Advancing in the face of conventional wisdom.

In recent issues of Drug Discovery Today [1,2], Jurgen Drews and David Cavalla discussed the future productivity of drug discovery. Although they made many insightful and valid comments, I would like to add some points to the overall discussion. My first point is that most small biotechnology companies are not funded enough to enter a Phase III clinical study. Often, it is not even in their business strategy to enter Phase III development without a major partner on board. Therefore, it might be that the lack of funding and increased discretion of the major pharmaceutical companies play the more important roles in determining which products enter Phase III drug development. This would explain many of David Cavalla’s observations, including why there has been an increase in Phase I and II investigations, with a 71% increase in the time taken in Phase II between 1997 and 2001 (Ref. [2] and references therein). My second point is that drug discovery could blossom if we recognized the need both for more accurate descriptions of drug–receptor interactions and for safer drugs. I believe that most readers would agree with these two points, although when it comes to Drews’ and Cavalla’s point that ‘...without the conviction based on scientific rectitude to advance into uncharted areas in the face of conventional commercial wisdom, medicine will advance little, and the future for the pharmaceutical industry is lacklustre.’ [2], we enter a rather strange realm in which we should promote the unusual and more creative scientific ideas to develop better drugs. However, the drug discovery process is not constructed to do this in a way that encourages the funding of the more creative young biotechnology companies or entrepreneurs. Much investor money is risk adverse, so this job is handed over to the well-funded pharmaceutical or biotechnology companies, or to the universities and National Institutes of Health. This is slightly better, although they are all invested in the conventional wisdom (which is often shaped by money and power) and, therefore, have no desire to upset it. Often, there are rather large egos involved in promoting and keeping scientific theories and ideas in press for possible prestige and potential fame. Yet some of the areas of most need are left wanting for the necessary cutting-edge research. Many diseases have only palliative treatments and many of the drug therapies have serious side effects that have increased morbidity and mortality. Much has been made of the Institute of Medicine report suggesting that from 44 000 to 98 000 deaths occur annually in the USA because of medical errors [3]. However, the side effects of drugs and drug combinations increase each year, despite increased vigilance from the health care community. Certainly, some of the reported medical errors are due to the improper use of drugs. For the most part, the Food and Drug Administration update discussion forum DDT Vol. 9, No. 3 February 2004