The formation of poisons by micro-organisms. A biological study of the germ theory of disease

Preface

The historical portion of this volume has been condensed from notes made from time to time in the study of the subject. With the view of making it as short as possible, I have given only those experiments and observations that seemed important to a proper understanding of the subject, avoiding all but the most necessary details; aiming at the same time to preserve all that will be of real advantage to the general student. Many familiar names will be missed, for the reason that many have written, and some of them very well indeed, who have developed no distinctive fact or thought that is of service in the farther progress of the subject. When we come to analyze any such subject, most men are surprised to find how few have been instrumental in the development of the real basic facts on which our knowledge of it rests. Therefore, if we can properly estimate the import of the matter presented, the history of the development of any such subject may be briefly written. Whether or not I have determined wisely, the intelligent reader must judge.

The second part was written because I had something to say that I thought ought to be said at the present time. The men who have been most instrumental in the development of this subject have given us little else than the experimental facts. These will satisfy the minds of but very few. Most of us appreciate any subject more if we understand why these things are so. It is this why that I have sought to supply. This I leave for intelligent discussion to sift, and separate the good grains from the chaff.

G. V. BLACK, M. D., D. D. S.

JACKSONVILLE, June 2d, 1884.

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Table Of Contents

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Preface iii

FIKST PART.

Part First. Acknowledgment

This volume contains a series of lectures, delivered before the students of the Chicago College of Dental Surgery and a number of practitioners who were ticketed especially for this course. The Lectures now appear in their present form through the co-operation and kindly assistance of the Officers and Faculty of that Institution, to all of whom I gratefully acknowledge myself indebted for many favors.

THE AUTHOR.

A STUDY

OF THE

GERM THEORY OF DISEASE.

HISTORICAL.

Introduction

In presenting an historical sketch of the Germ Theory of Disease, it will be my effort to review briefly the ideas, controversies and experiments, that have gradually led up to our present knowledge concerning it. At present I know of no single treatise on this subject from which those who have not followed its now extensive literature can gain a clear view of it, obtain a just conception of its magnitude, of the labor that has been bestowed upon it, or of its immense importance. The history of this subject in its completeness, would be a history of the efforts of men to stay the ravages of epidemic and contagious diseases ; a history of the efforts of men to understand the causes of plagues and pestilences ; a history of the efforts of men to see farther, and still farther, into the secret causes which produce sickness and diminish the longevity of the race. I cannot, however, give more than a brief synopsis of the principal thought, experiment and discussion, bearing most directly upon, and finally leading to the adoption of present theories. The literature of 2 11 the subject is DOW quite extensive, and is, for the most part, scattered through works upon disease in general, more especially works on surgery. Very few books were written especially on this branch of medicine until quite recently ; and these generally dealt with some particular phase of the subject, or with the very recent experimentation, giving little or no account of preceding inquiries. Therefore it is very difficult for one who takes up the subject now to gain a comprehensive view of it as a whole. It will be my object to supply such a view in a short and concise recital of the thought, experiment and discussion, that has been most eifective in leading to our present knowledge, and most essential to an understanding of the work now being done in this field.

FIRST TRACES.

For many centuries these ideas consisted in vague conjectures, arrived at from the study of contagion — an undefined something that could pass from the sick to the well, and cause disease. We find that Ulysses (Homer's Odyssy, Book XXII), used sulphurous acid to destroy the odor and toxic products of decomposition.

Early in the history of Greece we find that men had learned that certain localities were unhealthy. Their notion seemed to be that something obnoxious to health was being generated at these places; and we find them acting with judgment in regard to the location of their hospitals and important buildings. The physicians of antiquity observed that, in epidemic diseases the then existing theories were insufficient. They recognized that there was something extraordinary to deal with. They spoke of a " constitutio pestilens " and of a "genus epidemicus," but as to the nature of this constitution of disease they had few clear ideas.

