DIGESTIVE FERMENTS. 
Compliments of Parke, Davis & Co. CONTENTS. 
This pamphlet covers the following recent literature upon the subject 
of Digestive Ferments ; 
Packs 
1. OBSERVATIONS ON THE DIGESTIVE FERMENTS, by 
R. H. Chittenden, Ph. D., Professor of Physiological Chem- 
istry in Yale University 3-15 
2. PEPSIN IN SURGERY, by H. B. Douglass, M. D 16 
3. PEPSIN AND ITS INCOMPATIBLES, by John R. Winslow, 
B. A., M. D., Lecturer on Chemistry, Woman’s Medical 
College, Baltimore , 17 
4. THE DIGESTIVE FERMENTS, by J. Leßoy Webber, Ph. G. 20-21 
5. NOTE ON PEPSIN IN DIPHTHERIA, by Dr. A. G. Wil- 
kins, of Okaloosa, lowa 22 
6. COMPARATIVE PEPSIN TESTING, by F. A. Thompson, 
Ph. C 23-26 
7. COMPARATIVE ACTIVITY OF PEPSIN, by F. A. Thomp- 
son, Ph. C 27-29 
8. PEDIATRIC POINTS AND PICKINGS, by Dr. J. N. Love, 
of St. Louis 29 
9. PEPSIN AND ITS CONGENERS, by J. Le Roy Webber, Ph. G. 30 [FROM THE PHILADELPHIA MEDICAL NEWS, FEBRUARY 16, 1889.} 
Observations on the Digestive Ferments. 
READ BEFORE THE SECTION ON PEDIATRICS OF THE NEW YORK ACADEMY OF MEDICINE, 
JANUARY 23, 1889, 
R. H. CHITTENDEN, Ph. D., 
PROFESSOR OF PHYSIOLOGICAL CHEMISTRY IN YALE UNIVERSITY. 
Recent years have witnessed a marked development in our knowledge of the physio- 
logy of digestion. A great mass of histological and physiological details has been grad- 
ually accumulated by which a clearer insight has been obtained into many of the processes 
of secretion, digestion and absorption. Chemical science has lent its aid and given us light 
on the composition and character of the digestive juices, and on many hitherto obscure 
points in the metamorphism of the various food stuffs, and at the same time taught us to 
appreciate its value in the study of scientific medicine. 
There is, I think, no branch of medicine where a proper appreciation and true under- 
standing of physiological processes is so necessary as in the pathology of digestion. In the 
words of Dr. Ewald, “digestion is comparable to a complicated clock-work, the derange- 
ments of which are readily shown by the movements of the hands, but the causes of which 
are difficult to discover from the complexity and concealed position of the movement. 
Therefore, the pathology of digestion requires a well grounded knowledge of the complex 
processes which affect the transformation of our food into chyle.” 
Among the more recently acquired facts pertaining to digestion none are of more 
importance than those which relate to the digestive ferments. In the processes going on in 
the alimentary canal, by which the nutritive portions of the food are transformed into 
soluble and diffusible products fitted for the nourishment of the blood and of the tissues, 
ferments play an all-important part; without the action of the unorganized ferments, the 
nutrition and life of the organism would be impossible. As you well know, the more im- 
portant digestive ferments or enzymes are of two kinds, the amylolytic, acting on starchy 
matter and the proteolytic, acting on the albuminous food stuffs. As examples of the former 
we have the ptyalin of saliva and the amylopsin of pancreatic juice, as well as the diastatic 
ferment of the bile; as examples of the latter, the pepsin of the gastric juice and the trypsin 
of the pancreatic fluid. 
The terms fermentation and ferment may be variously defined, but yet after all we 
cannot add much to the definition current in the fourteenth century, viz.: “A force, which, 
without becoming weaker itself, can produce great effects in other masses.” We know that 
this is not strictly correct, yet the amount of ferment involved in any given fermentation is, 
as a rule, so infinitesimally small, so out of proportion to the magnitude of the chemical 
processes or changes caused by it, and at the same time so continuous in its action, that we 
may well marvel at its power and wonder at its methods. We feign knowledge, however, 
and call it a catalytic action, a term which clearly exposes our ignorance, but which helps to 
foster our self-esteem. 4 
The amylolytic and proteolytic ferments are alike in that they act only in the presence 
of water; that the products of their action contain, as a rule, more oxygen and hydrogen than 
the original matter, thus implying a hydration process; and that their action is most energetic 
at the temperature of body. They differ, however, in the medium in which they act; the 
amylolytic ferments being most energetic in a neutral fluid, wholly inactive in the presence 
of free acids; the proteolytic ferment pepsin, on the other hand, acting only when in combi- 
nation with an acid, preferably hydrochloric, while trypsin acts best in an alkaline medium, 
although also active in a neutral fluid. These, what may 'be called minor points of differ- 
ence, are essential ones, however, and serve important purposes in the economy. For the 
ferments are extremely sensilive‘to the action of foreign matters and the simple changes ot 
reaction from acid to alkaline and vice versa met with in the alimentary tract are sufficient 
to destroy the different ferments as they are exposed to the changed conditions in their 
journey onward and doubtless only such escape destruction as are absorbed and ultimately 
excreted through the kidneys. Thus, as we shall [see, the amylolytic ferment secreted by 
the salivary glands is undoubtedly'destroyed by the acid of the gastric juice, the proteolytic 
and rennet ferments, secreted by the gastric glands are destroyed by the conjoined action of 
trypsin and the alkaline salts of the pancreatic and intestinal secretions, while the ferments 
of the pancreatic juice are probably in turn destroyed, at least in great part, by the acids of 
the large intestines. 
Bearing in mind the extreme importance to [the economy of these unorganised fer- 
ments, it may not be amiss to consider briefly some of the conditions which modify their 
activity. lam aware, however, that lam dealing with a much abused subject, one possibly 
worn threadbare, certainly one, concerning which, of late years, much has been said and. 
written. But there are many conflicting statements, many downright contradictions, and I 
have ventured out of my experience in the laboratory to present to you the results of my 
own observations, enlarged somewhat by those of others which have seemed to me worthy 
of credence. A somewhat continuous study of the digestive ferments in their relation to 
normal digestive action has led to an accumulation of data (See Studies from the Labora- 
tory of Physiological Chemistry. Sheffield Scientific School of Yale University, Vols. 
I-III), most of which, to be sure, has come from bottle and test-tube study, but yet I think is 
not to be ignored on that ground, nor on the other hand to be accepted necessarily in its en- 
tirety, but to be looked upon as a statement of fact so far as it goes, and as a suggestion to 
be tested clinically when of sufficient importance. So far as the pure chemistry of digestion 
is concerned, the nature of the ferments and their action, the influence of various agents on 
their activity etc., the laboratory is the proper place for such study and the data so obtained 
may be of great advantage in pointing the way for clinical experiments. It is to be evei 
borne in mind, however, that the living alimentary tract is a somewhat different mechanism 
from a glass beaker, and that in the former we have to deal with a complication of conditions 
not met with in our artificial digestions. 
In considering first the action of the amylolytic ferments, we will speak only of 
the ptyalin of saliva and the diastase of mall, the one as an illustration of a normal digestive 
ferment, the other as a good example of a common remedial agent. 
What is true, however, of the ptyalin of saliva is also applicable to the amylolytic fer- 
ment of the pancreatic fluid. 
Human mixed saliva as ordinarily secreted has an alkaline reaction, the average of 51 
samples showing an alkalinity equal to 0.08 per cent, sodium carbonate. The highest 
amount found was 0.144 per cent, the lowest 0.059 percent. In spite of this being the 
normal reaction of the secretion, its power of digesting starch is far greater when the fluid is 
exactly neutral than when alkaline, a difference which shows still more distinctly the greater 
the fluid is diluted. The ferment acts most energetically in a neutral fluid. The same is 
true of the diastase of malt, its diastatic action showing stronger in a neutral fluid than in an 5 
alkaline medium. Increasing the alkalinity of the fluid, either diastase or saliva, tends to 
retard the amylolytic action of the ferment, the extent of retardation being in proportion to 
the amount of alkali carbonate present. The percentage of alkali, however, which hinders 
diastatic action can be designated only for definite mixtures, being dependent upon the dilu- 
tion of the fluid, and consequently upon the amount of albuminous matters and inorganic 
salts present. 
The presence of 0.3—0.5 per cent, sodium carbonate will almost entirely stop the ac- 
tion of undiluted saliva on starch, while with neutral saliva greatly diluted, the 
presence of even 0.005 per cent, sodium carbonate will diminish decidedly the 
action of the ferment. Dilute alkalies not only hinder the action of these amylolytic fer- 
ments, but they also destroy them, especially at the body temperature. Their destructive 
power, however, is not as great as their retarding action. While these facts plainly indicate 
the extreme sensitiveness of the ferments towards alkaline fluids, we must not be too hasty 
in assuming a destructive action whenever alkalinity becomes pronounced. Peptones and 
proteid matters in general all tend to diminish and even prevent in part the retarding and 
destructive action of dilute alkalies, hence in the intestinal canal and elsewhere where the 
products of proteolytic action or other forms of proteid matter are present, the amylolytic 
ferments may endure the presence of amounts of alkalies which alone would quickly 
lead to their destruction. 
Towards acids, the amylolytic ferments, both ptyalin and diastase are more sensitive 
even than towards alkalies. When diluted neutral saliva, or a solution of diastase, is mixed 
with diluted hydrochloric acid in such proportion that the mixture contains only 0.003 per 
cent, of the free mineral acid, amylolytic action is stopped almost completely. With 0.005 
per cent, of free hydro-chloric acid,, destruction of the ferment is complete in a very short 
time, especially at the body temperature. 
It has been generally held hitherto, and is even now to some extent, that the ferment 
of saliva and diastase as well, regain their power of transforming starch into sugar when they 
reach the small intestines, where the contents are alkaline, this view assuming that in the 
stomach the activity of these ferments is simply suspended by the acidity of the gastric juice. 
It has even been questioned whether the acidity of the stomach contents ever becomes suffi- 
ciently great to completely stop the solvent action of the amylolytic ferments on starch. 
Many eminent authorities stand committed to this view of non-destruction by the gastric 
juice, but it is a question easily settled by experiment and I am quite convinced that the 
presence of a few thousandths of one per cent, of free hydrochloric acid is sufficient to 
quickly stop all amylolytic action. We are to bear in mind, however, that because a fluid 
reacts acid, to test papers, it does not necessarily follow that it contains free acid. In gas- 
tric juice for example, especially after digestion is well under way, there are present com- 
paratively large amounts of albuminoses, peptones, etc., all of which unite with the 
acid of the gastric juice, forming a loose chemical combination to be sure, but 
yet one in which the acid is far less powerful towards ferments at least, then when un- 
combined. Hence the question of retardation and destruction of amylolytic ferments in the 
stomach needs further consideration; we need to know how the proteid matter affects the 
action of the acid of the gastric juice and we find by experiment that nearly all forms of 
albuminous matter prevent to a certain extent the destructive action of the acid. The acid- 
proteids formed, however, have more or less of a destructive action themselves and 
when all the proteid matter present in a given mixture is completely saturated 
with acid, although no free acid may be present, the amylolytic ferments soon lose 
their action on starch, and in a short time are completely destroyed. Hence, it 
follows, that while the proteids of the food probably protect for a time the ptyalin 
of the saliva, or other amylolytic ferments introduced, by combining with the hydrochloric 
acid as it is secreted, in a very short time these must become saturated and free acid be 6 
present, and as soon as free hydrochloric acid is present, or even before, a rapid des- 
truction of the amylolytic ferments must take place. And to this destructive action must 
be added also the slower action of the acid-proteids. That free acid is normally present 
in the stomach contents can be easily shown by several tests, notably with tropseolin 00. 
The length of time after the ingestion of food, before free acid makes its appearance in 
the stomach, must be variable, dependent in great part upon the amount and character 
of the food taken. There is, I think, among many physiologists a growing impression 
that for 15 to 30 minutes after taking food an active digestion of starch goes on in the 
stomach. Von Velden* found, by methods perhaps somewhat questionable, that for a time 
varying from three-quarters to two hours after eating, the fluid in the stomach, obtained by 
a stomach pump, gave no color reaction with methyl aniline violet or tropseolin for free 
acid, although the mixture showed an acid reaction to test papers. Uffelmanf likewise 
found a similar absence of free hydrochloric acid in the case of a boy with a gastric fistula 
and fed on a mixed diet, free acid appearing from forty-five to sixty minutes after the 
ingestion of food Kretschy and Seemann obtained similar results. More recent experi- 
ments of Ewald,f however, appear to show that the time of appearance of free acid de- 
pends entirely on the food; thus, in. one experiment, with a person where vomiting could 
be produced at will, a meal of 60 grams of wheat bread was followed by the appearance 
of free hydrochloric acid in the stomach contents in thirty minutes; with hard boiled eggs 
even after fifteen minutes. With a moderate meat diet (120 grams) free hydrochloric acid 
was detected only after 1% hours. Further, Ewald and Boas§ by experiments on inmates 
of the “Stoedtische Frauen-Siechen-Anstalt,” Berlin, have found that on feeding starch 
paste (200-300 c.c.) made from either potato or wheat starch, free hydrochloric acid ap- 
pears in the stomach contents very quickly. The experiments were conducted on pa- 
tients with sound stomachs, the stomach being empty and indeed rinsed out with water just 
prior to the experiment and the wash-water proved free from acid. In this way they 
found that the ingestion of the starch paste was followed in one case by the appearance 
of free hydrochloric acid in ten minutes, the fluid vomited containing 0.04 per cent. HCI, 
the acid increasing after 27 minutes to 0.28 per cent. HCI. In another experiment after 
the same order 0.13 per cent. HCI was found in the fluid ejected after fifteen minutes, 
while at the end of thirty minutes the acid had increased to 0.29 per cent. In no case 
was lactic acid found in the ejected matter. 
