Difference between revisions of "Book - A History of Science 17"

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Hitherto the cause of contagion, by which certain maladies spread from individual to individual, had been a total mystery, quite unillumined by the vague terms "miasm," "humor," "virus," and the like cloaks of ignorance. Here and there a prophet of science, as Schwann and Henle, had guessed the secret; but guessing, in science, is far enough from knowing. Now, for the first time, the world KNEW, and medicine had taken another gigantic stride towards the heights of exact science.
 
Hitherto the cause of contagion, by which certain maladies spread from individual to individual, had been a total mystery, quite unillumined by the vague terms "miasm," "humor," "virus," and the like cloaks of ignorance. Here and there a prophet of science, as Schwann and Henle, had guessed the secret; but guessing, in science, is far enough from knowing. Now, for the first time, the world KNEW, and medicine had taken another gigantic stride towards the heights of exact science.
 
===Preventive Inoculation===
 
 
The controversy over spontaneous generation, which, thanks to Pasteur and Tyndall, had just been brought to a termination, made it clear that no bacterium need be feared where an antecedent bacterium had not found lodgment; Listerism in surgery had now shown how much might be accomplished towards preventing the access of germs to abraded surfaces of the body and destroying those that already had found lodgment there. As yet, however, there was no inkling of a way in which a corresponding onslaught might be made upon those other germs which find their way into the animal organism by way of the mouth and the nostrils, and which, as was now clear, are the cause of those contagious diseases which, first and last, claim so large a proportion of mankind for their victims. How such means might be found now became the anxious thought of every imaginative physician, of every working microbiologist.
 
 
As it happened, the world was not kept long in suspense. Almost before the proposition had taken shape in the minds of the other leaders, Pasteur had found a solution. Guided by the empirical success of Jenner, he, like many others, had long practised inoculation experiments, and on February 9, 1880, he announced to the French Academy of Sciences that he had found a method of so reducing the virulence of a disease germ that when introduced into the system of a susceptible animal it produced only a mild form of the disease, which, however, sufficed to protect against the usual virulent form exactly as vaccinia protects against small-pox. The particular disease experimented with was that infectious malady of poultry known familiarly as "chicken cholera." In October of the same year Pasteur announced the method by which this "attenuation of the virus," as he termed it, had been brought about--by cultivation of the disease germs in artificial media, exposed to the air, and he did not hesitate to assert his belief that the method would prove "susceptible of generalization"--that is to say, of application to other diseases than the particular one in question.
 
 
Within a few months he made good this prophecy, for in February, 1881, he announced to the Academy that with the aid, as before, of his associates MM. Chamberland and Roux, he had produced an attenuated virus of the anthrax microbe by the use of which, as he affirmed with great confidence, he could protect sheep, and presumably cattle, against that fatal malady. "In some recent publications," said Pasteur, "I announced the first case of the attenuation of a virus by experimental methods only. Formed of a special microbe of an extreme minuteness, this virus may be multiplied by artificial culture outside the animal body. These cultures, left alone without any possible external contamination, undergo, in the course of time, modifications of their virulency to a greater or less extent. The oxygen of the atmosphere is said to be the chief cause of these attenuations--that is, this lessening of the facilities of multiplication of the microbe; for it is evident that the difference of virulence is in some way associated with differences of development in the parasitic economy.
 
 
"There is no need to insist upon the interesting character of these results and the deductions to be made therefrom. To seek to lessen the virulence by rational means would be to establish, upon an experimental basis, the hope of preparing from an active virus, easily cultivated either in the human or animal body, a vaccine-virus of restrained development capable of preventing the fatal effects of the former. Therefore, we have applied all our energies to investigate the possible generalizing action of atmospheric oxygen in the attenuation of virus.
 
 
"The anthrax virus, being one that has been most carefully studied, seemed to be the first that should attract our attention. Every time, however, we encountered a difficulty. Between the microbe of chicken cholera and the microbe of anthrax there exists an essential difference which does not allow the new experiment to be verified by the old. The microbes of chicken cholera do not, in effect, seem to resolve themselves, in their culture, into veritable germs. The latter are merely cells, or articulations always ready to multiply by division, except when the particular conditions in which they become true germs are known.
 
