With Compliments of the Author. 
THE CURE OF TUBERCULOSIS BY 
OXYTUBERCULINE, 
WITH EXPERIMENTS ON PATIENTS, 
ANIMALS AND CULTURES. 
BY 
J. O. HIRSCHFELDER, M. D., 
PROFESSOR OF CLINICAL MEDICINE, COOPER MEDICAL COLLEGE, 
SAN FRANCISCO, CAL. 
[Read before the Medical Society of the State of California, April, 1897.] THE CURE OF TUBERCULOSIS BY OXYTU- 
BERCULINE, WITH EXPERIMENTS 
ON PATIENTS, ANIMALS AND 
CULTURES. 
J. O. HIRSCHFELDER, M. D., San Francisco. 
[Read before the Medical Society of the State of California, April, 1897.] 
In the November number of the Occidental Medical Times 
of last year I described a method of treatment of tuberculosis 
that was based upon some original conceptions of the mode of 
generation of antitoxines in the animal body. Further re- 
search and clinical experience have enabled me to confirm the 
statements made at the time, and also those in an additional 
note published one month later. My clinical observations and 
those of my colleagues who have investigated the remedy, 
place the efficacy of oxytuberculine beyond doubt. Culture 
experiments, as you will see, show how the agent acts and 
enable us to measure the potency of each preparation of the 
oxytuberculine in a manner that has not yet been possible with 
any of the antitoxic serums. 
Before the year 1890 the attitude of the medical profession 
towards tuberculosis was that of absolute helplessness. We 
had learned to diagnosticate the disease in its early stages by 
the microscopic examination of the sputum through the pres- 
ence of the bacillus tuberculosis, but we felt that when we had 
discovered the dreaded disease, all that we could do was to 
send the hapless patient to a congenial climate in the hope 
that fresh air and exercise might benefit. As far as active 
therapeutic intervention was concerned, however, we knew 
that we could do nothing. Then came the glad tidings that 
Koch had found the long sought for specific; that his tubercu- 
line was the certain cure for tuberculosis, wherever it might 
be found. We shall probably never again witness such an 
enthusiasm in medical circles as that which was aroused by 
Koch’s demonstration. We had learned to look upon his 
statements as demonstrated facts, for he had never, until then, 
enunciated a doctrine that had not been found to be correct. 2 
Oxy tuberculine. 
We even felt that the secrecy of the remedy was to be forgiven 
in him—although in another such a procedure would have 
been considered quackish. Truly, it seemed marvelous that 
an infinitesimal quantity of an organic liquid injected under 
the skin of a tubercular individual should cause a violent feb- 
rile reaction, with congestion of the tubercular mass and no 
effect on other tissues. Every one was eager to try the new 
remedy, even if he did not know what it was, and happy was 
he if he were one of the favored few who could obtain it at 
any price. 
But the reaction came only too soon. The great Virchow 
showed at the post-mortem table what was really the influ- 
ence of the tuberculine. In a large number of cases death was 
hastened by its use, and dissemination of tubercle was induced 
by it, such as the great pathologist had not seen before. 
From that time on the credit of tuberculine began to wane, 
and soon it fell into disrepute with the vast majority of physi- 
cians, as a remedy for tuberculosis. It still holds its place for 
diagnostic purposes, for the febrile reaction following its in- 
jection is a certain sign that tuberculosis is somewhere present 
in the body. 
We now know what tuberculine is and how it is prepared. 
Upon the surface of veal boullion containing glycerine and pep- 
tone a pure culture of the bacillus tuberculosis is floated and 
cultivated at 38 degrees C. After six to eight weeks a pellicle 
will have covered the surface and sunk to the bottom of the 
vessel. The fluid is then sterilized by heat, filtered through 
a Pasteur filter and evaporated to one-tenth its volume. This 
is the crude tuberculine such as was formerly used. Now this 
crude liquid is precipitated with alcohol, washed and dissolved 
in water. 
Feeling that there was an element of truth in the state- 
ments of Koch that tuberculine cures consumption, and that 
the ill-effects resulting from its use must be due to some 
extraneous foreign elements that were the deleterious agents, 
several have attempted to purify it and have used what they 
supposed to be a purified tuberculine under various names. 
The most prominent of these preparations is that of Klebs, 
which he terms antiphthisine. Unfortunately, the claims 
made by Klebs have not been confirmed by experience. Tru- Oxytu berculine. 
3 
deau has clearly proved that antiphthisine is merely a very 
dilute tuberculine. We shall see during the course of these 
remarks that Trudeau was quite correct when he stated that 
Klebs erred in affirming that tuberculine inhibited the growth 
of the tuberculosis bacillus. Trudeau showed that it is the 
acid which develops in the culture fluid that acts as a pre- 
ventive of further growth. 