These same investigators have also in part confirmed our statements regarding the 
action of acids on the amylolytic ferment of saliva by a series of interesting chemical ex- 
periments on patients in the Frauen-Siechen-Anstalt. By feeding a one per cent, starch 
paste solution, to which a definite amount of hydrochloric or other acid had been added, to 
patients whose stomachs had been previously rinsed with water, they found that the smallest 
percentage of hydrochloric acid which would hinder the formation of reducing substances 
was 0.066 per cent, the stomach contents being ejected or withdrawn 5 to 45 minutes after 
the ingestion of the starch. With some patients, however, the acid could be raised to 0.1 or 
even to 0.12 per cent., and still have a trace of reducing bodies found, the latter being pre- 
sumably sugar. With lactic acid, the amount could be raised to between 0.1 and 0.2 per 
cent., and still have some starch converted. With butyric acid 0,2 per cent., 
allowed some conversion. It must be remembered, however, that these percentages 
are simply the percentages of acid in the starch mixture, introduced into the stomach, 
and not the percentage of acid in the stomach contents, where there would naturally 
*Zeitschrift fiir physiologische Chemie, 3, p. 205. 
tjahresbericht der Thierchemie, 1880, p. 302, 
Archives, Vol. 101, p. 362. 
Archives, Vol. 104, p. 272, 7 
occur a dilution and partial neutralization from the inflow of alkaline saliva, counterbalanced 
perhaps by the secretion of acid gastric juice. The most important point in this connection, 
however, is the fact that such conversion of starch as does occur in the stomach under these 
circumstances takes place during the first five minutes, the amount of sugar found in the 
ejected fluid being the same at the end of five minutes as at twenty minutes; further, the 
amount formed is quite small, implying that the ferment is quickly stopped in its action by 
the acid present, Ewald also concludes that the presence of 0.077 Per cent, of hydrochloric 
acid is sufficient under the above circumstances to completely destroy the ferment. Coup- 
ling these facts with those already mentioned, I think we can safely conclude that the action 
of the diastatic ferments can at the best continue only for a short time in the stomach, and 
that cessation of amylolytic action is quickly followed by destruction of the ferment, through 
the action of the free and combined hydrochloric acid. 
Further, it is obvious that the administration of diastatic ferments, however active, by 
the mouth, with the intention of supplementing the pancreative digestion of starch in the 
small intestines, can be of little value since the ferment must inevitably be destroyed before 
reaching the seat of action. 
The extreme sensitiveness of the amylolytic ferments towards acids is substantiated by 
their behavior towards many common therapeutic agents; for the quantitative data, showing 
the exact amount of retardation or stimulation of amylolytic action, see Vol. I of Studies in 
Physiological Chemistry, Yale University. Many of the so-called antiseptics and germi- 
cides likewise show marked action on these ferments even when present in very small quan- 
tities. Mercuric chloride or corrosive sublimate, also mercuric iodide and bromide retard 
the action of the amylolytic ferments, even when present in a few thousandths of one per 
cent. Curiously enough, mercuric cyanide, when present in small amounts, appears to in- 
crease the solvent action of these ferments on starch. Large percentages, however, retard 
their action. Sulphate of copper has a very marked inhibitory action, while lead acetate has 
a retarding action only when present to the extent of two or three per cent. Arsenious 
oxide and ammonium arseniate in small fractions of a per cent., both cause neutral saliva to 
convert a larger amount of starch into sugar than the saliva alone would do, while arsenic 
acid retards the action of the ferment. Tartar emetic in small amounts has a marked stimu- 
lating influence on the salivary ferment, but large amounts, as 5 per cent., very noticeably 
diminish the amount of sugar formed. Potassium chlorate in small quantities increases the 
amylolytic action of saliva, while the presence of even 5 per qent. of the salt has only a 
slight retarding effect. Sodium chloride likewise has a slight stimulating action and large 
percentages cause only a slight diminution in the amount of starch dissolved. Many of the 
alkaloidal salts Cbuse the salivary ferment to form an increased amount of sugar, apparently 
through stimulation of the ferment, notably morphine sulphate, quinine sulphate, cinchonine, 
and cinchonidine sulphates, atropine sulphate and brucine sulphate. Strychnine sulphate, 
on the other hand, has a slight retarding action on the ferment. Antipyrin and antifebrin 
both have a slight inhibitory action on the salivary ptyalin. Urethan, in small fractions of a 
per cent, has a slight stimulating action, while larger amounts diminish somewhat the quan- 
tity of sugar formed. Thallin sulphate in very small percentages has a noticeable stimula- 
ting action, while paraldehyde has a marked inhibitory effect. 
Of gases, oxygen and carbonic acid both decidedly increase the amount of sugar 
formed by neutral saliva, while hydrogen noticeably diminishes the action of the ferment. 
Pepsin, the best known of the proteolytic ferments, and perhaps the most import- 
ant, has been the subject of study for many years. Ever since Eberle in 1834 called at- 
tention to the solvent power of an acid extract of the stomach mucosa, investigators have 
been at work in a vain attempt to isolate the active principle in a pure state. Schwan 
named the hypothetical substance, pepsin, and Wasmann just fifty years ago made an 
elaborate but fruitless attempt to isolate the pure ferment. Even at that time the power- 8 
ful digestive properties of the ferment were recognized, for, Wasmann states that a weak 
acid solution containing only gff^?0-th part of the impure ferment will dissolve coagulated al- 
bumen in from six to eight hours. A long row of illustrious names may be added to 
the list of those who have endeavored to widen our knowledge of this proteolytic fer- 
ment; Pappenheim, Valentin, Elsasser, Frerichs, C. Schmidt, and many others may be men- 
tioned as among the first to work upon this subject, while nearly every prominent phy- 
siologist since has made some contribution to broaden our knowledge of this digestive 
ferment. 
Among the many facts connected with the proteolytic action of pepsin which it 
is important for us to remember is that the acidity of the gastric juice is mainly due to 
free hydrochloric acid. The elaborate experiments of Bidder and Schmidt still stand the 
test of criticism and while we have many times, especially in disordered conditions of 
the stomach, lactic, butyric, acetic and possibly other acids present in the stomach con- 
tents, we are to look upon them as the products of various forms of fermentation, rather 
than as secretory products from the stomach cells. 
Richet (Du sue gastrique chez I’homme et les animaux) has claimed that the hydro- 
chloric acid of the gastric juice does not exist free, but in a state of loose combination with 
leucin, as chloride of leucin. His experiments are of value, since they furnish 
added proof that the gastric juice contains but one mineral acid, but few physiologists 
are inclined to believe that it exists combined with leucin. Certainly for a vigorous 
gastric digestion, free acid is as indispensable as pepsin itself. Leucin is undoubtedly 
often present in natural gastric juice and in extracts from the stomach mucosa, but I 
have many times also found considerable quantities of xanthin, hypoxanthin and other 
similar crystalline extractives, and I see no reason for assuming a combination in the 
one case any more than in the other. As to the strength of hydrochloric acid in the 
sfastric juice, Richet, as the mean of seventy observations on a patient who had had gastro- 
tomy performed for an impermeable stricture of the oesophagus, found i.3-1.7 per mille. 
©ther physiologists give somewhat higher results and 0.2 per cent, is usually taken as the 
average content of acid in active gastric juice. It can be easily shown, however, by experi- 
ment that the strength of acid best fitted for digestion depends somewhat upon the amount of 
(ferment present and the character of the proteid to be digested. Using a pepsin extract of 
moderate strength and blood-fibrin as the proteid to be digested, we have found by quantita- 
tive trials that the most vigorous proteolytic action is usually obtained in the presence of 
0.1 per cent, pure HCI. Thus in one series of experiments where the amount of pepsin was 
the same throughout with 0.05 per cent. HCI 73.8 per cent, of the fibrin was dissolved; with 
o. r per cent., HCI 89.3 per cent, of the fibrin; with 0.2 percent. HCI 84 ‘per cent, of the 
fibrin; with 0.3 per cent, acid, 81.7 per cent.; while with 0.4 per cent. HCI only 63.8 per cent, 
of the fibrin was dissolved. It is also to be remembered that while the proteolytic action of 
the ferment is most vigorous in the presence of hydrochloric acid, other acids will to a greater 
or less extent take its place, viz., phosphoric, nitric, sulphuric, oxalic, acetic, lactic, etc. 
Thus with oxalic acid, proteolytic action is vigorous in the presence of o. 5-2.0 per cent, of 
the acid, most vigorous with 1.5 per cent, such a mixture dissolving about three-fourths as 
much proteid as the same amount of pepsin with o. 1 per cent, hydrochloric acid. 
With nitric acid, proteolytic action is most energetic in the presence of 0.2 per cent.; 
with sulphuric acid in the presence of 0.3 per cent. Compared with o. 1 per cent, hydro- 
chloric acid, nitric acid is more than four-fifths as active, while sulphuric acid is little more 
than one-fourth as active and acetic acid is practically worthless. Hydrobromic and 
hydriodic acids can, to a certain extent, replace the hydrochloric acid of the gastric juice as 
Putzeys (Jahresbericht der Thierchemie, 1877, p. 279), has previously found, although they 
are both much less active than the latter. Moreover, hydrobromic acid is much more 
efficient than hydriodic acid in connection with the ferment, for in comparatively large doses 
the latter will completely stop all proteolytic action. 9 
Whenever bromides and iodides are taken into the stomach they are supposed to be 
decomposed by the acid of the gastric juice with formation of hydrobromic and hydriodic 
acids respectively, by which the retarding action of these two salts on gastric digestion is 
produced. Hence, as a practical result the bromides and iodides should be given to i 
hour before meals. 
There are, I presume, many diseased conditions where imperfect digestion is due as 
much to the want of the necessary acid as to lack of ferment. Thus in fevers, as a rule, 
from whatever cause, a less active gastric juice is secreted than normal, one possessed of far 
less proteolytic action, though generally acid. The acidity, however, is frequently dimin- 
ished and, as Ewald remarks, confirms the old habit of prescribing phosphoric or hydrochloric 
acid in fever mixtures. The simple fact that the stomach contents are acid does not neces- 
sarily indicate that the fluid is of the proper degree of acidity or even contains the proper 
acid, suited to the ferment. Acetic, lactic or butyric acid may be present and render the 
stomach juices decidedly acid and yet it may be necessary to give acid, in order to bring the 
acidity up to the point suitable for the best action of the pepsin. It is also possible to give 
an acid, as possibly salicylic, which will have a double action; viz., an antifermentative one 
and a digestion-promoting one. Certainly in many forms of dyspepsia, as the researches of 
Ewald have shown, the derangement originates in the absence of the required degree of 
acidity rather than in insufficiency of pepsin. In many such cases there may be an “acid 
stomach ” and yet the secretion of normal gastric juice be practically suppressed, the acidity 
being due mainly to lactic acid doubtless formed by fermentation in the stomach; an acid 
which acts with pepsin only about \orJ as well as hydrochloric acid. Occasionally, as you 
know, the stomach contents have an alkaline reaction, as when a strongly alkaline transuda- 
tion is poured into the stomach in connection with diminished or entirely abolished secretion 
of acid. Again, there are many other forms of dyspepsia or gastric troubles where there is 
a relative insufficiency of secretion, where pepsin as well as acid is wanting and where arti- 
ficial digestive preparations are especially called for. 
With reference to the influence of drugs on the proteolytic action of pepsin-hydro- 
chloric acid we have considerable definite information, partly as the result of experiments 
with artificial gastric juice and partly from observation on patients and animals with gastric 
fistula. Nearly all metallic salts diminish the proteolytic action of the ferment quite decidedly, 
even a few hundredths of a per cent., as a rule, producing a noticeable effect. Thus cupric 
sulphate, lead acetate, mercuric chloride or corrosive sublimate, mercuric bromide, iodide 
and cyanide, salts of tin, zinc, manganese and iron, all have more or less of a retarding 
action on the digestive power of pepsin. Iron salts retard the action of the ferment much 
more than the corresponding salts of manganese. Mercurous chloride or calomel has been 
shown by Wassilieff to have no action whatever on the ferment. The action of these 
metallic salts is due, as a rule, to the combination of the metal with the proteid to be 
digested, forming an indigestible compound, and in part to a direct action on the ferment 
itself. We have determined with all of these salts the exact amount of retardation or stimu- 
lation of peptic action under definite conditions, but I refrain from troubling you with the 
figures, especially as I think that the extent of action of a given amount of any drug in the 
stomach is, as a rule, greatly dependent upon the conditions, which are naturally variable, 
especially the strength of the pepsin-acid solution, the amount and character of the proteid 
to be digested, etc., and that it is better in applying these results to content ourselves with 
statements regarding the general nature of the action. Arsenious acid has a noticeable 
stimulating or accelerating action on the ferment, the presence of even 0.5 per cent, of 
this substance causing the pepsin mixture to dissolve a much larger amount of albumen than 
the pepsin-acid alone will do. Arsenic acid has the same action, only still more pronounced, 
and the presence of even 2 per cent, of this compound leads to increased proteolytic 
action. This certainly accords with the generally accepted views as to the influence of 
arsenic on nutrition in general. Potassium permanganate as a very energetic action on pepsin, the presence of ever 
0.005 per cent, in a digestive mixture reducing the action of the ferment to one-quarter its 
normal. Potassium cyanide and ferrocyanide have marked inhibitory action on the fer 
ment. Potassium chlorate and nitrate likewise retard the action of pepsin, and when 
present to the extent of 1.5 per cent, both salts reduce the proteolytic action to one-quarter 
that of the normal ferment. . Sodium tetraborate or borax and the chlorides of sodium, 
potassium and ammonium, all retard the digestive power of the ferment. Sodium chloride 
in small amount, however, has a noticeable accelerating action. Potash and ammonia 
alum both retard digestive action. Sulphates of magnesia and soda likewise retard the 
action of pepsin, even 0.005 per cent., having a noticeable effect 
Nearly all the alkaloidal salts have more or less of a retarding action on pepsin; thus 
strychnine, brucine, veratrine, morphine, narcotine, quinine, cinchonine and atropine sul- 
phates all reduce the action of the ferment, morphine sulphate less than the others. 
