NERVEASE CO., MANUFACTURER
NERVEASE CO. BATTLESHIP REVENUE CANCELS
Nervease was one of the earliest patent medicines specifically advertised as a headache and fever remedy. The principal ingredient of virtually all of these pioneer products, classified in medical terms as analgesics (pain relievers) or antipyretics (fever reducers), was acetanilide. Most of those who used Nervease, and the many other proprietary medicines like it, never realized that acetanilide was a poison that could cause their death. However, acetanilide’s potentially poisonous nature became a major flash point during the Pure Food and Drug Act wars. Since proprietary medicine manufacturers regarded their formulae as private, they did not disclose their ingredients. From the end of the Civil War, when proprietary medicines became readily available, to 1906, they successfully blocked governmental efforts at all levels to force such disclosure. Even after the original 1906 federal legislation mandated listing contents on the packaging, product advertising remained completely unregulated. Not only did manufacturers who complied with the law by listing acetanilide in small print not warn of its potential harm, some even affirmatively averred in much larger print that their products contained no poison, or even in the accompanying literature denied its presence. The fight to banish acetanilide as medicine was one of the longest and most difficult waged by the Food and Drug Administration, continuing for a full generation after 1906.
Yet, acetanilide was regarded as a miracle drug when it was first found to be an antipyretic at the end of the Nineteenth Century. Actually, that entire century was an age of astounding chemical discoveries. As coal became an important source of fuel, the entire field of organic chemistry took shape, for the clever use of coal’s waste products, most notably coal tar, led to the discovery and exploitation of a multitude of useful chemical compounds. The earliest significant coal tar derivative was aniline discovered in 1826. It soon became the basis of synthetic dyes, giving rise to an entirely new industry. Acetanilide, discovered a few years later, also found use in the dyeing industry, but, by mid-century, had proved to be of only minor importance.
Suddenly, when acetanilide’s ability to reduce fevers was discovered in 1886, it was heralded as the newest wonder of the age. As with many such amazing drugs, the discovery was purely serendipitous. Arnold Cahn and Paul Hepp, two young assistants in the department of medicine at the University of Strassburg in Germany were assigned by the superior, Adolf Kussmaul, to investigate cures for intestinal worms by dosing patients with naphthalene, itself another coal tar derivative, which had already proved useful as an internal antiseptic in certain limited circumstances. However, the test results proved problematic. Cahn and Hepp found that the drug they were administering did not reduce worm infestations, but did reduce the fevers of patients, an effect never previously observed when treating subjects with naphthalene. Since naphthalene had never been shown to influence body temperature, Cahn and Hepp ultimately reasoned that they must have actually administered another substance to their patients. When they requested their chemical supplier, Kopp’s Pharmacy of Strassburg, to re-check its records, they discovered that Kopp’s had, in fact, sent Hepp acetanilide. Once Cahn and Hepp published their findings hailing the discovery of a new antipyretic, an acetanilide manufacturing industry immediately sprang up in Germany. Its low cost of production meant the proprietary medicine industry in the United States quickly adopted it both as an analgesic and an antipyretic, and obstinately clung to it as a principal ingredient of these classes of proprietaries long after its poisonous quality had been revealed.
To those who ingested large quantities of acetanilide, the danger manifested itself in the form of cyanosis, a bluish cast to the skin which people develop when their bodies are seriously starved for oxygen. When these cyanotic patients reported that they had recently taken the new acetanilide-based headache remedies, doctors quickly discovered that when acetanilide is metabolized by the body, it partially transforms to aniline. From treating a generation of poisoned dye plant workers, doctors already knew that aniline altered the structure of hemoglobin, the complex protein in the red cells of blood which carries oxygen from the lungs throughout the body. Aniline induces methemoglobinemia, a condition in which methemoglobin — oxygen binding sites structures (heme groups) containing ferric ions [FE+3] rather than ferrous ions [FE+2] — begins to supplant the normal four heme groups within the hemoglobin protein molecules as they travel in the blood through the lungs. Ferric ions (which eventually were demonstrated to have their crucial d sub-shell valence orbitals, where the oxygen electrons would orbit when they bonded, blocked by its own higher energy electrons) do not form the requisite bond with oxygen that the ferrous ions in hemoglobin do. As available oxygen binding sites fall within the hemoglobin protein, the shape of the entire hemoglobin protein alters causing the remaining ferrous ion heme groups to hold their own oxygen molecules more tightly, further reducing the normal oxygen exchange rate until the body can literally starve for oxygen. Blood starved for oxygen reflects blue, hence the cyanosis that doctors observed.