I can confirm Trudeau’s statements, for in equal parts of 
tuberculine and veal boullion that has been made alkaline, the 
tuberculosis bacillus grows as luxuriantly as in the plain veal 
boullion. Clinical observations have been as adverse to the 
claims of Klebs as have been laboratory experiments. 
In 1890 Behring enunciated the doctrine of the antitoxine 
substances which develop in the animal organism from the 
bacterial toxines and led to the introduction of the antitoxine 
of diphtheria into general medical practice. In spite of occa- 
sional adverse criticism and occasional death due directly to 
the remedy, it has proved its value in the treatment of diph- 
theria beyond a doubt and thousands of lives are yearly saved 
that would otherwise undoubtedly have been lost. 
Stimulated by these excellent results numerous investiga- 
tors have attacked tuberculosis in a similar manner, and have 
probably obtained some good results. This is true of Paquin, 
in our country, and Maragliano, in Italy. Their method of 
procedure is to inject gradually increasing quantities of 
tuberculine hypodermically into a horse until the animal be- 
comes immune to such large injections. The blood is drawn 
from the jugular vein into a sterile flask, allowed to coagulate 
in a cool place and the sterile serum drawn off for use as the 
antitoxine. It will require a long observation of results by 
many clinicians before we will be able to arrive at a knowledge 
of just how much may be accomplished by this serum. But 
even if it should be finally proved that an antituberculine 
develops in animals so treated, its use as a curative agent 
in man is attended with several obstacles and dangers. In 
the first place, the quantity of tuberculine used, and hence 
the quantity of antituberculine developed, is so infinitesimal 
that when dissolved in the blood and plasma of the animal, 
it is present in such minute proportions that the numeral 
would be far removed from the decimal point in its repre- Oxytuberculine, 
4 
sentation in figures. In the second place the antitubercu- 
line elaborated in the blood must be administered dis- 
solved in the serum of the animal. We know from several 
deaths that have immediately followed the administration of 
the diphtheria antoxine, that this is by no means an indiffer- 
ent substance which may be administered in unlimited quan- 
tities. The antitoxine we know develops in the animal body 
in some manner from the toxine. If we were able to discover 
by what process the body evolves the antitoxine from the tox- 
ine, it is clear that we might be able in our laboratories to imi- 
tate the method, and so produce the sought for remedy in un- 
limited quantities and free from deleterious admixture. Until 
now no satisfactory theory has been established, and no indi- 
cation had been given of the lines upon which to proceed. 
With regard to tuberculosis, however, it seems to me that 
the course to pursue has long been before the medical profes- 
sion, even though we were unable to read what nature had 
written for us in her hieroglyphics. 
The theory which lies at the foundation of the therapeutic 
measures about to be described, is even more important than 
the results themselves, for, if it should be found correct, it will 
be an addition to our biological knowledge of the greatest 
scientific importance. This theory was thought out early in 
October, 1895, and the various modes in which it might be 
practically applied were clear before a single step was taken. 
In other words, the theory was not evolved from the therapeutic 
results, but the method of treatment was a consequence of the 
biological proposition. The therapeutic success may therefore 
be looked upon as a verified prediction, and hence has far 
greater evidential value than it otherwise could have. The 
treatment of patients by the new method was very cautiously 
begun on October 22d, 1895, as the results warranted, the 
doses were gradually increased until after a few months effi- 
cient quantities were administered. I am pleased to be able to 
say that to my knowledge no patient has been injured by its 
use. 
In 1864, Spencer Wells performed laparotomy, inconsequence 
of an erroneous diagnosis, upon a case of tubercular peritonitis. 
Contrary to all expectations the patient recovered. Numerous 
cases have been since reported in which the same favorable re- Oxytu berculine, 
5 
suits occurred; indeed, the peritoneum that was seen at the 
operation to be studded with tubercles, has been found years 
after, at a second operation, to be smooth and free from all tu- 
bercular deposit. Distant tuberculosis has also been observed 
to disappear after such laparotomies upon tubercular perito- 
neums. It appears most probable that in these cases the en- 
trance of air into the peritoneal cavity must have been the 
important factor; that an oxidation of the tuberculine pres- 
ent in the effusion was thus brought about, and that it was 
this oxytuberculine which effected the cure both of the local 
and of the general tuberculosis. It certainly seems a very 
probable hypothesis that it is oxidation whereby the toxine is 
changed into the antitoxine in the animal body, for there is no 
process of the economy so universal as oxidation. The first 
and most evident result of the introduction of a toxine is fever 
with increased oxidation, as if nature was striving with all her 
power to change by this process the poisonous substance into 
its antidote. 
