I'HE ANIM AL ALKALOIDS 
 
 AND AUTO-I NTOXI CAT 1 ON 
 
 IN HEALTH AND DISEASE 
 
 . M. D, 
 
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The Animal Alkaloids 
 
 AND 
 
 AUTO-INTOXICATION IN HEALTH AND DISEASE. 
 
THE 
 
 ANIMAL ALKALOIDS, 
 
 CADAVERIC AN J? VITAL; 
 
 THE PTOMAINES AND LEUCOMAINES 
 
 Chemically, Physiologically and Pathologically 
 Considered in Relation to Scientific 
 Medicine. 
 
 r 
 
 By A. M. BROWN, M.D. 
 
 aattt an introliuctfon ftp 
 
 1' R O F E S S O R A R M A N D G A U T I E R , 
 
 O/ ^he Fiiculte de Mddicine of Paris, and Member of the Academic de Medicine, 
 and of the Academie des Sciences. 
 
 SECOND EDITION. 
 
 Xon^on : 
 
 HIRSCHFELD BROS., 
 BREAMS BUILDINGS, 
 Fetter Lane, E.C. 
 
PREFACE TO THE SECOND EDITION. 
 
 The author, in proposing to himself the issue of a 
 second and enlarged edition of his Treatise on the 
 Animal Alkaloids, believes that in so doing he will 
 supply a professional want. The original work is 
 now out of print, though only put through the press 
 within the last eighteen months. Its so rapid ex- 
 haustion he naturally attributes to the high and in- 
 trinsic interest attaching to the subject to which this 
 work has directed attention. 
 
 The startling problems involved in the study of the 
 Animal Alkaloids is no longer exclusively limited to 
 the special department of the experimental chemist 
 and physiologist ; laying claim as it does to a much 
 wider range, it should now be made accessible to the 
 student of medicine generally. The present work in 
 its revised and enlarged form the author thinks well 
 calculated to meet this requirement and purpose. 
 
 Strictly practical in arrangement, the work divides 
 itself into five parts, the first of which deals with the 
 
 99468 
 
vi. Preface. 
 
 ptomaines or cadaveric alkaloids. The second treats 
 of the leucomaines, or vital alkaloids, each class being 
 investigated under its various aspects, whether 
 chemical, toxic, or medico-legal. The third part in- 
 dicates the physiological origin of the leucomaines 
 and their role in auto-intoxication in disease. The 
 fourth and fifth parts, in which is traced out the 
 farther developments of the subject, is devoted to 
 material entirely new, which has been brought down 
 to the latest date. 
 
 Though not proposing to be a treatise that shall be 
 thoroughly exhaustive, it will admittedly be found 
 to supply what has hitherto not existed in print, 
 namely, an adequate introduction to the subject in all 
 its bearings. 
 
 The accompanying table of contents will be found 
 to exhibit with sufficient clearness the character and 
 objects of the present publication. 
 
 A. M. B. 
 
 15, Haver stock Hill. 
 
PREFACE TO THE FIRST EDITION. 
 
 In my essay on the Origin of Contagia, considered 
 from the evolutional point of view, two editions of 
 which were published in 1884, the genesis and trans- 
 formation of morbific elements, organic and inorganic, 
 were reviewed ; the physiological alkaloids as factors 
 in etiology and general pathology were noted, and 
 their action as auto-infectants, or as toxic agents in 
 poisoning from inoculation of putrid animal matter 
 prophylactically or otherwise, indicated. 
 
 The startling problems the study of the alkaloids 
 envolve, having hardly been submitted to the scientific 
 student here in England, I concluded by expressing 
 my intention of entering more fully and more closely 
 into the subject in a future work. The series of 
 papers on the animal alkaloids — a list of which is 
 here appended — which from time to time have been 
 published by me since, were an earnest that the 
 design was being carried out. The present treatise 
 which I have now the pleasure of submitting for the 
 
viii. Preface. 
 
 consideration of the competent is the fulfilment of 
 my promise. 
 
 Without the encouragement and aid of Continental 
 workers in this department, the task would have been 
 impossible ; it is, consequently, with no small plea- 
 sure I have to acknowledge my great indebtedness, 
 in the first place, to Professor Armand Gautier, whose 
 name occupies the chief position in connection with 
 the subject, and who has done me the honour of 
 contributing the lucid introduction to the treatise. 
 Secondly, to Professor Michel Peter, who has done 
 so much to advance the claims of the animal alka- 
 loidal factor in pathology and clinical medicine ; and, 
 thirdly, to Professor Hugounenq, author of an excel- 
 lent n'sinuc, and whose valuable bibliography, supple- 
 mented by myself to the present date, finds a suitable 
 place in the appendix, and which will doubtless be 
 estimated at its proper worth by all who are engaged 
 • or take an interest in this special department of re- 
 search. From these generous sources I have been 
 enabled not only to avail myself of what has been 
 hitherto recorded, but also of research material still 
 unpublished, and to note current investigations that 
 promise farther enrichment of this new departure in 
 science. Evidence of this will be seen in Bouchard's 
 " Lessons on Auto-intoxication in Disease," and Sir 
 
Preface. ix. 
 
 William Aitken's Netley lecture, " On the Animal 
 Alkaloids in their Pathological Relations," both now 
 in course of publication, and which will shortly be 
 available. 
 
 In a department of science so new and novel, many 
 points of controversial character necessarily present 
 themselves. I may be permitted to say that I have 
 neither courted nor avoided them. As regards my 
 own particular views, I trust that they are evident, 
 but not obtrusive. 
 
 A. M. Brown, M.D. 
 29, Keppel Street, Russell Square. 
 
CONTENTS. 
 
 Introduction. 
 
 Contributed by Prof. Armand Gautier. 
 
 Part I. 
 
 Cadaveric Alkaloids or Ptomaines. 
 
 Introductory. 
 
 Discovery of Animal Organic Bases — The work in Germany — 
 Dupre and Bence Jones — Gautier's work in connection with 
 the Albumenoids — Sehni's Toxicological Researches in 
 Italy ; his Report to the Academy of Science, Bologna. 
 
 I.— Putrefactive Origin and Genesis. 
 
 Ptomaines discovered in the Animal Economy after Death — 
 Putrefactive Fermentation — The Products of Putrefaction — 
 The Cadaveric Alkaloid is the Residual Skeleton of the 
 Proteid Molecule. 
 
 II.— Methods of Extraction. 
 
 Various methods of extracting Ptomaine or Cadaveric Alkaloids 
 — The Stas-Otto — Dragendorff's — Pouchet's — Gautier and 
 Etard's — Brieger's. 
 
 III.— Chemical Properties. 
 
 Gautier and Etard determine the precise Analysis of the Alka- 
 loid Bases — Ptomaines Solid, Liquid, or Volatile — Their 
 Chemical Reactions — The colour Reagents as a ready Test 
 — Close resemblance of Ptomaines and Vegetable Alka- 
 loids—Their behaviour under the same Reagents. 
 
xii. 
 
 Contents. 
 
 IV. — Classification and Definitions. 
 
 Two Classes of Ptomaines — I. Non-Oxygenous Alkaloids: Par- 
 voline ; Hydro-Collidine ; Collidine ; Neuridine ; Cada- 
 verine; Putrescine ; Mydaleine — 1 1. Oxygenous Alkaloids : 
 Neurine ; Choline ; Muscarine ; Gadinine ; other Bases, 
 Toxic and Non-Toxic— Brieger's latest Researches. 
 
 v.— Physiological Actions. 
 
 Toxic action of Alkaloids ; some Active, others Inert— Experi- 
 ments with Ptomaines extracted by Ether, Chloroform and 
 Alcohol — Physiological and Toxicological Experiments 
 with Ptomaines on Frogs and Dogs — Their effects com- 
 pared with Vegetable Alkaloids by Gautier, Brieger, and 
 Corona — Specific effects on various Organs. 
 
 VI. — Medico-Legal Import. 
 
 The Cadaveric Alkaloids and Toxicology — Experiments of 
 Selmi in Italy, and Otto in Germany — Lieberman experi- 
 ments by the Stas-Otto method in Medico-Legal Case — 
 Spica's Observations by Dragendorff's Method — Brouardel 
 and Boutmy experiment specified — Perplexing Question for 
 the Medico-legists — Hugounenq on the Question — The 
 Italian Ptomaine Commission Report —The best Methods 
 for separating Alkaloids in Medico-Legal Cases. 
 
 Part IL 
 
 The Vital Alkaloids or Leucomaines. 
 
 Introductory. 
 
 Gautier's Work ; his remarkable Memoire — Liebreich discovers 
 Betaine in Normal Urines— Gautier formulates the Theory 
 that such Alkaloids are Physiologically Produced during 
 Life — Bouchard supports this Theory ; Abnormal presence 
 of Alkaloids in Urines of Typhoid Patients— Experiments 
 with Saliva of Reptiles and Man. 
 
Contents. 
 
 xiii 
 
 I. — Classification and Definition. 
 
 Experimenters discover Alkaloids in Animal Tissues and 
 Secretions —Pouchet and Gautier separate and Classify 
 the Physiological Alkaloids — Two Principal Groups — 
 I. The Betaine, or Uric Leucomame Group : Betaine ; 
 Karnine ; Adenine ; Guanine ; Sarkine or Hypoxan- 
 thine ; Xanthine ; Pseudoxanthine — Their proper Extrac- 
 tives ; their peculiar Characteristics, Crystalline or Other- 
 wise. 
 
 II. — Classification and Definition. 
 
 Gautier's farther Studies in the Physiological Formation of 
 Alkaloids in the Living Organism--His experiments with 
 Fresh Meat ; the Results— II. The Kreatinic Leucomaine 
 Group : Kreatinine ; Xanthocreatinine ; Crusocreatinine : 
 Amphicreatinine ; Pseudoxanthine ; undefined Bases — Un- 
 broken circle of Chemical Affinities. 
 
 III.— Non-Seriate Group. 
 
 This group of Alkaloids but little defined as yet— Discovered in 
 Urines by Pouchet and others — In Blood and important 
 Viscera by Spica and others — In the Spleen by Morelle; in 
 the Intestines by Pouchet, Villiers, and others — in the 
 Saliva by Gautier — Experiments with these Leucomaines ; 
 their Characteristics — The Venoms of Snakes and Batra- 
 chians — Experiments with Molluscs and Fish. 
 
 IV.— Physiological Actions. 
 
 The Difficulties in the way — The Toxic Properties of Leuco- 
 maines— Experiments by Labord with the Alkaloids of the 
 Spleen — The Leucomaines of the Intestines — The Alka- 
 loids of Urines clinically considered— Lepine and Guerin's 
 observations on this Subject — Bouchard's elaborate ex- 
 amination of Urines— Experiments with the Alkaloids of 
 Human Saliva — Bases in Human Urine during Sleep and 
 Wakefulness — Experiments with the Lower Animals — 
 Shell-Fish Poisoning — Brieger separates the active Prin- 
 ciple, Mytilotoxine. 
 
xiv. 
 
 Contents. 
 
 V. — BiocHEMic Aspects. 
 Definition of Life— Chemical Actions with their Products— 
 The close Resemblance of the Animal and Vegetable 
 Alkaloids— The Impossibility of Clearly Distinguishing 
 Ptomaines from Leucomaines— No Great Difference in 
 the Physiological Action of Animal Alkaloids— The Origin 
 of Alkaloids must be Sought for in the Destruction of the 
 Albumenoid Molecule— The Aerobic and Anerobic Life of 
 Tissues— Micro-Organisms and the Origin of Animal 
 Alkaloids. 
 
 Part IIL 
 
 The Physiological Alkaloids or Leucomaines 
 IN Relation to Scientific Medicine. 
 
 Introductory. 
 
 Gautier's Aleinoire Deals with Pathology based on Positive 
 Data — Partial Return to Humoralism — The Elaboration of 
 Toxic Alkaloid substances in the Tissues during Life — 
 Peter's Memoire and Auto- Intoxication — The Question in 
 Germany in Connection with the Bacillar Theory — Diseases 
 are Processes, not Entities. 
 
 I.— Physiological and Pathological Significance. 
 
 Gautier discovers that Ptomaines are nearly always Present in 
 the Excretions of Healthy Living Animals ; his Experiments 
 — Tissue Transformations in the Superior Animals — Auto- 
 Intoxication — Processes by which it is Resisted — Elimina- 
 tion of the Alkaloids in the Healthy — The Practical Bearings 
 of the Subject on Medicine. 
 
 II.— A New Departure in Pathology. 
 
 Traditional Medicine and the Medicine of the future — The • 
 Alkaloids not only interesting Chemically and Medico- 
 Legally, but also Pathologically — Ptomaines originate in 
 the Putrefaction of Dead Tissues — Leucomaines physio- 
 logically elaborated in Living Tissues — Clinical Observations 
 
Contents. 
 
 XV 
 
 show the actions of the Various Bases — Thought, and the 
 effect of Neurine on the Brain— Aerobic and Anerobic 
 Life of Tissues — We resist Auto-Intoxication by Toxic 
 Bases, either by Normal Ehmination, or internal Combus- 
 tion — Accumulation of these Leucomaines in the body leads 
 to Auto- Intoxication — Fatigue Fever and the Leucomaines 
 — Ravilliod on Fatigue Fever — Ptomaines in over-kept 
 Meats. 
 
 PART IV. 
 Auto-Intoxication in Disease. 
 
 Introductory. 
 
 An Etiological Survey — Where are we now ? — The Problem 
 stated — Limitations of exact Investigation — The Changes 
 of Method— Changes of Pathological Doctrines — The 
 Theory of Germs — The Pneumono-coccus and its Vicissi- 
 tudes — The Products of Microbic Action Deleterious — 
 Investigation of the Cultivation Liquids of Specific Bacilli 
 — Contents found to be Alkaloid — Bearing on Disease — 
 Microbic Etiology enigmatical — The Germ Theory on the 
 Wane— New Departure in Pathology — ^^Physico-Chemical 
 Lines of Investigation. 
 
 I.— Recent Researches and their Results. 
 
 Bouchard's Investigations ; Man naturally possesses in himself 
 much that is potentially and actually Morbid — The Theo- 
 retic Import of Microbic Action in Etiology — Intoxication 
 by Disordered Nutrition, Inefficient Circulation, Nervous 
 Exhaustion and Putrefactive Processes — Normal Cellular 
 Life and the Production of Leucomaines— Elimination by 
 passing through the Blood— Blood a Toxic Agent— The 
 Toxic Substances are Organic and Inorganic — Secretion 
 and Excretion, importance of — The ' term Urotoxy — The 
 Alimentary Canal and Poisoning of the System — Gastric 
 Embarrassments and Morbid Symptoms — Jaundice and 
 Auto-Intoxication — The Bile and Bihary Salts— The Func- 
 tion of the Kidneys— Diseased Liver and Auto-Ihtoxication 
 — Cholera and the Animal Alkaloids. 
 
 B 
 
xvi. 
 
 Contents. 
 
 Part V. 
 Auto-Intoxication in Health. 
 
 Introductory. 
 
 Physiological and Chemical Characteristics of Sleep— Anoxia of 
 the Brain — The part played by Oxygen and Carbonic Acid 
 in the Respiratory and Circulatory Systems — The Chemical 
 History of Muscle Exhaustion. 
 
 I. — The Animal Alkaloids : their Probable Role in 
 Fatigue and Sleep. 
 
 The Phenomena of Muscular Exhaustion and Production of 
 Toxic Bases and Sleep — Ponogenes — German Experimen- 
 talists — Gautier's Discoveries — The Toxicity of Urines 
 during Wakefulness and Sleep— The Processes of Life and 
 the Production of Waste Materials— Repose necessary for 
 Eliminatory and Recuperative Purposes— The action of 
 Leucomaines as Soporifics — Sleep probably due to Direct 
 Intoxication — Nervous and Muscular Activity connected 
 with Chemical Reaction — Accumulation of Leucomaines in 
 the Ganglionic Centres gives Rise to Fatigue and Sleep — 
 During Sleep the Eliminatory Processes Active — Relative 
 Proportion of Leucomaines in connection with Activity and 
 Sleep — Antidotes to Action of 
 
 APPENDIX. 
 I. 
 
 French Text of Prof. Armand Gautier's Introduction. 
 
 II. 
 
 Bibliography. 
 INDEX. 
 
Introduction 
 
 BY 
 
 PROFESSOR ARMAND GAUTIER. 
 
INTRODUCTION. 
 
 The essential phenomena of cellular life, vege- 
 tal or animal, are still too little known in their 
 mechanism, and even in their effects, to permit 
 of our determining the intimate causes of their 
 evolution, normal or abnormal, on which health 
 and disease depend. What may, however, be 
 positively affirmed is, that these phenomena 
 are entirely physico-chemical in their nature, 
 and that if the reason of their succession still 
 escapes detection they are necessarily subject 
 to the general law which requires that force in 
 all its forms — heat, muscular activity, chemical 
 or nervous action, &c. — is the result of a trans- 
 formation of mechanical energy, potential or 
 actual, present in the material substance of 
 each cell. 
 
 It is now well known that in the case of 
 living things, as in that of inert substances, the 
 modifications which render force appreciable 
 and utilisable, are of two kinds. In the case of 
 the first, it results from molecular modifications 
 
XX. 
 
 Introduction. 
 
 brought about in matter without the intervention 
 of oxygen. Organisms which derive their force 
 vitahty entirely from this interior source, are 
 those which M. Pasteur has named anaerobic 
 and belong to the lower order of ferments. 
 But I have shown elsewhere that, contrary to 
 what was a priori supposed, the life of the 
 larger animals is in a great measure — nearly 
 one-fifth — also anaerobic. The second source 
 of vital force results from the chemical combi- 
 nation of substances, and particularly in the case 
 of those which are combustible, in their union 
 with oxygen. Those organisms which more 
 especially derive their force from internal com- 
 bustions are aerobic. Some of them are vege- 
 table, but in general they belong to the animal 
 kingdom. They absorb oxygen, burn the 
 material substance of their cells, incessantly 
 give off carbonic acid, water, urea, &c., corre- 
 ctively benefiting by the force resulting from 
 these combustions. 
 
 In both cases the vital products become un- 
 suitable for the maintenance of the vital func- 
 tions of the cell which formed them ; they must 
 be got rid of The animal would very soon 
 succumb were the carbonic acid, urea, water, 
 and even the heat, which it incessantly pro- 
 duces, to accumulate within its organism. But 
 
Litroduction. 
 
 xxi. 
 
 in the case of anaerobic life, the products that 
 arise and form without the intervention of 
 oxygen, and more particularly those which 
 result from the splitting up or disintegration of 
 albumenoid material, are especially dangerous. 
 They are of the nature of those substances 
 which result from all putrid bacterial fermenta- 
 tions. In the first part of the present work it 
 will be seen, that bacterial anaerobic life gives 
 rise to certain alkaloids, besides other very 
 poisonous bodies, which are also to be met 
 with in cadaveric matters, and which, by reason 
 of this, have received the name of ptomaines. 
 Those of this class which are constantly present 
 in prolonged putrefactive fermentations, belong 
 to the pyridic and hydropyridic series ; they do 
 not differ widely from the poisonous bases of 
 hemlock and tobacco. It is only recently that 
 there has been detected in the products of the 
 newer fermentations, the presence of alkaloid 
 substances more powerful still. Such, for in- 
 stance, is muscarine, the poisonous principle of 
 certain species of the mushrooms. If, then, I 
 have shown that we live in part anaerobically, 
 alkaloids analogous in nature ought to form in 
 the animal organism. This experiment has 
 confirmed, and I have given to these bases the 
 name of leucomaines, a term which is merely 
 meant to indicate their albumenoid origin. 
 
xxii. 
 
 Introduction. 
 
 The products of life, aerobic or anaerobic, 
 cannot be retained within the organism for any 
 length of time with impunity ; normally they 
 undergo destruction and excretion by economic 
 processes, which are constantly in operation. 
 But if from any cause the functional play is 
 interrupted ; should there be emotional distur- 
 bance of the nervous centres ; should sudden 
 chills suppress the action of the skin, or insuffi- 
 cient aeration of the blood take place ; or, 
 finally, if from any less obvious cause, leucomain 
 products are more abundantly formed within 
 the cells, or be so defectively absorbed, ex- 
 creted, or oxydized as that the blood becomes 
 charged with them, they are carried to the 
 nervous centres which regulate the central life 
 and function as a whole ; immediately disorder 
 becomes general, complete, and necessarily 
 assumes progressive forms — in a word, disease 
 declares itself and undergoes development. 
 
 This admitted, facts must not, however, be 
 too exclusively regarded. We must not too 
 hastily assume that the succession of morbid 
 phenomena are thus to be explained in every 
 case. Without doubt, many pathological con- 
 ditions arise from disarrangement of nutri- 
 tion, assimilation, disassimilation, secretion and 
 hcematose — are, in a word, veritable auto-infec- 
 
Introduction. 
 
 xxiii. 
 
 tions. Still, there are cases in which we cannot 
 possibly ignore the presence of causes, which 
 the organism would seem incapable of exciting 
 spontaneously. We do not, for instance, ob- 
 serve syphilis, measles, variola, anthrax, nor 
 the generality of maladies known as contagious 
 and specific — with possibly the exception of 
 army-typhus — appear spontaneously, even in 
 those unhealthily predisposed, without previous 
 contact or relation, direct or indirect, with in- 
 fected subjects. To M. Pasteur is due the 
 merit of having demonstrated that in the ma- 
 jority of such cases, we can obtain from the 
 disease subject a microbe, specific, cultivable 
 and capable of reproducing itself apart from the 
 animal organism, and which, when introduced 
 into a healthy organism, gives rise to the primi- 
 tive or original malady. But who does not see 
 that these important facts are phenomenally 
 characteristic of the life of the cells, as they 
 normally comport themselves in the higher 
 animal organisms.^ A ferment or specific mi- 
 crobe lives after the fashion of one of our tissue 
 cells now aerobically, as is the case in anthrax ; 
 again, anaerobically, as when septicemia is taken 
 as an example. It cannot escape that law 
 which requires that every cell that lives pro- 
 duces detritus — extractive matter, ptomaines, 
 
xxiv. 
 
 Introduction. 
 
 leucomaines — which are the proximate causes 
 of its powerful action on the organism. But in 
 this new case, the foreign cells comport them- 
 selves much in the mode that cancer cells, for 
 example, do, exhibiting a life, a power of pro- 
 lificity so active as to rapidily invade the whole 
 economy with the dangerous products of their 
 evolution. 
 
 It would, then, be erroneous to insist, with 
 the over-fervent followers of their master, that 
 all maladies result from the evolution of a 
 specific microbe in the organism. There are 
 causes of disease which are resident within 
 ourselves, that remain inoffensive whilst elimi- 
 nation and oxydation of detritus is normally 
 operative, that give rise to disease if from some 
 cause or other the detritus accumulates in the 
 economy and acts upon the nervous centres. 
 But to those morbific agents, which our living 
 tissues incessantly dispose of, must be added the 
 operation, though in rarer instances, of those 
 derivable from the normal life of those parasitic 
 cells which have been named microbes or fer- 
 ments, and which are found to accompany the 
 generality of contagious or virulent diseases. 
 
 The ptomaines and leucomaines, like the ex- 
 tractive matters, urea, urides, carbonic acid, the 
 oxalates and ammoniacal salts, are the vital re- 
 
Introduction, 
 
 XXV. 
 
 liquae or residue material, effete and pernicious, 
 which may become the cause of disease, no 
 matter how they originate, that is, arise in the 
 normal cells of the organism from within, or in 
 the microbic cell from without. Of all the ex- 
 tractive composite residua the alkaloids of ani- 
 mal origin, which the present work treats of, 
 are worthy of the deepest interest. It is only 
 now that they have become familiar to us. 
 They claim our special study from the fact of 
 their constant presence in normal secretions, 
 and must be classed with the most active agents 
 known. I am consequently of opinion that the 
 excellent work by Dr. A. M. Brown will have 
 a very special interest for competent enquirers ; 
 that it will give a stimulus to investigations, 
 new and fruitful in elucidation of a question the 
 most essentially humane — the cause and the 
 mechanism of life, health, and disease. 
 
 Armand Gautier. 
 
 Paris, y^//)/ 14, 1887. 
 
The Cadaveric 
 Alkaloids or Ptomaines. 
 
 PART I. 
 
The detection of animal organic bases, even 
 those of putrefactive origin, it must be admitted, 
 is not a recent fact in modern science. So very 
 little importance was, however, attached to the 
 few carelessly observed alkaline matters, that un- 
 til 1872, every toxic alkaloid substance detected 
 in the course of medico-legal investigations by 
 experts, was regarded as having been introduced 
 into the system during life. Theoretic precon- 
 ception sufficiently accounts for this ; scientific 
 conservativism is as difficult to overcome as any 
 other form. In the beginning of the century, 
 the power of plants to form alkaloids had been 
 conceded : for more than half a century later 
 the like privilege was dogmatically refused 
 to animal organisms, in entire ignorance of the 
 fact that the efficient agents of fermentation 
 were but the simplest forms of vegetable exis- 
 tence, — in fact, the connecting link between 
 the plant and animal 
 
4 
 
 It is true that the proof with which gra- 
 tuitous hypotheses could be confronted was 
 both obscure and incomplete. In 1822, Gas- 
 pard and Stick to begin with, had detected a 
 venomous principle in cadaverous extracts. 
 Panum in 1856, taking up the subject, found 
 that putrid matters contained a poison of great 
 activity which was neither albumenoid nor 
 alkaloid. In consequence of the interest ex- 
 cited by the investigations of the latter, which 
 promised to throw light upon the causes of 
 putrid infection, several of the German schools 
 instituted a comparative study of its etiological 
 action. Between 1856 and 1868, various me- 
 moirs appeared, of which those of Hemmer, 
 Schwerminger, Muller, Schmitz, Weidenbaum, 
 though important, did little more than confirm 
 the work of Panum. 
 
 In 1868, Bergmann and also Schmiedeberg 
 obtained from the extracts of putrid beer a 
 nitrogenous crystallizable substance which they 
 called sepsine. Its subsequent presumed dis- 
 covery in septicemic blood dependent on puru- 
 lent absorption, the pathological speculations 
 which it gave rise to, associating with them 
 the names of Dupre and Bence Jones, is now 
 a matter of medical history, and need not be 
 here disturbed — septicemia and purulent in- 
 
s 
 
 fection have passed through speculative phases 
 since, equally interesting, and quite as time- 
 serving. Following on the illusory sepsine 
 acquisition, Zuelzer and Sonnenschein made 
 known the fact of their obtaining from putrid 
 meat a venomous nitrogenous body, which 
 induced dilatation of the pupil, a property per- 
 mitting them to compare it with atropine. 
 
 When Selmi and Gautier entered on their 
 work, this included almost all that had been 
 done ; namely, observations for the most part 
 disconnected, ill-defined or questionable, of sub- 
 stances — Panum's putrid poison excepted — 
 whose genesis, nature, and chemical composi- 
 tion were but names and notions. As regards 
 those alkaline products normally present in the 
 animal economy during life, it is also well to 
 note that though positively, if not theoretically, 
 a greater advance had been attained. But, in 
 their turn the vital alkaloids, as will be seen 
 when they come to be treated of, were not less 
 subject to misconception and suspicion. 
 
 Such was the state of the enquiry when about 
 1870 M. Gautier, in the course of researches on 
 the albumenoids under various conditions, ob- 
 served that those substances when left to putrefy 
 became strongly ammoniacal. He observed 
 that on distilling normal urines which, in gen- 
 
6 
 
 eral, are acid, there passed into the recipient 
 an alkaHne Hquid, containing trimethylamine. 
 This fact confirmed led to the suspicion, that 
 the alkahnity of putrid Hquids was not entirely 
 due to the presence of ammonia ; closer inves- 
 tigation showed that such was the case. Later 
 on, in the course of 1872, he ascertained the 
 fact that fibrine of the blood, when left to 
 liquefy in water during the summer months, 
 furnished, besides the products then known, a 
 small quantity of various complex alkaloid sub- 
 stances fixed or volatile. His subsequent re- 
 searches on the bacterial destruction of the 
 albumenoids gave fullest confirmation of these 
 facts. 
 
 While in France Gautier as a chemico-phy- 
 siologist pursued his researches, in Italy Selmi, 
 as a medico-legal expert, was similarly engaged. 
 With different objects and from different aspects 
 both dealt with the problem, independently of 
 each other, both were experimentally and logi- 
 cally working out the same result. The Italian 
 toxicologist, in examining the dead body of a 
 subject supposed to have been poisoned, de- 
 tected an alkaloid which he was unable to 
 identify with any body then known as such. A 
 second instance, leading to a similar result, led 
 him to suspect that the presence of the alkaloid 
 
7 
 
 might be owing to physio-chemical action after 
 death rather than to accidents during life. 
 
 Early in 1872, Selmi communicated to the 
 Academy of Science of Bologna, a lengthy me- 
 moir, embodying his conclusions : — I. That the 
 stomach of persons who had died from natural 
 causes, contained substances which comport 
 themselves in the presence of reagents pre- 
 cisely as the vegeto-alkaloids do. II. That 
 these products are neither kreatine nor kreati- 
 nine, nor tyrosine. III. That similar substances 
 are present in alcohol, in which anatomical spe- 
 cimens have been preserved. Amongst toxi- 
 cologists these views w^ere received wath some 
 surprise, but the celebrated expert, by carefully 
 carrying on researches on exhumed bodies, 
 proved to demonstration that veritable organic 
 toxic alkaloids, analogous to those of vegetable 
 origin, were a constant accompaniment of the 
 process of putrefactive decomposition. 
 
 The objections raised, to be repeated later on 
 in the inquiry, were numerous. Might not the 
 presence of the substances be accounted for by 
 vegetable ingesta, or medicine taken during life. 
 And as no analysis had been made, it was sug- 
 gested that they might be some pseudo-alkaloid 
 or another, such as kreatine or kreatinine, 
 amides rather than alkalies, &c. : in fact, 
 
8 
 
 errors of the professor himself, owing to de- 
 fective mothods of investigation, left room for 
 doubt. 
 
 Replying to these objections, Selmi, in 1877, 
 conclusively announced that by subjecting pure 
 albumen to putrefaction, free from atmospheric 
 contact, he had been enabled to separate two 
 new alkaloids. 
 
 It would appear then that it was in 1876 that 
 Selmi satisfied himself that albumenoid material 
 undergoing putrefaction is the origin of those 
 cadaveric alkaloids which he had met with 
 in earlier operations. But this result, as we 
 have seen, had already been attained in 1873, 
 by Armand Gautier, and by a method that was 
 precise and clear beyond dispute ; fibrine washed 
 and free of all extractive matters, yielded alka- 
 loids in crystallizable salts, strictly derived from 
 albumenoid matters, these substances being 
 alone employed in his experiments. 
 
 It is well to be reminded of these facts, for 
 here an honour seems to have been somewhat 
 misawarded. While fully recognizing the claims 
 of Selmi, and the remarkable extension his re- 
 searches have given to this subject, it is incon- 
 testable that M. Gautier was the first to make 
 known the fact that it is really the proteid sub- 
 stances which supply the new class of alkaloids 
 
9 
 
 which he and Selmi had independently dis- 
 covered. This, however, Selmi himself amply 
 acknowledged. The circumstance is alluded 
 to with no view of disputing the importance 
 of his work. His researches on the alka- 
 loids, which he succeeded in extracting from 
 cadaveric products and which he first observed 
 showed none of the reactions of then known 
 alkaloids, is sufficient proof of his scientific 
 sagacity. If Selmi failed to explain the for- 
 mation of the new bodies he was, none the less, 
 quick to seize their origin, and the importance 
 of their discovery. His name must therefore 
 justly be regarded as first in modern toxicology. 
 
1. 
 
 Putrefactive Origin and Genesis, 
 
 The discovery of the cadaveric alkaloids known 
 as the ptomaines being fully treated, their origin 
 has now to be considered. These alkaloids 
 being the product of putrefaction, their origin 
 must be sought for in the bacterial destruction 
 of animal tissues, w^hich forms the necessary 
 introduction to their special study. Keeping 
 this fact in view, we now proceed to sift the 
 putrefactive process of nitrogenous organic sub- 
 stances, not precisely as a whole, but with refer- 
 ence rather to the elaboration of the alkaloid 
 albumenoid derivatives. 
 
 Detected in the animal economy after death, 
 the experimental extraction of the alkaline basic 
 residue is affected by operating on the dead 
 body of man or the carcases of animals. For 
 the investigator this difference of source is 
 immaterial. The nature and object of investi- 
 gation is the same in either case ; from first to 
 last phenomenally the destructive process being 
 
II 
 
 identical, they have the same significance and 
 must be so noted. When vitahty ceases and 
 the Hfeless body is abandoned to decay, it is 
 observed that putrefactive indications for a 
 time are neither well defined nor simultaneous. 
 Loss of heat, rigidity and discoloration of 
 the subject, follow in succession, and, as with 
 the carcase fragments, if not so markedly, soon 
 acquire an acid odour accompanied with 
 copious clear albumenous exudation, carbonic 
 acid and hydrogen gases are disengaged, and 
 during the first stage, without a trace of nitro- 
 gen. The mass medium exhibits a progressive 
 role of fermentation, at first lactic, then bu- 
 tyric, and looks as if it had been sweetened. 
 Towards the fifth or sixth day in the carcase 
 fragments, the albumenoid material, which till 
 now remained inactive, in its turn ferments ; 
 the disengagement of nitrogen, sulphuretted 
 and phosphoretted hydrogen mingled with car- 
 bonic acid, now takes place ; the medium soon 
 becomes alkaline ; ammonia is set free giving 
 the finishing characteristic of the putrefactive 
 condition, as it is ordinarily conceived to be. 
 
 When fish-flesh is substituted for animal 
 tissues, the sequence of phenomena is some- 
 what different. In the latter, lacto-butyric fer- 
 mentation due to a preliminary absence of the 
 
12 
 
 hydrates of carbon, which, in the living animal 
 tissues, are seemingly in union with the albu- 
 menoid matters, is most manifest. In putrefying 
 fish-material, on the contrary, this stage of the 
 process is transient and difficult to seize. 
 Water-breathing creatures expend proportion- 
 ately less force than those that breath in air, 
 their ternary substances, which constitute their 
 combustive reserve of tissue store, is consider- 
 ably less in quantity, the initial stage of hydro- 
 carbonic fermentation is consequently very 
 brief. Thus their putrefactive action, properly 
 so-called, follows close on death. The same 
 thing, however, obtains in man and the mamm- 
 ifera that succumb under violent exertion and 
 exhaustion. In other respects the process is 
 the same in both. 
 
 These remarks, however pertinent to the sub- 
 ject, enlighten us little in the lines of the enquiry. 
 Without following further the details of putre- 
 feiction which are familiar, let us trace the indica- 
 tions of the concomitant changes the organised 
 nitrogenous materials undergo in passing from 
 their organic condition in the tissues to that of 
 the organic alkaloids, so various in form and 
 constitution. On this point there is still much 
 to be learned. The action of the simpler kinds 
 of fernients aids us little in the matter. The 
 
13 
 
 residual products of the saccharine, for example, 
 are few, the elements of sugar being few in 
 number and simple in arrangement. The ni- 
 trogenous material of animal tissues, on the 
 contrary, is very complex, the ddbris of its 
 dislocations — its residual products — are, con- 
 sequently much more numerous. Here we are 
 groping, so to say, at our scientific limits. But 
 if our knowledge of the mechanism of physio- 
 chemical reduction is still very incomplete, by 
 noting and associating indications, a general 
 idea may be gained as to how the transforma- 
 tions are accomplished. 
 
 We know that the albumenoid element of 
 living tissue-structures is distinctively next to 
 insoluble in water, as becomes its function ; its 
 solution in the form of fibrine in the blood or in 
 albumen of the white of egg is only apparent. 
 Almost completely insoluble in water, it is abso- 
 lutely so in alcohol, such is its initial condition. 
 The first step in the process of putrefactive 
 destruction shows it to be soluble in water ; 
 and mark, a similar process is partially, but con- 
 tinuously, going on in the tissues during life ; 
 life being the equivalent of incessant tissue 
 transformations, effete constituents in this way 
 find elimination. On this first product classed 
 as extracts soluble in water, follows a further 
 
14 
 
 stage of degradation, affording us extracts solu- 
 ble in alcohol. The alterations now accom- 
 plished are notable. The initial albumenoid 
 characters, however, are not disposed of. The 
 extract, soluble in alcohol, does not crystallise 
 as yet, it persistently remains amorphous and 
 refuses to combine with other chemical bodies. 
 It still retains its complex constitution, consist- 
 ing of carbon, hydrogen, oxygen, nitrogen, with 
 traces of sulphur and phosphorus, but propor- 
 tionately the constituent elements are different 
 from what they were originally. In the main 
 the proportion of oxygen has increased, while 
 that of the others has diminished, precisely as 
 if the albumenoid material had undergone oxy- 
 dation or taken up one or more molecules of 
 water. Analyticall)' it is impossible to distin- 
 guish the two reactions ; this however matters 
 little. It is enough if we appreciate results 
 which, when read aright, show that the process 
 has been carried far below the initiid stage and 
 watery extract. 
 
 As the putrefactive process continues enrich- 
 ing and modifying in production, the extractive 
 matter, soluble in alcohol, is followed by sub- 
 stances capable of crystallising in that men- 
 struum : lucine, tyrosine, glycocolle, butaline, 
 and the various organic compounds, and notably 
 
15 
 
 the cadaveric alkaloids whose genesis we are 
 now investigating. But the process of reduction 
 still goes on ; the products become simpler, 
 volatilise, as phenol or phenic acid, indol and 
 skatol. Then follow those acids, volatile or 
 fixed, of simplest constitution, such as the acetic, 
 butyric, valerianic, and oxalic, in combination 
 with ammonia simple or its compounds, which 
 various ammoniacals are themselves the last 
 residual product of the nitrogen, originally an 
 element of the organic materials. The last 
 stage of decomposition is now reached, and 
 which need not be further followed. 
 
