Chapter VIII: Book IV: Modern Development of the Chemical and Biological Sciences (8)

"So much for the life and nutrition of this organism. In respect to its virulence, it is an extraordinary fact that it disappears entirely after eight days' culture at 42 to 43 degrees Centigrade, or, at any rate, the cultures are innocuous for the guinea-pig, the rabbit, and the sheep, the three kinds of animals most apt to contract anthrax. We are thus able to obtain, not only the attenuation of the virulence, but also its complete suppression by a simple method of cultivation. Moreover, we see also the possibility of preserving and cultivating the terrible microbe in an inoffensive state. What is it that happens in these eight days at 43 degrees that suffices to take away the virulence of the bacteria? Let us remember that the microbe of chicken cholera dies in contact with the air, in a period somewhat protracted, it is true, but after successive attenuations. Are we justified in thinking that it ought to be the same in regard to the microbe of anthrax? This hypothesis is confirmed by experiment. Before the disappearance of its virulence the anthrax microbe passes through various degrees of attenuation, and, moreover, as is also the case with the microbe of chicken cholera, each of these attenuated states of virulence can be obtained by cultivation. Moreover, since, according to one of our recent Communications, anthrax is not recurrent, each of our attenuated anthrax microbes is, for the better-developed microbe, a vaccine--that is to say, a virus producing a less-malignant malady. What, therefore, is easier than to find in these a virus that will infect with anthrax sheep, cows, and horses, without killing them, and ultimately capable of warding off the mortal malady? We have practised this experiment with great success upon sheep, and when the season comes for the assembling of the flocks at Beauce we shall try the experiment on a larger scale.

"Already M. Toussaint has announced that sheep can be saved by preventive inoculations; but when this able observer shall have published his results; on the subject of which we have made such exhaustive studies, as yet unpublished, we shall be able to see the whole difference which exists between the two methods--the uncertainty of the one and the certainty of the other. That which we announce has, moreover, the very great advantage of resting upon the existence of a poison vaccine cultivable at will, and which can be increased indefinitely in the space of a few hours without having recourse to infected blood."(8)

This announcement was immediately challenged in a way that brought it to the attention of the entire world. The president of an agricultural society, realizing the enormous importance of the subject, proposed to Pasteur that his alleged discovery should be submitted to a decisive public test. He proposed to furnish a drove of fifty sheep half of which were to be inoculated with the attenuated virus of Pasteur. Subsequently all the sheep were to be inoculated with virulent virus, all being kept together in one pen under precisely the same conditions. The "protected" sheep were to remain healthy; the unprotected ones to die of anthrax; so read the terms of the proposition. Pasteur accepted the challenge; he even permitted a change in the programme by which two goats were substituted for two of the sheep, and ten cattle added, stipulating, however, that since his experiments had not yet been extended to cattle these should not be regarded as falling rigidly within the terms of the test.

It was a test to try the soul of any man, for all the world looked on askance, prepared to deride the maker of so preposterous a claim as soon as his claim should be proved baseless. Not even the fame of Pasteur could make the public at large, lay or scientific, believe in the possibility of what he proposed to accomplish. There was time for all the world to be informed of the procedure, for the first "preventive" inoculation--or vaccination, as Pasteur termed it--was made on May 5th, the second on May 17th, and another interval of two weeks must elapse before the final inoculations with the unattenuated virus. Twenty-four sheep, one goat, and five cattle were submitted to the preliminary vaccinations. Then, on May 31 st, all sixty of the animals were inoculated, a protected and unprotected one alternately, with an extremely virulent culture of anthrax microbes that had been in Pasteur's laboratory since 1877. This accomplished, the animals were left together in one enclosure to await the issue.

Two days later, June 2d, at the appointed hour of rendezvous, a vast crowd, composed of veterinary surgeons, newspaper correspondents, and farmers from far and near, gathered to witness the closing scenes of this scientific tourney. What they saw was one of the most dramatic scenes in the history of peaceful science--a scene which, as Pasteur declared afterwards, "amazed the assembly." Scattered about the enclosure, dead, dying, or manifestly sick unto death, lay the unprotected animals, one and all, while each and every "protected" animal stalked unconcernedly about with every appearance of perfect health. Twenty of the sheep and the one goat were already dead; two other sheep expired under the eyes of the spectators; the remaining victims lingered but a few hours longer. Thus in a manner theatrical enough, not to say tragic, was proclaimed the unequivocal victory of science. Naturally enough, the unbelievers struck their colors and surrendered without terms; the principle of protective vaccination, with a virus experimentally prepared in the laboratory, was established beyond the reach of controversy.

That memorable scientific battle marked the beginning of a new era in medicine. It was a foregone conclusion that the principle thus established would be still further generalized; that it would be applied to human maladies; that in all probability it would grapple successfully, sooner or later, with many infectious diseases. That expectation has advanced rapidly towards realization. Pasteur himself made the application to the human subject in the disease hydrophobia in 1885, since which time that hitherto most fatal of maladies has largely lost its terrors. Thousands of persons bitten by mad dogs have been snatched from the fatal consequences of that mishap by this method at the Pasteur Institute in Paris, and at the similar institutes, built on the model of this parent one, that have been established all over the world in regions as widely separated as New York and Nha-Trang.

