THE' PHYSIOLOGICAL ACTION AND 
THERAPEUTIC USES OF YEAST 
NUCLEI NIC ACID, WITH SPECIAL 
REFERENCE TO ITS EMPLOYMENT 
IN TUBERCULOSIS. 
by’ 
VICTOR C. VAUGHAN, Ph.D., M.D., 
OF ANN ARBOR, MICH.; 
PROFESSOR OF HYGIENE AND PHYSIOLOGICAL CHEMISTRY IN THE UNIVERSITY 
OF MICHIGAN, AND DIRECTOR OF THE HYGIENIC LABORATORY. 
FROM f 
THE MEDICAL NEWS, 
Feb. 27 to March 27, 1897. [Reprinted from The Medical News, Feb. 27, 1897.] 
THE PHYSIOLOGICAL ACTION AND THERA- 
PEUTIC USES OF YEAST NUCLEINIC 
ACID, WITH SPECIAL REFERENCE 
TO / TS EMPLOYMENT IN 
TUBERCULOSIS. 1 
By VICTOR C. VAUGHAN, Ph.D.,M.D., 
OF ANN ARBOR, MICH.; 
PROFESSOR OF HYGIENE AND PHYSIOLOGICAL CHEMISTRY IN THE 
UNIVERSITY OF MICHIGAN, AND DIRECTOR OF THE 
HYGIENIC LABORATORY. 
Nucleins and Nucleitiic Acids.—I have elsewhere 
spoken of nucleins as follows: “Physiologically, 
nucleins may be said to form the chief chemical 
constituents of the living parts of cells. Speak- 
ing broadly, we may say that the nuclein is that con- 
stituent of the cell by virtue of which the histolog- 
ical unit grows, develops, and reproduces itself. It is 
the function of the nuclein of the cell to utilize the 
pabulum within its reach. It must be evident that 
those tissues most abounding in cellular elements con- 
tain relatively the largest amount of nuclein. It must 
also be seen that it is by virtue of their nuclein that 
the cells of various organs and organisms possess and 
manifest their individual peculiarities. We should, 
therefore, expect to find that the nuclein of the yeast 
cell is not identical with that of the bacillus tubercu- 
losis, and that the nuclein of the spleen differs from 
that of the thymus gland. The number of kinds 
of nuclein is limited only by the variety of cells. 
Nuclein is the chemical basis of that part of the cell 
1 This paper contains the material used in special lectures delivered 
to the students of the Department of Medicine and Surgery of 
Michigan University, November, 1896. designated by the histologist as the nucleus, some- 
times called chromatin on account of the readiness 
with which it absorbs and holds coloring agents. It 
is the nuclein of the bacterium which takes up and 
retains stains, and it is on account of the fact that 
the nuclein of the bacillus tuberculosis differs from that 
of other bacilli that we are able to distinguish the 
former from the latter by its tinctorial properties. 
Differences in reaction with staining agents so plainly 
seen under the microscope are only outward mani- 
festations of less apparent and more important differ- 
ences in chemical composition.1” 
Chemically, the nucleins are complex, proteid 
bodies, especially characterized by the large amount 
of phosphorus which they contain. Nucleins can 
be split up by the action of dilute mineral acids into 
albuminous bases and nucleinic acids. The nature 
of the base and the acid obtained in this way will vary 
with the nuclein in which they originate. Yeast 
nuclein differs in both its basic and its acid constitu- 
ents from leuco-nuclein as obtained from the thymus 
gland. The nucleinic acids on being further broken 
up by the action of dilute mineral acids yield the so- 
called xanthin bodies, and here again it is true that 
the products obtained will depend upon the kind of 
nucleinic acid acted upon. One nucleinic acid may 
yield only adenin, and for this reason it may be des- 
ignated as adenylic nucleinic acid, while another 
may furnish xanthin abundantly, possibly to the ex- 
clusion of other bases, and this may be termed xan- 
thylic nucleinic acid. Kossel has demonstrated some 
‘The Nucleins and Nuclein Therapy; Annual Address on Medi- 
cine. Transactions of the Michigan State Medical Society, 1894. 3 
of the chemical differences between nucleinic acids 
from diverse sources. Yeast nucleinic acid yields, 
on being broken up by the action of dilute mineral 
acids and heat, guanin and adenin ; while testicular 
nucleinic acid furnishes adenin, hypoxanthin, and 
xanthin; and thymus nucleinic acid gives adenin 
only. These are what might be called gross differ- 
ences. It is probable that finer distinctions exist be- 
tween members of the same group. I have fre- 
quently observed that different samples of yeast vary 
not only in the amount of nucleinic acid yielded, 
but that the products differ in the intensity of their 
germicidal action. Of course this may be due to 
differences in other constituents of the yeast cells, 
and the greater or less difficulty of obtaining the 
nucleinic acid in an approximately pure condition. 
In the first year of my work on this subject I used 
baker’s compressed yeast, and sometimes I wholly 
failed to obtain a nucleinic acid with distinct germi- 
cidal properties, while at other times the result was 
quite satisfactory, although at no time did I secure a 
product equal in germicidal strength to that subse- 
quently prepared from pure cultures of brewer’s yeast. 
It is within the range of possibility that by an inves- 
tigation of the different varieties of yeast cells and 
with due attention to the conditions under which the 
cells are grown, we may secure not only a richer 
yield of nucleinic acid, but an acid of greater germi- 
cidal strength. 
The difference in chemical composition and in 
germicidal action between nucleinic acids from differ- 
ent kinds of cells is, in some instances at least, ac- 
companied by differences in physiological action. 4 
Thus, while Lillienfeld1 has found that thymus nu- 
cleinic acid coagulates the blood when injected in- 
travenously in certain quantities, it will be shown in 
this paper that a much larger per cent, of yeast nu- 
clei nic acid may be injected intravenously without 
any such effects. 
Certain substances which are histologically and 
functionally nucleins do not yield any xanthin base 
as a decomposition product. These are called para- 
nucleins. Some of these are antecedents of true nu- 
cleins. Thus, the yelk of the egg contains a para- 
nuclein, which may be isolated by removing the 
accompanying proteids by peptic digestion. This sub- 
stance does not yield a xanthin base, but during the 
process of incubation it develops into a true nuclein. 
Generally speaking, nucleins and nucleinic acids 
are insoluble in dilute acids and soluble in dilute al- 
kalies. They are insoluble in alcohol. The last 
mentioned fact has not, however, prevented the quite 
extensive employment by the profession of alcohol 
said to contain nuclein. It is needless to say that 
any beneficial effects obtained by the use of this pre- 
paration should be attributed to alcohol and not to 
nuclein. The terms “nuclein” and “nucleinic 
acid ’ ’ are frequently used interchangeably. In fact, 
it is by no means always easy to determine whether 
in a given kind of cell the nucleinic acid exists free 
or combined with some basic substance ; and it is ex- 
tremely difficult to obtain the nucleinic acid in any 
quantity wholly free from albuminous substances, and 
as nucleinic acid combines with any albuminous sub- 
1 Ueber Blutgerinung Zeitschrift f. physiologische Chetnie, B. 
20, S. 89. 5 
stances present, the chemist is by no means always 
certain which of the terms “ nuclein ” or “ nucleinic 
acid ” will the more honestly fit a given product. 
Pure yeast nucleinic acid contains about nine per 
cent, of phosphorus. While a small quantity can be 
prepared in a sufficiently pure state to yield this 
amount I have so far found the preparation of such a 
pure article in quantities large enough for any exten- 
sive physiological experimentation or therapeutical 
use impracticable. The purest nucleinic acid which has 
been used in the work detailed in this paper contains 
a fraction less than seven per cent, of phosphorus. 
The Theory upon which these Studies of Nucleinic 
Acid have been Based.—The working hypothesis 
which I developed in beginning my researches on the 
nucleins, and which may be found in my address be- 
fore the Medical Section of the first Pan-American 
Medical Congress,1 may be condensed to the follow- 
ing propositions : 
1. The phagocytic theory of Metschnikofif, in so far 
as it teaches that the polynuclear white blood-cor- 
puscles are active agents in preventing or retarding the 
multiplication of pathogenic germs in the body, is 
true. 
As Metschnikoff has stated, there is no claim that 
there are not other agents which may also combat 
the progress of disease. 
2. The polynuclear corpuscles do not eat the 
bacilli, but they destroy the germ by virtue of the 
chemical action of some constituent or secretion. 
1 “ The Principles of Immunity and Cure in the Infectious Dis- 
eases.” Transactions of the first Pan-American Medical Congress. 
Vol. x, p. 152. 6 
3. The germicidal properties of blood-serum, de- 
monstrated by the researches of Fodor, Nutall, 
Buchner and others, are due to a substance, or to sub- 
stances, that originate in the polynuclear white blood- 
corpuscles. 
4. The natural resistance of the body to bacterial 
disease will be strengthened by a physiological in- 
crease in the production of polynuclear white blood- 
corpuscles. 
5. This increase in the polynuclear corpuscles may 
be induced by introducing into the animal the most 
distinctive constituent of these cells, which is nuclein. 
The foregoing statements were formulated in 1891 
and I then began my studies on nuclein from yeast 
and from certain animal glands. In 1892 the first 
experiments were made on healthy and tuberculous 
guinea-pigs, and in May, 1893, tuberculous patients 
were treated for the first time with this agent. 
The Germicidal Action of Nucleinic Acid.—In 
May, 1893, a paper by Novy, McClintock, and the 
writer,1 detailed experiments by which we demon- 
strated the germicidal action of testicular, thyroid, 
and yeast nucleins upon bacillus venenosus, staphylo- 
coccus pyogenes aureus, and albus, and bacillus an- 
thracis. Additional details of similar experiments 
were given in the address read before the Medical 
Section of the first Pan-American Medical Congress, 
already referred to. The paper by McClintock and 
myself2 read before the same congress, demonstrated 
1 The Germicidal Properties of Nucleins. Medical News, May 
30, 1893. 
a“ The Nature of the Germicidal Constituent of Blood-serum.” 
Transactions of the first Pan-American Medical Congress. Vol. 
1, p. 238. 7 
that the germicidal properties of blood-serum are due 
to the presence of nuclein. In February, 1894, 
Kossel1 published a paper which confirmed our re- 
sults. 
It is unnecessary to go into any detailed statement 
concerning the germicidal action of yeast nucleinic 
acid at this time, as any one desirous of doing so can 
consult the publications referred to. There is, how- 
ever, one point which seems to me to be of special 
importance, in view of certain recent German inves- 
tigations. While yeast nucleinic acid is a powerful 
germicide, it is not equally potent with all kinds of 
bacteria. Indeed, there are some germs on which 
this acid can scarcely be said to manifest a germi- 
cidal effect. This is true of certain putrefactive 
germs. This is of interest, in view of the discovery 
of Pfeiffer,2 that the blood-serum of an animal, im- 
munized against a specific bacterium, becomes deci- 
dedly more germicidal to that germ than to any 
other. This discovery is now being utilized in at- 
tempts to distinguish the typhoid and cholera bacilli 
from others which closely resemble them morpho- 
logically and tinctorially. It would seem from this 
that the germicidal constituent of the blood-serum 
can be trained to act more energetically upon a given 
bacillus. Pfeiffer states that the germicidal constit- 
uent of the blood-serum of his immunized animals is 
not a nuclein, and this makes the fact that yeast nu- 
1 “ Weitere Beitrage zur Kentniss der Nucleinsauren,” Archtv. 
f. Anatomie und Physiologie, Physiologische Abtheilung, 1894, S. 
194. 
2 “ Ein NeuesGrundgesetz der Immunitat.” Deutsche med. Woch- 
enschrift, 1896, S. 97. Also, Zeitschrift f. Hygiene und In/ections- 
krankheiten. B. 20. 8 
cleinic acid manifests its germicidal properties in a 
selective way all the more interesting. 
The Effect of Treatment with Yeast Nucleinic 
Acid Upon the Polynuclear White Blood-Corpus- 
cles.—As early as 1892, my colleague, Dr. Huber, 
kindly made for me a large number of counts of the 
white corpuscles in the blood of both healthy and 
tuberculous guinea-pigs, with and without injections 
of nuclein. He has since repeatedly made like de- 
terminations on the blood of my patients. I have 
elsewhere1 stated his results, as follows : 
(x) “The subcutaneous injection of nuclein in- 
creases the number of white blood corpuscles ; (2) this 
increase occurs in both healthy and tuberculous per- 
sons ; (3) with like quantities of nuclein injected, 
the increase varies with the person; it may be slight 
and it may be three-fold; (4) this increase occurs 
principally in the polynuclear cells ; (5) it is evident, 
as a rule, as soon as the third hour after treatment, 
and generally disappears by the forty-eighth hour. ’ ’ 
The following details of one series of counts may 
be of interest. All the persons tested in this Series 
were tuberculous : [See next page.] 
Recently Hahn,2 working under the direction of 
Buchner, in the Hygienic Institute of the University 
of Munich, and using the nuclein prepared by Parke, 
Davis & Co., the same as that employed in the treat- 
ment of the cases reported in this paper, has gone 
one step further than I have in this investigation. 
1 “ The Nucleins and Nuclein-Therapy.” Transactions of Mich. 
State Medical Society, 1894, p. 49. 
2 “ Ueber die Steigerung der naturalischen Widerstandsfaliigkeit 
durch Erzeugung von Hyperleukocytose.” Berliner klin. IVacli- 
en sc hr if t, September 28, 1896. 9 
He has shown that nuclein not only causes a hyper- 
leucocytosis, but that the defibrinated blood taken 
from the animal while in this condition of hyperleu- 
cocytosis, induced by the nuclein, has its germicidal 
properties increased. His experiments were made 
upon dogs, and are detailed as follows: “First, 
some blood was taken from the animal and the num- 
ber of leucocytes in the arterial blood was deter- 
mined. Then the animal received a hypodermic 
injection of some leucocytosis-producing substance. 
For this purpose, some albuminous body, as albu- 
Miss B.. 
Miss F.. 
Miss H.. 
Mrs. R.. 
Miss S... 
Mrs. D.. 
Miss M.. 
Mr. M... 
Miss A.. 
Mrs. N.. 
Miss S... 
Mrs. R.. 
Patient. 
3* 
II 
cr 
3 
00 00 COOx 00 
10 OiU Q Ox 04^ 
4* m K) OJ OvGJ Q 4* m (0 
- OOOj ~J 0 W 0 Cn h 
Total No. of white 
corpuscles per c.m. 
before treatment. 
a 
0> 
3 
M MMt-lMMMMM 
vo vo ooP P f* r r » 
Cn nxQ Ox « W VO 0Ol"J COGJ 
O 00 Cn W V>J Ov4» 00-J M O'VO 
0 vO 'O W 00 OO'J 4* 00 OJ O'On 
Total No. of white 
corpuscles per c.m. 
after treatment. 
m 4» to to P 4*- 0"4 OvW 
O VI to Ox H K) vO 
Cn H4vOi - W OOOn "0 004; 
vO w O' O'00 0 OJ m OO OOVO 
Total increase per 
c.m. 
a" 
ii 
m h Ln (ji CO 
K) 00 
++++++++++++ 
Per cent, of increase. 
Intervals between 
cr 
0-0- tro-o-B-o-B's-B'cro' 
3 
treatment and 
o 
c 
3 33 3333 
count. 
br 
Strength of nuclein 
CnOiC/iCaCyiCnCn w m m m w 
solution used, percent. 
_ =W1 s . . .w 
Amount of solution 
used. 
Method of adminis- 
tration. 
mose or nuclein, the latter in the form of a yeast 
nuclein, supplied us by the firm of Parke, Davis & 
Co. A nucleinic acid from the same source has given 10 
us good service. Since large quantities of this prep- 
aration can be employed, it was easy in a short time 
to double the number of leucocytes. At the same 
time, there was generally an elevation of tempera- 
ture, which, with this agent, was variable. In dogs, 
Table I. 
Number of Colonies on the Plates. 
ID 
13 
After 2 Hrs. 
After 5 Hours. 
After 24 
. Hours. 
T3 
<U 
a 
a 
Abso- 
lute. 
Per 
cent. 
Absolute. 
Per 
cent. 
a 
2 c.c. nor- 
mal blood 
6272 
512 
8.2 
210 
3-3 
Innumerable 
ai 
2 c.c. nor- 
mal blood 
4992 
1538 
00 
ft 
235 
4-7 
M 
a2 
Same as a 
& ai heat- 
ed to 55°. 
6912 
Innumerable 
b 
2 c.c. leu- 
cocyte 
blood .. 
7744 
194 
2.5 
89 
I. I 
7040 
bi 
2 c.c. leu- 
cocyte 
blood... 
4006 
139 
3-4 
94 
23 
Innumerable 
b2 
Same as b 
&bi heat- 
ed to 550. 
7552 
8576 
Innumerable 
“ 
STAPHYLOCOCCUS PYOGENES AUREUS. 
the elevation was seldom more than from i° to iy2°. 
When the number of leucocytes had reached near the 
double of the normal, a second portion of blood was 
drawn. At first we allowed an interval of only from 
five to six hours, later, from twelve to fifteen hours 
between the injection and the withdrawal of the 11 
second portion of blood. Even when the leucocy- 
tosis had begun to fall the results were not altered. 
The experimental proof that the leucocytosis was 
caused by the injection of the nucleinic acid was 
clear. The blood taken in the state of hyperleuco- 
Table II. 
BACTERIUM COLI. 
Number of Colonies on the Plates. 
>> 
<D 
After 
Hrs. 
After 5 Hours. 
After 24 
Hours. 
<V 
e 
a 
Abso- 
lute. 
Per 
cent. 
Absolute. 
Per 
cent. 
a 
2 c.c. nor- 
mal blood 
3904 
1664 
42.6 
256 
6.6 
Innumerable 
ai 
2 c.c. nor- 
mal blood 
4544 
1792 
39-6 
384 
8.5 
44 
a2 
Same as a 
&ai heat- 
ed to 55°. 
2112 
5120 
Innumerable 
«( 
b 
2 c.c. leu- 
cocyte 
blood... 
3986 
320 
8.0 
14 
0.4 
44 
bl 
2 c.c. leu- 
cocyt e 
blood... 
6080 
1472 
24.2 
56 
0.9 
45o 
b2 
Same as b 
&bi heat- 
ed to 550. 
7552 
7680 
Innumerable 
Innumerable 
cytosis was decidedly more markedly germicidal 
than the normal blood of the same animal. Control 
experiments, made morning and evening, without 
injection, demonstrated that the effect of the with- 
drawal of blood alone on an increase in the leuco- 
cytes was but small. ’ ’ 12 
Table I illustrates the results obtained. 
The results obtained by Hahn in a case of tuber- 
culosis in man are shown in Table II. 
Hahn states that in man the number of white 
corpuscles per c.m. must be increased to at least 
13-1400 before there is any marked increase in the 
germicidal action. In one of my cases, not included 
in the table given, the number reached 45,000. 
This, however, was exceptional, and followed a very 
large injection. Moreover, it was a patient in the 
last stages of the disease, and with numerous cavi- 
ties, as was demonstrated positively later at post- 
mortem, and Stein and Erbmann1 have shown that in 
this condition there often exists a marked leuco- 
cytosis. 
It must be admitted from the evidence before us 
that yeast nucleinic acid increases the number of 
polynuclear white blood-corpuscles. Hahn also found 
the increase to be among these elements, and that it 
intensifies the germicidal properties of the blood. 
Is Yeast Nucleinic Acid an Antitoxin l—With our 
present knowledge of the infectious diseases, we may 
hope to find curative agents in one or the other of 
two classes—(1) those which increase the germicidal 
action of the blood, and (2) the antitoxins. Indeed, 
the infectious diseases may be divided into two 
groups, one of which includes those diseases which 
we may reasonably hope to cure by antitoxins, and 
the other those which must be reached by directly or 
indirectly destroying the germs. The diseases for 
which antitoxins have been found—diphtheria and 
1 “ Zur Fnige der Leucocytose bei tuberculosen Processen.” 
Deutsches Archtv./, klin. med., B. 56, S. 323. tetanus—are the best representatives, possibly the 
only members, of that class. Cholera and typhoid 
fever may finally be placed in the same group by the 
discovery of their antitoxins, but, in my opinion, 
this is not highly probable. In fact, the researches 
of Pfeiffer, already referred to, render it quite cer- 
tain that cholera and typhoid fever are not to be com- 
bated successfully with antitoxins. The toxin dis- 
eases have the following characteristics : 
(i) Their germs live in the animal body relatively 
only a short time ; at least they manifest their viru- 
lence for only a short period. The bacillus of diph- 
theria may continue in the child’s throat for weeks, 
but only for a few days does it manifest for that child 
any virulent activity. (2) The germs are located 
superficially on a mucous membrane or under the 
skin. (3) The germs are confined to relatively a 
very small area. (4) The tissue-changes induced by 
the growth of the germs are relatively of but little 
import. Diphtheria may cause death by filling the 
larynx with membrane, but this is not the usual cause 
of death in this disease, and, if it were, tracheotomy 
and intubation would save life. (5) Within a few 
days at most, the bacteria elaborate and pour into 
the body fatal doses of a chemical poison; then the 
bacteria cease, in that person, to manufacture more 
of the poisons. (6) These diseases are acute intoxi- 
cations. The dangers to life, both those which are 
functional and those which are histological, are due 
to the chemical poison. The antitoxin does not de- 
stroy the germ, and the germ, after it has produced 
poison for a few days at most, is, for that individual, 
harmless. 14 
The other group of diseases possesses the following 
distinguishing characteristics: (i) The germs may 
live and continue to manifest their virulence for a 
long time. The bacillus tuberculosis may slowly 
multiply and continue its existence in the same in- 
dividual for many years. (2) The germs may be 
located either superficially or deeply; they may be 
confined to a small, or may extend over a large area. 