Diodorus found an explanation of the cause of the Athenian

INCENTIVES TO THE STUDY. 13

Plague in the circumstance that " a great multitude of people from all quarters streamed into the city, and being cramped for room, breathed corrupted air." Decomposing filth, social squalor, bad weather, etc., were regarded as causes of disease, by both physicians and laymen.

INCENTIVES TO THE STUDY.

When we turn our attention to the contagious diseases, to the great plagues of past times, and watch the progress of thought in regard to them, the absence of knowledge of the means of staying their progress, the utter helplessness of the people in times of pestilence, seems simply terrible. Without a knowledge of the diseases of a country, we find it difficult to understand aright its history or its civilization. These great diseases have often destroyed the army of the conqueror, or given the death blow to an advancing civilization, and have left a strange and enduring impress upon the intellectual life of great communities. It is generally known how, in the Fourteenth Century, the most deadly of all the pestilences that are recorded in past history — the Black Death — changed the direction of intellectual and social activity throughout the chief part of the civilized world, and showed its impress on the developments of succeeding centuries. We can gain but a faint idea to-day, through what we have seen around us, of the devastation that may be caused by epidemic diseases running without check ; or of the significance they have had in the progress of civilization.

The terrible results of epidemic and contagious diseases have furnished the strongest possible incentives to the study of the underlying causes. In all ages of the world the effort to understand them has been unceasing.

FIRST DEFINITE ANNOUNCEMENT.

The first definite announcement of a belief that disease is caused by organic germs, that I have found, was in the time of the Roman Empire.

De-re-Rustica, Varro and Columella, refer the origin of malarious fevers to the entrance of low organisms into the body. But they seem not to have given the special observations upon which their conclusions were founded. All along down the centuries, the idea was frequently expressed that the plague of the day was caused by minute organisms.

This doctrine, however, obtained wide recognition when some sort of basis for such theories was furnished by the microscopic demonstration of very minute living organisms, invisible to the naked eye. Especially after the discovery of the spermatozoa by Leuwenhoeck in 1677. These were then, and for years afterwards, supposed to be real animals. It having now been demonstrated, apparently, that real animals were living in the bodies of men, the doctrine that diseases were caused by minute organisms spread far and wide. Among the best known advocates of this theory were Kirchen, Lancici, Valisneri, Raumum, and Linne. But even those who best understood the theory never reached anything more than rough conceptions ; while many lost themselves in wild exaggerations. The animals causing disease were described as flying about in the air, something like swarms of insects, with crooked bills and sharp claws ; and one writer proposed to destroy them during epidemics by the blowing of horns and the firing of cannon. We can readily conceive that such fantasies would bring down ridicule upon the whole theory ; and in time these wild notions were dissipated and the germ theory slept.

ZYMOSIS. 15

PHLOGISTON.

But amid these fantasies there was a deep vein of earnest observation and thought. Physicians saw a pestilence strike a community as a spark strikes among shavings, and kindling, attack person after person in society, as fire would leap from house to house in a city. Sydenham says : " Ita ignis ignein generat et maligno infectus morbo socium inficit."

Stahl supposes a principle of inflammability or the matter of -fire in composition with other bodies, an hypothetical element supposed to be pure fire, fixed in combustible bodies, in order to distinguish it from fire in action or in a state of liberty. This was called " Phlogiston." A similar supposition obtained in regard to epidemic and contagious diseases, viz., that there was some substance or force in man himself, which, when once put in motion, acted similarly to fire and spread with deadly effect. To this day, remedies directed against inflammation or inflammatory conditions are called an tiph logistics. This theory of the origin and propagation of epidemic diseases seems to have been much discussed.

ZYMOSIS.