SERUM-THERAPY

In the production of the rabies vaccine Pasteur and his associates developed a method of attenuation of a virus quite different from that which had been employed in the case of the vaccines of chicken cholera and of anthrax. The rabies virus was inoculated into the system of guinea-pigs or rabbits and, in effect, cultivated in the systems of these animals. The spinal cord of these infected animals was found to be rich in the virus, which rapidly became attenuated when the cord was dried in the air. The preventive virus, of varying strengths, was made by maceration of these cords at varying stages of desiccation. This cultivation of a virus within the animal organism suggested, no doubt, by the familiar Jennerian method of securing small-pox vaccine, was at the same time a step in the direction of a new therapeutic procedure which was destined presently to become of all-absorbing importance--the method, namely, of so-called serum-therapy, or the treatment of a disease with the blood serum of an animal that has been subjected to protective inoculation against that disease.

The possibility of such a method was suggested by the familiar observation, made by Pasteur and numerous other workers, that animals of different species differ widely in their susceptibility to various maladies, and that the virus of a given disease may become more and more virulent when passed through the systems of successive individuals of one species, and, contrariwise, less and less virulent when passed through the systems of successive individuals of another species. These facts suggested the theory that the blood of resistant animals might contain something directly antagonistic to the virus, and the hope that this something might be transferred with curative effect to the blood of an infected susceptible animal. Numerous experimenters all over the world made investigations along the line of this alluring possibility, the leaders perhaps being Drs. Behring and Kitasato, closely followed by Dr. Roux and his associates of the Pasteur Institute of Paris. Definite results were announced by Behring in 1892 regarding two important diseases--tetanus and diphtheria--but the method did not come into general notice until 1894, when Dr. Roux read an epoch-making paper on the subject at the Congress of Hygiene at Buda-Pesth.

In this paper Dr. Roux, after adverting to the labors of Behring, Ehrlich, Boer, Kossel, and Wasserman, described in detail the methods that had been developed at the Pasteur Institute for the development of the curative serum, to which Behring had given the since-familiar name antitoxine. The method consists, first, of the cultivation, for some months, of the diphtheria bacillus (called the Klebs-Loeffler bacillus, in honor of its discoverers) in an artificial bouillon, for the development of a powerful toxine capable of giving the disease in a virulent form.

This toxine, after certain details of mechanical treatment, is injected in small but increasing doses into the system of an animal, care being taken to graduate the amount so that the animal does not succumb to the disease. After a certain course of this treatment it is found that a portion of blood serum of the animal so treated will act in a curative way if injected into the blood of another animal, or a human patient, suffering with diphtheria. In other words, according to theory, an antitoxine has been developed in the system of the animal subjected to the progressive inoculations of the diphtheria toxine. In Dr. Roux's experience the animal best suited for the purpose is the horse, though almost any of the domesticated animals will serve the purpose.

But Dr. Roux's paper did not stop with the description of laboratory methods. It told also of the practical application of the serum to the treatment of numerous cases of diphtheria in the hospitals of Paris--applications that had met with a gratifying measure of success. He made it clear that a means had been found of coping successfully with what had been one of the most virulent and intractable of the diseases of childhood. Hence it was not strange that his paper made a sensation in all circles, medical and lay alike.

Physicians from all over the world flocked to Paris to learn the details of the open secret, and within a few months the new serum-therapy had an acknowledged standing with the medical profession everywhere. What it had accomplished was regarded as but an earnest of what the new method might accomplish presently when applied to the other infectious diseases.

Efforts at such applications were immediately begun in numberless directions--had, indeed, been under way in many a laboratory for some years before. It is too early yet to speak of the results in detail. But enough has been done to show that this method also is susceptible of the widest generalization. It is not easy at the present stage to sift that which is tentative from that which will be permanent; but so great an authority as Behring does not hesitate to affirm that today we possess, in addition to the diphtheria antitoxine, equally specific antitoxines of tetanus, cholera, typhus fever, pneumonia, and tuberculosis--a set of diseases which in the aggregate account for a startling proportion of the general death-rate. Then it is known that Dr. Yersin, with the collaboration of his former colleagues of the Pasteur Institute, has developed, and has used with success, an antitoxine from the microbe of the plague which recently ravaged China.

Dr. Calmette, another graduate of the Pasteur Institute, has extended the range of the serum-therapy to include the prevention and treatment of poisoning by venoms, and has developed an antitoxine that has already given immunity from the lethal effects of snake bites to thousands of persons in India and Australia.

Just how much of present promise is tentative, just what are the limits of the methods--these are questions for the future to decide. But, in any event, there seems little question that the serum treatment will stand as the culminating achievement in therapeutics of our century. It is the logical outgrowth of those experimental studies with the microscope begun by our predecessors of the thirties, and it represents the present culmination of the rigidly experimental method which has brought medicine from a level of fanciful empiricism to the plane of a rational experimental science.

