than uninjured regions, as determined by our methods; and further that this increase in metabolic rate is the result of the stimulation of cutting, since it does not occur if the cutting is done under anesthesia. We have also shown that this alteration of metabolic rate as the consequence of injury occurs not only at the cut surface but involves adjacent uninjured regions also, in proportion to their distance from the cut. Tashiro13 has further found that injury invariably increases the carbon dioxide output of living material, and he believes this reaction to injury to be an infallible sign that the material is living.

In the text-books of physiology, explanations of the current of injury are usually based upon supposed alterations of membranes, concentrations of electrolytes, etc., at the cut surfaces, that is, the cut place is supposed to cause the phenomenon. But our observations show that the change in metabolic rate occurs not only at the cut surface but for some distance away from it; and an experiment of Bose11 demonstrates that the region of electronegativity also exists not merely at the site of injury but for a considerable distance away, diminishing in fact with distance. Here again the current runs parallel with the metabolic conditions at and near the injured regions. Bose concluded that the actual injury to the cells is not directly the cause of the electronegativity but that the stimulation due to the injury produces the electric change; and this stimulation, like many others, is transmitted with a decrement to surrounding regions. Injury is thus a form of stimulation and our experiments and those of Tashiro show that the stimulation of injury produces in the organism an increase in metabolic rate. Hence, as in the preceding case, we may suggest that the current of injury arises through the fact that the site of injury and adjacent regions are regions of increased metabolic rate and thus

13 A chemical sign of life.

14"Comparative Electro-physiology," 1907, pp. 154 ff. Bose has a great deal of interesting experimentation on the bioelectric currents but unfortunately it is often very difficult to grasp his exact meaning.

are electronegative to intact regions, where the rate is lower.

3. The Current of Action.-Whenever any living material is "stimulated," the stimulated region becomes ipso facto a region of electronegativity with respect to non-stimulated areas. In order to analyze this universal phenomenon, it is necessary to know what the nature of stimulation is. Physiologists are still very far from a solution of this difficult and fundamental problem. I venture to suggest, however, that everything that we know about stimulation indicates that increase in metabolic rate is its principal characteristic. Thus the oxygen consumption increases, the carbon dioxide output increases, the production of synthesized materials and of waste products is accelerated, the energy produced is augmented.15 Tashiro,16 for instance, after testing various kinds of plant and animal tissues, says: "In all cases stimulation causes an increase in carbon dioxide. We could never find any response unaccompanied by an outburst in carbon dioxide."

Every cell carries on a specific kind of metabolism, resulting in specific end products. As far as we know, each cell is always producing these whether it is in a stimulated condition or not, and the rate at which it does this is a measure of the degree to which it is alive. Thus Tashiro finds that all living substances give off carbon dioxide, and the rate of this output runs parallel to other manifestations of life, as relative irritability, rapidity of response, rate of conduction, etc. Let us consider very briefly the three chief active tissues of the body, gland, muscle and nerve. any particular kind of gland cell, barring special experimental or pathological conditions, there are in general the same kinds of granules to be found at all times. As far as one can determine, the rate of formation and discharge of granules alone is variable,-not their content. The essential effect of stimulating the gland cell through its nerve is an increase

In

15 These statements can be verified in any of the recent text-books of physiology as Bayliss, Howell, Stewart, etc.

16 Loc. cit., p. 99.

17

in the rate of production of its secretion. As is well known, this stimulatory increase in secretory products is always accompanied by large increases in the amount of oxygen consumed, CO, produced and heat evolved. In the case of muscle, the amount of lactic acid produced furnishes a certain criterion of the metabolic rate of the muscle. In the resting state, the lactic acid content is small; after the stimulation of injury and after contraction, it is greatly increased. And although molecular oxygen does not appear to be consumed in this process, the production of lactic acid from carbohydrates is nevertheless chemically an oxidation. In nerve, where it was long believed that no increase in metabolism occurred during the passage of the impulse, it is now known, thanks to the researches of Tashiro, that a relatively great increase in carbon dioxide output is associated with the process. He also presents some evidence that the oxygen consumption is likewise accelerated, during the conduction. In this connection it may be mentioned that Alexander and Revesz1s found that the oxygen consumption and the carbon dioxide elimination of the brain are increased when the retina is stimulated by light. In nervous, as in other tissues, the difference between the resting and the stimulated state is then largely quantitative. Further significant facts are that the rate of the passage of the current of action along the nerve bears a direct relation to the known irritability of the nerve and the rate at which it conducts the impulse; and as Tashiro's work shows that these factors are also directly related to rate of carbon dioxide production (more irritable nerves in the resting state giving off more of the gas than the less irritable ones), it becomes obvious that metabolic condition is the primary factor in the causation of the current of action.

