Banned

by Frederick Rowe Davis

  Although by 1958 the budget had expanded to $275,000, of which approximately half went to research and graduate training in toxicology, DuBois believed that a distinct toxicology laboratory would greatly enhance the Division of Biological Sciences at the university. His justification for such a program was that the discipline of toxicology had developed to such a degree that designated lectures in related courses on pharmacology could no longer encompass the breadth and depth of the burgeoning field: “However, the tremendous increase in the use of chemical agents for industrial, agricultural and household purposes, and the anticipated widespread use of atomic energy have introduced many toxicological problems. The field is expanding so rapidly that it is no longer possible to include adequate coverage of the subject in the formal courses of related disciplines nor for the teachers of other disciplines to keep abreast of developments in the field.”2 DuBois noted that at least one other university, the University of Rochester, was initiating a program in toxicology. Unfortunately, the administration at the University of Chicago did not approve DuBois’s proposal as the dean of biological sciences supported molecular approaches to the study of biology over whole animal studies.3

  The shift to molecular approaches at Chicago reflected a trend at many of the leading universities in the U.S. But what appeared to be a curse for the Tox Lab proved to be a blessing for the emerging field of toxicology: many of the Chicago toxicologists found positions at other universities where they developed programs that conformed to the model established in Chicago. Doull, for example, moved to the pharmacology and toxicology program at Kansas University Medical Center in 1967.4

  During the 1950s, when more and more departments of pharmacology were introducing courses devoted to toxicology, DuBois was writing the Textbook of Toxicology with E. M. K. Geiling, who had retired from the University of Chicago and moved to Washington, D.C., to join the Division of Pharmacology at the FDA. Published in 1959, the Textbook of Toxicology was the first of its kind in the United States. In its preface, DuBois and Geiling repeated verbatim DuBois’s argument for establishing departments of toxicology. In the text, they covered the subject of toxicology in fifteen chapters, emphasizing classes of toxic agents, for example, air-borne poisons, metals, radiation hazards, pesticides, and household poisons. The Textbook also treated the historical development, general principles, and medico-legal aspects of toxicology.

  In his chapter on pesticides, DuBois reviewed the “toxicity, pharmacological effects, and methods of prevention and treatment of accidental poisoning by the pesticides of greatest importance and usefulness at the time.”5 He divided the insecticides into three groups: the inorganic, the synthetic organic, and the botanical insecticides. DuBois neatly summarized the argument for and the challenges posed by the proliferation of insecticides.6 As a summary of risks and benefits, DuBois addressed many of the medical, economic, and biological aspects of insecticides, noting that the possibility of developing resistance necessitated a variety of insecticidal material, much like antibiotics. In describing the two major classes of synthetic insecticides, DuBois argued that individual members within each class of compounds “exhibit differences in chemical configuration and physiological actions, but their effects on mammals are essentially the same from the clinical standpoint and the compounds can, therefore, be described as a group.”7 Such thinking would eventually become very important from a regulatory, as well as a toxicological, perspective.8

  When they established the journal Toxicology and Applied Pharmacology in 1959, the inaugural editors—Frederick Coulston, Arnold J. Lehman, and Harry W. Hays—hoped that it would stimulate investigators to publish extensive toxicological studies, that it would provide an outlet for papers by students being trained in toxicology, and that it would serve to centralize important toxicological research which would in turn facilitate the work of the investigators.9 Like Geiling and DuBois, who became the managing editor of the journal in 1960, Coulston, Lehman, and Hays believed that toxicology needed to establish its independence as a discipline because toxicologists had greater responsibilities and thus needed specific training in toxicology, echoing views expressed by Dubois and Geiling in their textbook.10 Toxicology was such a broad and significant topic of study that it required disciplinary status. Doull recalled another reason for the establishment of Toxicology and Applied Pharmacology: “The reluctance of the Journal of Pharmacology and Experimental Therapeutics to publish tox studies on products or chemicals was not mentioned [in the editors’ preface] although it was widely recognized and was certainly one of the reasons for creating the new tox journal.”11 It seems appropriate that the very first paper published in Toxicology and Applied Pharmacology addressed the toxicity of organic phosphates: “The Subacute Toxicity of Four Organic Phosphates to Dogs” by Martin W. Williams, Henry N. Fuyat, and O. Garth Fitzhugh (FDA pharmacologists who had conducted many of the original studies on DDT).12

