Louis Pasteur 1

Louis Pasteur 1

Louis Pasteur, by Rene Vallery-Radot           PREFACE. In the _salon_ of a distinguished man, or of a great writer, there is often to be found a person who, without being either a fellow-worker or a disciple, without even possessing the scientific or literary qualities which might explain his habitual presence, lives nevertheless in complete familiarity with the man whom all around him call 'dear master.' Whence comes this intimate one? who is he? what is his business? He is only known as a friend of the house. He has no other title, and he is almost proud of having no other. Stripped of his own personality, he speaks only of the labours and the success of his illustrious friend, in the radiance of whose glory he moves with delight. The author of this work is a person of this description. Intimately connected with the life of M. Pasteur, and a constant inmate of his laboratory, he has passed happy years near this great investigator, who has discovered a new world--the world of the infinitely little. Since the first studies of M. Pasteur on molecular dissymmetry, down to his most recent investigations on hydrophobia, on virulent diseases, and on the artificial cultures of living contagia, which have been converted by such cultures into veritable vaccines--passing by the intermediate celebrated experiments on spontaneous generation, fermentation, the diseases of wine, the manufacture of beer and vinegar, and the diseases of silkworms--the author of these pages has been able, if not to witness all, at least to follow in its principal developments this uninterrupted series of scientific conquests. 'What a beautiful book,' he remarked one day to M. Pasteur, 'might be written about all this!' 'But it is all in the Comptes-rendus of the Academy of Sciences.' 'It is not for the readers of the Comptes-rendus that such a book needs to be written, but for the great public, who know that you have done great things, but who know it only vaguely, by the records of journals, or by fragments of biography. The persons are few who know the history of your discoveries. What was your point of departure? How have you arrived at such and such principles, and at the consequences which flow from these principles? What is the connection and rigorous bond of your method? These are the things which it would be interesting to put together in a book which would have some chance of enduring as an historic document.' 'I could not waste my time in going back upon things already accomplished.' 'No; but my desire is that someone else should consecrate his time to the work. And listen,' added this friend, with audacious frankness--'do you know by whom, in my opinion, this book ought to be written? By a man who, without having been in any way trained to follow in your footsteps, is animated by the most lively desire to understand the course which you have pursued; who, while living at your side, has been each day impregnated with your method and your ideas; who, having had the happiness of comprehending your life and its achievements, does not wish to confine the pleasure thus derived to himself alone.' 'Where, then,' interrupted Pasteur with a kindly smile, not without a tinge of irony, 'is this man, at once so happy, and so impatient to share his happiness with others?' 'He is now pleading his cause before you. Yes, I would gladly attempt such a work. I have seen your efforts and observed your success. The experiments which I have not witnessed you have always freely explained to me, with that gift of clearness which Vauvenargues called the "polish" of masters.[1] Initiated by affection, I would make myself initiator by admiration. It would be the history of a learned man by an ignorant one. My ignorance would save me from dwelling too strictly or too long on technical details. With the exposition of your doctrine I would mingle some fragments of your biography. I would pass from a discovery to an anecdote, and so arrange matters as to give the book not only the character of a familiar scientific conversation, which would hardly be more than the echo of what I have learnt while near you, but also to make it a reflex of your life.' 'You should postpone that until I am no longer here.' 'Why so? Why, before assigning to them their places, should we wait till those whose names will endure have disappeared from the scene? No; it is you, living, that I wish to paint--you, in full work, in the midst of your laboratory. And, in addition to all other considerations, I would add, that your presence in the flesh will be the guarantee of my exactitude.'   _July 1883._ FOOTNOTE: [1] 'Vernis des maitres.'                                CONTENTS.                                                          PAGE                 INTRODUCTION, BY PROFESSOR TYNDALL         xi                 RECOLLECTIONS OF CHILDHOOD                   AND YOUTH--FIRST DISCOVERIES              1                 FERMENTATION                               40                 ACETIC FERMENTATION--                   THE MANUFACTURE OF VINEGAR               66                 THE QUESTION OF SPONTANEOUS GENERATION     89                 STUDIES ON WINE                           112                 THE SILKWORM-DISEASE                      127                 DECISIVE EXPERIMENTS                      164                 STUDIES ON BEER                           168                 VIRULENT DISEASES--SPLENIC FEVER,                   SEPTICÆMIA                              176                 FOWL CHOLERA                              212                 ATTENUATED VIRUS, OR VACCINATION--                   THE FOWL CHOLERA VACCINE                220                 THE VACCINE OF SPLENIC FEVER              231                 THE RETURN TO VIRULENCE                   246                 ETIOLOGY OF SPLENIC FEVER                 250                 METHOD OF DISCUSSION AND CONTRADICTIONS   