STATEMENT OF OWNERSHIP Statement of the Ownership, Management, Circulation, etc., required by the Act of Congress of August 24, 1912, of Journal of the Outdoor Life, published monthly at New York, N. Y., for May 1, 1919: State of New York, County of New York. ac Before me, a Commissioner of Deeds in and for the State and County aforesaid, personally appeared Philip P. Jacobs, who, having been duly sworn cording to law, deposes and says that he is the Managing Editor of the JOURNAL OF THE OUTDOOR LIFE and that the following is, to the best of his knowledge and belief, a true statement of the ownership, management (and if a daily paper, the circulation), etc., of the aforesaid publication for the date shown in the above caption, required by the Act of August 24, 1912, embodied in section 443, Postal Laws and Regulations, printed on the reverse of this form, to wit: 1. That the names and addresses of the publisher, editor, managing editor, and business managers are: PUBLISHER, Journal of the Outdoor Life Publishing Co., 381 Fourth Ave., New York, N. Y. EDITOR, Philip P. Jacobs, Ph.D., 381 Fourth Ave., New York, N. Y. MANAGING EDITOR, Philip P. Jacobs, Ph.D., 381 Fourth Ave., New York, N. Y. BUSINESS MANAGERS, None. 2. That the owners are (Give names and addresses of individual owners, or, if a corporation, give its name and the names and addresses of stockholders owning or holding 1 per cent. or more of the total amount of stock): Journal of the Outdoor Life Publishing Co., 381 Fourth Ave., New York, N. Y.; Dr. Charles J. Hatfield, 2008 Walnut St., Philadelphia, Penna.; Dr. H. R. M. Landis, 11 South 21st St., Philadelphia, Penna.; Philip P. Jacobs, Ph.D., 381 Fourth Ave., New York, N. Y.; Dr. James Alexander Miller, 379 Park Ave., N. Y. C.; Dr. Livingston Farrand, American Red Cross, Washington, D. C. 3. That the known bondholders, mortgagees, and other security holders owning or holding 1 per cent. or more of total amount of bonds, mortgages, or other securities are (If there are none, so state): There are none. 4. That the two paragraphs next above, giving the names of the owners, stockholders, and security holders, if any, contain not only the list of stockholders and security holders as they appear upon the books of the company but also, in cases where the stockholder or security holder appears upon the books of the com. pany as trustee or in any other fiduciary relation, the name of the person or corporation for whom such trustee is acting, is given; also, that the said two paragraphs contain statements embracing affiant's full knowledge and belief as to the association, or corporation has any interest direct or indirect in the said stock, bonds, or other securities than as so stated by him. 5. That the average number of copies of each issue of this publication sold or distributed, through the mails or otherwise, to paid subscribers during the six months preceding the date shown above is (This information is required from daily publications only.) PHILIP P. JACOBS, Managing Editor. Sworn and subscribed before me this ninth day of April, 1919. Alva J. Leverton, Commissioner of Deeds, No. 329, New York County. (My commission expires January 14, 1921.) A Book For Those Who Have or May Have Tuberculosis Saints' Rest By SADIE FULLER SEAGRAVE Of the Iowa State Sanatorium, Oakdale, Iowa. 180 pages, with frontispiece, and jacket in two colors. Price, postpaid, $1.00. AN amusing and helpful sketch of sanatorium life, garnered from a four years' experience and close contact in institutions for the treatment of tuberculosis. An attempt is made to show the physical benefits that may be derived under the proper regime of regulated life, and the mental stimulus and fresh outlook on life that come with the increase of bodily vigor, and with the freedom from physical and mental overwork. The story is principally in the form of letters written by a girl to her fiance after she has been found to be tuberculous, and cover a period of one year. The letters combine the humor and pathos which are to be found in any such institution, and incidentally convey to the reader a considerable amount of reliable and helpful information respecting the proper treatment of tuberculosis. order from Journal of the Outdoor Life, 381 Fourth Avenue, New York When dealing with Advertisers please mention JOURNAL OF THE OUTDOOR LIFE DR. TRUDEAU IN THE SARANAC LABORATORY The original laboratory mentioned by Dr. Krause on page 132 was in a wing of Dr. Trudeau's residence Journal of the OUTDOOR LIFE IMPORTANT NOTICE TO SUBSCRIBERS When your subscription expires, renew at once. If it expires with this issue, your renewal EDITORIAL NOTE In the last essay Dr. Krause summarizes the various studies of infection published in these pages for several