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1 Introduction PROLOGUE I am an evil, poisonous smoke . . . But when from poison I am freed, Through art and sleight of hand, Then can I cure both man and beast, From dire disease ofttimes direct them; But prepare me correctly, and take great care That you faithfully keep watchful guard over me; For else I am poison, and poison remain, That pierces the heart of many a one. (Valentini, 1694845) The alchemists' symbol for arsenic, a menacing coiled serpent, proba- bly symbolizes very well the element's prevailing evil reputation. Anxiety about arsenic is not difficult to comprehend, inasmuch as arsenic compounds were the preferred homicidal and suicidal agents during the Middle Ages and arsenicals have been regarded largely in terms of their poisonous characteristics in the nonscientific literature. For example, an almost clinical description of acute arsenic poisoning appears in the novel Madame Bova~y.255 Flaubert's extensive account 1
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2 ARSENIC of Emma Bovary's prolonged death throes must have made a vivid impression on many a reader. Arsenic has also been referred to in more recent literature, such as Kesselring's drama, Arsenic and Old Lace. 423 Although arsenic was only one of three poisons used by the Brewster sisters to dispatch their guests, "Strychnine and Old Lace" or "Cyanide and Old Lace" would not have had as great an impact on the public. A famous case of hypothetical arsenic poisoning was the alleged attempt to do away with Napoleon Bonaparte on several occasions during his exile on St. Helena. After analyzing compilations of Napo- leon's signs and symptoms during his later years, Forshufvud et al. 259 concluded that the Emperor had suffered intermittently from chronic and acute arsenic poisoning. Neutron-activation analysis of hair repu- tedly taken from Napoleon's head showed considerably more arsenic than samples from unexposed people. An editorial concerning this controversial hypothesis577 set on a large measure of de- bate ~05 ~32 337 370 666 667 s65 The original hypothesizers later analyzed ad ditional hair samples attributed to Napoleon and found a distribution of arsenic along the length of the hair shaft that indicated a periodicity of exposure that coincided relatively well with the course of his dis- ease.260 744 However, the evidence of chronic arsenic poisoning of the Emperor was described as "unsatisfactory, irritating, and tortuous."~04 Another viewpoint was that Napoleon may indeed have received arsenic, but "only in an honest endeavour to help him."836 The possibility that arsenic compounds were prescribed for Napo- leon reveals another side of arsenic- its widespread use in eighteenth- and nineteenth-century medicine as a tonic, or "alterative." At about the same time that Flaubert was writing Madame Bovary, there were a half-dozen "official" arsenicals listed in the U.S. Dispensatory.870 The prevailing professional opinion at that time concerning the medicinal use of arsenic was summarized as follows :29 "Arsenic is a safe medicine; none of the respondents having found it permanently detri- mental. When given in a judicious manner, it did not even induce serious temporary effects. In the few cases apparently leading to a contrary inference, there was sufficient evidence of ignorant adminis- tration, or injudicious perseverance on the part of the patient." The heyday of arsenical chemotherapeutics occurred in the early part of the twentieth century, when Ehrlich discovered Salvarsan (arsphenamine), which was effective in treating human venereal diseases; but the use of these compounds declined after World War II, with the advent of the more specific antibiotics. The complex folklore surrounding arsenic might provide us with an
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Introduction 3 example of man's supposed ability to tolerate the element, inasmuch as peasants in the Styrian Alps of Austria during the nineteenth century were said to consume arsenic habitually as a means of promoting physical stamina.30 The origins of this custom are difficult to trace. One of the best early accounts was that of Roscoe,673 who concluded: "I. That arsenious acid is well known to and widely distributed amongst the peasants of Styria. II. That arsenious acid is taken regularly into the system, by certain persons in Styria, in quantities usually supposed sufficient to produce immediate death." Maclagan507 had reached similar conclusions. The nineteenth-century medical establishment, however, especially in the English-speaking world, remained highly skeptical of the phenomenon: "Upon the whole, it is not improbable that the accounts received of the habitual use of arsenic by the peasants of Styria are either untrue or greatly exaggerated."870 Maclagan508 later claimed that two habitual arsenic-eaters took their dose in the presence of a scientific meeting on the Continent, thereby providing "public testimony to the accuracy of the observations previously made." Unfortunately, this is one aspect of the biochemistry of arsenic that will probably never be totally resolved. Although the earlier medicinal uses and criminal abuses of arsenicals provide a helpful background of information about these compounds, the primary purpose of this report is not to determine the human hazards of such large direct exposures. Rather, this report is concerned primarily with assessing a more indirect hazard the possibility of man's harming himself by contaminating his environment with arseni- cals. There are potential ecologic dangers, in that large quantities of arsenicals are injected into the environment as a result of industrial and especially agricultural activities. Paris green (copper acetoarsenite) was the first pesticide widely used in modern agriculture (see Whor- ton856 for an account of early agricultural experience with this and other arsenicals), and several arsenic compounds continue to be used today (see Chapter 31. Moreover, recent studies have again raised the question of the carcinogenicity of inorganic arsenic compounds (see Chapter 61. For some applications, there appear to be no suitable substitutes for the arsenicals. Therefore, we must learn to manage carefully the toxic yet useful compounds of arsenic.