 As the condition under which the alkaloids 
 originate must now be evident, a word or two 
 regarding putrefactive signs, which sometimes 
 mark the process of bacterial action and the 
 presence of the alkaloid products, are needed. In 
 the process of putrefaction, as in other fermen- 
 tations, where bacterial action is aerobic, the 
 gaseous effluvium is not foetid. When it is on 
 the contrary anaerobic, as in the lacto-butyric, 
 for example, its presence is characteristic. The 
 sulphur and phosphorus alluded to, attacked 
 by the disengaged hydrogen, small quantities 
 of sulphuretted and phosphoretted hydrogen are 
 formed in the melange, imparting to it the fami- 
 liar putrescent odour. It is then and not till 
 
i6 
 
 then that putrefaction is vulgarly supposed to 
 take place. This is, however, incorrect. Odour 
 is so constantly an accompaniment of decom- 
 posing nitrogenous material, that if it is absent 
 the material is apt to be considered sound and 
 suitable for consumption should it be alimentary. 
 On scientific grounds the criterion is fallacious 
 and liable to lead to dangerous results ; injury 
 to health of the consumer, and, occasionally, 
 death itself is attributable to this cause. The 
 generation of foetid effluvia, it ought to be 
 remembered, is but a secondary factor in the 
 process of bacterial putrefaction. If its presence 
 is characteristic of putridity, putridity may still 
 be active in its absence, bacterides and poi- 
 sonous alkaloids included. It is for the micro- 
 scope and chemical analysis to decide the point. 
 
 En resume, the phenomena of albumenoid 
 putrefaction and alkaloid elaboration, being thus 
 succinctly treated and exposed, the mechanism 
 of the process which determines the formation 
 of the alkaloids divests the question of its 
 mystery, and we begin to see how substances, 
 differing so widely in their chemical constitu- 
 tion, chemical properties and physiological 
 action, may be similarly produced, and even 
 realise the fact that any given alkaloid, irres- 
 pective of its class and order, may often have 
 
17 
 
 several origins. It is not the original proteid 
 substance that determines their position in the 
 series. The simplicity or complexity of con- 
 stitution of these alkaloid bases is all the more 
 distinctive, according as the putrefactive pro- 
 cess is more or less advanced. We have seen 
 how the albumenoid constituents of the organic 
 tissues comport themselves in earlier stages of 
 bacterial destructive fermentation. In the more 
 advanced we have also seen how the proteid 
 molecule is, as it were, dissected by bacterial 
 action ; how the lateral or associated chains of 
 the cyclical nucleus successively disconnect 
 themselves by fixing water, and then we see arise 
 those unstable uric bodies so given to dissipate, 
 those complex amidic acids which analysis 
 detects in the putrid liquors precisely as it 
 detects them when albumenoid material at 
 280° C. is reduced or dislocated with baryta, 
 as has been shown by Schutzenberger in his 
 beautiful researches. According to the stage 
 at which the putrefactive process is experi- 
 mentally expressed, we observe imperfect albu- 
 menoid molecules, cyclical nuclei which still 
 retain some lateral chains in passing towards 
 yet simpler forms. Hence, we have first those 
 highly oxygenous alkaloids of M. Pouchet, then 
 the less oxygenous diamines of Brieger, and 
 2 
 
i8 
 
 finally, when the putrefactive process is com- 
 plete, the non-oxygenous pyridic alkaloids of 
 MM. Gautier and Etard, the simplest of all. 
 
 A cadaveric alkaloid or ptomaine thus pre- 
 sents itself as the residual skeleton, as it were, 
 of the proteid molecule which has undergone 
 continuous disintegrative action, the ultimate 
 terms of which are represented by the pyridic 
 bases ; so that considered from a purely chemical 
 point of view a ptomaine may be defined as 
 the cyclical nucleus of a proteid molecule, that 
 has undergone complete destruction in the 
 process of putrefaction. 
 
11. 
 
 Methods of Extraction. 
 
 The putrefactive origin and serial elaborations 
 of the ptomaine alkaloids, during the process of 
 bacterial destruction having been examined, the 
 means of extracting them must next be con- 
 sidered. 
 
 The methods devised and practised are very 
 numerous. Almost all who are in any way 
 authoritatively engaged with this department of 
 scientific research, have either modified those 
 long known, or wrought out new ones of their 
 own. Selmi, and the Italians who have con- 
 tinued investigating on his lines, have operated 
 according to the variously, if slightly modified, 
 method of Stas. The form most used by 
 the southern medico-legal experts and chemists, 
 is that known as the Stas-Otto method. 
 It consists in drenching to saturation hashed 
 putrescent materials with alcohol 90° C, adding 
 tartaric acid till acidulous reaction is appreci- 
 
20 
 
 able. Sufficient time for digestion at a tem- 
 perature of 70° to 75° C. being given, it is 
 then allowed to cool, afterwards filtered and the 
 residuum expressed. The operation repeated 
 several times, the alcoholic liquids are collected 
 and evaporated in vacuo at a temperature of 
 35° C. The liquid is then passed through a 
 moistened filter to remove fatty matters, to dis- 
 pose of other remaining impurities, and rapidly 
 agitated with ether. Thus exhausted, the liquid 
 is freed from the solvent, then it is mixed 
 with powdered glass and evaporated in vacuo 
 in presence of sulphuric acid, until it is 
 nearly dry. The residuum is then drenched 
 with pure alcohol, when it is allowed to mace- 
 rate for twenty-four hours, and afterwards again 
 evaporated in vacuo 35° C. The new residuum 
 obtained is dissolved in a small quantity of 
 v/ater, to which is added bicarbonate of soda 
 or of potash to alkalinity. The solution is 
 agitated with four volumes of pure ether, then 
 decanting and evaporating, the alkaloids remain 
 as the residuum. 
 
 Other methods varied by the introduction of 
 new solvents, such as chloroform, benzine 
 and petroleum, have also been much used in 
 Italy as well as in France and Germany. The 
 best known is that which bears the name of 
 
21 
 
 Dragendorff. It consists in first treating finely 
 divided putrid meat with sulphuric acid diluted 
 to I -5th — 15 cc. of acid to 100 cc. of clear 
 bouillie of the hash, left to digest for some hours 
 at 50'' C. ; it is then filtered and expressed ; the 
 residue is submitted to the same treatment. 
 The liquids collected are then evaporated to a 
 syrupy consistence, aud exposed in contact with 
 alcohol at 93° C. for twenty-four hours ; filtered 
 and evaporated the residuum is then agitated 
 with benzine and immediately decanted. The 
 operation is repeated, ammonia is added to 
 the residuum till alkaline reaction ensues. It is 
 then heated to 40° or 50" C, when it is again 
 exhausted with benzine. By several repeti- 
 tions we obtain a certain quantity of benzine 
 holding in solution impure alkaloids ; this is 
 purified by converting it into sulphates, decom- 
 posing with ammonia, recovering with suitable 
 dissolvents and submitting to treatment similar 
 to what we have just described. 
 
 The alkaloid extracts obtained by the above 
 described or indicated methods, certainly enable 
 operators to utilise alkaloid reagents with some 
 degree of success. The products responding 
 to ordinary tests are reliable in physiological 
 experimentation, still, it is to be observed that, 
 in separating the alkaloids from the extracts 
 
22 
 
 which they accompany by this method, it is 
 only possible, and with the utmost care, to 
 obtain even impure bases, in quantity sufficient 
 to admit of isolation and correct analysis. 
 Consequently, no product obtained by those 
 methods of procedure has been defined, differ- 
 entiated or physiologically tested in a suffi- 
 ciently conclusive manner. 
 
 M. Pouchet, who in 1880 succeeded in iso- 
 lating from the normal urines an alkaloid fixed 
 and toxic, later on adapted a method which con- 
 sisted in precipitating these bodies in solutions 
 slightly alkaline, by adding an excess of tannin, 
 and then decomposing the tannates formed with 
 the hydrates of lead in the presence of alcohol. 
 The evaporation of the alcoholic solution leaves 
 a syrupy mass which can be dialysed ; the bases 
 are to be found in the dialysed portion of 
 the solution, when they can be separated 
 with such solvents as ether, chloroform, or 
 petroleum. Although Pouchet obtained excel- 
 lent results, in fact, discovered two new alka- 
 loids, which he analysed, by this mode of 
 operating, it is not to be commended in less 
 experienced hands. As M. Gautier points out, 
 the tannin is very liable to oxydise and dete- 
 riorate in the presence of alkalies, and only 
 precipitates them very imperfectly, especially 
 on exposure in conducting operations. 
 
23 
 
 It is only so recently as 1881, that MM. 
 Gautier and Etard entered on the study of the 
 products of putrefaction of the albumenoids ; 
 researches which were continued until 1883. 
 In this important inquiry the material selected 
 for operations consisted for the most part of the 
 putrid ddbris of the horse, ox, fish, and shell 
 fish. In the course of investigations, the first 
 that had been conducted in a strictly scientific 
 manner, the methods adopted of separating the 
 ptomaines were somewhat different from those 
 already described. The putrescent liquors 
 were sparingly acidulated with sulphuric acid, 
 agitated, relieved of supernatant fats and oils, 
 and finally distilled in vacuo ; the syrupy re- 
 siduum relieved of its crystals was rendered 
 alkaline with baryta, filtered and exhausted with 
 chloroform, which dissolved the bases : the 
 excess of chloroform was evaporated in vacuo, 
 or in a current of carbonic acid gas, care being 
 taken to prevent access of atmospheric air, or 
 elevation of temperature which might destroy 
 the bodies sought for. The remaining liquor 
 after the removal of the chloroform was treated 
 with water and tartaric acid, which separates a 
 brownish resin from the liquor ; the latter 
 treated with potash disengages a pungent odour 
 of the carbylamines, whilst the ptomaines are 
 
24 
 
 set free : these are taken up with ether which 
 is disposed of by evaporating under reduced 
 pressure in vacuo and in presence of caustic pot- 
 ash for the purpose of preventing carbonisation. 
 
 By submitting the bases thus obtained to dis- 
 tillation or fractional precipitation by the aid of 
 chloride of platinum, or, if in sufficient quan- 
 tity, by distillation in vacuo, they can then be 
 methodically separated. 
 
 It is well to mention that Gautier has not 
 continued the above process. He has returned 
 to the method of his earlier operations, and it 
 is that he now makes use of with little altera- 
 tion. Sulphuric acid is no longer employed. 
 To the alkaline liquors of precipitation, he adds 
 oxalic acid to acidulation, allowing them to rest 
 so long as fatty acids form, and which, as they 
 come to the surface, are separated. By filtering 
 and distilling, the liquors are freed from pyrol, 
 skatol, phenol, indol ; the volatile fatty acids 
 and a portion of the ammonia are disposed of. 
 He then alkalises the undistilled portion with 
 chalk ; separates the precipitate which forms and 
 which contains the greater part of the fatty 
 acids ; distils the alkaline liquors to dryness in 
 vacuo ; and collects the vapours in very weak sul- 
 phuric acid, which retains the ammonia and the 
 volatile bases.. In order to neutralise the liquor 
 
25 
 
 of distillation, it is evaporated nearly to dryness 
 and the* ammonia sulphate removed, treating 
 the remaining mother-liquor with pure concen- 
 trated alcohol ; this dissolves the alkaloid sul- 
 phate and leaves the ammoniacal sulphate. 
 The ^dcohol removed, the solution is decom- 
 posed with an alkali, and the ptomaines set at 
 liberty and taken up with ether, chloroform, or 
 petroleum. 
 
 The latest method deserving notice is that of 
 Brieger ; though the last it is certainly not the 
 least in importance and is as follows : — Flesh 
 material is set aside to putrefy for some days in 
 contact with water. The mass is then boiled, 
 then filtered, then precipitated with the sub- 
 acetate of lead. Excess of lead is removed from 
 the liquor with sulphuretted hydrogen ; freed 
 from the sulphides of lead and evaporated to 
 a syrupy consistence, and exhausted with amylic 
 alcohol, the residuum is treated with water ; 
 this is concentrated, acidulated with sulphuric 
 acid and washed repeatedly with ether to get 
 rid of the oxy-aromatic acids. The liquor by 
 evaporation is reduced to one-fourth of its initial 
 volume in order to separate its fatty acids ; the 
 sulphuric acid is taken up with baryta, and the 
 excess of baryta with anhydride carbonic. The 
 liquor is then filtered and heated in a water 
 
26 
 
 bath ; when cooled, it is precipitated with 
 chloride of mercury. The precipitate wash is 
 then decomposed with sulphuretted hydrogen, 
 finally concentrated by evaporation. Organic 
 substances are first deposited, which are separ- 
 ated and washed in pure alcohol. Very 
 soon long needle-shaped crystals are seen to 
 form, which are soluble in water and weak 
 alcohol, insoluble in pure alcohol, benzine, 
 chloroform, &c. 
 
 The bodies which crystallise are afterwards 
 separated the one from the other by fractional 
 precipitation with the aid of chloride of platinum 
 or chloride of gold. 
 
 It may be well to note that Brieger has 
 recently somewhat simplified his process. The 
 putrid liquids are brought to the boiling point, 
 filtered, then immediately precipitated with chlo- 
 ride of mercury. The liquors are then pre- 
 cipitated by treating them separately with 
 sulphuretted hydrogen ; these furnish the pro- 
 ducts which are isolated as before. 
 
III. 
 
 Chemical Properties. 
 
 It is well to be reminded that Selmi never suc- 
 ceeded in obtaining alkaloids in sufficient quan- 
 tities for analysis, or to enable him to ascertain 
 their constitution and place in the family of bases 
 already known. It was not until between 1881 
 and 1883 that Armand Gautier and his asso- 
 ciate, M. Etard, first determined their precise 
 analysis. It was then they, for the first time, 
 recognised that of these substances, those that 
 were found in great abundance and consti- 
 tuted the alkaline products of bacterial putre- 
 factive processes in their completion, form two 
 distinct series, the one pyridic, the other hydro- 
 pyridic. At this time there was only one 
 example of the former known. What was 
 more particularly due to Selmi was the nume- 
 rous determinations in the examination of small 
 quantities by reagents of various kinds. It is 
 the determinations of Selmi, Gautier, and 
 others, that we will now proceed to summarise. 
 
28 
 
 Having traced historically the course of 
 investigation followed by various workers in 
 the putrefactive held, the qualities of the pecu- 
 liar alkaline basic products have only been 
 incidentally alluded to, it will now be necessary 
 to complete the examination of their pro- 
 perties. 
 
 The ptomaines are bases solid or liquid, very 
 alkaline and which combine with strong acids, 
 not as the amines, the salts of which are dis- 
 associated by water, do, but in the same man- 
 ner as the powerful metallic bases. They absorb 
 to saturation the strong acids, sometimes attract- 
 ing carbonic acid of the atmosphere. According 
 as they are solid or liquid in their properties, 
 they differ in many respects, so much so that 
 they come under two categories, as in the case 
 of the veget^ible series of alkaloids. The bases 
 of the one class, liquid, volatile, and of an odour, 
 sui generis, contain no oxygen; those of the 
 others are oxygenous, solid, and crystalline. 
 
 The liquid ptomaines possess a virous, cada- 
 veric odour, occasionally suggestive of musk or 
 odoriferous plants. It is possible that between 
 the products of bacterial putrefaction of animal 
 tissues and the perfumes of vegetable cells of 
 flowers, similarity is not altogether accidental. 
 As M. Gautier surmises, the resemblance has 
 
29 
 
 a deeper basis of reality than might at first 
 appear. The Hquid ptomaines are soluble in 
 alcoholic ether. 
 
 The solid ptomaines are white, generally 
 crystalline, very soluble in water, insoluble in 
 liquids such as alcohol, benzine, chloroform, 
 which readily dissolve substances rich in carbon. 
 The solubility of these ptomaines is, however, 
 disturbed by the presence of impurities, and 
 amylic alcohol which dissolves but slightly pure 
 neuridine, for example, on the contrary, dis- 
 solves it in notable quantity when the bases 
 are blended with extractive matters. 
 
 The chemical reactions are common, at least, 
 for the most part to the two categories. All 
 the ptomaines are isolable : they combine with 
 acids ; an excess of acid decomposes them, im- 
 parting at first a rose colour which becomes in 
 precipitation a resinous brown. They all com- 
 bine in a state of chloro-hydrates with chloride 
 of platinum, and form double salts which are 
 more or less crystallisable. An excess of chlo- 
 ride of platinum decomposes them ; decomposi- 
 tion is, however, effected by a great number of 
 reagents ; light of itself effects it. 
 
 In general the ordinary alkaloid reagents 
 precipitate the ptomaines ; the chloride of gold, 
 the double iodides of mercury and potassium, 
 
30 
 
 the iodides of bismuth and potassium, the re- 
 agents of Nessler, Froude, Schultz and Sonnen- 
 schein, picric acid and tannin. The chlorate ot 
 mercury does not always precipitate them, but 
 it frequently combines with the ptomaines to 
 form the crystallisable double chlorides, which 
 Brieger has frequently utilised in his researches 
 in separating the obtained alkaloids one from 
 the other. All the alkaloids are not pre- 
 cipitable by all the enumerated reagents ; 
 only one solitary body acts on all without ex- 
 ception, that is, phosphomolybdic acid. 
 
 Before the isolation of the alkaloids of putre- 
 faction in a pure state had been achieved, the 
 colour reactions which served to indicate their 
 presence, had more importance attached to 
 them than is awarded them to-day. Selmi had 
 ascertained and confirmed the fact, that hydro- 
 chloric and sulphuric acids, simple or combined, 
 developed, especially when heated, a red colour 
 by acting on the bases of putrefaction. When 
 a ptomaine is heated with nitric acid and after- 
 wards saturated with potash, a beautiful yellow 
 colour is developed. 
 
 The ptomaines by virtue of their oxydis- 
 ability ought to act as energetic reducing or 
 decomposing agents in a great number of re- 
 actions. Not only are the chromic and iodic acids 
 
31 
 
 decomposed by them, but so also is the nitrate of 
 silver. Furthermore, the bromide of silver and 
 frequendy the ferricyanide of potassium which, 
 transformed in contact with ptomaines into 
 ferricyanide, gives with the salts of iron the 
 Prussian blue. MM. Brouardel and Boutmy 
 regarded this reaction, first observed by Selmi, 
 as a means at once simple and of general appli- 
 cation in distinguishing the alkaloids of veget- 
 able origin from those of animal putrefactive 
 origin. Unfortunately, many of the vegetable 
 and artificial alkaloids decompose the ferri- 
 cyanide and ferric-chlorides. Gautier has clearly 
 shown that of the alkaloids, there are many that 
 do not decompose the ferricyanide, as anemo- 
 nine, peltierine, sabadelline, &c. ; other alkaloids 
 reduce slowly and feebly, and among them 
 veratrine, igasurine, colchicine, nicotine, eme- 
 tine, hyosciamine and apomorphine. 
 
 Thus we see some of the artificial or natural 
 vegetable alkaloids comport themselves exactly 
 as the ptomaines do by decomposing instanta- 
 neously the melange of ferricyanide of potassium 
 and ferrichloride. This class is numerous, 
 and comprehends among other bodies pyridine, 
 isodipyridine, collidine, naphtylamine, toluidine, 
 diallylene-diamine, morphine, atropine ; also the 
 alkalies acetonic, aldehydic, &c. The reduc- 
 
32 
 
 ing or decomposing power is far from being 
 a characteristic special of, or peculiar to, the 
 ptomaines. Many of them, according to M. 
 Pouchet, do not even possess it at all ; and 
 Brieger affirms that he has never observed- 
 it in the case of the pure oxygenous pto- 
 maines. He attributes the reduction observed 
 by Brouardel and Boutmy to the presence of 
 peptones which vitiate their products. This 
 view is certainly extreme. If we consider the 
 construction of the hydropyridic bases, it is 
 easy to conceive the energy of their reductive 
 action in the process. 
 
 This admitted from all that has been stated, 
 it must frankly be conceded that the reactions 
 of the ptomaines present the closest analogies 
 to those of the vegetable alkaloids ; that the 
 two intimately related classes of bodies possess 
 analogous properties, and that the general re- 
 agent which distinguishes the one group from 
 the other still remains to be discovered. 
 
IV. 
 
 Classification and Definitions. 
 
 The ptomaines are divided into two classes, the 
 non-oxygenous and oxygenous, which may be 
 studied apart. First come the pyridic bases of 
 Gautier, or those ptomaines which, besides 
 being the most abundant, persist throughout the 
 whole of the putrefactive process. 
 
 Non-Oxygenous Alkaloids. 
 
 Parvoline OH'^N. — This was the first 
 ptomaine chemically analysed and defined. It 
 was discovered by MM. Gautier and Etard in 
 the putrefactive products of the mackerel and 
 horse flesh, by means of the ordinary method 
 and operating on the chloroform extracts. It is 
 described by them as an oily base of an amber 
 colour and May odour, boiling a little below 
 200° C., slightly soluble in water, very soluble in 
 alcohol, ether and chloroform ; it resinifies 
 readily on exposure to the air. Its chloroaurate 
 3 
 
•34 
 
 is soluble, its chloroplatinate is little soluble, 
 it crystallises in flesh colour, intensifying on 
 exposure. 
 
 In heating to 200° C. in a closed tube the 
 crude product of the reaction of ammonia on 
 propionic aldehyde, Waage has obtained a base 
 C^H'^N, boiling at 193° to 196° C, and which 
 has the closest resemblance to the parvoline 
 of putrefaction. 
 
 Hydro-Collidine C^H'^N. — This base has 
 also been obtained from the putrefactive pro- 
 ducts of the mackerel and horse, and even ox 
 flesh. It is an almost cloudless liquid of 
 slightly oleaginous consistence, of a seringous 
 odour, boiling at 210° C. without alteration of 
 density, which at zero C. is equal to 1.0296. 
 It oxydizes on exposure, becoming viscous 
 and dark in colour ; it fixes the carbonic acid 
 of the atmosphere. 
 
 The chloride of gold forms with the hydro- 
 collidine a chloride very soluble but unstable 
 which decomposes readily when cold. The 
 instability of the double salts of the hydro- 
 pyridic bases is characteristic of this. MM. 
 Cahours and Etard, however, treating nicotine 
 with selenium, have obtained a dihydro-colli- 
 dine of C'H^^N, boiling at 210° C. On the 
 other hand, Gilchsner de Connick, in treating 
 
35 
 
 in a closed vessel with phosphorus and hydro- 
 iodic acid, the collidine which he had discovered 
 in products resulting from the action of potash 
 on cinchonine and brucine, has accomplished 
 the synthesis of a dihydrocollidine presenting 
 close affinities with the base of MM. Gautier 
 and Etard. 
 
 The ptomaine hydrocollidine is very poison- 
 ous, even in very small quantities. 
 
 Base C'^Hssn^. — The mother liquors of the 
 platinichlorides of the presiding bases are 
 capable on concentration of yielding flesh- 
 coloured crystals decomposible at loo' C. with 
 distinctly flowery odours. The analysis which 
 MM. Gautier and Etard have made of this 
 chloroplatinate enables them to establish the 
 formula (C^7H3^N^2HC1) PtCZ. 
 
 Base C'°H'5N. — This ptomaine was dis- 
 covered in 1883, by Guareschi and Mosso, 
 who isolated it by the Gautier- Etard method 
 from the putrid febrine of the bullock. And so 
 late as 1886, it has also been detected among 
 the basic products arising from the putrefaction 
 of the cephalopode pulps common to the shore 
 of the Mediterranean. This base is very alka- 
 line, of pyridic odour, little soluble in water, 
 and readily resinifiable. It is precipitated 
 by chloride of gold, chloride of platinum and 
 
36 
 
 corrosive sublimate, tannin, picric, phospho- 
 tungestic, and phosphomolybdic acids ; with the 
 ferricyanide of potassium and the salts of iron it 
 furnishes prussian blue. 
 
 This ptomaine is probably a pyridic base, 
 perhaps a new corindine, according to CEchsner 
 de Connick, the superior homologue of the 
 parvoline of MM. Gautier and Etard. 
 
 CoLLiDiNE C^H"N. — Was extracted by 
 Nencki, in 1876, from the putrefactive pro- 
 ducts of 600 grms. of gelatine and 200 grms. 
 of bullock pancreas to 10 litres of water. The 
 discoverer has not identified it with the collidine 
 of Anderson, the synthesis of which Baeyer and 
 Ador accomplished by heating the aldehydrate 
 of ammonia to 120° C, in contact with urea. 
 Nencki considered that ptomaine as an iso- 
 phenylethylamine. 
 
 OH^—CHC 
 
 Seemingly, however, this base only arises 
 under the conditions Nencki has indicated. If 
 the gelatine is allowed to putrefy without the 
 previous addition of pancreatic tissue, according 
 to Brieger no trace of collidine is to be found. 
 
 Neuridine C^H'^^N". — This base is one of 
 the most constemt products of the putrefaction 
 
37 
 
 of albumenoid substance. The ptomaine was 
 discovered in 1884 by Brieger, who has since 
 detected it in the putrescent matters of flesh, 
 fish, decaying cheese, &c. From the organic 
 structures of the human body, it has also been 
 obtained by his method already described. This 
 base is only known in the form of a salt, or in 
 combination with the chlorides of gold or plati- 
 num. If we try to isolate it from its chloro- 
 hydric combination by the aid of the moist 
 oxyde of silver, a gelatinous amalgam is ob- 
 tained which readily decomposes. 
 
 The salts of neuridine, the chlorides of gold 
 and platinum in particular, are well crystallized. 
 The chlorohydrate is precipitated by phospho- 
 tungestic, phosphomolybdic, picric acids, by the 
 reagents of Schultz, the double iodides of bis- 
 muth and potassium. 
 
 Soda in solution breaks up the chlorohydrate 
 of neuridine into a melange of dimethylamine 
 and of trimethylamine. 
 
 Chemically pure neuridine is not toxic. 
 
 Cadaverine C^H'^N^ — In bodies subjected 
 to prolonged putrefaction, Brieger has met with 
 a base very difficult of purification, and to 
 which he has given the name of cadaverine. 
 Bcecklisch has separated it from herring brine, 
 and quite recently — 1884 — the alkaloid has 
 been detected in marine cephalode pulp. 
 
38 
 
 It is a colourless liquid somewhat viscous, 
 boiling at 115° to 128° C, and of the disagree- 
 able odour of the conicine character. It 
 absorbs anhydride carbonic, and forms with the 
 acid definitely crystallized salts insoluble in 
 ether and alcohol. In contact with this base, 
 the melange of ferricyanide and ferrichloride 
 gives feebly the bluish tint ; ordinary alkaline 
 reagents precipitate the ptomaine. Heated with 
 potash and chloroform, cadaverine does not give 
 carbylamine. Dissolved in methylated spirit, it 
 fixes the iodide of methyl and gives a hy- 
 driodate of dimethylcadaverine C^H'^ (CH^)^ 
 N'2HI. Cadaverine gives with the chloride 
 of gold a double salt, and with chloride of plati- 
 num a chloroplatinate bright red orthorombic 
 crystals. The ptomaine is not toxic. 
 
 PuTRESCiNE C^H'^N^ — Like the preceding 
 ptomaines is obtained from the flesh of the 
 mammifera and herring brines. It is a limpid, 
 slightly oily liquid, the odour of which resem- 
 bles that of sperm and reminds us of the pyridic 
 bases. It boils at 135° C, and with difficulty 
 evaporates with the water. The very powerful 
 base presents the reactions of the vegetable 
 alkaloids, attracts the anhydride carbonic from 
 the atmosphere, and gives with the acid salts in 
 well defined crystals. Its bright microscopic 
 
39 
 
 crystalline pellets are little soluble in water, and 
 much resemble cholestrine. 
 
 The chlorohydrate of putrescine gives with 
 nitrate of potash a denitrilized derivative, 
 which may perhaps permit putrescine be- 
 ing regarded as an ethylenedemethyldiamine 
 
 NH.CH3 
 NH.CH3 
 
 Putrescine is not toxic. 
 
 Mydaleine. — Inthemotherliquorsfrom which 
 the preceding bases have been isolated owing 
 to the varying solubility of their chloroplatinate 
 there remains a toxic alkaloid which has also 
 been isolated, but in too small quantities to 
 permit of its complete study. The analysis of 
 it is suggestive of a diamine similar to those we 
 have been dealing with. 
 
 The action of mydaleine on the animal 
 economy is very interesting, as will be seen 
 when we come to treat of the physiological 
 properties of the ptomaines in general. 
 
 Oxygenous Alkaloids= 
 
 These bases serve as the connecting link 
 between the ptomaines and the leucomaines. 
 With the exception of gadinine they are to be 
 
40 
 
 met with in the normal tissues as well as in 
 putrescent animal materials. 
 
 (CH3)3 
 
 Neurine 0H"N (0H)= \N— oh. 
 
 Hydrate of trimethylvinylammonium. 
 
 It is known that the breaking up of a com- 
 plex compound with a watery solution of baryta, 
 the lecithine present in the animal economy, 
 by taking up or fixing the water, furnishes 
 besides phosphoglyceric and stearic acids, and a 
 base choline C^H'^NO^ the synthesis of which 
 Wurtz effected in treating trimethylamine with 
 oxyde of ethylene in the presence of water 
 
 CH* (CH3)3 ^ 
 
 This synthesis characterises choline as the 
 hydrate of trimethylhydroxethylene-ammonium. 
 Treated with hydriodic acid choline is converted 
 into an iodide of iodethylene-trimthylammonium 
 
 (CH3)3 (CH3)3 
 
 The oxyde of silver transforms this latter 
 body into a new base neurine which is a hydrate 
 of trimethylvinylammonium. 
 
41 
 
 (CH^^ (CH3)3^ 
 
 This is the neurine that has been met with 
 by Brieger in the products of cadaveric putre- 
 faction, when it arises from the breaking up of 
 lecithine. It is a syrupy base soluble in water 
 in any proportion, strongly alkaline ; its chloro- 
 platinate well crystallized may be removed from 
 the mother liquors of the neuridine. This base 
 is toxically interesting. 
 
 (CH3)3 
 
 Choline. C^H'^NO"^ OH 
 
 Hydrate of trimethylhydroxethylenine-ammo- 
 nium. 
 
 It is Strieker who has isolated this body from 
 the bile. It is distinguished from neurine by 
 the composition and formula of constitution as 
 given above. The choline is a base which is 
 elaborated both during normal life of the 
 tissues, and during their bacterial destruction, 
 and is, therefore, both ptomaine and leuco- 
 maine. Brieger has isolated it by crystallizing 
 in the form of picrate of choline in the mother 
 liquors from which he derives the neurine. 
 
 Choline is a syrupy liquid soluble in water, 
 
42 
 
 very alkaline, which unites with acids giving 
 salts in well defined crystals. The chloropla- 
 tinate being less soluble in water than the salts, 
 than the corresponding salts of neurine, this 
 property indicates the method of separating the 
 two bases so similar and so often blended to- 
 gether. Heat splits up choline into glycol and 
 trimethlamine OH^3NO=eH'03 + (CH3)3N ; 
 is that doubtless which explains the presence 
 of trimethylamine in the products of a great 
 number of putrefactions. 
 
 The ordinary alkaline reagents precipitate 
 both choline and neuridine. They do not reduce 
 the ferricyanide and ferrichlorides. 
 
 Choline is less toxic than the neurine. 
 
 Muscarine C^H'^NO' was discovered by 
 Schmiedberg and Koppe in the toadstool, — ■ 
 agaricus rnuscaritts. Schmiedberg and Har- 
 nack have accomplished its synthesis by oxy- 
 dizing choline with nitric acid ; this permits 
 muscarine to be regarded as an aldehydic 
 alkaloid. 
 
 (CH3)3 
 
 Brieger has isolated it along with ethylene- 
 diamine in putrid fish meat. Muscarine is 
 
43 
 
 found present in the mother Hquors, in which 
 the chloride of platinum has precipitated the 
 ethylene-diamine. 
 
 The muscarine is a solid crystalline deliques- 
 cent substance, which plays the role of a power- 
 ful base, attracts carbonic acid gas from the 
 atmosphere and is precipitated by the ordinary 
 alkaloid reagents, and gives with the choloride of 
 platinum and chloride of gold crystalline com- 
 pounds. Its aldehydic constitution explains, as 
 Professor Gautier has shown, why it reduces 
 the melange of ferricyanide, ferrichloride. 
 
 Muscarine is a violent poison. 
 
 Gadinine C^H'^NO^ — Brieger obtains this 
 body at the same time and along with the pre- 
 ceding base from the cod-fish — gadiis callarius — 
 in process of putrefaction. This alkaloid has 
 not been isolated in a free state. The chloro- 
 hydrate of gadinine crystallizes in colourless 
 needle-shaped prisms, is soluble in water, in- 
 soluble in alcohol, and does -not combine with 
 chloride of gold, but gives with the chloride 
 of platinum a yellow chloroplatinate. It is to 
 be remarked that the base only differs by addi- 
 tional H, from the composition of an aminoae- 
 nanthylic acid. 
 
 Its salts are not toxic. 
 
 Bases C^^^N^O^ and C^H^^N^O^.— M. G, 
 
44 
 
 Pouchet has published since 1880, quite a 
 series of interesting works on the ptomaines. 
 He endeavours to isolate by a somewhat similar 
 method to that of Stas and Dragendorff, the alka- 
 loids of the residuary liquors resulting from its 
 industrial treatment of bones, flesh and ddbris 
 of every kind, by dilute sulphuric acid. He 
 has been enabled in this manner to extract 
 from the material two alkaloids, which the un- 
 equal solubility of their chloroplatinates in alco- 
 hol admits of being separated. 
 
 The base OH^^N^O' is formed of thick short 
 prisms very readily alterable. The alkaloid 
 C^H'^N^O^ is needle-shaped, arranged in pencil 
 form, and appears to alter even less readily. 
 
 The ordinary alkaloid reagents precipitate 
 these two ptomaines. The precipitate obtained 
 by phosphomolybdate of sodium is reduced, 
 and in presence of ammonia gives the blue tint. 
 It is known that aconitine presents the same 
 reaction. 
 
 These two bases are toxic. 
 
 In the course of his researches, Brieger has 
 detected other alkaloids less defined or simply 
 indicated, but which are now receiving his 
 careful study. Nothing more need be said of 
 them until investigations are complete. The 
 same applies to those ptomaine extracts, and 
 
45 
 
 the various impurities of cadaveric putrefaction 
 characterised only by colour reactions and some 
 physiological properties. 
 
V. 
 
 Physiological Actions. 
 
 If the toxic actions of the alkaloids of putre- 
 faction remain to be considered, it must be 
 without pretention to completeness or precision ; 
 the present position of their history does not 
 permit of that. It may be affirmed that some are 
 powerfully energetic, others almost inert. In 
 general terms, they must be accepted as poison- 
 ous, and their mode of action on the animal 
 economy much the same as that of the hydro- 
 pyridic bases. Their effects, however, while 
 presenting certain characters in common, vary 
 according to their class or group. Consequently 
 the physiological actions of the ptomaines 
 supplement the chemical history, and form an 
 introduction to their medical toxicology. 
 
 The difficulty of isolating them in quantity 
 sufficient for the separated study of their effects 
 physiologically, has made it necessary to em- 
 ploy the ethereal, chloroformic and alcoholic 
 extracts for this purpose. By converting these 
 
47 
 
 into chlorohydrates, sulphates, &c., salts more or 
 less impure, their actions and effects have been 
 carefully observed. Sensibly, the free ptomaines 
 smell virous or cadaveric. When free from oxy- 
 gen they have a virous odour similar to that of 
 conicine or pyridine, sometimes aromatic and 
 agreeable resembling musk, orange flower or 
 Camilla, &c. They are bitter to the taste, and for 
 the most part piquant, benumbing the tongue 
 and palate, and give rise to a sense of constric- 
 tion of the throat. 
 
 The memoirs of Gautier and Corona will 
 perhaps supply the most instructive illustrations 
 as regards such properties. Let us cite the 
 series of experiments undertaken with pto- 
 maines, derived from a dead body exhumed 
 four months after interment. 
 
 Ptomaines Extracted by Ether. — One 
 gramme of the aqueous solution injected into 
 the skin of a dog of medium size induced, after 
 twenty minutes, irregular contraction of the 
 pupil, convulsive tremblings, increased heart's 
 action, congestion of the external ear, slight 
 increase of temperature ; the animal became 
 languid. Forty minutes after injection, there 
 appeared spasmodic action of the facial muscles 
 and limbs, diminished respiration ; death in 
 forty-four minutes. On opening, the thorax 
 
48 
 
 showed immobility of the auricles, irregular 
 contraction of the left ventricle, right side filled 
 with blood, left side empty. 
 
 Observations on the frog were somewhat 
 similar. 
 
 Ptomaines Extracted by Chloroform. — 
 The hydro-alcoholic solution of the alkaloid 
 was injected hypodermically into a dog of 
 medium size. Almost immediately respiration 
 rose to loo and 134 a minute, heart's action 
 increased with heat and congestion of ear 
 helices, normal state recovered in about twenty 
 minutes. The effects on the frog were slight 
 agitation, flaccidity of the muscles and loss of 
 motor power under galvanic current, nervous 
 sensibility maintained, but no contractility eli- 
 cited when the electroid was not in direct con- 
 tact with the muscle or muscles themselves. 
 
 Ptomaines Extracted by Alcohol. — Sub- 
 cutaneous injection induced in the case of the 
 frog confused movements, irregular dilatation of 
 the pupil, loss of cutaneous sensibility, followed 
 with general muscular relaxation. 
 
