WORKS
OF THE
CAVENDISH SOCIETY
FOUNDED 1846.
PHYSIOLOGICAL CHEMISTRY
BY
PROFESSOR C. G. LEHMANN
VOL. I.
TRANSLATED FROM THE SECOND EDITION
BY
GEORGE E. DAY, M.D., F.R.S.,
FELLOW OF THE BOYAL COLLEGE OF PHYSICIANS, AND PROFESSOR OF MEDICINE IN THK
UNIVERSITY OF ST. ANDREWS.
'
({ UNSVL
LONDON:
PRINTED FOR THE CAVENDISH SOCIETY,
BY
HARRISON AND SON, ST. MARTIN'S LANE.
MDCCCLI.
\
\
LIBRARY
G
TRANSLATOR'S PREFACE,
IN presenting Lehmann' s "Physiological Chemistry'5 to the
Members of the Cavendish Society, I feel that it would be super-
fluous to offer any remarks on the author's high reputation as a
general cultivator of chemical science ; to recapitulate his numerous
and important contributions to physiological chemistry ; or to refer
to the very favourable reception which this work has received in
Germany.
The first edition of this volume appeared in 1841, and the
second (from which this translation is executed) in the beginning
of last year.* If, during that interval, the progress of physiological
chemistry has been so rapid as to necessitate the entire remodelling
of the work (see p. vii), the shorter period that has elapsed since
the appearance of the second edition has been proportionally
fruitful in important discoveries. Need I advert to the detection
of succinic acid as a morbid product in the human organism, to
the later researches of Schwartz on hippuric acid and the hippu-~
rates, to the detection of hippuric acid in the blood of the ox, and
of oxalic acid in diseased human blood, to the discovery of hypo-
xanthine and inosite, or to Liebig's important memoir on the fibrin
of muscular fibre ?
As Professor Lehmann will probably append a supplement to
his third and concluding volume, so as to embrace a notice of the
discoveries which have been made during the progress of publica-
tion, I have abstained from anything beyond the very briefest
enunciation of any of these recently discovered facts, and have
frequently contented myself with a mere reference to the original
source of information.
I have deemed it advisable not to interfere with the thermo-
metric scale, weights, and measures, that are now almost univer-
sally adopted on the Continent. Degrees of temperature in this
work are always expressed in the centigrade scale, but at page xii,
* Lehrbuch der physiologischen Chemie. Von Prof. Dr. C. G. Lehmann.
Erster Band. Zweite ganzlich neu umgearbeitete Auflage. Leipzig, Verlag von
Wilhelm Engelmann. 1850.
b
.84604
vi TRANSLATOR'S PREFACE.
the reader will find a table by which he can, at a glance,
discover the degrees, according to Fahrenheit, corresponding
with every temperature referred to in this volume. The
gramme has now become a recognised standard weight in all our
laboratories ; in all the cases where it occurs in this work, sufficient
accuracy will be attained if we regard it as equal to fifteen grains
and a half.
The author, in his foot-notes, very commonly refers to German
translations or abstracts of French and English Memoirs; in
almost every case I have given the corresponding reference to
the original source. His numerous references to Dr. Golding
Bird's researches are made to Eckstein's translation of a Course
of Lectures by that gentleman, which appeared nine years ago in
the " Medical Gazette/' and I have deemed it expedient slightly
to modify a few sentences in the text, which express views some-
what different from those given in the third edition of the
" Urinary Deposits."
If, in a few cases, I have ventured to deviate from the ordinary
nomenclature,* I have not done so without due consideration, and
without the sanction of the most competent judges.
I cannot allow these pages to leave my hands without express-
ing my general obligation to the Council of the Cavendish Society
for the readiness with which they accepted my suggestion, that
a translation of Lehmann's " Physiological Chemistry " should
appear under their auspices, and for entrusting me with the office
of Editor. To Professor Graham, Dr. Hofmann, Mr. Redwood, and
Dr. Pereira, I am specially indebted, for much kind aid and many
valuable suggestions.
G. E. D.
ST. ANDREWS,
July 9th, 1851.
* I have, as a general rule, adopted the final syllable ine, both for the true
alkaloids, and for those allied substances which are described in the same section,
but do not present any very distinct basic characters, as, for example, creatine,
allantoine, and cystine. The terminal in refers to neutral bodies, as, for instance,
asparagin. I have felt considerable difficulty in the nomenclature of the acids :
most commonly I have converted the German antepenultimate in into ic ; thus,
Inosins'dure is translated inosic acid (except by inadvertence in p. 50), Vaccins'dure,
vaccic acid, &c.
AUTHOR'S PREFACE.
SINCE the publication of the first edition of this work, Che-
mistry— and more especially Physiological Chemistry — has been
so zealously and extensively cultivated, and has been enriched by
the acquisition of so large a mass of new facts and discoveries, that
we may regard the last ten years as one of the most important
periods in the history of this science. Hence a simple enlarge-
ment of the earlier edition would not have enabled us to consider
all the advances made within this short period, which rather
required that the whole work should be entirely remodelled, both
in relation to its form and contents. The most superficial compa-
rison of the two editions will suffice to show that this volume has
been subjected to so entirely new a mode of arrangement, that only
a few paragraphs have been borrowed from the earlier edition ; for
thus alone could a faithful representation of the present state of
this department of chemistry be afforded.
The rapid advance of science and the extraordinary accumu-
lation of a mass of crude materials, some of which may not even
be capable of acquiring form, must plead in extenuation of the
delay that has attended the publication of the second volume.
There are, however, two causes which render this delay in some
degree pardonable. The one depends upon the intimate connexion
of the objects under consideration with histology, the history of
development, and pathological anatomy ; and as the censure,
which has more or less justly been thrown on the writers on
physiological chemistry, may be traced to ignorance or neglect
of the kindred branches of science, the author has endeavoured
to fit himself for the task of critically reviewing the labours of
others, by acquainting himself, through personal observation and
experience, with the grounds on which these departments of
science are based. The great mass of voluminous and often
Vlll PREFACE.
obscure materials presented by physiological and pathological histo-
logy must necessarily be subjected to a critical examination before
they can be incorporated with physiological chemistry, and hence
the author regards such a course of self-training as indispensable
in the attempt to furnish his readers with a systematic arrange-
ment of facts. Moreover, those departments of science which
must serve as a basis to physiological chemistry, have been encum-
bered with an accumulated mass of observations, from which have
arisen numerous hypotheses successively displaced by others not
un frequently of an opposite character. We must, therefore, as far
as is possible, attempt to judge for ourselves if we would not be
continually drawn aside by the opinions which are ever rising and
falling amid the fluctuations of ephemeral literature.
But the most important reason for the delay that has occurred
in the publication of the second volume is, that in Physiological
Chemistry, even more than in Zoo-Chemistry, we are obliged to de-
part from the sure ground of exact enquiry, and to proceed to the con-
sideration of chemico-vital processes, which lie beyond the scope of
direct observation, and are thus called upon to admit the correct-
ness of deductions, whose logical authority is not always easy of
recognition. Modern science has directed its highest energies to
this point of physiologico- chemical investigation : and it was there-
fore to be expected that this yet imperfectly cultivated soil would
give birth to a number of more or less ingenious hypotheses, which
can only be sifted by independent examination and positive inves-
tigations. But since even this protracted delay and the frequent
reconsideration of all the materials at his command, do not give as
satisfactory a result as the author could wish, he has at length
determined to send forth this attempt at a History of Physiological
Chemistry, trusting to the indulgence of those who are labouring
in the same cause.
LEIPSIC,
September, 1849.
TABLE OF CONTENTS.
General formula, CnHn_2O34-HO
Translator's Preface
The Author's Preface to the Second Edition
METHODOLOGICAL INTRODUCTION
THE ORGANIC SUBSTRATA OF THE ANIMAL ORGANISM.
Non-Nitrogenous Acids ....
THE BUTYRIC ACID GROUP. General formula,
Oxalic acid ....
Formic acid
Acetic acid....
Metacetonic acid
Butyric acid
"Valerianic acid ....
Caproic acid
(Enanthylic acid ....
Caprylic acid
Pelargonic acid ....
Capric acid
Cetylic acid
THE SUCCINIC ACID GROUP.
Succinic acid ....
Sebacic acid
THE BENZOIC ACID GROUP. General formula, CnHn_g03-f-HO
Benzoic acid
•THE LACTIC ACID GROUP. General formula, CnHn_aO5-|- HO
Lactic acid
SOLID FATTY ACIDS. General formula, CmHm_1O3 + HO
Margaric acid ..,.
Stearic acid
OILY FATTY ACIDS.
Oleic acid ....
Doeglic acid
RESINOUS ACIDS
Lithofellic acid ....
Cholic acid ....
Nitrogenous Basic Bodies
NON-OXYGENOUS ALKALOIDS
Aniline
Picoline ....
Petinine
ALKALOIDS CONTAINING OXYGEN
Creatinc
Creatinine ,,
PAGE
V
vii
1
General formula, CmHra_3O3 + HO
31-127
... 31-73
41
48
51
,... 53
56
.... 63
65
,... 66
68
.... 69
70
.... 71
73-77
74
.... 76
78-84
80
84-105
.... 85
105-111
.... 106
109
112-116
112
.... 116
116-127
.... 116
118
127-183
128-132
.... 129
131
.... 132
133-183
.... 134
140
TABLE OF CONTENTS.
ALKALOIDS CONTAINING OXYGEN — continued.
Tyrosine
Leucine
Sarcosine
Glycine (Glycocoll)
Urea .... '
Xanthine ....
Hypoxan thine
Guanine
Allantoine
Cystine
Taurine
Conjugated Acids
Picric acid
Hippuric acid
Uric acid
Inosic acid ....
Glycocholic acid ....
Hyocholic acid
Taurocholic acid ....
Haloid Bases and Haloid Salts
Oxide of lipyl
Glycerine ....
Salts of oxide of lipyl (Fats)
Hydrated oxide of cetyl
Lipoids
Cholesterin
Serolin
Castorin
Ambrein
Non-Nitrogenous Neutral Bodies ....
Glucose
Milk-sugar....
Colouring Matters
Haamatin ....
Melanin
Bile-pigment
Urine-pigment ....
Extractive Matters
Nitrogenous Histogenetic Substances ....
PROTEIN-COMPOUNDS ....
Albumen
Fibrin
ViteUin
Globulin
Casein
Gluten
Legumin
Teroxide of protein (Proteintritoxyd) ....
PAGE
.... 142
143
.... 146
148
.... 153
169
.... 171
171
.... 174
177
.... 179
183-235
.... 186
188
.... 199
221
.... 222
228
.... 231
235-274
.... 239
240
.... 244
272
274-280
275
.... 279
280
.... 280
280-299
.... 281
295
299-319
299
.... 309
312
.... 318
319-321
321-403
326-391
.... 330
348
.... 364
366
.... 373
386
... 387
389
TABLE OF CONTENTS.
XI
DERIVATIVES OF THE PROTEIN-COMPOUNDS
Animal Gelatin
Glutin
Chondrin
Fibroin
Chitin
Mineral Constituents of the Animal Body
FIRST CLASS OF MINERAL SUBSTANCES ....
Water....
Phosphate of lime
Carbonate of lime
Phosphate of magnesia
Fluoride of calcium
Silica
SECOND CLASS OF MINERAL SUBSTANCES
Hydrochloric acid
Hydrofluoric acid
Chloride of sodium ....
Carbonate of soda
Alkaline phosphates ....
Iron
THIRD CLASS OF MINERAL SUBSTANCES ....
Alkaline sulphates
Carbonate of magnesia
Manganese
Alumina
Arsenic
Copper and lead
Salts of ammonia
Hydrocyanic acid
Hydrosulphocyanic acid ....
PAGE
391-403
392
.... 392
398
.... 400
401
405-456
412-428
.... 412
412
.... 418
422
.... 424
426
428-444
423
.... 429
430
.... 436
440
.... 443
444-455
.... 444
446
.... 448
449
.... 449
450
.... 451
453
454
Xll
TABLE OF TIIERMOMETRIC DEGREES.
TABLE OF THERMOMETRIC DEGREES.
C. F.
C. F.
C. F.
C. F.
-123° = -171°'4
- 20 — 4
44° = lll°-2
49 120-2
85° = 185°
90 194
155° = 11°
157 314-6
— • ZtVJ
- 15 + 5 1
— 9 15*8
50 122
55 . 131
92 197*6
99 210-2
160 320
165 329
— 1 30*2
56 132-8
100 212
170 338
0 32
56-3 133'3
105 221
176 348-8
4 39*2
76-5 133-7
106 222-8
178 352-4
6 42*8
57 1346
107 224-6
180 356
7 44-6
58 136-4
110 230
182 359-6
10 64*5
60 140
115 239
195 383
14 57'2
15 59
61 141-8
62 ' 143-6
116 240-8
117-3 243-1
200 392
202 395-6
16 60*8
63 145-4
118-5 245-3
205 401
17-5 63'5
64 147-2
120 243
210 410
20 68
65 T 149
125 257
215 419
25 77
65-5 149'9
127 260-6
220 428
26 78'8
68 154-4
130 266
228 442-4
30 86
70 158
133 271*4
232 449-6
32 89'6
35 95
73 163-4
75 167
135 275
136 276-8
236 456-8
239 462-2
36 96'8
76 168-8
137 278-6
240 464
37 98-6
78 172-4
140 284
250 4825
38 100-4
40 104
79 174-2
80 176
145 116
150 302
255 491
300 572
42 107*6
83 181-4
152 305-6
360 680
ERRATA.
Page 5, line 9 from bottom, for "causal" read "casual."
Page 32, „ 3
for "formiate" read "formate."
Page 39, last line, for "conjugate" read "adjunct."
Page 50, line 10 from top, for "inosinic " read "inosic."
Page 52, line 10 from bottom, for " ferricyanide " read "ferridcyaiiide."
Page 81, line 3 from top, for "benzoyle" read "benzoyl."
Page 81, line 18 from bottom for "throughout" read "through it."
Page 97, line 12 from top, for "and" read "under."
Page 139, line 19 from bottom, for "creatine" read "creatine as."
METHODOLOGICAL INTRODUCTION,
THE application of Chemistry to the elucidation of physiolo-
gical and pathological processes has been so universally admitted
during the last ten years, that it would appear almost superfluous
to commence this work with any observations on the importance of
this science. While at no very remote period we had occasion to
defend this recent department of chemical science from the
attacks and unfavourable criticisms called forth by its injudicious
application, and by the numerous misconceptions which characterized
its early development, we are now almost constrained to withhold
from it the confidence which has been too liberally awarded it.
Enthusiasm in the cause of organic chemistry has degenerated
amongst many physiologists and physicians into a fanaticism,
which, even in the best cause, tends to invalidate a host of truths
in its endeavours to uphold some single fact. We might be dis-
posed to ask, whether its most zealous partisans have not retarded
rather than accelerated the period at which it will attain its proper
share of appreciation, and its just recognition. In commencing,
therefore, the subject of physiological chemistry, nothing is more
important than clearly to understand the nature of the results
which this department of science is now capable of yielding, and
the requirements which, in its present stage of development, it fulfils;
and to ascertain the course, the means, and the methods most likely
to lead us safely within its domain, and at the same time the
best adapted to promote its further progress.
In entering upon this subject, it may not be altogether unpro-
fitable to begin by indicating the numerous errors into which
those most zealous in their endeavours to elucidate physiology and
medicine, have occasionally been led by chemical theories and
enquiries. These errors appear to us to have diverged in three
2 METHODOLOGICAL INTRODUCTION.
different directions. In the first place, too little attention has been
directed to the laws of a true natural philosophy, whose simplest rules
have in many cases been wholly disregarded ; in the next place, the
necessary causal connexion existing between chemistry and phy-
siology, as well as between histology and pathological anatomy,
has too often been entirely neglected ; and lastly, much miscon-
ception has arisen from the assumption that chemistry afforded a
satisfactory solution to many questions which it is either wholly
incompetent to answer, or which must at all events remain undecided
in the present state of our knowledge.
While we still find occasion to deplore the absence of the
steady influence of a true natural philosophy in the application of
chemistry to the science of general life, we do not refer to any of
those nearly exploded systems of natural science which may be
regarded almost in the light of poetic fictions, but to that Newto-
nian method of contemplating nature, which has carried Astronomy
to its present high state of perfection, and has led to the most
brilliant discoveries in physics. It is this method of viewing nature
which Fries alone understood how to raise into a system, and to
which the immortal Humboldt has given life and expression in his
' Cosmos/ It is only by the application of abstract physical laws,
by the establishment of certain momenta of empirically observed
phenomena, and by a steady adherence to safely guiding maxims,
— in short, by logical sequence, — that we can advance in the inves-
tigation of vital phenomena. It would almost seem as if medicine,
in the earlier periods of its history, had cast a shadow over those
kindred sciences which are able to afford it aid and support,
clouding even their brightest points. It has thus been found
impracticable at once to rid medicine, notwithstanding its assumed
physiological character, of the mania of attempting to explain every-
thing by the old system of hypotheses ; and hence this science has
derived less benefit than many others from the exact method of
physical enquiry, having simply borrowed certain materials from
chemistry and the kindred natural sciences, and substituted, in the
place of the older vagaries of natural philosophy, various chemical
phrases and high sounding terms, scarcely less devoid of true import
than the former. This deficiency in logical sequence, which we so
frequently at present encounter in medicine, has unfortunately also
infected animal chemistry ; for here likewise facts have not been
sufficiently distinguished from hypotheses, or hypothesis fromfiction.
This is more easily accounted for in physiological than in pure general
chemistry : for while the latter treats almost exclusively of palpable
METHODOLOGICAL INTRODUCTION. 3
phenomena and of well-established facts, which easily admit of
being reduced to definite laws, in the former we must necessarily have
recourse to experiments and natural investigations, whose success
must in a great measure depend on individual operations of the
mind. Zoo-chemical processes are the most complicated of any
comprised in the domain of natural enquiry ; but such processes
are not capable of tangible demonstration, but must be divined, or
rather, intellectually apprehended. Our senses are incapable of per-
ceiving the causal connexion of things, or the logical succession of
phenomena ; thus we do not see motion, but simply recognize it by
the result of the changes effected by it ; we do not perceive heat, but
simply the variations of the temperature, and the results to which
they give rise, &c. Hence it is not our senses which here deceive
us, but the judgment which we form regarding the objects pre-
sented to us by the perceptive faculties. The causal connexion of
several allied phenomena, (i. e., a process,) can therefore only be
comprehended by the subjective combination of individual objects
perceived by the senses, and not by sensuous intuition alone.
But as soon as we subject to investigation the highly compli-
cated chemical phenomena of life, we enter upon the actual domain
of hypothesis. It unfortunately happens, however, that the correct
logical conception of an hypothesis has been completely lost sight of,
and its place supplied by the vaguest fictions ; whence the term has
fallen into such discredit that many have been desirous of setting
aside all hypotheses, unmindful that even the simplest form of expe-
riment cannot be prosecuted without their aid. Hypotheses are
indispensable in every physical enquiry, and must constitute the base
of every experiment, as they are in fact merely the subjection of
our thoughts and mode of intuition to the reality of phenomena.
The question, however, always is, whether the facts at our command
logically justify such a procedure, since where such is not the case, the
deduction at which we arrive is undeserving the name of an hypothesis,
and is a mere fiction, supported at best on a hypothetical foundation.
Physiological chemistry has given rise to many delusions of
this nature, owing to its imperfect development, and to the
necessity presented by physiology and pathology for chemical
elucidation. Some few isolated deductions were drawn from
superficial chemical experiments, and arranged in a purely
imaginary connexion by the aid of chemical symbols and formulae,
for whose establishment analysis in many cases did not even afford
any sanction. Thus, for instance, in the attempt to form a con-
clusion regarding the metamorphosis of the blood from an elemen-
B 2
4 METHODOLOGICAL INTRODUCTION.
tary analysis of its solid residue and of the composition of the
individual constituents of the excretions, there is an utter absence of
all scientific groundwork ; for, independently of the fact that the
elementary analysis of so compound a matter as the blood is
incapable of yielding any reliable results, and cannot, therefore,
justify the adoption of any special chemical formula, it is assuredly
most illogical to attempt to compare the composition of the blood
collectively, with that of the separate excrementitious matters.
In such deductions, expressed by chemical formulae, the addition
of atoms of oxygen, and the subtraction of those of water, carbonic
acid, and ammonia are wholly arbitrary: for chemical analyses
do not afford the slightest grounds for the majority of these
equations. When, on the other hand, we have seen uric acid
decomposed by different oxidising agents into urea and other
bodies, and when, further, we find the quantity of uric acid in-
creased in the urine in those cases where a diminished quantity
of oxygen is proved to be contained in the blood, we are justified
in concluding that also in the animal organism a portion, at least,
of the urea found in the urine must have been produced by the
oxidation of the uric acid. In the formula which expresses this
deduction, we have an hypothesis, but a well-grounded one,
which, although requiring further confirmation, is yet wholly
different from the frequently condemned, but rarely avoided, abuse
of chemical symbols. Chemical equations having no other
foundation than the presumed infallibility of empirical formulae,
must, however, cause us to deviate from the path of physical
enquiry, and involve us in a chaos of the most untenable delusions.
Thus, for instance, a chemical equation might lead us to conclude
that glycine (glycocoll) was the source of urea and lactic acid in
the metamorphosis of the animal tissues ; for we might con-
clude that 2 equivalents of hydrate of glycine were decomposed
into the above-named substances according to the formula,
C8 H10 N2 O8 =C2 H4 N2 O2 + C6 H5 O5. H O. All experiments
hitherto instituted with glycine are, nevertheless, opposed to such
a disintegration. If, then, we would deduce urea and lactic acid from
glycine, which has not been proved to exist in the blood, we
should be neglecting the most comprehensive rule of logic,
according to which one hypothesis cannot be supported by
another. It has, however, unfortunately been too much the
practice in recent times to employ far more complicated equations
as supports for such purely subjective modes of contemplation, by
which a semblance of the most exact method of investigation has
METHODOLOGICAL INTRODUCTION. 5
been assumed. By these means a number of chemical fictions have
supplanted the fancies of that speculative natural philosophy which
in earlier times encumbered the study of physiology and pathology,
and have plunged medicine into the midst of a new labyrinth of
untenable theories.
We have indicated a further cause of the partial failure of the
application of chemistry to vital phenomena, in the imperfect causal
connexion among the different branches of natural science, without
which there can be no proper insight into the course of dif-
ferent phenomena, or any recognition of the complete vital process.
This is especially the case in reference to pathologico-chemical
enquiries, in the majority of which the data yielded by pathological
anatomy, and the diagnosis thus afforded, have been too little
regarded, whilst the adherents of the pathologico-anatomical school
have made free use of chemical phrases and fictions, without an
adequate acquaintance with the general science of chemistry.
If chemical investigations regarding objects belonging to patho-
logical anatomy would aspire to a scientific value, and if they are
to afford any true elucidation of pathological processes, it will
assuredly be admitted that the question should be adequately con-
sidered from an anatomical and diagnostic point of view. Yet
every day presents us with instances of the most flagrant neglect
of this self-evident proposition. How frequently we hear of the
chemical examination of diseased bones without any regard to a
diagnosis at all in accordance with the present condition of patho-
logical anatomy ! What numerous analyses have been made of the
bones in osteomalacia, notwithstanding that the morbid appear-
ances of these bones vary so much as to render a definite
diagnosis a matter of extreme difficulty to the pathological ana-
tomist ! We even more frequently meet with similar inconsis-
tencies in the investigation of diseased animal fluids. Here, as in
the statistical method of observing diseases, none but the simplest
form of a disease should be made the subject of such enquiries.
Yet the causal results yielded by an examination of the urine and
the blood in the most complicated forms of disease, are frequently
made the sole grounds for drawing conclusions regarding the mor-
bid process itself. In many cases even the true diagnosis of the
disease has not been given. Thus, for instance, we are told that the
blood has been analysed in typhoid pneumonia, yet when we read
the history of the case, we find that the disease was neither ordinary
abdominal typhus with pneumonic exudations, nor what is termed
pneumo-typhus, but simple pneumonia with cerebral symptoms.
6 METHODOLOGICAL INTRODUCTION.
More frequently still, we are obliged to rest content with vague
names of disease, unsupported by any history of the case. In most
cases certainly the name of the disease is unimportant. It is by
no means essential to the scientific comprehension of such enquiries
that the whole history of the case from beginning to end should
be given with the circumstantiality at present so much in requisi-
tion; but we undoubtedly ought to indicate the condition of the
patient, as ascertained by a physical examination, at the period of
the removal of any morbid product for chemical investigation. It
is the practice in reporting chemical investigations, to detail as
minutely as possible the method pursued, that the reader may be
able to judge for himself, and test the correctness of each individual
step. A similar rule should be observed with reference to the state
of the disease in all pathologico-chemical investigations, for it is only
by these means that we can impart scientific value to such enquiries.
We shall find, however, on examining our pathologico-chemical
literature, that this principle is too frequently neglected.
If we would render chemistry truly useful to other departments
of natural science, we must be careful to acquire a proper knowledge
and a due estimate of the advances made in each ; a point which
has unfortunately been too much disregarded in reference to his-
tology. We have passed the age when morbid tumours, without
regard to their histological constitution, were crushed and pounded
in a mortar, with the view of extracting from this artificially pro-
duced chaotic mass a principle peculiar to cancer or pus, — a scirrhin
or a pyin ; but at the present day the combustion tube is still mis-
used in the determination of the elementary composition of a mass
made up of the most heterogeneous organic parts. Such analyses
are wholly devoid of chemical or physiological value, and cannot, as
all chemists must allow, in any way contribute to extend the domain
of chemistry, while they are useless alike to the physiologist and the
pathologist, being utterly devoid of all scientific links of connexion.
If, however, wre take physiology for our guide in such researches,
we shall find support from that unity of character to which every
scientific enquiry, and every successive experiment should be
reduced.
Pathological tumours afford a good illustration of the extent
to which the success of a chemical investigation, and of the method
of analysis, depends on a correct physiological view of the question.
When we consider the most recent investigations made in relation
to this subject, we are led to regard malignant tumours, not as
secondary products or parasitic organs, but as exudations which
METHODOLOGICAL INTRODUCTION. 7
have been arrested in different stages of development and organ-
isation. If we adhere to this point of view, we shall no longer
attempt to discover the special matters of scirrhus, encephaloid,
&c., but shall rather look upon these objects as the means of
furnishing us with a clue to the physiologico-chemical processes by
which the plasma is developed into cells and fibres, which have
hitherto presented insuperable obstacles to the advance of chemical
enquiry.
In adverting to the false position assumed by pathological che-
mistry in reference to pathological anatomy, it must not be for-
gotten that the pathologico-anatomical school is equally deserving of
censure. Whence comes it, we may ask, that those who would set
aside pathological anatomy, and who profess to limit their investi-
gations to the actual facts of medicine, should threaten us with all
the horrors of a transcendental humoral pathology ? The solution
of this question is to be found in the circumstance that, strictly
speaking, pathological anatomy is occupied only with the external
palpable alterations experienced by the tissues and juices from the
action of disease, and that if any of the more gradual stages of
transition be made apparent in the course of such processes, these
are mere forms or facts, and afford no insight into the modus
of the organic changes. In a word, pathological anatomy is a
purely descriptive science, a natural history of morbid actions,
which may lead to the establishment of a system, but not to that of
a general principle and to conclusive deductions. It is the geognosy
of the morbid organism, and must be allied to a geology of disease
which, however, it is incapable of establishing. It is precisely the
purely descriptive character of pathological chemistry that places it
beyond the sphere of experiment. Like geognosy, it can only
attain its aim — the scientific recognition of objects — with the co-
operation of physics and chemistry. If, however, pathological
anatomy is to be regarded as the surest foundation of medical
science, we must endeavour, on speculative grounds, to ally it more
closely with pathology, and thus render it, to a certain extent,
more acceptable to the medical public. We are convinced that the
principal object had in view by the founder of German pathological
anatomy, Rokitansky, in writing the first volume of his celebrated
work, which has been so severely criticised, was simply to indicate
to pathologists the points of view from which the fruits yielded by
the pathological anatomy he had himself established might be most
fully comprehended. But it has unfortunately happened that his
followers have frequently borrowed from physics and chemistry
8 METHODOLOGICAL INTRODUCTION.
phrases and modes of representation, without seizing the spirit of
these sciences, or even comprehending their methods of operation.
Hence there has emanated from this school, notwithstanding the
positive observations on which it is based, a multitude of the most
unsubstantial medical fictions which, for shallowness, yield to none
of the earlier schools. Pathological views in reference to the
nervous system (Nervenpathologie) have been elevated to the
prejudice of physical views (Nervenphysik) ; for here, in conse-
quence of ordinary anatomy being inadequate to explain patholo-
gical changes, ideas, or rather mere words, have been unscrupulously
borrowed from organic chemistry (by those who were perfectly
ignorant of this science) to explain the most complicated processes,
of which scarcely anything was known but the final results.
Some adherents of the pathologico-anatomical school have pre-
sented us with a theory of the erases of the blood in different dis-
eases, although this is a view in which no chemist could at present
seriously concur. This theory of erases has been so thoroughly
investigated by physiologists in recent times, and its want of
foundation made so evident, that we need advert no further to it
than to observe that where admixtures and separations are con-
cerned, the chemist is the only competent guide.
A third circumstance which has led to misconceptions in
physiological chemistry depends upon an over-estimate of the value
of chemical auxiliaries, and a complete ignorance of the present
condition of organic chemistry. Have the numerous analyses of
morbid blood instituted during the last few years fulfilled the expec-
tations of physicians ? With all due gratitude to the indefatigable
investigators who, with no other aid than that which zoo-chemistry
could offer, boldly attempted to throw light on those obscure enqui-
ries, it must be admitted that, when we seriously enquire into the
recompense of all their labours and sacrifices, we find that the result,
although too dearly bought, was altogether inadequate to satisfy
the requirements of pathology. Have the numerous analyses of
the urine led to much more than the assumption of several new
species of disease, or so-called diatheses ? Although we might
have anticipated greater results, we can hardly wonder that the
efforts hitherto made should either wholly or partially have
deceived our expectations ; for although these investigations may
have rendered chemistry no unworthy auxiliary to a physical
diagnosis, analyses of morbid products could hardly afford an
insight into the chemical laboratory of the organism, while the
means were wanting to prosecute them with the scientific accuracy
METHODOLOGICAL INTRODUCTION. 9
attainable in the case of mineral analyses. Animal chemistry is
still wholly unable to afford us a precise, and at the same time a
practically useful method of investigating the blood; and how
should it be otherwise while we continue to be in doubt regarding
the chemical nature of its ordinary constituents ? The mineral
substances of normal blood are not yet determined, or, at all
events, continue to be made the subject of dispute ; we scarcely
know the names of the fatty matters it contains ; one of its most
important constituents, fibrin, cannot be chemically exhibited in
a pure state ; we are ignorant of the nature and mode of secretion
of the globulin of the blood-corpuscles ; we are still far from being
able to separate arid determine the so-called protein oxides ; and
we are also ignorant of the excrementitious substances occurring
in the blood. How then, amidst these and a thousand other
uncertainties and doubts, can an investigation of the blood be
scientifically and trustworthily conducted ? We analyse healthy
and morbid milk, and yet we are ignorant of the substances whose
admixture we have termed casein. The urine, in its morbid con-
dition, presents many varieties; and yet our knowledge of this
secretion, frequently as it has been analysed, amounts to little more
than an acquaintance with the quantitative relations of some of
its principal constituents ; creatinine and hippuric acid have not
been determined by any analysis, and doubts are still enter-
tained by some chemists, (although most unjustly,) regarding the
presence of the latter in human urine, while absolutely nothing
is known regarding the most important pigment of this secre-
tion. Many experiments have been made and theories broached
on nutrition and digestion, and yet to almost the present day
the existence of lactic acid in the gastric juice has been con-
tested. Although hypotheses are not wanting regarding the mode
of action of pepsin, we know nothing of its* chemical nature,
and we are wholly ignorant of the proximate metamorphosis
of albuminous bodies in the stomach during the process of
digestion. Will Mulder be able, even with his most accu-
rate analyses, to support his protein th3ory by the aid of sul-
phamule and phosphamide? or is this term destined merely to
indicate a past epoch of organic chemistry ? When such is the
state of animal chemistry, can we wonder that there should be
obscurity regarding the chemical processes in the animal body,
their various isolated and combined actions, their causal connexion
and their dependence on external influences and internal con-
ditions ? Unfortunately, we might be led to believe, from the
10 METHODOLOGICAL INTRODUCTION.
lectures and writings of many physicians, that, trusting to the
aphoristic and often highly apodictic assertions of certain chemists,
they felt secure of having reached the object of their enquiries.
Although at present little more than the direction is indicated, we
may hope in due time, and after innumerable efforts, to see our
endeavours crowned with success.
After having become acquainted with the deficiencies and errors
belonging to the chemistry of the vital processes, which was so pro-
minently brought forward at an earlier era, we will now pass to the
methods and principles by which alone this science can be made to
fulfil its just requirements. The final result of all physiologico-
chemical investigations is avowedly that of gaining an accurate
knowledge of the progress and causal connexion of the chemical phe-
nomena attending the vital processes. To attain to this knowledge,
it is not sufficient to detach separate parts from the mechanism of
the whole, and to form an opinion of the combined action of so com-
plicated a chemical structure from a more or less superficial exam-
ination. Attempts have already been made to establish a splen-
did theory of the metamorphosis of tissues, but notwithstanding
the many able heads and hands that have been engaged in the
labour, it is still deficient in the essential of a solid foundation.
It is unnecessary to prove that we must thoroughly understand
the substrata of the metamorphosis of the animal tissues before we
can venture an opinion on the nature of the processes. The surest
supports of physiological chemistry are to be sought, therefore, in
general organic chemistry ; while the study of the organic sub-
strata of the animal body, or zoo-chemistry considered in the
strict sense of the word, must necessarily constitute an integral
part of physiological chemistry and prove a most efficient aid
towards its development. If zoo-chemistry ever fulfil its object, it
must be by the joint aid of chemistry and physiology ; that is to
say, individual substances must not only be fully examined in refe-
rence to their chemical value and their place in the domain of pure
organic chemistry, but they must also be observed in the more
general relations which each may bear to the animal organism and
its metamorphosis. In a word, the physiological value of each
substance should be as carefully considered in zoo-chemistry
(the basis of physiological chemistry) as in pure chemistry. It
seems to us, that in treating of zoo-chemistry (in the first volume of
this work,) we shall the best attain this aim by adopting the follow-
ing arrangement : — namely, by treating of the chemical relations of
each body in reference to its properties, composition, combinations,
METHODOLOGICAL INTRODUCTION. 11
and mode of decomposition, its preparation, the method of testing
for it, and its quantitative determination ; in explaining the physio-
logical relations of each substance, we shall endeavour to deter-
mine its occurrence in the animal body, and its origin, (whether it
be produced within or without the body,) and from the above con-
siderations, we shall finally attempt to deduce its physiological value.
We shall treat of the properties of each organic substratum
before considering the remaining chemical relations, as it appears
to us both unpractical and illogical to begin with the mode of pre-
paration, as is usually done ; unpractical, because no student can
comprehend the mode of preparation when he is not in some degree
acquainted with the properties of the substance in question, and
illogical, because we must have some idea of a body before we can
attempt to prepare or exhibit it. The composition of a body must
necessarily constitute the most important subject of consideration
after its properties and its principal reactions have been duly noticed,
for it is only by such means that we can attain to an idea of the
nature of a substance, and of the place it occupies in the system
of organic chemistry. Hence this section must not be limited to
a mere enumeration of analyses or of empirical formulae, but must
embrace a consideration of the arguments that are adducible in
favour of the different views of the theoretical internal constitution
of a substance, and which are briefly expressed by the rational
formula. This method is of the greatest importance for the
recognition of the physiological relations of organic substances;
since without it, we are unable to arrive at any logically cor-
rect judgment regarding the origin and the physiological importance
of different substances. If a knowledge of the composition of
an organic substance were not necessary to the investigation of
its combinations and products of decomposition, we should have
placed it after the latter, since they constitute the safest grounds
from which we may form an opinion of the rational composition
of a body. A careful study of the products of decomposition
is however the more necessary, since it is mainly on these that
we must base our view of the metamorphoses experienced by any
given substance within the vital sphere.
It is only when all these relations have been considered, that
we shall deem it expedient to enter upon the different methods of
preparation or exhibition, for then only can the directions given
for the separation of substances be understood.
Before considering a substance from a physiological point of
view, we must examine the means by which we are best able to
12 METHODOLOGICAL INTRODUCTION.
demonstrate its presence in the animal juices and tissues. The
qualitative analysis of organic bodies is still far behind that of
inorganic bodies, but attention to this point is the more necessary,
since deficient investigations too often lead to hasty and erroneous
opinions. Nor does less importance attach to a correct estimate of
the methods that have been employed for the quantitative determi-
nation of the main constituents of animal fluids ; for it is only by
this means that we can form an opinion of the value of many of
the existing quantitative analyses of physiological and pathological
products, and of the conclusions which we are justified in deducing
from them.
The physiological consideration of every substance must of
necessity be primarily based on its mode of occurrence, for we
cannot form any opinion of the importance of a body in reference
to the changes of animal matter without knowing where, in what
relations, and in what quantity it occurs. When, however, we have
examined the origin and decomposition of a substance, we have
obtained the firmest base for the explanation of the vital chemical
processes.
After having, in this manner, familiarised ourselves with the
organic substrata of the animal body, we are still only on the
threshold of the study of the constitution and functions of the
animal juices and tissues. Before, therefore, we proceed to the
actual study of physiological chemistry, (namely, the theory of the
metamorphosis of matter, or of the zoo-chemical processes,) we
take into consideration the substances with which we have already
become acquainted in zoo-chemistry, regarding them topographi-
cally, in reference to their simultaneous occurence,[and their blend-
ing and admixture under the form of animal juices, tissues, and
organs. We may extend this classification to the animal fluids as
well as to the tissues and entire organs. No one will deny that
the knowledge of the chemical constitution of these more complex
and frequently variable parts of the animal body is another basis
of physiological chemistry, for it is evident that if we would treat of
chemical processes, we ought to have a knowledge of the sub-
stances implicated in them. This however, cannot yet be attained
in zoo-chemistry in the sense that we attach to this science. We
here enter the domain of physiology, in as far as we submit the
direct results of physiological actions to an investigation, which how-
ever must still be of a purely chemical and essentially analytical
character.
The province of chemistry in the consideration of the animal
METHODOLOGICAL INTRODUCTION. 13
fluids and tissues, is similar to that of mineralogical chemistry, for
as in the one case, we seek for elucidation respecting the proximate
constituents of often highly complicated compound minerals and
rocks, so in the other we endeavour analytically to determine
the constitution of animal fluids and solid organised parts by the
aid of the knowledge we have already obtained from zoo-chemistry.
It was in these data that the nature of physiological and patho-
logical chemistry was formerly studied, and it was believed that the
processes themselves might be determined directly from the know-
ledge afforded by such analyses. The fallacy of such a view is proved
no less by the state of our knowledge, some ten years since, regard-
ing the physiology of nutrition and secretion, than by the numerous
errors propagated since that period in reference to the chemical
processes in the animal body. What were analyses of the blood,
urine, milk, and bile before this epoch, but mere isolated facts
deficient in those links that ought to bind them to the theory of
nutrition and secretion ? Physiology then regarded such analyses
more as mere accessories than as necessary means for the compre-
hension of each process. A more exact, although by no means a
perfect knowledge of the chemical qualities of these juices was sub-
sequently acquired, and hence it was attempted to establish a more
intimate relation between the chemical constitution and the phy-
siological function ; but from the absence of a proper analytical
foundation, this method not unfrequently led to numerous perver-
sions and dangerous errors, as we have already stated, and as we
might illustrate by a large number of examples. Although the
results of the chemical analysis of the animal juices may afford
many indications of the processes, they by no means enable us to
judge of the function itself, however numerous and complete they
may be ; and it is only by means of experiments founded on the
composition of these fluids that we are able to arrive at any satis-
factory conclusion regarding the nature of the processes in question.
The study of the zoo-chemical processes based on zoo-chemistry
and the theory of the animal juices, appertains to the third section
of physiological chemistry, the theory of the metamorphosis of
tissues — of nutrition and secretion. It has already been observed,
that the actual object of physiological chemistry is to examine the
course of the chemical phenomena of the animal organism in their
causal connexion, and to deduce them from known physical and
chemical laws ; or in other words, to explain them scientifically.
Even if we regard the chemical substratum, as made known to us
by zoo-chemistry and the theory of the juices, in the light of a
14 METHODOLOGICAL INTRODUCTION.
satisfactorily investigated question, there are still several directions
to be pursued before we can reach the proper object of our enquiries.
It is here most essential that we should be well acquainted with the
paths to be followed, for in our search after truth we are compelled
to call to our aid hypotheses which might easily lead us into the
domain of pure fiction.
As long as zoo-chemistry and the theory of the juices continue
to occupy their present subordinate position, the only method by
which the foundation necessary to an exact investigation can be
obtained, is that which we may term the statistical. Liebig,
Boussingault, and Valentin have indeed, with a more correct view
of what was required, attempted to compare the final effects of the
whole with the material substrata supplied to the organism. We
cannot, it is true, arrive at any conclusion regarding the working of
the process itself by a mere juxtaposition and quantitative comparison
of the ingesta and excreta of the animal organism, any more than
we can judge of the causes and course of diseases by the number
of fatal cases recorded : but such experiments furnish us with
certain general results which serve as guides to further investiga-
tions. Some of the most important questions, whose solution was
specially necessary, were unanswerable by any other method.
Thus, for instance, it was ascertained, by an accurate investigation
of the food, and its comparison with the constituents of the excreta
and of the nutrient fluids, that in the ordinary food of animals,
albuminous substances occur in sufficient quantity to compensate
for the nitrogenous matters lost in the process of nutrition and in the
metamorphosis of tissue ; while it was thus at the same time shown,
that the animal organism does not necessarily possess the property
of generating albuminous matter from other substances containing
nitrogen. The question whether the animal organism possessed
the property of generating fat was answered in a similar manner ;
and it is well known that by means of such statistical observations,
(comparing the fat contained in the food with that secreted in the
cellular tissue and mixed with the excrements) the contest carried
on between Liebig on the one side, and Dumas and Boussingault
on the other, regarding the formation of fat, was finally decided
in favour of the former.
This statistical method preserves us from setting up unten-
able hypotheses, and prosecuting useless experiments. How long
were the minds of natural philosophers haunted with the illusion
that animal bodies possessed the power of generating mineral
elements, as lime, iron, sulphur, &c., from other elements, or even
METHODOLOGICAL INTRODUCTION. 15
from nothing ! It was this method alone which exposed the perfect
nullity of the obstinately defended dogma of the c vital force.'
Statistico-chemical investigations may serve as checks to, or
confirmations of other enquiries and methods of enquiry ; thus,
for instance, Boussingault, by a comparison of the amount of
nitrogen in the excrements with that in the food, has fully con-
firmed the experiments made by Dulong, Valentin, Marchand, and
others, which appeared to show that the animal body lost a slight
quantity of nitrogen by exhalation from the lungs.
The statistical method would, therefore, appear to be one of the
most important aids towards a solution of some of the more
general questions in reference to the metamorphosis of the animal
tissues. We must, however, be careful not to deduce more from
such experiments than what is'permitted by the simplest induction ;
for the results derived from this method have unfortunately too
often been made to yield support to the vaguest fictions and the
boldest speculations.
It need scarcely be observed that science should not rest satis-
fied with a knowledge of the final results of chemical processes in
the animal body, or with the assertion of the chemical dignity of
the vital process in summd, but should be made to enter more
deeply into the course of the separate processes, and into the
causal relations of phenomena. Here the statistical method cannot
of course afford any satisfactory solution to our enquiries ; for
when we have ascertained by this experimental method that fat is
formed in the animal body, we must learn from other methods the
manner in which this substance is formed.
The method by which we may examine the course of phe-
nomena and the cause of their succession, might be named compa-
rative analytical or chemico-experimental, in as far as the chemical
phenomena of the living body may be artificially imitated, and
the chemical metamorphoses of certain substances external to the
vital sphere be compared with those within the influence of the
vital processes. Liebig and his school have here done essential
service. He was led to believe from his statistical enquiries on
fats, that these substances in their transmission through the
organism, were in a great measure oxidised and reduced to water
and carbonic acid, by which means they specially contributed
towards the maintenance of animal heat. As Liebig was by no
means inclined to believe, as some have supposed, that fat was
consumed in the lungs, somewhat in the same manner as oil burns
in a lamp, it was necessary more accurately to investigate its
16 METHODOLOGICAL INTRODUCTION.
gradual metamorphosis, and its transition through different stages
of oxidation, and into bodies containing a larger quantity of oxygen.
He believed that he could most readily attain this object by the
comparative analytical method ; and hence he and his school
entered upon a series of experiments on the numerous products of
decomposition of fatty matters, and more especially on their pro-
ducts of oxidation ; and although we may still be far removed
from the object in view, these enquiries have enriched us with
many valuable results. A similar instance is afforded by the
gelatigenous tissues of the animal body; for although our histo-
logical and statistico-chemical investigations leave not the slightest
doubt that the gelatin is formed from the albuminous matters, the
process of this metamorphosis is still wholly unexplained ; and
before we shall be justified in forming an opinion regarding this
metamorphosis, and expressing it by a chemical equation, it is
indispensably necessary that we should investigate the metamor-
phoses experienced by albuminous bodies during their gradual
oxidation. We are indebted for these views to the admirable in-
vestigations prosecuted under Liebig's direction, by Schlieper
and Guckelberger, on the products of oxidation of albuminous
bodies and of gelatin.
As we learn more thoroughly to investigate the processes of
putrefaction and decomposition, and that of the dry distillation of
individual animal substances, and therefore the better to understand
their regressive metamorphoses, we may hope by this know-
ledge to arrive at a deduction, based on some probability, re-
garding their progressive metamorphoses. Among these probable
deductions we may place Dessaigne's discovery of the decomposi-
tion of hippuric acid into glycine and benzoic acid, Liebig's in-
vestigation of creatin, and his pupils' analyses of glycine (glyco-
coll), which although they do not yet afford us any perfect eluci-
dation of the metamorphoses of animal matter, nevertheless yield
many sure points of support for future enquiries on the vital pro-
cesses.
A third method, which although frequently employed, has
hitherto, from the imperfect state of our knowledge, yielded few re-
liable results, is the physiologico-exper intent aL By this term
we would designate that class of enquiries, in which obser-
vations are made in the living organism on the result of cer-
tain conditions on the progress of a physiologico-chemical pro-
cess, and on the different stages of that process. We are aware
that we shall never succeed in artificially reproducing all the
METHODOLOGICAL INTRODUCTION* 17
processes as they occur in the living body, since we are here as
little able to call forth the necessary conditions and relations, as in
the formation of minerals and rocks. It is, therefore, the more
necessary to observe a process, of which we cannot judge by imita-
tion, in its course in the living body, and for this end we must
chiefly employ natural physiological means. Among these we may
reckon the investigations that have been made in reference to
the contents of the stomach during the process of natural
digestion, to the chemical change of individual substances in
the development of the egg during incubation, and to the de-
pendence of the products of respiration on different external
conditions. We may further add those experiments that have
been made on the changes of individual substances during
their passage through the animal organism, or on the effect
of different kinds of food, and the metamorphoses of certain
nutrient substances during the process of nutrition. To the same
method belong all pathologico-chemical experiments, as for in-
stance, observations on the contents of the intestine after the closure
of the common bile duct, and on the blood and other fluids after
extirpating or tying the vessels of the kidneys. Chemistry, unfor-
tunately, too often fails us to permit of our deriving from this
method all the results which it appears to promise; it must
however, ultimately furnish the key- stone to all physiologico-
chemical enquiries, which, without its aid, would continue insoluble
enigmas, and would admit of hypothetical rather than actual
explanation. The theory of the metamorphosis of animal matter,
without the support of such a physiologico-experimental founda-
tion, must continue to be attended by no little risk.
In conclusion, we would advance a few remarks on the place
which physiological chemistry occupies, or at some future period will
occupy, among the auxiliary medical sciences. If the final result
of all physiologico-chemical enquiries be that of comprehending
the chemical phenomena of animal life in their different phases
and in their causal connexions, it is obvious that we must look to
this science for a solution of the most important questions of
physiology, and of medicine generally. It cannot be denied that
most of the phenomena of animal life either consist in or are
accompanied by chemical processes ; nor can we form an adequate
conception of the functions of the nervous system by which
sensuous perception and motion are regulated, without the simul-
taneous existence of chemical actions. For although we are as yet
unable to make nervous action fully harmonise with definite
c
18 METHODOLOGICAL INTRODUCTION.
physiological laws, or to identify it with certain physical forces or
imponderable fluids, all physiological experiments indicate that it is
always followed by a chemical reaction, and that the nervous system
experiences chemical changes by and through its own activity. It
must, indeed, be admitted that any actual proof of such chemical
metamorphoses is at present perfectly unattainable, and that our
chemical methods would here afford us no higher aid than that
which the scalpel yields to the pathological anatomist. But
ought we to despair of attaining our object, because we do not as
yet clearly perceive the direction we are to follow ? Weariness of
the senses is the diminished impressibility of the nerves of sense,
but its cause cannot reasonably be sought for in any other than a
chemical change, experienced by the conducting substance of the
nerves. Such a chemical metamorphosis of the nerves of sense
from external impressions can no longer greatly excite our
astonishment, since we have witnessed the unexpected pheno-
menon of a picture produced suddenly, and as it were by magic,
from the chemical changes effected by the rays of light on an
iodised silver plate. Should we not be equally justified in saying
that the iodised plate, which after being exposed for a few seconds
to a strong light gives only faint and half effaced images, is
wearied like the retina, when after repeated and continuous per-
ception of an image, it gives back only the faint outlines of the
object? We may rest assured that the nervous system is not
exempt from chemical action ; and if the nervous system itself
must fall within the domain of chemical contemplation, and a
chemical expression remains to be found for its action, no less
than for that of digestion and for the formation of blood, it is
scarcely necessary to offer further proof of the fact that chemistry
is destined to play the most important part in physiology and
medicine. However much we may endeavour to exclude chemistry
from certain physiological investigations, we shall always find that
it involuntarily forces itself upon our notice ; for without it we
shall be unable to find a physiological equation or a philosophical
expression for a process. In a scientific point of view chemistry must,
therefore, be regarded as an invaluable acquisition to physiology. We
have, then, little cause to dread that Cicero's observation " Suo
quisque studio delectatus alterum contemnit" will be applied to our-
selves, when we assert that physiological chemistry is the crowning
point of every physiological enquiry.
When we turn to practical physiology, to pathology, and
therapeutics, we are again reminded that chemistry is indis-
METHODOLOGICAL INTRODUCTION. 19
pensable. Is there a single disease that is not attended by
chemical changes ? Can we ever hope to comprehend or explain
the nature of any process, if we are ignorant of its integral factors ?
Life cannot exist without chemical movements, disease cannot exist
without chemical changes. Thus much in reference to pathology ;
while in respect to therapeutics, it is almost superfluous to observe
that chemistry here also plays the principal part, for where has
modern pharmacology sought its chief support, save in chemical
processes and principles ? And if we have advanced so far towards
a clear insight as no longer to ascribe supernatural forces to medi-
cines^ but to derive their efficiency specially from chemical
properties, then must chemistry be the supporting basis of phar-
macology. The physician acts upon the body mostly by the aid
of matter, which retains its characteristic powers within no less
than without the organism. If then nervous action likewise falls
within the sphere of chemical metamorphoses, the Nervina (or
Neurotica) of pharmacologists must primarily at least act chemi-
cally on this system.
