Chapter XVI: Introduction (6)

Most varied and numerous are the changes which we owe to the light and heat of the sun. The sun heats our atmosphere irregularly, the warm rarefied air ascends, while fresh cool air flows from the sides to supply its place: in this way winds are generated. This action is most powerful at the equator, the warm air of which incessantly flows in the upper regions of the atmosphere towards the poles: while just as persistently, at the earth’s surface, the trade wind carries new and cool air to the equator. Without the heat of the sun all winds must, of necessity, cease. Similar currents are produced by the same cause in the waters of the sea. Their power may be inferred from the influence which in some cases they exert upon climate. By them the warm water of the Antilles is carried to the British Isles, and confers upon them a mild, uniform warmth and rich moisture; while, through similar causes, the floating ice of the North Pole is carried to the coast of Newfoundland, and produces cold. Further, by the heat of the sun, a portion of the water is converted into vapour which rises in the atmosphere, is condensed to clouds, or falls in rain and snow upon the earth, collects in the form of springs, brooks, and rivers, and finally reaches the sea again, after having gnawed the rocks, carried away the light earth, and thus performed its part in the geologic changes of the earth; perhaps, besides all this it has driven our water-mill upon its way. If the heat of the sun were withdrawn, there would remain only a single motion of water, namely, the tides, which are produced by the attraction of the sun and moon.

How is it now, with the motions and the work of organic beings? To the builders of the automata of the last century, men and animals appeared as clockwork which was never wound up, and created the force which they exerted out of nothing. They did not know how to establish a connection between the nutriment consumed and the work generated. Since, however, we have learned to discern in the steam-engine this origin of mechanical force, we must inquire whether something similar does not hold good with regard to men. Indeed, the continuation of life is dependent on the consumption of nutritive materials: these are combustible substances, which, after digestion and being passed into the blood, actually undergo a slow combustion, and finally enter into almost the same combinations with the oxygen of the atmosphere that are produced in an open fire. As the quantity of heat generated by combustion is independent of the duration of the combustion and the steps in which it occurs, we can calculate from the mass of the consumed material how much heat, or its equivalent work is thereby generated in an animal body. Unfortunately, the difficulty of the experiments is still very great; but within those limits of accuracy which have been as yet attainable, the experiments show that the heat generated in the animal body corresponds to the amount which would be generated by the chemical processes. The animal body therefore does not differ from the steam-engine, as regards the manner in which it obtains heat and force, but does differ from it in the manner in which the force gained is to be made use of. The body is, besides, more limited than the machine in the choice of its fuel; the latter could be heated with sugar, with starch-flour, and butter, just as well as with coal or wood; the animal body must dissolve its materials artificially, and distribute them through its system; it must, further, perpetually renew the used-up materials of its organs, and as it cannot itself create the matter necessary for this, the matter must come from without. Liebig was the first to point out these various uses of the consumed nutriment. As material for the perpetual renewal of the body, it seems that certain definite albuminous substances which appear in plants, and form the chief mass of the animal body, can alone be used. They form only a portion of the mass of nutriment taken daily; the remainder, sugar, starch, fat, are really only materials for warming, and are perhaps not to be superseded by coal, simply because the latter does not permit itself to be dissolved.

If, then, the processes in the animal body are not in this respect to be distinguished from inorganic processes, the question arises, whence comes the nutriment which constitutes the source of the body’s force? The answer is, from the vegetable kingdom; for only the material of plants, or the flesh of plant-eating animals, can be made use of for food. The animals which live on plants occupy a mean position between carnivorous animals, in which we reckon man, and vegetables, which the former could not make use of immediately as nutriment. In hay and grass the same nutritive substances are present as in meal and flour, but in less quantity. As, however, the digestive organs of man are not in a condition to extract the small quantity of the useful from the great excess of the insoluble, we submit, in the first place, these substances to the powerful digestion of the ox, permit the nourishment to store itself in the animal’s body, in order in the end to gain it for ourselves in a more agreeable and useful form. In answer to our question, therefore, we are referred to the vegetable world. Now when what plants take in and what they give out are made the subjects of investigation, we find that the principal part of the former consists in the products of combustion which are generated by the animal. They take the consumed carbon given off in respiration, as carbonic acid, from the air, the consumed hydrogen as water, the nitrogen in its simplest and closest combinations as ammonia; and from these materials, with the assistance of small ingredients which they take from the soil, they generate anew the compound combustible substances, albumen, sugar, oil, on which the animal subsists. Here, therefore, is a circuit which appears to be a perpetual store of force. Plants prepare fuel and nutriment, animals consume these, burn them slowly in their lungs, and from the products of combustion the plants again derive their nutriment. The latter is an eternal source of chemical, the former of mechanical forces. Would not the combination of both organic kingdoms produce the perpetual motion? We must not conclude hastily: further inquiry shows, that plants are capable of producing combustible substances only when they are under the influence of the sun. A portion of the sun’s rays exhibits a remarkable relation to chemical forces,--it can produce and destroy chemical combinations; and these rays, which for the most part are blue or violet, are called therefore chemical rays. We make use of their action in the production of photographs. Here compounds of silver are decomposed at the place where the sun’s rays strike them. The same rays overpower in the green leaves of plants the strong chemical affinity of the carbon of the carbonic acid for oxygen, give back the latter free to the atmosphere, and accumulate the other, in combination with other bodies, as woody fibre, starch, oil, or resin. These chemically active rays of the sun disappear completely as soon as they encounter the green portions of the plants, and hence it is that in daguerreotype images the green leaves of plants appear uniformly black. Inasmuch as the light coming from them does not contain the chemical rays, it is unable to act upon the silver compounds.

