# Popular Science Monthly/Volume 48/April 1896/The Practical Results of Bacteriological Researches

 THE PRACTICAL RESULTS OF BACTERIOLOGICAL RESEARCHES.[1]
By GEORGE M. STERNBERG, M. D., LL. D.,

SURGEON GENERAL, U. S. A.

GENTLEMEN: In selecting a subject for my presidential address I have thought it best to restrict myself to that branch, of biological science with which I am most familiar; and, as a technical paper might prove uninteresting to many of those who constitute my present audience, I have chosen a title for my address which will enable me to speak in a general way of the development of our knowledge relating to the low vegetable organisms known as bacteria, and the practical results which have been the outcome of researches commenced in the first instance solely on account of their scientific interest.

Attention was first prominently called to the bacteria by the investigations relating to spontaneous generation. It was generally believed prior to the researches of Spallanzini, in 1776, that the development of micro-organisms in boiled organic fluids exposed to the air was by heterogenesis. Spallanzini showed by experiment that in some instances putrescible liquids when boiled and kept in hermetically sealed flasks could be preserved indefinitely without undergoing change. But he was not always successful in this experiment. Bastian, and other supporters of the theory of heterogenesis, at a later date, repeated these experiments with similar results, and maintained that when a development of micro-organisms occurred in a boiled fluid contained in a hermetically sealed flask it could only be by spontaneous generation. But Pasteur, in 1860, gave the true explanation of the appearance of living bacteria under such conditions. He proved that when development occurs it is because the organic liquid has not been completely sterilized, and that certain micro-organisms (spores of bacilli) withstand the boiling temperature, especially when they are suspended in a liquid having an alkaline reaction. At the present day this question is regarded as definitely settled, at least so far as known conditions are concerned; and we have an exact experimental knowledge of the thermal death-point of many micro-organisms of this class.

The principal pathogenic bacteria are destroyed at temperatures much below the boiling point of water. Thus, in experiments made by the present speaker in 1885 it was ascertained that the cholera spirillum is destroyed by ten minutes' exposure to a temperature of 52° C.; the typhoid bacillus by 56°; the micrococcus of pneumonia by 52°; the streptococcus of erysipelas (S. pyogenes) by 54°; etc. According to Loeffler, the bacillus of glanders is destroyed in ten minutes by a temperature of 55° C.; the bacillus of diphtheria by 60°. The experiments of Yersin show that the tubercle bacillus does not survive exposure for ten minutes to a temperature of 70° C. The practical value of such knowledge is apparent. Articles of clothing infected with any of the pathogenic bacteria mentioned would be speedily disinfected by immersion in water heated to 70° C. or above, and water or milk recently heated to the same temperature would evidently be without danger so far as infection by these "disease germs" is concerned. The recommendation of sanitarians that water or milk or food suspected of being contaminated by pathogenic bacteria should be exposed to a boiling temperature before it is used is based upon the experimental data referred to; and the knowledge that organic liquids can be sterilized by heat constitutes the foundation upon which the bacteriology of the present day has been established. To obtain reliable information with reference to the biological characters of any particular micro-organism it is necessary to experiment with pure cultures, and this requires a sterile culture medium.

It is hardly necessary to call attention to the fact that an immense industry in the preservation of food products depends upon the sterilization of these products by heat, and their preservation in hermetically sealed receptacles.

When Pasteur demonstrated the fact that sterile organic liquids, when protected by a sterilized cotton air-filter, can be kept indefinitely without undergoing any putrefactive or fermentative change, he also proved that such changes are due to the presence of micro-organisms; and, extending his investigations, he found that certain definite kinds of change are due to particular species of low organisms. Thus the alcoholic fermentation of a saccharine liquid was found to be due to a torula (Torula cerevisiæ), the acetic fermentation of an alcoholic liquid to a bacterial ferment (Pasteur's Mycoderma aceti), etc. Subsequent researches show that alcoholic fermentation may be induced by several species of torula, and even by certain bacteria; while the number of bacterial ferments now known to science is very considerable and is constantly being added to. Among the most important of these we may mention the Bacillus acidi lactici, which is the usual cause of the acid fermentation of milk; the various anaërobic bacilli which give rise to the formation of butyric acid in solutions containing starch, dextrin, sugar, or salts of lactic acid; the bacteria which cause the alkaline fermentation of urine; those which produce marsh gas by the fermentation of cellulose; those which effect the decomposition of albumin, with an evolution of hydrosulphuric acid; those which give rise to the putrefactive decomposition of organic material, the number of which is very large; the bacteria in the soil which reduce nitrates with liberation of ammonia and free nitrogen, and those which oxidize ammonia. The study of these bacterial ferments is still being vigorously prosecuted, and practical results of importance in agriculture and the arts have already been attained. In the future we may look for numerous additions to these practical applications of our knowledge. The use of pure cultures for producing useful fermentations must give the best result with the least liability to loss of material from the presence of undesirable species. It is known that the flavor of butter and of different kinds of cheese is due to various bacterial ferments, and there is good reason to suppose that a better product and greater uniformity would be attained by the use of pure cultures of the species upon which special flavors depend. I understand that in this country quite a number of dairies are now using pure cultures of a certain bacillus (Bacillus 41 of Conn) for giving flavor to their product. It is probable that similar methods will soon be introduced in the cheese-making industry. A recent English publication, which I have not yet seen, is entitled Bread, Bakehouses, and Bacteria. It will, no doubt, be found to contain information of practical value to those engaged in breadmaking.