262                 THE LABORATORY OF THE ECOLE NORMALE--                   VARIOUS STUDIES--HYDROPHOBIA            271                              INTRODUCTION. In the early part of the present year the French original of this work was sent to me from Paris by its author. It was accompanied by a letter from M. Pasteur, expressing his desire to have the work translated and published in England. Responding to this desire, I placed the book in the hands of the Messrs. Longman, who, in the exercise of their own judgment, decided on publication. The translation was confided, at my suggestion, to Lady Claud Hamilton. The translator's task was not always an easy one, but it has, I think, been well executed. A few slight abbreviations, for which I am responsible, have been introduced, but in no case do they affect the sense. It was, moreover, found difficult to render into suitable English the title of the original: '_M. Pasteur, Histoire d'un Savant par un Ignorant_.' A less piquant and antithetical English title was, therefore, substituted for the French one. This filial tribute, for such it is, was written, under the immediate supervision of M. Pasteur, by his devoted and admiring son-in-law, M. Valery Radot. It is the record of a life of extraordinary scientific ardour and success, the picture of a mind on which facts fall like germs upon a nutritive soil, and, like germs so favoured, undergo rapid increase and multiplication. One hardly knows which to admire most--the intuitive vision which discerns in advance the new issues to which existing data point, or the skill in device, the adaptation of means to ends, whereby the intuition is brought to the test and ordeal of experiment. In the investigation of microscopic organisms--the 'infinitely little,' as Pouchet loved to call them--and their doings in this our world, M. Pasteur has found his true vocation. In this broad field it has been his good fortune to alight upon a crowd of connected problems of the highest public and scientific interest, ripe for solution, and requiring for their successful treatment the precise culture and capacities which he has brought to bear upon them. He may regret his abandonment of molecular physics; he may look fondly back upon the hopes with which his researches on the tartrates and paratartrates inspired him; he may think that great things awaited him had he continued to labour in this line. I do not doubt it. But this does not shake my conviction that he yielded to the natural affinities of his intellect, that he obeyed its truest impulses, and reaped its richest rewards, in pursuing the line that he has chosen, and in which his labours have rendered him one of the most conspicuous scientific figures of this age. With regard to the earliest labours of M. Pasteur, a few remarks supplementary to those of M. Radot may be introduced here. The days when angels whispered into the hearkening human ear, secrets which had no root in man's previous knowledge or experience, are gone for ever. The only revelation--and surely it deserves the name--now open to the wise arises from 'intending the mind' on acquired knowledge. When, therefore, M. Radot, following M. Pasteur, speaks with such emphasis about 'preconceived ideas,' he does not mean ideas without antecedents. Preconceived ideas, if out of deference to M. Pasteur the term be admitted, are the vintage of garnered facts. We in England should rather call them inductions, which, as M. Pasteur truly says, inspire the mind, and shape its course, in the subsequent work of deduction and verification. At the time when M. Pasteur undertook his investigation of the diseases of silkworms, which led to such admirable results, he had never seen a silkworm; but, so far from this being considered a disqualification, M. Dumas regarded his freedom from preconceived ideas a positive advantage. His first care was to make himself acquainted with what others had done. To their observations he added his own, and then, surveying all, came to the conclusion that the origin of the disease was to be sought, not in the worms, not in the eggs, but in the moths which laid the eggs. I am not sure that this conclusion is happily described as 'a preconceived idea.' Every whipster may have his preconceived ideas; but the divine power, so largely shared by M. Pasteur, of distilling from facts their essences--of extracting from them the principles from which they flow--is given only to a few.                    *       *       *       *       * With regard to the discovery of crystalline facets in the tartrates, which has been dwelt upon by M. Radot, a brief reference to antecedent labours may be here allowed. It had been discovered by Arago, in 1811, and by Biot, in 1812 and 1818, that a plate of rock-crystal, cut perpendicular to the axis of the prism, possessed the power of rotating the plane of polarisation through an angle, dependent on the thickness of the plate and the refrangibility of the light. It had, moreover, been proved by Biot that there existed two species of rock-crystal, one of which turned the plane of polarisation to the right, and the other to the left. They were called, respectively, right-handed and left-handed crystals. No external difference of crystalline form was at first noticed which could furnish a clue to this difference of action. But closer scrutiny revealed upon the crystals minute facets, which, in the one class, were ranged along a right-handed, and, in the other, along a left-handed spiral. The symmetry of the hexagonal prism, and of the two terminal pyramids of the crystal, was disturbed by the introduction of these spirally-arranged facets. They constituted the outward and visible sign of that inward and invisible molecular structure which produced the observed action, and difference of action, on polarised light. When, therefore, the celebrated Mitscherlich brought forward his tartrates and paratartrates