 From these experiments, and others too 
 numerous to mention, these authorities con- 
 clude as follows : — The cadaveric alkaloids are 
 in general venomous to a high degree. The 
 free ptomaines are more energetic than their 
 
49 
 
 salts, those that are soluble in silver more par- 
 ticularly. On frogs the principal phenomena 
 observed are as follows : — I. Dilatation of the 
 pupil followed with contraction ; II. Tetanic 
 convulsions followed with muscular flaccidity ; 
 III. Diminished respiration and increased heart's 
 action ; IV. Total loss of cutaneous sensibility. 
 
 On the dog the phenomena observed are : 
 I. Irregular contraction of the pupil passing to 
 contraction ; II. Marked heat and injection of 
 the ear helices from paralysis of vaso-motor ; 
 III. Diminished respiration ; IV. Somnolence 
 soon followed by convulsions and death ; V. Loss 
 of muscular contractility to electric stimulus. 
 
 In these experiments the loss of muscular 
 contractility, even in the presence of the 
 electric stimulation, is very remarkable. The 
 peculiarity associates the ptomaines with the 
 poisonous alkaloids of the mushrooms and with 
 the muscarine in particular, which Brieger has 
 since detected in certain putrefactions. This 
 fact M. Gautier observed earlier than Selmi, 
 Corona or Brieger. Corona, on the contrary, 
 differentiated the ptomaines from some other 
 alkaloids, for example, the curara, which leaves 
 the muscle its contractility under the influence 
 of the electric current, or sulpho-cyanide of 
 potassium, which, it is true, destroys the con- 
 
 4 
 
• 50 
 
 tractile property in the presence of electric 
 stimulation, but leaves it not flaccid, but in 
 spasmodic tension. 
 
 Two experiments of Gautier made with the 
 base, not altogether pure, answering to the 
 formula C^H'^N — hydrocollidine — are interest- 
 ing to note. 
 
 First, 0.007 g™e. quantity injected under the 
 skin, beneath the wing of a small bird. In two 
 minutes ruffling of the plumage and vomiting 
 were excited, followed with loss of motor co- 
 ordination, paralysis, convulsions and death 
 in fifty minutes after injection. 
 
 Second injected under the skin of small bird 
 of the same species, 0.0017 grme. of same base, 
 but purer in quality. In two minutes, creature 
 loses co-ordinating power, turns over on its side, 
 flutters, unable to recover balance, paralysis 
 increases with loss of sensibility, death in fifty 
 minutes after injection. 
 
 According to M. Gautier's experiments on 
 the action of snake poisons, this base would 
 seem to be almost as powerful as the venom of 
 the corbi^a di capella. He has shown that a 
 milligramme of that virus kills a sparrow in 
 about sixty minutes ; as in the preceding in- 
 stance, there is paralysis of the posterior tract, 
 immobility ; but with the cobra venom we 
 
5i" 
 
 observe the panting, violent agitation, and after 
 death heart at systole and free of blood. 
 
 We have seen that the ptomaines of M. 
 Pouchet are oxygenous. Their action on ani- 
 mals has been studied much more closely than 
 that of the preceding bases. The two alkaloids 
 which he has studied are energetically toxic on 
 frogs, killing them rapidly, and producing torpor 
 and muscular paralysis, with abolition of the 
 reflexes ; after death heart at systole. 
 
 Several of Briegers bases are also toxic. 
 They have been so characterised, but the effect 
 which they gave rise to are but little known. 
 Mydaleine excites profuse diarrhoea, vomiting, 
 intestinal inflammation ; the heart after death 
 at diastole. One of the bases, we have said, is 
 identical with muscarine. Neurine itself is very 
 toxic ; a few milligrammes suffice to kill a cat. 
 It excites abundant secretions, diarrhoea, accele- 
 rating respiration and convulsion before death. 
 
VI. 
 
 Medico-Legal Import 
 
 Toxicology brings us in contact with the prac- 
 tical side of ptomaine investigation, that on 
 which its greatest value depends. Though 
 researches are numerous and the literature of 
 the subject considerable, it must be confessed it 
 yet leaves much to be desired. Investigations 
 still in progress, and others incomplete, obscure 
 the subject, and if they do not disarm the 
 medicolegist, render correct differentiation at 
 once delicate and difficult. 
 
 In the introductory historical notice, refer- 
 ence has been made to the impetus given to 
 this phase of the subject, by the evidence of 
 Selmi in Italy and Otto in Germany, in two 
 celebrated cases of criminal poisoning. Enabled 
 by previous researches to detect the presence 
 of ptomaine alkaloids in both instances, these 
 eminent toxicologists contested the conclusions 
 of the experts for the prosecution with com- 
 plete success. Scientific attention being much 
 
53 
 
 excited by these facts, numerous publica- 
 tions under various titles appeared ; researches, 
 colour reactions, physiological and chemical 
 properties, &c., all relating to cadaveric extracts 
 whose chemical compositions v/ere as yet un- 
 known or ill-defined. As a great portion of 
 these data must, therefore, be treated with cau- 
 tion and reserve, we select a few of the most 
 reliable results, beginning with the analyses of 
 experts, who have found themselves in the pre- 
 sence of organic alkaline bases, which they were 
 unable to identify with any known alkaloids. 
 
 In the examination of putrid bodies of sub- 
 jects, who were known to have died from natural 
 causes, Selmi succeeded in extracting by ether 
 from aqueous alkaline solutions, an alkaloid 
 which the chloride of mercury precipitated in 
 white ; sulphuric acid coloured it violet ; a 
 melange of sulphuric acid and dichromate 
 gave a greenish and phosphomolybdic acid a 
 bluish tint. The base reduced iodic acid, and 
 was precipitated by the chloride of gold. In 
 following the same method, but in employing 
 other solvents, Selmi succeeded in isolating 
 other substances which were only definable in 
 his hand by colour reactions. 
 
 In the course of another medico-legal exa- 
 mination, Lieberman obtained from the stomach 
 of a subject in a state of putrefaction, by 
 
54 
 
 the Stas-Otto method, a substance similar to 
 conicine, but differing from this base in two 
 properties — it was neither volatile nor toxic ; 
 that cadaveric conicine was precipitated in 
 white by tannin, in brown by iodized iodide of 
 potassium, in yellow by phosphomolybdic acid, 
 and again in white by aqueous solution of 
 chlorine and the perchloride of mercury. 
 
 Van Gelder, another medico-legal expert, has 
 extracted from various portions of a dead body, 
 which contained arsenic, a brownish residue 
 which chlorine solution, Meyer's test, perchloride 
 of mercury and tannin precipitated in white, the 
 chloride of gold and platinum in yellow. 
 
 In 1880, Spica published an interesting 
 observation which deserves attention. Called 
 upon to examine the liquid taken from the 
 dead body of a woman, the subject of extra- 
 uterine foetation, he applied the method of 
 Dragendorff. Exhausting the residue of his 
 operation with the solvents ordinarily em- 
 ployed, Spica obtained with the aid of chloro- 
 form an amorphous base, probably impure, 
 which gave with the iodized iodide of potassium 
 a red precipitate soluble in excess of the re- 
 agents, with a chromic melange a yellow pre- 
 cipitate, which finally became green ; with the 
 test of Meyer a white cheesy precipitate was 
 
55 
 
 given. That alkaloid, when injected into the 
 subcellular tissue of a frog, induced dilatation 
 of the pupil and increased respiratory action, 
 and death in forty minutes. 
 
 The same year, 1880, Gianetti and Corona 
 were commissioned to seek for poison in the 
 body of a young man. They obtained by ex- 
 hausting with various solvents the residuum 
 furnished by the Stas-Otto method, a quantity 
 of alkaloid material. They isolated roughly 
 several ptomaines of different odours, which 
 bases were very alkaline, and gave with the 
 solution of iodine in hydriodic acid, a brownish 
 precipitate, with the chloride of platinum a pre- 
 cipitate of a cannella colour ; their chlorides 
 underwent reduction when cold, converting into 
 Prussian blue the ferricyanide of iron. 
 
 The toxic action of these ptomaines pre- 
 sented the phenomena frequently observed in 
 similar instances. In injecting them hypo- 
 dermically, they determined pupilar dilatation, 
 followed with contraction, convulsions controlled 
 the heart's action, and after a little complete loss 
 of cutaneous sensibility followed. 
 
 To Brouardel and Boutmy we are indebted 
 for the following observations on a body eigh- 
 teen months in water. In this instance, by 
 Stas's method fixed alkaloids were detected that 
 
56 
 
 responded to the various tests — Meyer s to be- 
 gin with — precipitating with potash, reddening 
 with sulphuric acid and ferri-oxyde of baryum, 
 colouring to brick red when cold, violet when 
 hot ; the base gave prussian blue with ferri- 
 cyanide of potassium and the salts of iron. Its 
 toxic action resembled that of veratrine. In 
 another instance, but under different circum- 
 stances — the subject having died asphyxiated 
 with carbonic-oxyde was preserved for several 
 days at a low temperature — no traces of alkaloid 
 were to be detected. By increasing the tem- 
 perature putrefaction thoroughly declared itself, 
 when a fresh examination proved perfectly suc- 
 cessful. An alkaloid was then met with which 
 sulphuric acid coloured brown and Meyer's test 
 precipitated. Again the same toxicologists had 
 an opportunity of carrying out ptomaine re- 
 searches in the debris of a stuffed goose too 
 long kept, which poisoned some dozen per- 
 sons, with fatal effect on one. The organs of 
 this victim being likewise submitted to exa- 
 mination by the experts they were enabled to 
 extract an alkaloid liquid that smelled of mice- 
 piss, and whose reactions were characteristic 
 of the alkaline bases of vegetable origin, of 
 conicine in particular. Such examples might 
 be multiplied, but no more are required to 
 
57 
 
 strengthen the following legitimate conclusions. 
 Firstly, that in the bodies of persons who have 
 died a natural death, the methods of Stas and 
 Dragendorff were capable of detecting the 
 presence of toxic alkaline compounds possess- 
 ing properties resembling those of the well- 
 known vegetable alkaloids. Secondly, that the 
 quantity of those alkaloids becomes the more 
 appreciable as the process of decomposition 
 advances. 
 
 In the aforementioned examples from ex- 
 perts, we have intentionally avoided giving 
 conclusions or noting reactions on which might 
 be based a differentiation of ptomaines and 
 alkaloids that might have been criminally in- 
 troduced during life. The question now comes, 
 is this possible ? Is there any general reliable 
 and positive procedure applicable in all cases ; 
 or must we, on the contrary, have recourse to 
 special chemical and physiological reactions ? 
 In other words, has the discovery of the alka- 
 loids of putrefaction outrun the current medico- 
 legal resources and criteria ? 
 
 The question is most important, and it was 
 with a view to its solution that the Italian com- 
 mission of 1880, under the presidency of Selmi, 
 and after his death under that of Canizzaro, 
 was issued. In his voluminous reports Marino 
 
58 
 
 Zicco, who contributed so industriously, attri- 
 buted to neurine and choline alone the chemical 
 and physiological reaction with which the 
 ptomaines were being credited ; he also attri- 
 buted the origin of neurine to the splitting up 
 of lecithine from the action of the sulphuric 
 acid used in researches by the Dragendorff 
 method. This point, among others, the labours 
 of Gautier and Etard conclusively disposed of 
 Nevertheless, the labours of the commission 
 furnished data of much value in elucidation of 
 the points submitted for solution. 
 
 As has already been stated in dealing with 
 the chemical characters of the alkaloids, the 
 reducing action of the ptomaines on the ferri- 
 cyanide of potassium in the presence of the 
 ferric salts and the resultant prussian blue, 
 has not the general characteristic application 
 that either Brouardel or Boutmy had at first 
 awarded to it. M. Gautier has clearly shown that 
 that reaction is not peculiar to the putrefactive 
 alkaloids ; according to Pouchet and Brieger 
 a certain number of ptomaines do not give even 
 an indication of it. 
 
 M. Hugounenq of Lyons, who has so clearly 
 and concisely resumed the medico-legal di- 
 lemma, notices the complex reagent which 
 Wefers, Bettenk and Van Dessel have recently 
 
59 
 
 proposed. This is a combination of hydro- 
 chloric acid, chloride of iron, chromic anhydride, 
 and ferricyanide of iron. This, it was alleged, 
 gave Prussian blue with all the ptomaines, 
 while morphine alone of the vegetable alkaloids 
 was capable of yielding it. Brieger, however, 
 was unable to verify this reaction in the case 
 of any of the alkaloids discovered by him. 
 There is, then, no common method by which 
 in every case any given vegetable alkaloid can 
 be distinguished from any given ptomaine. A 
 particular alkaloid, however, may be distin- 
 guished from a ptomaine by a series of par- 
 ticular features. As they are of the utmost 
 importance, we refer those practically engaged 
 upon the subject to M. Gau tier's contributions ; 
 their consideration forms an invaluable page of 
 his masterly mdmoire ; from the nature of the 
 present study what is required of us is merely 
 to indicate them. 
 
 As may be known, the object of the Italian 
 Ptomaine Commission was not so much the 
 investigation of the nature and existence of 
 these alkaloids, as determining whether medico- 
 legally their presence might give rise to gross 
 miscarriage of justice from expert misappre- 
 hension. As those bases, fixed or volatile, of 
 cadaveric meiterials might be readily confounded 
 
6o 
 
 with other toxic alkaloids, animal or vegetable, it 
 was necessary to avert judicial error, and also 
 to determine those ptomaines which some in- 
 sisted on identifying with bases already known, 
 more particularly with neurine. Selmi vvas the 
 first to give warning, noting at the same time 
 the difference between that alkaloid — -though 
 admittedly impure, detected as pyridic by M. 
 Gautier — and conicine. If Marino Zicco did 
 not do this, he showed by his researches that 
 alkaloids of putrefaction were always minute in 
 quantity, that it was possible to distinguish 
 those ptomaines from a great number of vege- 
 table alkaloids when introduced in the system 
 during life, and that ptomaines, and particu- 
 larly neurine, in the impure state, are soluble 
 in amylic alcohol, chloroform, and benzine, 
 whilst in the pure state these solvents do not 
 affect or take them up. What is then required 
 in proving a ptomaine is to ascertain whether 
 such bases lose their primary solubility in the 
 process of putrefaction. It remains to be 
 seen whether this character is exceptional or 
 absolute. However this may be, the Italian 
 Ptomaine Commission creditably attacked a 
 problem which another similar effort may 
 perhaps successfully accomplish. 
 
 Profiting by criteria physiological action may 
 
6i 
 
 afford, there is the fact that Lieberman and 
 other toxicologists have in several instances 
 obtained from dead bodies an alkaloid closely 
 allied both in constitution and properties with 
 conicine ; that ptomaine, however, differs in two 
 respects so markedly as to show an absolute 
 distinction : it is neither volatile nor venomous. 
 During the examination of the body just alluded 
 to, which had been eighteen months in the water, 
 Brouardel and Boutmy met with an alkaloid, 
 blueing test paper, precipitating with Meyer's 
 test, giving with potash a flocculent precipitate, 
 a violet colour with nitric acid at 60". That 
 alkaloid at first might have readily been con- 
 founded with morphine, cadine, brucine, atro- 
 pine, or veratrine. The similarity to that latter 
 base continued to accompany it through a 
 certain number of reactions. A melange of 
 sulphuric acid and binoxyde of baryum turned 
 the ptomaine to a brick-red colour when cold, 
 to violet when hot, hydrochloric acid concen- 
 trated, and boiling developed a cherry hue. 
 Like the preceding tests the physiological 
 effects of the ptomaine seemed to belong espe- 
 cially to veratrine ; but whilst the vegeto-vera- 
 trine does not reduce the ferricyanide, the 
 cadaveric base of the drowned subject gave 
 immediately the prussian blue in the presence 
 of the ferricyanide and perchloride of iron. 
 
62 
 
 This instance might suffice to show the 
 liability to serious errors, when those intrusted 
 with an examination are either ignorant of the 
 subject of ptomaines or fail to duly exercise 
 the means of distinguishing the vegeto-alkaloid, 
 where every care is requisite in conclusions so 
 delicate and grave. 
 
 M. Hugounenq holds that an observation so 
 decisive confirms the possibility of distinguish- 
 ing, even in examinations the most difficult, a 
 vegetable alkaloid introduced into the system 
 during life from the ptomaine cadaveric alka- 
 loids developed after death ; that by submitting 
 the alkaloid extracts to all the tests which dif- 
 ferentiate them it is possible to succeed in 
 distinguishing the one from the other those 
 products which were liable to be confounded 
 before the labours of Gautier, Etard and 
 Brieger fixed the ptomaines in the organic 
 series with well-defined chemical characters. 
 
The Vital Alkaloids 
 
 OR 
 
 Leucomaines. 
 
 PART II. 
 
It is sometimes less difficult to make a dis- 
 covery than it is to comprehend its significance 
 or what it naturally leads on to. Before the 
 publication of Armand Gautier's remarkable 
 mdmoire, based on researches and deductions 
 the most complete, evidences as to the exist- 
 ence of a suspected function in animal physi- 
 ology were not wanting had they been read 
 aright. Singularly enough, no attempt was 
 made to read them. Though alkaline bases 
 had been detected in animal tissues, no one 
 had summarized the discoveries, or thought of 
 generalizing results. But this could not con- 
 tinue, and to Armand Gautier is due the 
 merit of overthrowing the artificial barriers, 
 which theoretic preconceptions had hitherto 
 recognised as separating the physiological 
 phenomena of the animal and vegetable 
 kingdoms, and in attributing exclusively to the 
 tissues of the latter, the power of elaborating 
 alkaloids. 
 
 This capacity of the economy in this function 
 5 
 
66 
 
 was not even suspected. Liebig and Petten- 
 kofer had long made known the existence of 
 kreatinine in urines ; this was the first body of 
 animal origin acknowledged as possessing 
 properties clearly alkaloid. It was known that 
 kreatine detected in animal tissues along with 
 kreatinine resulted from that latter substance 
 dishydrating in contact with salts, acids, or 
 heat ; but its presence and production was 
 thought to be explicable by the processes 
 involved. As for the kreatine itself, Liebig 
 declared that it did not possess any of the 
 properties which characterised organic bases. 
 Such was the influence of false theory on minds 
 the least prejudiced. Then, as largely still, it 
 was taken for granted that animal organisms 
 supplied no other nitrogenous substances than 
 those of the nature of amides, unless it were 
 methylamine and trimethylamine. 
 
 It was not till twenty years later Liebreich 
 detected the presence of the already known 
 vegetable alkaloid betaine in normal urine. 
 And it is only so recently as 1880 that Pou- 
 chet, as the result of long-continued and care- 
 ful examination of the human urine announced, 
 besides the presence of allantoine, since re- 
 garded by Meyer as a uride, karnine and an 
 alkaloid in well-defined chlorate crystals. An- 
 
67 
 
 alyses were incomplete, but the following year 
 Gautier confirmed the fact, that Pouchet's 
 alkaloid possessed the general properties of 
 a ptomaine, and thus was indirectly led to 
 the study of this new class of alkaloids, 
 the product physiologically of animals during 
 life. This preliminary advance was strength- 
 ened by Bouchard in 1882, when he disclosed 
 the fact, that not only were alkaloids present 
 in appreciable quantity in normal urines, but 
 that they augmented notably in the course of 
 certain maladies, in typhoid fever for instance. 
 Lepine and Guerin have since found that this 
 applies to a still wider pathological area. Again, 
 Lepine and Aubert, generalising facts acquired, 
 concluded that in the course of certain maladies 
 these poisonous products of the urinary secre- 
 tion notably increase in quantity until the crisis 
 is reached, when they finally diminish. 
 
 To return to 1880, Gautier having satisfied 
 himself that the urinary alkaloid obtained by 
 Pouchet really belonged to the order of pto- 
 maines, directed his investigations with a view 
 to ascertain whether the normal secretions, of 
 certain animals, notoriously toxic, might not 
 owe their activity to substances of a similar 
 nature and origin. By carefully operating on 
 the glands of snakes, he was enabled to elimi- 
 
68 
 
 nate materials unquestionably of the alkaloid 
 order. From the naja tripudians — cobra di 
 capello — in particular, two new substances were 
 obtained by him, and evidently of the nature 
 of ptomaines. From the salivas of the reptilia 
 to that of man was but a step. In the same 
 year Gautier, subjecting this human secretion 
 to examination, succeeded in isolating various 
 toxic elements in sufficient quantity to note 
 its action. Though the products in both in- 
 stances responded to the reagents of Meyer 
 and Nessler, and induced characteristic physi- 
 ological effects on the nervous and digestive 
 systems of smaller animals and birds, it is more 
 than doubtful if they constitute the direful ele- 
 ment of salivary venoms. 
 
 But these were not the first essays in this di- 
 rection. As early as 1852, Cloez, from exami- 
 nation in both reptiles and batrachians, had 
 made known similar results, which Zalesky 
 afterwards confirmed ; in 1874, Meisher and 
 Picard were even so successful, with one alkaloid 
 at least, as to give us both its formula and name 
 — Protomaine. 
 
 Facts such as these ought to have impressed 
 inquiring minds, but prevailing views did not 
 permit it. The presence of alkaloids in the 
 secretions was either doubted or allowed to pass 
 
69 
 
 unheeded. Gautier, as we have seen, was not 
 disposed to halt. That eminent professor felt 
 convinced of the pharmaceutic powers of the 
 animal organism in the elaboration of alkaloids, 
 and clearly set forth his views in a mdmoire 
 published in 1881, whilst later investigation, 
 consisting in exhaustive examination of the 
 muscular tissues, enabled him to give definite 
 confirmation to these preliminary observations. 
 But, before examining his brilliant results, the 
 labours of others who had been similarly en- 
 gaged require some notice. 
 
 A little before the death of Selmi, about 1879, 
 two other Italian investigators — Paterno and 
 Spica, advanced an objection to the effect, that 
 all or a part of the alkaloids derivable from 
 putrefactive materials might possibly have 
 existed during life. In order to decide the 
 point, blood, white of egg, and bread were 
 severally examined, but by inefficient methods ; 
 though alkaloidal traces were detected, no 
 analyses were given. Their labours were 
 taken up by the Italian Ptomaine Commis- 
 sion, and with more success. The conclusion 
 arrived at was, that alkaloid substance, ob- 
 tainable from animal tissues, was neurine re- 
 sulting from the decomposition of lecithine ; 
 that it increased in amount according as either 
 
70 
 
 body is more abundant. " Is that neurine 
 always accompanied with another alkaloid 
 which reagents separate with difficulty ? " was 
 a question which they left unsolved ; the 
 small quantity, however, deprived it of any 
 toxological importance. 
 
 It ought to be noted that the preceding authors 
 had neglected the extractive matters of normal 
 muscular flesh formerly examined by Liebig. In 
 1883, Professors Guareschi and Mosso resumed 
 its study from the special point of view which 
 now engages our attention. In their interesting 
 work, these last authors state they had obtained 
 directly from veal methylhydantoine, a body 
 apparently of the uride family, and intermediary 
 between the kreatinine, sarkine, and urea; but 
 that they had not found alkaloids properly so 
 called. 
 
 Such was the conclusion reached in one of the 
 most conscientious memoirs, which had been 
 published with a view to the elucidation of this 
 question of the production, and presence or 
 absence, of alkaloids in the living animal tis- 
 sues. It now remains to note, not the pre- 
 liminary experimental efforts and hypotheses 
 suggested by Armand Gautier in 1881, but 
 the positive results which this eminent investi- 
 gator has arrived at by a course of continuous 
 
71 
 
 examination and study since that date. The 
 results are most important, as they enable him 
 to affirm to-day positively, that the important 
 chemical function of all the animal tissues, 
 however much it may have been ignored, is 
 the incessant elaboration of alkaloidal products 
 formed at the expense of proteid materials, pre- 
 cisely as urea and carbonic acid are similarly and 
 simultaneously formed. Seeing their albume- 
 noid origin — and in order to distinguish this 
 new class from that of the cadaveric alkaloids 
 or ptomaines (Trrw/^a) — Armand Gautier has 
 conferred on those vital alkaloids, the name of 
 leucomames (kevKcofia'j, a term he limits to all 
 those alkaloids derivable from albumenoid 
 substances which appear in the animal tissues 
 during life. 
 
1. 
 
 Classification and Definitions. 
 
 In classifying those alkaloids which arise in the 
 animal economy during life, and which is now 
 methodically practicable, it will be necessary to 
 indicate more distinctly those bases which, if 
 misunderstood, were at least already known. 
 
 As has been observed, kreatinine, one of the 
 most energetic of the bases, had long been dis- 
 covered by Liebig as resulting from the action 
 of hydrochloric acid on kreatine. Vallenciennes 
 and Fermy had met with it in the muscular 
 tissues of crustaceans, finally Pettenkoffer has 
 detected it in urines. It was so far back as 
 1 819 that Marcet, while examining dead bodies, 
 detected xanthine ; he also succeeded in isola- 
 ting it, and even accomplishing its synthesis. 
 Sarkine or hypoxanthine, so widely distributed 
 in the organic world, both animal and vege- 
 table, had also been met with in the principal 
 organs of the economy, such as the brain, liver, 
 kidneys, &c., it is also now found present in 
 
73 
 
 albumenoid putrifying products ; Schuzenberger 
 even finds it in yeast waters. Guanine, dis- 
 covered by Unger in 1844, has been met with 
 in a great many products of animal nature ; in 
 the flesh organs and excrementitious matter of 
 mammifers, fowl and fish. Virchow had indi- 
 cated its presence in the cartilages of arthritic 
 pigs ; and quite recently Schultz and Bosshard 
 have detected guanine in association with sar- 
 kine and allantoine in the young sprouts of the 
 plane tree, vine, and other plants. To Weidel 
 we were indebted for karnine. This base he 
 isolated from American imported meat, and 
 which he ascertained might be generally esti- 
 mated to contain about one per cent. Schut- 
 zenberger found the base also in yeast waters. 
 Finally in chronological order comes betaine, 
 discovered by Scheibler in beet root (1866) 
 and which Leibrich in 1869 detected in urines, 
 and he has since made known its synthesis. 
 
 These widespread products of animal and 
 vegetable organisms, though the feeblest of all 
 the physiological alkaloid series in their alka- 
 linity, are none the less perfectly characterised. 
 Notwithstanding this, as has been pointed out, 
 they attracted but little notice until Pouchet in 
 his remarkable thesis announced the fact of his 
 having succeeded in isolating from human urine 
 
74 
 
 a base which he had carefully examined in its 
 double chlorides of gold, platinum and mercury, 
 and had tested with the ordinary alkaloid re- 
 agents. The subsequent researches of Armand 
 Gautier not only completed the series of alka- 
 loids of animal origin now known, but brought 
 the whole into a state for their natural and 
 systematic arrangement. It is in accordance 
 with the most recent light thus thrown upon the 
 subject that we are now enabled to enter on 
 their study under the general name of Leuco- 
 maines. 
 
 These bodies form two groups — the betaine 
 or uric and the kreatinic. To these must be 
 added that other group — the non-seriate — which 
 goes on rapidly increasing. As the nature and 
 definition of its contents become decided, they 
 will find their exact position m the above orders. 
 
 Betaines — Uric Leucomaine Group. 
 
 Betaine OH"N0^=^ ^ i i 
 
 CH^— CO 
 
 anhydride constituent of trimethyl-glycolaminic 
 acid. The base, C^H"NO^ is obtained by 
 adding slight excess of acetate of lead with 
 water ; the precipitate, separated by filtering, is 
 decomposed by diluted sulphuric acid. The 
 
75 
 
 acid solution gives, with phosophate-ungestic, a 
 precipitate which easily decomposes with milk 
 of lime. The bases are then separated in the 
 ordinary way. 
 
 The synthetic processes of extraction are the 
 more interesting, as also the more practical. 
 These consist in oxydizing neurine with perman- 
 ganate of potash, or by the action of iodide of 
 methyl on glycol. Betaine, C^H^NO'+H^O, 
 forms in abundant brilliant deliquescent crystals. 
 It unites with acids, as also w^th chlorides of 
 gold and zinc. The chloride of platinum gives 
 with chlorohydrate of betaine a platinichloride 
 in yellow crystals. 
 
 Karnine C^H^N^O^.— With this base the 
 natural series of the uric group of alkaloids 
 begins. It is obtained by precipitating a 
 watery solution of meat extract with baryta, 
 filtering, and again precipitating with acetate of 
 lead. Exhausting the washed precipitate with 
 boiling water, dissolves the plumbic karnine, 
 from which the karnine can easily be removed 
 by sulphuretted hydrogen. If the base is not 
 sufficiently pure, it may be converted into a 
 silver compound and re-treated with sulphur- 
 etted hydrogen. 
 
 This base is in white crystals, which are little 
 soluble in water, insoluble in alcohol ; reaction 
 neutral. It contains a molecule of water of 
 
76 
 
 crystallization ; with the soluble salts of lead and 
 silver, it forms metallic compounds ; it furnishes 
 with hydrochloric acid, salts which the chloride 
 of platinum converts into a crystalline chloro- 
 platinate of yellow colour. Karnine then com- 
 ports itself closely as a body of the uric group, 
 in which it merely differs from xanthine by the 
 elements of acetic acid. 
 
 Treated with watery solution of bromine, 
 karnine yields the anhydride carbonic ; bromide 
 of methyl and bromohydrate of hypoxanthine. 
 
 OH^N403+Br^=OH'^N^O.HBr+CH3Br+COr 
 
 Adenine C^H^N^. — This base opens the 
 series of the leucomaines of the uric group, 
 properly so called ; has been made known to us 
 so late as 1886. For the purpose of isolating 
 it, Kossel, the discoverer, adopts the following 
 process : — Hashed bullock pancreas is boiled 
 for two or three hours in water acidulated 0.5 
 per 1000 with sulphuric acid, neutralized with 
 baryta solution, and filtered. The liquor is pre- 
 cipitated with a solution of the ammoniated 
 nitrate of silver. The precipitate, dried on 
 porous plates, is afterwards treated with nitric 
 acid in presence of a little urea. It is then 
 heated in a water-bath and filtered. The 
 adenine is then deposited in the form of double 
 
77 
 
 salts of silver. Along with hypoxanthine and 
 guanine, the precipitate is decomposed with sul- 
 phuretted hydrogen. The addition of a slight 
 excess of ammonia to the filtered liquor, throws 
 down the guanine and the greater part of the 
 adenine, leaving the sarkine and traces of ade- 
 nine in solution. The mixed precipitate is 
 taken up by diluted hydrochloric acid hot. 
 When the liquor cools there is obtained first a 
 deposit of hydrochloride of guanine ; by subse- 
 quent evaporation the chlorohydrate of adenine 
 crystallizes, ammonia then permits of the re- 
 moval of the adenine, which may be purified in 
 the state of sulphate and recovered by am- 
 monia. 
 
 Adenine, C^H^NsSH^O, is in large trans- 
 parent crystals, contains three molecules of 
 water of crystallization. It is very little soluble 
 in cold, but soluble in hot water ; insoluble in 
 alcohol, ether, and chloroform ; acids and bases 
 on the contrary dissolve it very readily ; more 
 soluble in ammonia than guanine, but less so 
 than hypoxanthine. 
 
 In alkalinity adenine is neutral; it sublimates 
 at 278' C, emitting an odour of prussic acid ; it 
 unites with acids, yielding beautifully crystal- 
 lized salts. It also combines with a number of 
 saline compounds ; with the chloride of pla- 
 
78 
 
 tinum it furnishes a chloroid platinate in yellow 
 crystals. 
 
 Potassium acting on adenine at 200° C. gives 
 cyanide of potassium. 
 
 OH^N5+5KOH=5CNK5H^O 
 
 Nitrous acid converts adenine into sarkine. 
 
 Guanine C^H^N^O. — This base is in general 
 obtained from guano, by exhausting that sub- 
 stance with a milk of lime at ebullition ; filter- 
 ing, then treating the residuum with solution of 
 carbonate of soda ; adding to the acetate of 
 sodium and hydrochloric acid precipitates a 
 melange of guanine and uric acid. Boiling 
 hydrochloric acid converts the guanine into 
 soluble chlorohydrate from which the guanine 
 can be separated with ammonia. 
 
 Guanine is a white amorphous powder of 
 slight solubility ; acids and ammonia, however, 
 dissolve it, and this feature differentiates it 
 from xanthine and sarkine. 
 
 The oxydizing action of chloride of potash 
 and hydrochloric acid, converts guanine into 
 guanidine and parabanic acid, with disengage- 
 ment of anhydride carbonic. 
 
 With nitrous acid guanine C5H'^N40(NH) is 
 converted into xanthine C5H^N^0(0). 
 
79 
 
 With the bases guanine give compounds ; it 
 unites with salts ; its sulphates, nitrates, chloro- 
 hydrates are known. Picric acid and the 
 chloride of platinum combine with guanine ; 
 with the latter reagent it gives an orange 
 yellow crystalline precipitate, presenting the 
 formula OH^N^O. HCI.PtCP+2H^0, the 
 chloromercurate presents (C^HsNsO, HCP), 
 ^HgCP+H^O. 
 
 Sarkine or Hypoxanthine C^H^N^O. — This 
 base is usually obtained from the mother liquor 
 of kreatine by first separating a small quantity 
 of xanthine with the acetate of lead and am- 
 monia, filtering and precipitating the filtered 
 liquid with acetate of copper. The cupric com- 
 pound is dissolved in boiling nitric acid, and 
 the sarkine precipitated with nitrate of silver 
 which is accompanied with a combination, but 
 soluble, from which the silver is separated by 
 sulphuretted hydrogen. 
 
 Hypoxanthine is a white powder somewhat 
 crystalline. It is soluble in 300 parts of cold 
 water, almost insoluble in alcohol. Distilled to 
 dryness, alone or in contact with potassium, it 
 gives cyanhydric acid, a reaction it will be well 
 to remember, as it enables us to ascertain the 
 constitution of sarkine. 
 
 The base united with alkalies form with acids 
 
8o 
 
 crystalline salts ; acetate of copper and nitrate 
 of silver unite with it. In hydrochloric solu- 
 tion it is precipitated with chloride of platinum ; 
 in the presence of nitric acid by phosphomo- 
 lybdic acid, it gives the ordinary alkaline re- 
 actions. The sub-acetate of lead does not 
 precipitate it. 
 
 Xanthine — Neubauer obtained 
 
 this base from urine by adding baryta water 
 and the nitrate of baryta which precipitates the 
 sulphuric and phosphoric acids ; the liquor is 
 then filtered and evaporates to a syrupy consis- 
 tence and precipitates with the ammoniated 
 nitrate of silver. Precipitate is decomposed 
 with sulphuretted hydrogen in presence of hy- 
 drochloric acid, the xanthine may then be 
 obtained to the form of a hydrochlorate. 
 
 Xanthine may be extracted from muscular 
 tissues in the same way as the "sarkine. The two 
 bases are separated by the acetate of lead which 
 precipitates the xanthine, leaving the sarkine 
 in solution. When the primary material contains 
 much xanthine, urinary calculi for example, • we 
 can readily dissolve with potash, and precipitate 
 the pure base with carbonic acid, but occasion 
 rarely offers for the use of this ready method. 
 
 By whatever process this base is obtained, it 
 assumes the form of an amorphous powder con- 
 
8i 
 
 sisting of minute adhesive pellets. According 
 as we rise to the series of this leucomaine group, 
 their solubility diminishes ; the solubility of xan- 
 thine is one gramme to 14,500 of cold water, at 
 boiling point 1,156. It is more soluble in acids 
 and alkalies. 
 
 Heat destroys xanthine in forming ammonio- 
 cyanide, the resulting hydrogen reduces it to 
 the state of hypoxanthine. It combines with 
 the alkalies, with ammonia in particular, forming 
 xanthates. Acids unite with it to form salts — ■ 
 a certain number of compounds precipitate it : 
 chloride of platinum gives a yellow crystallized 
 chloroplatinate ; chloride of mercury and nitrate 
 act similarly. 
 
 Of all the reactions the most important is 
 that with the acetate of copper. It separates 
 xanthine at boiling point only, a character 
 which Gautier, Schutzenberger, and Destrem 
 have frequently utilised in the extraction of that 
 base from the melange in which it may have 
 arisen. 
 
 PsEUDOXANTHiNE OH^N^O. — This base was 
 discovered by Gautier, and is obtained from 
 animal muscular tissues by the same process 
 as the other physiological alkaloids which he 
 added to the series and which will be de- 
 scribed with the kreatinic group. 
 6 
 
82 
 
 Pseudoxanthine is a yellow-coloured powder, 
 sparingly soluble in water, soluble in alkalies 
 and hydrochloric acid ; with the acid it gives 
 a chlorohydrate, which resembles that of the 
 hypoxanthine. It forms star-shaped crystals, 
 and much resembling those of uric acid. The 
 ammoniacal acetate of lead, corrosive sublimate, 
 and nitrate of silver precipitate pseudoxanthine, 
 as well as xanthine, like the latter pseudo- 
 xanthine, gives the reaction of the murexide. 
 
 Between the two leucomaines there is conse- 
 quently a close affinity. Gautier not having 
 met with xanthine in the course of his re- 
 searches, Hugounenq thinks the substance 
 noted in different parts of the organism, and 
 described under the name of xanthine, was 
 often merely pseudoxanthine ; the strong re- 
 semblance of the physical , properties of the two 
 bases favour the confusion. 
 
II. 
 
 Classification and Definitions. 
 
