Drug research: dead end or new horizon?

Drug research: dead end or new horizon? Industrial drug research is facing a crisis. Higher investments are necessary for the discovery of fewer drugs, and the return on investment shrinks.1 2 Regulatory constraints3 and financial pressures4 have been blamed for slowing the development of new drugs at a time when truly new discoveries have become rare events. Among the new drugs established in recent years are the histamine H2-receptor antagonists, the angiotensin I converting-enzyme inhibitors, dopaminergics such as 2-bromo-criptine, the anthelmintic praziquantel, and the monobactam antibiotics-not all that bad a record, and one that may well be compared with earlier periods considered teeming and prosperous. What has changed is the much larger expenditure, the incomparable higher cost, and the huge investments necessary to achieve these results. One of the reproaches made to industrial drug research5 is that its efforts are concentrated on the common and chronic disorders while neglecting the rare diseases. Though understandable for economic reasons, such a one-sided research policy is medically undesirable. A second criticism is that drug research tends to be unimaginative, looking for quick results instead of waiting for the slowly ripening fruits of long-range projects. Both contain a core of truth. Drug research has arrived at a crossroads and has to decide where to go and how to proceed. These matters were discussed at a recent symposium on "Decision Making in Drug Research" in Camogli, Italy, supported by the Fondazione Smith Kline, Milan. A group of research directors of multinational drug companies and representatives of universities and government institutions met for two days to discuss the problems of modern drug research. The methods of industrial drug research were seen to be in a state of fundamental change. Though not completely abandoned, the classical approach of screening of new chemicals now has only a small place. Chemical drug design has, however, not quite come up to expectations, its main shortcoming still being our modest insight into structure-activity relations. One stimulating concept advanced at the meeting was an attempt to create new drugs by starting from a biological hypothesis and making use of new chemical substances to elucidate pharmacological or biological mechanisms. Such an integration of pathophysiological and pharmacological approaches may lead to new types of drugs. Systematic variation of known chemical structures should not, however, be deprecated as a means for the development of new drugs: talk of molecular manipulation or of me-too products is …