of ammonia and soda, and affirmed them to possess the same atoms, the same internal arrangement of atoms, and the same outward crystalline form, one of them, nevertheless, causing the plane of polarisation to rotate, while the other did not, Pasteur, remembering, no doubt, the observations just described, instituted a search for facets like those discovered in rock-crystal, and which, without altering chemical constitution, destroyed crystalline identity. He first found such facets in the tartrates, while he subsequently proved the neutrality of the paratartrate to be due to the equal admixture of right-handed and left-handed crystals, one of which, when the paratartrate was dissolved, exactly neutralised the other. Prior to Pasteur the left-handed tartrate was unknown. Its discovery, moreover, was supplemented by a series of beautiful researches on the compounds of right-handed and left-handed tartaric acid; he having previously extracted from the two tartrates, acids which, in regard to polarised light, behaved like themselves. Such was the worthy opening of M. Pasteur's scientific career, which has been dwelt upon so frequently and emphatically by M. Radot. The wonder, however, is, not that a searcher of such penetration as Pasteur should have discovered the facets of the tartrates, but that an investigator so powerful and experienced as Mitscherlich should have missed them. The idea of molecular dissymmetry, introduced by Biot, was forced upon Biot's mind by the discovery of a number of liquids, and of some vapours, which possessed the rotatory power. Some, moreover, turned the plane of polarisation to the right, others to the left. Crystalline structure being here out of the question, the notion of dissymmetry, derived from the crystal, was transferred to the molecule. 'To produce any such phenomena,' says Sir John Herschel, 'the individual molecule must be conceived as unsymmetrically constituted.' The illustrations employed by M. Pasteur to elucidate this subject, though well calculated to give a general idea of dissymmetry, will, I fear, render but little aid to the reader in his attempts to realise _molecular_ dissymmetry. Should difficulty be encountered here at the threshold of this work, I would recommend the reader not to be daunted by it, or prevented by it from going further. He may comfort himself by the assurance that the conception of a dissymmetric molecule is not a very precise one, even in the mind of M. Pasteur. One word more with regard to the parentage of preconceived ideas. M. Radot informs us that at Strasburg M. Pasteur invoked the aid of helices and magnets, with a view to rendering crystals dissymmetrical at the moment of their formation. There can, I think, be but little doubt that such experiments were suggested by the pregnant discovery of Faraday published in 1845. By both helices and magnets Faraday caused the plane of polarisation in perfectly neutral liquids and solids to rotate. If the turning of the plane of polarisation be a demonstration of molecular dissymmetry, then, in the twinkling of an eye, Faraday was able to displace symmetry by dissymmetry, and to confer upon bodies, which in their ordinary state were inert and dead, this power of rotation which M. Pasteur considers to be the exclusive attribute of life. The conclusion of M. Pasteur here referred to, which M. Radot justly describes as 'worthy of the most serious consideration,' is sure to arrest the attention of a large class of people, who, dreading 'materialism,' are ready to welcome any generalisation which differentiates the living world from the dead. M. Pasteur considers that his researches point to an irrefragable physical barrier between organic and inorganic nature. Never, he says, have you been able to produce in the laboratory, by the ordinary processes of chemistry, a dissymmetric molecule--in other words, a substance which, in a state of solution, where molecular forces are paramount, has the power of causing a polarised beam to rotate. This power belongs exclusively to derivatives from the living world. Dissymmetric _forces_, different from those of the laboratory, are, in Pasteur's mind, the agents of vitality; it is they that build up dissymmetric molecules which baffle the chemist when he attempts to reproduce them. Such molecules trace their ancestry to life alone. 'Pourrait-on indiquer une separation plus profonde entre les produits de la nature vivante, et ceux de la nature minerale, que cette dissymmetrie chez les uns, et son absence chez les autres?' It may be worth calling to mind that molecular dissymmetry is the _idea_, or _inference_, the observed rotation of the plane of polarisation, by masses of sensible magnitude, being the _fact_ on which the inference is based. That the molecule, or unit brick, of an organism should be different from the molecule of a mineral is only to be expected, for otherwise the profound distinction between them would disappear. And that one of the differences between the two classes of molecules should be the possession, by the one, of this power of rotation, and its non-possession by the other, would be a fact, interesting no doubt, but not surprising. The critical point here has reference to the power and range of chemical processes, apart from the play of vitality. Beginning with the elements themselves, can they not be so combined as to produce organic compounds? Not to speak of the antecedent labours of Wohler and others in Germany, it is well known that various French investigators, among whom are some of M. Pasteur's illustrious colleagues of the Academy, have succeeded in forming substances which were once universally regarded as capable of being elaborated by plants and animals alone. Even with regard to the rotation of the plane of polarisation, M. Jungfleisch, an extremely able pupil of the celebrated Berthelot, affirms that the barrier erected by M. Pasteur has been broken