a tangled skein. Some man in the dim and distant future-not so far distant, I believe-will get hold of the right thread and the whole thing will be plain, whether it is called opsonin, agglutinin, aggressin, antitoxin, lysin, no matter what the name. Again I congratulate the audience upon the presentation of this interesting subject. DOCTOR DOCK: I can only repeat Doctor Vaughan's congratulations to the speaker and audience for hearing this excellent address. Doctor Vaughan says, it is one of the clearest and most satisfactory expressions of the subject I have come across; and it is especially important because we have been fortunate to get here this evening a large number of men who in the next couple of years ought to be working on this subject. The young doctor with great advantage to himself and with great advantage to science can devote himself to it. The work is difficult and requires pains, but that it can be mastered comparatively easily we have been able to see in the work of one of our senior students, Mr. Walker. Unfortunately it is true that much of this will be detail work, but undoubtedly the complete relations will be cleared up in time. The glamour, too, will fall away from it; miraculous cures will not be so frequent, but that great practical and scientific gains will follow, I have no doubt. MR. WALKER: I am much interested in this subject, and would like to present some of the work I have done in order to see what Doctor Bradley thinks about it. First, Doctor Bradley states that the number of bacteria taken up in suspension would depend on the number of bacteria put in. My work seems to show that is not the case; beyond a certain limit there is no variation, or so little that it can be accounted for by incidental overlapping. That is quite reasonable when we think that the opsonin represents a definite amount of certain bodies in the blood, and if one or more take hold of each bacterium, and there are not enough bacteria put in to take up all the opsonin we would get a lesser phagocytosis; but, if we put in enough to take up all the opsonin, then no matter how many more we put in we would not get a greater phagocytosis. Second, about the opsonic index. Doctor Bradley states that the phagocytosis observed in several preparations is proportional directly to the opsonic content of the sera tested. My work shows that is not quite the case; for higher opsonic values of sera the phagocytosis observed is less than a direct proportion indicates. I made my tests by making up artificial sera, by diluting normal serum once, twice, three, and four times, and the results I got showed that for higher values of sera the phagocytosis was far less than what we would be led to expect. Using the opsonic index, we get indications of change in opsonic power, but we will not get accurate results if my work is right. Some time ago we made other experiments which seem to bear that out, and corroborate it, and it would be interesting to hear what Doctor Bradley would say about it. DOCTOR GEORG: I wish to thank Doctor Bradley for the clear dem onstration of Wright's method of working on an old substance and giving old things new names. I think those of us who were in practice when Koch first announced, a year in advance, that he had something that would cure tuberculosis, very well remember the terrible misery in which that announcement was afterwards written on the pages of German literature. The trouble with Koch's tuberculin was that the dose was overreached in the start, the same now as Wright shows in the negative phase of the index. We had the negative index and continued to work under the negative index until Virchow called attention to the dire results that were following, tuberculosis taking a form more virulent than seen for many years, and the thing was dropped, but not entirely. Some men in Germany continued to work and saw that the dose had been overreached, and where Koch worked with a milligram, they worked with one-five-hundredth of a milligram and saw beautiful results in certain cases. Of course at that time this was work that could not be understood. This was the first phase of using a germ to produce a cure of the disease that is caused by the same germ. Now the work has gone into new channels. Antitoxins have long been known as weapons of offence and defence produced by the organism after the injection of bacteria. It is a product of the living cell in combat against poison that has been introduced. It is a method of defence of the system against attack. The antitoxin is not formed until the toxin accumulates. Investigators have shown that bacteria make their attacks in several lines, and for each line the normal organism responds with a new weapon of defence, that is, provided the normal powers of reaction are yet equal to the occasion. Another point in regard to this is, that when these bodies are produced in an animal and taken out in pure form and reintroduced as vaccine, they stimulate the system enormously more for reproducing this