  Little more than a year later, in 1961, 9 toxicologists met to discuss forming a society devoted to toxicology. It should not be a surprise that Lehman attended (DuBois could not due to illness). A few academics and in-house toxicologists for chemical concerns also attended.13 They became the founding members of the Society of Toxicology. Some of the founders were concerned about the impact the new society might have on the Society of Pharmacology (the existing body that addressed aspects of toxicology). Still, they proceeded with their plans and elected Arnold Lehman as honorary president, Harold Hodge as president, and DuBois as vice president. By the time the first meeting was held (in Atlantic City in 1962), there were 183 charter members. The new society elected Torald Sollman, von Oettingen, and Geiling as honorary members.

  Geiling, in particular, assisted the new society by advising the founders on how they could distinguish themselves from the Society of Pharmacology. In this role, he drew on his association with J. J. Abel, who had endeavored to disentangle pharmacology from the disciplines of physiology and biochemistry. Doull recalled Geiling’s important advice to the society: focus on the unique aspects of the new discipline to separate it from the old while identifying the societal benefits of the new discipline. Describing pharmacology as the science of drugs had distinguished the field from physiology and biochemistry, and therapeutics provided a rationale for its benefit to society. Toxicology could be defined as the science of poisons to separate it from pharmacology, and safety evaluation would justify public support.14 According to Doull, Geiling believed that the society should accentuate its contribution to society and the greater good. From the outset, Geiling believed that the Society of Toxicology should stress the applications of toxicological research. Likewise, including the words “applied pharmacology” in the title of the new journal indicated a new commitment to applied research and distinguished its concerns from the pure research of the Journal of Pharmacology and Experimental Therapeutics (the main existing vehicle for publishing research reports).

  Geiling further expanded on the importance of clear definitions and boundaries: “When we define toxicology simply as the adverse effects of chemicals on living systems without including the use of that information to evaluate safety or predict risk we describe what we do but not why we do it. If our discipline focuses on this limited mission, we risk eroding public support for toxicology, the regulatory process and science in general.”15 In the very act of establishing toxicology as an academic discipline, Geiling (and the other founding and charter members of the Society of Toxicology) stressed the importance of public support. Such a preoccupation with public support seems out of place for an academic discipline, which by its very nature ought to be independent of public opinion. Perhaps Geiling, with his long association with crises that subjected science to public scrutiny dating to the Elixir Sulfanilamide tragedy, appreciated the ongoing responsibility of toxicology to regulators and the public. Although the toxicologists may have recognized the importance of public support, they left it to popular science writers to interpret toxicology’s findings for laypeopl
e.

  The consolidation of toxicology as a discipline among government and academic researchers had little impact on popular conceptions of changes in the natural world. Still, important insights could be gleaned from careful study of the growing body of toxicological literature. Several science writers simultaneously took up the subject of environmental contamination by pesticides, and it was these authors who educated the public. The best known of these writers was Rachel Carson, whose Edge of the Sea and Under the Sea Wind had informed countless Americans about the intricacies of the natural history and ecology of the seashore and oceans. There were, however, at least two other science writers examining what was known about environmental chemicals: Robert Rudd, a professor at the University of California, and Lewis Herber, who, like Carson, was a freelance writer.16

  In Silent Spring, published in 1962, Carson established a hierarchy of insecticides. She first took up the chlorinated hydrocarbons, starting with DDT, and progressively described other chemicals in the class, including chlordane, heptachlor, dieldrin, aldrin, and endrin. Carson wove details about their toxicity to mammals, birds, and fish into her descriptions of the chlorinated hydrocarbons. In just a few pages, Carson introduced such concepts as bioaccumulation, lipofelicity (the bonding of chemicals to fats), passage of chemicals from mother to offspring via breast milk, and liver toxicity, all of which occurred at the residual levels found in food. Among the chlorinated hydrocarbons, she identified endrin as particularly toxic: five times more toxic than dieldrin and many times more toxic than DDT.17 Nevertheless, Carson did not believe that chlorinated hydrocarbons posed the greatest threat to humans and wildlife: she had yet to address the organic phosphates.

