Zinc in the Treatment of Smallpox

History of Smallpox in Bioweaponry (1122 BC - 1899 AD)

1122 B.C., Earliest report of smallpox, in China. (Physicians in ancient China had long since immunized patients by removing scales from drying pustules of a person suffering from a mild case of smallpox, grinding the scales to a fine powder, and inserting the powder into the nose of the person to be immunized.)

1400s A.D., Pizarro presents South American natives with Variola-contaminated clothing.

1718. English noblewoman Lady Mary Wortley Montagu reports that the Turks have a habit of deliberately inoculating themselves with fluid taken from mild cases of smallpox. Lady Montague inoculates her own children in this manner.

1751. George Washington contracts smallpox.

1754 - 1767. During the French and Indian War, Sir Jeffery Amherst provides Indians loyal to the French with Variola-laden blankets.

1763. British officer Colonel Henry Bouquet proposes giving Indians at Fort Pitt, Pennsylvania, Variola-infected blankets.

14 May 1796. British physician Edward Jenner injects the fluid from a blister on the hand of a milkmaid with cowpox into a boy.

July 1796. Edward Jenner injects his experimental patient [see entry for 14 May 1796] with smallpox. The boy is immune.

1798. Edward Jenner repeats his cowpox inoculation experiment.

History of Smallpox in Bioweaponry (1900 to 2001)

looking up...... Detecting much unwarranted Western fear... Much buzz... Much static... Many mistakes... Much money flow into research... Much money wasted...

Summary of Properties of Ionic Zinc Useful in Treating Viral Infections

• Divalent zinc ions (Zn²⁺ ions) in aqueous solution have wide antiviral properties both in vitro and in vivo. Some of these viruses produce skin lesions "pox" similar to smallpox such as chickenpox, and cowpox.
• Antiviral effects of Zn²⁺ ions on herpes simplex 1 and 2 viruses and infection in animals and humans have been demonstrated.
• Avian myeloblastosis, bacteriophages, calicivirus, coxsackieviruses, equine herpes, herpes simplex I and II, polio, encephalomyocarditis, enterovirus, foot-and-mouth disease, mengovirus, Rous sarcoma, Semliki Forest, Sindbis, SV40, tobacco mosaic, vaccinia (causative agent of cowpox), viroids and prions, are all reported to have features controlled by Zn²⁺ ion usually at concentrations between 0.1 and 2.0 mMol without harm to cells.
• The divalent zinc ion in aqueous solution has broad cell membrane protective features that prevent cells from being damaged by cytotoxins, perhaps resulting from its astringent effects. Perhaps the most consistently reported effect of Zn²⁺ ion on mammalian cells is membrane stabilization. The exact mechanism by which zinc stabilizes cell membranes is not clear and may be different for different membranes. Hemolytic viruses, bacterial and animal toxins, components of activated complement, cytolysin (perforin), cationic proteins, and detergents have all been shown to induce a sequence of permeability changes at the plasma membrane that are in every case beneficially sensitive to changes in Zn²⁺ ion concentrations from normal levels up to 100 times normal serum concentration. Membrane damage induced by a wide variety of hemolytic agents can be prevented by zinc ions at normal to 100 times the normal concentration of zinc found in human serum without harm to cells. Within a range, as Zn²⁺ ion concentration is increased, the strength of protection also increases.
• The divalent zinc ion in aqueous solution has important immunologic properties affecting the T-cell lymphocyte system, and induction of interferon.
• The anti-inflammatory action of topical zinc preparations, often as zinc oxide, has long been used to inhibit inflammation of the skin (e. g., diaper rash, other dermatitis) in a safe and effective manner in over-the-counter preparations. Zinc deficiency is often found in dermatologic diseases where inflammation is characteristic; and treatment with zinc (usually as zinc oxide) to control inflammation is common. With elevated concentrations of Zn²⁺ ions, the cement substance of capillary endothelium of all cells is known to become hardened so pathologic transcapillary movement of plasma protein is inhibited and local edema, inflammation, and exudation are thereby reduced. Mucus and other secretions are reduced in tissues containing goblet cells and other secretory cells, and the affected area dries and heals faster with added zinc ions. Because of very limited ionizability at the pH of skin, zinc oxide ointments probably are not suitable for treating smallpox lesions, although it should be better than no zinc ion topical treatment.