(3) Their germs elaborate chemical poisons for weeks, 
sometimes for years. An antitoxin would be pos- 
sessed of no curative action in these diseases. It 
might be of temporary value, but the bacteria would 
continue to produce the poison. To cure these dis- 
eases, we must destroy the bacteria. All attempts 
to utilize chemical germicides in the curative treat- 
ment of disease have been failures. Our hope lies 
in the possibility of increasing the normal resistance 
of the animal body. 
Then there are the acute septicemias—those dis- 
eases in which the germs multiply rapidly in the 
blood. In these also, curative agents will most likely 
be found in substances which either directly or indi- 
rectly destroy the bacteria. 
Is yeast nucleinic acid an antitoxin ? I think that 
I can answer this quite positively. McClintock and 
I have made a long series of experiments on rabbits 
and guinea-pigs with the toxins of diphtheria and 
tetanus and yeast nucleinic acid. We have failed to 
find any evidence that yeast nucleinic acid possesses 
any antidotal value against these toxins. 
The Effect of the A di?iinistration of Nucleinic A cid on 
the Formation and Elimination of Uric Acid.—It was 
formerly supposed that uric acid resulted from the retrograde metabolism of proteids in the same way 
as urea is produced. Uric acid was supposed to rep- 
resent a condition of imperfect oxidation, the com- 
pleted product of which is urea. On this theory, an 
excess of uric acid was supposed to indicate the ad- 
ministration of oxidizing agents directly or of those 
substances which would favor oxidation processes in 
the blood. It was upon the last-mentioned hypothesis 
that alkalies were so largely given when uric acid 
was formed in excess. However, Horbaczewski1 
has shown that the amount of uric acid is increased 
by the administration of nuclein. This fits in with 
certain chemical and physiological facts. As has 
already been stated, the xanthin bases are deriva- 
tives of nucleinic acid, and the close chemical, physi- 
ological, and pathological relation of uric acid to the 
xanthin bases is well known. The experiments of 
Horbaczewski would indicate that the administration 
of nuclein increases the number of polynuclear white 
corpuscles, and in the disintegration of these the 
xanthin bases and uric acid result. If this be true, 
uric acid becomes the measure, as it were, of cellular 
disintegration in the body. This theory has been 
combated with some vigor, mostly upon theoretical 
grounds, aided by a few experiments upon lowrer 
animals. However, the correctness of Horbaczewski’s 
work has been confirmed by experiments made upon 
man by Weintraub2 and others. My own observa- 
tions are in accord with the teaching of Horbac- 
zewski, and I have frequently found an excess of uric 
1 Monatshe/te f. Chemie, 1889 and 1891. 
* “ Ueber den Einfluss des Nucleins der Nahrung auf die Harn- 
saurebildung,” Berliner klin. Woe hen sch rift, 1895, S. 405. 16 
acid in the urine after giving large doses of nucleinic 
acid. I have also, in persons suffering from rheu- 
matic pains accompanied by the so-called uric acid 
diathesis, found that these pains were greatly inten- 
sified by the administration of nucleinic acid. In at 
least one instance was this so markedly true that the 
treatment was seriously interfered with and could not 
be given with the usual frequency. Cases of this 
nature are, however, judging from my experience, 
rare among the tuberculous. 
Uric acid is not always increased in the urine after 
the administration of nuclein, but in all experiments 
on this point, in which proper tests have been made, 
it has been found that some one or more of the alloxan 
bodies is increased in amount. Uric acid is only 
one of the alloxan group, and failure to recognize this 
fact has led some writers into error which I cannot 
take the space to point out at this time. 
Method of Administration. —In the cases reported 
in this and the preceding paper, the treatment has 
consisted of hypodermic injections. I use the syringe 
of a small aspirator, holding 80 minims. The barrel 
of the syringe should be long and of a relatively 
small diameter. The greater the diameter, the more 
difficult it is to discharge the contents through a 
fine needle. For the injection of larger amounts 
than that mentioned above, I have had a long-barrelled 
syringe, holding io c.cm., made. I select small 
needles, one for each patient, and keep the needles, 
when not in use, in an Esmarch dish filled with a five- 
per cent, solution of carbolic acid, and with the name 
of the patient on the cover. The syringe is kept, 
when not in use, in a covered glass dish such as is used by bacteriologists, and known as a moist 
chamber. When the syringe and needle are kept in 
this way, no sterilization further than that due to the 
action of the carbolic acid on the needle is needed. 
The small amount of the acid adhering to the needle 
does no harm, and possibly may be of benefit, on ac- 
count of its slight local anesthetic effect. When 
ready to give a treatment, some nuclein solution is 
poured into a clean Esmarch dish, the syringe is 
filled from this, and the needle is taken from its 
dish between the thumb and finger, touching only 
the base, and screwed upon the syringe. I prefer 
the American form of syringe, with the needle 
screwed on the barrel, to the German form, in which 
the needle is more loosely attached. The point of 
injection being selected, the skin is rubbed vigorously 
with a sponge wet with a five-per-cent, solution of 
carbolic acid. This rubbing should be well done, 
and is beneficial in two ways. In the first place, it 
secures cleanliness, not absolute sterilization, of the 
part, and, in the second place, the acid slightly anes- 
thetizes the skin.- Then, with a firm hand, the 
needle is introduced deep into the tissue. It is not 
well to pinch up a fold of the skin between the thumb 
and finger, as some do in the administration of mor- 
phin hypodermically, but with the thumb of the left 
hand on one side of the point of injection and the 
fingers of the same hand on the other side, press 
down and outward, making the skin tense at the point 
entered by the needle. Having introduced the needle, 
I inject the fluid very slowly. When the treatment is 
given in this manner, the pain is not nearly so great as 
that following the injection of an equal volume of dis- 18 
tilled water, as I have frequently demonstrated. I 
generally inject in the infraclavicular areas, but the 
interscapular space is equally suitable. The subcu- 
taneous injections should not be made in the arms, 
because there is not enough tissue, especially on the 
arms of many consumptives, to accommodate the 
fluid without painful distension. The injections may 
be made over the abdomen, on the buttocks, or in 
the thighs. In fact, they may be made on any part 
of the body or into any accessible area of mucous 
membrane. In the treatment of a case of lupus of 
the nose, I injected into the tissue immediately ad- 
jacent, but it was quite painful. In a case of local 
trouble in the upper portion of the vagina, I have 
injected through the mucous membrane after cleans- 
ing the point selected with a cotton swab saturated 
with the carbolic-acid solution. 
The five- and ten-per-cent, solutions may be in- 
jected hypodermically, provided the reaction is not 
excessively acid or alkaline. When properly used, 
the stronger solutions cause no more pain than the 
weaker ones. 
There is always more or less objection to hypo- 
dermic medication, especially when it must be con- 
tinued for a long time. There are nervous patients 
who always dread the needle, and it is often incon- 
venient, sometimes quite impossible, for the physician 
to give the time to the treatment necessitated by the 
hypodermic method. I have fully realized these 
difficulties, and have given attention to the question 
of the absorption of nucleinic acid when administered 
by the mouth. 
Since nuclein is separated from other albuminous 19 
substances by digesting the latter with artificial gas- 
tric juice, it has been generally assumed that nuclein 
wholly escapes peptic digestion. Miescher first ob- 
tained nuclein in the residue left after the peptic 
digestion of pus corpuscles. However, since we 
have learned that the various nucleins differ so widely 
in many properties, this question has been re-inves- 
tigated, with results that do not altogether confirm our 
previous knowledge. Popoff1 digested a mixture of 
acid albumin and yeast nucleinic acid with pepsin- 
hydrochloric acid. The result was that a portion of 
the nucleinic acid remained in solution. 
A like experiment was made on thymus. This 
gland, from a calf, was finely divided and separated 
into three unequal portions. The first portion, con- 
stituting about three-fifths of the weight of the entire 
gland, was digested for one hour with pepsin-hydro- 
chloric acid. The mixture was then filtered, and the 
amount of phosphorus in both the residue and the 
filtrate determined after incineration with soda and 
saltpeter. The residue after extraction with alcohol 
and ether contained 2.56 per cent, of P. calculated 
for the dry substance, which weighed 35.5 grams and 
therefore contained 0.89 grams of P. The filtrate 
contained altogether 0.243 grams of P. This would 
indicate that not more than one-fourth of the P. of 
the thymus passed into solution. 
A second portion, constituting about one-fifth of 
the gland, was submitted to like digestion for two 
1 “Ueber die Einwirkung von Eiweissverdauenden Fermenten 
auf die Nucleinstoffe,” Zeitschrift /. Physiologische Chemie, B. i8, 
S- 533- 20 
hours. The result was that a greater quantity of the 
nuclein was thrown out of solution. 
A third portion was digested for four hours. This 
resulted in the precipitation of a still larger per cent, 
of the nuclein. 
Popoff found, however, that nucleinic acid is dis- 
solved in the pancreatic juice. 
Gumlich1 has shown that the administration of nu- 
cleinic acid by the mouth is followed by marked in- 
crease in the phosphoric acid eliminated in the urine. 
The statement of Horbaczewski2 that the admin- 
istration of nuclein increases the uric acid eliminated, 
has been repeatedly confirmed. 
In our investigations, as has already been shown, 
yeast nucleinic acid given by the mouth increases the 
number of polynuclear white blood corpuscles. 
These facts leave no room to doubt the absorption 
of nucleinic acid from the intestines. However, the 
dose by the mouth must be very much larger than 
that required to accomplish a like result given hypo- 
dermically. One cannot be certain in a given in- 
stance what proportion of that administered by the 
mouth is absorbed. For these reasons I regard the 
hypodermic method the more exact and otherwise 
preferable. 
With care, nucleinic acid may be injected intra- 
venously. I have at one time injected 5 c.cm. of a 
ten-per-cent, solution in this way without any bad re- 
sults. Intravenous injections are painless, and theo- 
retically this is the ideal method of administration, 
1 “ Ueber die Aufnahme der Nucleine in den thierischen Organ- 
ismus,” Zeitschrift f. Physiologische Chemie, B. 18, S. 508. 
2 Monatshefte f. Chemie, 1889 and 1891. 21 
but a larger number of experiments must be made 
upon lower animals before the dangers in this method 
can be accurately measured. Therefore, I do not at 
present recommend it. I have elsewhere1, with Mc- 
Clintock and Perkins, reported the employment of 
very large quantities of solutions of yeast nucleinic 
acid intravenously in rabbits, and have shown that 
with care this may be successfully done. Certainly, 
yeast nucleinic acid differs from leuconucleinic acid, 
inasmuch as the former does not coagulate the blood 
when injected intravenously. 
Incompatibles.—Quinin and all the coal-tar anti- 
pyretics are to be avoided in the nuclein treatment. 
Atropin is probably physiologically antagonistic to 
the action of the nucleinic acids, and should not be 
given for night sweats in the nuclein treatment of 
tuberculosis. 
Effect of Nuclein on Intestinal Fermentation.— 
Yeast nucleinic acid has a markedly retarding effect 
upon fermentation in the small intestines, as we have 
shown by determining its influence upon the con- 
jugate acids eliminated in the urine. 
THERAPEUTIC USES OF YEAST NUCLEINIC ACID. 
Acute and Sub-Acitte Inflammation of the Upper 
Air-passages.—I have used yeast nucleinic acid in 
the form of a spray with compressed air for nearly 
four years, in the treatment of acute inflammations of 
the upper air-passages as coryza, tonsillitis, pharyn- 
gitis, and non-specific laryngitis, and it has given me 
better results than any other form of medication I 
1 Transactions of the Association of American Physicians, 1896, 
p. 72. 22 
have ever tried. I have employed for this purpose 
the one-per-cent, solution diluted with an equal 
volume of a saturated solution of boric acid. This 
preparation has also been of great service in the 
treatment of hay fever. It has not relieved all such 
cases, but it has given complete relief to some, has 
ameliorated others, and has failed to benefit but few. 
In hay fever, success is rendered more certain if, after 
spraying the nose, throat, and larynx thoroughly with 
the above-mentioned preparation, a small amount of 
a four-per-cent, solution of cocain be employed, also 
in the form of a spray. 
Typhoid Fever.—The action of yeast nucleinic acid 
on fermentation in the small intestine induced me to 
try this agent in typhoid fever. I have had no op- 
portunity to use it in any extensive epidemic of this 
disease. Dr. Harkins of Marquette, Mich., has re- 
ported very favorably upon his results with the one- 
per-cent. solution in an epidemic of typhoid fever at 
that place. I have used it only in sporadic cases, and 
as these vary so widely in their clinical history I am 
not prepared to draw any conclusions from my exper- 
ience. I think, however, that it is worthy of more 
extensive trial and would recommend for this pur- 
pose drachm doses of the five-per-cent, solution every 
two to four hours by the mouth. 
In Cancer.—I have tried nucleinic acid in three 
cases of carcinoma of the breast. All of these had 
been submitted to operation, the cancer had returned, 
and the cases were inoperable. The treatment was, 
therefore, employed as a last resort. Injections were 
made into the healthy tissue around the growth. 
2 Therapeutic Notes, 1896, p. 30. 23 
There was no evidence of beneficial action in any of 
these. I have employed similar treatment in two in- 
operable cases of epithelioma. There was no cura- 
tive action in these. It is true that I did find a wash 
of nucleinic acid beneficial in these cases of epithe- 
lioma, inasmuch as it destroyed those germs which 
produced a most disagreeable stench. For this pur- 
pose I can commend a five- or ten-per-cent, solution 
as a wash for the diseased surface. In all of these 
cases, both of carcinoma and epithelioma, the growths 
were examined microscopically, and there was no 
doubt of the correctness of the diagnosis. In a case 
pronounced a sarcoma by some eminent specialists, 
nucleinic acid apparently wrought a marvelous cure. 
The patient, the wife of a prominent physician on 
the Pacific coast, was brought to her home near Ann 
Arbor in February, 1895, with what was pronounced 
a sarcoma of the pelvis. She was greatly reduced in 
weight and strength, weighing 73 pounds, and being 
unable to walk across the room. In fact, she was un- 
able to sit up. There was a hard tumor, round and, 
as correctly as I could estimate, three inches in 
diameter, easily felt through the vagina, and appar- 
ently growing out from the ilium on the left side. 
The one-per-cent, solution of nucleinic acid was em- 
ployed in the treatment which was administered by 
her husband. At first the injections were made directly 
into the growth through the walls of the vagina by 
means of a specially prepared needle. Later, the in- 
jections were made into the gluteal muscles. Treat- 
ment was given daily for six months, and then less 
frequently for some months longer. The strength and 
weight of the patient gradually increased, and the 24 
size of the growth diminished pari passu. By the 
first of July, 1895, the patient weighed more than 
ever before, and she was able to walk several blocks. 
Her husband writes me as follows: “ In January, 1896, 
there was some pain in the left side of the pelvis, and 
a small hardened mass appeared, quite tender and 
apparently occupying a fold of the broad ligament. 
Nuclein was used for about two months, injected into 
the gluteal region. By May, there was no sign of the 
trouble and an increase of weight was noticed, as 
well as an improvement of the general condition. 
At present writing (October 30, 1896) she weighs 
123 pounds, which is about ten pounds more than 
she ever weighed. She is in good spirits and able 
to perform ordinary duties. ” Of course, this growth 
might not have been a sarcoma. The fact that it 
disappeared so completely is presumptive proof that 
it was not a malignant growth, but in a similar case 
I should certainly try the nuclein again. 
Septicemia.—Boise1 and Hofbauer2 have reported 
good results from treatment of puerperal septi- 
cemia with nuclein, the former using my preparation, 
and the latter that of Hobaczewski. Hofbauer states: 
“ Among the clinical symptoms which were observed 
during the course of treatment, the following may be 
mentioned: (1) Effect on the general condition. 
This was manifested in a very marked and often sur- 
prising manner. Patients who previously lay apathetic 
and half asleep now give a clear and satisfactory an- 
swer when questioned as to their condition. Though 
1 “ The Treatment of Puerperal Septicemia.” Transactions of 
Mich. State Medical Society, 1896. 
5 Centralblatt f. Gyncecologie, 1896, 25 
the temperature remained above the normal, never- 
theless the improved appearance and the calm ex- 
pression of countenance offered a decided contrast to 
what had previously been observed. At the same 
time the icteric tint of the skin disappeared, and the 
appetite was improved. (2) Influences on the local 
condition. Puerperal ulcers soon took on a healthy 
appearance and healed. The discharges from the 
septic uterus rapidly lost their odor and purulent 
character, and lessened in quantity. The first dose 
increased the temperature, followed by a gradual de- 
crease. The remissions were longer and more pro- 
nounced, and the exacerbations slighter till restora- 
tion to the normal resulted. 
TUBERCULOSIS. 
The principal object in writing this paper is to 
continue the record of my experience in the treat- 
ment of tuberculosis with yeast nucleinic acid. Be- 
fore taking up the report of cases I wish to make 
some inquiry concerning the curability of tuber- 
culosis. 
The incorrect ideas of Virchow concerning the 
pathology of tuberculosis, and the equally erroneous 
clinical teaching of Niemeyer concerning the malig- 
nancy of this disease, have been so deeply impressed 
upon the profession that, although more than thirty 
years have passed since Villemin laid the founda- 
tions of correct knowledge by the discovery of the 
transmissibility of the disease from man to animal, 
and from animal to animal by inoculation, the 
shadow of the older teaching still falls upon us. If 
I may be permitted to modify and condense one of 26 
Cohnheim’s statements on this point I should say: It 
happened fortunately that at the very time when 
Virchow was proclaiming the perfection of his 
teaching concerning the pathology of tuberculosis a 
discovery which was destined to prove his teaching 
erroneous was made in France. 
Virchow attempted to make a sharp distinction 
between true tuberculosis and those processes in 
which caseation is, according to his teaching, due to 
inflammatory and hyperplastic processes. He taught 
that caseous pneumonia and scrofulous glands were 
not tubercular. The result of this teaching was 
that tuberculosis came to be regarded as a progressive 
process in which small malignant growths were 
formed, and which only exceptionally terminated 
otherwise than in death. Niemeyer founded his 
clinical teaching upon this pathology, and in doing 
so he employed statements more forcible in diction 
than true in fact, and these statements have not lost 
their influence upon the profession, although science 
has demonstrated their falsity. “ The end of tuber- 
culosis, as a rule, is death,” is a statement which to- 
day largely determines the attitude of the medical 
profession towards the disease. “The greatest 
misfortune'that can happen to one with phthisis is 
that he should become tubercular ” is still practical- 
ly repeated in much that is said about a “pretuber- 
cular ” condition. The discovery of Villemin en- 
abled investigators to demonstrate that the active 
virus in scrofulous glands, in granulation disease of 
the joints, in caries of the bones, and in caseous 
pneumonia is one and the same thing, and that sus- 
ceptible animals inoculated with matter from any of 27 
these sources become tuberculous. With this evi- 
dence before him the pathologist repeated his studies 
from a vantage point and the researches of Schuppel, 
Buhl, Ziegler, Senftleben, Cohnheim, Baumgarten, 
Koster, Friedlander, and others in Germany, and of 
Ranvier, Cornil, Grancher, Charcot, Lepine, Thaon, 
and others in France, completely demolished the 
pathology of tuberculosis as taught by Virchow and 
demonstrated the existence of tubercular lesions in 
parts of the body once supposed to be free from such 
invasion, such as the conjunctiva, the cornea, the 
choroid, the iris, the skin, the muscles, the bones, 
and the blood vessels. Finally, the discovery by 
Koch of the specific cause of tuberculosis has given 
positive proof of the etiological unity of its various 
manifestations. 
The erroneous teachings of Virchow as to the 
pathology of tuberculosis have lost their force for all 
except the few who professionally live in the distant 
past; but the clinical teaching founded upon this 
false pathology, and as especially exemplified in the 
writings of Niemeyer, is still a controlling factor in 
our treatment of this disease. We have been too 
slow to perceive that our advanced knowledge of 
the etiology and pathology of this disease has given 
us just cause for a more hopeful attitude toward it. 
