Discovering a novel potential antifungal agent with activity in vivo is not easy or cheap. When I began my research career in the immediate post Second World War years, it was a relatively simple matter to get a compound active in an animal model of infection tested in humans. Toxicology was in its infancy and the disciplines of drug metabolism and pharmacokinetics embryonic. Some compounds became useful and established drugs, others just did not make the grade. As time progressed, preclinical investigations increased, but for example griseofulvin in the late 1950s was evaluated in humans by Harvey Blank in the USA within weeks of Gentle’s letter to Nature describing its activity against ringworm in guinea pigs and has sub-sequently become a valuable drug which has stood the test of time. It was only after the thalidomide tragedy in the early 1960s that extensive preclinical evaluation and regulatory procedures burgeoned in the hope of avoiding a similar situation in the future. Sally Eardley, a colleague from ICI, has written a delightful chapter (11) chronicling regulatory developments over the past 3500 years. Although she has had no experience with antifungal drugs, I find her contribution fascinating to read, since it so graphically explains the situation in which we find ourselves at this time. It is important to realise that of the £100 million which may be spent today before a new drug can be marketed, at least two-thirds of this will be spent on the various aspects of development covered in this section, while only one-third will have been spent discovering the drug in the first place. Consideration of such figures emphasises the fact that drug development, if not drug discovery also, can only be handled by large multinational pharmaceutical companies with their vast resources. Consideration of such figures stresses too the hard fact of life that the management of such companies will not sanction research into therapeutic areas in which there is no hope of recouping the enormous costs of research and development from ultimate sales. As I have worked on various aspects of tropical medicine and medical mycology over the past 40 years, this has been personally one of the most difficult lessons to learn and situations with which to come to terms.
KeywordsHard Fact Medical Mycology Preclinical Investigation Enormous Cost Screening Cascade
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