 Gautier in 1881 having distinctly raised the 
 question, whether in the normal state animal 
 tissues, like the organs of plants, might not be 
 capable of elaborating alkaloids, determined to 
 decide it. The existing bases just enumerated, 
 the analogy of biological phenomena and 
 putrefactive reactions and the production of 
 ptomaines in the course of bacterial fermenta- 
 tion of proteid materials, led him to that series 
 of investigations which were so brilliant in 
 results. They not only confirmed his theoretical 
 conceptions, but established demonstratively the 
 formation of leucomaines by the normal cellular 
 activities of all living things, animal as well as 
 vegetable. 
 
 In working out this problem he occupied 
 himself with the study of the alkaloidal products 
 of muscular tissues, because they were abund- 
 ant, and the nature of the material homo- 
 geneous. The new alkaloids discovered by him 
 
84 
 
 are consequentiy all of fresh meat origin. His 
 researches were conducted with great difficulty 
 but with the greatest care, so as to avoid all 
 suspicion that the alkaloid basic products could 
 have been formed artificially in the course of 
 operations. 
 
 According to the method adopted, and laid 
 down for others to follow, fresh hashed meat is 
 first subjected to digestion for twenty-four hours 
 in double its weight of tepid water, to which has 
 been added o gr. 25 of oxalic acid and oxygen- 
 ated water 2 cc. per litre, to prevent fermenta- 
 tion. The residue is filtered by pressure, and 
 the united strainings are subjected to boiling or 
 evaporation, in order to coagulate albumen. 
 The albumen is separated by filtration and 
 evaporated at a temperature of 50" C, and the 
 tissue-residue is then retreated with alcohol at 
 gg° ; this, when evaporated, gives a new resi- 
 due which is further treated with alcohol at 99° 
 this time hot. The liquid having been set aside 
 for some time, ether at 65° is added until pre- 
 cipitation ceases. Examined after twenty-four 
 hours the liquor presents a yellowish thick ap- 
 pearance, and is of a bitter taste. Very soon — • 
 but hastened by the use of pure ether — a 
 magma of crystals is deposited, which may be 
 separated. These primary crystals are washed 
 
85 
 
 in cold alcohol of 99° ; this removes from them 
 without dissolving them, their impregnating 
 liquors. 
 
 Boiling alcohol of 95° relieves these crystals 
 first, of a base described as xanthocreatinine ; 
 and, secondly, of crystals which are deposited 
 in the mother liquors of the first alkaloid, which 
 are examined successively. 
 
 The primary crystals — free from precedent 
 compounds, and washed with alcohol, leave 
 a residue which is taken up with boiling water. 
 From this aqueous solution is deposited first a 
 primary base — amphicreatinine, and by further 
 concentration of the mother liquors a second 
 — crusocreatinine. 
 
 The alcoholic solutions, from which these 
 three earliest bases have been obtained, on 
 being properly treated with acetate of copper, 
 and the precipitate decomposed with sulphu- 
 retted hydrogen, gives a new alkaloid which 
 has been already classified as pseudoxanthine. 
 
 Thus, in isolating all these alkaloid crystals, 
 the analytical process is speedy and simple. 
 There is no need of any other reagents than 
 alcohol, ether and water. These crystalline 
 substances constitute the new bases, whose 
 pathological, as well as chemical, relations are 
 now exciting so much interest ; investigation 
 in this direction has all the prospect of a wide 
 
86 
 
 and fertile field before it. These processes do 
 not exhaust the muscular basic products. 
 
 In briefly describing these new compounds, 
 whose discovery is also due to Gautier, it 
 will be necessary to note that long-known base, 
 kreatinine, which heads the list. 
 
 Kreatinic Leucomaine Group. 
 
 NH— CO 
 Kreatinine OH^N^O NH=C i 
 
 N(CH3)— CH^ 
 
 anhydride of guadinine derived from methyl- 
 aminacetic acid. 
 
 The method of isolating the base is that of 
 Pettenhofer, modified by Neubauer. 300 cc. 
 of urine is first alkalised with milk of lime. After 
 some hours the whole is filtered and evaporated 
 to dryness by the water bath ; 30 to 40 cc. of 
 alcohol is then added ; a deposit soon appears, 
 which is disposed of by filtration. The mother 
 liquors of concentrated alcohol, to which has 
 been added the chloride of zinc, supplies 
 the well-known combination (C'^H^N^Oj^ZnCz 
 whence the kreatinine pure may be easily re- 
 moved by the aid of the hydrate of lead. 
 
 The constitution of this important base is 
 difficult to grasp, and would not only necessitate 
 a review of the synthetic chain of reactions by 
 
8/ 
 
 which we are enabled to obtain kreatinine, 
 commencing with its elements, but a knowledge 
 of the modes of syntheses of glycocol or amin- 
 acetic acid and cyanide. The method of dealing 
 with these two bodies, and the reactions in- 
 volved, is not required of us, the object of this 
 present study being rather indicative than syn- 
 thetic. 
 
 Kreatinine forms into clinorhombic prisrris 
 soluble in water, slightly soluble in alcohol ; it 
 unites with acids, displaces ammonia in its com- 
 bination, precipitates nitrate of silver, corrosive 
 sublimate, and gives with the chlorides of zinc 
 or cadmium characteristic crystalline combina- 
 tions long familiar. Kreatinine gives with acids 
 crystallized salts. 
 
 It may be well to note that the facility with 
 which kreatinine yields methylhydantoine and 
 urea, may probably claim for it an important 
 intermediary role in the physiological genesis of 
 that latter substance, at the expense of the pro- 
 teid materials. 
 
 Xanthocreatinine C^H'^N^O. — This is the 
 most abundant of these bases, and it closely re- 
 sembles kreatinine, from which it merely differs 
 by CH^N. It shows in pellets of sulphur 
 yellow, of slightly cadaveric odour. The base 
 is soluble in cold water, and boiling alcohol of 
 99° ; reaction strongly alkaline. It unites with 
 
88 
 
 chlorohydric acid. The chlorides of gold, zinc 
 and mercury, give compounds in various cry- 
 stalline forms ; neither nitric nor oxalic acids 
 precipitate it. The same with the acetate of 
 copper, a character which alone distinguishes 
 that leucomaine from xanthine and hypoxan- 
 thine. Of the ordinary alkaline reagents, tan- 
 nin phosphomolybdate of sodium precipitates 
 the xanthocreatinine. 
 
 This base is toxic, and induces somnolence, 
 purgation and vomiting. 
 
 Crusocreatinine C^H^N^O. — This beauti- 
 ful base differs from the previous one by only 
 two atoms of hydrogen. It possesses the general 
 properties of kreatinine, which it strongly 
 resembles in elements and alkalinity ; differing 
 only by the elements CNH of cyanhydric, and 
 which here again plays a diatomic role. Crystals 
 are orange yellow, with chlorides of platinum 
 and gold, and give crystalline compounds. This 
 base is neither precipitated by oxalic or nitric 
 acid ; the acetate of copper does not act upon it 
 when heated, consequently it cannot belong to 
 the uric series ; has no affinities with guanidine 
 xanthine, or such like bodies. 
 
 Amphicreatinine OH'^N^O^ — Prisms bright 
 pale yellow ; slightly bitter to the taste, little 
 soluble in cold water ; exposed to a temperature 
 
89 
 
 of iio^ C. they become opaque in colour 
 without changing the^' form. The chlorohy- 
 drate chlorides and chloroplatinate of amphi- 
 creatine are soluble and crystalline. Neither 
 the acetate of copper, nor the chloride of mer- 
 cury precipitates it. The phosphomolybdate 
 gives a powdery yellow precipitate. It does 
 not give the reaction of the murexide, this con- 
 sequently excludes it from the leucomaines of 
 the uric group. It has the closest analogy to 
 the kreatinic. Though its crude formula would 
 seem widely to differentiate it, in reality it 
 corresponds to two molecules of kreatine, plus 
 the C N H groupment. 
 
 PsEUDOXANTHiNE. — This base, whose resem- 
 blance to xanthine has led to some confusion, 
 has been sufficiently noticed under the uric 
 group, to which it properly belongs. Nothing 
 more need be said of it. 
 
 To terminate the analytical indications of the 
 complete work, in which Gautier has described 
 for the first time the kreatinic leucomaines, it 
 only remains to mention two more complex 
 bases, which are found to accompany the pre- 
 ceding in the muscular tissues. As they have 
 not yet been perfectly studied, we will rest 
 satisfied with giving their formula — C"H'^N'°0^ 
 
go 
 
 — C^'ii^^N^'O^ and their difference from each 
 other by CNH. 
 
 The constitution and affinities of these bases 
 with those named would lead to the conclusion 
 that the kreatinic leucomaine group forms a 
 natural series, the terms of which are homo- 
 logous, as regards CNH ; that is to say, that 
 they differentiate by the cyanhydric arrange- 
 ment, as the carbonate homologues, for example, 
 differ by the CH^ groupment. Thus the con- 
 ception again and again announced by Gautier, 
 of the importance of the CNH unity in the 
 molecule of proteid material, finds here fresh 
 confirmation. 
 
 It is, however, well to observe, that the ques- 
 tion of constitution is not yet definitely known ; 
 but as Gautier thinks, it would perhaps be as 
 well represented by cyclical nuclei analogous to 
 those of the uric leucomaines, though somewhat 
 modified. 
 
 If we recognise the presence of an unbroken 
 circle of chemical affinities linking together the 
 betaine, kreatinine, and the alkaloids of the uric 
 group, we are forced to admit the existence of 
 a cyclical nucleus in the leucomaines best known. 
 This peculiarity may not be altogether acci- 
 dental. The question, however, need not now 
 be followed farther, as it lies beyond the scope 
 of the present summary. 
 
III. 
 
 Non-Seriate Group. 
 
 This class comprises those leucomaines which 
 do not come within either of the two preceding 
 orders to which all the well-known leucom.aines 
 belong. Being, for the most part, still un- 
 defined, any attempt at a rational arrangement 
 would be useless. It is, therefore, best to notice 
 them according to their origin, or that organ or 
 secretion of the animal economy whence they 
 are derived. 
 
 When treating of these alkaloids in their 
 pathological and toxical relations, it will be seen 
 how very interesting is the study which they 
 promise — the urinary leucomaines in particular. 
 Their variations in quantity and quality, indi- 
 cating the condition of health and disease, 
 merit the close attention of competent ob- 
 servers. 
 
 According to their sources, we have to note 
 as follows : — 
 
 The Urine. — Pouchet's inaugural thesis of 
 
92 
 
 t88o is an important event in alkaloid investiga- 
 tion. It was then that this investigator made 
 known the fact that he had obtained from nor- 
 mal urines a uride, allantoine — a primary base 
 already known — karnine, and a second alkaloid 
 which, as researches have advanced, he has 
 since analysed. 
 
 The method of extraction he adopts has al- 
 ready been described, so its principles need only 
 be referred to. It consists in treating the ma- 
 terial containing the alkaloids with tannin, de- 
 composing the tannates with hydrate of lead, 
 and submitting the liquors to dialysis. From 
 the dialyzed portion, Pouchet obtained a body 
 in deliquescent fusiform crystals of feeble alka- 
 line reaction, which, when uniting with acid, 
 gave crystalline salts. The chlorohydrate of 
 this base furnished, with the chlorides of gold, 
 platinum and mercury double salts. The analy- 
 sis of the chloroplatinate lead either to the 
 formula C''H'^N^O^ or to a formula which 
 merely differs from it by FP additional, that is 
 to say, C^H^-^N^O^ 
 
 According to Pouchet, urine contains in 
 addition to the above, small quantities of 
 hydropyridic bases, either similar to or identical 
 with those obtained in the putrefaction of fish- 
 substance by Gautier and Etard. 
 
93 
 
 Besides these eminent workers, Villiers, 
 Lepin, Guerin, Bauchard, and others, have 
 been dihgently engaged in this field. 
 
 Blood and Important Viscera. — -Reference 
 has already been made to the joint mdinoire of 
 Spico and Paterno to the Academy of Lincei, 
 1882. With a modification of the Stas-Otto 
 method these authorities were enabled to ob- 
 tain, from bullocks' blood in particular, traces 
 of a substance precipitable with phosphomolyb- 
 date, and capable, after a time, of reducing 
 the chlorides of gold and iron. But in conse- 
 quence of the blood being used in insufficient 
 quantity for carrying out reliable researches of 
 this nature, they were necessarily unable to 
 secure any analysis of such alkaloidal traces as 
 were obtained. The examination of white of 
 egg afforded similar results. 
 
 These investigations were resumed by the 
 Italian Ptomaine Commission, whose reports, 
 published in 1885, are interesting to refer to. 
 The Italian chemists, engaged in this enquiry, 
 isolated alkaloid material from the blood, the 
 brain ; and from the liver, traces of basic pro- 
 ducts whose alkaloids were characterisable by 
 their qualitative reactions only. By Stas's 
 method they were enabled to separate from 
 the liver two leucomaines, one in the form of 
 
94 
 
 a sulphate of a violet colour, and capable of 
 reducing ferricyanide ; the second base which 
 gave a crystalline chloride appeared to be neu- 
 rine. The two alkaloids were determined by 
 general reagents, but without analytical defini- 
 tions. 
 
 Though these investigations were incomplete 
 in many respects, they have not been fruitless. 
 The labours of Guareschi and Mosso have 
 added to the data. Though attaching less im- 
 portance to the question as a whole, they de- 
 tected traces of leucomaines in fresh liver, brain, 
 and veal fibre ; this they attributed to the action 
 of reagents or unsoundness of the proteid 
 material, thus ignoring the positive results of 
 their researches. Finally, these authorities 
 found a base, probably neurine, in the fresh 
 heart and lungs. Similar observations have 
 been made by Coppola on the blood of dogs. 
 
 The examination of the blood requires to be 
 taken up afresh. This is being done. Aided 
 by the method indicated by Gautier, Wartz has 
 been engaged in investigating the leucomaines 
 in the material drawn fresh from the vein of 
 the animal in order to avoid all possible error 
 arising from impurity of change. By this 
 means, and operating on quantities of fifteen 
 litres at a time, Wartz has obtained crystallized 
 
95 
 
 products of alkaline reaction, which give chlo- 
 rides of platinum, gold and mercury in well- 
 defined crystals. He has also succeeded in 
 isolating from bullocks' blood volatile bases in 
 the state of chlorohydrates, but in quantities 
 too small to admit of reliable analysis. 
 
 The Spleen. — From this organ Morelle, of 
 Lille, has determined the presence of an 
 alkaloid which he has isolated in the form of 
 chlorohydrate in deliquescent crystals and trans- 
 formable into chlorides of gold and platinum. 
 Labord has now been able to ascertain its phy- 
 siological effects. 
 
 The Intestines. — Pouchet and Villiers 
 have isolated with chloroform, from choleraic 
 dejections, a base which seems to belong to the 
 pyridic group. This substance, which is appa- 
 rently the product both of physiological diges- 
 tion and albumenoid bacterial destruction, is 
 highly oxydizable, and energetically reduces the 
 ferrocyanide and chloride of gold and platinum. 
 Its physiological action has also been ascer- 
 tained. 
 
 The Saliva. — The presence of alkaloids in 
 human saliva has been ascertained by Gautier. 
 If the soluble extract of normal saliva is 
 treated with a little ferricyanide, immediately 
 an abundant precipitate of Prussian blue re- 
 
96 
 
 suits. Taking the soluble extract, he treats 
 it with hydrochloric acid and precipitates by 
 Meyer's reagent. This new precipitate being 
 washed is decomposed by sulphuretted hydro- 
 gen, which on being filtered gives a solution 
 that by evaporation leaves fine minute hydro- 
 chlorate crystals. The effect of the substance on 
 small animals has been attested. We merely 
 indicate the fact, as it will be more fully noticed 
 when treating of the leucomaines in their physio- 
 logical relations. 
 
 The Venoms of Certain Snakes and Ba- 
 TRACHIANS. — Investigations in this direction, if 
 not fruitful, are at least interesting. Following 
 the traces given by Cloez and Gratiolet, who ob- 
 tained alkaloids from the cutaneous pustules of 
 toads, Zalesky succeeded in isolating from a spe- 
 cies of lizard, a base of the formula C^^H^^N'O^ ; 
 while Gautier, operating on the venom glands 
 of the Naja tripudians, has been enabled to 
 separate two more. 
 
 Certain Molluscs and Fishes. — Of this 
 class little need be said. The reason of the 
 poisonous effects of certain shell-fish and fish 
 proper is no longer a mystery. Though it is 
 long since Salkowski, Schmidtmann and Vir- 
 chow drew attention to the subject, it remained 
 for Brieger to identify the active principle in the 
 mytilotoxine and give its formula, CT-i'^NO^ 
 
97 
 
 Such in summary is the hst of the chief un- 
 classified leucomaines. Their characters, Hke 
 those embraced in the preceding groups, will be 
 made more evident when their toxic properties 
 come to be considered. From the nature of our 
 introductory survey of the subject, the physio- 
 logical actions of the leucomaine animal alkaloids 
 will be more intelligible treated separately and 
 as a whole. In indicating the number of recent 
 researches, or of those still in progress, whilst 
 noting the work of earlier observers, the object 
 of the present paper is accomplished. 
 
 7 
 
IV. 
 
 Physiological Actions, 
 
 To render the review complete so far as it is 
 at present possible, it will be necessary to con- 
 sider the toxic and physiological actions of the 
 leucomaines. In this respect their study has 
 not yet acquired the development which it pre- 
 sents in the case of the ptomaines ; particular 
 estimates consequently do not come before us 
 with the definiteness which might be desired. 
 In other words, conclusions cannot be adopted 
 without a certain disregard of investigations, 
 which are incomplete or still in progress. 
 
 The discovery of the leucomaine alkaloids is 
 too recent to admit of tabulation as regards 
 their physiological action. It may, however, 
 be safely affirmed, that where they have been 
 obtained in sufficient quantity for experimental 
 purposes, they have in general been found to be 
 deleterious to the animal economy, and this 
 irrespective of the group to which they belong ; 
 that in variety and toxic intensity they are com- 
 
99 
 
 parable with those of the ptomaine or cadaveric 
 alkaloids, as these latter are with those of vege- 
 table origin which supply us with the most 
 active known as yet. 
 
 The kreatinic leucomaines, Gautier assures 
 us, are deleterious, — xanthine for example, — • 
 in very small traces. They exert a powerful 
 influence on the nervous centres, producing 
 sleepiness, lassitude, or occasionally vomiting and 
 purgation ; they operate, in fact, in the manner 
 of the alkaloids derived from venoms, though 
 less actively. 
 
 The spleen alkaloid of Morelle, as re- 
 ported by Labord, may be taken as typical of 
 the toxic bases of the structures, special or gene- 
 ral. This observer noted its action as em- 
 bracing stupor, paralysis of reflexes, convulsions 
 and death. Injected into the cellular tissues of 
 the guinea pig, frog, &c., there is immediate 
 toxic action, followed by collapse, gradual 
 functional subsidence, with death in a few 
 hours. The post mortem appearances may also 
 be regarded as of general application. There is 
 marked and rapid visceral ecchymosis and 
 oedematous infiltration, with cardiac systolic 
 arrest. 
 
 Interest obviously increases as we approach 
 the excremental products. The study of the 
 
100 
 
 intestinal and urinary excreta to begin with, 
 notwithstanding all that has been done, shows 
 new and yet more complex .aspects of the 
 chemical problem to be dealt with. 
 
 The probable double origin of the intestinal 
 leucomaines, for example, does not materially 
 affect that of toxic action. The alkaline base 
 that Pouchet isolated in the form of chloro- 
 hydrate, is unquestionably poisonous, a fact 
 of which this eminent investigator had serious 
 personal experience. It is found sufficiently 
 energetic to control the heart's action, and to 
 induce death, followed rapidly with cadaveric 
 rigidity. This authority has also met with 
 traces of alkaline substances in the cultivation 
 liquid of the comma bacillus of Koch, and 
 which would appear to be identical with the 
 preceding. The more recent examination by 
 Villiers of dejections of choleraic subjects, goes 
 to strengthen this impression. 
 
 Whether defined or undefined, as has already 
 been remarked, the urinary leucomaines stand 
 first, in interest and importance, in a physio- 
 logical sense. It was through the urines that 
 their discovery and investigation was first en- 
 tered on ; it is through them that the presence 
 of the alkaloid in varying traces is being recog- 
 nised as a valuable index of the state of the 
 
lOI 
 
 animal economy, so variable in the conditions, 
 of health and disease. Clinically, this must soon 
 come to be admitted. Facts such as these 
 explain the value some would attach to them, 
 and encourage the study rather of their patho- 
 logical significance than of their chemical defi- 
 nitions, a field where much more caution is 
 requisite. 
 
 Though scarcely traceable at times in normal, 
 healthy urine, the alkaloids show, as Gautier 
 has clearly established, their amount to be 
 relatively increased in disease. Lepine and 
 Guerin find that in the course of certain fevers, 
 for instance, their poisonous quality increases 
 in due proportion until the crisis is attained. 
 But their presence is not perceptible in all 
 maladies indiscriminately, nor always in a like 
 degree in those where they are perceptible. 
 The above-named investigators, for example, 
 have detected the presence of alkaloids in the 
 urines of typhoid and pneumonic patients, but 
 not in those diabetic. Again, it has been ascer- 
 tained experimentally that the basic products 
 vary according to the morbid conditions, not 
 only in their toxic activity but also as regards 
 their chemical characters. On this point we 
 are indebted to Bouchard for his extensive 
 and delicate examination of urines. He has, for 
 
102 
 
 instance, given averages of the alkaline pro- 
 ducts of given typhoid fever patients within 
 a space of twenty-four hours, and shown that 
 the leucomaines in certain forms of this fever, 
 and under certain morbid conditions, are not so 
 potent as might be supposed ; experimentally, 
 they need not even pass beyond simple dila- 
 tation of the pupil and acceleration of the 
 heart's action. 
 
 The later researches of Bouchard, however, 
 have led him to think the poisonous symp- 
 toms induced are neither altogether nor always 
 attributable to the alkaloid material. The 
 agent of intoxication, and the intoxication 
 itself are, he believes, often affected by 
 influences which are as yet imperfectly repre- 
 sented. Observations on the venous injections 
 of urine tend to confirm the impression, while 
 still more recent investigation would seem to 
 show that the day urine affords a narcotic, 
 sedative principle ; the night urine, on the 
 contrary, is marked by a stimulant, convulsi- 
 vant principle. 
 
 Supposing that we turn from human urines 
 to human salivas. In these, as we have seen, 
 Gautier has also found extractive matters 
 which respond to alkaloid reagents, and 
 which further investigation will show to be 
 
103 
 
 not without analogies with the preceding, 
 should their toxic properties be verified. 
 The extract, obtained from about twenty 
 grammes of pure saliva secreted during the 
 day, when injected into the subcellular tissue 
 of a small bird, produced intense stupor 
 and drowsiness, which lasted for some hours. 
 Bouchard's day urine alkaloid induced the 
 same effects, while that of the night was 
 exciting even to convulsions. It is not im- 
 possible, as Hougenenq suggests, that the 
 night salivas of man might exhibit a similar 
 action, and be also convulsive. The observa- 
 tion is worthy of the attention of the physio- 
 logical experimentalist, as there is a possibility 
 that the toxic principles of the human saliva, 
 if not identical with that of human urine, at 
 least obey the same laws, though widely differ- 
 ing in their elementary natures. As it is un- 
 necessary to discuss the probabilities of the 
 secretion of such antagonistic principles, we 
 merely note the singularity which ascertained 
 facts in some sense suggest. It would certainly 
 be remarkable, if true, to find the alkaloid in 
 the interrupted succession of physiological 
 effects, guaranteeing, as it were, the alterna- 
 tions of sleep and wakefulness. 
 
 From man to the inferior animal is but a 
 
104 
 
 step. Passing from the salivas of man to 
 those of the poisonous reptiles, the difficul- 
 ties of the subject increase, and the greater 
 caution is required in dealing with them. 
 If the venoms of certain snakes, for in- 
 stance, have long excited scientific interest 
 and attention, it has been more with a view 
 to the controlling of their terrible effects, 
 and the discovery of specific antidotes, than 
 to their chemical nature and constitution. 
 It was not until Armand Gautier undertook 
 his comprehensive investigations in this di- 
 rection, that the mystery of their nature and 
 action could be in some sense disposed of By 
 operating on the venom of snakes of India, 
 more particularly the cobra-hooded snake, he 
 has succeeded, as we have seen, in isolating 
 their alkaloidal bases. His partial examination, 
 analytically and physiologically, are but details 
 in the net results of his researches. Starting 
 with the pure secretion, Gautier found that 
 a milligramme induced immediate disturbance 
 of the primary functions, and was followed with 
 convulsions, whilst death exhibited the charac- 
 teristic systolic arrest with muscular insensibility 
 to electrical stimulation. He further ascertained 
 the fact that the venom, when submitted to a 
 temperature of 120 to 125' C, underwent no 
 
105 
 
 appreciable alteration, thus clearly showing that 
 its active principle could not be of the nature 
 of a diastase. Its toxic action remaining con- 
 stant when relieved of all its proteid elements, 
 made it further evident that its poisonous pro- 
 perty could not be attributable to the presence 
 of alkaloids alone. Perchloride of iron and 
 the essences had no sensible influence on the 
 venom. Tannin, and the nitrate of silver 
 moderated its action, while ammonia and alka- 
 line carbonates produced but little effect. Weak 
 caustic potash arrested the action of the secre- 
 tion ; while previous alkaline saturation of the 
 material did not revive its toxity. The gastric 
 juice, on the contrary, seemed to increase its 
 activity. 
 
 Gautier's researches are by no means ex- 
 haustive, but there is little doubt that he is jus- 
 tified in his conclusions, namely, that the toxic 
 action of the snake-venoms is not simple but 
 multiple, due to the presence of various nitro- 
 genous principles, of which the most energetic 
 is not of an alkaloidal nature. He has, however, 
 as already stated, been enabled to isolate two 
 leucomaines, — precipitable with Nessler's re- 
 agent and the iodide of potassium, — which give 
 salts and metallic chlorides in well defined cry- 
 stals, and induce in smaller animals well-marked 
 physiological effects. 
 
io6 
 
 The fact is well attested that certain classes 
 of fish possess the power of secreting a toxic 
 principle somewhat similar in physiological pro- 
 perties to the venoms of the ophidians. Those 
 known, are met with chiefly on the Chinese and 
 Australian coasts. Carri and Gautier have 
 given attention to this fact, and the latter is of 
 opinion that the venomous glands secrete alka- 
 loid material as a normal function. The active 
 principle has not yet received sufficient experi- 
 mental examination — either chemical or physio- 
 logical — to warrant conclusions on this point. 
 
 Poisoning with shell-fish too frequently 
 occurs to escape notice. Here, again, it is 
 only very recently that the probable nature of 
 the poisonous principle has been suspected. 
 That of the common mussel is an example. 
 Brieger has succeeded in isolating from that 
 mollusc its active principle — mytilotoxine. 
 He has even studied and defined its chemical 
 and physiological properties. Its formula is 
 C^H'^NO^ ; its effects curaraizing or convulsi- 
 vant on animals, inducing death by accumulation 
 of carbonic acid in the blood, and paralysis of the 
 motor nerves. It thus resembles the impure 
 extracts in its effects. This base is, however, not 
 the only one ; Brieger has detected several 
 others, which are less active, or altogether in- 
 offensive. 
 
10/ 
 
 The same authority also confirms the obser- 
 vation made by Salkowski, relative to the 
 removal of its toxic properties by distillation 
 with carbonate of soda. This supplies a fact 
 in physiology and hygiene, of important prac- 
 tical application, which has not been lost sight 
 of by consumers. 
 
 In taking leave of this subject, it is but proper 
 to repeat that though the presence of poisonous 
 alkaloids in the foregoing secretions is not to be 
 questioned, they do not alone explain the whole 
 of the toxic phenomena, and leave us still in 
 doubt as to their import in those cases where, 
 as Gautier has concluded, the activity of other 
 azotized principles preponderate. 
 
 The notice of the leucomaine alkaloids is now 
 complete, at least in summary. A number of 
 recent researches still in progress has been 
 reviewed ; it has also been endeavoured to make 
 evident the fact, — no longer questioned, — of the 
 presence of alkaloids varying in their nature 
 and action according to the physiological and 
 pathological conditions of the economy itself 
 Some of the leucomaines, it has been shown, 
 belong to types already known, and thus group 
 themselves in the natural order of organic com- 
 pounds ; while others, again, form a class as yet 
 ill defined and awaiting further examination. 
 
io8 
 
 Now come the important questions : What 
 is the origin of the singular products of Hving 
 animal tissues ? What is the mode of elimination 
 of the alkaloids, whose physiological action occa- 
 sionally reminds us of that of the most violent 
 poisons ? What can be the mode or mechanism 
 by which the cellular stroma, in health and 
 disease, accomplishes those gradual and succes- 
 sive simplifications which the albumen undergoes 
 in running the pyridic circle ? The solution of 
 the problems involved, were it possible to follow 
 them, would form the most interesting chapter 
 of normal physiology and pathology of cellular 
 life. If a completely satisfactory reply to the 
 above questions may be hoped for, it must be 
 admitted the time has not yet arrived. The 
 genesis and role, — the complete history of the 
 leucomaines, in fact, — is too closely bound up 
 with the essentially vital to permit of it. Fol- 
 lowing on the present lines of investigation 
 where so much has been accomplished, it 
 remains to be seen what that amounts to. 
 
V. 
 
 Biochemic Aspects. 
 
 Since 1882 investigation has thrown muchhght 
 on facts in bio-chemics which were Httle under- 
 stood, and very disconnected. It would seem, 
 for example, that the common origin of the 
 cadaveric and physiological alkaloids asserts 
 itself with evidence sufficiently clear to justify 
 a consideration of the question. Seeing how 
 much the prevailing pathological and therapeu- 
 tical notions would lose as well as gain were this 
 confirmed, it is, perhaps, surprising that the at- 
 tempt should not have been made sooner. Until 
 to-day, however, both data and induction were 
 wanting. How, then, does the matter stand at 
 present ? 
 
 Life, I presume, may be scientifically regarded 
 as the incessant mutation of organic elements 
 and tissues. The chemical reactions on which 
 it depends give rise to a number of substances 
 allied to different types which form the basis of 
 a natural classification of organic compounds. 
 The formation of essential oils, sugars, acids, and 
 
1 10 
 
 fatty substances, at the expense of organic 
 economies, had not escaped the observation of 
 the chemists ; but theoretic pre-conceptions and 
 practical difficulties in experiment long prevented 
 them from seeing the presence of alkaloidal pro- 
 ducts in the tissues of plants to begin with. In 
 1817 Sertuerner recognised as an alkaline base 
 one of the crystalline compounds — morphine — • 
 which he obtained from opium some years earlier 
 — 1804. All know the development which the 
 question soon assumed in connection with the 
 discoveries of Pelletier, Caventou, de Robequiet, 
 and others. 
 
 If the history of nations repeats itself so does 
 that of science. Some yet living can remember 
 with what hesitation chemists acknowledged the 
 alkaloidal fabricating powers of plants, and all 
 have witnessed a like hesitation in accepting the 
 discovery of the same function in animals. It 
 is true, that prior to recent researches, some 
 alkaline extracts of animal tissues were known. 
 This is not disputed ; but until more recently no 
 one had looked upon the discovery otherwise 
 than as a solitary or isolated fact. 
 
 It was in the products of putrefaction of 
 albumenoid material that the alkaloids of 
 animal origin were first discovered by Armand 
 Gautier, in 1872. Much interest this event 
 
1 1 1 
 
 excited when some time afterwards Selmi, of 
 Bologna, published his observations confirming 
 the discovery of the French savant, in their 
 medico-legal applications. The question, how- 
 ever, in Italy, confined itself to researches in 
 toxicology, whilst in France first, and next in 
 Germany, it took a position more important and 
 wider in its range. When Gautier, Etard, 
 Brieger, and others by their labours gave pre- 
 cision to the data previously acquired, adding 
 largely to the varied and careful examination of 
 cadaveric tissues, they forced upon us the conclu- 
 sion that, during the putrefaction of nitrogenous 
 animal material, there are formed organic bases, 
 fixed or volatile, presenting, by their chemical 
 and physiological properties, the closest resem- 
 blance to the vegetable alkaloids. Such were the 
 results arrived at in the series of researches 
 which form the first stage of the history of the 
 discovery of organic alkalies derivable from the 
 animal economy. 
 
 Now, are we to regard this discovery as of a 
 chemical value only, or as merely a conquest, in- 
 teresting but isolated, of chemical putrefaction 
 Surely not. The elaboration of alkaloids must not 
 be regarded as depending solely on the presence 
 of micro-organisms which derive their vital nutri- 
 ment from the destruction of proteid material : 
 
112 
 
 this is a function much more general, one com- 
 mon to all living cells, — belonging as much to 
 the superior animal as to bacterial activities. 
 Thus regarded, the discovery of alkaloids arising 
 in tissues — whether undergoing bacterial de- 
 struction, or during their vital physiological 
 growth — appeals to us as a chemical discovery. 
 Very naturally it does this, but much more than 
 this ; for it must be regarded as indicating an 
 entirely new function. 
 
 Again, the second stage of the history of the 
 detection of alkaloids in the animal economy is 
 associated with the name of Armand Gautier. 
 It is to this savant that we are chiefly indebted 
 for the examination separately of alkaloids formed 
 during bacterial destruction of albumenoids, and 
 of those which owe their formation to the 
 chemical activities of normal tissues. This dis- 
 tinction is useful, and lends itself to the require- 
 ments of methodical classification. But does it 
 follow that the terms ptomaines and leuco- 
 maines should be considered as absolutely dis- 
 tinct ; and as it were, opposed to one another 
 This is not admissible. It is often in vain, to 
 try to trace rigorously where the one series of 
 alkaloids begins or the other terminates. 
 
 In studying the death of the tissues, we find 
 it to be a complex phenomenon of long duration, 
 
113 
 
 and to consist of transitions from biological re- 
 actions to reactions of the purest chemical nature. 
 This process is carried on through the medium 
 or intervention of organisms with, which the two 
 kingdoms — animal and vegetable — are alike 
 identified, and which in destroying the proteid 
 materials leaves as a residuum of its molecule 
 those alkaloids of putrefaction which are studied 
 under the name of ptomaines. This tissue- 
 death is but a prolongation of life, and the role 
 of the bacterides does not mask, so much as 
 might be supposed, the chemico-biological re- 
 actions of normal tissues. The discovered resi- 
 duum being now detected in the disassimilations 
 of muscular structures and various organs of the 
 vital economy, we are enabled to confirm the 
 fact that a certain number of alkaloids are com- 
 mon to the ptomaine and leucomaine series. 
 To satisfy ourselves of this we have only to trace 
 backwards the history of xanthine, choline, and 
 some other bases met with in both the physi- 
 ological and putrefactive products. The double 
 source of these alkaloids clearly shows that it 
 is by virtue of reactions identical, or at least 
 analogous, that they originate in the two cases, 
 and that nothing more nearly resembles the 
 phenomena of life ; that is to say, the reactions 
 of proteid materials undergoing destruction, are 
 8 
 
114 
 
 strictly analagous to the phenomena of putrefac- 
 tion which arise out of the destruction of the 
 same materials under the influence of ferment. 
 Must we thea recognise an absolute distinction 
 between the alkaloids of animal origin and those 
 of vegetation. Experiments in this direction 
 carefully studied are in formal contradiction 
 with such a view. The physiology even more 
 than the morphology of organisms confirms the 
 adage of Linnaeus, so often and fitly cited, 
 Natura non facit saltus : and nowhere is this 
 more evident or more easily realised than in the 
 study of comparative biology. Of all plants the 
 mushrooms are those which, in their nature, bear 
 the closest resemblance to the animal organisa- 
 tion. Now, the mushroom alkaloid — muscarine 
 — has been detected in the products of putre- 
 faction of animal tissues. The beetroot, higher 
 in the organic scale than the agaric^ elaborates 
 betaine, which Liebrich has succeeded in iso- 
 lating in the human urine ; even those leuco- 
 maines of the uric group, adenine, guanine, 
 sarkine, regarded until yesterday as peculiar 
 to and characteristic of animal tissues, are to- 
 day detected by Schultz and Bosshard in the 
 tender shoots of plants. It is true that the 
 ptomaines and leucomaines exhibit simpler 
 chemical formulas than vegetable alkaloids for 
 
115 
 
 the most part do. The constitution of these 
 latter being less known, their synthesis has not 
 been accomplished, whilst a number of the 
 leucomaines can be manufactured artificially. 
 
 The physiological action of alkaline bases of 
 animal origin does not present the diversity of 
 action which gives to the study of the vegetable 
 alkaloids so much interest and importance ; still 
 the physiological effects of some ptomaines and 
 leucomaines are powerful enough to bear com- 
 parison with those of the muscarine, curara, and 
 some other vegetable poisons. To summarise 
 matters, the differences in detail do not invali- 
 date the very marked resemblance which group 
 all the alkaloids into one large class. For 
 whether they be the product of the organs of 
 plants, or elaborated at the expense of the albu- 
 men of animal origin by bacterial action, or the 
 cell-vitality of superior organisms, vegetable al- 
 kalies, ptomaines and leucomaines have the same 
 origin, the proteid materials, and are identical in 
 their genesis ; that is, proteid disintegration. 
 