Hence a certain portion of force disappears from the sunlight, while combustible substances are generated and accumulated in plants; and we can assume it as very probable, that the former is the cause of the latter. I must indeed remark, that we are in possession of no experiments from which we might determine whether the vis viva of the sun’s rays which have disappeared, corresponds to the chemical forces accumulated during the same time; and as long as these experiments are wanting, we cannot regard the stated relation as a certainty. If this view should prove correct, we derive from it the flattering result, that all force, by means of which our bodies live and move, finds its source in the purest sunlight; and hence we are all, in point of nobility, not behind the race of the great monarch of China, who heretofore alone called himself Son of the Sun. But it must also be conceded that our lower fellow-beings, the frog and leech, share the same ethereal origin, as also the whole vegetable world, and even the fuel which comes to us from the ages past, as well as the youngest offspring of the forest with which we heat our stoves and set our machines in motion.

You see, then, that the immense wealth of ever-changing meteorological, climatic, geological, and organic processes of our earth are almost wholly preserved in action by the light and heat-giving rays of the sun; and you see in this a remarkable example, how Proteus-like the effects of a single cause, under altered external conditions, may exhibit itself in nature. Besides these, the earth experiences an action of another kind from its central luminary, as well as from its satellite the moon, which exhibits itself in the remarkable phenomenon of the ebb and flow of the tide.

Each of these bodies excites, by its attraction upon the waters of the sea, two gigantic waves, which flow in the same direction round the world, as the attracting bodies themselves apparently do. The two waves of the moon, on account of her greater nearness, are about three and a half times as large as those excited by the sun. One of these waves has its crest on the quarter of the earth’s surface which is turned towards the moon, the other is at the opposite side. Both these quarters possess the flow of the tide, while the regions which lie between have the ebb. Although in the open sea the height of the tide amounts to only about three feet, and only in certain narrow channels, where the moving water is squeezed together, rises to thirty feet, the might of the phenomena is nevertheless manifest from the calculation of Bessel, according to which a quarter of the earth covered by the sea possesses, during the flow of the tide, about 25,000 cubic miles of water more than during the ebb, and that therefore such a mass of water must, in six and a quarter hours, flow from one quarter of the earth to the other.

The phenomena of the ebb and flow, as already recognized by Mayer, combined with the law of the conservation of force, stand in remarkable connection with the question of the stability of our planetary system. The mechanical theory of the planetary motions discovered by Newton teaches, that if a solid body in absolute vacuo, attracted by the sun, move around him in the same manner as the planets, this motion will endure unchanged through all eternity.

Now we have actually not only one, but several such planets, which move around the sun, and by their mutual attraction create little changes and disturbances in each other’s paths. Nevertheless Laplace, in his great work, the _Mecanique Celeste_, has proved that in our planetary system all these disturbances increase and diminish periodically, and can never exceed certain limits, so that by this cause the external existence of the planetary system is unendangered.

But I have already named two assumptions which must be made: first, that the celestial spaces must be absolutely empty; and secondly, that the sun and planets must be solid bodies. The first is at least the case as far as astronomical observations reach, for they have never been able to detect any retardation of the planets, such as would occur if they moved in a resisting medium. But on a body of less mass, the comet of Encke, changes are observed of such a nature: this comet describes ellipses round the sun which are becoming gradually smaller. If this kind of motion, which certainly corresponds to that through a resisting medium, be actually due to the existence of such a medium, a time will come when the comet will strike the sun; and a similar end threatens all the planets, although after a time, the length of which baffles our imagination to conceive of it. But even should the existence of a resisting medium appear doubtful to us, there is no doubt that the planets are not wholly composed of solid materials which are inseparably bound together. Signs of the existence of an atmosphere are observed on the Sun, on Venus, Mars, Jupiter, and Saturn. Signs of water and ice upon Mars; and our earth has undoubtedly a fluid portion on its surface, and perhaps a still greater portion of fluid within it. The motions of the tides, however, produce friction, all friction destroys _vis viva_, and the loss in this case can only affect the _vis viva_ of the planetary system. We come thereby to the unavoidable conclusion, that every tide, although with infinite slowness, still with certainty, diminishes the store of mechanical force of the system; and as a consequence of this, the rotation of the planets in question round their axes must become more slow; they must therefore approach the sun, or their satellites must approach them. What length of time must pass before the length of our day is diminished one second by the action of the tide cannot be calculated, until the height and time of the tide in all portions of the ocean are known. This alteration, however, takes place with extreme slowness, as is known by the consequences which Laplace has deduced from the observations of Hipparchus, according to which, during a period of 2000 years, the duration of the day has not been shortened by the one-three-hundredth part of a second. The final consequence would be, but after millions of years, if in the mean time the ocean did not become frozen, that one side of the earth would be constantly turned towards the sun, and enjoy a perpetual day, whereas the opposite side would be involved in eternal night. Such a position we observe in our moon with regard to the earth, and also in the case of the satellites as regards their planets; it is, perhaps, due to the action of the mighty ebb and flow to which these bodies, in the time of their fiery fluid condition, were subjected.