IX. THE NEW SCIENCE OF EXPERIMENTAL PSYCHOLOGY

BRAIN AND MIND

A little over a hundred years ago a reform movement was afoot in the world in the interests of the insane. As was fitting, the movement showed itself first in America, where these unfortunates were humanely cared for at a time when their treatment elsewhere was worse than brutal; but England and France quickly fell into line. The leader on this side of the water was the famous Philadelphian, Dr. Benjamin Rush, "the Sydenham of America"; in England, Dr. William Tuke inaugurated the movement; and in France, Dr. Philippe Pinel, single-handed, led the way. Moved by a common spirit, though acting quite independently, these men raised a revolt against the traditional custom which, spurning the insane as demon-haunted outcasts, had condemned these unfortunates to dungeons, chains, and the lash. Hitherto few people had thought it other than the natural course of events that the "maniac" should be thrust into a dungeon, and perhaps chained to the wall with the aid of an iron band riveted permanently about his neck or waist. Many an unfortunate, thus manacled, was held to the narrow limits of his chain for years together in a cell to which full daylight never penetrated; sometimes--iron being expensive--the chain was so short that the wretched victim could not rise to the upright posture or even shift his position upon his squalid pallet of straw.

In America, indeed, there being no Middle Age precedents to crystallize into established customs, the treatment accorded the insane had seldom or never sunk to this level. Partly for this reason, perhaps, the work of Dr. Rush at the Philadelphia Hospital, in 1784, by means of which the insane came to be humanely treated, even to the extent of banishing the lash, has been but little noted, while the work of the European leaders, though belonging to later decades, has been made famous. And perhaps this is not as unjust as it seems, for the step which Rush took, from relatively bad to good, was a far easier one to take than the leap from atrocities to good treatment which the European reformers were obliged to compass. In Paris, for example, Pinel was obliged to ask permission of the authorities even to make the attempt at liberating the insane from their chains, and, notwithstanding his recognized position as a leader of science, he gained but grudging assent, and was regarded as being himself little better than a lunatic for making so manifestly unwise and hopeless an attempt. Once the attempt had been made, however, and carried to a successful issue, the amelioration wrought in the condition of the insane was so patent that the fame of Pinel's work at the Bicetre and the Salpetriere went abroad apace. It required, indeed, many years to complete it in Paris, and a lifetime of effort on the part of Pinel's pupil Esquirol and others to extend the reform to the provinces; but the epochal turning-point had been reached with Pinel's labors of the closing years of the eighteenth century.

The significance of this wise and humane reform, in the present connection, is the fact that these studies of the insane gave emphasis to the novel idea, which by-and-by became accepted as beyond question, that "demoniacal possession" is in reality no more than the outward expression of a diseased condition of the brain. This realization made it clear, as never before, how intimately the mind and the body are linked one to the other. And so it chanced that, in striking the shackles from the insane, Pinel and his confreres struck a blow also, unwittingly, at time-honored philosophical traditions. The liberation of the insane from their dungeons was an augury of the liberation of psychology from the musty recesses of metaphysics. Hitherto psychology, in so far as it existed at all, was but the subjective study of individual minds; in future it must become objective as well, taking into account also the relations which the mind bears to the body, and in particular to the brain and nervous system.

The necessity for this collocation was advocated quite as earnestly, and even more directly, by another worker of this period, whose studies were allied to those of alienists, and who, even more actively than they, focalized his attention upon the brain and its functions. This earliest of specialists in brain studies was a German by birth but Parisian by adoption, Dr. Franz Joseph Gall, originator of the since-notorious system of phrenology. The merited disrepute into which this system has fallen through the exposition of peripatetic charlatans should not make us forget that Dr. Gall himself was apparently a highly educated physician, a careful student of the brain and mind according to the best light of his time, and, withal, an earnest and honest believer in the validity of the system he had originated. The system itself, taken as a whole, was hopelessly faulty, yet it was not without its latent germ of truth, as later studies were to show. How firmly its author himself believed in it is evidenced by the paper which he contributed to the French Academy of Sciences in 1808. The paper itself was referred to a committee of which Pinel and Cuvier were members. The verdict of this committee was adverse, and justly so; yet the system condemned had at least one merit which its detractors failed to realize. It popularized the conception that the brain is the organ of mind. Moreover, by its insistence it rallied about it a band of scientific supporters, chief of whom was Dr. Kaspar Spurzlieim, a man of no mean abilities, who became the propagandist of phrenology in England and in America. Of course such advocacy and popularity stimulated opposition as well, and out of the disputations thus arising there grew presently a general interest in the brain as the organ of mind, quite aside from any preconceptions whatever as to the doctrines of Gall and Spurzheim.

Prominent among the unprejudiced class of workers who now appeared was the brilliant young Frenchman Louis Antoine Desmoulins, who studied first under the tutorage of the famous Magendie, and published jointly with him a classical work on the nervous system of vertebrates in 1825. Desmoulins made at least one discovery of epochal importance. He observed that the brains of persons dying in old age were lighter than the average and gave visible evidence of atrophy, and he reasoned that such decay is a normal accompaniment of senility. No one nowadays would question the accuracy of this observation, but the scientific world was not quite ready for it in 1825; for when Desmoulins announced his discovery to the French Academy, that august and somewhat patriarchal body was moved to quite unscientific wrath, and forbade the young iconoclast the privilege of further hearings. From which it is evident that the partially liberated spirit of the new psychology had by no means freed itself altogether, at the close of the first quarter of the nineteenth century, from the metaphysical cobwebs of its long incarceration.