In 1882, Baumgarten1 wrote in sum and substance 
as follows : “ Tuberculosis is in and of itself not so 
bad a disease. We do not believe that it possesses, 
as a constant property, ‘ the considerable local ma- 
lignancy ’ which Friedlander believes he must still 
unconditionally attribute to it. When we see indi- 
1 Ueber latente 7'uberculose, Volkmann’s “Vortrage,” No. 218. 28 
viduals who as children had thickened, tuberculous 
cervical glands or tuberculous disease of the joints 
develop into the strongest and handsomest men ; 
when we see people who in childhood had Pott’s 
disease, which is always due to tuberculous caries of 
the vertebrae, live for years with this deformity, and 
reach advanced age ; with such observations as these 
so frequently before us, we must conclude that tuber- 
culosis is not so deadly as is usually supposed.” 
“The curability of phthisis pulmonalis was 
well known to the older pathologists. The distin- 
guished Carswell wrote: ‘ In no other disease has 
pathological anatomy furnished more positive evi- 
dence of curability than it has for tuberculous dis- 
ease of the lungs.’ Under the dualistic theory, when 
a case recovered it was said to be one of simple in- 
flammatory nature, and not tuberculous. However, 
since we know that caseous phthisis is tubercular, we 
must admit that tuberculosis is curable. The ten- 
dency to heal is much more evident in the ‘ true 
tuberculosis’ of Virchow than it is in his caseous 
pneumonia. We will, therefore, come much nearer 
the truth if we take the oft-quoted saying of Nie- 
meyer, ‘ The greatest misfortune which can happen 
to one with phthisis is that he should become tuber- 
cular,’ and make it read as follows: ‘The greatest 
misfortune which can happen to one with pulmonary 
tuberculosis is that he should become phthisical.’ ” 
Tuberculosis, so long as it remains an unmixed 
infection, is not a deadly disease, and I believe it to 
be, in this stage, one of the most easily curable of 
the bacterial diseases. Except in the forms of acute 
miliary and meningeal tuberculosis, it is but seldom the direct cause of death. However, as soon as it 
becomes a mixed infection, and is something more 
than tuberculosis, it then takes rank as the most fatal 
of all the diseases now afflicting mankind. In com- 
bating this disease, there are two points of attack, 
and if the wisdom and skill of the profession be di- 
rected to these, the death rate from tuberculosis will 
be much reduced in the near future. The first and 
most important method of dealing with this disease 
consists of the application of preventive measures. 
With these, however, I have at this time nothing to 
do. The second, the one with which I am now con- 
cerned, consists of the treatment of the disease while 
it remains an unmixed infection. When this is done, 
tuberculosis will cease to be “the terror of the laity 
and the cross of the physician.” In order to ac- 
complish this work, however, we must put aside cer- 
tain dogmas, which we have so long mistaken for 
facts that their shadows frighten us. We must be 
convinced that as an unmixed infection it is curable. 
We must be able to recognize the disease while it 
remains an unmixed infection. We must cease re- 
garding certain conditions as evidence of the exist- 
ence of an indefinite, imaginary, so-called “ pretu- 
bercular ’ ’ state, and must learn to look upon these 
conditions as proof of the actual existence of tuber- 
culosis. I will now give attention to these points, 
and in so doing I will consider them quite apart from 
the claims which I may make for nuclein or any 
other agent employed for curative purposes. 
Is tuberculosis a curable disease ? If so, to what 
extent is it curable ? What shall we understand by 
“ the curability of tuberculosis”? Are tubercular 
29 deposits ever absorbed? Do such deposits ever 
wholly disappear and leave no trace of their former 
existence? May tissues once invaded by the bacil- 
lus tuberculosis regain histological continuity? Is 
there ever a restitutio ad integrum ? 
One-seventh of all men die of tuberculosis and one- 
third of all men have the disease. The first part of 
the preceding statement is shown to be true by the 
mortality statistics of all civilized countries. The 
second part of the same statement is shown to be 
true by the records of autopsies in various parts of 
the world. Massini1 found evidence of tuberculosis 
as shown by scars, indurations, cheesy and chalky 
foci in eighty-nine out of 228 autopsies made upon 
persons who had died of diseases other than tubercu- 
losis at the Basle Hospital. Muller2 found in the 
Munich Pathological Institute that tuberculosis caused 
29.4 per cent, of deaths in adults, and 30 per cent, in 
children, and that 11.8 percent, more of the children 
had tuberculosis. Bollinger’s3 researches confirm 
these statements. Baumgarten4 states that from one- 
fourth to one-third of all the bodies sectioned show 
tubercular lesions. Queyrat5 found tuberculosis in 
31.4 per cent, of the children examined. Lundonzy6 
reports that 30.4 per cent, of the children brought 
1 As quoted by Hahn, “ Ein Beitrag zu den Fieberverhaltnissen 
bei der Phthise,” S. io. 
2 “ Zur Kentniss der Kindertuberkulose.” Miinchener Med. 
Wochenschrift, 1889. 
* “ UeberEntstehungundHeilbarkeitderTuberkulose.” Miinch. 
Med. Wochenschrift, 1890. 
4 “ Ueber latente Tuberkulose,” Volkmann’s “Beitrage,” No. 
218. 
6 “ Surla tuberculose infantile,” Progrts Medical, 1896, p. 335. 
6 “ Dela frequence de la tuberculose au premier age.” Revue de 
Medicine, 1887, p. 383. to autopsy are tuberculous. Babes1 found tuber- 
cular deposits in one-half the children dying from 
all diseases at Bucharest. In 1887 he sectioned 
ninty-three children, sixty-five of whom had tuber- 
cular glands. Haitnel2 claims that one-third of the 
children examined at L'hospice des Enfants assistes 
show tubercular lesions. Simmonds, Schwer, and 
Boltz3 state that autopsies at the Anatomical Institute 
at Kiel of 781 children, aged from one to five years, 
showed tubercular lesions in 230; of 228 between 
five and ten years, 78 were tubercular; of 162 be- 
tween ten and fifteen years, 56. Wolff4 states that 
autopsy reveals either recent or old tubercular lesions 
in from forty to fifty per cent, of adults and in from 
sixty to seventy per cent, of children; also that thirty 
per cent, of adults and forty per cent, of children 
have latent tuberculosis. Schlenker5 found in 100 
consecutive autopsies at Zurich 66 bodies tubercular; 
35 of these had died ot tuberculosis ; in 4 others the 
disease was marked, but had not caused death; while 
in 27 it was latent and had not been suspected dur- 
ing life. In this examination no lesion was pro- 
nounced tubercular unless it was evident and charac- 
teristic to the unaided eye. He points out the fact 
that had the indurations been examined microscop- 
ically, the percentage of cases of latent tuberculosis 
would have been increased. According to Ados- 
1 “ Recherches sur les associations bacteriennes du bacilli de la 
tuberculose,” Progris Med. Roumain, 1888. 
2 “La tuberculose hereditaire et la tuberculose du premier age. ” 
3 Quoted by Gartner. “ Ueber die Erblichkeit der Tuberku- 
lose,” Zietschrift fur Hygiene. B. 13, S. 132. 
4 Deutsche Med. Wochenschri/t, 1892. 
8 “Beitage zur Lehre von menschlichen Tuberculose.” Berlin, 
1S93. 32 
sides1 of 4815 bodies sectioned at Halle from 1882 
to the middle of 1893, 1066 showed gross tubercu- 
lar lesions. 
These and other statistics of like import justify the 
assertion that about one-third of all men are, at some 
period of life, infected with tuberculosis. Now, if 
one-third be infected and one-seventh die of the 
disease, it must be that the difference between one- 
third and one-seventh, a little more than one-fifth, 
are tubercular but do not die of this disease. Of 
the sixty-three millions of people living in the 
United States in 1890, nine millions have died or 
will die of tuberculosis, while twenty-one millions 
have been, are, or will be infected with the bacillus 
tuberculosis. Does this not demonstrate that tuber- 
culosis does not possess the malignancy attributed 
to it? 
The fact that one may be infected with tuberculo- 
sis and such infection remain localized for many 
years is shown by the study of cases of lupus. Out 
of 27 cases of lupus studied by Doutrelepont2 the in- 
fection spread and the patient died of tubercular 
meningitis in only one instance. Hasland found 6 
cases of what he regarded as metastatic involvement 
of the internal organs in 53 cases of lupus, and Holm3 
observed ix in 62. 
The study of instances of accidental inoculation 
with the bacillus of tuberculosis in wounds, some- 
1 “ Ueber den heutigen Stand der Therapie der Peritonis tubercu- 
lose,” Halle, 1893. 
2 “ Meningitis tuberculosa nach Lupus,” Deutsche Med. Wochen- 
schrift, 1886. 
3 Quoted by Schmidt, “ Ein Fall von lokaler Impf-Tuberkulose 
der Haut.” 33 
times known as cadaver (Leichen) tuberculosis tends 
to similar results. It is true that the infection in 
these cases may extend to the internal organs, but 
often the disease remains a local infection and not 
infrequently a spontaneous cure occurs. 
Verneuil1 reports the case of an assistant who be- 
came inoculated at the root of a finger-nail while 
sectioning a tubercular body. Four or five days 
later a small point of suppuration appeared. Three 
years later the finger was amputated at the second 
phalanx and at the same time a tubercular abscess on 
the back of the hand was opened. Three years later 
still a bruise of the stump of the finger was followed 
by tubercular sequestration. Up to this time the in- 
ternal organs had remained sound and subsequently 
the man died of spinal meningitis. Karg2 reports 
the case of a physician who developed a wound tu- 
bercle on the thumb. For six years this remained 
without any signs of extension. Then the thumb 
became swollen and red and several tubercular ab- 
scesses developed along the lymphatics. These were 
opened and the bacillus found in the contents. 
Riehl3 states that Dr. Karg inoculated himself in an 
interdigital fold. Two small tubercles were removed 
and found to contain bacilli. Kraske4 observed a 
boy, who, after a surgical operation became infected 
from his tuberculous sister. The tuberculous growth 
was removed and the boy remained well. According 
1 Semaine Medicate, 1885. 
3 “ Tuberkelbacillen in einem sogenanten Leichentuberkel.” 
Centralblatt fur Chirurgie, B. 12. 
3 “ Tuberkelbacillen in Leichentuberkel.” Centralblatt fur Chir- 
urgie, B. 12. 
* “ Ueber tuberkulose Erkrankung von Wunden.” /bid. 34 
to Tscherning 1 a servant inoculated her finger with 
the broken cuspidor of her tuberculous master. The 
tubercle at the point of inoculation and some swollen 
axillary glands were removed and in these the bacilli 
were found. The servant remained in good health. 
Lehmann2 observed ten Jewish children with local 
tuberculosis after circumcision by a tuberculous rabbi. 
Three died of marasmus, three of tubercular menin- 
gitis, one of intercurrent diphtheria, and three re- 
covered. Many other cases of wound tuberculosis 
have been reported and a valuable review of the sub- 
ject has been written by Schmidt.3 The study of 
these cases shows that inoculation with the bacillus 
tuberculosis does not always cause death, and that 
man is much less susceptible to the disease, when 
thus acquired, than are rabbits and guinea-pigs. 
Further evidence that one infected with tuber- 
culosis may recover from the disease is furnished in 
the observation of other forms of local tuberculosis. 
Tuberculous joints often heal, and the child afflicted 
in this way may develop into the most robust adult. 
Konig4 says that coxitis may heal at any stage of the 
disease. Tubercular abscesses may disappear and 
leave scar tissue as the only evidence of their exist- 
ence. Tubercular orchitis and tubercular pericardi- 
tis have been known to disappear. These evidences 
of the possibility of the healing of tissue once in- 
vaded with tubercles should encourage-us, because in 
1 “ Inokulationtuberkulose beim Menschen,” Fortschritte der 
Medicin, 1886. 
2“Ueber einen Modus der Impftuberkulose,” Deutsche Med. 
Wochenschrift, 1886. 
3 “ Ein Fall von lokaler Tuberkulose der Haut,” 
4 Specialle Chirurgie, B. 3, S. 445. all cases tuberculosis begins as a local disease, and 
the tissue at first involved is only of microscopic ex- 
tent. The germ is inhaled, and finds lodgment, and 
begins to multiply somewhere in the lung. The 
sooner the inoculation is recognized the greater are 
the chances of so improving the resistance of the 
tissue that extension of the infecting agent does not 
occur, and then it dies out or remains localized. I 
have stated that every case of tuberculosis begins as a 
local disease. The researches of Buhl and others 
have shown that this is true even in acute miliary 
tuberculosis and in tubercular meningitis. In these 
the systemic infection comes from a pre-existing 
tubercular focus. Friedlander1 and others have de- 
scribed quite thoroughly the changes which take 
place in the spontaneous healing of local tuber- 
culosis. 
The evidence that tuberculosis of the peritoneum 
occasionally undergoes a spontaneous cure and 
frequently heals after laparotomy is no longer ques- 
tionable. 
Since the publication of the now classical paper by 
Konig2 in 1884, on laparotomy in peritoneal tuber- 
culosis, surgeons in every part of the world have re- 
sorted to this operation as a curative agent, with a 
fair degree of success. These cases have been col- 
lected and the results summed up by Phillips,3 
Lauser,4 and others. 
1 “ Ueber locale Tuberkulose,” Volkmann’s Vortrdge No. 64. 
3 Centralbla.lt fur Chirurgie, 1884. 
3 Die Resultate operation Behandlung der Bauchfell tuber- 
kulose. Gekronte Preisschnft, Gottingen, 1890. 
* Ueber Tuberkulose-Peritonitis und ihre Behandlung durch 
Laparotomie. Regensburg, 1893. 36 
Adossides 1 has tabulated 405 laparotomies for tu- 
bercular peritonitis with thirteen per cent, of cures, 
counting as cured all those who lived two years or 
longer after operation. 
It will be interesting to learn, so far as we are able, 
the histological changes involved in these cases of 
cure of tubercular peritonitis after operation. Is there 
a complete disappearance of the tubercles ? Richelot2 
opened the abdominal cavity on account of strangu- 
lated hernia in a woman upon whom he had twice 
before performed laparotomy for tubercular perito- 
nitis. The last operation for tuberculosis had been 
made one year before that for the hernia. He found 
the peritoneum perfectly smooth, of normal color, 
and free from adhesions. Knaggs8 performed lapar- 
otomy for tuberculosis, and five and one-half years 
later operated on the same woman for hernia. At 
the second operation there was no trace of tubercu- 
losis detectable, although at first the intestines, mes- 
entery, and parietal peritoneum were thickly covered 
with tubercles. Clarke 4 reports a case in which an 
ovariotomy was made eighteen months after a lapar- 
otomy for tubercular peritonitis, and the second 
operation showed that the tubercles had wholly dis- 
appeared. Similar cases with similar findings have 
been reported by Schede, Winiwater, Ahlfeld, Hirsch- 
berg, Schmalfuss, Tait, Feldmann, Terillon, Esmarch 
and Werth (see monograph by Adossides). 
These observations demonstrate not only that tu- 
1 “Ueberden heutigen Stand der Therapie der Peritonitis tu- 
berculosa,” Halle, 1893. 
2 Revue de CJrirurgie, 1893. 
3 Lancet, November 11, 1892. 
4 Ibid. bercular peritonitis may be cured by laparotomy, but 
that the cure may mean a complete restitutio ad 
integrum. 
The following experiments bear upon this point: 
On December 31, 1895, we inoculated three full- 
grown rabbits intra-abdominally with a pure culture 
of the bacillus tuberculosis. No. 1 was employed as 
a control, and received no treatment of any kind. It 
died May 25, 1896. The peritoneum, omentum, 
liver, and spleen were tuberculous. There was also 
a large tubercular abscess in the abdominal wall at 
the point of inoculation. 
No. 2 was placed in the holder January 25, 1896, 
and the abdominal cavity opened. In the wall at 
the place of inoculation there was a tubercular in- 
duration as large as a nickel. In the mesenteric fold 
of the colon there was a tubercle as large as a pin-head 
and many smaller ones. The omentum was filled 
with small nodules, and the border of the liver was 
dotted with pin-point tubercles. After noting these 
facts, the abdomen was closed and nothing more was 
done to this animal until July 24, 1896, when it was 
killed. What had been a tubercular induration in 
the wall was at the autopsy only a lump of yellow 
fat. No sign of tubercle could be found in it. The 
liver was perfectly sound. There were heavy de- 
posits of fat of a deep yellow color in the omentum 
and mesentery, and in these the tubercles observed 
at the time of the laparotomy were found. These 
nodules had not increased in size, but they contained 
a caseous center in which tubercle bacilli, which 
stained normally, were found. 
No. 3 had its abdominal cavity opened January 38 
25, 1896. There was an induration in the wall a 
the point of inoculation similar in size and appear- 
ance to that observed in No. 2. The mesentery and 
omentum were filled with nodules the size of flax- 
seed and the border of the liver dotted with fine 
tubercles. One nodule was cut from the omentum 
and examined for bacilli, which were abundantly 
present. The abdomen was closed, and 45 c.c. of 
a one-half per cent, solution of nucleinic acid was 
injected into the jugular vein. Nothing further was 
done to this animal until July 24, 1896, when it was 
killed. Not the slightest evidence of tubercle could 
be found anywhere. The induration in the wall had 
wholly disappeared and the mesentery and omentum 
were perfectly smooth. The deposits of yellowish 
fat observed in No. 2 were not found. 
The following details will show that the skin and 
muscles may also regain histological continuity after 
tubercular invasion. November 18, 1895, two rab- 
bits, which may be designated as A and B, were in- 
oculated intra-abdominally with tuberculous sputum. 
The weight of A was 1552 and that of B 1402 grams. 
On December 6, 1895, A died. There was a 
caseous infiltration extending for one and one-half 
inches longitudinally and one-fourth inch trans- 
versely under the skin of the abdomen. The 
muscles of the abdomen were, infiltrated with a 
creamy, semi-solid exudate, in which the diplococcus 
pneumoniae, in great numbers, and the bacillus tu- 
berculosis, in small numbers, were found. There 
was some effusion in the peritoneal cavity, and in 
this also both the above-mentioned germs were 
present. Death was due to the septicemia induced 39 
by the diplococcus. At this time B showed a sup- 
purating sore two inches in length and one-fourth 
inch broad on the abdomen, and a round ulcer three- 
fourths of an inch in diameter and extending deep 
into the muscles on the right thigh. Tubercle 
bacilli were repeatedly found in the pus from each 
of these sores. December 6, 1895, 50 c.c. of a one 
per cent, solution of nucleinic acid was injected into 
the jugular vein and the next day 15 c.c. more was 
injected into the vein of the ear. On December 7 
B weighed 1394 grams, on December 14, 1480, and 
on December 21, 1592. On December 27, B was 
found to be losing in weight, falling to 1542 grams. 
At this time the sore on the abdomen had healed 
over, but a nodule had appeared at the point of in- 
oculation and had grown to the size of a filbert. 
The sore on the hip was still discharging, although 
it had decreased very much in size. On December 
27, 1895, B received hypodermically about the 
nodule on the abdomen 30 c.c. of the one per cent, 
solution, and two days later 40 c.c. more. After 
this B received no further treatment, but continued 
to grow fat and strong. On July 23, 1896, B was 
killed ; weight at that time was 2030 grams. There 
was some adhesion of the skin to the muscles over 
the abdomen where the sore had been, but nothing 
more. The hard nodules had wholly disappeared. 
All internal organs were in perfectly normal condi- 
tion. The ulcer on the hip had wholly disappeared 
and there had been complete reconstruction of the 
injured tissues. There was not even a scar to mark 
the place of the former lesion. 
I have brought forward these observations on the 40 
rabbits at this time not for the purpose of making 
any claims for nuclein, but in order to show that 
there may be a restitutio ad integrum in tissue after 
tubercular invasion. For my present purpose it 
matters not what be the nature of the agent that 
brings about the restitution. 
Many theories have been advanced to explain the 
curative effect of laparotomy on tubercular perito- 
nitis. It has been attributed to the influence of the 
light, which reaches the peritoneum during the 
operation (Lauenstein), to the entrance of air 
(Mosetig-Moorof), to mechanical irritation and the 
presence of air (Caspersohn), to the bacterium termo, 
which is supposed to enter the cavity with the air 
(Cantani), to a digestive action of the peritoneum, 
that is assumed to be called into action by ths opera- 
tion (Sanger), to a suction action, “ aufsaugende 
kraft ” of the peritoneum, due to the relief ot 
pressure (Fritsch), to the oxygen of the air (Braatz), 
to improved resorption (Lindner), to inflammatory 
adhesions (Kbnig, Breisky, Hartman, and Aldibert), 
to a connective tissue reaction (Phillips), to im- 
proved circulatory and respirating action, and to 
relief of the autointoxication (Vierordt), and to the 
use of disinfectants used in the operation and some- 
times in washing out the cavity (Preindlsberger and 
Ceccherelli). However, the explanation suggested 
by Kischenski1 that the cure is due to the leucocytosis 
which follows the operation is the most reasonable. 
Adossides accepts this explanation and sensibly adds 
that the action of the leucocytes is favored by (1) 
the relatively small number of bacilli present, and 
i Centralblatt fiir Chirurgie, 1893. (2) the great extent of the peritoneal membrane and 
its great vascularity. 
