Historical Context

In order to place the impact of fluoxetine into the context of medicine, an examination of the history of the drug industry will be made. There have been many reports of amazing drugs, many of which were later found to be false. The phrase "drugs on the market" was used in the early part of this century to indicate items that had lost their market value. The expression originated after so many drugs that had great public attention and prolific sales failed to have the wonderful curative effects that they were advertized to have (Walsh, 1923). The modern state of the industry can be compared to its origins in apothecary, the era of "miracle cures," and the period of major and often accidental scientific discoveries during the middle of the twentieth century.

The American pharmaceutical industry has been operated for almost two centuries. From a cottage industry, it has grown into a large number of corporations creating thousands of different pharmaceuticals. The foundation for the pharmaceutical industry in the United States can be traced back to Philadelphia in the period between 1818 and 1822. The American market was formerly dependent on Britain, but as a result of the economic disorder created by the War of 1812 and its aftermath, the flow of British pharmaceuticals was cut off and the American industry was born (Liebenau, 1987).

The industry had an easy start. There was a lucrative market for pharmaceuticals, demand was universal and constant, and profits were high. Production began by turning the laboratories of pharmacies into manufacturing plants. Any apothecary could be outfitted for competition on the wholesale market by having a boiler room, a drying room and a storage area (Liebenau, 1987).

In Britain, apothecaries had formed a guild and were in direct and open competition with doctors for the same types of pharmaceutical services. In the United States, the relationship was more cooperative. The "prescription" drug manufacturers controlled information available to the public. Instead of providing information directly to the consumer, advertizing was instead directed toward the medical profession. When consumers received information about the products, it would come from their physician, a highly trusted source. In this way, the consumers would judge the information as more scientific, since the source was perceived as an expert on such matters. This lead the image of the prescription drug manufacturers to be tied to science and medicine. This scientific image was forcefully contrasted to the crude production methods of the "patent" medicine makers (Liebenau, 1987).

The "patent" medicine makers were the main competition to the companies that made medicines prescribed by doctors. These "remedies" were advertized extensively to have "cure-all" powers when, in actuality, they were controversial and had questionable value. The remedies might be sold under the name of a fictitious doctor, although this doctor may not have invented the remedy. The recipe was often said to be an "old indian secret," passed down though the generations. It was sometimes said to be revealed to an "old negro" or other character, who would act as an informant to another "old negro" or to the fictitious doctor. The nostalgic belief in the folktales of "ancient experts" was the key to the credibility of these remedies (Liebenau,1987).

In the middle of the Nineteenth Century, one patent medicine called the Theriac Cure-all, was used more than any other medicine. Many elderly people swore that they could not have survived the winter, lived so long, and felt so good without it. They reported that without the medication, they were "languid and depressed" but after taking the medication, they "felt like new people" (Walsh, 1923 p. 37).

Claude Bernard, a famous French physiologist, had once worked as a druggist's apprentice. He was astounded to discover that the "Theriac Cure-all" made by the druggist consisted of a mixture of all the spoiled, mismeasured and unlabeled medicines diluted with water (Walsh, 1923). Other remedies that people swore by were laxatives and purgatives such as antimony and calomel (Walsh, 1923).

Questionable remedies were not limited to unscrupulous druggists and profit minded charlatans alone. The highly acclaimed Bishop Berkeley, who influenced the American philosopher Jonathan Edwards, also had his panacea. Berkeley's recipe was to take a gallon of water and stir in a quart of tar. This would sit for two days, and the clear water would be poured off. Berkeley claimed that the remedy cured "gout, fevers, coughs, pleurisy, peripneumony,...scurvy, liver disease and dropsy. It was also reported to cure what was later known as cancer, and was said to be "excellent for teeth and gums" (Walsh,1923 p. 44). In contrast, in the same time period, the process of anaesthesia was condemned as flying in the face of nature and opposing the will of God (Weatherall, 1990).

The prescription medicine makers tried to distance themselves and their medications from folk remedies by cultivating a modern, scientific image. In retrospect, the beginning of the pharmaceutical industry was not necessarily as well grounded in scientific research as advertized, however there were notable advances that brought reality closer to the image portrayed by the industry (Liebenau, 1987).