I would not have brought forward these conclusions, which again plunge us in the most distant future, if they were not unavoidable. Physico-mechanical laws are, as it were, the telescopes of our spiritual eye, which can penetrate into the deepest night of time, past and to come.

Another essential question as regards the future of our planetary system has reference to its future temperature and illumination. As the internal heat of the earth has but little influence on the temperature of the surface, the heat of the sun is the only thing which essentially affects the question. The quantity of heat falling from the sun during a given time upon a given portion of the earth’s surface may be measured, and from this it can be calculated how much heat in a given time is sent out from the entire sun. Such measurements have been made by the French physicist Pouillet, and it has been found that the sun gives out a quantity of heat per hour equal to that which a layer of the densest coal ten feet thick would give out by its combustion; and hence in a year a quantity equal to the combustion of a layer of seventeen miles. If this heat were drawn uniformly from the entire mass of the sun, its temperature would only be diminished thereby one and one-third of a degree centigrade per year, assuming its capacity for heat to be equal to that of water. These results can give us an idea of the magnitude of the emission, in relation to the surface and mass of the sun; but they cannot inform us whether the sun radiates heat as a glowing body, which since its formation has its heat accumulated within it, or whether a new generation of heat by chemical processes takes place at the sun’s surface. At all events the law of the conservation of force teaches us that no process analogous to those known at the surface of the earth, can supply for eternity an inexhaustible amount of light and heat to the sun. But the same law also teaches that the store of force at present existing, as heat, or as what may become heat, is sufficient for an immeasurable time. With regard to the store of chemical force in the sun, we can form no conjecture, and the store of heat there existing can only be determined by very uncertain estimations. If, however, we adopt the very probable view, that the remarkably small density of so large a body is caused by its high temperature, and may become greater in time, it may be calculated that if the diameter of the sun were diminished only the ten-thousandth part of its present length, by this act a sufficient quantity of heat would be generated to cover the total emission for 2100 years. Such a small change besides it would be difficult to detect even by the finest astronomical observations.

Indeed, from the commencement of the period during which we possess historic accounts, that is, for a period of about 4000 years, the temperature of the earth has not sensibly diminished. From these old ages we have certainly no thermometric observations, but we have information regarding the distribution of certain cultivated plants, the vine, the olive tree, which are very sensitive to changes of the mean annual temperature, and we find that these plants at the present moment have the same limits of distribution that they had in the times of Abraham and Homer; from which we may infer backwards the constancy of the climate.

In opposition to this it has been urged, that here in Prussia the German knights in former times cultivated the vine, cellared their own wine and drank it, which is no longer possible. From this the conclusion has been drawn, that the heat of our climate has diminished since the time referred to. Against this, however, Dove has cited the reports of ancient chroniclers, according to which, in some peculiarly hot years, the Prussian grape possessed somewhat less than its usual quantity of acid. The fact also speaks not so much for the climate of the country as for the throats of the German drinkers.

But even though the force store of our planetary system is so immensely great, that by the incessant emission which has occurred during the period of human history it has not been sensibly diminished, even though the length of the time which must flow by, before a sensible change in the state of our planetary system occurs, is totally incapable of measurement, still the inexorable laws of mechanics indicate that this store of force, which can only suffer loss and not gain, must be finally exhausted. Shall we terrify ourselves by this thought? Men are in the habit of measuring the greatness and the wisdom of the universe by the duration and the profit which it promises to their own race; but the past history of the earth already shows what an insignificant moment the duration of the existence of our race upon it constitutes. A Nineveh vessel, a Roman sword awakes in us the conception of grey antiquity. What the museums of Europe show us of the remains of Egypt and Assyria we gaze upon with silent astonishment, and despair of being able to carry our thoughts back to a period so remote. Still must the human race have existed for ages, and multiplied itself before the pyramids of Nineveh could have been erected. We estimate the duration of human history at 6000 years; but immeasurable as this time may appear to us, what is it in comparison with the time during which the earth carried successive series of rank plants and mighty animals, and no men; during which in our neighbourhood the amber-tree bloomed, and dropped its costly gum on the earth and in the sea; when in Siberia, Europe and North America groves of tropical palms flourished; where gigantic lizards, and after them elephants, whose mighty remains we still find buried in the earth, found a home? Different geologists, proceeding from different premises, have sought to estimate the duration of the above creative period, and vary from a million to nine million years. And the time during which the earth generated organic beings is again small when we compare it with the ages during which the world was a ball of fused rocks. For the duration of its cooling from 2000° to 200° centigrade, the experiments of Bishop upon basalt show that about 350 millions of years would be necessary. And with regard to the time during which the first nebulous mass condensed into our planetary system, our most daring conjectures must cease. The history of man, therefore, is but a short ripple in the ocean of time. For a much longer series of years than that during which man has already occupied this world, the existence of the present state of inorganic nature favourable to the duration of man seems to be secured, so that for ourselves and for long generations after us, we have nothing to fear. But the same forces of air and water, and of the volcanic interior, which produced former geological revolutions, and buried one series of living forms after another, act still upon the earth’s crust. They more probably will bring about the last day of the human race than those distant cosmical alterations of which we have spoken, and perhaps force us to make way for new and more complete living forms, as the lizards and the mammoth have given place to us and our fellow-creatures which now exist.