down; and though M. Pasteur questions this affirmation, it is at least hazardous, where so many supposed distinctions between organic and inorganic have been swept away, to erect a new one. For my part, I frankly confess my disbelief in its permanence. Without waiting for new facts, those already in our possession tend, I think, to render the association which M. Pasteur seeks to establish between dissymmetry and life insecure. Quartz, as a crystal, exerts a very powerful twist on the plane of polarisation. Quartz dissolved exerts no power at all. The molecules of quartz, then, do not belong to the same category as the crystal of which they are the constituents; the former are symmetrical, the latter is dissymmetrical. This, in my opinion, is a very significant fact. By the act of crystallisation, and without the intervention of life, the forces of molecules, possessing planes of symmetry, are so compounded as to build up crystals which have no planes of symmetry. Thus, in passing from the symmetrical to the dissymmetrical, we are not compelled to interpolate new forces; the forces extant in mineral nature suffice. The reasoning which applies to the dissymmetric crystal applies to the dissymmetric molecule. The dissymmetry of the latter, however pronounced and complicated, arises from the composition of atomic forces which, when reduced to their most elementary action, are exerted along straight lines. In 1865 I ventured, in reference to this subject, to define the position which I am still inclined to maintain. 'It is the compounding, in the organic world, of forces belonging equally to the inorganic that constitutes the mystery and the miracle of vitality.'[2] Add to these considerations the discovery of Faraday already adverted to. An electric current is not an organism, nor does a magnet possess life; still, by their action, Faraday, in his first essay, converted over one hundred and fifty symmetric and inert aqueous solutions into dissymmetric and active ones.[3] Theory, however, may change, and inference may fade away, but scientific experiment endures for ever. Such durability belongs, in the domain of molecular physics, to the experimental researches of M. Pasteur.                    *       *       *       *       * The weightiest events of life sometimes turn upon small hinges; and we now come to the incident which caused M. Pasteur to quit a line of research the abandonment of which he still regrets. A German manufacturer of chemicals had noticed that the impure commercial tartrate of lime, sullied with organic matters of various kinds, fermented on being dissolved in water and exposed to summer heat. Thus prompted, Pasteur prepared some pure, right-handed tartrate of ammonia, mixed with it albuminous matter, and found that the mixture fermented. His solution, limpid at first, became turbid, and the turbidity he found to be due to the multiplication of a microscopic organism, which found in the liquid its proper aliment. Pasteur recognised in this little organism a _living ferment_. This bold conclusion was doubtless strengthened, if not prompted, by the previous discovery of the yeast-plant--the alcoholic ferment--by Cagniard-Latour and Schwann. Pasteur next permitted his little organism to take the carbon necessary for its growth from the pure paratartrate of ammonia. Owing to the opposition of its two classes of crystals, a solution of this salt, it will be remembered, does not turn the plane of polarised light either to the right or to the left. Soon after fermentation had set in, a rotation to the left was noticed, proving that the equilibrium previously existing between the two classes of crystals had ceased. The rotation reached a maximum, after which it was found that all the right-handed tartrate had disappeared from the liquid. The organism thus proved itself competent to select its own food. It found, as it were, one of the tartrates more digestible than the other, and appropriated it, to the neglect of the other. No difference of chemical constitution determined its choice; for the elements, and the proportions of the elements, in the two tartrates were identical. But the peculiarity of structure which enabled the substance to rotate the plane of polarisation to the right, also rendered it a fit aliment for the organism. This most remarkable experiment was successfully made with the seeds of our common mould, _Penicillium glaucam_. Here we find Pasteur unexpectedly landed amid the phenomena of fermentation. With true scientific instinct he closed with the conception that ferments are, in all cases, living things, and that the substances formerly regarded as ferments are, in reality, the food of the ferments. Touched by this wand, difficulties fell rapidly before him. He proved the ferment of lactic acid to be an organism of a certain kind. The ferment of butyric acid he proved to be an organism of a different kind. He was soon led to the fundamental conclusion that the capacity of an organism to act as a ferment depended on its power to live, without air. The fermentation of beer was sufficient to suggest this idea. The yeast-plant, like many others, can live either with or without free air. It flourishes best in contact with free air, for it is then spared the labour of wresting from the malt the oxygen required for its sustenance. Supplied with free air, however, it practically ceases to be a ferment; while in the brewing vat, where the work of fermentation is active, the budding _torula_ is completely cut off by the sides of the vessel, and by a deep layer of carbonic acid gas, from all contact with air. The butyric ferment not only lives without air, but Pasteur showed that air is fatal to it. He finally divided microscopic organisms into two great classes, which he named respectively _ærobies_ and _anærobies_, the former requiring free oxygen to maintain life, the latter capable of living without free oxygen, but able to wrest this element from its combinations with other elements. This destruction of pre-existing compounds and formation of new ones, caused by the increase and multiplication of the organism, constitute the process of fermentation. Under this head are also rightly ranked the phenomena of putrefaction. As M. Radot well expresses it, the fermentation of sugar may be described as the putrefaction of sugar. In this particular field M. Pasteur, whose contributions to the subject are of the highest value, was preceded by Schwann, a man of great merit, of whom the world has heard too little.