Another hypothesis was based on the known action of ferments, which is maintained to this day, the present germ theory being considered within the limits of this hypothesis. It was seen that yeast, when added to certain compounds containing sugar, caused certain phenomena. That a very small quantity of the yeast was necessary for a beginning, and that this would be reproduced continuously. It could be carried from vat to vat of grape juice for any number of times, and the more fermentation accomplished the more the ferment increased. It was found, also, that this kind of fermentation would begin, but less promptly, without the addition of yeast, and that in this case also the yeast was formed. Now they reasoned that the action of epidemic and contagious diseases was the same. From the sick person it seemed that a substance or force was conveyed to the well. Thus, one sick person may infect a dozen, and each of these a dozen more, etc., so that the disease is rapidly diffused through a community. It will be seen at once that the similarity between the phenomena of these diseases and the phenomena of fermentation is very close. These two hypotheses gave rise to much discussion. They seem to have stood side by side until the one merged into the other, for the more they were discussed the more similar they seemed to become. Finally, the first is lost sight of and the Zymotic theory of epidemics and contagions, as developed by Willis in 1659, has continued to be the generally accepted theory.

JENNER.

When Jenner discovered the relation of the vaccine disease to smallpox, and began the use of the vaccine virus as a protective against that malady in 1798, there came a much greater confidence in the fermentation, or as it is called, the zymotic theory of contagion. Here the physician had a body that he could carry about and use at will, as he could yeast. He could introduce this disease-producing yeast, or virus, into the skin of a healthy person, and after a certain time, a disease would manifest itself; just as he could introduce yeast into a solution of sugar, and after a certain time, find the phenomena of fermentation. A small amount of either was sufficient ; in each case a certain period of rest was observed before the characteristic manifestations declared themselves ; a stage of incubation. In each case the peculiar product first used was largely increased. In case of the vaccine, a dozen could be vaccinated from the product of the first vaccination, just as from the product of the fermentation of a single butt of must

NINETEENTH CENTURY. 17

enough yeast could be produced to quickly start fermentation in a dozen more; and so on, ad infinitum, in both cases. The phenomena of the one following precisely the role of the phenomena of the otfcpw* in every respect, only one was the fermentation of sugar, and the other was the production of the disease, Vaccina.

Neither did the likeness stop here; but, as we shall see, it went much further. It was then well known that a certain amount of heat destroyed the power of yeast forever. Trial showed that precisely the same thing happened with the vaccine virus. Furthermore, it was well known that when a solution of sugar has been under the process of fermentation until that process has spontaneously ceased, a further fermentation could not be had by adding more yeast; although unfermented sugar may remain in the solution. The results when completed are completed once for all; and for a new trial a new mixture must be had. Or in other words, the result of fermentation prevents fermentation of the same character again taking place. These phenomena are again repeated by the vaccine virus. A person once vaccinated is rendered insusceptible to further vaccination; at least for some years. All these facts taken together furnished the strongest possible proof of the identity of the two processes, at least in mode of operation; however wide the difference in the results. And the well known fact, that in the great majority of the then known contagious diseases, one attack rendered the subject of it incapable of again taking the same malady, served to extend the theory to all diseases of this class.

NINETEENTH CENTURY.

This is the condition in which we find the theory of zymotic diseases at the beginning of the present century. To say that this theory was universally accepted and satisfactory, would be untrue. Very many denied the relevance of the facts brought forward, and sought other explanations; but without gaining much favor. Earnest men were examining the act of fermentation ; and especially seeking the causes of putrefaction. Why should a dead body pass so quickly into a state of putrefaction? Enough was known to convince many thoughtful men that putrefaction was not caused by anything inherent in the flesh itself; for, under some circumstances, decomposition did not take place. They had learned to prevent it, at least for a long time, in meats that were preserved for food. Many other circumstances came up which furnished food for thought, and which shook the faith in the idea that fermentation of vegetable substances and putrefaction of animal tissues were truly spontaneous and inherent in the nature of such bodies.

EARLY DISCOVERIES.

