INTRODUCTION

Within the past 100 years our understanding of the functioning of the human body has increased exponentially. Along with our increasing understanding of normal physiology has come insight into what can go wrong. The identification of the role of DNA heralded the beginning of the era of molecular medicine. The molecular basis of many diseases is now known. As diseases began to be understood at the molecular level, drugs directed against precise abnormalities have been developed. This allows a more rational approach to treatment selection and drug design.

In addition, it is now appreciated that there are significant differences in individuals’ responses to drugs. Many of these differences are the result of variation at the genetic level. For example, a polymorphism may cause a pharmacological agent to be processed in a different manner, changing the effect of the drug. This has led to the realisation that response to some agents can be predicted by the identification of polymorphisms before therapy is commenced. In this manner, therapy can be tailored to ‘fit’ the individual. This is known as pharmacogenomics.

The development of new drugs has also been assisted by the increasing sophistication of information technology, which has enabled us to process large amounts of data. In addition, computer programs allow prediction of the structure and folding of complex molecules such as proteins. The interaction of a drug and its target can be modelled in silico.

Globalisation has also changed the face of medicine. In the past, the individual intrepid explorer would return from journeys to foreign lands clutching a strange root with suspected medicinal properties. Now there is large-scale merging of cultures with sharing of medical traditions and practices. The Internet, of course, facilitates this exchange and allows crosscontinental collaboration.

In this chapter, concepts such as drug discovery, molecular modelling and rational drug design will be discussed. A brief look at the evolution of the science of drugs may also provide some insights into our practices today.

LOOKING BACKWARDS

Disease has always been explained in the context of the prevailing belief system of the day. Of course, the perception of the cause of the disease affected the choice of treatment.