Acting upon this hypothesis it became the problem to find a 
method of oxidizing the toxine without completely destroying 
it, and various methods of accomplishing this result were in- 
vestigated. I will not weary you with a description of the 
different forms of experiment that were attempted, nor of the 
steps that were taken until the method was finally perfected, 
but shall describe to you in as detailed a manner as I can the 
mode in which oxytuberculine is now manufactured. I found 
very soon, in the course of my experiments, that the peroxide 
of hydrogen is the substance for which I was seeking, that it was 
a powerful oxidizer but not so destructive as was generally 
supposed. When I added it to tuberculine, in the cold, and in- 
jected the latter into a tubercular patient or animal, even after 
the mixture had stood for some time, it produced the same reac- 
tion as if pure tuberculine had been used. I found that in 
order to avoid such reaction it was necessary to heat the mix- 
ture for at least ninety-six hours. I have lately found it wise 
to lengthen the period of heating even more, and now sterilize 
for 120 hours, obtaining better results that I did when the ac- 
tion was continued only 96 hours. I formerly used the tuber- 
culine prepared by Koch in Berlin, but have been able to ob- 
tain still better results with one of my own growth made by the 
development of a highly virulent bacillus of tuberculosis upon 6 
Oxy tuberculine. 
veal bouillon containing four per cent glycerine, one per cent 
peptone, and one-half per cent of chloride of sodium, to every 
liter of which when neutralized 3 c.c. of a normal solution of 
carbonate of sodium is added. In this culture fluid the germ 
has developed with gradually increasing rapidity so that, 
whereas, ordinarily it takes six weeks for the culture fluid to be 
completely covered with the growth, this now occurs with our 
germ in less than three weeks. Injected into guinea pigs it 
kills many of them in less than three weeks, the organs being 
overwhelmed with tubercular nodules, as you can see from this 
specimen. 
After the germ has fully grown so that the tubercular scum 
that floats on the surface begins to sink, the flask is sterilized 
by heat for two hours and the contents filtered. This is the 
tuberculine I use. A measured quantity is put into a stone 
jug and one-tenth the quantity of a ten volume solution of the 
peroxide of hydrogen is added, the jug stoppered with cotton 
and put into a sterilizer at ioo° C. Every twelve hours the 
same quantity of the same peroxide of hydrogen is added until 
the process shall have been repeated the tenth time, so that in 
all the quantity of solution of peroxide of hydrogen added shall 
equal the quantity of tuberculine used. This is then heated 
to ioo° C. for twelve hours longer, and at the end of that time 
(120 hours in all) it is still found to contain free peroxide of 
hydrogen, is highly acid and decidedly darker than was the 
original tuberculine. It is made alkaline with caustic soda 
and reheated to drive off the excess of peroxide of hydrogen; 
5 per cent of boric acid is added to keep it from decomposing. 
It is filtered into sterile vessels and is ready for use. It now 
does not contain a trace of the peroxide of hydrogen which 
has all been changed to water. 
Theoretical objections have been made to the process by some 
who claim that the peroxide of hydrogen must be rapidly de- 
stroyed by the organic substances present in the liquid. It is 
very easy to prove that this supposition is incorrect, for at any 
stage of the process up to the final addition of the alkali, free 
peroxide of hydrogen may be found by the usual chemical tests, 
such as the blue color that develops in the iodide of starch, and 
the pretty reaction with a mixture of bichromate of potash and 
sulphuric acid. In this the free peroxide of hydrogen causes 
a beautiful blue color from perchromic acid developed, which Oxytu berculin e. 
7 
will dissolve in ether and float as a blue liquid on the surface. 
The greatest possible care is necessary in the preparation of 
this oxytuberculine, for if any appreciable quantity should es- 
cape oxidation, fatal tuberculine poisoning might result from 
the large quantities that must be administered. It should be 
carefully tested, first on animals and then on patients. This 
oxytuberculine, after it has been carefully prepared and tested, 
is injected hypodermically into any part of the body. I prefer 
the back, and inject the remedy well under the skin. The 
most scrupulous care must be taken. If the lymph should be 
in the least clouded or any other condition be present that 
would suggest infection, it should be sterilized by heat for at 
least 15 minutes. Ordinary syringes should not be used but 
such as are employed with antitoxine. I have made many 
thousand such injections without a single abscess, or even an 
induration of the skin. I show you here a patient into whose 
back many hundred injections have been made. You will find 
no sign of irritation or infiltration. In order that the method 
of using the remedy may be made clear I will now inject a 
syringe full. I begin with 5 c.c. injected daily and increased 
by 5 c.c. every three days until the dose 20 c.c. is reached, 
at which quantity I usually remain, but in many cases that has 
been far exceeded. I have injected as much as 100 c.c., over 
three ounces, or the equivalent of 5 c.c. of Koch’s concentrated 
tuberculine, at one time into a patient without a rise of tem- 
perature, or any other immediate or subsequent unpleasant 
symptom. 