Thus the thread which was spun in darkness by those who sought a perpetual motion has conducted us to a universal law of nature, which radiates light into the distant nights of the beginning and of the end of the history of the universe. To our own race it permits a long but not an endless existence; it threatens it with a day of judgment, the dawn of which is still happily obscured. As each of us singly must endure the thought of his death, the race must endure the same. But above the forms of life gone by, the human race has higher moral problems before it, the bearer of which it is, and in the completion of which it fulfils its destiny.

FOOTNOTES:

[Footnote 34: Translated from _Über die Erhaltung der Kraft_ (Berlin, 1847).]

XXXII

LOUIS PASTEUR

1822-1895

_Louis Pasteur was born at Dôle, France, December 27, 1822, the son of a tanner. Educated at Arbois, Besançon, and the École Normale, he was appointed assistant professor of chemistry at the last-named institution. His first important work was in demonstrating the asymmetry of molecules. In 1863 he investigated fermentation and showed that it was caused by the growth of bacteria and later proved that it was also the cause of putrefaction, a suggestion which Lister employed in developing antiseptic surgery. In 1865 Pasteur discovered the bacillus which caused the silkworm disease. Taking up the principle of inoculation he applied it to small-pox and later extended it to other infectious diseases. He died September 28, 1895._

INOCULATION FOR HYDROPHOBIA[35]

Gentlemen:--Your Congress meetings are the place for the discussion of the gravest problems of medicine; they serve also to point out the great landmarks of the future. Three years ago, on the eve of the London Congress, the doctrine of micro-organisms, the ætiological cause of transmissible maladies, was still the subject of sharp criticisms. Certain refractory minds continued to uphold the idea that “disease is in us, from us, by us.”

It was expected that the decided supporters of the theory of the spontaneity of diseases would make a bold stand in London; but no opposition was made to the doctrine of “exteriority,” or external causes, the first cause of contagious diseases, and those questions were not discussed at all.

It was there seen, once again, that when all is ready for the final triumph of truth, the united conscience of a great assembly feels it instinctively and recognises it.

All clear-sighted minds had already foreseen that the theory of the spontaneity of diseases received its death-blow on the day when it became possible reasonably to consider the spontaneous generation of microscopic organisms as a myth, and when, on the other hand, the life-activity of those same beings was shown to be the main cause of organic decomposition and of all fermentation.

From the London Congress, also, dates the recognition of another very hopeful progress; we refer to the attenuation of different viruses, to the production of varying degrees of virulence for each virus, and their preservation by suitable methods of cultivation; to the practical application, finally, of those new facts in animal medicine.

New microbic prophylactic viruses have been added to those of fowl-cholera and of splenic fever. The animals saved from death by contagious diseases are now counted by hundreds of thousands, and the sharp opposition which those scientific novelties met with at the beginning was soon swept away by the rapidity of their onward progress.

Will the circle of practical applications of those new notions be limited in future to the prophylaxis of animal distempers? We must never think little of a new discovery, nor despair of its fecundity; but more than that, in the present instance, it may be asserted that the question is already solved in principle. Thus, splenic fever is common to animals and man, and we make bold to declare that, were it necessary to do so, nothing could be easier than to render man also proof against that affection. The process which is employed for animals might, almost without a change, be applied to him also. It would simply become advisable to act with an amount of prudence which the value of the life of an ox or a sheep does not call for. Thus, we should use three or four vaccine-viruses instead of two, of progressive intensity of virulence, and choose the first ones so weak that the patient should never be exposed to the slightest morbid complication, however susceptible to the disease he might be by his constitution.

The difficulty, then, in the case of human diseases, does not lie in the application of the new method of prophylaxis, but rather in the knowledge of the physiological properties of their viruses. All our experiments must tend to discover the proper degree of attenuation for each virus. But experimentation, if allowable on animals, is criminal on man. Such is the principal cause of the complication of researches bearing on diseases exclusively human. Let us keep in mind, nevertheless, that the studies of which we are speaking were born yesterday only, that they have already yielded valuable results, and that new ones may be fairly expected when we shall have gone deeper into the knowledge of animal maladies, and of those in particular which affect animals in common with man.