FUNCTIONS OF THE NERVES

While studies of the brain were thus being inaugurated, the nervous system, which is the channel of communication between the brain and the outside world, was being interrogated with even more tangible results. The inaugural discovery was made in 1811 by Dr. (afterwards Sir Charles) Bell,(1) the famous English surgeon and experimental physiologist. It consisted of the observation that the anterior roots of the spinal nerves are given over to the function of conveying motor impulses from the brain outward, whereas the posterior roots convey solely sensory impulses to the brain from without. Hitherto it had been supposed that all nerves have a similar function, and the peculiar distribution of the spinal nerves had been an unsolved puzzle.

Bell's discovery was epochal; but its full significance was not appreciated for a decade, nor, indeed, was its validity at first admitted. In Paris, in particular, then the court of final appeal in all matters scientific, the alleged discovery was looked at askance, or quite ignored. But in 1823 the subject was taken up by the recognized leader of French physiology--Francois Magendie--in the course of his comprehensive experimental studies of the nervous system, and Bell's conclusions were subjected to the most rigid experimental tests and found altogether valid. Bell himself, meanwhile, had turned his attention to the cranial nerves, and had proved that these also are divisible into two sets--sensory and motor. Sometimes, indeed, the two sets of filaments are combined into one nerve cord, but if traced to their origin these are found to arise from different brain centres. Thus it was clear that a hitherto unrecognized duality of function pertains to the entire extra-cranial nervous system. Any impulse sent from the periphery to the brain must be conveyed along a perfectly definite channel; the response from the brain, sent out to the peripheral muscles, must traverse an equally definite and altogether different course. If either channel is interrupted--as by the section of its particular nerve tract--the corresponding message is denied transmission as effectually as an electric current is stopped by the section of the transmitting wire.

Experimenters everywhere soon confirmed the observations of Bell and Magendie, and, as always happens after a great discovery, a fresh impulse was given to investigations in allied fields. Nevertheless, a full decade elapsed before another discovery of comparable importance was made. Then Marshall Hall, the most famous of English physicians of his day, made his classical observations on the phenomena that henceforth were to be known as reflex action. In 1832, while experimenting one day with a decapitated newt, he observed that the headless creature's limbs would contract in direct response to certain stimuli. Such a response could no longer be secured if the spinal nerves supplying a part were severed. Hence it was clear that responsive centres exist in the spinal cord capable of receiving a sensory message and of transmitting a motor impulse in reply--a function hitherto supposed to be reserved for the brain. Further studies went to show that such phenomena of reflex action on the part of centres lying outside the range of consciousness, both in the spinal cord and in the brain itself, are extremely common; that, in short, they enter constantly into the activities of every living organism and have a most important share in the sum total of vital movements. Hence, Hall's discovery must always stand as one of the great mile-stones of the advance of neurological science.

Hall gave an admirably clear and interesting account of his experiments and conclusions in a paper before the Royal Society, "On the Reflex Functions of the Medulla Oblongata and the Medulla Spinalis," from which, as published in the Transactions of the society for 1833, we may quote at some length:

"In the entire animal, sensation and voluntary motion, functions of the cerebrum, combine with the functions of the medulla oblongata and medulla spinalis, and may therefore render it difficult or impossible to determine those which are peculiar to each; if, in an animal deprived of the brain, the spinal marrow or the nerves supplying the muscles be stimulated, those muscles, whether voluntary or respiratory, are equally thrown into contraction, and, it may be added, equally in the complete and in the mutilated animal; and, in the case of the nerves, equally in limbs connected with and detached from the spinal marrow.

"The operation of all these various causes may be designated centric, as taking place AT, or at least in a direction FROM, central parts of the nervous system. But there is another function the phenomena of which are of a totally different order and obey totally different laws, being excited by causes in a situation which is EXCENTRIC in the nervous system--that is, distant from the nervous centres. This mode of action has not, I think, been hitherto distinctly understood by physiologists.

"Many of the phenomena of this principle of action, as they occur in the limbs, have certainly been observed. But, in the first place, this function is by no means confined to the limbs; for, while it imparts to each muscle its appropriate tone, and to each system of muscles its appropriate equilibrium or balance, it performs the still more important office of presiding over the orifices and terminations of each of the internal canals in the animal economy, giving them their due form and action; and, in the second place, in the instances in which the phenomena of this function have been noticed, they have been confounded, as I have stated, with those of sensation and volition; or, if they have been distinguished from these, they have been too indefinitely denominated instinctive, or automatic. I have been compelled, therefore, to adopt some new designation for them, and I shall now give the reasons for my choice of that which is given in the title of this paper--'Reflex Functions.'

"This property is characterized by being EXCITED in its action and REFLEX in its course: in every instance in which it is exerted an impression made upon the extremities of certain nerves is conveyed to the medulla oblongata or the medulla spinalis, and is reflected along the nerves to parts adjacent to, or remote from, that which has received the impression.