The liquid causes no greater local disturbance than any in- 
different fluid would produce. There is no reddening of the 
skin or other sign of localized inflammation. In a few min- 
utes the fluid injected is absorbed, and the patient has no fur- 
ther inconvenience except sometimes a little smarting at the 
site of injection; there is no rise of temperature, nor any other 
unpleasant constitutional effect. Within a few days the cough 
and the expectoration diminish, and the most striking effect is 
the rapid improvement in the appearance of the patient. His 
eyes become bright and his color changes from the gray hue of 
tuberculosis to one more nearly resembling that of health. The 
appetite rapidly returns, and with it a feeling of vigor that is 
most pleasing to the patient and to the physician. That is es- 
pecially evident in the very early cases in which there is little 8 
Oxytuberculine 
or no fever. In cases in which only slight fever is present, the 
higher temperature soon diminishes, and in many instances be- 
comes entirely normal. At the same time the infiltration of 
the lung gradually disappears, so that most careful examin- 
ation fails to reveal any deviation from the normal whatsoever 
after the treatment is completed. The bacilli of tuberculosis 
in the sputum may rapidly diminish and finally disappear alto- 
gether, as I have found in a number of cases. 
Every physician has seen cases of tuberculosis recover, but 
it has never before been my good fortune to witness such rapid 
changes as have taken place with several cases which have 
been examined by other physicians, both before and during 
the treatment. The patients that have recovered have thus 
far remained well. If any test of the method should be made 
by members of the profession, I would earnestly request that, 
provisionally, only early cases be treated in which there is no 
development of cavities in the lung, in whom fever is slight, 
and the constitutional effect such that a return to health may 
reasonably be expected. 
One of the most striking demonstrations of the value of the 
remedy occurred in a local tuberculosis of the hand. A physi- 
cian infected the dorsum of his right hand, and an ulceration 
developed which microscopic examination showed to be tuber- 
cular. It was treated in the usual manner without results, so 
that the surgeon was about to make an extensive excision, to 
be followed by skin-grafting. Instead thereof, local applica- 
tions of the oxytuberculine were made, and very rapid healing 
took place, leaving behind the same kind of scar as would have 
resulted from a non-infected ulcer. The doctor has kindly con- 
sented to appear before you. You observe the scar upon his 
knuckle which shows no sign of the trouble which gave rise to 
it The section prepared for microscopic examination by Dr. 
Rixford is open to your inspection. As a confirmation of this 
observation I show you here a dog that was vaccinated upon 
the back in a large number of places with a virulent pure cul- 
ture of tuberculosis. After a short time numerous tubercular 
ulcers developed, in the pus of which the bacilli of tubercu- 
losis were demonstrated; a section made by Dr. Rixford shows 
bacilli in the tissues. The dog was then chloroformed, and a 
piece of the skin with the tubercular ulcers was removed. 
This I have here preserved in formaline alcohol. The dog Oxytuberculine. 
9 
was then treated with daily hypodermic injections of oxytuber- 
culine. The ulcers rapidly healed, and you now see the ani- 
mal with the scar resulting from the removal of part of the 
tubercular skin, but with no sign of the disease that was vac 
ciliated into him. I will say that since the injections of oxy- 
tuberculine, the dog that was ailing, feeble and without desire 
for food, has become bright, strong and vigorous, and has de- 
veloped a voracious appetite. You here see the photograph 
of the dog cured, and 'here an enlargement of the skin with 
the tubercular ulcers. (See Plate I.) 
Of the cases that have been treated by me with the oxytu- 
berculine those who came in the very early stage of the disease 
before cavities were present were rapidly cured. By cure I 
mean a complete cessation of cough and disappearance of all 
symptoms of disease on the part of the patient, together with 
the return of a normal condition of the lung as shown by phy- 
sical examination. Above all do I demand that the bacilli of 
tuberculosis shall no longer be found in the sputum. 
Cases that were moderately advanced have likewise rapidly 
improved, and some have entirely recovered, as you will see. 
Of the very advanced cases many have shown marked im- 
provement, and many whom I had declined to treat as being 
too far advanced but who pleaded so hard for the treatment 
that I could not refuse, have surprised me by the wonderful 
improvement they have shown. 
Some in the last stages of the disease who presented them- 
selves with high fever, cyanotic and gasping, have died. No 
treatment should be expected to reach such cases. Of course 
they throw a cloud upon the statistics, for they must be hon- 
estly reported with the most favorable cases. I shall therefore 
present to you all of the cases I have treated with oxytuber- 
culine, but request you not to judge by the advanced cases for 
which I make no claim whatsoever. In order to systematize 
our observations I will divide the cases into four sets depend- 
ing upon the stage of the disease. In the first stage we find 
infiltration of the lungs with more or less pallor, loss of weight, 
cough with sputum containing bacilli of tuberculosis. These 
may be absent at repeated examinations and yet be finally found. 