The evidence then clearly indicates that each cell is always carrying on a specific kind of metabolism and that stimulation consists essentially in the temporary acceleration of 17 Loc. cit., Chaps. II. and III., also p. 53. 18 Biochem. Zeitsch., XLIV., p. 95.

the rate of metabolism. From this point of view regarding the nature of stimulation, the current of action is readily explicable. Any stimulated region is a region whose metabolic rate has been temporarily increased by the stimulation, and as in the preceding cases, it must necessarily form with non-stimulated regions of lower rate a concentration cell with respect to rate of metabolism. It must there

fore be electronegative to such non-stimulated regions. The various kinds of bioelectric currents are thus conceived as referable to the same cause, differences in metabolic rate; and they are, apparently, merely the consequence of such differences, and of no significance in themselves.

This explanation of the current of action has been long held by Waller (loc. cit.), who on scanty and indirect evidence and in the face of skepticism from other physiologists maintained that the metabolism of nerves is the same as that of other protoplasm, that the current of action is due to sudden increase in their rate of metabolism, and that this current is merely a sign of that metabolic change. Waller's idea has received strong confirmation through Tashiro's work.

Certain interesting corollaries follow if this conception of the nature of stimulation is true. Thus if an increase in metabolic rate is the essential feature of stimulation, it follows that any organ or cell whose rate of metabolism is already sufficiently high will function without stimulation—in other words, it will be automatic. Some physiologists deny that there are any truly automatic organs, but surely the facts that are known about the heart, the medullary centers, and the digestive tract sufficiently prove that automaticity is a real phenomenon. Consider, for instance, the embryonic heart, which in all known cases, has a beat of myogenic origin. The metabolic rate of this young muscle tissue is in all probability so high that it contracts in the absence of stimulation from without. Later, as the rate falls with age, the aid of the nervous system must be evoked to keep the apparatus going. The nervous system is, indeed, the automatic structure par excellence of the body and,

as our conception demands, it is characterized by an exceedingly high rate of metabolism. This is demonstrated not only by its blood supply, its great susceptibility to lack of oxygen, to anesthesia, to cyanide and other poisons, but also by direct measurements of its rate of oxygen consumption. Thus, Alexander and Cserna19 find that the oxygen consumption of the brain is vastly greater than that of equal weights of any other organs, and MacArthur and Jones20 that the cerebrum and cerebellum respire faster than any other parts of the central nervous system, the rate decreasing gradually from these parts posteriorly. The nervous system by virtue of its intrinsically high metabolic rate is able to control other parts of the body, and to increase their metabolic rates by sending impulses along the nerves.

It should be mentioned that stimulation is characterized not only by the acceleration of the metabolic processes but also by other changes, which may well be the consequences of this acceleration, such as alteration of the colloidal state (probably in the direction of liquefaction), increase in permeability, and other effects.

4. Galvanotaxis.-The metabolic gradient also furnishes us with a logical explanation of the phenomena of galvanotaxis. It is well known that many animals when placed in an electric current will turn their anterior ends toward the cathode and travel to the cathode, maintaining such an orientation. Now as I pointed out in the first section of this paper, the anterior ends of a variety of organisms have been shown to have a higher metabolic rate than other parts of the body and to be electropositive (internally) to other parts. Since then the anterior end is positively charged or at least possesses the properties of an anode, it must when placed in the current be directed toward the cathode and it will tend to travel towards the cathode like any other positively charged material. Animals on the same basis might also travel backwards to the anode. Galvanotaxis is then a real taxis, or 19 Biochem. Zeitsch., LIII., p. 106. 20 Jr. of Biol. Chem., XXXII., p. 259.