A great increase in the production capacity of pharmaceuticals was made by the introduction of steam driven stirring and grinding apparatus. This allowed pharmacists to concentrate on production, and transformed them from operating apothecary stores for the public into manufacturers who provided supplies of medication. The image of scientifically oriented manufacturing was brought closer to reality by George K. Smith of Smith Kline and Co.in the 1850's, when he began to make precisely measured amounts to supply physicians (Liebenau, 1987). The advent of the Civil War brought conditions which encouraged pharmacists to produce on a larger scale. The government initiated contracts for large amounts of medication, which caused a necessary increase in production capacity.

An advance in the public understanding of medications occurred at the turn of the century, that was the reclassification of drugs based on physiological action. This was urged by Horatio C. Wood, and changed the perception of the medications to a more modern perspective. A major event in scientific medicine was Emil Behring's discovery of the diphtheria antitoxin in the 1890's. This was the first of the biological therapeutics. The antitoxin dramatically demonstrated the possibilities of a bacteriological understanding of disease. This opened up a whole new area for the expansion of the pharmaceutical industry. This was also a conceptual advance, for diseases would now be considered to be caused by outside agents instead of a misfunction of the human body (Liebenau, 1987).

Influences on the industry from the outside became more prevalent at this time. The practice of reviewing pharmaceuticals in journals such as the Journal of the American Medical Association came into effect. Physicians reviewed these articles for information about the drugs, and even wrote to the journals with excerpts from their professional experience. This set into place a mechanism to review the effects of the drugs, and evaluate them outside of the industry (Liebenau, 1987). Government regulation was another influence on the industry. In 1902, Congress passed an act to control the production and sale of biological pharmaceuticals. Manufactures were required to be licensed by the Secretary of the Treasury. Each package of medication was required to be labeled and dated. The requirement of a revenue stamp was brought about when tonics that consisted mostly of whisky, water and bitter herbs were recommended to be given to pregnant women and young children (Weatherall, 1990).

The next intervention was the 1906 Pure Foods and Drugs Act. This act occurred partially due to the reaction to Upton Sinclair's novel, The Jungle. The story of poor manufacturing conditions and product quality inspired individuals like Harvey Wiley at the Department of Agriculture. Wiley was a major proponent of the bill and his major concern was the food adulterers. Wiley asked for and received the legal power to enforce reasonable standards of purity for processed foods. Support for government regulation also came from within the pharmaceutical industry itself. Large drug manufacturers like Smith Kline who already standardized drug amounts found it to be to the advantage of their laboratories to enforce regulation. These manufacturers had already met the proposed standards, and regulated amounts would give them the advantage of a head start when the law took effect. Although there were abuses, very few of the early legal cases of violation of the Pure Foods and Drugs Act were bought against pharmaceutical manufacturers. Most of these cases resulted in small fines (Liebenau, 1987).

In 1911, Julius Morgenroth found that mice infected with a strain of Trypanosoma brucei could be cured with large doses of quinine. Ethylhydrocuperine, a derivative of quinine, was marketed as a remedy for pneumonia and was prescribed until the advent of sulfapyridine in 1938. This was the first anti-bacterial chemotherapeutic agent used by modern medicine (Sneader, 1985).

The next major influence on the industry came in 1935, when a group of German scientists and physicians discovered sulfanido-chrysoidine. Marketed under the brand name Prontosil, it was used in the treatment of staphylococcal, streptococcal and other infections. Although not greatly significant in itself, Prontosil launched a chain of events that led to "the great drug therapy era" (Silverman, 1974).

During the middle of the century came the conquests of many different types of infections and relief from crippling diseases such as polio. There was also a great increase in the number of prescriptions written by doctors, creating greater public expenditures for drugs, and growth of the drug industry (Silverman, 1974).

In this era, it was easy to think of the pharmaceutical industry as working for the good of humankind. The Salk vaccine for polio had a great effect on the American public. After a polio epidemic in the early 1950's, polio was a great concern to American parents. The relief brought by the vaccine had a uplifting effect on the populace (Rogers, 1992). It would have been difficult to argue against the financial gains to the pharmaceutical industry from these innovations.

Today pharmaceutical manufacturing is a multi-billion dollar industry (Silverman, 1974; Breggin, 1991). The industry is connected to physicians through medical and psychiatric journals, and to the government through the Food and Drug Administration. The FDA regulates the approval process for the sale of pharmaceuticals.