100 Years “Schlüssel‐Schloss‐Prinzip”: What Made Emil Fischer Use this Analogy?

Abstract

Abstract Emil Fischer's famous lock‐and‐key analogy (Schlüssel‐Schloss‐Prinzip) for the specifity of enzyme action has provided successive generations of scientists with a mental picture of molecular recognition processes, and thus has shaped to a marked degree the development not only of organic chemistry, but, through its extension to basic live processes, that of biology and medicine as well. The hundredth anniversary of the first use of this most fertile metaphor provides a welcome opportunity not only for highlighting its paramount importance, but for gaining an understanding and appreciation of the creative processes involved, of the constructive reasoning and the thought patterns underlying the fundamental insight. Accordingly, this account attempts to trace how Fischer was led to the lock‐and‐key analogy, based on the state of knowledge and the views prevailing at the time. It reveals that Fischer, who had a pronounced tendency against any sort of theoretical speculation, refrained from taking this metaphor any further, that is to the obvious extensions of what turns the key, and what kind of doors are then opened. Except for a small refinement–the differentiation of main key and special keys to account for the fact that some yeasts can ferment a larger number of hexoses than others—he rather expounded on the scope of the lock‐and‐key picture: “I am far from placing this hypothesis side by side to the established theories of our science, and readily admit, that it can only be thoroughly tested, when we are able to isolate the enzymes in a pure state and thus investigate their configuration.” Others, most notably P. Ehrlich und F. Lillie, by introduction of the concept of stereocomplementarity into medicine and biology, induced the lock‐and‐key analogy to become something of a dogma for explaining principal life processes.