The desire to penetrate farther forward in that double study led me to choose rabies as the subject of my researches, in spite of the darkness in which it was veiled.

The study of rabies was begun in my laboratory four years ago, and pursued since then without other interruption than what was inherent to the nature of the researches themselves, which present certain unfavourable conditions. The incubation of the disease is always protracted, the space disposed of is never sufficient, and it thus becomes impossible at a given moment to multiply the experiments as one would like. Notwithstanding those material obstacles, lessened by the interest taken by the French Government in all questions of great scientific interest, we now no longer count the experiments which we have made, my fellow workers and myself. I shall limit myself to-day to an exposition of our latest acquisitions.

The name alone of a disease, and of rabies above all others, at once suggests to the mind the notion of a remedy.

But it will, in the majority of cases, be labour lost to aim in the first instance at discovering a mode of cure. It is, in a manner, leaving all progress to chance. Far better to endeavour to acquaint oneself, first of all, with the nature, the cause, and the evolution of the disease, with a glimmering hope, perhaps, of finally arriving at its prophylaxis.

To this last method we are indebted for the result that rabies is no longer to-day to be considered as an insoluble riddle.

We have found that the virus of rabies develops itself invariably in the nervous system, brain, and spinal cord, in the nerves, and in the salivary glands; but it is not present at the same moment in every one of those parts. It may, for example, develop itself at the lower extremity of the spinal cord, and only after a time reach the brain. It may be met with at one or at several points of the encephalon whilst being absent at certain other points of the same region.

If an animal is killed whilst in the power of rabies, it may require a pretty long search to discover the presence here or there in the nervous system, or in the glands, of the virus of rabies. We have been fortunate enough to ascertain that in all cases, when death has been allowed to supervene naturally, the swelled-out portion, or bulb, of the medulla oblongata nearest to the brain, and uniting the spinal cord with it, is always rabid. When an animal has died of rabies (and the disease always ends in death), rabid matter can with certainty be obtained from its bulb, capable of reproducing the disease in other animals when inoculated into them, after trephining, in the arachnoid space of the cerebral meninges.

Any street dog whatsoever, inoculated in the manner described with portions of the bulb of an animal which has died of rabies, will certainly develop the same disease. We have thus inoculated several hundreds of dogs brought without any choice from the pound. Never once was the inoculation a failure. Similarly also, with uniform success, several hundred guinea-pigs, and rabbits more numerous still.

Those two great results, the constant presence of the virus in the bulb at the time of death, and the certainty of the reproduction of the disease by inoculation into the arachnoid space, stand out like experimental axioms, and their importance is paramount. Thanks to the precision of their application, and to the well-known daily repetition of those two criteria of our experiments, we have been able to move forward steadily and surely in that arduous study. But, however solid those experimental bases, they were, nevertheless, incapable in themselves of giving us the faintest notion as to some method of vaccination against rabies. In the present state of science the discovery of a method of vaccination against some virulent malady presupposes:

1. That we have to deal with a virus capable of assuming diverse intensities, of which the weaker ones can be put to vaccinal or protective uses.

2. That we are in possession of a method enabling us to reproduce those diverse degrees of virulence at will.

At the present time, however, science is acquainted with one sort of rabies only--viz., dog rabies.

Rabies, whether in dog, man, horse, ox, wolf, fox, etc., comes originally from the bite of a mad dog. It is never spontaneous, neither in the dog nor in any other animal. There are none seriously authenticated among the alleged cases of so-called spontaneous rabies, and I add that it is idle to argue that the first case of rabies of all must have been spontaneous. Such an argument does not solve the difficulty, and wantonly calls into question the as yet inscrutable problem of the origin of life. It would be quite as well, against the assertion that an oak tree always proceeded from another oak tree, to argue that the first of all oak trees that ever grew must have been produced spontaneously. Science, which knows itself, is well aware that it would be useless for her to discuss about the origin of things; she is aware that, for the present at any rate, that origin is placed beyond the ken of her investigations.

In fine, then, the first question to be solved on our way towards the prophylaxis of rabies is that of knowing whether the virus of that malady is susceptible of taking on varying intensities, after the manner of the virus of fowl-cholera or of splenic fever.

But in what way shall we ascertain the possible existence of varying intensities in the virus of rabies? By what standard shall we measure the strength of a virus which either fails completely or kills? Shall we have recourse to the visible symptoms of rabies? But those symptoms are extremely variable, and depend essentially on the particular point of the encephalon or of the spinal cord where the virus has in the first instance fixed and developed itself. The most caressing rabies, for such do exist, when inoculated into another animal of the same species, give rise to furious rabies of the intensest type.

