Hamilton’s research documented effects of lead poisoning, but it remained for other researchers to determine pathways of toxic insult. In 1921, several researchers at Harvard Medical School, where Hamilton had joined the faculty as professor, launched what became known as the “lead study.” Cecil Drinker and Joseph Aub, the Harvard faculty members who led the lead study, envisioned a study of occupation disease grounded in science. Both strove to distinguish their work from Hamilton’s socially conscious efforts. Although David Edsall, Drinker, and Hamilton negotiated with the lead companies for “full scientific liberty,” Aub never forgot his obligations to the companies he studied, even as he developed a clinical and scientific research agenda. In a critical early move, Aub called upon a chemist—Lawrence Fairhall—to develop a more reliable method of analyzing minute amounts of lead in biological material. In addition to the chemist, Aub would soon incorporate a pathologist and physiologists into the research of the lead study, which anticipated the spirit of interdisciplinary collaboration that exemplified the study of toxicology. Moreover, Sellers argued, the lead study placed the toxicological approach at the core of studies of industrial disease.17 The Harvard study shaped the toxicological approach to the study of industrial disease in other important ways. Fairhall’s method of quantitative analysis provided a uniform basis for comparing lead levels in workers to the levels in their surroundings. Researchers could compare lead levels within factories and between industries. With the development of accurate techniques of analyzing other chemical hazards, dangers could be placed along single quantitative scales, typically in the same units (milligrams per ten cubic meters). Aub and the Harvard researchers also incorporated laboratory experiments into the lead study. These experiments, using both humans (volunteers) and animals, enabled the researchers to isolated specific workplace causes and effects. Such experiments transferred the research out of the workplace, to laboratories where researchers could study the more dangerous effects of lead and other toxins on cats or rabbits including pathological examination, which was unthinkable for humans, even volunteers. Finally, even as Aub and the other researchers in the Harvard lead study shifted the locus of the study from the workplace to the laboratory, they maintained strong ties to managers and doctors at some of the largest corporations in the U.S. Sellers argued somewhat ironically that the independent course of their research depended on continued corporate support.18
One of the first corporations to develop its own toxicological laboratory happened to be the largest chemical company in the U.S.: DuPont. Wilhelm C. Hueper (1894–1978) lobbied for what became the Haskell Laboratory at DuPont. Hueper made many important contributions to the study of occupational and environmental carcinogenicity over the course of a long career.19 After completing his medical education in Germany, Hueper immigrated to the United States, where he held various posts in academia, industry, and government. As chief pathologist at the University of Pennsylvania’s Cancer Research Laboratory and director of pathology at the American Oncologic Hospital, he asked to visit the DuPont Dye Works at Deepwater, New Jersey. At the factory he discovered in use aromatic amines that he knew, based on his experience in German factories, to cause bladder cancer. Through channels, Hueper notified Irénée du Pont, vice chairman of the board, of this potential hazard and recommended that DuPont establish an in-house biological laboratory to conduct toxicity studies. Internally, George Gehrmann advocated for a new lab, and DuPont’s Haskell Laboratory open on January 22, 1935, under the directorship of Wolfgang F. von Oettingen. Hueper joined Haskell after the University of Pennsylvania declined to renew his contract in the spring of 1934. Dow and Union Carbide established similar laboratories in the same year.20
Oettingen set as the first priority to determine the mechanism of the formation of bladder tumors. By late 1935, seventy DuPont workers had developed bladder tumors, and Hueper and his colleagues Frank Wiley and Humphrey D. Wolfe launched a long-term experimental study of dogs that were fed chemicals, including beta-naphthylamine (“beta”). After three years, the beta-fed dogs developed tumors, whereas those fed the other chemicals remained tumor free. Hueper and his colleagues published their findings, much to the chagrin of the DuPont board, which soon barred Hueper and other Haskell scientists from publishing their results. In a productive three years, Hueper conducted animal studies on a range of DuPont products, including seed grain vermicides, carbon disulfide, ethylene glycol and related solvents, refrigerant gases such as Freon, and Teflon coatings for kitchen utensils, but DuPont management fired him in November 1937 and stipulated that he never publish his research from Haskell. Hueper refused to comply with Du-Pont’s stipulation. Historian Robert Proctor has argued that, as a result of his refusal, DuPont hounded Hueper for the rest of his career, even threatening him with a lawsuit when he was invited to speak before the International Union against Cancer.21
Nevertheless, Hueper set to work on his magnum opus in 1938 and published his authoritative Occupational Tumors and Allied Diseases in 1942. Although Hueper recognized that acute poisonings represented a significant problem in the workplace, he argued that long-term chronic effects, like cancer, were far more important. But since chronic effects often did not manifest until months or years after exposure, physicians might not consider the particular cause of a particular disorder. In addition, Hueper suggested that most occupational cancers were preventable with proper procedures to protect workers, but he doubted that society would accept the necessary precautions to prevent cancer in the workplace.22 Still, support and participation of U.S. corporations proved to be critical to the development of toxicology and, as Sellers has shown, the toxicological approach to occupational medicine. Notwithstanding these developments in corporations, regulators and consumer advocates found recent legislation lacking.