"It is by this reflex character that the function to which I have alluded is to be distinguished from every other. There are, in the animal economy, four modes of muscular action, of muscular contraction. The first is that designated VOLUNTARY: volition, originated in the cerebrum and spontaneous in its acts, extends its influence along the spinal marrow and the motor nerves in a DIRECT LINE to the voluntary muscles. The SECOND is that of RESPIRATION: like volition, the motive influence in respiration passes in a DIRECT LINE from one point of the nervous system to certain muscles; but as voluntary motion seems to originate in the cerebrum, so the respiratory motions originate in the medulla oblongata: like the voluntary motions, the motions of respirations are spontaneous; they continue, at least, after the eighth pair of nerves have been divided. The THIRD kind of muscular action in the animal economy is that termed involuntary: it depends upon the principle of irritability and requires the IMMEDIATE application of a stimulus to the nervo-muscular fibre itself. These three kinds of muscular motion are well known to physiologists; and I believe they are all which have been hitherto pointed out. There is, however, a FOURTH, which subsists, in part, after the voluntary and respiratory motions have ceased, by the removal of the cerebrum and medulla oblongata, and which is attached to the medulla spinalis, ceasing itself when this is removed, and leaving the irritability undiminished. In this kind of muscular motion the motive influence does not originate in any central part of the nervous system, but from a distance from that centre; it is neither spontaneous in its action nor direct in its course; it is, on the contrary, EXCITED by the application of appropriate stimuli, which are not, however, applied immediately to the muscular or nervo-muscular fibre, but to certain membraneous parts, whence the impression is carried through the medulla, REFLECTED and reconducted to the part impressed, or conducted to a part remote from it in which muscular contraction is effected.

"The first three modes of muscular action are known only by actual movements of muscular contractions. But the reflex function exists as a continuous muscular action, as a power presiding over organs not actually in a state of motion, preserving in some, as the glottis, an open, in others, as the sphincters, a closed form, and in the limbs a due degree of equilibrium or balanced muscular action--a function not, I think, hitherto recognized by physiologists.

"The three kinds of muscular motion hitherto known may be distinguished in another way. The muscles of voluntary motion and of respiration may be excited by stimulating the nerves which supply them, in any part of their course, whether at their source as a part of the medulla oblongata or the medulla spinalis or exterior to the spinal canal: the muscles of involuntary motion are chiefly excited by the actual contact of stimuli. In the case of the reflex function alone the muscles are excited by a stimulus acting mediately and indirectly in a curved and reflex course, along superficial subcutaneous or submucous nerves proceeding from the medulla. The first three of these causes of muscular motion may act on detached limbs or muscles. The last requires the connection with the medulla to be preserved entire.

"All the kinds of muscular motion may be unduly excited, but the reflex function is peculiar in being excitable in two modes of action, not previously subsisting in the animal economy, as in the case of sneezing, coughing, vomiting, etc. The reflex function also admits of being permanently diminished or augmented and of taking on some other morbid forms, of which I shall treat hereafter.

"Before I proceed to the details of the experiments upon which this disposition rests, it may be well to point out several instances in illustration of the various sources of and the modes of muscular action which have been enumerated. None can be more familiar than the act of swallowing. Yet how complicated is the act! The apprehension of the food by the teeth and tongue, etc., is voluntary, and cannot, therefore, take place in an animal from which the cerebrum is removed. The transition of food over the glottis and along the middle and lower part of the pharynx depends upon the reflex action: it can take place in animals from which the cerebrum has been removed or the ninth pair of nerves divided; but it requires the connection with the medulla oblongata to be preserved entirely; and the actual contact of some substance which may act as a stimulus: it is attended by the accurate closure of the glottis and by the contraction of the pharynx. The completion of the act of deglutition is dependent upon the stimulus immediately impressed upon the muscular fibre of the oesophagus, and is the result of excited irritability.

"However plain these observations may have made the fact that there is a function of the nervous muscular system distinct from sensation, from the voluntary and respiratory motions, and from irritability, it is right, in every such inquiry as the present, that the statements and reasonings should be made with the experiment, as it were, actually before us. It has already been remarked that the voluntary and respiratory motions are spontaneous, not necessarily requiring the agency of a stimulus. If, then, an animal can be placed in such circumstances that such motions will certainly not take place, the power of moving remaining, it may be concluded that volition and the motive influence of respiration are annihilated. Now this is effected by removing the cerebrum and the medulla oblongata. These facts are fully proved by the experiments of Legallois and M. Flourens, and by several which I proceed to detail, for the sake of the opportunity afforded by doing so of stating the arguments most clearly.

"I divided the spinal marrow of a very lively snake between the second and third vertebrae. The movements of the animal were immediately before extremely vigorous and unintermitted. From the moment of the division of the spinal marrow it lay perfectly tranquil and motionless, with the exception of occasional gaspings and slight movements of the head. It became quite evident that this state of quiescence would continue indefinitely were the animal secured from all external impressions.

"Being now stimulated, the body began to move with great activity, and continued to do so for a considerable time, each change of position or situation bringing some fresh part of the surface of the animal into contact with the table or other objects and renewing the application of stimulants.

"At length the animal became again quiescent; and being carefully protected from all external impressions it moved no more, but died in the precise position and form which it had last assumed.

"It requires a little manoeuvre to perform this experiment successfully: the motions of the animal must be watched and slowly and cautiously arrested by opposing some soft substance, as a glove or cotton wool; they are by this means gradually lulled into quiescence. The slightest touch with a hard substance, the slightest stimulus, will, on the other hand, renew the movements on the animal in an active form. But that this phenomenon does not depend upon sensation is further fully proved by the facts that the position last assumed, and the stimuli, may be such as would be attended by extreme or continued pain, if the sensibility were undestroyed: in one case the animal remained partially suspended over the acute edge of the table; in others the infliction of punctures and the application of a lighted taper did not prevent the animal, still possessed of active powers of motion, from passing into a state of complete and permanent quiescence."