Might we then perhaps make use of the duration of incubation as a means of estimating the intensity of our virus? But what can be more changeful than the incubative period? Suppose a mad dog were to bite several sound dogs: one of them will take rabies in one month or six weeks, another after two or three months or more. Nothing, too, is more changeful than the length of incubation according to the different modes of inoculation. Thus, other circumstances the same, after bites or hypodermic inoculation rabies occasionally develops itself, and at other times aborts completely; but inoculations on the brain are never sterile, and give the disease after a relatively short incubation.

It is possible, nevertheless, to gauge with sufficient accuracy the degree of intensity of our virus by means of the time of incubation, on condition that we make use exclusively of the intra-cranial mode of inoculation; and secondly, that we do away with one of the great disturbing influences inherent to the results of inoculation made by bites, under the skin or in the veins, by injecting the right proportion of material.

The duration of incubation, as a matter of fact, may depend largely on the quantity of efficient virus--that is to say, on the quantity of virus which reaches the nervous system without diminution or modification. Although the quantity of virus capable of giving rabies may be, so to speak, infinitely small, as seen in the common fact of the disease developing itself after rabid bites which, as a rule, introduce into the system a barely appreciable weight of virus, it is easy to double the length of incubation by simply changing the proportion of those very small quantities of inoculated matter. I may quote the following examples:--

On May 10, 1882, we injected into the popliteal vein of a dog ten drops of a liquid prepared by crushing a portion of the bulb of a dog, which had died of ordinary canine madness, in three or four times its volume of sterilised broth.

Into a second dog we injected 1/100th of that quantity, into a third 1/200th. Rabies showed itself in the first dog on the eighteenth day after the injection, on the thirty-fifth day in the second dog, whilst the third one did not take the disease at all, which means that, for the last animal, with the particular mode of inoculation employed, the quantity of virus injected was not sufficient to give rabies. And yet that dog, like all dogs, was susceptible of taking the disease, for it actually took it twenty-two days after a second inoculation, performed on September 3, 1882.

I now take another example bearing on rabbits, and by a different mode of inoculation. This time, after trephining, the bulb of a rabbit which had died of rabies after inoculation of an extremely powerful virus is triturated and mixed with two or three times its volume of sterilised broth. The mixture is allowed to stand a little, and then two drops of the supernatant liquid are injected after trephining into a first rabbit, into a second rabbit one-fourth of that quantity, and in succession into other rabbits, 1/16th, 1/64th, 1/128th, and 1/152nd of that same quantity. All those rabbits died of rabies, the incubation having been eight days, nine and ten days for the third and fourth, twelve and sixteen days for the last ones.

Those variations in the length of incubation were not the result of any weakening or diminution of the intrinsic virulence of the virus brought on possibly by its dilution, for the incubation of eight days was at once recovered when the nervous matter of all those rabbits was inoculated into new animals.

Those examples show that, whenever rabies follows upon bites or hypodermic inoculations, the differences in respect of length of incubation must be chiefly ascribed to the variations, at times within considerable limits, of the ever-undeterminate proportions of the inoculated viruses which reach the central nervous system.

If, therefore, we desire to make use of the length of incubation as a measure of the intensity of the virulence, it will be indispensable to have recourse to inoculation on the surface of the brain, after trephining, a process the action of which is absolutely certain, coupled with the use of a larger quantity of virus than what is strictly sufficient to give rise to rabies. By those means the irregularities in the length of incubation for the same virus tend to disappear completely, because we always have the maximum effect which that virus can produce; that maximum coincides with a minimum length of incubation.

We have thus, finally, become possessed of a method enabling us to investigate the possible existence of different degrees of virulence, and to compare them with one another. The whole secret of the method, I repeat, consists in inoculating on the brain, after trephining, a quantity of virus which, although small in itself, is still greater than what is simply necessary to reproduce rabies. We thus disengage the incubation from all disturbing influences and render its duration dependent exclusively on the activity of the particular virus used, that activity being in each case estimated by the minimum incubation determined by it.

This method was applied in the first instance to the study of canine madness, and in particular to the question of knowing whether dog-madness was always one and the same, with perhaps the slight variations which might be due to the differences of race in diverse dogs.

We accordingly got hold of a number of dogs affected with ordinary street rabies, at all times of the year, at all seasons of the same year or of different years, and belonging to the most dissimilar canine races. In each case the bulbar portion of the medulla oblongata was taken out from the recently dead animal, triturated and suspended in two or three times its volume of sterilised liquid, making use all along of every precaution to keep our materials pure, and two drops of this liquid injected after trephining into one or two rabbits. The inoculation is made with a Pravaz syringe, the needle of which, slightly curved at its extremity, is inserted through the dura-mater into the arachnoid space. The results were as follows: all the rabbits, from whatever sort of dog inoculated, showed a period of incubation which ranged between twelve and fifteen days, without almost a single exception. Never did they show an incubation of eleven, ten, nine, or eight days, never an incubation of several weeks or of several months.

Dog-rabies, the ordinary rabies, the only known rabies, is thus sensibly one in its virulence, and its modifications, which are very limited, appear to depend solely on the varying aptitude for rabies of the different known races. But we are going now to witness a deep change in the virulence of dog-rabies.

