GEORGE WALD 739 



eye for visual fields of moderate size lies at about 10-^ millilaniberts. 

 At this luminance a single rod absorbs a quantum on the average 

 about once in 38 minutes. At 10-^ millilaniberts — about 10 times 

 the dark-adapted threshold — a rod absorbs a quantum about once 

 every 4 minutes; and even at 1 ()-•'' millilamberts, some 1000 times 

 above the absolute threshold, a rod absorbs a quantum less than 

 once in two seconds. It nuist be clear that if the dark-adapted rods 

 did not serve as single quantum detectors, they could do nothing for 

 us, for above 10-- millilamberts, when their chances of capturing 

 quanta are improving, cones have already begun to play the primary 

 role in vision. 



A single quantum of light is absorbed by a single molecule of 

 rhodopsin, and one must try to understand how so minuscule an 

 event can have the relatively enormous consequence of exciting a 

 rod. I have suggested two possible mechanisms that might enter this 

 situation (44, 45) . 



One such mechanism rests on the realization that the membranes 

 forming the transverse flattened sacs which constitute the outer seg- 

 ments of rods and cones (40) are composed in large part of visual pig- 

 ment (42) . For this reason the attack of light on a molecule of visual 

 pigment might have the immediate effect of knocking a unimolecular 

 hole in one such membrane. One can imagine situations in which even 

 so small a hole might have a large effect. It might result in a local 

 depolarization, perhaps self-propagating as in other excitatory struc- 

 tures. Or if the sacs form a voltaic pile — essentially an electric 

 organ — the puncture of one of them might result in a change of the 

 generated potential sufficient to excite. 



Whatever such mechanism is considered, clearly some large ampli- 

 fication over the initial effect is needed. Biochemically, such an ampli- 

 fication might be achieved through catalysis. If rhodopsin, for ex- 

 ample, were a zymogen, a pro-enzyme, activated by the action of light, 

 then it might catalyze the formation of many molecules of product 

 in return for the absorption of a single photon. This would con- 

 stitute one stage of amplification. If the product of this catalysis were 

 a second enzyme, prepared to catalyze in turn a further reaction, that 

 would constitute a second stage of amplification. 



It is some encouragement to this suggestion to realize that all the 

 examples we know of the activation of zymogens involve the breaking 

 off from the inactive protein of a small fragment of its structure, 

 one or a few amino acids in length, and so exposing the active 

 catalytic center (20, 31) . The process has been called "uncorking." 



