with a piece of zinc a momentary flash-like wave of activation is seem to pass rapidly along the whole wire; the local reaction lasts for only a small fraction of a second and is instantly reversed; a slight temporary darkening of the metallic surface and a trace of brown coloration (due to reduction of the acid to lower nitrogen oxides) are the only visible effects; in 90 per cent. acid a similar though somewhat more prolonged reaction takes place; in 80 per cent. acid there is slight visible effervescence for a fraction of a second; in 70 per cent. the effervescence lasts for about one second and the darkening of the metallic surface is more pronounced; while in 60 per cent. the reaction occupies two or three seconds and in 55 per cent. five seconds or more, and a considerable accumulation of brown oxide is formed at the surface of the metal. It would thus appear that in the stronger solutions the oxidation which forms the protective surface film takes place so rapidly that only a momentary reaction of the metal with the acid is possible; as the concentration of acid decreases the surface film forms more slowly and the reaction lasts longer, until at a certain critical concentration (about 50 per cent.; ca. 1.20 s. g.) the surface oxidation becomes so gradual that its passivating influence is insufficient to interfere with the continued solution of the metal in the acid.

Two chemical reactions of opposite character thus take place successively as the activation wave passes any region of the metallic surface; first, the local cathodic reduction which removes the protecting layer of oxide and enables the metal to react with the acid; and second, the immediately succeeding oxidative process which reforms the protective surface film and arrests the reaction. A factor of importance in this process of repassivation is apparently the electrochemical oxidative action at the local anode. As the activation wave advances, the surface film is disintegrated at the cathodal region immediately in advance of the wave front; this region then instantly becomes active, i. e., anodal; in other words, it undergoes a change of condition which in itself tends to check or arrest the reaction.

This is because of the characteristic passivating influence at the anode; the reaction of a piece of active iron wire in 1.20 HNO, may in fact be brought to rest and the wire rendered passive by passing a strong current through it as anode for a few seconds. As the activation wave passes, each region of the metallic surface thus becomes alternately cathodal and anodal. Making the passive metal cathode has an activating effect, while making the active metal anode tends to passivate. This latter electrochemical action is added to the direct passivating action of the acid. Hence in acid of a sufficient strength the local reaction is automatically self-limiting as well as selfpropagating. This peculiarity depends directly upon the properties of the surface film, which when the metal is cathode undergoes dissolution, and when the metal is anode is reformed. Apparently in strong acid the metal is in a condition where a slight local increase of reducing influence initiates the activating reaction and a slight increase of oxidizing influence inhibits it. We have here another parallel to the condition in an irritable element like a nerve fiber, where cathodal polarization promotes and anodal polarization inhibits the local reaction (electrotonus). In both cases the alternate disintegration and reformation of a surface film under electrochemical influence appear to be the essential features of the local process.

The passage of the wave of activation can be observed with especial clearness in a passive iron wire which has been dipped in a test-tube containing 1.42 HNO, and is then suspended vertically in air and touched at its lower end with zinc. The adhering layer of acid is so thin as to increase greatly the resistance of the local circuit between active and inactive regions, and the local reaction spreads with corresponding slowness, at a rate of only a few (5 to 10) centimeters a second. As the

6 Contact of a piece of platinum foil with a reacting iron wire has the same effect; near the platinum the iron soon ceases reaction and becomes passive, and the effect then spreads over the whole wire. This phenomena is biologically interesting, as a case of transmission of inhibitory influence.

reacting region extends upward the bright surface of the iron is darkened locally for a distance of two or three centimeters; behind this advancing active region the wire again becomes bright and inactive. The visible effect is that of a slight temporary darkening or clouding which travels upward along the wire. After the wave has passed over the whole length of the wire the latter, when tested by dipping in 1.20 acid, is found to be again passive; the temporary and reversible character of the activation is thus shown. A similar slow spreading of the active state takes place in a passive wire dipped in weaker (1.20) acid and then activated as above, but in this case there is no spontaneous return to passivity; the whole wire remains dark, and when again placed in 1.20 acid at once reacts vigorously in the usual manner of active iron. Spontaneous reversal thus takes place only in the strong acid.

