iS 



NA TURE 



[May 7, 1896 



screened by a dew-cap. A diaphragm in the middle carries a 

 lens to form an image of the sensitometer on the plate. A simpler 

 way is to obtain the negative by direct contact, in which case 

 the sensitometer should be screened from the general sUy 

 illumination of the horizon. 



OBSERVATIONS ON ISOLATED NERVE. 



"T^HE work which Dr. Waller has recently summed up in the 

 Croonian Lecture, is an exjjerimental study of the influence 

 of reagents upon excitable — that is to say, living — protoplasm. 

 The choice of nerve as the most convenient form of living matter 

 in such an inquiry is justified by the consideration that nerve, as 

 is now generally adinitted, is practically inexhaustible. That 

 nerve fibre, a|5art fr<jm its end organs, is peculiarly responsive to 

 even slight changes of chemical condition ; and, further, that 

 with this tissue there is the advantage of a wide and regular range 

 between minimal and maximal efiects. A previous research 

 had shown (Brain, 1S95) that in nerve, contrary to what obtains 

 in muscle, stimulus and response, cause and effect are propor- 

 tional, the curve expressing their relation to one another being a 

 straight line. Probably, however, the autographic records of 

 these nerve experiments will afford the most convincing 

 argument for the employment of nerve fibre as a test tissue. 



The main principle upon which the inquirj' is based is the 

 proposition of Du Bois-Reyniond and of Hermann, that dis- 

 turbed protoplasm is electro-negative to the normal ; that 

 excited is electro-negative to resting protoplasm. The excised 

 and still living nerve of the frog gives off to the galvanometer a 

 current, called by Hermann "the current of inquiry," which 

 current, on .stimulation of the nerve, undergoes a reversal of 

 direction, the "negative variation," or "current of action.'' 

 Supposing the nerve to be set up so that the current of inquiry 

 is manifested as a northward deflection of the galvanometer (the 

 arrangement followed in these experiments), the negative varia- 

 tion will be south. It is the magnitude of this negative variation 

 which is taken as the index to the magnitude of chemico-physical 

 change aroused in the nerve under various chemical conditions. 

 To a series of stimuli of uniform intensity and duration, given at 

 regular intervals, the nerve responds by a series of uniform de- 

 flections or negative variations, which per.sist for an indefinite 

 time in tlie absence of modifying agents. A short series of such 

 normal deflections precedes, in these experiments, the applica- 

 tion of a reagent, after which, the stimuli being continued, the 

 effect of the drug appears as increase, diminution, or abolition of 

 the negative variations, as the case may be. The galvanometer 

 deflections are recorded on a slowly-moving photographic plate. 



The nerve, it should be said, is enclosed in a moist chamber, 

 and rests on two pairs of electrodes, those leading off to the 

 galvanometer, and a pair of wires from an induction coil by which 

 the .stimulations are sent in ; the.se consist of weak tetanising 

 currents of 8 sees, duration, given at minute intervals. Where 

 gases are used, they are simply driven through the nerve chamber 

 by pressure ; where drugs in solution are employed, the nerve is 

 removed from the electrodes and bathed in the solution for one 

 minute. 



Such is, briefly, the method employed. Of the results hitherto 

 obtained, those which relate to the action of anaesthetics upon 

 living matter will have a wide interest from their bearing upon a 

 great practical i.ssue. There is, of course, no question of the 

 crude application of laboratory experience to therapeutics ; yet 

 a test so delicate and regular in its working, cannot but have its 

 value in any estimate of the relative advantages and perils of 

 various annssthetic agents. 



The comparative action of carbon dioxide, of ether, and of 

 chloroform has been studied at lenglh. All these in small 

 quantity produce primary augmentation, and a pretty experiment 

 consists in simply blowing through the nerve chamber, when the 

 characteristic rise is produced by the carbon dioxide contained 

 in the expired air. In larger quantity carbon dioxide gives aboli- 

 tion or diminution (I'igs. 5 and 6) ; several minutes may elapse 

 during which there is no response to the regularly repeated 

 stimuli, but the abolition is not pernuinent, the deflections re- 

 appear, attain to, and for a time surpass their normal size. 

 Ether vapour produces a more prolonged an;i;sthesia, followed 

 by complete recovery of excitability (Kig. i). Chloroform vapour 

 gives a still more prolonged and often final abolition, recovery, 

 where it takes place, being much less complete than in the case 

 of ether (Fig. 2). Carbon dioxide added to chloroform counter- 



NO. 1384. vol. 54] 



acts the toxic effect and renders it more perfectly anitsthetic — 

 that is to say, there is complete abolition followed by complete 

 recovery. 



Of the many other gases tried, oxygen (Kig. 3), carbon mon- 

 oxide, and nitrous oxide (Fig. 4) give little or no effect, anaes- 

 thesia by the last is probably a carlron dioxide effect. 



Passing by many groups of chemical substances of which the 

 action has been tested, we may note merely that the study of the 

 comparative action of haloid salts brings out with much clearness 

 the analytical value of the method. 



In regard to the acids, a fundamental question to be determined 

 was as to whether their action upon living protoplasm was in 

 proportion to acidity or to a\ idity. The answer obtained is to 



-JtM ^^H ^^^ii' 



~ I ' ^Hr T 



the effect that acidity is the chief determining factor. Three 

 acids of widely different avidities, viz. nitric, sulphuric and 

 acetic, have approximately equal effects at the same acid 

 strength. Vet acids have also their specific action, a comparison 

 of, for instance, lactic and oxalic acids of equal strength shows 

 the former to be far more powerful than the latter. 



But the most interesting result of these experiments, from the 

 purely physiological point of view, is the demonstration of the 

 evolution of carbon dioxide in the nerve itself. As the chief 

 terminal product of protoplasmic activity carbon dioxide had re- 

 ceived a large share of attention, and its influence had been 

 recognised as giving the clue to a curious puzzle with regard to 

 the nerves. In the earlier experiments, when a frog was killed, 

 one sciatic nerve was removed for use, while the other was 



I 



The light hand ; 



the plates 



p.issage of the gas through the 



left in the body until required. It was noticed that the second 

 nerve was usually more excitable than the first, and when, as 

 sometimes hajjpened, a nerve had been left in the body all night, 

 the negative variation was often a very large, though a declining 

 one. To recognise that this augmentation was due to carbon 

 dioxide given oft" by the surrounding tissues, was to have a fresh 

 example of the delicacy of nerve as an indicator of the presence 

 of the gas ; and the question .suggested itself : Supposing carbon 

 dioxide to lie evolved during nerve activity, i.e. prolonged 

 tetanisation, ought not its presence to be marked by the now 

 fainiliar augmentation of the negative variation ? To test this, 

 recourse was had to a very simple experiment : but before 

 making il, a Inrecast of its probable course was drawn upon a 