Pasteur's studies relating to the micro-organisms causing abnormal and injurious fermentations in wine, the results of which he published in 1866 (Études sur le Vin, ses Maladies, etc.), have resulted in an enormous saving to the wine-making industry in France and other countries where wine is produced upon a large scale; and his investigations relating to the cause and prevention of the infectious diseases of the silkworm, which threatened to destroy the silk industry in France, have resulted in even greater benefits to the material interests of his country and of the Vv'orld (published in 1870).

Agricultural chemists predict that in the near future cultures of the nitrifying bacteria of the soil will be made on a large scale for the use of farmers, who will add them to manures for the purpose of fixing the ammonia or perhaps will distribute them directly upon the soil. Should this prove to be a successful and economic procedure, the extent of the interests involved will make it a "practical result" of the first importance. Another application of our recently acquired knowledge which has already proved useful to farmers in certain parts of Europe relates to the destruction of field mice by distributing in the grain fields bread moistened with, a culture of a bacillus which causes a fatal infectious disease among these little animals.

In Greece, in Hungary, and in other parts of Europe the quantity of grain consumed by field mice constitutes a very serious loss. Recent experiments made with cultures of two different bacilli (Bacillus typhi murium of Löffler and the bacillus of Lasar) show that it is practicable to destroy these pests, in the fields where their depredations are committed, in the manner indicated. Mice which consume the bread moistened with cultures of one of the pathogenic bacilli referred to die within a short time from general infection, and their bodies are consumed by other mice, which also become infected. Thus a veritable epidemic is induced by which their numbers are very materially reduced.

This leads us to the subject of the prevention of infectious diseases among domestic animals. We have now a precise knowledge of the specific infectious agents ("germs") in the diseases of this class which have caused the greatest losses. The most important of these are anthrax, glanders, tuberculosis, infectious pleuro-pneumonia, swine plague, hog cholera, hog erysipelas, and fowl cholera. All of these have been proved to be due to bacterial parasites, the morphological and biological characters of which are now well known. The infectious agent and usual mode of infection being known in any given disease, we have a scientific basis for measures of prophylaxis. These naturally include the destruction of the specific micro-organism to which the disease is due wherever it may be found. An enormous amount of experimental work has been done for the purpose of determining the comparative value of disinfecting agents and the practical advantages of each, having in view questions relating to cost, stability, solubility, odor, toxic properties, etc., also to the difference in resisting power of different pathogenic bacteria, the presence or absence of spores, the character of the material with which they are associated, etc. As a result of this extensive laboratory work our knowledge with reference to the efficiency and availability of agents of this class is very complete, and enables those who are familiar with the experimental evidence to formulate rules for the destruction of the various pathogenic bacteria wherever they may be found. The infected animal is itself a focus of infection which under certain circumstances had better be destroyed in toto, the individual being sacrificed and the body put out of the way of doing harm by means of cremation or burial. Under other circumstances it may be sufficient to isolate the infected animal and to disinfect all discharges containing the pathogenic germ and all objects contaminated by such discharges. By such measures the extension of epidemic diseases fatal to domestic animals may usually be arrested. But it may happen that the extent of the epidemic prevalence and the number of animals already exposed to infection make these measures inadequate or difficult of execution. In this case we have, for certain diseases, another method of prophylaxis which has been extensively employed with excellent results. I refer to the method of protective inoculations, which we owe largely to the genius and patient researches of the distinguished French chemist Pasteur and his pupils.