In the experiment just cited the rate of transmission is lowered by increasing the electrical resistance of the local circuit, but in other respects there is no essential difference from the conditions observed in immersed wires. A noteworthy feature of these phenomena is that after a wire has been activated while immersed in strong acid (e. g., 80 per cent. 1.42) some time elapses before a complete reaction can be again excited; i. e., a period of insensitivity and imperfect transmission. always follows the spontaneous return of passivity. Contact with zinc within the first four or five minutes after activation causes typically only a local reaction which may be transmitted slowly for a few centimeters but then dies out; some minutes later transmission takes place more rapidly and through a longer distance; but it is usually only after ten or fifteen minutes (the exact time varying with the conditions) that perfect transmission through an indefinite distance becomes again possible. The recovery of the original condition thus requires some time, the exact interval varying with the concentration of acid, and in general decreasing with decreasing concentration. This phenomenon also has its biological analogies, and may be compared to

fatigue, or possibly to the refractory period which typically follows stimulation in all irritable tissues. Evidently the reformed surface film regains its former sensitive properties by a progressive and somewhat gradual

process.

This tendency to an automatic restoration of the protective surface layer of oxide after local removal is probably the essential condition underlying another characteristic feature of the electrical activation of passive iron, namely, that a slowly increasing current passed through the wire (as cathode) is much less effective in causing activation than a current of similar strength which attains its full intensity rapidly or instantaneously. In this respect also the passive metal resembles the living irritable tissue. If the current leading to the two passive wires immersed in 1.20 HNO, is derived by means of a stationary and a movable zinc electrode from a bath of zinc sulphate solution forming part of a circuit of several storage cells-an arrangement enabling the potential of the "shunt current" to the iron wires to be varied at will-it is found that a gradual increase of the current, from near zero to an intensity which in itself is amply sufficient to activate with sudden closure, is typically without effect. Evidently a sudden change of surface polarization is needed; if the change is gradual it seems that the oxidative action of the acid in contact with the metal has time to reform the passivating protective layer as fast as it is reduced by the cathodal action.

The chief of the foregoing resemblances between the passive iron wire and the irritable living element may now be briefly summarized as follows: (1) Mechanical, electrical and chemical agencies have the same activating effect; (2) electrical activation is a polar phenomenon (analogy to the law of polar stimulation); (3) the local state of activity is propagated along the wire at a velocity which is similar in its order to that of the excitation wave in living tissues; (4) whenever activation is excited by any means in a passive wire immersed in a definite solution of acid (e. g., 70 per cent. 1.42 HNO3) the whole wire is

involved and the reaction lasts for a definite time; i. e., the character, intensity and duration of the reaction are independent of the nature of the activating agent; the metal either reacts completely or not at all (analogy to the "all-or-nothing" behavior of irritable living elements); (5) a wire which is polarized anodically while immersed in acid is activated with difficulty and the activation wave tends to travel for only a short distance (analogy to anelectrotonus in nerve); (6) the spontaneous return of passivity in strong acid is immediately succeeded by a period during which the metal is less responsive than before (analogy to fatigue effect or refractory period); (7) a current which reaches its full intensity gradually is less effective than one which reaches the same intensity suddenly; and finally (8) the local chemical surface reaction of activation is constantly associated with a variation of electrical potential, the active region becoming negative relatively to the inactive regions (analogy to the bioelectric variation or action current" of an active living tissue).