Bearing in mind that pepsin acts far less energetically with sulphuric and acetic acids 
than with nitric acid and with the latter less actively than with hydrochloric, we can easily 
see that, as a rule, everything else being equal, sulphates will retard the digestive action of 
pepsin more than nitrates, and the latter more than chlorides, and if we are to apply such 
results as these to our practice it would be to use chlorides of the alkaloids, where practica- 
ble, rather than sulphates, and the same of inorganic salts. To be sure, after a short time 
the alkaloid or its salt will have passed into the circulation and the stomach be freed from 
its influence, but it is well to heed the small things as well as the great, and if we can accom- 
plish the same physiological effect with a chloride as with any other salt and thus avoid or 
lessen possible disturbance in the stomach it is perhaps as well to do so. 
With alcohol we have a double effect to consider; the results of many experiments 
have shown plainly that the presence of alcohol impedes the proteolytic action of pepsin, 
even though it is present in comparatively small quantity, but as Gluzinski (Jahresbericht der 
Thierchemie, 18S6, p. 263) has shown, alcohol rapidly disappears from the stomach, even 
100 c. c. of 25 per cent, alcohol disappearing inside of 15 minutes. While in the stomach, 
alcohol undoubtedly retards the solution of proteid matter. Shiitz finds that 2 per cent, has 
a retarding action, while 10 per cent, causes a very great retardation and 15 per cent, allows 
only a slight digestive action. Bikfalvi finds similar results as do likewise Ogata and Kli- 
kowicz. The disappearance of the alcohol, however, is followed by the secretion of an 
active, strongly acid gastric juice, which continues generally long after the food is entirely 
digested. Hence, under the influence of alcohol there is often an accumulation of large 
quantities of fluid in the stomach, frequently colored yellow by bile. With small quantities 
of alcohol, therefore, especially with an abundance of food, there is an undoubted stimula- 
tion of proteolytic action induced mainly, if not wholly, by the increased secretion of hydro- 
chloric acid. Under such circumstances the first stage of retardation is hardly to be consid- 
ered, since the alcohol disappears so rapidly. With large amounts of alcohol, the mechani- 
cal functions of the stomach are interfered with, and thus the food compelled to remain a 
much longer time in the stomach than normally. 
Beer, wine and stronger spirits all have retarding action according to the experiments 
of Ogata (Archiv. f. Hygiene 3, p. 204) on a dog with gastric fistula. In the case of beer, 
Ogata found that the retarding action was due equally to the alcohol contained in it and to 
the extracted matters. Even sugar, both grape sugar and cane sugar, when taken in quan- 
tities above to grams, tend to retard the digestive action of pepsin, but on account of their 
rapid absorption such action is of course only temporary. Soda-water or carbonic acid 
water in quantities of 200 c. c. or more, moderately strong infusions of tea and coffee and 
200 or 300 c. c. of spring water were all found to have no appreciable influence on gastric 
digestion in the stomach itself. 
Sodium salicylate (Klikowicz, Jahresbericht der Thierchemie, 1885, p. 277) in doses of from 2.5 to 5 grams has a marked retarding influence on the digestive action of pepsin. 
Chloral hydrate, according to Klikowicz, is without action on pepsin in doses up to 1 gram. 
With 2-3 grams, however, there is noticeable retardation of digestive action, which with 
larger doses becomes still more pronounced. 
Among the newer drugs, antipyrin and antifebrin, both retard the action of pepsin; 
antipyrin, when present to the extent of 3 per cent., almost entirely stopping the action of 
the ferment. Paraldehyde has a very pronounced stimulating effect when present in small 
quantities, and even 2 per cent, has only a slight retarding effect. Urethan has a very 
slight inhibitory effect, while thallin tends to increase the digestive action of pepsin. 
In contact with dilute sodium carbonate, pepsin is very quickly destroyed, especially 
at the body temperature. Experiments made with scale pepsin and pepsin extracts from the 
stomachs of various animals have shown plainly that destruction invariably takes place in 
the presence of 0.05 per cent, of the alkali carbonate, hence when the acidity of the gastric 
juice is neutralized in the small intestines and the mixture becomes alkaline, there will be a 
rapid destruction of the pepsin, aided, as Langley has found, by the trypsin of the pancreatic 
fluid. 
Trypsin, the proteolytic ferment of the pancreatic juice acts freely only in neutral or 
alkaline fluids, slowly and imperfectly in feebly acid fluids. Thus in an experiment on 
fibrin a neutral solution of trypsin digested 77 per cent, of the proteid, while the same 
amount of ferment in the presence of 0.4 per cent, sodium carbonate digested g6 per 
cent, in the same length of time, and in the presence of o. 1 salicylic acid only 44 per 
cent, of the proteid; under ordinary circumstances the ferment appears to act most ener- 
getically in the presence of 0.5 per cent, sodium carbonate, but will act even in the 
presence of 5 per cent, of the alkali salt. In no case will a salicylic acid solution act as 
vigorously as a neutral solution of the ferment. It appears, however, that in the acid- 
reacting fluid the ferment simply acts more slowly and if time be given, will ultimately 
approach the action of the neutral fluid. In such cases, however, the salicylic acid is not 
free, but combined with the proteid matter; free acids, either mineral or organic, even a 
few thousandths of a per cent, completely stop the proteolytic action of trypsin and the 
addition of dilute hydrochloric acid to a neutral trypsin solution will prevent all proteo- 
lytic action, even before the proteid matter is completely saturated; after which the acid 
quickly causes the death of the ferment. A glycerin extract of the pancreas, for ex- 
ample, on being warmed at the body temperature with even 0.05 per cent, hydrochloric 
acid soon loses its proteolytic action, and, as Langley has shown, the presence of pepsin 
aids in the destruction. Hence it is obvious that pancreatic extracts or ferments given 
by mouth can be of no value whatever, since the proteolytic ferment at least will un- 
doubtedly be destroyed in the stomach before reaching its normal sphere of action. It 
seems to me very desirable, however, to be able to use the pancreatic ferments as an aid 
to pancreatic digestion in the small intestines. The use of such preparations, however, 
even though fortified by doses of sodium carbonate or bi-carbonate can avail little, since 
destruction must inevitably follow their entrance into the stomach. I have seen, how- 
ever, proclaimed somewhere a form of capsule insoluble in dilute acid, but soluble in 
alkaline fluids, which if truly possessed of such properties could be made an easy means 
of introducing both the amylolytic and proteolytic ferments into that portion of the ali- 
mentary tract where they are capable of performing their characteristic functions. With- 
out some such method of protection, it is of course useless to administer trypsin by 
mouth with any hope of gain to the economy. 
As you doubtless know, the action of trypsin is peculiar in that there is no swell- 
ing of the proteid matter as in the action of pepsin and acid, but the albuminous sub- 
stance is eaten into, crumbles, falls apart and then dissolves. Further, the action of 
trypsin is peculiar in that it not only converts the albumen into peptone, but also de-  12 
composes a portion of the latter with formation of leucin, tyrosin, and other products. 
With pancreatic digestion, the digestive function of the alimentary canal reaches its 
highest point, and so far as proteolytic action is concerned, trypsin is undoubtedly more 
highly organized than its neighbor pepsin; the changes produced by it are more pronounced 
and deep-seated. 
I would be glad to give you some idea of the relative activity of pepsin and trypsin, 
as proteolytic ferments, but this I can hardly do with exactness. In normal digestion 
the two ferments work under such divergent conditions and the products of their action 
are so different that it would perhaps be hardly correct to measure their relative action 
by the amounts of albumen they are capable of dissolving. Again, so far as lam aware, 
attempts to obtain the pure ferments for pharmaceutical purposes have not as yet been 
as successful with trypsin as with pepsin. Looked at from the purely physiological 
standpoint, I am of the opinion from my own experiments with the two ferments, that 
pure trypsin will prove to be more energetic in its action than pepsin, but the manu- 
facturing chemists have yet to make a trypsin preparation equal in action to many of the 
brands of pepsin now in the market. 
As a solvent of pseudo-membranes, as in diphtheria and in croup, the digestive fer- 
ments are certainly destined to prove of considerable value. Both pepsin and trypsin are 
recommended, but from a partial study of the various digestive ferments at present obtain- 
able, lam inclined to consider pepsin as the more efficacious. If a trypsin preparation 
could be obtained in strength equal to many of the preparations of pepsin I should be in- 
clined to its use, for the reason that it acts best in an alkaline medium, that it will eat into 
and disintegrate the fibrinous membrane, rather than first cause it to swell up, that the alka- 
line secretions of the buccal and other glands will favor its action, that the alkaline fluids 
possible to introduce with the trypsin may have a slight solvent action in themselves on the 
diphtheritic membrane, and that the ferment will act after the excess of alkaline carbonate 
has disappeared. 
These minor advantages, however, are, at present at least, far more than counter- 
balanced by the much greater activity of the ordinary pepsin preparations. Further, a large 
number of experiments to demonstrate the influence of various therapeutic agents on the 
proteolytic action of trypsin have shown me that as a rule this ferment is far more sensitive 
to the presence of foreign salts and drugs than pepsin is, and while this fact need not be con- 
sidered here, yet it may influence us somewhat in favor of the latter ferment. Trypsin, 
however, is not much affected by the powerful oxidizing salt potassium chlorate, the presence 
of even 5 per cent, of this salt causing only a slight diminution in the solvent potver of the 
ferment. 
As we have seen, the solvent action of pepsin on proteid matter is most pronounced 
in the presence of o. 1-0.2 per cent, hydrochloric acid, but a thin solution of pepsin with this 
acid would very quickly rinse down when sprayed into the throat, for the dissolving of 
pseudo-membranes. Admixture of glycerin will in part prevent this and keep the ferment 
for a longer time in contact with the surfaces to be dissolved. Obviously, the operation of 
painting or spraying must be frequently repeated in order to keep the surface well moistened 
with the digestive fluid. Again, since pepsin will not act at all in a neutral or alkaline 
fluid, it is plainly better to have the digestive mixture at the outset contain at least o. 3-0.4 
per cent, actual hydrochloric acid. This will in part provide somewhat for the natural dilu- 
tion of the acid and also for the neutralizing action of the saliva and other fluids. Further, 
acid of this dilution is innocuous and is a not unpleasant and cleansing mouth-wash. So long 
as the fibrinous tissue can be kept acid the solvent power of the ferment will be exerted, and 
in this connection it is to be remembered that there exists a mutual attraction between the 
acid and the proteid matter of the membrane by which the acid will be retained longer than 
by perfectly inert matter. It is to be remembered, however, that such dilute acid has a ten- dency to swell up proteid matter and we can conceive of cases where such application might 
be deemed inexpedient. The capability of pepsin for dissolving blood fibrin is very great, 
and at the body temperature its action is quite rapid, and hence one Would expect that 
under suitable conditions the fibrinous portion of a diphtheritic membrane would be attacked 
with considerable rapidity. 
The ferment solution, however, should, be carefully brought to the body tempera- 
ture prior to its introduction and the ferment itself should be of the strongest 
kind, so as to favor immediate action. The widespread use of pepsin for 
this and other purposes has led to the manufacture of large numbers of preparations 
of this ferment, some of which at least are of doubtful quality. This fact has been im- 
pressed upon me many times in the laboratory, where for various physiological purposes 
commercial pepsin has been employed. Further, during the last six months I have 
made a comparative study of a number of the more prominent pepsins in the market, 
determining quantitatively their relative proteolytic action. The general use of pepsin as 
a remedial agent in gastric troubles may well make us solicitous as to the character and 
strength of the preparation at our disposal, but as a solvent for pseudo-membranes, 
where rapidity of action is of the utmost importance and the life of the patient hinges 
on the result we should be doubly sure of the character of the ferment employed. The 
methods at present suggested by the different pharmacopoeias for testing the digestive 
strength of pepsins or pepsin solutions are somewhat variable, both in respect to the 
strength of acid employed and in the character and condition of the proteid matter to 
be dissolved, and it may also be questioned whether the standard adopted is sufficiently 
high. 
Nearly all of the methods now in vogue, either for pharmaceutical or physiological 
purposes, are based upon the older methods of Bidder and Schmidt, Ebstein and Greutzner 
Gruenhagen (Lee Herman’s, Handbuch der Physiologic Band 5, 2ter Theil., p. 75-77), and 
shorn of their details consist essentially in a determination of the amount of coagulated egg- 
albumen or blood fibrin, which can be dissolved by the ferment in a given time, an excess of 
proteid matter being present, and the amount of albumen dissolved being taken as a measure 
of the proteolytic action. 
Such a method does indeed show which mixture or pepsin has the stronger digestive 
action but does not give a very correct idea of the relative proteolytic power, for while the 
conditions in such an experiment or series of experiments appear to be the same in each 
case, they are in reality often very unlike. For as Thompson (The Druggist’s Bulletin, Vol. 
2, page, 261,) in a recent article on “ comparative pepsin testing ” has well said, the amount 
of albumen in each test may be the same and also the volume of the fluid and the amount of 
apparent ferment, and yet as soon as the digestion commences the weaker pepsins quickly 
have more surface of albumen or fibrin to work upon than the stronger and therefore show 
belter than they should. Again all who are familiar with pepsin testing can easily see that 
the condition of the proteid matter to be acted upon becomes a very important factor in 
such a test whether blood fibrin or hard boiled egg, the fineness of its division, the com- 
pleteness of its coagulation, the thoroughness with which it is kept suspended in the diges- 
tive fluid, all tend to exercise a very important influence on the final result and are 
necessarily a source of frequent error. 
Still again, the strength of acid recommended by several of the pharmacopoeias is 
such as to be at least suggestive of the formation of considerable acid albumen, by which 
the apparent strength of the ferment is correspondingly increased. To obviate these diffi- 
culties and, if possible, to insure more accurate results in pepsin testing, I have devised 
the following method, based upon the fact that fluid egg albumen is essentially of the same 
degree of digestibility as coagulated albumen (Wawrinski. Hermann’s Handbuch der Phy- 
siologic, Band V., 2ter Theil, p. 83), and that the ability to form albumose and peptone is rpossibly a more accurate measure of proteolytic action than the power of simply dissolving 
coagulated proteids. 