Historical Use of Zinc Sulfate to Treat Smallpox.

Smallpox Remedy from "The Home Cook Book, 1877".

"The following remedy a friend in Ohio tried in a case of confluent smallpox, when the doctor had little hope of saving the patient, and it saved the woman's life. The remedy is sure in scarlet fever. 'I herewith append a recipe that has been used to my own knowledge in a hundred cases. It will prevent or cure the small pox, even though the pittings are filling. When Jenner discovered cow pox in England, the wold of science hurled an avalanche of fame upon his head, and when the most scientific school of medicine in the world (that of Paris), published this panacea for the small pox it passed unheeded. It is unfailing as fate, and conquers it in every instance. It is harmless when taken by a well person. It will also cure scarlet fever. Take sulfate of zinc, one grain; fox glove (digitalis) one grain; half a teaspoon of water. When thoroughly mixed, add four ounces of water. Take a spoonful every hour, and either disease will disappear in twelve hours. For a child, smaller doses, according to age.'"

Possible Treatment Modalities for Viral Smallpox Infection

1. To rapidly maximize T-cell function, provide dietary supplements of highly ionizable zinc sufficient to maximize T-cell lymphocyte function (approximately 2 mg / kg body weight / day), or that amount sufficient to increase zinc serum concentration to about 130 to 140 mcg/dL. Zinc chloride, zinc acetate, zinc sulfate, and zinc gluconate are representative of highly ionizable zinc compounds.
2. To directly treat skin lesions, apply solutions of highly ionizable zinc compounds directly to smallpox lesions and replace bandages or pastes at a frequency sufficient to maintain sterility. Zinc gluconate solutions can be applied in saturated solutions (approximately 400 mMolar) or in an wet aqueous pastes without concern for tissue burning. However, other highly zinc compounds applied in high concentrations will usually cause tissue burns.
3. To utilize the non-specific cell membrane protective action of Zn²⁺ ions, increase total body ionic zinc in tissues, blood, serum and skin. Most serum zinc ions are used by the body to stabilize cell membranes and close pores in cell membranes. In vitro, Charles A. Pasternak, PhD, MD (Hon), of St. George's Medical Hospital, University of London, has found that increasing zinc ion concentrations to be a novel and newly recognized form of host defense. Zn²⁺ ions strengthen cell membranes and protect them from damage from many cytotoxins, including viruses, venoms, and complement. His writings, and similar writings of others, on these general protective effects of Zn²⁺ ions can be found in references 1, 11, 63-67, 70, 79, and 104-106 in Chapter 2 of Handbook for Curing the Common Cold. A cytotoxin protective dosage of zinc gluconate (a safe source of Zn²⁺ ions) has been used to prevent tissue necrosis and death from multiple, severe bites by brown recluse spiders (Loxosceles reclusa), and should provide equal relief in treating smallpox. Dosage is oral 500 to 1000 milligrams of zinc from zinc gluconate four times per day until lesions disappear or until side effects occur. This dosage has provided immediate relief from cytotoxic symptoms from brown recluse spider bites in 4 out of 4 cases. Upon elimination of the cytotoxin, whether from a brown recluse spider or smallpox, continuing the dosage will cause violent nausea, vomiting and diarrhea. No further treatment is needed after side effects occur. Skin lesions become absent within the same day leaving no scars in the treatment of brown recluse spider bites. This dosage can only be used in smallpox treatment or the treatment of other extremely cytotoxic conditions and never in healthy people. In healthy people this dosage always causes immediate nausea and vomiting followed by diarrhea. No palliative treatment for these side effects is needed or desired. Rehydrate, provide outstanding nutrition with electrolytes. Side effects last less than 24 hours. This dosage of zinc is likely to cure smallpox within 4 days. The serum concentration of zinc is likely to approach 1 mMolar until the body readjusts to normal over the following few days. There is no known sequela or long term side effects. Alternately, give zinc chloride solutions by IV.