kind than the bacteria at first did and without the danger of the bacteria and the products. This is the present state of knowledge: that this antitoxin is produced and this is injected and used for therapeutic measures instead of bacteria or dead. bacteria or any extract of bacilli; for, mind you, the dead bacteria contain many poisons that are thrown off; the toxin poison that only comes into the system after the bacilli die and the body is digested, resulting in general toxemia under which the organism finally succumbs when its resistance has been overcome. At the Tuberculosis Congress held at The Hague, Netherlands, last September, Professor Maragliano, of Genoa, read a résumé of his work on the specific treatment of tuberculosis, tracing this work during the last fifteen years. First it was observed that living bacilli, and also the bodies of dead bacilli, when introduced experimentally into animal organism were followed by the production of specific protective bodies. These bodies were later demonstrated as antitoxic, bacteriolytic, and agglutinins, each body a distinct specific weapon of defence and offence against the invasion. These antitubercular substances are obtained when the injected poison (bacilli) is small in quantity and produces no toxic conditions, but when tuberculosis is developed and infection spreads, then these protective bodies diminish in quantity. These antitubercular bodies are produced by the healthy organism always in the same method of defence against the various bacillary substances and toxins. Living bacilli are not needed for the production of antibodies useful for treatment of the disease, and the injection of antitubercular bodies is followed by the further production of these substances. Maragliano proves that there is absolutely no danger in the use of his antitubercular preparation consisting of definite quantities of antitoxic, bacteriolytic, and agglutinating substance. In Italy these antitubercular serums have now been in use in the practice of physicians for ten years, and according to Maragliano, with positive curative results when the injections are given before the disease has ended in structural changes of the lungs, for then antitubercular bodies cannot undo the ravages of tubercle bacilli any more than quinine can cure a chronic interstitial hepatitis or deep seated changes in the spleen, both the result of the malaria plasmodium, itself easily destroyed by quinine. These injections are now made directly into the lung tissue. In localized tuberculosis the injections are always followed by positive cures a restoration of the tissues to normal conditions. Maragliano's work is a decade in advance of the much heralded cures of tuberculosis by Professor Behring, and I consider it high time that the profession in America were furnished with these antitubercular serums by American bacteriologic manufacturers. All that we have so far is the watery extract of tubercle bacilli, a dangerous product which needs an opsonic index for guidance. From the physician's standpoint, whatever good there is in Wright's opsonic index becomes inaccessible, for it needs the constant supervision of the bacteriologist, and, be it remembered, he uses a toxin not an antitoxin, and it depends entirely on the condition of the system. whether the result will be positive or negative. With the prepared antibody the system always receives much needed help in its fight with the enemy even when general toxemia from mixed infection has already taken place, a time when any further injection of toxins adds greatly to the disadvantage of the fighting organism. Maragliano demands that the diagnosis must be made before the microscope reveals the bacilli in sputa, for that denotes already brokendown tissue, a cavity, however small, has formed. A focus can form in an apex and cause for a time no more general symptoms than if located around the knee-joint. This is already an advanced time for beginning with the injections, but to wait still longer, until larger cavities have formed and general toxemia has taken place and the entire organism is at the point of collapsing, then we have a state of things very complicated and you cannot expect to get a medicine to cure a case of cavities of the lung, restoring the tissue to the normal condition -that could not be expected. DOCTOR HUTCHINS: I have been interested in this question of opsonins and all of Wright's work, and have attempted to do some work with it in a practical way. I have succeeded in producing the vaccine, but have not done enough work to be justified in giving any conclusions. The so-called Tr tuberculin of Koch is difficult to procure in this country, and Wright uses only one kind, which is made in Germany, and it is hard to obtain it. As Doctor Nancrede said a moment ago, this sounds too good to be true. Some reports published are most encouraging. The Boston Medical and Surgical Journal, of October 27, cites a number of cases of tuberculosis of the lungs. In one case tuberculin injections