The albumen solution is prepared after the manner recommended by Schutz (Zeit- 
schrift fur Physiologische Chemie, Band IX, p. 581). A quantity of the undiluted white of 
egg is freed from globulin by the addition of hydrochloric acid of specific gravity 1.12, 4,2 
c. c. to 300 c. c. of albumen, shaken gently, and after standing some hours filtered. The 
fluid will then be found to have lost its viscosity and to be perfectly clear. The acid will 
likewise have neutralized the alkali carbonate present and converted the phosphates into 
acid salts. The solution, however, will not contain any free acid. 10 c. c. contain approxi- 
mately one gram of dry albumen. The exact amount can be determined in a sample by 
coagulation. The solution can be kept for some days, and so used in a large number of 
experiments. The testing is conducted as follows: Ten or twenty c. c. of the albumen 
solution are measured out with a pipette and introduced into a suitable receptacle, a definite 
volume of the pepsin solution, say 50 c. c., previously prepared by dissolving a weighed 
amount of the pepsin (50-500 milligrams of the pepsin in 1 litre of the acid, according to its 
proteolytic power), in 0.2 per cent, hydrochloric is added, and enough more 0.2 per cent, 
acid to make the entire mixture xoo c. c. The fluids are then placed in a bath at 40° C. and 
allowed to remain there for five or six hours. (The conditions to be so arranged as not to 
have more than 50-60 per cent, of the albumen at the most converted into soluble products). 
No stirring is needed, no attention of any kind other than to keep the mixtures at the proper 
temperature, and there is no possible error from variations in the mechanical condition of 
the proteid. At the end of the allotted time, the mixtures are heated to boiling and the acid 
neutralized by addition of the equivalent amount of sodium carbonate, best in approximately 
one per cent, solution. The unaltered albumen as acid albumen is at once thrown down as a 
heavy flocculent precipitate, and while still hot it is collected at once on a dry, weighed filter, 
washed thoroughly with boiling water and dried at no0 C. From this is easily calculated 
the amount of albumen converted into soluble products under the conditions of the experi- 
ment from which in turn can be calculated the relative proteolytic action of the pepsins 
tested. The figures so obtained, if the conditions have been properly arranged, give a much 
closer approach to the true proteolytic power of a ferment that any similar method with 
solid proteids, but even this does not tell the whole truth. There is still felt the influence 
already mentioned of the relative excess of unchanged albumen in those digestions where 
the ferment action is weakest and hence after having used the above method as a prelim- 
inary test it is necessary to have recourse to a modification of the principle made use of by 
Brucke (Vorlesungen fiber Physiologic, p. 303), years ago, and recently recommended by 
Thompson, of using sufficient of each pepsin or pepsin solution to convert the same percent- 
age of albumen into soluble products. In this way only, so far as lam aware, can the true 
proteolytic power of pepsin or pepsin extract be determined. 
After these methods I have tested the following brands of pepsin, obtaining as a 
preliminary result the following figures expressive of their relative proteolytic action. 
The “ Pepsinum Purum in Lamellis ” having the highest digestive power is taken as 
the standard (100): 
Preliminary test of Rela- 
tive Proteolytic action, 
x. Parke, Davis & Co.’s Pepsinum Purum in Lamellis xoc 
2. Fairchilds’ Pepsin in Scale 73 
3. Scheffers’ dry Pepsin concentrated 70 
4. Jensen’s Crystal Pepsin 56 
5. Ford’s Pepsin in Scales 54 
North’s Pure Pepsin 36 
Boudault’s Pepsin 33 
8. Royal Chem. Co.’s Pure Pepsin 27 
g. Scheffer’s Saccharated Pepsin 16 
10. E. Merck’s Pepsin Germ. Pur. Pulv 11 
si. Lehn & Fink’s Powdered Pure Pepsin o From these data, which are the average of many results, we might infer that Fair- 
child’s pepsin, for example, contains three-fourths as much active ferment as the Pepsinum 
Purum of Parke, Davis & Co. and that Ford’s and Jensen’s pepsin contain approximately 
half as much true ferment as the Pepsinum Purum. Such a conclusion, however, would be 
fallacious and to obtain the true measure of proteolytic action we must proceed further and 
determine next the relative amounts of the different preparations needed to produce a like 
result in each case. After this method we find, for example, that it requires about twice as 
much of Fairchild’s and Scheffer’s Pepsin to form a given percentage of peptone as of the 
Pepsinum Purum, and that of Ford’s and Jensen’s preparations about three times as much, 
thus showing that the true difference in proteolytic power is considerably greater than the 
preliminary results alone indicate. As a final result then we may consider the true proteolytic 
power of the above ferments compared with the one of highest digestive power to be as 
follows: 
Relative Proteolytic 
Action. 
1. Parke, Davis & Co.’s Pepsinum Purum in Lamellis 100 
2. Fairchild’s Pepsin in Scale 52 
3. Scheffer’s dry Pepsin, concentrated 48 
4. Jensen’s Crystal Pepsin 35 
5. Ford’s Pepsin in Scales 32 
6. North’s Pure Pepsin >6 
7. Boudault’s Pepsin 14 
8. Royal Chem. Co.’s Pure Pepsin 9 
In considering these results it is to be borne in mind that the same brand of pepsin is 
liable to slight variations in its digestive power, doubtless dependent in part upon the con- 
dition of the membranes from which it is prepared. Thus in many instances I have found 
one or two of nearly the same digestive strength changing their relative positions, notably. 
Nos. 2 and 3 and Nos. 4 and 5. 
As to the actual strength of these preparations I milligram of the strongest pepsin 
converted into soluble products 198 milligramms of the pure dry albumen, which would be 
practically equal to 2000 parts of fluid egg-albumen. [f ROM THE MEDICAL RECORD, DEC. 22, xBBB,] 
PEPSIN IN SURGERY. 
H. B. DOUGLASS, M. D. 
The digestive ferments have only recently attained that state of perfection which 
enables the physician to use them successfully in the various derangements of the diges- 
tive tract, and as a solvent by local application to the diphtheritic membrane. This last 
use of the ferments suggested to me their use in surgical cases, and for some months past 
I have been using pepsin in surgical work. Pepsin is best applied in the form known as 
14 pepsin in scales,” or as an ointment with lanolin as a base; 
Pepsin, gr. 50. 
Lanolin, tss. 
M. 
The cases cited below will illustrate some of its applications. 
1. In ulcerations. . 
Case I.—Mrs. T had a varicose ulcer of the leg covered with thin adherent mem- 
brane, beneath which were weak granulations. Around the ulcer for an area of two inches 
was an acute eczema. The ulcer was foul smelling Pepsin ointment with cotton dressing 
was applied. In five days the dressing was removed. The eczematous patch was less 
inflamed, the discharges not offensive, and the membrane was entirely dissolved. The 
granulations were healthy. Bismuth was now applied and the ulcer was soon healed. 
Case ll.—Mrs. M. D presented upon the middle of the tibial crest a varicose 
ulcer. The base of the ulcer was covered with a thick yellowish membrane. “ Pepsin in 
scales” was applied to this ulcer. In one week the membrane had entirely disappeared 
and the ulcer was in a healthy condition. 
Case 111.—M. D has a large epitheliomatous ulcer (rose cancer) of the neck. 
The centre of the ulcer is sloughing rapidly. The whole surface of granulations is 
covered with a membrane. The secretion from the ulcer is abundant and very foul. 
Pepsin ointment was applied daily to ulcer. In two days the surface of granulations was 
free from membrane and they looked smaller and red. Wherever the ointment was ap- 
plied the sloughing ceased, but, from the deeper parts of ulceration the discharge was un- 
changed. 
2. In cicatricial contractions. 
Case I.—D. H. J two weeks ago had a periostitis of first phalanx of middle 
finger with cellulitis of palm of hand. The resulting abscess was lanced in two places. 
When he came under my observation the suppurative process had left much inflammatory 
induration in the palm of the hand, extending to the second phalanx. There was a small 
sinus leading to bare bone on the first phalanx. The patient was unable to flex the 
finger because the flexor tendon was adherent to its sheath, and could not extend it on 
account of the cicatricial condition fol'owing the abscess. Pepsin ointment was applied to 
the palm, and the whole covered with a cotton dressing. In three days the sinus had 
closed and the cicatrix was much softer. After six days the palm was markedly less in- 
durated, and the patient could flex the second phalanx completely. In ten days the pa- 
tient was able to resume his employment as a cutter, and was fully able to hold the knife 
steadily in his hand. 
Case II.—Mrs. M. W had a parotid abscess complicating pyremia. The abscess 
opened spontaneously and soon healed. There resulted much induration and consider- 
able thickened cicatricial tissue, extending from the angle of the lower jaw to the zygoma, 
and from the sterno-mastoid muscle to the border of the rrasseter muscle. This cicatri- 
cial tissue produced anchylosis of the lower jaw on the affected side, so that the patient 
was enabled to open her mouth enough to admit solid food. Pepsin ointment was ap- 
plied twice daily. In one week there was marked improvement in opening and closing 
the mouth, and the tumor had nearly disappeared. In two weeks there was no trace of 
the swelling, and movements of the jaw were perfect. 
Remarks: I. In all ulcerations covered with a slough, or having a membranous base, 
pepsin is of use to digest this slough and bring about a healthy condition. 2. The efficiency 
of pepsin ceases when the slough has dissolved 3 In cicatricial tissue causing anchylosis 
pepsin is of use by dissolving the cellular element. In this condition pepsin may act simi- 
larly to mercury and the iodides, or as a digestive. PEPSIN AND ITS INCOMPATIBLES, WITH EXHIBITION 
OF TESTS.* 
BY JOHN R. WINSLOW, B, A.. M. D., LECTURER ON CHEMISTRY, WOMAN’S MEDICAL COLLEGE, 
BALTIMORE. 
Mr. President and Gentlemen.—Having had my attention directed to the sub- 
ject of pepsin by complaints of failure or disappointment in its action, some physicians 
going to such an extreme as to cast it out of their armamentarium, and having before 
me the statement of so eminent an authority as Prof. H. C. Wood, of Philadelphia, that 
“probably four-fifths of the drug used is inefficient or inert from the method either of its 
preparation or its administration,” I was led to make certain investigations, to ascertain, 
if possible: 
1. Are the pepsins with which we are furnished active drugs? 
2. Being supplied with such a drug, cannot failure in its action be in large meas- 
ure attributed to its maladministration? 
The literature of the subject I have found to be brief, incomplete and scattered, 
and deeming it a matter of importance to every general practitioner to decide how far 
pepsin is reliable as a medicine. I beg your attention to the conclusions reached, not so 
much on account of their originality as of their practical interest. 
All facts go to show that the solvent action of the gastric juice is essentially due 
to the presence of an enzyme or ferment, termed pepsin. This converts albuminous and 
albuminoid food matters into soluble and dialysable form. Since the majority of these 
substances belong to the class of proteids this action has been designated as proteolytic. 
The products of the proteolytic action of pepsin are successively syntonin or acid 
albumen, intermediate products termed parapeptones and true peptones. In the stomach 
this peptonization is usually incomplete, and a large amount of sj ntonin and parapeptone 
is passed on into the intestines. 
Pepsin is a colloidal nitrogenous body, which has been but proximately isolated 
and whose properties are as yet uncertain. It in many respects, however, does not cor- 
respond in its reactions to proteids. 
It readily undergoes decomposition, particularly when moist, and loses its activity. 
This is greatest, that is, it accomplishes the maximum amount of work at about 130° F. 
It is completely destroyed by boiling (even by 140° F.) and is checked by cold. Pepsin 
acts only in the presence of an acid, being completely destroyed by an alkali. The tie 
between the acid of the gastric juice and its pepsin is so strong that it has been termed 
by some writers pepto-hydrochloric acid. A commercial pepsin should present the follow- 
ing physical characteristics: 
x. It should be light colored and free from disagreeable odor. A marked odor 
indicates the presence of peptones which render the pepsin hygroscopic and hasten its 
decomposition. 
2. It should be freely soluble in water. Insolubility shows the presence of in- 
spissated mucus, which retards its action, aids its decomposition and detracts from its 
true weight. 
Any good influence derived from pepsin is manifestly due to its solvent power, so 
that this is a measure of its value. Wishing to determine the relative strength of various 
commercial pepsins, I have employed the following test, which is designed to reproduce 
as far as possible the conditions found in the human body: 
Test;—Fresh eggs are boiled 15 minutes, plunged in cold water and opened. The 
coagulated albumen is then freed from all yolk and superficial moisture, and pressed with 
a spatula through brass gauze containing thirty meshes to the linear inch. Two hundred 
grains are then weighed out and triturated in a mortar with distilled water containing 
Tsw per cent, absolute HCI. This is then placed in a tube and treated with enough of 
the acidulated water to make five ounces. To this mixture pepsin gr. is added, and 
the test tube is then immersed in a water bath and heated at a constant temperature of 
104° F. until one pepsin has completely dissolved all the albumen, usually requiring about 
four hours. As the accumulation of peptones about the albumen hinders digestion, each 
tube is stirred at intervals of three to five minutes. At the end of four hours the pep- 
sin is destroyed and further digestion stopped by boiling the mixture. To this test I 
have subjected the following pepsins, which are arranged in the order of their superiority. 
• Read before the Clinical Society of Maryland, January 18,1889. (exhibition of comparative tests.) 
1. Parke, Davis & Co.’s. 
2. Fairchild Bros. & Foster’s. 
3. Jensen’s. 
4. Boudault’s. 
5. Ford’s. 
6. Lehn & Fink’s (German scale). 
7. Merck’s. 
The pepsins used were purchased by myself in the open market, and were weighed 
upon the analytical balance of the Johns Hopkins University. The investigations were 
conducted at my residence. 
The foregoing method serves to give us an idea of the relative digestive activity 
of the pepsins, but it is by no means an accurate test of their actual proteolytic power. 