To those who stand on the grounds of exact investigation,
holding fast to the fundamental principle that it is from physical
laws alone we must deduce a true explanation, and that by induc-
tion only can we investigate the causal connexion of vital pheno-
mena, no further proof need be adduced of the truth of our
assertion that physiological chemistry occupies the highest place
among the sciences auxiliary to medicine. Even those who deem
special forces and special laws necessary to the explanation of vital
phenomena must admit that chemical methods are the most
important for the investigation of these actions, and for the solution
of such questions, if, as indeed cannot be denied, it is only by a
thorough investigation of the physical forces acting in the living
body that we can become acquainted with a true vital force or vital
law. With those who judge of vital forces by subjective feelings,
and would stamp nature with the impress of their own ideas, we
will not contest the point of view we have adopted; but leave
them to regard chemistry, like physics and anatomy, as a mere
auxiliary towards an adequate appreciation and contemplation of
nature.
It now only remains for us to add a few words on the relation
of pathological to physiological chemistry. Neither from a theo-
retical nor a practical point of view can we concur in the assertion
that pathological chemistry is separate and different from physi-
ological chemistry. Experience shows us the impracticability of
c 2
20 METHODOLOGICAL INTRODUCTION.
such a separation, for how much mental energy has been wasted,
as it were, in the investigation of unattainable things ; and among
these we may class pathological chemistry, when not based on
physiological principles. It would assuredly be going too far, to
assert that the natural enquirer should undertake no experiment that
could not afford a definite solution to a well-grounded question ;
but it must be admitted that there is an almost countless number of
pathologico-chemical experiments which have yielded no result, and
which obviously could yield none ; and indeed it seems scarcely
comprehensible that we should attempt to understand that
which is abnormal, while we continue ignorant of that which is
normal. Before we can institute a comparison between two things,
we must be familiarly acquainted with at least one. Here we do
not by any means wish to maintain that no pathologico-chemical
enquiries should be prosecuted, for this would be as absurd as to
withhold our attention from pathology until we supposed ourselves
fully enlightened on the subject of physiology. We would, on
the contrary, limit our objections to those analyses of pathological
products which have no relation to any one leading idea, are devoid
of connexion with any scientifically established fact, and do not bear
upon general chemical or physiological propositions. Such inves-
tigations are so numerous, that our weekly periodicals are seldom
without one or more analyses of diabetic urine. These results
would, doubtless afford additional proof of the well-established
fact that sugar is present in diabetic urine, if we did not feel
assured that the diabetes was not diagnosed until the existence of
sugar had been demonstrated in the urine. We seldom meet with
any observation on the relation existing between the quantity of
sugar excreted in a given time, and the quantity of food taken
during the same period ; while other and similar considerations of
equal importance are also usually disregarded.
The severance of pathological from physiological chemistry is
even less admissible in a scientific than in a practical point of
view. We will not here pass judgment on the obscure abstract
idea of disease, but whatever value such a view may have in
reference to life and medical practice, and however pathologists
may strive artistically to define it, it must continue illogical in
reference to theory and science. But whatever view we may
here adopt, it must be admitted that pathological and physio-
logical chemistry cannot exist independently, — a view requiring no
circumstantial proof. The power and the law remain the same,
whether the points of application be more or less remote from the
METHODOLOGICAL INTRODUCTION. 21
fulcrum of the lever ; the result alone is different. Pathologico-
chemical phenomena do not originate in the occurrence of new
forces or special laws, but merely from the chemical points of
application being somewhat different; that is to say, the relations
are changed under which the substrata develope their actions of
affinity. Pathological phenomena can, therefore, only be recognised
when manifested preponderatingly in some one direction, but they
of necessity obey one and the same law. As the result of indis-
pensable conditions we cannot then regard them as anomalous or
abnormal. If protoxide of iron is no longer precipitable by
alkalies when organic acids are present, and if fibrin loses its
capacity for coagulating in the presence of certain salts, we no
more apply the term diseased to these substances than to a clock
which stops because the weight has run down. When, in conse-
quence of any influence, the capillaries become dilated, and the
blood contained in them stagnates, exudes, or coagulates, we
do indeed recognise the occurrence of something singular and
not of ordinary occurrence, but nothing independent of a law. The
physician may designate inflammatory symptoms as abnormal and
morbid, but the philosophical enquirer sees only the necessary result
of laws acting under different relations, for he has to deal only with
fixed laws and not with rules abounding in exceptions. The chemist
is an investigator of nature even when occupied in studying patho-
logical processes, as the physiologist is still engaged in physiology,
when turning his attention to the less frequent phenomena of the
living body, for there is no special science for the exceptional phe-
nomena of nature but only one physiology as there is one all-powerful
law of nature.
We are tempted, notwithstanding the above observations, to
cast a glance at the position occupied by physiological chemistry, in
relation to what is called metaphysiology. The recent advances of
organic chemistry have unfortunately been interwoven with a fan-
tastic physiology, which designates itself as a comparative science.
This is not a science comparing together the functions of the
organs of different animals, as comparative anatomy compares
their structure, but a system founded on abstractions and ideal
comparisons ; that is to say, on figurative representations of sub-
jective conceptions, in which the results of objective investiga-
tion are advanced in defiance of the most contradictory facts.
We entertain all due respect for that form of metaphysics which oc-
cupies the same rank among the speculative sciences as physiology
and chemistry hold among the exact sciences. Metaphysics and
22 METHODOLOGICAL INTRODUCTION.
physiology resemble two diverging lines which coincide only in
their starting-point, and differ so widely at all other points, that
they cannot be united unless to the detriment of true science.
The physicist has maintained his stand more firmly and securely
than the speculative natural philosopher, who never relaxed in his
attempts to force his complex ideas, constructed according to a sub-
jective standard, upon the objective experiments of the physicist.
On this principle it has been attempted to anticipate intellectually
the discoveries and general propositions which the physicist
endeavours to attain by practical evidence, and thus science has
been confused in a manner that cannot fail to retard its advance.
There are now indeed but few remaining followers of the school
of speculative natural philosophy, which emanated from the same
exaggerated bias of the age, which in poetry gave rise to the
romantic school. Men created for themselves an Ideal to which
they gave the name of nature.
Although such a system of metaphysics* completely mistakes
its province, it is yet essential that " the chemist should raise
himself above the vital, no less than the chemical process, in order
to compare them both in their principal properties and results, and
to represent them in their co-existence, founded as it is in objective
processes." This is, however, a point of view from which no mere
chemist should observe the phenomena of nature ; for no exact
investigation is compatible with imaginative speculation, which can
exhibit only artificial comparisons and obscure reflections of dimly
comprehended physical phenomena. We have not hesitated to
avow that we have assumed a thoroughly radical point of view, in
reference to specific vital phenomena and vital forces ; for we
cannot rest satisfied with the mysterious obscurity in wliich
they have been artificially enveloped. With the physicist we
would uphold the reality of phenomena, and while we admit that
the consciousness of the reality of matter is only the result of an
abstraction, we must regard this abstraction, by which we recognise
the Immaterial, the Spiritual, and the Force, as originating in reality.
We therefore believe, with the diffidence beseeming a genuine
student of nature, that it would be wiser and more conducive to
the spread of true knowledge, to adhere, in the study of vital
processes, to matter, and to the laws by which it is determined,
than, following the fictitious abstractions of dynamical processes, to
* Geubel, Grundzuge der wissenschaftlichen Chemie, Frankf. a. M. 1846, and
L. Miillcr, Berzelius' Ansichten, Bfeslau, 1846.
METHODOLOGICAL INTRODUCTION. 23
assume that there exists in life a higher power of the spiritual force
pervading matter. While, therefore,, in opposition to the views of
these natural philosophers, we must refer all force to matter, we
have no fear of degrading "vital phenomena to mere mechanical,
physical, and chemical processes,'5 since our most exalted concep-
tion of nature and the sublimest natural philosophy emanate from
the very simplicity of physical laws, and the unlimited variety of
phenomena to which they give rise.
We are firmly convinced that even metaphysiology will be
unable to deprive physiological chemistry of the consideration due
to it among physical studies, in its explanation of vital processes ;
and we will, therefore, leave it to the poetic and the imaginative to
depict the romance of the protecting activity and sturdy contest
maintained by the vital force, and of a struggle between different
powers, — between the attraction and repulsion of polarities. Does
it not need a superabundant richness of fancy to believe with meta-
physiologists, that apparent death, trance, or (as it has been termed)
latent life, is the predominance of the spiritual over the material (the
metamorphosis of matter being at its minimum) rather than a pre-
dominance of the material over the spiritual, as sounder minds
would be led to assume ? It would be well if these spiritualists
would look down from the high stand they have chosen, and deign
to believe that there are some among those experimentalists, who,
clinging to matter, and gathering their facts with ant-like industry
from the lowly earth, notwithstanding that they have long held
communion with the poet-philosopher, Plato, and the philosophical
natural enquirer, Aristotle, and have some familiarity with the Pa-
raphrases of Hegel and Schelling, are yet unwilling to relinquish
their less elevated position. If these happy admirers of their own
Ideal had descended from their airy heights and closely examined
organic and inorganic matter, they would not have deemed it neces-
sary to assume, that besides carbon, hydrogen, nitrogen, and oxygen,
organic substances must also contain an organogenium or latent
vital force, or whatever else they may be pleased to call it. Had
they sought information from a chemist, they would have learnt,
that when exposed to the clear light of rigid logic, there is no
essential difference between organic and inorganic bodies; a
chemist totally unacquainted with organic matter, would a
priori have deduced all these incidental differences of matter,
from the doctrine of affinity and the science of stoichiometry,
evolved from dead matter. However these advocates of a romantic
poetry of nature may despise the swarm of industrious investi-
24 ORGANIC SUBSTRATA OF THE ANIMAL ORGANISM.
gators, who are often unwearyingly occupied for years together in
endeavouring to collect a few firm supports for the great edifice
of a true philosophy of nature, we do not despair of seeing our
work rise in simple grandeur., more durable and lasting than those
sophisms of natural philosophy which, passing through ages from
Pythagoras and Empedocles to Schelling and Hegel, have, like the
sand of the ocean shore, been alternately upborne by one wave
and engulphed by the next.*
THE ORGANIC SUBSTRATA OF THE ANIMAL ORGANISM.
While we admit that the general investigation of nature must
derive its chief support and stability from the investigation of
particulars ; and while we deplore the evils that have accrued
to the natural sciences from the premature abstractions and hazard-
ous generalisations, deduced from data, which are in themselves
correct ; we must remember that no department of natural science,
however limited its domain, should be entered upon without the aid
of certain leading maxims, and without a definite aim. These
must be sought by physiological chemistry in physiology, no
less than in general chemistry; for without these aids zoo-
chemistry will continue a confused mass of loosely connected
facts, from which every fanciful enquirer may select whatever suits
his views, to beguile himself or others with short-lived dreams and
illusions.
The general principles and recent acquisitions of chemistry are
as essential to the consideration of the properties and chemical meta-
morphoses of animal substances, as an intimate acquaintance with
physiological theories is to the deeper insight into the chemistry of
the animal functions. It would be both inappropriate, and detri-
mental to this branch of science, to borrow from general chemistry
only such matters and facts as refer to the animal body, in order to
accumulate a mass of disjointed bodies, and group them together
simply according to their physiological import; as if we considered
zoo-chemical processes in a purely chemical light, depending upon
combination or decomposition, on chemical dualism, the theory of
acids and bases, &c. : we should rather adhere in our study of the
chemical substrata of the animal organism to the more general che-
* If any of my readers have chanced to meet with the article, " Chemismus in der
Medicin," which appeared in the " Gegenwart," they have probably been struck by the
similarity existing between the ideas expressed in the present work and the line of thought
followed in that essay ; I therefore feel called upon to avow the authorship of it.
ORGANIC SUBSTRATA OF THE ANIMAL ORGANISM. 25
mical points of view, from which we may consider the chemical
nature of these heterogeneous substances ; or, in fine, we must not
leave it to chance in zoo-chemistry, whether or not we examine a
chemical substance according to its occurrence in, or absence from
the animal organism. We must pay special attention to the place
occupied by each member of the group of chemical substances,
while the contiguous members and allied substances, that may not
have occurred in the same order in other animal bodies, must not
be disregarded. It would be illogical to regard the metamorphic
products of those animal matters that we have not hitherto been
able to detect in the excreta of animal bodies, as excluded from
zoo-chemistry, or at all events, as constituting only a less essen-
tial and more supplementary portion of the science. Zoo-chemistry
should not only embrace, according to the principles of pure
chemistry, all substances standing in a more or less intimate relation
to the matters actually found in animal bodies, but it should like-
wise make the fullest and most extended application of the various
propositions and theories by which general chemistry has at differ-
ent times been enriched. At the first glance it might appear as if
the physiological momentum were entirely lost in such a con-
ception of zoo -chemistry, but so far from this being the case, we
find that by such a method physiology is made to afford the
greatest aid.
The physiological importance of a body is mainly dependent on
its chemical composition and quality. If this proposition be true,
the assertion that a chemical conception of animal substances must
likewise be a physiological one, can no longer be called in question.
The physiological capacities of the material substrata of animate
beings can be referred only to their chemical qualities, and no form
of physiology, that was not tinctured with sophisms of the spiritualist
school, could hold that a chemical substance should depose all its
integral properties in the animate body, to assume higher or more
spiritual capacities in the vital sphere. But while we would endea-
vour in the following pages to establish the principle of the purely
chemical arrangement of zoo-chemical substances, we at the same
time most fully award to physiology what is its due. A chemical
arrangement of animal substances must be in perfect accordance
with a physiological one ; while the latter would neither be rational,
correct, or in accordance with nature, if it were to associate
substances having different chemical qualities, and artificially
separate others of analogous chemical characters. Thus, it is self-
evident, that substances containing no nitrogen, as starch, sugar,
26 ORGANIC SUBSTRATA OF THE ANIMAL ORGANISM,
&c., must be associated with very different physiological functions
from albuminous bodies, containing a large quantity of nitrogen :
but we should hardly have expected that the difference between
nitrogenous and non-nitrogenous bodies should be so clearly shown
in the two great kingdoms of living organisms ; the vital pheno-
mena of animals and plants, in a great measure owe their differences
to the diversity of these two classes of chemical substances. We
shall find in the course of our observations, that pure chemistry
cannot sever or group together organic substances, otherwise than
as physiological conditions shall require.
When we speak of applying a purely chemical principle to the
classification of the objects embraced in zoo-chemistry, — under-
standing by the term, the theory of the chemical substrata of
animal organisms, — we do not refer to the old and bye-gone classi-
fication of organic substances into acids, bases, and indifferent or
amphoteric bodies ; for we are of opinion that a classification of
animal substances, according to their combined chemical relations and
their chemical import, (but not according to a single property, as for
instance their basicity or acidity), must be physiologically correct,
since it is a natural method of arrangement. On the other hand we
regard a purely physiological principle of classification in zoo-che-
mistry (such as we followed in the first edition of the present
work) as 110 less irrational and unnatural than that which has
originated in views based merely on a theory of affinities. Although
we might at first sight be disposed to regard as appropriate a
classification of organic substrata into nutrient matters and excreta,
the practical application of such a mode of treatment will exhibit
numerous deficiencies, which completely nullify the advantages
it might have been supposed to possess. For it soon becomes
apparent, that a body which appears in one part of the animal
organism, or in one process, strictly as a product of decomposition,
is applied in another to the formation of a tissue, or the accom-
plishment of a purely physiological function. A separation of
zoo-chemical substances into secreted and excreted matters, leads
to the greatest uncertainty and the most intricate confusion. We
must, however, admit that every systematic mode of arrangement
seems impracticable in a purely empirical science, which ought
only to follow a genetic or eetiological, and not a teleological method ;
since the latter can, at most, only indicate the direction in which
investigation should be pursued in an immature science. A new
phrase has, however, been recently employed by which it was con-
jectured that zoo -chemical processes might, according to their nature,
ORGANIC SUBSTRATA OF THE ANIMAL ORGANISM. 27
be separated into two wholly different classes, viz. progressive and
regressive metamorphosis of matter. However deserving these
words may be of being retained in physiological chemistry to serve
as concise and generalising designations, they do not express definite
ideas in relation to the abstruser study of this science, or of pure
zoo-chemistry. Without dwelling upon the fact that it is impos-
sible to prove, in the case of many zoo-chemical substances,
whether they belong to the progressive or the regressive meta-
morphosis of matter, we will only observe, that even in the animal
processes no limits can be drawn between the termination of pro-
gressive and the commencement of regressive metamorphosis. Car-
nivorous animals only introduce into their organism well-elaborated
animal matter, and hence in them the extent of the progressive
metamorphosis must be very inconsiderable; yet an opinion has
long been entertained, that in animal life there is a regressive
formation alone, and in vegetable life only a progressive develop-
ment of organic matter. The acrimonious discussion that arose,
as to whether the fibrin of the blood belonged to the progressive or
the regressive metamorphosis, is sufficient proof that no leading
principle is embodied to these terms. We perceive, therefore, that
a purely physiological mode of classification is as untenable as those
chemical methods which have been borrowed from the individual,
and, in most cases, incidental properties of substances.
No chemist at all acquainted with the present state of organic
chemistry,, will be disposed to place such bodies as albumen and
urea in one genus, because both these substances are nitrogenous
and amphoteric, any more than the physiologist, who is well aware
that a nutrient substance must of necessity have a very different
chemical constitution from an excreted substance. We would, there-
fore, again observe that chemists and physiologists must perfectly
coincide in their views respecting the mode of classifying and
considering animal bodies, and that where they differ in their
description, both cannot be true to nature; for where, for instance,
a physiologist should regard a substance as a product of secretion,
while the chemist classed it with albuminous substances in accord-
ance with bis observation of its constitution, one or the other must
be in error ; since the chemical qualities of a body cannot be at
variance with the physiological. That method which fulfils the
requirements of both sciences, chemistry as well as physiology,
can therefore be the only correct mode of treating zoo-chemistry.
Although zoo-chemistry constitutes the firmest basis of physio-
logical chemistry, and although the chemical element should be
28 ORGANIC SUBSTRATA OF THE ANIMAL ORGANISM.
duly considered, we ought not wholly to lose sight of the physio-
logical relations of individual substances. It is not enough to
describe the properties, composition, preparation, and decomposi-
tion of matters without also considering their physiological cha-
racter. The occurrence of a substance in certain parts of the animal
body and in certain processes, its relation to the general metamor-
phosis of matter, and its progressive or regressive formation,
are all questions for whose solution we do not look to pure che-
mistry, although physiology alone is equally incompetent to the
task.
A structure such as we have endeavoured to sketch, appears to
us indispensable to zoo-chemistry, before we can expect that
physiology and medicine will furnish an exact reply to those
general questions in chemistry which refer to the more important
processes. Similar views have undoubtedly guided most true
natural enquirers in their labours in this field of scientific investi-
gation. Nor have such men as Berzelius, Wohler, Liebig, and
Mulder, ever undertaken investigations which from their deficiency
in all scientific bases could not lead to any scientifically reliable
results. We find that such men have always endeavoured to afford
that internal scientific support to pure zoo-chemistry without which
it must continue a mere medley composed of disjointed facts. In
the present day we are, however, justified in expecting well-
grounded physiological results from pure zoo-chemistry, nor do
we exaggerate in stating that more light has been thrown on the
metamorphosis of animal matter by such zoo-chemical investiga-
tions, as Mulder's on albuminous substances, Liebig's on creatin,
and Wohler's on uric acid, than by many hundred analyses of the
blood and urine.
In accordance with the views already advanced, we shall in
the following sketch of the zoo-chemical elements, retain those
groups that have been established by the most recent investiga-
tions of pure chemistry. Bodies of homologous chemical value
must also possess common physiological relations. We shall begin
with bodies of the simplest composition, most of which have seldom,
if ever, been found developed in the animal organism ; but with
which it is necessary we should become acquainted as the derivatives
of animal substances. By thus passing from the groups of simply
constituted bodies to those of more complicated composition, we
shall gradually become more familiar with the mechanism of the
association and separation of organic matter, until we are finally
enabled to form a correct judgment of the most complicated sub-*
ORGANIC SUBSTRATA OF THE ANIMAL ORGANISM. 29
stances of the animal organism. We must, however, submit the
facts before us to a careful and critical enquiry, if we would employ
zoo-chemistry as the firmest support of physiological chemistry.
For there is scarcely any department of scientific enquiry in which
truth and error, suppositions and facts, acquired and presumed
results, and positive and hypothetical deductions, have been more
confounded. We need only refer to the fanciful trifling with che-
mical formulae which, from bearing the impress of the words and
symbols of an exact science, have deceived many unaccustomed to
such characters. The cause of the many erroneous views which
have passed from physiological chemistry to physiology and medi-
cine, mainly depends upon the inadequate knowledge of what is
necessary for the establishment of a formula for the chemical consti-
tution of a body. It seems, therefore, not wholly inappropriate, in
an introduction to zoo-chemistry, to refer to the points in pure che-
mistry, from which alone the chemist is able to deduce a formula.
We might indeed draw some conclusions regarding the atomic
composition of a body from the mere result of one or more
elementary analyses, or, in other words, we might, from the per-
centage composition of a body, construct an empirical formula
which would serve to exhibit the relation of the separate elements
to one another. But this method can alone possess any scientific
value when, on the one hand, we are convinced that the substance
under consideration is chemically pure, and when, on the other hand,
after the former fact has been fully proved, the errors incidental
to every analysis are considerably smaller, (i. e. when the varia-
tions in the percentage results of the analysis are less,) than would
be afforded by any other formula than the one calculated. Such
variations by which an entire analysis may be rendered unavailable
are of common occurrence in the determination of hydrogen ; the
atomic weight of this element being so small that the slightest
variations in the percentage composition derived from the individual
analyses may cause the formula of a body to differ by one or
more atoms of hydrogen. Moreover, another reason why element-
ary analyses often exhibit the most marked variations in the quan-
tity of hydrogen, is that the drying of an organic substance is only
relative, and as many of these substances are extremely hygro-
scopic, it is impossible, even with the greatest care, to prevent them
from condensing water from the atmosphere during the process of
weighing. We call this drying relative, because in many substances
we are unable to determine at what degree of temperature, and after
what time they should be regarded as dried, as decomposed, or as
30 ORGANIC SUBSTRATA OF THE ANIMAL ORGANISM.
still retaining water. Hence it is evident that the number of atoms
of hydrogen will be computed with the least certainty in the most
important elements of zoo- chemistry, as in the albuminous matters
arid their derivatives, which are bodies of very high atomic weight.
In consequence of the atomic weights of these substances being
so high, and considering the great uncertainty whether they are free
from all admixtures, excepting the salts with which they are insepa-
rably connected, the number of atoms of carbon cannot be computed
with certainty from the empirical result of the analysis. As, more-
over, we possess no means of directly determining the oxygen con-
tained in an organic body, and can only estimate it by the loss in
weight of the substance analysed, that is to say, by the subtraction
of the quantities of carbon, hydrogen, and nitrogen, the collective
errors in the investigation will frequently affect the number repre-
senting the oxygen, which must therefore be regarded as the most
uncertain number in the analysis.
When all the errors which attach to the calculation of atomic
formulae from the direct results of elementary analyses have
been as thoroughly as possible avoided, and even when they
may be regarded as = 0, the formula will still only have a
problematic value until the saturating capacity of the body has
been determined by direct experiment, that is to say, until the
atomic weight derived from the saturating capacity of the body shall
be found to accord with that deduced from the analysis. We have
therefore no guarantee for the true atomic weight of a body, or
for its atomic composition, without a previous knowledge of the
saturating capacity, even supposing that all the other data were per-
fectly correct, and free from doubt. Thus, for instance, we should
not know whether lactic acid and starch were composed according
to the formula C6H5O5, or C12H10O10, or according to other
multiples. But there are, unfortunately, many animal substances
of a higher order, whose atomic composition cannot be tested by
a comparison with their saturating capacity. Such substances either
do not combine in definite proportions with other substances, or
do so in various relations, so that it is impossible to determine
which combination is actually to be regarded as the neutral one.
The variations in the numbers of the saturating capacity, are fre-
quently much more important in such bodies (partly owing to the
admixture of mineral substances with them) than those of the num-
bers of the elementary analysis ; that is to say, the atomic weight
derived from the saturating capacity is frequently no less uncertain
than that derived from the elementary analysis.
NON-NITROGENOUS ACIDS. 31
If these well-established rules be followed, and the properties
of most albuminous matters and their derivatives be compared in
accordance with these considerations, we shall easily perceive what
credit should be attached to the formulae established for the compo-
sition of these bodies, and with what temerity these most proble-
matic of all formulce have been transferred to physiology only to
involve it in a new labyrinth of vague dreams and fantastic fictions.
This absence of reasoning power, this perfect ignorance of all leading
maxims having any scientific import, this superficial knowledge of
the true requirements of science, has led many physicians to make
elementary analyses of admixtures of several substances of a highly
variable composition : as, for instance, of blood, bile, muscle, &c.,
and to establish chemical formulae from the data thus afforded.
Even were it not known that these animal fluids are composed in
their physiological condition of constituents having very variable
and different proportions, and that microscopic observation had
shown the muscular bundles to be composed of very distinct and
separate morphological elements, this offence against the first prin-
ciples of chemistry ought not to be palliated, on the supposition
that unchemical experiments might chance to yield valuable phy-
siological results ; for physiology demands from chemistry exact
and scientifically established facts, and not the mere ignes fatui of
chemical illusions.
NON-NITROGENOUS ACIDS.
= CnHn_I03+HO.
The acids of this group possess (as is indicated by the above
formula) the following property ; in their isolated state, that is to
say when not combined with bases, they contain 4 atoms of oxygen
and a multiple of a carbo-hydrogen polymeric with olefiant gas ;
in their combination with bases they lose, however, 1 atom of water,
so that the resulting salt contains an acid in which 3 atoms of
oxygen are combined with a carbo-hydrogen whose hydrogen is
always too little by 1 equiv. exactly to produce olefiant gas with
the carbon.
The number of this class of acids is considerable ; we have
Formic acid C2H O3.HO=(CH)2O4.
Acetic acid C4H3O3.HO=(CH)4O4.
Metacetonic acid C6H5O3.HO=(CH)6O4.
Butyric acid C8H7O3.HO=(CH)8O4.
32 THE BUTYRIC ACID GROUP.
Valerianic acid C10 H9 O3. H O=(C H)10 O4.
Caproic acid C12 Hn O3. H O=(C H)12 O4.
GEnanthylic acid C14 H13 O3. H O=(C H)14 O4.
Caprylicacid C16 H15 O3. H O=(CH)16 O4.
Peiargonic acid C18 H17 O3. H O=:(C H)18 O4.
Gapricacid C20 H19 O3. H O=(C H)20 O4.
Closely approximating to them in their composition is another
somewhat extensive group of organic acids, the " fatty acids,"
which, however, we shall consider separately, because they possess
certain distinctive characters which would interfere with the general
view which we propose to take of these acids.
It is not surprising that as these acids present a perfect analogy
in their composition (homology), they should also present very many
similarities in their physical and chemical properties. They are
all fluid at an ordinary temperature, and, when freed as much as
possible from water, are mostly oleaginous ; they do not crystallise
and solidify at a higher temperature than 0°, but are so volatile that
at an ordinary temperature they more or less powerfully irritate the
eyes and nostrils ; they are colourless, but have a peculiar burning
or acrid taste. They are soluble in almost every proportion in
water, alcohol, and ether ; they redden litmus powerfully ; they
may be distilled without being decomposed ; their boiling point
ascends with the number of the atoms of the carbo-hydrogen
(according to Kopp, at the rate of 19° [34°-2 F.] for 2 atoms of
CH), and the densities of the vapours of these acids have a similar
relation to the number of the atoms of the carbo-hydrogen ; more-
over these vapours are inflammable when too much aqueous vapour
is not mixed with them.
Combined with bases, these acids form salts which are for the
most part soluble, and some of which crystallise readily. With
organic haloid bases, — the oxides of methyl, ethyl, amyl, and
lipyl, — they form what are called haloid salts, which are produced
either by direct union of the acid and the base, or by double
decomposition. Almost all the compounds of the first three are liquid,
and extremely volatile ; their boiling point is lower by a definite
number of degrees than that of the corresponding acids when de-
prived as thoroughly as possible of water. In no class of bodies
have so large a number of metameric substances been hitherto found
as in this ; thus, for instance, metacetonic acid=C6 H5 O3. HO,
formiateof oxide of ethyl. =C4 H5 O. C2 HO3, and acetate of oxide
of methyl = C2 H3 O. C4 H3 O3, containing equal numbers of the
atoms of the individual elements— C6 H6 O4, are metameric; so
THE BUTYRIC ACID GROUP. 33-
also are oenanthylic acid=C14H13O3. HO, acetate of oxide of amyl=
C10HnO.C4H3O3, caproate of oxide of methyl^C^O.C^I^Og,
and valerianate of oxide of ethyl=C4H5O.C10H9O3— C14H14O4.
Most of these acids were formerly called volatile fatty acids
from having first been made known through the decomposition of
many fats ; but this designation ought no longer to be retained,
because while a large number of these acids cannot be prepared
from fats, others again may be obtained with equal facility, as
educts and products of many other animal or vegetable substances.
Thus, for instance, butyric acid, which was formerly regarded as the
representative of these acids, may be as easily obtained by the
putrefaction or artificial oxidation of albuminous substances, or by
the fermentation of sugar and starch, as by the saponification of
butter.
Before we enter upon the consideration of the individual acids
belonging to this group, we must draw attention to some of the
relations possessed in common by all of them, and which depend
upon the substances with which they are intimately connected, upon
the series of homologous bodies from which they are either pro-
duced, or into which they are converted under like conditions,
and more especially upon their chemical constitution.
We would first draw attention to the fact that by following
the theory of organic radicals, we discover a number of bodies
which may be regarded as lower stages of oxidation of the carbo-
hydrogen radical of these acids. Thus we have bodies of the
general formula C^H^O-f HO[= (CH)nO2] and CnHn-1O2+HO
Q=(CH)nO3], The substances composed in accordance with the
first of these formulae have been named oxides of the radicals of the
acids, or more commonly aldehydes. These .bodies are for the most
part liquid, very volatile, and oxidise rapidly when exposed to the
air, becoming thus converted into their corresponding acids. Up to
the present time, the following bodies of this classhave been accu-
rately studied.
Aldehyde of acetic acid C4H3O.HO.
Aldehyde of metace tonic acid .... C6H5O.HO.
Aldehyde of butyric acid C8H7O.HO.
The stage of oxidation=CnHn__1O2.HO, existing between these
oxides and the acids in question, is only found in a few cases ; as
Acetylous acid C4 H3 O2.HO.
(Enanthylous acid C14H13O2.HO.
Moreover they are rapidly oxidised by the air, and converted
into the corresponding acids.
D
34 THE BUTYRIC ACID GROUP.
From the dry distillation of the baryta-salts of several of these
acids, substances isomeric with the aldehydes have been obtained.
They are known by the terminal syllable al ; they occur as oily,
very volatile, pungent fluids, which can be distilled without under-
going decomposition, dissolve freely in alcohol and ether, but not
in water, possess neither acid nor basic properties, are not so
easily converted into the corresponding acids by the action of the
atmosphere as by means of oxidising substances, and readily
exchange a portion of their hydrogen for chlorine. At present we
are acquainted with —
Butyral C8 H3 O2.
Valeral C10H10O2.
(Enanthal C14H14O2.
Another series of derivatives is obtained from these acids by
heating their salts with strong bases, the acid losing the elements
of an atom of carbonic acid, and becoming converted into a sub-
stance which, in addition to a carbo-hydrogen polymeric with olefiant
gas, (but composed of an odd number of atoms,) contains 1 atom
of oxygen ; thus, for instance, Ca O. C8 H7 O3 — C O2==:C7 H7 O.
These bodies are distinguished by the terminal syllable one ; they
are colourless and very volatile oils with a penetrating odour, readily
soluble in alcohol and ether, insoluble in water, very inflammable,
and not capable of combining with acids or bases.
In these acids, as in many other organic bodies, certain
atoms of hydrogen may be replaced by the corresponding number
of atoms of chlorine, bromine, or iodine; thus, for instance, the
formation of chloracetic acid is explained by the equation
C4H3O3.HO + 6C1=:3 HC1 + C4C13O3.HO. In butyric acid,
various numbers of atoms of hydrogen may be replaced by an
equal number of atoms of chlorine ; thus, we have two chloro-
butyric acids represented by C8(H5C12)O3, and C8(H3C14)O3.
However strongly Berzelius, even to the very close of his life, may
have contended against the substitution-theory, yet we must not
disregard it in the consideration of the constitution of organic
bodies. For although this mode of indicating the composition of
organic bodies containing chlorine is opposed to the electro-
chemical views that have hitherto prevailed in chemistry, it ought
not to be wholly rejected, since it is the mode of representing the
constitution of such bodies, which approximates most closely to
the empirical composition. It necessitates no rigorous adhesion
to the metaleptic views of Dumas and Laurent, if for the sake of
greater facility of enquiry, and a better comprehension of the
,, THE BUTYRIC ACID GROUP. 35
subject, we employ this mode of representation, arid arrange the
formulae of these bodies so as to substitute chlorine in the place of
hydrogen.
But putting out of the question the practical advantages afforded
by this mode of viewing the subject, and independently of the cir-
cumstance that Berzelius's mode of indicating the composition of
such bodies is very far-fetched, and cannot without great difficulty
be brought in accord with other experiments, this mode of investi-
gation is recommended by the circumstance that, in most cases, not-
withstanding the loss of atoms of hydrogen, and the introduction
of negative chlorine, bromine, or iodine, or of the complex atom=:
N O4, corresponding to hyponitric acid, the new body retains the
chemical character of the original compound ; that is to say, if the
mother-substance were an acid, the newly-formed substance would
be so also ; if it were neutral, the new compound would likewise
be neutral ; and it is very remarkable, that basic bodies, like the
alkaloids, continue bases when the above elements, or hyponitric
acid, are substituted for the atoms of hydrogen.
All the acids of this group likewise form amide-compounds.
The term amide is known in inorganic chemistry. The atomic
group H2N, which cannot be exhibited in an isolated state, is
found in many metallic preparations produced by treating com-
pounds of the metallic oxides with ammonia. It might thence be
assumed, that the atom of oxygen of the metallic oxide, as for
instance of the oxide of mercury, has united with an equivalent of
hydrogen of the ammonia to form water, and that the metal then
unites with what remains of the ammonia =:H2N to form the
so-called amide. In organic chemistry the amides are produced in
a similar manner, with this difference only, that in this department
it is chiefly acid substances which have a tendency to enter into
such combinations. We can best realise the production and
decomposition of organic amides, by assuming that the hypothetical
anhydrous ammonia-salt of the organic acids loses an equivalent of
water, while an equivalent of hydrogen is withdrawn from the am-
monia, and an equivalent of oxygen from the acid. Thus acetamide
is equal to acetate of ammonia, minus 1 atom of water, since
H3N. C4H3O3— HO=H2N. C4H3O2=:C4H5NO2.
According to the theory of substitutions, one atom of the
oxygen of the acid in these combinations is replaced by the
complex atom H2N, but this mode of viewing the subject cannot
be adopted, since the acids, by this union, entirely lose their acid
character, and even basic bodies, on their entering into combina-
D 2
36 THE BUTYRIC ACID GROUP.
tion with amide completely lose their basicity. The knowledge of
these amide-compounds, and of their general characters, which have
only recently attracted the attention of chemists, is of great
importance, because there is reason for believing that several
substances occurring in the animal and vegetable kingdoms belong
to this class of bodies.
While the amides of many other acids can be artificially
produced, by the exposure of the ammonia-salt to heat, or by the
treatment of the chlorine-compounds writh ammonia, the amides
of the acids of this group are best obtained from their salts of oxide
of ethyl and ammonia. Thus acetamide is formed on digesting
acetate of oxide of ethyl (acetic ether) with fluid ammonia, since
As is shown in this formula, the oxide of ethyl becomes con-
verted in this process into the hydrated oxide, or, in other words,
the ether becomes converted into alcohol ; the water necessary for
this change is formed from 1 atom of the oxygen of the acetic acid
and 1 atom of the hydrogen of the ammonia.
The amides of these acids are solid, crystallisable, and colour-
less ; they are soluble in water and alcohol, sublime without
undergoing decomposition, have no action on vegetable colours,
and are indifferent towards weak acids and bases. If, however,
they be treated with strong acids or bases, they assimilate water
and become decomposed into ammonia and the corresponding
acid.
Acetamide, treated with caustic potash, yields ammonia and
acetate of potash : C4H5NO2 + KO.HO^ KO. C4H3O3 + H3N.
The behaviour of this amide, as well as that of all others,
towards nitrous acid, is very characteristic ; for, by the action of
this acid, these amides are converted into the original acids,
ammonia being at the same time developed. (Piria.*)
We may explain this process by supposing that hydrogen is
assimilated through the action of the nitrous acid on the amide, and
that ammonia and the organic acid are formed, the ammonia,however,
in statu nascenti, becoming decomposed with the nitrous acid into
water and nitrogen ; thus, for instance_, acetamide and nitrous acid
yield water, acetic acid, and nitrogen, for C4H5NO2 + NO3 =
C4H3O3 + 2 HO + 2 N. In this way we may hope that several
nitrogenous animal matters may be discovered to be amides, as in
the case of asparagin, which has been shown to be the amide of
malic acid.
* Ann. de Chim. et de Phys. 3 Ser, t. 22, pp. 170-179.
THE BUTYRIC ACID GROUP, 37
If the amides of these acids be treated with anhydrous phos-
phoric acid, they lose 2 atoms of water, and nitrogenous bodies rich
in oxygen remain, which contain the radical of the acid and have
1 equiv. of nitrogen in place of the 3 atoms of oxygen. These bodies
have been named nitriles. Notwithstanding the similarity of their
composition with that of the volatile oxygenous alkaloids, they
possess no basic properties.
Valeramide and phosphoric acid form hydrated phosphoric acid
and valeronitrile : C10HHNO2 + PO5=PO5.2HO +C10H9N.
The amides of this group are finally distinguished by a property
which is not common to the amides of most other acids ; when
treated with potassium they yield cyanide of potassium and a carbo-
hydrogen. Hence it seems probable that cyanogen exists pre-formed
in these amides, since, from their total want of basic properties, it
cannot be supposed that they contain a conjugated ammonia and
that 1 atom of oxygen can be replaced by amide.
Taking this view, acetamide must be regarded as hydrocyanate
of wood-spirit, and metacetamide as hydrocyanate of alcohol, for
C4H5NO2= C2H4O2. HC2N,and C6H7NO2= C4H6O2. HC2N.
The amides lead us at once to a further consideration of
the nitrites, which are equally important in reference to our
knowledge of the arrangement of atoms and the metamorphosis
of matter.
These bodies are, in part, formed during the decomposition of
animal substances by oxidising agents; they may, however, be
obtained by treating the corresponding ammonia-salt or the amide
with anhydrous phosphoric acid. This mode of preparation is
especially applicable for the nitriles of this group of acids ; others
are prepared either by the mere exposure of the ammonia-salt to
heat, or by passing the vapour over heated caustic lime.
The nitriles are oily, very volatile fluids, less soluble in water
than in alcohol and ether, and having a peculiar odour ; they can
be distilled without undergoing decomposition, have no action on
vegetable colours, and do not unite with acids to form salts. They
unite, however, directly with sulphuretted hydrogen, assimilating
2 equivalents of it, so that sulphurous substances analogous to the
amides are produced ; thus, for instance, benzonitrile, with sul-
phuretted hydrogen, forms sulphobenzamide, which is analogous
to benzamide: C14H5N + 2HS==C14H7NS2coC14H7NO2.
Alkalies and strong acids reduce most of the nitriles to their
original component parts, that is to say, to ammonia and the cor-
38 THE BUTYRIC ACID GROUP.
responding acid, by assimilating 3 atoms of water ; thus, for instance,
in the case of valeronitrile : C10H9N + 3HO=:H3N + C10H9O3.
Several of the properties of the nitriles, and especially the
modes in which they are decomposed, indicate that in their chemical
constitution they are not to be regarded as compounds of the radical
of the corresponding acid with nitrogen, but rather as combinations
of cyanogen and certain carbo-hydrogens ; — a view which throws
a perfectly new light on the theoretical composition of the acids of
this group.
If we first glance at the nitriles of the simplest acids of this
group, — those of formic acid, acetic acid, and metacetonic acid, — it
becomes manifest that these are bodies which have been long
known, but never have been, nor can be, regarded as nitriles. The
nitrile of formic acid must = C2HN; this, however, is the com-
position of hydrocyanic acid, which, as is well known, is also
obtained by heating formate of ammonia, three atoms of water
being separated. Hydrocyanic acid can, however, as we know, be
readily converted, like the nitriles, into ammonia and the corre-
sponding (formic) acid.
If, farther, with the view of preparing the nitrile of acetic acid,
acetamide be mixed with anhydrous phosphoric acid, another long-
known body, supposed to be otherwise constituted,isformed,namely,
cyanide of methyl, for C4H3N=C2H3. C3N. The nitrile of meta-
cetonic acid which corresponds to cyanide of ethyl, behaves in
a perfectly similar manner, for C6H5Nr=C4H5.C2N. An intelli-
gent observer, Kolbe,* who has instituted very excellent observations
on the subject, struck upon the idea of preparing metacetonic
acid from the cyanide of ethyl, (obtained by the distillation of
sulphate of oxide of ethyl and potash, and cyanide of potassium),
by treating it with solution of potash ; and the attempt completely
succeeded, for the cyanide of ethyl (perfectly corresponding in its
nature to the aforesaid nitrile), took up 3 atoms of water, and became
decomposed into ammonia and metacetonic acid, according to the
formula, C4H5.C2N-f3HO=H3N-f C6H5O3.
From these facts he was led to regard the nitriles (as far as they
are yet known) of the acids of this group as combinations of cyano-
gen with a radical of the haloid bases pertaining to the ether group,
that is to say, with a carbo-hydrogen in which there are contained a
large number of atoms of carbon, and the next higher odd number
* Phil. Mag. Vol. 31, pp. 266-271.
THE BUTYRIC ACID GROUP. 39
of atoms of hydrogen. Thus, these substances arrange themselves
in the following arithmetical proportion : —
Nitrile of formic acid = hydrocyanic acid = H . C2 N.
acetic acid ... = cyanide of methyl =C2 H3. C2 N.
metacetonic acid = cyanide of ethyl =C4 H5. C2 N.
Butyronitrile =C6H7. C2N.
Valeronitrile =C8 H9. C2 N.
While in the first three of these combinations the existence of
cyanogen may be regarded as established, Kolbe * believed that he
could recognise the existence of t such carbo-hydrogens as C6H7 and
C8 H9; and, indeed, he fully proved their presence, by exposing to an
electric current the potash-salts of the acids corresponding to the
two last-named nitriles, namely, butyric acid and valerianic acid ;
besides other products, he then obtained the carbo-hydrogens
C6 H7 and C8 H9. In further investigations^ by decomposing
cyanide of ethyl by potassium, he established the existence of the
radicals, methyl and ethyl, C2H3 and C4H5.
From these facts relating to the nitriles of these acids, we are
almost involuntarily led to Kolbe's original view, and to regard the
acids of this group as conjugated oxalic acids, that is to say, as acids
in which oxalic acid is so combined with one of the above-named
carbo-hydrogens =CnHn+1, as not to affect the saturating capacity
of the acid.
This view is supported by the following experimental evidence.
Butyric and valerianic acids are decomposed under the influence
of the galvanic current ; assimilating an atom of oxygen, they yield
2 equivs. of carbonic acid and the corresponding carbo-hydrogen.
Cyanogen with water becomes decomposed, as is well known,
into oxalic acid and ammonia (C2N-f 3HO=rH3N-r-C2O3) ;
conversely, on heating oxalate of ammonia, cyanogen, together
with oxamide, is formed. The production and decomposition of
valeronitrile may hence be explained in the following manner : if
valerianic acid be an oxalic acid conjugated with the carbo-
hydrogen, #a/y/=C8H9, the latter is converted into cyanogen by
the metamorphosis of the ammonia-salt into nitrile; and the cya-
nogen combining with the adjunct C8H9, yields the empirical
formula for valeronitrile. If, however, the latter be regarded as
cyanide of valyl, and be decomposed by alkalies, the conjugated
cyanogen, just as if it were isolated, becomes converted into
ammonia and oxalic acid, which then remains in combination with
the conjugate C8H9.
* Chem. Gaz. Vol. 5, p. 228.
f Ann. d. Ch. u. Pharm. Bd. 65, S. 271-288.
40 THE BUTYRIC ACID GROUP.
Considering the subject in this point of view, we must regard
the acids of this group as constituted in the following manner : —
Formic acid ^hydrogen-oxalic acid= H. C2O3.
Acetic acid =methy oxalic acid =C2 H3. C2O3.
Metacetonic acid ^ethyloxalic acid =C4 H5. C2O3.
Butyric acid =metethy oxalic acid =C6 Hr C2O3.
Valerianic acid — valyloxalic acid — C8 H9. C2O3.
Caproic acid =amyloxalic acid =C10Hn.C2O3.
Closely allied to this view of the constitution of these acids is
another consideration, which has reference to the production of
these homologous acids from the series of the ether-like, homolo-
gous haloid bases. The general formula of the haloid bases, — oxide
of methyl, oxide of ethyl, and oxide of amyl, is=CnHn+1O, while
the formula of the acids is CnHn_1O3; we have explained the pro-
duction of the acids from the corresponding haloid bases by the
simple assimilation of 4 atoms of oxygen, and loss of 2 atoms of
water; as, for instance, in the conversion of oxide of ethyl into
acetic acid : if, however, the above conclusions, which have been de-
rived from simple inductions, be correct, it must be assumed that
(to take a definite case) in the conversion of oxide of ethyl into acetic
acid, the complex atom, C2H2, leaves the'radical of the oxide of
ethyl, C4H5O, and unites with 4 extraneous atoms of oxygen, and
with the 1 atom which is present in oxide of ethyl, to form water
and oxalic acid, which combines with the radical of the next
lower haloid base, methyl, and represents acetic acid.
Oxide of amyl yields valyloxalic acid :
(C10Hn)0 + 40=2HO+(C8H9) C2O3.
Oxide of valyl yields metethyl oxalic acid :
(C8H9)0 + 40=2HO+(C6H7)C203.
Oxide of metethyl yields ethyloxalic acid :
(C6H7)0 + 40=2HO + (C4H5)C203.
Oxide of ethyl yields methyloxalic acid :
(C4H5)0+40=2HO + (C2H3).C203.
As, according to this view, oxalic acid constitutes the acidify-
ing principle of the bodies of this group, we shall consider it the
first in the series of acids.
OXALIC ACID. 41
OXALIC ACID.— C2O3.HO.
Chemical Relations.
Properties. — This acid crystallises with 3 atoms of water in
oblique rhombic prisms, is devoid of smell, has a sharp acid taste,
and effloresces on exposure to the air, losing 2 atoms of water
and becoming disintegrated into a white powder ; on heating it care-
fully to 150° or 160°, it sublimes undecomposed in acicular crys-
tals ; but at 1700 (or if the crystallised acid be rapidly heated to
155°), it becomes decomposed into carbonic oxide and carbonic
acid, a little formic acid, and water ; it dissolves in 8 parts of cold
and 1 part of boiling water, and in 4 parts of spirit of wine ; its
solutions redden litmus strongly. On boiling oxalic acid with solu-
tion of oxide or chloride of gold, carbonic acid is evolved, and the
gold is precipitated in the form of extremely fine black powder.
Treated with concentrated sulphuric acid, it becomes decomposed
into carbonic oxide and carbonic acid, and effects no change in the
colour of the sulphuric acid.
Composition. In accordance with the above formula, this acid,
which cannot exist in the free state without water, contains in 100
parts :
Carbon 2 atoms = 26-667
Hydrogen 3 „ = 53*333
Water 1 „ = 20-000
100-000
The atomic weight of the hypothetical anhydrous acid= 450*0 ;
its saturating capacity = 22*222.
In reference to the history of this acid, we may observe that
while some chemists regard it as the oxide of an oxygenous radical,
oxalyl=C2 O2, in consequence of the preponderance of its acidity
over that of carbonic acid, others regard it as a hydrogen acid
=C203.H.
Combinations. Oxalic acid combines with alkalies in three pro-
portions, in which the oxygen of the base is to that of the acid as
1 : 3, 1 : 6, and 1:12 respectively. These salts are soluble in
water, but all other oxalates are insoluble, or only very slightly
soluble, in that fluid; none of the oxalates are soluble in alco-
hol. These salts do not char when heated. The combinations of
oxalic acid with the more easily reducible oxides, yield carbonic
acid and the reduced metal (thus, for instance, CoO.C2O3=:2CO2
-f Co) ; while those with less easily reducible bases evolve carbonic
oxide gas, and are converted into carbonates.
Omlate of Amminia, neutral oxalate of oxide of ammonium,
42 THE BUTYRIC ACID GROUP.
H4NO.C2O3-f-2HO, is obtained by neutralising oxalic acid with
carbonate of ammonia, and evaporating the solution; it crystallises
in needles, has a saline taste, effloresces on exposure to the atmo-
sphere, and its solubility in water is less than that of oxalic acid.
Oxamide, C2H2NO2(=:H2N.C2O2) is obtained either by the
dry distillation of oxalate of ammonia, or by the treatment of neu-
tral oxalate of oxide of ethyl with ammonia ; it has a crystalline
powdery appearance, is of a glistening white colour, has no smell or
taste, and dissolves very slightly in cold, but rather more freely in
hot water ; when strongly heated it becomes decomposed into water,
carbonic oxide, hydrocyanic acid, and a little urea. If a sufficient
quantity of water be present, a very small quantity of oxalic acid
can convert an infinite quantity of o'xamide into oxalate of ammonia.
Oxamic Acid, C4H2NO5.HO, is an acid in which we assume
that oxalic acid is conjugated with oxamide (C2H2NO2.C2O3.HO);
it is produced by the dry distillation of binoxalate of ammonia;
it occurs as a colourless granular inodorous powder, which is not
readily soluble in water, and reddens litmus. When heated with
sulphuric acid it becomes decomposed into ammonia and oxalic
acid ; its salts are for the most part soluble ; at least its baryta,
lime, and silver salts dissolve in boiling water.
Oxalate of Lime, CaO.C2O3, is a very important substance in
pathological chemistry; it occurs as a white, tasteless, and inodorous
powder, which, however, under the microscope, is found to exhibit
a distinct crystalline form. These crystals, whose crystallographic
relations have been carefully studied by C. Schmidt*, appear, when
seen with a low power, as envelope-formed, sharply defined
bodies; but when more highly magnified, they may easily be recog-
nised as obtuse square octohedra; some, however, among them,
are very acute. These crystals contain 1 atom of water, which they
lose at 180°. Oxalate of lime is all but insoluble in water, and
it is almost proof against the action of acetic and oxalic acids ; it
readily dissolves, however, in the stronger mineral acids.
Artificially prepared oxalate of lime only shows these crystals,
when very dilute solutions of salts of lime have been mixed with
diluted boiling solutions of alkaline oxalates ; under other circum-
stances it appears under the microscope merely in spherical or no-
dular masses. Crystals of oxalate of lime may be distinguished from
those of chloride of sodium which they much resemble in form, by
the easy solubility of the latter in water, and by their transparency.
Larger crystals of oxalate of lime sometimes occur, having some re-
* Entwurf finer allg. Untersuchungsmethode der Safte und Excrete des thierischen
Organismus. Mitau u. Leipz. 1846, S. 63-65.