In summing up this long paper Hall concludes with this sentence: "The reflex function appears in a word to be the COMPLEMENT of the functions of the nervous system hitherto known."(2)

All these considerations as to nerve currents and nerve tracts becoming stock knowledge of science, it was natural that interest should become stimulated as to the exact character of these nerve tracts in themselves, and all the more natural in that the perfected microscope was just now claiming all fields for its own. A troop of observers soon entered upon the study of the nerves, and the leader here, as in so many other lines of microscopical research, was no other than Theodor Schwann. Through his efforts, and with the invaluable aid of such other workers as Remak, Purkinje, Henle, Muller, and the rest, all the mystery as to the general characteristics of nerve tracts was cleared away. It came to be known that in its essentials a nerve tract is a tenuous fibre or thread of protoplasm stretching between two terminal points in the organism, one of such termini being usually a cell of the brain or spinal cord, the other a distribution-point at or near the periphery--for example, in a muscle or in the skin. Such a fibril may have about it a protective covering, which is known as the sheath of Schwann; but the fibril itself is the essential nerve tract; and in many cases, as Remak presently discovered, the sheath is dispensed with, particularly in case of the nerves of the so-called sympathetic system.

This sympathetic system of ganglia and nerves, by-the-bye, had long been a puzzle to the physiologists. Its ganglia, the seeming centre of the system, usually minute in size and never very large, are found everywhere through the organism, but in particular are gathered into a long double chain which lies within the body cavity, outside the spinal column, and represents the sole nervous system of the non-vertebrated organisms. Fibrils from these ganglia were seen to join the cranial and spinal nerve fibrils and to accompany them everywhere, but what special function they subserved was long a mere matter of conjecture and led to many absurd speculations. Fact was not substituted for conjecture until about the year 1851, when the great Frenchman Claude Bernard conclusively proved that at least one chief function of the sympathetic fibrils is to cause contraction of the walls of the arterioles of the system, thus regulating the blood-supply of any given part. Ten years earlier Henle had demonstrated the existence of annular bands of muscle fibres in the arterioles, hitherto a much-mooted question, and several tentative explanations of the action of these fibres had been made, particularly by the brothers Weber, by Stilling, who, as early as 1840, had ventured to speak of "vaso-motor" nerves, and by Schiff, who was hard upon the same track at the time of Bernard's discovery. But a clear light was not thrown on the subject until Bernard's experiments were made in 1851. The experiments were soon after confirmed and extended by Brown-Sequard, Waller, Budge, and numerous others, and henceforth physiologists felt that they understood how the blood-supply of any given part is regulated by the nervous system.

In reality, however, they had learned only half the story, as Bernard himself proved only a few years later by opening up a new and quite unsuspected chapter. While experimenting in 1858 he discovered that there are certain nerves supplying the heart which, if stimulated, cause that organ to relax and cease beating. As the heart is essentially nothing more than an aggregation of muscles, this phenomenon was utterly puzzling and without precedent in the experience of physiologists. An impulse travelling along a motor nerve had been supposed to be able to cause a muscular contraction and to do nothing else; yet here such an impulse had exactly the opposite effect. The only tenable explanation seemed to be that this particular impulse must arrest or inhibit the action of the impulses that ordinarily cause the heart muscles to contract. But the idea of such inhibition of one impulse by another was utterly novel and at first difficult to comprehend. Gradually, however, the idea took its place in the current knowledge of nerve physiology, and in time it came to be understood that what happens in the case of the heart nerve-supply is only a particular case under a very general, indeed universal, form of nervous action. Growing out of Bernard's initial discovery came the final understanding that the entire nervous system is a mechanism of centres subordinate and centres superior, the action of the one of which may be counteracted and annulled in effect by the action of the other. This applies not merely to such physical processes as heart-beats and arterial contraction and relaxing, but to the most intricate functionings which have their counterpart in psychical processes as well. Thus the observation of the inhibition of the heart's action by a nervous impulse furnished the point of departure for studies that led to a better understanding of the modus operandi of the mind's activities than had ever previously been attained by the most subtle of psychologists.

PSYCHO-PHYSICS

The work of the nerve physiologists had thus an important bearing on questions of the mind. But there was another company of workers of this period who made an even more direct assault upon the "citadel of thought." A remarkable school of workers had been developed in Germany, the leaders being men who, having more or less of innate metaphysical bias as a national birthright, had also the instincts of the empirical scientist, and whose educational equipment included a profound knowledge not alone of physiology and psychology, but of physics and mathematics as well. These men undertook the novel task of interrogating the relations of body and mind from the standpoint of physics. They sought to apply the vernier and the balance, as far as might be, to the intangible processes of mind.

The movement had its precursory stages in the early part of the century, notably in the mathematical psychology of Herbart, but its first definite output to attract general attention came from the master-hand of Hermann Helmholtz in 1851. It consisted of the accurate measurement of the speed of transit of a nervous impulse along a nerve tract. To make such measurement had been regarded as impossible, it being supposed that the flight of the nervous impulse was practically instantaneous. But Helmholtz readily demonstrated the contrary, showing that the nerve cord is a relatively sluggish message-bearer. According to his experiments, first performed upon the frog, the nervous "current" travels less than one hundred feet per second. Other experiments performed soon afterwards by Helmholtz himself, and by various followers, chief among whom was Du Bois-Reymond, modified somewhat the exact figures at first obtained, but did not change the general bearings of the early results. Thus the nervous impulse was shown to be something far different, as regards speed of transit, at any rate, from the electric current to which it had been so often likened. An electric current would flash halfway round the globe while a nervous impulse could travel the length of the human body--from a man's foot to his brain.