months past. In this essay he begins to lay the foundation for further development of certain fundamental theses concerning infection. A digression from the definite subject of infection into the field of resistance, immunity, and reinfection will take up the next three or four essays. These studies will give some of the most valuable and helpful information on this difficult and much discussed question that the JOURNAL OF THE OUTDOOR LIFE has ever published. Readers of the JOURNAL are referred to some of the earlier essays dealing with Dr. Koch, particularly that published in the April, 1918, number. The entire series of essays is available in numbers of the JOURNAL running from January, 1918. Single copies may be secured for fifteen cents each. ESSAYS ON TUBERCULOSIS XVI. THE FIRST EXPERIMENTS ON RESISTANCE: THE DISCOVERY OF TUBERCULIN: TRUDEAU AND KOCH BY ALLEN K. KRAUSE, M.D. Robert Koch's interest in tuberculosis did not die with his discovery of the tubercle bacillus. This achievement placed Koch at the head of the acknowledged geniuses of biological investigation, with the usual consequence, that the world called upon talents that had been nourished and had flowered in comparative solitude and obscurity to step out into broader fields and undertake the direction of public work. Cholera was raging in the East and in 1883 Koch was sent to Egypt and to India as head of the German Cholera Commission to study this disease and, if possible, to discover its cause. The commission was successful in bringing to light a great deal of information of the first importance; and Koch added the germ of cholera, the cholera vibrio, to the rapidly-increasing family of disease-producing bacteria that were being isolated from human beings stricken with infections. On his return home the Emperor rewarded him with a grant of money and a decoration; while further marks of distinction kept crowding in. In 1885 a new chair was created for him at the University of Berlin; he became Professor of Hygiene and Bacteriology. Nothing could be more fitting than that Koch should become the first Professor in his country's leading university of a new branch of knowledge that his own explorations into the mists of the unknown had created. Burdened as he must have been with the direction of many large projects and the development of his new science, the subject of tuberculosis was never far from his thoughts, though in the five years that immediately followed 1884 little on the topic appeared from his pen. Meanwhile a small army of men, particularly in Germany and France, were busily engaged in ferreting out every detail of the life history of the tubercle bacillus, its habits, its nesting places, its modes of conveyance, its effects, that could be detected by the methods then in use. Between 1880 and 1890 no microorganism of disease received more intensive and devoted study than the tubercle bacillus. Great names had been built on or had gained something from the pursuit of this study. To this era Orth, Cornet, Baumgarten, Gaffky and Weichselbaum in Germany, Grancher, Martin, Nocard, Yersin, Metchnikoff and Richet in France and Mafucci in Italy owe not a little of their prominence in medical annals. Yet England and America remained remarkably passive throughout this decade of great activity on the continent; and nothing can better illustrate the low estate of the experimental method in medicine in which both of these countries still lay submerged than their almost complete sterility in publications on laboratory studies on tuberculosis during the eighteen-eighties. With the example of the incomparable Pasteur ever before them the French savants turned largely to practical matters. Too impatient to await the many minutiae of information that more systematic minds were continually digging up, a considerable body of French investigators at once set out upon experiments to prevent tuberculosis. Daremberg attempted to immunize guinea pigs by inoculating them with the dried spinal cords of tuberculous rabbits before he subjected them to virulent tuberculous infection. Grancher and Ledoux-Lebard sought immunization by inoculating susceptible animals with gradually-increasing doses of tubercle bacilli; Grancher and Martin, by treating animals with successive inoculations of tubercle bacilli of increasing virulence; Héricourt and Richet, by giving animals the soluble products of cultures of tubercle bacilli before they infected the former, and by protecting against virulent inoculation by preliminary injections of the more or less harmless avian bacilli; and Berlioz by using bacilli which he tried to reduce in virulence by first introducing them into refractory animals like pigeons. All these immunizing methods were familiar Pastorian