Toussaint, a pioneer in researches relating to protective inoculations, has a short paper in the Comptes-Rendus of the French Academy of Sciences of July 12, 1880, entitled Immunity from Anthrax (charbon) acquired as a Result of Protective Inoculations.

In this paper he announces his discovery of the important fact that the anthrax bacillus does not form spores in the tissues or liquids of the body of an infected animal, but multiplies alone by binary division: "Sa multiplication se fait toujours par une division du mycélium."

In the same communication he reports his success in conferring immunity upon five sheep by means of protective inoculations, and also upon four young dogs. We must therefore accord him the priority in the publication of experimental data demonstrating the practicability of accomplishing this result.

In a communication made to the French Academy of Sciences, September 27, 1880, Pasteur gave an account of an experiment made July 14, 1879, upon two cows, which, in connection with a subsequent experiment, made August 6, 1880, upon four cows, led him to the conclusion that a single attack of anthrax protects from subsequent attacks.

The next important steps in the line of experimental research leading to protective inoculations in the disease under consideration were reported by Pasteur in his communication to the French Academy made at the séance of February 28, 1881 (with the collaboration of Chamberland and Roux), entitled De l'Atténuation des Virus et de leur Retour à la Virulence. In this connection Pasteur announces his discovery of the fact that when cultivated at a temperature of 42° to 43° C. the anthrax bacillus no longer forms spores and rapidly loses its virulence.

In a later communication (March 21, 1881) Pasteur says that he has found by experiment that when attenuated varieties of the anthrax bacillus form spores, these again reproduce the same pathogenic variety, so that cultures of each degree of attenuation can be maintained indefinitely.

On June 13, 1881, Pasteur communicated the results of his famous experiment at Pouilly-le-Fort, near Melun. He says:

"On the 5th of May, 1881, we inoculated, by means of a Pravaz syringe, twenty-four sheep, one goat, and six cows, each animal with five drops of an attenuated culture of the anthrax bacillus. On the 17th of May we reinoculated these animals with a second virus, also attenuated, but more virulent than the first.

"On the 31st of May we proceeded to make a very virulent inoculation in order to test the efficacy of the preventive inoculations made on the 5th and 7th of May. For this experiment we inoculated the thirty vaccinated animals, and also twenty-four sheep, one goat, and four cows which had not received any previous treatment.

"The very virulent virus used on the 31st of May was obtained from spores preserved in my laboratory since the 21st of March, 1877.

"In order to make the experiments more comparable, we inoculated alternately a vaccinated and a non-vaccinated animal. When the operation was finished, all those present were invited to reassemble on June 2d—i. e., forty-eight hours after the virulent inoculation was made.

"Upon the arrival of the visitors on June 2d, all were astonished at the result. The twenty-four sheep, the goat, and the six cows which had received the attenuated virus all presented the appearance of health. On the contrary, twenty of the sheep and the goat which had not been vaccinated were already dead of anthrax; two more of the non-vaccinated sheep died before the eyes of the spectators, and the last of the series expired before the end of the day. The non-vaccinated cows were not dead. We had previously proved that cows are less subject than sheep to die of anthrax. But all had an extensive œdema at the point of inoculation, behind the shoulder. Certain of these œdematous swellings increased during the following days to such dimensions that they contained several litres of liquid, deforming the animal. One of them even nearly touched the earth. The temperature of these cows was elevated 3° C. The vaccinated cows did not experience any elevation of temperature, or tumefaction, or the slightest loss of appetite. The success, therefore, was as complete for the cows as for the sheep."

Subsequent experience has fully established the value of protective inoculations in this disease, and the method of Pasteur has been practiced on a large scale in France, Austria, Russia, and Switzerland.

The results of anthrax inoculations made in France by Pasteur 's method during twelve years were summarized by Chamberland in 1894. The veterinarians who made the inoculations were each year called upon to answer the following questions: 1. Number of animals inoculated. 2. Number of deaths from first inoculation. 3. Number of animals dying within twelve days after the second inoculation. 4. Number of animals dying of anthrax within a year after protective inoculations. 5. The yearly average loss before inoculations were practiced. The total number of animals inoculated during the period to which this report refers was 1,788,077 sheep and 200,962 cattle. The average annual loss before these protective inoculations were practiced is said to have been about ten per cent for sheep and five per cent for cattle. The total mortality from this disease among inoculated animals, including that resulting from the inoculations, was 0·94 per cent for sheep and 0·34 per cent for cattle. Chamberland estimates that the total saving as a result of the inoculations practiced has been five million francs for sheep and two million francs for cattle.