OXALIC ACID. 43
semblance to crystals of phosphate of ammonia-magnesia, which in
the projection resemble a square octahedron ; but a more accurate
microscopic examination and the solubility of the triple phosphate in
acetic acid enable us to discriminate between these crystals and
those of oxalate of lime. GoldingBird* also describes crystals of oxalate
of lime shaped-like dumb-bells or rather like two kidneys with their
concavities opposed, and sometimes so closely approximating as to
appear circular, the surface being finely striated. These crystals
are produced, in all probability, by a zeolitic arrangement of minute
acicular crystals presenting a physical structure resembling that of
spherical crystals of carbonate of lime. [Dr. Golding Birdf has
recently shown that in all probability these dumb-bell crystals con-
sist of oxalurate of lime. — G. E. D.]
Other oxalates have at present excited no physiological in-
terest.
Preparation. — Oxalic acid is a final product of the oxidation of
most animal and vegetable bodies ; hence it may be prepared from
very different substances by strong oxidising agents : it is most
commonly obtained by the decomposition of sugar by not too con-
centrated nitric acid, by evaporation to crystallisation, and finally
by recrystallisation in water.
Tests. — Oxalic acid and its salts are so well characterised that
it is hardly possible to mistake them for any other bodies. In the
animal organism oxalic acid is almost always combined with lime,
and with a little practice this salt may be readily discovered by the
microscope, and by the insolubility of its crystals in acetic acid.
Should a further investigation appear necessary, the presence of
oxalic acid might be determined by its property of reducing gold from
its solutions, and by its not charring either in the free or in the
combined state when heated, or on the application of sulphuric acid.
Oxalate of lime can be separated from most of the sub stances with
which it is likely to be mixed either by acetic acid or by dilute
solution of potash.
Physiological Relations.
Occurrence. — Frequently as oxalic acid, combined either with
the alkalies or with lime, occurs in the vegetable kingdom (Schlei-
den,J Carl Schmidt,§ and others), it is very seldom found in the
* Urinary Deposits ; their diagnosis, pathology, and therapeutical indications.
Third edition, p. 208.
f Op. cit. p. 212.
Grundziige der Botanik. 2 Aufl. 1846.
Entwurf u. s. w.
44 THE BUTYRIC ACID GROUP.
animal organism, at least in large quantities. It only occurs in
the latter in combination with lime, never being present in suffi-
cient quantity to combine with the alkalies as well as with lime.
Moreover it is much more frequently met with in pathological
than in physiological conditions.
It is in the urine that the presence of oxalate of lime has been
most frequently observed; it was for a long time regarded as a mor-
bid product in this fluid, but independently of the circumstance
that this body is constantly present, together with carbonate of
lime, in the urine of herbivorous animals, it has frequently been
found in normal human urine by myself,* Hofle,t and others.
In examining microscopically the morning urine of healthy men
I have frequently discovered isolated crystals of oxalate of lime ;
this is not, however, always the case : and further, the oxalate of
lime recognisable in such cases by the microscope is not all that is
contained in the urine, for it forms in larger quantities after some
time, and during the acid urinary fermentation so admirably
described by Scherer. After allowing morning urine to stand for
a considerable time we often find a great many of these crystals,
when the perfectly fresh urine presented no trace of them. The
following is an excellent mode of demonstrating the existence of
oxalate of lime in normal urine. If it be winter we must expose
fresh urine out of doors till it freezes ; in this process, as in the
freezing of wine and vinegar, a great part of the water crystallises
in a comparatively pure state, and after its removal we obtain a
concentrated saline solution in which microscopic crystals of oxalate
of lime may be discovered. That oxalate of lime is at first actually
held in solution in filtered urine, and that it does not, as C. Schmidt
supposes, proceed from the mucus of the bladder, is a view which
is supported by the experiment which I have often repeated, that in
urine, which after thoroughly cooling was freed from its mucus and
urate of soda by filtration, the most distinct crystals of oxalate of
lime might after a time be recognised, while no traces of them could
either previously be detected in the mucus of the fresh urine, or found
after the residue on the filter had been for some time in contact
with water. The oxalate of lime, with a few crystals of uric acid,
does not separate from filtered urine until after it has stood for some
time. We may very easily convince ourselves that oxalate of lime
is present in a state of solution, by extracting the solid residue of
filtered urine with not too concentrated spirit, and agitating the
spirituous extract with ether ; after the extraction with ether, there
* Wagner's Handworterbuch der Physiologic, Bd. 2, S. 6.
t Chemie und Mikroskop am Krankenbette. Erlangen, 1848 S. 385.
OXALIC ACID. 45
may be observed, in the alcoholic extract, a sediment insoluble in
water, which consists of the most beautiful crystals of this salt.
While in the acid urinary fermentation the separation of the oxalate
of lime increases with the augmentation of the free acid of the urine,
in the latter case the salt is separated by the removal of the free acid.
The quantity of oxalate of lime in ordinary urine is so minute,
that, till recently, chemists, from the want of sufficiently accurate
means of analysis, were unable to recognise it; good analysts
have, however, always found, in the insoluble part of the ash of
the extract of urine, a little carbonate of lime, which, at all events,
owes part of its origin to the oxalate of lime.
Crystals of oxalate of lime are most frequently found in the
urine after the use of vegetable food, especially of such kinds as
contain ready formed oxalates (Wilson.*) Donne found that after
the use of sparkling wines, the quantity of the salt is increased in the
urine ; and my own experiments show that there is an increased
secretion of oxalate of lime after the use of beer containing much
carbonic acid and of the alkaline bicarbonates and vegetable salts.
I cannot confirm Bird's view that highly nitrogenous food causes
a precipitate or even an augmentation of the oxalate of lime. It is
often found in the urine of pregnant women. (Hofle.)t
From a series of direct experiments on the subject, C. SchmidtJ
is led to deny that oxalate of lime introduced into the stomach,
passes into the urine; and in this point I can perfectly confirm
him, without, however, going so far as to assert that the food exerts
no influence on the formation of this body. In the excrements of
caterpillars we often find much oxalate of lime which is not formed
directly from the ingesta, since I§ have very often found the crystals
in the biliary ducts of these animals. Preparations can be easily
made of these organs, and in consequence of their contractility a
large quantity of their contents may be expressed from the cut
tubes, and submitted to microscopic examination.
With reference to the occurrence of oxalate of lime in certain
morbid conditions, Prout, Bird, and others, make very different
statements, none of which are yet fully established. Numerous
examinations of morbid urine have convinced me, that in this
country, at least, the sediments of oxalate of lime are much rarer
than they are represented to be by English writers. These inves-
tigations have led me to the following results ; when the respi-
* Provincial Medical and Surgical Journal, 1846, p. 413.
f Chemie u. Mikroskop u. s. w. S. 385.
J Entwurf u. s. w. S. 70.
§ Jahresbericht d, ges. Med. 1844. S. 25.
46 THE BUTYRIC ACID GROUP.
ratory process is in any way disturbed, we most frequently observe
a copious excretion of oxalate of lime; it is most common either
in fully developed pulmonary emphysema, or when the pulmonary
tissue has lost much of its elasticity after repeated catarrhs ; on the
other hand, it is not present nearly so often in inflammatory or
tuberculous affections of the lungs (Hofle) ;* moreover, it is com-
mon in convalescence from severe diseases, as for instance, typhus,
mucus-corpuscles being then often associated with a trifling sedi-
ment of oxalate of lime. [The frequent occurrence of oxalate of lime
in the urine during convalescence has been independently observed
by Professor Walsh. See his paper on the oxalates in the
Monthly Journal of Medical Science, Jan. 1849. G. E. D.] I have
only met with actually pure sediments of this salt in three persons,
who, sometimes, (at somewhat considerable intervals), suffered
from epileptic attacks. It is by no means constant, according to
my experience, in the urine of rachitic children (Simon),t of gouty
adults with osteoporosis, of women with leucorrhoea, of patients
with heart-disease, or in urine containing semen. (Donna ) J
In the dyspeptic conditions in which Prout and Bird have found
sediments of oxalate of lime, I have failed in discovering anything
of the sort; on the contrary, I have generally found the sediments
in the urine of such patients to be free from these crystals. The
reason why the English have so often found this salt in the urine,
may be, that in England (as we shall further notice at a future
page), the urine is generally in a more concentrated state than in
Germany, and as Bird very correctly remarks, oxalate of lime is more
rapidly separated from a concentrated than an aqueous urine.
Moreover, experience at the bed-side teaches every unprejudiced
observer that the appearance of oxalate of lime in the urine is
by no means accompanied by the group of symptoms which certain
English physicians describe as pertaining to what they call the
oxalic diathesis. QFor the arguments in opposition to this opinion
the reader is referred to Dr. Golding Bird's Urinary Deposits, 3rd
Ed., p. 230. G. E. D.]
That the mulberry calculus consists for the most part of oxalate
of lime, has been long known; but most other urinary calculi,
whether they consist principally of earths or urates, almost always
contain a little oxalate of lime.
This salt has only rarely been found in other places besides the
urine. C. Schmidt has remarked that it is often present in the
* Chemie u. Mikroskop u. s. w. Nachtrag, S. 176.
t Hufeland's Journal, 1841. Dec. S. 73-88.
J Cours de microscopic, pp. 249, 322.
OXALIC ACID. 47
/
mucus of the gall-bladder, and that it is scarcely ever absent from
the mucous membrane of the impregnated uterus. I once discovered
oxalate of lime in expectorated matter, but whether it was produced
from the pulmonary mucus, or from fragments of food in the mouth,
I could not decide. [Dr. Garrod* has recently detected oxalic acid
in the blood in a case of chronic hiccup and vomiting, and in
several cases of gout. G. E. D.]
Origin. — As the use of vegetable food, of which many varieties
contain oxalates, increases the quantity of oxalate of lime in the
urine, the inference would seem a legitimate one, that the
oxalates are transmitted from the food to the urine. The source
of this salt must, however, not be sought for only in the pre- formed
oxalates, but in the amount of alkalies in combination with vegetable
acids present in the food ; for, as we have already mentioned, they
induce an augmentation of the oxalate of lime. In all the well-
marked cases to which I have alluded, the increase of the oxalate
of lime seemed to be combined with disturbance of the respiratory
process. Thus it may easily be understood why, after the use of
drinks rich in carbonic acid, of alkaline bicarbonates, or vegetable
salts, oxalic acid is increased in the urine ; the superfluous carbonic
acid which has entered the blood, or been generated there from the
salts of organic acids, must obstruct the absorption of oxygen and
the perfect oxidation of certain substances in the blood ; hence also
the quantity of oxalate of lime has been found to be increased by the
partially impeded exchange of oxygen and carbonic acid in the
lungs, consequent on emphysema, pulmonary compression during
pregnancy, &c. We might, in such cases, assume, according to a
formerly prevalent belief, that the kidneys in some degree acted
vicariously for the lungs, since under the form of oxalic acid they
remove from the organism the carbon which the latter organs would
have excreted as carbonic acid.
Although certain chemists hold a contrary opinion, it is an
undoubted fact that the nervous system has an influence on the
oxidation of the blood. The occurrence of oxalate of lime in cases
of epileptic convulsions, in convalescent persons, &c., might be
referred to the disturbance induced in such cases in the nutrition
or in the function of the nervous system, and to its diminished
influence on the process of respiration, without there being any
necessity for the assumption of a special diathesis.
It seems, moreover, unreasonable to set up such a diathesis,
since the establishment of a special disease from a single symptom
* Medico-chirurgical Transactions. Vol. 32, p. 171.
48 THE BUTYRIC ACID GROUP.
— that sympton being only the occurrence of oxalate of lime — is
entirely opposed to the spirit of rational medicine.
From Wohler and Liebig^s discovery that uric acid is decom-
posed by peroxide of lead into urea, allantoin, and oxalic acid, it
has been pretty generally assumed that the oxalic acid of the urine
is due to an oxidation of the uric acid ; the oxalic acid, in this case,
not being converted into carbonic acid, as usually occurs in the
healthy organism. That the formation of oxalic acid may be in part
thus explained, is unquestionable, but there are many other substances
in the animal organism besides uric acid, which by oxidation yield
oxalic acid. No definite numerical ratio between the uric acid, urea,
and oxalate of lime in the urine, has been yet established.
C. Schmidt * has propounded a very ingenious view regarding
the origin of oxalate of lime in the urine. He believes that we must
seek for the source of its secretion in the mucous membrane of the
urinary passages, and that the oxalate of lime is first produced by
the decomposing action of the acid urine on a soluble compound,
oxalate of albumen-lime, secreted by the mucous membranes ; for
oxalate of lime as an insoluble body could not penetrate with the
urine through a series of renal cells : oxalate of lime is also formed
from the mucus of the gall-bladder by this mode of decomposition.
When oxalate of lime occurs in the urine, we always find an aug-
mentation of the mucus. These reasons do not, however, appear
to be so decisive as to induce us to exchange the view we have
already given for that of Schmidt ; and indeed in another place we
find Schmidt f himself maintaining that the urea is in part com-
bined with oxalic acid.
FORMIC ACID.— C2HO3.HO.
Chemical Relations.
Properties. — This acid possesses the general characters of the
acids of this group ; with water it forms two distinct hydrates, one
of which becomes solid at — 1°, boils at 4- 99°, and has a specific
gravity of 1*2353, while the other, which contains 48'35-g or 2 atoms
of water, does not solidify at a temperature of — 15°, boils at + 106°
and has a specific gravity of 1*1104. By concentrated sul-
phuric acid it is decomposed into water and carbonic oxide
(C2HO3:=:HO + 2CO) ; the salts of oxide of silver and of oxide
of mercury are reduced when warmed in it.
* Ann. d. Ch. u. Pharm. Bd. GO, S. 55, ff.
f Entwurf u. s. w. S. 47.
FORMIC ACID. 49
Composition. — In correspondence with the above formula, 100
parts of this acid must contain : —
Carbon 2 atoms .... 26*087
Hydrogen 1 „ .... 2'174
Oxygen 3 „ .... 52*174
Water 1 „ .... 19-565
100-000
The atomic weight of the hypothetical anhydrous acid = 462'5 ;
its saturating capacity =2 1*62. According to the theory which we
have laid down, formic acid should be regarded as an oxalic acid
conjugated with hydrogen ==H.C2O3-J- HO ; but according to
ordinary views it is assumed to contain a radical /ontty/=C2Hj
which is believed to occur in several other combinations, as for
instance in chloroform.
Combinations. — The salts of formic acid are soluble; with
alkalies, it also forms acid salts.
Formate of ammonia is known by its property of becoming
converted on heating into hydrocyanic acid (H4NO.C2HO3=
H.C2N + 4HO), and hence the hydrocyanic acid which often
appears during the decomposition of animal substances may be
dependent on the previous formation of formate of ammonia.
There are certain combinations, which in reference to their
empirical composition, may be regarded as formic acid, but in
which the whole of the oxygen is replaced by chlorine, bromine,
iodine, or sulphur ; the best known of these is chloroform or per-
chloride offormyl, C2HC13, which is employed in place of ether to
induce anaesthesia.
Preparation. — This acid was most commonly obtained in
former times by distilling a large quantity of ants with water or
spirit : from the distillate, which naturally only contained the acid
in a very dilute state, the concentrated acid was obtained according
to the ordinary methods by saturation with a base, and by the de-
composition of the crystallised salt with sulphuric acid. As, how-
ever, we have since ascertained that formic acid is a product of
the oxidation of many animal and vegetable substances, we are
now in the habit of obtaining it from various sources by the action
of oxidising agents, as peroxide of manganese and sulphuric acid,
chromic acid, or hypermanganic acid. It is best obtained by
adding a little water and sulphuric acid to a mixture of three parts
of sugar and one part of bichromate of potash (2 atoms of SO3
to 1 atom of KO. 2CrO3) and by distilling.
Tests. — This acid may be readily distinguished from most other
50 THE BUTYRIC ACID GROUP.
acids by its volatility, and from other acids of this group by its
power of reducing the oxides of mercury and of silver ; but it must
be recollected that if we obtain formic acid by the distillation of a
mixture with sulphuric acid, this formic acid may have been pro-
duced by the action of the sulphuric acid on organic matter, or on
already formed hydrocyanic acid. We may separate it from the
other acids of this group by fractional distillation, since the boiling
point of this acid is lower than that of all other homologous acids.
Physiological Relations.
Occurrence. — Formic acid has hitherto been much more fre-
quently found as a product of the decomposition of many organic
substances, as for instance in the gradual decay (Eremacausis) of
coal, than as an educt of the animal body. It has only as yet been
positively proved to exist pre-formed in ants (especially Formica
rufa) ; Bouchardat and Sandras* believe, however, that they have
found it in the blood of dogs which for a long time had been fed
with sugar. According to Scherer,t there are contained in the
juice of flesh not only lactic, inosinic, and phosphoric acids, but
also formic, acetic, and several other acids of this group.
[Will of Erlangen has recently shown that the active poisonous
principle in certain caterpillars is formic acid. It exists in a free,
concentrated state in all parts of the animal, particularly in the
faeces, in the greenish-yellow matter that exudes when the animal
is cut, and in the hollow bristles. G. E. D.]
Origin. — Notwithstanding that the principal processes in the
animal organism are based on an oxidation, and that, on the other
hand, in the artificial oxidations of animal substances, formic acid
is produced, we do but rarely meet with this acid in the animal
kingdom : indeed, even with reference to the ants, it is by no means
certain that they actually produce formic acid, for we know that
juniper berries and the cones of several kinds of pine contain formic
acid, and that these substances are much sought after by ants. We
must leave this question unanswered, since it is only by direct
experiments that we can determine whether ants take up exactly
the same amount of acid as they yield.
Bouchardat and Sandras are of opinion that the lactic acid
formed from starch and sugar in the blood is first decomposed into
formic acid before its elements are finally reduced to water and
carbonic acid.
* Compt. rend. T. 20, pp. 1026 et 1085.
t Ann. d. Ch. u. Pharm. Bd. 69, S. 196-201.
ACETIC ACID. 51
ACETIC ACID.— C4H3O3. HO.
Chemical Relations.
Properties. — Acetic acid has the general characters of the acids
of this group. In its most concentrated state, as first hydrate, it
forms a crystalline mass below + 16°; above this temperature it
is fluid, has a specific gravity of 1*080, and boils at 117°*3; its
second hydrate, containing 2 atoms of water, has a specific gravity of
1-078 and boils at 140°.
We shall notice only the most important points regarding acetic
acid and its compounds, and those having an especial bearing on
animal chemistry ; the other compounds of acetic acid pertaining
to pure rather than to physiological chemistry.
Composition. — According to the above formula, acetic acid con-
sists of: —
Carbon 4 atoms 40*000
Hydrogen 3 „ .... 5-000
Oxygen 3 „ .... 40'000
Water 1 15-000
100-000
The atomic weight of the hypothetical anhydrous acid =637*5 ;
its saturating capacity = 15 '686. Kolbe's hypothesis that acetic acid
is oxalic acid conjugated with methyl = C2 H3. C2 O3. HO, was an-
ticipated by Berzelius. Till then it was assumed that the radical
C4H3 existed in acetic acid, and aldehyde and aldehydic acid were
regarded as lower stages of oxidation of the same radical.
Combinations. — The only acid acetate with which we are
acquainted is a potash-salt ; with the oxides of the heavy metals
it has a strong tendency to form basic salts.
Acetamide, H2N. C4H3O2=C4H5NO2, is prepared from acetic
ether and ammonia ; it forms a white, crystalline, diffluent mass,
which fuses at 78° and boils at 228° ; it has a sweetish, cooling
taste ; by anhydrous phosphoric acid it is converted into cyanide
of methyl ; hence it has been considered as hydrocyanate of wood-
spirit (C4H5N02=C2H30 + HC2N + HO).
By dry distillation of the acetates with strong bases, we obtain
acetone or hydrated oxide of cenyl, C6H5O.HO, which presents
much similarity with the alcohols of the haloid bases.
On heating equal parts of acetate of potash and arsenious acid
in a retort, we obtain alkarsin or oxide of kakodyl, C4H6As5O,
which is distinguished by its very specific odour.
E 2
52 THE BUTYRIC ACID GROUP.
Preparation. — The methods of producing and obtaining acetic
acid are so well known that we need not here advert to them.
Tests. — Some light will be thrown on the importance of the
modes of testing for acetic acid when we have to treat of the
assumed or actual occurrence of acetic acid in the animal fluids.
As in the case of most organic substances, we must first sepa-
rate it from most of the substances with which it is mixed, before
we can apply the appropriate tests. This separation is compara-
tively easy because the acid admits of being distilled ; hence it can
only be confounded with volatile acids exhibiting reactions homo-
logous or similar to it. It may be readily distinguished from
formic acid, in consequence of the property which this latter acid
possesses of being decomposed by oxide of mercury; hence these
two acids can hardly be mistaken for one another. How it is to
be separated and distinguished from the homologous acids, as, for
instance, metacetonic acid, &c.5 will be explained when we treat of
these acids.
If we have isolated acetic acid as completely as possible by
distillation, and then by crystallisation of one of its salts, the fol-
lowing reactions may be established, independently of the examination
of the form of the crystals ; nitrate of suboxide of mercury added to
a not too dilute solution of an acetate at first yields no precipitate,
but, after a short time, minute crystalline specks are formed which
slowly gravitate in the fluid like fatty glistening scales. Since the
acetates, in common with the meconates and sulphocyanides, yield a
somewhat intense red colour on the addition of a solution of a per-
salt of iron, acetic acid, in a mixed fluid, might be mistaken for one of
these acids; but acetic acid maybe readily distinguished from meconic
aci6$ by the solubility of the acetate of lime (the meconate of lime
being insoluble in water), and from sulphocyanic acid by the circum-
stance that the red solution of sulphocyanide of iron, on the addition
of ferricyanide of potassium, and on being warmed, very soon preci-
pitates Prussian blue, which is not the case with . any other persalt
of iron.
Physiological Relations.
Occurrence. — We learn from pure chemistry that acetic acid is
formed in various processes of decomposition of vegetable sub-
stances—in their fermentation as well as in their dry distillation :
we shall, however, presently see that it often occurs as a product
of distillation of several nitrogenous animal substances. It was
formerly believed that it much more frequently existed pre-formed
ACETIC ACID. 53
in the animal juices than has now been shown to be the case. On
this point there was formerly a controversy between Gmelin and
Berzelius ; the former regarding the acid which formed the soluble
salts occurring in the animal fluids as acetic acid, while the latter
maintained it was lactic acid ; Gmelin's idea was that the volatility
of the acetic acid was heightened by its combination with an
organic matter. The question has finally been settled in favour of
the view maintained by Berzelius.
I have never been able to recognise it as a normal constituent
in any of the animal juices. Scherer has however found it, as I
have already mentioned (p. 50), in the juice of flesh, together with
other acids of this group. It may often occur in the gastric juice
in cases of disordered digestion. In a case where, after vegetables
and a little meat, but no vinegar had been taken, the vomited
matters were analysed, and I satisfied myself with certainty regarding
the presence of acetic acid. It has often been observed by others
in vomited matters, but its presence has not always been demon-
strated with sufficient chemical accuracy ; for, on the one hand,
vinegar or brandy might have been taken previously to the vomiting,
or on the other hand, this acid might be confounded with metacetonic
or butyric acid. The proof that spirit of wine is converted in the
stomach into acetic acid during normal digestion, will be given
when we treat of the process of gastric digestion.
Bouchardat and Sandras* think that they have sometimes dis-
covered traces of acetic acid in the blood of animals whose food has
been steeped in brandy.
The answer to the question, what change acetic acid undergoes
in the animal organism when conveyed into it from without,
belongs to the department of pure physiological chemistry.
Whether the acids of this group found by Scherer in the fluids
of flesh have their origin in the fleshy fibre which has become effete,
or whether they arise from the decomposition of other matters,
and are only isolated in the muscular juice, are questions which can
only be decided by further investigation.
METACETONIC ACID. — C6H5O3.HO.
h,
Chemical Relations.
Properties. — This acid, which has also been named butyro-acetic
acid and propionic acid, forms, when in a concentrated state, a
* Ann. de Chein. et de Phys. 3 Sen, T. 21, pp. 448-457.
54 THE BUTYRIC ACID GROUP.
colourless, oily fluid, which at a low temperature solidifies in a
crystalline form, boils at about 140°, has a peculiar sauer-kraut-like
taste, and in its general character deports itself like the acids of
this group ; it is not perfectly soluble in a small quantity of water,
but forms oily drops on it.
Composition. — According to the above formula it consists of : —
Carbon 6 atoms .... 48'649
Hydrogen 5 „ .... 6'757
Oxygen 3 „ .... 32'432
Water 1 „ .... 12-162
100-000
The atomic weight of the hypothetical anhydrous acid = 815*5 ;
its saturating capacity = 12*31.
According to the investigations of Kolbe, to which we have
already referred, this acid may, or indeed must be regarded as
ethyloxalic acid = C4H5.C2O3.HO.
Combinations. — With bases this acid forms soluble salts of a fatty
and glistening appearance, some of them also conveying a fatty
feeling to the touch.
M etacetonate of. baryta crystallises in small rectangular octo-
hedra or rectangular prisms with oblique terminal surfaces.
Metaceionate of silver forms glistening white granules or small
prisms, which are little changed by the action of light, are difficult
of solution in water, and when heated fuse, and at length noise-
lessly smoulder away.
Metacetonate of oxide of ethyl in contact with ammonia
becomes converted into the colourless crystalline substance called
metacetamide, H2N. C6H5O2, which, by the agency of anhydrous
phosphoric acid, is converted, more easily even than metacetonate
of ammonia, into cyanide of ethyl.
Metacetone, C6H5O, cannot be obtained from metacetonic acid,
but is yielded by the decomposition of one part of sugar or starch
with three parts of caustic lime; it forms a colourless, oily, volatile
fluid that is essentially different from oxide of cenyl which is isomeric
with it.
Aldehyde of metacetonic acid, C6H5O.HO, was discovered by
Guckelberger,* among the products of distillation, during the
oxidation of nitrogenous matters by sulphuric acid and peroxide of
manganese ; it is a colourless fluid, having an ethereal odour ; its
specific gravity = 0'79j it boils at about 50°, is miscible with water
* Ann. d. Ch. u. Pharm. Bd. 64, S. 46 ff.
METACETONIC ACID. 55
in every proportion, gradually becomes acid when exposed to the
air, but does not reduce a solution of a silver-salt ; hence, it is still
questionable whether this fluid should be ranked among the alde-
hydes.
Preparation. — Metacetonic acid is formed during the sponta-
neous decomposition of many vegetable substances, as, for instance^
peas, lentils, and tan ; by the action of hydrated potash on sugar,
starch, gum, &c. ; also during the fermentation of tartrate of lime
in contact with nitrogenous bodies, in the decomposition of cyanide
of ethyl by caustic potash ; and lastly, (and, in a zoo-chemical view,
this mode of its formation is the most important) in the oxidation
of fats by nitric acid (Redtenbacher),* in the oxidation of albumi-
nous bodies by chromic acid, or by sulphuric acid and peroxide of
manganese (Guckelberger),t and in the fermentation of glycerin,
the well known product of decomposition of the fats, by means of*
common yeast (Redtenbacher).{ This acid is obtained most easily
and in the purest form either by distillation of the product of the
fermentation of yeast and glycerin, or by treating metacetone with
chromic acid or hydrated potash ; otherwise, it is ordinarily pre-
pared by treating 1 part of sugar with 3 of hydrated potash, in
which, however, it has to be separated from the • other acids which
are simultaneously developed, namely oxalic, formic, arid acetic acids.
Tests. — Metacetonic acid must, in the first place, be separated
by distillation from other non-volatile organic substances with
which it may have been mixed, and then by oxide of mercury,
from any formic acid that may be present. If acetic acid be
also present, the best method is to combine both acids with
soda, when, on evaporating the saline solution, the acetate crystal-
lises sooner than the metacetonate. The salt which metacetonic
acid forms with lead is not crystallisable, while, as every one knows,
the acetate of lead crystallises very readily. How this acid is to
be separated and distinguished from the remaining acids of this
group, will be described when we treat of those acids. Since, how-
ever, nothing can be concluded regarding the identity of any given
substance with metacetonic acid either from the forms of its salts,
which have not yet been determined with crystallographic accuracy,
or from the boiling point of the fluid, it is only by the elemen-
tary analysis of a pure salt that the presence of metacetonic acid
can be scientifically determined.
* Ann. d. Ch. u. Pharm. Bd. 59, S. 41-57.
f Ibid. Bd. 64, S. 46 ff.
J Ibid. Bd. 57, S. 174-177,
56 THE BUTYRIC ACID GROUP.
As we proceed in the subject of zoo-chemistry we shall become
acquainted with a number of bodies whose characteristic properties
are so feebly marked that it is only by an elementary analysis
that we can satisfy ourselves regarding their presence. Often as
the combustion-tube may have been mis-used in physiological
chemistry, we are yet convinced that no one can flatter himself
that he will advance zoo-chemistry and physiological chemistry,
if he be not conversant with the methods of elementary analysis
as now practised. It has unfortunately happened that physio-
logical chemistry has too long remained in the hands of chemical
dilettanti, who looked upon an elementary analysis as a great piece
of art, and have based on the elementary analyses of others those
lamentable fictions which, even yet, have hardly been eradicated
from physiological chemistry.
Physiological Relations.
Occurrence. — Since acids homologous to metacetonic acid have
so frequently been found in the animal system, at least as products
of decomposition, we may rationally suppose that this acid may,
at least occasionally, occur in pathological conditions of the
organism; to this we may add that, on the one hand, metacetonic acid
is, in its chemical composition, very closely allied to lactic acid,
which is of such frequent occurrence in the animal body (for with 2
atoms of oxygen metacetonic acid yields lactic acid : C6H5O3.HO
+ 2O = C6H5O5.HO), and that on the other glycerin, (of which
we are ignorant what becomes of it in the decomposition of the
fats in the animal body) is so readily converted into metacetonic
acid (for C6H?O5 - HO=C6H5O3. HO); but, unfortunately,
metacetonic acid has been only so recently known to chemists,
that little or no search has as yet been instituted for it in the
animal organism.
BUTYRIC ACID.— C8H7O3. HO.
Chemical Relations.
Properties. — This acid is an oily fluid, which remains in that
state at a temperature of — 20°, and can only be solidified at a cold
of — 113° induced by mixing condensed carbonic acid and ether,
when it crystallises in plates ; it evaporates even at the ordinary
temperature, but it does not boil at a lower temperature than
BUTYRIC ACID. 57
157°; its specific gravity at 0°=0*9886; when inflamed, it burns
like an ethereal oil.
Composition. — According to the above formula it consists of :
Carbon 8 atoms .... 54-545
Hydrogen 7 „ .... 7'955
Oxygen 3 „ .... 27'273
Water 1 „ .... 10'227
100-000
The atomic weight of the hypothetical anhydrous acid=987'5 ;
its saturating capacity = 1 0*1 26.
According to the beautiful investigations of Kolbe, butyric acid
may be regarded as an oxalic acid conjugated with the carbo-
hydrogen C6 H7~C6 H7.C2O3.HO.
Combinations. — The alkaline butyrates are deliquescent, and not
crystallisable ; the compounds of butyric acid with the metallic
oxides lose a portion of their acid when heated, and even at an
ordinary temperature evolve a strong odour.
Butyrate of baryta, BaO. Bu-f4HO, crystallises in smooth
prisms, grouped together in a wart-like form, and having a fatty
glistening appearance ; it retains its water of crystallisation at 100°,
and dissolves readily in water ; if thrown in small pieces on water,
it assumes, like camphor, a rotatory motion till it is dissolved.;
further, it turns red litmus blue.
Butyrate of lime, CaO. Bu + HO, crystallises in fine needles; it
has the odour of butyric acid, dissolves readily in cold water, but
separates almost entirely on boiling, and on dry distillation yields
bodies similar to ethereal oils, namely, butyrone, C7H7O, and
butyral, C8H8O2.
Butyrate of magnesia, MgO.Bu + 5HO, forms white plates
resembling boracic acid.
Butyrate of zinc decomposes on boiling into a strongly basic
insoluble salt.
Butyrate of copper, CuO.Bu-H2HO, occurs in eight-sided,
bluish-green prisms, has a strong odour of butyric acid, and is only
slightly soluble in water. At a temperature of about 100° most of
the acid is expelled from this salt.
Butyrate of lead does not crystallise, and is only to be obtained
in a syrupy form.
Butyrate of silver forms white nacreous plates, is almost inso-
luble, and smoulders at a glow-heat without explosion.
58 THE BUTYRIC ACID GROUP.
Butyr amide, H2N.C8H7O2, is obtained from butyrate of oxide
of ethyl when acted on by ammonia ; it forms colourless crystalline
tablets, which resist the action of the atmosphere ; it communicates
a taste which is at first sweetish but afterwards bitter; it fuses at
115°, and at a higher temperature sublimes without change; it is
soluble in water, alcohol, and ether ; by anhydrous phosphoric acid
it is converted into butyronitrile, C8H7N, whose theoretical
formula, according to Kolbe, must=C6H7.C2N. Butyronitrile
is an oily fluid, with an agreeable, somewhat aromatic odour; its
specific gravity is 0'795, and its boiling point 118°'5 ; treated
with potassium it yields cyanide of potassium, hydrogen, and
certain carbo-hydrogens.
Aldehyde of butyric acid, C8H7O.HO, has hitherto only
been found by Guckelberger,* in the products which are obtained
by the action of peroxide of manganese and sulphuric acid on albu-
minous or gelatinous substances. It is a colourless fluid, its specific
gravity is O8, and its boiling point 68° ; it is slightly soluble in
water, but dissolves freely in alcohol and ether ; it soon becomes
acid when exposed to the air ; it reduces solutions of the silver-salts,
and, like aldehyde of acetic acid, it yields with ammonia a crystal-
lisable compound, H3N. C8H7O. HO + 10 aq.
Butyrate of glycerin has been prepared by Pelouze and Gelis,t
by gently heating butyric acid and glycerin with concentrated sul-
phuric acid, and separating the new compound from the mixture
by means of water; or by passing hydrochloric acid gas through a
mixture of butyric acid and glycerin ; on the addition of water it
separates as a yellow oil, soluble in concentrated alcohol and ether,
which, when treated with caustic alkalies, again resolves itself into
butyric acid and glycerin. Whether this body be identical with the
butyrin (butyrate of oxide of lipyl) occurring in the fat of milk
but not yet isolated, cannot at present be decided, since no elemen-
tary analysis of it has been instituted.
Preparation. — Butyric acid, which was originally discovered by
Chevreul in the products of the saponification of butter, is also
formed when Jhis substance becomes rancid, and occurs amongst
the products of decomposition when oleic acid is submitted to dry
distillation, and especially when it is acted on by fuming nitric acid ;
it is likewise produced from non-fatty nitrogenous matters, as albu-
men, fibrin, and gelatin, during their putrefaction or their decom-
position by strong oxidising agents ; and, contrary to expectation,
• Ann. d. Ch. u. Pharm. Bd. 64, S. 46 if.
t L'Institut. No. 494.
BUTYRIC ACID. 59
it has been found in certain processes of fermentation of non-
nitrogenous bodies, as starch and sugar, where the nitrogenous
admixtures only act as ferments. Lactate of lime, in the presence
of nitrogenous matter, becomes converted into butyrate of lime.
To obtain pure butyric acid on a large scale, we should have
recourse to the last-named method. The most simple mode of
procedure is to expose carob (the fruit of Ceratonium siliqua), or
sugar, with sour milk and a little cheese, and with some car-
bonate of lime, at a temperature of 30° to 35°, as long as gas conti-
nues to be evolved, namely for five or six weeks; the filtered
fluid is then decomposed with carbonate of soda, which causes a
precipitation of carbonate of lime ; the solution of butyrate of soda
is now strongly concentrated, and, after being decomposed with
sulphuric acid, is distilled ; finally, the butyric acid is freed from
water and acetic acid by fused chloride of calcium.
Tests. — This acid must first be separated by distillation from
the non-volatile substances, as, for instance, lactic acid, with which
it is not unfrequently associated; in the distillate we can then only
have the acids of this group. We shall here refer to the means of
distinguishing it from the acids which have been already described,
namely, formic acid, acetic acid, and metacetonic acid. The first
may be very easily removed by means of its property (to which
we have frequently referred) of reducing the oxides of the noble
metals. The acids must then be combined with soda, when the
greater part of the acetate of soda may be removed by crystallisa-
tion. The soda-salts of the mother-liquid are afterwards to be
decomposed by tolerably concentrated sulphuric acid, yielding in
the receiver metacetonic and butyric acids, with a little acetic acid;
from these the butyric acid may be pretty well separated by frac-
tional distillation, since that which passes over at 140° is only
metacetonic acid, with traces of acetic acid, and it is not till the
temperature is raised to 160° or 165°, that tolerably pure butyric
acid enters the receiver. If other analogous acids be also present,
we must not be contented with this mode of procedure ; specific
as it may appear to be, we must not rely on the peculiar odour of
butyric acid, but we must convert the butyric acid into one of the
above-described butyrates, and after comparing the salt thus
obtained with the corresponding salt of pure butyric acid, we must
institute an elementary analysis, or at the least we must determine
the atomic weight or the saturating capacity.
The atomic weight of the hypothetical anhydrous butyric acid
is 987*5 (for 8 at. carbon =600*0, 7 at. hydrogen = 8 7'5, and 3 at.
60 THE BUTYRIC ACID GROUP.
oxygen =300). Now if, in a baryta-salt, we have found 49£ of
baryta and 51% of butyric acid, then 49 : 51 must be the ratio in
which the known atomic weight of baryta (=955*3) stands to the
atomic weight of butyric acid (49 : 51 : : 955*3 : x)= 994*4.
By a similar determination of the quantity of a base contained
in a salt, we calculated the saturating capacity, by which, as is
well known, we understand the number which expresses the quan-
tity of oxygen contained in that quantity of base which is required by
100 parts of an anhydrous acid to form a neutral salt. Hence the
saturating capacity of butyric acid is = 10*126. If we regard the
above instance as an empirical result, 49 BaO saturate 51 Bu, or
100 Bu saturate 96*076 BaO; in this, however, there are con-
tained 10*06 parts of oxygen, which is a tolerably close approxi-
mation to the required number.
Physiological Relations.
Occurrence. — In the contents of the stomach, or rather in food
which has been ejected by vomiting, we sometimes meet with a
nauseous acrid or rancid-smelling volatile acid, which, beyond all
question, is butyric acid. Tiedemann and Gmelin often obtained
a fluid resembling butyric acid by distillation of the contents of the
stomachs of sheep, oxen, and horses, fed with oats. Since the con-
tents of the stomach can pass into the acetous, and, as we shall
presently see, also into the lactic fermentation, there is nothing
surprising in the circumstance of their also passing into the
butyric fermentation : but even in abnormal conditions, butyric
acid has not been recognised in the contents of the stomach with that
absolute certainty which is as necessary in physiologico-chemical
researches as in all other departments of natural enquiry.
Free butyric acid was long ago discovered in the urine by Ber-
zelius, who, however, did not think that it was often to be found
there. In the urine of pregnant women, and of those who, after
delivery, do not suckle their children, I have sometimes found
butyric acid, or, at all events, a fat which, on saponification, yielded
a volatile acid, with the odour of butyric acid.
In the sweat, especially in that of the genitals and lower extre-
mities of corpulent persons, we find volatile matters, with an acid
reaction, and having an odour partly of butyric acid and partly of
other acids of this group. Berzelius thought that the acid reaction
was due to butyric acid alone, but in the present state of our
knowledge it must remain doubtful whether the homologous, highly
BUTYRIC ACID. 61
carbonaceous acids, do not occur in the sweat with or in place of
butyric acid. In examining the watery extract of a night-dress
steeped in perspiration, taken from a woman a few days after
delivery, I found, on saponification, a rancid-smelling, volatile
acid.
In the milk, in addition to other fats, as olein and margarin,
there occurs a fat which has never yet been isolated in a state
of purity, and which, on saponification, yields butyric acid,
together with other acids of this group, namely, caproic, ca-
prylic, and capric acids. The best investigations in reference
to this substance were made, first by Chevreul*, in his classical
work on the fats ; subsequently by Bromeisf ; and lastly by
LerchJ> under the direction of Redtenbacher. Even in butter
there is only a little of this substance, which yields butyric acid.
From 100 parts of tolerably pure butyrin, Chevreul§ only obtained
7 parts of volatile acids; Simon || and Herbergerlf were able to
obtain only very minute quantities of volatile acids from the fat of
woman's milk.
That there are fats in the blood which, on saponification, yield
volatile acids, may be demonstrated by any one who operates with
care on large quantities of the fatty matter collected from this fluid.
From the blood taken from a woman within the first few days after
her delivery, I obtained, by distillation with dilute sulphuric acid,
volatile acids whose general properties coincided with those of this
group.
[Free butyric acid has likewise been detected in the/tf«?s by
Ragsky and Percy.** G. E. D.]
Origin. — After what has been stated regarding the different ways
in which butyric acid may be formed, we need not wonder that it
is sometimes met with in the primes vice ; since it may, and indeed
must principally be formed from the non-nitrogenous constituents of
the food. The belief that farinaceous and saccharine foods are
converted into butyric acid in the primce vice, and that they thus
constitute the first step in the formation of fat, is based on a fiction
regarding the possible formation of fat in general, which is at pre-
sent devoid of any scientific proof. No one has as yet succeeded
in ascertaining the presence of butyric acid, either in the prima
• Recherches sur les corps gras.
t Ann. d. Ch. u. Pharm. Bd. 42, S. 46 ff.
t Ibid. Bd. 49f S. 212 ff.
§ Recherches sur les corps gras, p. 193.
II Frauenmilch, S. 41.
f Brande's Arch. Bd. 20, S. 3.
** Chemical Gazette. Vol 8, p. 104.
62 THE BUTYRIC ACID GROUP.
vice or in the chyle ; we know not what becomes of the other ele-
ments which are eliminated during the conversion of starch into
butyric acid ; and finally, chemically considered, butyric acid has
no greater claim to the name of a fatty acid, than acetic or formic
acid. We do not think that the conclusion can be justly deduced,
that starch must be converted into butyric acid in order to be
transformed into fat, simply because it accidentally happens that
butyric acid was first prepared from a (very rarely occurring) fat,
for we know that it may just as easily be obtained from albumi-
nous bodies, and in far larger quantities from gelatin.
There is much stronger evidence in favour of the view which
regards the butyric acid found in the blood, sweat, and urine, as a
product of decomposition, arising from the disintegration of nitro-
genous animal matters, effected by the oxygen dissolved in
the juices, (in the same way as the acid is formed from these
substances by artificial means,) or as probably resulting from a
gradual oxidation of some of the carbo-hydrogens of the fats. This
latter view is, however, only an hypothesis ; but it is supported
by the simplest induction. The fats are almost all combinations
of fatty acids with a haloid base, glycerin or oxide of lipyl; these
acids are, however, so similarly constituted to those of this group,
that they have the same general formula=CnHn_1O3. HO, with
only this difference, that the carbo-hydrogens pertaining to them
are expressed by higher atomic numbers (thus, for instance, mar-
garic acid=zC34H33O3.HO). In the complicated apparatus of
oxidation which we recognise in the animal organism, the fats do
not burn like the oil in the wick of a lamp, but they undergo an
extremely gradual oxidation, as we learn from direct experiments,
which have given us a knowledge of a very large number of fatty
acids, with the most varied polymeric carbo-hydrogens, or, if we
please so to express it, in the lowest stages of oxidation. From
experiments instituted on this group of acids, we may assume that
in the gradual oxidation, C2 H2 is always abstracted from the radical
of n.argaric acid, and that this gradual abstraction may proceed
with various degrees of rapidity, so that, in our investigations, we
meet with carbo-hydrogen compounds of a lower order, which then
progressively pass into the carbo-hydrogens of the acids of this group.
As the radical C4 H5 of ethyloxalic acid passes into methyloxalic
acid, we are justified in believing that the radical of margaric acid
passes into cetylic acid. A gradual decarbonisation of the fats
must occur in the animal organism ; and there are at present no
scientific reasons for assuming that it takes place in any other
way than that which has been described. We regard butyric acid,
VALERIANIC ACID. 63
and the acids analogous to it, in so far as they occur in the animal
body, as products of regressive metamorphosis of tissue, while
in the different fatty acids of the vegetable kingdom the progres-
sion gradually ascends, step by step, to margaric acid.
VALERIANIC ACID. — C10H9O3. HO,
Chemical Relations.
Properties. — This acid possesses the general properties of this
group, has a well-known characteristic odour, an acrid burning,
taste, and produces a white spot upon the tongue: it does not
become solid at a temperature of— 15°; it boils at 176°, and dis-
solves in 26 parts of water: it also forms a second hydrate=
VaT.SHO.
Composition. — According to the above formula it consists of :
Carbon 10 atoms .... 58*824
Hydrogen 9 „ .... 8-823
Oxygen 3 „ .... 23-530
Water 1 „ .... 8'823
100-000
The atomic weight of the hypothetical anhydrous acid=1162'5 ;
its saturating capacity=S'602. According to Kolbe's hypothesis,
its theoretical formula=C8H9. C2O3. HO.
Combinations. — The valerian ates are for the most part soluble :
the alkaline salts do not crystallise, but most of the other salts crys-
tallise in nacreous plates, similar to cholesterin or boracic acid ;
they have a sweetish, but at the same time a valerian-like taste.
Valeriariic acid is separated from its salts by acetic and succinic
acids, but not by benzoic acid. The lime-salt effloresces on expo-
sure to the air; the zinc-salt dissolves in 160 parts of water, and
in 60 parts of spirit of wine; the aqueous solution becomes turbid
when warmed, but clears again upon cooling: moreover it reddens
litmus. The silver-salt is very insoluble.
Valeronitrile, C10H9N (or C8H9 . C2N)5 was first discovered
by Schlieper*, in the oxidation of gelatin by chromic acid ; it may
however, be obtained from valerianate of ammonia, or valeramide
(H2N. C10H9O.2), by anhydrous phosphoric acid. It is a thin,
liquid, colourless, strongly refracting oil, smelling like alder leaves,
and having a hot aromatic taste ; its specific gravity is = 0*81 ; it
boils at 125°, inflames readily, dissolves in water, alcohol, and
* Ann. d. Ch.u. Pharm. Bd. 59, S. 1-32.
64 THE BUTYRIC ACID GROUP.
ether, and, when treated with potassium, yields cyanide of potas-
sium, hydrogen, and carbo-hydrogens.
Valeral, C10H10O2, is produced by the dry distillation of
valerianate of baryta ; it is a very fluid inflammable oil, which, on
exposure to the air, soon becomes converted into valerianic acid.
Preparation. — This acid occurs preformed in certain plants;
it is, however, like the preceding acids, a not unfrequent product
of decomposition both of vegetable and animal substances : it is
obtained from fusel-oil (hydrated oxide of amyl) in precisely the
same manner as acetic acid is obtained from alcohol (hydrated
oxide of ethyl), and from oil of valerian by simple oxidation by
means of an alkali ; it is formed, together with other acids of this
group, from the fats by oxidising them with fuming nitric acid
(Redtenbacher*) ; from animal nitrogenous matters, both by putre-
faction (Iljenko and Laskowskif), and on decomposing them by
strong oxidising agents (Schlieper,t Guckelberger,§ Liebig||) ; and
finally, if leucine be treated with caustic potash, or allowed to
putrefy, it becomes converted into valerianic and no other acid,
ammonia and hydrogen being evolved.
It is most easily obtained in a state of purity by the action of
spongy platinum and atmospheric air on potato fusel-oil.
Tests. — In most of the ways in which valerianic acid is formed,
it occurs mixed with other acids of this group ; and it is as impos-
sible in this case, as in that of the homologous acids, to detect it in
a mixture by any special reagent; it must, therefore, be separated
from these acids before it can be accurately examined. As its
boiling point is so high, it can readily be separated from the first-
described acids of this group by fractional distillation ; it may still
remain contaminated with butyric acid, from which it can be tole-
rably well separated by crystallisation of the baryta-salts, the vale-
rianate and butyrate of baryta assuming different forms. But an
elementary analysis, or a determination of the atomic weight must
be made with the valerianate thus obtained, since mistakes may
very easily arise between the salts of valerianic acid and those of
certain acids afterwards to be described.
[Liebig^f has recently published a paper on the separation of
valerianic, acetic, and butyric acids, to which we may refer the
reader. G. E. D.]
* Ann. d. Ch. u. Pharm. Bd. 59, S. 41-57.
f Ibid. Bd. 55, S. 78-95, and Bd. 63, S. 264-273.
J Ibid. Bd. 59, S. 375-378.
§ Ibid. Bd. 64, S. 50.
|| Ibid. Bd. 57, S. 127-129.
If Ibid. Bd. 71 ,S. 355.
CAPROIC ACID. 65
Physiological Relations.
Occurrence. — Although this acid is so easily and so variously
obtained from animal substances, it has never yet been found pre-
formed in the animal organism ; and it is a striking fact that, so
far as we yet know, the acids of this group, whose amount of carbon
is divisible only by 2, and not by 4, are not found in the animal
organism.
We shall consequently only have occasion to refer to these acids
in the following pages, inasmuch as they sometimes occur as
products of the artificial decomposition of animal substances.
CAPROIC ACID. — C12HHO3.HO.
Properties. — It is a somewhat thin liquid, with an odour resem-
bling sweat; its specific gravity at +26=0*922; it remains fluid
at — 9°, boils at 202°, and dissolves somewhat difficultly in ether.
Composition. — According to its formula it consists of:
Carbon 12 atoms .... 62-069
Hydrogen 11 „ .... 9'483
Oxygen 3 „ .... 20'689
Water 1 „ .... 7'759
100-000
The atomic weight of the anhydrous acid =r 1337*5 ; its
saturating capacity = 7'476. According to the views of Kolbe,
this acid should hypothetically be regarded as amyloxalic acid —
C10Hn.C2H3.HO.
Combinations. — The caproates have the same taste and smell as
the acid itself; and are mostly soluble in water and crystallisable.
The baryta-salt crystallises in long silky needles, united in tufts, is
anhydrous, and unaffected by exposure to the atmosphere; the
silver-salt is not crystallisable, and is very difficult of solution.
Preparation. — Like butyric acid, this acid is not only formed
when butter is saponified or becomes rancid, but also when oleic
acid is decomposed by fuming nitric acid, and when albuminous
bodies are acted on by peroxide of manganese or bichromate of
potash and sulphuric acid. In the products of the decomposition
of saponified butter we find caproic acid mixed with butyric,
caprylic, and capric acids, which may be removed by the crystal-
lisation of their baryta-salts. On boiling the dried mass of the
baryta-salts with 5 or 6 parts of water, the butyrate and caproate
66 THE BUTYRIC ACID GROUP.
are taken up, while the salts of caprylic and capric acid remain
undissolved. The caproate of baryta is the first to crystallise from
the solution, and the acid may easily be isolated from the salt.
Tests. — The caproate of baryta not only crystallises sooner than
the butyrate, but also sooner than the valerian ate, if this should
happen to be present; caproate of baryta forms small clusters,
consisting of microscopic prisms, while the valerianate, as we
have already mentioned, appears in minute plates like cholesterin.
This separation of caproic acid from its allied acids, is more easily
explained theoretically than effected practically. There are no
special means of determining the presence of caproic acid, except
by an elementary analysis, and the determination of the atomic
weight.
Physiological Relations.
Occurrence. — The remarks which we made regarding the occur-
rence of butyric acid in the animal organism, apply equally to
caproic acid. From its peculiar sweat-like odour, it is not impro-
bable that it exists in sweat; but of this we have as yet no proof. No
one, so far as I know, has yet sought for it in the urine or in the
contents of the stomach. In our observations on butyric acid we
alluded to the fatty matters contained in the milk, and probably also
in the blood, which, on saponification, yield this acid.
CENANTHYLIC AdD. C14H13O3.HO.