Let us take one, any one, of our numerous rabbits, inoculated with the virus of an ordinary mad dog, and, after it has died, extract its bulb, prepare it just as described, and inject two drops of the bulb-emulsion into the arachnoid space of a second rabbit, whose bulb will in turn and in time be injected into a third rabbit, the bulb of which again will serve for a fourth rabbit, and so on.

There will be evidence, even from the first few passages, of a marked tendency towards a lessening of the period of incubation in the succeeding rabbits. Just one example:

Towards the end of the year 1882 fifteen cows and one bull died of rabies on a farm situated in the neighbourhood of the town of Melun. They had been bitten on October 2 by the farm dog, which had become mad. The head of one of the cows, which had died on November 15, was sent to my laboratory by M. Rossignol, a veterinary surgeon in Melun. A number of experiments were made on dogs and rabbits, and showed that the following parts, the only encephalic (or those pertaining to the brain) ones tested, were rabid: the bulb, the cerebellum, the frontal lobe, the sphenoidal lobe. The rabbits trephined and inoculated with those different parts showed the first symptoms of rabies on the seventeenth and eighteenth days after inoculation. With the bulb of one of those rabbits two more were inoculated, of which one took rabies on the fifteenth day, the other on the twenty-third day.

We may notice, once for all, that when rabies is transferred from one animal to another of a different species, the period of incubation is always very irregular at first in the individuals of the second species if the virus had not yet become fixed in its maximum virulence for the first species. We have just seen an example of that phenomenon, since one of the rabbits had an incubation of fifteen days, the other of twenty-three days, both having received the same virus and all other circumstances remaining apparently the same for them.

The bulb of the first one of those last rabbits which died was injected into two more rabbits, still after trephining. One of them took rabies on the tenth day, the other on the fourteenth day. The bulb of the first one that died was again injected into a couple of new rabbits, which developed the disease in ten days and twelve days respectively. A fifth time two new animals were inoculated from the first one that died, and they both took the disease on the eleventh day after inoculation: similarly, a sixth passage was made, and gave an incubation of eleven days, twelve days for the seventh passage, ten and eleven for the eighth, ten days for the ninth and tenth passages, nine days for the eleventh, eight and nine days for the twelfth, and so on, with differences of twenty-four hours at the most, until we got to the twenty-first passage, when rabies declared itself in eight days, and subsequently to that always in eight days up to the fiftieth passage, which was only effected a few days ago. That long experimental series which is still going on was begun on November 15, 1882, and will be kept up for the purpose of preserving in our rabies virus that maximum virulence which it has come to now for some considerable time, as it is easy to calculate.

Allow me to call your attention to the ease and safety of the operations for trephining and then inoculating the virus. Throughout the last twenty months we have been able without a single interruption in the course of the series to carry the one initial virus through a succession of rabbits which were all trephined and inoculated every twelfth day or so.

Guinea-pigs reach more rapidly the maximum virulence of which they are susceptible. The period of incubation is in them also variable and irregular at the beginning of the series of successive passages, but it soon enough fixes itself at a minimum of five days. The maximum virulence in guinea-pigs is reached after seven or eight passages only. It is worth noting that the number of passages required before reaching the maximum virulence, both in guinea-pigs and in rabbits, varies with the origin of the first virus with which the series is begun.

If now this rabies with maximum virulence be transferred again into the dog from guinea-pig or rabbit, there is produced a dog-virus which in point of virulence goes far beyond that of ordinary canine madness.

But, a natural query--of what use can be that discovery as to the existence and artificial production of diverse varieties of rabies, every one of them more violent and more rapidly fatal than the habitual madness of the dog? The man of science is thankful for the smallest find he can make in the field of pure science, but the many, terrified at the very name of hydrophobia, claim something more than mere scientific curiosities. How much more interesting it would be to become acquainted with a set of rabies viruses which should, on the contrary, be possessed of attenuated degrees of virulence! Then, indeed, might there be some hope of creating a number of vaccinal rabies viruses such as we have done for the virus of fowl-cholera, of the microbe of saliva, of the red evil of swine (swine-plague), and even of acute septicæmia. Unfortunately, however, the methods which had served for those different viruses showed themselves to be either inapplicable or inefficient in the case of rabies. It therefore became necessary to find out new and independent methods, such, for example, as the cultivation _in vitro_ of the mortal rabies virus.

Jenner was the first to introduce into current science the opinion that the virus which he called the grease of the horse, and which we call now more exactly horse-pox, probably softened its virulence, so to speak, in passing through the cow and before it could be transferred to man without danger. It was therefore natural to think of a possible diminution of the virulence of rabies by a number of passages through the organisms of some animal or other, and the experiment was worth trying. A large number of attempts were made, but the majority of the animal species experimented on exalted the virulence after the manner of rabbits and guinea-pigs; fortunately, however, it was not so with monkey.