 
"The yeast of beer is a striking example of these cellular productions, being able to multiply themselves indefinitely without the apparition of their original spores. There exist many mucedines (Mucedinae?) of tubular mushrooms, which in certain conditions of culture produce a chain of more or less spherical cells called Conidae. The latter, detached from their branches, are able to reproduce themselves in the form of cells, without the appearance, at least with a change in the conditions of culture, of the spores of their respective mucedines. These vegetable organisms can be compared to plants which are cultivated by slipping, and to produce which it is not necessary to have the fruits or the seeds of the mother plant.
 
 
The anthrax bacterium, in its artificial cultivation, behaves very differently. Its mycelian filaments, if one may so describe them, have been produced scarcely for twenty-four or forty-eight hours when they are seen to transform themselves, those especially which are in free contact with the air, into very refringent corpuscles, capable of gradually isolating themselves into true germs of slight organization. Moreover, observation shows that these germs, formed so quickly in the culture, do not undergo, after exposure for a time to atmospheric air, any change either in their vitality or their virulence. I was able to present to the Academy a tube containing some spores of anthrax bacteria produced four years ago, on March 21, 1887. Each year the germination of these little corpuscles has been tried, and each year the germination has been accomplished with the same facility and the same rapidity as at first. Each year also the virulence of the new cultures has been tested, and they have not shown any visible falling off. Therefore, how can we experiment with the action of the air upon the anthrax virus with any expectation of making it less virulent?
 
 
"The crucial difficulty lies perhaps entirely in this rapid reproduction of the bacteria germs which we have just related. In its form of a filament, and in its multiplication by division, is not this organism at all points comparable with the microbe of the chicken cholera?
 
 
"That a germ, properly so called, that a seed, does not suffer any modification on account of the air is easily conceived; but it is conceivable not less easily that if there should be any change it would occur by preference in the case of a mycelian fragment. It is thus that a slip which may have been abandoned in the soil in contact with the air does not take long to lose all vitality, while under similar conditions a seed is preserved in readiness to reproduce the plant. If these views have any foundation, we are led to think that in order to prove the action of the air upon the anthrax bacteria it will be indispensable to submit to this action the mycelian development of the minute organism under conditions where there cannot be the least admixture of corpuscular germs. Hence the problem of submitting the bacteria to the action of oxygen comes back to the question of presenting entirely the formation of spores. The question being put in this way, we are beginning to recognize that it is capable of being solved.
 
 
"We can, in fact, prevent the appearance of spores in the artificial cultures of the anthrax parasite by various artifices. At the lowest temperature at which this parasite can be cultivated--that is to say, about +16 degrees Centigrade--the bacterium does not produce germs--at any rate, for a very long time. The shapes of the minute microbe at this lowest limit of its development are irregular, in the form of balls and pears--in a word, they are monstrosities--but they are without spores. In the last regard also it is the same at the highest temperatures at which the parasite can be cultivated, temperatures which vary slightly according to the means employed. In neutral chicken bouillon the bacteria cannot be cultivated above 45 degrees. Culture, however, is easy and abundant at 42 to 43 degrees, but equally without any formation of spores. Consequently a culture of mycelian bacteria can be kept entirely free from germs while in contact with the open air at a temperature of from 42 to 43 degrees Centigrade. Now appear the three remarkable results. After about one month of waiting the culture dies--that is to say, if put into a fresh bouillon it becomes absolutely sterile.
 
 
"So much for the life and nutrition of this organism. In respect to its virulence, it is an extraordinary fact that it disappears entirely after eight days' culture at 42 to 43 degrees Centigrade, or, at any rate, the cultures are innocuous for the guinea-pig, the rabbit, and the sheep, the three kinds of animals most apt to contract anthrax. We are thus able to obtain, not only the attenuation of the virulence, but also its complete suppression by a simple method of cultivation. Moreover, we see also the possibility of preserving and cultivating the terrible microbe in an inoffensive state. What is it that happens in these eight days at 43 degrees that suffices to take away the virulence of the bacteria? Let us remember that the microbe of chicken cholera dies in contact with the air, in a period somewhat protracted, it is true, but after successive attenuations. Are we justified in thinking that it ought to be the same in regard to the microbe of anthrax? This hypothesis is confirmed by experiment. Before the disappearance of its virulence the anthrax microbe passes through various degrees of attenuation, and, moreover, as is also the case with the microbe of chicken cholera, each of these attenuated states of virulence can be obtained by cultivation. Moreover, since, according to one of our recent Communications, anthrax is not recurrent, each of our attenuated anthrax microbes is, for the better-developed microbe, a vaccine--that is to say, a virus producing a less-malignant malady. What, therefore, is easier than to find in these a virus that will infect with anthrax sheep, cows, and horses, without killing them, and ultimately capable of warding off the mortal malady? We have practised this experiment with great success upon sheep, and when the season comes for the assembling of the flocks at Beauce we shall try the experiment on a larger scale.
 