Tubercular peritonitis has been cured not only by 
surgical means, but under medicinal treatment also. 
Such cases have been reported by Bouilard, Vierordt, 
Anderson, Comby, Fagge, and others. 
Cases of tubercular meningitis terminating in re- 
covery have been reported, but from the nature of 
the disease it is difficult to furnish positive evidence 
to this effect. However, such able diagnosticians as 
Rilliet and Trosseau have reported cures. I have 
carefully studied the monograph by Zwicke1 on this 
subject, and must conclude that he does not supply 
convincing proof of the correctness of his diagnosis 
in the case of cure reported by himself. 
The researches of Orth,2 Fraenkel,3 and Progn- 
binsky4 have demonstrated that tuberculosis may be 
located primarily and exclusively in the larynx, 
and Schmidt5 claims to have cured five cases of this 
disease by tracheotomy. He attributes the curative 
action to the rest given the larynx and to the more 
direct action of the oxygen of the air. Glockner6 has 
reported two cases treated by tracheotomy without 
benefit, but in both of these the lungs were extensive- 
ly involved and the ulceration of the larynx was 
probably secondary; certainly the disease was not 
1 “ Beitrag zur Heilung der Meningitis basilaris tuberculosa,” 
Bonn, 1868. 
3 Lerhbuch der Patholog. Anatomie.” 
3 Primare Kehlhopftuberkulose. Deutsche Med. Wochenschri/t, 
1883, S. 490. 
4 Medycyna, 1887. 
6 Deutsche Med. Wochenschrift, 1885 and 1886. 
6 “ Ein Beitrag zur Behandlung der Laryngo-Phthisis tubercu- 
losa,” 1890. 42 
confined to the larynx. Krause1 has claimed suc- 
cess in the treatment of laryngeal tuberculosis by his 
method, with lactic acid, and his observations have 
been confirmed by von Schroetter,2 Keimer,3 
Heryny,4 Jellinick,5 and others. Like good results 
are claimed for iodoform by Beschorner,6 Schultzer,1 
and others. 
In regard to the cure of pulmonary tuberculosis, 
either spontaneously or under climatic or medicinal 
treatment, there is much information to be found in 
medical literature, but it can not be so positive as 
that given concerning peritoneal tuberculosis. If 
there be histological restoration there can be no evi- 
dence after death of the existence of the disease dur- 
ing life. Scars and chalky deposits are frequently 
observed, and the fact that these contain tubercle 
bacilli demonstrates the former existence of the dis- 
ease in an active form. Carswell8 states, as has al- 
ready been quoted, “that pathological anatomy has 
probably not given such positive proof of the cur- 
ability of any other disease as it has of phthisis. ’ ’ 
Weber 9 says: “It seems to me impossible for any 
one acquainted with the literature of the subject to 
1 “ Milclisaure gegen Larynxtuberkulose," Berlin Med. Wochen- 
schrift, 1885, and Deutsche Med. Woe hen., 1886. 
2 “ Verlosungen fiber die Krankheiten des Kehlkopfe." 
3 Ueber Kehlkopftuberculose, ihre Behandlung und Heilung.” 
Deutsche Med. Wochenschrift, 1886. 
4 Deutsche Med. Wochenschrift, 1886. 
6 “ Ueber Milchsaurebehandlung im Kehlkopf, Rachen und der 
Nasse, Centralblatt fur die gesamte Therapie.” 
s “ Die localer Behandlung der Laryngo-Phthiso-tuberculosa,” 
Dresden, 1888. 
7 Ueber Diagnose und Heilbarkeit der Kehlkopfschwindsucht 
unter dem Einflusse des Iodoforms Wiener Med. Presse, 1882. 
8 Pathological Anatomy, London, 1838. 
9 “Lectures on the Hygienic and Climatic Treatment of Chronic 
Pulmonary Phthisis ” (German edition), Leipzig, 1888. 43 
the curability of phthisis.” Rlihle1 asserts 
that tuberculous processes in the lungs may heal. 
Green2 says: “It lies in the very nature of the 
case that there can be no absolute cure, no restitutio 
ad integrum, and the very best that can happen is 
the formation of a scar or of a chalky deposit. ’ ’ 
“One frequently has the opportunity of seeing 
these healed foci in various stages; sometimes as 
scars, again as connective tissue nodules, or as cavi- 
ties filled with chalky concretions. The size of these 
cavities varies from that of a hemp seed to that of a 
hazelnut. Generally the remainder of the lung is in 
a normal condition. These healed places are gener- 
ally found in the apices, where tuberculosis most 
frequently begins. They lie near the surface; the 
apex is more or less contracted ; the pleura pulmo- 
nalis is thickened and more or less adherent to the 
pleura costalis. To the finger these points feel like 
hard lumps. The interior of the nodule consists of 
a well encapsuled mass of variable consistency de- 
pending upon the length of continuance of the heal- 
ing process. The center is hard, generally calcified, 
while the periphery is softer, incompletely calcified. ’ ’ 
Green has examined a number of these healed cav- 
ities microscopically and in some the bacilli were 
detected, while in others the result was negative. 
Dejerine3 has made a similar study with like results. 
He also inoculated guinea-pigs with the wholly cal- 
cified material and failed to induce tuberculosis. 
1 Ziemssen’s Handbuch. 
2 Ueber Tuberkelbacillen in alten ausgeheilten Lungenherden, 
Berlin, 1889. 
3 Recherche des bacilles dans la tuberculose calcifiee et caseo- 
calcifiee, Revue de Medicine, 1884. 44 
Kurlow1 obtained the following results from his 
inoculations : 
1. Using scar nodules in which no bacilli could be 
found ; two inoculations ; both negative. 
2. Using completely calcified nodules in which no 
bacilli could be found ; four inoculations ; all nega- 
tive. 
3. With caseo-chalky nodules about which no 
tubercles could be found. In many of these nodules 
no bacilli could be detected; twelve inoculations; 
all the animals became tuberculous. 
4. With caseo-chalky material about which tuber- 
cles were found; seven inoculations with positive 
results in all. 
Nauwerk,2 Demme,3 and others, have given the 
clinical histories of cases of recovery from pulmonary 
tuberculosis with death from some other disease and 
the findings at autopsy. 
Wolff and Saugmann4 have given us valuable in- 
formation concerning the possible cure of pulmonary 
tuberculosis. In 1862 Brehmer began the treatment 
of tuberculosis in his hospital at Gorbersdorf. In 
1890 Wolff and Saugmann sought out many of the 
earlier cases treated by Brehmer, and reported upon 
their condition. The number found and studied was 
142. In some of these the evidence of the previous 
existence of the disease and its arrest cannot be 
1 Ueber die Heilbarkeit der Lungentuberkulose, Deutsches 
Archiv. fur klin. Med., B. 44. 
2 “ En Fall von geheilter Lungentuberkulose,” Deutsche Med. 
Wochenschrift, 1883. 
3 “ Jahresbericht liber die Thatigkeit des Jennerschen Kinder- 
hospital in Bern,” 1884. 
4“ Ueber Dauerende Heilung der Lungentuberkulose,” Wies- 
baden, 1891. 45 
doubted. One of these is reported as follows : In 
1876, a woman entered Brehmer’s hospital with in- 
filtration of the right lung to the third rib, and a less 
marked infiltration over the same area of the left 
lung. She had fever and night sweats, and was re- 
duced in flesh. She remained in the institution thir- 
teen months, and was dismissed “ cured.” Fourteen 
years later she was operated upon for myomata uteri 
and died. A few days before death her lungs were 
carefully examined, and the only evidence of disease 
that could be found was a slight prolongation of the 
expiratory sound over the upper right lung. Section 
showed a cicatricial contraction, with a circumfer- 
ence of about 4 cm. in the right apex; otherwise 
no abnormality could be found in the lungs and no 
tuberculosis in any part of the body. In micro- 
scopical sections of the scar tissue tubercle bacilli, 
which stained well, were found. The authors are 
certainly justified in the conclusion drawn from the 
case. Considering the severity of the case when it 
came under treatment, fourteen years before, the 
cure must be regarded as ideal, but, nevertheless, it 
was not absolute, because the bacilli remained and, 
as indicated by the tinctorial reaction, retained their 
vitality, and in this respect the patient showed a 
condition no more serious than that exhibited by 
“ one-half, or at least one-third, the bodies that reach 
the autopsy table.” 
These authors conclude that at least eight per cent, 
of those treated at Gorbersdorf from 1862 to 1891 
were permanently cured. 
I have gone into the question of the curability of 
tuberculosis thus specifically (and I might say that 46 
the evidence on each point might be confirmed more 
fully did space and time permit) because 1 believe 
that the present attitude of the profession in general 
toward this disease is radically wrong and harmful. 
I believe that I am right in saying that the average 
physician does not strive to recognize this disease as 
early as is possible, but that he wilfully disregards 
all evidence of its existence until, in the majority of 
instances, it is altogether too late. I shall have 
something to say concerning the means of an early 
diagnosis in another part of this paper. 
I will now proceed to state the results obtained in 
the treatment of tuberculosis with yeast nucleinic 
acid. In doing this I will make the reports of cases 
as short as is possible, and at the same time consist- 
ent with clearness. In order to avoid repetition, I 
may state here that in all of the seventy-five cases 
reported the tubercle bacilli were found ; and in all 
of the urinary cases guinea-pigs were inoculated and 
tuberculosis developed, in order to be certain that I 
had not mistaken the smegma bacillus for that of 
tuberculosis. No case is reported in this list which 
first came under observation later than December, 
I^95- 
Review of Cases Reported in 1894.—Two years 
ago I reported twenty-four cases treated with yeast 
nucleinic acid.1 At the time of that report twelve 
of these patients were living. It will certainly be of 
interest to give the further history of these cases, and 
this I will now proceed to do as briefly as is consistent 
with accuracy. 
1 “ Treatment of Tuberculosis with Yeast Nuclein,” Medical 
News, 1894. 47 
Case II.1—I began treating this young man May 
i, 1893. At that time “ moist rales were heard over 
both lungs, both anteriorly and posteriorly. No 
cavities could be detected. The sputum contained 
numerous tubercles, which on being crushed and 
stained were found to be filled with bacilli. The 
daily maximum temperature for three days before be- 
ginning the treatment averaged 100.3° F. Night 
sweats were constant.” 
The treatment was continued through May and 
June of 1893. ‘ ‘ The temperature did not reach 1 oo° 
F. after June 2d; it seldom went higher than 990 F., 
and during the last four days of treatment it was normal 
continuously. Night sweats were occasional and 
slight during June. The cough and expectoration 
decreased, and some mornings during the latter part 
of June, he failed to raise anything when asked to 
bring the sputum for examination ; but when the 
sputum was raised and examined the bacillus was al- 
ways found.” 
In July, 1893, this young man went, by my ad- 
vice, in a wagon from Kansas City to Boulder, Col., 
where he has continued his residence. He has had no 
medicinal treatment since going to Colorado. He 
considers himself well, but his weight is practically 
the same as it was when he was under treatment in 
1893, and the sputum, a little of which is coughed 
up nearly every morning, contains from two to six 
bacilli in each field. I have not seen the patient 
since June, 1894, when a physical examination 
showed practically the same condition of the lung as 
that existing one year before, and consisting wholly 
of diminished resonance over both upper lobes. 
From this case, I have drawn the following con- 
clusions, subject of course, to revision, as all such 
conclusions must be, by future observations: (1) 
1 Refers to number of case in first report. 48 
Physical examination of the lungs in tuberculosis 
shortly after a hemorrhage (this patient had a hemor- 
rhage the day before the first examination) may give 
a very erroneous impression of the extent of the in- 
volvement. The moist rales heard over the greater 
portion of both lungs in the first examination of this 
case were due to the pneumonic infiltration induced 
by the hemorrhage, and the area of tubercular in- 
volvement was not so great as I at first supposed. (2) 
The sputum may contain tubercle bacilli long after 
the patient supposes himself well. This is certainly 
true when the disease has been arrested by residence 
in a favorable climate. This explains the frequently 
observed fact that consumptives apparently cured by 
long residence in a suitable climate suddenly develop 
an active and rapidly progressive form of the disease 
on returning to a less favorable climate; or the equally 
well known fact that such persons may remain in 
apparent health so long as they live out of doors, but 
soon die of tuberculosis on changing their occupation 
to one more sedentary, especially when a large por- 
tion of the time is spent under unsanitary local con- 
ditions. 
Webber 1 gives the following interesting history of 
a tubercular family, which suggests the possibility of 
the tubercle bacillus remaining in an inactive state 
in the body for many years: 
‘ ‘ Thirty years ago I treated a woman in a small street 
in Bloomsbury Square for galloping consumption. Her 
husband, a teacher of languages, had died shortly before, 
at the age of thirty-eight, in the German hospital, of chronic 
tuberculosis. Both his and her family were tuberculous. 
1 “ Lectures on the hygiene and climatic treatment of chronic 
pulmonary phthisis” (German translation), p. 31. 49 
They had seven children, one of which had already died 
of tuberculosis. Of the six remaining children all save 
the youngest, a rachitic boy, were apparently healthy. 
On the death of the mother, intelligent and well-to-do 
friends took the children to one of the most healthful parts 
of Germany and brought them up under the best hygienic 
conditions. The eldest son remained perfectly well so 
long as he lived out of doors, but at the age of twenty- 
three he became deeply interested in philological studies 
and worked day and night, confining himself to his study- 
room, in which he took most of his meals. Eighteen 
months later he died of quick consumption. The second 
son interested himself in agriculture until he reached the 
age of twenty-nine. Up to this time he apparently en- 
joyed perfect health. At the above-mentioned age he 
changed his occupation, and worked in an office, confining 
himself closely. Two years later he began to have 
hemorrhages and ultimately died of tuberculosis. The 
third son entered and continued in a cavalry regiment, 
and is the picture of health. The fourth child, a girl 
of five years of age at the time of the death of her mother, 
is now the healthy wife of a German farmer. The youngest 
son, the rachitic boy, is now a robust farmer in Manitoba, 
and the youngest daughter, also in perfect health, lives 
with her Canadian brother.” 
Of course it is possible that the first and second 
sons might have become infected for the first time 
after entering upon their sedentary occupations, but 
it is also possible that they might have carried the 
infection from their early childhood. The presence 
of living tubercle bacilli in calcified cavities in the 
lungs is mentioned in another part of this paper. 
The point which I wish to emphasize here is that 
one in apparent health may carry the tubercle bacillus 
in his lungs for many years. 
Under date of November i, 1896, this patient 
(Case II) writes me as follows: “I have examined 
my sputum and find b. tuberculosis in it in such small numbers that in a cover-glass preparation it 
takes a little hunting to find them. My general 
health is excellent. I spent the summer out of doors 
and climbed Long’s Peak (14,270 feet) without 
difficulty. ’ ’ 
Case IV.—This was an aggravated case of urinary 
tuberculosis. Hypodermic injections of iodin and 
gold, and boric acid, salol, quinin and iodoform by 
the mouth, had been tried. One gallon of cod-liver 
oil was taken within seven weeks. The nuclein solu- 
tion was administered hypodermically and also in- 
jected into the bladder. This treatment was begun 
in June, 1893, and continued for nearly one year. 
In November, 1894, the patient, a practitioner in 
Nebraska, reported no incontinence, scarcely any 
irritation of the bladder, and that he weighed more 
than he had for twelve years. No bacilli could be 
found in the urine. In March, 1896, he wrote me 
that he remained free from any evidence of a return 
of the disease, and that he had been engaged in a 
very laborious country practice. January, 1897, he 
reported himself as being perfectly well. 
Case V.—This was also a case of urinary tuber- 
culosis of several years’ duration. I closed my 
report on this case in 1894 with the following para- 
graph : 
“ The greatest weight reached before the illness 
was 132 pounds. The decrease was gradual and con- 
stant to the time of beginning the treatment, when 
he weighed 114 pounds. Since that time there has 
been a steady increase, and the figure is now 138. 
The temperature at first often reached 1 o 2.5 0 F., some- 
times 103° F. It has not been above the normal since 
early in October, 1894. The urine will be wholly 
free from sediment for several consecutive days, and 
then there will be a little pus in which the bacilli 
can be detected. There is still some undue fre- 51 
quency of micturition, and at times a sensation that 
the bladder has not been wholly emptied at the close 
of this act. The kidney has decreased in size, but 
is still abnormally large. There has been no pain 
from the passage of tuberculous masses through 
the ureter since the latter part of May, 1894. Of 
course it is possible that the disease may extend again. 
I shall not call this a cure until the urine becomes per- 
manently normal, and this may never happen. But 
even should this not occur, the history of the case is 
unique.” 
The wisdom of the caution expressed in the sen- 
tences now italicized soon became evident. In the 
spring of 1895, this young man, notwithstanding the 
continued use of the nuclein, developed acute general 
miliary tuberculosis and, although he hastened to 
Colorado, died within a few months. This is the 
most marked case of the temporary abatement and 
subsequent rapid spread of the disease under the con- 
tinued employment of the nuclein that has fallen 
under my observation. The remedy lost completely 
its apparent value, and was wholly without effect. 
This case illustrates the relation between local and 
acute miliary tuberculosis and the inadequacy of 
the nuclein treatment in the latter. 
Case VI.—This, the third case of urinary tuber- 
culosis reported in my article of 1894, has continued 
without any evidence of the existence of the disease. 
Ur. R. remains well, is engaged in a laborious prac- 
tice, and one year ago published an interesting re- 
port of his own case.1 
Case XVII.—This man continued this treatment 
until February, 1895. I last saw him in June, 1895. 
1 Therapeutic Gazette, October 15, 1895. 52 
At that time there was still a marked prolongation 
of the expiratory sounds over both upper lobes, and 
the afternoon temperature generally registered 990 F. 
His weight remained at 140 pounds, and he raised 
some sputum each morning, which contained a few 
bacilli. Since June, 1895, I have not been able to 
ascertain his residence, and consequently have no 
knowledge of his present condition. The conclusion 
concerning this case, as stated in my report of 1894, 
was as follows: “I believe that in this case the 
disease has been retarded by the treatment—I will 
not say arrested, because so long as the infection 
remains there also remains the probability that it 
may at any time become progressive.” 
As this was a colored man, living from “ hand to 
mouth,” I shall expect should I hear from him again, 
that the disease has progressed. 
Case XVIII.—This was a patient with a cavity in 
the upper lobe of the right lung and an extensive tu- 
berculous pleurisy on the opposite side. Germs were 
abundant in the sputum and some were present in 
the effusion drawn with a needle from the left side. 
Treatment was begun February 19, 1894, and con- 
tinued to November 23d of the same year. During 
this time the young man continued his work as book- 
keeper and general office boy, cleaning the rooms, 
etc., in a bank. The weight practically remained 
unchanged during treatment but the average temper- 
ature slightly increased and “judging by this more 
than by the physical signs, I think that the disease is 
slowly progressing.” A few days after discontinuing 
this treatment the young man went to Colorado, but 
the progress of the disease continued and he died in 
September, 1895. 
Case XIX.—This is a saleswoman in a dry-goods 
store. The weight had fallen from 148 to 115 at the 
time of beginning the treatment, January, 1894. 
There was bronchial breathing over the right apex 53 
and subclavicular area and moist rales over the upper 
lobe of the left side. “ The sputum was non-purulent 
but contained tubercle bacilli. ’ ’ The treatment was 
begun January 4, 1894, and continued daily until 
the middle of July of the same year, when it was 
given twice a week until the first of October, 1894, 
and then once a week until June, 1895, since which 
time no nuclein has been given. The germs disap- 
peared in March, 1894, and whenever on account of 
cold there has been any sputum, it has been exam- 
ined, always with negative results. The patient con- 
tinues her duties as a saleswoman and the conditions 
under which she lives are highly unfavorable. It is 
of interest to state that she is the third among the 
women clerks in the same store known to have devel- 
oped consumption in the past six years. I have 
recently examined her lungs and fail to find any evi- 
dence of disease. Her weight varies from 125 to 
135 pounds. This I have regarded as practically a 
case of unmixed infection. For two and one-half 
years the germs have not been found. 
Case XX.—In the report of 1894 I stated that in 
this case the tubercle bacilli had not been found in 
the sputum since the last of March of that year, but 
that the tubercular cervical glands remained enlarged. 
This young lady continued under my charge until 
May, 1895. At that time her condition remained 
the same practically as stated in my last report. 
About this time her betrothed died very suddenly of 
appendicitis and since then the young lady has re- 
fused to take further treatment. Shortly after this I 
was called to see her on account of a pulmonary 
hemorrhage. I have examined the sputum and the 
blood and found the bacilli. She has been to my 
office a few times since and I have examined her 
lungs. The disease is slowly progressing. She still 
refuses further treatment. 
Case XXI.—I last examined Mrs. M. in Septem- 54 
ber, 1895. At that time there was no evidence of 
any disease in the lungs. She had no cough, and 
was, so far as I could ascertain, in good health. I 
have not seen her since that time, but she remains 
apparently well, and wholly free from cough. 