Despite the general sense of satisfaction with the passage of the 1906 food and drug law and the 1910 insecticide law, as well as the advances in toxicology emerging from research in industrial hygiene, regulators soon confronted the limitations of the legislation. By 1933, several distinct groups questioned the efficacy of the laws. As chief of the Food and Drug Administration, Walter Campbell struggled with the law, particularly because it often fell to him to explain its deficiencies. In one case, the assistant secretary of agriculture, Rexford Tugwell, returned a routine spray-residue letter with a question along the lines of, if lead arsenate was a poison, why didn’t the FDA prohibit its use? Reflecting on the moment years later, Campbell’s assistant, Paul Dunbar, wrote: “The effect on all of us after these long years of fighting a lone battle against spray residues was like a kick in the teeth.”23 No one was more certain of the FDA’s inability to ban lead arsenate based on the 1906 law than its chief. Regulators could not address adequately cosmetics, patent medicines, adulteration of food, and even false advertising under the provisions of the current statute.24
In the 1930s a new generation of consumer advocates emerged, voicing a sharp critique of the inadequacy of federal food and drug law. In 1933, Arthur Kallet and F. J. Schlink, both with Consumers’ Research, Inc., wrote 100,000,000 Guinea Pigs: Dangers in Everyday Foods, Drugs, and Cosmetics, which constituted a broad indictment of the gaps in existing policy. The title suggested that food, drug, and cosmetic producers treated the 100,000,000 Americans like guinea pigs by exposing them to unknown and unrecognized risks. Kallet and Schlink cited numerous cases that the FDA could not (or would not) prosecute, ranging from food residues to prescription drugs to cosmetics, not to mention cases of false advertising. They split their critique between the 1906 law and the companies that flouted the spirit (if not the letter) of the law. They wrote: “Using the feeble and ineffective pure food and drug laws as a smokescreen, the food and drug industries have been systematically bombarding us with falsehoods about purity, healthfulness, and safety of their products, while they have been making profits by experimenting on us with poisons, irritants, harmful chemical preservatives, and dangerous drugs.”25
The boo
k 100,000,000 Guinea Pigs became a model for other consumer advocates, among them Ruth deForest Lamb, who published American Chamber of Horrors: The Truth about Food and Drugs in 1936. Lamb ratcheted up the level of concern, focusing particularly on American housewives and their families. In her first chapter, “Why Doesn’t the Government Do Something about It?,” Lamb commanded her readers’ attention right from the opening paragraph: “You’ve been told you take your life in your mouth every time you bite into an apple or brush your teeth. All of your food is injurious, and your drugs and cosmetics are dripping with poisons. Anesthetic ether is always adulterated, and the ergot on which physicians depend to stop the hemorrhages of childbirth is impotent—unless, of course, it comes from Spain.”26 Thus she asserted that American consumers faced grave dangers through callous abuses on the part of the companies that produced foods, drugs, and cosmetics. Residues of pesticides on fruit were among the most worrisome to scientists and advocates.