 
<nowiki>"Already M. Toussaint has announced that sheep can be saved by preventive inoculations; but when this able observer shall have published his results; on the subject of which we have made such exhaustive studies, as yet unpublished, we shall be able to see the whole difference which exists between the two methods--the uncertainty of the one and the certainty of the other. That which we announce has, moreover, the very great advantage of resting upon the existence of a poison vaccine cultivable at will, and which can be increased indefinitely in the space of a few hours without having recourse to infected blood."[8]</nowiki>
 
 
This announcement was immediately challenged in a way that brought it to the attention of the entire world. The president of an agricultural society, realizing the enormous importance of the subject, proposed to Pasteur that his alleged discovery should be submitted to a decisive public test. He proposed to furnish a drove of fifty sheep half of which were to be inoculated with the attenuated virus of Pasteur. Subsequently all the sheep were to be inoculated with virulent virus, all being kept together in one pen under precisely the same conditions. The "protected" sheep were to remain healthy; the unprotected ones to die of anthrax; so read the terms of the proposition. Pasteur accepted the challenge; he even permitted a change in the programme by which two goats were substituted for two of the sheep, and ten cattle added, stipulating, however, that since his experiments had not yet been extended to cattle these should not be regarded as falling rigidly within the terms of the test.
 
 
It was a test to try the soul of any man, for all the world looked on askance, prepared to deride the maker of so preposterous a claim as soon as his claim should be proved baseless. Not even the fame of Pasteur could make the public at large, lay or scientific, believe in the possibility of what he proposed to accomplish. There was time for all the world to be informed of the procedure, for the first "preventive" inoculation--or vaccination, as Pasteur termed it--was made on May 5th, the second on May 17th, and another interval of two weeks must elapse before the final inoculations with the unattenuated virus. Twenty-four sheep, one goat, and five cattle were submitted to the preliminary vaccinations. Then, on May 31 st, all sixty of the animals were inoculated, a protected and unprotected one alternately, with an extremely virulent culture of anthrax microbes that had been in Pasteur's laboratory since 1877. This accomplished, the animals were left together in one enclosure to await the issue.
 
 
Two days later, June 2d, at the appointed hour of rendezvous, a vast crowd, composed of veterinary surgeons, newspaper correspondents, and farmers from far and near, gathered to witness the closing scenes of this scientific tourney. What they saw was one of the most dramatic scenes in the history of peaceful science--a scene which, as Pasteur declared afterwards, "amazed the assembly." Scattered about the enclosure, dead, dying, or manifestly sick unto death, lay the unprotected animals, one and all, while each and every "protected" animal stalked unconcernedly about with every appearance of perfect health. Twenty of the sheep and the one goat were already dead; two other sheep expired under the eyes of the spectators; the remaining victims lingered but a few hours longer. Thus in a manner theatrical enough, not to say tragic, was proclaimed the unequivocal victory of science. Naturally enough, the unbelievers struck their colors and surrendered without terms; the principle of protective vaccination, with a virus experimentally prepared in the laboratory, was established beyond the reach of controversy.
 
 
That memorable scientific battle marked the beginning of a new era in medicine. It was a foregone conclusion that the principle thus established would be still further generalized; that it would be applied to human maladies; that in all probability it would grapple successfully, sooner or later, with many infectious diseases. That expectation has advanced rapidly towards realization. Pasteur himself made the application to the human subject in the disease hydrophobia in 1885, since which time that hitherto most fatal of maladies has largely lost its terrors. Thousands of persons bitten by mad dogs have been snatched from the fatal consequences of that mishap by this method at the Pasteur Institute in Paris, and at the similar institutes, built on the model of this parent one, that have been established all over the world in regions as widely separated as New York and Nha-Trang.
 