manoeuvres or modifications of them. All failed. All had found their way to the printed page by 1890 and all came from France. The scientific world was becoming pessimistic about the possibility of preventing tuberculosis by direct specific measures, when of a sudden a bombshell was hurled into it. In the summer of 1890 the International Medical Congress convened in Berlin. And here on the fourth of August the discoverer of the tubercle bacillus arose and, at the conclusion of a long address that dealt in the main with general bacteriological principles (Concerning Bacteriological Investigation: Ueber bakteriologische Forschung), made the momentous announcement that in consequence of prolonged meditation and work he had in his possession a substance which would not only prevent tuberculosis but would also cure 1 it, and it was a substance, moreover, that was harmless. The excitement that followed this astonishing announcement was the excitement of commotion. "Medical men from all over the civilized world flocked to Berlin to witness the effect of the remedy and to obtain some for their own use if possible. A thousand dollars was freely offered for a bottle . . . which contained about a teaspoonful, and the substance could not be procured at that price from those who had been fortunate enough to procure same. Crowds paraded the streets of Berlin chanting rhymes in Koch's honor and shouting his name.' In his first communication Koch gave no description whatever of his remarkable remedy. He merely said that it was "a substance which when inoculated into a guinea pig renders this animal insusceptible to inoculation of the tuberculous virus. This same substance, in guinea pigs that are already afflicted with advanced and generalized tuberculosis, brings about a complete arrest of the development of the disease although the animal_organism does not suffer the least harmful effect under the influence of the remedy." Purposefully or otherwise, Koch invested what if true would have been the greatest discovery in the history of medicine with a great deal of secrecy and mystery, and left the world in complete ignorance of the origin and constitution of his remedy. A few months later he published a more detailed description of it and its effects. It was a clear, brown liquid that was easy to keep although dilutions of it would deteriorate unless these were made in a special way. Koch then went on to describe how it should be administered to man and animals and described the effects it produced in both the healthy and the tuberculous. Finally in January, 1891, Koch drew apart the curtain and gave the world a peep at his mystery. "The remedy with which we aim to cure tuberculosis is a glycerine extract of pure cultures of tubercle bacilli," he wrote. By this time other men had suspected as much and were announcing the presumption. Hueppe and Scholl had made chemical analyses of "Koch's lymph" that led them to the conclusion that it was the product of concentrated liquid cultures of tubercle bacilli, which contained peptone and glycerine; while by concentrating glycerinated liquid cultures of the bacilli Bujwid (1891) obtained a substance that acted exactly like Koch's mysterious medicine. To this substance Bujwid gave the name tuberculin, a name that Koch adopted later and which has ever since remained the generic term for specific remedies that are derived from the tubercle bacillus. The tuberculin that has come down to us and that we use to-day in the form of Koch's Original Tuberculin (O. T.) is a clear, brown, * Trudeau, E. L.: Some Personal Reminiscences of Robert Koch's Two Greatest Achievements in Tuberculosis. JOURNAL OF THE OUTDOOR LIFE, 1910, vii, P. 189. The oily liquid. It is made from broth cultures of tubercle bacilli. After Nocard and Roux had devised the method of cultivating the germs on broth that contained glycerin* this became a favorite medium with all students of the tubercle bacillus. If a small particle of a "culture" of bacilli is placed on the surface of perfectly clear broth in a flask, the germs, obtaining proper nourishment from the broth and the glycerin, common table salt and peptone, that have been added to it, soon begin to show signs of growth. The area of the particle begins to increase appreciably by an extension of the entire circumference. If the proper conditions of temperature are maintained the germs continue to grow in such a way that they form a wrinkled film or pellicle over the entire surface of the broth. fluid beneath them remains clear and it is manifest that the multiplication of bacilli is restricted to the surface pellicle. Some bacilli become detached from this film and gradually settle down through the broth until they come to rest on the bottom of the flask. A