Chemical Relations.
Properties. — It is a colourless oily liquid, of a faint aromatic
odour and taste; it boils at about 215°, may be distilled with only
partial decomposition, dissolves slightly in water, and when inflamed
burns with a clear but smoky flame.
Composition. — According to the above formula it consists of :
Carbon 14 atoms .... 64-615
Hydrogen 13 „ .... lO'OOO
Oxygen 3 „ .... 18'462
Water I 6'923
100-000
The atomic weight of the hypothetical anhydrous acidrr
1512-5, and its saturating capacity =6*611. Its rational formula
=C12H13.C203.HO.
CENANTHYLIC ACID. 67
Combinations* — With the exception of the alkaline salts, most
of its salts are difficult of solution, generally resembling tablets of
cholesterin : moreover this acid has a strong tendency to form
acid salts. The baryta-salt crystallises in nacreous scales, which
are soluble in water and in alcohol.
(Enanthylous acid, C14H13O2.HO, formerly also named
oenanthic acid, occurs combined with oxide of ethyl in various
fusel oils, especially in that of wine. Whether it be actually to be
regarded as a lower state of oxidation of oenanthylic acid, or as a
special acid, cannot at present be decided.
(Enanthal, aldehyde of oenanthylic acid, C14H14O2, is obtained
by the simple distillation of castor oil ; like the other aldehydes,
when exposed to the atmosphere, it readily oxidises into the cor-
responding acid, and forms a compound (although somewhat
unstable) with ammonia.
Preparation. — This acid, which Laurent formerly discovered
amongst the products of distillation of the oils, and named azoleic
acid, is formed, together with other acids of this group, during the
decomposition of wax, oleic acid, and especially of castor oil, by
concentrated nitric acid. In using castor oil, however, we obtain
this acid unmixed with any others, so that we have only to combine
it with baryta, and recrystallise the salt, in order to obtain it in a
state of purity.
Tests. — As the baryta-salt of this acid separates from the mother-
liquid earlier than caproate of baryta, and more slowly than the
caprylate, and as, further, it crystallises in plates, while the two
latter salts form minute needles, which are grouped together so as
to have a wart-like appearance, we have a means of separating, at
least roughly, this acid from those which are most closely allied to
it. We cannot, however, be perfectly certain regarding its actual
presence, without an elementary analysis, or the determination of
its atomic weight.
Physiological Relations.
Occurrence. — As has been already mentioned, this acid is only
of interest in relation to animal physiology, inasmuch as it is one of
the products of oxidation of the fats : and the observations which
were made regarding the occurrence of valerianic acid are here
equally applicable, except that oenanthylic acid is not produced
during the decomposition of nitrogenous complex atoms.
P 2
68 THE BUTYRIC ACID GROUP.
CAPRYLIC ACID. — C16H15O3.HO.
Chemical Relations.
Properties. — At the ordinary temperature this acid forms a soft,
semifluid mass, which crystallises in needles below + 10°, boils at
236°, has a sweat-like odour, an acid and acrid taste, is difficult of
solution in water, and is inflammable.
Composition. — According to the above formula it consists of:
Carbon 16 atoms .... 66-667
Hydrogen 15 „ .... 10-416
Oxygen 3 „ .... 19-667
Water J 1 „ .... 6-250
100-000
The atomic weight of the anhydrous acid = 1687'5, and
its saturating capacity = 5*926. Its rational formula is
C14H15.C203.HO.
Combinations. — The salts of this acid are more difficult of solu-
tion than the corresponding salts of the acids already described.
Its baryta-salt crystallises in white granules of the size of poppy
seeds, is anhydrous, resists the action of the atmosphere, and does
not fuse at 100°. The silver-salt is white and almost insoluble.
The lead-salt is also very difficult of solution.
Caprylone, C15H15O, was discovered by Guckelberger* among
the products of the dry distillation of caprylate of baryta ; it crys-
tallises in fine needles of a silky lustre, but when fused resembles
Chinese wax ; it is perfectly white, fuses at 40°, solidifies at 38°,
and boils at 178°, is devoid of taste, has a waxy smell, is lighter
than water and insoluble in it, but dissolves readily in strong
alcohol, in ether, and in ethereal as well as fatty oils. With nitric
acid of 1 '4 specific gravity it yields an acid nitrogenous oil (nitro-
capry Ionic acid?).
Preparation. — We have become acquainted with this acid as a
product of the saponification of butter, and as a product of the
oxidation of oleic acid when acted on by nitric acid ; as in the latter
case it is mixed with several substances, it is best obtained by the
recrystallisation of the baryta- salts of the volatile acids of butter.
In the observations on caproic acid it was mentioned that the dry
mass of the baryta-salts of all four acids, when treated with five or six
parts of water, separates into a soluble portion containing the buty-
* Ann. d. Ch. u. Pharm. Bd. 69, S. 201-6.
PELARGONIC ACID. 69
rate and caproate, and an undissolved portion, containing the
caprylate and caprate of baryta. If now the undissolved portion
be dissolved in boiling water and filtered while still hot, most of
the caprate separates while the caprylate remains in solution. In
order to effect a perfect purification, the baryta-salt must be several
times recrystallised before we separate the acid from it.
Tests. — We must separate the caprylic acid from the other acids
in the manner just described, and then determine the atomic
weight.
Physiological Relations.
Occurrence. — All that has been remarked regarding the physio-
logical relations of butyric and caproic acids applies equally to
caprylic acid.
PELARGONIC ACID. — ClsH1(,Oo.HO.
lo 17 O
Chemical Relations.
Properties. — It is an oily, colourless fluid which at a lower tem-
perature than + 10° becomes solid, but liquefies at and above
that temperature ; it has a faint odour resembling that of butyric
acid, is almost insoluble in water, but communicates to it an acid
reaction, and boils at about 232°.
Composition. — In accordance with the above formula it con-
sists of:
Carbon 18 atoms .... 68-350
Hydrogen 17 „ .... 10'760
Oxygen 3 „ .... 15'190
Water 1 „ .... 5'700
100-000
The atomic weight of the anhydrous acid = 1862*5 ; its satu-
rating capacity = 5 -369; its rational formulae C16H17.C2O3. HO.
Combinations. — The baryta-salt of this acid crystallises like the
valerianate and cenanthylate of baryta in glistening scales ; it con-
tains no water of crystallisation, is unaffected by the atmosphere,
and is less soluble than the osnanthylate and caprylate of baryta,
but rather more soluble than the caprate.
Preparation.— As this acid, unmixed with other volatile acids,
occurs in the leaves of Pelargonium roseum, its preparation from
that plant is preferable to that from the products of decom-
position of oleic and choloidic acids by nitric acid, amongst which
70 THE BUTYRIC ACID GROUP.
it was first discovered by Redtenbacher.* Gerhard tf has obtained
this acid by oxidising oil of rue, C.20H19O3, with nitric acid.
Tests. — By the crystallisation of its baryta-salt we must pre-
pare this acid so that we can make an elementary analysis and
determine its atomic weight.
Physiological Relations.
The remarks already made regarding the physiological relations
of oenanthylic acid are equally applicable here.
CAPBIC ACID.— C20H19O3.HO.
Chemical Relations.
Properties. — Little is yet known regarding this acid in a state
of purity, for what was formerly regarded as capric acid was a mix-
ture of capric and caprylic acids. It constitutes a soft, greasy
mass which fuses at + 30°, and evolves a faint goat-like odour, is
somewhat soluble in hot water, but separates on cooling in glis-
tening crystalline particles ; its boiling point is higher than that of
any of the other acids of this group, but is considerably below
300°.
Composition. — According to the above formula it consists of :
Carbon 20 atoms .... 69'7f>7
Hydrogen .... 19 „ .... 11*046
Oxygen 3 „ .... 13-954
Water 1 „ .... 5*233
100-000
The atomic weight of the hypothetical dry acid= 2037*5; its
saturating capacity^ 4-909 ; its rational formula=:C18H19.C2O3.HO.
Combinations. — The salts of this acid are more insoluble than
those of the other acids of this group. The baryta-salt crystallises
in delicate, glistening needles ; it is unaffected by exposure to the
atmosphere, and contains no water.
Oil of rue, C.20H19O, the ethereal oil of Ruta graveolens, may be
regarded as anhydrous aldehyde of capric acid ; in point of fact it
is converted into capric acid by the action of nitric acid ; but by
more prolonged action, into pelargonic acid.
* Ann. d. Ch. u. Pharm. Bd. 59, S. 41-57, and Bd. 57, S. 170-174.
t Aua.de Ch. et dc Phys. T. 24, pp. 112-116.
CETYLIC ACID. 71
Preparation. — This may be readily inferred from what has been
stated regarding the preparation of caprylic acid.
Tests. — We must obtain a pure salt according to the method
described in our observations on caprylic acid, and then analyse it.
R. Wagner* has, however, discovered a method of detecting this
acid when mixed with other substances; for on heating such a
mixture with concentrated sulphuric acid, it always appears asso-
ciated with its aldehyde, and on supersaturation with potash, an
intense odour of oil of rue is developed.
Wagner has in this way discovered this aldehyde in butter, in
cod-liver oil and other fish-oils, in old cheese, in a piece of her-
ring, &c.
Physiological Relations.
The remarks on the physiological relations of caprylic acid
apply equally to this acid.
In the saponirication of butter we sometimes obtain only a
single acid, vaccic «c^,C20H18O5.2HO instead of butyric andcaproic
acids. This acid reduces silver-salts, and taking up 1 atom of oxygen,
becomes converted into butyric and caproic acids (C20H18O5 + O
= CgH7O3 + C12H11O3) ; it undergoes the same conversion when
exposed to the atmosphere, and so also does its baryta-salt.
Delphic and hircic acids which were formerly regarded as inde-
pendent acids are probably identical with, or mixtures of some of
the acids of this group.
CETYLIC ACID. — C32H31O3.HO.
Chemical Relations.
Properties. — The body, which is also known as ethalic acid,
forms colourless glistening needles, fuses at 57°, but is solid at 55°,
may be distilled without undergoing decomposition, and is inso-
luble in water.
Composition. — This acid, which is isomeric with the non-volatile
palmitic acid, obtained from palm-oil, consists according to the
above formula of:
Carbon .... .... 32 atoms ....
Hydrogen .... 31 „
Oxygen 3 „
Water 1 „
100-000
* Journ. f. pi*. Ch. Bd. 46, S. 155-157.
72 THE BUTYRIC ACID GROUP
The atomic weight of the hypothetical anhydrous acid =
3()87»5 ; its saturating capacity = 3'239. This acid which was
originally discovered by Dumas and Stass,* has subsequently been
accurately examined by Smith.f
If Kolbe's theory be applicable to this acid, cetylic acid must
be regarded as C30H31.C2O3.HO, which would explain why it
differs from the isomeric palmitic acid. Two isomeric acids can-
not appropriately be placed in the same group ; hence we place
cetylic acid here instead of considering it with the solid fatty acids.
We also find in this relation an additional reason why the solid fatty
acids whose general formula may be regarded as = CnHn_1O3.HO,
should not be regarded as simple continuations or ascending
members of this group.
Combinations. — The alkaline salts of this acid are soluble in
water, and crystallise readily in white nacreous scales.
Preparation. — Spermaceti, from which this acid is obtained, is a
haloid salt like the other fats, but instead of this acid being com-
bined with oxide of lipyl, it is united to another haloid base en-
tirely corresponding with the ethers of pure chemistry ; this haloid
base when treated with solid caustic alkalies is converted into
cetylic acid. We obtain the acid which exists pre-formed in the
spermaceti, by saponifying the latter with a caustic alkali, decom-
posing the soap with hydrochloric acid and digesting the newly
formed mixture of cetylic acid and ethal (C32H33O.HO) with milk
of lime ; the ethal is then extracted with cold alcohol while the
cetylate of lime remains. The lime-salt is then decomposed by
hydrochloric acid, and the separated cetylic acid purified by solu-
tion in ether.
This haloid base, ethal or hydrated oxide of cetyl, which is
obtained on the saponification of spermaceti, bears exactly the
same relation to cetylic acid that alcohol bears to acetic acid or
fusel oil to valerianic acid. Moreover, as we shall further more
fully describe, cetylic acid may in a similar way be prepared from
this body by heating one part of it in six parts of a previously heated
mixture of equal parts of hydrated potash and caustic lime to a
temperature of 210° — 220° ; in this process, hydrogen is developed
and an alkaline cetylate formed (C32 H33 O. HO + KO + HO =
4 H + KO. C32 H31 O3) which must be purified by solution in
water and crystallisation, and then combined with baryta, from
* Ann. dc Chim. et de Phys. T. 72, pp. 5-11.
t Ann. d. Ch. u Pharm. Bd. 42, S. 40—51.
CETYLIC ACID. 73
which on the addition of hydrochloric acid we can separate the
cetylic acid.
Tests. — When the acid occurs pure and isolated, it is not diffi-
cult to distinguish it from other acids ; its crystallisability and its
comparatively high boiling point distinguish it from the other acids
of this group, and its volatility from the solid fatty acids. On
finding it in a body in which it has not been previously recognised,
we should always institute an elementary analysis, and determine
its saturating capacity, since it is not only possible but very
probable that several similar acids remain to be discovered.
Physiological Relations.
Occurrence. — This acid has hitherto only been found in an
animal fat, namely spermaceti, in combination with hydrated oxide
of cetyl, and in Japanese wax (Meyer) in combination with oxide
of Hpyl.
Origin. — If margaric acid were actually an acid homologous to
cetylic acid and to the acids of this group generally, we might easily
understand that cetylic acid was produced from this acid in the same
manner as acetic is formed from metacetonic acid, for margaric acid
stands in the same relation to cetylic acid as metacetonic acid does to
acetic acid ; the difference between each pair being C2H2.
It is impossible at present to form any conjectures regarding
the special importance of these acids in the few positions in which
they are principally deposited. For a description of hydrated
oxide of cetyl see " haloid bases and fats"
NON-NITROGENOUS ACIDS.
= CaHn_203.HO.
The acids of this group are only interesting in reference to zoo-
chemistry inasmuch as, like many acids of the previous group, they
are products of decomposition of very common animal matters, and
especially of fats. These acids may also be regarded as conjugated
oxalic acids, combined with a carbo-hydrogen isomeric with olefiant
gas ; at least some of the reasons which have been advanced by
Kolbe in support of the theoretical composition of the preceding
group, favour this hypothesis. These acids with their empirical
and hypothetical formulae are as follows : —
74 THE SUCC1NIC ACID GROUP.
Succinic acid .... =C4 H2 O3. HO=C2 H2. C2 O3. HO
Lipic or pyrotartaric acid =C5 H3 O3. HO=C3 H3. C2 O3. HO
Adipic acid ... =C6 H4 O3. HO=C4 H4. C, O3. HO
Pimelic acid .... =C7 H5 O3. HO=C5 H5. C2 O3. HO
Suberic acid .... =C8 H6 O3. HO=C6 H6. C2 O3. HO
Sebacic acid .... =C10H8.O3. HO=C8 H8. C2 O3. HO
It is, moreover, worthy of remark that the acids of this group,
which contain an even number of atoms of carbon, form a series
very analogous to the acids of the preceding group, the acid of one
series differing from the corresponding acid of the other merely by
one equivalent of hydrogen.
Succinic acid .... C4 H2 O3 + H=acetic acid .... C4 H3 O3
Adipic acid .... C6 H4 O3 + H=metacetonic acid C6 H5 O3
Suberic acid .... C8 H6 O3 + H=butyric acid .... C8 H7 O3
Sebacic acid .... C10HS O3 + H=valerianic acid .... C10H9 O3
Moreover, the acids of this group (like those of the preceding
group) are formed when oleic acid is oxidised by nitric acid.
These acids possess the following characters in common : they
crystallise readily and well, do not fuse till they attain a temperature
of from 100° to 200°, and at a higher temperature they sublime in
needles, developing at the same time a suffocating vapour ; more-
over at an ordinary temperature they are devoid of odour, have an
acid taste, dissolve readily in water, alcohol, and ether, and have
an acid reaction ; none of them, with the exception of sebacic acid,
are decomposed by boiling nitric acid ; fused with hydrated potash
they yield oxalic acid together with volatile products. As in the
preceding group, the solubility of their salts stands nearly in an
inverse ratio to the height of the atomic weight of the acid.
As these acids are only of importance in animal chemistry as
products of decomposition, and belong strictly to pure chemistry,
we shall restrict ourselves to the consideration of two of the most
important of them, namely, succinic and sebacic acids. As, how-
ever, none of them occur pre-formed in the animal body, there is
obviously nothing to be said regarding their physiological rela-
tions.*
SUCCINIC ACID.— C4H2O3.HO.
Properties. — When perfectly anhydrous it occurs in very deli-
cate needles which fuse at 145° and boil at 250° ; with one atom
* [Succinic acid has recently been detected by Heintz, in a cyst containing Echino-
cocci in the liver. See Jenaische Ann. f. Physiol. u. Med. Bd. 2, S. 180, and Poggen-
dorff's Ann. Bd. 80, S. 118, or Chemical Gazette, vol. 7, p. 477, and vol. 8, p. 425. —
G. B. D.]
SUCCINIC ACID. 75
of water (corresponding with the above formula) it crystallises in
oblique rectangular prisms, which fuse at 180° and sublime at 250°
in the form of needles or plates, containing only half an atom of
water, and fusing at 160°. In other respects it has the common
characters of this group.
Composition. — According to the above formula it consists of : —
Carbon 4 atoms .... 40-678
Hydrogen .... 2 „ .... 3-390
Oxygen 3 „ .... 40-678
Water 1 „ .... 15-254
100-000
The atomic weight of the anhydrous acid =625 '0 ; its saturating
capacity =16-000. Its rational formula=C2H2.C2O3.HO.
Combinations. — With alkalies this acid forms neutral and acid
salts, which are soluble and crystallisable ; with earths it forms
only neutral salts ; and with the oxides of the heavy metals it
forms neutral and basic salts, some of which are soluble and others
insoluble.
Succinamide, H2N.C4H2O2, is formed by the action of ammonia
on succinate of oxide of ethyl ; it occurs in the form of gra-
nular crystals, insoluble in cold water ; like all the amides, it is
decomposed by alkalies or stronger acids into the corresponding
acid and ammonia.
Bisuccinamide, or Succinimide, C8H5NO4, is formed on sub-
mitting succiiiamide to dry distillation, or on bringing dry ammo-
niacal gas in contact with anhydrous succinic acid ; it is a white,
crystallisable, fusible, soluble body, which, on being boiled with a
solution of potash, takes up 2 atoms of water, and becomes decom-
posed into ammonia and succinic acid (HN.C8H4O4 + 2HO =
H3N+C8H406).
Preparation. — This acid was, as its name implies, originally
obtained from the dry distillation of amber. It was discovered in
the sixteenth century. It has since been found to exist pre-formed
in certain kinds of turpentine and in certain plants. It, however,
occurs much more frequently as a product of the decomposition of
fats, as wax, stearic acid, spermaceti, margaric acid, &c., and in
various kinds of fermentation : thus, for instance, malate of lime,
in contact with nitrogenous bodies, becomes gradually converted
into succinate of lime (CaO.C4H2O4-O=CaO.C4H2O3).
According to C. Schmidt,* succinic acid is found in greater or
* Handworterbuch der Cheinie, von Liebig^ Wohler, u, Poggendorff. Bd. 3, S. 224.
76 THE SUCCINIC ACID GROUP.
lesser quantity in all fermented fluids, and it is possible that
it is formed from glucose, together with mannite (C12H12O12=
C8H9O8 + C4H2O3.HO, Liebig).* This acid is usually obtained
by the distillation of amber, to which a little sulphuric acid has
been added ; the sublimate is then purified by boiling with nitric
acid.
Tests. — As this acid exhibits no very characteristic reactions
towards other bodies, we can only determine its presence by
separating it in a state of purity and then analysing it.
SEBACIC ACID. — C10H8O3.HO.
Properties. — This acid (known also as pyroleic acid) is. in its
external appearance, very similar to benzoic acid, forming white,
nacreous, acicular crystals, grouped together in loose heaps : the
microscope, however, readily reveals the difference in the external
characters of these two acids. It forms either whorled clusters,
similar to margaric acid, or large plates extending from a centre,
and intersecting one another at various angles, which run into sharp
points, without forming an angle capable of measurement ; in their
mode of grouping, these crystals most closely resemble well-formed
crystals of margaric acid ; the individual crystalline leaflets are, how-
ever, far greater. This acid fuses at 127°, without losing its basic
water, into a colourless oil, which, on cooling, solidifies into a
crystalline mass ; at a higher temperature it sublimes undecom-
posed ; it is only slightly soluble in cold water, but in hot water
as well as in alcohol and ether, it dissolves readily; it has a
pungent rather than an acid taste, and reddens litmus. By pro-
longed boiling with nitric acid of 1*4 specific gravity, it is gradually
(in six or eight days) converted into pyrotartaric acid. (C.
Schlieper.)f
Composition. — According to the above formula it consists of—-
Carbon 10 atoms .... 59-406
Hydrogen .... 8 „ .... 7*921
Oxygen 3 „ .... 23'762
Water 1 „ .... 8-911
100*000
The atomic weight of the hypothetical anhydrous acidm
* Handwbrterbuch der Chemie, von Liebig, Wohler, u. Poggendorff. Bd. 3, S. 124.
t Ann. d. Ch. u. Pharm. Bd. 70, S. 121-129.
SEBACIC ACID. ?7
1150; its saturating capacity —8-696 ; its rational formula is
C8H8.C203.HO.
Combinations. — Its salts are very similar to those of benzoic
acid; the alkaline salts are very soluble, the earthy salts are
difficult of solution, while those of the oxides of the heavy metals
are insoluble.
Pyrotartaric acid, C5H3O3.HO, is formed when nitric acid acts
on sebacic acid, each atom of the latter assimilating 5 atoms of oxy-
gen, thus C10H8O3+5O=2(C5H3O3.HO); itis cry stallisable, white,
resists the action of the air, fuses at a little above 100°, and
sublimes at a higher temperature, developing at the same time a
white suffocating vapour ; it has a strongly acid taste, dissolves
readily in water, alcohol, and ether, and in sulphuric acid without
blackening, and expels carbonic acid from its salts ; most of its
salts are soluble in water and in spirit of wine; with neutral
acetate of lead it yields no precipitate, but with the basic acetate,
and with nitrate of silver, we have a white, gelatinous deposit
which, on drying, becomes brownish white, and translucent. This
acid is isomeric, or probably identical, with the lipic acid which has
been examined by Laurent and Bromeis, and is mentioned in page
74 ; hence it belongs to the same group of acids as sebacic acid.
Preparation. — This acid is formed during the dry distillation of
oleic acid. As it is produced from no other kind of fat, we may
determine the presence and amount of olein in a fat, from the
presence and amount of the sebacic acid. In order to prepare it,
the distillate must be boiled with water as long as crystals continue
to be deposited from it on cooling. By a repetition of the crystal-
lisation, the acid may be obtained in a state of purity.
Tests. — In this distillation scarcely any other acid can occur
which could be confounded with sebacic acid. It can be distin-
guished from benzoic acid, to which, as we have observed, it is very
similar, by the circumstances that there is a precipitate on the
addition of nitrate of silver or of one of the salts of the suboxide of
mercury to its hot solution (which is not the case with benzoic
acid ;) that the sublimed acid crystallises far less readily ; that a
microscopic examination of the crystals obtained from the aqueous
solution, reveals a difference of form; and finally that by the
action of nitric acid it is converted into lipic acid.
78 THE BENZOIC ACID GROUP.
NON-NITROGENOUS ACIDS.
= CnHn_903.HO.
This is also a group of acids which has little relation to animal
chemistry, and to which we should make no reference in this place,
if it were not that their representative, benzole acid, sometimes
occurs in animal fluids, and that its conversion in the animal body
has already thrown much lighten the metamorphosis of the tissues.
In accordance with the above general formula we have the
following acids belonging to this group : —
Benzoic acid = C14H5O3. HO.
Myroxylic acid =C15 H 6 O3. HO.
Toluylic acid =C16 H 7 O3. HO.
Cumic acid =0^ Hn Os. HO.
and Copaivic acid =C40 H31 O3. HO.
but there are certain other acids, as, for instance, cinnamic acid,
C18H7O3.HO, which, partly from their physical properties, and
partly on account of the analogy of the products of decomposition,
must be regarded as homologous to these acids, although the ratio
of the carbon to the hydrogen is not in accordance with the above
formula. Moreover, we are acquainted with certain higher stages
of oxidation of the same radical, to which stages we assign specific
names, and which are impressed with the general character of this
group. They contain 5 atoms of oxygen, and are —
Salicylic acid .... C14 H 5 O5. HO corresponding to Benzoic acid
Anisic acid .... C16 H 7 O5. HO „ Toluylic acid
Curaaric acid .... C18 H . Os. HO „ Cinnamic acid
and Copalic acid .... C40 H31 O5. HO „ Copaivic acid.
All these acids have the following properties in common ; they
are solid, crystallise readily in needles or scales, are devoid of odour
when pure, are fusible, sublime without decomposition, and are
slightly soluble in cold water ; they dissolve freely in hot water,
and crystallise as the solution cools ; they are readily soluble in
alcohol and ether, and they redden litmus. Their salts present the
same analogies.
Physiology itself shows us that cinnamic acid, although not
constituted in accordance with the above formula, should be
included in this group, for Marchand* has experimentally proved
that cinnamic acid, like benzoic acid, is converted in the animal body
into hippuric acid.
* Journ. f. pr. Ch. Bd. 18, S. 35.
THE BENZOIC ACID GROUP. 79
Hypotheses of the most varied kinds, chiefly grounded on the
products of decomposition, have heen set up regarding the rational
constitution of these acids. These hypotheses are, however, for
the most part limited to the constitution of benzoic acid, and as
but few of them are applicable to the other members of this group,
we may regard this as an evidence of their untenability. This is
partially the case with the hypothesis of Fehling, who, previously
to Kolbe, regarded benzoic acid as a conjugated oxalic acid, whose
adjunct was phenyl, C12H5. Hitherto, however, the evidence in
favour of any one of these hypotheses has not been sufficiently pre-
ponderating to warrant its unconditional acceptance.
All these bodies present an analogy in their relations of com-
bination and decomposition. Thus each of these acids presents a
series of lower stages of oxidation not dissimilar to the aldehydes
of the first group, and containing 1 atom of hydrogen more and 1
atom of oxygen less than the corresponding acid in the anhydrous
state. These lower oxides are sometimes acid, sometimes basic,
sometimes indifferent volatile oils, some of which occur pre-formed
in the vegetable kingdom.
Volatile oil of bitter almonds C14H6 02 corresponds with benzoic acid C14H5 O3
Salicylous acid C14H6 O4 „ salicylic acid C14H5 O5
Hydride of cinnamyl .... C18H8 O2 „ cinnamic acid C18H7 O3
Cumarin .... .... .... C18H8 O4 „ cumaric acid C18H? O6
Cumin C20H12O2 „ cumic acid ^so^ii^s
In all these combinations 1 equivalent of hydrogen may be
replaced by 1 equivalent of chlorine, bromine, iodine, or sulphur.
From the chlorine-combinations of this class, we can obtain the
corresponding amides by the action of ammonia ; thus, for instance,
in the case of benzamide, the action is shown by the equation,
C14H502C1 + HgN^ HC1 + H2N.C14H502.
On submitting to dry distillation, the ammonia-salts of the
acids containing 3 atoms of oxygen we obtain the corresponding
nitriles, which, like the nitriles of the first group of acids, are
volatile, inflammable fluids. They are likewise decomposed both
by strong acids and alkalies into ammonia and the corresponding
acid, and when heated with potassium they yield cyanide of
potassium and carbo-hydrogens.
The hydrates of the acids containing 3 atoms rof oxygen,
when heated with caustic alkalies, lime, or baryta, yield to them
2 atoms of carbonic acid, and become converted into non-
oxygenous oils :—
80 THE BENZOIC ACID GROUP.
Hydrated benzoic acid C14H6 O4-2CO2=C12H6 = Benzole or Benzin
Hydrated cumic acid C20H12O4— 2CO2=ClsH12=Cumole or Cumin
Hydrated toluylic acid C16H8 O4 -2CO2=C14H8 =Toluole or Toluin
In these carbo-hydrogens we may again replace 1 equivalent
of hydrogen by 1 equivalent of chlorine, bromine, iodine, or
hyponitric acid (HO4) ; and in this way there are formed, for
instance, chlorobenzide, C12H5C1, bromocumide, C18HnBr, iodo-
toluide, C14H7I, and nitrobenzide, nitrocumide, and nitrotoluide,
CI2H5.N04,C18HU.N04 and CI4H,.NO4.
These last-named nitrogenous compounds form yellow, oleagi-
nous bodies, from which, by the action of sulphuretted hydrogen,
we obtain the organic, non-oxygenous, volatile bases, benzidine,
C12H7N, cumidine, C18H13N, and toluidine, C14H9N (according
to the equation C14H7.NO4 + 6HS=4HO + 6S + C14H9N).
BENZOIC ACID. — C14H5O3.HO.
Chemical Relations.
Properties. — In its sublimed state this acid occurs in colourless,
delicate needles ; in the moist way it crystallises in scales, or small
prisms, or six-sided needles (the primary form of the right
rhombic prism) ; it fuses at a temperature exceeding 120°, boils
at 239°, and then becomes converted into a thick, irritating vapour ;
it is not decomposed either by nitric or by sulphuric acid ; in other
respects it has the general properties of the acids of this group.
Composition. — In accordance with the above formula, it con-
sists of: —
Carbon Hatoms .... 68*853
Hydrogen 5 „ .... 4*098
Oxygen 3 „ .... 19*672
Water .„ 1 „ .... 7'377
-^
100-000
The atomic weight of the hypothetical anhydrous acid = 1412*5,
and its saturating capacity = 7*079.
Combinations. — Most of the benzoates are soluble in water ; the
alkaline and magnesian salts are very soluble, but do not readily
crystallise; the combinations of benzoic acid with the oxides of the
heavy metals are for the most part difficult of solution, but are
taken up more freely by hot than by cold water »
BENZOIC ACID. 81
Products of its metamorphosis. — Oil of bitter almonds is usually
regarded as a combination of a hypothetical oxygenous radical
(benzoyl) with hydrogen ; it is thus a hydride of benzoyle,
C14H5O2.H ; it is a thin, colourless liquid whose specific gravity
is 1*043 and whose boiling point is 180°; when exposed to
the air it oxidises and becomes converted into hydrated benzole acid.
It not only occurs in oil of bitter almonds, but is often found as a
product of decomposition when albuminous or gelatinous sub-
stances are treated with strong oxidising agents (Guckelberger).*
The one equivalent of hydrogen of this body may not only be
replaced by chlorine, bromine, or iodine, but also by sulphur or
cyanogen.
Benzamide, H2N.C14H5O2? whose preparation is noticed in
the introductory remarks on this group, is a beautifully crystal-
lisable body which is soluble in water, alcohol, and ether, and
possesses all the known properties of the amides.
Benzonitrile, C14H5N, whose formation has also been alluded
to, is a colourless oil, which boils at 191°, dissolves in 100 parts
of boiling water, and in alcohol and ether in every proportion ;
as, when treated with potassium, it yields cyanide of potassium,
many regard it as cyanide of phenyl, C12H5.C2N.
If azobenzide, C12H4N, be dissolved in alcohol, the solution
saturated with ammonia, and sulphuretted hydrogen passed
throughout, we obtain the organic base, benzidine, C12H6N.
Benzoin, C14H6O2, (isomeric with oil of bitter almonds) is
formed by the contact-action of the caustic alkalies on oil of bitter
almonds containing hydrocyanic acid ; it occurs in prisms which
are devoid of colour, taste, and smell, and which may be sublimed
without undergoing decomposition ; it dissolves in concentrated
sulphuric acid, and in an alcoholic solution of caustic potash, com-
municating in each case a blue tint to the mixture ; on passing its
vapour through a red hot tube it is again converted into oil of
bitter almonds. By the action of chlorine it loses 1 equiv. of hydro-
gen, and is converted into benzile, C14H5O2, which is isomeric
with the hypothetical radical, benzoyl, crystallises in sulphur-
yellow six-sided prisms, and is fusible and capable of sublimation.
Benzine or benzol, C12H6, is obtained, as has been already
mentioned, on treating benzoic acid with an excess of hydrated
lime ; it is a colourless inflammable fluid with an ethereal odour,
is solid at 0°, boils at 86°, is insoluble in water, but dissolves in
alcohol and ether. Amongst the many other substances which
* Ann. d. Ch. u. Pharm. Bd, 64, S. 46 ff.
G
82 THE BENZOIC ACID GROUP.
have been obtained from benzine, we may mention nitrobenzide,
C12H5NO45 a yellow fluid with a sweetish taste and a cinnamon-
like odour, which is not decomposed by the alkalies. If an
alcoholic solution of this nitrobenzide be treated with hydrated
potash and then distilled, there is produced a non-oxygenous,
nitrogenous body, azobenzide, C12H4N, forming large, red, fusible,
and volatile crystals, which neither corresponds with the nitriles
nor possesses basic properties like the organic, non-oxygenous
bases.
Preparation. — Benzoic acid is found in many of the resins or
balsams, but occurs in the largest quantity in the resin known as
gum-benzoin, from which it is ordinarily prepared either by subli-
mation, or, in the moist way, by dissolving the resin in spirit of
wine, adding an aqueous solution of carbonate of soda, and then
precipitating the benzoic acid by the addition of hydrochloric acid
to the filtered and concentrated fluid.
Tests. — Benzoic acid is less to be distinguished from other
substances by its volatility, than by its property of separating in
crystalline scales from very concentrated aqueous solutions on
the addition of an acid. But in carrying on investigations
in relation to benzoic acid we must be especially careful
respecting the evaporation of the fluid, since it volatilises very
readily with the steam ; we may easily perceive delicate crystals
on the paper covering of the evaporating basin, when acid
fluids of this nature have been evaporated without due
care ; it is therefore better not to add an acid to the fluid till
after evaporation, or if it be already acid, to render it alka-
line previously to evaporating it. I have found the following
method applicable to the discovery of small quantities of benzoic
acid in the animal fluids : the alcoholic extract of the fluid in
question (for the alkaline benzoates and benzoate of lime are
soluble in alcohol) must be mixed with a little acetic, hydrochloric,
or lactic acid ; if distinct crystals of benzoic acid do not now
separate, the mass must be extracted with ether, and the ethereal
solution submitted to spontaneous evaporation ; from this ethereal
extract, which is usually of an oily fluid character, the benzoic acid
separates in a crystalline form on the addition of water. When
too much fat is present, we must treat the separated mass with
dilute spirit, which dissolves the benzoic acid without acting on
the fat ; on the evaporation of this spirituous solution, we obtain
the benzoic acid in a tolerably pure crystalline state, mixed with
other free but fluid acids. Under the microscope it appears in
BENZOIC ACID. 83
rectangular tablets, which, for the most part, are arrayed in rows,
being linked together by their opposite angles. Its slight solubility
in water, the facility with which it sublimes (as may be seen
with a minute quantity between two pieces of flat glass or shallow
watch-glasses), together with its crystalline form, afford strong pre-
sumption of its presence. Since the remaining acids of this group,
which in other respects are very similar to benzoic acid, are not
found in the animal body, they cannot give rise to any confusion
or mistake in testing for this acid. We have already explained in
p. 77> how it may be distinguished from succinic acid, and from
sebacic acid, which, however, can scarcely be regarded as existing
preformed in the animal body. The mode of distinguishing it
from hippuric acid, which closely resembles it in physical pro-
perties, will be given in a future page. If we can obtain a
sufficient quantity, an elementary analysis and a determination of
the atomic weight are by no means superfluous.
Physiological Relations.
Occurrence. In a physiological point of view, benzoic acid
deserves a full consideration, although numerous experiments
render it probable that it does not exist preformed in any animal
fluid. No one has suspected its presence in any animal fluid but
the urine ; and in this, both in the case of herbivora and carnivora,
it occurs very often in the place of hippuric acid. Liebig*, in his
classical essay on Fermentation, Putrefaction, and Decay, attributed
the occasional occurrence of benzoic acid, in place of hippuric
acid, in the urine of horses, solely to a process of fermentation
which the latter acid underwent when the urine began to decom-
pose; benzoic acid being formed from it, together with other
products. Subsequently,! however, he changed his opinion,
believing that he had ascertained that horses, when very hardly
worked, and living on insufficient fodder, discharged urine contain-
ing benzoic acid, while, under the opposite conditions, the urine
contained hippuric acid. In order to ascertain which, or whether
either of these views were correct, 1 1 analysed the urine of a large
number of horses, both well-fed and half-starved, and healthy and
diseased ; but invariably found hippuric acid and no benzoic acid,
unless when the urine had been a good deal exposed to the air at
an ordinary temperature. But, on the other hand, when it had
stood for some time in the stable, and began to be ammoniacal, it
* Ann. d. Ch. u. Pharm. Bd. 30, S. 261 ff.
f Ibid. Bd. 41, S. 272.
t Handworterbuch d. Physiol. Bd, 2, S. 14.
G 2
84 THE BENZOIC ACID GROUP.
never contained hippuric acid, but only benzoic acid. Hence, too,
it is that we so often meet with only benzoic acid in human urine,
which, as it contains a far smaller proportion of hippuric acid,
must be employed in larger quantities ; and if some portions of it
have been long exposed to the air, which can hardly be avoided,
they produce such a change that only benzoic acid is found in the
whole urine. Hence it appears to be the fact, as Liebig assumed,
that a ferment is formed in the urine through which the nitro-
genous hippuric acid is converted into benzoic acid; for if we mix
a specimen of urine containing benzoic acid, whether from man or
from the horse, with another specimen containing hippuric acid, on
separating the acids from the mixture we almost constantly obtain
benzoic acid alone, the ferment of the urine containing benzoic acid
probably acting on the hippuric acid of the fresh urine even during the
evaporation of the mixture. Moreover, the conversion of benzoic
acid conveyed into the organism, into hippuric acid, which was
invariably observed by Wohler and Keller*, Ure,f and sub-
sequent experimenters, is in accordance with the idea that the
former, when it occurs in the urine, is only a product of decom-
position of the latter.
Action. We shall return to the behaviour of benzoic acid in
the living animal body when we treat of hippuric acid. We will
here only remark that the ingestion of this acid causes an extremely
disagreeable irritation in the throat, and subsequently a very profuse
diaphoresis ; and, finally, that it is one of the very few acids which
produce a marked augmentation of the acidity of the urine.
NON-NITROGENOUS ACIDS.
We make a special group of these acids, although their sole
representative is lactic acid. Although this acid deserves a special
chapter in every work on physiological chemistry, we see good
reason for classing it in a special group of acid bodies. We have
already remarked (see p. 56) that in its composition lactic acid
presents a close analogy to metacetonic acid ; it is more than pro-
bable that many other acids exist which stand in the same relation
to the individual members of the first-described group of acids, as
* Ann. d. Ch. u. Pharm. Bd. 43, S. 108.
t Medico-Chirurgical Transactions. Vol. 24, p. 30 .
LACTIC ACID. 85
lactic acid stands to metacetonic acid ; and, in point of fact,
Cahours,* and subsequently Strecker,f arrived at the discovery of
some such acids by a perfectly different train of ideas from that
which we have pursued. The latter, in employing Piria's method
of decomposing the amide compounds, (given in p. 36,) with the
view of ascertaining whether certain nitrogenous animal substances
were amides, found two such acids constituted according to the
above general formula. In treating glycine with nitrous acid, he
discovered an acid=C4H3O5.HO, corresponding to acetic acid,
and on treating leucine in a similar manner, he obtained an acid
= C12H11O5.HO, analogous to caproic acid.
Acetic acid .... C4 H3 O3. HO corresponds to glycic acid C4 H3 O5. HO
Metacetonic acid .... C6 H5 O3. HO „ lactic acid C6 H5 O5. HO
Caproic acid ... C12HUO3. HO „ leucic acid C12HUO5. HO
In the decomposition of hippuric acid, according to the same
method, Strecker obtained a new acid, whose composition is not
in accordance with the above formula, but is very similar to that of
lactic acid: it is represented by the formula C18 H7 O7. HO; hence
it is analogous in its constitution to the neutral carbo-hydrates of
the vegetable kingdom (starch, sugar, woody fibre) ; that is to say,
in addition to carbon it contains hydrogen and oxygen in the
exact proportions to form water. Here, too, we should place the
cholestericacid=C8H4O4.HO, discovered by Redtenbacher, which
also presents much similarity in its characters with the above-
named acids of the carbo-hydrates.
There is little to be said regarding the general properties of the
acids of this group, as in truth, lactic acid is the only one of them
with whose characteristics we are accurately acquainted. It appears,
however, from Strecker's communications, that all these acids,
when deprived as much as possible of water, occur as oily, non-
crystallisable fluids, redden litmus strongly, undergo decomposition
when heated, and form soluble and in part crystallisable compounds
with bases.
LACTIC ACID. — C6H5O5.HO.
Chemical Relations.
Properties. — In its most concentrated state lactic acid is a colour-
less, inodorous, thick, syrupy fluid, which cannot be solidified by
the most intense cold; its specific gravity = 1*215; it dissolves
* Compt. rend. T. 27, p. 267.
t Ann. d. Ch. u. Pharm. Bd. 68, S. 52-55.
86 THE LACTIC ACID GROUP.
readily in water, alcohol, and ether, attracts water from the atmo-
sphere, has a strongly acid taste and reaction, decomposes when
heated, and displaces not only volatile acids but even many of the
stronger mineral acids from their salts. Heated with concentrated
sulphuric acid, it yields almost pure carbonic oxide gas, and is con-
verted into a substance resembling humin; it gives, however, no
trace of formic acid.
Composition. — According to the above formula it consists of :
Carbon 6 atoms .... 40'000
Hydrogen 5 „ .... 5'555
Oxygen 5 „ .... 44'445
Water 1 „ .... 10-000
100-000
The atomic weight of the hypothetical anhydrous acid= 101 2'5,
and its saturating capacity =9*8 76.
Combinations. — With bases lactic acid generally forms neutral
salts, all of which are soluble in water, and many in alcohol, but
none in ether. Most of the lactates may be heated to 150° or 170°,
and some even to 210°, without undergoing decomposition. The
alkaline lactates are not crystallisable, and by the greatest concen-
tration can only be reduced to syrupy fluids ; and the same is the
case with the lactates of baryta, alumina, sesquioxide of iron,
and binoxide of tin ; but all other lactates crystallise with tolerable
facility, and are capable of resisting the action of the atmosphere.
The following peculiar relation has recently been observed in the
crystallisable lactates ; the lactic acid obtained from animal fluids,
and that produced by the fermentation of sugar, form, with the
same base, salts which present certain differences in the amount of
their water of crystallisation, in their degree of solubility, and in
their decomposition by heat, (Liebig,* Engelhardt and Maddrell,t
Engelhardt J). This is, however, a subject requiring further
investigation ; at least Liebig thinks that he has obtained from the
acid of Sauer-kraut a zinc-salt which corresponds with that yielded
by the muscular juice ; and in my own researches, whenever I
have analysed the lactic acid of the gastric juice in combination
with magnesia or zinc, I have always found it corresponding with
that obtained from sugar. Engelhardt distinguishes the acid
obtained from muscular juice as a lactic acid, and that produced
bythe fermentation of sugar as b lactic acid.
Lactate of lime, CaO,« La + 4HO, CaO.£ La-f 5HO, occurs in
* Ann. d. Ch. u. Pharm. Bd. 62, S. 312.
f Ibid. Bd. 63, S. 83-120.
$ Ibid. Bd, 65, S. 359-366.
LACTIC ACID. 87
the form of white hard bodies, which under the microscope are seen
crystallising in tufts of delicate needles, each two of which are so
placed in relation to the other, that collectively they resemble
overlapping tufts or pencils : their form is tolerably charac-
teristic, and they cannot be confounded with other organic
lime-salts, as for instance, the butyrate. Lactate of lime loses all
its water at 100°, and is soluble in almost every proportion in
boiling water and in alcohol ; the salt of the a lactic acid dissolves,
however, in 12'4 parts of water, and that of the b lactic acid in
9-5 parts ; both salts may be heated to 180° without decomposi-
tion.
A crystallographic investigation shows that the b lactates of
magnesia, of protoxide of manganese (which is colourless or of a
pale amethystine tint,) of protoxide of iron (which is of a pale
yellow colour), of cobalt (which is of a peach-colour), of nickel,
and of zinc, are isomorphous, since with three atoms of water of
crystallisation, they form vertical prisms with horizontal terminal
surfaces, or with superimposed obtuse horizontal prisms.
Lactate of magnesia. — The salt of a lactic acid contains 4 atoms
of water of crystallisation, and is somewhat more soluble in spirit
than that of b lactic acid.
Lactate of nickel is of an apple-green tint, and is difficult of
solution in cold water and in spirit ; the salt of a lactic acid loses
all three of its atoms of water at 100°, while that of b lactic acid
does not part with its third atom at a lower temperature than 130°.
Lactate of zinc. — The a lactate of zinc contains only 2 atoms of
water of crystallisation, which it very slowly loses at a temperature
of 100°; it begins to decompose at 150°, is soluble in 5'7 parts of
cold and 2'88 of hot water, and in 2' 23 parts of alcohol ; the b
lactate loses its water of crystallisation very rapidly at 100°,
bears exposure to a temperature of 210° without decomposition,
and dissolves in 58 parts of cold and 6 of boiling water, but is
almost insoluble in alcohol. C. Schmidt,* who is the only observer
who has devoted great attention to the forms of microscopic crystals
with the object of diagnosing such bodies in the animal fluids, gives
a very accurate description and figure of the form of lactate of
zinc; he mentions the club-like shape of the crystals during their
process of formation, and their curved surfaces, as especially cha-
racteristic of this salt.
Lactate of cadmium crystallises in anhydrous needles, and is
almost insoluble in alcohol.
* Entwurf e. allg. Untersuchungsmeth. der Safte u. Excr, 1846, S. 78 ff.
88 THE LACTIC ACID GROUP.
Lactate of copper formed with the a lactic acid crystallises in
hard, light blue, warty masses, dissolves in T95 parts of cold and
1*24 of hot water, and very readily in alcohol; at 100° it begins
slowly to lose a portion of its water, and at 140° it decomposes,
with a separation of suboxide of copper. Lactate of copper formed
with the b lactic acid, with 2 atoms of water of crystallisation, occurs
in much larger crystals of a dark blue or green tint ; it dissolves in
6 parts of cold and 2*2 of boiling water, in 115 parts of cold and 26
of boiling alcohol ; it parts with its water very readily and per-
fectly, both at 100°, and in vacuo, and does not become decom-
posed at a temperature lower than 200°, when it inflames and
smoulders.
Basic lactate of protoxide of tin, 2SnO. La, is a crystalline,
anhydrous powder, which is very insoluble in water, and absolutely
so in alcohol,
Lactate of suboxide of mercury, Hg2O. La + 2HO, forms red
crystals which are difficult of solution, and which, on boiling, become
decomposed into a salt of the oxide, and into metallic mercury.
Basic lactate of protoxide of mercury, 2HgO.La, forms anhy-
drous glistening prisms, difficult of solution.
Lactate of silver, AgO. La + 2HO, occurs in needles of a silky,
glistening appearance, which blacken when exposed to light. This
salt is almost insoluble in cold, but dissolves very readily in hot
alcohol; it decomposes at 100°; the aqueous solution, when boiled
gradually, assumes a blue tint and deposits brown flocculi.
Products of its metamorphosis. — Lactide, C6H4O4, On heat-
ing the ordinary, colourless, hydrated lactic acid to 130°, water and
a little lactic acid distil over, whilst there remains a yellowish white
solid substance, which is very fusible, very bitter, almost insoluble
in water, but dissolves readily in alcohol and ether, and whose com-
position is expressed by the formula, C6H5O5. This product, when
boiled with water, or for a long time exposed to the atmosphere,
becomes again converted into ordinary hydrated lactic acid, and
with milk of lime it yields the ordinary lactate of lime (Pelouze*.)
If, however, either this so-called anhydrous acid or the hydrated
lactic acid be heated to 250°, the products of decomposition are
carbonic acid, carbonic oxide, lactide and lactone, but no carbo-
hydrogen. The lactide occurs as a sublimate which must be puri-
fied by solution in boiling alcohol. It crystallises from this fluid
Jn white tablets which fuse at 107° and volatilise at 250° ; the fused
* Compt. rend. T. 19, p, 1219-1227.
LACTIC ACID. 89
crystals solidify on cooling, into a crystalline mass which is devoid
of odour, has a slightly acid taste, and dissolves slowly in water; its
conversion into lactic acid is more rapid than that of the so-called
anhydrous lactic acid.
Lactone, C10H8O4 (produced according to the formula
2C6H5O5.HO— [2CO2 + 4HO] = C10H8O4) is obtained on dis-
tilling anew the fluid products of distillation of lactic acid, washing
the distillate with water, and drying the insoluble portion with
chloride of calcium ; the pure lactone is a colourless fluid with an
aromatic odour and a burning taste, which boils at 92°, and when
inflamed, burns with a blue tint.
Lactamide, C6H7NO4==H2N.C6H5O4, is formed from lactide
and dry ammoniacal gas : it crystallises in colourless, right rectan-
gular prisms, and is decomposed into ammonia and lactic acid.
This body is moreover isomeric with the powerful base, sarcosine,
discovered by Liebig, and with the longer-known indifferent sub-
stance, urethran.
Preparation. — Lactic acid is very often formed during the fer-
mentation of fluids containing sugar or starch, and it might as well
be maintained that there is a specific lactic fermentation, as that
there is a distant acetic or butyric fermentation. Hence lactic acid
is not only found in milk which is turned sour, but also in the acid
waters of starch fabrics, in Sauer-kraut, in sour cucumbers, in fer-
mented beet-root juice, &c. (The conditions under which this con-
version takes place are explained in a future part of this work under
the head of " fermentation of milk/5)
The best method of obtaining lactic acid is by exposing sugar
to this kind of fermentation, under the combined influence of milk
and cheese.
Bensch* has employed the following practical method of ob-
taining it : 6 parts of cane-sugar, TVtn Part °f tartaric acid, 8 parts
of sour milk, J part of old cheese, and 3 parts of levigated chalk, are
mixed with 26 parts of water, and exposed to a temperature of 32°.
In the course of eight or ten days a semi-solid magma of lactate of
lime is formed ; on boiling it with 20 parts of water and ^h Part
of caustic lime, filtering it at a boiling temperature, and slightly
evaporating it, the lactate of lime separates in a few days in gra-
nules. The salt must be drained and pressed, again dissolved in
twice its weight of water, decomposed with -/-% parts of sulphuric
acid, the precipitated gypsum removed by filtration, and the acid
fluid saturated with T% of carbonate of zinc. The crystallised zinc-
* Ann. d. Ch. u, Pharm. Bd. 61, S. 174-176.
90 THE LACTIC ACID GROUP.
salt must then be decomposed by sulphuretted hydrogen, and the
fluid concentrated, first by warmth, and afterwards in vacua : the
hydrated lactic acid is finally obtained in a state of purity by solu-
tion in ether.
