Since early civilizations, people have been concerned about the quality, safety, and integrity of foods and medicines. Curiosity about these matters began thousands of years ago.

In the Bible’s Old Testament, the first chapter of the Book of Daniel describes a clinical trial. After conquering Israel, Nebuchadnezzar, the king of Babylon, ordered that several Jewish youths be brought to his palace to serve for 3 years. The children would be fed and taught just like the king’s own children. Among the youths was Daniel, who did not wish to defy Jewish law by eating the king’s meat or drinking his wine. Daniel asked that the Jewish youth be allowed to eat peas and beans (“pulse”) and to drink water instead of wine. Melzar, the eunuch assigned to watch over the youth, was hesitant, fearing Nebuchadnezzr’s wrath should Daniel and the other youth become ill. Daniel suggested a 10-day experiment of feeding the Jewish youth pulse and water, while the king’s servants continued the rich meats and wine as prescribed by the king.

The result: Daniel 1:15–1:16, King James Version:

And at the end of ten days their countenances appeared fairer and fatter in flesh than all the children which did eat the portion of the king’s meat.

Thus Melzar took away the portion of their meat, and the wine that they should drink; and gave them pulse.

The first known English food law was enacted in 1202, when King John of England proclaimed the Assize of Bread, a law prohibiting the adulteration of bread with ingredients such as ground peas or beans (1). One of the earliest food and drug laws in the United States was enacted in 1785, when the Commonwealth of Massachusetts passed the first general food adulteration law regulating food quality, quantity, and branding.

Since these early times, many events, often accompanied by tragic outcomes, have raised additional concerns related to food and drug safety.

As we progressed toward more modern times, clinical trials began using specific experimental designs and collected information in numbers rather than in statements such as “looked healthier and better nourished.”

One of the earliest examples of an experimental design can be traced to 1767 and William Watson, who was the physician for the Hospital for the Maintenance and Education of Exposed and Deserted Children in London, England. At that time, the leading cause of death among children in London was smallpox, and the governors of the hospital ordered that all children who were not already immune to smallpox be inoculated. Although inoculation was already an accepted practice, Watson was curious about the benefit of routinely using mercury as a concomitant treatment with the inoculum.

In October 1767, Watson performed his first experiment, giving 31 children the same inoculum and then dividing them into three similar groups:

• 10 children (5 boys and 5 girls) received a mixture of mercury and jalap (a laxative)
  
• 10 children (5 boys and 5 girls) received an infusion of senna and syrup of roses (a mild laxative)
  
• 11 boys received no concomitant medicines

Watson understood that he would need to clearly show a lack of efficacy in the use of mercury to convince others to abandon its use. Therefore, he made every effort to create similar groups for comparison. He not only included groups of children of similar ages and both sexes but also demanded that all of the children eat the same diet, wear similar clothes, play in the same fields, and sleep in the same dormitories. In each experiment, the children were inoculated at the same time and place with the same material. Watson understood that “it was proper also to be informed of what nature unassisted, not to say undisturbed, would do for herself” (2). His introduction of an untreated control group, the 11 boys who received no concomitant medicines, was his way of determining the outcome when nature was “unassisted.” Watson’s method allowed him to compare the results in the three groups (3).

Also during the mid-18th century, James Lind was investigating the cause of and cure for scurvy among seamen. In at least two respects, Lind’s Treatise of the Scurvy (4) is a good illustration of the basis for mid-18th century judgment and decision making, in that it quotes the contributions of others at length, and its therapeutic recommendations had little impact (5).

When Lind began to read the literature on scurvy, he realized that the only existing descriptions of the disease were written either by seamen who were not doctors or by doctors who had never been to sea. Lind felt that this was one of the reasons why there was so much confusion about the diagnosis, prevention, and cure of the disease.

Although he was a physician, Lind’s experiment was not based on pathophysiological theory. He gave no reason for his choice of possible treatments—vinegar, cider, elixir of vitriol, seawater, and lemons and oranges—each of which was given to two seamen. His trial succeeded because one of the treatments contained vitamin C. Lind knew how to perform a comparative experiment and how to control well for time and environment, but he knew perhaps less well which experiment he should do. Had his experiment been based on theory, his work might have been more likely to receive credit with the medical establishment rather than take more than 40 years to be put into practice.

The US Food and Drug Administration (FDA), an agency of the Department of Health and Human Services, is charged with the regulation and supervision of most food products, human and animal drugs, biologics, medical devices, cosmetics, and animal feed.

Efforts to protect consumers were first made in the 1800s as early scientific studies continued to develop products for use in humans (Table 1–1). In the 1820s, the first US Pharmacopeia was produced, which set standards for the strength, purity, quality, and consistency of drugs (6). In 1848, Lewis Caleb Beck was appointed to the Patent Office to carry out chemical analyses of agricultural products; many view his appointment as a crucial early step in the development of what is now the FDA. Shortly, thereafter, the Drug Importation Act was passed in response to the deaths of American soldiers from adulterated quinine. This act charged US Customs officers with inspecting and prohibiting the entry of adulterated drugs from overseas.