 
  
 
===Serum-Therapy===
 
===Serum-Therapy===

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العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Williams HS. A History of Science. (1904) Harper and Bros. New York.

A History of Science: Arabian Medicine | Mediaeval Science in the West | The Great Anatomists | The coming of Harvey | Leeuwenhoek Discovers Bacteria | Medicine in the 16th and 17th Century | Philosopher-Scientists and new Institutions | 18th Century Anatomy and Physiology Part 1 | 18th Century Anatomy and Physiology Part 2 | 18th Century Anatomy and Physiology Part 3 | 19th Century Anatomy and Physiology Part 1 | 19th Century Anatomy and Physiology Part 2 | 19th Century Anatomy and Physiology Part 3 | Theories Of Evolution Part 1 | Theories Of Evolution Part 2 | 18th Century Medicine | 19th Century Medicine Part 1 | 19th Century Medicine Part 2 | Brain and Mind | Brain Structure | Embryology History
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19th Century Medicine Part 1

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العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Williams HS. A History of Science. (1904) Harper and Bros. New York.

A History of Science: Arabian Medicine | Mediaeval Science in the West | The Great Anatomists | The coming of Harvey | Leeuwenhoek Discovers Bacteria | Medicine in the 16th and 17th Century | Philosopher-Scientists and new Institutions | 18th Century Anatomy and Physiology Part 1 | 18th Century Anatomy and Physiology Part 2 | 18th Century Anatomy and Physiology Part 3 | 19th Century Anatomy and Physiology Part 1 | 19th Century Anatomy and Physiology Part 2 | 19th Century Anatomy and Physiology Part 3 | Theories Of Evolution Part 1 | Theories Of Evolution Part 2 | 18th Century Medicine | 19th Century Medicine Part 1 | 19th Century Medicine Part 2 | Brain and Mind | Brain Structure | Embryology History
Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

19th Century Medicine Part 2

Pasteur and the Germ Theory of Disease

The discovery of the anaesthetic power of drugs was destined presently, in addition to its direct beneficences, to aid greatly in the progress of scientific medicine, by facilitating those experimental studies of animals from which, before the day of anaesthesia, many humane physicians were withheld, and which in recent years have led to discoveries of such inestimable value to humanity. But for the moment this possibility was quite overshadowed by the direct benefits of anaesthesia, and the long strides that were taken in scientific medicine during the first fifteen years after Morton's discovery were mainly independent of such aid. These steps were taken, indeed, in a field that at first glance might seem to have a very slight connection with medicine. Moreover, the chief worker in the field was not himself a physician. He was a chemist, and the work in which he was now engaged was the study of alcoholic fermentation in vinous liquors. Yet these studies paved the way for the most important advances that medicine has made in any century towards the plane of true science; and to this man more than to any other single individual--it might almost be said more than to all other individuals--was due this wonderful advance. It is almost superfluous to add that the name of this marvellous chemist was Louis Pasteur.


The studies of fermentation which Pasteur entered upon in 1854 were aimed at the solution of a controversy that had been waging in the scientific world with varying degrees of activity for a quarter of a century. Back in the thirties, in the day of the early enthusiasm over the perfected microscope, there had arisen a new interest in the minute forms of life which Leeuwenhoek and some of the other early workers with the lens had first described, and which now were shown to be of almost universal prevalence. These minute organisms had been studied more or less by a host of observers, but in particular by the Frenchman Cagniard Latour and the German of cell-theory fame, Theodor Schwann. These men, working independently, had reached the conclusion, about 1837, that the micro-organisms play a vastly more important role in the economy of nature than any one previously had supposed. They held, for example, that the minute specks which largely make up the substance of yeast are living vegetable organisms, and that the growth of these organisms is the cause of the important and familiar process of fermentation. They even came to hold, at least tentatively, the opinion that the somewhat similar micro-organisms to be found in all putrefying matter, animal or vegetable, had a causal relation to the process of putrefaction.