Podmolinoff gives the following summary of results obtained in 1893 and 1893 in the government of Kherson (Russia): Number of sheep inoculated, 67,176; loss, 294 ${\displaystyle {\ce {=}}}$0·43 per cent. Number of horses inoculated, 1,452; loss, 8. Number of cattle inoculated, 3,652; loss, 2. The conclusion is reached that Pasteur's method of inoculation affords an immunity against infection with virulent anthrax bacilli in greater amounts than could ever occur under natural conditions.

Another disease in which inoculations have been practiced on a large scale is erysipelas of swine (rouget of French authors), which prevails extensively in France and other parts of Europe.

Pasteur's first studies relating to the ætiology of rouget were made in collaboration with Chamberland, Roux, and Thuillier in 1882. Pasteur found that the virulence of his cultures was increased by passing them through pigeons and diminished by passing them through rabbits. By a series of inoculations in rabbits he obtained an attenuated virus suitable for protective inoculations in swine. In practice he recommended the use of a mild virus first, and after an interval of twelve days of a stronger virus. These inoculations have been extensively practiced in France, and the fact that immunity may be established in this way is well demonstrated.

In a paper published in 1894 Chamberland states that in the preceding seven years, during which time protective inoculations had been practiced in France on a large scale, the mortality from rouget had been reduced to 1·45 per cent, whereas before these inoculations were practiced the mortality from this disease was about twenty per cent.

Hutyra has given the following statistics of inoculations made in Hungary during the year 1889 with "vaccines" obtained from the Pasteur laboratory in Vienna: 48,637 pigs were inoculated on 117 different farms. Of these, 143 (0·29 per cent) died between the first and second inoculations. After the second inoculation 59 animals died (0·1 per cent). During the year following the inoculations 1,082 inoculated pigs died of Rothlauf. Before the inoculations the annual loss in the same localities is said to have been from ten to thirty per cent.

In a communication (1894) to the Central Society of Veterinary Medicine (of France), Arloing claims that he has demonstrated the ætiological relation of a bacillus first described by him in 1889 (Pneumobacillus liquefaciens bovis) to the infectious disease of cattle known as pleuro-pneumonia. The demonstration was not complete until recently, because of failure to reproduce the disease by inoculation with a pure culture of the bacillus.

Although this demonstration is of such recent date, protective inoculations against this disease have long been successfully practiced. For this purpose serum obtained from the lungs of an animal recently dead has been employed, this having been proved by experiment to be infectious material, although the exact nature of the infectious agent present in it was not determined.

In the Bulletin of the Central Society of Veterinary Medicine of May 24, 1894, M. Robcis reports the results of inoculations made with cultures of Arloing's Pneumobacillus liquefaciens bovis, and with injections of pulmonary serum. His statistics with reference to the last-mentioned "legal" inoculations he has obtained from official documents relating to the Department of the Seine.

The total number of infected localities in this department during the years 1885 to 1891 was 1,253; total number of contaminated animals, 18,356; total number inoculated, 18,359; total number of deaths prior to inoculation, 1,753; total number of deaths after inoculation, 2,741; total number of deaths due to the inoculation, 94; total percentage of mortality, 22·8 per cent. After discussing these and other statistics Robcis arrives at the conclusion that Arloing's method of preventive inoculations with cultures of the Pneumobacillus liquefaciens bovis gives better results than the legal method with serum from an infected animal, the total loss among animals exposed to contagion not being over twelve to fourteen per cent.

In the infectious disease of cattle known under the names of "black leg," "quarter evil," or symptomatic anthrax, protective inoculations have also been practiced with success. The disease prevails during the summer months in various parts of Europe, and to some extent in the United States. It is characterized by the appearance of irregular, emphysematous swellings of the subcutaneous tissues and muscles, especially over the quarters. The muscles in the affected areas have a dark color and contain a bloody serum in which the bacillus is found to which the disease is due. This is an anaërobic bacillus which forms large oval spores.

The ætiology of the disease was first clearly established by the researches of Arloing, Cornevin, and Thomas (1880 to 1883).

