THE JOURNAL OF EXPERIMENTAL MEDICINE.

"Baltimore, July 6, 1896.

"DEAR DR. - : I have mailed you to-day a reprint of my article on the treatment of diphtheria by antitoxin. The reason that I have not done so before is that all of my reprints were exhausted, as well as the edition of the Hospital Bulletin containing the paper. I have, however, secured a reprint, which you can retain. I regret the delay in complying with your request. Very Truly Yours,

"WILLIAM H. WELCH."

"The treatment of Diphtheria by Antitoxin," by William H. Welch, M.D., professor of pathology, Johns Hopkins University of Baltimore. The following is an abstracted historical sketch, in part, with some special points and a few extracts, winding up with his conclusions on his last page.

Dr. Welch gives Behring credit for the first conception of serumtherapy in 1890, showing the immunizing and curative quality of blood and its serum of artificially immunized animals for tetanus, diphtheria being implied, which was publicly announced in London in August, 1891; following this, in 1892, Behring & Wernicke published an article, in which these experiments were fully described, and which sets forth the fundamental principles underlying serum-therapy of diphtheria: “The first trial of immune serum in the treatment of human diphtheria was made in von Bergmann's clinic, in Berlin, in the autumn of 1891. This trial, together with those made in 1892 by Henoch in Berlin, by Heuber in Leipzig, and in the Institute for Infectious Diseases in Berlin, were of a tentative nature and made with weak serum and insufficient doses.

"It was not until early in 1893 that Behring succeeded in obtaining anti-diphtheritic serum equaling the strength of even his so-called normal serum, of which sixty times the strength is that of the weakest Behring serum at present in use. In April, 1893, Behring referred to thirty cases treated with this normal serum.

"From this period on Behring & Ehrlich succeeded in obtaining healing serum of greater and greater strength, until in August, 1893, Ehrlich and Wasserman obtained from goats healing serum twenty to sixty times the strength of Behring's normal serum.”

The era of serum treatment of human diphtheria by approximately sufficient doses of antitoxin really begins with this publication of Ehrlich, Kossel and Wasserman in April, 1894:

"It is evident from this brief historical summary that the general principles of serum-therapy of diphtheria were fully established, and its

application to human beings in active operation before Roux delivered his memorable address on the subject at the Eighth International Congress of Hygiene and Demography, held in Budapest, September 1-9, 1894, three years after Behring's original communication to the preceding congress in London. Roux, however, presented the subject with such clearness and force, and with such an array of convincing and carefully analyzed statistical evidence, that the attention of the great body of physicians throughout the world, who had paid little heed to the previous work, was arrested, and the question of the healing power of diphtheria antitoxin became and has continued to be the foremost medical question of the day."

Having gotten such statistical data from other sources will omit this from Dr. Welch's paper, and simply content myself with quoting from him one very important one, as follows:

"A most convincing demonstration of the healing power of antitoxin is furnished by the experience of Baginsky during an involuntary pause in the serum treatment caused by failure in the supply of serum. Between March 15, 1894, and March 15, 1895, there were treated in Baginsky's service by antitoxin 525 children, with a fatality of 15.6 per cent. During the period of forced interruption the serum treatment, this period being chiefly the months of August and September, 126 children were treated without antitoxin, with a fatality of 48.4 per cent. There was absolutely no selection of cases in either group. In his comments upon this experience Baginsky says:

"It is all the more remarkable as the ratio of mortality of those treated with the serum, both before and after the period of interruption, varied within very small percentage figures. If one will permit figures to speak at all, there has scarcely been made on human beings a more demonstrative test of the curative power of a therapeutic agent. It was an experiment forced upon us, but it proved to us how terrible was the form of disease which we were treating, and how numerous would have been the victims without the use of the healing serum.""

"Dosage and timely administration are factors of prime importance in determining the efficacy of antitoxic treatment."

He thinks proper dosage can be obtained with more facility for diphtheria than for tetanus, which, however, must be after all "empirical," even for diphtheria; age of patient, and duration and severity of case are points for judgment to be exercised upon, and because of expensiveness and liabilities, better use inexcessive doses, but repeated.

Disclaims knowing much of the nature of antitoxin, or of the modus operandi, but says this is no argument against using therapeutic

ally the antitoxin. He's inclined to accept the "vital theory" of its action, viz: "That the antitoxin acts through the agency of the living body, and probably in the sense that it renders the cells tolerant of the toxin." Animal experimentation and clinical experience teach early use of antitoxin.

Dr. Welch is right, and for two reasons of my own experience, or earlier thoughts, as follows:

Riding on an electric car in the streets of Richmond, 1888, the conductor confessed he didn't understand it, but could work it. When thirty years ago I first began to practice medicine I didn't exactly know the modus operandi of quinin. And who would have dared not to have used it, in the malignant ague? Before 1881 did the bacteriologist know all about it? Does everybody accept the Binz-Laveran theory (Bartholow, p. 196)? And yet we rely on the remedy-relied on it--and justly, do we did we! Sanctions use of antitoxin from a "clinical diagnosis" and then can go on with bacteriological process.

