The Relation between Quantal and Graded Responses to Drugs

A curious dichotomy exists in the study of biological responses to drugs. Responses, justifiably enough, are regarded as of two distinct types-quantal and graded. Quantal responses are those which classify an organism or other unit of biological material as having responded or not; for example, death, paralysis, etc. A graded response is such that the single organism gives a response in quantitative terms; for example, a change in weight, or a change in blood pressure. The statistical treatments of the two types of response show some similarities, largely because regression techniques are used for both; but biologically speaking the quantitative descriptions of the two types of response have been kept rigidly separate. No attempt seems to have been made to discover any connection between the dose-response relationships for quantal responses on the one hand and those for graded responses on the other. 2. The purpose here is to view the events following the strictly controlled administration of a drug in such a way that the probable interrelationships of succeeding graded and quantal responses can be seen and formulated quantitatively. First, however, it is necessary to comment on the interpretation of functions relating quantal responses to dose. 3. We shall, as is commonly done, assume that the relation between a quantal response and dose represents a cumulative distribution of tolerances, where the tolerance of an individual organism (or other unit of biological material) is the dose of drug just insufficient to make it show the quantal response concerned. It is fitting that a concept such as that of a tolerance should be scrutinized from time to time: Berkson (1951) has in fact challenged the concept, but he proposed no alternative interpretation. He cited ani experiment in which individual men reacted differently on different occasions; but an interpretation in terms of tolerances of the results of dosage on a certain occasion does not depend upon the tolerance of each organism remaining constant