 It is, in effect, in the molecules of the albu- 
 men that the origin of the alkaloid has to be 
 sought ; it is by processes of molecular simplifi- 
 cation that these ptomaines, these leucomaines 
 are formed, every species of which represents a 
 degree in the retrogressive disassimilation of the 
 
Ii6 
 
 primitive compound. We have observed nu- 
 cleine under the influence of slight acidity giving 
 up the uric compounds, which in their affinities 
 are so closely allied to cyanhydric acid, as 
 Professor Gautier has so ably demonstrated ; 
 and this irrespective of the source of the nu- 
 cleine and the condition of the cells which 
 supply it. But this proteid breaking up is not 
 always accomplished in the manner here indi- 
 cated. According to the recent observation of 
 Kossel, the nucleine of the unhatched fecun- 
 dated egg refuses to split up, and consequently 
 affords neither xanthine, nor hypoxanthine, 
 nor guanine, nor adenine ; the dislocation only 
 takes place by incubation in the hatched egg, in 
 the embryo, and here we touch on one of the 
 most obscure facts of cellular life — fecundation. 
 The action of the spermatozoon upon the egg, 
 however necessary, is not sufficient, it can only 
 operate by favour of incubation. In the same 
 way bacterides at a low temperature may remain 
 in contact with albumen without exciting putre- 
 faction ; in the same way, also, the spermato- 
 zoon may be brought in contact with the egg 
 without formation of the embryo resulting. When 
 incubation raises the temperature, embryonic 
 evolution commences, and the nucleine of the 
 cells undergoes a transformation which renders 
 
117 
 
 it capable of dislocating like putrid albumen, 
 and thus of furnishing those uric leucomaines 
 which we have frequently met with. 
 
 This is an interesting example of the pheno- 
 mena of putrefaction, and those of normal life ; 
 it is also evidence of the part bacteria play in 
 the genesis of the leucomaines. And how sug- 
 gestive also of analogies in the physiology of 
 common life is this. Free expiration of car- 
 bonic acid, for example, would seem, in a great 
 measure, to correspond to the aerobic life of 
 the tissues ; whilst the greater part of the ex- 
 cretive products correspond to their anaerobic 
 life. Is it not alter sleep or perfect repose that 
 the economy is more especially anaerobic, and 
 consumes more oxygen than it receives ? It 
 might give an interesting turn to physiological 
 investigation if we endeavoured to determine 
 the parts of the organisms of the vertebrata in 
 which the functions aerobic and anaerobic are 
 localised. The rapid march on lines more as- 
 sured would seem, however, to render this un- 
 necessary. The various facts acquired prove 
 too definitely the uniformly constant forma- 
 tion of alkaloids in the economy of animals to 
 permit us to assign the elaboration of these 
 leucomaines to a particular category of cells. 
 It is well to note that in the case of the 
 
ii8 
 
 superior animals the preponderant role of cel- 
 lular elements in the production of these bases 
 does not prevent bacterial action in certain 
 organs from resulting in ptomaine formation. 
 The excrementitious products are evidence 
 of this. It is, however, as difficult to trace the 
 mode of operation of bacterides, and the cells 
 of the alimentary or digestive canal in the gene- 
 sis of the intestinal alkaloids, as it is to limit the 
 domain of physiological putrefaction and di- 
 gestion to that ensemble of multiple complex 
 relations which constitute complete digestion. 
 
 From this point of view, and without entering 
 into the broad question of pathology, it may be 
 said that the comportment and origin of animal 
 alkaloids have been misunderstood if it be as- 
 serted that their properties exclude the play of 
 micro-organisms in the history of maladies ; it 
 is pangermic extravagances that are to be con- 
 demned. Contagion, incubation, and the benefit 
 of antiseptic precautions secure for bacterial 
 conceptions, when properly understood, the 
 importance they legitimately claim, and which 
 no scientific mind wishes to deny them. The 
 formation in the economy of animal alkaloids by 
 bacterial and cellular processes unquestionably 
 explains the genesis of many maladies. It does 
 not exclude the role of the infinitely little in the 
 
119 
 
 category of affections admittedly micro-germal, 
 parasitic ; within demonstrable limits it explains 
 and confirms it. In the actual state of science 
 our knowledge of the respective operations of 
 bacterides and leucomaines in the genesis and 
 evolution of disease is necessarily incomplete ; 
 neither the chemistry of the one nor the physi- 
 ology of the other have yet been fully seized. 
 The leucomaines, however, clearly belong to 
 both provinces, and their discovery, origin, and 
 properties suggest comparison with putrid re- 
 action. Comparative study of this point has 
 enabled Gautier to ascertain the fact that 
 four-fifths of our tissues live aerobically ; and 
 that the remaining fifth part, on the contrary, 
 lives anaerobically, that is, after the fashion 
 of putrid ferment. Certain tissue transforma- 
 tions then present the same cellular action as 
 the anaerobic ferments do. Thus, during life, in 
 health and disease, miasmatic or enthetic, toxic 
 alkaloids are elaborated, as also in putrefaction 
 where life has ceased. Under conditions of 
 imperfect oxidation and physiological combus- 
 tion, the natural emunctories, the kidneys and 
 the intestinal canal, evert, by elimination, the 
 risks of disturbance to the organism by the 
 poisonous elements of its own production. 
 
 Thus, from one extremity of the scale of 
 
120 
 
 living things to the other, biological chemistry 
 presents us with a character of unity the most 
 striking. Bacterides and cells of superior or- 
 ganisation may lead the same existence, and ob- 
 serve the same laws, and leave as a residue of 
 their activity the same principles alike toxic for 
 all. Life, according to Gautier, is not bound 
 by any externally anatomic form, much less by 
 the cell and its granules. Life is the conse- 
 quence and the resultant of the mode of aggre- 
 gation, and the mechanical and chemical 
 properties of plasmic materials and their formal 
 parts. They perpetuate and undergo modifica- 
 tion by continuity in transformation of the 
 molecular conditions and the physico-chemical 
 phenomena which take place in these aggrega- 
 tions developed under the influence of similar 
 aggregations pre-existent. 
 
121 
 
 TABLE. 
 
 The following is a list of the principal Animal Alkaloids, 
 which have been submitted to ultimate analysis, arranged 
 according to the classification observed in the foregoing 
 pages : — 
 
 PTOMAINES 
 
 OF CADAVERIC OR PUTREFACTIVE ORIGIN. 
 
 /. N on- oxygenous. 
 
 Parvoline, C9 H^sN 
 Hydro-collidine, H^sN 
 Collidine, HuN 
 Neuridine, H^4N2 
 Cadaverine, Cs H^6N2 
 Putresceine, O H^2N^ 
 Mydaline 
 
 //. Oxygenous. 
 
 Neurine, Cs H^^NO 
 Choline, Cs H^sNO^ 
 Muscarine, Cs H^sNO^ 
 Gadinine, O H^^^O^ 
 
 LEUCOMAINES 
 
 OF VITAL OR PHYSIOLOGICAL ORIGIN. 
 
 /. Uric Group. 
 
 Betaine, Cs H"NO^ 
 
 Carnine, O N4 03 
 
 Adenine, Cs Hs Ns 
 
 Guanine, Cs Ns O 
 
 Sarkine, or Hypoxanthine, Cs H4 O 
 
 Xanthine, Cs H4 N4 
 
 Pseudo-xanthine, C4 Hs Ns O 
 
 //. Kreatinic Group. 
 
 Kreatinine, C4 H7 N3 0 
 Xantho-creatinine, Cs Hi°N4 O 
 Cruso-creatinine, Cs N4 O 
 Amphi-creatinine, C9 H^9N7 04 
 
The Physiological Alkaloids 
 
 OR 
 
 Leucomaines 
 In Relation to Scientific Medicine. 
 
 PART III. 
 
GaTjtier, whose name stands first in connec- 
 tion with the discovery and investigation of the 
 vital alkaloids, has had the courage to approach 
 some problems of physiology and pathology, 
 the most abstruse and complex in their nature. 
 His recent 77iemoire, which abounds in startling 
 inductions, opens up a wide territory that has 
 hitherto escaped investigation. If the indica- 
 tions he submits meet with the attention they 
 deserve, a sweeping reformation may be looked 
 for in our modern medicine. His method of 
 dealing with the questions they involve reminds' 
 us little of pangermic and bacterial theoris- 
 ings ; he takes his stand on data which are posi- 
 tive, precise, and easy of verification. Organic 
 chemistry being a science which is eminehtly 
 exact, investigating minds may therefore very 
 profitably bestow on it a share of the attention 
 
126 
 
 they have hitherto directed so exclusively to 
 bacterial and bacillar biologies. In any case, 
 what is most devoutly to be wished, is, that 
 efforts will be made to hnd how the two theories, 
 apparendy opposed to each other, actually har- 
 monise, and how they mutually complete and 
 complement one another. 
 
 In bringing to the aid of the medicine of 
 the present, the medicine of the past, Peter 
 has also rendered signal services to science. 
 Though the grand time-honoured doctrine 
 has of late lain somewhat in eclipse, he, 
 like many others, knows full well that, from 
 him of ancient Cos to Sir John Forbes, tra- 
 ditional medicine supplies the only glimpse of 
 truth to be met with in Hygeia's dimly-lighted 
 corridors. No one should blink the fact that 
 antiquated humoralism is still a fundamental 
 principle of the healing art, though some have 
 not been told so, and others have forgotten 
 it. Those who are aware of this, and feel 
 ashamed to own it, are to be pitied. As for the 
 judicious who have been dreading recent doc- 
 trinal caprices, they may feel perfectly assured 
 that when the prevailing etiological mania loses 
 its intensity or subsides, it will be found to 
 have been much less revolutionary than was 
 generally supposed. 
 
127 
 
 Since Selmi first called the attention of toxi- 
 cologists to the existence of cadaveric alkaloids, 
 and Gautier ascertained more definitely their 
 characters, the questions they involve have 
 been very much advanced by them and others, 
 Brouardel and Boutmy in* particular. Besides 
 proving the fact that animal tissues in pro- 
 cess of putrefaction and decomposition in- 
 variably elaborate certain alkaloids of power- 
 ful toxetic properties, they and others have 
 had reason to suspect that substances of a poi- 
 sonous nature are variably elaborated in animal 
 tissues, even during life ; and that through the 
 medium of tissue-transformations, or indepen- 
 dently and alone, their action is sufficient to 
 determine specified maladies and death. Thus 
 the exciting and proximate cause of the condi- 
 tions of those under clinical observation pro- 
 mises to become more accessible and available 
 to the practitioner in a numerous class of cases. 
 These suspicions they have to some extent 
 verified. In their hands, analysis of the various 
 secretions and excretions of patients represent- 
 ing a variety of morbid conditions, has led to 
 the detection of substances closely resembling, 
 if not identical with, the alkaloids of putrefac- 
 tion. Subjects suffering from rheumatic tetanus, 
 progressive paralysis, and progressive imbecility, 
 
128 
 
 for example, yielded bases allied to aconitine and 
 conia ; the first, experimentally observed, showed 
 a specific action on the nervous centres, destroy- 
 ing their activity, diminishing general sensibility, 
 the respiration, and the action of the heart. 
 
 But such suggestive data, in part acquired, 
 in part foreseen by others, demanded closer 
 sifting and more reliable adjustrrient, in order 
 to make clear their scientific purport. To 
 Gautier, the eminent French chemist, is en- 
 tirely due the credit of reducing them to a 
 consistent whole, and thus presenting their prac- 
 tical significance in theoretic form. He con- 
 firms the fact that not only after death, but 
 even during life, the animal organism, in accord- 
 ance with physiological chemical processes easy 
 to determine, has the power of elaborating a 
 numerous class of alkaloids ; that these alkaloids 
 — which he calls leucomaines— are essentially 
 toxic in their properties and actions on the 
 economy that gives rise to them ; that an 
 auto-intoxication characterised by hyperthermia, 
 hypothermia and allied morbid phenomena in- 
 dicate the process of their physiological action. 
 Some, with all the force of preconceived ideas, 
 may naturally exclaim, " Well, admitting this to 
 be true, what is to become of the bacterial im- 
 pedimenta with which we have been harnessed ? 
 
129 
 
 These alkaloids we have never heard of!" W ell, 
 we can only reply, that the circumstance is much 
 to be regretted ; that their existence is by no 
 .means a thing of yesterday ; some workers have 
 been familiar both with them and with their 
 probable action for years. But in any case, it is 
 never too late to learn ; and to begin with, all 
 must know that we are busy chemically manu- 
 facturing alkaloids every instant of our lives. As 
 the organism can form alkalies, ammonia for ex- 
 ample — seeing how marvellous are its pharma- 
 ceutical potentialities — why should it surprise 
 us to find it forming alkaloids ? It is only a 
 question of chemical degree. And this most 
 certainly it does, whether the fact we are con- 
 tending for be accepted or rejected. 
 
 This function may certainly be a dangerous 
 one, and might oftener prove fatal than it will 
 be found to do, were it not that the action of 
 its products are ingeniously frustrated and they 
 themselves got rid of in one way or another. 
 Their deleterious manufacture is, in reality, an 
 essential element of life itself. Life is a con- 
 tingent phenomenon, consisting of a series of 
 partial births and partial deaths. It has been 
 said, and truly said, in the midst of life we 
 are in death ; " for, scientifically speaking, it 
 must be admitted that the living body always 
 9 
 
130 
 
 bears with it the components of the dead one. 
 If the organism is to survive, the organic and 
 the inorganic must march hand-in-hand till 
 death severs them. 
 
 It is principles such as these, whether under- 
 stood or not, that sound traditional medicine 
 has always recognised. What Gautier has 
 been showing, and shows so admirably, is 
 simply that the school of the past and the 
 school of the future will be found to mutually 
 support each other, and further, that humor- 
 alism, if you will, so far from being van- 
 quished, has been only stolidly refurbishing its 
 arms and reinspecting its resources ; whilst 
 pangermism has been exhausting its energies 
 in sensational demonstrations of bacterial sur- 
 prises and bacillar blunderings. 
 
 The still more recent memoire of Peter 
 ouofht to make this evident to those who are 
 unshackled and capable of thinking for them- 
 selves. In a passage as remarkable for frank 
 originality as for sound scientific force, he treats 
 us to retrospective glimpses from personal ex- 
 perience, and admirably illustrates the type of 
 mind of those who profit by the current of the 
 day while swimming with it. 
 
 The import of authoritative teachings such as 
 these has neither escaped the attention of the 
 
131 
 
 germ theorists on the one hand, nor of the ad- 
 vocates of the unity of poisons on the other. 
 In Germany the intoxication of the system by 
 substances which are the product of abnormal 
 physiological processes has received the name 
 of Botulism. The classes of cases towards 
 which the observation of clinicists has chiefly 
 been directed hitherto are those exhibiting the 
 symptoms and conditions which Asiatic cholera 
 presents. The patients so affected have all the 
 appearance of toxication, and by the poisonous 
 alkaloids — that is, the vital alkaloids or leuco- 
 maines. The symptoms which usher in the 
 seizure indicate a form of poisoning so ob- 
 viously that the chiefs of the bacillar theory of 
 cholera — Koch to begin with — have been 
 compelled to hesitate and ask themselves 
 whether, after all, some ptomaine or other 
 may not be the specific cause of the chole- 
 raic mischief, while claiming for it a bacillar 
 origin. Klein, it would appear, is clearly of this 
 view. 
 
 Peter has submitted similar facts observed, 
 in order to point out more fully the purely 
 physiological method by which Gautier deals 
 with the problem, which for medicine is of 
 such etiological importance. Gautier, in fact, 
 has clearly shown that four-fifths of our dis- 
 
132 
 
 assimilations are the result of internal economic 
 combustion, and that the remaining fifth is pro- 
 duced at the expense of the tissues themselves. 
 This, in a certain sense, leads us back in the 
 direction of would-be discarded humoralism, 
 because poisoning by a soluble alkaloid is 
 poisoning by blood which has already under- 
 gone decided deterioration. 
 
 We instance cholera as the aptest illustra- 
 tion of this view. Monopolising, as it does, 
 so much scientific interest, it supplies the freest 
 field for airing the respective claims of two 
 pathological theories v/hich for the moment 
 are apparently in mutual opposition. The one 
 bacillar, organic and strictly biological ; the 
 other toxic, inorganic, and strictly biochemical. 
 The first, so high in favour, and with the 
 entire field to itself, has failed egregiously in its 
 assumed solution. The various expeditions — 
 Indian, African, and European — undertaken in 
 bacterio-bacillar interests, have proved as prac- 
 tically hopeless and unprofitable as the dis- 
 covery of a north-east passage to Cathay. By 
 such missions Koch has only added to his 
 hypothetical perplexities, while Klein, with 
 modified appreciations, preserves his germ 
 proclivities, and hopes by veiled, but truly 
 humoralistic concessions, to solve the cholera 
 problem among others. 
 
133 
 
 Taking their stand on the natural history of 
 disease and physiological chemistry, neither 
 Peter nor Gautier are given to speculation. 
 The first observes the course of maladies and 
 the nature of their products. The second 
 demonstrates the bio-chemical data with which 
 they are intimately associated, and only with 
 a prudent caution looks beyond them. The 
 recently discovered ptomaine alkaloids have 
 given us the measure of nature's pharmaceutical 
 potentialities in death ; Gautier, in directing our 
 attention to the more recently discovered leu- 
 comaine alkaloids, has given us the measure of 
 the same potentialities during life ; he demon- 
 strates their toxic properties and the means by 
 which the living organism escapes their dele- 
 terious action, and shows that they will be 
 found to constitute materies morbi as various 
 as the conditions with which they are associated, 
 and that they are the cause of some of the most 
 serious accidents to health that medicine has to 
 fight against or man is liable to suffer from. 
 
 The objects of these comments must now be 
 evident. It is merely to advance those claims 
 which the views of Peter and Gautier, with 
 reference to the causes and nature of disease, 
 have on our acceptance. Our contrasting such 
 claims with those of the advocates of the bac- 
 
134 
 
 terial theories now dominant, may, as a natural 
 result, cause alarm, if not amusement, in many 
 quarters. But those who know that diseases 
 are not entities but processes, concern them- 
 selves but little with time-serving theories ; they 
 are well aware that even where they do perhaps 
 contain a grain of truth, they still form but a 
 part and not the whole in that broad concep- 
 tion of pathology which is at the same moment 
 ever old and ever new. 
 
 Seeing the interest which Gautier's work is 
 likely to give rise to, and how much it is calcu- 
 lated to correct and mitigate the excesses, both 
 in the theory and practice of germ pathology, 
 still in the ascendant, we will now proceed to 
 briefly summarise the work on which Gautier 
 has been so long and arduously engaged, and 
 which promises so much of what our — so-called 
 scientific — medicine stands in very sad need of. 
 
1. 
 
 Physiological and Pathological 
 Significance. 
 
 Generalising his researches, Gautier an- 
 nounced, in 1885, that with the excretions of 
 healthy Hving animals there were substances of 
 the nature of ptomaines almost uniformly pre- 
 sent. He showed that the alkaloids of the 
 urine of Leibrecht and Pouchet ought to be 
 classified with the putrefactive alkaloids then 
 known ; he detected similar alkaloids in the 
 muscular tissues and saliva. To these he gave 
 the name of leucomaines, in order to distin- 
 guish them from ptomaines or cadaveric alka- 
 loids. In another memoire, which he has 
 published since, he pointed out what appeared 
 to him the important relation which these pro- 
 ducts bore to the genesis of maladies, when 
 their elimination by the kidneys, liver, skin, 
 and intestinal mucous membrane was defective 
 or suppressed. 
 
 With a view to confirming these preliminary 
 observations, he took up the study of the sub- 
 
136 
 
 ject, carefully examining the muscular juices of 
 the larger animals. He succeeded in adding to 
 the list five new alkaloids, all perfectly defined, 
 crystallised, and having a specific action on the 
 nervous centres, more or less marked ; inducing 
 somnolence, lassitude, some of them even ex- 
 citing vomiting and purgation — effects similar 
 to those of poisonous alkaloids, but less active 
 than the cadaveric alkaloids. He satisfied him- 
 self of the fact that these bases originate during 
 life as naturally and legitimately as carbonic 
 acid and urea. It only now remained for him 
 to ascertain by what mechanism, or process, 
 those alkaloids originate and assume their de- 
 finite forms and characters ; how they comport 
 themselves in the physiological, pathological, 
 or putrefactive, correlations ; what follows from 
 their incessant formation in the economy ; what 
 becomes of them, and finally, how the organism 
 itself escapes their deleterious effects. In com- 
 mon with previous and contemporary scientists, 
 he found the lines of the enquiry vague and 
 disconnected. Here want of space forbids our 
 following him ; we push on to his conclusions, 
 and nothing in induction can be clearer. 
 
 While profiting by physiological facts ac- 
 quired, and the knowledge that the oxygen of 
 the atmosphere, by means of the respiration 
 
137 
 
 and the circulation of the blood, finds every- 
 where its way throughout the animal organism, 
 he cannot admit, as is generally assumed, that 
 animal life — in other words, the successive 
 phenomena of assimilation and disassimilation 
 of the tissues — consists entirely in this fact. 
 Gautier holds that if the tissue-transformations 
 in inferior animals are almost wholly aerobic, 
 the tissue-transformations of the superior ani- 
 mals are, on the contrary, anaerobic in a notable 
 proportion. According to conclusions hitherto 
 accepted, this looks something like assumption, 
 and seems paradoxical besides, but he carefully 
 attacks the problem, and we think successfully ; 
 the force of his conclusions, whether we regard 
 them practically or theoretically, amount to 
 demonstration. 
 
 Tissue-Transformations in the Superior 
 Animals. — Investigating on the lines here in- 
 dicated, he has been enabled to show experi- 
 mentally, that while four-fifths of our internal 
 combustions are the result of a veritable aerobic 
 process analogous to, if not identical with, 
 the oxydation of alcohol under the influence 
 of mycoderma vini or aceti, the combustions, 
 secretive and excretive that remain — to the 
 extent of one-fifth — are produced at the cost 
 of the tissues themselves, independently and 
 
138 
 
 exclusively of foreign oxygenous intervention ; 
 in other words, that a portion of our living 
 tissues comport themselves precisely as fer- 
 ments a7iaerobic or putrescent do. This point 
 attained, he was naturally led to infer that, if 
 the intimate organic life of such portion of 
 animal tissue of cellular aggregates is inde- 
 pendent of oxygenous supply from atmospheric 
 sources, it resembles the bacterial ferments in 
 the mode and manner of assimilating and dis- 
 assimilating organised material, and we ought to 
 find in the products of secretion and excretion, 
 those substances that are to be met with in an 
 aerobic albumenoid fermentation — that is, the 
 putrefactive fermentations ; and he shows, as a 
 matter of fact, that this is so. In the normal 
 secreta and excreta are to be found the whole 
 of the products of putrefactive processes pro- 
 perly so called — such as carbonic acid and 
 ammonia — in part free, in part in the form of 
 urea, salts, phenol, endol, scatol, of our faecal 
 and urinary excrementa ; the butyric, acetic, and 
 other superior adipose acids ; the lactic, suc- 
 cinic phenylactic acids of our muscular tissues, 
 and in the glandular and renal secretions. In 
 the processes of putrefaction, nitrogen, sulphur- 
 etted and phosphuretted gases, together with 
 the hydrogen of the intestinal canal, are also to 
 
139 
 
 be met with. The identity is consequently 
 complete, or nearly so, and he very logically 
 asks, why ought we not to suspect and be able 
 to detect the presence in the urine, glandular 
 secretions, muscular fibres, &c., of these toxic 
 alkaloids, whose history forms the subject of 
 the remarkable memoire he has recently sub- 
 mitted for the benefit of scientific workers ? 
 
 He has here unmistakeably ascertained their 
 existence in operating in a wide area of ani- 
 mated nature ; venoms, salivas, various glan- 
 dular secretions, those even of the silkworm 
 receiving close examination. Devoting special 
 attention to study of these in relation to the 
 muscular tissues in the blood of man and the 
 mammalia generally, he draws attention to 
 the fact of the perceptible increase and accu- 
 mulation of these alkaloids in the circulation, 
 when from any cause the bowels, kidney, liver, 
 skin, &c., fiag, or become defective in their 
 functional activity. He has further insisted 
 that it is under these circumstances that they 
 are permitted to exert their toxic action on the 
 nervous centres, and so give rise to a great 
 variety of morbid phenomena whose determinate 
 successive development and combination, when 
 considered as a whole, make up the portraiture 
 of particular cases or classes of cases of disease. 
 
140 
 
 For those who give attention to the conser- 
 vative character of" our economic physiological 
 principles, but know little of the organism's 
 liability to perversion and deterioration by its 
 own inherent forces, it will be pleasing to see 
 how Gautier proceeds to show in what way 
 in health a normal balance is preserved, how 
 the body escapes disturbance and disintegra- 
 tion by processes purely auto-infective which 
 are ever ready to declare themselves. 
 
 The Processes by which Auto-intoxica- 
 tion IS Resisted. — Gautier goes on to show 
 that the organism is enabled to resist the in- 
 cessant dangers from auto-intoxication by two 
 distinct methods : first by the separation of the 
 effete toxic elements, and their destruction by 
 oxygenation more or less efficiently. Elimi- 
 nation by the kidneys more particularly betrays 
 this fact, and this he strongly urges, for he 
 has almost invariably found slight traces of 
 ptomaines in the normal urine ; very slight, it is 
 true, some would even deny their presence, but 
 it is attested by others besides himself, as also 
 by the fact that they increase and become 
 considerable in quantity in many pathological 
 conditions. Creatinine, for example, has been 
 extracted in cases of uraemia. Their elimination 
 by the bowels seems to him just as certain ; 
 
141 
 
 though here, by reason of the difficulties of ex- 
 amination, it is less capable of demonstration. 
 
 The process which enables the economy to 
 resist auto-intoxication from the alkaloids, and 
 which he holds to be more powerful than eli- 
 mination, is their incessant combustion in 
 contact with the oxygen of the blood. For the 
 most part, those deleterious compounds are 
 markedly oxydizable, and it is under the vivi- 
 fying influence of the incessantly maintained 
 supply of oxygen that they consume themselves 
 and disappear, at least in part, facts which 
 sufficiently explain why — under normal condi- 
 tions — only traces of the muscular leucomaines 
 are already detected in the urines ; in large 
 proportion they having undergone combustion 
 in the current of the circulation, if not in the 
 tissues themselves. 
 
 In any case, if from any cause whatever the 
 free and normal aeration of the blood is inter- 
 fered with, or materially diminished, Gautier 
 has always found the quantity of haemoglobine 
 decreased, as in anaemia and chlorosis, and 
 should there be introduced into the blood, sub- 
 stances which interfere with the hcematose or 
 blood formation, immediately materials of the 
 ptomaine and leucomaine order are generally 
 found accompanying them. The appearance of 
 
142 
 
 the allantoine in the urine of dogs, whose 
 means of respiration has been gradually re- 
 duced — according to Frerichs and Stadeler — 
 and the reality of asphyxic glycemia — accord- 
 ing to Daster — is evidence of the fact. 
 
 The Practical Bearings of the Subject 
 ON Medicine. — The physiological researches 
 of Gautier as a chemist — fortunately for us — 
 have taken a most important direction. Both 
 as regards their special application to pathology 
 and practical medicine, it is impossible to ignore 
 the great value of his work to medical science. 
 Labours in this direction have been consider- 
 able but far from exact. Gautier's contribution 
 will do much to remedy our position, and afford 
 an explanation of the morbid phenomena we 
 are daily called upon to deal with, and yet 
 know but little of essentially. As examples of 
 this take the nervous disturbances associated 
 with anaemia, chlorosis, pregnancy, and the 
 beneficial effects derived in such cases from the 
 inhalation of pure air. Oxygen, for instance, is 
 often the sole means known for combating effec- 
 tually the persistent vomiting which arises from 
 the retention of imperfectly burnt, or imperfectly 
 eliminated, materials in the tissues or the blood. 
 Again, is it not admissible for us to ask whether 
 fever itself — which is coincident with the 
 
143 
 
 smallest alimentary consumption, and an inverse 
 proportional increase of carbonic acid eliminated 
 and of oxygen consumed, with acceleration of 
 the circulation to boot — may not have for its 
 physiological aim and object the destruction of 
 these deleterious substances which, under cer- 
 tain conditions, are formed, or form themselves 
 so abundantly in the economy ? 
 
 Thus far it has been no small pleasure to 
 follow Gautier in his lucid inductions. And 
 much averse as he is to venturing beyond the 
 limits justified by a judicious scientific spirit of 
 inquiry, based on data that are positively re- 
 liable, it only remains for us to acknowledge 
 that to him belongs the largest share of merit 
 in having indicated — without deducting all the 
 pathological and therapeutic consequences legi- 
 timately available — the principles of those bene- 
 ficent agencies which excite the functions of 
 the kidneys, skin, and intestinal mucous mem- 
 brane, and, what is still more important, the 
 necessity of the constant disinfection of the 
 economy by all that promotes the processes of 
 respiration, and hceinatose, in other words, re- 
 newal of the healthy blood. 
 
 It only remains to be added that the work of 
 Gautier is not yet completed. He feels con- 
 vinced that however actively poisonous to the 
 
144 
 
 animal economy the alkaloids we have been deal- 
 ing with may be, there exist azotised substances 
 non-alkaloidal w^hich accompany them, and are 
 endowed with activities still more remarkable. 
 He points out that Panum's septic poison con- 
 tains little or no alkaloid ; that the extractive 
 and crystallisable matters are extremely toxic : 
 furthermore, the essentially active principle of 
 the venom of snakes he believes is nitrogenous 
 but not alkaloidal. These substances are in 
 other respects more important quantitatively 
 than the ptomaines and the leucomaines oxy- 
 disable and azotised like them, and require that 
 they should be studied still more closely than 
 they have yet been. He expresses the firm 
 conviction that their investigation will prove 
 one of the most instructive sources reserved 
 for the medicine of the future. 
 
11. 
 
 A New Departure in Pathology. 
 
 In his recent Md moire Peter affirms that his 
 object is to draw upon traditional medicine in 
 confirmation of the medicine of the future. In 
 other words, he desires to advance the facts 
 of observation in support of the beautiful re- 
 searches with which Gautier is now enriching 
 medicine as a science. These researches, apart 
 from their chemical and medico-legal value, he 
 affirms, have the important merit of confirming 
 what we already know of the intoxication of the 
 animal economy with its own products ; whilst, 
 at the same time, they add to our previous 
 knowledge and to pathological investigation a 
 greater degree of method and precision. 
 
 But what are really the terms of the ques- 
 tions involved ? 
 
 Gautier informs us that in dead animal tissues 
 undergoing the process of putrefactive decom- 
 position, there are elaborated the alkoloids 
 which Selmi called ptomaines. He further in- 
 
 lO 
 
146 
 
 forms us that in the living animal tissues, and 
 by virtue of their vitality, there are elaborated 
 alkaloids which are analogous to these. Some 
 of these he has discovered, and he names them 
 leucomaines. This is not all ; he has ascer- 
 tained that in the living animal economy there 
 are also elaborated azotised uncrystallisable 
 substances which are still undetermined, and 
 which are the extractive matters. In addition 
 to this, we are assured that if the ptomaines 
 are toxic, the leucomaines are also toxic, and 
 that the extractive matters are more toxic than 
 either. 
 
 So much for the chemical aspect of the ques- 
 tion. Now comes the clinical one. 
 
 Here he has unquestionably discovered that 
 according to the different sources of intoxication, 
 there is a corresponding indication. Intoxica- 
 tion by the extractive matters is accompanied 
 by hyperthermia, whilst intoxication by the 
 animal alkaloids is accompanied by hypother- 
 mia ; that in the living organism a variation 
 or succession of extremes in temperature may 
 manifest itself, according to the combination or 
 alternation of poisonings by these deleterious 
 physiological products. But what is of addi- 
 tional interest, and must be gratifying to many 
 to learn in connection with Gautier's re- 
 
147 
 
 searches, is the fact of their emancipating us 
 from the tyranny of micro-germism. They ex- 
 plain the formation of poisonous alkaloids and 
 still more poisonous extractive matters,by means 
 alone of the physiological processes continually 
 at work. He discloses the fact that in auto-in- 
 toxication, the spontaneous or self-infection of the 
 living organism by the alkoloids and extractive 
 matters, there is, by reason of their essentially 
 normal physiological origin, no question of 
 quality but simply one of quantity to be con- 
 sidered ; that, in other words, the healthy living 
 organism may become poisoned by the ac- 
 cumulation within itself of deleterious sub- 
 stances normally elaborated but imperfectly or 
 defectively eliminated. 
 
 The important question then presents itself — 
 in what way does auto-intoxication or spontan- 
 eous infection of the economy take place ? And 
 here a word or two regarding life may not be 
 superfluous or out of place. Life Gautier 
 regards as a phenomenon essentially relative 
 and contingent ; it is a series of partial deaths ; 
 the organism only lives on condition of inces- 
 sant elementary disintegration ; we bear about 
 with us, within us, the effete dSbris of our living 
 selves. That phase of it called health is a phe- 
 nomenon quite as relative and contingent, and 
 
148 
 
 may be regarded as life's equilibrium between 
 organic good and evil. Normal health is con- 
 ditional on an incessant transformation and 
 elimination of the effete or old organic material 
 which has to give place to renewal by the new. 
 Nervous. phenomena, central or peripheral, may 
 modify the phenomena and so complicate the 
 fact, but nothing can do away wath it. 
 
 The series of partial deaths which constitute 
 life is the result of organic functional operations. 
 When thought is evolved the brain generates 
 heat, and the material product of the cerebral 
 action is neurine, an alkaloid prejudicial to 
 normal life ; when movement is exerted heat is 
 evolved, and the material result of muscular 
 action is the creatine, creatinine, and still other 
 alkaloid congeners, which Gautier proves to 
 be equally prejudicial to the health of life. The 
 tissues and organs perform a function of dis- 
 integration, and in the process they fabricate 
 those alkaloids and extractive matters which 
 must be regarded as veritable scoria, resulting 
 in the processes of physiological combustion of 
 the elements of the organic tissues. The 
 organism is always dying, and, strange as the 
 paradox may sound, could not live unless it 
 died. We thus perceive how precarious a con- 
 dition is that which we call health, and why, by 
 
149 
 
 the modifications of the organism in vital 
 activity, disorder or disease may manifest itself 
 in consequence of the simple accumulation of 
 cadaveric materials. 
 
 It has been clearly shown, and must now be 
 freely accepted, that the animal alkaloids are 
 a necessary product of vital physiological pro- 
 cesses ; this is both synthetically and analytic- 
 ally proved by Peter and Gautier, who press 
 the important fact with all its consequences 
 on our attention. In 1881 Gautier announced 
 that there were to be detected in the excre- 
 tions of living animals in good sound health, 
 as well as during disease, substances of the 
 nature of ptomaines. Since then he has 
 abundantly confirmed the fact, and further 
 announced that about four-fifths of our disas- 
 similations are the result of veritable internal 
 combustions, aerobic transformations compar- 
 able to the oxydation of alcohol under the in- 
 fluence of mycoderma vini or aceti, and that the 
 remaining fifth of the disassimilations are formed 
 at the expense of the living tissues themselves, 
 free of all demands on foreign oxygen ; in a 
 word, that a fifth part of our tissues live after 
 the manner of ferments anaerobic or putrefac- 
 tive. Confronted with these facts, and studying 
 their organo-chemical bearings, he was naturally 
 
ISO 
 
 forced to infer that if the essential life of that 
 portion of the animal cells grouped in tissues 
 and living without oxygen derivable from at- 
 mospheric sources, is analogous to the bacterial 
 ferments in the mode by which it assimilates 
 and disassimilates the organic elementary ma- 
 terial, we ought to be able to detect in the 
 animal secretions the substances themselves 
 which characterise and constantly accompany 
 anaerobic fermentation of the albumenoids, and 
 this Gautier was happily enabled to demon- 
 strate to be really the case. 
 
 All this should not surprise us. If the 
 animal economy is not purely a chemical ap- 
 paratus, it is far less a fermentating vat. It 
 therefore requires no imaginative license to 
 conceive of alkaloids being formed within the 
 living organism and independent of bacterial 
 fermentation, though somewhat resembling it. 
 Do we not every instant of our lives, and quite 
 normally, elaborate acids and bases, not merely 
 carbonic acid, but uric acid Uric acid is a 
 product of animal life, and one which is incon- 
 ceivable apart from it. Do we not spon- 
 taneously and normally fabricate bases such as 
 urea, which can combine with azotic and oxalic 
 acid, and which, by simply splitting up chemi- 
 cally, may go to the formation of carbonate of 
 
151 
 
 ammonia? Such being the case, why then 
 should we not admit that the Hving organism — 
 which by virtue of vital activities, by means of 
 the living and acting cells, and in the absence 
 of all bacterial intervention, is capable of fabri- 
 cating urea — is also capable of fabricating 
 various alkaloids ? That which might seem a 
 priori evident, is now bio-chemically proved to 
 demonstration. Undoubtedly it is in conse- 
 quence of the splitting up of disassimilations, 
 brought about at the expense of the tissues 
 themselves, and in contact with oxygen, that all 
 the disintegrative phenomena are accomplished 
 in the animal economy, and by the physiological 
 activities of animal cellules grouped in tissues. 
 
 According to Gautier, we resist auto-intoxica- 
 tion by two modes or mechanisms — by the 
 elimination of the toxic products, and by their 
 destruction by oxygenation. Elimination is 
 accomplished by the kidneys and the liver. As 
 to their destruction, this consists in a continuous 
 combustion of the leucomaines by the oxygen 
 of the blood ; the leucomaines are there burnt, 
 consumed in the circulatory current, and it may 
 be, partially in the tissues. 
 
 Accumulation may take place under two 
 widely different conditions ; as when there is 
 excess of extractive matters and alkaloids, with 
 
152 
 
 normal but inadequate emunction, or when the 
 production of deleterious materials is normal, 
 but emunction insufficient, the emunctories 
 being diseased or deranged. 
 