Liebig* prepares lactic acid from the juice of flesh, in the fol-
lowing manner. Flesh from which the fat has been most carefully
removed, is very finely chopped, repeatedly kneaded with water^
and exposed to strong pressure ; the fluid thus obtained is heated
till it boils, filtered to remove the coagulated matters, decomposed
with baryta-water, again filtered, and very strongly concentrated by
evaporation. In the course of a few days the creatin crystallises ;
the milky liquid poured away from these crystals is rather more
strongly concentrated ; and then gradually treated with small por-
tions of alcohol, which causes the crystallisation of the inosinates
of baryta and potash. The mother-liquid, after the separation of
the inosinates, is evaporated, and the residue extracted with
alcohol ; after this alcoholic extract has stood for a considerable time
crystals are formed from it, while nearly pure lactate of potash
remains in the mother-liquid. To this we must add sulphuric acid
or a solution of oxalic acid (containing one-third of the acid), and
then precipitate the sulphate or oxalate of potash by means of
alcohol. The fluid filtered from the potash-salt is treated with
ether, as long as any precipitation continues ; the solution is then
evaporated to a syrup, and treated with half its volume of spirit
and five times its volume of ether, which takes up nearly pure
lactic acid.
From this we may prepare lactate of lime, whose spirituous
solution must be purified by animal charcoal, and evaporated, so
that the salt may crystallise ; the lactic acid is then readily separated
from the lime-salt by sulphuric or oxalic acid with the aid of alcohol
and ether.
Tests. — To determine the presence of lactic acid is one of the
most difficult tasks in analytical animal chemistry, as is indeed
evinced by the prolonged contest that existed regarding the pre-
sence or absence of this acid in the animal organism. In order to
determine its presence with certainty, it must in the first place be
separated from all other organic substances, but in this lies one of
the great difficulties ; for there is scarcely any other acid to which
foreign bodies adhere so tenaciously. Liebig^s method (which
we have given) of preparing lactic acid from muscular juice is one
of the best means of separating this acid from animal fluids. If we
* Ann. d. Ch. u. Pharm. Bd. 62, S. 312.
LACTIC ACID. 91
are sufficiently acquainted with the properties of lactic acid and its
salts, we may modify this method in many respects, which is indeed
the more necessary, since, in investigations relating to animal che-
mistry, we rarely ha^ e so large a quantity of material to work upon
as is required in accurately following the steps laid down by Liebig.
From most of the other animal fluids we can rarely obtain a suffi-
cient quantity of lactic acid to serve for an elementary analysis.
Indeed it often happens that we cannot even obtain enough of a
pure lactate to enable us to determine the atomic weight. Hence,
it is very often necessary to found our decision regarding the pre-
sence of lactic acid almost entirely on the crystalline form of its
salts. Although many of the other properties of the lactates may
contribute to establish the proof of the presence of this acid, yet a
crystallometric investigation, made with the aid of the microscope,
can alone be regarded as approximating in certainty to an elemen-
tary analysis.
In consequence of the extremely minute quantity of lactic acid
to be obtained from the animal fluids, I am in the habit of adopt-
ing the following method, which may be readily modified in parti-
cular cases, with the view of studying the forms of the different
salts under the microscope. The impure lactic acid prepared from
the alcoholic extract by sulphuric or oxulic acid is treated with
baryta-water, and the excess of the baryta removed by carbonic
acid ; the solution of lactate of baryta is evaporated to the con-
sistence of a syrup, treated with alcohol, filtered, again evaporated,
and then allowed to stand for some time, in order that the other
baryta-salts, (for instance, the butyrate and inosinate) may crystal-
lise ; the syrup is then allowed to trickle away, or if it be not with-
drawn, is dissolved in water and decomposed with a solution of
gypsum ; the fluid from which the sulphate of baryta has been
removed by filtration is strongly concentrated, and on examining it
under the microscope we can readily perceive the double brushes of
lactate of lime which we have already described, in addition to
crystals of gypsum. On dissolving these crystals of lactate of lime
in alcohol, and adding sulphate of copper to the alcoholic solution,
the fluid, after standing for some time (in order that the excess of
of sulphate of copper and the gypsum that is formed may separate
as completely as possible) is evaporated so as to crystallise, and the
crystals of lactate of copper are then microscopically examined. If,
by the above process, we do not succeed in obtaining distinct and
measurable crystals, we must dissolve the residue in a little water ; and
(in order to decompose or separate any butyric acid that may be
92 THE LACTIC ACID GROUP.
present) we must boil it strongly, filter it, and, after concentrating
it, place on it a small zinc bar. Since, as we have already mentioned,
lactate of copper is far more soluble in water than lactate of zinc,
the zinc very soon becomes covered with white crystals of lactate
of zinc, if the fluid be sufficiently concentrated, and these crystals,
if they be allowed to remain for some time, may usually be easily
measured under the microscope. Distinct crystalline forms may
even be distinguished with the naked eye. If, however, in conse-
quence of the want of a Goniometer, an accurate crystallometric inves-
tigation cannot be instituted, we must precipitate the solution of the
zinc-salt with a boiling solution of protochloride of tin, and allow
it to stand for some time ; on then making a microscopic exami-
nation, we shall find clusters of crystals whose groups are composed
of thick rhombic tablets lying close upon one another. When we
have in this way prepared and explored the different lactates, (and
after some practice, tolerably small quantities are sufficient for this
purpose,) we hardly require to make an elementary analysis or to
determine the atomic weight, to enable us to decide regarding the
presence of lactic acid.
Physiological Relations.
Occurrence. — The doubts regarding the nature of the free acid
of the gastric juice have given rise to a great number of investiga-
tions on this point. Prout* and Braconnott believed that their
experiments showed that the gastric juice contained no lactic acid,
but only hydrochloric acid. Subsequently, I thought that I had
satisfactorily provedj the existence of lactic acid in the gastric juice
of various carnivorous and herbivorous animals, (by obtaining from
it several of the lactates, and referred the occurrence of free hydro-
chloric acid simply to the decomposition of the metallic chlorides
by the lactic acid during the evaporation or distillation of the
gastric juice. Hiinefeld § supported this view. A period now arrived
when Liebig totally denied that lactic acid occurred in any of the
animal fluids, and, consequently, in examining the gastric juice of a
criminal immediately after he had been beheaded, Enderlin || was just
as unable to detect lactic acid, as he has been to find carbonate of
soda in the blood-ash. Blondlot,^[ also, in examining pure gastric
* Phil. Trans, for 1824, p, 45.
t Ann. de Chim. T. 59, p. 348.
J First edition of this work, 1840. Bd. 1, S. 284. Bericht uber d. Fortschritte der
physiol. u. path. Ch. im J. 1842. Leipzig. S. 10.
§ Chemie u. Medicin. Bd. 2, S. 81 ff.
|| Ann. d. Ch. u. Pharm. Bd. 46, S. 123.
T[ Traite analytique de la Digestion. Paris et Nancy. 1843. p. 244.
LACTIC ACID. 93
juice from dogs, found no lactic acid, and ascribed the acid reaction of
the fluid to acid phosphate of lime, while Lassaigne,* in opposition
to this view, attempted to prove the presence of free hydrochloric
acid. Subsequently, experiments have been instituted by Bernard
and Barreswil,f Pelouze,{ and Thomson,§ which have led all these
chemists to believe that they have proved the existence of lactic
acid in pure gastric juice. Very recently 1 1| prepared the lactates
from a larger amount of pure gastric juice than had hitherto been
employed, and obtained them in such quantities that I was enabled
to make an ultimate analysis of several of them, and to determine
the atomic weight, which proved that the acid of the gastric juice is
perfectly identical with lactic acid. I found that pure gastric juice,
even on mere evaporation in vacuo, undoubtedly developes hydro-
chloric acid (in one case it amounted to 0'125£), but that there is
then always an acid residue left, which, besides free lactic acid,
contains lactate of lime and alkaline chlorides ; whence we may
conclude that there are in the gastric juice both free lactic acid and
lactates, in addition to free hydrochloric acid.
According to my observations, chloride of calcium, but not
chloride of sodium, (as Bernard and Barreswil maintain,) is decom-
posed during evaporation with free lactic acid, even in vacuo ; hence
it is not surprising that pure gastric juice should develope vapours
in vacuo, which, when passed into a solution of nitrate of silver,
should form chloride of silver. I must further remark, that
the lactates obtained from the pure gastric juice, as well as from the
contents of the stomach, had not the composition of the a lactic
acid, but that of the b lactic acid obtained from sugar. Bernard
and Barreswil allege, in opposition to Prout's opinion, that pure
gastric juice is rendered decidedly turbid by a drop of a dilute
solution of oxalic acid, while an equal quantity of oxalic acid in a
solution of lime containing only rs^th part of free hydrochloric
acid, causes no precipitate. Further, starch, when boiled with
hydrochloric acid, loses its property of being coloured blue by
iodine, while lactic acid does not induce this change. On boiling
a solution of a lactate with a little hydrochloric acid and starch, the
properties of the last-named body remain unaffected : starch boiled
with gastric juice retains the property of being coloured blue by iodine.
* Journ. de Chim. med. T. 10, p. 73 et 189.
f Journ de Pharm. et de Chim. Janv. 1835. p. 49.
% Compt. rend. T. 19, p. 1227.
§ Philos. Mag. 3rd series. Vol. 26, p. 420.
|| Berichte d. Gesellschaft d. Wiss. zu Leipz. Bd. 1, S. 100-105.
94 THE LACTIC ACID GROUP.
Various authors have assumed that alkaline lactates are present
in normal saliva, and have referred the acid reaction which is
occasionally noticed in that fluid to the presence of free lactic acid,
but in the small amount of solid residue which is left by the
saliva, I have never been able to establish with certainty the
presence of lactates, even when operating on considerable quan-
tities (obtained both from man and from the horse) ; I had, how-
ever, an opportunity of collecting large quantities of the saliva
of a patient labouring under Diabetes mellitus, and in this case
I convinced myself beyond all doubt of the presence of free lactic
acid.
In all the cases of Diabetes mellitus which I have observed, the
saliva has had an acid reaction : associated with this symptom and
with intense thirst, we sometimes find a copious secretion of saliva,
which we have thus a good opportunity of analysing. As the
saliva of such patients sometimes (but not always) contains sugar,
I took care that it should flow directly from the mouth into alcohol,
so as to avoid any possible formation of lactic acid from the sugar.
The zinc-salt which was obtained, showed very distinctly the crys-
talline form of the lactate.
Notwithstanding the assumed neutralising property of the bile,
the contents of the small intestines of herbivorous, carnivorous,
and omnivorous animals, always exhibit an acid reaction, which,
however, diminishes towards the ileum ; the acid reaction is strong-
est in the duodenum, especially in herbivorous animals. That the
acid reaction here depends on the presence of lactic acid, may be
most readily shown in the horse, in whose duodenum we find
lactate of lime and free lactic acid, especially after the ingestion of
amylaceous food.
Whether the acid reaction of the mucous secretion of fasting
animals depends on lactic acid, cannot with certainty be decided,
in consequence of the small quantities in which it can be collected.
I have repeatedly allowed the contents of the duodenum of a
recently killed horse (healthy, and killed either in consequence of
an accident or from its being affected with malleus) to flow directly
into alcohol, and after filtering the fluid while hot, and concentrating
it, I have obtained a white granular sediment, which, under the
microscope, exhibited the well-known double-brush form of lactate
of lime: a quantity collected for analysis contained 2S-97& of water,
and in the anhydrous state, 25'831£ of lime, 32'982£ of carbon,
and 4'513# of hydrogen ; this salt was therefore b lactate of limCa
The lactic acid was separated in the ordinary mariner from the
LACTIC ACID. 95
alcoholic solution, and the magnesian and zinc salts were crystal-
lometrically examined and quantitatively analysed, so that there
can be no doubt regarding the existence of lactic acid in this fluid.
Tiedemann and Gmelin*, and Valentinf, attribute the acid
reaction of the mucus of the small intestines to lactic acid, because
this mucus, on incineration, yields an ash abounding in carbonates,
which, at all events, could not be the case to such a degree, if the
free acid of this mucus were a mineral acid.
Moreover, the contents of the large intestine have often an acid
reaction, and indeed constantly after the use of vegetable food:
in two cases in which I was able to collect large quantities of these
contents from a preternatural anus in the ascending colon, I
obtained quite sufficient lactic acid to test crystallometrically the
zinc and magnesian salts.
The fluid secreted by the large intestine (and indeed by the
lower portion of the ileum) has always an alkaline reaction ; hence
the outer parts of the contents of the large intestine are for the
most part neutral or alkaline; after the use of vegetable food
the inner portion is, however, always acid, as was ascertained by
Steinhauser.*
Whether lactates constantly occur in the chyle must for the
present remain undecided. In the chyle obtained in two cases
from the thoracic duct of the horse (one horse having been fed with
oats two hours before he was killed, and the other with starch-balls),
lactic acid was recognised with certainty.
Here, as well as in the investigation of the alcoholic extract of
lymph or blood, we must be careful in reference to the salts of the
fatty acids ; and, consequently, after the separation of the pure
lactic acid by ether, the extract should be boiled with water to
remove the non- volatile fatty acids, and the solution, when cooled,
should be filtered ; the lactic acid should then, in the manner we
have already described, be transferred to baryta, from this to oxide
of copper, and from the latter to oxide of zinc, so as to separate
as much as possible the volatile fatty acids. This investigation
leaves no doubt regarding the existence of lactates in the chyle of
horses during the digestion of amylaceous food.
No one has yet definitely established the presence of lactic acid
in the lymph, although its presence in the fluid is by no means
* Verdauung. Bd. 1, S. 349.
t Lehrb. d. Physiol. d. Menschen. Bd. 1, S. 343.
% Experimenta nonnulla de sensibilitate et functionibus intestini crassi, Diss. inaug.
Lips. 1842.
96 THE LACTIC ACID GROUP.
improbable ; since, independently of the circumstance that Mar-
chand and Colberg,* as well as Geiger and Schlossberger,t found
much carbonated alkali in the ash afforded by lymph, whose albu-
minous constituents were removed previously to incineration, and
whose reaction was scarcely, or not at all, alkaline, we cannot readily
perceive in what other way than through the lymph the large
quantities of the lactic acid formed in the muscles can be carried
away.
The recognition of lactates in healthy blood is just as difficult
or impossible as that of urea in the same fluid. It is probable that
we shall never obtain a positive demonstration of the existence of
alkaline lactates in healthy blood by direct experiment, but the
simplest induction proves that they must be present there, even if
they only remain in it for a very short period. We know from
numerous experiments how rapidly effete matters, and especially
salts of easy solubility, are removed from the animal organism by
the kidneys ; we know with what extreme rapidity iodide of potas-
sium appears in the urine after it has been swallowed ; and we know
that it is only on that account that urea has not yet been detected
in healthy blood, (notwithstanding the assertions of certain persons),
for its sojourn in the blood is so very short that the quantity occur-
ing in that fluid at the same time is scarcely to be recognised with
our present chemical appliances. (MarchandJ). Hence it is not
surprising that the presence of lactic acid has never yet been
demonstrated, with all the necessary scientific accuracy, in normal
blood, especially when we consider that it is removed from the
circulating fluid in more ways than one. The combustion of
the alkaline lactates — that is to say, their conversion into alka-
line carbonates — exceeds in rapidity and extent their passage
into the urine. Until we can prove that the lactic acid, which
is accumulated in large quantity in the muscular tissue, and is found
in the chyle and in the lymph, undergoes decomposition on the
spot, we must assume that it passes into the blood, and the
more so because we well know that chemical analysis has not yet
attained such a degree of accuracy as to enable us to demonstrate
the presence of lactic acid in the blood with due scientific preci-
sion. In what other way than through the blood could the lactic
acid of the chyle or the muscular fibre pass into the urine ? Lactic
acid, like urea, may collect abnormally in such quantities in the
* Poggend. Ann. Bd. 43, S. 625.
f Arch. f. physiol. Med. Bd. 5, S. 394.
J Journ. f. prakt. Ch. Bd, 11, S. 49,
LACTIC ACID. 97
blood as to be capable of detection by chemical analysis. Scherer*
has paid especial attention to the occurrence of lactic acid in morbid
blood; he observed that, during an epidemic of puerperal fever, the
blood had often an acid reaction, and, as this fluid frequently con-
tained only free albumen and no albuminate of soda, it was clear
that it must contain a free acid. Scherer certainly did not demon-
strate the actual presence of lactic acid in the blood ; but, as he
actually separated lactic acid from the exudations which were simul-
taneously present, and recognised it by the form of its salts, we
cannot reject his conclusion that the acid reaction of the blood was
also due to lactic acid. I have only thrice observed an acid reac-
tion of the blood, and conditions similar to those described by
Scherer, namely, in a case of pyaemia in a man, and in the blood
of two women (from six to ten weeks after delivery.) In no case
could I obtain sufficient material to demonstrate the lactic acid with
certainty.
The following experiments,t instituted on myself, exemplify the
rapidity with which the lactates in the blood are converted into
carbonates. Within thirteen minutes after taking half an ounce of
lactate of soda, (calculated as dry,) my urine had an alkaline reaction.
Moreover, that the conversion of the alkaline salts of the organic
acids into carbonates (as was first proved by Wohler) does not take
place in the primae vies, but in the blood itself, is proved by direct
experiments which I made on dogs, by injecting various quantities
of lactate of soda into the jugular vein; after five, and at 'latest
after twelve minutes, the urine exhibited an alkaline reaction.
In opposition to the view that lactates exist in the blood, it has
been urged that the ash of blood has not an alkaline reaction, and
further, that it contains no alkaline carbonates. We have shown in
another part of this work that this observation of Enderlin's has
not been made or confirmed by any one who has preceded or suc-
ceeded him, (see "Ash of the blood",) but that, on careful incine-
ration, carbonated alkali always occurs in the blood; and even if
this were not the case, it would be no evidence against the presence
of lactic acid, since, on incinerating the blood, there is a combus-
tion of sulphur and phosphorus sufficient to saturate the alkali
previously combined with lactic acid. Further, carbonic acid is
expelled from the carbonate by ordinary phosphate of soda, which
is thus converted into tribasic phosphate of soda.
* Untersuchungen zur Fathol. Wurzburg. 1843. S. 147-194.
t Jahresber. 1843. S. 10.
98 THE LACTIC ACID GROUP.
In exudations — those, namely, after puerperal fever — Scherer*
found both free and combined lactic acid, often in very considerable
quantity. (In one case there was 0'105£ of free lactic acid.) In
the exudations in a case of empyema, he found albumen uncom-
bined with soda, from which he concluded that the latter had been
abstracted from the former in consequence of the presence of lactic
acid.
Lactic acid, which was originally discovered by Scheele in milk,
does not occur in the healthy milk of man and animals : it is only
in an abnormal state, or after a strictly animal diet, that milk
which reddens litmus and probably contains lactic acid, is secreted.
It is only after exposure to the atmosphere that healthy milk
acquires an acid reaction, which is dependent on the formation of
lactic acid from the sugar of milk by fermentation.
It is now forty-two years since Berzeliusf recognised the existence
of free lactic acid in the muscular fluid ; and no one who hasrepeated
the experiments of this most faithful and accurate experimentalist,
can confound this acid with any other, since its properties, and
those of its salts, have been made known by more recent investiga-
tions. Berzelius did not deem it necessary at that time to confirm
the proof of the presence of lactic acid in this fluid by an elemen-
tary analysis, although he might readily have made one. Liebig,
so long as he relied on the investigations of his pupils, absolutely
denied the existence of lactic acid in the living animal body; but on
instituting and publishing his own admirable inquiry respecting the
fluids of the muscular tissue of animals, he could no longer question
its presence in the muscular fluid, and even admitted its existence
in the gastric juice. Moreover, the free acid exists in so prepon-
derating a quantity in the muscles, that Liebig is of opinion that it
is more than sufficient to saturate the alkali of all the alkaline fluids
of the animal body. Berzelius thought that he had convinced
himself that the amount of free lactic acid in a muscle is propor-
tional to the extent to which it has been previously exercised.
Berzelius separated the lactic acid from the alcoholic extracts
of the animal fluids in the following manner. The alkalies having
been precipitated by tartaric acid, the filtered acid solution was
digested with carbonate of lead ; the alcoholic solution of lactate
of lead, having been separated from the other lead- salts by filtration,
was then treated with sulphuretted hydrogen, which left the lactic
* Op. cit.
t Lehrb. d. Cb. Bd. 9, S. 573 ; Ann. d. Ch. u. Phann. Bd. 1, S. 1 ; Jahres-
ber. Bd. 27, S. 585-594.
LACTIC ACID. 99
acid in solution contaminated merely with extractive matter. After
the evaporation of the alcohol the acid was filtered through animal
charcoal, from which the earthy salts had been separated, and
treated with hydrated oxide of tin, on which the comparatively
insoluble lactate of tin was separated. This was again decomposed
with sulphuretted hydrogen, and the lactic acid further examined.
Anselmino, Thenard, and Berzelius,* believe that they have
found lactic acid and lactate of ammonia in the sweat.
Berzeliusf also conjectures that alkaline lactates exist in the
bile.
In consequence of the rapidity with which the alkaline lactates
undergo a transformation in the blood, it would naturally follow
that lactic acid, when it occurs in the urine, would exist there
as an extremely variable constituent : and this assumption is con-
firmed by experience. Earnestly as I formerly maintained the
view that lactic acid constantly occurs in animal urine, and that the
acid reaction of this fluid is solely dependent on its presence, I
have since convinced myself that my earlier modes of analysis,
(when I rested satisfied with the mere exhibition of the zinc-salt)
though most carefully conducted, were open to deceptions in refer-
ence to this acid; but to maintain that the urine of healthy men
and animals never contains lactic acid or lactates, under any phy-
siological relations, is to err just as much in the opposite direction.
A more extended investigation has led me to the following results.
In all cases where the supply of lactates to the blood is very great,
— whether this depends on an excess of acid being formed in the
muscles, or on the use of a diet tending to produce it, or on an
imperfect process of oxidation in the blood, — lactic acid may be
detected in the urine with all the certainty which in the present
state of chemistry can be expected in such researches. Hence we
can understand why it is that, in the urine of the same individual,
lactic acid may on one day be present and 011 another absent; — why,
in many persons, no lactic acid can be detected in the urine, and in
others again (and especially in those who in consequence of repeated
catarrhs suffer from partial relaxation of the pulmonary tissue, and
yet often think themselves perfectly well) it is constantly present
in the urine ; — why stall-fed animals, living on amylaceous fodder,
excrete lactic acid by the kidneys (and in part also by the mammary
glands,) while under other conditions this acid cannot be discovered
* Lehrb. d. Ch. Bd. 9, S. 393.
t Ibid. S. 293.
H 2
100 THE LACTIC ACID GROUP.
in their urine ; — and why, finally, in most febrile diseases, lactic
acid may be recognised in the urine.
The details of these investigations, which will be given in
another place, afford numerous confirmations of the experiments
which I formerly instituted on the urine.* Berzeliusfj during his
later years, entertained no doubt regarding the correctness of the
results which he had so long before obtained in reference to the
presence of lactic acid in the urine. BoussingaultJ has quite
recently found lactic acid in the urine of pigs fed with potatoes, as
well as in that of cows and horses. (In the urine of the horse he
found 1-128$ of lactate of potash, and 0'881£ of lactate of soda.)
In accordance with this view is the almost universal occurrence
of lactic acid in urine containing a considerable quantity of oxalate
of lime, so that by a microscopic examination of a specimen of urine,
a conclusion may often be drawn regarding the presence or absence
of lactic acid. Hence in those diseases in which there is an increase
in the amount of oxalate of lime, as in pulmonary emphysema,
disturbances of the nervous system, rachitis, &c., lactic acid is
always associated with this salt. Scherer§ and Marchand|| have
sometimes observed a considerable augmentation of lactic acid in
the urine in rachitic children, and I have also noticed it in the
osteomalacia of adults.
In determining the presence of lactic acid we must always
employ fresh urine, if we wish to draw any conclusion regarding
the composition of the renal secretion. The admirable investi-
gations of Scherer^[ regarding urinous fermentation, were the
first to direct attention to the circumstance that there is a gradual
augmentation of the free acid, when the urine is exposed to the
atmosphere. The lactic acid must then be formed from some
unknown matter, — probably from what we term an extractive
matter. I** had formerly observed something similar occur in
diabetic urine, since, when freshly passed, I always found it neutral,
although subsequently it became acid ; in consequence, however,
* Journ. f. prakt. Ch. Bd. 25, S, 1, and Bd. 27, 8. 257; Handworterb. d. Phy-
siol. Bd. 2, S. 10.
t Jahresber. Bd. 27, S. 590.
Z Ann. de Chim. et de Phys. 3 S6r. T. 15, p. 97-114.
§ Untersuclmngen z. Pathol. S. 74 ff.
|| Lehrbuch d. phys. Ch. S. 105.
U Ann. d. Ch. u. Pharm. Bd. 42, S. 171 ; andUnters. z. Pathol. S. 1-16.
** De urina diabetica. Diss. inaug. Lips. 1835.
LACTIC ACID. 101
of diabetic urine containing sugar, these experiments were of less
weight than those of Scherer. We may hence fairly conclude
that the urine, after its excretion from the kidneys, undergoes a
similar acidification in the bladder, and consequently that the
lactic acid which is often found in the urine discharged from that
viscus is a product of decomposition which is formed externally
to the sphere of vital activity. If, however, the occurrence of
crystals of free uric acid warrants us in inferring the existence of
the lactic fermentation, it is only very seldom that it can occur in
the bladder, for the cases are extremely rare in which urine on its
emission from that organ contains free uric acid; the statement
that has found its way into various books, to the effect that fresh
urine often contains free uric acid, being a very erroneous one.
C. Schmidt * has separated lactic acid in the form of lactate of
zinc, from the strongly acid fluid yielded by the long bones in a
case of osteomalacia. He measured the angles of the crystals, and
submitted the salt to an elementary analysis.
Origin. — If we might be permitted to hazard a conjecture
regarding the production of lactic acid from its occurrence in the
animal body, we should ascribe to it a double origin. No one can
entertain a doubt that the lactic acid, found in the contents of the
intestine and in the chyle after the digestion of vegetables, owes its
formation to the amylaceous or saccharine matters contained in the
food, which in their passage through the primce vice become
converted into that acid, in the same manner as takes place in the
fermentation of milk. But the true genesis of the lactic acid
which accumulates in such large quantity in the muscles is not so
immediately obvious ; we may certainly assume that the lactic
acid formed in the primoe vice from vegetables is especially
attracted by some mechanical or chemical influence of the
muscular fibre, and is accumulated there to serve certain definite
purposes; but this view is in some measure opposed by the
circumstances that the muscles of carnivorous animals contain as
much lactic acid as those of herbivorous animals, and that free
lactic acid is always found in the urine of carnivora and of men
when living on a strictly animal diet, which would scarcely be
the case if the acid conveyed to the muscles solely proceeded
from the lactic acid contained in the flesh which had been taken
as food. But if we regard the lactic acid of the juice of flesh,
merely as a product of metamorphosis which is formed while the
* Ann. d. Ch. u. Pharm. Bd. 61, S. 302-306.
102 THE LACTIC ACID GROUP.
muscular fibre is discharging its function, (i. e. during the con-
traction of muscle,) the only objection to the view that this acid
proceeds from the decomposition of the muscular substance itself,
is, that hitherto lactic acid has not been produced either by
fermentation or otherwise, from any nitrogenous animal matter,
either albuminous or gelatinous. We should, however, not make
much progress in our physiological enquiries, if we set down
as impossible all the processes which we happen not yet to
have recognised external to the living body. Recent investigations
respecting the various modes of decomposition and the products
of albuminous bodies, show that a partial conversion of albuminous
matter into lactic acid is by no means an absurd impossibility;
for Guckelberger*, who found aldehyde among the products of
oxidation of albuminous bodies, points out that in these substances
there must be hidden a group of atoms, from which sugar of milk
or lactic acid might be produced. He further proved, experi-
mentally, that sugar of milk with chromic acid also yields aldehyde ;
and, on the other hand, Engelhard t found aldehyde of acetic acid
among the products of distillation of lactate of copper. We have
already directed attention to the analogy existing between lactic
acid, and that frequent product of the metamorphosis of animal
matter, metacetonic acid. Hence it would be not at all surprising,
if lactic acid were in some manner obtained from the gelatinous or
protein compounds.
Moreover, this view is supported by the consideration that,
besides lactic acid, creatine, which is found in the muscular fluid,
is often a product of decomposition of muscular substance, since
otherwise it would be found in other places besides the urine.
Moreover, according to Liebig^s discovery, creatine is decomposed
by alkalies into urea and sarcosine, a substance isomeric with
lactamide ; hence there would be nothing incongruous in assuming
that in the natural metamorphosis of creatine in the animal body,
where no sarcosine is found, the creatine is still decomposed into
urea, but that, in place of sarcosine, there is an abstraction of water,
and that lactic acid and ammonia are formed, in which case,
however, we should have to explain what becomes of the ammonia.
Moreover, it cannot be supposed that lactic acid passes into the
muscular substance from the blood, where it is so easily and
rapidly consumed ; yet such must be the case if it comes from the
acid formed in the intestinal canal from amylaceous food.
* Ann. d. Ch. u. Pharm. Bd. (J4, S. 99.
LACTIC ACID. 103
Finally, after the discovery made by Redtenbacher, that
glycerine is convertible into metacetonic acid, there seems to be
something attractive in the hypothesis that glycerine, which, in the
metamorphosis of the fats, obviously undergoes an independent
change, is converted into lactic acid, which, as we have already
shown, is allied to metacetonic acid. As we have no probable
conjectures regarding the further course of the haloid base of the
fats in the animal body, it is possible that these substances may
contribute, through their base, to the formation of lactic acid.
We have endeavoured, in the above sketch of the occurrence of
lactic acid in the animal body, to restrict ourselves most rigidly to
established facts, and we have rejected all those of our own experi-
ments on which the slightest doubt appeared to rest: without
referring to authorities, we have allowed the facts to speak for
themselves, and have attached as little credit to the negative
assertions of Liebig, as to the older experiments of Berzelius,
regarding the occurrence of lactic acid in bile, sweat, &c., with that
impartiality which becomes every one wishing to be an honest
scientific observer. We shall now consider the advantages which
may accrue to the animal organism from the occurrence of lactic
acid in this or that organ, without any reference to the views and
errors which we formerly maintained. Although we no longer
regard lactic acid as one of the most important elements in relation
to the metamorphosis of the animal tissues, it is yet of sufficient
importance to attract the attention of physiologists. It is more-
over obvious that questions regarding the function of a substance
in the animal body, can never receive more than a hypothetical
answer; for purposes may indeed be conjectured or understood,
but they cannot be palpably demonstrated. If, therefore, we judge
of the physiological importance of an animal substance on hypo-
thetical grounds, we do not necessarily adopt lax and untenable
illusions of the fancy, but shall confine ourselves to logical con-
clusions.
Uses. — In ascribing to lactic acid an essential influence on the
digestion of nitrogenous food, our opinion is based, not on a mere
conjecture derived from the constant occurrence of this acid in
the gastric juice, but on the result of direct experiments* with
artificial digestive fluids, from which it appears that lactic and
hydrochloric acids cannot be replaced in the process of digestion,
by any other animal or organic acids. The question how the acid
acts, will be entered into in our observations on " Digestion."
* Berichte der Gesellsch. der Wiss. zu Leipzig. 1849.
104 THE LACTIC ACID GROUP.
It is not probable that the lactic acid and lactates found in the
contents of the stomach and intestines, are entirely derived from
the acid of the secreted gastric juice ; indeed it is certain that the
greater part of the lactic acid, occurring both there and in the chyle,
may be traced to the conversion of the starch or sugar of the
food; we should, however, on the other hand, be drawing too
general a conclusion, if we assumed that all the starch and all the
sugar of the food must be converted into lactic acid, in order that
the functions of the organism may be duly fulfilled. In the course
of our subsequent physiological considerations, we shall explain the
grounds why we cannot accept this view, notwithstanding that it
is apparently supported by positive observations. This much is,
however, supported by facts, that a portion of these substances is
actually converted into lactic acid, and passes into the blood in the
form of alkaline lactates. If we adopt Liebig's ingenious division
of food, into true food for nutrition and food for the respiration, we
know of no substitute which could better act in the blood as food
for the respiration than the alkaline lactates, which, as we have
seen, undergo rapid combustion in the blood, and are thus converted
into carbonated alkali, — in a word, nothing could be a better sup-
porter of animal heat than the alkaline lactates.
If the lactic acid in the fluid saturating the muscles, although
undoubtedly derived from the effete muscular tissue, be not a
pure product of decomposition, there is much in favour of
Liebig's* hypothesis, that an electric tension influencing the
function of the muscles, is established by the acid muscular juice
and the alkaline contents of the capillaries.
In the urine and sweat, lactic acid occurs only as a product of
excretion; for even if, in some cases, it may contribute to the
solution of the earthy constituents of the urine, its occasional
absence in this fluid shows that other substances effecting that
object are also present.
I formerly regarded lactic acid as one of the most important
agents in the solution and transportation of many of the animal sub-
stances and earthy salts of the animal organism; but a more
thorough insight into the processes of animal chemistry, has led me
almost entirely to renounce this view ; for although If have recently
convinced myself that the solvent power which lactic acid exerts
over basic phosphate of lime, farvexceeds that of acetic acid, and
* Op. cit,
t Jahresb. der gee. Med. 1843, 8. 10.
SOLID FATTY ACIDS. 105
is indeed very considerable — a fact long ago asserted by Berzelius,*
and directly proved by the experiments of Gay Lussac,t but whose
accuracy has been called in question by Liebig,{ — yet I cannot
overlook the circumstance that the albuminous bodies, which are
never devoid of phosphate of lime, and often contain a large
quantity of it, afford far better means of transport for the bone-
earth in the animal body than lactic acid can do.
How far my former view, that lactic acid is the most important
factor in the metamorphosis of the animal tissues, can still be
maintained, may be seen from the preceding observations.
SOLID FATTY ACIDS.
=CmHm_lO,.HO.
FROM this formula it is obvious that these acids stand in a
close alliance with those which we have described in the com-
mencement of this work ; — indeed, we have already associated
them with the latter in a single group, to which we have applied
the name of fatty acids ; but we meet here with the same diffi-
culties which present themselves in inorganic chemistry, in the
definition and classification of the metals. Nature recognises no
limits corresponding with our artificial systems, but for the
purposes of study a separation or arrangement is always useful,
provided it be not altogether at variance with nature. These fatty
acids have, however, certain essential characters, which distinctly
separate them from the first-named acids. Independently of
the high atomic weight of the acids we are now considering, and
of the circumstance that a very differently constituted group of
fluid acids is closely allied to them, the following are the
properties which characterise them as a special group. At an
ordinary temperature they are solid, white, and crystalline,
devoid of smell and taste, leave on paper a fatty spot which
does not disappear, are lighter than water, fuse below 100°, can
only be distilled unchanged in vacua, are perfectly insoluble in
water, dissolve in boiling alcohol, and again separate from it in
crystalline forms as the solution cools, dissolve readily in ether,
decompose when heated in the air, and are inflammable; their
* Lehrb. d. Ch. Bd. 9, S. 423.
t Pogg. Ann. 13d. 31, S. 399.
J Chemie in Anwendg. f . Physiologic.
106 SOLID FATTY ACIDS.
alcoholic solution only faintly reddens litmus ; with a gentle heat
they expel carbonic acid from its salts; with most bases they form
insoluble salts, (the alkaline salts alone being soluble in water,)
and they have a strong tendency to form acid salts with bases.
Very few of these acids have been found in the animal body ;
one of them, however, margaric acid, is the principal constituent of
all the fats yet found in the animal body. Associated with it is
another fatty acid, stearic acid, whose composition, although not in
accordance with the above formula, approximates so nearly to it
that it may be regarded as produced from 2 equivalents of mar-
garic acid, from which 1 equivalent of oxygen has been abstracted.
We place before our readers the whole group of these acids with
their chemical formulae, restricting, however, our observations, to
the two above named acids.
Cocinic acid ., C22H21O3. HO.
Laurostearic acid C24H23O3. HO.
Myristicacid C28H2J,O3. HO.
Palmitonic acid C31H30O3. HO.
Palmitic acid C32H31O3. HO.
Bogie acid C^H^Og. HO.
Margaric acid C34H33O3. HO.
Cocostearic acid .... C35H34O3. HO.
Behenic acid C42H41O3. HO.
Ceroticacid C54H53O3. HO.
Stearic acid C68H6605.2HO=2C34H33O3.HO - O.
MARGARIC ACID. — C34H33O3.HO.
Chemical Relations.
Properties. — This acid has all the properties which we have
enumerated above as pertaining to this group. It crystallises from
a hot alcoholic solution in groups of very delicate nacreous needles,
which under the microscope appear interlaced like tufts of grass,
and arranged in ensiform plates, or grouped in star-like forms.
The acid, when thoroughly dried, fuses at 56° ; even when most
carefully heated in vacuo, it can only be partially distilled un-
changed, carbonic acid and margarone (C33H33O) being always
formed ; by prolonged contact with nitric acid, it becomes finally
decomposed into succinic, suberic and carbonic acids, and water.
Composition. — According to the above formula this acid con-
tains :
MARGARIC ACID. 107
Carbon 34 atoms
Hydrogen .... 33 „
Oxygen 3 „
Water 1
1 OO'OOO
The atomic weight of the hypothetical anhydrous acid =3262*5,
and its saturating capacity =3*065.
Combinations. — Margaric acid forms both neutral and acid
compounds with alkalies ; the acid salts are principally formed by
the addition of much water to the neutral salts ; with oxide of lead
it forms acid, neutral, and basic salts, all of which are soluble in
petroleum and oil of turpentine, and the first two in heated alcohol.
Margaramide, H2N.C34H33O2, is formed when olive oil is
digested in alcohol saturated with ammonia ; it crystallises in fine,
silky, glistening needles, is insoluble in water, and is more soluble
in hot alcohol and ether than in cold, from which it separates in
glistening plates ; it fuses at 60°, and when ignited, burns like
tallow,
On treating margaric acid with peroxide of lead, Bromeis*
obtained a fatty acid which separated in granules and contained
1 atom more of oxygen than margaric acid ; its composition being
represented by the formula C34H33O4.HO.
Preparation. — Since margaric acid, in the compound which we
call margarin, occurs in almost all vegetable fats (the fatty oils) as
well as in the most common animal fats, it may be prepared from
any of these sources. The best method of obtaining it is to take
the fat of man or of the pig, or a vegetable fat, and to saponify it
with potash so as to form a clear, viscid, soapy solution ; this must
be treated with sulphuric acid, which causes a separation of a mix-
ture of stearic, margaric, and oleic acids ; this fatty mass must be
then well washed with water, dried as thoroughly as possible, and
strongly pressed between paper, which causes the removal of a
great part of the oleic acid. The solid acids must now be recrys-
tallised in alcohol. The stearic acid is the first to separate from
the hot alcoholic solution, and it thus admits of separation and
removal ; the margaric acid always separates somewhat later ; in
order, however, that the stearic acid may be perfectly removed,
this process must be several times repeated.
We thus obtain margaric acid with no impurity beyond a little
oleic acid, which may be removed by saturating the acids with an
alkali and precipitating with acetate of lead ; as the oleate of lead
* Anu. d. Ch. u. Pharm. Bd. 42, 8. 56.
108 SOLID FATTY ACIDS.
is soluble in boiling ether, while the margarate of lead is insoluble,
we have an easy means of separating the two salts. The marga-
rate of lead must then be decomposed by an alkaline carbonate,
and the resulting alkaline salt by a stronger acid. The margaric
acid which is thus separated may be further purified by solution in
hot alcohol.
Tests. — From the properties, as well as from the mode of pre-
paring this acid, we perceive that it can only be distinguished from
other similar acids when it is perfectly free from any admixture with
them : we may derive some information on this head from its
boiling point ; but it is only by an elementary analysis that we
can arrive at any certain conclusion. In the investigation of small
quantities, when a separation or an analysis is out of the question,
we must trust solely in a microscopical examination, which, how-
ever, in this case yields by no means such uncertain results as
is generally supposed.
Physiological Relations.
Occurrence. — It has already been remarked that margaric acid
is the principal constituent of most animal fats ; but this acid is
here ordinarily combined with the hypothetical haloid base, oxide
of lipyl) which, in its separation from this and similar acids, is con-
verted into the well-known body, glycerine. Of margarin itself we
shall speak in a future part of this volume, and we shall con-
sequently defer for the present all remarks on the physiological
function of margaric acid and its organic salts. But margaric
acid occurs both in a free state and in combination with alkalies in
most of the animal fluids, with the exception of urine ; being free
in acid fluids, and in a state of combination in those with an alka-
line reaction ; it is always accompanied by oleic acid or its salts.
Its presence in the saliva, in the blood, in exudations of all kinds,
in pus, and in the bile, is so easily recognised, that it is unneces-
sary to quote authorities regarding its existence in these fluids ;
moreover, in our remarks on these fluids we shall return to this
subject. We will here only remark that it may also be discovered
in the solid excrements after the use of vegetable food, and that
it occurs in considerable quantity in dejections which have been
caused by purgatives or mineral waters. As already mentioned,
we must here always have recourse to the microscope, by which,
independently of any chemical process, free margaric acid may
often be detected in acid pathological fluids ; thus, in acid pus
discharged from what are termed cold abscesses, or in pus in
STEARIC ACID. 109
which acid fermentation has with all due caution been established,
the most beautiful crystals of margaric acid are formed ; more
beautiful indeed than we could artificially prepare.
We shall postpone our observations regarding the origin of
margaric acid in the animal organism, and the rank and position it
holds in the metamorphosis of the animal tissues, till we take into
consideration the formation and the physiological importance of
the fats in the animal body.
STEARIC ACID.— C68H66O5.2HO.
Chemical Relations.
Properties. — This acid crystallises in white, glistening needles
or leaflets, which, however, under the microscope, appear as very
elongated, lozenge-shaped plates, with the obtuse angles rounded
off, as in the microscopical whet- stone-like crystals of uric acid ;
these crystals are, however, much longer, and have a far shorter
transverse diameter than the similar crystals of uric acid. They
often collect at one spot, the acute angles slightly overlapping one
another, so that when seen under the microscope the crystals
present the arrangement of whorl-shaped clusters. This acid begins
to fuse at 75°, but again solidifies if the temperature is reduced
to 70°. Submitted to dry distillation it yields hydrated margaric
acid, margarone, and an oleaginous carbo-hydrogen ; by prolonged
digestion with nitric or chromic acid it becomes perfectly converted
into margaric acid. In the cold, stearic acid decomposes the car-
bonated alkalies to the amount of one-half, but with the aid of heat
a perfect decomposition is effected.
Composition. — According to the above formula, stearic acid
contains :
Carbon .... .... 68 atoms .... 76'692
Hydrogen .... 66 „ .... 12'406
Oxygen 6 „ .... 7'519
Water 2 „ .... 3-383
100-000
The atomic weight of the hypothetical dry acid =6425 : its
saturating capacity, (if we regard as neutral the salt containing 2
atoms of base) =3*113.
Combinations. — The neutral alkaline stearates (containing 2
110 SOLID FATTY ACIDS.
atoms of fixed base) dissolve unchanged in from 10 to 20 parts of
water ; in a very large quantity of water they become decomposed,
an acid salt separating, and the fluid becoming very strongly alka-
line ; the alcoholic solution of the acid salt reddens litmus, but on
the addition of water to this solution the reddened litmus again
becomes blue. The compounds of stearic acid with all other bases
are insoluble in water. For stearate of oxide of lipyl (or of glycerin)
see " Stearin."
Preparation. — As this acid does not occur in vegetable fats,
and exists only in very small quantity in most of the animal fats,
except in mutton fat, it is from this last-named source that it is
most advantageously prepared ; we obtain it in accordance with the
method indicated in our remarks on margaric acid, by boiling with
alcohol of 0*83 spec. gray, the fatty acids separated by sulphuric
acid from the soap ; this leaves a residue of stearic acid tolerably
free from margaric acid ; by repeated solution in absolute alcohol
it becomes purified, till we finally obtain a mass possessing the
known fusing point of this acid. The following method of pre-
paring it may also be recommended. Dissolve saponified mutton
fat in 6 parts of warm water, and then wash it well with a large
quantity of cold water; a gradual separation of a glistening nacrous
mass now ensues, consisting of bistearate and bimargarate of
potash. This must be dissolved in 20 times its bulk of hot
alcohol, from which, as it cools, the stearate alone separates ; on
decomposing this salt with hydrochloric acid, the free acid may be
obtained by remelting it in water.
Tests. — An elementary analysis can only be instituted as a
test for the presence of stearic acid, when there is a sufficiently
large quantity of fat present to admit of the above-mentioned sepa-
ration of stearic and margaric acids, — a separation which, unfortu-
nately, is only practicable when we have very large quantities to
deal with. Hence this, the most certain method, is only applicable
in determining the amount of stearin in an animal fat. In dealing
with smaller quantities we must rest content with the microscopic
investigation of the fatty acids separated from hot alcoholic solu-
tions. In order to obtain a scale for the approximate ratios of a
mixture of margaric and stearic acids, Gottlieb* has determined the
fusing points of various mixtures of these acids. His results are
as follows :
* Ann. d. Ch. u. Pharm. Bd. 57, S. 35.
STEARIC ACID. Ill
Stearic acid Margaric acid Fusing point
1) .... 30 parts to 10 parts .... 65°'5
2) .... 25 „ 10 „ .... 65°
3) .... 20 „ 10 „ .... 64°
4) .... 15 „ 10 ,, .... 61°
5) .... 10 „ 10 „ .... 58°
6) .... 10 „ 15 „ ... 57°
7) .... 10 „ „ 20 „ .... 56°'5
8) .... 10 „ ,, 25 „ .... 56°'3
9) .... 10 „ „ 30 „ .... 56°
Both pure margaric and pure stearic acids, after having been
fused and again allowed to solidify, are perfectly crystalline ; stearic
acid, however, forms small confused crystals, while margaric acid
forms larger acicular crystals ; a mixture of the two acids is however,
in this state, far less crystalline, and presents rather a porcelain-
like, opaque, and brittle appearance.
Physiological Relations,
Occurrence. — Like margaric acid, stearic acid occurs in most
animal fats ; it is, however, always found in less quantity than
margaric acid, and in some cases appears to be altogether absent ;
or, at least, our present chemical appliances fail in detecting it. In
the fat of the cellular tissue it exists like margaric acid in combina-
tion with glycerine ; it never occurs free unless in association with
margaric acid ; it is, however, of much rarer occurrence than free
margaric acid, and occurs in much smaller quantity.
Origin. — As stearic acid is never found in vegetable fats, it
must be primarily formed in the animal body, where, indeed, its
formation may be readily explained. As it consists of 2 atoms of
margaric acid minus 1 atom of oxygen, we may regard it as pro-
duced from margaric acid, to which it stands, as we have seen, in
the same relation as hyposulphuric acid to sulphuric acid, for
S205 : S03=(C34H33)205 : (C34H33)O3.
In which part of the system this conversion occurs we do not at
present know : that it takes place in the blood is improbable,
because we assume that the fats are directly oxidised in the blood,
and are decomposed into the oxides of simpler radicals. That this
conversion takes place in the primte vice is, at all events, incapable
of demonstration.
We shall speak of the uses of stearic acid in the animal
organism, in our remarks on the fats in general.
112 OILY FATTY ACIDS.
OILY FATTY ACIDS.
This group of bodies contains a far smaller number of members
than the preceding groups. At present the following are the only
oily fatty acids with which we are acquainted :
Oleic acid ................ C
Erusicacid
Doeglicacid
Erusicacid ................ C44H41O3.H(X
Ricinoleic acid, containing the same group of atoms of carbon
and hydrogen with 5 atoms of oxygen (=C38H35O5.HO), bears
the same ratio to the last of these acids, which salicylous acid bears
to benzoic acid.
Dissimilar as, on the whole, is the composition of the oily and
the solid fatty acids, they are yet similar in most of their physical
and even in many of their chemical properties.
Whether campholic acid C20H17O3.HO, and the two isomeric
acids, campheric acid and angelic adc?=zC10H7O3.HO, belong to
this group (for their composition accords with the general formula
CmHm_3O3.HO) is as yet undecided ; several of their physical
properties (for instance., they are solid, crystallisable, and volatile,)
do not accord with this view, but these acids may possibly bear the
same relation to the oily acids, that the acids of the first group
bear to the solid fatty acids, and the low atomic weight of the
radical may also be the cause of this difference in their properties.
OLEIC ACID.— C36H33O3.HO.
Chemical Relations.
Properties.— This body, known also as elaic acid, is, when
perfectly pure, and at a temperature above + 14°, of an oily con-
sistence, limpid, devoid of colour, taste, and smell, and exerts no
action on litmus ; at + 4° it forms a white, crystalline mass, which,
at the moment when it solidifies, strongly contracts and expresses the
still oily portion ; it is then very hard, and is unaffected by ex-
posure to the atmosphere ; on exposing an alcoholic solution to
extreme cold it crystallises in long needles. In its fluid condition,
that is to say, as oil, it rapidly absorbs oxygen and becomes changed.
When heated, it becomes decomposed, yielding not only carbon
OLEIC ACID. 113
carbon, carbonic acid, and carbo-hydrogens, but capric and caprylic
acids, and especially sebacic acid. Finally, on treating oleic acid with
hyponitric acid, the whole mass becomes solid and converted into
elaidic acid. By prolonged treatment with nitric acid, oleic acid
yields (according to Laurent* and Bromeisf) the acids of the suc-
cinic acid group (CnHn_2O3.HO) namely, suberic, adipic, pimelic,
and lipic acid, and, besides these, cenanthylic acid, but no oxalic acid.
With fuming nitric acid it yields, on the other hand, according to
Redtenbacher J almost all the acids of the first group (CnHn_1O3.HO) .
In the oily products of the dry distillation of oleic acid
Schneider§ found that the atoms of carbon were to those of
hydrogen in the ratio of 6 : 5 ; and on treating these products with
concentrated nitric acid, he obtained the same volatile acids which
Redtenbacher obtained by the direct action of nitric acid on oleic
cid.
Composition. — According to the above formula this acid con-
ains :
Carbon .... .... 36 atoms ....
Hydrogen .... 33 „
Oxygen .... 3 „
Water 1 „
100-000
The atomic weight of the hypothetical anhydrous acid = 34 12*5 ;
its saturating capacity=2'930.
Combinations. — The oleates are soft and greasy, and do not
crystallise; like all the fatty acids, oleic acid has a strong ten-
dency to form acid as well as basic salts. The neutral oleate of
lead is a white powder which fuses at 80° into a yellow fluid, and
is distinguished, by its solubility in boiling ether, from the lead-
salts of all the solid fatty acids.
Products of its Metamorphosis. — Gottlieb, || who was the first to
obtain pure oleic acid, and who, from his analyses, deduced the
above formula, states that at an ordinary temperature, and when
freely exposed to the atmosphere, this acid absorbs about 20 times
its volume of oxygen, without developing carbonic acid. The thick
fluid acid which is thus formed, and which now reddens litmus,
* Ann. d. Chim. et de Phys. T. 66, pp. 154-204.
f Ann. d. Ch. u. Pharm. Bd. 35, S. 86-103.
t Ibid. Bd. 59,8.41-57.
§ Ibid. Bd. 70,.S. 107-121.
II Ibid. Bd. 57,"s. 37-67.
114 OILY FATTY ACIDS.
contains 1 atom more of oxygen and 1 atom less of hydrogen
than the pure oleic acid, being represented by the formula
C36H32O4.HO. This acid yields no sebacic acid on dry distillation.
Hence it is that oleic acid, when not perfectly pure, that is to say,
when changed by the access of oxygen, often yields only very little
sebacic acid, while the quantities of capric and caprylic acids which
are developed, remain constant.
