High Throughput Discovery: Search and Interpretation on the Path To New Drugs

摘要

Search and interpretation occupy places of special importance in discovery. Search uncovers phenomena; interpretation gives them meaning. Search underlies the development of hypotheses from theories, and the design of experiments from hypotheses (Klahr & Dunbar, 1988); interpretation connects observations and experimental results back to hypotheses, and thus to theories (Shrager, 1990). In theory revision, search and interpretation work hand-in-hand: scientists search among possible abstract theories and then, in interpretive steps, revise their emerging concrete theories based upon the selected abstractions (Shrager, 1990). In this chapter, I examine the roles of search and interpretation in drug discovery, one of the most important and exciting areas of modern science. Throughout history, medicinal chemists have relied upon massive search among candidate drugs, often trying hundreds or thousands of possibilities before finding a promising lead. This technique is so common that modern chemists give it a special name: High Throughput Screening (HTS), and conferences and books are devoted to it. The massive search involved in HTS can be easily automated by robots, permitting drug researchers to screen—that is, test for possible activity against disease— thousands of candidates in the space of a few weeks or even a few days. The result is uncountable quantities of data that must be analyzed to 11