This view, particularly as to the nature of putrefaction, was expressed even more outspokenly a little later by the French botanist Turpin. Views so supported naturally gained a following; it was equally natural that so radical an innovation should be antagonized. In this case it chanced that one of the most dominating scientific minds of the time, that of Liebig, took a firm and aggressive stand against the new doctrine. In 1839 he promulgated his famous doctrine of fermentation, in which he stood out firmly against any "vitalistic" explanation of the phenomena, alleging that the presence of micro-organisms in fermenting and putrefying substances was merely incidental, and in no sense causal. This opinion of the great German chemist was in a measure substantiated by experiments of his compatriot Helmholtz, whose earlier experiments confirmed, but later ones contradicted, the observations of Schwann, and this combined authority gave the vitalistic conception a blow from which it had not rallied at the time when Pasteur entered the field. Indeed, it was currently regarded as settled that the early students of the subject had vastly over-estimated the importance of micro-organisms.

And so it came as a new revelation to the generality of scientists of the time, when, in 1857 and the succeeding half-decade, Pasteur published the results of his researches, in which the question had been put to a series of altogether new tests, and brought to unequivocal demonstration.

He proved that the micro-organisms do all that his most imaginative predecessors had suspected, and more. Without them, he proved, there would be no fermentation, no putrefaction--no decay of any tissues, except by the slow process of oxidation. It is the microscopic yeast-plant which, by seizing on certain atoms of the molecule, liberates the remaining atoms in the form of carbonic-acid and alcohol, thus effecting fermentation; it is another microscopic plant--a bacterium, as Devaine had christened it--which in a similar way effects the destruction of organic molecules, producing the condition which we call putrefaction. Pasteur showed, to the amazement of biologists, that there are certain forms of these bacteria which secure the oxygen which all organic life requires, not from the air, but by breaking up unstable molecules in which oxygen is combined; that putrefaction, in short, has its foundation in the activities of these so-called anaerobic bacteria.

In a word, Pasteur showed that all the many familiar processes of the decay of organic tissues are, in effect, forms of fermentation, and would not take place at all except for the presence of the living micro-organisms. A piece of meat, for example, suspended in an atmosphere free from germs, will dry up gradually, without the slightest sign of putrefaction, regardless of the temperature or other conditions to which it may have been subjected. Let us witness one or two series of these experiments as presented by Pasteur himself in one of his numerous papers before the Academy of Sciences.

Experiments with Grape Sugar

"In the course of the discussion which took place before the Academy upon the subject of the generation of ferments properly so-called, there was a good deal said about that of wine, the oldest fermentation known. On this account I decided to disprove the theory of M. Fremy by a decisive experiment bearing solely upon the juice of grapes.

"I prepared forty flasks of a capacity of from two hundred and fifty to three hundred cubic centimetres and filled them half full with filtered grape-must, perfectly clear, and which, as is the case of all acidulated liquids that have been boiled for a few seconds, remains uncontaminated although the curved neck of the flask containing them remain constantly open during several months or years.

"In a small quantity of water I washed a part of a bunch of grapes, the grapes and the stalks together, and the stalks separately. This washing was easily done by means of a small badger's-hair brush. The washing-water collected the dust upon the surface of the grapes and the stalks, and it was easily shown under the microscope that this water held in suspension a multitude of minute organisms closely resembling either fungoid spores, or those of alcoholic Yeast, or those of Mycoderma vini, etc. This being done, ten of the forty flasks were preserved for reference; in ten of the remainder, through the straight tube attached to each, some drops of the washing-water were introduced; in a third series of ten flasks a few drops of the same liquid were placed after it had been boiled; and, finally, in the ten remaining flasks were placed some drops of grape-juice taken from the inside of a perfect fruit. In order to carry out this experiment, the straight tube of each flask was drawn out into a fine and firm point in the lamp, and then curved. This fine and closed point was filed round near the end and inserted into the grape while resting upon some hard substance. When the point was felt to touch the support of the grape it was by a slight pressure broken off at the point file mark. Then, if care had been taken to create a slight vacuum in the flask, a drop of the juice of the grape got into it, the filed point was withdrawn, and the aperture immediately closed in the alcohol lamp. This decreased pressure of the atmosphere in the flask was obtained by the following means: After warming the sides of the flask either in the hands or in the lamp-flame, thus causing a small quantity of air to be driven out of the end of the curved neck, this end was closed in the lamp. After the flask was cooled, there was a tendency to suck in the drop of grape-juice in the manner just described.