If, however, oleic acid be exposed at a higher temperature to
the action of oxygen, it rapidly assumes a rancid odour, becomes
yellowish and more easily fusible, does not solidify so perfectly
when exposed to cold, and its composition is represented by the
formula C34H33O5 ; hence it may be regarded as a higher stage of
oxidation of the radical of margaric acid than that obtained by
Bromeis, and noticed in page 107-
Elaidic acid is, according to Gottlieb, perfectly isomeric with
pure oleic acid, and is therefore represented by the formula
C36H33O3.HO. It is produced, as we have already mentioned, from
oleic acid by the action of nitrous acid, without any development
of gas ; it crystallises from an alcoholic solution, not in needles like
oleic acid, but in large plates ; it fuses at 45°, may be partially
distilled undecomposed, dissolves readily in ether and alcohol, and
strongly reddens litmus. On dry distillation elaidic acid yields no
caprylic and capric acids, in which respect it differs essentially
from oleic acid. In the fluid state this acid abstracts oxygen from
the air, although less rapidly than oleic acid, and becomes con-
verted, according to Gottlieb, into a higher stage of oxidation of
the same radical, which we may assume to exist in oleic and elaidic
acids, namely into (C36H33)O8. How the metamorphosis of oleic
into elaidic acid exactly takes place, or on what it depends, are
points on which as yet we have no certain knowledge.
Preparation. — This acid also is obtained by the saponincation
of vegetable and animal fats ; the oleate of potash is extracted from
the soap with cold absolute alcohol ; the aqueous solution of oleate
of potash is then precipitated with acetate of lead, and the oleate
of lead (free from the margarate) is taken up from the dried preci-
pitate by boiling ether. If the lead-salt, after the removal of the
ether, be decomposed with carbonate of soda, and if the resulting
soda-salt be decomposed with sulphuric acid, we obtain a somewhat
brownish oleic acid mixed with products of oxidation. In order to
obtain the acid in a state of perfect purity, we must, according to
the directions of Gottlieb, treat it with an excess of ammonia, and
precipitate it with chloride of barium : the baryta-salt is then to be
OLEIC ACID.
repeatedly crystallised in moderately concentrated boiling alcohol,
till it form a dazzling white flocculent powder, which must be
decomposed with tartaric acid and thoroughly washed with water.
Pure oleic acid may be more rapidly obtained by causing it to solidify
by exposing it to a temperature of 6° or 7°, and then submitting it to
strong pressure; as the above-mentioned products of oxidation
of oleic acid remain fluid, they become absorbed in the filtering
paper, and leave the oleic acid in a state of purity. Further, the
water must only be removed while the oleic acid is exposed to a
stream of carbonic acid, and all operations upon it should be con-
ducted at a temperature below + 10°, since it very rapidly becomes
decomposed.
Tests. — If it be required to test a fat or a mixture of fatty acids
accurately for oleic acid, we must first isolate this acid by one of
the methods which we have described, and obtain it in a state of
at least tolerable purity, so as to enable us to ascertain the solubility
of the lead-salt in hot ether. Moreover, oleic acid possesses the
distinctive character of being the only one either of the oily or
solid fatty acids which, on dry distillation, yields sebacic acid — an
acid which may be distinguished from the simultaneously formed
capric and caprylic acids by its crystallisability, and which we may
easily separate from them and recognise, by forming and crystal-
lising its baryta-salt.
Physiological Relations.
Occurrence. — Oleic acid, in combination with alkalies, exists in
the blood and in the bile, and, in lesser quantity, in most of the
other animal fluids, except the urine : in combination with oxide
of lipyl, as a haloid salt, it occurs in the fat of the cellular tissue,
and, indeed, wherever free fat is found in the animal body.
Uses. — As the vegetable fats are, for the most part, far richer
in oleate of oxide of lipyl (olein) than animal fats, there seems to
be a reason for the assumption that one of the uses of oleic acid in
the animal body, is to form the more solid fats, margaric and stearic
acids ; — a view which is supported by the nature of the action of
atmospheric air on oleic acid, (to which we have already referred,)
and by its conversion into an acid having the radical of margaric
acid. It might, however, have been expected d priori that animal fat
would contain more margarate than oleate of oxide of lipyl, since
oleic acid or an oleate is more rapidly consumed than margaric acid.
We must, however, here, as in many other departments of phy-
siological chemistry, rather abstain wholly from all conjectures
i 2
116 OILY FATTY ACIDS.
than allow ourselves to be led astray by mere fancy. Let us rather
wait for further facts to serve as substrata on which to establish a
strictly logical hypothesis. Generally speaking, the function of
oleic acid in the animal body coincides with that of the other fatty
acids : but we shall return to this subject in a future part of this
volume.
Origin. — In our remarks on the fats, we shall consider the
question whether the animal body possesses the power of forming
margaric and oleic acids as well as stearic acid.
DOEGLIC ACID. — CooHocOo. HO.
38^35^3'
This acid, which was discovered by Scharling * in the train oil
of Ealosna rostrata, is obtained from the lead-salt which is taken up
by ether, precisely in accordance with Gottlieb's method of purify-
ing oleic acid. At+ 16° it is perfectly fluid, but solidifies at a few
degrees above 0° : it is yellow and reddens litmus ; on dry distillation
it yields no sebacic acid. This acid is, moreover, not combined
with oxide of lipyl in the Doegling train-oil, (at least it yields no
glycerine on saponification,) but probably with doeglic oxide,
C24H25O, a body similar to the ether-like haloid bases, whose
existence and composition Scharling, however, only infers from the
analysis of the unsaponified Doegling train-oil and the absence of
glycerine.
NON-NITROGENOUS RESINOUS ACIDS.
LlTHOFELLIC AciD. — C40H3607.HO.
Chemical Relations.
Properties. — This acid crystallises in small, six-sided, right
prisms, is readily pulverisable, fuses at 205°, and solidifies again
* Journ. f. pr. Ch. Bd. 43, S. 257-271.
LITHOFELLIC ACID. 117
in a crystalline form, if it has not been too highly heated ;
if, however, this has been the case, it solidifies into a
vitreous, negatively idio-electric mass ; in this condition it fuses at
105° to 116°; by solution in, or mere moistening with, alcohol, it
returns to its former condition, being difficult to fuse again ; when
heated in the air, it volatilises in white vapours with an aromatic
odour ; when inflamed it burns with a bright, smoky flame ; it is
decomposed by dry distillation ; it is insoluble in water, dissolves
readily in hot alcohol, but only slightly in ether; acetic acid
dissolves it freely ; acids precipitate it from its soluble salts as an
amorphous coagulum.
Composition. — Ettling and Will,* from their analyses, calculated
for it the formula C42H36OS ; W6hler,f from his analyses, deduced
the formula C40H3GO8 ; and Berzelius,J judging from the saturating
capacity of the acid, considers the formula C40H36O7.HO as the most
correct : hence it must be regarded as containing :
Carbon 40 atoms .... 70-381
Hydrogen .... 36 „ .... 10'557
Oxygen 7 „ .... 16-422
Water 1 „ .... 2-640
100-000
Hence the atomic weight of the hypothetical anhydrous acid
(according to the above formula) =4150, and its saturating capacity
= 2-41.
Combinations. — This acid dissolves readily both in caustic
ammonia and in carbonate of ammonia, but on evaporation of the
solution it remains free from ammonia ; the salts of baryta and
lirne throw down no precipitate from this solution : moreover, it
dissolves readily in caustic potash, but is precipitated by an excess
of potash as well as hy hydrochlorate of ammonia; on the addition
of the salts of lead or silver to a saturated potash-solution of this
salt with only a faintly alkaline reaction, there is a white precipi-
tate which, on warming, becomes plaster-like. Ettling and Will
have obtained a silver-salt which crystallised in needles ; Wohler,
however, only obtained an amorphous salt.
Preparation. — This acid, which was originally discovered by
Gobel,§ is extracted from certain intestinal concretions by hot
* Ann. d. Ch. u. Pharm. Bd. 39, S. 237-244.
t Pogg. Ann. Bd. 54, S. 255.
t Jahresber. Bd. 22, S. 580.
§ Ann. d. Ch. u. Tharm. Bd. 39, S. 237.
118 RESINOUS ACIDS.
alcohol ; the solution is decolorised by animal charcoal, and gra-
dually evaporated.
Tests. — This acid may be recognised with tolerable certainty by
the properties which we have already enumerated. If, however, it
be found in other places than in intestinal concretions, it should
always be submitted to an elementary analysis.
Physiological Relations.
Occurrence. — According to the researches of Merklein and
Wohler,* as well as those of Taylor,t this body exists only in
certain bezoars, which are obtained from the intestines, and espe-
cially from the stomach of many species of goats inhabiting the
East ; other bezoars contain ellagic acid.
Origin. — Whether lithofellic acid takes its origin in the bile,
or is dependent on the use of resinous food, is as yet undecided,
since its similarity to the resins is as great as to the resinous acids
of the bile. Its analogy with ellagic acid certainly speaks in favour
of its origin from the food ; if, however, Taylor's view, that con-
cretions containing lithofellic acid are frequently found in the
stomach, be confirmed, it is obvious that they cannot owe their
origin to the bile.
CHOLIC AciD.—C48H39O9.HO.
Chemical Relations.
Properties. — This acid crystallises in tetrahedra, and more
rarely in square octohedra, is colourless, glistening, and easily
pulverised ; the crystals effloresce on exposure to the air ; the acid
is bitter, leaving a faint sweetish after-taste ; it is soluble in 750
parts of boiling, and in 4000 parts of cold water ; it dissolves very
readily in alcohol, especially when heated, and in 27 parts of ether.
The acid, in crystallising from ether, forms rhombic tablets, and in
this form it contains 2 atoms of water, while from alcohol it crys-
tallises in tetrahedra with 5 atoms of water ; the acid separated
from alcohol by the addition of water contains 2 atoms of water,
which it loses at 100°, while the tablets only lose 1 atom at that
temperature. Moreover, this acid strongly reddens litmus, fuses at
195°, and at a higher temperature undergoes decomposition; above
195° it loses its atom of basic water, and is converted into choloidic
* Ann. d. Ch. u. Pharm. Bd. 55, S. 120-143.
t Lond., Edinb., and Dubl. Phil. Mag. vol. 28, pp. 192-200.
CHOLIC ACID. 119
acid, and at 290° it becomes converted into dyslysin (Strecker*) ;
when inflamed it burns with a clear flame. It dissolves in sulphuric
acid ; and if to this solution we add a drop of syrup (1 part of sugar
to 4 of water), the fluid assumes a beautiful purple-violet tint. If
cholic acid be boiled for some time with hydrochloric acid it ceases
to be crystallisable, and is converted into the resinous choloidic
acid; and on further prolonging the boiling,, the body, at the same
time that it loses its solubility in alcohol and alkalies, also parts
with its acid properties and then forms dyslysin. By the action of
boiling nitric acid, it is for the most part converted into capric,
caprylic, and cholesteric acids, without yielding oxalic acid or the
volatile acids of the first group.
Composition. — This acid, which was first obtained in a state of
purity by Demarcay, has been recently examined with much care
by Strecker.f He found that it was constituted in accordance with
the above formula. It consequently consists of :
Carbon 48atoms .... 70'588
Hydrogen 39 „ .... 9'559
Oxygen 9 „ .... 17'647
Water 1 „ .... 2-206
100-000
Consequently the atomic weight of the hypothetical anhydrous
acids =4987*5, and its saturating capacity = 2-005.
Mulder,! from his analyses of this acid, has deduced for it the
the formula, C50H36O64-5HO.
Strecker, who by his admirable memoir on the bile of the ox,
has done so much to advance our knowledge regarding this very
obscure fluid, has unfortunately increased the existing confusion
regarding cholic acid by giving it the new name of cholalic acid,
while he applies the name of cholic acid to another acid which we
shall subsequently describe. It is, however, true that Gmelin
applied the term cholic acid to that acid of the bile in whose salts
he recognized a sweet taste, and regarded it as a nitrogenous acid ;
but the non-nitrogenous acid first obtained in a state of purity by
Demarcay, which in its mode of preparation and in its properties
is identical with that which is here described, has so long been
known as cholic acid that this name ought to be retained, and the
more so because the new name of cholalic acid is by no means
* Ann. d. Ch. u. Pharra. Bd. 58, S. 375-378.
t Ibid. Bd. 66, S. 1-61.
| Unters. ub. d. Galle, ubers. v. Vdlkel., Frank, a. M. 1847. 6. 26.
120 CHOLIC ACIDS.
more expressive of its nature. We therefore retain the denomina-
tion which Demarcay, its discoverer, applied to it.
Combinations. — The cholates possess a bitter and at the same
time a slightly sweet taste ; they are all soluble in alcohol, but
water dissolves only the alkaline cholates and cholate of baryta,
and, to a very slight extent, cholate of lime. Cholic acid, with the
aid of heat, expels the carbonic acid from solutions of the alkaline
carbonates.
Cholate of potash, KO.C48H39O9 is obtained in acicular crystals,
by the evaporation of the alcoholic solution, or by the addi-
tion of ether to it. By spontaneous evaporation of the aqueous
solution it forms a kind of varnish ; the salt is insoluble in an excess
of solution of potash, and on the addition of caustic potash is
precipitated in a gelatinous state. Cholate of soda and cholate
of ammonia are very similar to it ; the latter of these two salts loses
the greater part of its ammonia on mere evaporation. Cholate of
lime, when obtained by precipitation, is amorphous, but it crystal-
lises on the addition of ether. Cholate of silver is only very slightly
soluble in water ; it crystallises, however, from a boiling solution.
Products of its metamorphosis. — Choloidic acid, as it exists in its
salts, is perfectly isomeric with cholic acid ; it is formed as we have
already mentioned, by boiling cholic acid with stronger acids. It
may, however, be obtained by boiling together for some hours
hydrochloric acid and that portion of the alcoholic extract of bile
which is precipitable by ether ; by solution in alcohol and precipi-
tation by ether, it may be readily purified. It is a peculiarity of
choloidic acid that in its isolated state it contains no basic water,
and may therefore be prepared in an actually anhydrous state ;
it forms a white, amorphous, resinous, pulverisable mass which is in-
soluble in water, but dissolves freely in alcohol, and slightly in ether.
The addition of water or of ether to the alcoholic solution causes a
milky appearance, and finally precipitates the acid in a resinous
form ; the alcoholic solution reddens litmus. When warmed, cho-
loidic acid softens; at 150° it fuses, and at 295° it becomes con-
verted into dyslysin, with the loss of 3 atoms of water. With con-
centrated sulphuric acid and sugar it gives the same reaction as
cholic acid. When distilled with nitric acid, it yields not only the
same volatile acids as oleic acid when similarly treated, but addi-
tionally choloidanic, cholesteric, and nitrocholic acids, and chola-
crole (Redtenbacher.*)
Its salts have a purely bitter taste, without any sweet after-
* Aim. d. Ch. u. Pharm. Bd. 57, 8. 145-170.
CHOLIC ACID. 121
taste ; the acid is displaced from them by stronger acids, and even
by carbonic acid, although, on the other hand, choloidic acid
expels carbonic acid when heated with carbonates. The alkaline
salts of this acid are soluble in water and in alcohol, but not in
ether ; they cannot be obtained in a crystalline state. Choloidate
of baryta., although isomeric with the cholate, is not crystallisable,
and is insoluble in water, With earths and metallic oxides this
acid forms salts which are soluble in alcohol but insoluble in water.
Dy sly sin C48H36O6 (Strecker), C50H36O6 (Mulder,) is obtained
from cholic or choloidic acid by one of the methods which we have
already mentioned ; the mass thus formed is extracted with water
and alcohol, arid dissolved in ether, from which it is again precipi-
tated by alcohol ; it is now of a grayish-white colour, and the
extent of its solubility depends upon the degree of its purity ; it is,
however, insoluble in acids and alkalies. When fused with hydrate
of potash, or boiled with an alcoholic solution of potash, dyslysin
is reconverted into choloidic acid.
From the choloidic acid of Demargay, Berzelius has separated
two acids, which he has named fellic and cholinic acids ;* he, like
Mulder, regards choloidic acid as an admixture of these two acids ;
it is to be regretted that Strecker, in his otherwise admirable in-
vestigation, has not made that reference to these substances which
they deserve ; for other chemists as well as Mulder may repeat the
experiments and confirm the statements of Berzelius, We shall
content ourselves in the present place, with indicating the most
important points of difference between these two acids.
Cholinic acid (C50H38O8 Mulder) forms white and bright
flocculi, insoluble in water, and which, on drying, become brown
and pulverisable. Its baryta and lead-salts have a tendency to
cake together, and are almost insoluble in alcohol; the ammonia-
salt of this acid separates as a white, saponaceous mass.
Fellic acid (C50H40O10) forms snow-white flocculi, which
when dried become pulverisable ; it is slightly soluble in water,
and its solubility in ether is even less than that of cholinic acid.
Its baryta and lead-salts are soluble in alcohol.
Redtenbacher distilled nitric acid over choloidic acid as long as
vapours of nitrous acid continued to be developed, and he found in
the receiver acetic, butyric, valerianic (?) caproic, O3nanthylic, capry-
lie, pelargonic, and capric acids (precisely the same as he obtained
* [In the German these acids are termed Fellins'dure and Cholins'dure : we adopt
the phrase cholinic acid for the latter word, as cholic acid is a pre-engaged name.—
o. E. v.]
122 RESINOUS ACID.
when oleic acid was similarly treated), and besides these, a heavy,
stupifying oil, which, when treated with alkalies, was decomposed
into nitrocholic acid and cholachrole ; while in the retort there
remained, as if proof against the further action of nitric acid, oxalic,
choloidanic and cholesteric acids.
Cholacrole, C8H5N2O13, is a yellow oil with a pungent, over-
powering, cinnamon-like odour, dissolving readily in alcohol and
ether, but difficult of solution in water ; it is indifferent towards
both acids and alkalies, and is decomposed at 100° with the deve-
lopment of nitrous acid, and sometimes with slight decrepitation.
Nitrocholate of potash, KO.C2HN4O9, occurs in lemon-yellow,
square tablets, has a faintly overpowering odour, decrepitates at 100°,
is decomposed when boiled with water, and is not precipitated by
metallic salts.
On pouring into a large test glass the thick, brownish yellow
mass which remains in the retort, it separates on cooling into two
layers, of which the upper is frothy, and consists of crystals of cho-
loidanic acid, while the lower is of a yellowish brown colour, acid
and bitter.
Choloidanic acid, C16H12O7, crystallises in satiny, hair-like
prisms ; when dry, it resembles asbestos ; it is difficult of solution
even in hot water, but dissolves freely in alcohol; it reddens
litmus, and is decomposed at a high temperature, but is unaffected
by hydrochloric or nitric acid. Its salts, even those of the alkalies,
are insoluble or difficult of solution, and do not crystallise.
In this yellowish brown mother-liquid there are also contained
oxalic acid, a resinous mass, and cholesteric acid.
Cholesteric acid, C8H4O4.HO, occurs as a light yellow mass,
resembling cherry-gum ; it has a well-marked acid and bitter taste,
abstracts water from the air, dissolves both in water and in alcohol,
the solution being of a yellow tint, and decomposes when heated 5
its compounds with alkalies and alkaline earths do not crystallise,
and are soluble in water, but its compounds with metallic oxides
are insoluble. The silver-salt dissolves in boiling water, from
which it is deposited, on cooling, in crystalline incrustations.
Preparation. — Cholic acid, which occurs in the bile conjugated
with nitrogenous bodies, is most readily obtained by boiling the
resinous masses precipitated by ether from the alcoholic solution
of the bile with a dilute solution of potash for twenty-four to thirty-
six hours, till the potash-salt that has separated begins to crystallise.
The potash-salt must then be dissolved in water and the acid
removed from it by hydrochloric acid. By the addition of a few
CHOLIC ACID. 123
drops of ether, the acid which was previously resinous becomes
crystalline, solid, and admits of trituration ; it must be pulverised,
washed with water, recrystallised in alcohol, and finally treated
with a little ether in order to remove any colouring matter that
may be attached to it.
Tests. — Cholic acid even when not perfectly pure may be recog-
nised by its reaction with sugar and sulphuric acid. This reaction,
which was first discovered by Pettenkofer,* occurs with no other
substance than cholic acid ; it is, however, perfectly immaterial
whether the cholic acid be already metamorphosed into choloidic
acid, or whether it be combined with its adjuncts, as a conjugated
acid. Hence we can apply this admirable test to discover generally
either the presence of bile or of one of its derivatives. The following
is the best method of proceeding. The alcoholic extract of the
fluid to be tested for biliary matter must be dissolved in a little
water, with which we must then mix a drop of a solution of sugar,
(in the proportion of 1 part of sugar to 4 of water) ; and pure
English sulphuric acid, free from sulphurous acid, must be added
by drops to the mixture ; the fluid now becomes turbid from the
separation of the cholic acid, but on the gradual addition of sul-
phuric acid the turbidity disappears, and the fluid again becomes
perfectly clear ; for the first few moments its colour is yellowish, it
very soon however becomes of a pale cherry colour, then of a deep
carmine, of a purple, and finally, of an intense violet tint. As,
indeed, in all experiments, some practice and attention to certain
rules are requisite, without which we may easily fail to apply this
test successfully to the detection of bile. For instance, we must
avoid the addition of too much sugar, as this is a substance which
is easily rendered brown or black by sulphuric acid ; and we must
be especially careful, as Pettenkofer himself showed, while adding
the concentrated sulphuric acid, not to allow the temperature much
to exceed 50° ; but the reaction equally fails when we carry our
caution too far, and attempt to avoid any elevation of temperature
when the sulphuric acid is added ; indeed, my own experience
leads me to believe that an elevation of the temperature nearly to
50° is requisite for the success of the experiment. Should the
fluid at first assume only a cherry-red or a deep carmine tint, it
must be allowed to stand for some time, after which the intense
violet colour becomes developed. It is, moreover, immaterial
which kind of sugar is used for this test : acetic acid may also be
employed in place of sugar.
* Ann. d. Ch. u. Pharm. Bd. 53, S. 90-96.
124 RESINOUS ACIDS.
Van den Broek* maintains that the reaction also takes with
mere biliary matter independently of the sugar, but I have never
found this to be the case ; without sugar the fluid has at most
attained a red or reddish brown tint, but never the characteristic,
deep violet colour. But although van den Broek is wrong on this
point, there are other reasons why his view is correct, that this
reaction is inapplicable as a test for sugar ; in the first place, because
we have the same reaction when other bodies, as for instance, acetic
acid, are substituted for sugar, and, secondly, because we have many
better arid more certain means of discovering this substance.
If it should be necessary to separate the cholic acid from the
conjugated biliary acids, or from choloidic acid, as is sometimes
required in the examination of the blood, urine, and excrements,
the best method is to acidulate the alcoholic extract with a little
sulphuric acid, and to extract with ether, in which the conjugated
biliary acids and choloidic acid are all but insoluble. As the cho-
late of baryta is soluble and cry stalli sable, which is not the case
with the choloidate, we may thus as well as by the crystallisability of
free cholic acid, readily distinguish between cholic and choloidic
acids ; the biliary acids are not only perfectly insoluble in ether,
but one of them, when boiled with potash, yields ammonia, and
the other, when similarly treated with hydrochloric acid, yields
taurine, which, as we shall presently show, may be easily recognised
under the microscope by the form of its crystals.
Physiological Relations.
Occurrence. — In the bile we neither find cholic nor choloidic
acid isolated from its respective adjunct ; hence either within the
animal body, in the gall-bladder, or after removal from the organism,
it seems to have already passed into a state of decomposition, or else
one of these acids must have been produced by the chemical treat-
ment to which the bile has been subjected.
In examining the blood and the urine of patients suffering from
diseases in which the liver is not directly implicated, we not unfre-
quently meet with substances yielding the above-described reaction
for bile ; I have, however, never satisfied myself in such cases, by
any method, that either the one or the other of the biliary acids
could be recognised with certainty. We shall treat more fully of
the occurrence of these biliary matters in the blood and urine in
our observations on the conjugated biliary acids. (See also " Blood "
and « Urine.")
* Hollandische Beitrage. Utrecht u. Diisseld. 1846. 8. 100-102.
CHOLIC ACID. 125
In healthy solid excrements Pettenkofer* found no substance
yielding this biliary reaction ; the dejections in cases of diarrhoea, on
the other hand, always contained a substance yielding this reaction.
I have, however, always been able to detect a little cholic acid in
perfectly normal excrements.
The alcoholic extract of previously dried solid excrement pre-
sented no reaction with sulphuric acid and sugar ; but on further
treating this extract with ether, and on purifying the residue of the
ethereal solution, by means of water, from the fatty acids which
are always mixed with it, I found that the somewhat concentrated
aqueous solution (of this ethereal extract) presented the biliary
reaction most beautifully. On using a larger quantity of material,
the acid was obtained in a crystalline state; as it yielded no am-
monia when treated with potash, and as its baryta-salt was soluble,
it could hardly have been any other than cholic acid.
In the intestinal canal we can detect the presence of bile in the
contents of the whole of the small intestine, by the addition of
sulphuric acid to the alcoholic extract, in the manner above
described.
If I rightly recollect, Pettenkofer informed me, in a private
communication, that he had already made this observation. I
have repeatedly convinced myself of its accuracy in animals; in
the case of an intestinal fistula, where it could not be determined
with certainty whether the perforation was in the small or large
intestine, and where no conclusion could be drawn from the absence
of villi, the diagnosis was established by the bile- test. It was sub-
sequently proved that the fistula occurred in the small intestine.
That substances containing or yielding cholic acid sometimes
occur in exudations, requires no proof, as the blood is frequently
overloaded with such matters.
I will here only mention that in the dropsical exudations occur-
ring in a case of granular liver, and in another case of insufficiency
of the mitral valves with stoppage of the biliary ducts, I found a
considerable quantity of biliary matter. This subject is more fully
noticed in the chapter on " Exudations."
The presence of biliary matters in morbid saliva and expectora-
tion, is asserted by Wright, f but has not been proved.
Origin. — As we must return, in a future page, to the different
opinions which are maintained regarding the origin of the essential
constituents of the bile, we shall here only notice such points as
* Ann. d. Ch. u. Pharm. Bd. 53, S. 90-96.
f The Lancet, 1842-3. Vol. 1, p. 559.
126 RESINOUS ACIDS.
chemically elucidate the formation of cholic acid. That cholic and
choloidic acids proceed from conjugated biliary acids, has been
already mentioned ; but according to the theoretical views which
are at present maintained, cholic acid exists preformed in these
biliary acids, just as in every conjugated acid we regard the true
acidifying group of atoms as already formed. Without alluding here
to the question whether the bile is primarily formed in the blood
or in the cells of the liver, we will merely enquire what substances
in the animal body yield that group of atoms which we call cholic
acid ? Even if many physiological and pathological facts did not
support the view that the fats yield the principal material for the
formation of the bile, the experiments of which we have made
mention regarding the products of oxidation of cholic and choloidic
acids, would lead us to the belief that these bodies are closely allied
to the fats, and especially to oleic acid ; for we have seen that Red-
ten bacher has obtained from choloidic acid when treated with nitric
acid precisely the same volatile acids (of the first group) as were
yielded by oleic acid under similar treatment, independently of
other specific substances. These latter may appropriately be
regarded as arising from a group of atoms still hidden in the cholic
acid, which group must be assumed to be an adjunct in the cholic
acid. For if it be not improbable that such simple acids as acetic
acid, butyric acid, &c., are to be regarded as conjugated acids, we
are almost compelled to regard an acid like cholic acid with so high
an atomic weight, and so considerable an amount of oxygen (that is
to say, with so small a saturating capacity) as a conjugated acid.
From the circumstance of cholic acid yielding these pro-
ducts of decomposition, we may conjecture that it is a conjugated
oleic acid ; and, assuming this to be the case, there remains as the
adjunct the group of atoms (C48H39O9 — C36H33O3nr) C12H6O6
whose per-centage composition is the same as that of the choles-
teric acid found by Redtenbacher in the products of decomposition
of choloidic acid, arid which is therefore polymeric with it (for
C12H6O6 : C8H4O4=3 : 2). That such polymeric groups of atoms
frequently occur in the animal body as conjugated compounds, is
obvious from Strecker's* discovery, that hippuric acid is, like the
amides (see p. 36), decomposed into nitrogen, water, and an acid
whose composition was found to be C18H8O8, but which probably
exists as a hydrate C18H9O9, and in that case is polymeric with
cholesteric acid. That cholic acid is oleic acid conjugated with the
atomic group C12H6O6 is merely a hypothetical view which,
* Ann. d. Ch. «. Pharm. Bd. 68, S. 52 ff.
BASIC BODIES. 127
founded on certain chemical facts, may seem to indicate a direction
for future experimental investigations, but cannot warrant us in
advancing further in this domain of the imagination. We post-
pone for the present entering into the consideration of other
hypotheses tending to elucidate the origin of the group of atoms
conjugated with oleic acid.
We must necessarily defer our remarks on the possible use of
cholic acid in the animal body, till we treat of the uses of the con-
jugated cholic acids and of the bile generally.
NITROGENOUS BASIC BODIES.
Substances of this nature occur principally in the vegetable
kingdom ; those requiring a notice in animal chemistry are almost
all only artificial products of known animal matters: in as far how-
ever, as they, like many of the acids which have been already
described, throw much light on the constitution of the bodies from
which they are derived, they must not be passed over in a work of
this nature. As there exists no true alkaloid without nitrogen, the
basicity of this class of bodies may be regarded as essentially
depending on the amount of nitrogen which they contain ; and in
further confirmation of this view, we may bring forward the fact
that the saturating power of these bodies is perfectly independent
of the amount of oxygen which they contain. Indeed it rather
depends in most cases on the amount of nitrogen ; that is to say,
1 equivalent of the nitrogen of the base requires 1 equivalent of
acid in order to form a neutral salt. Berzelius has, therefore,
advanced the opinion that the nitrogenous bases are merely
ammonia-compounds, with either a non-nitrogenous or a nitro-
genous body as an adjunct. The principal argument in favour of
.this view is, that these bases, like pure free ammonia, cannot unite
with oxygen acids, without simultaneously assimilating an atom of
water, but that, on the other hand, they combine with hydrochloric
and other hydrogen acids, without a separation of water : finally,
128 BASIC BODIES.
they resemble ammonia in this respect, that the combination of
their hydrochlorates with bichloride of platinum, are, like ammonio-
chloride of platinum, 'difficult of solution. Moreover, that the
nitrogen is not the direct cause of the basicity seems probable,
from the circumstance that the saturating power of the substance,
even when it contains several equivalents of nitrogen, for the most
part corresponds with only one equivalent ; so that only this one
equivalent is to be regarded as pertaining to the ammonia, and the
remainder of the nitrogen to the adjunct.
These organic bases are divisible into two tolerably well-marked
groups, according as they contain or are devoid of oxygen : as the
former are, without exception, volatile, and the latter not so, we
might also class them as volatile and non-volatile bases.
NON-OXYGENOUS ALKALOIDS.
The bodies of this group are very similar in their empirical
composition to the nitriles which we have already described: in
their rational composition there can, however, be no similarity, as
they are essentially different in their chemical properties. The
nitriles never show any basic properties, while the alkaloids cannot
be decomposed into oxygen acids and ammonia either by acids or
by alkalies, nor with potassium do they form cyanide of potassium.
If, therefore, Berzelius's view, that the alkaloids are conjugated
ammonia, find a confirmation in any substances, it must be in the
non-oxygenous alkaloids, which in all their combining relations
present so many analogies with ammonia that we might regard it
as the representative of this group. Even the mode of preparing
certain alkaloids, as, for instance, thiosinnamine, affords evidence in
favour of this view of the subject.
It is well known that, on treating cyanic acid with potash,
there is a development of ammonia (C2NO.HO + 2HO + 2KO=:
2KO.CO2 + H3N); on heating cyanate of oxide of methyl or cya-
nate of oxide of ethyl with potash, a strongly basic alkaloid, similar
ANILINE. 129
to ammonia, is produced; here we feel almost compelled to assume
that ammonia is formed from the cyanic acid just as from the free
acid, and that this ammonia is conjugated with the carbo-hydrogen
of the methyl or the ethyl, (C2H2 or C4H4,) and thus produces the
alkaloid.
Urea presents perfectly similar reactions: when treated with
alkalies it developes ammonia ; and Wurtz* has shown that these
alkaloids may be prepared in such a manner that acetate of urea,
when heated with potash, shall yield the same alkaloid as is
obtained by the action of potash on cyanate of oxide of methyl,
namely C2H5N, while metacetonate of urea, similarly treated, gives
the same alkaloid as is obtained by the action of potash or cyanate
of oxide of ethyl, namely C4H7N. Although these substances may
either be regarded as pertaining to the class of ethers in which the
oxygen is replaced by amide, C4H5.Oc\}C4H5.H2N, or as ammonia
in which the. third atom of hydrogen is replaced by methyl or
ethyl, the most simple and probable explanation seems to be, that
they should be regarded as conjugated ammonia-compounds
= C2H2.H3N, and C4H4.H3N.
As was already mentioned, we shall here only notice those alka-
loids which may be obtained from the decomposition of certain
animal matters.
Many of these volatile alkaloids are liquid, like the nitriles,
but most of them are crystallisable. They have generally a nau-
seous odour and an acrid burning taste, are slightly soluble or alto-
gether insoluble in water, dissolve readily in alcohol, are most
soluble in ether and in fatty and volatile oils, and react on vege-
table colours. Their salts are, for the most part, crystallisable and
readily soluble ; but their combinations with bichloride of platinum
are nearly or entirely insoluble.
ANILINE. — C12H7N.
Chemical Relations.
Properties. — This alkaloid forms a colourless, strongly refract-
ing, oily fluid, with an aromatic odour; its specific gravity = 1'020,
it remains fluid at — 20°, evaporates very rapidly at an ordinary tem-
perature, begins to boil at 182°, dissolves slightly in water, and in
every preparation in alcohol and ether, coagulates albumen, dis-
solves phosphorus and sulphur, and colours Dahlia (Georgina) paper
* Compt. rend. T. 38, pp. 223-227.
130 BASIC BODIES.
green ; when exposed to the air it becomes yellow, and is converted
into a resinous mass ; a solution of hypochlorite of lime, on the
addition of a few drops, assumes a violet colour ; with nitric acid, on
the other hand, aniline yields an indigo colour, and, by prolonged
action, is converted into picric acid ; with dilute chromic acid it
yields a black or greenish blue precipitate,
Composition. — According to the above formula aniline con-
tains :
Carbon 12 atoms .... 77*419
Hydrogen 7 „ .... 7'527
Nitrogen 1 „ .... 15'054
100-000
Its atomic weight =11 62*5. According to Berzelius, aniline
consists of ammonia conjugated with a carbo-hydrogen=C12H4.
Combinations. — Aniline forms very characteristic, and, for the
most part, crystallisable salts, both with the oxygen and the hydro-
gen acids ; in the former, but not in the latter case, the salts assi-
milating an atom of water.
The analogy between aniline and ammonia is further shown by
the circumstance that it, like the latter, under certain conditions,
may lose a portion of its hydrogen, and be converted with an acid
deprived of a portion of its oxygen (and therefore with the forma-
tion of water) into combinations analogous to the amides, to which
the term anilides has been applied. (Gerhardt.*)
As the elements of cyanate of ammonia, immediately after they
are brought together, group themselves in a different manner and
form urea, so cyanic acid and aniline do not form a simple salt, but
a body, from which neither aniline nor cyanic acid can be again
obtained, namely, aniline-urea, C14H8N2O2. (Hofmann.t)
Aniline may so assimilate cyanogen that the latter may be
regarded as an adjunct, the newly-formed body, cyaniline, entirely
retaining its basic properties. (Hofmann.J)
Aniline probably affords stronger evidence than any other body
yet examined in reference to this point, in favour of the substitution
theory, since not merely one, but several of its equivalents of
hydrogen, may be replaced by chlorine, bromine, iodine, or hypo-
nitric acid, without the group of atoms entirely losing its basic
* Journ. do Pharm. et deChim. 1845, Juill. pp. 53-56.
t Quart. Journ. of the Chem. Soc. of Lond. 1848. Vol. i., pp. 159-174.
| Ann. d. Ch. u. Pharm. Bd. 57, S. 247 ff.
PICOLINE. 131
properties. (Hofmann,* and Hofmann and Muspratt.f) Finally,
a base has been discovered in which aniline is combined with the
adjunct cyanilide, C12 (H6Cy) N ; to this the name of melaniline
has been applied. ( Hofmann. J)
Preparation. — This body very frequently occurs as a product of
the decomposition of nitrogenous matters ; thus, for instance, it is
found among the products of the dry distillation of animal
substances, as bone-oil (Anderson. §). As it had previously
been obtained in various ways, it received several different names,
as cyanol, benzidame, and crystalline, before its identity was fully
established. It is most easily obtained in a state of purity by
heating anthranilic acid, (C14H6NO3+HO=:2CO2 + C12H7N,) or
phenate of ammonia, (H4NO.C12H5O=2HO + C12H7N,) or from
nitrobenzide and sulphuretted hydrogen, (C12H5NO4 + 6HS=6S
+ 4HO + C12H7N.)
Tests. — We have already pointed out the manner in which
aniline reacts with hypochlorite of lime, and nitric and chromic
acids; by these tests we can easily recognise it even when it is not
exhibited in a perfectly pure state.
Physiological Relations.
It is remarkable that this substance, which affects the organism
so unpleasantly from its smell and taste, should, according to
Wohler and French's experiments, || be free from all poisonous
action.
PICOLINE. — C12H7N.
Properties. — This body, which was formerly called pyrrol, is
also a thin fluid, having a penetrating, rank, aromatic odour, and
a burning bitter taste ; it remains fluid at— 20°, evaporates at an
ordinary temperature, boils at 133°, and its specific gravity =0*95 5 ;
it turns red litmus blue, does not change on exposure to the atmo-
sphere, and does not coagulate albumen. It is not coloured by
chloride of lime, and experiences no alteration from chromic acid.
Its Composition resembles that of aniline.
Combinations. — With acids it forms bitter tasting salts, soluble
* Ann. d. Ch. u. Pharm. Bd. 53, S. 40-57.
t Ibid. Bd. 57,8.201-224.
J Ibid. Bd. 67, S. 61-78, and Bd. 68, S. 129-174.
§ Phil. Mag. 3 Ser., vol. 33, p. 185.
|| Ann. d. Ch. u. Pharm. Bd. 65, S. 340.
K 2
132 BASIC BODIES.
in water and alcohol, and partially deliquescent, although not so
easily crystallised as those of the aniline, and less readily changed
by the action of the air.
Preparation. — This body was first discovered in coal-tar, and
subsequently in the products of the distillation of bones from which
the fat has been removed. (Anderson*). It is obtained by frac-
tional distillation.
This body is isomeric, or rather identical with the aniline or
benzidine==:Cll2H.jN (see p. 80) obtained from nitrobenzide by
ammonia and sulphuretted hydrogen ; this benzidine must not be
confounded with the benzidine = C12H6N, (see p. 81), which was
obtained by Zinin,t from azobenzide, ammonia, and sulphuretted
hydrogen.
PETININE. — C8H10N.
Properties. — This alkaloid is a colourless, highly refracting
fluid, having a sharp pungent odour and taste; it boils at 79°, is
easily soluble in water, alcohol, and ether, gives a blue tint to red
litmus, is the strongest base of all these alkaloids, and is not
coloured but decomposed by chloride of lime.
Composition. — According to the above formula it consists of:
Carbon 8 atoms .... 66*666
Hydrogen 10 „ .... 13-890
Nitrogen 1 „ .... 19*444
100-000
Its atomic weight is=900'0. According to Berzelius, the theo-
retical formula of this body would be=H3N.C8H7.
Combinations. — The compounds of petinine with acids are
readily crystallisable, unaffected by the atmosphere, and soluble in
+
water and alcohol. Chloride of platinum and petinine, P.HCl.PtCl2
forms golden yellow crystals resembling iodide of lead, pretty
soluble in cold water.
Preparation. This base is the most volatile of those yielded by
the dry distillation of gelatinous tissues. It is obtained from the
mixture of basic bodies and ammonia by fractional distillation.
* Phil. Mag. 3 Ser., vol. 33, pp. 174-186.
t Journ. f. pr. Cli. Bd. 35, 8. 93.
ALKALOIDS CONTAINING OXYGEN. 133
ALKALOIDS CONTAINING OXYGEN.
Few substances of this group belong to zoo-chemistry ; but
they are more important in reference to physiological chemistry
than the non-oxygenous alkaloids which we have just considered, as
they have either been found preformed in the animal body, or are
able to throw considerable light on the constitution of the sub-
stances yielding them, and on organic chemistry generally. We
shall therefore only consider in any detail the following substances,
viz. : — creatine, creatinine, tyrosine, leucine, sarcosine, glycine,
(glycocoll) urea, guanine, xanthine, taurine, and cystine ; and here
it will be necessary to obtain some acquaintance with the general
chemical relations of all these bodies before we enter upon the con-
sideration of each individually.
The oxygenous alkaloids do not yield in respect to their basicity
to those containing no oxygen ; for many of these bodies not only
separate the oxides of the heavy metals from their salts but also
liberate ammonia. Their basicity, however, exhibits such gradual
differences that no accurate line of demarcation can be drawn
between decidedly basic and indifferent nitrogenous bodies. Thus
leucine and creatine are perfectly indifferent bodies, while sar-
cosine, which is homologous to leucine, and creatinine, which is so
similar to creatine, are strongly basic; but as these indifferent
bodies present a close theoretical relation to the basic bodies, or
actually possess weak basic properties, we do not think that it is
expedient to separate them.
There is no direct ratio between the saturating capacity of these
bodies and the quantity of oxygen or even of nitrogen that they
contain, for in creatinine, for instance, only the third part of the
nitrogen contained in the body corresponds to the saturating capa-
city, while in xanthine it is the fourth, and in guanine only the fifth
part. In these bodies the nitrogen may be similarly incorporated
with other elements as an adjunct of the base ; thus we have seen
that nitrogen may be artificially added to aniline under the form of
cyanogen or hyponitric acid, and that harmaline (from Peganum
harmala) takes up hydrocyanic acid without changing its saturating
capacity.
The greater number of the alkaloids containing oxygen are
crystallisable ; none are fluid at an ordinary temperature ; the ma-
jority have a more or less bitter taste ; not being volatile, they have
134 BASIC BODIES.
no odour; all are soluble in alcohol, a few in water, and none that
we have here considered, in ether ; although most alkaloids act on
vegetable colours, none of those under consideration, excepting
creatinine and sarcosine, exhibit this property.
Their salts are almost universally crystallisable and soluble in
water as well as in alcohol ; with bichloride of platinum their hydro-
chlorates form compounds which are either insoluble or difficult
of solution ; their oxygen salts cannot exist without 1 equivalent
of water. The most strongly basic alkaloids are precipitated by
tannic acid from dilute aqueous solutions.
Although many of the substances which we shall have to con-
sider in this group do not possess any basic properties, and there-
fore do not, strictly speaking, belong to it, we have arranged them
together, partly on account of the analogy exhibited in their
empirical composition, and partly, because in a physiological point
of view, they exhibit tolerably equal values, that is to say, they are
derivatives of nitrogenous tissues. The bodies which we shall now
consider, are : —
Creatine C8 H9 N3 O4
Creatinine C8 H7 N3 O2
Tyrosine C16H9 N O5
Leucine .... C12HnN O4
Sarcosine C6 H? N O4
Glycine (Glycocoll) C4 H5 N O4
Urea C2H4N2O2
Xanthine C5 H2 N2 O2
Guanine C10H5 N5 ^O2
Allantoine C8 H5 N4 O5
Cystine C6 H6 NS2O4
Taurine C4H7NS2O6
CREATINE. — C8H9N3O4.
Chemical Relations.
Properties. — This body forms transparent, very brilliant crystals,
belonging to the clinorhombic system and containing 2 atoms of
water of crystallisation ; it is of a bitter, strongly pungent taste,
and irritates the pharynx; it loses its 2 atoms of water at 100°, and
at a higher temperature becomes decomposed ; it dissolves in 74*4
parts of cold water, and in boiling water in such quantity that, on
cooling, the solution becomes consolidated into a mass of delicate
CREATINE. 135
glistening needles ; it does not dissolve in less than 9410 parts
of alcohol^ and not at all in ether ; it does not act on vegetable
colours, and forms no definite salts with acids. It dissolves in
baryta-water without undergoing any change, but when boiled with
it, it becomes decomposed into ammonia and carbonic acid or into
urea and sarcosine. It also dissolves unchanged in dilute acids ;
but when heated with strong acids, it becomes converted into
creatinine, giving off 2 atoms of water.
Composition. — This body has recently been most carefully
examined by Liebig ;* from whose analyses the above formula is
derived, and from which we find creatine to consist of :
Carbon 8 atoms .... 36'64
Hydrogen 9 „ .... 6'87
Nitrogen 3 „ .... 32'06
Oxygen 4 „ .... 24'43
100-00
The 2 equivalents of water correspond to 12'08£ of crystal-
lised creatine. The atomic weight of the anhydrous substance is
— 1637*5. Notwithstanding the various modes of decomposing
creatine, no probable hypothesis can be adduced regarding its theo-
retical constitution. As it is almost wholly deficient in basic pro-
perties, it can hardly be regarded, according to Berzelius's view,
as a conjugated ammonia; for it would in that case stand as
H3N.C8H6N2O4, by which the deficient basic character is made
more conspicuous ; while Liebig's view of regarding crystallised
creatine as a combination of ammonia and 2 equivalents of gly-
cine, (glycocoll,) (C8HnN3O6=H3N + C8H8N2O6,) is opposed
both by the constitution of anhydrous creatine and by the
deficiency in basicity. The decomposition of creatine by baryta-
water into urea and sarcosine might indeed indicate that these
bodies are its proximate constituents (for C2H4N2O2 + C6H7NO4=:
C8HnN3O6), but this is not probable; for although we know that
water is expelled on the union of two organic substances, we can
no more assume that urea and sarcosine are present in the dry
substance, than we could maintain that oxalic acid and ammonia
are contained in oxamide, or valerianic acid and ammonia in vale-
ronitrile.
Preparation. — Creatine is obtained, according to Liebig, from
finely chopped flesh, that has been well kneaded with water
and the fluid removed by pressure. The coagulable matters are
* Ann. d. Ch. 11. Pharm. Bd. 62, S. 257-290.
136 BASIC BODIES.
then removed by boiling, from the fluid which is thus obtained, and
the phosphates by caustic baryta; during the evaporation of the
fluid filtered from these precipitates the surface will be continually
covered with a membranous coating which must from time to time
be removed ; after the fluid has been evaporated to -^th of
its volume it must be left to stand for some time, when the creatine
will separate in needles. The crystals, when separated from the
mother-liquid by filtering paper, must be washed with water and
spirit of wine, and then again suffered to crystallise from hot
water.
The following method is likewise given by Liebig for obtaining
creatine from urine. The urine, after being treated with lime-water
and chloride of calcium, and being filtered, is evaporated, and the
greater part of the salts removed by crystallisation ; the mother-
liquid poured off from the crystals is then decomposed with -^-th
of its weight of a syrupy solution of chloride of zinc ; after some
days, roundish granules of a compound of chloride of zinc and
creatinine, with which some creatine is mixed, become separated ;
these granules, after being dissolved in boiling water, are treated
with hydrated oxide of lead until there is an alkaline reaction.
The fluid, after the removal of the oxide of zinc and chloride of
lead by filtration, is freed from the lead and colouring matter by
means of animal charcoal, and evaporated to dryness. The residue,
consisting of creatine and creatinine, is treated with boiling alcohol,
in which the latter dissolves readily, while the former is almost
insoluble in it ; by this means the two bodies can therefore be
easily separated.
Tests. — In order to examine whether creatine be present in a
fluid, (for which purpose a large amount of material is required,)
one of the above methods should be adopted, and the properties
of any creatine-like substance compared with those of pure
creatine. As, however, the determination of the atomic weight
is not so readily made as in the acids, an elementary analysis is
indispensable for the attainment of perfect certainty.
Physiological Relations.
Occurrence. — Chevreul long since drew attention to this sub-
stance as a constituent of the decoction of flesh, but its presence
was not again detected by any of the analysts who sought for
it, until Schlossberger* found it in the muscular tissue of an
* Ann. d. Ch. u. Pharm. Bd. 49, S. 341,
CREATINE. 137
alligator, and Heintz* proved its existence in beef, and was at the
same time the first observer who accurately determined the com-
position of this body. Liebig may, however, l^e regarded as the
first who made us thoroughly acquainted with it by his conclusive
investigations regarding its chemical relations and the various
situations in which it occurs. Liebig has examined so many different
kinds of flesh for creatine, and so universally discovered it, that
scarcely a doubt can now be entertained that creatine forms a
constituent of the muscles of all the higher classes of animals.
The quantity of creatine found in muscle is, however, exceedingly
small. Liebig obtained only36 grammes (consequently only 0*072^)
of creatine from 100 pounds of lean horse-flesh; 30 grammes
(or 0'07£) from 56 pounds of beef; but 72 grammes ( = 0-32^)
from 47 pounds of the flesh of lean fowls ; consequently for every
100 parts of flesh there were only 0*07 or at most 0'32 parts of
creatine, or 1 part of creatine to 1400 parts of flesh. Liebig
has further convinced himself that lean flesh contains more creatine
than fat flesh ; and this may probably be the cause of propor-
tionally a large quantity of creatine being found in the tissue of the
heart of the ox.
Liebig obtained the largest quantity of creatine from the flesh of
fowls and martens ; the quantity diminished progressively in the
flesh of horses, foxes, roes, stags, hares, oxen, sheep, pigs, calves,
and fishes. Liebig could frequently obtain only traces of creatine
from fat flesh.
Gregoryf has examined several kinds of flesh, according to
Liebig' s method, in reference to their amount of creatine. He
found in 100 parts of bullock's heart from 0-1375 to 0*1418 parts
of creatine, in the flesh of the cod-fish (Gadus morrhua) from
0*0935 to 0*17 parts, in the flesh of pigeons 0*0825 parts, and in
the flesh of the skate (Raja bails) 0*0607 parts. Gregory especially
recommends the flesh of the cod-fish, partly because it contains
a proportionally large quantity of creatine, and partly because
it most readily yields a pure, finely crystallised creatine. Sea-
fish appears to contain much more creatine than fresh-water
fish.
SchlossbergerJ has shown by direct experiment that human
flesh presents no exception to the rule ; 6 pounds of human flesh
yielding about 2 grammes of creatine (therefore =0*067^).
* Fogg. Ann. Bd. 70, S. 476-480.
t Ann. d. Ch. u. Pharm. Bd. 64, S. 100-108.
J Arch. f. phys. Heilk. Bd. 7, S. 209-211.
138 BASIC BODIES.
No creatine could be found in the substance of the brain, liver,
or kidneys.
Creatine, together with creatinine, was first separated from the
urine in the chloride of zinc compound by Heintz* and Petten-
koferf although they did not recognise its nature; Heintzf sub-
sequently obtained pure creatine from the zinc compound, and
employed this substance for his analysis. Liehig, however, showed
that the chloride of zinc compound, as yielded by urine, contained
for the most part creatinine in chemical combination, the creatine
being only mixed with it.
Origin. — When we remember that creatine occurs in the decoc-
tion of flesh, and is a highly nitrogenous body, we might be led to
regard it as an important nutritive agent, and as taking an active
part in progressive metamorphosis. The analogy which, in its
chemical relation, and in its constitution, it presents to caffeine,
might moreover tend to mislead those who class that substance
among nutrient bodies, from its occurrence in certain kinds of
food and in certain stimulants. But this analogy is here of very
little moment, for we cannot place caffeine among the nutritive
agents without giving a very great latitude to the term. A sub-
stance, of which a quantity from 2 to 10 grains will produce the
most violent excitement of the vascular and nervous systems — pal-
pitation of the heart, extraordinary frequency, irregularity, and often
intermission of the pulse, oppression of the chest, pains in the head,
confusion of the senses, singing in the ears, scintillations before
the eyes, sleeplessness, erections, and delirium, — can scarcely be
reckoned among articles of nutrition even by the homoeopath ist,
and certainly not by physiologists, when they learn how quickly
caffeine becomes decomposed in the organism, and gives rise to an
increased secretion of urea.