In the first decade of the sixteenth century, Von Helmont had shown that the gas arising from fermentation was different from common air ; was carbon dioxide. And the other product, alcohol, had been known from the earliest historic times, but it was not isolated until the fifteenth century, though its distillation was regularly practiced in the eighth. It had been shown by Gay-Lussac, that grape juice does not ferment in vacuo. This was discovered in a now classical series of experiments, in which this experimenter caused clean grapes to ascend through the mercury of a large barometer into the Toricellian vacuum, and then crushed them by means of a mercurial column. This juice remained unchanged, but the addition of small quantities of air set up fermentation. Stahl, in 1731, arrived at the conclusion that fermentation and putrefaction were similar or identical processes. This was also the opinion of Justus Liebig, one hundred years later.

EARLY DISCOVERIES. 19

In 1680 the Dutch professor Leuwenhoeck began the examination of yeast under the microscope, and found it to consist of minute ovoid or globular particles. But the imperfection of the instruments of his time prevented the discovery, which seemed so near, of the nature of these particles. Experiments of various kinds were instituted by many persons, a few of which may be mentioned : A bladder was filled with a solution of sugar and suspended in another solution of sugar, to which yeast had been added. While fermentation went regularly on in the fluid in the containing vessel, the fluid in the bladder did not partake in the fermentation. A vessel was divided into two compartments by a partition of filtering paper, a solution of sugar placed in each and yeast added to one. Fermentation went on promptly in the compartment to which the yeast was added, but the other remained free from fermentation. Many other experiments are also recorded, all tending to show that fermentation is something different from ordinary chemical action. But the men of the time seemed unable to understand the significance of their experiments, which, to us, prove conclusively that the substance causing fermentation is participate and not soluble, otherwise it would pass through the filters and produce its results.

In 1787 Fabroni affirmed that " the matter which decomposes sugar is a vegeto-animal substance; it resides in particular utricles in grapes, as well as in corn. When grapes are crushed this glutinous matter is mixed with the sugar. Directly the two substances come in contact, effervescence and fermentation commence."

Astier, in 1813, asserted that "the matter of ferment, recognized by Fabroni as an animal substance, was alive and derived its nourishment from the sugar, whence resulted the rupture of the equilibrium between the elements of this body. By this theory," said he, "it is easily explained that all the causes which kill animals or hinder their development must be opposed to fermentation " (Schutzenberger, page 38). This seems to be the first appearance of the modern germ theory in a definite form, and the first announcement of the true theory of the antiseptics. Astier, however, regarded the living substance as composed of animalcules. A number of observers within the next few years seem to have arrived at the same conclusion.

SCHWAK

The next real advance was made about the year 1838, when Schwan and La tour, each independently, took up the microscopic inquiry, with improved instruments, and discovered that the granules of yeast were membranous bags, which exhibited all the morphological characters of vegetable cells, and under proper conditions increased and multiplied, in the biological sense. The conclusion was quickly reached by them, that it was the life and growth of the plant which caused the chemical changes of fermentation ; and that the products, carbon dioxide and alcohol, were excrementitious products of the plants.

At this time Schwan was working on spontaneous generation, which he very distinctly negatived. He also, together with Schultz and Helmholtz, was the first to establish the fact that putrefaction would not occur without the presence of certain minute organisms, which might be destroyed by boiling; and then, that air deprived of these organisms by being heated, or by filtering through sulphuric acid, might be admitted and yet no decomposition would occur. This destroyed the hypothesis previously held, that oxygen was the active agent in decomposition ; yet it was not generally accepted. It is to this discovery that we owe our ability to preserve fruits, meats, etc., in cans hermetically sealed, which has conferred such blessings upon mankind.

LIEBIG'S OPPOSITION. 21

EFFECTS OF SCHWABS DISCOVERIES.