Case XXII.—In this case the sputum was abun- 
dant, but non-purulent, and contained only a few 
bacilli. The bacilli disappeared in July, 1894, and 
none have been found since. Mrs. R. has borne 
one child since my last report. Her weight is now 
128; at the time of beginning the treatment it was 
106. Her work renders her susceptible to frequent 
attacks of acute nasal catarrh, but her lungs have re- 
mained free from involvement. This case illustrates 
what may be done even under adverse conditions, in 
the treatment of tuberculosis so long as it remains an 
unmixed infection. 
Case XXIII.—Mrs. C. continues in good health, 
weighing 135 pounds. She has had no treatment 
and no cough since the summer of 1894. She is the 
wife of a poor farmer and the mother of ten chil- 
dren. This is another illustration of the good that 
may be accomplished by treating the disease in its 
earliest stages. 
Case XXIV.—E. H. went to Colorado in No- 
vember, 1894, and I am told that he continues well 
there. I have no more definite information concern- 
ing him. 
Summary of the Cases Reported in 1894.—In my 
article of two years ago I reported twenty-four cases 
of tuberculosis treated with yeast nucleinic acid. 
Many of these were in the last stages of the disease 
when the treatment was begun. For details I must 
refer readers to the article. At the time of the re- 
port twelve (fifty per cent.) had died. Of the twelve 
then living, two have since died of tuberculosis (Cases V. and XVIII.). Of the others, three (Cases 
II., XVII., and XX.) are certainly still infected 
with the disease. Of the seven others, I have re- 
cent knowledge of five (Cases IV., VI., XIX., 
XXII., XXIII.), and these now show no evidence 
of the disease. So far as I know, two others (XXI. 
and XXIV.), remain well. This gives 20.8 per cent, 
known to be free from the germs for the past two 
years, and 29.1 per cent, counting the two who were 
free from the germs when last examined. It will be 
seen that these percentages are figured on the twenty- 
four cases, many of which were in a hopeless condi- 
tion when first seen. 
Case XXV.—Miss E., a student, has been undej 
my observation since first coming to the University, 
in October, 1892. Her history is briefly as follows : 
Her father died at the age of sixty-seven, after suf- 
fering for some months from cystitis. (There is a 
possibility that the affection of the bladder may have 
been tubercular.) Her mother is living and well. 
Mother had one sister and one brother die of con- 
sumption. She has four brothers, all of whom are 
well with the exception of one who has some irregu- 
larity of the action of the heart, supposed to be due 
to the excessive use of tobacco. She has one sister, 
who is well. She knows of no special exposure to 
tubercular infection. During the first two winters 
of her residence in this place she suffered from fre- 
quent attacks of subacute bronchitis, coughed much 
and raised abundantly. In the spring of 1894 this 
cough was very persistent, and I several times exam- 
ined the sputum, but with negative results. In June, 
1894, she went to her home in Iowa, and apparently 
improved much. For some reason she delayed her 
return to the University in the fall, and was still in 56 
Iowa when she was attacked as herewith described : 
About 4 a.m., October 16, 1894, she awoke in an 
extremely nervous condition, and soon began to suf- 
fer from a severe cutting pain in the region of the 
left kidney. This pain soon became paroxysmal and 
excruciating. A physician was summoned and ad- 
ministered one-fourth of a grain of morphin hypo- 
dermically. This was followed during the day with 
repeated doses of chloranodyn, the pain continuing, 
but partly subdued by the medicines. Vomiting, 
possibly due to the anodynes, occurred in the after- 
noon. During the night she had a high fever, and 
her side remained sufficiently sore to keep her in bed 
for six days, and indoors four days longer. When 
she began to walk, she noticed that for some days 
every unexpected jar caused pain over the left kid- 
ney. Four weeks later she had a second similar, but 
less severe attack. After this she started on her re- 
turn to Ann Arbor, but was compelled to stop for 
four days on the way on account of the pain in her 
side. This pain now returned daily, and was suffi- 
ciently intense to lead to the use of morphin. On 
November 27, 1894, this lady came to me and, after 
hearing the history of the attacks, as stated above, 
I did not doubt the correctness of the diagnosis of 
the Iowa physician, who had pronounced it renal 
calculi. I examined the urine, and was much sur- 
prised to find in it numerous tubercles, some quite as 
large as peas, rolled up, as it were, in epithelial cells. 
These contained bacilli in great numbers, and guinea- 
pigs inoculated with them developed tuberculosis. 
The urine contained no pus, blood, or albumin. 
Evidently the paroxysmal pains had been caused by 
the passage of these tubercular masses down the ure- 
ter. Nuclein injections were begun immediately, 
and continued daily for six months, then two or 
three times per week for another six months. Since 
October, 1895, no treatment has been given. The 57 
injections were made deep into the muscles directly 
over the affected kidney. The renal pain became 
gradually less pronounced, and the urine has been 
found to be constantly normal since June, 1895. 
The patient passed through the winter of 1895 and 
1896 without any of the “bad colds” which had 
been so frequent and persistent during the winter of 
1893 and 1894. 
Case XXVI.—Mrs. W., of Marshall, Mich., came 
to me in October, 1894. She had several small cavi- 
ties in the upper lobe of the right lung and there was 
only bronchial breathing over the corresponding 
lobe of the left lung. The larynx was involved and 
deglutition painful. Her weight was 116. An un- 
favorable prognosis was given and treatment was 
begun under protest. This patient has been most 
faithful and persistent in her endeavors to carry out 
the advice of her physician in every respect. With 
the exception of cocain in spray and lozenges for the 
throat, nothing but the nuclein has been employed. 
For one year the injection was given -every day. At 
the expiration of that time, I insisted that the treat- 
ment should be discontinued for a time, but the pa- 
tient felt that she was losing ground without it, and 
since then she has had injections nearly every day. 
She has kept a record of every treatment and has 
missed it only twenty days in two years. The 
weight has increased and during the past year has 
varied from 126 to 132 pounds. The condition of 
the larynx is much improved; deglutition is pain- 
less, and the urine normal. The cavities remain 
practically unchanged. I examined this lady No- 
vember i2, 1896. The left lung reveals no abnor- 
mality. The breathing over the right apex and 
subclavicular area is bronchovesicular. I do not 
think that I am attributing too much to the action 
of the nuclein when I say that it has retarded the 
progress of the disease. Indeed, her condition is 58 
much better than it was two years ago. The tempera- 
ture for the first year of treatment seldom had a maxi- 
mum for the day less than ioi° F. The maximum 
from September 17 to September 28, 1896, was 990; 
from September 28th to October 2d, 98.3°; from 
October 2d to October 9th, 98.4°. It has been 
taken four times a day every day for the two years. 
Dr. Foote of Marshall has been associated with me 
in the treatment of this and the following case. 
The patient now raises but little, but bacilli are 
present. 
Case XXVII.—Mrs. T., of Marshall, Mich., was 
first seen in December, 1894. Two brothers and 
one sister died of consumption. Patient has always 
had enlarged cervical glands. She lived in the same 
house with her consumptive sister during the illness 
of the latter. Patient has coughed for fifteen years, 
but this cough has been more constant for past six 
months. At the time of examination she was rais- 
ing freely. Bronchial breathing and moist rales 
were heard over both upper lobes, showing that the 
area of involvement was large ; but there were no 
cavities and the bacilli were found only after most 
minute search and frequently samples of sputum in 
which no bacilli could be detected were examined. 
This patient continued the use of the nuclein to June, 
1895, when she had gained some ten pounds in 
weight and coughed much less. In the fall of 1895 
the cough returned and she went to Florida. Dr. 
Foote writes me that this patient continued to im- 
prove so long as medicine was administered, but 
that she returned from the South with the disease 
much advanced and that he now regards her condi- 
tion as hopeless. 
Case XXVIII.—Mrs. K., of Holland, Mich., 
aged forty-four, was first seen December 5, 1894. 
Father died at sixty-five with some obscure trouble 
not named by the physician in attendance. Mother 59 
died at fifty-six of consumption. Brothers and 
sisters have been free from tuberculosis. One 
of her mother’s sisters and one of her father’s 
brothers died of consumption. Patient has been 
coughing and raising for past three years. Some 
three weeks ago she went to Dr. King of Grand 
Rapids, who examined sputum and found tubercle 
bacilli. There is bronchial breathing over both 
upper lobes. The apices are retracted and there 
are probably small cavities in left lung. The after- 
noon temperature for three successive days before 
beginning the treatment averaged 101.50 F. This 
patient remained with me only three weeks. Since 
then she has been under the care of Dr. Kremers of 
Holland and Dr. King of Grand Rapids. 
Dr. King sends me the following notes of this case : 
1895. January 24. Returned from Ann Arbor, 
where patient had been under the care of Dr. 
Vaughan, who had employed nuclein solution hypo- 
dermically. The examination of the chest was made 
with much the same result as upon first examination, 
with exception that moist gurgling rales could now be 
heard at the left apex and bronchial breathing at the 
internal borders of both scapulae. Cough and ex- 
pectoration very slight. Appetite and digestion 
poor. At twelve o’clock noon, pulse 100; tem- 
perature, 990 F. 
Patient placed upon “phospho-albumen,” 3 iit.i.d., 
and benzoate of guaiacol, gr. iii t.i.d. Evacuant mix- 
ture when necessary for bowels ; 70 minims one per 
cent, nuclein solution hypodermically, daily. 
October 21st. Patient has been steadily improv- 
ing. The treatment has been continued, and in 
addition, inhalations of creosote, eucalyptus and 
menthol are employed daily. At five o’clock p. m., 
temperature normal; pulse 100. 60 
October 26th. Nuclein solution increased to 100 
minims daily. 
November 5th. Intercurrent “cold.” Patient 
not so well. 
November 10th. Improvement. Patient returned 
to Holland and the injections continued daily by 
husband. 
1896. March 7th. Patient has been steadily 
improving in general condition. The areas of dul- 
ness have not increased and the rales, dry and moist, 
are entirely absent. For the past two weeks the 
nuclein solution one per cent, has been increased to 
200 minims daily with good effect. 
May 6th. Examination discovers no material 
change since March. About one week ago slight 
bloody expectoration ; none since, however. 
June 28th. The five per cent, solution of nuclein 
substituted for the one per cent. , in daily hypodermic 
injections of 30 to 50 minims. 
July 31st. Patient caught cold from exposure ; 
increase of cough and expectoration. 
August 5th. The five per cent, solution has been 
used continuously since June 28th, with success, 
although patient has not been quite so well as before 
the middle of July. 
October 9th. The five per cent, solution has 
been continued, at times increasing the dose to 100 
minims, with steady improvement. The areas of 
dulness are unchanged. There has been no exten- 
sion of consolidation, and the patient enjoys com- 
paratively good health. 
The result up to date is eminently satisfactory to 
both the patient and myself. 
Case XXIX.—J. R., of LaPorte, Ind., came to 
me in October, 1894. There was no family history 
of tuberculosis, or known source of contagion. This 
patient, aged twenty, is under size and weight, his 
greatest weight having been 118 ; weight at time of 61 
beginning treatment 113. He began to have con- 
tinued sore throat and hacking cough three years ago, 
but had been coughing up phlegm only during last 
two months. There were crepitant rales over apex 
and subclavicular area on right side. There was a 
small cavity between second and third rib on right 
side. The right lung showed general dulness on 
percussion. The left lung showed no abnormality. 
The amount of sputum was not more than two ounces 
in twenty-four hours, but it was rich in tubercle ba- 
cilli. There were no night sweats, and the afternoon 
temperature seldom exceeded ioo° F. This patient 
improved rapidly. By January x, 1895, the cough 
had ceased, the temperature was constantly normal, 
and the weight had reached a few pounds above the 
maximum. From this time to first of March, 1895, 
injections were made two or three times weekly. In 
March, 1895, the only evidence of disease in the 
lung was some dulness and prolongation of expira- 
tory sound on the right side. However, an inter- 
esting bit of the history of this case follows: As has 
been stated, the cough ceased by January 1, 1895. 
In August of the same year, the young man coughed 
up a few mouthfuls of sputum and sent this to me. 
It contained a few tubercle bacilli. The cough did 
not continue. From October 1, 1895, to January, 
1896, this patient had from two to three injections 
per week. By June the cough had stopped, and he 
felt so well that he discontinued the treatment. 
From June, 1896, to August 1, of same year, this pa- 
tient had from two to three injections per week, as a 
precautionary measure. Since August 1, he has had 
no treatment. He now (October, 1896,) weighs 
eight pounds more than ever before and has no 
cough. Examined his lungs carefully October 22, 
1896. A very slight prolongation of the expiratory 
sound over the right apex is the only evidence of ab- 
normality. 62 
This case is of especial interest inasmuch as it de- 
monstrates that apparent cures do not always mean 
the complete destruction of the bacilli in the body. 
Case XXX.—C. F., ofYpsilanti, Mich., a boy of 
seventeen, had numerous small cavities in both upper 
lobes when I first saw him in November, 1894. The 
treatment was given until February 1, 1895, when 
the patient was sent to Colorado. The first month 
of treatment seemed beneficial, but after that the dis- 
ease progressed. In Colorado he had influenza and 
came home after four months and soon died. 
Case XXXI.—Miss A., aged twenty-six, of Sagi- 
naw, Mich., had bronchial breathing over both up- 
per lobes. Consumption had been diagnosed twTo 
years before, and she had spent the preceding win- 
ter in the Adiro'ndacks. She had treatment, begin- 
ning in November, 1894, and continued for six 
months. She gained in weight, and coughed and 
raised less. The bacilli continued in the sputum and 
the physical signs showed but little change. I have 
not seen her since she discontinued the treatment. 
Case XXXII.—Mrs. D., a colored woman, aged 
forty-two, living in great poverty, came under treat- 
ment in November, 1894. It was difficult to get any 
satisfactory family history. “ Father died of chronic 
inflammation of the lungs, and one brother who was 
sick for a long while, died of pneumonia. ’ ’ She had 
been with both her father and brother in their last 
illness. Her bad cold had begun about one year before. 
During this time she had lost in weight, from 140 to 
119 pounds. She coughed and raised profusely, and 
the sputum was rich in bacilli and in elastic tissue. 
There was a cavity in the right upper lobe and 
bronchial breathing on both sides. Treatment was 
continued as long as the patient was able to come to 
the office, which was about two months. The dis- 
ease rapidly progressed and there was no evidence of 63 
any beneficial effect of the nuclein. Death occurred 
a few months later. 
Case XXXIII.—J.H., of Yale, Mich., aged thirty- 
four. His mother died of consumption at the age of 
fifty-six, three years ago. He was her principal at- 
tendant during her last illness. In January, 1894, 
he began to cough, and could not speak above a 
whisper: He had been coughing ever since, and had 
lost thirty pounds in weight, when I first saw him, 
which was in December, 1894. He had a large 
cavity in the right lung, bronchial breathing over 
the left lung, and tubercular laryngitis. He remained 
under treatment for three months. During the first 
six weeks he improved in flesh, gaining nearly four- 
teen pounds in weight. His throat was treated with 
a spray consisting of equal volumes of the one-per- 
cent. solution of nucleinic acid and a saturated solu- 
tion of boric acid. The condition of the larynx was 
much improved and the voice regained. However, 
during the latter half of his stay here, the condition 
of his lungs grew worse, and after going home he 
rapidly failed. The improvement was only tem- 
porary and, as stated above, the disease progressed 
while the treatment was being continued. 
Case XXXIV.—Miss B., aged seventeen, came to 
me December 4, 1894. She had tuberculosis of the 
right elbow-joint, which had been inflamed and pain- 
ful for three years. This had been called rheumatism. 
The joint was discharging at the time of the first ex- 
amination, and tubercle bacilli were found in this 
discharge. There was prolonged expiration over 
both apices, but no cough and no expectoration. 
There was a purulent discharge from the umbilicus. 
The afternoon temperature ranged from ioo° to 
ioi°F. The one-per-cent, solution of nucleinic 
acid was injected into the tissue about the joint and 
the sore was dressed with iodoform gauze. The nu- 
clein was also injected for a few weeks about the um- 64 
bilious. The patient at that time remained under 
treatment until the first of July, 1895. Within six 
weeks after beginning the treatment, the temperature 
became normal, and has so remained, with one ex- 
ception to be mentioned. By the first of June, 1895, 
the joint had so far improved that the young woman 
could use the hand in playing on the piano, could 
feed herself with the right hand and could use the 
arm in dancing. The discharge had ceased, the 
wound healed, and further treatment was considered 
unnecessary. This favorable condition continued 
until February, 1896, when the joint received two 
bad blows. Once it was struck with considerable force 
on the tire of a carriage wheel, and the second time 
the patient fell on the ice striking on that elbow. 
March 24, 1896, she returned with a swollen joint 
and a temperature of ioo°F. Dr. Nancrede made 
an incision, and with a curette removed some tuber- 
cular matter. The arm has been carried in an alum- 
inum splint since that time, and the wound washed 
out daily with the one-per-cent, solution of nucleinic 
acid. The five-per-cent, solution has been admin- 
istered by the mouth in teaspoonful doses three times 
a day. Her general health remains good, and there 
is no abnormality detectable in the lungs. 
[March, 1897. The wound has healed and the 
general health of the patient is excellent. ] 
I may call attention in this connection to the 
favorable reports made by Hitchcock 1 on nuclein in a 
case of hip-joint disease. 
Case XXXV.—S. M., aged twenty-seven, of Bed- 
ford, Mich., was sent to me February 22,1895, by Dr. 
G. W. Lowry of Hastings. His wife died of con- 
sumption August 8, 1894, after an illness of one year. 
The husband took care of her during this sickness. 
About three weeks before her death he began to 
1 American Lancet, January, 1895. 65 
have a sensation of great weariness and some eleva- 
tion of temperature. At the time of the first ex- 
amination, the only physical evidence of the disease 
was a marked retraction of the left apex and a pro- 
longation of the expiratory sound over this region 
and the subjacent area. He coughed very rarely in 
the morning and then raised some sputum, in which 
a few bacilli were found. The loss in weight had 
been about ten pounds. The afternoon temperature 
ranged from 990 to ioo° F. After four weeks of 
treatment the normal weight was regained, the cough 
ceased entirely and the patient has remained ap- 
parently in perfect health since. 
Case XXXVI.—E. A. R., a farmer,aged fifty-four, 
from Covert, Mich., came to me in November, 1894. 
His mother died of consumption many years ago. 
He was not with her in this illness. His mother’s 
sister also died of consumption. One of his own 
sisters had been an invalid for fifteen years from a 
fall, and coughed much before her death. Another 
sister had died some seven years before of quick 
consumption. He had occasionally visited these 
sisters during their illness. Five years ago he had a 
hemorrhage, “followed by pneumonia.” In 1890 
he had a severe hemorrhage. From the time of the 
first hemorrhage, in 1889, he had not been well and 
had steadily lost flesh. In 1893 he had another 
hemorrhage, and still another about one month 
before he came to me. He was coughing and rais- 
ing freely. The sputum contained numerous bacilli 
and some elastic tissue. His greatest weight had 
been 175, and at the time of the examination it was 
152 pounds. There were numerous small cavities 
in the upper lobes. This patient remained with me 
only four weeks, but continued the treatment with 
Dr. Carnes, of South Haven. Dr. Carnes wrote me 
under date of March 1, 1895, as follows: “Mr. R. 
has been under the nuclein treatment now for three 66 
months, in addition to the one month spent with 
you. He now weighs four-and-a-half pounds more 
than he did at Christmas. His temperature is prac- 
tically normal all the time, seldom reaching 990 F. 
However, he coughs much, a clear, ringing cough, 
without much expectoration. He never before had 
a three-months’ rest, and this has probably contributed 
to his gain.” 
A second report from Ur. Carnes under date of 
November 22, 1895, states: “ He coughs much, and 
says that he cannot endure hard work, but it is plain 
to see that he is in better flesh and far more vigor- 
ous than he was last spring. He has for several 
years vacillated in this way, so I can see but little 
difference between the last year and several preced- 
ing years.” 
Recently (October 24, 1896,) Dr. Carnes wrote 
that this patient, who has had no nuclein now for 
more than a year, is gradually, but slowly failing in 
health. 
Case XXXVII.—Miss K., aged thirty-one, of 
Marinette, Wis., came to me for treatment in Janu- 
ary, 1895. There was no known tuberculosis in the 
family, nor was there any discoverable direct expo- 
sure to the contagion. The patient had always been 
rather frail, her greatest weight having been 120 
pounds. However, she had never been ill, until 
three years before, when she developed a “chronic 
bronchitis,” accompanied by constant cough and 
profuse expectoration. Sixteen months before com- 
ing to me she had gone to Oregon, where she spent 
a winter, during which she gained thirteen pounds 
in weight and felt much improved, but even before 
her return home she began to fail again. Her appe- 
tite was very poor and her tongue heavily coated. 
