History of Pharmacology

Prehistoric people undoubtedly recognized the beneficial or toxic effects of many plant and animal
materials. The earliest written records from China and from Egypt list remedies of many types,
including a few still recognized today as useful drugs. Most, however, were worthless or actually
harmful. In the 2500 years or so preceding the modern era there were sporadic attempts to introduce
rational methods into medicine, but none were successful owing to the dominance of systems of
thought that purported to explain all of biology and disease without the need for experimentation
and observation. These schools promulgated bizarre notions such as the idea that disease was
caused by excesses of bile or blood in the body, that wounds could be healed by applying a salve to
the weapon that caused the wound, and so on.
Around the end of the 17th century, reliance on observation and experimentation began to replace
theorizing in medicine, following the example of the physical sciences. As the value of these
methods in the study of disease became clear, physicians in Great Britain and on the Continent
began to apply them to the effects of traditional drugs used in their own practices. Thus, materia
medica—the science of drug preparation and the medical use of drugs—began to develop as the
precursor to pharmacology. However, any understanding of the mechanisms of action of drugs was
prevented by the absence of methods for purifying active agents from the crude materials that were
available and—even more—by the lack of methods for testing hypotheses about the nature of drug
actions.
In the late 18th and early 19th centuries, François Magendie and later his student Claude Bernard
began to develop the methods of experimental animal physiology and pharmacology. Advances in
chemistry and the further development of physiology in the 18th, 19th, and early 20th centuries laid
the foundation needed for understanding how drugs work at the organ and tissue levels.
Paradoxically, real advances in basic pharmacology during this time were accompanied by an
outburst of unscientific promotion by manufacturers and marketers of worthless "patent medicines."
It was not until the concepts of rational therapeutics, especially that of the controlled clinical trial,
were reintroduced into medicine—about 50 years ago—that it became possible to accurately
evaluate therapeutic claims.
About 50 years ago, there also began a major expansion of research efforts in all areas of biology.
As new concepts and new techniques were introduced, information accumulated about drug action
and the biologic substrate of that action, the receptor. During the last half-century, many
fundamentally new drug groups and new members of old groups were introduced. The last 3
decades have seen an even more rapid growth of information and understanding of the molecular
basis for drug action. The molecular mechanisms of action of many drugs have now been identified,
and numerous receptors have been isolated, structurally characterized, and cloned. In fact, the use of
receptor identification methods (described in Chapter 2: Drug Receptors & Pharmacodynamics) has
led to the discovery of many orphan receptors—receptors for which no ligand has been discovered
and whose function can only be surmised. Studies of the local molecular environment of receptors
have shown that receptors and effectors do not function in isolation—they are strongly influenced
by companion regulatory proteins. Decoding of the genomes of many species—from bacteria to
humans—has led to the recognition of unsuspected relationships between receptor families.
Pharmacogenomics—the relation of the individual's genetic makeup to his or her response to
specific drugs—is close to becoming a practical area of therapy (see Pharmacology & Genetics).
Much of that progress is summarized in this resource.
The extension of scientific principles into everyday therapeutics is still going on, though the
medication-consuming public, unfortunately, is still exposed to vast amounts of inaccurate,
incomplete, or unscientific information regarding the pharmacologic effects of chemicals. This has
resulted in the faddish use of innumerable expensive, ineffective, and sometimes harmful remedies
and the growth of a huge "alternative health care" industry. Conversely, lack of understanding of
basic scientific principles in biology and statistics and the absence of critical thinking about public
health issues has led to rejection of medical science by a segment of the public and a common
tendency to assume that all adverse drug effects are the result of malpractice. Two general
principles that the student should always remember are, first, that all substances can under certain
circumstances be toxic; and second, that all therapies promoted as health-enhancing should meet the
same standards of evidence of efficacy and safety, ie, there should be no artificial separation
between scientific medicine and "alternative" or "complementary" medicine.