The chief characteristics of this electrical variation are readily demonstrated as follows. When two iron wires connected with the binding-posts of a voltmeter of suitable scale are passivated and placed side by side in a vessel containing 1.20 HNO,, no potential difference is shown. If then one wire is activated the instrument at once indicates a P.D. of 0.7 to 0.8 volt, with the active wire negative; this P.D. remains constant while the reaction continues in the one wire; if then the other wire is also activated the P.D. again falls to zero. The active wire is thus anodal, the passive wire acting like a noble metal. If the same experiment is performed with stronger acid (55 per cent. 1.42 or higher) a similar but temporary excursion of the needle is seen, lasting for the period of the reaction. In acid of 55 or 60 per cent. the potential exhibits irregular rhythmical fluctuations for the few seconds during which the reaction continues, and the needle swings by degrees back to zero and somewhat beyond as the reaction subsides and ceases. Immediately after the

return of the passive condition the activated wire is always found slightly more positive than before, usually by ca. 0.02 volt; after an interval of some minutes-corresponding apparently in its duration to the insensitive or refractory period above described-the original potential returns. The wire may then be again reactivated and the same process is repeated. This tendency to overpass the original potential after the return of passivity recalls the similar phenomenon in nerve known as the "positive after-variation," and suggests a similarity in the general conditions under which the surface film is reconstituted in the two cases.

The variation of potential associated with the transmission of the activation wave may be demonstrated in a single wire which is connected near its opposite ends with a sensitive string galvanometer (by means of thin passive iron wires) and immersed in 70 or 80 per cent. acid. If the wire is activated at one end the string shows a quick excursion, first in the one direction, then in the other, the deflection showing that at each leading-off region the wire becomes first negative and then positive. The curve of movement is thus comparable to the typical "diphasic" action current curve of a nerve conducting an impulse.

The amplitude of these variations of potential in metals is of course much greater than that found in living tissues, but in their general characteristics both classes of phenomena give unmistakable evidence of being conditioned in the same manner. In the case of the metal it is certain that the effect depends upon a sudden alteration of the electromotor properties of the surface layer. In living tissues and cells there is also much evidence that a change in the protoplasmic surface layer (or so-called plasma-membrane) involving increased permeability and altered metabolism is constantly associated with stimulation, and that the variation of electrical potential is due primarily to this change. Thus in both living system and metal the electrical variations are the expression or indication of changing chemical and structural conditions in the surface layer. The local interruption

or removal of the surface film of oxide in the metal is comparable with the increase of permeability in the living element.

A significant general analogy to physiological conditions is also to be seen in the readiness with which the active state is transmitted from an active to a passive metal by contact. Transmission of excitation from one cell or cell element to another by contact is frequent in organisms; and many characteristic structural arrangements, especially in the nervous system, give evidence that such transmission is a normal and constant physiological process; the interlacing of dendrites from different neurones, contact of nerve cells with one another by "end-feet" and similar structures, the histological characters of the myoneural junctions and other nerve endingswhich typically form contact with the surface of the cell-may serve as examples. Instances of transmission by contact in metals have been given above. A good demonstration is the following: if a number of passive iron wires are placed in contact with one another in a dish of nitric acid, and any single wire is touched with zinc, all immediately become active. A long fine passive wire in contact at one end with a large piece of passive iron, e. g., a nail, will on activation at its other end rapidly conduct and transmit the state of activation to the terminal object. Another remarkable feature of this phenomenon is that the transmission between different metals may be irreciprocal; this may be shown by using wires of the two metals, iron and nickel, which differ in the readiness and rate with which activation takes place. A momentary contact with active nickel will instantly activate a piece of iron wire in 1.20 HNO3, but under the same conditions a piece of passive nickel is activated slowly and only after prolonged contact. Consequently, while briefly touching passive iron with active nickel immediately and completely activates the iron, touching passive nickel with active iron is typically ineffective or has only slight local effect. In other words, transmission of activation takes place rapidly and readily from nickel to iron, but not in the reverse direction. The differ

ence depends upon the relative slowness of the activation process in nickel; in this metal the local reaction tends to start slowly and to reach its maximum slowly, and the rate of transmission is correspondingly gradual. Such facts suggest the possibility that the characteristic irreciprocality of transmission in reflex arcs may depend upon similar differences in the time factors of excitation of the interacting neurones at the synapses. The recent work of Lapicque and Keith Lucas has shown clearly the fundamental importance of the time factor in the excitation process."