Zinc in National Food Supplies and Likely Impact of Smallpox in Nations

Considering the role of zinc in fighting viral infections, variations in zinc dietary content of foods in the nations of the world suggest that many nations would not have adequate zinc to survive smallpox epidemics. In the following figures by Ken Brown, M.D., Professor of Nutrition at the University of California at Davis, zinc is shown in national food supplies as percent of weighted mean per capita requirement. This data suggests that populations of nations illustrated in green would have sufficient zinc in their diets to reasonably well fight off smallpox infection. Populations of nations shown in yellow would have difficulty in fighting off smallpox, and populations of nations shown in orange would be severely impacted by smallpox. Populations of nations shown in red would be extremely impacted by smallpox.

However, if the effect of zinc deficiency on stunting growth of children (from WHO data) is considered then...

The impact of zinc deficiency in resisting smallpox is considerably greater for children in more nations, particularly African nations. The difference between these two figures suggests that the impact of smallpox outbreak would be devastating in children in most third-world nations.

Some Cowpox and Zinc In Vitro References:

1. Katz E, Margalith E. Inhibition of vaccinia virus maturation by zinc chloride. Antimicrobial Agents and Chemotherapy. 1981;19:213-217 and
2. Zaslavsky V. Inhibition of vaccinia virus growth by zinc ions: effect on early RNA and thymidine kinase synthesis. Journal of Virology. 1979;29: 405-408
   represent work done with zinc ion on cowpox virus, a close relative of the smallpox virus (variola) suggesting antiviral effects of zinc ion for smallpox.

U. S. Center for Disease Control

U.S. Center for Disease Control facts about Smallpox

Smallpox infection was eliminated from the world in 1977.

Smallpox is caused by variola virus. The incubation period is about 12 days (range: 7 to 17 days) following exposure. Initial symptoms include high fever, fatigue, and head and back aches. A characteristic rash, most prominent on the face, arms, and legs, follows in 2-3 days. The rash starts with flat red lesions that evolve at the same rate. Lesions become pus-filled and begin to crust early in the second week. Scabs develop and then separate and fall off after about 3-4 weeks. The majority of patients with smallpox recover, but death occurs in up to 30% of cases.

Smallpox is spread from one person to another by infected saliva droplets that expose a susceptible person having face-to-face contact with the ill person. Persons with smallpox are most infectious during the first week of illness, because that is when the largest amount of virus is present in saliva. However, some risk of transmission lasts until all scabs have fallen off.

Routine vaccination against smallpox ended in 1972. The level of immunity, if any, among persons who were vaccinated before 1972 is uncertain; therefore, these persons are assumed to be susceptible.

Vaccination against smallpox is not recommended to prevent the disease in the general public and therefore is not available.

In people exposed to smallpox, the vaccine can lessen the severity of or even prevent illness if given within 4 days after exposure. Vaccine against smallpox contains another live virus called vaccinia. The vaccine does not contain smallpox virus.

The United States currently has an emergency supply of (antique) smallpox vaccine.

There is no proven treatment for smallpox but research to evaluate new antiviral agents is ongoing. Patients with smallpox can benefit from supportive therapy (intravenous fluids, medicine to control fever or pain, etc.) and antibiotics for any secondary bacterial infections that occur.