These brilliant discoveries very soon attracted general attention to the subject from the scientific world, and as identical theories, as we have shown, had long been held as to the modes of propagation and action of contagious diseases, and of fermentation and putrefaction, the theory of a contagiurn vivum again came to -the front, and was urged by some of the strongest minds of the time. The new theory, however, was destined to fight its way inch by inch. Every new fact that was put forth had to pass the most rigid criticism that the opponents of the theory could bring to bear upon it ; and for a time it seemed as if it would be crushed out of existence notwithstanding its apparent demonstration.

LIEBIG'S OPPOSITION.

The strongest opponent of the vital theory, as it seems to me, was the then comparatively young Professor of Chemistry at Giessen, Germany, Justus Liebig. Liebig' s view of fermentation is practically the same as that enunciated by Willis in 1659, and maintained by others in the succeeding years ; but it is in Professor Liebig's writings that the view reached its highest stage of development and can be best studied. It merits the closest scrutiny, for it has been the principal opponent with which the germ theory has had to contend. If we follow the contests between the chemists on the one side and the vitalists on the other, up to the present time, and analyze the arguments adduced by the chemists, we will find that the very few new facts which they have brought forward have all been based on the plan of Liebig's arguments. There has been nothing essentially new, nor has his argument been strengthened. In the years 1840-42, in response Jx) an invitation of the British Association for the Advancement of Science, Professor Liebig wrote a series of papers upon animal, vegetable and agricultural chemistry and the chemical transformations, including the action of the different ferments, yeast, putrefaction, contagion, miasrn, etc., in which he antagonized the vital theory of each of these with all the vigor of his wonderful intellect, and for the time crushed the rising confidence in the new theory.

The arguments brought forward by Liebig may be summed up as follows : u Fermentation is a result of the catalytic action of a decomposing body in contact with compounds of feeble molecular affinity, which is brought about in accordance with the following law of dynamics: A molecule set in motion by any power can impart its own motion to another molecule with which it may be in contact." Yeast, he argued, is a product of the decomposition of gluten, and is necessarily a decomposing body, and when added to must or wort, sets up in these bodies a motion of their molecules similar to its own, by which their saccharine elements are converted into the simpler and more stable compounds, carbonic acid and alcohol.

But the action upon the gluten is to convert it into a body identical with the original yeast. And thus the yeast seemed to grow ; but it is not a growth in the biological sense. This, he contended, is demonstrated by adding yeast to a pure solution of sugar, in which case, although the fermentation proceeds promptly, the quantity of the yeast not only did not increase, but actually diminished, being expended in the act of decomposition.

Putrefaction, he says, is just the same process, but with a different molecular motion. These molecular motions might reproduce themselves or not, as the substance on which they acted contained the substance from which they were produced or not. Miasms and contagions were considered as being of the same character.

His idea of a chemical force more powerful than the vital force appears, also, in his explanation of the manner in which poisons and medicines act. The manner in which inorganic poisons (medicines) gain admission to the tissues is -owing, in most cases, to the formation of a chemical compound by the union of the poison with the constituents of the organ upon which it acts ; it is owing to a chemical affinity more powerful than the vitality of the organ. Each of these substances, in its transit, produces a peculiar disturbance in the organism ; in other words, they exercise a medicinal action upon it, but they, themselves, suffer no decomposition. It is only when the solutions are diluted to a certain degree with water that they are absorbed by auimal tissues. In respect to this physical property of the animal tissues, alcohol resembles the inorganic salts.

Miasms and contagions were thus explained: "A miasm is a form of molecular force developed during the decomposition of vegetable bodies under certain peculiar circumstances, which has the power of setting up similar decompositions in the human blood ; but not finding in the blood or tissues the proper substance for its own reproduction, like yeast in sugar, it is not reproduced. Therefore, such diseases are not contagious."

" Contagious poisons find in the human blood and tissues substances from which they reproduce themselves, as yeast in must or wort is reproduced from the gluten ; consequently, these diseases are conveyable from the sick to the well ; in some instances by contact only, as in syphilis, in which case the physical form of the substance is that of a solid. In other instances through the air, in which case the physical form is that of a gas." He says, "several kinds of contagions are propagated through the air ; so that, according to the view already mentioned (of a contagium vivum), we must ascribe life to a gas, that is, to an aeriform body."