Strebel, in 1885, published the results of protective inoculations made in Switzerland in 1884. The inoculations were made in the end of the tail with two "vaccines" with an interval between the two of from nine to fourteen days. The vaccines were prepared by exposure to heat, as recommended by Arloing, Cornevin, and Thomas. The most favorable season for inoculations was found to be the spring, and the most favorable age of cattle for inoculation from five months to two years.

In seven Swiss cantons 2,199 cattle were inoculated; 1,810 inoculations were made among animals which were exposed in dangerously infected pastures. Of these but two died, one two months and the other four months after the protective inoculations. Among 908 inoculated cattle, which were pastured with 1,650 others not inoculated, the mortality was 0·22 per cent, while the loss among the latter was 6·1 per cent. The following year (1885), according to Strebel, the number of inoculations, exclusive of those made in the canton of Bern, was 35,000. The losses among inoculated animals are reported as having been about five times less than among those not protected in this way.

In the Bulletin of the Central Society of Veterinary Medicine of France (1893) Guillod and Simon give the results of 3,500 inoculations made since 1884. The mortality among cattle in the region where these inoculations were practiced had been from ten to twenty per cent, but fell to 0·5 per cent among the inoculated animals.

The success of Pasteur's method of prophylaxis against hydrophobia is now well established, although the specific germ of this disease has not yet been demonstrated.

Perdrix (1890), in an analysis of the results obtained at the Pasteur Institute in Paris, calls attention to the fact that the mortality among those treated has diminished each year, and ascribes this to improvement in the method. He says:

"At the outset it was difficult to know what formula to adopt for the treatment of each particular case. Upon consulting the accounts of the bites in persons who have died of hydrophobia, notwithstanding the inoculations, we have arrived at a more precise determination as to the treatment suitable for each case, according to the gravity of the lesions. In the cases with serious wounds we inject larger quantities of the emulsion of cord and repeat the inoculations with the most virulent material. For the bites upon the head, which are especially dangerous, however slight their apparent gravity may be, the treatment is more rapid. and, above all, more intensive—that is to say, the virulent cord is injected several times."

The statistics arranged with reference to the location of the bite are given by Perdrix as follows:

 Bitten upon the head, 684; died, 12 = 1 ·75 per cent; Bitten upon the hands, 4,396; died, 9 = 0 ·2; per cent; Bitten upon the limbs, 2,839; died, 5 = 0 ·17 per cent.

In the infectious diseases of man, which have been proved to be due to pathogenic bacteria, the most satisfactory evidence of the value of protective inoculations has been obtained in cholera and in diphtheria. In the first-mentioned disease protective inoculations were practiced on a large scale in Spain, during the epidemic of 1884 and 1885, by the method of Ferran. This consisted in the introduction of a small amount of a pure culture of the cholera spirillum into the subcutaneous connective tissue, by means of a hypodermic syringe. Shakespeare, who was sent by our Government to investigate the merits of this method of prophylaxis, was disposed to think well of it. He says:

"There is still another result of the preventive inoculations of Ferran apparently shown by these statistics. I refer to the apparent marked shortening of the course of the epidemic after a large percentage of the inhabitants have become inoculated. It would seem, therefore, from analysis of the official statistics, that the practice of the anticholeraic inoculation after the method of Ferran, besides giving the subject inoculated a considerable immunity from attack and death by cholera, furnishes a means of bringing an epidemic rapidly to an end."

More recently Haffkine has advanced evidence in favor of the protective value of subcutaneous inoculations with cholera cultures. His experiments in India have been made in Calcutta, Gaya, Cawnpore, and Lucknow. Those exposed, during the epidemic prevalence of cholera, under the same conditions as to locality, water supply, etc., are divided into two groups, the inoculated and the non-inoculated. In the first group, which includes 500 inoculated individuals, 21 cases occurred, of which 19 were fatal, a mortality of 3·8 per cent. In the second group were 1,735 individuals; the number of cases in this group was 174; number of deaths, 113; percentage of mortality, 6·51.

Whether this method will be found to have any great practical value can only be determined by more extended experiments. But in view of the fact that other measures of prophylaxis, well known to sanitarians, are sufficient for the prevention of cholera epidemics, and that nurses and others who necessarily come in contact with cholera patients are not likely to contract the disease if they use proper precautions with reference to their food and drink, the disinfection of their hands, etc., we doubt whether protective inoculations will ever come into general use as a measure of prophylaxis against this disease. Certainly they can not take the place of those sanitary measures which have been proved to be sufficient for the prevention of epidemics namely, exclusion by a proper inspection service at ports of entry ("quarantine"), isolation of the sick, disinfection of excreta, general sanitary police of exposed towns and cities, boiling the water used for drinking purposes, etc.