The above-named results were yielded by experiments insti-
tuted on myself and several of my pupils with pure caffeine. Five
persons (one of whom was Professor Buchheim, now at Dorpat),
after taking from 5 to 10 grains of this substance, were unfit for
any business during the next day, while, in an experiment which I
formerly made on myself, 10 grains scarcely produced any percep-
tible action. In all the cases there was found to be augmentation
of the total amount of urea excreted in twenty-four hours.
If, however, the analogy between creatine and caffeine does not
* Pogg. Ann. Bd. 62, S. 602-606.
t Ann. d. Ch. u. Pharm. Bd. 53, S. 97-100.
t Pogg. Ann. Bd. 62, S. 602.
CREATINE. 139
demonstrate the nutrient qualities of the former, it must be asked,
whether its occurrence in a substance so nourishing as the decoction
of flesh, and its large amount of nitrogen, afford more conclusive
evidence in this respect ? With reference to the latter, it may be
assumed that nature would not suffer substances even more highly
nitrogenised than creatine, as the creatinine discovered by Liebig in
the urine and the urea, to escape through the kidneys, if they could
be employed to further advantage in the organism, since we find so
careful a providence over recognised nutrient matters, as for
instance, albumen, &c., that even in disease they are only rarely
found to escape with the excreta. The occurrence of creatine in the
decoction of flesh affords even less evidence of its nutrient powers,
for when we consider the small quantity in which it occurs in flesh,
and the truly homoeopathic nature of the dose which we take with
the meat and broth we eat, we must regard its simultaneous
appearance in the urine as a proof that its properties are not very
highly esteemed in the organism, since, if they were so, this sub-
stance would probably not be discharged from the kidneys, but be
retained in the same manner as albumen and gelatin. We think,
however, that Liebig's complete chemical investigations of creatine,
which were conducted in a manner worthy of so great a chemist,
constrain us, even if unsupported by physiological proof, to regard
creatine as a product of excretion. From its chemical qualities we
regard creatine a member of the series indicating the regressive
metamorphosis from the point of the highest atomic weights to
bodies of the simplest composition. The readiness with which
creatine becomes decomposed into creatinine, urea, and sarcosine,
which is isomeric with lactamide, all of which are undoubtedly
products of excretion, proves beyond a doubt, that creatine
approximates more nearly to these substances than to albumen
and fibrin, and indicates the great probability of creatine being
decomposed even in the living body into these and other similar
substances. Although such bodies as lactic acid, &c., may be
employed for special purposes in the animal organism, they cannot,
strictly speaking, be regarded as nutrient substances, that is to say,
as materials for the renovation of nitrogenous tissues; and it is
only in this light, and not in that of a supporter of heat, that we
must consider creatine. Creatine is, however, a substance of the
highest importance in relation to physiological chemistry, as it
affords us a glimpse at the ever-recurring chemical changes which
are associated with the functions of organs, and of which we have
at present so little general knowledge.
140 BASIC BODIES.
CREATININE. — C8H^N3O2.
Chemical Relations.
Properties. — This alkaloid forms colourless, very glistening
crystals, belonging to the monoclinometric system : has almost as
burning a taste as caustic ammonia, dissolves in 11 '5 parts of water
at an ordinary temperature, but more readily in hot water ; while
it requires about 100 parts of cold spirit to dissolve 1 part of crea-
tinine, it is so freely soluble in hot spirit that, on cooling, it again
separates in crystalline masses ; it is also slightly soluble in ether ;
it shows a strong alkaline action on vegetable colours, and it even
separates ammonia from its salts. A moderately concentrated
solution of nitrate of silver added to a solution of creati-
nine, causes a coagulation into a net-work of acicular crystals,
which dissolve on being boiled with water, and again appear when
it cools. A solution of corrosive sublimate yields a curdy preci-
pitate, which soon becomes crystalline; chloride of zinc likewise
forms a crystalline granular precipitate. Bichloride of platinum,
however, yields no precipitate when the solution is somewhat
dilute.
Composition. — We are indebted solely to Liebig* for our
knowledge of the composition of this substance. From the analyses
of its salts he deduced the above formula, according to which it
consists of:
Carbon 8 atoms .... 42'48
Hydrogen 7 „ .... 6'19
Nitrogen 3 „ .... 37'17
Oxygen 2 „ .... 14'16
100-00
Its atomic weight— 1412-5. As this body possesses such strong
basic properties, we may accept the hypothesis of Berzelius regarding
its theoretical composition as the most probable one, namely, that
it is ammonia conjugated with a highly nitrogenous body, con tain-
ing exactly 1 atom less of hydrogen than caffeinerr H3N.C8H4N.2O2.
Moreover, a comparison of the formulae shows that creatinine con-
tains exactly 2 atoms of water less than anhydrous creatine.
Combinations. — The combinations of creatinine with acids are,
as far as is yet known, soluble in water and readily crystallisable.
Hydrocldorate of creatinine, K.HC1, crystallises from hot alcohol
* Ann. d. Ch. u. Pharm. Bd. 62, S. 257-290.
CREATININE. 141
in short transparent prisms ; from water, in broad leaves ; with
bichloride of platinum it yields an easily soluble compound which
+
crystallises in crimson prisms = K.HCl + PtCl2.
+
Sulphate of creatinine, K.HO.SO3, forms concentrically grouped,
transparent, square tablets, which lose no water at 100°, and remain
perfectly translucent.
With the above-named metallic salts creatinine yields crystal-
lisable compounds, all of which are basic double salts ; with the
salts of the oxide of copper it forms crystallisable double salts of a
beautiful blue colour.
Preparation. — The most simple method of obtaining creatinine
is from creatine, by exposing a mixture of the latter and of hydro-
chloric acid to evaporation, till all excess of acid is volatilised.
The base is best separated from the hydrochlorate, which is thus
formed, by digestion with hydrated oxide of lead. The mode
of preparing creatinine from urine has been already indicated in our
remarks on creatine ; moreover, when it is to be prepared from the
juice of flesh, the chloride of zinc compound must be employed and
decomposed by hydrated oxide of lead ; the creatinine may then
be readily separated from the creatine by alcohol.
Tests. — This body may generally be distinguished with facility
from other animal substances, when it is separated as much as
possible from adherent organic substances. Its alkaline reaction,
its property of forming crystalline compounds with the above-
named metallic salts, the easy solubility of the compounds which
it forms with bichloride of platinum and similar salts, are more
than sufficient to characterise it.
Physiological Relations.
Occurrence. — It is only in the muscles and in the urine that
Liebig has found creatinine. Regarding the quantity in which it
exists, nothing is yet known, except that from Liebig^s investiga-
tions it appears that in the muscles there is far more creatine than
creatinine, while in the urine the amount of creatinine very much
exceeds that of creatine.
According to Scherer* it is highly probable that the Liquor
Amnii contains creatinine.
Origin. — From the facts which have already been communicated
it can hardly be doubted that creatinine is produced from creatine ;
for even if Liebig had not afforded the most decisive proof, by the
* Zeitschr. f. wissenschaftl. Zoologie. Bd. 1, S. 91.
142 BASIC BODIES.
artificial conversion of one substance into the other,, the facts that
they occur in an inverse ratio in muscle and in urine, and that
putrid urine yields no creatine, but only creatinine, tend to show that
also, in the living body, the latter substance proceeds from the
former, and consequently is to be regarded purely as a product of
excretion.
TYROSINE.— C16H9NO5.
Properties. — This body forms silky, glistening, dazzlingly white
needles, is of very difficult solubility in water, and is altogether
insoluble in alcohol and ether; it dissolves readily in alkaline
solutions, and enters into combination with acids, with the excep-
tion of acetic acid.
Composition. — This body was discovered and analysed byLiebig.*
He regards, however, a repetition of the analysis as necessary for
the confirmation of the formula which he deduced.
Preparation. — Cheese, well pressed and freed from adherent
butter, or well-dried fibrin or albumen, must be fused, according to
Liebigand Boppt5 with an equal weight ofhydrated potash, till, in
addition to ammonia, hydrogen begins to be developed, or, in other
words, till the original dark brown colour merges into a yellow ; on
then dissolving the mass in hot water, and slightly supersaturating
it with acetic acid, the tyrosine separates in needles, which are
obtained in a state of perfect purity by solution in potash-water
and a second acidulation with acetic acid. The adherent brownish
red pigment may be removed by treating the hydrochlorate of
tyrosine with animal charcoal, and boiling the colourless fluid with
an excess of acetate of potash ; chloride of potassium is then
formed, and the tyrosine, free from acetic acid, separates, on cooling,
in finely matted needles. This substance is also formed, together
with leucine and several acids of the first group, during the putre-
faction of albumen, fibrin, and casein. Finally, since tyrosine is
also formed in the decomposition of the above-named protein-
compounds by concentrated hydrochloric acid or by sulphuric acid,
(in which latter case leucine is also formed), this mode of procedure
may also be adopted for the preparation of this substance. For this
purpose we dissolve 1 part of the protein-compound in 4 times the
quantity of concentrated hydrochloric acid, and then add 4 parts of
* Ann. d. Ch. u. Pharm. Bd. 57, S. 127.
t Ibid. Bd. 69, S. 19-37.
LEUCINE. 143
sulphuric acid, and evaporate in the water-bath. The hydrochloric
acid is expelled by evaporation, from the syrupy, blackish brown
residue, which is then dissolved in water and boiled with milk of lime;
the excess of lime is removed from the filtered fluid by sulphuric
acid, whose excess is removed by acetate of lead, and the lead by
sulphuretted hydrogen : in this syrup crystals of tyrosine and leucine
are formed, which are separated from one another in the manner
already described.
LEUCINE.— C12H13NO4.
Properties.— It occurs in the form of glistening, colourless
leaves, which craunch between the teeth, and convey to them the
sensation of a fatty matter ; it is devoid of taste or odour, is lighter
than water, fuses at above 100°, sublimes unchanged when care-
fully heated to 170°, is soluble in 27*7 parts of water at 17°'5, and
in 625 parts of alcohol of 0'828 specific gravity, and in much smaller
quantities of hot water and alcohol, but is insoluble in ether ; it
has no reaction on vegetable colours. No reagent, with the excep-
tion of nitrate of suboxide of mercury, precipitates it from its
aqueous solution. It dissolves more readily in a solution of caustic
ammonia than in water. It dissolves unchanged in concentrated
sulphuric and hydrochloric acids, and the solution may even be
warmed without the occurrence of decomposition ; it dissolves
unchanged in cold nitric acid, but, on boiling, is entirely converted
into volatile products.
One hundred parts absorb about 28 parts of hydrochloric acid
gas. Chlorine gas destroys it. On heating its aqueous solution with
nitric oxide or any other oxidising agent, leucic acid, C12HHO5.HO,
is formed, nitrogen being developed.
If, on the other hand, it is fused with hydrated potash, there is a
simultaneous formation of carbonic acid, hydrogen, and valerianate
of ammonia (C12H13NO4 + 3KO+3HO = 2KO.CO2 + H3N + 4H
+ KO.C10H9O3). It undergoes the same decomposition during the
putrefaction which a solution of pure leucine very readily undergoes
when a small quantity of muscular fibre or of albumen has been
added.
Composition. — Mulder, following Braconnot's investigations
regarding leucine, has recently analysed it, and from his analyses has
deduced the formula C12H12NO4 ; but still later analyses, instituted
144 BASIC BODIES.
almost simultaneously by Laurent and Gerhardt,* by Cahours,f
and by Horsford, indicate that in leucine there is contained 1 equi-
valent of hydrogen more than Mulder had assumed, and continues
to assume, in his most recent investigations.J Hence leucine,
which, moreover, crystallises without water of crystallisation,
contains :
Carbon 12 atoms .... 54'96
Hydrogen 13 „ .... 9'92
Nitrogen 1 „ .... 10'68
Oxygen 4 „ .... 24'44
100-00
Its atomic weight =163 7 "5.
Since leucine possesses scarcely any basic properties, the view
that it is a conjugated ammonia=H3N.C12H10O45 is the least pro-
bable hypothesis regarding its theoretical composition. From
Liebig's§ experiment, to which we have already alluded, that
leucine with hydrated potash yields valerianic acid besides volatile
products, no theoretical formula for this body can be provisionally
deduced ; but Gerhardt and Laurent, as well as Cahours, have in
part proved it to belong to the series of homologous bodies with
the formula CnHn+1NO4, to which, as we shall presently see,
sarcosine and glycine pertain. But Cahours, || and subsequently
Strecker,^[ availed themselves of Piria's mode of proceeding, by
which he decomposed the amide-compounds by nitric oxide (see
p. 36) into water, nitrogen, and the original acid, in order to
obtain the above-mentioned leucic acid from leucine. According to
this view, leucine should be regarded as the amide of this acid: since
H4NO.C12HUO5— 2HO = C12H13NO4, the theoretical formula for
this substance must be = H2N.C12HnO4.
Combinations. — According to Gerhardt and Laurent, leucine, in
combination with acids, yields very beautifully crystallisable salts,
but they bear much more the character of conjugated acids, so that
we might regard leucine in itself as an adjunct ; against which view,
however, it may be observed that here the adjunct loses no water,
as in other cases it usually does on entering into combination, and
on separation takes up no water; these combinations are, however,
* Corapt. rend. T. 27, pp. 256-258.
t Ibid. pp. 265-278.
J Scheikund. Onderzoek. D. 5, pp. 371-377.
§ Ann. d. Ch. u. Pharm. Bd. 57, S. 128.
II Compt rend. T. 27, pp. 265-268.
f Ann. d. Ch. u. Pharm Bd. 68, S. 52-55.
LEUCINE. 145
not to be compared with the acid oxide- of-ethyl salts, since only 1
atom of acid ever combines with leucine; they are, in one respect,
most similar to those ethers which may be equally represented as
true neutral salts or conjugated acids, as, for instance, the salicylates
of oxide of methyl and of oxide of ethyl; but still more to the
compounds of the alkaloids with neutral metallic salts, such as we
treated of in our remarks on creatinine.
Nitrate of leucine } leiiconitric acid, C12H13NO4.HO.NO5, sepa-
rates in crystals on saturating moderately concentrated nitric acid
with leucine ; it has an acid but not sharp taste ; the salts decrepitate
on being heated, and some of them are crystallisabta
Hydrochlorate of leucine, C12H13NO4.HC1, also crystallises
readily.
Leucic acid, C12HUO5.HO, is not only formed in the above
manner by oxidising agents on leucine, but also, when an aqueous
solution of this substance has been for a long time exposed to the
air, it then developes a nauseous odour, and in the solution we
find the ammonia-salt of this acid. It is not crystalline, but
oleaginous, dissolves freely in alcohol and ether, and forms crystal-
Usable salts with bases.
Cahours has pointed out the analogy of leucine with the base
thialdine, discovered by Liebig and Wohler ; * both bodies contain-
ing the same equivalents of carbon, hydrogen, and nitrogen, and the
2 atoms of oxygen of the leucinebeing replaced by 2 atoms of sulphur
in thialdine. This body is produced when aldehyde-ammonia is
brought into contact with caustic ammonia and sulphuretted
hydrogen ; it forms large, colourless, rhombic tablets, which fuse
readily, but again solidify at 42°, volatilise when exposed to the
air, and can be distilled unchanged in the presence of water, but
not in the dry state ; they are slightly soluble in water, but dis-
solve readily in alcohol, and still more so in ether, and exhibit no
reaction on vegetable colours. The salts that have been examined are
C12H13NS4.HCland C12H13NS4.HO.NO5; this substance also forms
compounds perfectly analogous to those of leucine. On dry dis-
tillation with hydrated potash its behaviour is very different from
that of leucine, since it yields leucoline (otherwise called
chinoline.)
Preparation. — According to Mulder, the caseous oxide disco-
vered by Proust, and Braconnot's aposepidine, are perfectly iden-
tical with leucine. It is principally formed in the putrefaction of
* Ann. d. Ch. u. Pharm. Bd. 61, S. 1-11.
146 BASIC BODIES.
casein (Iljenko* and Bopp,f) and of gluten (Walter Crum.J) I
casein, or any other albuminous body, be fused with equal part;
of hydrated potash, and the tyrosine extracted from the dissolvec
mass in the manner already described, the leucine crystallises fron
the mother- liquid, and is readily purified by recrystallisation frorr
alcohol. If gelatin be treated in a similar manner, or boiled for i
long time in potash ley, we obtain leucine and glycine after saturating
with sulphuric acid and removing the sulphate of potash by alcohol
and as glycine is far the less soluble of the two in alcohol, the sub-
stances may be thus easily separated from one another. Leucine is
however, also formed by the action of concentrated sulphuric 01
hydrochloric acid on albuminous substances; if, for instance, flesh
be gently warmed with an equal volume of concentrated sulphuric
acid, then boiled for nine hours with double its weight of water,
the acid saturated with lime, and the residue of the filtered solution
extracted with alcohol, we obtain on evaporation impure crystals
of leucine, which must be purified by recrystallisation. On fusing
equal parts of a protein-compound and hydrated potash, but inter-
rupting the operation before the mass has become yellow, (as was
necessary for the preparation of tyrosine,) we obtain only leucine
according to the method given for tyrosine, since the latter seems
to be formed from the former by prolonged action.
Tests. — If the leucine be obtained in a state of tolerable purity,
and the properties coincide with those known to pertain to leucine,
its decomposition into valerianic acid, &c., and its behaviour with
nitric acid afford tolerably certain means of distinguishing it. An
elementary analysis might, however, be not altogether superfluous,
since it may be expected that there are a number of similar bodies
for whose discovery and detailed description we may daily look.
SARCOSINE. — C6H7NO4.
Properties. — Broad, colourless, transparent plates or right
rhombic prisms, acuminated on the ends by surfaces set perpendi-
cular on the obtuse angles, melting at 100°, and subliming unchanged
at a somewhat higher temperature. Sarcosine is extremely soluble
in water, sparingly soluble in alcohol, and insoluble in ether; the
* Ann. d. Ch. n. Phann. Bd. 58. S. 264-273.
t Ibid. Bd. 69, S. 19-37.
$ Berzelius, Lehrb. d. Ch. Bd. 9, S. 684.
SARCOSINE. 147
aqueous solution has a sweetish, sharp, faintly metallic taste, has
no action on vegetable colours, and is not affected by nitrate of
silver or corrosive sublimate ; with salts of the oxide of copper
it yields the same deep blue colour as is produced by ammonia.
According to Laurent and Gerhardt,* when fused with hydrated
potash, it yields, like leucine, hydrogen, ammonia, and carbonic
acid, but acetic in place of valerianic acid. (C6H7NO4 + 3KO +
3HO=2KO.C02 +4H + H3N + KO.C4H3O3.)
Composition. — For the discovery and analysis of this body we
are also indebted to Liebig. In accordance with the above formula
calculated by Liebig,t it consists of:
Carbon 6 atoms .... 40'45
Hydrogen 7 „ .... 7'86
Nitrogen I „ .... 1573
Oxygen 3 „ .... 35'9f>
100-00
Its atomic weight=1112'5.
It is worthy of remark that this body is isomeric with the
lactamide discovered by Pelouze, (see p. 89,) and the urethrane pre-
pared by Dumas from chloro- carbonic ether ; hence it is the more
important to ascertain the theoretical composition or the proximate
grouping of the atoms in these bodies. We might take the com-
monly accepted view that lactamide is amide with lactic acid
deprived of one atom of oxygen = H2N.C6H5O4, and according to
the hypothesis of Berzelius, regard sarcosine as a conjugated
ammonia= H3N.C6H4O4, which indeed is the most probable ; but
it is worthy of remark that lactamide, as has already been observed
in p. 89, is exhibited from lactide (a body isomeric with the adjunct
of ammonia in sarcosine) and ammonia; hence we should have
anticipated the formation of sarcosine, but not that of an amide.
The disintegration of lactamide by potash into lactic acid and
ammonia, and on the other hand that of sarcosine into acetic acid,
&c., would in itself be sufficient to show that these bodies were dif-
ferently constituted, even if their other properties did not prove it.
If, as Laurent and Gerhardt, as also Cahours,J expect, sarcosine is
actually decomposed by nitric oxide into lactic acid, then, seeing
that we are acquainted with actual lactamide, Piria's test for amide
would not prove very much, and the evidence of the amide-nature
of leucine and of glycine (which we are about to describe) would
fall to the ground.
* Compt. rend. T. 27, pp. 256-25R.
t Ann. d. Ch. u. Pharm. Bd. 62, S. 272.
t Comp. rend. T. 27, pp. 265-268.
L 2
148 BASIC BODIES.
Combinations. — Sarcosine forms very crystallisable salts with
several acids.
Hydrochlorate of sarcosine, C6H7NO4.HC1, crystallises in small,
transparent needles and granules ; its solution, like that of the
hydrochlorate of creatinine, yields no precipitate with bichloride of
platinum, but on evaporation we obtain a soluble double compound.
C6H7NO4.HCl + PtCl2 + 2HO, which crystallises in honey-
coloured octohedral segments.
Sulphate of sarcosine, C6H7NO4.HO.SO3 + Aq., crystallises
either in large, feathery plates, or in four-sided, strongly lustrous
prisms ; it is soluble in water and hot alcohol, and reddens litmus.
With acetate of copper sarcosine yields a deep, dark blue, double
salt, which crystallises in thin plates.
Preparation. — This base has not yet been found preformed in
the animal body, and is only known as a product of the decomposi-
tion of creatine, from which it is obtained in the following manner.
If a "boiling saturated solution of creatine be digested with pure
crystallised caustic baryta, in the proportion of ten parts by weight
of baryta to one part of creatine, and, after ammonia ceases to be
developed, the carbonate of baryta is removed by filtration, sarco-
sine will separate in crystals from the filtrate ; it must be purified by
the precipitation of its sulphate by alcohol, and by the decomposi-
tion of this salt by carbonate of baryta.
Tests. — The mode in which it is obtained and the properties
which we have described, afford sufficient evidence to identity their
substance.
GLYCINE.— C4H5NO4.
Properties. — This body which was formerly named sugar of gela-
tin, and has more recently been known as glycocoll, crystallises in
colourless rhombic prisms belonging to the monoclinometric system,
which craunch between the teeth, taste less sweet than cane-sugar,
and are devoid of odour ; these prisms are unaffected by exposure to
the atmosphere; at 100° they lose no water ; at 178° they melt and be-
come decomposed ; they dissolve in 4'3 parts of cold water, more dif-
ficultly in cold, but more easily in hot spirit of wine; they are almost
insoluble in absolute alcohol and quite so in ether ; these solutions
have no effect on a ray of polarised light or on vegetable colours.
Exposed to the action of the galvanic circuit glycine is very readily
decomposed, at the negative pole there being an alkaline reaction
GLYCINE. 149
from the separation of ammonia, while at the positive pole there
is an acid reaction. Glycine dissolves unchanged in the mineral
acids, and in alkaline solutions, if not too concentrated. Sulphate
of copper and potash yield with glycine a deep blue solution from
which no suboxide of copper separates on the application of heat.
Further, on boiling glycine with a concentrated solution of potash,
or with hydrated baryta or oxide of lead, the fluid developes
ammonia and assumes a brilliant 6ery red tint, which, how-
ever, disappears on the prolonged application of heat. In
this process, in addition to the ammonia, there are formed, hydro-
gen, oxalic acid, and hydrocyanic acid (Horsford). If on the
other hand it be fused with hydrated potash, it undergoes a decom-
position analogous to that of leucine and sarcosine, into formic acid,
ammonia, carbonic acid, and hydrogen gas (C4H5NO4 + 3KO.HO=
2KO.CO2 + 4H + KO.C2HO3. Gerhardt and Laurent.*) If, finally,
an aqueous solution of glycine be treated with nitrous acid or nitric
oxide, glycic acid== C4H3O5.HO (Strecker,t) is formed, nitrogen
gas being developed. Moreover, a non-nitrogenous acid, which in
all probability is identical with glycic acid, is produced by chlorine
gas and other strongly oxidising influences, as, for instance, hyper-
manganate, nitrate, and chlorate of potash. (Horsford.)
Horsford has analysed the baryta-salt, and deduced for the
acid the formula C3H3O6, but the analysis yielded less hydrogen
and more carbon than are represented by this formula ; if Hors-
ford had accidentally omitted to calculate for the organic substance
the carbonic acid retained in the baryta, the formula of the baryta-
salt would be = BaO.C4H3O5, and consequently would correspond
with that of Strecker's acid. The baryta-salt was somewhat inso-
luble, but crystallised well.
Composition. — According to the above formula which is deduced
from the coincident analyses of Laurent,{ Mulder, § and Horsford,
free glycine, dried at 100°, consists of:
Carbon 4 atoms 32-00
Hydrogen 5 „ .... 6'67
Nitrogen 1 „ .... 18'67
Oxygen 3 „ .... 42'66
lOO'OO
* Corapt. rend. T. 27, pp. 256-258.
t Ann. d. Ch. u. Phann. Bd. 68, S. 54.
i Compt. rend. T. 20, p. 789.
$ Journ. f. pr. Ch. Bd. 28, S. 294-297,
150 BASIC BODIES.
Its atomic weight= 937.5. Horsford,* who has recently made
the most complete investigation regarding this substance,, is led,
from a consideration of its compounds with acids, as well as with
certain metallic oxides, to assign to free glycine the formula
C4H4NO3.HO, regarding it as containing 1 atom of combined
water ; thus throwing doubts on the homology of leucine, sarcosine,
and glycine, maintained by Laurent and Cahours. The analogy in
the constitution of these three bodies is undeniable ; independently
of the fact that the empirical formula CnHn+1NO4 is also appli-
cable to hydrated glycine, its relation towards hydrated potash as
well as towards nitric oxide, indicates its extreme similarity to the
two other bodies. Strecker's discovery that glycic acid is produced
when glycine is decomposed by nitric oxide would lead to the
inference that glycine is the amide of glycic acid, just as leucine might
be regarded as the amide of leucic acid. Berzeliusf assumes for
glycine double the above atomic weight, and hence he writes its
empirical formula=C8H8N2O6+ 2HO ; theoretically he regards it
as an alkaloid, namely, as ammonia conjugated with a nitrogenous
body, so that its rational formula is H3N.C8H5NO6-f2HO.
Here, indeed, the homology with sarcosine entirely fails. Berze-
lius bases his view regarding the establishment of the doubled
atomic weight on the strong acidity of the salts containing 1 atom
of this acid, C4H4NO3 ; but in such weak basic bodies, little stress
should be laid on this acidity, while, moreover, the compound of
glycine with salts, and especially with chlorides, entirely supports
the atomic weight assigned by Horsford. It is chiefly from the
behaviour of glycine when acted on by the galvanic current that
Horsford is inclined to regard it as a salt-like compound, namely,
as a compound isomeric with the hypothetical anhydrous fumarate of
ammonia, since C4H4NO3=H3N + C4HO3. Probably, however,
Laurent and Strecker's hypothesis still holds good, since, in organic
nature, we much more frequently meet with amide-compounds than
with compounds of anhydrous acids with ammonia.
Combinations. — All the combinations of glycine with acids are
crystallisable, of tolerably easy solubility, and have a strong acid
reaction.
Neutral hydrochlorate of -glycine, C4H4NO3.HO.HC1, crystal-
lises in long flat prisms which are transparent and glistening, soon
deliquesce when exposed to the atmosphere, and dissolve readily
in water and in spirit of wine, but slightly in absolute alcohol.
* Ann. d. Ch. u. Pharm. Bd. 60, S. 1-57.
t Jahresber. Bd. 27, S. 655.
GLYCINE. 151
Horsford has prepared the following basic hydrochlorates : —
2C4H4NO3 + HO + HC1, rhombic prisms not affected by the
atmosphere; 2(C4H4NO3.HO) 4-HC1, which crystallises well;
3C4H4NO3 + 2HO + 2HC1 was obtained from dry glycine in
hydrochloric acid gas; in a similar way the same salt was
obtained with only 1 atom of water ; these basic salts ^ might
possibly be mixtures of two salts. Berzelius* obtained a combi-
nation of hydrochlorate of glycine and bichloride of platinum, by
extracting a mixture of these two compounds with absolute alcohol,
and then precipitating the excess of hydrochlorate of glycine from
the solution by ether; the double compound which he thus
obtained, occurred in the form of yellow, oily drops, which when
exposed to the air crystallised in yellow needles like wavellite ;
this compound is easily soluble in water and in alcohol, and con-
tains much water of crystallisation, in which respects it is very dif-
ferent from the analogous double compounds of most of the alka-
loids. If, however, free glycine be mixed with bichloride of
platinum, a compound is formed which is represented by
C4H4NO3 + 2HO + PtCl2, and occurs in black (Berzelius) or red
crystals, (Horsford.) The following compounds with sulphuric acid
were obtained by Horsford : C4H4NO3.SO3; C4H4NO3.HO.SO3;
3(C4H4NO3.HO) + 2(SO3.HO); 3C4H4NO4 + 2SO3 + HO ;
3(C4H4NO3.HO) +2SO3 + HO.
Nitrate of glycine, C4H4NO3.HO + NO5.HO., usually occurs in
the form of acicular crystals, but sometimes as large tabular crystals
of the monoclinometric system ; these crystals are unaffected by
exposure to the atmosphere and have an acid taste.
Nitrate of glycine was formerly regarded as a conjugated acid,
but these compounds which result from the union of nitrate of
glycine with bases, are true nitrates, since, as Horsford has
shown, they are directly produced on digesting the nitrates with
glycine.
Oocalate of glycine, C4H4NO3.HO.C2O3, occurs in wavellite-
like crystals which are unaffected by exposure to the atmosphere.
Acetate of glycine, C4H4NO3.HO.C4H3O3H-2HO, is crystal-
Usable, and insoluble in alcohol.
Horsford further observed that glycine formed crystallisable
compounds with many salts, (similar to that which it forms with
bichloride of platinum,) most of which contain 1 atom of glycine to
1 atom of the salt. With bases, especially with hydrated baryta
and potash, crystallisable compounds are also formed. Protoxide
* Jahresber. Bd. 27, S. 658.
152 BASIC BODIES.
of copper- ffly cine was obtained by Boussingault, and found to be
represented by the formula C4H4NO3.CuO ; Horsford found 1
atom of water, in this compound which crystallised in brilliant blue
needles. Similarly to the hydrated oxide of copper, the hydrated
oxide of lead, and oxide of silver, may be dissolved in an aqueous
solution of pure glycine, and the compound after being precipitated
by the addition of alcohol, may be obtained in a crystalline form.
The lead-compound crystallises in prisms, the silver-compound in
wart-like masses.
There is much regarding these compounds that still remains to
be investigated ; we have, however, entered more fully into the
subject of their composition than we should otherwise have
done, because it is on this point that we must form our judgment
respecting the constitution of glycine, and decide in favour of one
or the other of the above hypotheses.
Preparation. — Glycine has not yet been found in an isolated state
in the animal body : there is, however, reason for believing that this
substance is contained preformed as an adjunct in certain known
animal acids ; moreover, the relations of this body towards acids,
bases, and salts, (which we have already described,) support this
view ; while, in many cases with which we shall become acquainted
as we proceed, it is more than probable that glyciue is formed on the
separation of the acid from its proper adjunct, as glycerine is pro-
duced in the saponification of the hypothetical oxide of lipyl. As
instances, we may mention hippuric and glycocholic acids ; and
when we treat of these acids, we shall enter into the physiological
relations and the genesis of glycine.
It has long been known that glycine is a product of the decom-
position of animal substances, especially of gelatin, by the action
of concentrated mineral acids or caustic alkalies. The following is
the best method of obtaining it from gelatin. If the gelatin be
boiled with a strong solution of potash till ammonia ceases to be
developed, it becomes entirely decomposed into a mixture of 4
parts of glycine and 1 of leucine ; the fluid neutralised with sulphuric
acid is evaporated to dryness, and the residue extracted with spirit
of wine which dissolves both the glycine and the leucine ; the glycine
as being the least soluble in alcohol, crystallises first, while the
leucine subsequently crystallises; by recrystallisation and treat-
ment with a little animal charcoal, the glycine can be obtained per-
fectly pure.
The method of obtaining glycine from hippuric acid is even
simpler ; for if 1 part of this acid be boiled for half an hour with
GLYCINE. 153
4 parts of concentrated hydrochloric acid, it becomes decomposed
into glycine and benzoic acid ; on the addition of water to the boiled
fluid, a great part of the benzoic acid separates and must be
removed by nitration ; the clear fluid is then evaporated nearly to
dryness, and the residue (hydrochlorate of glycine) decomposed with
caustic ammonia ; finally the glycine is precipitated by, and washed
with, absolute alcohol.
Tests. — When the substance suspected to be glycine is separated
as much as possible from all other matters, the most striking of the
properties by which it may be distinguished are its relation towards
a hot solution of potash, its difficult solubility in alcohol, and the
blue solution which it yields with caustic potash and sulphate of
copper, without any separation of the suboxide; and if, further,
we study its power of combining with acids as well as with baryta,
oxide of copper, oxide of lead, &c., and forming crystallisable bodies,
there can hardly remain any doubt regarding its nature. It may
easily be distinguished from leucine by the form of its crystals and
by its becoming decomposed on exposure to heat.
According to Horsford the quantities of urea and uric acid in
the urine are increased after the ingestion of glycine, but no
unchanged glycine is found in the urine.
UREA.— C2H4N2O2.
Chemical Relations.
Properties. — Urea crystallises, when it separates rapidly, in
white, silky, glistening needles; but when the crystallisation is
effected slowly, in flat, colourless, four-sided prisms full of cavities
and appearing to be formed of numerous parallel crystalline lamellae:
at the ends the prism is terminated by one or two oblique surfaces.
According to C. Schmidt*, these forms do not pertain to the mono-
clinometric system, but rather to a hemihedral form belonging to
the rhombic system, and bounded by parallel surfaces. These
crystals contain no water. Urea is devoid of smell, of a saltish,
cooling taste, and is unaffected by exposure to the atmosphere;
it dissolves readily in its own weight of water, giving rise to a
marked evolution of heat ; in hot water it dissolves in every
proportion ; it is also soluble in 4 or 5 parts of cold and in
2 parts of warm alcohol ; it is insoluble in ether, if anhy-
drous and devoid of alcohol, and in etherial oil, and exerts no
* Entwurf u. s. w. S. 41.
154 BASIC BODIES.
action on vegetable colours. Its concentrated aqueous solution is
not changed by boiling or by long keeping, but a dilute solution
suffers change.
At about 120° urea fuses without suffering change, but at a
little above that temperature it begins to develope ammonia, to
become pulpy, and to change into cyanuric acid (3C2H4N2O2=
3H3N + C6HN3O4.2HO) ; when rapidly heated it also yields
cyanic acid which is produced from the previously formed cyanuric
acid (C6HN3O4.2HO=3C2NO.HO). On heating urea very slowly,
it becomes converted (according to Wohler and Liebig*) into a
glistening white body, insoluble in water but soluble in acids and
alkalies, carbonic acid and ammonia being evolved during the
process. This body=C4H6N4O2, for 3C2H4N2O2- (2CO2 +
2H3N)=zC4H6N4O2. If, on the other hand, urea be kept for some
time in a state of fusion at from 150° to 170°, not only are the
above-named compounds formed, but also (according to Wiede-
mannf) the biuret, C4H5N3O4, whose production is explained by
the equation, 2C2H4N2O2-H3N=C4H5N3O4.
If chloride of sodium or hydrochlorate of ammonia be present
in a solution of urea, the former will crystallise in octohedra and
the latter in cubes ; if, however, the crystals be again dissolved in
water, and allowed to crystallise anew, they separate in the ordinary
manner, namely, the chloride of sodium into cubes, and the
hydrochlorate of ammonia into octohedra or feathery forms.
Urea will combine only with certain acids and a few bases;
neither the metallic salts, tannic acid, nor any other re-agent, can
precipitate it from its solutions.
On heating a concentrated solution of urea with nitrate of
silver, cyanate of silver separates, while nitrate of ammonia re-
mains in solution. (C2H4N2O2 + AgO.NO5 = AgO.C2NO +
H3N.HO.NO5).
By nitrous acid urea is decomposed into nitrogen, water, and
carbonic acid; (C2H4N2O2 + 2HO + 2NO3=6HO + 2CO2 + 4N ;)
by chlorine into nitrogen, carbonic acid, and hydrochloric acid ;
(C2H4N202 + 2 HO + 6C1 ^ 6HC1 + 2C02 + 2N.)
On boiling urea either with strong mineral acids or with caustic
alkalies, it takes up 2 atoms of water and is decomposed into
ammonia and carbonic acid (C2H4N2O2 + 2HO = 2H3N + 2CO2.)
If organic matters, either putrefying or capable of undergoing
putrefaction, be mixed with an aqueous solution of urea, the latter
is soon converted into carbonic acid and ammonia.
t Ann. d. Ch. u. Pharm. Bd 54, S. 3? I.
J Journ. f. pr. Ch. Bd. 43, S. 271-280.
UREA. 155
Composition. — According to the above formula urea consists
of:
Carbon 2 atoms .... 20'000
Hydrogen 4 „ .... 6'666
Nitrogen 2 „ .... 46-667
Oxygen 2 „ .... 26'667
lOO'OOO
Its atomic weight— 750*0. Although there have been many
discussions regarding the rational constitution of urea, much still
remains to be cleared up. Dumas, after his discovery of oxamide,
started the hypothesis, that urea is an amide of carbonic acid, since
2H3N + 2CO2 - 2HO= C2H4N2O2, and the relation of urea towards
nitrous acid, and its ready decomposition into carbonic acid and
ammonia, seem to support this view. But Berzelius justly points
out the analogy, in their combining relations with acids, between
the alkaloids and urea, and regards the latter as ammonia conjugated
with a nitrogenous body which he names urenoxide, so that the
rational formula for urea would be :±=H3N.C2HNO2. Independ-
ently of the analogy between the salts of urea with those of the
alkaloids, the following consideration mainly supports this view :
cyanate of ammonia =H3N.HO.C2NO, is convertible, as we shall
presently see, into urea ; the grouping of the atoms in urea must
be perfectly different from that in this salt, since urea has lost all
the properties of a salt. But we know that free hydrated cyanic
acid is spontaneously converted by a transposition of its atoms
into the so-called cyame}ide=Ct2HNO2 ; now, nothing is more
obvious than to assume that in the combination with ammonia
the cyanic acid becomes incorporated with the water of the am-
monia-salt, in the same manner as in the free state, and that this
cyamelide, if not identical with, is highly analogous to the urenoxide
of Berzelius, and thus forms the adjunct of the ammonia in urea.
Probably, also, the existence of the biuret might be made available
in the support of this hypothesis, since the most simple view of
the biuret is to regard it as consisting of 2 atoms of urenoxide and
1 atom of ammonia, for C4H5N3O4=H3N + 2C2HNO2.
Combinations.— It is only with some acids that urea has a
tendency to combine. Cap and Henry* fancied that they had
prepared compounds of urea with sulphuric, lactic, hippuric, and
uric acids, but the existence of those compounds is very correctly
* Journal de Pharra. T. 25, p. 133.
156 BASIC BODIES.
doubted. We know with certainty only three salts of urea, namely,
the hydrochlorate, the nitrate, and the oxalate.
Hydrochlorate of urea, C2H4N2O2.HC1, was simultaneously
obtained by Erdmann* and Pelouzef. They prepared it by passing
a stream of dry hydrochloric acid gas over urea. The compound is
white and hard, and crystallises in plates ; it attracts water from the
atmosphere, arid from this water the hydrochloric acid escapes by
evaporation, and pure urea crystallises ; in water the salt becomes
rapidly decomposed into hydrochloric acid and urea.
Nitrate of urea, C2H4N2O2.HO.NO5 (according to the analysis
of Regnault, which has been repeated by MarchandJ, Heintz§,
Fehling,|| and Werther,^[) is formed by mixing a concentrated
solution of urea with an excess of nitric acid ; the compound at
once separates (on cooling, almost perfectly,) in large nacreous,
shining scales, or in small, glistening, white plates ; on examining
under the microscope the contact of the urea and the nitric acid,
we first observe very obtuse rhombic octohedra, at whose acute
angles ( — 82°) more particles are gradually accumulated, so that
they appear to increase in size, and the octohedra become
converted into rhombic tablets, or form hexagonal tablets (whose
opposite acute angles likewise are 82°) ; these crystals always occur
isolated, or in uniformly superimposed masses (C. Schmidt**).
This salt is uninfluenced by the atmosphere, has an acid taste, is
more soluble in pure water than in water containing nitric acid,
and dissolves in alcohol, producing considerable depression of
temperature ; on evaporating its aqueous solution, the salt very
readily effloresces ; it reddens litmus ; a concentrated solution is
not affected by boiling, but a dilute solution is converted into
carbonic acid, carbonate of ammonia, water, and nitrous oxide
(C2H4N202.HO.N05=H3N + 2C02 + 2HO + 2NO). On heating
dried nitrate of urea rapidly, it decrepitates, but on heating it slowly
to 140°, it becomes decomposed into carbonic acid, nitrous oxide,
urea, and nitrate of ammonia. If the solution of this salt be not
too dilute, a solution of oxalic acid precipitates oxalate of urea.
Oxalate of urea, C2H4N2O2.HO.C2O3 (sometimes, according to
* Journ. f. pr. Ch. Bd. 25, S. 506.
•*• Ann. de Ch. et de Phys. 3 Sdr. T. 6, p. 63.
t Journ. f. pr. Ch. Bd. 35, S. 481.
§ Pogg. Ann. Bd. 66, S. 114-122.
|| Ann. d. Ch. u. Pharm. Bd. 55, S. 249.
11 Journ. f. pr. Ch. Bd. 35, S. 51-66.
** Entwurf u. s. w. S. 42-45.
UREA. 157
March and, taking up 2 atoms of water of crystallisation) is also
obtained by the direct union of the constituent parts, and forms,
as far as the unaided eye can perceive, long thin plates or prisms ;
under the microscope it is usually seen in hexagonal plates, similar
to those of nitrate of urea, interspersed occasionally with four-sided
prisms with planes of truncation proceeding from the broader sides
of the rectangular section. The form of this oxalate, like that of
the nitrate of urea, belongs to the monoclinometric system. This
salt has an acid taste, dissolves at 16° in 22*9 parts of water and in
62*5 of alcohol ; it is precipitated from its aqueous solution by
an excess of oxalic acid. On exposure to heat it is decomposed
into carbonate of ammonia and cyanuric acid.
Like glycine, urea also unites with salts, which hold it in such
firm combination, that not only does no decomposition ensue when
their solutions are boiled, but even oxalic and nitric acids fail to
separate the urea from some of their compounds (Werther*).
On mixing concentrated solutions of urea and nitrate of silver,
there are formed thick prisms with a rhombic base which are readily
soluble in water and alcohol =C2H4N2O.2.AgO.NO5. On the
addition of a solution of soda to the solution of these crystals, a
yellow precipitate is obtained = 5 AgO + 2C2H4N2O2. Besides
these, Werther has also obtained the following combinations: —
C2H4N2O2 + 2AgO.NO5; CaO.NO5 + 3C2H4N2O2; MgO.NO5 +
2C2H4N2O2; NaO.NO5 + C2H4N2O2 + 2HO; NaCl + C2H4N2O2 +
3HO, crystallising in deliquescent rhombic prisms ; 2HgCl +
C2H4N2O2, flat prisms glistening like mother-of-pearl. Urea can-
not be separated from the solutions of these compounds either by
nitric or oxalic acid.
Products of its metamorphosis. — Biuret, C4H5N3O4, is, as we
have already mentioned, the chief product (together with cyanuric
acid) which is obtained on heating pure urea or its nitrate to a tem-
perature of 152° — 1700 ; the cyanuric acid is precipitated by basic
acetate of lead from the aqueous solution of the fused product, and
the excess of lead removed by sulphuretted hydrogen ; the biuret
is then obtained by the evaporation of the solution. It forms small
crystal which dissolves readily in water, and still more readily in
alcohol ; it exerts no action on vegetable colours, does not combine
with bases, and dissolves unchanged in concentrated sulphuric and
nitric acids ; with sulphate of copper and potash it yields a red
solution. Its rational formula = H3N + 2C2HNO2.
Preparation. — Urea not only occurs preformed in the animal
* Journ. f. pr .Ch. Bd. 35, S. 51-66.
158 BASIC BODIES.
body, but can also be artificially prepared. When Wohler made
the beautiful discovery that urea was formed by the union of cyanic
acid and ammonia, the physiologists of that day who were still
imbued with ideas of vital forces, were astonished that a matter
which appeared only capable of formation by organic force, could
also be formed by the hand of the chemist from so-called inorganic
matters. The astonishment of the physiologists has, however,
gradually ceased, not only because they have for the most part
shaken off their adherence to irrational vital forces, but also
because since that time many other substances have been artificially
produced, which are identical with, or at all events most similar to
previously known organic matters. We have learned to regard
urea as one of the most common products of decomposition, not
only of natural organic bodies, but also of artificial substances. It
would occupy too much of our present space, were we to enumerate
all the cases in which urea occurs as a product of the decomposition
of a nitrogenous substance ; we will here only mention its formation
on the union of cyanogen and water, of fulminate of copper and
hydrosulphate of ammonia (Gladstone*), in the decomposition of
allantoine by nitric acid, of creatine by the alkalies, of alloxan by a
boiling solution of acetate of lead, &c.
There are various ways in which urea may be obtained from
urine, but it is chiefly effected by nitric or oxalic acid ; it is more
advisable to use the alcoholic extract of urine than the residue left
by its direct evaporation ; if nitric acid be used, the nitrate of urea
must be exposed to due pressure between tiles and filtering paper,
and after it has been dissolved in a little water, must be decom-
posed with carbonate of lead or of baryta ; crystals of nitrate of
lead or baryta soon separate from the filtered fluid, which must be
evaporated and extracted with alcohol ; this alcoholic solution may
contain, in addition to urea, a little nitrate of lead, but it takes up
no nitrate of baryta; when baryta has been used, the alcoholic
solution must be decolorised with animal charcoal ; when the salt
of lead has been used, the solution is often perfectly colourless
after the precipitation of the metal by sulphuretted hydrogen. The
urea separates in a crystalline form, on the evaporation of the
alcoholic solution.
In order to prepare urea from cyanate of ammonia, we raise a
mixture of 28 parts of ferrocyanide of potassium, from which all the
water has been expelled, and 14 parts of well-dried, good peroxide
of manganese, to a faint red heat; (even when the mixture is suffi-
* Ann. d. Ch. u. Phann. Bd. 6fi, S. 1-5.
UREA. 159
ciently heated at a single spot, the whole mass assumes a phos-
phorescent appearance ;) from this glowing residue the cyanate of
potash which has been formed must be extracted with cold water,
and mixed with 20J parts of dry sulphate of ammonia ; most of
the sulphate of potash separates in a crystalline form, while the
cyanate of ammonia, now converted into urea, remains in solution.
The remaining sulphate is separated by crystallisation, but more
perfectly by alcohol.
Tests. — Urea may generally be very easily recognised by its
properties, especially by its behaviour towards nitric and oxalic
acids ; but when we have to discover very minute quantities of this
substance in albuminous fluids, it is often very difficult to determine
its presence with scientific precision. It is in alcoholic extracts
that we must always seek for urea, but before we proceed to search
for it, there are several precautionary measures to be adopted, the
neglect of which would render our attempt to discover it futile.
In the first place, in reference to the presence of albuminous
substances, if we wish to discover small quantities of urea in
albuminous fluids, we must not be satisfied with the removal of the
albumen by simple boiling ; since by the coagulation of the albumen
the fluid becomes more alkaline, and might, during evaporation,
induce a decomposition of the urea ; moreover, all albuminous
matter is not precipitated by boiling, but a portion remains dissolved
by the alkali, and is taken up in the alcoholic extract ; on evapo-
ration this albumen undergoes a change which probably cooperates
with the alkali in inducing the decomposition of the urea. This may
explain how it was that Marchand could only recover 0'2 of a gramme
of urea from a mixture of 200 grammes of serum and 1 gramme
of urea. Hence, before boiling the albuminous fluid, we must add
a few drops of acetic acid, so as to give it a slightly acid reaction,
whereby not only is the alkalescence of the fluid prevented, but a
much more perfect separation of the coagulable matters is effected.
If the residue of the fluid from which the coagulated matters have
been filtered be extracted with cold alcohol, and the solution rapidly
evaporated, so as to cause the chloride of sodium (taken up by
the cold alcohol) to separate as much as possible in crystals, on then
bringing a drop of the mother-liquid in contact with nitric acid
under the microscope, we shall observe the commencement of the
formation of the rhombic octohedra, and the hexagonal tablets, in
which, if the investigation is to be unquestionable, the acute angles
(=82°) must be always measured. After the determination of the
nitrate we may also obtain the oxalate, and submit it to microscopic
160 BASIC BODIES.
examination. A good crystallometric determination yields, how-
ever, the same certainty as an elementary analysis which, in these
cases, would never, or extremely seldom, be possible.
Formerly the presence of small quantities of urea was supposed
to be established when chloride of sodium crystallised in the octo-
hedralform; but independently of the circumstance that other sub-
stances besides urea may induce a similar action on the form of the
crystals of this salt, it must be borne in mind that chloride of
sodium, when we trace the formation of its crystals under the
microscope, presents itself in combinations of the regular system,
with a complexity varying with the minuteness of the crystals.
This occurs when we allow pure chloride of sodium to crystallise ;
and it is still more the case when organic matters are mixed with
the solution. I am acquainted with no other substance of the
regular system which presents such uncommon crystals under the
microscope as chloride of sodium. We need only expose the alco-
holic extract of any animal fluid to spontaneous evaporation, in
order to recognise with the naked eye, in the greater crystals, the
combinations which we have perceived on examining the crystalli-
sation of a solution of pure salt under the microscope.
In order to determine the amount of urea in urine, most ana-
lysts have followed the method proposed by Mitscherlich,* and have
availed themselves of the insolubility of the nitrate. There are
several causes of error in this method which cannot be altogether
avoided, but with due care may be made very inconsiderable.
They chiefly consist in the imperfect insolubility of this salt,
and on the adherence of the so-called extractive matters to it ; if,
however, we use an excess of nitric acid for the purpose of sepa-
rating the urea, cool the fluid artificially, filter after some time,
rinse the salt with cold nitric acid, and, after it has been submitted
to pressure, dry it at a temperature not exceeding 110°, we shall not
have so great a loss of urea as Heintzf maintains must always occur
in adopting this method ; but in relation to accuracy, the results fall
far short of those obtained in the determination of mineral sub-
stances. The idea occurred almost simultaneously to RagskyJ and
Heintz§ that the urea in urine might be determined quantitatively
by its decomposition by sulphuric acid. Both investigators have
satisfied themselves that the so-called extractive matters of the
* Pogg. Ann. Bd. 31, S. 303.
t Ibid. Bd. 66, S. 114-160.
t Ann. d. Ch. u. Pharm. Bd. 56, S. 29-34.
§ Pogg. Ann. Bd. 68, 8. 393-410.
UREA. 161
urine do not modify the result of the experiment ; the essential
point in this method, which is somewhat more complicated, but
doubtless more accurate than that by nitric acid, consists in our
determining, by means of bichloride of platinum, the amount of
potash and ammonia (if the latter be present) in a specimen of
urine, and in our then treating a second specimen with sul-
phuric acid, and gradually heating it to 180° or 200°, or as long
as any effervescence continues ; the fluid is then filtered, and the
amount of ammonia determined by bichloride of platinum ; deduct-
ing from the precipitate thus obtained that which was yielded by the
other specimen (corresponding to the potassio-chloride of platinum,)
we can easily calculate the amount of urea from the ammonio-
chloride of platinum, or from the platinum itself left on the inci-
neration of the residue.