The sputum contained numerous bacilli and much 
elastic tissue. There was bronchial breathing over 
the whole area of both upper lobes. There were 67 
numerous small cavities in the same region. The 
patient remained under my treatment until June, 
1895, when she returned to her home, and the 
nuclein treatment was continued by Dr. Hicks of 
Menominee, Mich. The result of the treatment was 
the same in this case as it has been in all others of 
the same class. There was temporary improvement, 
with increase in weight, reaching and even passing 
the previous maximum, and then retrogression, not- 
withstanding the continued employment of the 
nuclein. 
Case XXXYIII.—Mrs. Q., aged thirty-two, of 
Gaylord, Mich., was brought to me in January, 
1895. I say that she was “brought ” to the office, 
and this is literally true. She was in the last stages 
of consumption, and after an examination, in which 
I found numerous cavities in both lungs, I advised 
her husband to take her home as soon as possible. 
However, he thought that an immediate return 
would discourage her so greatly that he insisted on a 
trial of the remedy for nothing more than its mental 
effect. This case illustrates what hope and nuclein, 
probably as much should be attributed to the former 
as to the latter, may do in the way of temporary im- 
provement. This lady insisted on having full doses 
every day, and they were given. When I state that 
she gained twenty-five pounds in five weeks I expect 
to tax the confidence of the reader in my statements 
to the utmost; but such was the case. Her afternoon 
temperature fell from an average of 102° F. to less 
than 1 oo°, and while she had to be brought in her hus- 
band’s arms from the carriage into the office when she 
first came, before she left the city she walked many 
blocks at a time without feeling great fatigue. At the 
end of five weeks she insisted that she was practically 
well, and desired to go home. Believing that the 
arrest of the progress of the disease was only tem- 
porary, I made no objection. She returned home, 68 
soon lost what she had gained, and died in Septem- 
ber, 1895. I desire it distinctly understood that I 
do not attribute this great temporary improvement 
wholly to nuclein. It was one of those phenomenal 
cases of temporary improvement in which the 
bacillus seems for a time to have lost its virulence, 
and the vitality of the patient seems to spring into 
increased vigor at a bound. The nuclein was not 
used after she left, but I know that even had its em- 
ployment been continued the relapse would have 
come with equal certainty. 
Case XXXIX. —M. G., a student, aged twenty- 
four, came to me in February, 1895, on account of a 
slight pulmonary hemorrhage which he had at that 
time. He was coughing up blood. This was exam- 
ined and found to contain tubercle bacilli. Treat- 
ment was begun immediately and continued for two 
months. On the first examination moist rales were 
heard over the apex and subclavicular area of the left 
lung. The afternoon temperature frequently reached 
ioi° F. for two weeks. After this it gradually fell to 
the normal. The young man continued his studies 
until June, 1895, when a physical examination failed 
to reveal any abnormality. He spent the winter of 
’95 and ’96 in Colorado as a precautionary measure, 
and there has been no evidence of any disease since 
the treatment was discontinued. 
Case XL.—W. S., a stone cutter from Bluffton, 
O., came in February, 1895. This case is almost a 
duplicate of the one just described and several others 
of a similar character will be mentioned later. A 
brother-in-law of this man had died of consumption 
in his house, after a long illness, some months before. 
S. had a hemorrhage and came to me still raising 
sputum containing some blood. Bacilli were found 
but were not abundant. There were rales in the 
apex and subjacent area of the left lung. There was 
the characteristic fever curve. After four weeks of 69 
treatment the lung cleared up and the man has con- 
tinued in apparently the most robust health. 
Case XLI.—Miss C., of Allen, Mich., came under 
treatment in March, 1895. There is no need of de- 
tail in this case. The disease was in an advanced 
stage with cavities and an afternoon temperature often 
as high as 103° F. There was temporary improvement 
indicated by a fall in the temperature and a gain in 
weight. This was followed by retrogression and a 
gradual decline. 
After her return home Miss C. was under the 
charge of Dr. Williams of Jonesville, Mich., who 
has kindly furnished the following: 
“After her return home from Ann Arbor, some 
time in the early summer of 1895, I continued the 
nuclein treatment, at first by internal administration, 
with negative results, as demonstrated by rise of 
temperature from 994° to 103° F. Pulse 130. Res- 
piration 22 to 24. Increase of cough, profuse expec- 
toration, and return of night sweats. I then sent for 
a large syringe and treated her hypodermically, 
with the result that temperature, pulse, and respira- 
tions, were reduced. Appetite in a measure returned. 
Cough and expectoration modified, and a seeming 
arrest of the progress of the disease. This condition 
continued for about four months, or until late fall. 
During this time I gave her daily treatments at first, 
then as better symptoms returned, she came for treat- 
ment every other day. I injected from 30 to 80 
drops of a one per cent, solution, and without the 
slightest symptom of an abscess at any time. 
“From the first of November, until her death— 
some three months—the history of her case is that of 
tuberculosis in the last stage of the dread disease. 
“ While ‘ nuclein ’ hypodermically did not entirely 
arrest the progress of the disease I am satisfied it 
prolonged her life several months.” 
Case XLII.—Miss O., aged twenty-six, a student, 70 
came under observation in March, 1895. Her mother 
and a sister and a brother of her mother and a 
brother of her father died of consumption. The 
mother died five years ago, after a long illness, dur- 
ing which the daughter attended her. This patient 
has always been frail and anemic. Four years ago 
her physician told her that one lung was diseased, 
and three years ago she had a long-continued low 
fever, which was called typhomalarial. She has 
coughed for four years. The quantity of sputum 
raised was small, but I never saw another specimen 
so rich in bacilli as was this. There was a large 
cavity on the right side, and rales wrere heard over 
the whole of the upper lobe on this side, and from 
the apex to the base in the left lung. The weight 
at the time of beginning the treatment was 98 
pounds. The patient remained under my treatment 
until October 7, 1895, having an injection of nuclein 
nearly every day during this time. In October I could 
not see that her condition was materially different 
from what it was in the preceding March. Her 
weight was 100 pounds, and the physical signs re- 
mained practically unchanged. I advised her to go 
to Colorado, and she did so in October, 1895, and 
placed herself under the care of Dr. Henry Sewall, of 
Denver. In February, 1896, Dr. Sewall sent me the fol- 
lowing condensed record : “ Miss O., aged twenty- 
seven, with poor development and very anemic. Some 
percussion dulness and fine rales throughout upper 
half of right lung, and similar sounds found through 
the left lung nearly to its base; rather dry, cavern- 
ous sounds under right clavicle ; pallor of pharynx 
and larynx, and slight swelling of mucous membrane 
over and between arytenoids. She has received 
nuclein injections every second day, or oftener, for 
two-and-one-half months,and has gained four pounds. 
Her lungs are drier and the morbid signs are less 
extensive.” In September, 1896, Dr. Sewall reported the con- 
tinued improvement of this patient. 
Case XLIII.—Miss G., aged twenty-five,of Brigh- 
ton, Mich., came under my care in March, 1895. Her 
father died of consumption in 1891, and this young 
woman, always frail, was a constant attendant in his 
last illness. The mother is living and well. The patient 
has one sister, who has been married and away from 
her father’s home for several years. This sister is in 
good health. A brother, who also was with the 
father during his sickness, has recently been decli- 
ning in weight and failing in health. As stated above, 
the patient had always been frail. Her maximum 
weight was ro8 pounds, and she has always been 
anemic. In 1893, while at the fair in Chicago, she 
caught cold, and has been coughing and expectora- 
ting ever since. The greater part of the winter of 
r894 and 1895 had been spent in the South, but the 
disease had apparently made rapid progress during 
this time. At the time of her coming to me she was 
having “chilly sensations, followed by flushed 
cheeks, every day.” There were small cavities in 
the right upper lobe, and bronchial breathing over 
the upper half of the left lung. She continued 
with me until October, 1895 ; and her history differs 
materially and favorably from the others of the same 
class. Up to the middle of August there seemed to 
be no improvement, and the afternoon temperature 
frequently went up to 103° F. At the time mentioned, 
the maximum daily temperature began to fall, the 
appetite improved and the weight increased. The 
physical signs showed marked improvement. Dur- 
ing the latter half of September the temperature sel- 
dom exceeded 990 F. I thought this a good time to 
send the patient to Colorado. She went in October, 
aud has slowly improved without further medication. 
Case XLIV.—Mrs. E., aged thirty-one, of Ann 
Arbor,came to me in April, 1895. One sister had con- 72 
sumption for some years, but died in labor. This 
sister lived with Mrs. E., and as no precautionary 
measures were taken, the chance of transmission of 
the contagion was great. A brother, also, developed 
the disease, and his case will be mentioned later. 
For nearly a year Mrs. E. had been losing flesh and 
complaining of great lassitude. A pulmonary hem- 
orrhage sent her to me. For five or six days she 
coughed up blood, and this was repeatedly examined. 
Tubercle bacilli were present, but were not numerous. 
The source of the hemorrhage was evidently in the 
left apex. Over the whole of the upper left lobe 
there was dulness, and moist rales could be heard. 
The afternoon maximum temperature was for some 
days as high as 102° F. Treatment was begun imme- 
diately, and continued daily until October, 1895. 
From this time to March, 1896, the injections were 
made twice a week. Since March the patient has 
had no treatment. She weighs now 25 pounds more 
than her maximum weight before April, 1895. I 
can now (October, 1896) find no trouble in the 
lungs. 
Case XLV.—Mrs. S., aged twenty-six, of Ches- 
ter, Mich., came under my observation in April, 
1895. There was a history of direct contagion. She 
had helped to care for a consumptive neighbor and 
no precautions against infection had been taken. The 
patient was in an advanced stage of the disease. 
There were numerous small cavities on the left side 
and consolidation on the right in the upper lobes. 
The maximum temperature was from 102° to 103° F. 
The treatment was administered for three weeks with- 
out any appreciable effect on the rapid progress of 
the disease. Death occurred within a few weeks af- 
ter the patient’s return home. In this case there was 
not even a temporary improvement. 
Case XLVI.—V. F., aged twenty-four, a medical 
student, had a hemorrhage in April, 1895, Tuber- cle bacilli were abundantly present in the blood. 
There was the pneumonic infiltration and the charac- 
teristic fever of tuberculosis. Treatment was given 
daily to October, 1895, then omitted to February 
25, 1896, then three time per week until June, 1896. 
The summer of 1896 was spent in the Adirondacks 
without treatment. During this time the disease 
progressed. When he left Ann Arbor in June, 1896, 
he had no cough. On his return he was raising some 
sputum every morning and this contained bacilli. 
October, 1896, he has returned to college and I find 
bronchial breathing over the right apex. He now 
weighs 145 pounds, more than he ever weighed be- 
fore, but, as stated above the sputum contains ba- 
cilli. 
Case XLVII.—G., aged twenty-one, of Ann Ar- 
bor, is the first of a class which has furnished me 
with only a few representatives. There was no 
hemorrhage, but the patient was brought to me on 
account of a “ bad cold ” and a cough which had 
persisted for “some days.” The maximum daily 
temperature was between 10T and 102° F. going oc- 
casionally, but exceptionally, to 103° F. There was 
bronchial breathing with moist rales over the upper 
half of the left lung. The sputum contained numer- 
ous tubercle bacilli. Treatment was continued un- 
til October, 1895. The bacilli disappeared in Au- 
gust, and the cough ceased a little later. The 
temperature became constantly normal about the time 
the bacilli disappeared. The rales and the dulness 
disappeared, and the only suspicious sound heard on 
auscultation was due to some prolongation of the ex- 
piratory act. Late in the fall of 1895 this patient 
went to Colorado as a precautionary measure. He 
remains there and reports himself well. I believe 
that in this case the tubercular invasion had not ex- 
tended very far when the treatment was begun. 
Case XLVIIL—Mrs. D., aged thirty, of Ann Ar- 74 
bor, belongs to the same class as the preceding one. 
She had a cough in February, 1895, when I exam- 
ined her lungs, and believed from the evidence thus 
obtained that she had tuberculosis, but repeated ex- 
aminations of the sputum which she was then raising 
quite freely failed to reveal any tubercle bacilli and 
the nuclein was not used. After continuing for two 
weeks the cough ceased. In April another bad cold 
with cough and expectoration brought her to me 
again. This time the bacilli were found. Treatment 
was given for three months and then wholly discon- 
tinued. The cough ceased in a few weeks as it had 
done before, and she passed through the winter of 
1895 and 1896 without a “ bad cold.” She was 
pregnant at the time of treatment and has borne a 
healthy child since. Now, there is no evidence of 
the existence of tuberculosis. 
Case XLIX.—K., a medical student, aged twenty- 
five, spent the summer of 1894 partly in taking care 
of several tuberculous patients. In May, 1895, he had 
a hemorrhage. In the bloody sputum the tubercle ba- 
cillus was easily found. The nuclein treatment was 
begun immediately and continued for two months. 
He then went to Colorado and located at Fort Col- 
lins where he practices medicine. He reports him- 
self as being quite well. 
Case L.—Mrs. L., of Jackson, Mich., aged thirty- 
two, came to me in June, 1895. She had three 
children, all of whom were well. The father was 
then living and well. Her mother died at the age 
of forty-one of consumption. Four of her mother’s 
and one of her own sisters died of consumption. She 
had been with this sister during her illness. The pa- 
tient began to recognize the fact that she was not 
well early in the fall of 1894. She began to cough 
and raise about January 1, 1895. At the time of the 
first examination she was coughing and raising very 
profusely. She had exhausting night sweats. The average afternoon temperature for four days before 
the first injection of nuclein was 102° F. There was 
bronchial breathing over both upper lobes. The ap- 
petite was poor. This patient improved temporarily, 
then lost what she had gained. The treatment was 
continued about three months, and the condition at 
the close of this period showed no improvement. 
She died in August, 1896. 
Case LI.—Mrs. VV., aged thirty-eight, of Lima, 
O., was first seen early in June, 1895. She had 
been married fifteen years, and had two healthy chil- 
dren. Her father had died at the age of seventy-six 
and her mother was then living at the age of eighty. 
She had seven sisters, one of whom had died about 
two years before of consumption. She had been 
with this sister during her illness. She had her first 
hemorrhage in May, 1894, and had coughed and 
raised some ever since. Strange to say that during 
this year she had gained in flesh. She was in good 
flesh (I find that I failed to record her weight), and 
did not by any means present the appearance ordi- 
narily supposed to be characteristic of consumption. 
There was bronchial breathing over the whole of the 
left upper lobe and over the greater part of the right 
upper lobe. The amount of sputum raised was small, 
but it contained the bacilli in great numbers. Her 
appetite was good, and she retained her healthy ap- 
pearance as long as she was with me, which was un- 
til the middle of October, 1895. This patient did 
not do well. Hemorrhage followed hemorrhage. 
The quantity of blood raised at a time was small, but 
it was continuous. I cannot say that there was even 
temporary improvement. The temperature seldom 
went as high as ioo° F. In October, 1895, she went 
to Denver, where she continues to reside. The hem- 
orrhages still occur. 
Case LII.—Miss R., aged twenty-eight, was sent 
to me by Dr. Steiner of Lima, O., in June, 1895. 76 
Father and mother were living and well. One 
brother died of consumption six years ago. The 
patient was with this brother during his illness. She 
had been teaching for eleven years in the public 
schools of Lima. She had influenza four years ago, 
and has been more or less hoarse, with some cough, 
since that time, but she has attributed this condition 
to the unwholesome air of the schoolroom and to the 
constant use of her voice. During the vacation of 
1894 she worked in the slums of Chicago, although 
at that time she was feeling much out of health. She 
first consulted a physician in May, 1895, when she 
went to Dr. Steiner, who immediately recognized 
the true nature of her trouble. Respiration over 
both upper lobes was wholly bronchial. The sputum 
was purulent and contained numerous bacilli. The 
maximum temperature averaged ioo° F. She rap- 
idly improved temporarily until the middle of Au- 
gust, when she had a chill every other day for a 
week, her tongue was heavily coated, and she loathed 
food. A mercurial, followed by large doses of 
quinin, seemed to remove this trouble, which I re- 
garded as an intercurrent attack of malaria. She 
soon began to improve, and I consented to her re- 
turning to Lima and resuming her work as a teacher. 
Some three weeks later she suddenly developed a 
pleuritic effusion on the left side. Some of the fluid 
was drawn by Dr. Goebel and sent to me. It contained 
tubercle bacilli. Notwithstanding the most intelli- 
gent treatment by Dr. Goebel, the patient rapidly 
failed, and died in February, 1896. 
Case LIIL—Mr. G., aged thirty-two, of Detroit, 
was examined July 5, 1895. There was no family 
history of tuberculosis. Both parents were then liv- 
ing, and his two brothers were healthy, active busi- 
ness men. The patient has been for some years 
given to the abuse of alcoholic drinks. Within the 
preceding twelve months his weight has fallen from 170 to 120 pounds. Examination showed extensive 
involvement of the lungs and larynx. Both apices 
were retracted. There was a large cavity on the 
left side under the third interspace. Crepitant rales 
were heard over the upper half of the right lung. 
Moist rales were heard posteriorly both above and 
between the scapulae. The expectoration was 
abundant, purulent, and full of bacilli. Considering 
the condition of his lungs, this is in some respects 
one of the most satisfactory cases which has come 
under my treatment. During the first two months 
I could not see the slightest evidence of improve- 
ment. Indeed, the disease steadily progressed. The 
afternoon temperature frequently went as high as 
103° F, and the weight slowly diminished, but early 
in September, 1895, the appetite improved, the 
cough became much less continuous, the sputum lost 
its purulent character, and in several samples no 
bacilli could be found. This would be true sometimes 
when all the sputum raised in twenty-four hours was 
collected and examined. At other times a few 
bacilli could be found. This condition of the 
sputum continued as long as the patient was with me, 
which was until December 21, 1895. There was 
also marked improvement in the physical signs. The 
cavity remained, and there was bronchial breathing 
over both upper lobes, but there were no rales. Dr. 
McClintock has examined this patient (October, 
1896), and reports that there has been further im- 
provement, and that he is now using the nuclein 
again. 
Case LIV. — Miss B., aged twenty-seven, of 
Owosso, Mich., a stenographer, was examined July 
9, 1895. Her father died at forty-five from some 
stomach trouble. Her mother is living, and ap- 
parently well, but earlier in life she had pulmonary 
hemorrhages. A sister of her mother and a brother 
and sister of her father died of consumption. Miss B. has been “out of health’’ for three or four years, 
but did not begin to cough until four months ago, 
when she had an attack of influenza. Since then she 
has been coughing and raising abundantly. She had 
heavy night sweats, and the menses have been sup- 
pressed for some months. There was at least one 
cavity in the left lung, and there was bronchial 
breathing over the upper lobe on the right side. 
The patient remained under treatment with me until 
about October i, 1895, when she went to Talapoosa, 
Ga., where the nuclein injections were continued by 
a very intelligent physician. The result in this case 
conforms to the general rule for this class. There 
was temporary improvement, gain in weight of about 
ten pounds, restoration of the menses, diminished 
cough and expectoration, and then under the con- 
tinued use of the nuclein, retrogression and gradual 
failure. She died in August, 1896. 
Case LV.—A. B., aged twenty-one, farmer, 
Hersey, Mich. One brother and one sister had died 
of consumption within the past five years. Patient 
was with both brother and sister during their illness. 
He had lost about twenty pounds during the last year. 
Right lung: Bronchial breathing throughout upper 
lobe; crepitant rales in the superior axillary region. 
Posteriorly a large cavity was detected above the 
scapula. There was bronchial respiration between 
the scapulae. Left lung: Bronchial respiration over 
upper lobe; crepitant rales through the lower part of 
the lung and throughout the axillary area. Bubbling 
rales were heard posteriorly. 
There was an ischiorectal abscess, which had been 
opened by his physician in March, 1895, and which at 
the time of my examination was discharging freely. 
This abscess was opened more freely and dressed with 
nuclein and iodoform, and healed completely within 
one month. This patient remained under treatment 
until October 1, 1895. His lungs showed some im- 79 
provement in physical signs, and the weight in- 
creased four pounds. The temperature was not ma- 
terially altered, that for 4 p.m. averaging ioo° F. dur- 
ing the first and last weeks of treatment. When he 
went home, October 1, 1895, I gave him a prescrip- 
tion for capsules, containing one grain each of iodo- 
form and sulfate of quinin and one-sixtieth of a 
grain of strychnin sulfate. I have been unable to 
obtain further information concerning this patient. 
Case LVI.—Miss W., aged twenty-five, of Ann 
Arbor, was examined July 10, 1895. er mother died 
five years ago of consumption. Miss W. was with her 
mother during the illness of the latter. Her mother 
had two sisters, both of whom died of consumption. 
Miss W. had not felt well since the death of her 
mother. She had lost ten pounds since June 1, 1895. 
She had been having night sweats for two months, 
and felt “ flushed and hot ” every afternoon. The 
cough was slight, and the sputum consisted of glairy 
mucus, containing a few tubercle bacilli. The only 
abnormality which could be found in the lungs con- 
sisted of crepitant rales in the right apex. The 
afternoon temperature ran from 99.5 0 to 1 oo° F. The 
rales disappeared, and no germs could be found after 
three weeks of treatment. The injections were con- 
tinued until October 1, 1895. The patient has 
shown no signs of disease since, and raises nothing. 