In the second stage, we have extensive infiltrations of the 
lungs with hectic fever, emaciation, large quantity of sputum 
containing bacilli of tuberculosis, but no cavities. 10 
Oxytu be rculme. 
In the third stage we have cavities but still a fair degree of 
vigor. There is no dyspnoea when the patient is quiet, but 
marked shortness of breath on exertion. 
In the fourth stage we have large cavities with the usual 
signs of advanced consumption—the dyspnoea is very decided 
even when the patient is sitting or lying. 
The distinctive features: 
First stage—slight infiltration of the lungs. 
Second stage—extensive infiltration of the lungs. 
Third stage—cavities with dyspnoea on exertion, and none 
when at rest. 
Fourth stage—cavities with dyspnoea when at rest. 
Many of the cases here presented in person and in table have 
been seen by other physicians before and during the treatment. 
My colleagues have confirmed my observations, and I am cer- 
tain that they will agree that I have not erred in making my 
reports too favorable. It has been my purpose to be as skep- 
tical as possible, and I have striven to make the showing rather 
less favorable than too much so. I find that the cases that 
had been treated with oxytuberculine insufficiently oxidized, 
did not give the same results as those treated with the newer 
preparation, and have, therefore, separated them into a distinct 
table. 
FOURTH STAGE—OLD METHOD. 
No. 
Name. 
Days 
Treated. 
Bac 
Before. 
illi. 
After. 
Cured. 
Much 
Improved. 
Slightly 
Improved. 
Unchanged. 
Worse. 
Died. 
i... 
M. A. 
123 
Large. 
Large. 
1 
2... 
E. B. 
48 
II 
Not. Ex. 
1 
3-.. 
F. B. 
77 
Cl 
II 
1 
4... 
H. C. 
72 
<1 
1 
5... 
M. G. 
106 
II 
II 
1 
6... 
G. A. H. 
132 
II 
II 
1 
7... 
A. H. 
48 
II 
II 
I 
8... 
G. H. 
54 
II 
II 
I 
9... 
T. H. 
30 
II 
II 
1 
10... 
J. Me. 
100 
II 
II 
1 
11... 
R. 
102 
II 
II 
1 
12... 
G. St. D. 
77 
II 
II 
1 
13... 
0. R. 
120 
II 
II 
I 
14... 
J. H. 
39 
Mod. 
II 
I 
15... 
A. V. 
135 
Large. 
Few. 
1 
16... 
H. F. 
90 
Not Ex. 
I Oxytuberculine. 
11 
FOURTH STAGE—NEW METHOD. 
No. 
Name. 
Days 
Treated. 
Bacilli. 
O 
c 
M 
Ik 
M 
3 03 
*$(«• 
0 
B 
0 
B* 
3 
0 
a 
Before. 
After. 
rt> 
P* 
9 0 
% 
Oi 
§5: 
re 
ps< 
B 
OQ 
rt> 
cu 
Vi 
fP 
a> 
Oi 
I... 
D. A. C. 
172 
165 
104 
57 
481 
365 
363 
54 
235 
199 
130 
Large. 
Mod. 
I 
2... 
C. F. 
I 
3... 
T. J. 
G. A. K. 
Not Ex. 
<< 
I 
4... 
<< 
I 
5... 
J. M. 
J. M. 
ii 
None. 
I 
6... 
a 
Hrdly any 
Very few 
Large. 
Mod. 
I 
7... 
B. M. 
a 
I 
8... 
W. R. P. 
n 
I 
9... 
P. P. 
a 
I 
10... 
G. P. A. 
<< 
I 
11... 
D. H. 
u 
<( 
I 
THIRD STAGE. 
I... 
D. B. 
26 
Mod. 
Not Ex. 
1 
2... 
S. D. 
254 
37 
136 
162 
Large. 
None. 
I 
3... 
E. E. 
Not Ex. 
I 
4... 
A. G. 
Mod. 
Large. 
None. 
I 
5... 
F. J. 
M. L. 
J. M. 
S. M. 
Large. 
<< 
I 
6... 
3i 
141 
365 
30 
22 
Large. 
Hrdly any 
Mod, 
Not Ex. 
I 
7... 
<< 
I 
8... 
<< 
I 
9... 
A. M. 
<< 
I 
10... 
C. M. 
Mod. 
I 
II... 
R. M. 
237 
285 
33 
40 
198 
42 
146 
254 
250 
300 
280 
Large. 
Mod. 
I 
12... 
H. P. 
None. 