Despite a quickly accumulating body of medical evidence demonstrating its danger, and warnings published in medical journals from the 1890s to the 1930s, acetanilide was cheap and accessible, so the proprietary industry capitalized on its availability and continued to use it for fifty more years. The argument made by the industry then, as it is still made in certain kinds of disputed cases today, is that even if a product is poison, if its administration is properly controlled, the benefit experienced by the patient outweighs the potential harm. The difficulty in the case of acetanilide was that it was readily available and control, in the form of dosage, was left completely in the hands of the individual consumer.
Nervease was a typical fever reducer. It manufactured by the Nervease Co. in the Jamaica Plains district of Boston. The proprietor of the Nervease Co. was Joseph B. Locke, a pharmacist who otherwise ran a modern drugstore. In 1892 he is recorded as having petitioned the City of Boston for the latest in technology, an electric street light, to illuminate the corner where his store was located, and, in 1899, his store was praised in a trade magazine as featuring the latest and most up-to-date features:
However, little now can be ascertained about Locke himself, perhaps, in part, because he bears a fairly commonly occurring name. While there are historical entries about many different Joseph Lockes, this particular Joseph Locke, having never been a grandee of the proprietary medicine industry, was never profiled in the kind of Whos-Who-type booster books of the pre-World War I era. Census records do outline the barest bones of his life. They reveal he was born in Waltham, Massachusetts in 1857 of parents, Hozea and Elizabeth Locke, who themselves had come from Maine. In 1882, he married Marietta Skinner, and had a son, Edward. His wife died in 1897. In 1900, his son still lived with him, but by 1910, he listed himself as a widower, living only with a housekeeper. By 1920, he was living with his son’s family and in 1930 he disappears even from his son’s household. Possibly he died as late as 1936. Modern records reveal that his grandson and namesake died in 2003 at age 86.
As a product, Nervease gained greater prominence than its maker. Locke began to place ads for it around 1890, just as soon as acetanilide became available commercially, and by 1893, Locke was actively promoting Nervease in a grand manner:
By 1898, Locke was employing an ad agency to handle the Nervease account, and it was a significant enough client so the advertising trade papers took note when J. J. Riegel of Boston carried its business with him during his move from the Pettingall & Co. ad agency to the newly formed Walter C. Lewis Co. ad agency.
Despite the continual warfare over the use of acetanilide and the gradually more stringent standards, hewing toward “truth in advertising” by insisting on demonstrable scientific evidence to support advertised claims imposed by amendments to the Pure Food and Drug Act, Nervease continued to be manufactured and sold for almost fifty years with acetanilide as its principal medicinal ingredient. In 1939, the government finally brought this action against Nervease:
Two significant observations shed light on this proceeding and decision. Note by this late date the company was both disclosing that acetanilide is present in the medicine, as was required by the letter of the law, and even was counseling in its literature that too many doses could not be taken too close together in time, as medical prudence had by that time certainly suggested. Nevertheless, the government alleged that the false and misleading claims lay in the company’s reliance on testimonials only to prove medical efficacy and the potential for poisoning in the dosage frequency and duration suggested in the company’s literature.
Note also that the legal action was brought in the peculiar way authorized in the 1906 act, not against the company, but rather in the form of a “libel,” or a literal seizure action of the product itself. The company did not contest the government’s charge, as the small proprietary companies like the Nervease Co. often did not. The court would then enter judgment against the product seized by the government and order it destroyed. This form of litigation did limited harm to the company and conveyed limited benefit on the public. The company’s business was disturbed only to the extent that it lost that particular seized shipment of its goods and could otherwise still continue with its established business patterns. The public good was served to the extent that the judgments were published and distributed by the FDA, and read and heeded by medical professionals and the public. Fearing such bad publicity, wiser proprietary companies altered their ingredient formulas or advertising literature after a single judgment entered against them. A second similar judgment had to be entered against Nervease in 1951. After that encounter with the law, Nervease Co. disappears from the public record.
Ultimately science itself, not the law, effaced acetanilide as an ingredient in headache and fever reducers. In 1948, doctors finally established that the analgesic and antipyretic properties of acetanilide were contained in paracetamol, the other by-product produced when acetanilide is metabolized in the body. Paracetamol is equivalent to acetaminophen, which by then, could be manufactured cheaply and safely by itself. No longer did any manufacturer have to use acetanilide to produce the relief the antipyretics and analgesics were meant to provide. Thus, cost efficiency rather than medical safety removed acetanilide from consumer products. Self-medicators and current buyers of over-the-counter medications should pay heed for the same dangers still lurk in the market place.
© Malcolm A. Goldstein 2016