  Rachel Carson, photograph by Richard Hartmann, Courtesy of Magnum Photos.

  Carson left no doubt where organic phosphates stood in the hierarchy of insecticides: “The second major group of insecticides, the alkyl or organic phosphates, are among the most poisonous chemicals in the world.”18 Carson went on to describe ironically the development of the organic phosphates as nerve gases during World War II and the incidental discovery of insecticidal properties; but it is her powerful description of the major effect of the organic phosphates on organisms, insects and warm-blooded animals alike, that sets her account apart from previous reports.

  Aware that her subject demanded precision, Carson described the normal function of the central nervous system in detail, including the critical role of a “chemical transmitter”: acetylcholine, which under normal conditions facilitated passage of nerve impulses and then disappeared. Excess acetylcholine or its continued presence could wreak havoc on the central nervous system, leading to tremors, muscular spasms, convulsions, and death. Carson proceeded to describe the critical role of cholinesterase in ensuring that the body never built up a dangerous amount of acetylcholine. By inhibiting cholinesterase, organophosphate insecticides disrupted this process: “But on contact with the organic phosphorus insecticides, the protective enzyme is destroyed, and as the quantity of the enzyme is reduced that of the transmitting chemical builds up. In this effect, the organic phosphorus compounds resemble the alkaloid poison muscarine found in a poisonous mushroom, the fly amanita.”19 Thus Carson elucidated the relation between the symptomology of cholinesterase inhibition and the normal function of the nervous system in a way that made clear the risk organophosphate insecticides, such as parathion, posed to humans.

  But what was the risk to people who were not exposed on a regular basis? Carson answered this question with additional data showing that seven million pounds of parathion was applied in the United States and the amount used on California farms alone could “provide a lethal dose for 5 to 10 times the whole world’s population.”20 What saved the people of the world was the rate at which the organophosphate chemicals decomposed, as we have already seen. They broke down into harmless components rapidly, in comparison to the chlorinated hydrocarbons, and their residues did not remain as long. Yet Carson challenged this view citing a case in which parathion posed a real threat to workers weeks after spraying: “The grove had been sprayed with parathion some two and a half weeks earlier; the residues that reduced [eleven out of thirty men picking oranges] to retching, half-blind, semi-conscious misery were sixteen to nineteen days old.” Carson noted that similar residues had been found in orange peels six months after the trees had been treated with standard doses. On this point, recall the pointed questions directed to Fred Bishopp and others during the Delaney Hearings (see chapter 5).

  Not even malathion, the least toxic of the organophosphate insecticides, escaped Carson’s perceptive analysis. Malathion, according to Carson, was almost as familiar to the public as DDT. It was used in gardens, household insecticides, and mosquito spraying. Carson revealed that nearly a million acres of Florida communities had been sprayed with malathion in an attempt to control the Mediterranean fruit fly. She questioned the assumption of many people that they could use malathion freely and without harm. According to Carson, it was only an enzyme in the mammalian liver that rendered malathion “safe,” but without the enzyme, an exposed person would receive the full force of the poison.21

  Citing research on potentiation by the FDA and DuBois, Carson explained that the synergy between two organophosphate chemicals could significantly exacerbate the effects of either or both in that one compound could destroy the enzyme in the liver responsible for the detoxification of another organophosphate. Workers could encounter different organophosphates. She noted that a salad bowl could present a combination of insecticides. Moreover, Carson cited evidence that potentiation was not limited to the organic phosphates. Parathion and malathion intensified the toxicity of certain muscle relaxants, and others (malathion included) dramatically increased the effect of barbiturates.

