7 Medicinal

At the start of World War II, about half of all pharmaceutical drugs included botan - ical derivatives in their formulations. Drug shortages were anticipated because many medicinal were imported, some from Europe and others from the tropics, and concern increased with global hostilities. Trade in botanical drugs occurred in European cities, including Hamburg and Rotterdam, which drastically affected worldwide access to pharmaceuticals.

Essential Drugs

Critical drug plants in limited supply included belladonna ( Atropa belladonna ), hen - bane ( Hyocyamus niger ), quinine ( Cinchona spp.), red squill ( Urginia maritima , now rec - ognized as maritima ), and lavender- cotton ( Santolina chamaecyparissus ). European growers supplied belladonna, henbane, and red squill; quinine was obtained from feverbark trees cultivated in the Dutch East Indies, and santonin was derived from lavender- cotton plants imported from Asia. These plants had diverse medicinal uses. Belladonna and henbane were sources of potent tropane alkaloids such as atropine and scopalomine, which had narcotic and seda - tive properties, and they appeared in formulations ranging from laxatives to painkillers. Atropine from belladonna was a known antidote to organophosphate nerve agents such as sarin and tabun. Germany produced these chemical weapons in large quantities but never used them against Allied troops, but stockpiles of atropine- loaded syrettes resulted in a wartime belladonna shortage. Originally imported from Europe, belladonna was cultivated in New Jersey, Pennsylvania, Tennessee, Virginia, Ohio, and Wisconsin. Huge dryers desiccated two tons of leaves daily. 1 Quinine was used to prevent and treat malaria, but the compound was also used in cases of shingles, whooping cough, psoriasis, and sepsis. Lavender- cotton was a vermifuge against intestinal parasites. Red squill, a - producing species in the lily family (Lili - aceae), is native to the Mediterranean region, and its cardiac glycosides were used to regu - late heartbeat. The was also widely used as a wartime poison; known doses of scil laren glycosides can be cardiotonic, but uncontrolled levels added to rat bait were lethal. In addi - tion to destroying stored food, were potential vectors of disease. Biological warfare was a legitimate concern; the Japanese experimented in the infamous Unit 31 with the aerial spraying of the plague bacterium ( Yersinia pestis ) that is spread by rat- borne fleas.

1 7. Medicinal Botany 1

In the Pacific theater, wild rats were reservoirs for the microbe that causes scrub typhus, and red squill rat poison was standard military issue for many years.2 Thus rat poison reserves were considered essential to national security and military health, but imports of red squill were blocked by German submarines. Rather than seeking alterna- tives, the USDA Agricultural Research Service cloned European for successful cul- tivation on experimental farms in California. The individual bulbs weighed up to a kilogram and were macerated into chips or powder for drying and long term use. There were also attempts to select cultivated strains with high glycoside concentrations that could thrive in the California climate.3 All of these species were originally imported from areas potentially affected by war with Germany and Japan. Even before the attack on Pearl Harbor, practical concern resulted in the cultivation of medicinal plants in the U.S. In the spring of 1941, Harvard University botanists worked with faculty of the Massachusetts College of Pharmacy to plant a medicinal plant garden at the Arnold Arboretum. The two- acre experimental site was landscaped with woody medicinal species including witch hazel, sweet gum, sassafras, buckthorns, bayberry, and sugar maples, while herbaceous species were transplanted into beds. Much of resembled a colonial garden, including yarrow, bugle- weed, tansy, angelica, sage, thyme, parsley, and rosemary, herbs with known medicinal properties. However, the goal was not to recreate a historic garden. Plant choice was clearly strategic, to identify easily cultivated species for use in treating ailments from congestive to wound care.4 Belladonna, henbane, red squill, and lavender- cotton (all temperate species) were planted in the Massa- chusetts College of Pharmacy garden, but the National Formulary (now merged with the United States Phar- macopeia) sought safe substitutes for wartime use. For instance, thorn apple (Datura stramonium) was cul- tivated for use in cathartics as a bella- donna alternative. Both species are members of the family (a family known for producing tropane alkaloids) that synthesize atropine and related compounds, but thorn apple naturalizes widely and grows aggressively, and it was collected from the wild for wartime use. Even- tually wartime crops of belladonna were successfully cultivated in Wis- consin and Pennsylvania, and hen- bane was collected from naturalized populations in Montana. There were other wartime sub- stitutions, including the temporary use of Indian species of valerian 1 Plants Go to War

(Valeriana wallichii) and rhubarb (Rheum australe) to replace European valerian (V. offic- inalis) and Chinese rhubarb (R. palmatum). However, not all plants of a single shared similar medicinal properties. Shortages of aconite root ( napellus) from the central European Alps resulted in investigations of Asian aconites, but either the potent alkaloids (primarily aconitine) were lacking or undesirable side effects occurred. Other plants cultivated in the garden included tansy (Tanacetum vulgare) and pink- root (Spigelia marilandica), both effective vermifuges when administered in controlled doses. Lily of the valley (Convallaria majalis) and foxglove (Digitalis spp.) were grown for their cardiac glycosides. Autumn crocus (Colchicum autumnale) was used to treat both gout and typhus. Although European supplies were low, the bulbs multiplied easily in the New England climate, and the alkaloid colchicine was also used to develop polyploid strains of agricultural plants (see Chapter ). Meadowsweet (Filipendula ulmaria) was a possible substitute for the European willows used in manufacturing aspirin. These species all produce salicin, isolated by German chemists and valued for its anti-inflammatory and analgesic properties. Ironically, Germany lost the aspirin trade- mark as part of the reparations negotiated in the Treaty of Versailles at the end of World War I. Plants were also cultivated with military uses in mind, including species used his- torically for wound treatment. Yarrow (Achillea millefolium) was known since ancient times as a hemostat, and garlic and onions (Allium spp.) were used as antibiotic dressings. Various mints had antibiotic potential, including bugleweed (Ajuga reptans, a folk cure for gangrene) and species of Mentha, Hyssopus, Monarda, and Lavandula. Various mus- tards (Brassica spp.) were also potentially antibiotic. New World medicinal plants included several used by Native Americans and adopted as folk remedies; at least three of these were used historically to treat malaria, including fringe tree (Chionanthus virginicus), jack- in-the-pulpit (Arisaema triphyllum), and Oregon grape (Mahonia aquifolium).

Home Front Medicine

Civilian health was considered part of patriotic duty, and proprietary medicines advertised their products in light of wartime preparedness. Over- the-counter remedies included Vaporub and Va- tro-nol from the Vick Chemical Company of North Carolina. Vaporub was intended for external use and was compounded with botanical terpenes and terpenoids, including camphor, menthol, and thymol, and oils of nutmeg, eucalyptus, and cedar leaves. Va- tro-nol was a similar aromatic combination, with the addition of the alkaloid ephedrine from Ephedra, and advertisements for the “Vicks plan” suggested that it be used as a throat medication to treat colds. Menthol, thymol, and camphor are all derived from various mints, and the latter is also isolated commercially from a cin- namon relative, the camphor laurel (Cinnamomum camphora). All have antimicrobial and antiviral properties, so the advertising claims may have had a medical basis. Home front medicine included first aid. With the threat of bombing in England, families were advised to have on hand a kit of basic items that included several botanical products. Basic medicines included ammoniated tincture of quinine, used as a home remedy for colds and fevers. Now obsolete, it appeared in the British Pharmaceutical Codex until 193 and was a medical carryover from tropical colonies, where quinine from feverbark (Cinchona spp.) was used to treat malaria. Tincture of myrrh (prepared