It has been repeatedly proven that the action of pepsin is entirely superficial and in- 
creases proportionately to the relative amount of albumen present, whether in excess or 
not. Now, under the preceding conditions, all of the pepsins except the most active, 
have during the entire test an excess of albumen to act upon, and make a showing which 
is falsely good when compared with it. The only accurate method of determining the 
comparative preteolytic power of pepsins is to determine the maximum amount of albu- 
men that the most active pepsin can digest under proper conditions in a given time; and 
using this as a standard, determine empirically the number of grains of the other pepsins 
required to accomplish the same amount of work under like conditions, stating the results 
in per cent. 
With this understanding as to their inaccuracy, we may utilize the result of the 
preceding tests. Having determined by this means the pepsin manufactured by Messrs, 
Parke, Davis & Co. to be the most active upon our market, digesting 2,000 times its 
weight of albumen, I have employed it as the standard in the succeeding tests. 
In order to demonstrate the action of drugs upon pepsin and the digestive process, 
I have used a standard preparation containing: 
Parke, Davis & Co.’s pepsin, gr. x-10. 
Coagulated egg albumen, 200 grs. 
Acid dist. water (3-10 per ct. HCI), 5 ozs. 
To which the following drugs have been added and the mixture digested at a constant 
temperature of 104° F. for four hours. The influence they have exerted can be deter- 
mined by comparison with the standard preparation. 
(exhibition of incompatibles.) 
Test No. 1.—This contains gr. j. sodium carbonate. The pepsin gr. was first 
treated with the soda, and both were then added to a standard preparation. As you may 
observe, the albumen is entirely undissolved. This shows that the activity of the pepsin 
has been permanently destroyed by the alkaline salt, and is not regenerated by the addi- 
tion of acid. 
This fact is well known to many of you, but it is by no means universally borne 
in mind. I have recently seen large quantities of the alkaline salt ordered by prominent 
physicians in conjunction with pepsin, both in powder and as the glycerole. 
Test No. 2 contains tr. ferri chloride ifi, v, which interferes decidedly with the pro- 
cess. 
Test No. 3 contains a solution of the bichloride of mercury. This in com- 
mon with all decided antiseptics, exerts an inhibitory action. 
It is a well known fact that large percentages of alcohol precipitate pepsin from 
solution and destroy its digestive power. Alcohol is contained in the ordinary beverages 
in the following proportions; 
Mild Beer, 2 to 3 per cent. 
Light Wines (Claret), 8 per cent. 
Whisky Brandy and Rum, 60 to 75 per cent. 
On this account wines of pepsin are unscientific preparations. 
Wishing to ascertain the effect of small percentages of alcohol I have prepared; 
Tests No, 4 and 5. These contain respectively 1 and 5 per cent, absolute alcohol, 
both of which exert a decidedly inhibitory action. 
Now as these solutions contain in the one case 5 and in the other 25 minims of 
alcohol to the ounce, the practical conclusion is that alcohol cannot, in efficient doses, be 
safely prescribed with pepsin. Test No. 6 contains bismuth subnitrate gr. v., which exerts no deleterious action 
whatever, the deposit in the bottle consisting of the insoluble salt itself. 
Test No. 7 contains ammonio-citrate of bismuth gr. v. 
In this the albumen is entirely dissolved, but the solution is milky from the pre- 
cipitation of the oxychloride of bismuth by the action of HCI. on the bismuth salt. In 
the presence of an alkali, however, the soluble bismuth salts form a colorless solution, 
and on account of this desideratum nearly all elixirs of pepsins and bismuth are alkaline. 
This at once destroys the activity of the pepsin, as you may see in 
Test No. 8, which contains 5 j of an elixir of pepsin, bismuth and strychnine, and 
has no digestive value whatever. 
Moreover the reactions of pepsin with organic matters are not well understood, so 
that it is better to avoid such elixirs. 
Test No. 9, contains tannin gr. v. The tannin and pepsin were first brought into 
contact and then added to the standard solution. 
As you see, this has an injurious effect upon the pepsin. 
A practical conclusion to be drawn from this, is that wines used in connection with 
pepsin (wines of pepsin) should be detannated. 
Test No. io, contains quinia sulphate, gr. iii, which exerts a slight inhibitory 
action. 
Test No. ii, contains saccharine, gr. x. This decidedly interferes with the activity 
of pepsin and should not be employed in connection with it. 
Test No. 12, contains pulv. (Willow) charcoal, gr. x, which has no deleterious action 
upon digestion, the deposit in the bottle being the charcoal itself. 
In order to demonstrate the results obtained by ordering “ saccharated pepsin” with- 
out specification, I have purchased specimens of 4 prominent druggists. 
Four grains of each have been added to a standard preparation containing 5 ounces 
acidulated (T®7 per cent. HCI) distilled water, 200 grs. coagulated albumen and digested at a 
constant temperature 104° F. for hours. The digestive activity*of the same quantity of 
the different preparations is seen by the result to vary greatly. 
The conclusions to be drawn, gentlemen are obvious: 
1. There is a difference, and a marked difference, in the activity of the many 
varieties of this drug. And it is to our own interest to decide for ourselves and to specify 
the variety we will employ, 
2. Having a drug so delicate in its nature, whose reactions with other sub- 
stances are so intricate and ill-understood, we cannot be too particular in our method 
of its administration. The best results may be expected from pepsin when given 
alone, either in powder, or solution in glycerin, or in a freshly prepared solution in 
acidulated water. 
While the action of pepsin seems to be catalytic and a small quantity of it should 
digest an almost unlimited amount of albumen, the conditions necessary for such action 
do not exist in the living stomach, particularly one in those conditions of disorder or 
disease in which this drug is indicated. We can not then rationally expect a minute 
quantity of the drug to efficiently digest unreasonable amounts of improperly prepared 
food. Not only must a drug of high digestive activity be employed, but the dose must 
be sufficient. Of course the more active the drug the smaller may be the amount em- 
ployed. 
Since the condition of the stomach most favorable to the activity of pepsin would seem 
to exist at that time, it is best administered during or immediately after a meal.  20 
[from THE PHARMACEUTICAL FEBRUARY 4, 1589.] 
DIGESTIVE FERMENTS. 
J. LE ROY WEBBER, PH. G. 
At a meeting of the Detroit Pharmaceutical Association, held 2 at their 
rooms in the Cowie Building, in Detroit, Mich., by invitation, a lecture on the digestive fer- 
ments was delivered, of which we present the following abstract; 
Every mental and physical process or effort causes a waste of bodily tissue. This 
waste is repaired in the conservation of living organisms by the assimilation or incorpora- 
tion of matter formerly extraneous. As much needed material exists in the external world 
in an unassimilable form, this must first be converted. The processes of conversion known 
as digestion and assimilation are therefore eminently deserving of our intelligent and care- 
ful study. 
Passing over, for the present, the preliminary subdivision of mastication—an import- 
ant matter, however—we are met at the outset, or very entrance to the alimentary canal, by 
the beginning of an interesting series of changes, all essential to the existence of the 
individual. 
In the human animal, as in many others, where the starch of the vegetable kingdom 
is to be converted, we find this provided for by the ferment ptyalin, secreted by the salivary 
glands. The action of ptyalin is similar to that of the ferment of the pancreas, known as 
amylopsin—in fact, the latter provides for, or disposes of, much work that is left uncom- 
pleted by the former. The sweet taste of bread, noticed by those blessed with an abundant 
secretion of healthy saliva, is due to the transmutation of a portion of the cooked starch and 
dextrin, contained in the bread, to glucose. 
The process of cooking, as is well known, brings about preliminary changes which 
greatly facilitate the action of the digestive ferments. Therefore, man, the “cooking ani- 
mal,” possesses advantages over the rest of living beings, because he pursues the most fruit- 
ful and economical methods of preparing food for conversion into a readily assimilable 
condition. 
The action of the salivary ferment being confined almost wholly to starchy matters, 
the portions of food consisting of proteids depend for their conversion into soluble, crystal- 
loid or assimilable forms upon the action of the gastric and pancreatic secretions. 
Considering the gastric secretion first, we find several distinct ferments present. One 
of these has the property of curdling milk, as we know from the use of rennet. Another, 
and a highly important one, pepsin, is devoted to the conversion of proteids, hence the term 
proteolytic action. In this class we include such bodies as albumin, syntonin, globulin, 
casein, fibrin, the albuminoids, etc. In taking up this subject of peptic digestion we 
consider: 
1. The reaction and properties of pepsin. 
2. Its mode of action. 
3. The products of peptic digestion. 
4. Manufacture of commercial pepsin. 
5. Pepsin testing. 
6. Its application as a remedial agent. 
Properties of Pepsin.—ln a condition as pure as has been obtained, pepsin is shown 
to be a colloid, differing from albumin in its reaction with nitric acid; it does not give the 
xanthoproteic reaction (yellow on heating), is not precipitated by acetic acid and potassium 
ferrocyanide, nor by tannic acid, mercuric chloride, silver nitrate or iodine. When in solu- 
tion its activity is destroyed by heat at temperatures above 1600 F. 
With reference to its mode of action, it may be said that the changes produced in 
bodies with which it comes in contact are not yet very clearly understood. The energy 
displayed by ferments in general has been happily compared by Dr. Roberts, as, in its 
nature, resembling the mode of motion displayed in the magnet, and which is capable of 
exciting a similar condition or molecular disturbance in other bodies subjected to its in- 
fluence. The action of the peptic ferment is entirely superficial. This is the natural re- 
sult of its being a colloid. It cannot permeate or infiltrate the substance to be acted 
upon, because albumin and foods containing albumin, such as eggs, meat and many vege-  21 
table matters, are, when cooked, in the nature of a septum analagous to parchment paper, 
into which the pepsin cannot readily penetrate or be absorbed; so that its work consists 
essentially in a wearing away of the surface. A better use should be made by the eater, of 
the knowledge that the action of pepsin is superficial. Increase the surface to be acted 
upon by thorough mastication or other methods. The advantage of increasing the surface 
of food to be exposed to the digestive fluids by proper comminution has long been 
recognized; in fact, in what may be called pre-scientific times. The grinding of grain, 
the chopping of meat, as in the case of sausages and hash, mashed potatoes, etc., are all 
a practical recognition of the necessity of dividing the food well, so as to enlarge the surface 
acted upon. 
The difference in the amount dissolved under the opposite conditions supposed can be 
happily illustrated by the process of dissolving rock candy in water. In two separate por- 
tions of water stir respectively an ounce of this form of sugar in lumps and an equal amount 
in powder. The results convey an instructive lesson, applicable in ordinary nutrition in the 
use of digestive ferments and in testing them. 
As stated further on, the products of gastric digestion are complex, consisting in 
addition to undigested food, of syntonin, or acid albumin, and various peptones. 
Considering the manufacture of pepsin, we have gradually advanced from its prepara- 
tion in the crudest form, by scraping and drying the mucus from the inner lining membrane 
of the animal stomach, to products which are entirely soluble, nearly odorless, permanent 
and extremely active. Various pepsins were here shown to illustrate the progress made 
in purity, digestive power, freedom from odor, and other sensible properties, while some 
of the tests showed that a degree of activity had been reached enabling 2000 parts of 
coagulated albumin to be digested by one part of dry pepsin. The superiority of the 
present processes of manufacture depends upon a previous solution of the pepsin in a 
feebly acid liquid, and its purification from contaminations, such as mucus, by appro- 
priate means. To Scheffer is due the credit of first practically developing this improved 
method of manufacture. An extract from minced stomachs, by 1 per cent hydrochloric 
acid, was here subjected to filtration, with the result of obtaining a turbid liquid. The 
lecturer now showed how admirably purified talc was adapted to securing a perfectly clear 
filtrate. Ordinary commercial talc contains iron, which, as will be demonstrated later on, 
seriously impairs the proteolytic power of the product, hence the importance of using only 
the purified article. The separation of the crude pepsin, in the form of a magma, by salt in 
excess, was also shown. 
The testing of pepsin was next demonstrated with an exhibit of appropriate ap- 
paratus for examinations on a large scale. Particular stress is to be laid on an accurate 
and uniform division of properly coagulated albumin. If forced through a sieve of 30 
meshes to the linear inch with a spatula, it is obtained in a satisfactory stale of comminu- 
tion. On this point the Pharmacopoeia is not explicit, nor does the acidity of the test liquid 
therein specified approximate sufficiently to that of the gastric juice. The average amount 
of absolute hydrochloric add should not be over 0.2 to 0.3 per cent., whereas the pharma- 
copoeia! percentage is 0.48. 
In its application as a remedial agent prescribers have had to encounter many per- 
plexing questions. What should be the dose of pepsin ? When should it be administered ? 
What are its incompatibles ? These questions have to a large extent been solved. There 
is no doubt but that the prevalent doses of pepsin have been altogether too small and 
entirely disproportionate to the results expected. Owing to the improved methods of 
testing pepsin, we are now in a position to correctly indicate the dosage. 
The proper time for administering pepsin, under ordinary conditions, is from one 
to two hours after meals, when sufficient acid has been secreted to render it operative. 
If desirable to administer it immediately after meals it should be accompanied by lactic 
or hydrochloric acid. 
Lactic acid is now generally conceded to be produced from food matters, as it is not 
a constant constituent of the gastric juice. Hydrochloric acid, on the contrary, is uniformly 
present in health, being derived from the chlorides, and absent only in certain diseased con- 
ditions. This dissociation of the chlorides takes place in the pyloric glands. 
Concerning incompatibilities, quite a few of the commonly prescribed remedies exert 
an inhibitory effect. Apart from any possible action on the mucous membrane during 
digestion, when a decided nervous tension may be said to exist, certain medicinal agents 
interfere with the action of pepsin itself. Thus, mercuric chloride was shown, in the test 
submitted, to have interfered materially with the peptic power. Also ferric chloride notably 
decreased the amount of dissolved albumin. 
Alkaline substances, such as the bicarbonates, in combination with pepsin, are 
immediately destructive to it in the presence of water. If pepsin be first treated with sodium bicarbonate and the solution afterward acidified it will be found to have lost its 
digestive power. 