U. S. Federal Trade Commission Position On Zinc For Smallpox

See the official position of the U.S. Federal Trade Commission on the treatment of smallpox with zinc. This position against commercialization of zinc as a treatment for smallpox is warranted simply because no clinical trials have been performed and no clinical evidence of efficacy or side effects has been published, perhaps because no smallpox virus is available for testing. Catch-22? Will zinc cure smallpox? Who knows, we will probably wait until Osama bin Laden leading Al Qaeda using Iraq's smallpox virus supply attacks the United States or its allies to see. Plan ahead with a simple approach? HA!

·         Bashford CL, Alder GM, Pasternak CA. Fluctuation of surface charge in membrane pores. Biophys J. 2002 Apr;82(4):2032-40.

·         Pasternak CA, Alder GM, Bashford CL, Korchev YE, Pederzolli C, Rostovtseva TK. Membrane damage: common mechanisms of induction and prevention. FEMS Microbiol Immunol. 1992 Sep;5(1-3):83-92.

·         Korchev YE, Bashford CL, Pasternak CA. Differential sensitivity of pneumolysin-induced channels to gating by divalent cations. J Membr Biol. 1992 May;127(3):195-203.

·         Alder GM, Arnold WM, Bashford CL, Drake AF, Pasternak CA, Zimmermann U.  Divalent cation-sensitive pores formed by natural and synthetic melittin and by Triton X-100. Biochim Biophys Acta. 1991 Jan 9;1061(1):111-20.

·         Pasternak CA.  Transmembrane communication and disease. Indian J Biochem Biophys. 1990 Dec;27(6):363-4.

·         Pasternak CA, Bashford CL, Menestrina G. Mechanisms of attack and defence at the cell surface: the use of phospholipid bilayers as models for cell membrane. Biosci Rep. 1989 Aug;9(4):503-7.

·         Bashford CL, Rodrigues L, Pasternak CA. Protection of cells against membrane damage by haemolytic agents: divalent cations and protons act at the extracellular side of the plasma membrane. Biochim Biophys Acta. 1989 Jul 24;983(1):56-64.

·         Pasternak CA.  A novel role of Ca2+ and Zn2+: protection of cells against membrane damage. Biosci Rep. 1988 Dec;8(6):579-83.

·          Bashford CL, Menestrina G, Henkart PA, Pasternak CA. Cell damage by cytolysin. Spontaneous recovery and reversible inhibition by divalent cations. J Immunol. 1988 Dec 1;141(11):3965-74.

·         Bashford CL, Alder GM, Graham JM, Menestrina G, Pasternak CA.  Ion modulation of membrane permeability: effect of cations on intact cells and on cells and phospholipid bilayers treated with pore-forming agents. J Membr Biol. 1988 Jul;103(1):79-94.

·         Pasternak CA, Mahadevan D.  Novel role of extracellular calcium and zinc: protection against membrane damage induced by cytotoxic agents. Indian J Biochem Biophys. 1988 Feb-Apr;25(1-2):1-7..

·         Micklem KJ, Alder GM, Buckley CD, Murphy J, Pasternak CA.  Protection against complement-mediated cell damage by Ca2+ and Zn2+. Complement. 1988;5(3):141-52.

·         Pasternak CA.  A novel form of host defence: membrane protection by Ca2+ and Zn2+. Biosci Rep. 1987 Feb;7(2):81-91.

·         Pasternak CA.  Virus, toxin, complement: common actions and their prevention by Ca2+ or Zn2+. Bioessays. 1987 Jan;6(1):14-9.

·        Pasternak CA.  Viruses as toxins. With special reference to paramyxoviruses. Arch Virol. 1987;93(3-4):169-84.

·        Bashford CL, Alder GM, Menestrina G, Micklem KJ, Murphy JJ, Pasternak CA.  Membrane damage by hemolytic viruses, toxins, complement, and other cytotoxic agents. A common mechanism blocked by divalent cations. J Biol Chem. 1986 Jul 15;261(20):9300-8.