But it must be remembered that these measures of prophylaxis, which have undoubtedly resulted in the saving of thousands of lives, are based upon exact knowledge obtained as a result of bacteriological researches. Since the discovery of the cholera spirillum by Koch in 1884, a very large number of skilled investigators have devoted themselves to researches relating to it, and especially to questions relating to its resistance to various destructive agencies. These researches show that it is quickly destroyed by a comparatively low temperature (60° C), by desiccation, and by all known germicidal agents. It is especially susceptible to the action of acids, in comparatively dilute solutions. Our measures of sanitary prophylaxis are therefore established upon a sound experimental basis, and the extension of the disease in civilized countries is the result of a failure to apply well-known means of prevention. As a matter of fact, these measures have been successful in excluding the disease from this country during the last two widespread epidemics in Europe, and have enabled sanitarians to greatly restrict the epidemic spread of the disease in those countries into which it has recently been introduced.

The prevalence of typhoid fever has also been greatly restricted by measures based upon an exact knowledge of the biological characters of the typhoid bacillus, and if the recommendations of sanitarians were fully complied with there is reason to believe that it would be practically banished from our cities and towns.

The bacteriological examination of the water supply of towns and cities is now generally recognized as an important matter, as indicating the sanitary purity of the supply. The detection of the dangerous pathogenic species should lead to the disuse of a water for drinking purposes, or to the recommendation that it be boiled before it is used. The presence of certain other bacteria indicates sewage contamination and consequent danger to those drinking the water without proper precautions as to filtration or sterilization. In Berlin, where the water supply is taken from a river known to be contaminated by sewage, it is passed through carefully constructed "filter beds," and expert bacteriologists make frequent tests to ascertain how well these filter beds are accomplishing their purpose. In France the Pasteur-Chamberland filter is largely used, and recent reports indicate that it has been instrumental in effecting a great reduction in the rate of mortality from typhoid fever, especially among the French soldiers in certain parts of the country where this disease a few years since caused a considerable mortality, and where the civil population, not using the filters, still furnishes many victims to this disease.

The exact knowledge which we now possess with reference to the micro-organisms which are the cause of erysipelas, puerperal fever, septicæmia, wound infection, etc., has also led to the employment of intelligent measures of prophylaxis. The brilliant success which has attended the carrying out of these modern antiseptic and aseptic methods in surgical and obstetrical practice are too well known to call for extended remark. But some statistics relating to this branch of our subject may serve to impress the matter upon the minds of those who have not fully appreciated the saving of life which has resulted from the employment of methods based upon a knowledge of the usual modes of wound infection and the micro-organisms to which such infection is due. Lister, the distinguished pioneer in the employment of antiseptics in surgical practice, reports that during the years 1864, 1865, and 1866, before he resorted to the use of antiseptics, the mortality in his surgical cases exceeded forty-five per cent, largely from septic complications. During the period from 1871 to 1876, in a total of 453 surgical cases treated by him with strict antiseptic precautions, the mortality from such complications was only 0·36 per cent.

The German surgeon Volkmann reports that prior to the introduction of antiseptic methods the mortality from compound fractures in his practice was forty per cent. After adopting Lister's methods he had 135 successive cases of compound fracture without a death from septic causes; two deaths only occurred out of the whole number of cases; one of these was the result of delirium tremens and the other of fatty embolism of the lungs.

Brignot, a French surgeon, reports that in French hospitals the mortality from major surgical operations before the introduction of antiseptic methods was 52·5 per cent, and that since it has been reduced to a little less than eleven per cent. In a series of 736 cases of compound fracture collected by Prof. William White, of Philadelphia, all of which occurred before the introduction of antiseptic methods, the mortality was forty per cent. In a second series of similar cases in which these methods were employed the mortality was only four per cent. Dennis, of New York, has reported a series of 516 cases of compound fracture without a single death from septic causes. Thirty years ago the mortality from puerperal septiæemia in lying-in hospitals was frequently something frightful. In the Maison d'Accouchements in Paris the mortality rate at times was as high as one out of every three patients delivered. Similar conditions existed in Berlin and in other European cities. At the present day the mortality from septic infection in similar cases is even less than in private practice. In the Maternity Hospital of New York, for example, in one thousand deliveries there were but six deaths, and but one of these was due to puerperal septicæmia.