From what has been said it is easy to infer the proper time for administration of 
medicinal agents known to have an inhibitory effect. They should be given only when 
gastric digestion is well under way or nearly completed. 
Considering finally the pancreatic secretion, we find it composed of a number of dis- 
tinct ferments active in an alkaline medium and capable of disposing of or converting 
not only amylaceous and albuminous food, but having also an action on fatty substances by 
which the latter are rendered easy of absorption. 
Amylopsin promptly converts starch paste into glucose and thus supplements the 
action of the salivary ferment; trypsin, capable of acting on proteids, ranks in import- 
ance with pepsin itself, and the products of its proteolytic action, peptones, deserve an es- 
pecial consideration. 
Peptic digestion usually results in an incomplete conversion of proteids into pep- 
tones. Syntonin or acid-albumin (bearing about the same relation to albumin that dextrin 
does to starch), is almost always present in the final gastric tssue. and the provision for 
its ultimate conversion to peptone exists in the presence and action of trypsin itself. 
A very servicable application of pancreatin is in the preparation of predigested 
foods—that is, foods capable of immediate assimilation, and in which the proteids and 
starchy matters are presented as peptones and glucose. 
As an illustration, we may take peptonized milk, prepared by warming a pint of milk 
with 4 ounces of water, 5 grains of pancreatin and twenty grains of sodium bicarbonate, for 
half an hour, at a temperature of about 120° F. 
The occurrence of a slight bitter taste offers a sufficient indication of the proper 
time to end the process. Pancreatin is preferable to pepsin for this purpose, because 
the letter always results in causing a degree of bitterness verging on the unpalatable. 
Pancreatin should be administered shortly before a meal, if it is desired to 
obviate its possible contact with, or exposure to, the gastric juice. In contact with acid 
and pepsin—a condition it must at certain times encounter in the stomach—it is de- 
stroyed. 
Peptones show interesting reactions. They are not coagulated by heat or by nitric 
acid. The latter, however, when aided by heat, produces what is known as the xantho- 
proteic reaction. This color reaction is undoubtedly familiar to every one whose fingers 
have been stained by strong nitric acid, and where ammonia, the neutralizer, has heightened 
the effect. 
A recent application of pepsin and pancreatin in the removal of diphtheritic and 
croupous membranes has resulted from the perfection attained in the quality of the digest- 
ive ferments. 
The membranes or false tissues are dissolved, just as would be the case with meat or 
fibrin. Pancreatin in an alkaline solution, and pepsin in an acid liquid, both of liberal 
strength, have been used with marked success. 
[FROM THE MEDICAL AGE, FEB. IX, 1889.] 
NOTE ON PEPSIN IN DIPHTHERIA. 
DR. A. C. WILKINS, OSKALOOSA, lOWA. 
Patient, young man; 30 years of age. He was attacked with malignant form of diph- 
theria, engrafted upon an old catarrh. 
The membrane covered the entire fauces, was thick, ash colored, and leathery; it was 
completely dissolved or digested by P., D. & Co’s pepsinum purum pulvis in twelve hours 
time. 
The catalytic changes commenced almost immediately after the pepsin was applied, it 
being used in an insufflator. 
I have used the pepsin in a number of cases with equally good results. 
I claim that by dissolving the membrane with pure powdered pepsin that reabsorption 
and contamination of the system, of the diphtheritic poison is prevented. 
The pepsinum purum pulvis, on account of its higher digestive power, its solubility, 
its pasty and adhesive properties, when brought in contact with a moist or dampened surface, 
gives it an advantage over every other form or make of pepsin, for dissolving diphtheritic 
membrane. It may be blown through a tube or quill. (Reprinted from Druggists’ Bulletin, Sept. 1888.] 
Comparative Pepsin ‘Testing.* 
F. A. THOMPSON, Ph. C. 
Pepsin is a drug which is conceded to be one of the most important of our materia 
mcdica, and it is with a view to determining the true and relative value of the various 
makes in use that I present this paper in as concise a form as possible, on the subject of 
comparative pepsin testing. 
Reviewing the tests laid down in the different pharmacopoeias and in the recent issue 
of the National Formulary, I find a great variance in the conditions, as can readily be seen 
at a glance, in the schedule given below. The three Pharmacopoeia tests may be criticised 
on the point that an excess of acid is used, i. e., far more than in the gastric juice. 
It is not my intention to criticise the value of these various official tests, as they are 
intended only for the purpose of determining whether a pepsin is above or below the require- 
ment of that test; but I hope to show that the usual application of any one of these tests in 
determining the comparative proteolytic action of various pepsins, gives fallacious results. 
The prevailing rule in making comparative tests of pepsin, is to use the same amount 
of albumen, water, acid and pepsin, all being subjected to the same temperature and treat- 
ment during a like period of digestion. This apparently prescribes like conditions, but 
here comes in the fallacy, for the conditions so soon become unlike during the test, that the 
comparative result is vitiated. 
SCHEDULE OF VARIOUS TESTS. 
Tests. 
Parts of water 
to one part 
of albumen. 
Percentage of 
absolute HC1. 
Period of 
Digestion. 
T emperature— 
Farenheit 
(Celsius). 
Treatment 
during 
Digestion. 
Requirements 
for one part of 
pepsin. 
Condition of 
Albumen. 
U. S. P. 
r88o. 
IO 
<M7 
S to 6 hours. 
ioo° to 104° F. 
(38° to 400.) 
Should digest 
at least 50 parts. 
Brit. Ph. 
1885- 
4-5 
O.38 
30 minutes. 
i3o«. 
(54.4°.J 
Well 
stirred. 
Will dissolve 
50 parts. 
Albumen 
through a 
wire gauze 
of 36 meshes. 
Germ. 
Ph. 
18S*. 
>5 
O.4O 
5 to 6 hours. 
104* 
(4°*-) 
Often and 
violently 
shaken. 
Dissolves 100 
parts to an 
opalescent 
solution. 
Albumen in 
pieces the 
size of a 
lentil. 
Natn’l 
Form’y 
1888. 
IO 
0.16 
60 minutes. 
125°. 
(5i.«°.) 
Shaken 
well at in- 
tervals of 
5 minutes. 
To dissolve 500 
parts, which is 
% the amount 
taken. 
Through a 
No. 36 hair 
sieve. 
Author’s 
Modified 
U. S. P. 
IO 
0.30 
6 hours. 
Constant at 
104°. (40° ). 
Constant 
and 
uniform 
stirring. 
Shall promptly 
digest the 
amount taken. 
Albumen 
through a 
No. 30 brass 
sieve. 
*Read before the American Pharmaceutical Association, Detroit, September, 1888. The usual result of such a test is that one brand has nearly or completely digested the 
entire amount of albumen taken, and the rest have only digested various fractions of the 
amount of albumen originally taken, which shows that the pepsins have a different proteo, 
lytic action, but does not represent the true comparative action of the various digestive ferments. 
The fallacy of such a test lies in the fact that the conditions are not the same 
when one pepsin completely digests the total albumen subjected and the others digest only 
fractions of the same. For the action of pepsin being only superficial, the weaker pepsins 
soon have more surface of albumen to act on than the stronger, and therefore show better 
than they should. The reasons for this reside in the fact that an increase in the proportion 
of albumen to that of pepsin increases its digestive power as the surface of albumen has 
been increased. 
I claim that the only proper way to determine the true comparative proteolytic action 
of pepsins, is to take sufficient of each pepsin to completely digest the same amount of albumen 
under exactly like conditions, or use sufficient of each to digest the same per cent, of the total 
albumen taken. In testing pepsins, we cannot accept that there is as much ferment in one 
grain of one product as there is in the same amount of another, so the only correct way is to 
take for a basis of calculation, what a pepsin of high digestive power can do in a given time, 
and call this for convenience, too per cent., and then determine by comparative assays, how 
many grains of the other makes under examination, it requires to do the same amount of 
work or completely digest the amount of albumen taken, stating the results in per cent. 
This can be explained in a simple way, for example, (A) by digesting 5 grains of one 
pepsin with 500 grains of egg albumen in ir fluidounces of acidulated water, containing 0.3 
per cent, of absolute hydrochloric acid, and 5 grains of another sample subjected to like 
conditions for an hour. At the end of this time we find that the former sample has completely 
digested the-albumen taken, while the latter has failed to dissolve completely the albumen taken, 
or about go percent, upon weighing the residue, showing that there is a difference by this test- 
in their digestive power. Example (B). Now, if 3 grains of the former and 5 grains of the 
latter are taken and subjected to the same conditions as the foregoing, if it be found that at the 
end of an hour and a half, that both samples have nearly completely dissolved the entire 
albumen, it indicates that there must have been as much active ferment in j» grains of ike 
former as there is in g grains of the latter, and calculating this out in per cent., we would say 
that the latter contained or 60per cent, as much ferment as the former sample. 
By experiment (C) I wish to show how dissimilar results in digestive power can be 
obtained from the same pepsin. If one part of a pepsin of high digestive power, such as 
possessed by the one experimented with, is allowed to act upon 2000 (x), 2500 (2), 3000 (3), 
4000 (4) parts of albumen for six hours by modified U. S. P. test, (see schedule) it is found 
that the 2000 grains have been completely digested, and weighing the residue in the others, 
No. 2has digested 2400 parts; No. 3, over 2700 parts and No. 4, fully 3400 times its weight of 
albumen in the same length of time. Now we have four digestive powers ranging from 
2000 to 3400, and which one of these are we to accept as the true digestive power of this 
sample? 
Why are such different results obtained by this test ? The reasons are that in all 
above the 1:2000, there has been different percents, of excess of albumen exposed to the 
action of the ferment, and as an increase of the proportion of albumen to the pepsin in- 
creases the digestive power, the cause of the above results is easily explained. 
If the results of the foregoing experiment are compared optically with those we have 
when comparing various pepsins by an official test, and also with the florid advertisements 
in the form of photographs which are intended to show the comparative strength of various 
pepsins, the similarity is very striking, and illustrates the principle that the weaker pepsins 
have an advantage over the stronger in having an excess of albumen to act upon, in propor- tion to the actual amount of ferment contained in them, otherwise they would have com- 
pletely digested as much as the stronger sample. 
In testing pepsins, the change of temperature and amount of stirring during digestion 
being important to reach any uniformity of results from day to day, I have used an im- 
proved apparatus, devised to give a constant temperature and fairly uniform stirring, a de- 
scription of which I give, as stated by Chas. E. Parker, Ph. C., in the “Druggists’ Bul- 
letin” of May, 1888. 
APPARATUS FOR TESTING PEPSIN. 
The apparatus consists of a water bath with an attachment for agitating the mix- 
ture under examination. 
The water bath is constructed to receive twelve large test tubes (5 ozs), in which are 
placed the mixtures for artificial digestion. The heat of the water bath is maintained with- 
in half a degree of constancy by a Reichert thermo-regulator automatically controlling the 
gas supply. A thermometer is inserted in the bath to indicate the temperature. Over the cover of the bath is balanced a rocking frame to which twelve glass rods are 
suspended, in sets of six, so that they have an equal up and down motion of about two 
inches. These rods hang in the test tubes when in position, and each has secured to it by 
friction two discs of thick sheet rubber a little smaller than the tubes, one being at the 
lower end, the other two inches above it. The stirring is effected by the motion of the 
rods and discs. 
The rocking frame is actuated by a motor which should be placed in the sink 
and is connected by a stiff rod to a side arm on the rocking frame. This motor is a 
simple device of two triangular cups united, turning upon pivots at the lower angle. It 
is placed centrally under a water tap so that when full the weight of water tilts the 
upper cup over and discharges its contents, at the same time bringing the other cup up- 
right under the tap in a position to be filled. Thus a jerky reciprocating motion is ob- 
tained which is conveyed by the rod attached to the side arm. 
The frequency of its action is regulated by adjusting the water tap. It may be 
made to rock constantly or at intervals of several minutes. 
It should be adjusted to act so often that a new impulse is given to the discs be- 
fore the albumen has subsided after the previous motion. 
This simple and cheap little motor may .be useful in pharmaceutical operations 
where a uniform motion is not indispensable; it is, however, rather too sudden and violent 
for stirring during evaporation. [from the medical AGE, JAN. 25, 1889.] 
COMPARATIVE ACTIVITY OF PEPSINS. 
F. A. THOMPSON, PH. C.. DETROIT, MICH. 
Probably during the past few years, no subject has received more attention from 
prominent chemists than pepsin, which carries force as an argument that it is one of the 
leading drugs of our materia. In presenting this subject it would seem almost certain 
that it must be more or less a resume of what has already been written, but it is hoped 
that the reader, especially the physician, may find something of interest and worthy of 
some consideration. 
The present era is rapidly conceding the importance of having galenical prepara- 
tions of a certain definite strength, based on the amount of active principle, e.g., 
atropine in belladonna leaves, and now let us ask, is it not just as essential that we should 
know the activity of the pepsins in use, based on a similar standard? 
The greatest difficulty to overcome, in adopting a standard for pepsins, is the 
selection of a test that will give impartial and more uniform results. It is a well 
known fact to those familiar with the examining of pepsins, that the various 
official tests, as well as those prescribed for some special brands, give entirely un- 
like conditions and consequently discordant dissolving powers for the same sample of 
pepsin. 
This is certainly an embarrassing fact to face the practicing physician who is always 
anxious to prescribe the best medicines attainable. What we sadly need, is a test or a rule 
that can be applied to any test, which will give approximately the comparative dissolving 
powers, the conditions being equal. 
Many chemists have experimented for some time past, with a view of discovering 
a practical and reliable method of determining quantitatively the amount of peptone formed, 
and it is to be regretted that none satisfactory has been found, as it is without doubt the 
true constituent by which to judge the value of a pepsin. It seems highly probable then, 
that we must be content for the present with the comparative dissolving powers for a 
guide, and to the writer this does not mean the usual method of testing, when the same 
amounts of albumen, acid, water, and pepsin are used but when modified or subjected to the 
following rule:* “ Take sufficient of each pepsin to completely dissolve the same amounts 
of albumen under exactly like conditions, or sufficient of each to dissolve the same per cent, 
of the total albumens taken.” 
