demonstrate the real and positive advance that had been made in a field which, up to this time, had been regarded as absolutely hopeless. He did not doubt that there were those who would still remain skeptical about the value of the toxins in spite of the evidence presented. Such persons must either fail to see any logical connection between the accidental erysipelas and the toxins, or they must go even farther and deny that there are any authentic cases of malignant tumors that were cured by accidental erysipelas. The only explanation they can have to offer for the results which cannot be questioned is, that in all the successful cases there must have been an error of diagnosis.

Such an explanation might be entitled to some consideration were a single case only involved, but those who would seriously propose it as a satisfactory explanation, in view of the results in more than twenty cases, could not claim to be guided by scientific principles. The writer stated that he had carefully examined the literature of the subject of spontaneous disappearance of tumors supposed to be malignant, but had failed to find a single instance in which the diagnosis had been confirmed by the microscope. It would appear remarkable that these cases should be the first on record with a clinically and microscopically confirmed diagnosis to disappear spontaneously, and it would seem more remarkable still that this disappearance should be coincident with the beginning of the treatment with the toxins.

Furthermore, it would be clearly unfair to rule out these cases on the ground of error in diagnosis, without ruling out the cases of cure following operation for the same reason.

The writer then briefly referred to the various theories that had been offered in explanation of the action of the toxins. He still adhered to his opinion, expressed in his earlier paper, published in December, 1892, that the micro-parasitic origin of malignant tumors furnished the only rational explanation of this action. His conclusion were, (1) that the mixed toxins of erysipelas and bacillus prodigiosus exercise an antagonistic and specific influence upon malignant tumors, which influence in a certain proportion of cases may be curative. (2) That the influence of the toxins is very slight in most cases of carcinoma, including epithelioma, most marked in sarcoma, but that it varies greatly with the different types, the spindle-celled form being by far the most responsive to the treatment. (3) That the action of the toxins is not merely local in character, but systemic. (4) That the toxins should be reserved for use in clearly inoperable cases of sarcoma, or in cases after primary operation, to prevent

recurrence.

DISCUSSION.

DR. WELCH. I have been very much impressed by this personal statement from Dr. Coley, and I see no way of gainsaying the evidence which he has brought forward, that there is something specifically and genuinely curative in his method of treatment. A single undoubted cure of a demonstrated cancer or sarcoma by this treatment would be enough to establish the fact that the treatment exerts some specific curative effect, for the spontaneous disappearance of undoubted malignant growths of this character is almost unknown. Dr. Coley has, however, presented to us positive proof of the cure, not of one only, but of several cases of malignant tumor by his method. Although I suppose that in any given case the chances of cure by this method are at present not great, still the demonstration that cure is possible gives every encouragement for perseverance in this line of investigation and work, and for efforts to perfect the method of treatment.

It is interesting to learn that the most strikingly beneficial results have been obtained in the treatment of spindle celled sarcomata. There are certain kinds of sarcomata which some pathologists are inclined to rank rather among the infectious tumors than among the genuine tumors, in the sense in which these terms are used by Cohnheim; but it is rather certain sarcomata of the lymphoid type than the fusiform-celled sarcomata which are thus believed to be possibly outside of the class of genuine tumors, according to Cohnheim's classification.

As Dr. Coley suggests that the variations in his results may depend in part upon variations in the virulence of his cultures, and as it is well known that streptococci vary notably in virulence, I would like to ask if he has as yet utilized the methods of Marmorek in order to obtain cultures of uniformly high degrees of virulence. Dr. Livingood, in my laboratory, has confirmed the results of Marmorek and succeeded repeatedly by his method in transforming streptococci of low virulence into those of very exalted virulence.

It seems to me that it would be practicable and most interesting, and possibly demonstrative of the specific effects of the treatment, if Dr. Coley, in carrying out his researches, would occasionally cut out small bits of tissue from the tumor, and by their examination endeavor to determine the details of the process of cure.

It does not seem to me absolutely necessary to adopt the hypothesis of the parasitic causation of these malignant growths in order to explain their disappearance under this treatment. It is conceivable that the peculiar biological properties of the tumor cells-and peculiar they unquestionably are--may render them particularly susceptible to the toxic substances injected. The evidence that the curious bodies often seen in malignant

demonstrate the real and positive advance that had been made in a field which, up to this time, had been regarded as absolutely hopeless. He did not doubt that there were those who would still remain skeptical about the value of the toxins in spite of the evidence presented. Such persons must either fail to see any logical connection between the accidental erysipelas and the toxins, or they must go even farther and deny that there are any authentic cases of malignant tumors that were cured by accidental erysipelas. The only explanation they can have to offer for the results which cannot be questioned is, that in all the successful cases there must have been an error of diagnosis.

Such an explanation might be entitled to some consideration were a single case only involved, but those who would seriously propose it as a satisfactory explanation, in view of the results in more than twenty cases, could not claim to be guided by scientific principles. The writer stated that he had carefully examined the literature of the subject of spontaneous disappearance of tumors supposed to be malignant, but had failed to find a single instance in which the diagnosis had been confirmed by the microscope. It would appear remarkable that these cases should be the first on record with a clinically and microscopically confirmed diagnosis to disappear spontaneously, and it would seem more remarkable still that this disappearance should be coincident with the beginning of the treatment with the toxins.