If we take a more general view of the results attained in preventive medicine by the application of modern methods based upon our knowledge of the causes of infectious diseases, we shall find that a very large saving of life has been accomplished, as shown by diminished mortality rates in all parts of the civilized world. This is well illustrated by the carefully kept English statistics. The facts are very concisely stated by Sir Edwin Arnold in an address recently delivered at St. Thomas's Hospital upon Medicine, its Past and Future. He says:

"One of the high authorities already quoted has furnished a calculation of the salvage of life effected, even during the early years of the present reign, by the commencing improvements in preventive and curative medicine. In the five years from 1838 to 1842 London, with an average population of 1,840,865 persons, had an average annual mortality of 2,557 in every 100,000. In the five years from 1880 to 1884 the average metropolitan population was 3,894,261, and the average annual death-rate 2,101 in each 100,000. A calculation will show that these figures represent a saving or prolonging of lives during that lustrum to the number of 96,640. The mean annual death-rate has now been reduced to a point lower than shown in these. It was 22·16 per 1,000 for England and Wales at the commencement of the reign, and it is to-day better than 19·0 per thousand, while in her Majesty's army and navy the diminution of mortality apart from deaths from warfare has proved even more remarkable, and in India, where we used to lose 69 per 1,000 yearly, this has been reduced to 16 per 1,000."

We can not claim that this reduction in the mortality rate is due alone to the development of our knowledge relating to the pathogenic bacteria, for much had been accomplished by practical measures of sanitation before we had any exact knowledge of disease germs. But this exact knowledge has added greatly to our sanitary resources, and has doubtless been an important factor in the reduction in the mortality rate which has occurred within the past twenty-five years. Sir Edwin Arnold, in the address above referred to, says:

"A great authority has declared that 'a day will come when in London, in Berlin, in Paris, man will not die of diphtheria, of typhoid, of scarlet fever, of cholera, or of tuberculosis, any more than he dies in these cities to-day of the venom of snakes or of the tooth of wolves.'"

But it is not alone in preventive medicine that important practical results have been accomplished. Therapeutics has also been greatly and favorably influenced by the discovery of the specific germs of a considerable number of infectious diseases. Naturally, the effort is to destroy these germs at the focus of infection, or to render the conditions in the body of the infected individual unfavorable for their development. When the focus of infection is superficial or within comparatively easy reach, as in erysipelas or diphtheria, local treatment with germicidal agents is often attended with favorable results. But when the deeper tissues and organs of the body are invaded, or the germ multiplies abundantly in the blood, but little can be accomplished by the use of agents of this class. Our bacteriological researches have, however, recently resulted in the discovery of a method of treatment which has been employed with remarkable success in two of the infectious diseases of man, and which there is reason to believe may eventually be found to have a more extended application. I refer to the therapeutic use of antitoxins contained in, or obtained from, the blood of animals rendered immune by repeated inoculations with cultures of a specific disease germ. The diseases in which the greatest success has been attained by this mode of treatment are tetanus and diphtheria. As the last-mentioned is by far the most important from a practical point of view, I will confine my remarks to the results of treatment in this disease. Fortunately, I have at hand a recent summary of the clinical evidence in favor of this mode of treatment, made by a very competent and conservative physician—Prof. William H. Welch, of the Johns Hopkins University. Prof. Welch concludes his paper as follows:

"The principal conclusion which I would draw from this paper is that our study of the results of the treatment of over seven thousand cases of diphtheria by antitoxin demonstrates beyond all reasonable doubt that antidiphtheric serum is a specific curative agent for diphtheria, surpassing in its efficacy all other known methods of treatment for this disease. It is the duty of the physician to use it."

A recent report on antitoxin treatment in Germany, obtained by collective investigation, on a total of 10,312 cases occurring in a period of six months from October 1, 1894, gives very striking results. Of the whole number, 5,833 were treated with serum, and 4,479 without it. The proportion of deaths in the former group was 9·6 per cent, in contrast to 14·7 per cent in the latter. In 401 cases of children under the age of two years, in which the serum treatment was used on the first and second day, the mortality rate was 11·8, in contrast with 39·7 where under similar conditions it was not used. Of 2,556 children between two and ten years of age, the death-rate was 4 per cent after antitoxin treatment, instead of 15·2 per cent in the other group.