Case LVI I.—Mr. R., aged thirty-two, of Toledo, 
O., was examined July 10, 1895. He had no family 
history of tuberculosis, but there was sufficient 
evidence of direct exposure to the infection. A 
young man with tuberculosis had worked for many 
months in his office. This clerk had coughed and 
expectorated freely, and there had been no attempt 
to disinfect the sputum, and it was R.’s recollec- 
tion that the clerk had expectorated on the floor. 
This was some five years before he came to me. He 
had known himself to be tuberculous for about two 80 
years, and had spent a part of one winter at Ashe- 
ville, N. C. There were numerous small cavities in 
both upper lobes. The afternoon temperature went 
as high as iox° F. The treatment was continued until 
the middle of September, 1895, when he went to 
Utah for permanent residence. I have not heard 
from him since. 'There was a slight gain in weight 
during treatment, but no essential improvement in 
physical signs. 
CaseLVIII.—Charles M.,aged seventeen,of North- 
field, Mich., was examined August 13, 1895. There 
was no history of tuberculosis in the family, and no 
evidence of direct contagion. In March, 1895, he 
began to cough, and from that time to the date of 
examination he had lost fifteen pounds in weight. 
'The amount of sputum raised daily averaged about 
two ounces. There were a few bacilli. Moist rales 
could be detected in the right subclavicular area. No 
other abnormality could be found. The average tem- 
perature for three days before beginning the treatment 
was at 8 a.m. 990; at 12 m., 99.40; at 4 p.m., ioo°; 
and at 8 p.m., 98.6°. The treatment was continued 
until the middle of September, 1895. By this time 
the temperature had become constantly normal. 
The cough and expectoration had ceased, and he 
had gained ten pounds. He remains well, and has 
no cough. 
Case LIX.—Miss L., aged twenty-eight, of De- 
troit, was first examined August 13, 1895. One 
sister had died of consumption at the age of twenty, 
eight years ago. Miss L. had been with this sister 
during her illness. She had been coughing for three 
years, and was in the last stages of the disease. There 
were numerous small cavities in both upper lobes. 
The afternoon temperature went as high as io2.5°F. 
The treatment was continued for eight weeks, and 
without effect on the progress of the disease. She 
died about three months later, 81 
Case LX.—Mr. C., aged thirty-seven, of Amster- 
dam, N. Y., a druggist. There was no family his- 
tory of tuberculosis and no evidence of direct con- 
tagion. Patient had influenza six years ago, and has 
been coughing and expectorating ever since. There 
were cavities in both upper lobes. Treatment was 
given for two months without benefit. He died the 
last of December, 1895. During the last week of 
his life there was involvement of the meninges. 
Case LXI.—Mrs. C. of Amsterdam, N. Y., wife 
of the patient whose history has just been given. 
There was no family history of tuberculosis, but she 
undoubtedly acquired the disease from her husband. 
It may be remarked here that Mr. C. was exceedingly 
careless about expectorating about him wherever he 
happened to be. This was so noticeable and he was 
so persistent in the neglect of my admonitions so 
frequently given, that I once forbade his coming to 
my office. This caused him to heed my advice while 
in my office, but he continued to disregard all pre- 
cautions elsewhere. Mrs. C. also had numerous 
small cavities. The treatment was given for about 
two months, but without any evidence of improve- 
ment. She died a few weeks after her husband. 
Case LXII.—E.B., aged twenty-eight, of Saginaw, 
Mich., was examined August 14, 1895. The family 
history has already been given. One sister died, while 
tuberculous, in child-birth, and another sister was 
under treatment (Mrs. E., Case LXIV). This man 
had always considered himself especially healthy and 
robust. About six weeks before coming to me, he 
began coughing and spitting up blood. He had had 
three slight hemorrhages in that time, and had lost 
twelve pounds in weight. The only abnormality 
that could be detected consisted of a prolonged 
expiratory movement over the left apex and sub- 
clavicular area. The sputum contained numerous 
bacilli. He remained with me only three weeks and 82 
went home with the intention of having the treatment 
continued. October 23, 1895, he wrote me that he 
had gained eight pounds. He sent me some of the 
sputum at that time, and there were bacilli in it. 
November, 1896, he reports to me that he is quite 
well, weighing more than he ever did before, but I 
have not seen him. 
Case LXIII.—Mrs. H., aged thirty-eight, of To- 
ledo, Ohio, came for treatment August 18, 1895. She 
had been coughing and expectorating for two years, 
and had spent one winter at Colorado Springs. The 
expectoration was free, but contained very few bacilli. 
There was only bronchial breathing over the upper 
half of the left lung and over the right apex. She 
remained under treatment for two months, during 
the latter half of which she coughed and expectorated 
much less and no bacilli could be found, although 
frequent and careful examinations were made. I last 
examined the sputum in December, 1895, and at that 
time could find no bacilli. 
Case LXIV.—Miss P., aged eighteen, of Grass 
Lake, Mich., had been seen by me in consultation 
early in July, 1895. She was in the last stages of 
the disease, very much emaciated, and with extensive 
cavities. There was no family history of the disease, 
except that a cousin had it, and this cousin had 
visited at her father’s house. The treatment in this 
case was without effect, and the patient died in No- 
vember, 1895. 
Case LXV.—Miss M. S., aged twenty-one, of Ann 
Arbor, in the last stage of the disease had the treat- 
ment for three weeks without effect. 
Case LXVI.—Miss E. S., aged twenty-nine, of 
Ann Arbor, came for examination August 29, 1895. 
There was no family history and no known direct 
contagion. The apex and subclavicular area of the 
left side showed crepitant rales. The sputum was 
small in amount but contained numerous bacilli. Miss S. is a farmer’s daughter and lives about five 
miles from my office. She drove this distance every 
day, rain or shine, cold or hot, from the time of be- 
ginning the treatment until March i, 1896. I 
attribute much of the good results secured in this case 
to that drive. The germs disappeared in December, 
1895, and she has not coughed any since early in 
January, 1896. Physical examination fails to show 
any abnormality. The temperature never went above 
1 oo° F. and has been normal since December, 1895. I 
believe in the curative value of out-door life. This 
adjunct to treatment is especially applicable to those 
cases in which there is but little elevation of temper- 
ature. 
Case LXVII.—Mr. W., aged twenty-eight, a 
paperhanger, of Ann Arbor, came for examination 
the last of August, 1895. There was no history of 
the disease in his family, and no evidence of direct 
contagion. He came on account of a hemorrhage, 
having supposed himself well except that he had lost 
about fifteen pounds in weight during the preceding 
year. The bloody sputum contained numerous tu- 
bercle bacilli. The left lung showed in its upper 
portion moist rales. The afternoon temperature was 
xoo° F. After four weeks of treatment the rales disap- 
peared and there has been no cough since. He took 
the injections daily for nearly six months. He now 
weighs more than he ever did before, and has not 
lost more than one month from his work during the 
whole time. 
Case LXVIII.—Mrs. W., aged twenty-eight, of 
Grand Rapids, Mich., was examined early in Sep- 
tember, 1895. There was no history of the disease 
in her family, and none of direct contagion. There 
was bronchial breathing over both upper lobes. 
Treatment was given for six weeks, during which 
time the patient gained a few pounds in weight and 
the night sweats, which had been profuse, ceased. 84 
She then went to Colorado, and I have known 
nothing of her since. 
Case LXIX.—Miss R., of Goshen, Ind., was ex- 
amined late in September, 1895. She had numerous 
small cavities, profuse night-sweats, and high after- 
noon temperature. The treatment did not retard the 
progress of the disease. 
Case LXX.—Mr. J., aged twenty-seven, an in- 
structor in the University, came under treatment 
early in October, 1895. There was no history of the 
disease in his family. He had worked in the same 
room with a consumptive two years before. There 
was bronchial breathing over the upper half of both 
lungs. The afternoon temperature averaged ioo° F. 
The treatment was continued until the middle of 
February, 1896, at which time he went west for per- 
manent residence. There was some improvement 
during the treatment, as shown by gain in weight and 
decrease in temperature. However, the bacilli re- 
mained in the sputum and the physical signs were not 
materially altered. November, 1896. He has steadily 
declined in health since going to Colorado. 
Case LXXI.—Miss S., aged eighteen, of Bay 
City, Mich., October 13, 1895. There are certain 
points in this case which justify some detail. Miss 
S. had studied very continuously in the Bay City 
High School, the very moderate means of her parents 
having rendered it necessary that her studies should 
be pursued under certain disadvantages. During the 
last year of her high school course she lost flesh and 
suffered from a sensation of general weariness from 
which she constantly strove to relieve herself by work- 
ing all the harder, and the stimulation of work actu- 
ally gave her temporary relief. In October, 1895, 
she entered the University and soon thereafter con- 
sulted me concerning the feeling of lassitude. Nothing 
had called her attention to her lungs. She had ob- 
served that she felt a shortness of breath, even when walking at an ordinary gait, and much more plainly 
on ascending stairs, but she had supposed that this 
was due to a weak heart. 
There was bronchial breathing over both upper 
lobes and both apices were retracted. There had 
never been any cough. The extent of lung involve- 
ment was certainly unusually great considering the 
entire absence of cough. The physical examination 
left no possible doubt in my mind as to the nature 
of the trouble and subsequent developments con- 
firmed the testimony of the physical signs. The 
patient was put on creosote, and the administration of 
nuclein was not begun until later. In November, she 
had a slight hemorrhage and the blood raised at 
the time was carefully examined, but with negative re- 
sults. The cough accompanying the hemorrhage soon 
ceased. I had requested the patient to keep a wide- 
mouthed bottle in her room and to bring me anything 
and everything she should cough up. Several times 
she brought me samples of saliva and mucus from the 
throat and nares. Early in January, 1896, I found the 
bacilli for the first time ; then the nuclein was given. 
However, the lungs rapidly broke down. She 
was carried to Colorado in February and died there 
about three weeks later. This case illustrates in an 
unusual manner how extensively the lungs may be 
involved in tubercular processes before the bacillus 
appears in the sputum, and indeed before there is 
any sputum. 
Case LXXII.—Mr. M., of Grass Lake, Mich., 
principal of the high school, was examined Novem- 
ber 21, 1895. He had considered himself well un- 
til about three weeks before this examination, when 
he began to cough and raise. There was no phys- 
ical sign except prolonged expiration accompanied by 
feeble moist rales over the left apex and subjacent 
area. The sputum was small in amount, but con- 
tained numerous bacilli. He remained under treat- 86 
ment for about four weeks, when on having an op- 
portunity to accept a position in New Mexico, he 
went there. He improved slightly in weight during 
the treatment. There was no family history of tu- 
berculosis; but he and his wife had during the sum- 
mer of 1895 occupied the house of Mr. P., father of 
Case LXIII. Of course he might have been infected 
much earlier than this. However, I think this coin- 
cidence of sufficient importance to be recorded. 
Case I,XXIII.—C. M., aged twenty-five, of Pin- 
konning, Mich., a fireman on a locomotive. There 
was no family history of tuberculosis and no known 
direct exposure to contagion. In December, 1893, 
he fell on a switch-stand, bruising the abdomen and 
injuring one testicle, which has gradually decreased 
in size until it is not more than one-third as large as 
the other one. The injury to the abdomen caused 
a dull pain, which continued for some months. This 
pain grew so severe in February, 1894, that he sum- 
moned a physician and was in bed for one week. 
The physician said that he had inflammation of the 
bowels. Some six months later he began to cough. 
He had been under the charge of a physician for 
three months before coming to me. He had suf- 
fered during this time from a persistent diarrhea. 
Had profuse night-sweats, and was raising abun- 
dantly. It seemed to me that the disease had ex- 
tended from the abdominal cavity upward. Both 
lower lobes were involved and there was a pleuritic 
effusion on the left lung. The afternoon tempera- 
ture went as high as 103° F. This man had the 
nuclein injections for three weeks, during which 
time there was some improvement in the diarrhea, 
but none in the lungs. He was anxious to go west, 
the railroad company offered him transportation, 
and as I did not believe that his condition would be 
materially benefited by the nuclein treatment, I con- 
sented. He went to Arizona and I have heard noth- 87 
ing further from him. I should be much surprised 
if the change in climate has done him good. 
Case LXXIV.—C. T., aged twenty-three, a stu- 
dent from Lansing, Mich. His father’s half-brother 
had died of consumption eight months before, after 
a long illness in his father’s house. T. had always 
been frail. He began to cough and raise some one 
year ago. Since October i, 1895, the amount of 
sputum had greatly increased. His hands and feet 
grow cold every afternoon. There was roughened 
breathing over the whole of left upper lobe and some 
dulness over the right side. The first examination 
failed to reveal any bacilli, but subsequently a few 
were found. The injections were given for four 
weeks, when the cough ceased, the fever disappeared, 
and six pounds in weight was gained. The only 
evidence of any trouble in the lungs on his discon- 
tinuance of the treatment was a prolonged expiratory 
murmur on the left side. November, 1896, he 
writes that he is perfectly well. 
Case LXXV.—Mrs. C., aged twenty-nine, of 
Seattle, Wash. There was no family history of the 
disease and no known exposure. She had left Seat- 
tle in September, 1895, and gone to her father’s 
at Towanda, Pa., where she had been under the 
treatment of Dr. C. M. Pratt, who wrote me as fol- 
lows : “Mrs. C. has been under my care for the 
past month for symptoms of incipient phthisis, 
cough, rapid pulse, night-sweats, delayed menstrua- 
tion, etc. She is now somewhat better, weight in- 
creased, cough less, night-sweats better, and she has 
menstruated. Her treatment has been creosote, 
phosphate of iron, and one-sixtieth of a grain of 
picrotoxin for night-sweats.” I found bronchial 
breathing over the upper part of the left lung. 
The quantity of sputum was small and bacilli few. 
Her weight was 116 pounds. She had the nuclein 
injections for nearly three months, before which 88 
time her cough had ceased altogether and no ab- 
normality could be detected in the lungs. Under 
date of August 16, 1896, she wrote me from Sidney, 
Wash., that she weighed 133 pounds and had never 
felt' so strong and well. She has not been troubled 
with colds and has no cough. 
Case LXXVI.—Mr. H., aged twenty-four, of De- 
catur, 111., came to me in August, 1895. It will be 
seen that this case is reported out of chronological 
order. This is done because it was not a case of 
pulmonary tuberculosis. The disease was located in 
the bladder. He had been troubled about three 
months before consulting me with frequent and 
painful micturition. He had been sounded for stone 
with negative results. Examination of the bloody 
urine showed the presence of numerous pin-head 
lumps, which, on being crushed between cover 
glasses and stained, revealed great numbers of tu- 
bercle bacilli. Guinea-pigs inoculated with the 
urinary sediment developed tuberculosis. The treat- 
ment was begun by me and continued by Dr. Barnes 
of Decatur. Early in September, 1895, he began 
his work as teacher in the Decatur High School. At 
that time his afternoon temperature frequently rose 
as high as 103° F. Before December, 1895, the urine 
had become normal, and had so remained. There 
is now no evidence of the existence of any disease. 
Summary.—The cases reported in this and the 
preceding paper include all those in which the tu- 
bercle bacillus was found, treated by me with yeast 
nucleinic acid, from May, 1893, to December, 
1895. There has been no selection of cases to re- 
port, and no exclusion. Many were in the last 
stages of the disease when the treatment was begun. 
Indeed, some of them were at that time confined to 
' # 
their rooms, and died within a few weeks. In my 89 
study of the value of yeast nucleinic acid in the 
treatment of tuberculosis, I have endeavored to carry 
out the investigation as I would a series of laboratory 
experiments and, above all, not to deceive myself. 
Of the seventy-six cases reported, seventy are those 
of pulmonary tuberculosis. Of these, thirty (42 
per cent.) have died. Of these, at least nine were 
temporarily benefited. 
Of the seventy, seventeen (24I per cent.) have 
been continuously free from the bacillus for from 
one month to two and one-half years, so far as can 
be determined from the sputum; i.e., either there has 
been during this time no sputum to examine or that 
examined has failed to reveal the bacillus. To the 
best of my knowledge, another (No. 47) has been 
free from the bacillus for more than a year, and an- 
other (No. 29) has been free from the bacillus with 
the exception of a short time, and still another (No. 
24) was free when last examined. Twenty (28! per 
cent.) were still infected at the last examination. Of 
these, sixteen have been apparently improved by the 
treatment. It should be stated that none of these 
were hospital cases. I was not able to control their 
diet. Most of them were not rich, and had only 
inexpensive food. The hygienic conditions under 
which many of them have lived have not been satis- 
factory. 
Of the five cases of urinary tuberculosis, four have 
apparently been cured. One was temporarily bene- 
fited, but developed acute miliary tuberculosis and 
died. The one case of joint tuberculosis has been 
benefited. 
Since the first of January, 1896, I have treated be- 90 
tween thirty and forty additional cases of pulmonary 
tuberculosis with nuclein, but since most of these have 
been given the five and the ten-per-cent, solutions of 
nucleinic acid by the mouth, some with and some 
without hypodermic injections of the one-per-cent, 
solution, and since sufficient time has not elapsed to 
draw positive conclusions concerning the value of this 
method of administration, I will defer further details 
until another time. Moreover, to report additional 
cases would require that this paper be lengthened 
beyond all proper limits. 
I have treated several cases which I believed to be 
tuberculous, but the bacilli could not be found. 
These are not included in the list already given, and I 
will now proceed to detail two which seem to me of 
special interest: 
In May, 1895, I was called to Battle Creek, Mich., 
where I saw, in consultation with Dr. Alvord, a Mr. 
D. His mother’s family had furnished several con- 
sumptives, and a brother had had one leg amputated 
by Dr. John B. Hamilton of Chicago on account of 
tuberculosis of the knee-joint. The patient, who was 
unmarried and twenty-eight years old, had been failing 
in health for the past six months, latterly very rapid- 
ly. February 1, 1895, he weighed 136 pounds; at 
the time of my visit eighty-two pounds. He had an 
exhaustive mucus diarrhea, with night-sweats, and 
the temperature curve of tuberculosis. The lungs 
were normal and the heart very weak, but without 
organic disease. The abdomen was retracted, and 
no enlarged glands could be found. A few weeks 
before my visit Dr. Alvord had operated upon him for 
fistula in ano. The wound was still discharging. I 
examined the stools and the pus from the wound for 
tubercle bacilli, but with a negative result. I ad- 91 
vised that the bowels be irrigated two or three times 
a day with large volumes of water, and that after 
each irrigation two drams of the one-per-cent, 
solution of yeast nucleinic acid with fifteen drops 
of laudanum be injected. Teaspoonful doses of the 
nucleinic-acid solution were also given by the mouth 
three times a day. From the time of my visit until 
September i, 1895, about one gallon of the nuclein 
solution was used, and the patient gradually improved. 
By September, 1895, he was able to walk out, and in 
January, 1896, he resumed his work. He has continued 
well. His present (November, 1896,) weight is 130 
pounds. He eats without discrimination, has daily 
normal movements, and attends to his duties as pro- 
prietor of a dry-goods house. 
Miss S., of Port Huron, Mich., aged eighteen, 
came to me by the advice of Dr. Wilson of that 
place, April 4, 1895. Father and mother are both 
living and well. In short, the only consumptive in 
the family is a cousin, with whom the young lady 
has occasionally visited. Her weight had fallen 
from 129 pounds to 105 pounds within six weeks. 
Night-sweats were profuse and exhausting. The fol- 
lowing letter from Dr. Wilson forms the best state- 
ment of the history of the case : 
Port Huron, April 9, 1895. 
Dear Doctor:—I had intended to send with the pa- 
tient a statement of the origin and progress of the lung 
involvement, but I misunderstood the time fixed for the 
departure and was too late. 
I think it was February 18th, that her mother brought 
Miss S. to me. She was very anemic, weak, and feverish. 
I made no examination of the lungs at that time, but did 
four days later. I was again struck with the great 
anemia. The exertion of walking across the room would 
cause very rapid pulse and breathlessness. 1 found the 
upper part of the left lung involved. About two weeks 
after this, Dr. Stewart, on my invitation, examined the 
lung, and found a small area of dulness about the line 92 
of junction of the upper and middle lobes of the right 
lung. On examination I confirmed this discovery. The 
dulness spread up and down and in all directions from 
this focus, and within two weeks involved the whole of the 
right lung. I watched its progress closely, and know this 
to be a fact. The afternoon temperature soon reached 
ioo° F., then ran up to 102°, to 103°, and sometimes to 
104° F. At times I doubted my diagnosis of tubercular 
infection, as the cause of the dulness, but could find no 
other solution for it. At the time she left, the dulness 
was not quite so marked in the right apex as it had been. 