forced orientation, in the sense of Loeb. A crucial test of this hypothesis can be made upon the oligochaete worms, where, as we know from experiment, there are two regions of high metabolic rate and of electropositivity, -namely, the anterior and posterior ends. These animals should then when placed in a current bend themselves into a U-shape, head and posterior end directed towards the cathode, and middle towards the anode, and travel to the anode maintaining such a' posture. This is exactly what they do as first pointed out by Moore and Kellogg21 and since confirmed by Mr. Bellamy.

5. Other Electric Phenomena.-Since regions of high metabolic rate are electropositive (internally) to regions of lower metabolic rate, it follows that if any region can be made electropositive by running a current through it, that region must then have its metabolic processes accelerated and must thereby be stimulated, must become more irritable. That this is true is a familiar fact in electrophysiology. A constant current stimulates at the cathode when the current is made that is, the region around the cathode becomes positively charged (or possibly becomes an anode in some other way), and hence has a higher metabolic rate, and serves as the source of the response. Similarly on the break of the current, the area of stimulation is that surrounding the anode, it having been shown that on the break the anode is really temporarily a cathode. Electrotonus is the same phenomenon. After prolonged passage of the electric current through a tissue, a large region around the cathode becomes excessively irritable because it is full of positively charged particles, 22 and a large region around the 21 Biol. Bull., XXX., p. 131.

22 I do not wish to be understood as stating positively that the electrical sign of various parts of the organism is actually due to their containing free particles of that sign. This seems the most convenient way of putting the matter but the facts in themselves do not serve to determine whether the charge is on the inside or on the surface or indeed what condition is responsible for it. The facts of electrotonus would seem to favor the idea that the charged particles are inside.

THE two-hundredth regular meeting of the society was held at Columbia University on Saturday, October 26, 1918. War conditions were reflected in an attendance of only eleven members. Professor E. W. Brown, of Yale University, presided at the morning session, and Professor O. E. Glenn, of the University of Pennsylvania, at the afternoon session. The following new members were elected: Professor R. A. Arms, Juniata College; Professor M. D. Earle, Furman University; Professor Ernest Flammer, Queen's University; Professor Gillie A. Larew, Randolph-Macon Woman's College; Dr. Flora E. LeStourgeon, University of Chicago; Professor John Matheson, Queen's University; Mr. F. R. Morris, University of California; Professor Susan M. Rambo, Smith College; Dr. W. G. Simon, Adelbert College. One application for membership was received.

A list of nominations for officers and other members of the Council was prepared and ordered printed on the ballot for the annual election in December. A committee was appointed to audit the accounts of the Treasurer for the current year. A committee was also formed to collect funds for a suitable memorial to the late Professor Maxime Bôcher, of Harvard University, who was president of the society in 1909-1910.

The following papers were read at this meeting:

J. E. McAtee: "The transformation of a regular group into its conjoint."

E. W. Chittenden : "On the Heine-Borel property in the theory of abstract sets."

G. A. Larew: "Necessary conditions for the problem of Mayer in the calculus of variations."

D. M. Y. Sommerville: "Quadratic systems of circles in non-euclidean geometry." M. B. Porter: "Derivativeless continuous functions."

G. H. Hallett, Jr.: "Concerning the definition of a simple continuous arc."

R. L. Moore: "A characterization of Jordan regions by properties having no reference to their boundaries."

R. L. Moore: "Concerning simple continuous curves."

Edward Kasner: "Fields of force and Monge equations."

It was decided to hold the annual meeting of the society at Chicago in the Christmas holidays. No eastern meeting will be held at that season. But members attending the Baltimore meeting of the American Association are invited to read their papers before Section A, after registering titles and abstracts with the Secretary of the Society for record in the report of the Chicago meeting.

The southwestern section will not hold its Thanksgiving meeting this year. The February, 1919, meeting of the society will also be omitted. A regular meeting will be held in New York on April 26. The official list of officers and members will not be published in 1919. F. N. COLE, Secretary