It seems clear that variations in the electromotor properties of the surfaces concerned— respectively the metallic surface and the cell surface-form the essential feature of activity which is common to both types of system and upon which the above various similarities of behavior depend. These variations are due to changes in the physical and chemical character of the surface layer, which in both cases is water-insoluble, chemically unstable, and in contact with an electrolyte solution. Experiment shows that in the passive metal this surface film is in a characteristic state of equilibrium which is readily disturbed, and the same appears to be true of the protoplasmic surface film in an irritable cell or cell element.

This general similarity probably explains another peculiarity of behavior common to both systems, namely a tendency to automatic rhythmical fluctuations of potential and chemical action; this phenomenon is seen in the solution of many metals in nitric acid, and also in the well-known rhythmical catalytic decomposition of hydrogen peroxide in contact with mercury. Alternation of activity and passivity, due to rhythmical formation and dissolution of a surface film of oxide or other protective material, appears to underlie these phenomena in metals. In living organisms rhythmical action is also highly characteristic, and is presumably due to analogous conditions. The general view that the semi-permeable

7 Similarly with transmission from element to element. Lapicque's work indicates that the failure of transmission from nerve to muscle in curare poisoning is due to "heterochronism.'

cell surfaces may have electromotor properties similar in certain respects to those of metallic surfaces has long been familiar to physiologists; and the so-called "membrane theory" (or theories) of the bioelectric potentials, which originated in a suggestion of Ostwald in 1890 and has been developed in considerable detail by Bernstein, Höber and others, has referred the physiological variations of potential to variations of permeability or to other changes in the plasma-membrane. It seems best, however, to avoid for the present too special conceptions of the precise nature of the processes concerned in these phenomena and to regard the latter from a broader and more generalized point of view. Variations of phase-boundary potentials, with associated or dependent chemical effects, appear to constitute the general type of phenomenon involved. More recently the work of Haber, Beutner and especially of Loeb and Beutner in collaboration, has demonstrated many fundamental resemblances between such potentials and the bioelectric potentials, and is of the highest interest in relation to this general problem. The work of Loeb and Beutner, together with that of Macdonald, indicates that organic membranes and cell-surfaces behave as if reversible (in the electrochemical sense) to cations as a class; in this respect they resemble the surfaces of solutions of lipoids in organic solvents; and it seems probable that the demarcation-current potentials are thus to be explained. I am inclined, however, in view of the conditions in passive iron as well as for more purely biological reasons, to regard the local bioelectric circuits accompanying normal cell activity as representing primarily some type of oxidation reduction element. In general the physiological effects observed at the respective regions where the electric current enters and leaves the cell-surface are opposite in character, and the same must be true of the underlying chemical or metabolic processes. Oxidation at one area, simultaneously with reduction at another areathese chemical changes involving synthesis as well as decomposition-seems to be a more probable source of the normal currents of

THE Inter-Allied Scientific Food Commission now sitting in London has already at previous meetings accomplished a good deal of work, and if its recommendations are carried out, the provisioning of allied countries will be placed on a sound scientific basis. That its recommendations will be carried out seems to be more or less guaranteed by the fact that it was established as a result of a decision of the Inter-Allied Conference held in Paris last November. The Conference directed that the inter-allied scientific commission should consist of representatives of France (Professors Gley and Langlois), Italy (Professors Botazzi and Pagliani), United States (Professors Chittenden and Lusk), and the United Kingdom (Professors E. H. Starling and T. B. Wood). It was instructed to meet periodically in order to consider from a scientific point of view the food problems of the Allies and in agreement with the interallied executives to make proposals to the allied Governments. The commission held its first meeting in Paris on March 25, and its second in Rome on April 29. Before its present meeting in London a representative of Belgium, Professor Hulot, was added. A memorandum upon the work of the commission, furnished to us by the food controller, contains some particulars enlarging the information published in previous issues.

At its first meeting last March in Paris the commission came to an agreement as to the minimum food requirements of the average man. It was laid down that for a man weigh1 From the British Medical Journal.