were used more as a prophylactic measure. The patient had no cough or physical signs, but was given tuberculin and the opsonic index was lowered for the tubercle germ; then the index increased. The patient gained in weight and the general health improved. One of the most striking cases reported is that of a woman, thirty-nine years old, confined to bed with hectic fever and consolidation of the right apex. She lost weight and yielded sputum in which considerable numbers of tubercle bacilli were found. She was given injections of tuberculin and after some months the physical signs were negative; the cough disappeared. She gained nineteen pounds in weight, considered herself cured, and went about her usual employment. Another phase requires more confirmation than obtains at present. Probably you all know that Doyen, in Paris, claimed to have discovered. the germ that produces cancer, the micrococcus neoformans. Doyan did not possess the best reputation as a scientific man, but he wrote a book and produced a serum which he claimed cured carcinoma. This caused so much comment that the French Cabinet of Surgery investigated it and came to the conclusion that the serum was worthless. It was also investigated by others and they arrived at the same conclusion. In the London Lancet, of the 7th of April, appears an abstract of a paper read before the Belgian Health Association, giving an account of an experimenter who took this serum, heated it to 60° for an hour, cooled it, and injected small amounts into patients. He found that if after the first injection a positive phase was obtained there was no chance of curing the carcinoma, but if the phase was negative, and in a number of cases this was accomplished, the tumors decreased in size. For example, in a case of carcinoma of the uterus, inoperable, by following this treatment for a considerable length of time, the carcinoma was diminished in size, the patient operated upon and all tissue removed. You see what this means. It is not claimed that carcinoma can be cured with any vaccine; but if in inoperable carcinoma the glands can be reduced so that the surgeon can take them out, the effect is something tremendous. This is only one phase of the work and must be confirmed before proper estimate can be made of its value. But another line of work can be undetaken, namely, that of measuring the phagocytic power of the blood resistance to infection. We can begin to realize what can be done if we succeed in increasing the general resistance before undertaking an operation. Suppose a patient is to have an abdominal operation, and something can be administered in the evening to increase resistance so that when he wakens next morning he is in better condition to operate-what a great gain it would be. This is only suggestive, but there are great possibilities in it for someone to work out. DOCTOR CHARLES W. EDMUNDS: One of the greatest obstacles is the development of the technic. For four months, working every day, Doctor Bradley was simply learning how to perform the technic. In order to save time, Doctor Bradley will give a demonstration tomorrow in Doctor Dock's clinic. DOCTOR BRADLEY: Doctor Walker has asked two questions: first, about the number of bacteria taken up being limited in the serum. We have never found it so. But the staphylococci differ so in appearance; one stain will take up such an amount that you cannot count them; and if you take one that is virulent that would not take them up at all. About the dilution, I cannot answer that. A Baltimore worker has gotten results that are the opposite of ours. About the treatment of cancer, I remember of reading it and wondering how much immunity. would result, because it is beyond belief, it seems to me. I did not know about these newer cases that Doctor Hutchins reports. Doctor Wright has suggested the advisability of inoculating in advance of operations, especially on the mouth and nose, raising the index to 1.8 or 1.4 so that the danger of infection would not be quite so great. If that can be done it would be well. I do not know whether it can or not. CLINICAL SOCIETY OF THE UNIVERSITY OF MICHIGAN. THE PRESIDENT, HUGO A. FREUND, M. D., IN THE CHAIR. REPORTS OF CASES. SPECIMEN FROM A CASE OF ANEURYSM OF THE ARCH OF THE AORTA RUPTURING INTO THE LEFT BRONCHUS. DOCTOR DOCK: I wish to present this specimen which came from a patient who was in the hospital just a year ago. The case illustrates the class of aneurysms which may produce very few signs and still be capable of detection. The man did not come on account of symptoms, but being in the hospital with his sick wife sought the clinic on account of slight shortness of breath. On examination by Doctor Morris it was found that the patient, a man of forty-nine years, had an inequality of the pupils, a fact of interest in connection with the existence of aneurysm, but negative in this case as it had existed for twenty years. Physical examination at first showed no other abnormality than weak vesicular breathing and |