentis, M, Shvets,
I, Beard, RB, Pourreyzaei, K, Trans 20 th Annual Meeting – Society for
Biomaterials, Boston (1994).
Beard, RB, DeLaurentis,
M, Pourrezaei, K, Adrian, S, “Stimulation, Recording Potential and Antimicrobial
Medical Catheter Coatings,” Metal-Based Drugs Vol 1, 5-6
(1994):445-458, Freund Pub House Ltd, London.
Posted with permission from Dr. Eric J.
Rentz. In recognition of his elegant style and rich content.
from: http://www.hydrosolinfo.com/articles/history-of-silver.php
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