[4] Schwann placed decoctions of meat in flasks, sterilised the decoctions by boiling, and then supplied them with calcined air, the power of which to support life he showed to be unimpaired. Under these circumstances putrefaction never set in. Hence the conclusion of Schwann, that putrefaction was not due to the contact of air, as affirmed by Gay-Lussac, but to something suspended in the air which heat was able to destroy. This something consists of living organisms which nourish themselves at the expense of the organic substance, and cause its putrefaction.                    *       *       *       *       * The grasp of Pasteur on this class of subjects was embracing. He studied acetic fermentation, and found it to be the work of a minute fungus, the _mycoderma aceti_, which, requiring free oxygen for its nutrition, overspreads the surface of the fermenting liquid. By the alcoholic ferment the sugar of the grape-juice is transformed into carbonic acid gas and alcohol, the former exhaling, the latter remaining in the wine. By the _mycoderma aceti_ the wine is, in its turn, converted into vinegar. Of the experiments made in connection with this subject one deserves especial mention. It is that in which Pasteur suppressed all albuminous matters, and carried on the fermentation with purely crystallisable substances. He studied the deterioration of vinegar, revealed its cause, and the means of preventing it. He defined the part played by the little eel-like organisms which sometimes swarm in vinegar casks, and ended by introducing important ameliorations and improvements in the manufacture of vinegar. The discussion with Liebig and other minor discussions of a similar nature, which M. Radot has somewhat strongly emphasized, I will not here dwell upon.                    *       *       *       *       * It was impossible for an inquirer like Pasteur to evade the question--Whence come these minute organisms which are demonstrably capable of producing effects on which vast industries are built and on which whole populations depend for occupation and sustenance? He thus found himself face to face with the question of spontaneous generation, to which the researches of Pouchet had just given fresh interest. Trained as Pasteur was in the experimental sciences, he had an immense advantage over Pouchet, whose culture was derived from the sciences of observation. One by one the statements and experiments of Pouchet were explained or overthrown, and the doctrine of spontaneous generation remained discredited until it was revived with ardour, ability, and, for a time, with success, by Dr. Bastian. A remark of M. Radot's on page 103 needs some qualification. 'The great interest of Pasteur's method consists,' he says, 'in its proving unanswerably that the origin of life in infusions which have been heated to the boiling point is solely due to the solid particles suspended in the air.' This means that living germs cannot exist _in the liquid_ when once raised to a temperature of 212° Fahr. No doubt a great number of organisms collapse at this temperature; some indeed, as M. Pasteur has shown, are destroyed at a temperature 90° below the boiling point. But this is by no means universally the case. The spores of the hay-bacillus, for example, have, in numerous instances, successfully resisted the boiling temperature for one, two, three, four hours; while in one instance _eight hours'_ continuous boiling failed to sterilise an infusion of desiccated hay. The knowledge of this fact caused me a little anxiety some years ago when a meeting was projected between M. Pasteur and Dr. Bastian. For though, in regard to the main question, I knew that the upholder of spontaneous generation could not win, on the particular issue touching the death temperature he might have come off victor. The manufacture and maladies of wine next occupied Pasteur's attention. He had, in fact, got the key to this whole series of problems, and he knew how to use it. Each of the disorders of wine was traced to its specific organism, which, acting as a ferment, produced substances the reverse of agreeable to the palate. By the simplest of devices, Pasteur, at a stroke, abolished the causes of wine disease. Fortunately the foreign organisms which, if unchecked, destroy the best red wines are extremely sensitive to heat. A temperature of 50° Cent. (122° Fahr.) suffices to kill them. Bottled wines once raised to this temperature, for a single minute, are secured from subsequent deterioration. The wines suffer in no degree from exposure to this temperature. The manner in which Pasteur proved this, by invoking the judgment of the wine-tasters of Paris, is as amusing as it is interesting.                    *       *       *       *       * Moved by the entreaty of his master, the illustrious Dumas, Pasteur took up the investigation of the diseases of silkworms at a time when the silk-husbandry of France was in a state of ruin. In doing so he did not, as might appear, entirely forsake his former line of research. Previous investigators had got so far as to discover vibratory corpuscles in the blood of the diseased worms, and with such corpuscles Pasteur had already made himself intimately acquainted. He was therefore to some extent at home in this new investigation. The calamity was appalling, all the efforts made to stay the plague having proved futile. In June 1865 Pasteur betook himself to the scene of the epidemic, and at once commenced his observations. On the evening of his arrival he had already discovered the corpuscles, and shown them to others. Acquainted as he was with the work of living ferments, his mind was prepared to see in the corpuscles the cause of the epidemic. He followed them through all the phases of the insect's life--through the eggs, through the worm, through the chrysalis, through the moth. He proved that the germ of the malady might be present in the eggs and escape detection. In the worm also it might elude microscopic examination. But in the moth it reached a development so distinct as to render its recognition immediate. From healthy moths healthy eggs were sure to spring; from healthy eggs healthy worms; from healthy worms fine cocoons: so that the problem of the restoration to France of its silk-husbandry reduced itself to the separation of the healthy from the unhealthy moths, the rejection of the latter, and the exclusive employment of the eggs of the former. M. Radot describes how this is now done on the largest scale, with the most satisfactory results. The bearing of this investigation on the parasitic theory of communicable diseases was thus illustrated: Worms were infected by permitting them to feed for a single meal on leaves over which corpusculous matter had been spread; they were infected by inoculation, and it was shown how they infected each other by the wounds and scratches of their own claws. By the association of healthy with diseased worms, the infection was communicated to the former. Infection at a distance was also produced by the wafting of the corpuscles through the air. The various modes in which communicable diseases are diffused among human populations were illustrated by Pasteur's treatment of the silkworms. 'It was no hypothetical, infected medium--no problematical pythogenic gas--that killed the worms. It was a definite organism.'[5] The disease thus far described is that called _pebrine_, which was the principal scourge at the time. Another formidable malady was also prevalent, called _flacherie_, the cause of which, and the mode of dealing with it, were also pointed out by Pasteur. Overstrained by years of labour in this field, Pasteur was smitten with paralysis in October 1868. But this calamity did not prevent him from making a journey to Alais in January 1869, for the express purpose of combating the criticisms to which his labours had been subjected. Pasteur is combustible, and contradiction readily stirs him into flame. No scientific man now living has fought so many battles as he. To enable him to render his experiments decisive, the French Emperor placed a villa at his disposal near Trieste, where silkworm culture had been carried on for some time at a loss. The success here is described as marvellous; the sale of cocoons giving to the villa a net profit of twenty-six millions of francs.[6] From the Imperial villa M. Pasteur addressed to me a letter, a portion of which I have already published. It may perhaps prove usefully suggestive to our Indian or Colonial authorities if I reproduce it here:-- 'Permettez-moi de terminer ces quelques lignes que je dois dicter, vaincu que je suis par la maladie, en vous faisant observer que vous rendriez service aux Colonies de la Grande-Bretagne en repandant la connaissance de ce livre, et des principes que j'etablis touchant la maladie des vers a soie. Beaucoup de ces colonies pourraient cultiver le murier avec succes, et, en jetant les yeux sur mon ouvrage, vous vous convaincrez aisement qu'il est facile aujourd'hui, non-seulement d'eloigner la maladie regnante, mais en outre de donner aux recoltes de la soie une prosperite qu'elles n'ont jamais eue.'                    *       *       *       *       * The studies on wine prepare us for the 'Studies on Beer,' which followed the investigation of silkworm diseases. The sourness, putridity, and other maladies of beer Pasteur traced to special 'ferments of disease,' of a totally different form, and therefore easily distinguished from the true _torula_ or yeast-plant. Many mysteries of our breweries were cleared up by this inquiry. Without knowing the cause, the brewer not unfrequently incurred heavy losses through the use of bad yeast. Five minutes' examination with the microscope would have revealed to him the cause of the badness, and prevented him from using the yeast. He would have seen the true _torula_ overpowered by foreign intruders. The microscope is, I believe, now everywhere in use. At Burton-on-Trent its aid was very soon invoked. At the conclusion of his studies on beer M. Pasteur came to London, where I had the pleasure of conversing with him. Crippled by paralysis, bowed down by the sufferings of France, and anxious about his family at a troubled and an uncertain time, he appeared low in health and depressed in spirits. His robust appearance when he visited London, on the occasion of the Edinburgh Anniversary, was in marked and pleasing contrast with my memory of his aspect at the time to which I have referred.                    *       *       *       *       * While these researches were going on, the Germ Theory of infectious disease was noised abroad. The researches of Pasteur were frequently referred to as bearing upon the subject, though Pasteur himself kept clear for a long time of this special field of inquiry. He was not a physician, and he did not feel called upon to trench upon the physician's domain. And now I would beg of him to correct me if, at this point of the Introduction, I should be betrayed into any statement that is not strictly correct. In 1876 the eminent microscopist, Professor Cohn of Breslau, was in London, and he then handed me a number of his 'Beitrage,' containing a memoir by Dr. Koch on Splenic Fever (_Milzbrand_, _Charbon_, Malignant Pustule), which seemed to me to mark an epoch in the history of this formidable disease. With admirable patience, skill, and penetration, Koch followed up the life history of _bacillus anthracis_, the contagium of this fever. At the time here referred to he was a young physician holding a small appointment in the neighbourhood of Breslau, and it was easy to predict, as I predicted at the time, that he would soon find himself in a higher position. When I next heard of him he was head of the Imperial Sanitary Institute of Berlin. Koch's recent history is pretty well known in England, while his appreciation by the German Government is shown by the rewards and honours lately conferred upon him. Koch was not the discoverer of the parasite of splenic fever. Davaine and Rayer, in 1850, had observed the little microscopic rods in the blood of animals which had died of splenic fever. But they were quite unconscious of the significance of their observation, and for thirteen years, as M. Radot informs us, strangely let the matter drop. In 1863 Davaine's attention was again directed to the subject by the researches of Pasteur, and he then pronounced the parasite to be the cause of the fever. He was opposed by some of his fellow-countrymen; long discussions followed, and a second period of thirteen years, ending with the publication of Koch's paper, elapsed, before M. Pasteur took up the question. I always, indeed, assumed that from the paper of the learned German came the impulse towards a line of inquiry in which M. Pasteur has achieved such splendid results. Things presenting themselves thus to my mind, M. Radot will, I trust, forgive me if I say that it was with very great regret that I perused the disparaging references to Dr. Koch which occur in the chapter on splenic fever. After Koch's investigation, no doubt could be entertained of the parasitic origin of this disease. It completely cleared up the perplexity previously existing as to the two forms--the one fugitive, the other permanent--in which the contagium presented itself. I may say that it was on the conversion of the permanent hardy form into the fugitive and sensitive one, in the case of _bacillus subtilis_ and other organisms, that the method of sterilising by 'discontinuous heating' introduced by me in February 1877 was founded. The difference between an organism and its spores, in point of durability, had not escaped the penetration of Pasteur. This difference Koch showed to be of paramount importance in splenic fever. He, moreover, proved that while mice and guinea-pigs were infallibly killed by the parasite, birds were able to defy it. And here we come upon what may be called a hand-specimen of the genius of Pasteur, which strikingly illustrates its quality. Why should birds enjoy the immunity established by the experiments of Koch? Here is the answer. The temperature which prohibits the multiplication of _bacillus anthracis_ in infusions is 44° Cent. (111° Fahr.). The temperature of the blood of birds is from 41° to 42°. It is therefore close to the prohibitory temperature. But then the blood globules of a living fowl are sure to offer a certain resistance to any attempt to deprive them of their oxygen--a resistance not experienced in an infusion. May not this resistance, added to the high temperature of the fowl, suffice to place it beyond the power of the parasite? Experiment alone could answer this question, and Pasteur made the experiment. By placing its feet in cold water he lowered the temperature of a fowl to 37° or 38°. He inoculated the fowl, thus chilled, with the splenic fever parasite, and in twenty-four hours it was dead. The argument was clinched by inoculating a chilled fowl, permitting the fever to come to a head, and then removing the fowl, wrapped in cotton-wool, to a chamber with a temperature of 35°. The strength of the patient returned as the career of the parasite was brought to an end, and in a few hours health was restored. The sharpness of the reasoning here is only equalled by the conclusiveness of the experiment, which is full of suggestiveness as regards the treatment of fevers in man.                    *       *       *       *       * Pasteur had little difficulty in establishing the parasitic origin of fowl cholera; indeed, the parasite had been observed by others before him. But by his successive cultivations, he rendered the solution sure. His next step will remain for ever memorable in the history of medicine. I allude to what he calls 'virus attenuation.' And here it may be well to throw out a few remarks in advance. When a tree, or a bundle of wheat or barley straw, is burnt, a certain amount of mineral matter remains in the ashes--extremely small in comparison with the bulk of the tree or of the straw, but absolutely essential to its growth. In a soil lacking, or exhausted of, the necessary mineral constituents, the tree cannot live, the crop cannot grow. Now contagia are living things, which demand certain elements of life just as inexorably as trees, or wheat, or barley; and it is not difficult to see that a crop of a given parasite may so far use up a constituent existing in small quantities in the body, but essential to the growth of the parasite, as to render the body unfit for the production of a second crop. The soil is exhausted, and, until the lost constituent is restored, the body is protected from any further attack of the same disorder. Such an explanation of non-recurrent diseases naturally presents itself to a thorough believer in the germ theory, and such was the solution which, in reply to a question, I ventured to offer nearly fifteen years ago to an eminent London physician. To exhaust a soil, however, a parasite less vigorous and destructive than the really virulent one may suffice; and if, after having by means of a feebler organism exhausted the soil, without fatal result, the most highly virulent parasite be introduced into the