 Gautier affirms that auto-intoxication may 
 thus result from excessive production and in- 
 efficient emunction — the emunctories however 
 remaining sound. Peter teaches that this is 
 what we observe in physical over-taxation, 
 over-exertion, a condition which he graphically 
 illustrates : It was in 1852," says he, "when 
 entering on my clinical studies, and ardent in 
 my attendance in the clinique of Chomel, I was 
 witness of the following instance : A young 
 man was received under the celebrated pro- 
 fessor's charge, suffering from prostration, 
 muscular pain, and rachialgia. Chomel made 
 the examination with all the care and attention 
 usual with him, then, as also usual with him, in 
 the presence of the patient, he gave the diag- 
 nosis in Latin, which was — atit febris peyerica^aut 
 variola incipiens — it is either typhoid fever, or 
 incipient small-pox. I felt rather dissatisfied to 
 hear a diagnosis so little precise pronounced by 
 one so eminent in his art, and yet how very 
 correct was he in this. The truth of the matter 
 was, though Chomel was not aware of it, this 
 young fellow, in a state of destitution, had 
 
153 
 
 walked from Compiegne to Paris, sleeping by 
 the way-side at night and nourishing himself 
 with such refuse food as chance supplied. 
 
 " It was under such circumstances the patient 
 had developed febrile symptoms. The day 
 after his admission, and simply from rest in 
 bed, he felt better, and the day following he 
 was altogether well. Simple rest had enabled 
 the muscular system, and economy generally, to 
 rid itself of the proteid embarrassment resulting 
 from the functional combustion of the tissues. 
 His ailment was merely the fever of over- 
 taxation, brought on by the accurnulation in the 
 system of material elaborated in excess, and 
 consequently inefficiently eliminated ; the tem- 
 porary poisoning of the system had lit up the 
 fever of prostration. So much for the hesitating 
 diagnosis, /edris peyerica ; muscular and nervous 
 pain expressed itself in rachialgia, so much for 
 variola incipiens included in the same. Now 
 supposing that in this given case, the elabora- 
 tion of extractive matters and alkaloids we take 
 to have been as ten, and the eliminated as 
 eight, we have a storing up of two. But sup- 
 posing, on the other hand, that instead of 
 walking from Compiegne to Paris in two days, 
 the patient had walked from Marseilles to Paris 
 in twenty,- instead of storing up twice two he 
 
154 
 
 would have stored up twice twenty, and conse- 
 quently instead of a simple attack of toxic 
 over-exertion, auto-infective fever of short 
 duration, he might have suffered from febrile 
 intoxication, more complete, more persistent, 
 and more serious ; he would in all probability 
 have developed the typhus of the soldier on a 
 harassing march." 
 
 It is in this way, making due allowance for 
 massing of men in large bodies, that the typhus 
 of armies originates and spreads. In this case 
 there is a co-operation of auto-typhusation with 
 hetero-typhusation. For those who are in the 
 position of observing and appreciating such 
 facts, says he, it is scarcely possible to escape 
 the conviction that there exists a morbid series, 
 which is as natural as it is evident, leading from 
 the simple form of fatigue-fever to that of 
 typhus, w^hich is the highest expression of the 
 poisoning of the organism by itself, or by 
 contact with others under conditions such as 
 now referred to. It is consequently something 
 like an absurdity to introduce micro-germs into 
 the question. The specific microbe has yet to 
 be discovered. It requires, he thinks, no such 
 flight of fancy as to suppose microphytes way- 
 laying armies on the march, and no such dream 
 of rank and file conveying them in their haver- 
 sacks or cartridge boxes. 
 
155 
 
 For the military medical officer who has seen 
 this form of typhusation develop itself, its origin 
 is not to be doubted ; it accompanies prolonged 
 fatigue, over-crowding, and privation generally. 
 He would no more question it appearing spon- 
 taneously than he would its being contagious, 
 and as this is based on observation also, he is 
 forced to admit the view, apparently irreconcil- 
 able, of spontaneity and contagiousness. What 
 is true of fatigue fever and typhus fever is 
 equally true of typhoid fever, in the spontaneity 
 of which all physicians of a certain age who 
 have had opportunities of observing it exten- 
 sively, are convinced. Does this imply its non- 
 contagiousness, or that a spontaneous attack of 
 A may not be communicable to B ? On the 
 contrary, all know it to be very contagious : 
 whether it have as its agent of transmission the 
 bacillus of Eberth, displaced by that of Gohky 
 and Artaud, and this in turn to be displaced by 
 some other future bacteride, matters little. 
 
 What Peter insists on chiefly is the existence 
 of a natural typhoid morbid series, in which or- 
 dinary typhoid fever stands between the simple 
 fever of over-taxation and typhus properly so- 
 called. He tells us that when occupying the 
 chair of medicine for Gresolle at the Faculty 
 of Medicine, in 1869, he taught the doctrine of 
 
156 
 
 auto-typhusation, using this term to clearly de- 
 fine the nature of the accidents, the principal 
 of which are in all cases hyperthermia, innerva- 
 tion and haemorrhages. In his Clinique Mddi- 
 cale, he points out that typhus may arise in 
 various ways, and illustrates the question by 
 its appearance in the navy, army, prison, and 
 hospital establishments. Under such condi- 
 tions there is unquestionably inhalation of mor- 
 bific matter, organic emanations, productive of 
 typhoid vitiations. But what does it matter, 
 he asks, whether morbific matter finds its way 
 into the organism from without, or whether it 
 is elaborated from within ? The individual 
 suffering from attack is none the less contamin- 
 ated because he is self contaminated, and this is 
 what Peter calls auto-typhusation, no matter 
 what the form may be. Should functional dis- 
 turbance cause difference in some respects from 
 typhus of a given type, difference in morbid 
 phenomena will depend largely on the various 
 toxic elements in the blood, and here must be 
 sought the explanation of the modifications of the 
 distinctive forms, putrescent, cerebro-spinal, bil- 
 iary, atheramic, or uraemic. The etilogical factor 
 extends to all the typhoid morbid series in all 
 such maladies ; he insists on the presence of an 
 animal poison of cadaveric nature in the living 
 
157 
 
 organism, either communicated from without or 
 originating from within, but not eHminated — an 
 organic product so highly prejudicial to life that 
 it disturbs the vital activities of the living organ- 
 isms with which it comes in contact, and this 
 quality is what constitutes infection. The sys- 
 tematic expression common to the etiological 
 factor is the stupor, ruc^o?, typhus. Again, the 
 difference in species of the animal poison consti- 
 tutes the difference of the typhus in such a way 
 that in every form dependent on this cause we 
 observe facts of innervation, but in each form 
 presenting something specifically different. In 
 the common and ordinary form the dominant 
 nervous factor is the delirium ; in the cerebro- 
 spinal it is the tetaniform ; in the typhoid it is 
 the coma and delirium ; in the biliary or chole- 
 mic the delirium and convulsion; in the uraemic 
 it is the coma and convulsions, that is to say, the 
 eclampsia. Nor must we omit that the other 
 pathological factor, haemorrhage, is conmion to 
 all the typhoid series ; of their association from 
 the simplest form of epistaxis to melaena it is 
 needless to be reminded. 
 
 Inefficient elimination while the emunctories 
 are sound is only one aspect of the question ; but 
 supposing the emunctories are diseased, suppos- 
 ing the kidney in particular permits of percola- 
 
158 
 
 tion of the serum of the blood, its albumen, then 
 we observe another series of accidents embraced 
 under the term uraemia, and which to Peter 
 constitutes typhusation, for in proportion as the 
 cypher of albumen increases in the urine, that 
 of urea and extracted matters diminish ; that is 
 to say, the non-eliminated extractive material 
 retained increases in the blood. This Ouin- 
 quand has abundantly demonstrated. Nothing 
 is more simple ; in replying on the data which 
 explain the clinical facts in appearance contra- 
 dictory — that is, that in certain cases of uraemia 
 there is to be observed an elevation of tempera- 
 ture, and that in certain other cases the tem- 
 perature is sometimes stationary, at others it 
 falls — nothing is easier of comprehension than 
 that if there is an accumulation of extractive 
 matter in the blood we detect hyperther- 
 mia ; if there is accumulation of the alkaloids, 
 there is, on the other hand, hypothermia ; but 
 should the two factors co-exist they neutralise 
 each other, and the temperature remains sta- 
 tionary. Let one or other turn the scale, and 
 immediately a thermometric variation may be 
 noted. Add to this the typhoid accompani- 
 ments, perturbation of the nervous system and 
 haemorrhagic accidents. If, again, it is the liver 
 which is the seat of the functional disturbance, 
 
159 
 
 or is so structurally affected that elimination is 
 incomplete, and that there is cholemic typhusa- 
 tion, then we shall have also elevation of tem- 
 perature, innervation, haemorrhage, and disorders 
 the most varied and serious. 
 
 Here it is my duty to mention the indepen- 
 dent views of Professor Ravilliod on this sub- 
 ject. He described under the name of extra- 
 tihemie the numerous cases of over-taxation, 
 fatigue, fever. Now what is curious is that 
 sometimes the patients present the symptoms 
 of typhoid fever, sometimes those of endocar- 
 ditis, and sometimes even those of acute albu- 
 minuria ; that is to say, that there is present, in 
 sketch or outline as it were, the types of the 
 morbid series of which I have spoken. And 
 what is not less interesting in the close and 
 precise observation of Professor Ravilliod, is 
 the fact that recovery, when it takes place, does 
 so in consequence of veritable breaking up and 
 rout of the urates and probably the extractive 
 matters ; that is to say, that ailments cease by 
 a disembarrassment of the organism. 
 
 What Peter chiefly insists upon is that here 
 clinics and biochemics are in accord in show- 
 ing that the morbid accidents are the effects 
 of the same cause — which is auto-typhusation. 
 
 I shall now briefly deal with the question of 
 
i6o 
 
 intoxication by the alkaloids, that is to say, 
 those cases in which hypothermia is present. 
 In Germany it is known by the term botulism, a 
 form of poisoning of the organism observed to 
 result from the ingestion of putrefying meats, 
 pork sausages in particular. 
 
 What in reality are aliments of flesh or meat 
 origin if they are not dead animal material ? 
 If fresh they are wholesome, if in process of 
 putrefaction they cease to be so — why, and in 
 what way, both Selmi and Armand Gautier 
 have made known to us. It is by reason of 
 their containing cadaveric alkaloids — the pto- 
 maines. This being the case poisoning ex- 
 hibits itself in the form of cholera, by diarrhoea, 
 vomiting, cramps, algidity, &c. This is evi- 
 dently induced by the ptomaines which have 
 been elaborated in the articles of animal diet in 
 a progressive state of decomposition. Poisoning 
 of the kind has been observed in France as 
 elsewhere. It will suffice to" mention that case 
 in which the scientific penetration of Peter's 
 colleague, Brouardel, was so happily verified. 
 A whole family presented symptoms of poison- 
 ing; a crime was suspected. There was nothing 
 of the kind however. It was simply a case of 
 poisoning, the consequence of indulgence at a 
 family fete in stuffed goose, but stuffed goose 
 
i6i 
 
 too far gone, too high. Brouardel and Boutmy 
 both detected analytically the presence of cada- 
 veric alkaloids, the ptomaines of putrefaction, in 
 the ddbris and ingesta. 
 
 In all such cases there is hypothermia, pre- 
 cisely as is to be observed in ordinary poison- 
 ing by tartar-emetic or arsenic. In cholera, 
 which presents such close analogies, the same is 
 manifest ; diminished temperature, algidity, ac- 
 companying digestive troubles — all play a pro- 
 minent role throughout. Who will not admit 
 in those affections poisoning by a toxic alka- 
 loid, alkaloid of putrefaction, — or refuse to 
 see that nutritive ingesta may give rise to the 
 formation of toxic alkaloids ? Whether the 
 alkaloids are produced or administered may 
 involve a question not always easy to decide, 
 but in either case there can be little doubt as to 
 the choleraic nature of the poisoning. Guided 
 by facts such as these, it requires no specula- 
 tive or scientific licence to conceive, for we can 
 actually trace a morbid series of a very natural 
 order leading from botulism to Asiatic cholera. 
 We are, in fact, justified in holding that there 
 are in pathology morbid series, as legitimate as 
 those observed in chemistry, geology, palaeon- 
 tology, or botany. Nature does not proceed by 
 leaps but by gradations ; she proceeds from the 
 1 1 
 
1 62 
 
 simpler term to the more complex ; each having 
 an existence of its own, but presenting in its 
 terms antecedent and succedent analogies, 
 which are the bonds of union in the series, 
 while each preserves its stamp of individuality. 
 
 It is a pleasure to note, in closing these re- 
 marks, that Gautier has approached these pro- 
 blems of life not only as a chemist but as a 
 physiologist ; what is more, he has given pro- 
 minence to the fact that the animal alkaloids can 
 be elaborated by the spontaneous physiological 
 processes of life. It is very apparent that we 
 have in this view a partial return to humoralism, 
 poisoning by soluble alkaloids being in reality 
 nothing short of poisoning by an organic liquid 
 which has undergone change, in a word, de- 
 terioration, and, that this spontaneity goes on 
 in 'health as it does in disease is equally es- 
 tablished by the chemical demonstrations of 
 Gautier, and the chemical observations of Peter. 
 
 A few words in conclusion. Scientific missions 
 inspired in the interests of germ pathology have 
 visited Egypt, India, and Southern Europe, in 
 the quest of a specific microbe ; they have sig- 
 nally failed. Dr. Koch, the leader of one of 
 them, thought he had found the pathogermic 
 entity, but confronted and constrained by 
 facts, the learned bacteriologist has felt himself 
 
i63 
 
 obliged to admit that the said bacillus does not 
 directly engender cholera, that it can only do 
 so indirectly and by the intervention of a 
 ptomaine which it secretes. But this implies 
 two suppositions : firstly, the existence of the 
 specific bacillus which Koch has not discovered ; 
 secondly, the supposition of the secretion of the 
 ptomaine by that bacillus which Koch is just 
 as far from discovering. 
 
 Hypothetical assumptions may easily be 
 carried too far. Something simpler and more 
 evident is needed to justify the theorising mania, 
 The German physician, Koch, assumes ; the 
 French physician, Gautier, demonstrates ; he 
 shows the spontaneous elaboration of the 
 ptomaine-leucomaines in the living organism, 
 — demonstrates the formation of these leuco- 
 maines by the splitting up of disassimilations, 
 — demonstrates that these chemical divisions 
 are accomplished by the vital processes of the 
 living cells ; that these processes are peculiar 
 to the living organism and altogether in- 
 dependent of the intervention of vegeto-micro- 
 organisms ; Gautier also demonstrates their 
 toxicity and the mechanism chemico-dynamical 
 by which the healthy organism escapes intoxica- 
 tion and disease. Can the medical mind hence- 
 forth hesitate between pangermic doctrines 
 
i64 
 
 bolstered up by hazy, vague hypotheses, and the 
 doctrines we are maintaining, which are clear 
 and precise, and which explain the phenomena 
 of life, normal and abnormal, by life itself in 
 action ? Obviously not. Let us now proceed a 
 little farther, that what is here evident, may 
 become self-evident. 
 
Auto- 1 ntoxication 
 In Disease. 
 
 PART IV. 
 
If the student interested in pathology, and 
 more particularly pathogenesis, may well ex- 
 claim — Where are we now? — the practitioner of 
 thirty years' experience may safely assure him- 
 self that we are pretty much where we were be- 
 fore. The speculative gropings of the period 
 above-mentioned may have added some brilliant 
 pages to the romance of medicine, but very 
 little to our knowledge of disease and still less 
 to its alleviation or cure. It must now be 
 evident to many thinking minds that the so- 
 called scientific method in medicine is no 
 substitute for judicious observation, seeing that 
 mathematical accuracy is out of the question. 
 Precision in medicine is possible only in the 
 direction of the fact realised — that is to say, 
 in the evidence of physical alterations of living 
 substance, as seen in lesion and its signs. As 
 to the morbid act, that is to say, disease in its 
 evolution, it escapes all efforts at precision, for 
 the simple reason that the act which is the 
 to be is always subordinate to the vitality of 
 
i68 
 
 the organism affected, and so necessarily de- 
 pendent on the forces of that organism and 
 infinitely variable as these forces themselves. 
 
 Chiefly due to Lcennec, instrumentation has 
 gradually usurped the place of observation and 
 the unaided senses. The stethoscope has sug- 
 gested the still increasing list of scopes, and 
 the microscope has long been thought essential 
 in the autopsy of the living as well as of the 
 dead body wherever morbid results, processes, 
 or even causes are in question. The ex- 
 amination of all that is physical in the 
 phenomena of life is doubtless of much im- 
 portance in pathology ; mathematical precision 
 may even be desirable, but only, be it observed, 
 where precision is possible, that is, in the 
 domain of the physio-chemical phenomena of 
 life, in the domain of accomplished facts. In 
 the order of dynamical processes it cannot be 
 reckoned on. In medicine the danger which 
 it threatens is a disregard of clinical obser- 
 vation. The undue study of lesion is liable 
 to lead us to lose sight of the patient, and 
 to indulge in estimates, illusory and incomplete, 
 and of the malady as a whole from which the 
 patient may be suffering. It is the living 
 organism as a whole reacting on itself that 
 we chiefly have to deal with in disease. 
 
169 
 
 This great guiding principle has been lost 
 sight of. The change of method has led to 
 change of doctrines, and wondrous is the his- 
 tory thereof. The generalisers of disease be- 
 came localisers of disease, and now we witness 
 another transformation, wherein ardent sup- 
 porters of localisation are becoming equally 
 ardent for generalisation. Having con- 
 fined a given malady to a given organ, then 
 to some part of its parenchyma and later to 
 its elementary cells, they have finally displaced 
 it altogether and find in the alien microbe the 
 cause and essence of the morbid evil. For 
 example, pneumonia which used to be regarded 
 as a general affection with a local pulmonary 
 manifestation, became in the hands of the pre- 
 cisian pure inflammation of the lungs, a disease 
 of plastic exudation. Histology, triumphant 
 for a time, cellular caprices monopolised the 
 attention ; finally the morbid micro-germ 
 found favour and the pneumono-coccus was 
 discovered. But anatomical pathology, ana- 
 tomical histology and bacillography do not 
 exhaust the phases of the study of this illus- 
 trative malady. For some reason or other 
 the pneumo-coccus is not permanent, not pa- 
 thognomonic of pneumonia. It would appear 
 that the pneumono-coccus may become an 
 
I/O 
 
 endocardo-coccus in endo-carditis, or a me- 
 ningo-coccus in meningitis ; thus it loses all 
 claim to specificity, and now we are in 
 the presence of another transformation ; from 
 humoralism we have passed to solidism, from 
 solidism we return again to humoralism, and 
 the microbe is only the connecting link. The 
 first authorities, Pasteur, Koch and Brieger 
 are now convinced that the cocci, as we have 
 already pointed out, are not dangerous in 
 themselves, but only through certain delete- 
 rious matters which they give rise to in the 
 animal economy. 
 
 Investigation is now in the direction of the 
 animal alkaloids and their effects. The re- 
 searches of Brieger have most important bear- 
 ings on the subject. His recent work abounds 
 in views and facts, which to some extent were 
 utilised in our first edition. The author en- 
 deA.vours to demonstrate the great importance 
 of the relations that exist between the three 
 orders of study, microbes, ptomaines and 
 maladies, supporting them by a series of in- 
 vestigation rigorously carried out according to 
 methods of his own, and exposes the fact that 
 microbes have the property in the course of 
 action of forming nitrogenous bases of chemical 
 species perfectly defined, and he then proceeds 
 
i;i 
 
 to show that these alkaloids, even in the minutest 
 quantities, are capable of giving rise to disorders 
 more or less serious, and even to death itself — 
 disturbances which frequently present relations 
 analogous to those observed in the course of 
 well-known infectious and other maladies. Re- 
 searches on these lines Brieger has applied to 
 septicaemia, where the tendency is in our day to 
 award the preponderant role to chemical phe- 
 nomena accompanying bacterial invasion. 
 
 Leading theorists loudly attribute to microbes 
 the power, very enigmatical, of engendering 
 maladies, but until now imperfect chemical 
 processes have been employed with a view to 
 clearing up the mystery that envelops these pa- 
 thological properties. The subject is, however, 
 of the highest importance to the clinicist, as indi- 
 cated by the morbid phenomena which present 
 themselves in the course of experiment. Ab- 
 normal temperatures, functional arrest, weaken- 
 ing of the mental faculties, disturbance of the 
 most important acts of nutrition and digestion 
 — all force us to admit that in morbid condi- 
 tions the organism is profoundly affected by 
 abnormal chemical activities. Brieger points 
 out, for instance, that the organism attacked 
 with septicaemia is the theatre of chemical phe- 
 nomena of an order very different from that 
 
172 
 
 which exist in the healthy state. He finds 
 very striking evidence of this in the increase 
 of phenol eliminated in the case of certain 
 infectious maladies, such as diphtheria, ery- 
 sipelas, pyemia, and scarlatina, but at the same 
 time repudiates the hypothesis based on in- 
 testinal putrefaction, which was admitted in 
 cases of such maladies ; and he confirms the 
 fact that typhoid maladies, whether abdominal 
 or recurrent, develop themselves without in- 
 crease of phenol in the urines, irrespective of 
 relaxation or constipation of the bowels. He 
 further shows that in the greater number of 
 cases of scarlatina observed by him this pro- 
 duct increased during the period of the erup- 
 tion, whilst, on the contrary, it decreased in 
 the corresponding period in the case of 
 measles. Yet we know the close resemblance 
 of these maladies. He observed the same in 
 erysipelas and pneumonia, and thinks it to be 
 therefore erroneous to suppose that intestinal 
 fermentation plays a part in, or has anything to 
 do with the matter. Thus it follows that the 
 marked augmentation of the normal products 
 of elimination which accompany infectious 
 maladies justifies the conclusion that there are 
 parallel gradations of consecutive chemical 
 phenomena going on — processes of infection — = 
 and which are certainly not putrefactive. 
 
173 
 
 It follows that the figured species of the 
 cocci, bacilli and the rest are now of little con- 
 sequence ; it is the physio-chemical processes 
 which they initiate that is all-important in the 
 problem. The microbes are now discovered to 
 be merely the porters, the carriers of disease, in 
 infection. But how they act under the new con- 
 ditions is the question. Formerly they were 
 supposed to act mechanically on the mass, by 
 emboli, &c., or traumatically by destruction 
 of the living cells or organs by some more 
 delicate physio-chemical action, as depriving the 
 hsemoglobine of its oxygen and thus causing 
 asphyxia ; but according to each hypothesis the 
 microbes acted per se. Now all is changed. 
 Leading bacillographers admit that it is not the 
 bacilli but the animal alkaloids which their 
 action gives rise to, or genders, and these in turn 
 become the object of research. The cultiva- 
 tion liquids of the particular form of bacilli 
 associated with all these particular maladies 
 specified now undergo chemical investigation 
 with a view to the detection of the alkaloidal 
 poisons, and apparently with much success. 
 
 But leaving germ-pathologists to exploit 
 their new position, we must insist that the 
 phenomena of disease, even to the most essential 
 processes, are possible without the intervention 
 
174 
 
 of micro-organisms, bacillar or otherwise ? And 
 why not ? Seeing there are so many diseases 
 without them, such as hydrophobia, to begin 
 with ? The term animal alkaloid has been 
 sufficiently explained. Those vital, or leuco- 
 maines, having been discovered to be true 
 poisons which are formed during the transfor- 
 mations of the living cells, are liable at all 
 times to lead to auto-intoxication, if we had 
 not the power of getting rid of them by 
 physiological combustion and excretion. Gau- 
 tier has succeeded, as we have seen, in isolat- 
 ing some of the agents which the healthiest of 
 them are ever producing, as xantho-creatinine 
 and cruso-creatinine, for example. Some of the 
 maladies attributed to this cause we have al- 
 ready indicated : ursemo-typhus, — uremia, cholo- 
 typhus, — fatal jaundice, athero-typhus, — ulcera- 
 tive endocarditis, puerpero-typhus, — puerperal 
 fever, and the like. 
 
 It is surprising that such poisons should 
 result from healthy cell life, but the venom of 
 the cobra is analogous. Their presence has 
 been demonstrated in the breath even by 
 Brown-Sequard and Arsonval, and also in the 
 perspiration and the urine without any ac- 
 companying trace of microbes. The clinical 
 observer ought then to turn attention seriously 
 
175 
 
 in this direction, and while trying to get rid of 
 the new errors, add to the store of old truths. 
 The clinical teaching in vogue for some years 
 past has become altogether speculative, is in- 
 capable of affording a correct or adequate con- 
 ception of the nature and mechanism of disease. 
 This is not denying some indebtedness to the 
 efforts of eminent experimentalists in hazy 
 regions of germ-pathology. But we must not 
 forget bio-chemical elements which occupy the 
 most important part in our analyses of disease. 
 Neither in the teacher, far less in the prac- 
 titioner, should theory usurp the place of care- 
 ful clinical observation. Here it is above all 
 where the claims of nature and art in the 
 cure of disease can be made evident with 
 satisfaction to ourselves and also to the patients. 
 
1. 
 
 Latest Investigations and Results. 
 
 The new departure in pathology finds an 
 able exponent in Professor Bouchard. This 
 eminent teacher, by the publication of his 
 course of lectures, must now be regarded as 
 heading the movement. Medical investigation, 
 if it has not undergone complete transfor- 
 mation, has, it must be frankly admitted, 
 changed its objective ; having been succes- 
 sively directed to the study of symptoms, 
 anatomic lesions, and anatomical pathology, it 
 has now as its chief aim physiological patho- 
 geny. If this new direction of research has its 
 speculative dangers, it nevertheless promises a 
 future brilliant in positive results. As I have 
 elsewhere shown, it conducts analysis of mor- 
 bid phenomena with a view to ascertain how 
 far they may be productive of or dependent on 
 the action of material obnoxious to nutrition 
 and nervous reaction, and to demonstrate that, 
 whether introduced into the system from with- 
 
i;; 
 
 out or resulting from perversion of metabolism, 
 secretion, and elimination from within, these 
 poisonous principles explain the origin and 
 mechanism of much of what is called disorder 
 and disease. As the reality of auto-intoxica- 
 tion and auto-infection of the organism abounds 
 in novelty and interest, and is every day re- 
 ceiving more and more the attention of the 
 practical pathologist, a notice of the subject 
 in relation to the lessons of Professor Bouchard 
 may be welcome to the studious practitioner, 
 who may have little opportunity of sifting his 
 well-stored page for himself The pathological 
 field which the survey covers is sufficiently 
 comprehensive. Recognising disease as aris- 
 ing from four leading processes, Bouchard 
 commences by observing that man constitu- 
 tionally and naturally possesses in himself much 
 that is both potentially and actually morbid. 
 His vital condition may be abnormal — in other 
 words, nutrition may be defective ; its vitiations 
 or derangements being either hereditary or 
 acquired, we have maladies of antecedent nu- 
 tritive disturbance. The organism may be 
 morbidly affected by external causes, physical, 
 mechanical, .or chemical, as by wounds, burns, 
 poisons — causes which, by operating directly 
 on the cells, excite immediate reactions. These 
 
 12 
 
178 
 
 pathogenic processes, we know, rarely remain 
 simple ; they are rendered complex by reason 
 of mere reflexes. External causes may also 
 act on the economy indirectly through the 
 medium of the nervous system, and it is by 
 that pathogenic process that maladies which 
 Bouchard calls maladies of nervous reaction, 
 are developed. Finally, the economy may be 
 invaded by contagious or infectious elements, 
 however these may be causally regarded. 
 
 It may not always be an easy matter to 
 distinguish the ens niali from the agens mali in 
 disease. Bouchard, though subscribing to the 
 theoretical import of a microbic role in etiology, 
 unquestionably shows that as yet its range is 
 very limited, and leaves things pretty much 
 as they were. In the vast variety of ailments 
 man is heir to, some, we know, are contagious 
 or infectious, or are liable to assume that char- 
 acter. His method of investigation, however, 
 clearly discloses the fact that whatever the 
 essential nature of contaminating elements may 
 be, the more their operation on the organism 
 is observed, the more evident it becomes that 
 the vito-chemical processes involved, and their 
 modes of manifestation are in no wise excep- 
 tional. Organic reaction is the law of disease, 
 whether its processes are destructive or con- 
 
179 
 
 servative in their issues. It is always with the 
 nutritive and sensible nervous reactions that 
 pathological inquiry properly commences. 
 
 Intoxication when acting primarily, that is, 
 directly, Bouchard includes in the four patho- 
 genic processes, but he upholds conclusively 
 the view that the process of disordered nutrition, 
 as well as those of nervous reaction and con- 
 tagion or infection, may also cause intoxication ; 
 if in a secondary mode, that is, indirectly, and 
 he instances gout in those of flabby habit, accom- 
 panied with listlessness, depression, indisposition 
 to exertion, and the like. In the renal, cuta- 
 neous and pulmonary secretions of such are 
 detected incompletely oxidised products of disas- 
 similations, such as oxalates, volatile fatty acid, 
 &c. Substances, which it may be reasonably 
 assumed in some way set up the nervous symp- 
 toms, and thus supply a tracing sufficiently 
 indicative of intoxication due to antecedent 
 nutritive disorder. Again, in subjects ordinarily 
 healthy, the same deleterious substances, by 
 excessive accumulation or imperfect destruc- 
 tion, in consequence of loss of sleep, mental 
 anxiety, bodily fatigue or defective hygiene, may 
 induce the same result, and are quite as clearly 
 outlined. Again, in the case of the more per- 
 nicious maladies, whether arising infectiously 
 
i8o 
 
 or not, among substances elaborated, some are 
 powerfully toxic even in small quantity, and are 
 analogous to those which are the product of the 
 putrefactive processes, and may become patho- 
 genic agents of systemic poisonings. Bouchard 
 cites in illustration septicaemia. If in such case, 
 says he, the malady is accompanied with no im- 
 portant organic lesions, if lesion is confined to 
 the cellular tissues of the region affected, such as 
 he believes is generally the case in septicaemia, 
 we naturally attribute the general accident to 
 the absorption of toxic materials, alkaloidal or 
 otherwise, elaborated in the course of morbid 
 action. We can hardly understand their hav- 
 ing any other origin. To all appearance, then, 
 there are certain classes of disease in which 
 infection leads to secondary intoxication. But, 
 even in normal physiological conditions, and in 
 the best of health, the animal organism is a 
 laboratory and receptacle of what is poisonous. 
 It develops them in disassimilation and secre- 
 tion. The animal economy is thus the theatre 
 of toxic evolution and elimination — phenomena 
 which are even brought about by putrefactive 
 processes, and which are always normally 
 present in the fascal contents of the intestines. 
 Faecal putrid products defectively eliminated in 
 the course of health, as in disease may be ab- 
 
i8i 
 
 sorbed and induce intoxication. It is in this 
 way Bouchard accounts for many accidents 
 which accompany dyspepsia and intestinal in- 
 action. 
 
 Seeing the importance of the part played by 
 disordered nutrition, nervous reaction and the 
 putrefactive infectious processes continually at 
 work in the economy, we are brought face to 
 face with the luminous conceptions with which 
 Armand Gautier more particularly has enriched 
 modern medical science. We are confronted 
 with physio- and bio-chemical processes of 
 animal organic growth and decay, their chemi- 
 cal products, particularly those now known as 
 the ptomaines and leucomaines, and finally 
 with the grand facts that in life as in death, 
 apart from and irrespective of microbic inter- 
 ventional activities, the so-called aerobic and 
 anaerobic processes co-exist ; that in the higher 
 animals, man included, cellular life, to a very 
 notable extent, is independent of inspired oxy- 
 gen ; that the anatomical elements undergo 
 their transformations and other phenomena 
 of oxidation, but that it is in the organised 
 substance they find it. This is evident from 
 the fact that if we note the amount of oxygen 
 derived from respiration, food and liquids on 
 the one hand, and that returned in carbonic 
 
l82 
 
 acid by the kings, skin, and intestinal excreta 
 on the other, they are found equal. But what 
 of the difference in excess of oxygen by water 
 and carbonic acid ? It is obviously derived 
 from the reserve in tissue and cellular elemen- 
 tary combinations. Thus, it is now estimated 
 that at least one-fifth of the vital processes 
 is maintained by oxygen, which is not directly 
 derivable from without, but from within ; that 
 the processes of metabolism and disassimilation 
 are in a notable part carried on by processes 
 analagous, if not identical, to those of putrefac- 
 tion or fermentation. In the removed excreta 
 and ingesta are to be found the products of the 
 putrefactive processes properly so-called. The 
 comparative study of these processes in the 
 physiology of health, as in disease, is conse- 
 quently necessary from the pathological point 
 of view. The constituent material of organic 
 substances, that is, the cellular elements having 
 served their purpose, break up, and then their 
 effete noxious material products are set free. 
 Passing into the extra cellular liquids the result- 
 ing products of disintegrative activities are 
 taken up by the lymphatics and thrown into the 
 blood, in whose circulating current all effete 
 transformed material — that found in the intes- 
 tines, in part at least, included — finds its way. 
 
i83 
 
 Elimination being completed in the process of 
 emunction where the skin, lungs, kidneys, and 
 bowels, perform their respective roles. 
 
 Thus, all poisons come through the blood. 
 As we have seen, the blood necessarily disposes 
 of its poisonous accessories through the various 
 organs of elimination, so consumes them in 
 the circulatory current in contact with the red 
 globules. This being the case, can the blood 
 be regarded as otherwise than toxic ? Con- 
 stantly traversed by noxious impurities it must 
 necessarily and invariably contain toxic ele- 
 ments. Bouchard has shown that it is really 
 toxic, and has succeeded in very closely 
 defining the limits within which it is so ; and 
 this has enabled him to conclude that man 
 would die from poisoning if the blood contained 
 ten times more toxic material than it normally 
 contains. But it is to the plasma that this 
 applies. Its cells, like all other cells of the 
 organism, contain elements potentially dele- 
 terious. The constituents, however, can only 
 be set free by disassimilation or destruction 
 of the cells themselves. Some are remarkably 
 toxic and form two orders : the organic, largely 
 alkaloidal ; the other inorganic, mineral matter. 
 
 In co-operative combustion and elimination, 
 then, lies the safeguard of the economy. This 
 
i84 
 
 physiological conception admitted, its experi- 
 mental verification has to be considered, say 
 in the kidneys and their functions to begin 
 with. The urine gives the key to the problems 
 of intoxication, and forms the necessary intro- 
 duction to the subject as a whole. This secre- 
 tion has always been held as toxic, but of 
 experimental proof of it there was little until 
 Feltz's and Ritter's study of the point. But 
 even their work left much to do, at least in 
 detail. It remained for Bouchard to accom- 
 plish it. He found the urine toxic, and set 
 himself to a systematic course of venous injec- 
 tion, conducted on the lower animal ; he ascer- 
 tained the intensity and variation of toxicity in 
 a given weight of animal substance furnished in 
 a given time, and in this way arrived at the com- 
 paritive unity of urinary toxicity present. Pro- 
 ceeding on these lines he has been enabled to give 
 numerical expression to these, and in doing so 
 has endowed pathology with yet another term 
 — urotoxy ; that is, the standard of toxicity of 
 urine necessary to kill a kilogramme of living 
 substance. It is very singular to read these 
 values, in terms, of living animal matter that may 
 be killed by given quantities of urine under ex- 
 amination ; but it is not an easy matter to detect 
 a fallacy in the procedure, one which promises 
 
i85 
 
 a ready method of estimating specific actions of 
 multiple poisonous constituents. By examining 
 the normal urine passed in twenty-four hours he 
 forms his urotoxic standard, and studies care- 
 fully the variations of toxicity in physiological 
 conditions, and in various pathological states. 
 In this way he establishes the fact that urine 
 per kilogramme fabricates in twenty-four hours 
 sufficient toxic matter to kill 464 grammes of 
 living substance, or nearly the half of what 
 would kill himself in forty-eight hours, all things 
 equal. Variations are significant, and are de- 
 pendent, in normal urine, on vital conditions, 
 muscular and cerebral activity, alimentation, 
 sleep, &c., &c. Whilst dealing with familiar 
 phases of investigation, Bouchard presents us 
 with others which are altogether new and start- 
 ling. He finds, for example, that night-urine is 
 denser and richer in solid material, and always 
 less toxic than day-urine ; that during the hours 
 of sleep man eliminates from two to four times 
 less poisonous material than he does during an 
 equal time of wakefulness or cerebral activity ; 
 further, that the toxicity of night and day urine 
 not only differs in quantity and quality, they are 
 also antagonistic in their action, and neutralise 
 each other. The urines of the sleeping hours 
 are always distinctly convulsivant — stimulant — ■- 
 
i86 
 
 while those of the working hours are soporific 
 — narcotic — the organism by this mechanism 
 thus eHminating during wakefulness material, 
 which, if accumulated in the system, would in- 
 duce sleep, and during the hours of sleep elimi- 
 nating that which would induce wakefulness, 
 thus opening up fresh lines of physiological 
 speculation and research of the most vital and 
 interesting kind. 
 
 But the degree of toxicity of the urine is only 
 one stage of the investigations Bouchard aims 
 at establishing. He carries his enquiries much 
 farther, and dissects them, as it were, examining 
 each of the toxic elements in their chemical, 
 physiological, and pathological relations. By 
 varying his experimental procedure, he has 
 shown that urine contains not one poison but 
 several. In treating urines with alcohol and 
 other solvents in order to separate their mater- 
 ials, with charcoal he has succeeded in disas- 
 sociating three various toxic elements, and 
 ascertains the fact that there exist at least 
 seven, which may be classed thus : one is a 
 diuretic, a second is a narcotic, and a third sia- 
 logenic. There are two other products, one 
 organic, the other inorganic, which are convul- 
 sivant ; the mineral he finds is potash. Then 
 comes a body which induces powerful myosis — 
 
187 
 
 contraction of the pupil — and which is also met 
 with in colouring matters. Lastly there is an 
 agent which reduces temperature. Analysis of 
 these chemical constituents in their physiological 
 effects are as yet very imperfectly obtained. 
 With few exceptions it has not been possible 
 to isolate them in sufficient quantity for this 
 purpose. 
 