As we have seen, chemical insecticides such as lead arsenate and Paris green proliferated during the nineteenth century. Use of these heavy metal insecticides rose dramatically during the first three decades of the twentieth century (table 1). Agricultural applications of arsenates quadrupled in the decade between 1919 and 1929. The arsenates appealed to farmers as broad-spectrum insecticides, which is to say, they were very effective against a wide range of insects. In Before Silent Spring, Whorton analyzed the toxicological studies of insecticide residues conducted between 1900 and 1920. Entomologists found themselves caught in a tug of war between the need to protect people from poisons while simultaneously protecting them (and their foods) from insects. The insect threat could be measured in precise fiscal terms, but the language of toxicology lacked the sense of immediacy and precision. Thus, Whorton concluded, “The imbalance between these opposed considerations easily tipped entomologists toward optimistic conclusions, and spray residues were generally dismissed as being considerably less dangerous than they actually were.”27 English regulators had been far more aggressive about limiting exposures to arsenic residues, limiting arsenic to 1/100 of a grain per pound (equivalent to 1.43 mg/kg)28 on fruit in 1903 in direct response to the findings of a Royal Commission on Arsenical Poisoning, which was led by Lord Kelvin.29 U.S. regulators ignored this standard until 1925, when the English threatened to ban American fruit imports. In 1927, the FDA restricted apples intended for export to 1/100 of a grain per pound of arsenic trioxide (the 1903 British standard), but apples intended for domestic consumption could have as twice as much arsenic per pound.30
Table 1
Insecticide Use (estimated) in the U.S., in Pounds, 1919, 1923, and 1929
In 1933, C. N. Myers, a physiologist, and Binford Throne, a clinician, jointly presented the results of several years of research into the risks of spray residues at the eighty-fifth meeting of the American Chemical Society. The researchers acknowledged the considerable costs of international legislation regulating pesticide residues, but they wondered about the costs in terms of human life and health. Previous studies had quantified the arsenic residues on fruit from 0.08 to 0.77 mg per apple and concluded, “No fruit carried sufficient lead arsenate to cause fatal poisoning through the consumption of one piece.” But such a statement regarding acute toxicity (resulting in death) neatly sidestepped the problem of chronic toxicity as did subsequent comments, for example, “The case is not clear as to the possible injurious effects from long continued daily consumption of fruits carrying relatively small residue.”31 Although there were cases of acute poisoning in which victims died within days of consuming contaminated fruits or vegetables, Myers and his collaborators worked to sharpen the picture of risks associated with increased arsenic use in a variety of products, among them glucose, drugs, lotions, tobacco, foods, fruits, vegetables, larvicides, and especially insecticides. The risks included eczema, keratosis, peripheral neuritis, disturbance of vision, and neurological symptoms. In addition to the risks borne by humans, Myers noted the destruction of large numbers of bees and birds as a direct result of lead arsenate spraying.32
In 100,000,000 Guinea Pigs, Kallet and Schlink decried spray residues and condemned the FDA for apparent indifference to the problem. The Guinea Pigs authors cited arsenic poisonings in the U.S. and England and wondered why the U.S. had been so slow to adopt stricter standards for arsenic residues on fruits and vegetables despite ongoing scientific research and congressional hearings. Of greater concern, however, were lead residues (concern about lead exposures drove the development of occupational medicine, see below). The FDA recognized the considerable hazard posed by lead and banned from the market fruits and vegetables containing residues of lead. However, there was little evidence of enforcement of this strict standard. One researcher tested apples for residues of lead and arsenic and found that none of the forty-five samples were free of either chemical. More troubling, some of the apples carried sixty times as much lead as arsenic trioxide.33
It is this sorry state of affairs that returns us to the frustration of Walter Campbell, administrator of the FDA. When the new assistant secretary of agriculture, Rexford Tugwell, queried him on the FDA’s failure to ban spray residues, Campbell responded that the department’s commitment to the agricultural industry forced the FDA to adopt a lenient policy with respect to growers. The surprisingly receptive Tugwell agreed with Campbell that the 1906 food and drug law needed revision and within hours secured approval from the president for a revision of the act.34 Tugwell promptly introduced a complete revision of the 1906 law into Congress, but industry representatives universally condemned the bill, particularly a provision that would have required drugs to be licensed. A conservative homeopathic physician named Royal S. Copeland, however, strove to forge a compromise, which would produce a bill with the potential to pass through Congress. The compromise bill passed the Senate but remained stuck in a House committee.