Prof. Welch very truly and forcibly remarks: "The discovery of the healing serum is entirely the result of laboratory work. It is an outcome of the studies of immunity. In no sense was the discovery an accidental one. Every step leading to it can be traced, and every step was taken with a definite purpose and to solve a definite problem."

The importance of prompt treatment in this very fatal malady is shown by the following figures which we take from Prof. Welch's paper. The cases referred to were reported by nineteen different observers, and the total number treated was 1,489, with a mortality of 14·2 per cent. Of these cases, 222 were treated with the antitoxic serum on the first day of sickness, with a mortality of 2·2 per cent; 456 cases on the second day, with a mortality of 8·1 per cent; 311 on the third day, with a mortality of 13·5 per cent; 168 on the fourth day, with a mortality of 19 per cent; 116 on the fifth day, with a mortality of 29·3 per cent; 44 on the sixth day, with a mortality of 34·1 per cent; 104 after the sixth day, with a mortality of 33·7 per cent; 68 undetermined.

The time at my disposal will not permit me to dwell longer upon the practical results already attained in preventive medicine and in specific therapeutics as a result of bacteriological investigations. But before closing I desire to call attention, as briefly as possible, to the value of the recent additions to our knowledge relating to the causes of disease, in the way of an exact and early diagnosis. In certain infectious diseases such knowledge is of great importance, not only in the interest of the patient, but of others liable to infection. This is especially true in diphtheria and in tuberculosis of the lungs. In the first-mentioned disease an early differentiation of true diphtheria from pseudo-diphtheria is often impossible without resort to methods by which the bacteriologist is able to detect the presence of the diphtheria bacillus. In pulmonary tuberculosis, also, the bacteriologist can usually detect the tubercle bacillus in the sputa before the clinical expert can recognize with certainty the physical signs of the disease. Scientific physicians in all parts of the world now resort to the use of the microscope and the staining methods by which this bacillus is recognized for making an early diagnosis in cases of this nature. Other diseases in which the recognition of the specific germ establishes the diagnosis are relapsing fever, typhoid fever, glanders, and anthrax—the two last mentioned being diseases of lower animals which, may be transmitted to man. And in tuberculosis and glanders affecting domestic animals we have still another method of establishing the diagnosis in suspected cases. This is by the subcutaneous injection of a proper dose of a filtered culture of the specific pathogenic bacteria. These filtered cultures, containing the soluble toxic products developed during the growth of the bacillus, are known in the one case (tubercle bacillus) as tuberculin, and in the other (glanders bacillus) as mallein. The effect is similar in each case. When an animal infected with tuberculosis receives a suitable dose of tuberculin a characteristic febrile reaction is produced. In the non-infected animal this reaction does not occur. The same is true as regards animals infected with glanders which receive a dose of mallein. This test of infection is now extensively used both in this country and in Europe with very satisfactory results. The importance of an early recognition of these chronic infectious diseases is apparent. The danger from infected animals is not limited to the extension of the disease to others of the same species, but in tuberculosis those who consume the milk are exposed to the danger of infection, especially in cases where the udder of the animal is the seat of a tubercular infection.

I have by no means exhausted my subject, and an attempt to do so would probably exhaust the patience of my audience. In conclusion, I would say that the painstaking laboratory work which has led to the important practical results referred to is still being prosecuted with unabated vigor, and without doubt we may look for further valuable additions to our knowledge. These, together with a wider appreciation of the present status of this department of scientific investigation, can not fail to add largely to the practical results which will hereafter be achieved in the field of preventive medicine and of specific therapeutics, and in agriculture, in the dairy, etc., as heretofore indicated.

The Prince of Monaco recently reported to the French Academy of Sciences on the results of his deep-sea dredging expedition of 1895, from Portugal to the Azores and back to the English Channel. The dredgings were carried to the depth of forty-two hundred metres, where weirs were deposited; and numerous soundings were made, some of them as far down as five thousand metres, and specimens of the water drawn up. Fine captures weie made in the weirs from fifteen hundred metres, in which echinoderms, mollusks, and fishes were plentiful. Thus, three hundred and fifty-five animals were taken in twenty-four hours in the same net three hundred of them fishes, large red shrimps, and cephalopods. Besides the usual fauna of such profundities, crayfishes eighty centimetres long and superb holothurias of forty-six centimetres were drawn up from the depth of four thousand metres.
1. Address of the President of the Biological Society of Washington, delivered December 14, 1895, under the auspices of the Joint Commission of the Scientific Societies of Washington.