The three important figures in the early history of pharmacology are (left to right) Rudolf Bucheim, Oswald Schmiedeberg, and John Jacob Abel. They not only created new laboratories devoted to the laboratory investigation of drugs but also firmly established the new discipline through the training of future faculty, the writing of textbooks, and the founding of scientific journals and societies.

academic institutions and the training of a sufficient number of talented investigators to occupy these positions. The latter task was accomplished largely by Bucheim's pupil and successor at Dorpat, Oswald Schmiedeberg (1838-1921), undoubtedly the most prominent pharmacologist of the nineteenth century (Fig. 1.1). In addition to conducting his own outstanding research on the pharmacology of diuretics, emetics, cardiac glycosides, and so forth, Schmiedeberg wrote an important medical textbook and trained approximately 120 pupils from more than 20 countries. Many of these new investigators either started or developed laboratories devoted to experimental pharmacology in their own countries.

One of Schmiedeberg's most outstanding students was John Jacob Abel, who has been called the founder of American pharmacology (Fig 1.1). Abel occupied the chair of pharmacology first at the University of Michigan and then at Johns Hopkins University. Among his most important research accomplishments is an examination of the chemistry and isolation of the active principles from the adrenal medulla (a monobenzyl derivative of epinephrine) and the pancreas (crystallization of insulin). He also examined mushroom poisons, investigated the chemotherapeutic actions of the arsenicals and anti-monials, conducted studies on tetanus toxin, and designed a model for an artificial kidney. In addition, Abel founded the Journal of Experimental Medicine, the Journal of Biological Chemistry, and the Journal of Pharmacology and Experimental Therapeutics. His devotion to pharmacological research, his enthusiasm for the training of students in this new discipline, and his establishment of journals and scientific societies proved criti cal to the rise of experimental pharmacology in the United States.

Pharmacology, as a separate and vital discipline, has interests that distinguish it from the other basic sciences and pharmacy. Its primary concern is not the cataloguing of the biological effects that result from the administration of chemical substances but rather the dual aims of (1) providing an understanding of normal and abnormal human physiology and biochemistry through the application of drugs as experimental tools and (2) applying to clinical medicine the information gained from fundamental investigation and observation.

A report in the Status of Research in Pharmacology has described some of the founding principles on which the discipline is based and that distinguish pharmacology from other fields of study. These principles include the study of the following:

• The relationship between drug concentration and biological response

• Drug action over time

• Factors affecting absorption, distribution, binding, metabolism, and elimination of chemicals

• Structure-activity relationships

• Biological changes that result from repeated drug use: tolerance, addiction, adverse reactions, altered rates of drug metabolism, and so forth

• Antagonism of the effects of one drug by another

• The process of drug interaction with cellular macromolecules (receptors) to alter physiological function (i.e., receptor theory)

In the past 100 years there has been extraordinary growth in medical knowledge. This expansion of information has come about largely through the contributions of the biological sciences to medicine by a systematic approach to the understanding and treatment of disease. The experimental method and technological advances are the foundations upon which modern medicine is built.

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