The official as well as other tests are satisfactory to determine whether a brand is 
above or below its respective requirement or claim, but as we now have products far 
above the requirements of the official standards, especially the pharmacopoeia test for 
saccharated, it would seem desirable that we have some means of determining the true 
value of these superior products, and to this end I would earnestly request that the reader 
try the application of the above rule, and compare the results with the usual way of testing, 
other conditions being equal. 
I hold that the above rule is applicable to any test, whether official or not, the 
only requirements necessary, are, that the conditions and treatment during the time of 
digestion shall be the same for each container. I do not wish to be understood that 
the application of the above rule to two unlike tests will give the same dissolving power, 
even for the same sample, but, that it will give the same relative value of two or more 
products. As, for example, if two are capable of just completely dissolving 2,000 and 
1,200 grains respectively, by a six-hour test, they also will be found capable of completely 
dissolving about 165 and 100 grains respectively by a one-hour test, other conditions be- 
ing the same. 
The reasons for using various amounts of pepsins, are that we can’t accept that 
there is as much active ferment (or active principle) in one grain of one product as there 
is in the same quantity of another; second, that pepsins act entirely superficially, so the 
more surface of albumen exposed the more the same amount dissolves; third, that the 
ferment is not destroyed by dissolving albumen, and consequently dissolves more rapidly 
in the first than in the last stage of the test. After carefully considering these points, it 
certainly must seem obvious why different amounts of various pepsins should be used to 
* From paper on “ Comparative Pepsin Testing,” by the writer, read before the A. P. A.. September, 
188 S. dissolve exactly like amounts of albumen, if we wish to give each one an impartial basis 
to establish its peptic value. 
In my experience in pepsin testing, I have never found it practical or satisfactory, 
and often impossible, to try to estimate the amount of undissolved albumen, by filtering, 
drying and weighing the residue. When a solution, containing partially dissolved par- 
ticles of albumen, is thrown upon finely scraped asbestos, in a Goosch filter, attached to 
a strong filtering pump, it will immediately become clogged by these particles, and 
further filtration rendered impossible, at least so slow as to be practically useless. For this 
reason I have never been able to use the test given by the new National Formulary. I 
have, however, estimated the amount of undissolved egg-albumen, by immersing the con- 
tainer or tube in cold water (40° to 50° F.) and removing the supernatant fluid by de- 
cantation, but as this requires a day or two to complete, I considered it impracticable; 
therefore, 'I have always taken a complete solution of the albumen as a basis or standard 
requirement. It is also desirable in pepsin examinations to use a standard for control, 
as I have sometimes experienced mysterious results, which I could not account for, and 
might have accepted the results as satisfactory, if I had omitted my standard, which acts 
as a check. I might add here that I am disposed to believe that the nearest pure 
pepsins I have handled deteriorate after some time, and, therefore, one must closely 
watch their standard. 
For convenience of computing, I selected from the many samples I have examined, 
the one having the highest digestive power (sample number 1 in table) and called it a 100 
per cent, pepsin, which does not mean that it is absolute, as such a product is unknown. 
Then by repeated assays, I ascertained how much of the other samples it required to 
completely dissolve the same amount albumen as the standard, under the same conditions, 
and from this calculated the per cent, of active ferment. 
In conjunction with these notes I have decided to publish in tabular form the com- 
parative activity of the leading brands found in the market, the results being based on the 
foregoing. 
This summary represents six scale and four powdered products arranged in accord- 
ance with dissolving powers. 
As previously stated, I have also used a standard on the basis of too per cent, which 
was a soluble pepsin in large scales and possessing a high digestive power. I would beg to 
add here in justice to the manufacturers of this highly potent product that it was made by 
Parke, Davis & Co. and known under the name of pepsinutn purum in lamellis. 
In reviewing the table one finds a great difference in activity and that some do what 
is claimed, while others come far from it, when subjected to a comparative test. 
The various strengths stated are based on repeated assays, conducted in a most care- 
ful and satisfactory manner by the use of an improved pepsin tester* and the following gen- 
eral rule which can be modified to suit the convenience of the experimenter but without 
changing the conditions of test. 
Preliminary Test; Boil the eggs 15 minutes, cool, and after removing all the yolk 
and superficial moisture, press the coagulated albumen through a No. 30 brass sieve by 
means of a stiff spatula. After thoroughly mixing the finely divided albumen. 10 grams are 
carefully weighed out and transferred to a medium sized mortar; then 95 c. c. of distilled 
water previously warmed to about ioo° F., are measured out and small portions added to the 
albumen in the mortar and the mixture carefully triturated to ensure uniform division of the 
particles and finally transferred by means of the remaining water to a large test tube (capa- 
city about 130 c. c.) having a flat bottom. Add sc.c. of 6 per cent, hydrochloric acid (s. g, 
1.0296 at 590 F.) and place the tube in the water bath and when the temperature reaches 104° 
F. (40° C.) various amounts of the pepsin under examination are added and the mixture sub- 
jected to a constant temperature and fairly uniform shaking for six hours. When examining 
soluble pepsins I have found it more convenient to make a solution of definite strength sub- 
stracting the amount of pepsin solution taken from the amount of water added to each tube. 
After digesting the required time, the tubes are removed, filled with ice cold distilled water, 
immersed in very cold running water, and after one-half hour they are taken out and placed 
in a suitable rack in order of their digestive power, i. <r.,.from the lowest to the highest pro- 
portions. 
• Druggists’ Bulletin, May, 1888. SUMMARY OF COMPARATIVE PEPSIN EXAMINATIONS. 
Number. 
PHYSICAL PROPERTIES. 
CLAIMS FOR ACTIVITY ON THE LABELS. 
ACTUAL 
(compara- 
tive.) 
DISSOLVING 
POWER OF 
ONE GRAIN. 
COMPARA- 
TIVE 
VALUE 
REPRESENT- 
ED IN 
PER CENT, 
I. 
Semi-transparent, permanent scales, readily 
soluble and free from objectionable odor 
or taste. 
Will completely dissolve 2,000 times its 
weight of albumen in 6 hours. 
2000 grains. 
100 per cent. 
2. 
Opaque, amber scales, putrefactive odor 
and comparatively insoluble. 
Will dissolve 1,000 grains in 4 hours 
1200 U 
60 “ 
3- 
Yellowish scales, strong putrefactive odor 
and exceedingly hygroscopic. 
Will dissolve 700 to i,coc grains in a 
few hours. 
IOOO U 
5° 
4- 
A permanent sparingly soluble, gray pow- 
der, and quite odorless and almost taste- 
less. 
Will dissolve 1,000 to 1,450 grains in 
4 to 6 hours. 
750 “ 
37-5 “ 
5- 
A light colored, permanent powder, largely 
soluble. 
Unequalled in digestive power. 
35° “ 
17-5 “ ' 
6. 
Soluble amber colored scales, nearly odor- 
less, but very hygroscopic. 
A potent and speedy solvent of al- 
bumen. 
25O “ 
12*5 “ 
7- 
Permanent, readily soluble and almost 
colorless scales 
200 U 
10 “ 
8. 
Permanent, grayish and soluble powder; 
odor suggestive of lactated compounds. 
Will dissolve 250 to 450 grains raw 
beef in 6 hours. 
200 “ 
10 '* 
9- 
A soluble grayish powder; odor suggestive 
of lactated compounds. 
None on activity. 
200 U 
10 “ 
JO. 
Almost transparent, soluble scales quite 
free from odor and permanent. 
Will dissolve 555 to 600 parts of al- 
bumen speedily. 
5° “ 
2.5 “ 
The tube found next in order to the last one free from albumen, is accepted as near 
the true dissolving power of the sample. 
After making the preliminary test, a second or more accurate one must be made, 
i. e., under the same conditions and treatment, but using amounts of pepsin, nearer the pro- 
portion found in the preliminary test, reading the results in a similar manner, which will in- 
dicate the amount of albumen the sample is capable of completely dissolving. 
Dec. 1888. 
PEDIATRIC POINTS AND PICKINGS. 
Among some interesting notes on the treatment of diseases of children which Dr. 
I. N. Love, of St. Louis, has grouped under the above heading,in the Weekly Medical Review, 
Jan. 26, 1889, p. Q7, is the following on pepsin in diphtheria; 
The application of pepsin to digest away the membrane in diphtheria and membranous 
croup is not new, and is more or less commended and resorted to by physicians in the treat- 
ment of these diseases. 
Naturally, however, its utility depends entirely upon its digestive activity, and on 
account of the many preparations of pepsin of feeble or no digestive power heretofore at 
the disposal of physicians the results obtained have been in some cases discouraging. 
As to the value of pepsin, however, in these affections, when of proper purity and 
strength, there can be no question. We believe that the recent improvements in pepsin, 
securing greater purity, strength and permanence (we allude to the pepsinum purum in 
lamellis of Parke, Davis & C 0.,) will lead to its extensive use in diphtheria and membran- 
ous croup, maladies now attended with such grave results even when combatted by the 
most expert medical care. [from the druggists’ bulletin, dec., i 883.] 
PEPSIN AND ITS CONGENERS.* 
J. LE ROY WEBBER, PH. G. 
Gentlemen: The digestive ferments are now so extensively employed, and with 
such acknowledged benefit in the treatment of disease, that their, study is well worthy of 
your attention. 
The term ferments seems to have been unfortunately or unhappily chosen to 
designate this class of bodies and is frequently misleading to the student. This arises 
from the fact that our usual conceptions of fermentation are connected with some such sub- 
stance as yeast and physical phenomena attended with the disengagement of gas and a split- 
ting up of sugar into alcohol and other bodies. In science, however, the word ferments has 
come to cover a class of Substances which exercise merely an action designated by some as 
catalytic, meaning that they produce certain changes simply by their contact or presence, 
without themselves undergoing any notable change. 
Regarding the mode of action of pepsin and unorganized ferments generally, a 
very beautiful comparison has been employed by Dr. Wm. Roberts. I consider it a 
much happier illustration than referring it to catalysis and will here quote from his 
work: 
“The digestive ferments are all the direct products of living cells, and may be 
regarded as the repositories of cell-force. They are quite unknown in the domain of 
ordinary chemistry. Their mode of action bears no resemblance to that of ordinanr 
chemical affinity, and has a distinctly physiological character. They do not derive their 
marvellous endowments from their material substance. They give nothing material to, 
and take nothing material from, the substance acted on. The albuminoid matter which 
constitutes their mass is evidently no more than the material substratum of a special 
kind of energy—just as the steel of a magnet is the material substratum of the magnetic 
energy—but is not itself that energy. This albuminoid matter of the ferment may be said to 
become charged at the moment of elaboration by the gland-cells, with potential energy of a 
special kind—in the same way that a piece of steel becomes charged with magnetism by 
contact with a preexisting magnet. The potential energy of the ferment is changed into 
the active form (i. e., becomes kinetic) when it is brought into contact with the alimentary 
substance on which it is designed to act.” 
Unorganized ferments are distributed very widely throughout the vegetable and 
animal kingdoms, and, while acting on the utmost variety of organic substances, their chief 
function appears to be the conversion of insoluble matters into soluble forms in which they 
are capable of assimilation. 
Thus the plant converts, by appropriate ferments, its store of starch into soluble 
glucose, which can then be readily transported to the point where it is needed for cell 
growth or tissue elaboration. These ferments, while adapted to certain purposes, and con- 
ducive to the welfare of the plant, do not always affect the human organism in a kindly 
manner. Thus many fruits, tubers, roots, barks, cereals, etc., contain a lactic or other 
ferment which is often capable of producing injurious effects when the substances containing 
it are partaken of in an uncooked condition. 
A noteworthy point of dissimilarity between the greater part of the vegetable kingdom 
and animals is, that in the former we find, in opposition to the law of gravitation, and 
by means of capillary attraction, osmosis and evaporation, the juice or sap is drawn in an 
upward direction from its first source, the earth; while in animals, on the contrary, the food 
is usually elevated first, and in obedience to the natural law pursues a downward course. 
What happens in this downward course, and at the way stations, it will be my task to 
explain to the best of my ability, and consistently with our present knowledge of the subject. 
Now, gentlemen, it will be well for us to consider the action of unorganized fer- 
ments without reference to any connection or interference of any vital force with these pro- 
cesses. I am justified in saying that these processes are largely mechanical and physical. 
They hardly deserve the term of chemical actions, being rather of a quasi-chemical nature. 
* A lecture delivered on invitation before the faculty and students of the Detroit Medical College, 
Dec. sth, 1888, Reported especially for The Druggists’ Bulletin by H. F. Meier. To begin, then, with a consideration of the operations taking place in the alimentary 
canal, we first must consider the action of the saliva. This fluid contains a ferment named 
ptyalin, very similar to the diastase of vegetables, which is concerned chiefly in a prepara- 
tory conversion of starchy matters. This ptyalin is most active in feebly alkaline media; 
and, indeed, the healthy human saliva has a feebly alkaline reaction. That the action of 
ptyalin is in general only transient and incomplete, must be evident when we consider that 
it is destroyed in the gastric juice. The work thus begun and arrested is, however, com- 
pleted by ferments derived from the pancreatic glands, which we will consider later on. 
We will now take up the question of pepsin, which merits our careful investigation. 
The gastric juice contains in reality two distinct ferments, one of which curdles the 
casein of milk, as I have here shown you by adding a small quantity of pepsin solution to 
warmed milk; and the other has the more important property and power of converting into 
soluble forms such food-matters as fibrin, albumin, and albuminoids generally. As these are 
classified as proteids, the term proteolytic action has been applied to both this effect of 
pepsin and also to a similar effect of trypsin, one of the pancreatic ferments. 
I have here a number of flasks in which the solvent and digestive action of pepsin is 
illustrated, showing also the interfering effects on digestion, of various medicinal agents 
which are very commonly prescribed. Here is also a control-flask for the purpose of com- 
parison. In each one we have too c. c. of water containing 3-10 per cent, of hydrochloric 
acid (absolute),* to which I have added 10.0 grams of albumen and 5 milligrams of pure 
pepsin. They have been digested for a period of six hours at a temperature of 1040 F 
(40° C.). 