The tendency to bridge the gulf that hitherto had separated the physical from the psychical world was further evidenced in the following decade by Helmholtz's remarkable but highly technical study of the sensations of sound and of color in connection with their physical causes, in the course of which he revived the doctrine of color vision which that other great physiologist and physicist, Thomas Young, had advanced half a century before. The same tendency was further evidenced by the appearance, in 1852, of Dr. Hermann Lotze's famous Medizinische Psychologie, oder Physiologie der Seele, with its challenge of the old myth of a "vital force." But the most definite expression of the new movement was signalized in 1860, when Gustav Fechner published his classical work called Psychophysik. That title introduced a new word into the vocabulary of science. Fechner explained it by saying, "I mean by psychophysics an exact theory of the relation between spirit and body, and, in a general way, between the physical and the psychic worlds." The title became famous and the brunt of many a controversy. So also did another phrase which Fechner introduced in the course of his book--the phrase "physiological psychology." In making that happy collocation of words Fechner virtually christened a new science.

FECHNER EXPOUNDS WEBER'S LAW

The chief purport of this classical book of the German psycho-physiologist was the elaboration and explication of experiments based on a method introduced more than twenty years earlier by his countryman E. H. Weber, but which hitherto had failed to attract the attention it deserved. The method consisted of the measurement and analysis of the definite relation existing between external stimuli of varying degrees of intensity (various sounds, for example) and the mental states they induce. Weber's experiments grew out of the familiar observation that the nicety of our discriminations of various sounds, weights, or visual images depends upon the magnitude of each particular cause of a sensation in its relation with other similar causes. Thus, for example, we cannot see the stars in the daytime, though they shine as brightly then as at night. Again, we seldom notice the ticking of a clock in the daytime, though it may become almost painfully audible in the silence of the night. Yet again, the difference between an ounce weight and a two-ounce weight is clearly enough appreciable when we lift the two, but one cannot discriminate in the same way between a five-pound weight and a weight of one ounce over five pounds.

This last example, and similar ones for the other senses, gave Weber the clew to his novel experiments. Reflection upon every-day experiences made it clear to him that whenever we consider two visual sensations, or two auditory sensations, or two sensations of weight, in comparison one with another, there is always a limit to the keenness of our discrimination, and that this degree of keenness varies, as in the case of the weights just cited, with the magnitude of the exciting cause.

Weber determined to see whether these common experiences could be brought within the pale of a general law. His method consisted of making long series of experiments aimed at the determination, in each case, of what came to be spoken of as the least observable difference between the stimuli. Thus if one holds an ounce weight in each hand, and has tiny weights added to one of them, grain by grain, one does not at first perceive a difference; but presently, on the addition of a certain grain, he does become aware of the difference. Noting now how many grains have been added to produce this effect, we have the weight which represents the least appreciable difference when the standard is one ounce.

Now repeat the experiment, but let the weights be each of five pounds. Clearly in this case we shall be obliged to add not grains, but drachms, before a difference between the two heavy weights is perceived. But whatever the exact amount added, that amount represents the stimulus producing a just-perceivable sensation of difference when the standard is five pounds. And so on for indefinite series of weights of varying magnitudes. Now came Weber's curious discovery. Not only did he find that in repeated experiments with the same pair of weights the measure of "just-{p}erceivable difference" remained approximately fixed, but he found, further, that a remarkable fixed relation exists between the stimuli of different magnitude. If, for example, he had found it necessary, in the case of the ounce weights, to add one-fiftieth of an ounce to the one before a difference was detected, he found also, in the case of the five-pound weights, that one-fiftieth of five pounds must be added before producing the same result. And so of all other weights; the amount added to produce the stimulus of "least-appreciable difference" always bore the same mathematical relation to the magnitude of the weight used, be that magnitude great or small.

Weber found that the same thing holds good for the stimuli of the sensations of sight and of hearing, the differential stimulus bearing always a fixed ratio to the total magnitude of the stimuli. Here, then, was the law he had sought.

Weber's results were definite enough and striking enough, yet they failed to attract any considerable measure of attention until they were revived and extended by Fechner and brought before the world in the famous work on psycho-physics. Then they precipitated a veritable melee. Fechner had not alone verified the earlier results (with certain limitations not essential to the present consideration), but had invented new methods of making similar tests, and had reduced the whole question to mathematical treatment. He pronounced Weber's discovery the fundamental law of psycho-physics. In honor of the discoverer, he christened it Weber's Law. He clothed the law in words and in mathematical formulae, and, so to say, launched it full tilt at the heads of the psychological world. It made a fine commotion, be assured, for it was the first widely heralded bulletin of the new psychology in its march upon the strongholds of the time-honored metaphysics. The accomplishments of the microscopists and the nerve physiologists had been but preliminary--mere border skirmishes of uncertain import. But here was proof that the iconoclastic movement meant to invade the very heart of the sacred territory of mind--a territory from which tangible objective fact had been supposed to be forever barred.