"The drop of grape-juice which enters into the flask by this suction ordinarily remains in the curved part of the tube, so that to mix it with the must it was necessary to incline the flask so as to bring the must into contact with the juice and then replace the flask in its normal position. The four series of comparative experiments produced the following results:

"The first ten flasks containing the grape-must boiled in pure air did not show the production of any organism. The grape-must could possibly remain in them for an indefinite number of years. Those in the second series, containing the water in which the grapes had been washed separately and together, showed without exception an alcoholic fermentation which in several cases began to appear at the end of forty-eight hours when the experiment took place at ordinary summer temperature. At the same time that the yeast appeared, in the form of white traces, which little by little united themselves in the form of a deposit on the sides of all the flasks, there were seen to form little flakes of Mycellium, often as a single fungoid growth or in combination, these fungoid growths being quite independent of the must or of any alcoholic yeast. Often, also, the Mycoderma vini appeared after some days upon the surface of the liquid. The Vibria and the lactic ferments properly so called did not appear on account of the nature of the liquid.

"The third series of flasks, the washing-water in which had been previously boiled, remained unchanged, as in the first series. Those of the fourth series, in which was the juice of the interior of the grapes, remained equally free from change, although I was not always able, on account of the delicacy of the experiment, to eliminate every chance of error. These experiments cannot leave the least doubt in the mind as to the following facts:

Grape-must, after heating, never ferments on contact with the air, when the air has been deprived of the germs which it ordinarily holds in a state of suspension.

"The boiled grape-must ferments when there is introduced into it a very small quantity of water in which the surface of the grapes or their stalks have been washed.

"The grape-must does not ferment when this washing-water has been boiled and afterwards cooled.

"The grape-must does not ferment when there is added to it a small quantity of the juice of the inside of the grape.

"The yeast, therefore, which causes the fermentation of the grapes in the vintage-tub comes from the outside and not from the inside of the grapes. Thus is destroyed the hypothesis of MM. Trecol and Fremy, who surmised that the albuminous matter transformed itself into yeast on account of the vital germs which were natural to it. With greater reason, therefore, there is no longer any question of the theory of Liebig of the transformation of albuminoid matter into ferments on account of the oxidation."

Foreign Organisms and the Wort of Beer

"The method which I have just followed," Pasteur continues, "in order to show that there exists a correlation between the diseases of beer and certain microscopic organisms leaves no room for doubt, it seems to me, in regard to the principles I am expounding.


"Every time that the microscope reveals in the leaven, and especially in the active yeast, the production of organisms foreign to the alcoholic yeast properly so called, the flavor of the beer leaves something to be desired, much or little, according to the abundance and the character of these little germs. Moreover, when a finished beer of good quality loses after a time its agreeable flavor and becomes sour, it can be easily shown that the alcoholic yeast deposited in the bottles or the casks, although originally pure, at least in appearance, is found to be contaminated gradually with these filiform or other ferments. All this can be deduced from the facts already given, but some critics may perhaps declare that these foreign ferments are the consequences of the diseased condition, itself produced by unknown causes.


"Although this gratuitous hypothesis may be difficult to uphold, I will endeavor to corroborate the preceding observations by a clearer method of investigation. This consists in showing that the beer never has any unpleasant taste in all cases when the alcoholic ferment properly so called is not mixed with foreign ferments; that it is the same in the case of wort, and that wort, liable to changes as it is, can be preserved unaltered if it is kept from those microscopic parasites which find in it a suitable nourishment and a field for growth.


"The employment of this second method has, moreover, the advantage of proving with certainty the proposition that I advanced at first--namely, that the germs of these organisms are derived from the dust of the atmosphere, carried about and deposited upon all objects, or scattered over the utensils and the materials used in a brewery-materials naturally charged with microscopic germs, and which the various operations in the store-rooms and the malt-house may multiply indefinitely.


"Let us take a glass flask with a long neck of from two hundred and fifty to three hundred cubic centimetres capacity, and place in it some wort, with or without hops, and then in the flame of a lamp draw out the neck of the flask to a fine point, afterwards heating the liquid until the steam comes out of the end of the neck. It can then be allowed to cool without any other precautions; but for additional safety there can be introduced into the little point a small wad of asbestos at the moment that the flame is withdrawn from beneath the flask. Before thus placing the asbestos it also can be passed through the flame, as well as after it has been put into the end of the tube. The air which then first re-enters the flask will thus come into contact with the heated glass and the heated liquid, so as to destroy the vitality of any dust germs that may exist in the air. The air itself will re-enter very gradually, and slowly enough to enable any dust to be taken up by the drop of water which the air forces up the curvature of the tube. Ultimately the tube will be dry, but the re-entering of the air will be so slow that the particles of dust will fall upon the sides of the tube. The experiments show that with this kind of vessel, allowing free communication with the air, and the dust not being allowed to enter, the dust will not enter at all events for a period of ten or twelve years, which has been the longest period devoted to these trials; and the liquid, if it were naturally limpid, will not be in the least polluted neither on its surface nor in its mass, although the outside of the flask may become thickly coated with dust. This is a most irrefutable proof of the impossibility of dust getting inside the flask.