 The elimination of such substances rendering 
 the urine toxic, explains why the system escapes 
 their deleterious action. The method and 
 mechanism of their formation now claims a 
 closer examination, especially the co-operative 
 role of the liver and intestines. The bile which 
 periodically flows into the alimentary canal con- 
 tains poisonous elements, particularly in the 
 colouring matters ; much less so are the biliary 
 salts. Normally, however, secreted bile is little 
 dangerous to the economy, and this by reason 
 of the colouring matter and the salts in a great 
 measure finding their way into the bowels. The 
 intestinal ingesta undergoing putrefaction gives 
 rise to the formation of toxic substances, but in 
 the slow and intermittent passage of the faeces, 
 a part, at least, of the toxic elements is liable to 
 absorption through the mucous surfaces, and 
 finds its way into the vena porta where it is 
 arrested, when what is not rejected again into 
 intestines passes into the general circulation. 
 
1 88 
 
 The alimentary canal is in this way a cause 
 of poisoning to the system, and the question of 
 intoxication from this source has consequently 
 received much attention from observers such as 
 Gautier, Brieger, Mosso and others. But it is 
 to Bouchard we are chiefly indebted for our in- 
 formation. He has taken up the subject, ex- 
 tending it in its physiological and pathological 
 applications more particularly. He has inves- 
 tigated the subject, and shown that alkaloids 
 exist in the faecal materials ; these alkaloids are 
 of several kinds, and that when markedly 
 present in the intestines they are found to be 
 markedly present in the urine also. After 
 Stick, he has confirmed the fact of the toxicity 
 of the faecal matters. He has examined .the 
 toxicity and shown that it is due in great part to 
 potash and ammonia ; but that, even when 
 relieved of these elements, they still retain a 
 certain degree of toxicity which must not be 
 disregarded. He shows that intestinal anti- 
 sepsis, which disposes of the alkaloids of the 
 faecal and urinary matters at the same time, 
 diminishes the toxicity of both. Thus, knowing 
 the urinary poisons and their various sources, 
 he has been enabled to study that form of in- 
 toxication which is due to their retention, and 
 known as uraemia. Whilst carefully keeping 
 
i89 
 
 clear of the urotoxic accidents liable to intrude 
 themselves and complicate matters in disease 
 of the kidneys, such as albuminuria, arterial 
 oedemas, including, for example, that of the 
 brain. By this means he has obtained decided 
 proofs of the fact of the reality of toxic uraemia, 
 while showing that the urine is not toxic. He 
 shows that the uraemic urines are not toxic, for 
 the reason that all the toxic substances which 
 the urine normally eliminates are found to be 
 retained in the organisms of those affected. To 
 the question : " Is all that is retained toxic, or 
 is only a portion of it, and, if so, which por- 
 tion ? " he finds it is neither the urea nor the 
 potash exclusively. Neither of these of itself 
 explains the intoxication. Each of them con- 
 tributes in part, though differently, to that 
 condition as a whole ; the colouring matters 
 three-tenths, the extractive matter one to two- 
 tenths, potass and mineral matters four to five- 
 tenths. A knowledge of the multiplicity of the 
 toxic agents enables us to understand, according 
 as one or other of these eliminates, the various 
 clinical forms uraemic poisonings may assume, 
 the convulsive or comatose in particular. The 
 presence of certain special symptoms, such as 
 hypothermia, contraction of the pupil, and 
 pathological intoxications, which he endeavours 
 
1 90 
 
 to show, not only satisfy scientific curiosity, but 
 are suggestive of practical application and have 
 a therapeutic value. 
 
 Next he proceeds to examine the morbid 
 conditions which are caused by gastric embar- 
 rassments, of which excessive accumulations, 
 constipation, and intestinal obstructions are 
 examples. He traces the history of a variety 
 of intoxications of intestinal origin, citing that 
 of Senator, in which the offending element was 
 sulphohydric acid. Poisoning from fish, which 
 he personally observed, and in which the pre- 
 sence of an excess of alkaloidal substances, 
 to which the same might be charged, was pre- 
 sent, and refers to the instance of over-kept 
 stuffed goose, in which Brouardel and Boutmy 
 succeeded in isolating toxic alkaloids, showing 
 that all these cases had actually passed through 
 infection to intoxication. There was detected 
 between the ingestion of the putrid aliments 
 and the setting in of toxic symptoms a period 
 of incubation. It appeared to him that the 
 poison, elaborated by microbic action of the 
 goose meat, was too small in quantity to induce 
 poisoning, but the microbic putrefaction acquir- 
 ing a greater intensity in the intestinal canal 
 became much increased, and then the toxic 
 products were sufficiently abundant to produce 
 
191 
 
 intoxication. Here, again, incubation compels 
 us to admit infection ; but that the infectious 
 agents manufacture a poison, and infection 
 results in intoxication. Bouchard holds that 
 the usual circumstances under which such acci- 
 dents of toxicity take place, in consequence of 
 the formation of poisonous elements in the 
 digestive tube, is in the singular condition he 
 recognises as dilatation of the stomach, and 
 which — apart from dyspeptic troubles as ner- 
 vous derangements always acknowledged in 
 the cortdge of dyspeptic disorders — seems to 
 him to be capable of setting up many other 
 disorders, such as albuminuria, a condition 
 usually chronic, and liable to become per- 
 manent, but amenable to treatment, and that 
 successfully when the real cause has been 
 discerned. It is by setting up anomalous 
 gastic fermentations, which extending to the 
 intestinal canal, give rise to the formation of 
 poisons, particularly acetic acid, that dilata- 
 tion of the stomach vitiates nutrition of vari- 
 ous structural tissues, even of the bones and 
 cartilages, and may not be a stranger to ostio- 
 malacia, nodular rheumatism, perhaps includ- 
 ing rickets. Of other maladies dependent on 
 matured intoxications caused by dilatation of 
 the stomach, he thinks the most manifest are 
 chlorosis and pulmonary phthisis. 
 
192 
 
 This may take some by surprise. It is, 
 however, dealt with in a most exhaustive man- 
 ner by the learned experimentalist, who, if he 
 does not convince, at least makes it very 
 probable that dyspeptic and gastric affections 
 must henceforth be given a wider range in 
 pathological research. It may be difficult to 
 accept the lengthened list of maladies dilatation 
 of the stomach is parented with. Still it must 
 be owned that it is precisely with respect to 
 this question of etiology that we are most 
 ignorant, and any rational examinations of it 
 based on demonstrated fact ought not to be 
 lightly estimated, thus indicating the role 
 which secondary or indirect poisoning plays, 
 even in infectious maladies. Bouchard pro- 
 ceeds to lay down his views regarding the 
 treatment of typhoid fever in which he sees 
 chiefly indicated intestinal antisepsis, and gene- 
 ral balnear anti-thermics, and a particular line 
 of dietary, thus laying down, apropos of enteric 
 fever, general rules which might be found 
 applicable to other acute maladies. 
 
 He next goes on to show that part intoxica- 
 tion holds in jaundice, pointing out that here 
 intoxication is twofold. The bile, contrary to 
 to what has been hitherto supposed, is toxic, 
 particularly in its colouring matter, and that 
 
193 
 
 what protects the organism from the action of 
 this element is the urine, which ehminates 
 incessantly one part of it ; there is also the 
 cellular tissue, the white fibres of the fibrous 
 tissues of which, fix or take up colouring 
 matter not eliminated, and which, should it 
 remain in the circulation, would seriously affect 
 the functional play of the nerve cells. As for 
 the other part, the biliary salts, they go to 
 augment disassimilations, to destroy the mus- 
 cular cells and blood globules, thus liberating 
 the poisons, organic and mineral, particularly 
 potash. 
 
 In maladies that give rise to jaundice, the 
 liver, which is normally charged with the pro- 
 tection of the organism from intestinal poison- 
 ing, is deranged or obstructed in its functional 
 action. It ceases to fulfil its part ; it ceases to 
 manufacture urea — the diuretic par excellence. 
 It is the urea, which, by forcing the renal barriers, 
 conveys with it the other toxic materials. 
 By its means a complex process takes place of 
 intoxication, whose successive phases are chol- 
 semia, acholia, and uraemia. There consequently 
 can be but little question that the safeguard of 
 the organism from intoxication lies chiefly in the 
 kidneys. So long as this organ is functionally 
 active, the urines of jaundiced subjects are very 
 13 
 
194 
 
 toxic, not from the bile which they contain, but 
 from the material resulting from the unusual 
 and increased disassimilation. When the kid- 
 neys cease to discharge their function of depur- 
 ation, the urine of the jaundiced patient ceases 
 to be toxic ; and the patient becomes poisoned 
 from the retention in the system of the poisons 
 that failed of a normal discharge. 
 
 But the normal poisons are not alone in 
 question in all intoxications. Bouchard points 
 out in the acute atrophy of the liver the pre- 
 sence of a singular substance produced by the 
 organism, which elaborates vitiated material, 
 and further points out unusual albumen, unusual 
 transformation of medical agents, such as naph- 
 thalin, which ceases, in the case of hypatic 
 atrophy, to be eliminated in the state of 
 naphthy-salphite of soda ; some of these are 
 toxic. Again, we are reminded that in gly- 
 cosuric patients, besides accidents resulting 
 from the complete destruction of sugar formed 
 by the organism, this body may give rise to 
 substances which, in the urines of subjects 
 suffering from diabetic coma, take a wine red 
 colour in contact with perchlorate of iron. 
 These substances, however, are not alone met 
 with in the diabetic, for they have been de- 
 tected in the cases of dyspeptic coma, in 
 certain cases of cancer of the stomach, and 
 
195 
 
 permanent anuraeia, leucocythaemia, and more 
 recently Bouchard has met with them in ty- 
 phoid fever. These substances, as experimen- 
 tally proved, are toxic. Contrary for the most 
 part to the auto-intoxications hitherto exposed, 
 that called acetonaemia is an intoxication by 
 an anomalous poison, a morbid poison. 
 
 In cholera, also, there is sometimes the 
 formation of anomalous material, and some of 
 these are obviously alkaloidal ; this is detected 
 by the violet colour given by the urines of 
 cholera patients, even on emission, while under 
 naphthalin medication. But cholera is an ex- 
 ample of multiple intoxication, and Bouchard 
 has shown that in choleraics there is present 
 a special poison, practically unknown, elabora- 
 ted by the organisms. This substance ap- 
 peared to Bouchard to be clearly evidenced 
 from the specific toxicity of the urines of 
 choleraic subjects when injected into the veins 
 of rabbits ; they determined in definite symp- 
 toms characteristic of cholera, though not the 
 malady itself He has also pointed out that, 
 besides the accidents which choleraic intoxica- 
 tion exhibits the persons attacked are subject 
 to secondary intoxication consequent upon sup- 
 pression of urine. This is from the retention 
 of the normal poisons. Myosis— pupilar con- 
 
196 
 
 traction — is present as the clinical criterion of 
 uraemic intoxication having taken place. 
 
 Bouchard's admirable course on auto-intoxi- 
 cation closes with therapeutical applications 
 deduced from the pathological conception which 
 the study imposes. The treatment of auto-intoxi- 
 cation draws largely on the antiseptic method ; 
 and we naturally wish to know what may legi- 
 timately be expected of antisepsis in general. 
 We know that the mastery of the mechanism 
 of maladies does not bear with it the mastery 
 of the remedy, but from the lucid exposition 
 on this head, good results, if limited, may be 
 reasonably looked for. 
 
Auto- 1 ntoxication 
 In Health. 
 
 PART V. 
 
The periodical suspension of the activity of 
 the superior nerve-centres is the dominant char- 
 acter of sleep. The attempt to explain it by 
 the condition of the cerebral circulation has 
 often been made ; but, by a singular contra- 
 diction, some authors set up the intervention 
 of congestion, whilst others insist on anaemia. 
 Recent researches seem decidedly favourable to 
 this latter hypothesis however, in support of 
 which somnolence from great loss of blood, and 
 that kind of sleep that Fleming was able to pro- 
 duce by the compression of the carotids may be 
 cited. The variations of the cerebral circula- 
 tion present then a certain relation with the 
 alternations of sleep and wakefulness, but as 
 these variations themselves require explana- 
 tion, they do not suffice for any theory of 
 sleep. The capital importance of oxygen in 
 keeping up the activity of the tissues once 
 recognised, it was very natural to make it play 
 a part in the explanation of sleep, and to at- 
 tribute it to a less absorption of oxygen — to 
 
200 
 
 an anoxia of the brain. This is an idea which 
 goes back to Alexander von Humboldt, at the 
 end of the last century, and which has been 
 since maintained with certain variations by 
 Purkinje, Pfluger, and others ; but this affords 
 no explanation of the cause of the periodicity 
 of normal sleep. Why should the quantity of 
 oxygen received by the brain diminish at cer- 
 tain times and increase at others ? 
 
 Sleep is not the only phenomenon which 
 returns regularly and in some sort rhythmically 
 in the life of the organism. The movements 
 of respiration and the contractions of the heart 
 are in point. The study of them ought to 
 simplify the problem. 
 
 It is generally admitted, thanks to the la- 
 bours of Rosenthal, that the respiratory system 
 is essentially regulated by the richness of the 
 arterial blood in oxygen and carbonic acid. 
 When the blood is charged with oxygen, the 
 nerve-centre which governs respiration, sus- 
 pending its activity, the tissues take up the 
 oxygen of the blood, replace it by carbonic 
 acid, and thus the blood, becoming modified, 
 excites the respiratory centre. A respiratory 
 movement is then produced, the provision of 
 oxygen is renewed, the carbonic acid eliminates 
 itself; things restored to their initial condition, 
 
201 
 
 the process recommences. It is instability, 
 even in the condition of the blood, which 
 excites the movements necessary to recovery 
 of the primary equilibrium. 
 
 The exhaustion of a muscle by labour, and 
 the restoration of its excitability by rest, are 
 phenomena still more comparable with the sen- 
 sation of fatigue and the restorative effects of 
 sleep. The researches of J. Ranke, which date 
 more than twenty years back, tend to the ad- 
 mission that the exhaustion of the muscle 
 results from the accumulation of substances 
 produced by its contraction, in particular that 
 of lactic acid. If we inject these fatigue sub- 
 stances, as Ranke calls them, into a fresh 
 muscle, it becomes incapable of working — it is 
 exhausted ; if we remove them by an artificial 
 washing, or if we allow the circulation of the 
 blood time to carry them away and to replace 
 them by other materials, the fatigue disappears, 
 the muscle acquires again its contractility, it 
 renews itself Ranke supposed that fatigue 
 substances operate by monopolising the oxy- 
 gen to the detriment of the muscle. In any 
 case it would here be still the instability in the 
 chemical condition of the organ — its temporary 
 intoxication — which forces it into a state of 
 rest, until it be disencumbered of the products 
 
202 
 
 of its activity, and finds itself in some sort 
 changed. 
 
 To M. Leo Errera, of Belgium, we are 
 indebted for one of the most interesting con- 
 tributions to this subject. Well known for 
 researches in connection with the alkaloids of 
 plants, this accomplished teacher has recently- 
 directed attention to those of animals in ex- 
 planation of the physiological conditions of 
 Fatigue and more particularly sleep. 
 
 To the questions involved, and still awaiting 
 solution, the best informed, as Exner and 
 Beaunis, had declared that we know nothing 
 definitely on the subject. More recently, how- 
 ever, new facts have come to light which mate- 
 rially alter the position ; in both conditions the 
 principal phenomena, at least, may shortly cease 
 to be a mystery. With M. Errera's work before 
 us, let us see how far this is probable. 
 
L 
 
 The Animal Alkaloids : 
 Their probable Role in Fatigue 
 and Sleep. 
 
 M. Errera in his remarkable paper entitled 
 Why sleep, and How ? " of which the follow- 
 ing is a rdsttmd, enters on the subject by asking 
 whether a theory of toxicity, analogous to 
 those of respiration and of muscular fatigue, 
 would not apply to sleep. Heynsius and Dur- 
 ham have assented to this view ; since Ober- 
 steiner and Binz also declare in the same sense. 
 These latter think that the products of ex- 
 haustion are continually forming within the 
 brain when active ; that their accumulation 
 brings on sleep ; and that they are then elim- 
 inated by the blood which passes through that 
 organ. But what are those products } From 
 what we know of the reaction of the grey 
 substance and tetanised nerves, Obersteiner 
 was of opinion that it operated essentially as 
 
204 
 
 an acid ; and such also was the opinion of Heyn- 
 sius and Durham, and of Binz. Preyer has 
 expanded this idea, and ingeniously combined 
 it with the theory of sleep by default of oxygen. 
 He arrives also at a conception altogether par- 
 allel to that which Ranke had formulated for 
 the muscles. According to Preyer all organic 
 activity gives rise to products of exhaustion, to 
 substances which he calls ponogenes — from irovo^ 
 — labour, and \eveoL^ — origin — which accumu- 
 late during wakefulness, and, being very oxidis- 
 able, terminate by diverting to their profit the 
 oxygen destined to keep up the activity of the 
 different glands, muscles and brain, in such 
 a fashion as that the mental acts and voluntary 
 movements are depressed ; and cause the or- 
 ganism to fall asleep. 
 
 Among the ponogenic substances it is to 
 lactic acid that Preyer ascribes the principal 
 part, and he has made the attempt to demon- 
 strate experimentally that this product entering 
 into the organism induces sleep. These ex- 
 periments have been repeated in different ways. 
 Unfortunately, as Preyer himself has recog- 
 nised, the results are not constant, either in the 
 case of man or of animals ; thus the theory has 
 not been generally adopted by physiologists. 
 
 At the time that Obersteiner, Binz and 
 
205 
 
 Preyer made known their ideas, we knew of 
 no product of the animal organism similar to 
 the somniferous alkaloids of certain plants. 
 Recent researches have shewn that such do 
 exist, and the question of sleep now naturally 
 presents itself under quite a new aspect. 
 
 Extending to animals, alive and healthy, the 
 researches which Selmi had made on the dead 
 body, Armand Gautier has succeeded in ex- 
 tracting from the flesh of mammifera — beef — 
 a series of five organic bases more or less akin 
 to creatin : creatinine, xanthine, &c. He desig- 
 nates them under the name of leucomaines, so 
 as to recall the fact that they are analogous to 
 the cadaveric bases or ptomaines. Pouchet 
 and Bouchard found the alkaloids in the urine 
 of human beings. Gautier himself had indica- 
 ted it in their saliva in its normal state, and he 
 concluded that animals normally produce alka- 
 loids after the fashion of vegetables. What 
 are the physiological actions of these leuco- 
 maines ? The aqueous extract of the saliva 
 ''is poisonous or narcotic, at least for small 
 birds ; " next as to alkaloids from muscular juice, 
 Gautier speaks of them as endowed with an 
 action more or less powerful on the nerve 
 centres, producing somnolence, fatigue, and 
 sometimes vomiting and purging. There is 
 
206 
 
 here clearly a question of substances fatiguing 
 and somniferous, such, in one word, as the 
 toxic theory of sleep requires them to be. 
 Curiously, the memoirs of Gautier and their 
 subsequent discussion at the Academie de 
 Medecine, where the importance of leuco- 
 maines as regards pathology has been so 
 clearly brought into relief, their signification 
 physiologically seems to have been almost 
 overlooked, and their probable relation to 
 sleep has not, so far as I know, been men- 
 tioned. What could be more natural than to 
 bring together the work of Gautier with those 
 above mentioned ? The idea was in the air, and 
 was incidentally alluded to by De Parville in a 
 scientific article of the Journal des DSbats. 
 The writer in stating the results that Gautier 
 had just obtained, quotes from him this 
 phrase : "It is after perfect sleep or rest that 
 the animal is more particularly anaerobic and 
 consumes more oxygen than it receives," and 
 he adds, in a note, ''during sleep the oxygen 
 absorbed does not correspond to the carbonic 
 acid exhaled. We should be tempted to believe 
 that the excess burns the toxic matters, and 
 that sleep would principally be caused by the 
 accumulation in the blood of leucomaines or 
 analogous substances." It is to be observed 
 
207 
 
 that the accumulation of oxygen during sleep, 
 on which De Parville insists, seems to be dis- 
 proved. Voit expresses himself thus on this 
 subject : "It was in consequence of error in 
 the mode of conducting the experiment that 
 Pettenkofer and myself had concluded at the 
 time that the oxygen is stored up in con- 
 siderable quantity during the night, and util- 
 ised afterwards in the daytime and during 
 labour. 
 
 Quite recently Bouchard, in his researches on 
 the toxicity of the urine of a healthy human 
 being, has compared the urine secreted during 
 wakefulness and during sleep, and, in so doing he 
 makes passing allusion to the theory of sleep. 
 Without specifying the nature of the poisons 
 with which the question has to do, he says : "The 
 urines of waking and sleeping not only present 
 differences in intensity, they differ also as to 
 quantity. The urines of the sleeping hours are 
 convulsivant, the urines of the waking hours 
 are very little so or not at all ; but they are 
 narcotic." It is at this stage that one might 
 ask whether Preyer's toxic theory of sleep 
 should not be accepted. What is certain is, 
 that during wakefulness the body fabricates a 
 substance, which if accumulated would produce 
 sleep ; and that during sleep it elaborates in 
 
208 
 
 place of this narcotic substance, a convulsi- 
 vant, which if accumulated, would produce 
 the muscular shock which is provocative of 
 waking. It perhaps might be objected that if 
 the poison which is narcotic brings on sleep 
 by its accumulation in the organism, it is in 
 the tissues and not in the urine that one ought 
 to meet with it during wakefulness. But to 
 express oneself on this point safely, as on many 
 others, it will be well to await the continuation 
 of the labours of Bouchard, and notably the 
 extraction and the dosage of toxic substances. 
 In any case, it appears rational to base a theory 
 of sleep on the products that may be detected 
 in the tissues of the organism itself rather than 
 upon those which it eliminates by its secre- 
 tions. 
 
 According to a profound remark of Claude 
 Bernard, all vital manifestation is connected 
 with the destruction of organic matter. This 
 is a consequence of the great principle of the 
 conservation of force. When a muscle con- 
 tracts, when a nerve feels, when a brain thinks, 
 it is at the expense of organic substance ; there 
 is a corresponding destruction and consumption 
 of elementary material. In a certain sense life 
 is thus but a prolonged partial suicide, to adopt 
 an expression which Peter recently made use of 
 
209 
 
 If it be a commonplace to say that to labour, 
 the living being must burn organic matter as 
 the steam engine burns coke or coal, it is clear 
 that in the one case as in the other, waste, 
 ashes, and ponogenes ought incessantly to be 
 produced. No more in the living than in the 
 artificial machine can these ashes accumulate 
 without inconvenience, as they tend to the de- 
 triment of the tissues by engrossing the space 
 which the new utilised elements ought to oc- 
 cupy. But there is more than this, the cellular 
 scoriae are probably injurious in another way. 
 Besides positively encumbering, they may in 
 their turn react upon the vital phenomena. 
 
 We have no difficulty, then, in conceiving 
 that the animal machine cannot continue to 
 work if it does not disencumber itself of its 
 waste, — its ashes, — and if it does not procure 
 fresh combustible matter ; the elimination of 
 ponogenes and organic reparation appear to us 
 as the inevitable necessities of work. It is pos- 
 sible, especially when the activity is intense, 
 that these two functions may be accomplished 
 less quickly than the inverse phenomena. The 
 organism will then be at the end of a certain 
 time impaired by its overwaste, and find itself 
 incapable of continuing to work until it can 
 
 14 
 
210 
 
 be purified and reinvigorated by rest. And 
 here, to begin with one cause of alternations 
 more or less regular, we foresee that phases of 
 activity and repose must necessarily in turn 
 succeed each other. It is, moreover, no other 
 than a manifestation of the character which dis- 
 covers itself in all movement : rhythm. 
 
 But if general considerations permit us to 
 understand the necessity of repose, they are 
 insufficient to explain to us the mechanism of 
 sleep. This phenomenon signifies something 
 more than the functional incapacity. It is 
 eminently a question of a nervous order. All 
 cellular waste, every ponogenic body is not 
 actively somniferous. It requires for that : 
 firstly, that this body should operate in a 
 special manner upon the superior nerve cells ; 
 secondly, that it should suspend this activity 
 for a time. 
 
 Now, do we know any substances possessing 
 these properties ? Undoubtedly ; ether, chlo- 
 roform, hydrate of chloral, and in an eminent 
 degree the alkaloids which are narcotic ; mor- 
 phia, narcein, &c. And if we now pass in 
 review the products fabricated by the or- 
 ganism, there is certainly none of them which 
 will better satisfy us than the leucomaines 
 under the conditions which we have just 
 theoretically indicated. 
 
211 
 
 The study of the leucomaines is scarcely as 
 yet begun, but an analogy which seems in- 
 teresting becomes evident even now. Accord- 
 ing to Gautier, the greater part of the leuco- 
 maines, as well as of the ptomaines are very 
 oxidizable, and morphia is precisely that which 
 makes itself observed by reason of its great 
 oxidizability. Bettink and Van Dissel assure 
 us also, that out of forty-two vegetable alka- 
 loids tested by them, morphia alone divides 
 with the ptomaines the property of forming 
 Prussian blue, by reduction of the perchloride 
 of iron and ferricyanide, and that notwith- 
 standing the presence of an oxidizer so power- 
 ful as chromic anhydride. 
 
 It may be asked, in what way do leucomaines 
 act upon the nerve cells. Is it directly or in- 
 directly in the taking up of oxygen, as Preyer 
 supposed, in regard to his ponogenes ? It would 
 be premature to wish to settle the question 
 definitely, but in the actual state of investigation 
 the first hypothesis appears much the more 
 probable. If we take as terms of comparison 
 the vegetable alkaloids, no one will be likely to 
 suppose that morphia brings on sleep by the 
 subtraction of oxygen ; for one centigramme 
 of a salt of morphia, a sufficient quantity of 
 itself to cause sleep, does not require for its 
 
212 
 
 complete oxidation more than two centigram- 
 mes of oxygen — say, less than the eightieth 
 of what we inhale every minute. Again, we 
 do not know what quantity of each leucomaine 
 is necessary to occasion fatigue and som- 
 nolence, of which Gautier speaks, but the 
 quantity is certainly small. The moment, 
 moreover, one comes to think how little abun- 
 dant the leucomaines are in the normal or- 
 ganism, it becomes difficult, if not impossible, 
 to attribute sleep to the privation of oxygen, 
 which may result from their oxidation. An- 
 other fact also makes against the theory of 
 sleep by anoxia, it is that many oxidizers — 
 halogenium, ozone, oxygenised water — are 
 narcotic. There are, on the contrary, good 
 reasons in favour of a direct action of leuco- 
 maines on the brain. Rossbach has seen that 
 many vegetable alkaloids, morphia, quinine, 
 atropia, veratria, strychnine, modify the albu- 
 minoidal matters, such as the white of egg, 
 the serum of the blood, the muscular juice, 
 and that by augumenting their coagulability, 
 the albuminoidal precipitate thus obtained pre- 
 serves always a certain quantity of alkaloid 
 even after prolonged washing. This precipi- 
 tate exercises no coagulating action upon the 
 white of egg when dissolved, and Rossbach 
 
213 
 
 thence concludes that the alkaloids must be 
 in chemical combination with the precipitated 
 albuminoid material. Binz tells us that so- 
 porifics, such as morphia, chloral, chloroform, 
 and ether put into contact with the grey sub- 
 stance, renders it turbid. This is the sign of 
 a species of coagulation which other non-so- 
 porific bodies would not occasion : atropine, 
 caseine, chlorox-alethylin, camphor, pyrogallic 
 acid. Claude Bernard was also of opinion, at 
 least as regards ether, that anesthesia is caused 
 by a sort of coagulation. Let us observe that 
 muscular fatigue could no longer be attributed, 
 as Ranke thought, to a monopolising of the 
 oxygen by the products of contraction, but 
 much rather to a direct influence of the acids 
 formed ; for the phosphate acid of soda, which 
 is not oxidizable, absolutely fatigues " the 
 muscle just as lactic acid does. Leucomaines 
 might, again, act indirectly in another manner 
 by modifying the cerebral circulation. It is a 
 hypothesis which has already been put forward 
 to explain the action of narcotics, and in this way 
 the vaso-motor theory of sleep is arrived at. But 
 such opinion seems contradicted by the direct 
 observations of Binz. In the dog and rabbit 
 when trepanned, he saw that anaemia of the 
 cerebral surface only supervened slowly in the 
 
214 
 
 complete state of sleep. Anaemia is then in 
 this case a consequence of sleep, and not sleep 
 the consequence of anaemia." The author adds, 
 after instancing the case of the alimentary 
 canal, which is pale and bloodless during a state 
 of fasting, and filled abundantly with blood dur- 
 ing digestion : " Cerebral anaemia in prolonged 
 narcosis is in harmony with this general rule, 
 that the flow of blood towards the organs dim- 
 inishes when they are at rest." 
 
 The influence of ponogenes may then proba- 
 bly be summed up in these terms : not anoxia, 
 not anaemia, but direct intoxication. A theory 
 of sleep ought to account for the normal link- 
 ing together of these three things : work, fa- 
 tigue, and sleep. It is easy to see that the 
 toxic theory satisfies this condition. All work, 
 whether it be muscular or cerebral, engenders 
 loss of material. This deterioration renders 
 the continuation of labour painful : this is fa- 
 tigue. Finally, the waste ddbris, and notably 
 the leucomaines, finish by intoxicating the su- 
 perior nerve centres — as morphia would do — 
 to the extent of inaction : this is sleep. Here 
 we have the phenomena reduced to their most 
 simple expression. But a mass of accessory 
 circumstances arise to complicate the consider- 
 ation of the question. The most important it 
 
215 
 
 is necessary to note. First of all, the living 
 being struggles incessantly against the intoxi- 
 cation by which it is menaced. It seeks to 
 disencumber itself of its refuse material ; the 
 circulation drains them off and expels them by 
 respiration and secretions ; the liver, it seems, 
 arrests or destroys one portion of them. The 
 more intense any labour is the more do all these 
 functions become active : the circulation in- 
 creases, washing and cleansing the organs ; the 
 respiration accelerated, eliminates more car- 
 bonic acid ; the emission of urine is often 
 augmented ; perspiration makes its appear- 
 ance, refreshing the organism, and taking 
 away from it, moreover, a considerable quantity 
 of refuse products, such as urea and creatin. 
 These multiple depurations enable the organ- 
 ism to maintain activity for a certain time, 
 but not indefinitely. Why so ? 
 
 If, by an excess of work, certain of our 
 organs have consumed all their utilizable ma- 
 terials, and thus grow encumbered by pono- 
 genes, it is clear that they are, until a new order 
 of things succeeds, incapable of further work. 
 But we do not arrive under ordinary conditions 
 at this extreme degree of exhaustion ; it is 
 even doubtful whether we ever do arrive at it. 
 It is a fact that the sensation of fatigue has 
 
2l6 
 
 already become invincible, before the physical, 
 the real fatigue, has attained its ultimate or 
 extreme limits. The ponogenes operate, not 
 only upon these organs where they have begun 
 their existence, but even upon the nervous 
 extremities which border on these organs and 
 upon the centre themselves. To this triple 
 influence of the ponogenes three significations 
 of the word "fatigue" correspond. In effect, 
 there is room to distinguish between the true 
 fatigue of the muscular fibres of the arm, for 
 example, which is measured by the diminution 
 of their excitability, the fatigue which is sub- 
 jective, which we feel locally in this arm ; and 
 the general sensation of fatigue lassitude which 
 explains itself by the desire of sleeping. After 
 having lifted for some time a weight, we may 
 experience an intense fatigue in the arm, but no 
 need of sleep, whilst we may fall, as they say, 
 asleep, without experiencing any considerable 
 local fatigue. Of these two sensations, one is 
 peripheric, the other is central. It is this latter 
 which interests us the most, and it is its genesis 
 that it behoves us to study most clearly. 
 
 Cerebral activity, such as manifests itself 
 during the state of wakefulness, is connected 
 with reactions of a chemical nature, with dis- 
 charges which occur in this eminently explosive 
 
217 
 
 matter of the protoplasm of the nerve-cells, and 
 the gray cortex. Now, among the ponogenes 
 constantly engendered within the different 
 organs which are in operation, we know that 
 there are narcotic compounds, comparable to 
 alkaloids. In all probability these bodies have 
 a particular affinity for the nervous corticle 
 cellule ; m any case they act upon it, they 
 modify it, they fix themselves there more or 
 less steadfastly. Their elimination by the 
 emunctories, as already mentioned, will never 
 be other than partial ; whilst one portion will 
 be drained by the secretions, another will pos- 
 sibly be undergoing destruction by oxidation, 
 a third will be retained within the brain. It is 
 believed that the nerve centres, thus modified, 
 perform with less and less facility their function 
 of explosion, and it will require excitements 
 more and more vigorous to maintain the con- 
 dition of wakefulness ; after a certain stage our 
 movements become tardy, our sensations be- 
 come blunted, our thoughts are clogged — in a 
 word, we feel ourselves fatigued. There comes 
 at length a moment in which the ordinary ex- 
 citements are no longer sufficient to permit 
 the explosion of the cerebral protoplasm ; its 
 activity is provisionally suspended ; we sleep. 
 By this theory, it is obvious that the ponogenes 
 
2l8 
 
 only operate on those of the nerve-cells into 
 which they penetrate. This localised action 
 explains to us what we may call ''partial 
 slumbers." The profoundest sleep, says Ex- 
 ner, with reason, is connected by insensible 
 transitions with perfect wakefulness. If one is 
 observant whilst falling asleep, it may be re- 
 marked that the circle of ideas with which one 
 is occupied becomes more and more contracted. 
 We can say that certain groups of ideas are 
 still wakeful, whilst others are already subject 
 to sleep. The cells of the organism fall asleep 
 one by one, even as they die one by one, fol- 
 lowing a hierarchical order. Whilst admitting 
 a great latitude for the intervention of accessory 
 causes, we foresee, nevertheless, that the most 
 elevated of the centres are in general the first 
 to become drowsy, then sleep overtakes by 
 degrees the inferior centres. 
 
 These remarks explain in a certain measure 
 the phenomena of somnambulism ; for Jean 
 Muller has already shown that the question 
 there is one of partial sleep. On the other 
 hand, certain superior centres the first asleep, 
 are capable of awaking themselves separately 
 or in groups. Perhaps one may come by this 
 means to understand the variety and the want 
 of connection in dreams, and painful night- 
 
219 
 
 mares, during which we endeavour to perform 
 a movement, and feel ourselves restrained ; 
 here the motor centres would be asleep, whilst 
 certain intellectual centres would be awake. 
 In somnambulism, on the contrary, it would be 
 the motive centres which were awakened, and 
 the intellectual centres that continued asleep. 
 Contrary to Preyer, Errera is led to regard the 
 somniferous action of the ponogenes as direct, 
 and not as the indirect result of a subtrac- 
 tion of oxygen. The reasons have been stated. 
 However, the oxidizability of the leucomaines, 
 in place of being the cause of sleep, explains 
 according to our view the cessation of it. 
 
 If the accumulation of a certain quantity of 
 leucomaines within the ganglionary cells brings 
 on fatigue, then sleep, the sound awaking and 
 refreshed feeling which accompanies it, must be 
 due to the disappearance of the leucomaines. 
 Have they been simply removed by the circula- 
 tion, or are they destroyed ? Both factors might 
 intervene, but since it is probable that the leuco- 
 maines are chemically retained in the cerebral 
 nerves, as were the alkaloids in the experiments 
 of Rossbach, the mere blood-washing would 
 not remove them except with difficulty ; and 
 since from other sources we have a knowledge 
 
220 
 
 that they are oxidizable, it is natural to think 
 that the oxygen whose oxidizing power still 
 is being exercised in the living organism, attacks 
 them and burns them little by little. Does 
 this only take place during sleep ? There is 
 no reason for thinking so. The accumulations 
 of leucomanies during the state of wakefulness 
 does not prove that their production is sus- 
 pended. It signifies only that the production 
 is then in excess of the oxidation and elimi- 
 nation united, which is only very plausible. 
 During the condition of waking, the activity of 
 the organs continually engenders new quantities 
 of them ; during sleep the production is, at least 
 very much reduced, for the muscles are then in 
 repose, the pulsation has become lessened, many 
 secretions and respiration are diminished, the 
 brain is out of gear. Now, the normal adult 
 requires as near as may be about eight hours 
 of sleep as against sixteen of waking, so we 
 may conclude that the ponogenes are formed 
 on an average, during waking, one and a half 
 sooner than they oxidize and eliminate them- 
 selves. It is useless to adduce that here a mass 
 of factors are overlooked, and that this figure 
 represents only a crude approximation. As 
 there is no reason to admit that the products 
 of oxidation of the leucomaines can have, like 
 
221 
 
 them, a special affinity for the protoplasm of 
 the gray substance, we conceive their being 
 immediately swept away in the circulatory cur- 
 rent. The nerve-cell, therefore, is cleansed, 
 it becomes again accessible to impressions from 
 without, and a slight exciting cause suffices to 
 bring about waking. But this is not the whole. 
 Sleep does not consist alone in the elimination 
 of ponogenic matter. That is only one phase 
 of things, and we have already said that we 
 must regard also the organic reparation. Side 
 by side with the cleansing there is the repar- 
 ation. When once the leucomaines have in- 
 vaded and paralysed the cortical cells, all the 
 organism is relieved of the tyranny of the brain, 
 and each tissue is capable of restoring itself 
 tranquilly by inmost nutrition. Thus we under- 
 stand that man rises up in the morning, not 
 only freed from his fatigue, but armed with new 
 strength for a fresh activity, and that sleep, 
 even when artificial, may be of benefit. As 
 regards the amount, the quantity of leucomaines 
 contained in the organism is doubtless subject 
 to continual variation ; it increases or lessens 
 according as the productive phenomena or the 
 disassimilation preponderate. We see, thus, 
 that an increase of work may be capable of 
 leading to a decrease of fatigue, if this work 
 
222 
 
 increases at the same time and in a stronger 
 proportion, the oxidation and expulsion of waste. 
 Perhaps in this we reach one of the causes why- 
 exercise in the open air is so healthy. At other 
 times the decrease of fatigue is only apparent. 
 In proportion as an excessive weariness takes 
 hold upon the body, and as the cells which 
 intervene in conscious perception are finally 
 exhausted in their turn, consciousness becomes 
 more and more obscure, and fatigue, in so 
 far as regards the sensation experienced by 
 the patient, may thus diminish, because of the 
 very excess of work. It may happen, from an 
 opposite- cause, that the beginning of rest, far 
 from resting us, augments the subjective fa- 
 tigue. But this kind of phenomenon requires 
 another explanation, about which we shall say 
 a few words. 
 