On December 6, 1883, a monkey was trephined and inoculated with the bulb of a dog, which had itself been similarly inoculated from a child who had died of rabies. The monkey took rabies eleven days later, and when dead served for inoculation into a second monkey, which also took the disease on the eleventh day. A third monkey, similarly inoculated from the second one, showed the first symptoms on the twenty-third day, etc. The bulb of each one of the monkeys was inoculated, after trephining, into two rabbits each time. The rabbits inoculated from the first monkey developed rabies between thirteen and sixteen days, those from the second monkey between fourteen and twenty days, those from the third monkey between twenty-six and thirty days, those from the fourth monkey both of them after the twenty-eighth day, those from the fifth monkey after twenty-seven days, those from the sixth monkey after thirty days.

It cannot be doubted after that, that successive passages through monkeys, and from the several monkeys to rabbits, do diminish the virulence of the virus for the latter animals; they diminish it for dogs also. The dog inoculated with the bulb of the fifth monkey gave an incubation of no less than fifty-eight days, although it had been inoculated in the arachnoid space.

The experiments were renewed with fresh sets of monkeys and led to similar results. We were therefore actually in possession of a method by means of which we could attenuate the virulence of rabies. Successive inoculations from monkey to monkey elaborate viruses which, when transferred to rabbits, reproduce rabies in them, but with a progressively lengthening period of incubation. Nevertheless, if one of those rabbits be taken as the first for inoculations through a series of rabbits, the rabies thus cultivated obeys the law which we have seen before, and has its virulence increased at each passage.

The practical application of those facts gives us a method for the vaccination of dogs against rabies. As a starting point, make use of one of the rabbits inoculated from a monkey sufficiently removed from the first animal of the monkey series for the inoculation--hypodermic or intra-venous--of that rabbit’s bulb not to be mortal for a new rabbit. The next vaccinal inoculations are made with the bulbs of rabbits derived by successive passages from that first rabbit.

In the course of our experiments we made use, as a rule, for inoculation, of the virus of rabbits which had died after an incubation of four weeks, repeating three or four times each the vaccinal inoculations made with the bulbs of rabbits derived in succession from one another and from the first one of the series, itself coming directly from the monkey. I abstain from giving more details, because certain experiments which are actually going on allow me to expect that the process will be greatly simplified.

You must be feeling, gentlemen, that there is a great blank in my communication; I do not speak of the micro-organism of rabies. We have not got it. The process for isolating it is still imperfect, and the difficulties of its cultivation outside the bodies of animals have not yet been got rid of, even by the use, as pabulum, of fresh nervous matter. The methods which we employed in our study of rabies ought all the more perhaps, on that account, to fix attention. Long still will the art of preventing diseases have to grapple with virulent maladies the micro-organic germs of which will escape our investigations. It is, therefore, a capital scientific fact that we should be able, after all, to discover the vaccination process for a virulent disease without yet having at our disposal its special virus and whilst yet ignorant of how to isolate or to cultivate its microbe.

As soon as the method for the vaccination of dogs was firmly established, and we had in our possession a large number of dogs which had been rendered refractory to rabies, I had the idea of submitting to a competent committee those of the facts which appeared destined in future to serve as a basis for the vaccination of dogs against rabies. That course was suggested to me in prevision of the later practical application of the method, by the recollection of the opposition with which Jenner’s discovery met at its beginning.

I spoke of my project to M. Fallières, the Minister of Public Instruction, who was pleased to approve of it and gave commission to the following gentlemen to control the facts which I had summarily communicated to the Academy of Sciences in its sitting of May 19 last: Messrs. Béclard, Paul Bert, Bouley, Aimeraud, Villemin, Vulpian. M. Bouley was appointed president, Dr. Villemin, secretary, and the commission at once set to work. I have the pleasure of informing you that it has just sent in a first report to the Minister. I was acquainted with it here, and the following are in a few words, the facts related in that first report on rabies. I had given to the commission nineteen vaccinated dogs in succession--that is to say, dogs which had been rendered refractory by preventive inoculations. Thirteen only of them had after their vaccination been already submitted to the test-inoculation on the brain.

The nineteen dogs were, for the sake of comparison, divided into sets along with nineteen more control dogs brought from the pound without any sort of selection. To begin with, two refractory dogs and two control dogs were on June 1 trephined and inoculated under the dura-mater, on the surface of the brain, with the bulb of a dog affected with ordinary street rabies.

On June 3 another refractory dog and another control dog were bitten by a furious street mad dog.

The same furious mad dog was on June 4 made to bite still another refractory and another control dog. On June 6 the furious dog which had been utilised on June 3 and 4 died. The bulb was taken out and inoculated, after trephining, into three refractory dogs and three control dogs. On June 10 another street mad dog, having been secured, was, by the commission, made to bite one refractory and one control dog. On June 16 the commission had two new dogs, a refractory one and a control one, bitten by one of the control dogs of June 1, which had been seized with rabies on June 14 in consequence of the inoculation after trephining which it had received on June 1.