I 
13.. 
14.. 
15- 
16.. 
T. P. 
<< 
Not Ex. 
I 
L. F. 
Mod. 
I 
F. A. S. 
(( 
Mod. 
I 
C. H. W. 
Large. 
Mod. 
Large. 
Few. 
I 
17.. 
18.. 
M. W. 
I 
T. H. W. 
Large. 
{( 
None. 
I 
19.. 
20.. 
T. M. 
Mod. 
I 
F. D. R. 
«< 
None. 
I 
21... 
W. H. 
< < 
Mod. 
I 
22... 
M. W. 
120 
Small. 
Small. 
I 
23.. 
24.. 
25.. 
P. S. 
40 
30 
80 
Mod. 
Mod. 
I 
J. D. 
Large. 
Large. 
Mod. 
I 
T. T. 
I 12 
Oxytuberculine, 
SECOND STAGE. 
No. 
Name. 
•-J 
Bacilli. 
n 
a 
Much 
Improved. 
M 
a 
d 
| 
0 
0* 
3 
0 
I'S 
Before. 
After. 
0U 
0 cr 
< 
S.H 
so 
a 
00 
tt 
a- 
8. 
i... 
E. G. 
258 
75 
83 
91 
99 
100 
Large. 
Mod. 
None. 
1 
2... 
W. M. 
Not Ex. 
I 
t... 
N. R. 
Large. 
II 
Hrdly any 
None. 
< < 
I 
4... 
F. C. 
I 
5... 
Father S. 
Mod. 
1 
6... 
V. C.1 
None. 
II 
1 
7... 
C. V. 
90 
180 
Mod. 
II 
1 
8... 
T. L. 
Large. 
None. 
II 
1 
9... 
R. W. R.* 
36 
II 
I 
FIRST STAGE. 
I... 
F. A. A. 
134 
Mod. 
None. 
1 
2... 
M. L. 
16 
None. 
II 
1 
3... 
W Q. 
305 
II 
1 
4... 
1 R. W. R. 
106 
<1 
II 
1 
GENERAL SUMMARY. 
Stage. 
Total No. 
Treated. 
Cured. 
Much 
Improved. 
Slightly 
Improved. 
Unchanged. 
Worse. 
Died. 
Fourth Stage—Old Method 
16 
I 
2 
1 
6 
4 
Fourth Stage—New Method 
ii 
I 
5 
1 
2 
1 
1 
Third Stage 
25 
2 
18 
2 
3 
Second Stage 
9 
A 
c 
First Stage 
4 
4 
65 
11 
29 
5 
8 
7 
5 
Clinical observation having thus shown the very marked 
effect of oxytuberculine, it remains for us to establish in what 
manner is this cure effected. There are two modes in which 
the body may rid itself of an invading micro-organism. The 
one is by the enfeeblement of the germ, and the other is by the 
invigoration of the body so that it becomes sufficiently potent 
to expel the invader. We know that we are all constantly 
taking the bacillus of tuberculosis into our bodies. It has been 
1 Sputum (through oversight) not examined until the patient had been 
treated one month. 
* Bacilli found by former physician who sent the patient to me. Oxytu berculine. 
13 
shown by Loomis, at post-mortem examinations of healthy in- 
dividuals who have died of accident, that many have the ba- 
cillus of tuberculosis stored up in the bronchial glands out of 
harm’s way, but alive and able to infect guinea pigs when in- 
jected into them. Yet we cannot call such individuals tuber- 
cular. Again, we constantly observe that tuberculosis devel- 
ops when the patient becomes physically depressed, when the 
vital forces are at low ebb. On the other hand, innumerable 
cases of consumption recover under the influence of favorable 
hygienic conditions. The antitoxines of the infectious diseases 
probably act in a somewhat similar manner, for experiment has 
proved that they neutralize the pernicious toxines which are 
formed by the germs and which enfeeble the body by their 
poisonous influence. 
Upon the germs themselves they have little influence, for we 
know that the pathogenic organisms flourish in the very serum 
which is used to antagonize their effect upon the body. How 
is it with oxytuberculine ? It will be my pleasant privilege 
to prove to you this evening that oxytuberculine directly pre- 
vents the growth of the bacillus of tuberculosis, that its action 
is specific upon that germ, and not due to a general antiseptic 
effect. If we take veal bouillon containing 4 per cent glycer- 
ine, 1 per cent peptone and one-half per cent salt, and add to 
every 1000 c.c. thereof, when neutralized to litmus, 3 c.c. of a 
normal solution of carbonate of soda, we will find that the ba- 
cillus tuberculosis will grow vigorously upon it. If we mix 
this veal bouillon with equal parts of tuberculine made simi- 
larly alkaline the germ will flourish just the same. But if we 
use oxytuberculine made from the same tuberculine rendered 
alkaline to the same degree the bacillus of tuberculosis will not 
grow. In other words, the oxytuberculine inhibits in the cul- 
ture tube the growth of the germ of tuberculosis just as it cures 
the consumption in the patient. Not only can this be proved 
by the simple culture experiment, but the strength of the oxy- 
tuberculine can be most accurately gauged by the same process. 