"The wort thus prepared remains uncontaminated indefinitely, in spite of its susceptibility to change when exposed to the air under conditions which allow it to gather the dusty particles which float in the atmosphere. It is the same in the case of urine, beef-tea, and grape-must, and generally with all those putrefactable and fermentable liquids which have the property when heated to boiling-point of destroying the vitality of dust germs."[7]


There was nothing in these studies bearing directly upon the question of animal diseases, yet before they were finished they had stimulated progress in more than one field of pathology. At the very outset they sufficed to start afresh the inquiry as to the role played by micro-organisms in disease. In particular they led the French physician Devaine to return to some interrupted studies which he had made ten years before in reference to the animal disease called anthrax, or splenic fever, a disease that cost the farmers of Europe millions of francs annually through loss of sheep and cattle. In 1850 Devaine had seen multitudes of bacteria in the blood of animals who had died of anthrax, but he did not at that time think of them as having a causal relation to the disease. Now, however, in 1863, stimulated by Pasteur's new revelations regarding the power of bacteria, he returned to the subject, and soon became convinced, through experiments by means of inoculation, that the microscopic organisms he had discovered were the veritable and the sole cause of the infectious disease anthrax.


The publication of this belief in 1863 aroused a furor of controversy. That a microscopic vegetable could cause a virulent systemic disease was an idea altogether too startling to be accepted in a day, and the generality of biologists and physicians demanded more convincing proofs than Devaine as yet was able to offer.


Naturally a host of other investigators all over the world entered the field. Foremost among these was the German Dr. Robert Koch, who soon corroborated all that Devaine had observed, and carried the experiments further in the direction of the cultivation of successive generations of the bacteria in artificial media, inoculations being made from such pure cultures of the eighth generation, with the astonishing result that animals thus inoculated succumbed to the disease.


Such experiments seem demonstrative, yet the world was unconvinced, and in 1876, while the controversy was still at its height, Pasteur was prevailed upon to take the matter in hand. The great chemist was becoming more and more exclusively a biologist as the years passed, and in recent years his famous studies of the silk-worm diseases, which he proved due to bacterial infection, and of the question of spontaneous generation, had given him unequalled resources in microscopical technique. And so when, with the aid of his laboratory associates Duclaux and Chamberland and Roux, he took up the mooted anthrax question the scientific world awaited the issue with bated breath. And when, in 1877, Pasteur was ready to report on his studies of anthrax, he came forward with such a wealth of demonstrative experiments--experiments the rigid accuracy of which no one would for a moment think of questioning--going to prove the bacterial origin of anthrax, that scepticism was at last quieted for all time to come.


Henceforth no one could doubt that the contagious disease anthrax is due exclusively to the introduction into an animal's system of a specific germ--a microscopic plant--which develops there. And no logical mind could have a reasonable doubt that what is proved true of one infectious disease would some day be proved true also of other, perhaps of all, forms of infectious maladies.


Hitherto the cause of contagion, by which certain maladies spread from individual to individual, had been a total mystery, quite unillumined by the vague terms "miasm," "humor," "virus," and the like cloaks of ignorance. Here and there a prophet of science, as Schwann and Henle, had guessed the secret; but guessing, in science, is far enough from knowing. Now, for the first time, the world KNEW, and medicine had taken another gigantic stride towards the heights of exact science.

Serum-Therapy

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


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


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


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


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


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


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


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


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

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Cite this page: Hill, M.A. (2021, October 23) Embryology Book - A History of Science 17. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_A_History_of_Science_17

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19th Century Medicine Part 2


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Cite this page: Hill, M.A. (2021, October 23) Embryology Book - A History of Science 17. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_A_History_of_Science_17

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© Dr Mark Hill 2021, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G