Furthermore, it would be clearly unfair to rule out these cases on the ground of error in diagnosis, without ruling out the cases of cure following operation for the same reason.

The writer then briefly referred to the various theories that had been offered in explanation of the action of the toxins. He still adhered to his opinion, expressed in his earlier paper, published in December, 1892, that the micro-parasitic origin of malignant tumors furnished the only rational explanation of this action. His conclusion were, (1) that the mixed toxins of erysipelas and bacillus prodigiosus exercise an antagonistic and specific influence upon malignant tumors, which influence in a certain proportion of cases may be curative. (2) That the influence of the toxins is very slight in most cases of carcinoma, including epithelioma, most marked in sarcoma, but that it varies greatly with the different types, the spindle-celled form being by far the most responsive to the treatment. (3) That the action of the toxins is not merely local in character, but systemic. (4) That the toxins should be reserved for use in clearly inoperable cases of sarcoma, or in cases after primary operation, to prevent

recurrence.

DISCUSSION.

DR. WELCH.-—I have been very much impressed by this personal statement from Dr. Coley, and I see no way of gainsaying the evidence which he has brought forward, that there is something specifically and genuinely curative in his method of treatment. A single undoubted cure of a demonstrated cancer or sarcoma by this treatment would be enough to establish the fact that the treatment exerts some specific curative effect, for the spontaneous disappearance of undoubted malignant growths of this character is almost unknown. Dr. Coley has, however, presented to us positive proof of the cure, not of one only, but of several cases of malignant tumor by his method. Although I suppose that in any given case the chances of cure by this method are at present not great, still the demonstration that cure is possible gives every encouragement for perseverance in this line of investigation and work, and for efforts to perfect the method of treatment.

It is interesting to learn that the most strikingly beneficial results have been obtained in the treatment of spindle celled sarcomata. There are certain kinds of sarcomata which some pathologists are inclined to rank rather among the infectious tumors than among the genuine tumors, in the sense in which these terms are used by Cohnheim; but it is rather certain sarcomata of the lymphoid type than the fusiform-celled sarcomata which are thus believed to be possibly outside of the class of genuine tumors, according to Cohnheim's classification.

As Dr. Coley suggests that the variations in his results may depend in part upon variations in the virulence of his cultures, and as it is well known that streptococci vary notably in virulence, I would like to ask if he has as yet utilized the methods of Marmorek in order to obtain cultures of uniformly high degrees of virulence. Dr. Livingood, in my laboratory, has confirmed the results of Marmorek and succeeded repeatedly by his method in transforming streptococci of low virulence into those of very exalted virulence.

It seems to me that it would be practicable and most interesting, and possibly demonstrative of the specific effects of the treatment, if Dr. Coley, in carrying out his researches, would occasionally cut out small bits of tissue from the tumor, and by their examination endeavor to determine the details of the process of cure.

It does not seem to me absolutely necessary to adopt the hypothesis of the parasitic causation of these malignant growths in order to explain their disappearance under this treatment. It is conceivable that the peculiar biological properties of the tumor cells-and peculiar they unquestionably are--may render them particularly susceptible to the toxic substances injected. The evidence that the curious bodies often seen in malignant

tumors are genuine parasites is, in my opinion, far from conclusive at the present tine.

DR. FINNEY.-I have had the opportunity of observing the action of both the erysipelas organism and the toxin in a number of cases, both in hospital and private practice. One point which Dr. Coley has not mentioned to-night, but which he has referred to previously, I will speak of, because I think it of great value. It is the influence of the treatment on cases which may not finally result in a cure. The first case in which I used the erysipelas occurred about the time Dr. Coley began to make his observations in New York. It was a case of a woman with inoperable carcinoma of both breasts. Against my will, but at the urgent request of herself and her husband, I inoculated with a pure culture of the erysipelas streptococcus. She had at the time a very distressing and severe cough, with intense pain, evidently from involvement of the pleura. She had also evidences of internal metastases. After the first reaction from the erysipelas the pain almost entirely disappeared, and did not reappear with severity while the patient lived. She had been almost constantly under the influence of morphia up to the time of the inoculation, and after that time she had only a little codein from time to time to relieve her cough, which persisted after the pain had disappeared. I observed a similar action in another case. I think this patient lived three months after the inoculation. She gradually wasted away, more from inanition resulting from the internal metastases.

I had one case of inoperable carcinoma of both breasts, in which it was impossible to produce any reaction from the erysipelas. I injected it under the skin, I scarified and dressed the wounds in pure cultures in large amounts in very virulent erysipelas without getting the slightest reaction. Of course there was no result from this case.

I would like to ask Dr. Coley whether he has ever observed any cumulative effect of the toxins? In one or two cases it seemed as if that had happened. After a number of injections with gradually increasing doses, without any reaction, a sudden tremendous explosion would take place which slowly subsided, and then for a varying length of time there would be no reaction, even with larger doses than were used previously.

a cure.

I have observed no cases up to the present time where there has been But, unfortunately, all the cases in which I have used it, except one under treatment at the present time, have been either carcinoma or cases of sarcoma that were beyond hope from any source.

DR. COLEY.—I have been very much interested in the discussion, and I think I have gained as much from it as anyone. I was particularly interested in the remarks of Dr. Welch. I did not mean to make quite so strong a statement in regard to the parasitic theory; I should have said that that was the way it appeared to me.