He seems confident that "Loeffler bacillus is the cause of diphtheria." The only prominent opposer of this view is Hanseman, but well met by Frænkel.

Dr. Welch admits experimental diphtheria more amenable to favorable results than clinical ("human") diphtheria, because the former is less apt to be contaminated or complicated with "streptococcus pyogenes,” a large portion of fatal cases showing this element.

"Without doubt the remedial role of diphtheria antitoxin is materially restricted by its inability to combat developed streptococcus sepsis, broncho-pneumonia, and other complications referable to secondary infections, or to stop impending suffocation by immediate removal of mechanical obstacles in the form of false membranes in the air-passages; but the antitoxic serum is the most powerful agent which we possess to prevent the development of these complications and secondary infections."

"So far, then, as the testimony of physicians, based upon their clinical experience is concerned, this, as I have already said, is overwhelmingly in favor of the antitoxic treatment, wherever their experience in its employment has been a large one. Those with less experience are often even more enthusiastic; but many of these, in view of their limited experience, are wisely conservative and a few are hostile to the new treatment."

"These occasional untoward effects of the healing serum are annoying, but, being unattended with danger to life and without serious consequences, they do not contra-indicate the use of the serum.

"There have been a few cases reported in which the writers, without any satisfactory evidence whatever, have referred the death of the

patient to the use of the serum. The essential harmlessness of the serum has been demonstrated by over a hundred thousand injections, and if future investigations should show that through some idiosyncrasy on the part of the patient, death ever is attributable to the injection of the serum, this would probably count for about as much as the rare deaths from the use of ether or chloroform. I shall leave untouched the question of the immunizing properties of antitoxin.

"The principal conclusion which I would draw from this paper is that our study of the results of the treatment of over 7,000 cases of diphtheria by antitoxin demonstrate 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.

"The later reports show in general a decided improvement in the results of the treatment over the earlier ones, and there is every reason to believe that the results of the second year's employment of the new treatment will make a much more favorable showing than those of the first year. We shall come to a clearer understanding of the mode of action of the healing serum. Improvements in the methods of preparation and preservation of the serum, and possibly the separation of the healing substance, at least from other ingredients which produce the undesired effects, may be expected.

"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.

"These studies and the resulting discoveries mark an epoch in the history of medicine. It should be forcibly brought home to those whose philosophic sentiments outweigh sentiments of true philanthropy that these discoveries, which have led to the saving of untold thousands of human lives, have been gained by the sacrifice of the lives of thousands of animals, and by no possibility could have been made without experimentation upon animals."

The following from the Bulletin of the Maryland University Hospital, Baltimore, Md., June 1, 1896; by J. E. Atkinson, M.D., professor of materia and therapeutics, clinical medicine and dermatology, University of Maryland. Subject, "The Present Status of Therapeutics," is so full of truth I may be excused for copying:

"In 1796 Jenner first practiced vaccination against smallpox. It was a marvelous, glorious discovery of incalculable value to mankind and sheds an undying fame upon its discoverer. It resulted from the accidental observation of phenomena by a mind great enough to under

stand their significance. It was a purely empirical discovery, and such it remains to-day. Almost a century later the antitoxin of diphtheria was discovered, but under what different conditions! Conditions that in Jenner's time were impossible, were impossible, indeed, until within a decade. Purely scientific inductions led to the discovery, only less important than that of Jenner, but still in a measure empirical, for the exact nature and the methods of its operation remain unknown as yet, though there is little doubt that the new therapeutic and prophylactic procedure will be understood before long.

"Thus has the empiricism of to-day, by marvelous subtlety of reasoning and of scientific research, discovered that the animal organism is capable, not only of building up bulwarks against the enemies that wage incessant war against it, but of creating weapons of offense and munitions. of war with which they may be attacked and routed. Henceforward, the vis medicatrix naturæ (an old phrase with a new meaning), will be harnessed to the car of the therapeutist, and from the body itself will be derived the most potent of the remedies with which to destroy the disease which assails it. What has been accomplished in the treatment of hydrophobia, tetanus and other animal diseases, but above all in the prevention and cure of diphtheria, is an indication of what is yet to be achieved in the treatment of specific disease, and is the noblest triumph of the therapeutic art."

Dr. S. C. Chew, of the University of Maryland, kindly gives me his opinion as concerns diphtheria toxin. Here is his letter to show. Have crossed out that part of which there is no need of printing.

BALTIMORE, September 22, 1896.

"DR. E. W. ROBERTSON :

E. W. R.

"DEAR DOCTOR: I have had no personal experience with serumtherapy, except in the treatment of diphtheria, the results of which are no longer questionable and are common property of the profession. I think that there is good reason for believing that serum-therapy will make great advances in the next few years, and will be productive of most important results. Very truly yours,

"S. C. CHEW."

Its march is onward, and its fate will be different, too, from the brave six hundred at Balaklava, for I feel sure its final victory will be certain. For, as a quiet worker in silent night the "phagocytic function" of leucocytes may be going on for cure (which I have thought may be mere theory), yet we know that vaccination is a tangible weapon, and antitoxin almost equally as conspicuous in its effects, though as it were seen "through a glass darkly;" but with less prejudice, more light,