Before going further I wish to direct your attention to the preparation and treatment 
of the albumen. Sound, fresh eggs have been boiled for 15 minutes, placed in cold water, 
and, after being wiped dry from superficial or exuded moisture, the albumen is forced, by 
means of a spatula, through a sieve having 30 meshes to the linear inch. This insures a 
uniform subdivision of the albumen. A few explanatory words about the purity of the 
pepsin itself may not be amiss. We have never yet been able to obtain pepsin as a distinct 
principle in a state of absolute purity; and, indeed, the same may be said about ferments 
generally. They are all contaminated, in a greater or less degree, with substances which 
are themselves inert, but present almost insurmountable difficulties of separation, since the 
ferments themselves are exceedingly delicate and unstable, and do not bear rough handling 
as would occur in the interaction of ordinary chemicals. 
In the case of the pepsin here employed, a high degree of purity has been attained 
as is evidenced by its behavior in the control flask, where it has dissolved and partially 
converted into peptone 2000 times its weight of coagulated albumen. It is capable, 
indeed, of doing more than this under favorable conditions. These conditions it 
is well to understand and apply, particularly in the testing of pepsins. I have 
here repeated parallel experiments, first made by Prof. Baden Benger, and which 
demonstrate two important points; First, that the action of pepsin is entirely super- 
ficial; and secondly, that the amount of syntonin and peptone formed is largely depend- 
ent on the amount of albumen present, whether this be in excess or not, that is, as pro- 
portioned to the pepsin used. In these two flasks we have respectively 100 grains and 
1000 grains coagulated albumen, the acidulated liquid (5 ozs.) containing besides in each 
case exactly grain pepsin; while in the too grain flask the albumen is just entirely 
dissolved, a comparison of the other with a control flask containing merely the albumen 
with acidulated water (minus pepsin) shows that a much larger quantity of the albumen 
has dissolved, as is demonstrable to the eye alone. Were Ito weigh the undissolved 
residue of albumen I would undoubtedly get a result corroborative of Prof. Benger’s. In 
his case while 100 grains went into complete solution in one flask, the undissolved 
residue in the other weighed only 220 grains, showing 780 grains to have been 
dissolved. 
A practical application in dietetics may be made of this knowledge, as showing the 
importance and value, especially to enfeebled digestion, of proper comminution, whether 
this be performed by mastication or other means of subdivision, a matter which is too often 
neglected by the laity. 
I will next call your attention to the inhibitory effect exerted by several medicines 
and which must occur when they are administered at improper times, that is, immediately 
before, during, or too soon after a meal, before the digestive process can be con- 
sidered as fairly established and under way. To the contents of this flask, otherwise 
identical with the control, I have added x minim tincture of iron to the 100 c. c. The 
* Equivalent in round numbers to 1 per cent, of U. S. P, acid which contains 31.9 per cent. gas. amount of albumen undissolved will show you to what extent ferric chloride is capable of 
interfering with digestion. The next flask, instead of acidulated water, contains a one per 
cent, solution of sodium bicarbonate; here you see the pepsin is rendered incapable of 
accomplishing anything and the albumen is entirely undissolved. The moral of this ex- 
periment would therefore be unfavorable to the conjunction of pepsin and bicarbonate of 
sodium, which is quite a favorite prescription in infantile cases. A single experiment of 
this kind will convince the physician that such an association of pepsin with alkaline 
substances is irrational and destructive to the pepsin, as nature has intended and per- 
mitted it to act only in an acid medium. After the pepsin solution is once rendered 
alkaline, addition of hydrochloric acid fails to restore its activity. The next flask shows 
the inhibitory effect of mercuric chloride 1:5000. While this does not very seriously 
interfere, it nevertheless exerts some deleterious action. It may here be pointed out that 
most substances which rank high as antiseptics have also the property of delaying or 
seriously inhibiting the action of pepsin. 
In this last flask, I have perhaps the most important and interesting experiment, as it 
is a remedy which is almost universally employed. I have here, in addition to the usual 
ingredients, two grains of ammonio-citrate of bismuth. You will observe that the albumen is 
entirely dissolved, while the white turbidity is due to the formation of oxychloride of bis- 
muth from the soluble ammonio-citrate at the moment it is brought into contact with hydro- 
chloric acid. This action occurs, of course, also in the gastric juice. The albumen has 
here gone into solution because the bismuth salt has been brought into contact with the 
pepsin in an acid medium. Were this to take place, however, in a feebly alkaline solution, 
which is almost invariably the case in elixirs of bismuth and pepsin, the peptic power would 
be destroyed. Even in neutral solutions carefully prepared, the soluble bismuth salts, and, 
in general, the salts of the heavy metals, sooner or later, exert an injurious effect. The 
conclusion to be herefrom deduced would therefore be, to give the pepsin and bismuth 
separately, or else mix them in a feebly acid solution. The latter course always results, 
however, in an unsightly mixture. 
Now, a few remarks as to the general properties of pepsin and we will then consider 
the products formed during peptic digestion. Pepsin is a colloid and differs from albumen 
by not giving the yellow xanthoproteic reaction with nitric acid. In common with all other 
known ferments, it is a nitrogenized body, and putrescible under appropriate conditions; its 
tendency to putrefaction is enhanced by association with peptones, mucus and similar 
substances, which confer a hygroscopic character. Therefore caution should be exercised 
in the selection of pepsins, and the sense of smell may be depended upon as a guide in this 
particular. Any pepsin which presents an offensive odor, even though active, should, for 
prudential reasons, be rejected, as it is certainly unwise to ingest any substance in which 
the germs of decomposition are already rife, and which may possibly impart this propensity 
to food matters and food products in an enfeebled organism, where the secretions are 
defective and cannot exert the protective action provided in healthy conditions. 
We can justly make the following requirements of commercial pepsin: It should be 
light colored, practically free from odor, soluble in water, and be capable of demonstrating 
its activity in the digestion of albumen as described. As pepsin is itself freely and readily 
soluble in water, insoluble pepsin should be rejected as self-condemned, and consisting 
largely of foreign matters. 
The temperature at which pepsin is most active, or when it accomplishes its work in 
the shortest possible time, is 130° F. (54.50 C.), Like all ferments, it is destroyed com- 
pletely at temperatures much above a scalding heat. For pepsin, a temperature above 160° 
F. is sufficient. Alcohol, when in sufficient excess, precipitates it from its aqueous solution. 
The products of the action of pepsin upon proteids are various, according to the time 
and other conditions, being syntonin or acid-albumen, other intermediate grades (parapep- 
tones, etc.), and finally true peptones. 
True peptones are soluble in water, are not coagulated by heat, nor precipitated 
from aqueous solutions by boiling nitric acid. They give the yellow reaction with nitric 
acid, however, corresponding in this respect with albumen, and are precipitated by mercuric 
chloride from neutral and feebly acid solutions. 
In the digested fluids before us peptonization can be shown to be only partial; 
thus, if I neutralize a portion of the liquid with sodium bicarbonate solution a precipi- 
tate forms showing that syntonin or acid-albumen is still present. An excess of sodium 
bicarbonate redissolves it however. 
The next reaction is an important one and characteristic of peptones. It is known 
is the biuret-reaction. If to another portion of the fluid from the control flask I now 
add some solution of caustic soda, and then a small quantity of a weak cupric sulphate 
solution, you will notice the beautiful crimson coloration appearing, and which is plainly visible to you against this white back-ground. Fehling’s solution can be conveniently 
employed to produce this reaction. 
We will now consider the pancreatic secretion and its properties. This consists 
of a combination of four distinct ferments, which seem happily designed to supplement 
and complete the work left unfinished by the ferments of the saliva and stomach. The 
ferments are varied in their properties and offices. Thus we have: i. Amylopsin, similar 
in action to diastase, converting starch into dextrine and sugar. 2. A curdling ferment, 
acting upon milk in an analagous manner to rennet or the curdling ferment of gastric 
juice. 3. Trypsin, having powerful peptonizing properties; and, 4. Steapsin, known as the 
fat splitting or emulsifying ferment. I have here a very thick starch paste, made by 
boiling powdered starch with ten times its weight of water. You can see how speedily the 
starch is liquified as I now add a small quantity of powdered pancreatin. The liquefac- 
tion is succeeded in a very few minutes by gradual conversion of the starch into dextrin 
and glucose. I have here a series of jars containing very weak iodine water (about 1:25000). 
For some time we can obtain a distinct blue color reaction with the iodine water, char- 
acteristic of starch. As the conversion progresses, however, the blue coloration becomes 
feebler and feebler, finally being entirely absent. During the changes the violet-red colora- 
tion characteristic of dextrin succeeds to the blue of the starch, and when the conversion 
into glucose is complete, this also fails to make its appearance. 
Now, to demonstrate the presence of glucose in the liquid, which but a few minutes 
ago was merely a starch solution, I will make use of an extremely sensitive test, namely, 
a test tablet of indigo (soluble) with sodium carbonate. The demonstration of the pres- 
ence of glucose depends upon its property of deoxidizing the indigo, thus rendering it 
colorless by conversion into indigo-white. I will first heat the tube and contents (one 
indigo tablet and about two drachms of water) to the boiling point and introduce from 
the tip of this rod a single drop of the converted starch solution. I purposely avoid an 
excess of the sugar solution here so that you may perceive the gradual fading of the 
indigo solution as I hold it against this sheet of white paper. You will notice that I 
have avoided shaking the contents, in which case I would rein corporate oxygen by the 
admixture of air bubbles, and restore the blue color. Now that decoloration is complete, 
you can at once see the blue color reappear on shaking, and a repetition of the heating 
will again decolorize it, if I have sufficient unchanged glucose still present. Chemical 
agents which bleach the indigo by destructive changes, do not permit of the restoration 
of the color by re-oxidation. 
The ferment which is the chief constituent of the pancreatic juice and of paramount 
importance, trypsin, also acts to the best advantage in a slightly alkaline medium, the 
alkalinity of the intestinal secretions being considered as about equivalent to a one-per- 
cent. solution of sodium carbonate, the actual secretions of this tract being, however, of 
a complex nature and permitting also, eventually, of extraneous or putrefactive changes. 
A very instructive illustration of the promptness and vigor displayed in tryptic 
digestion is exhibited in the conversion or digestion of milk. I have here in this water- 
bath several bottles of milk which have been warmed to about 1150 F. On the addition 
of ten grains of sodium bicarbonate and ten grains of pure pancreatin dissolved in two 
ounces of water to eight ounces of milk, we can observe the digestion as it proceeds and watch 
its several stages by testing the liquid with nitric acid. At first this produces a copious 
precipitate, decreasing in amount rapidly as the action of the pancreatin progresses. 1 have 
purposely taken double the amount of pancreatin necessary, to hasten the operation. 
The soda and water have been added to prevent curdling, which would otherwise 
occur on the addition of pancreatin alone to pure milk, owing to the action of the second 
named ferment. 
As the digestion proceeds, you will soon be able to detect a very faint suggestion of 
a bitter taste, indicating the proper time to end the process, if we wish to use the pro- 
duct as an alimentary substance. This is, indeed, now predigested food, being virtually 
the peptone of casein with fats and salts of the milk unchanged. You will perceive how 
easy it is to prepare such food, which is often of the greatest service in extremely de- 
bilitated conditions, when it is advisable to relieve the fevered or weakened digestive 
organs of the patient or invalid of all unnecessary work. A thermometer is even un- 
necessary. If the milk employed be- first warmed to a little above blood heat, and after 
addition of pancreatin, soda and water, the bottle or vessel containing it be then placed 
in hot water to keep up the temperature, the appearance and taste may be noted as a 
reliable indication of the right moment to check the further action. This can be done 
by either boiling, which destroys the pancreatin, or by placing on ice, which simply in- 
hibits and yet permits of further action on other food matters, starchy, or of the albu- 
minous or proteid class. Chopped meat, oysters, biscuit, toast, etc., may likewise be predigested by the aid 
of pancrealin, and be made to furnish very palatable and nutritive articles of food for the 
invalid and convalescent. Pancreatin is always selected in the preparation of artificially 
digested food in preference to pepsin, owing to the fact that the latter gives rise to the 
formation of certain by-products which are of an exceedingly bitter, unpleasant taste. This 
taste can often be perceived during eructations from the stomach. 
I here apply, a chemical test, nitric acid, showing that the albumen has been converted 
into peptone, as no coagulation takes place; indeed, trypsin maybe said to be the peptonizer 
par excellence, being much superior in this respect to pepsin. It is a curious fact, however, 
that the properties of the two chief ferments of the pancreas are impaired by long contact 
with weak acids, and in the presence of pepsin and acid, pancreatin is itself digested and 
destroyed. 
Inasmuch as the action of the fat-splitting ferment is a tedious matter and rather 
difficult of demonstration, I must for the present forego its practical illustration; enough is, 
however, known about its action to assure us that the fatty matters are thereby notably 
comminuted or emulsified, and presented to the lacteals in a favorable mechanical state of 
division for absorption. 
As a consequence of the knowledge which has thus gradually been acquired by patient 
investigation, we are now in a condition to prescribe these remedies to the best advantage, 
both by means of a better knowledge of the quantities required, which can not be infinites- 
mal because the results are commensurate to the quantity employed, and also the time of 
administration. Pancreatin should be administered prior to a meal or before any acid fluids 
are secreted in the stomach, which might be prejudicial or destroy it, and pepsin either 
during or immediately after the ingestion of food, so that it can act thereon in an appro- 
priate menstruum. 
When used for the removal of diphtheritic membrane by swabbing, a strong solution 
of pepsin should be employed in an acid liquid (X8W per cent, hydrochloric acid), or a strong 
pancreatin solution, the latter always being prepared fresh and containing 2-per-cent, 
sodium bicarbonate. 
The method of insufflating the pure ferments in a powdered form is also highly 
recommended. 
As far as the classification of digestive ferments is concerned, while they are true 
remedial agents, they cannot with propriety be called drugs, being identical in properties 
and behavior with the normal secretions of the body.