If to our standard alkaline glycerine veal bouillon we add oxy- 
tuberculine in varying proportions, it will be a simple matter 
to find the weakest dilution of the oxytuberculine in which the 
growth of the bacillus will be inhibited, and thus may it be 
standardized. In this photograph you see represented the 
growth of tuberculosis bacillus on mixtures of standard veal 14 
Oxytuberculine. 
bouillon with varying portions of oxytuberculine made three- 
tenths per cent normal alkaline and water, also made three- 
tenths per cent normal alkaline. You see a gradual diminu- 
tion of the development as the addition of oxytuberculine 
becomes stronger. When the mixture contains 7 parts of oxy- 
tuberculiue in 20, growth ceases, and beyond this strength no 
growth occurs. That is to say, a dilution of this oxytubercu- 
line to 30 per cent prevents the development of the germ. We 
may therefore call this preparation 300 per cent strong. (See 
Plate II.) 
In a similar manner any oxytuberculine may be standard- 
ized so that when we use it we may know accurately how 
potent is the remedy that we are employing. Such a method 
of estimating the strength of a preparation is infinitely superior 
to that of judging it from its effect upon more or less resistant 
animals. 
From the very beginning of the experiments it has been my 
purpose to find some means of knowing how long I should con- 
tinue the oxidation in order that all of the tuberculine should 
be changed to oxytuberculine and none of the latter destroyed. 
There was no chemical test known, and all my efforts to find 
one were in vain. I was, therefore, compelled to make use of 
the reaction of tubercular guinea pigs to find the point when 
no effective tuberculine could be found. It is clear that a cer- 
tain amount of the tuberculine might be present, but neutral- 
ized in its effects by the oxytuberculine. Under such circum- 
stances we would get no deleterious tuberculine influence, but 
still not the best possible oxytuberculine action. In the manu- 
facture of the oxytuberculine I had gradually come to lengthen 
the time during which I heated the tuberculine with the per- 
oxide of hydrogen, and had finally decided upon the method 
of sterilizing for four days. Oxytuberculine so prepared gave 
excellent results and no reactions until I happened to use 
large doses, 40 c.c., with a highly sensitive hospital patient 
named Stewart. A slight rise of temperature occur red that 
made me feel that all of the tuberculine had not been converted. 
About this time I had discovered the inhibitory influence of 
the oxytuberculine, and I immediately concluded that this in- 
fluence would teach me what was the best length of time to Oxyhiberculine. 
15 
continue the oxidation. I reasoned that, if my theory were 
right, as I continued the oxidation, this inhibitory power must 
gradually increase until the maximum is reached, and as the 
oxytuberculine produced is gradually destroyed by further oxi- 
dation, from this point on there must be a gradual decline of 
this inhibitory power. Such, indeed, was the result obtained. 
I sterilized tuberculine with peroxide of hydrogen for 176 
hours, adding the peroxide every 12 hours, and removing por- 
tions of the lymph for comparison at 96, 120, 144, and 156 
hours. The final oxytuberculine, that sterilized 176 hours, 
contained but 53 per cent of the quantity that was present in 
that sterilized only 96 hours, and in order to make a fair com- 
parison after free peroxide in all the preparations was removed 
by rendering them alkaline and heating, all were diluted to the 
same proportion with distilled water, the quantity added de- 
pending upon the degree to which it had been diluted in the 
process of preparation by addition of peroxide of hydrogen, 
which, of course, had become changed to water. All of the 
preparations were then neutralized, and three-tenths per cent 
normal carbonate of soda was added. Each of the oxytuber- 
culines was mixed with an equal quantity of standard veal 
bouillon and inoculated with a pure culture of the bacillus tu- 
berculosis. As a control, standard veal bouillon was mixed 
with an equal quantity of water, to which three-tenths per cent 
normal carbonate of soda was added and was likewise inocu- 
lated with the same germ. The relative growth is shown by 
the photograph of the bottles in which they have developed. 
(See Plate III.) 