 In the present day it will scarcely be doubted 
 that certain chemical decompositions of the mole- 
 cules of the nervous protoplasm are the condition 
 of cerebral activity. From all that precedes we 
 are led to attribute sleep also to a cliemical 
 reaction between this protoplasm and the leu- 
 comaines. Now, in virtue of principles of me- 
 chanics, it is in general more difficult to impress 
 on a body a determinate form of vibrations 
 when it is already vibrating than when at rest. 
 
223 
 
 Without quitting the domain of physiological 
 chemistry, NageH has shown that the existence 
 of fermentation hinders more or less completely 
 a different fermentation from establishing itself 
 in the same medium. If we apply the like 
 idea to the ganglionary cells, a mass of facts 
 which are familiar to us become at once intel- 
 ligible. In normal life we are conscious of no 
 fatigue during the greater portion of the day, 
 because the cerebral protoplasm defends itself 
 against the ponogenes by its very activity, and 
 it is only towards evening, when the army of 
 the ponogenes is become more formidable, that 
 the nerve centres commence to become feeble. 
 One may up to a certain point struggle against 
 fatigue, or betake oneself to repose ; the vig- 
 orous and varied sort of excitements retard 
 sleep, whilst tranquillity, monotony, inaction, 
 ennuiy and silence are favourable to it. Im- 
 mediately that the nerve-cells give way before 
 the enemy, they lessen their activity, the leu- 
 comaines invade them with more and more 
 facility'; first fatigue, then sleep, supervenes. 
 Fatigue appears to us, from this point of view, 
 like a conflict between the activity of the pro- 
 toplasm and the invasion of the waste matter ; 
 and sleep is the temporary victory of the waste 
 matter over the protoplasm. 
 
224 
 
 These observations give the key to a phe- 
 nomenon that, at first sight, might seern to be 
 opposed to our theory, which is this : — A.l- 
 though the formation of narcotic substances 
 goes on all clay, the passage from wakefulness 
 to sleep is usually rapid enough. Our day of 
 work has but little twilight. 
 
 This leads to a delicate question, and one 
 which as yet has been very little studied — the 
 soundness of sleep. Let us try to enter upon 
 it. According to Errera's theory the soundness 
 of sleep must be at all times in proportion to the 
 number of the molecules of the cortical centres, 
 which are in combination with the leucomaines. 
 At the beginning of sleep, everything facilitates 
 the arrival of the leucomaines ; they are rela- 
 tively in abundance in the organism, and the 
 central cells being inactive, leaves them free to 
 numb them. Thus sleep becomes soon more and 
 more profound, till the maximum is attained, 
 when all the stock of leucomaines combines. 
 But during this time the destruction and the 
 elimination of leucomaines have continued 
 going on more actively in proportion as the 
 gray substance appeared to be a favourable 
 medium of oxidation ; a portion then of the 
 leucomaines will be constantly destroyed within 
 the brain, and the intensity of the sleep will not 
 
225 
 
 take long to decrease, but that with a decreasing 
 rapidity, seeing that oxidation takes place on 
 less and still less quantities of leucomaines. 
 
 Experiment agrees very satisfactorily with 
 these deductions. Kohlschutter determined, 
 from half-hour to half-hour, the soundness of 
 sleep in the case of the same individual, ac- 
 cording to the intensity of sound necessary to 
 excite awakening. In spite of the sources of 
 error in a similar proceeding, the following re- 
 sults might, according to Exner, be regarded as 
 established. The intensity of sleep increases 
 promptly during the first hour ; it then decreases, 
 at first rather rapidly, and then more and 
 more slowly until awakening is complete. Kohl- 
 schutter has given us a curve which indicates 
 these variations ; a thing of some interest, and, 
 as we may foresee, the form of this curve remains 
 the same, whatever may be the intensity of the 
 sleep absolutely. It applies as well to sleep 
 produced by a slight degree of alcoholic intoxi- 
 cation as to normal sleep. In forming a suitable 
 hypothesis as to the proportion of leucomaines 
 which are being continually oxidized, Errera's 
 theory would furnish a curve of the same kind. 
 An observation of Brever, which it is easy for 
 one to repeat on himself, deserves here to be 
 mentioned. We often go to sleep whilst pass- 
 es 
 
226 
 
 ing through oscillations of consciousness and of 
 unconsciousness more or less distinct. The fact 
 seems sufficiently explicable. At the precise 
 moment at which we lose consciousness of what 
 surrounds us, the least diminution in the flow 
 of the leucomaines towards the brain may per- 
 mit the protoplasm to escape sufficiently their 
 action for consciousness to return ; but, the flow 
 again augmented, consciousness vanishes anew, 
 and so continues until the reign of sleep is defi- 
 nitely established. 
 
 If this theory of sleep is correct, it may be 
 asked whether there may not be counter-poisons, 
 antidotes of our ponogenes which are soporific 
 — ponolytes, if you will — which might counter- 
 act the fatiguing action of the products of 
 activity. Why not ? Grutzner and Gscheidlen 
 have established that reducing substances are 
 formed in the muscle by the effect of contrac- 
 tion ; and reciprocally, it appears, according to 
 Kronecker, that oxidizers, such as the per- 
 manganate of potash, in very feeble solution, 
 restores to the fatigued muscle its excitability 
 and strength. We likewise know that the 
 leucomaines are oxidisable, and it is probable 
 that one might destroy them by means of oxi- 
 dizers. Yawning, that deep inspiration of the 
 tired man — might its purpose not be that of 
 
furnishing him with a precise increase of 
 oxygen ? But, besides the oxidizers, might it 
 not be possible to discover veritable antidotes 
 to the narcotic leucomaines ? For example, al- 
 kaloids antagonistic to these substances, as 
 atropine is antagonistic to pilocarpine ; coffee, 
 which wakes up the brain ; coca, which sup- 
 presses, they say, for several days together, 
 hunger and fatigue, are perhaps of the number. 
 We must frankly add, however, that if a phar- 
 maceutic product happen to obviate fatigue 
 artificially, that does not imply that it procures 
 by the same time organic restoration — the re- 
 storative effect of a good sleep. 
 
 It would be well, however, to guard against 
 explaining too many things by alkaloids ; as 
 M. Guerin has remarked, "having abused the 
 microbes we must endeavour to avoid abusing 
 the ptomaines." But it is just to observe that it 
 Selmi has seen all the importance of animals 
 alkaloids, as regards forensic medicine, if Gau- 
 tier, Bouchard, and others have indicated their 
 role in the genesis of diseases, their important 
 place in normal physiology still remains, to a 
 larger extent, a virgin study, and one which 
 promises fresh harvests in discovery. Already 
 we catch a sort of glimpse that inebriation from 
 work, inebriation from success, inebriation from 
 
228 
 
 love, might well cease to be mere metaphors, 
 and range themselves with the actions of differ- 
 ent toxicants upon our nerve centres. Errera 
 hopes to have shown the probability that fatigue 
 is, in the proper sense of the word, an intoxica- 
 tion, of which sleep is the normal antidote. 
 Who knows whether many physiological acts — 
 respiration, movements of the heart, micturition, 
 defaecation — may not be like sleep dependent 
 on specific bodies, acting, be it on the nerve- 
 centres or upon the peripheral organs ? Or- 
 ganic rhythm would be due to the fact that a 
 given physiological act gave rise to substances, 
 which tend to provoke the contrary act, just as 
 the descent of the pendulum provides the ne- 
 cessary power to cause it to rise again. A very 
 recent work by Zuntz and Geppert concludes 
 that over and above the holder of the blood in 
 oxygen and in carbonic acid, there is yet a par- 
 ticular and unknown substance produced, and 
 chiefly by the muscular activity, which normally 
 intervenes to regulate the respiratory move- 
 ments. 
 
 Errera, in conclusion, sums up the theory of 
 sleep in a few lines : The activity of all the 
 tissues and, in the first line, of the two most 
 active, the nervous and the muscular, give 
 rise to bodies more or less analogous to alka- 
 
229 
 
 loids, the leucomaines. These leucomaines 
 are productive of fatigue, and are narcotic. 
 These leucomaines, then, must necessarily occa- 
 sion fatigue, and bring on sleep. In awaking, 
 if the organism be thoroughly refreshed, it is be- 
 cause these bodies have disappeared ; because 
 in such case, they are destroyed and eliminated 
 during normal sleep, the restorer." All this ap- 
 pears logically indisputable ; but it pertains to 
 direct experiment to furnish the proofs where we 
 as yet have only arguments. The quantity of 
 leucomaines, their presence in the brain, the 
 more complete study of their physiological pro- 
 perties are the first problems which offer them- 
 selves for solution. 
 
 It may be asked whether the leucomaines of 
 Gautier have so close an affinity to the pto- 
 maines and the alkaloids, properly so-called, as 
 that author asserts. There is here a question 
 of degree which admits of difference of opinion. 
 What appears to be established by his re- 
 searches, is the very general formation of 
 organic alkaloids in living beings, many of 
 which possess narcotic properties. Here we 
 have all that is necessary to serve as a starting- 
 point for the toxic theory of sleep such as 
 M. Errera has so ably brought before our 
 notice. 
 
APPENDIX. 
 
APPENDIX. 
 
 INTRODUCTION BY PROF. ARMAND GAUTIER, 
 
 Of the Faciilte of Medicine of Paris 
 and Member of the Academie de Medecine 
 and of the Academic des Sciences. 
 
 (FRENCH TEXT.) 
 
 Les phenomenes intimes qui se passent dans les 
 cellules vivantes, vegetales ou animales, sont encore 
 trop peu connus dans leurs mecanismes, et meme dans 
 leurs effets, pour qu'on puisse essayer de determiner 
 les causes profondes de leur Evolution normale ou anor- 
 male d'ou resultent la sante ou la maladie. Mais ce 
 qu'il est possible d'affirmer nettement c'est que ces 
 phenomenes sont tous physico-chimiques, et que si 
 la raison de leur succession nous echappe encore, ils 
 ne sauraient ne point obeir a cette loi naturelle tout a 
 fait generale qui veut que I'energie sous toutes ses 
 formes, — chaleur, travail musculaire, action chimique 
 ou nerveuse, &c., — resulte d'une transformation de 
 I'energie mechanique, potentielle ou actuelle, prdalable- 
 ment contenue dans la matiere de chaque cellule. 
 
 Or Ton sait aujourd'hui que chez les etres vivants,' 
 comme dans les substances inertes, les modifications 
 qui rendent I'energie sensible et utilisable sont de 
 deux sortes. Dans un premier cas, elle resulte des 
 modifications moleculaires produites dans la matiere 
 sans intervention de I'oxygene. Les organismes 
 qui empruntent entierement leur energie a cette 
 
234 Appendix. 
 
 source interieure sont ceux que M. Pasteur a nom- 
 mes anaerobics ; ce sont generalement des ferments 
 inferieurs ; mais j'ai montre ailleurs, que contraire- 
 ment a ce qu'on supposait a p7'iori la vie des grands 
 anirnaux est pour un large part, le cinquieme 
 environ, anaerohie. La seconde source de I'energie 
 resulte de la combinaison des substances chimiques et 
 particulierement, pour celles qui sont combustibles, 
 de leur union a I'oxygene. Les etres qui empruntent 
 surtout leur energie aux combustions internes sont les 
 aerobics. II en est de vegetaux, mails ils appartiennent 
 generalement au regne animal. Ils absorbent I'oxy- 
 gene, brullent les materiaux de leurs cellules, rejettent 
 incessament I'acide carbonique, I'eau, I'uree . . . ct 
 correlativement benencient de I'energie qui resulte 
 de ces combustions. 
 
 Dans les deux cas, les produits de la vie deviennent 
 impropres a entretenir les fonctions de la cellule qui 
 les a formes ; ils doivent disparaitre. L'animal suc- 
 comberait rapidement si I'acide carbonique, I'uree, 
 I'cau, et meme la chaleur qu'il forme sans cesse, 
 s'accumulaient dans son organisme. Mais dans le 
 cas de la vie anaerobic les produits qui se fabriquent, 
 sans intervention d'oxygene, surtout ceux qui derivent 
 du dedoublement des matieres albuminoides, sont 
 particulierement dangereux. Ils sont de la nature 
 de ces substances qui se produisent dans toute fer- 
 mentation bacterienne putride. L'on verra dans la 
 Premiere Partie de cet ouvrage que cette vie bac- 
 terienne anaerobic, donne lieu (outre d'autres corps 
 tres veneneux) a des alcaloides, rencontres aussi dans 
 
Appendix. 
 
 235 
 
 les matieres cadaveriques, et qui portent pour cette 
 cause le nom de ptomaines. Ceux de ces corps qui 
 sont constants dans toute fermentation putride pro- 
 longee appartiennent aux series pyridiques et hy- 
 dropyridiques ; ils ne sont pas eloignes des bases 
 veneneuses de la cigue et du tabac. On a depuis 
 demontre dans les produits de fernrientations plus 
 recentes la presence de substances alcaloi'diques plus 
 puissantes encore, telles que la ntuscarine, le poison de 
 la fausse-oronge, &c. Si done, comme je I'ai fait voir, 
 nous vivons en partie anaerobiquement, des alcaloides 
 analogues peuvent et doivent se former dans I'or- 
 ganisme : e'est ce qu'a confirme I'experience. J'ai 
 donne a ces bases le nom de leucomames, qui se borne 
 a indiquer seulement leur origine albuminoide. 
 
 Les produits de la vie aerobic ou anaerobic ne 
 sauraient sans domage, etre longtemps, ou en quan- 
 tite, retenus dans Torganisme. Regulierement nous 
 les excretons et les detruisons sans cesse. Mais 
 qu'une emotion frappe les centres nerveux ; qu'un 
 refroidissement arrete le fonctionement de la peau ; que 
 Fair arrive insuffisament au sang ; ou bien que pour une 
 cause plus cachee, les leucomai'nes se produisent plus 
 abondamment dans nos cellules que ces bases soient 
 plus difficilement resorbees, excretees ou oxydees ; 
 et que des lors le sang s'en charge abondamment et 
 les porte aux centres nerveux qui reglent nos fonc- 
 tions et president a la vie d'ensemble, aussitot le 
 desordre se generalise, se complete, et suit fatalement 
 sa marche; en un mot, la maladie apparait et se 
 deroule regulierement. 
 
236 Appendix. 
 
 Toutefois, il ne faudrait point etre trop exclusif, et 
 penser qu'ainsi s'explique, dans tous les cas, la suc- 
 cession des phenomenes morbides. Sans aucun doute 
 beaucoup d'etats pathologiques resultent des troubles 
 de la nutrition, de I'assimilation, de la desassimilation 
 des secretions, de I'hematose, &c. . . . et sont, en un 
 mot, de veritables auto-infections. Mais il est des cas 
 oil Ton ne saurait meconnaitre I'influence de causes que 
 I'organisme parait impuissant a produire spontane- 
 ment. On n'a jamais vu la syphilis, la rougeole, la 
 variole, le charbon lui-meme . . . ni la plupart des 
 maladies dites contagieuses et specifiques (a I'excep- 
 tion peut-etre du typhus des armees) apparaitre spon- 
 tanement, meme dans les organismes affaiblis, sans 
 contact prealable ou rapport direct ou indirect avec 
 un etre prealablement infecte. C'est la gloire de 
 M. Pasteur d'avoir demontre que dans la plupart de 
 ces cas Ton peut retirer de I'organisme malade un 
 microbe specifique cultivable apte a se reproduire au 
 dehors de I'etre infecte, et a faire reparaitre la mala- 
 die specifique primitive lorsqu'on I'introduit dans un 
 organisme sain. Mais qui ne voit que ces faits tres 
 importants sont un cas particulier de la vie des 
 cellules, telles qu'elles fonctionnent normalement dans 
 les grands animaux ? Le ferment ou microbe speci- 
 fique vit a la fagon d'une des cellules de nos tissus, 
 tantot aerobic^ com me lorsqu'il s'agit du charbon ; 
 tantot anaerobie, s'il s'agit par exemple du ferment de 
 la septicemic. II ne saurait echapper k cette loi qui 
 veut que toute cellule qui vit produise des detritus, des 
 matieres extractives, des ptomaines et leucomaifnes, 
 
Appendix. 
 
 237 
 
 causes prochaines de leur puissante action sur I'or- 
 ganisme. Mais, dans ce nouveau cas, ces cellules 
 etrangeres jouissent, a la fagon de celles du cancer par 
 exemple, d'une vie, d'une faculte regeneratrice intense, 
 et remplissent bientot toute I'organisme dcs produits 
 dangereux de leur puissante evolution. 
 
 Ce serait done une erreur de dire, avec les eleves 
 trop fervents du Maitre, que toute maladie resulte de 
 revolution dans I'organisme d'un microbe specifique. 
 II est des causes de maladie qui resident en nous ; 
 elles restent inoffensives tant que se continue I'elimi- 
 nation ou I'oxydation des detritus ; elles eveillent la 
 maladie, si pour une cause quelconque elles s'accu- 
 mulent dans I'economie et agissent sur les centres 
 nerveux. Mais a ces agents morbigenes dont se 
 debarrassent sans cesse nos tissus vivants, viennent 
 aussi, dans des cas plus rares, se surajouter ceux qui 
 proviennent de la vie normale de ces cellules parasites 
 qu'on a nommees microbes ou ferments, et qu'on 
 rencontre dans la plupart des maladies contagieuses 
 ou virulentes. 
 
 Les ptomaines et leucomai'nes, comme les matieres 
 extractives — I'uree, les ureides, I'acide carbonique, les 
 oxalates, les sels ammoniacaux — sont done des r^si- 
 dus de la vie, des materiaux inutiles ou dangereux. 
 lis peuvent devenir des causes directes de maladie, 
 quelle que soit leur origine, cellules normales de 
 I'organisme ou cellules microbiennes etrangeres. De 
 tout ces composes de dechet, les alcaloi'des d'origine 
 animale que la presente publication est destinee a 
 decrire, sont les plus dignes d'interet. lis avaient ete 
 
238 Appendix, 
 
 inconnus jusqu' a notre epoque ; et meritent d'autant 
 plus d'etre etudies que leur presence est constante 
 dans nos excretions normales, et qu'ils peuvent etre 
 ranges parmi les agents les plus actifs. Aussi je 
 pense que I'excellent livre de M. le Dr. Brown inter- 
 essera tres particulierement le public competent, et 
 qu'il contribuera a faire naitre de nouvelles recherches 
 profitables a I'eclaircissement de Tune des questions 
 les plus essentiellemcnt humaines : les causes et le 
 mecanisme de la vie et de la maladie. 
 
 Armand Gautier. 
 
 Paris, le 14 juillet, 1887 
 
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 245 
 
 F. Marino Zuco. — Berichte der deutschen Ges., p. 1043. 
 
 Gautier. — Compt. rendus de I'Acad. des Sc.^Monit. scien- 
 tific de Quesneville et Soc. chim., 27 Juin. 
 
 Calmeil. — Monit. scientific de Quesneville. 
 
 PoucHET. — Compt. rendus de I'Acad. des Sc., t. 99. 
 
 ViLLiERS. — Compt. rendus de I'Acad. des Sc., t. 99. 
 
 Bouchard. — Soc. de Biologic, p. 665. 
 
 Lepine et GuERiN. — Rev. de med., p. 765. 
 
 HusEMANN. — Archiv. fur Pharmacie, t. 222. 
 
 GuARESCHi e Mosso. — Riv. di chim., vol. VII, fasc. 3, p. 
 190. 
 
 RosENBACH. — Mikro-Organismen bei den Wundinfections- 
 krankheiten des Menschen. Wiesbaden. Berg- 
 man n. 
 
 A. M. Brown, — Origin of Contagia. 
 
 1885 
 
 O. BcECKLiscH. — Berichte der deutschen chem. Ges., p. 86 
 and 1922. 
 
 Villiers. — Compt. rendus de I'Acad. des Sc., t. 100, p. 
 91-93- 
 
 PoucHET. — Compt. rendus de I'Acad. des Sc., t. 100, p. 
 220-222. 
 
 KosSEL. — Berichte der deutschen Chem., p. 1928. 
 MoRiGGiA. — Atti della R. Acad, dei Lincei. Randiconti, p. 
 
 441-447 et 519-521. 
 Salkowski. — Virchow's Archiv. 
 Breiger. — Deutschen med. Wochenschrift. 
 
 Ueber Ptomaine. Berlin. Hirschwald. 
 Wirtere Untersuchungen iiber Ptomaine. Berlin. 
 Hirschwald. 
 
 Cervello.— Sur Taction physiol. de la neurine. Milan. 
 
246 Appendix 
 
 MoRiGGiA. — Experiences de physiotoxicologie sur le chlor- 
 hydrate de trimethylvinyl-ammonium et le chlor- 
 hydrate de trimcthylamine. Rome. 
 
 F. Marino Zuco. — Relazione delle esperienze fatte nel 
 laboratorio della commissionne annesso all'Istituto 
 chimico della R.. Universita di Roma, sulli cosi 
 delle ptomaine, in reguardo alle perizie tossicholo- 
 giche. Roma. R. Tipografia. 
 
 Lepine et AuBERT. — Compt. rendus de I'Acad. des Sc. 
 Juillet. 
 
 Lebon.— Compt. rendus de I'Acad. des Sc. Septembre. 
 Laborde. — Soc. de Biol., 27. 
 
 CECHSNER DE CONINCK. — SoC. dc Biol., loS. 
 
 Gautier. — Bull. Soc. Chim. 
 Gautier et MouRGUES. — Bull. Soc. Chim. 
 Ehrlich. — Das Sauerstoffbedlirfniss des Organismus. Ber- 
 lin. Hirschwald. 
 WiiRTZ. — Traite de chimie biologique. Paris. Masson. 
 
 1886 
 
 ScHULTZ und BossHARD. — Berichte der deutschen chem. 
 Ges., p. 261. 
 
 KossEL. — Zeitschrift fiir physiol. Chemie, 11. Marz, und 
 Berichte der deutschen chem. Ges., p. 316. 
 
 Lepine et Aubert. — Soc. de Biol., Janvier. 
 
 Victor C. Vaughan. — Zeitschrift fiir physiol. Chemie, p. 
 119. 
 
 Deutschen med. Wochenschrift, 10. Juni. 
 Bouchard. — Compt. rendus de I'Acad. des Sc., 21 mars et 
 17 mai. 
 
 A. PcEHL. — Berichte der deutschen chem. Ges., 24. Mai. 
 8, p. 1157. 
 
Appendix. 247 
 
 A. Gautier. — Bull, de I'Acad. de Med. Seances du. 12, 19 
 
 Janvier et suivantes. 
 A. M. Brown. — Contributions to the study of the Animal 
 
 Alkaloids. 
 
 L. HuGOUNENQ. — Les Alkaloides d'origine Animal. 
 
 1887 
 
 A. M. Brown. — The Animal Alkaloids, Cadaveric and 
 Vital ; or the Ptomaines and Leucomaines in 
 their Relations to Scientific Medicine. 
 
 Leo Errera. — Pourquoi Dormons-Nous ? Bruxelles. 
 
 Sir William Aitken. — The Animal Alkaloids : Pto- 
 maines, Leucomaines and Extractives in their 
 Pathological Relations. 
 
 Bouchard. — Legons sur les Auto-intoxications dans les 
 maladies. 
 
 1888 
 
 A. M. Brown. — Auto-Intoxication in Disease. Prov. Med. 
 
 Journ. The Probable Role of the Animal Alka- 
 loids in Fatigue and Sleep : A Resume. Prov. 
 Med. Journ. 
 
 Vaughan and Nory. — Ptomaines and Leucomaines, or the 
 Putrefactive and Physiological Alkaloids. Phila- 
 delphia, U.S. America. 
 
 A. P. Luff. — The Ptomaines or Animal Alkaloids, and 
 their Relations to Disease. Transactions of the 
 British Med. Assoc. 
 
 J. F. Knott. — The Fever of Over-Exertion. Transactions 
 of the Royal Academy of Medicine in Ireland. 
 
GENERAL INDEX. 
 
 Adenine, 76 
 
 Baccillar theory of cholera. 
 
 Albumenoids, various, 5 
 
 131 
 
 Leucomaines, 71 
 
 Bacterial ferment, 15, 120 
 
 Proteid substances, 8 
 
 Bergmann, 4 
 
 Putrefactive of, 23 
 
 Bernard, 208, 213 
 
 Alkaloids of Plants, no, 112 
 
 Betaine, 66, 73, 75 
 
 Cadaveric (see Ptoviaines^ 
 
 Bettenk, 56 
 
 see Leucomaines) 
 
 Biochemics, 109 
 
 Elaboration of, in 
 
 Blood, 93, 139 
 
 Non-Oxygenous, 33 
 
 Botulism, 131, 160 
 
 Oxygenous, 37 
 
 Bouchard, 100, 16^, passi?n 
 
 Quantity pf, 55 
 
 Boutmy, 31, 32 
 
 Spleen, 99 
 
 Brieger, 17, 25, 96 
 
 Aerobic, 117 
 
 Binz, 263 
 
 Allantoine, 92 
 
 Brouardel, 31, 53 
 
 Amides, 66 
 
 
 Amphicreatinine, 86 
 
 Cadaveric Alkaloids (see Pto- 
 
 Anaemia, 211 
 
 maines) 
 
 Anaerobic, 117 
 
 Cadaverine, 35 
 
 Army, fever of, 50 
 
 Canizzaro, 55 
 
 Aubert, 67 
 
 Carri, 106 
 
 Auto-intoxication, 139 
 
 Caventou, no 
 
 Auto-intoxication in disease. 
 
 Chemical Properties, 27 
 
 167 
 
 Chlorohydrate, 100 
 
 Auto-intoxication in health, 
 
 Cholera, 131 
 
 199 
 
 Choline, 40 
 
 Auto-typhusation, 154, 157 
 
 Chomel, 152 
 
 
 Clinics, 148, 196 
 
250 Appendix. 
 
 
 X C VCl , iVJi, l^U 
 
 152 
 
 Jbisn, II, 96, TOO 
 
 rioez 68 
 
 Krvrnpc; ^ir Tonn 
 
 XWLLJCOj oil JVJIlIij X^L/ 
 
 r^/-\Kvn aQ. r\(^ /(-/ly) Qn r,h 
 
 L^ODra, 40) t)o, 90 \see c>ualzes) 
 
 Frogs, 49 
 
 Combustion, 128, 138, 147 
 
 l^rouae, 30 
 
 Conicine, 54, 59 
 
 
 Coppola, 94 
 
 C\c\c\'\y\\y\(^ /IT 
 vjrciLiiiiiiic;, (ij. i. 
 
 Corona, 47, 53 
 
 vjrd.bpdl, ^ 
 
 Crusocreatinine, 88 
 
 vjij. liner, ^, 0, pcissiiii 
 
 Curara, 115 
 
 rrPiinfi'l" ? R 
 
 VJC^JJ |Jd L, ^ ^ (J 
 
 uianeiti, 53 
 
 UcclLO, 140 
 
 vJlULZ/llCl, 
 
 Definition, 33 
 
 Gscheidlen, 226 
 
 UcpcllLUXC, d, IlCW, 145 
 
 Guanine, 73? 7^ 
 
 De Parville, 206 
 
 Guareschi, 70 
 
 Dogs, 47, 94 
 
 Guerin, loi 
 
 Dragendorfif, 52, 56 
 
 
 Dupre, 4 
 
 Health ia8 
 
 Durham, 203 
 
 Heynsius, 203 
 
 Dyspepsia, 88 
 
 Hugounenq, 56 
 
 Humoralism, 26, 30 
 
 Egg, 116 
 
 HydrocoUidine, 32 
 
 Errera, 202, pctsshn 
 
 Hypoxanthine {see Sarki/ie) 
 
 Ftnrrl 
 
 Intestines, 95 
 
 
 TTo f 1 rrn 
 
 Jaundice, 192 
 
 i ypnolu 
 
 Jones, Dr. Bence, 4 
 
 Typhus 
 
 Extraction, Methods of, 19 
 
 ivarnine, 00, 90 
 
 HiXirdtiiciiiic, 159 
 
 -LViLiiicya, J- 
 
 
 Klein, 131 
 
 Fecundation, 116 
 
 Koch, 100, 131 
 
 Fermentation, 11 
 
 Kohlschutter, 225 
 
 Fermy, 73 
 
 Kossel, 115 
 
Appendix. 
 
 Kreatine, 70 
 
 Obersteiner, 204 
 
 Kreatinine, 86 
 
 Otto, 50 
 
 Kronecker, 226 
 
 Oxygen, 41 
 
 Labord, 99 
 
 "P o i'\ n m A 
 Xclulllll, 4 
 
 Lecithine, 69 
 
 Paralysis, 106 
 
 Lepine, 67^ loi 
 
 X dl. V UllllC, 
 
 Leucomaines {see Alkaloids) 
 
 Paterno, 69 
 
 Lieberman, 51 
 
 Pathology, 121, 
 
 Liebig, 72 
 
 Pelletier, 110 
 
 Liebreich, 73 
 
 Peter, 144 
 
 Life, 118, 147 
 
 Pettenkoffer, 70 
 
 A/Tnrrpf" 11 
 
 Physiology, 97 
 
 Medical import, 142 
 
 Picard, 68 
 
 TVTpfiirn-lpo'al c;o 
 
 Plant, Alkaloid, no 
 
 
 Pneumonia, loi 
 
 ivicLuy ixiy Lidiituiiic, 
 
 Ponogenes, 204 
 
 ivicycr b Lcbi, 54j 9^ 
 
 Pouchet, 17 
 
 A/ri(^rr»_o'Pr'miQm t /t f 
 
 XVX1(--1U gClllJloliJ, J- 4 J 
 
 Preyer, 204 
 
 
 Protomaine, 68 
 
 IVlloblUilb, ov-lcIiLlliL, yyj z 
 
 Prussian Blue, 57 
 
 lVrnlln<?rs n6 to6 
 
 Pseudoxanthine, 81 
 
 Morelle, 95 
 
 Ptomaine, Skeleton of. 
 
 Morphine, 100 
 
 Solid, 29 
 
 Miiller, 21 
 
 Putrescine, 36 
 
 Muscarine, 40 
 
 Putrefaction, 10 
 
 Mydaleine, 37 
 Mytilotoxine, 106 
 
 Quanquand, 158 
 
 NaTpli 2 2 '2 
 
 Ranke, 201 
 
 Nessler, 30, 105 
 
 Ravilliod, 159 
 
 Neuridine, 34 
 
 Respiration, 141 
 
 Neurine, 38, 148 
 
 Robequiet, no 
 
 Nucleine, ti6 
 
 Rosenthal, 200 
 
252 
 
 Rossbach, 212 
 
 Saliva, 68, 95, 103 
 Salkowski, 107 
 Sarcasine, 70 
 Saikine, 72, 79 
 Schmidtmann, 96 
 Schmiedeberg, 4 
 SchmitZj 2 
 Schuzenbeiger, 73 
 Schwerminger, 4 
 Selmi, 7 
 Sepsine, 4 
 Sertuerner, no 
 Shell-fish, 106 
 Sleep, 103, 203 
 Snakes {see Cobra) 
 Solvents — Alcohol, 19, 46 
 
 Chloroform, 46 
 
 Ether, 45 
 
 Benzine, 21 
 Somnambulism, 218 
 Sonnenschein, 3 
 Spica, 62, 69 
 Spleen, 95, 99 
 Stas, 19 
 
 Sulphuric Acid, 24 
 Tannin, 22 
 
 Tissue, 113, 119, 137, 
 Toxicology, 55, 57 
 
 Appendix, 
 
 Typhus, 102, 157 
 
 linger, 73 
 Urea, 150 
 
 Uric Leucomaine Group, 63 
 198 
 
 Urine, 92, 100 
 
 Day and Night, 207 
 Urotoxy, 184 
 
 Vallenciennes, 72 
 Van Dessel, 56 
 Van Gelder, 52 
 Veal, 70 
 Veratrine, 54 
 Villiers, 100 
 Virchow, 73 
 Viscera, 93 
 Vomiting, 142 
 
 Wartz, 94 
 Wefers, 56 
 Weidel, 73 
 
 Xanthine, 80 
 Xanthocreatinine, 87 
 
 Zalesky, 96 
 Zicco, Marino, 56, 58 
 Zuelzer, 3 
 Zuntz, 228 
 
PRESS OPINIONS. 
 
 " L'auteur termine son traite par un chapitre de considerations tres 
 interessantes sur le role physiologique at pathologique de ces curieuses 
 substances. Je crois que les lecteurs frangais et anglais trouveront dans 
 ce livre clairement et brievement expose tout ce qu'il leur importe de 
 connaitre sur ce sujet." — Bull, de PAcad. de Medicine. 
 
 "The book is brief, well-written, and easily studied. . . . ; 
 As a tirst edition of an advanced and most important subject it promises 
 a distinguished career." — The Asclepiad. 
 
 "The pages in which these views are elaborated are full of interest." 
 — Lancet 
 
 " As among the notable books, mention must be made of Dr. Brown's 
 'Animal Alkaloids,' which stands out as the most original work of the 
 year ; one opening up a new line of thought and investigation." — The 
 Medical Press and Circular. 
 
 " We have here a treatise on a new department of science. 
 The author, bringing to bear a wide knowledge of his subject, has . 
 accomplished his task with credit." — Provincial Medical journal. 
 
 Those readers " wishing to go deeply into the subject should read the 
 exhaustive treatise of Dr. Brown, whose name is well known as an 
 authority on the subject," — The Hospital Gazette. 
 
 " On the medico-legal aspect of the subject. Dr. A. M. Brown has 
 much that is of importance to communicate to us. . . , Enough 
 has been said to indicate the high interest which the present volume 
 must have for the student of medical jurisprudence." — The Law Maga- 
 zine and Kevieui. 
 
 " Those who wish to investigate further will find ample directions 
 in Dr. Brown's work. ... It is not merely a question interesting 
 to medical men and specialists. . . but one which must appeal to 
 all intellectual beings." — Llealth. 
 
 There are also reviews of the book in the British Medical Journal ; 
 The Westminster Review ; The PJiarniacetitical Journal ; The Analyst ; 
 Edinlncrgh ALonthly Medical Journal; Life-Lore; Scientijc News ; 
 St. Jaj?ies^s Gazette, dfc. 
 
J^y THE SAME AUTHOR. 
 
 A SERIES OF 
 
 Contributions TO the Study of the 
 Animal Alkaloids: 
 
 THE PTOMAINES AND LEUCOMAINES. 
 
 Origin of Confagia in relation to Theoretic Views and 
 Practical Application: 
 
 A STUDY IN EVOLUTION. 
 
 Comments on the VleY/s of MM. Armand Gautiep 
 and Michel Petep with Reference to the Animal 
 Alkaloids and their Role in Scientific Medicine. 
 
 The Physiological Alkaloids-The 
 leucomaines : 
 
 Their Discovery and Antecedents. 
 
BY THE SAME AUTHOR. 
 
 A RESUME OF 
 
 Armand Gautier's Researches on the 
 Animal Alkaloids: 
 
 Their Physiological and Pathological SigJiificance. 
 
 THE ANIMAL ALKALOIDS-PTOMAINES AND 
 LEUCOMAINES: THEIR COMMON ORIGIN. 
 
 A Fresh Page in Biochemics. 
 
 PTOMAINES, LEUCOMAINES AND MICROBES : 
 
 Their Physiological, Pathological and Clinical 
 Significance, 
 
 A Rdsicme of Michel Peter's Views. 
 
BY THE SAME AUTHOR. 
 
 Guy Patin : A Medical Study, 
 MoLiERE : A Medical Study. 
 
 An Hour with Hartmann ; or a Resume of the Philosophy 
 OF THE Unconscious. 
 
 Maupertius and Contemporary Pessimism. A Philosophic 
 Causerie. 
 
 Wintering on the Riviera. 
 
 The Influence of Climate in the Modification of Disease. 
 
 Report on Belladonna as a Prophylactic in an Epidemic 
 OF Scarlet Fp:ver, 
 
 Medical Notes on the Eucalyptus. 
 
 Comments on Lethargic Stupor or Trance. ' 
 
 The Origin of Contagia in Relation to Prevailing 
 Theoretic Views and Scientific Applications. 
 
 Ethics and ^Esthetics. A Causerie Intime. 
 
 The Genesis of Germs. 
 
 Latah and Myrachit; or, Maladies of Nervous Mimicry. 
 
 Some Comments on Leprosy in its Contagio-Syphilitic and 
 Vaccinal Aspects.