system, it will prove powerless. This, in the language of the germ theory, is the whole secret of vaccination. The general problem, of which Jenner's discovery was a particular case, has been grasped by Pasteur, in a manner, and with results, which five short years ago were simply unimaginable. How much 'accident' had to do with shaping the course of his enquiries I know not. A mind like his resembles a photographic plate, which is ready to accept and develop luminous impressions, sought and unsought. In the chapter on fowl cholera is described how Pasteur first obtained his attenuated virus. By successive cultivations of the parasite he showed, that after it had been a hundred times reproduced, it continued to be as virulent as at first. One necessary condition was, however, to be observed. It was essential that the cultures should rapidly succeed each other--that the organism, before its transference to a fresh cultivating liquid, should not be left long in contact with air. When exposed to air for a considerable time the virus becomes so enfeebled that when fowls are inoculated with it, though they sicken for a time, they do not die. But this 'attenuated' virus, which M. Radot justly calls 'benign,' constitutes a sure protection against the virulent virus. It so exhausts the soil that the really fatal contagium fails to find there the elements necessary to its reproduction and multiplication. Pasteur affirms that it is the oxygen of the air which, by lengthened contact, weakens the virus and converts it into a true vaccine. He has also weakened it by transmission through various animals. It was this form of attenuation that was brought into play in the case of Jenner. The secret of attenuation had thus become an open one to Pasteur. He laid hold of the murderous virus of splenic fever, and succeeded in rendering it, not only harmless to life, but a sure protection against the virus in its most concentrated form. No man, in my opinion, can work at these subjects so rapidly as Pasteur without falling into errors of detail. But this may occur while his main position remains impregnable. Such a result, for example, as that obtained in presence of so many witnesses at Melun must surely remain an ever-memorable conquest of science. Having prepared his attenuated virus, and proved, by laboratory experiments, its efficacy as a protective vaccine, Pasteur accepted an invitation from the President of the Society of Agriculture at Melun, to make a public experiment on what might be called an agricultural scale. This act of Pasteur's is, perhaps, the boldest thing recorded in this book. It naturally caused anxiety among his colleagues of the Academy, who feared that he had been rash in closing with the proposal of the President. But the experiment was made. A flock of sheep was divided into two groups, the members of one group being all vaccinated with the attenuated virus, while those of the other group were left unvaccinated. A number of cows were also subjected to a precisely similar treatment. Fourteen days afterwards, all the sheep and all the cows, vaccinated and unvaccinated, were inoculated with a very virulent virus; and three days subsequently more than two hundred persons assembled to witness the result. The 'shout of admiration,' mentioned by M. Radot, was a natural outburst under the circumstances. Of twenty-five sheep which had not been protected by vaccination, twenty-one were already dead, and the remaining ones were dying. The twenty-five vaccinated sheep, on the contrary, were 'in full health and gaiety.' In the unvaccinated cows intense fever was produced, while the prostration was so great that they were unable to eat. Tumours were also formed at the points of inoculation. In the vaccinated cows no tumours were formed; they exhibited no fever, nor even an elevation of temperature, while their power of feeding was unimpaired. No wonder that 'breeders of cattle overwhelmed Pasteur with applications for vaccine.' At the end of 1881 close upon 34,000 animals had been vaccinated, while the number rose in 1883 to nearly 500,000.                    *       *       *       *       * M. Pasteur is now exactly sixty-two years of age; but his energy is unabated. At the end of this volume we are informed that he has already taken up and examined with success, as far as his experiments have reached, the terrible and mysterious disease of rabies or hydrophobia. Those who hold all communicable diseases to be of parasitic origin, include, of course, rabies among the number of those produced and propagated by a living contagium. From his first contact with the disease Pasteur showed his accustomed penetration. If we see a man mad, we at once refer his madness to the state of his brain. It is somewhat singular that in the face of this fact the virus of a mad dog should be referred to the animal's saliva. The saliva is, no doubt, infected, but Pasteur soon proved the real seat and empire of the disorder to be the nervous system. The parasite of rabies had not been securely isolated when M. Radot finished his task. But last May, at the instance of M. Pasteur, a commission was appointed by the Minister of Public Instruction in France, to examine and report upon the results which he had up to that time obtained. A preliminary report, issued to appease public impatience, reached me before I quitted Switzerland this year. It inspires the sure and certain hope that, as regards the attenuation of the rabic virus, and the rendering of an animal, by inoculation, proof against attack, the success of M. Pasteur is assured. The commission, though hitherto extremely active, is far from the end of its labours; but the results obtained so far may be thus summed up:-- Of six dogs unprotected by vaccination, three succumbed to the bites of a dog in a furious state of madness. Of eight unvaccinated dogs, six succumbed to the intravenous inoculation of rabic matter.