They show rapid growth in the veal bouillon, less in the 96 
hour oxytuberculine, and hardly any in the 120 hour oxytu- 
berculine, which you will remember had been diluted with 
water and veal bouillon to onty 26)4 per cent. In the 144 hour 
oxytuberculine growth increased, and was greater in the 156 
hour preparation, and in that sterilized in the 176 hour was 
almost as great as in the veal bouillon. This simple little ex- 
periment not only confirmed our previous culture tests, but 
likewise taught that at least 120 hours and less than 144 hours 
are necessary to get best results. In point of fact, as soon as 
I began to use oxytuberculine so prepared upon my patients, 
immediate and striking results occurred such as I had not wit- 16 
Oxytuberculine, 
nessed before. I shall now narrow the range still more by 
tests of the oxytuberculines heated for different periods be- 
tween 120 and 144 hours. I have done this in part with 
another sample of oxytuberculine that was sterilized 144 
hours and a portion removed after 134 hours sterilization. 
These were made three-tenths per cent normal alkaline, and 
each mixed with equal quantities of standard veal boullion. 
They were inoculated with the tuberculosis at the same time 
as was veal boullion. Three cultures of veal boullion and 4 
each of 134 and 144 hours oxytuberculine were made. All 
of the veal boullion and all of the 144-hour oxytuberculine 
flasks showed vigorous growth, and none of the 134-hour 
tuberculine flasks, as you can see from this photograph. (See 
Plate IV.) 
Provisional experiments made with cultures of staphylococ- 
cus, micrococcus ureae, bacillus typhosus, and bacillus diph- 
theriae have given results analogous to those obtained with 
the bacillus tuberculosis. Cultures of these germs were ster- 
ilized and filtered in the same manner and were oxidized sim- 
ilarly with the peroxide of hydrogen for various periods and 
then treated in the same manner. They were likewise mixed 
with veal boullion and inoculated with the respective germs, as 
was likewise a control with veal boullion. In all of them a 
complete suppression of the growth of the micro-organisms 
occurred, but the length of time of oxidation that was neces- 
sary to produce this result differed with different germs. The 
presence of the inhibitory action of theoxytoxine upon growth 
of the germ in 4 cases in addition to that observed with tuber- 
culosis, proves the universality of the law, and permits us to 
reason from analogy that not only will all of these diseases 
yield to oxytoxic treatment, but that this must be true of 
every disease whose germ we can cultivate. 
I will now call your attention to these tables, which show 
the effect of the oxytoxines of the various germs. As my 
attention had been directed to the faint possibility that the in- 
hibitory influence might be due to the reaction of peroxide of 
hydrogen on veal boullion, I treated that liquid with the oxi- 
dizer in the same manner as the cultures, sterilizing for 130 
hours, and found that it had no effect whatsoever in any case. 17 
Oxytu berculine 
MICROCOCCUS UREAS. 
Hours of 
Hours of Growth. 
Oxidation. 
1 
24 
30 
43 
70 
43 
? 
Growth 
Growth 
Growth 
65 
No 
No 
No 
No 
90 
No 
No 
No 
No 
125 
No 
No 
No 
No 
130 
No 
No 
No 
No 
Veal Bouillon 
Growth 
Growth 
Growth 
Growth 
TYPHOID. 
43 
Growth 
Growth 
Growth 
Growth 
65 
Growth 
Growth 
Growth 
Growth 
90 
Growth 
Growth 
Growth 
Growth 
125 
Growth 
Growth 
Growth 
Growth 
130 
No 
No 
No 
No 
Veal Bouillon 
Growth 
Growth 
Growth 
Growth 
DIPHTHERIA. 
43 
Growth 
Growth 
Growth 
Growth 
No 
No 
No 
No 
90 
No 
No 
No 
No 
125 
No 
No 
No 
Slight 
130 
Growth 
Growth 
Growth 
Growth 
Veal Bouillon 
Growth 
Growth 
Growth 
Growth 
STAPHYLOCOCCUS. 
43 
Growth 
Growth 
Growth 
Growth 
65 
Growth 
Growth 
Growth 
Growth 
90 
Growth 
Growth 
Growth 
Growth 
125 
Growth 
Growth 
Growth 
Growth 
130 
No 
No 
No 
No 
Veal Bouillon 
Growth 
Growth 
Growth 
Growth 
All of these tests show conclusively that the oxytubereuline 
inhibits the growth of the bacillus tuberculosis. That this is 
a specific effect and not due to a general antiseptic action is 
proved by the facility with which other germs develop in the 
fluid. I have here a bottle of oxytubereuline in which air- 
born germs have grown vigorously. The readiness with 
which this occurs has made it necessary to add boric acid to 
prevent the decomposition of the lymph. 18 
Oxytuberculine. 
From all of the statements made I believe I have proved 
beyond reasonable doubt that consumption may be cured with 
oxytuberculine, if administered before the later stages of the 
disease and that the cure is effected by a direct action upon 
the causal germ. PI.ATE I. Plats II. Pl,ATE HI. Plate IV. WOODWARD & CO., PR INTERS, 19 SUTTIR Rf.. 8 9.