There was very little cough, for the amount of lung in- 
volved, and she had certainly gained in strength, but had 
lost in weight. Her appetite had also improved, and 
there was a morning remission in the fever, which before 
had been continuous. I had the nuclein and thought of 
using it, but concluded that it promised nothing in a case 
of such acute nature, so I prescribed tonics and remedies 
to meet symptoms as far as possible, I will be glad 
to hear from you concerning her. Yours, 
Mortimer Wilson. 
Menstruation had not appeared for three months 
past. The mother told me at the time of examina- 
tion that the patient had been failing in health notice- 
ably since early in December, 1894. My notes taken 
at the examination read : “ Upper lobe of right lung 
partially consolidated and numerous rales heard 
throughout upper lobe of left lung. There is a dis- 
tressing cough, but the patient has never raised any- 
thing. ” The temperature the day before beginning 
the treatment was as follows: 8 a.m., 98.5° ; 1 p.m., 
ioi° 1 4 P.M., 103°; 8 p.m., I02f° F. 
The treatment was begun April 5th with 40 minims, 
which was doubled the next day, and kept at 80 min- 
ims during the course of the treatment. The tem- 
perature gradually fell as is shown by the following : 
May 8, 8 a.m., 98.5°; 12 m., ioo|°; 4 p.m., 
ioi |° ; 8 p.m., ioo|° F. By the middle of June the 
temperature remained normal, and there has been 93 
no fever since that time. When I state that the 
temperature gradually declined I would not have it 
understood that there were no exceptional days. In 
the latter part of April the temperature for some days 
ran high at 4 p.m., and once reached io4°F. The 
treatment was discontinued the last of June, and 
there has been no occasion to resume it since. At 
that time the lungs were quite normal and the cough 
and night-sweats had ceased. In October, 1895, 
Miss S. wrote me that she weighed 130 pounds and 
was quite well. In March, 1896, I saw her and 
she was apparently in the best of health. I did not 
examine her lungs. 
I have reached certain positive and definite con- 
clusions concerning the value of the one-per-cent, 
solution of yeast nucleinic acid in tuberculosis ad- 
ministered daily in doses of from 60 to 80 minims 
hypodermically, and these conclusions I will now 
give : 
1. In advanced stages of the disease, in which the 
area of involvement is great, with or without cavi- 
ties, the best that can be expected from this treat- 
ment is temporary improvement. Even this does 
not occur in all cases. 
2. In inital cases, when the area of infection is 
limited, this treatment may and often does, not only 
arrest the progress of the disease, but it acts as a 
curative agent. 
If these conclusions be correct, it follows that in 
order to save our tuberculous patients by the em- 
ployment of this treatment, we must recognize the 
disease in its incipiency. How can we best do this ? 
That the presence of the bacillus tuberculosis in the 
sputum is a positive and conclusive proof of the ex- 94 
istence of pulmonary tuberculosis, I assume that no 
one will deny. If the sputum were examined for 
the bacillus in every case in which there is any spu- 
tum, and as soon as there is any, thousands of cases 
of tuberculosis would be recognized in time for ther- 
apeutic measures to be effective. I employ the 
word “ sputum ” here as I think it is generally un- 
derstood by the profession, and not as it is defined 
in our medical dictionaries, nor do I use it in strict 
accord with its etymology. I mean to designate by 
the word “sputum” any secretion which has its 
origin in the air passages below the epiglottis, and 
which is ejected from the mouth. It will be seen 
that according to this definition saliva is not sputum, 
though the latter may be mixed with the former. 
With this definition, I say that in any instance in 
which the patient raises any sputum, an examination 
for tubercle bacilli should be made. Neither the 
robust appearance of the patient nor his previous ex- 
cellent health, nor his family history, possibly free 
from any taint of tuberculosis, should cause the phy- 
sician to neglect this examination. As a profession, 
we have been so long, so forcibly, and so painfully 
impressed with the old, classical picture of this dis- 
ease, when it was known only in its last stages, that 
even now we too often fail to recognize it in the 
distance from failure to employ the aids to our vis- 
ion with which science has recently equipped us. It 
is my belief that, so far as tuberculosis is concerned, 
our profession is to-day in greater need of skill 
among its members in the early recognition of 
the disease than it is of therapeutical agents with 
which to combat it. 95 
While the careful examination of the sputum 
would be of great service in the early recognition of 
tuberculosis, I believe that in many cases the diagnosis 
of this disease may be and should be made before there 
is any sputum to examine. I will illustrate this point 
by the history of the following case, which I have 
just examined, and which might be duplicated al- 
most any day in the practice of one giving special 
attention to this disease : 
Miss G., aged twenty-six, a saleswoman in a dry- 
goods store. Her mother died, twenty years ago, of 
consumption. One sister died twelve years ago of 
the same disease. The family has lived during all 
this time in the same house. During the summer of 
1894, Miss G. weighed 130 pounds, and was ap- 
parently a robust, vigorous woman. In August, 
1895, she weighed 118 .pounds, and consulted a 
physician for the first time in her life. She com- 
plained of great and constant weariness, loss of ap- 
petite and chilly sensations, followed by slight fever, 
every afternoon. The physician to whom she went 
in August, 1895, has treated her from that time until 
now for malaria and “ liver trouble. ” In March, 
1896, she had the grippe, and began to cough, for 
the first time in her life. She has been coughing 
ever since. Now she weighs 104 pounds, has pro- 
fuse night-sweats, coughs almost constantly, and 
there is not a normal respiratory sound to be heard 
in any portion of her lungs. 
Now, I wish to ask, When should the treatment 
for tuberculosis have been begun in this case ? Did 
the grippe of March, 1896, develop the tuberculosis ? 
What caused the loss in flesh so plainly recognized 
in August, 1895 ? What caused the daily chilly 
sensations and the afternoon fever at that time ? Are 96 
not the chances ten to one—yes, one hundred to 
one—that she was tuberculous then ? Are we to 
wait until the bacillus grows vigorously and lung 
tissue begins to break down before we even suspect 
the existence of a disease so frequently present that 
it destroys one-seventh of the race ? Does the sur- 
geon wait until the inflammed appendix ruptures and 
every doubt of the nature of the trouble is removed 
by the collapse of the patient before he operates ? If 
he did this, would the operation statistics for appen- 
dicitis be as favorable as they now are ? I have no 
doubt that a healthy appendix is sometimes found by 
the operator, and it might happen, did we not wait 
for the appearance of the bacillus, that some non- 
tuberculous person would be treated for that disease, 
but the operation, skilfully done, does not kill, nor 
would the treatment for tuberculosis do harm. In 
many cases tuberculosis can be recognized before the 
bacillus appears in the sputum, with as much cer- 
tainty as appendicitis can be diagnosed before rupture 
occurs. 
Have we not a well-known method for the recog- 
nition of malaria when it has a real existence ? Have 
we not in quinin, the one specific known to scien- 
tific medicine, a test for malaria ? We have these, 
but we do not take the trouble to examine a drop of 
blood from the finger for the plasmodium, and 
although quinin fails to prevent the daily return of 
the afternoon “flush,” we excuse our neglect, con- 
sole our patients, and give the bacillus tuberculosis 
ample time to destroy the lungs, while we fire our 
quinin pills and capsules at a phantom.1 
1 It is an interesting fact that malaria was once regarded as an- 97 
The physician who desires to recognize tubercu- 
losis in its earliest stages must take into considera- 
tion all the known signs and symptoms of the disease. 
In one instance the bacillus may appear in the spu- 
tum early, in another late, and in a third not at all. 
In our reliance on the detection of the bacillus, we 
must not neglect the evidence which we may gain 
by auscultation, by percussion, by carefully watching 
the temperature, etc. I will put in condensed form 
my ideas concerning the means which should be em- 
ployed in the early recognition of tuberculosis : 
1. Whenever there is any sputum it should be 
examined for tubercle bacilli. If the bacilli are not 
found in the first examination the search for them is 
to be repeated. When the bacilli are present the 
diagnosis of tuberculosis is positive. Failures to find 
bacilli, even after repeated examinations, does not 
prove the absence of tuberculosis. The complete 
absence of cough and of sputum is not proof of the 
non-existence of tuberculosis. 
2. Apical catarrh, even when no bacilli are found 
in the sputum, is in the great majority of instances 
due to tuberculosis. Leube is certainly right when 
he says: “ Marked dulness of the percussion note 
over the apex is always (‘ fast immer’) a symptom of 
pulmonary tuberculosis, especially when the dulness 
is unilateral, and is detectable also in the infra- 
clavicular fossa or in the regio supraspinata. . . . Still 
more certain is the diagnosis when the dulness on 
tagonistic to tuberculosis. This view was especially championed 
by Buffalini and other Italians, and this supposed antagonism was 
cleverly used hy Brehmer in explaining his theories. See “ Die 
Gesetze und die Heilbarkeit der Chronischen Tufierculose der 
Lunge,” Berlin, 1856. 98 
percussion is accompanied by auscultatory variations 
from the normal. The slightest variations in the 
respiratory sounds suffice here, such as jerky breath- 
ing, prolonged expiration, feeble or intensified, or 
rough vesicular breathing, and indefinite respiratory 
sounds. If the breathing be of bronchial character, 
or if there be rales, even when these are isolated, 
the slightest percussion dulness in the apex becomes 
of great diagnostic significance. ’ ’ 
Among the very earliest variations in respiratory 
sounds in tuberculosis is a prolonged expiratory 
movement. When this is accompanied by retraction 
of the apex and dulness on percussion, there can be 
but little doubt about the diagnosis. This prolonga- 
tion of the expiratory sounds is so easily and so cer- 
tainly recognized and its diagnostic value is so great 
that I wish to emphasize this mention of it. 
There is a tendency among medical men at present 
to pronounce no disease of the lung tuberculous unless 
the bacillus is found in the sputum. I had myself 
fallen for awhile into this error. Such cases as the 
following lead me to believe that this is an error: 
P., now aged fifty-six, had consulted me occasion- 
ally for years. As early as 1893 he began to lose 
weight and to complain of weariness upon slight ex- 
ertion. This decrease in weight has slowly contin- 
ued. During the winter of 1894-95, he had frequent 
and persistent colds, during which he coughed up 
mucus. There was at that time only a prolonged ex- 
piratory sound over the right apex and subclavicular 
region. The sputum was examined during these 
colds, but always with negative results. In the fall 
of 1895, he returned from his vacation with a well 
marked apical catarrh on the right side. The sputum 99 
was examined repeatedly during the following win- 
ter, but again negatively. On account of the failure 
to find the bacilli, the nuclein was not employed. 
In September, 1896, he returned from a three- 
months’ vacation with a cavity under the clavicle on 
the right side, with the left upper lobe involved and 
his sputum laden with bacilli. 
3. I will again quote from Leube as follows : “It 
has recently become more and more certain that the 
apparently spontaneous pulmonary hemorrhages which 
occur in those supposedly well are not causes of tu- 
berculosis, but are the results of a disease already 
established.” The teaching of Niemeyer1 that pul- 
monary hemorrhage is a cause of tuberculosis was 
founded upon erroneous ideas of both the etiology 
and pathology of the disease and should have been 
discarded years ago. I have already called attention 
to the desirability of examining the blood for tubercle 
bacilli in every case of pulmonary hemorrhage. The 
germs will not always be found, even when the 
hemorrhage is of tubercular origin, as it is in the 
great majority of instances, but when they are found 
there can be no longer any doubt about the nature 
of the lesion. I have seen so many cases in which 
the golden opportunity for beginning proper treat- 
ment, medicinal or climatic, has been indicated by 
hemorrhage, the warning has been disregarded, and 
the disease has next manifested itself in a grave 
form, that I desire to briefly report one such case : 
A young lady of eighteen had in February, 1895, 
a slight hemorrhage and continued for some days to 
cough up blood. A physician pronounced it vica- 
1 “ Klinische Vortrage iiber die Lugenschwindsucht,” 1869. rious menstruation, finding some reason for this in 
the fact that the monthly flow had been somewhat 
scanty. The young lady began to cough late in the 
spring of 1896, and an examination of the lungs in 
July of this year showed dulness over both upper 
lobes, bronchial breathing with bubbling rales, a 
small cavity in the left subclavicular area, and an 
extensive pleuritic effusion over the lower half of the 
right lung. The sputum contained innumerable pin- 
head tubercles, and these crushed between cover 
glasses and stained were found to be full of bacilli. 
Now, can any one with the subsequent history 
known doubt that this patient was tuberculous in 
February, 1895? With instances of this kind coming 
under professional observation constantly it does seem 
that we should interpret the significance of early 
hemorrhage more correctly. 
The studies of Rindfleisch have made us acquainted 
with the pathology of hemorrhage in initial tubercu- 
losis. The tubercular process extends into the wall 
of the artery destroying the media and at times the 
intima, thus forming a spot where the rupture occurs. 
Fortunately this usually happens in one of the very 
small end arteries, and the hemorrhage is consequently 
slight. According to Riihle, late hemorrhages are of 
somewhat different origin and are more likely to be 
serious. Here the arteries in the walls of cavities, 
being left unsupported by the destruction of the ad- 
jacent tissue form aneurismal sacs which break. 
There is considerable difference of opinion among 
the authorities concerning the effects of hemorrhages 
in pulmonary tuberculosis upon the temperature. Ac- cording to Wunderlich,1 Lebert,2 and Schwarz,3 even 
slight hemorrhages in any and all stages of the disease 
are followed by at least a temporary depression of 
temperature. While Niemeyer4 and Uhrig5 state that 
hemoptosis is usually followed by an elevation of 
temperature, and Simonsohn,6 that there is no uni- 
formity in the effects, I wish to state in this connec- 
tion that when a supposedly healthy person has come 
to me on account of pulmonary hemorrhage I have 
always found at some time of the day, usually in the 
afternoon, an elevation of temperature. Of course I 
cannot say whether these persons were febrile before 
the hemorrhage or not. 
4. It is stated by good authorities that some cases 
of pulmonary tuberculosis run their entire course 
without any elevation of temperature. I have never 
seen such a case. I fail to find any such case re- 
ported in sufficient detail to justify me in believing 
the statement to be true. When the temperature is 
taken only morning and evening, the record may 
show no elevation ; especially is this likely to be 
true when the evening record is made late. How- 
ever, this is not the correct method of taking the 
temperature in this disease. The maximum tempera- 
ture is, in the great majority of instances, in the 
afternoon, and not in the evening. My experience 
leads me to believe that the temperature curve of 
i “ Eigenwarme in Krankheiten.” 
a “ Veranderungen der Korperwarme im Laufe der Tubercu- 
losis.” 
3 “ Ueber den Fieberverlauf bei Phthisis pulmonalis.” 
4 “ Klinische Vortrage uber die Lungenschwindsucht.” 
5 “ Welchen Einfluss hat das Blutspeien auf die Temperatur bei 
Phthisis,” 1885. 
6 “ Hat das Haemoptoe einen charakteristischen Einfluss auf die 
Temperatur,” 1887. 102 
tuberculosis is as characteristic as that of typhoid 
fever ; and, indeed, there are fewer variations than in 
typhoid. While there are exceptions and while ex- 
ercise often markedly alters the temperature of a given 
hour, the rule holds that the maximum is between 
three and six p. m. The record should always be made 
at eight a.m., twelve m., four p. m., and eight p. m. 
When this is done the maximum will, in the majority 
of instances, when averaged for a week, be at four p. m. 
In acute miliary tuberculosis the temperature curve 
is very irregular and my observation confirms the 
statement of Rtihle1 who says : “The irregularity of 
the fever curve of miliary tuberculosis is of impor- 
tance in distinguishing it from other febrile diseases 
from which it otherwise might be confounded.” 
It would seem to be superfluous to say that but 
little reliance can be placed on the patient’s state- 
ment that there is no fever. However, I have this 
day received a letter in which a physician writes 
substantially as follows: “Mrs. A. has been tuber- 
culous for two years. She states that she has been 
free from fever, but I find that since I began the 
nuclein her afternoon temperature sometimes goes as 
high as 1 o 10 F. ” In all cases it is well to have a tem- 
perature record for a week before treatment is begun. 
Burkhardt, working under Strumpell, has written 
a monograph on the temperature in tuberculosis.2 
This monograph is a good illustration of the careless 
mannner in which the temperature in tuberculosis 
has been studied even in some of the most renowned 
1 “ Die Lungenschwindsucht und die Acute Miliartuberkulose.” 
Ziemssen’s Handbuch. 
2 “ Ueber das Verhalten der Eigenwarme bei der Lungentuber- 
culose,” 1891. clinics. Burkhardt makes five classes of temperature 
curves in tuberculosis : 
(i) Afebrile, both in the beginning and during the 
course of the disease. (2) Subfebrile : “In a large 
number of cases the morning temperature is (zwar) 
normal, while the evening temperature shows a slight 
elevation (from 38° to 38.5° C.). ” (3) Hectic fever : 
“ The morning temperature is normal, while the 
evening temperature goes to 390 or 39.50 C.” (4) 
Continued fever (Volliges Verschwinden normaler 
Eigenwarme). (5) Irregular temperature (Grosse 
Unregelmassigkeit des Warmeganges). 
5. Loss of weight is practically a constant and 
frequently an early accompaniment of tuberculosis. 
However, before any significance can be attached to 
loss of weight in our endeavor to make an early 
diagnosis, other causes of the loss must be excluded. 
Loss of weight, when coupled with the characteristic 
temperature curve furnishes very strong presumptive 
evidence of the existence of tuberculosis in some 
part of the body. Much has been said about a 
“ pretubercular ” condition, in which there is a de- 
crease of weight, a sensation of general weariness, 
and loss of appetite, and which is supposed to render 
the person especially susceptible to tuberculosis. It 
is in these cases that an attack of influenza, measles, 
whooping-cough, pleurisy, pneumonia, or a “bad 
cold” is so frequently supposed to be the starting 
point of consumption. The physician recognizes 
this so-called “pretubercular” condition. Some- 
times he administers iron, quinin, and other tonics, 
and thus tries to prepare the patient for the disease 
to which he is supposed to be specially susceptible, 104 
and I am by no means ready to deny that this treat- 
ment is beneficial. However, the mistake is made 
in looking upon this condition as “ pretubercular ; ” 
it is tubercular, and the time to treat it is before the 
tuberculosis becomes a mixed infection by the ad- 
vent of some intercurrent disease. 
In taking the weight it is well to use the tables of 
Quetelet1 or some modification of the same as a basis 
of comparison. Conradi2 has given us a valuable 
paper on the decrease in body weight in tuberculosis, 
and he has pointed out the fact that decrease in 
weight is important evidence of the disease in its 
early stages. This decrease is due to want of as- 
similation ; later, it may be in part due to fever. 
Conradi has pointed out the following facts : (i) The 
decrease in weight is greater in proportion to the 
prostration accompanying it than in most diseases. 
(2) The younger the patient the greater will be the 
loss in weight necessary to induce prostration. (By 
prostration the author here means inability, from 
weakness of the patient, to attend to his ordinary 
duties.) (3) After prostration decrease in weight 
continues, but, as a rule, not so rapidly. 
Besides the above-mentioned evidences of tuber- 
culosis there are many other conditions which should 
lead us to suspect the existence of this disease. Al- 
though thirty years have passed since Flemming* 
showed that pleurisy is due in a large per cent, ot 
the cases to coexisting and preexisting tuberculosis, 
1 “ Sur l’homme et le development de ses facultes.” 
3 “ Ueberdas Korpergewicht des Menschen und die Abnahme 
bei der Tuberculose.’’ Leipzig, 1843. 
3 “ Ueber die Haufigkeit der Combination von Pleuritis und 
Tuberkulose und das Abhangigkeitverhaltniss beider Krankheiten 
von Einander,” Weimar, 1876. the profession has given but little attention to this 
matter, and attack after attack of pleurisy in the 
same individual is treated, while the tuberculosis, 
which is the cause of the pleurisy, is never thought 
of until the lungs are practically destroyed. 
In 106 post-mortems Schlenker1 found the pleura 
normal in twenty-one bodies (19.8 per cent.); 
pleura diseased in eighty-five (80.2 per cent.). The 
pleurisy was associated with extensive tubercular 
changes in the lungs in twenty-eight (26.4 per 
cent.); with latent tuberculosis of the lungs or bron- 
chial glands in thirty-three (31.1 per cent.). There 
was tuberculosis without pleurisy in four (3.4 per 
cent.); and pleurisy without tuberculosis in twenty- 
four (22.6 per cent.). The author states that if 
tubercular lesions had been sought for microscopic- 
ally the number of cases of pleurisy without tuber- 
culosis would have been decreased.. 
I have come to believe that when physicians ac- 
quire and practise in the diagnosis of tuberculosis a 
degree of skill equal to that employed by surgeons 
in the recognition of appendicitis, pulmonary 
tuberculosis will be detected in its earliest stages; 
and when this is done it will be placed among 
the most easily curable of the graver infectious 
diseases. 
1 “ Beitr3.ge zur Lehre von der menschlishen Tuberkulose.” See 
Deutsche Med. Wochenschrift, 1883, Nos. 31 and '32. Also Vir* 
chow’s Archtv., B. 108, S. 233. The Medical News. 
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