broth culture of tubercle bacilli usually appears to us then as a clear golden yellow fluid which supports a grayish-white and wrinkled pellicle on top while at the bottom is a thin granular deposit of small crumbs of the bacilli that have broken away from the growing mass above. Numbers of these undoubtedly die and then undergo dissolution, upon which their more soluble elements go into solution in the broth. As time goes on, therefore, the broth begins to undergo important changes in its original composition, because the growing bacilli make demands upon it and take something from it for their nourishment, because the dead ones upon disintegration yield up something to it, and very likely too because the bacilli can by their activity and as one of their functions bring about certain chemical changes in the medium. After tubercle bacilli have grown upon it the broth, therefore, of a broth culture is, chemically, no longer the same broth that was originally prepared as food for the germs. By their growth and by their death the latter have wrought a change in their medium; yet the broth still looks the same; and, if properly preserved it has its original clear golden yellow appearance and has undergone no appreciable change in consistence. It is from the contents of a number of such flasks or bottles that we prepare Old Tuberculin. Into one larger receptacle we pour all the cultures,-broth, superficial pellicles of germs and granular deposits. We then boil this mixture for an hour, while in this process the material gradually changes from a golden yellow to a browner hue. This done, we pass the thin, brown liquid through a filter which will rid it of all the bacilli that have been killed by boiling and of all insoluble particles. We are now ready to begin the last stage of our process, in which we carefully evaporate and concentrate the light *See May, 1918 number, p. 136. brown filtrate to one-tenth of its original volume. As evaporation with a moderate degree of heat proceeds the material gradually becomes a darker brown and as concentration increases it take on a thicker and thicker consistence and a more and more oily appearance. This latter change is largely due to the glycerin in the broth, for we must remember that we began with a medium that contained 5 per cent. of glycerin. When, therefore, we finish the process and have concentrated the media to one-tenth of their original volume, we end with a substance that is 50 per cent. glycerin. During partial evaporation most of the water has disappeared. The end product, the O. T., is a very mixed and impure product. It is a concentrated broth containing 50 per cent. of glycerin, 5 per cent. of common salt, 10 per cent. of peptone, and whatever elements were taken up from the tubercle bacilli in relatively concentrated form. And this is the material which Koch, enveloping himself in a cloak of mystery and secrecy, said cured tuberculosis and prevented tuberculous infection in our most susceptible animals and, best of all, did all this without harm. At this very time the fires of scientific curiosity and enthusiasm were not all extinguished in America. It is true that they burned low. "It is curious how slow physicians were in this country to accept Koch's discovery (of the bacillus) or realize its practical value in the detection of the disease."* The professionals in their infant laboratories were for the most part busied in collecting data in the good old Virchovian way,-in piling up gross and microscopic observations of changes brought about by disease and in correlating these with the manifestations of disease that they encountered in the sick man. And the general point of view had advanced but little beyond Virchovian dogma of innate constitutional vice or inherited predisposition. So far as tuberculosis is concerned one could learn little to-day by a perusal of communications that came from American medical schools in the eighteen-eighties. America was to take its place in the history of tuberculosis through the exploits of one whose endowments consisted not in state and private munificence but in personal experience with the stings of disease, in Gallic imagination and enthusiasm, in a native curiosity and compulsion to burrow into the secrets of nature, and a passion for service that is always the shining ornament of real education, breeding and discipline. It was now almost twenty years since Villemin's virus drove the flagging steps of a high-spirited and gifted young man to his hermitage in a remote and well-nigh inaccessible spot in the mountain forest. Throughout a long and tedious decade, with little outside companionship save Trudeau, Edward Livingston: An Autobiography. Lea and Febiger, Philadelphia and New York, 1916, p. 184. |