Meanwhile, by 1930 insecticide use in the United States had exploded to unprecedented levels. Farmers sprayed nearly sixty million pounds (27,215,542.2 kg) of the two most popular insecticides (calcium arsenate and lead arsenate) on crops in 1929. Only rarely did spray residues result in cases of acute poisoning and death, but scientists and physicians began to link common ailments like eczema and stomach upset with chronic arsenic and lead toxicity. International regulation of spray residues on fruit imported from the United States prompted review and revision of standards, but levels remained much higher for fruit sold in the U.S.35 Even Kallet and Schlink’s exposé provoked a relatively minor protest. Most Americans remained complacent, assuming that the 1906 law protected them from contaminated food and drugs, and farmers relied on the Insecticide Act of 1910 to keep insecticides free from adulterants. Nevertheless, by 1933 regulators had received executive approval to revise the pure food law. Tragically, an epidemic of poisonings failed to accelerate the legislative process.
During Prohibition following passage of the Eighteenth Amendment, many people sought alternatives to alcohol. Alcoholic extract of ginger had been available since the nineteenth century as a patent medicine and as such it provided a source of ethanol that could be marketed legally. “Jamaica ginger” or “jake” referred to a fluid extract of ginger that was sold widely during Prohibition. The United States Pharmacopoeia (USP), the official body established to monitor patent medicines, attempted to curb abuse of Jamaica ginger by requiring that the content of the extract contain five grams of ginger per one milliliter of solvent, which was usually ethanol. But this formulation tasted so bitter that consumers rejected it as non-potable. Pharmacies and roadside stands sold Jamaica ginger, typically in two-ounce bottles, as a remedy for a host of ills. The high alcohol content (up to 80 percent) meant that consumers could buy a two-ounce (56.7 g) bottle of jake for thirty-five cents and mix it with a soft drink, thus creating an inexpensive intoxicating beverage. USDA agents monitored producers by boiling samples of jake and weighing the remaining solids to ascertain that they conformed to the proportion dictated by t
he USP. Jake manufacturers cut costs by substituting various adulterants, such as castor oil, glycerin, and molasses, for the more expensive ginger solids.36
Triorthocresyl phosphate or TOCP appealed to some jake producers as an additive because, unlike other compounds, it would not evaporate away upon analysis by USDA agents (thereby upsetting the ratio of five grams of ginger per one milliliter of solvent). One researcher referred to TOCP as one of the most stable esters used in commercial organic chemistry. It was used in large quantities under various trade names as a liquid plasticizer and in lacquers, leather dopes, and even airplane finishes. Most manufacturers used castor oil as the adulterant to produce a palatable ginger extract that maintained the appropriate ratio of key ingredients. But Harry Gross, president and general manager of Hub Products Corporation, sought alternatives when the price for castor oil climbed at the end of the 1920s. Gross consulted a Boston chemical wholesaler for suggestions of other stable solvents. The wholesaler initially recommended ethylene glycol, which Gross rejected as too volatile, having subjected the resulting Jamaica ginger compound to mock testing. Next, Gross tried diethylene glycol, which produced similar results. Note: Gross rejected ethylene glycol and diethylene glycol on the grounds that the two compounds were too volatile rather than for their toxicity (see below for detailed discussion of diethylene glycol and the Elixir Sulfanilamide tragedy) Finally, Gross settled on Lyndol, which was a mixture of TOCP. When it passed the volatility test, Gross asked the chemical wholesaler about its toxicity. The wholesaler relayed this question to the Celluloid Corporation, which produced Lyndol, and the chemical company noted that it was presumably nontoxic. Gross purchased 135 gallons (511 liters) of Lyndol and began mixing and shipping the new jake.37
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