PHYSIOLOGICAL PSYCHOLOGY

Hardly had the alarm been sounded, however, before a new movement was made. While Fechner's book was fresh from the press, steps were being taken to extend the methods of the physicist in yet another way to the intimate processes of the mind. As Helmholtz had shown the rate of nervous impulsion along the nerve tract to be measurable, it was now sought to measure also the time required for the central nervous mechanism to perform its work of receiving a message and sending out a response. This was coming down to the very threshold of mind. The attempt was first made by Professor Donders in 1861, but definitive results were only obtained after many years of experiment on the part of a host of observers. The chief of these, and the man who has stood in the forefront of the new movement and has been its recognized leader throughout the remainder of the century, is Dr. Wilhelm Wundt, of Leipzig.

The task was not easy, but, in the long run, it was accomplished. Not alone was it shown that the nerve centre requires a measurable time for its operations, but much was learned as to conditions that modify this time. Thus it was found that different persons vary in the rate of their central nervous activity--which explained the "personal equation" that the astronomer Bessel had noted a half-century before. It was found, too, that the rate of activity varies also for the same person under different conditions, becoming retarded, for example, under influence of fatigue, or in case of certain diseases of the brain. All details aside, the essential fact emerges, as an experimental demonstration, that the intellectual processes--sensation, apperception, volition--are linked irrevocably with the activities of the central nervous tissues, and that these activities, like all other physical processes, have a time element. To that old school of psychologists, who scarcely cared more for the human head than for the heels--being interested only in the mind--such a linking of mind and body as was thus demonstrated was naturally disquieting. But whatever the inferences, there was no escaping the facts.

Of course this new movement has not been confined to Germany. Indeed, it had long had exponents elsewhere. Thus in England, a full century earlier, Dr. Hartley had championed the theory of the close and indissoluble dependence of the mind upon the brain, and formulated a famous vibration theory of association that still merits careful consideration. Then, too, in France, at the beginning of the century, there was Dr. Cabanis with his tangible, if crudely phrased, doctrine that the brain digests impressions and secretes thought as the stomach digests food and the liver secretes bile. Moreover, Herbert Spencer's Principles of Psychology, with its avowed co-ordination of mind and body and its vitalizing theory of evolution, appeared in 1855, half a decade before the work of Fechner. But these influences, though of vast educational value, were theoretical rather than demonstrative, and the fact remains that the experimental work which first attempted to gauge mental operations by physical principles was mainly done in Germany. Wundt's Physiological Psychology, with its full preliminary descriptions of the anatomy of the nervous system, gave tangible expression to the growth of the new movement in 1874; and four years later, with the opening of his laboratory of physiological psychology at the University of Leipzig, the new psychology may be said to have gained a permanent foothold and to have forced itself into official recognition. From then on its conquest of the world was but a matter of time.

It should be noted, however, that there is one other method of strictly experimental examination of the mental field, latterly much in vogue, which had a different origin. This is the scientific investigation of the phenomena of hypnotism. This subject was rescued from the hands of charlatans, rechristened, and subjected to accurate investigation by Dr. James Braid, of Manchester, as early as 1841. But his results, after attracting momentary attention, fell from view, and, despite desultory efforts, the subject was not again accorded a general hearing from the scientific world until 1878, when Dr. Charcot took it up at the Salpetriere, in Paris, followed soon afterwards by Dr. Rudolf Heidenhain, of Breslau, and a host of other experimenters. The value of the method in the study of mental states was soon apparent. Most of Braid's experiments were repeated, and in the main his results were confirmed. His explanation of hypnotism, or artificial somnambulism, as a self-induced state, independent of any occult or supersensible influence, soon gained general credence. His belief that the initial stages are due to fatigue of nervous centres, usually from excessive stimulation, has not been supplanted, though supplemented by notions growing out of the new knowledge as to subconscious mentality in general, and the inhibitory influence of one centre over another in the central nervous mechanism.

THE BRAIN AS THE ORGAN OF MIND

These studies of the psychologists and pathologists bring the relations of mind and body into sharp relief. But even more definite in this regard was the work of the brain physiologists. Chief of these, during the middle period of the century, was the man who is sometimes spoken of as the "father of brain physiology," Marie Jean Pierre Flourens, of the Jardin des Plantes of Paris, the pupil and worthy successor of Magendie. His experiments in nerve physiology were begun in the first quarter of the century, but his local experiments upon the brain itself were not culminated until about 1842. At this time the old dispute over phrenology had broken out afresh, and the studies of Flourens were aimed, in part at least, at the strictly scientific investigation of this troublesome topic.

In the course of these studies Flourens discovered that in the medulla oblongata, the part of the brain which connects that organ with the spinal cord, there is a centre of minute size which cannot be injured in the least without causing the instant death of the animal operated upon. It may be added that it is this spot which is reached by the needle of the garroter in Spanish executions, and that the same centre also is destroyed when a criminal is "successfully" hanged, this time by the forced intrusion of a process of the second cervical vertebra. Flourens named this spot the "vital knot." Its extreme importance, as is now understood, is due to the fact that it is the centre of nerves that supply the heart; but this simple explanation, annulling the conception of a specific "life centre," was not at once apparent.