  Carson stressed that the advantages that organophosphates possessed over the chlorinated hydrocarbons, such as rapid decomposition, were significantly offset by the dangers of cholinesterase inhibition and potentiation. Her remarks on the acute toxicity of the various pesticides were only a preamble to her larger case: namely, the long-term risks of pesticides (particularly the chlorinated hydrocarbons) to landscapes, wildlife, and humans. In the remainder of Silent Spring, the organophosphate insecticides recede to the background. Although Carson thoroughly documented and dramatized the lingering damage to soil, water, flora, and fauna associated with chlorinated hydrocarbons, her research revealed few such problems with the organophosphates. Her one example of the effects of organophosphates on wildlife was typically dramatic. In an attempt to control flocks of blackbirds that fed on corn-fields, a group of farmers engaged a spray plane to spray a river bottom-land with parathion. More than 65,000 red-winged blackbirds (Agelaius phoenicus) and European starlings (Sturnus vulgaris) died, and Carson wondered how many other animals perished from the acute effects of this universally toxic substance. Had rabbits, raccoons, and opossums succumbed as well? Carson was most concerned, however, about unintended effects on humans, specifically workers and children who were most likely to come into contact with organophosphates.22

  Most of Silent Spring focused on the more subtle chronic effects of chlorinated hydrocarbons. Were any such effects tied to organophosphate insecticides? To support her claim that there might be, Carson recounted the case of ginger paralysis, a condition brought about when people consumed Jamaica ginger as an alternative to the more expensive medicinal products substituted for liquor during Prohibition. The artificial ginger contained triorthocresyl phosphate, which Carson noted destroyed cholinesterase in the same way that parathion did. As we saw in chapter 1 more than 50,000 people were permanently crippled by a paralysis of their legs accompanied by destruction of nerve sheaths and the degeneration of spinal cord cells. Carson compared the effects of organophosphate poisonings to ginger paralysis. Even malathion had induced muscular weakness in chickens and, just as in ginger paralysis, the sheaths of the sciatic and spinal nerves were destroyed. Carson even found evidence that regular exposure to o
rganophosphate insecticides might induce mental disease.23

  By now it should be clear that Carson believed that the organophosphates posed an equivalent, if not greater, risk to wildlife and humans than the chlorinated hydrocarbons. When she turned to solutions, Carson advocated biological control. She cited numerous cases in which natural predators and diseases had been introduced to control insect outbreaks. Judicious use of insecticides played a minor role in Carson’s vision of pest control, but they needed to be phased out eventually. An awareness of ecological relationships should guide all endeavors to reduce the depredations of insects and other organisms deemed pests, according to Carson: “Only by taking account of such life forces and by cautiously seeking to guide them into channels favorable to ourselves can we hope to achieve a reasonable accommodation between the insect hordes and ourselves.”24 No chemical insecticide offered a genuine solution: “As crude a weapon as the cave man’s club, the chemical barrage has been hurled against the fabric of life… . These extraordinary capacities of life have been ignored by the practitioners of chemical control who have brought to their task no ‘high-minded orientation,’ no humility before the vast forces with which they tamper.”25

  A number of historians and biographers have analyzed the dramatic response to Silent Spring on the part of consumers, scientists, industry representatives, and legislators.26 In general, the response to Silent Spring split along predictable lines. Carson found her greatest support from environmental activists like Roland Clement, who presented the book’s chief arguments in many presentations to the public and various branches of government. Predictably, chemical companies mounted a savage campaign to discredit Carson and the claims she made in Silent Spring. One threatened to bring suit against the New Yorker after Carson’s articles appeared; William Shawn, longtime editor, allegedly relished the possibility of unexpected publicity for the magazine. Still, some environmental scientists who were apparently impartial distanced themselves and criticized some of Carson’s interpretations of the evidence of environmental and human health hazard. One wrote that Silent Spring was “full of truths, half-truths, and untruths as far as the wildlife was concerned, and I have nothing to say about the human health thing.”27