He thus recognized a gaseous form of ferments.

We have already spoken of the fact that when fermentation spontaneously ceased, it could not again be set up ; and its application to those contagious diseases which can, ordinarily, be had but once by the same individual. This theory was elaborated anew by Liebig, with telling effect against the vital theory. It was considered that in must or wort there is a certain substance that is decomposed by the peculiar molecular motion of vinous fermentation, namely, sugar; while the other portions of the compound are not necessarily affected. The blood is a very complex substance, containing many compounds held together by feeble molecular affinities, any one of which may be decomposed. In case of the contagious diseases, the decomposing body which causes the particular disease acts upon some single compound of the blood, decomposing it. If this particular component of the blood be very important to the vital processes, the disease will be very grave. If, on the other hand, this particular compound be not very important, the disease will be correspondingly light. Now in the progress of the disease this particular compound is all decomposed, as the sugar in grape juice, and if the patient has been able to withstand the shock, he returns to health with this one compound of the blood lacking, and it often happens that it is replaced very slowly, if at all ; therefore, the patient is protected for a time or permanently.

•Liebig explained the susceptibility of children to certain diseases while adults were insusceptible, by assuming that the constituent of the blood upon which the molecular motion poison acted in the child was absent in the adult. He also explained the differences in susceptibility of different individuals in the same way.

Finally, Liebig says, "all the supposed proofs of the vitality of contagions are merely ideas and figurative representations, fitted to render the phenomena more easy of apprehension by our senses, without explaining them. These figurative expressions, with which we are so willingly and easily satisfied in all sciences, are the foes of all inquiries into the mysteries of nature; they are like the Fata Morgana, which show us deceitful views of seas, fertile fields and luscious fruits, but leave us languishing when we have most need of what they promise. It is certain that the action of contagions is the result of a peculiar influence dependent upon chemical forces, and in no way connected with the vital principle.77

Liebig claimed that this poisonous substance could not be isolated, because it consisted of a peculiar form of molecular motion. But in many cases the substances containing this molecular motion poison could be had, which substance in itself was not poisonous, as was shown by exposing it to heat, thus rendering it innocuous by destroying this peculiar molecular power.

He also points out the fact that very many of these poisons are destroyed in the human stomach in the act of digestion, and that others are not. He explains these phenomena in this way. All of these ferment poisons owe their power to the peculiar molecular movement started and maintained by the act of decomposition. Now, when they come in contact with stable compounds they are unable to communicate their own movements to these associated molecules, and are consequently inert, or unable to propagate decomposition. But, if the intermixed substance is composed of molecules held together feebly, the molecular movement is communicated to them, and they pass into a state of decomposition.

Now the juices of the stomach are acid, and among the noxious substances many are alkaline, but some are acid. It therefore happens that when an alkaline organic poison or ferment is introduced into the stomach, its molecular force is antagonized by the acid juices it meets there and its molecular movement destroyed.

If, however, the noxious element be acid in its reaction, the juices of the stomach do not interfere with its molecular movement, but rather favor it. And instead of being destroyed, it is rendered even more virulent. This action of the stomach, he argues, is a very positive proof of the chemical nature of these poisons.

It is a noteworthy fact that in this essay Prof. Liebig practically ignores the microscopic demonstrations of the yeast plant. He evidently regarded it as, to a large extent, a fiction of the brain of over-zealous investigators, using what was in that day considered very high powers of the microscope. Not believing in the existence of the yeast plant, or the organisms of disease, he says, "The vital principle is only known to us through the peculiar forms of its instruments; that is, through the organs in which it resides. Hence, whatever kind of energy a substance may possess, it is amorphous and destitute of organs from which the impulse, motion or change proceeds ; it does not live."