No single definition of a drug is universally accepted. Instead, there are many definitions ranging from narrow and restricted ones to those that are extremely broad. The broadest definition of a drug is any chemical agent that affects living processes (Gillman 1985). An example of a narrower definition is any substance, other than food, used in the prevention, diagnosis, alleviation, treatment, or cure of disease in humans and animals (Williams and Wilkins 1972). Over the past few decades, the
word “drug” has, unfortunately become increasingly associated with abused, usually illegal substances. The author believes (as do many others) that the time has come to differentiate between drugs used for therapeutic (or preventive, diagnostic or curative purposes) and those that are abused. While it would be desirable to use two separate terms for the beneficial and abused (usually illegal) substances the author has found that professionals are not ready to accept two separate terms. The definition of a drug in this book is therefore the more commonly used one of a chemical substance that affects living tissue and is used to achieve a desired biological effect in a living organism. Some aspects of this definition are a little vague or may be debated [e.g., when are foods considered as drugs (i.e., medical foods) and what drugs are present in foods?]. Nonetheless, this general definition allows for great latitude in discussing drug development and uses. No distinction is made between drug and medicine, although the term medicine is used in this book to infer that the drug is marketed.

Thus, a compound is a molecule from inception until it has reached human testing; a drug (using the previous definition) is an investigational product until it has reached the market and after that it is referred to as either a drug or medicine.

A pro-drug is defined as a substance that is converted inside the body into an active drug, usually by metabolic processes in the liver or blood. A pro-drug may be inactive or it may have the same biological profile as the active drug. Some people (including the author) believe that a chemical compound should first be referred to as a drug when it is initially given to humans (i.e., this usually occurs in Phase 1 studies). Others prefer to make this distinction when the compound is first shown to be active in patients, which occurs in Phase 2 studies, and yet others call a substance a drug after it is formulated and contains excipients or is in solution to be given to patients, and compound or active substance the active moiety of the drug.

Medical facts are relative and dependent on the scientific, social, and political environment in which they are established and may be eventually replaced by more accepted or stronger facts. Most people understand that when facts are shown to be wrong, they are usually replaced by others. No one can say that we have the correct facts in any area of medicine. Experts agree that most currently accepted medical facts will be replaced by others, and they in turn will eventually be replaced, and so on. The perceptions and consensus of the most influential scientists and clinicians are the bases of how facts are established.

Many people have the perspective that the field of medicine has made so much progress over the past century that we are getting to know a substantial percent of what there is to know. The fallacy of this view can be commented on by describing an analogy.

Understanding the workings of a single cell has been described as analogous to viewing the island of Manhattan from above. Scientists are said to be in a helicopter high over the island. A few centuries ago, scientists were so far above the island that they did not know of its existence. As scientific and technical abilities improved, especially through invention of the microscope, the island (i.e., a single cell) was discovered.

Over the past 200 or so years, our helicopter has moved steadily closer to the island and now we are able to identify not only Central Park (which was an early observation), but a number of specific buildings (i.e., organelles inside the cell). We can often determine which buildings are bigger than others (e.g., nucleus versus mitochondria). Traffic patterns can also be observed and we can identify where most of the outdoor activities are occurring. The buildings, traffic, parks, and bodies of water we observe are analogous to the structural details of a cell that can now be identified with electron and scanning microscopes plus other sophisticated equipment.

The interesting questions, however, are what the many managers are doing in each of the buildings and also what motivates them to make the decisions they reach. Trying to answer these questions based on the gross details of the buildings and vehicles we observe on the streets below is impossible. We do not know the identity of most managers (e.g., proteins and chemical substances), let alone their actual activities. Nonetheless we make many hypotheses and develop theories. Inside our bodies and cells, it is estimated that there are approximately 50,000 proteins, only one-tenth of which have been discovered. There is clearly a long way to go.

Diseases are usually a fixed concept in our minds that are all-ornone entities, even though we know we may get a mild or severe case of any disease. We may remember diseases that our parents or grandparents had and, in some cases, think how lucky we are to be vaccinated and therefore protected against them. In other cases, we know that we too may get the same disease as our parents. If so, there may or may not be effective treatments available.

Diseases are not fixed entities but have their own natural history and characteristics that evolve over time. A disease may change in such aspects as severity, after effects, frequency, types of symptoms, or rate of mortality. These changes may occur because people who get the disease change or because the cause of the disease changes. People may become better protected against the disease because of immunological resistance or improved nutritional status. Resistance may be acquired genetically over a long period of time or may be acquired artificially, as with vaccines. Some characteristics of a disease change because of altered environmental factors that affect health, such as sanitation, crowding, nutrition, and personal hygiene. Also, as humans get to know more about each disease, ways of eradicating some diseases are found, as was done with the once-dreaded disease smallpox. The development of vaccines has allowed us to think in terms of eventually eradicating a number of other diseases as well (e.g., measles). Finally, a disease may change over decades, centuries, or millennia because of genetic changes within the viruses or bacteria that cause the disease (e.g., syphilis has been transformed from one of the most feared diseases in the 16th and 17th centuries to a fairly well controlled disease that does not cause as much morbidity as many others).

Trying to control or even effectively treat a number of diseases is a difficult battle when the cause of the disease is rapidly changing. A good example is the common influenza virus disease or “flu.” This disease changes every couple of years as a new strain emerges and requires development of a new vaccine to prevent effectively the disease in those inoculated.

New diseases emerge for numerous reasons including mutations in the genetic makeup of viruses, bacteria, or other disease-causing agents. New diseases may emerge in a country because people, animals, or plants may carry diseases from one place to another. Diseases may move (or return to) a place where people have little natural resistance. In such a situation, the disease may not only spread rapidly but may occur in a more severe form than in the original population. An example of this reportedly occurred when syphilis was brought to Europe from either the New World or from Africa in the 15th century. Interestingly, the Italians called syphilis the “French pox” and the French called it the “Italian pox.” English called it the “Spanish pox,” Poles called it the “German pox,” and Russians called it the “Polish pox” (Gottfried 1983).