Rang & Dale’s Pharmacology: with STUDENT CONSULT Online Access, 7e

Book Preface

PHARMACOLOGY IN THE 20TH AND 21ST CENTURIES

Beginning in the 20th century, the fresh wind of synthetic chemistry began to revolutionise the pharmaceutical industry, and with it the science of pharmacology. New synthetic drugs, such as barbiturates and local anaesthetics, began to appear, and the era of antimicrobial chemotherapy began with the discovery by Paul Ehrlich in 1909 of arsenical compounds for treating syphilis. Further breakthroughs came when the sulfonamides, the first antibacterial drugs, were discovered by Gerhard Domagk in 1935, and with the development of penicillin by Chain and Florey during the Second World War, based on the earlier work of Fleming.

These few well-known examples show how the growth of synthetic chemistry, and the resurgence of natural product chemistry, caused a dramatic revitalisation of therapeutics in the first half of the 20th century. Each new drug class that emerged gave pharmacologists a new challenge, and it was then that pharmacology really established its identity and its status among the biomedical sciences.

Some of our most distinguished pharmacological pioneers made their careers in industry: for example, Henry Dale, who laid the foundations of our knowledge of chemical transmission and the autonomic nervous system (Ch. 11); George Hitchings and Gertrude Elion, who described the antimetabolite principle and produced the first effective anticancer drugs (Ch. 54); and James Black, who introduced the first β-adrenoceptor and histamine H2-receptor antagonists (Chs 13 and 17). It is no accident that in this book, where we focus on the scientific principles of pharmacology, most of our examples are products of industry, not of nature.

In parallel with the exuberant proliferation of therapeutic molecules-driven mainly by chemistry-which gave pharmacologists so much to think about, physiology was also making rapid progress, particularly in relation to chemical mediators, which are discussed in depth elsewhere in this book. Many hormones, neurotransmitters and inflammatory mediators were discovered in this period, and the realisation that chemical communication plays a central role in almost every regulatory mechanism that our bodies possess immediately established a large area of common ground between physiology and pharmacology, for interactions between chemical substances and living systems were exactly what pharmacologists had been preoccupied with from the outset. The concept of ‘receptors’ for chemical mediators, first proposed by Langley in 1905, was quickly taken up by pharmacologists such as Clark, Gaddum, Schild and others and is a constant theme in present day pharmacology (as you will soon discover as you plough through the next two chapters). The receptor concept, and the technologies developed from it, have had a massive impact on drug discovery and therapeutics. Biochemistry also emerged as a distinct science early in the 20th century, and the discovery of enzymes and the delineation of biochemical pathways provided yet another framework for understanding drug effects. The picture of pharmacology that emerges from this brief glance at history (Fig. 1.1) is of a subject evolved from ancient prescientific therapeutics, involved in commerce from the 17th century onwards, and which gained respectability by donning the trappings of science as soon as this became possible in the mid-19th century. Signs of its carpetbagger past still cling to pharmacology, for the pharmaceutical industry has become very big business and much pharmacological research nowadays takes place in a commercial environment, a rougher and more pragmatic place than the glades of academia.4 No other biomedical ‘ology’ is so close to Mammon