The open field of pharmacology.

Contemporary pharmacologists are in the same position as experimental animals in an open field test. Animals are placed on a large table and their interest in the surroundings may be measured by their number of explorative movements. In some modifications of this test the table is full of holes and the "curiosity" of the animals is evaluated by the number of times in which the animals put their heads in the holes. We are now more or less in the same situation. Modern pharmacology is like an open field where we learn new things every moment and where our drugs always become more complicated in their number of sites of action and in their multiple interactions with the living organism. We must therefore admit that our knowledge is still very limited and that we know only an infinitesimal part of what should be known in order to predict therapeutic effects of drugs and to avoid their toxic actions. Nevertheless the history of drugs has shown that important results may be achieved even if the mechanism of action of new drugs is not fully elucidated. But we must face two different aspects of the same problem at the same time: on one hand we must be careful about possible toxic actions of new or known drugs and on the other we must avoid a too critical approach that would paralyse progress. Even if the therapeutic armory is overflowing with new drugs we must admit that many diseases are still waiting effective remedies. It is enough to mention cancer, atherosclerosis, cardiac infarctions and schizophrenia in order to emphasize how limited are our therapeutical means in combatting diseases which represent the major causes of death or disability of mankind. But even diseases which are relatively rare but severe such as multiple sclerosis or certain types of muscular dystrophies are still without therapy and they require a coordinated effort. In this situation the governments and the pharmaceutical industries are justly concerned about the possibility of the appearance of a new "thalidomide". However, instead of stimulating new and deep knowledge the temptation of many official agencies is to complicate the number of assays and bureaucratic procedures before releasing any new drug even for limited clinical evaluations. Furthermore, the request of prolonged treatments using several animal species and high doses of the drug under study is often a form of defence rather than the result of a precise scientific judgement about the importance of such studies for the extrapolation of data from animals to men. In this way we may create at the experimental level problems which will never exist in the clinic or we may miss important aspects of drug toxicity. An important point for the discussion of these problems is related to the modern findings of biochemical pharmacology. It may be stated that the