A still better method, by which urea may be determined quan-
titatively, although not perfectly free from error, has been given by
Millon.* It is based on the fact that urea is decomposed by nitrous
acid into nitrogen and carbonic acid; to effect this object a solu-
tion of nitrite of suboxide of mercury is dissolved in nitric acid,
and added to a weighed portion of urine ; on warming this mixture
there is a development of nitrogen and carbonic acid, which latter
gas is caught in a potash-apparatus and weighed. Some of the
extractive matters might yield carbonic acid, even if none of the
other constituents of the urine did so ; this, however, is denied by
Millon. It must also be recollected that the urine always contains
free carbonic acid in solution.
Finally, a method has been proposed by R. Bunsenf for the
quantitative determination of urea, founded on the property that its
solutions undergo decomposition in closed vessels at a temperature of
from 120° to 240°; the carbonic acid which is thus formed is com-
bined with baryta, and the amount of urea is calculated from that
of carbonate of baryta.
Physiological Relations.
Occurrence. — Urea is one of the principal products of excretion
of the kidneys : hence it chiefly occurs in the urine. Although it
constitutes the greatest part of the solid constituents of the urine,
it is contained in the liquid urine in very variable quantities in con-
sequence of the physiological relations, in accordance with which
the amount of water in the urinary secretion varies in so extraor-
* Compt. rend. T. 26, pp. 119-121.
t Ann. d. Ch. u, Pharm. Bd. 65, S. 375-387.
M
162 BASIC BODIES.
dinary a degree. In order to convince ourselves of the quantity of
urea excreted in the urine, we must examine the urine collected in
a definite interval in relation to its proportion of urea. As, in the
consideration of " Urine/' we shall return to this subject, we will
here only remark that the urine of a healthy man contains generally
from 2-5 to 3'2% of urea, that the ratio of urea to the other solid
constituents is aboutr=9 : 11 or *J : 9, and that a healthy man in
twenty-four hours excretes from 22 to 36 grammes.
My experiments* show that the amount of urea which is
excreted is extremely dependent on the nature of the food which
has been previously taken. On a purely animal diet, or on food
very rich in nitrogen, there were often two-fifths more urea
excreted than on a mixed diet ; while, on a mixed diet, there was
almost one-third more than on a purely vegetable diet ; while,
finally, on a non-nitrogenous diet, the amount of urea was less than
half the quantity excreted during an ordinary mixed diet.
In my experiments on the influence of various kinds of food on
the animal organism, and especially on the urine, I arrived at the
above results, which in mean numbers may be expressed as follows:
on a well regulated mixed diet I discharged, in 24 hours, 32*5
grammes of urea, (I give the mean of 15 observations) ; on a
purely animal diet 53*2 grammes (the mean of 12 observations);
on a vegetable diet 22*5 grammes (the mean of 12 observations) ;
and on a non-nitrogenous diet 15*4 grammes (the mean of 3 ob-
servations).
It is especially worthy of remark, that the augmentation of the
urea in the urine occurs very soon after the use of highly nitro-
genous food, and that in such cases often five-sixths of the nitro-
gen taken in the food in 24 hours are eliminated as urea by the
kidneys.
When I took 32 boiled hens' eggs daily, I consumed in them
about 30*16 grammes of nitrogen, but in the above-mentioned
quantity of urea I discharged only about 25 grammes in 24 hours.
On the morning following the day on which I had taken only flesh
or eggs, the urine was so rich in urea that immediately on the
addition of nitric acid it yielded a copious precipitate of nitrate of
urea ; hence Prout's assertion may be correct in reference to
England, that freshly passed urine often gives a precipitate of
nitrate of urea immediately on the addition of nitric acid, although
on the continent, where less animal food is taken, no one, so far as
I know, has made a similar observation : and hence also the urine
* Journ. f . pr. Ch. Bd. 25, S. 22-29, and Bd. 27, S. 257-274.
UREA. 163
of carnivorous animals is very rich in urea (Vauquelin*, Hieronymif,
Tiedemann and GmelinJ,) while the urine of graminivorous
animals is comparatively poor in this constituent (Boussingault§).
Notwithstanding the considerable influence which the nature of
the food exerts on the quantity of urea excreted by the kidneys,
there is as much urea in the urine after prolonged abstinence from
all food (after a rigid fast of 24 hours) as after the use of perfectly
non-nitrogenous food.
Lassaigne|| found urea in the urine of a madman who had taken
no food for 14 days ; and we observe something similar almost
daily in patients with typhus fever and other diseases, who for 14
days or more have taken nothing but an oily emulsion or an emol-
lient decoction, and yet always pass urine containing urea, and
often rich in it. After living for three days on a perfectly non-
nitrogenous diet, I still found, in the morning urine, more than 1 g-
of urea.
Strong exercise of the bodily powers causes an increased
excretion of urea.
While, from numerous observations, I ascertained that, during
my ordinary habits of life, I discharged about 32 grammes in 24
hours, I found that after strong bodily exercise, I, on one occasion,
passed 36 grammes, and on another 37'4 grammes in 24 hours.
The urine of women and children contains, according to
Becquerel,1f less urea than that of men.
Becquerel found the ratio of urea excreted in 24 hours by
women, to that excreted by men=15'582 : 17*537.
Like Becquerel, I have failed in establishing the fact that there
is an augmentation of urea in certain forms of disease, although
English physicians have shown an inclination to assume an urea-
diathesis.
Although we are, a priori, prejudiced against all these diatheses
which English physicians have attempted to establish on certain
urinary analyses, (see p. 473) we must especially protest against such
an urea- diathesis ; for how does this indicate a morbid process ? The
nature of this or that disease does not depend on an increased
excretion of urea, which is only a consequence of another process.
* Schweigg. Journ. Bd. 3, S. 175.
f Journ. de Ch. et de Pharm. T. 3, p. 322.
J Verdauung u. s. w. Bd. 2, S. 4.
§ Ann. de Chim. et de Phys. 3 Ser. T. 15, pp. 97-1 U.
|| Journ. de Chim. me'd. T. 1, p. 272.
1f Seme'iotique des Urines &c. Paris, 1841, p. 34.
M 2
164 BASIC BODIES.
The urea is possibly only excreted in increased quantity when
material for its formation is sufficiently supplied ; now if poly-
phagia be not combined with this urea-diathesis,, the source of the
urea must be sought in the waste or consumption of the nitro-
genous tissues ; this is not based on the tendency of the tissues to
be converted into urea, but depends on other processes which
accompany many morbid processes. In diseases where such a
consumption actually occurs, I have never found the urea passed
in twenty-four hours exceed the normal quantity, and have very
often found it far beneath the average.
A diminution in the amount of urea excreted during disease
in twenty-four hours is very frequently observed: this, however,
in most cases, may be dependent on the low diet.
Becquerel has made the best observations in reference to this
subject ; it appears, however, to us, that such investigations may
rather serve to enable us to form an opinion of the morbid process
in a special case, than to establish general rules regarding the di-
minution of the urea in the urine in certain classes of disease.
It is by careful observation of the urine in individual cases,
and not by drawing general inferences, that we can make these
examinations useful.
Many chemists have long sought in vain to detect urea in nor-
mal blood ; Simon believed that he had found it in calves5 blood,
and Strahl and Lieberkiihn,* and recently Garrod,f maintain that
they have detected it in human blood : without doubting the cor-
rectness of the observations of these chemists, it is only recently
that I have been able to convince myself with precision by deci-
sive experiments that urea is present in normal blood.
In my investigations regarding the amount of alkaline carbon-
ates contained in the blood, I often operated on four or six pounds
of fresh ox -blood : in order to avoid the decomposition and re-ar-
rangement of the soluble mineral constituents of blood which always
occur in ordinary incineration, I first separated the coagulable
matters of the blood, after diluting it with four times its volume of
water, and neutralising it with acetic acid ; the residue left by the
evaporation of the fluid, from which the coagulated albumen had
been removed by filtration, and the films that formed during
evaporation had been skimmed off, was treated with absolute
alcohol, and then, in the manner we have already described,
examined for urea ; the measurements of the angles of the crystals
* Preuss. Vereins-Zeit. No. 47, 1847.
t Medico-Chirurgical Transactions. Vol. 31, p. 83.
UREA. 165
both of nitrate and oxalate of urea, which were made according to
Schmidt's method under the microscope, exactly coincided with
the measurements given by Schmidt for these crystals.
StrahPs method, which I have repeatedly tried, and which con-
sists in the extraction of the urea from four ounces of blood by the
addition of alcohol, and in diagnosing the existence of urea from
the crystallisation of the oxalate, does not appear to me to be
sufficiently conclusive ; for, in the first place, the quantity of urea
in four ounces is very small, even for microscopic observation ;
secondly, alcohol extracts from the blood certain organic matters
which partly separate on evaporation ; thirdly, oxalic acid always
precipitates mineral matters which render the object indistinct ;
and, finally, if its crystals be not crystallographically determined,
it is often very hard to distinguish oxalate of urea from crystallised
alkaline oxalates ; all of which reasons led me to think that Strahl's
experiments required to be confirmed in some other manner.
Urea increases abnormally in the blood of persons suffering
from degeneration of the kidneys,wherebythefunction of those organs
is destroyed. Under the general term of Bright' *s disease, we usually
include the various conditions in which there is a mechanical disturb-
ance of the urinary secretion, however different the histological alter-
ation in the renal tissue may be ; and we use the word uraemia to
indicate the group of symptoms which depend on the retention of
urea in the blood.
Christison* was the first who recognised the occurrence of urea
infcthe blood in this disease. In any other disease, urea is only
rarely found in the blood ; hence, it is by no means requisite that
the symptoms of ureernia should be combined with the presence of
urea in the blood, since every physician knows how often Bright's
disease occurs without this group of symptoms ; it is only when
the urine is very scanty that these symptoms occur: that of vomiting
is not by any means a necessary one, as is generally supposed.
Moreover urea has been found by Raineyt and Marchand, in the
blood of cholera patients, but only when there was ischuria ; and
GarrodJ thinks that he has found it in the blood of a gouty
patient.
Rees§ and Wohler|| have detected urea in Liquor Amnii, which,
* On granular degeneration of the kidneys, &c. Edinburgh, 1839, p. 20.
t Lond. Med. Gaz. Vol. 23, p. 518.
J Op. cit.
§ Lond. Med. Gaz. Vol. 23, p. 462.
|| Ann. d. Ch. u. Pharm. Bd. 58, S. 98.
166 BASIC BODIES.
they are convinced, contained none of the mother's urine. Mack*
and Schererf however, failed in detecting any urea in this
fluid.
[ReesJ has frequently met with small quantities of urea in milk.
— G. E. D.]
Millon§ found urea in the vitreous and aqueous humours of the
eye, and W6hler|| confirms the fact.
Urea has very often been found in dropsical exudations.
I have never been able to discover urea in serous exudations,
unless at the same time there was disease of the kidneys ; previous
statements may possibly only have reference to dropsical fluids
depending on Bright's disease, and not to those accumulations of
fluid which arise from enlargement of the liver.
In Bright's disease, urea is found in all the serous fluids ; thus
Schlossberger^j" once found it in an aqueous effusion in the cerebral
ventricles.
The matters vomited in ureemia not unfrequently contain urea.
(Nysten** and others).
Wrightft has found urea in the saliva of a patient with Bright's
disease, and also in that of a dog poisoned with corrosive
sublimate.
Urea has been found by O. B. Ktihn in a biliary concretion;
and Strahl and Lieberkiihn have recently detected it in the bile
after the extirpation of the kidneys.
Origin. — Physiologists were long undecided regarding the seat
of the actual formation of urea. Since urea had not been dis-
covered in normal blood, many believed that they must adhere to
the old view, that the excreta are formed in the excreting organs
from the constituents of the blood, and that urea is thus first
produced in the kidneys. They accounted for the circumstance
that urea is, in certain morbid conditions, sometimes found in the
blood and other fluids, by assuming that it was then resorbed from
the kidneys or the urinary bladder. To overthrow this opinion,
Prevost and Dumas, JJ and subsequently Gmelin, Tiedemann,
* Arch. f. phys. u. pathol. Ch. u. Mikr. Bd. 2, S. 218-224.
t Zeitschr. f. wissenschaftl. Zoologie. Bd. 1, S. 88-92.
I Guy's Hospital Reports. New series. Vol. 1, p. 328.
§ Compt.rend. T. 26, p. 121.
II Ann. d. Ch. u. Phann. Bd. 66, S. 128.
IF Arch. f. phys. Heilk. Bd. 1, S. 43.
** Joum. de Chim. med. 1837. p. 257.
tt Lancet, 1844. Vol. 1, p. 150.
W Ann. de Chim. et de Phys. T. 23, p. 90.
UREA. 167
and Mitscherlich,* extirpated the kidneys of animals, and then
found no inconsiderable quantity of urea in the blood ; indeed,
Marcharidf induced all the symptoms of uraemia in a dog by the
mere ligature of the renal nerves, and was able to recognise the
presence of urea with the greatest certainty, not only in the blood,
but also in the vomited matters.
The investigations of Marchand have thrown much light upon this
subject; this accurate observer could only recover 0'2 of a gramme
of urea from 200 grammes of serum to which 1 gramme of urea had
been added ; he shows that, even if the urea were only separated from
the blood at the end of each successive hour, it could not have
accumulated in such quantity as to have been discoverable by the
present mode of investigation. The following consideration will
give us an idea of the small quantity of urea which, according to
Marchand's hypothesis, at the most can accumulate in the blood in
one hour. From the experiments of Ed. Weber, which I have in
part confirmed, we may assume that there are in an adult man at
most 6 or 7 kilogrammes [16 to 19 pounds] of circulating blood;
now, if in 24 hours 30 grammes of urea are discharged, at most
only 1*25 grammes could accumulate in one hour in the whole
mass of the blood, so that only 0*021^ could be contained in it ;
this minute quantity can, however, as we have already shown,
only be detected in operating on very large masses of blood, and
by the aid of the microscope. Hence it is easy to understand
why, during my experiments with an animal diet, while the urine
was loaded with urea, none of this substance could be discovered
in the blood.
If it be now established, that the urea is not primarily formed
in the kidneys, the question still remains to be answered, whether
it is produced in the circulating blood or in the individual living
organs, (as for instance, the muscles,) and from what materials it is
principally formed. In the present state of our knowledge, we may
answer, that the urea is formed in the blood, and that it is produced
from materials that have become effete, the detritus of tissues, as well
as from unserviceable and superfluous nitrogenous substances in the
blood. No animal tissue presents such vital activity, is so much
used, and so rapidly worn out, as muscular tissue ; it is in this tissue
that the metamorphosis of matter proceeds most rapidly and
abundantly, and yet, in the large quantities of muscular fluid on
which Liebig worked, he could detect no trace of urea, although he
* Pogg. Ann. Bd.31, S. 303.
t Journ. f. pr. Ch. Bd. 11, S. 149.
168 BASIC BODIES.
found substances from which he could produce urea artificially.
We must therefore assume that these substances, as creatine and
probably inosic acid, are decomposed in the blood, by the action
of the alkalies and of free oxygen, into urea and other matters to
be excreted. Moreover, my experiments showing that the super-
fluous nitrogenous food which enters the blood, and the fact that
caffeine, glycine, (Horsford) uric acid, and alloxantin, (Wohler and
Frerichs*) soon after they have been taken, perceptibly increase the
amount of urea in the urine, support the view that urea is formed in
the blood. It is impossible to suppose that this nitrogenous food
is first converted into tissue, and subsequently into urea^ &c., for
we cannot think that a process occurs here, analogous to that exhi-
bited by the percussion -apparatus of Physicists, where a certain
number of parts, effecting a percussion, give rise to the repulsion
of an equal number of parts. Hence the conversion of this matter
can occur in no other place than in the circulating blood, and
therefore it is here that the urea must be formed.
That the urea is formed from nitrogenous matters could not be
doubted, even if it did not contain nitrogen (and that in so large a
quantity) ; for it is especially after the use of highly nitrogenous
food that we find an augmentation of its quantity in the urine. If,
however, we should further inquire — from what substances is it
produced, and what tissues principally contribute to its formation ?
we could not, in the present state of our knowledge, give any
satisfactory answers to these questions. All that we know is, that
urea is a very general product of the decomposition of nitrogenous
matters, both naturally within the animal body, and artificially in
the laboratory of the chemist. We have already said enough to
show that urea is so common a product of the decomposition of
nitrogenous bodies, that we could hardly any longer enumerate it
among true organic substances, if we tried to establish a distinction
between organic and inorganic matter. Moreover, when we treat
of uric acid we shall show that, in all probability, a great part of
the urea separated by the kidneys from the blood is the product of
the decomposition of that acid.
What is the importance of urea in the fluids of the eye, and
whether it has any importance, are questions which, at present,
cannot be answered.
* Ann. d. Ch. u. Pharm. Bd. 65, S. 337-8.
XANTHINE. 169
XANTH i NE. — C5H2N2O2.
Chemical Relations.
Properties. — This body, which has also been named uric oxide
and urous acid, occurs, when freshly precipitated, as a white powder,
which is neither crystalline nor gelatinous ; when dried, it forms
pale, yellowish, hard masses, which, on being rubbed, assume a
waxy brightness : it is very slightly soluble in water, is insoluble
in alcohol and ether, has no action on vegetable colours, arid when
heated, becomes decomposed without undergoing fusion, developing
much hydrocyanic acid and a very peculiar odour, but yielding no
urea. It dissolves with considerable facility in ammonia, but on
evaporation it loses the greater part of the ammonia, and separates
into a yellowish foliaceous mass. It dissolves freely in the caustic
fixed alkalies, from which, however, carbonic acid will separate it ;
it dissolves also in nitric acid without the development of gas, and
in sulphuric acid, to which it communicates a yellowish colour ; it is
all but insoluble in hydrochloric and oxalic acids. It does not
combine in definite proportions with acids, alkalies, or salts.
Composition. — As, from the want of definite combinations, the
atomic weight of this body cannot be ascertained, we can only give
the empirical formula which expresses the simplest relation of the
elements in xanthine. This substance was analysed many years
ago by Liebig and Wohler*, and recently by Bodo Ungerf, with
similar results :
Carbon 5 atoms .... 39'47
Hydrogen 2 „ .... 2'63
Nitrogen 2 „ .... 36'84
Oxygen 2 „ .... 21-06
100-00
This body has been regarded as uric acid (C5H2N2O3) in a lower
state of oxidation ; but till some of its compounds or products of
decomposition are analysed, scarcely an hypothesis can be suggested
regarding its theoretical constitution.
This body is only classified here with the animal bases, amongst
which it cannot properly be reckoned, because, in its elementary
composition it presents much similarity with them, and in a
* Pogg. Ann. Bd. 41, S. 393.
t Ann. d, Ch. u. Pharm. Bd. 58, S. 18.
170 BASIC BODIES.
physiological point of view, it approximates to urea, guanine, and
cystine.
Preparation. — Urinary calculi, in which this body occurs, are
dissolved in a solution of potash, and the xanthine is precipitated
from the filtered fluid by carbonic acid.
Tests. — From the circumstances under which it occurs, this
body can only be confounded with uric acid or cystine ; under the
microscope it may, however, be readily distinguished from them
by its amorphous condition. It differs chemically from uric acid,
firstly, in its ready solubility in ammonia, (hence it is not precipi-
tated from its potash-solution, like uric acid, by hydrochlorate of
ammonia;) secondly, in its being separated from its potash-
solution by carbonic acid, as a precipitate, free from the alkali ;
thirdly, in its dissolving in nitric acid without effervescence, and
on evaporation, leaving a (not red, but) yellow mass, which does not
become red on the addition of ammonia. It differs from cystine,
not only in its amorphism, but also in its insolubility in hydro
chloric and oxalic acids.
Physiological Relations.
Occurrence. — This body was discovered in a urinary calculus
by Marcet, who, from its behaviour with nitric acid, gave it the
name of xanthic oxide. It has only been found once since, by
Stromeyer, in a large calculus removed from a child ; and it was
from this source that both Liebig and Wohler, and Unger, obtained
the materials for their analyses. Jackson* thought that he had
found it in a specimen of diabetic urine, but his experiments do not
prove that he actually met with this substance. Although I have
repeatedly sought for it, I have never been able to find xanthine in
diabetic urine ; indeed it has never been found in any specimen of
urine.
Strahl and Lieberkiihnf believe that they have discovered
xanthine in human urine, but from the reactions which they describe,
the substance in question appears to have been guanine.
[Dr. Dav)Tt believes that the urinary secretion of scorpions and
spiders consists for the most part of xanthine. The substance he
has discovered is doubtless the same as that which Gorup-Besanez
and F. Will have regarded as guanine. See p. 173. — G. E. D.]
* Arch. d. Pharm. Bd. 11, S. 182.
t Harnsaure im Blut u. s. w. Berlin, 1848, S. 112 ff.
$ Ediii. New Phil. Jouru. Vol. 40, p. 338, and vol. 44, p. 125.
GUANINE. 171
Origin. — So little is known of this substance in reference
either to its chemical nature, or its occurrence in the animal body,
that we cannot offer any conjecture regarding its genesis.
Many attempts have been made to convert uric acid into
xanthine, but they have all been unsuccessful.
HYPOXANTHINE.
[Since the publication of the first volume of Professor Lehmann's
work, Scherer* has discovered the occurrence of a white, crystalline,
pulverulent substance in the spleen, and in the heart of man and
the ox. On analysis it yielded :
Carbon "^ 44*257
Hydrogen 3*219
Nitrogen .... .... .... .... 40*820
Oxygen 11'704
100-000
Its formula is C5H2N2O. Hence it is xanthine minus 1 equi-
valent of oxygen. Scherer has given it the name of hypoxanthine. —
G. E. D.]
G UANINE.-z=C10H5N5O2.
Chemical Relations.
Properties. — This body is a yellowish-white crystalline powder,
devoid of odour or taste, which can bear a temperature of 220°
without loss of weight, is insoluble in water, alcohol, and ether,
has no action on vegetable colours, and dissolves freely in hydro-
chloric acid and caustic soda ; it unites with acids, forming unstable
salts ; on mixing its sulphate with a very large quantity of water,
there is a separation of the hydrate of guanine, which does not lose
its combined water till it is raised to a temperature of 100°.
Composition. — This body was discovered by Bodo linger :f it was
at first mistaken for xanthine, but subsequently, by analysis of the
free body and its salts, it was ascertained to be a distinct, weak
base. According to the formula deduced from his analyses, it
consists of:
* Ann. de Ch. u. Pharm. Bd. 73, S. 328.
t Ann. d. Ch. u. Pharm. Bd. 51, S. 395 ff, and Bd. 58, S. 28-31 ; Pogg. Ann.
Bd. 65, S. 222-239, and Ann. d. Ch. u. Pharm. Bd. 59, S. 58-73.
172 BASIC BODIES.
Carbon 10 atoms .... 39'73
Hydrogen .... 5 „ .... 3'31
Nitrogen 5 „ .... 46'36
Oxygen 2 „ .... 10'60
100-00
Its atomic weight=1887'5. The hydrate consists, according
to Unger, of 2 atoms of water and 3 atoms of guanine. On account
of its basic nature, Berzelius* regards it as ammonia with a nitro-
genous adjuncts H3N.C10H2N4O2.
Combinations. — Like caffeine and theobromine, and other weak
bases, guanine readily unites in several proportions with acids, but,
like the above-named substances, parts with them readily on the
addition of large quantities of water, so that the pure base, mostly
as a hydrate, is separated, while an acid salt remains in solution.
Hydrochlorate of guanine: the neutral salt,3(C10H5N-O2.HCl) +
7 HO, crystallises in bright yellow needles, loses all its water under
100°, and all its hydrochloric acid above that temperature: the acid
salt, C10H5N5O2 4 2HC1, loses half its hydrochloric acid at a mode-
rate temperature : with bichloride of platinum it forms a crystal-
line compound, C10H5N5O2.HCl + PtCl2 + 4HO, which is as inso-
luble in cold water as the ammonio-chloride of platinum, but
dissolves very freely in hot water. The following basic hydrochlo-
rate has also been obtained: 2C10H5N5O2+HC1.
Sulphate of guanine, C10H5N5O2.HO.SO3+ 2HO, crystallises in
yellow needles, often an inch in length.
Nitrate of guanine was obtained by Unger in several proportions :
3C10H6N5O2+3NO5+12HO.
3C10H5N502+4N05+12HO.
3C10H5N502+5N05+16HO.
3C10H5N502+6N05+18HO.
The phosphate, oxalate, and tartrate of guanine may also be
obtained.
Guanine-soda, C10H5N5O2+2NaO + 6HO, is precipitated from
the soda-solution on the addition of alcohol: it is a foliaceous crys-
talline mass, which attracts carbonic acid from the air, and effloresces.
At 100° it loses all its water; on the addition of water one portion
of the guanine separates, and another portion remains in solution
with an excess of soda. Guanine also unites with certain salts, as,
for instance, with nitrate of silver, forming crystalline compounds.
Products of its metamorphosis. — Guanic acid, C10H3N4O7, (termed
* Jahresber. Bd. 27, 8. 678.
GUANINE. 173
hyperuric acid by Unger,) is obtained by digesting for 24 hours,
at a temperature of 125°, 3 parts of guanine, 5 of chlorate of potash,
5 of water, and 30 of hydrochloric acid ; it crystallises in short
rhombic prisms with oblique terminal surfaces, is devoid of colour,
odour, and taste, reddens moistened litmus, is slightly soluble in
water and in acids, but dissolves freely in the caustic alkalies and
their carbonates, and on dry distillation yields hydrated cyanic acid,
together with water and carbon.
Preparation. — Guanine was obtained by linger from guano,
which he digests with diluted milk of lime till the fluid, when
boiled, no longer appears brown, but assumes a faint greenish-
yellow colour; it is then filtered and treated with hydrochloric
acid ; in the course of a few hours the guanine, with a little uric
acid, separates ; the sediment is then dissolved in hydrochloric
acid, from which it is deposited in a crystalline form as a hydro-
chlorate ; from this the guanine is finally separated by ammonia.
Tests. — Guanine is especially to be distinguished both from
xanthine and from uric acid by its forming distinctly crystallisable
salts with acids. Moreover, the difference of its behaviour with
nitric acid is quite sufficient to prevent it from being mistaken for
uric acid.
Physiological Relations.
Occurrence. — Unger has, as we have already mentioned, found
guanine in guano (the excrements of certain sea fowls) ; it has
recently also been found in the excrements of spiders by F. Will
and Gorup-Besanez,* who think it very probable that this substance
occurs in the green organ of the river craw-fish, and in the Bojanian
organ in the fresh-water mussel.
If the constant occurrence of this substance in the urine, which
Strahl and Lieberkuhnf regarded as xanthine, (but which, from its
solubility in hydrochloric acid, would rather seem to be guanine,) be
confirmed by further investigations, we should have to classify
guanine among the general products of excretion of the animal
organism.
Origin. — From everything connected with the occurrence of
guanine there can be no doubt that, like the nitrogenous compounds
to which it is allied, it is a product of the metamorphosis of the
nitrogenous matters of the animal body. Nothing is, however,
* Gelehrte Anz. d. k. bair. Ak. d. Wiss. 1848, S. 825-828, [and more fully in
a memoir *' on guanine as an essential constituent of certain secretions of the in-
vertebrata," in Ann. d. Ch. u. Pharm. Bd. 69, S. 117.— G. E. D.]
t Op. cit.
174 BASIC BODIES.
known, on which we can even hazard a conjecture regarding the
conditions under which it is formed.
ALLANTOIXE.— C8H5N4O5.IIO.
Chemical Relations.
Properties. — This body forms colourless, hard prisms, of therhoin-
bohedric primitive form, which have a strong vitreous brilliance; it is
devoid of smell and taste, dissolves in 160 parts of cold water,
and more easily in hot water ; it crystallises from its hot alcoholic
solution, is insoluble in ether, is unaffected by exposure to the
atmosphere, does not redden litmus, and chars, when heated,
without fusing. It dissolves in solutions of the caustic alkalies and
their carbonates, when these are warmed, but crystallises from them
in an unchanged condition as they cool ; it is decomposed by con-
centrated caustic alkalies, taking up water and resolving itself into
oxalic acid and ammonia (C8H5N4O5+ 7HO=r4H3N + C2O3) ;
when boiled with concentrated sulphuric acid, it also takes up
water, developing carbonic acid and carbonic oxide, and leaving
sulphate of ammonia. On warming it with nitric acid (of 1*2 to
1'4 specific gravity,) it becomes decomposed into urea and allantoic
acid, (3 atoms of allantoine, taking up 7 atoms of water, yield 2
atoms of urea and 2 atoms of allantoic acid, for C.24H15N12O5 +
7HO= C4H8N404 + C20H14N8018.)
Allantoine enters into combination with the oxides of lead and
silver.
Composition. — Liebig and Wb'hler* were the first who accurately
determined the composition of crystallised allantoine, and they
deduced the above formula from its silver-compound, according to
which it consists of :
Carbon 8 atoms .... 30'38
Hydrogen 5 „ .... 3*16
Nitrogen 4 „ .... 35-44
Oxygen 5 „ .... 25'32
Water 1 „ .... 570
100-00
The atomic weight of the hypothetical dry allantoine= 1862.5.
This body cannot be reckoned amongst the organic bases, since
it does not combine with any acid ; but from the analogy of its
* Pogg. Ann. Bd. 31, S. 501.
ALLANTOINE. 175
composition, and the circumstance that we cannot find a more
appropriate position for it than amongst the nitrogenous products
of the metamorphosis of animal matters, we deemed it best to insert
it in this place. No rational formula can be assigned for it ; we
may, however, remark, that it exactly contains the elements of 4
atoms of cyanogen and 5 atoms of water.
Combinations. — The silver-compound, C8H5N4O5.AgO, is ob-
tained by mixing nitrate of silver with a boiling saturated solution
of allantoine, and then adding ammonia as long as a precipitate
continues to be produced : it forms a white powder which, when
examined microscopically, is found to consist of clear, perfectly
spherical particles.
The lead-compound is obtained on boiling an aqueous solution
of allantoine with oxide of lead ; it is crystallisable.
Products of its metamorphosis. — Allantoic acid, C10H7N4O9,
which is obtained in the manner we have already described, occurs
as a tough, amorphous, white mass, soluble in water, but insoluble
in alcohol and ether, and forms soluble salts with the alkalies and
earths. (Pelouze.*) Attention has been drawn to the fact that this
acid contains exactly 3 atoms of water more than uric acid under the
older formula, (C10H4N4O6 + 3HO=C10H7N4O9.)
Preparation. — On evaporating the allantoic fluid of the foetus of a
cow or the urine of a young calf to a thin syrup, without permitting it
to boil, and then allowing it to stand for a few days, we obtain crystals
of allantoine mixed with phosphate and urate of magnesia; by
stirring it with cold water and decanting, most of the viscid matter,
consisting of urate of magnesia, is removed, while the crystals of
allantoine and phosphate of magnesia rapidly sink to the bottom; hot
water extracts the allantoine, leaving the magnesian salt un dissolved;
the solution of allantoine is then decolorized with animal charcoal,
and evaporated till it recrystallises.
Allantoine may also be obtained artificially from uric acid (see
" Uric acid") by boiling it with peroxide of lead, the products of
decomposition being oxalate of lead, urea, and allantoine ; when
the boiling fluid has been freed by filtration from oxalate of lead,
and allowed to cool, the allantoine separates in crystals.
Tests. — This body can only be recognised with certainty by an
accurate determination of its crystalline form, or by an elementary
analysis either of itself or its silver-compound.
* Ann. de Chim. et de Phys. 3 S&-. T. 6, p. 69.
176 BASIC BODIES.
Physiological Relations.
Occurrence. — Vauquelin and Buniva thought that they had
found allantoine in the Liquor Amnii of a cow, but Lassaigne*
proved that it is peculiar to the Liquor Allan toidis. It has
recently been found by Wohlerf in considerable quantity, in the
urine of young calves. It has as yet been found nowhere else in
the animal organism.
According to Wohler, the allantoine from calves' urine presents
the peculiarity that it differs in the character of its crystals from
that which is obtained from the allantoic fluid or from uric acid ;
the crystals grow together in bundles, and their terminal .surfaces
are no longer distinct, while pure allantoine appears in isolated well-
formed prisms. This difference, however, only depends on the
admixture of a foreign substance, whose quantity is much too
minute to produce any appreciable influence on the result of its
elementary analysis. By combining it with oxide of silver, and
then decomposing the compound, we obtain it in as pure and
isolated a state as when we prepare it from the allantoic fluid or
from uric acid.
Origin. — That allantoine is a product of the metamorphosis of
nitrogenous food or of tissue in the animal organism, is sufficiently
obvious from the circumstances under which it occurs, but any
nearer indication of the chemical process on which its formation
depends is impossible, since we have no idea of its rational com-
position. The two following facts may, however, probably
indicate the way in which its formation may at some future time
be explained : firstly, it only occurs in the urine of the foetus and
of recently-born animals, and disappears after the use of vegetable
food ; secondly, as has been discovered by Wohler, it occurs in the
urine of sucking calves, together with uric acid and urea, but without
hippuric acid ; hence the idea suggests itself that allantoine and
hippuric acid exclude or stand in the place of one another, which
might rather have been expected of uric acid, from which allantoine
may be artificially prepared.
* Ann. de Ch. et de Phys. T. 17, p. 301.
t Nachrichten der k. Gesellsch. d. Wiss. zuGottingen, 1849. No. 5, S. 61-64 ;
[and more fully in Ann. d. Ch. u. Pharm. Bd. 70, S. 229.— G. E. D.]
CYSTINE. 177
CYSTINE.— C6H6NS2O4.
Chemical Relations.
Properties. — This body occurs in colourless, transparent, hexa-
gonal plates or prisms, is devoid of taste and smell, and is insoluble
in water and alcohol ; it dissolves in oxalic acid and in the mineral
acids, forming with them saline combinations, most of which are
crystallisable, but it does not unite with acetic, tartaric, or citric acid :
it is decomposed by nitric acid, leaving, on the evaporation of the
fluid, a reddish brown mass ; it dissolves freely in the caustic fixed
alkalies and their carbonates. It dissolves in caustic ammonia, but
does not unite with it, so that on evaporation it crystallises un-
changed. It is insoluble in carbonate of ammonia ; hence it is best
precipitated from its acid solutions by carbonate of ammonia, and
from its alkaline solutions by acetic acid.
Cystine does not fuse on the application of heat, but it burns
with a bluish green flame, developing at the same time a very pecu-
liar acid odour ; on dry distillation it developes a stinking empy-
reuma and ammonia, and leaves a voluminous porous coal. On
boiling it with alkalies, ammonia is first developed, and subsequently
an easily inflammable gas, which burns with a blue flame.
Composition. — Cystine has been analysed by Prout, Baudri-
mont, Thaulow,* and Marchand,f with perfectly identical results,
yielding the above formula, according to which this substance
contains :
Carbon 6 atoms .... SO'OOO
Hydrogen .... 6 „ .... 5-000
Nitrogen 1 „ .... 11 '606
Sulphur 2 „ .... 2«'667
Oxygen 4 „ 26'667
100-000
Its atomic weight=1336'0.
Since cystine, which has also received the name of cystic oxide,
unites with certain acids to form crystalline salts, Berzelius classi-
fies this body with the combinations of conjugated ammonia
= H3N.C6H3S2O4. If, however, this view be correct, much is still
wanting for the establishment of the rational formula of cystine, for
* Ann. d. Ch. u. Pharm. Bd. 27, S. 197.
t Journ. f. pr. Ch. Bd. 10, S. 15-18.
N
178 BASIC BODIES.
the most important question regarding its constitution still remains
unexplained, namely, in which form or combination the sulphur is
contained, in the cystine or in this adjunct. The chemical investi-
gations regarding cystine, which have been hitherto instituted, do
not tend to support any hypothesis.
Combinations. — Hydrochlorate o/c?/s#me,C6H6NS2O4.HCl, crys-
tallises without water in plates grouped in a star-like form. Berze-
lius* obtained the combination with bichloride of platinum by
direct union; this salt is not crystallisable; it dissolves easily in
water and alcohol, but is insoluble in ether.
Nitrate of cystine, C6H6NS2O4.HO.NO5 + HO, crystallises
readily, losing its one atom of water at 85°.
Preparation. — Urinary calculi, in which cystine occurs, are dis-
solved in a solution of potash, and the cystine is precipitated from
this solution by acetic acid ; or we dissolve them in ammonia, and
allow the filtered fluid to evaporate in the air.
Tests. — Cystine is characterised by the readiness with which it
crystallises in well-formed hexagonal plates, which may be distin-
guished with great ease under the microscope, and by its solubility
both in alkalies and mineral acids. Further, it may be known by
the peculiar odour which it developes on dry distillation and on
burning, which is unlike that evolved by any other similar substance.
Liebig has given the following test for cystine. The potash-extract
of the substance in which we are searching for cystine must be
decomposed with a solution of oxide of lead in caustic potash; if,
on the application of heat, there be a precipitation of sulphide of
lead, cystine is probably present; we must, however, previously
satisfy ourselves that no other sulphurous body, as, for instance,
mucus, albumen, &c. be simultaneously present.
If cystine be mixed with a small quantity of the urates, the two
substances may be separated by the aid of boiling water, in which
the former is insoluble. Uric acid occasionally appears under the
microscope in the form of hexagonal tablets, but we should never
trust in these cases to microscopic examination alone.
Physiological Relations.
Occurrence. — Cystine was originally discovered by Wollaston,f
in a urinary calculus. Calculi of this nature, although very rare,
have since been found by many other chemists, as, for instance,
Prout, Taylor, Baudrimont, Lassaigne, Dranty, Civiale, Buchner,
* Jahresber. Bd. 27, S. 631.
t Phil. Trans., 1810, p. 223.
TAURINE. 179
and Bird. Bird* and Mandlf remark that they have often found
cystine dissolved in the urine, from which Bird precipitates it by
acetic acid ; it also occurs as a sediment mixed with urate of soda.
The pathological process accompanying the appearance of cystine in
the urine is altogether unknown. Bird thinks there is some con-
nexion between it and the scrofulous diathesis ; others fancy that
they see a connexion between cystine and diabetes ; but none of
these conjectures are supported by the results of experience. In
the examination of 129 urinary calculi, Taylor found only two
that contained cystine. This substance has been found nowhere
but in the urine.
Origin. — As no other urinary constituent contains sulphur J, the
occurrence of this highly sulphurous body in the urine is the more
singular, and we should consequently expect that some essential al-
teration of the chemico-vital processes must have taken place before
this substance could be produced, but all that we learn from the si-
multaneous morbid phenomena completely disappoints us in the as-
sumption that the excretion of cystine must probably be preceded by
a certain group of symptoms, from which something might be con-
cluded regarding the production of this body. Taurine is the only
other body with which we are acquainted that is equally rich in
sulphur; no other animal bodies in which sulphur occurs, as albu-
men, casein, fibrin, &c. contain at most more than 2^-, while in this
substance there is 25^. Hence, in a chemical point of view, a con-
nexion might be suspected between taurine and cystine, and the
rational physician should consequently direct his attention to the
manner in which the functions of the liver are performed, when-
ever cystine presents itself in the urine.
TAURINE.— C4H7NS2O6.
Properties. — This substance which was formerly termed biliary
asparagin, crystallises in colourless, regular hexagonal prisms with
four and six-sided sharp extremities, (the elementary form is that
of a right rhombic prism, the angles formed by the edges of the
sides being 111°44 and 68°16) ; it is hard, craunches between the
teeth, has a cooling taste, resists the action of the atmosphere,
* Urinary Deposits, &c. 3rd Edition, p. 188.
f Journ de Chim. med. 1838, p. 355.
$ [This statement is too general. Dr. Ronalds has shewn that the extractive
matters of the urine contain an unknown sulphur-compound. See Phil. Trans.
1846, p. 461. G. E. D.]
N 2
180 BASIC BODIES.
dissolves in 15 '5 parts of water, and in 573 of spirit of wine (of
0'835 specific gravity,) but is insoluble in anhydrous alcohol and
ether, and has no action on vegetable colours. It dissolves, with-
out undergoing change, even at the boiling point, in the mineral
acids, but forms no compounds with them. It is not precipitated
from its solution either by tannic acid or by the metallic salts. On
heating, it fuses, puffs up, and developes much acetate of ammonia,
and a thick brown oil ; if it be inflamed in the air, it developes
much sulphurous acid ; if it be dissolved in caustic potash, and the
solution boiled down till it becomes thick, it developes pure am-
monia gas, and leaves a residue consisting solely of sulphite and
acetate of potash. The sulphur in taurine cannot be detected in
the moist way either by nitric acid or by aqua regia.
Composition. — Taurine was first discovered by Gmelin in the
bile, and was soon afterwards analysed with very similar results by
Dema^ay, Pelouze, and Dumas ; these chemists, however, entirely
overlooked the existence of sulphur in this body, the discovery of
which was reserved for Redtenbacher,* from whose analyses it was
found to consist of :
Carbon 4 atoms .... 19'20
Hydrogen 7 „ .... 5*60
Nitrogen 1 „ .... 11'20
Sulphur 2 „ .... 25-60
Oxygen 6 „ .... 38'40
100-00
As this body has not yet been combined with any other in a
definite proportion, its atomic weight cannot be determined with
accuracy ; but it must not be reckoned among the bases, and we are
still perfectly in the dark regarding its rational composition. Red-
tenbacherf attempted to elucidate this point ; finding that by the
action of potash taurine was decomposed into ammonia, acetic acid,
and sulphurous acid, he was somewhat inclined to believe that taurine
is a combination of sulphurous acid with aldehyde and ammonia (since
2SO2 + H3N + C4H4O2=C4H7NS2O6), and that it might probably
be artificially prepared from these substances, as urea is obtained
from cyan ate of ammonia. Indeed, on passing sulphurous acid into
an alcoholic solution of aldehyde-ammonia he obtained a white crys-
talline body isomeric with taurine ; it is however not identical with
taurine, but must be regarded as an acid sulphite of aldehyde-am-
* Ann. d. Ch. u. Pharm. Bd. 57, S. 170-174.
t Ibid. Bd. 65, S. 37-45.
TAURINE. 181
monia; it reddens litmus, gradually changes on exposure to the
air, turns yellow at 100°, and at a higher temperature becomes
brown, and finally developes an odour resembling that of burned
taurine. Hence, notwithstanding these ingenious experiments of
Redtenbacher's, the rational constitution of taurine remains still
unexplained.
Preparation. — Taurine is usually obtained from ox-gall. The
bile, freed from its mucus by an acid, or its alcoholic extract, is
mixed with hydrochloric acid, and boiled for some hours till the
choloidic acid is completely formed from the nitrogenous acids of
the bile ; the acid fluid, after the removal of the choloidic acid by
nitration is rapidly evaporated, causing the chloride of sodium to
crystallise ; the acid mother-liquid is then treated with five or six
times its bulk of boiling alcohol, from which, as it cools, the taurine
separates in needles ; by recrystallisation in water it is obtained in
a state of purity.
Tests. — Taurine may be distinguished from every other sub-
stance by its crystalline form (which under the microscope is as
distinct in small crystals as in large ones), by its property of
developing sulphurous acid when heated in a glass tube open at
both ends, or on a platinum spatula, and finally, by the circum-
stance that when boiled with caustic potash, it does not form
a black solution, but developes ammonia, and leaves a residue
consisting solely of sulphurous and acetic acids in combination with
potash.
Physiological Relations.
Occurrence. — Taurine has never been found isolated in the
healthy organism ; it appears to be contained preformed in normal
bile, and to occur there as an adjunct of the already described
cholic acid; at all events it only occurs in an isolated state in
decomposed or morbid bile. After the removal of the mucus,
the only sulphur-compound, in those animals in which the bile con-
tains sulphur, is taurine conjugated with cholic acid. At the
present time we know, by the researches of Bensch,* that sulphur
exists in the bile of the ox, the sheep, the fox, the bear, the dog,
the wolf, the goat, the domestic hen, and certain fresh-water fish;
and Schlieperf has found it most abundant in the bile of serpents.
From the bile of the pig Strecker and GundelachJ were unable to
* Ann. d. Ch. u. Pharm. Bd. 65, S. 194-203.
t Ibid. Bd. GO, S. 109-112.
J Ibid. Bd. 62, S. 205-232.
182 BASIC BODIES.
obtain taurine, and they found no sulphur in it, although Bensch
had detected a small quantity. Doubts have been expressed whe-
ther sulphur, and consequently taurocholic acid, exists in human
bile, but Gorup-Besanez* has so completely set this point at rest,
that my evidence founded on the crystallometric determination of
taurine artificially obtained from human bile is superfluous. In
diseased bile taken from the dead body taurine is especially found
when, as is sometimes the case, the bile has an acid reaction ; thus
Gorup-Besanez found taurine in the bile of a person who had died
from arachnitis.
Although some of the products of the decomposition of bile
occur in the excrements, especially in cases of diarrhoea, taurine has
never yet been found there : neither has it been detected in bilious
urine.
Origin. — If we consider that the excreted products of the
animal organism are usually highly oxidised organic matters, and
that most of the matters separated from the blood and even depo-
sited in the tissues, differ from the food in containing a larger
amount of oxygen, it must at first sight strike us as singular that
a substance so rich in sulphur as taurine either alone or in combi-
nation, should be produced, even in the normal state of the body, from
the animal fluids, which are almost universally saturated with free
oxygen. Although Redtenbacher failed in obtaining taurine artifi-
cially, his admirable researches render it highly probable that the
sulphur in taurine exists in an oxidised state, as indeed may be
inferred from the fact that it cannot be recognised in this substance
by means of the ordinary fluid oxidising agents. The genesis of
taurine should therefore not be sought in a de-oxidising process in
the blood, (a very improbable process,) but rather in a process of
oxidation. If, however, taurine be the product of an oxidation,
the source of its formation should hardly be sought in the liver,
since the blood that is poorest in oxygen is supplied to this organ.
This simple induction leads us to refer the seat of the formation of
taurine, or at least of its proximate constituents, to the blood, where,
however, it cannot be detected for the same reason that so long
prevented the presence of urea from being ascertained. Nothing
is at present known regarding the different steps that occur in the
formation of taurine; it is, however, not improbable that the sul-
phur of the albuminous food in its conversion into the elements of
tissues, which are either free from or poor in sulphur, yields in
part the materials for the formation of taurine.
* Uiiters. ub. Galle. Erlangen, 1846. S. 31-37.
CONJUGATED ACIDS. 183
Uses. — If we can conjecture with some probability regarding
the origin of taurine, we are even less fortunate in reference to the
function which the taurine excreted with the bile in the intestine,
exerts in the animal organism, since in this point of view we are
entirely devoid of facts on which to hang even a bare induction. No
conclusion can be drawn regarding the further use of this substance
in the animal body, from the negative fact that hitherto no taurine
has been found in normal excrements, since accurate and sufficiently
minute experiments have not yet been made on this subject. As
there are some animals, as, for instance, the pig, which, although
they secrete bile copiously, separate no taurine by the hepatic organs,
it appears that at all events it is unimportant to the process of
digestion. But that taurine, even if first separated from the blood,
should be again resorbed from the intestine into the blood, and
being there burned, should serve as a material for supporting the
animal heat, appears to us not impossible, but certainly impro-
bable. (See " Taurocholic Acid.")
CONJUGATED ACIDS.
Although we may not feel justified in directly introducing into
physiological chemistry all the transient views which have arisen in
theoretical chemistry ; and although we would wish to abstain from
those more than hypothetical opinions regarding the theoretical
constitution of organic bodies, which are for ever rising, and as
rapidly disappearing ; yet we ought not to omit all reference to the
present state of theoretical chemistry, but should be ready to
appropriate to physiological chemistry every acquisition which
seems likely to be fruitful in results. It would by no means
further the progress of physiological chemistry at once to transfer
to it all the hypotheses or fictions that may have been advanced in
pure chemistry. If we were to attempt to support these chemical
hypotheses with others of a physiological nature, the foundation of
physiological chemistry would be very unstable, and finally the
whole superstructure would be an aerial image of the fancy (and of
these images we have already an abundance) rather than an experi-
184 CONJUGATED ACIDS.
mental science based on pure induction. It is, however, necessary
for the progress of science, that in accordance with the present
state of chemical theory we should establish certain general propo-
sitions, which not only furnish us with a comprehensive expression
for a number of frequently recurring facts, but guide inquiry in
various directions, and finally present us with certain points of
support for the due understanding of our scientific material.
Amongst these general propositions we reckon the method which
is now becoming tolerably common in theoretical chemistry, of
considering certain bodies as conjugated or copulated combinations.
We shall, however, place no more exclusive dependence on this
theory, as it has been carried out by Laurent and Gerhardt,* or
Strecker,f or Kolbe^ than on the theory of organic radicals and
of electro-chemical dualism of a Berzelius, or on the theory of
substitutions and metalepsy of a Dumas. If we even venture on a
reference to eclecticism, it must be in the choice of those supports
which one branch of science, in its early stage, is compelled to
borrow from another. It is only in this point of view that we
wish to justify the establishment of the group of conjugated acids
in zoo-chemistry.
We have already had occasion to refer to a series of organic
acids which, according to the excellent investigations of Kolbe,
may be regarded as carbo-hydrogens conjugated with oxalic acid :
indeed, Kolbe is inclined to regard all the groups of acids we have
noticed, which contain 3 atoms of oxygen, as combinations of oxalic
acid with carbo-hydrogens. These illustrations are sufficient to
indicate the idea which we attach to the expression, conjugated or
copulated acids. We have become acquainted with acids which,
in opposition to the ordinary rules of chemistry, not only lose
nothing of their acidity, but (which is most singular) perfectly
retain their former saturating capacity, when united with another
and a more basic body ; after being combined with the so-called
adjunct (copula), this acid still saturates the same quantity of
base as if the organic matter associated with it did not exist;
and this dependent — the adjunct — which follows the acid as an
integral constituent in all its combinations, exerts an essential
influence on its physical and even on many of its chemical proper-
ties. Thus, for instance, oxalic acid, which in its ordinary state
is so readily decomposed by heat, becomes volatile by its conjuga-
* Ann. de Chim. et de Phys. 3 Se'r., T. 24, p. 200-208.
t Ann. d. Ch. u. Pharra. Bd. 68, S. 47-55.
I llandworterb. d. Cheraie. Bd. 3, S. 439-444.
CONJUGATED ACIDS. 185
tion (accouplement) with the above-named carbo-hydrogens ; the
stability is, however, most obvious in those acids in which such
easily decomposable bodies as hyposulphurous or hyponitric acid
are conjugated ; their salts being altogether dissimilar from those
of the non-conjugated acids in their crystalline form, solubility,
amount of water, &c.
In combinations of this kind the electro-chemical polarity is
entirely lost ; the older dualistic views of chemistry here altogether
fail us; we must therefore here assume another ground of chemical
attraction than that of opposite polarity, and this view is confirmed
by the circumstance that these compounds cannot be decomposed
according to our ordinary chemical principles, that is to say, by
simple or double elective affinity. They also no more admit of being
decomposed into their proximate constituents, that is to say, into
the acid and the adjunct, than of being directly formed from them.
Most of the conjugated acids are only formed when the adjunct in
its nascent state comes in contact with the acid ; and conversely it
is only very few of them that can be decomposed into the acid and
the adjunct, and even in this case the adjunct invariably assimi-
lates water, and it is impossible to determine with certainty whe-
ther the isolated hydrated body in its anhydrous condition actually
constituted the adjunct, or whether the latter body was represented
by some other group of atoms. This favourable condition, how-
ever, very rarely aids us ; for generally, in our attempts to sepa-
rate the adjunct from the acid, the former becomes so decomposed
that we can arrive at no conclusion regarding its nature : and this
is the reason why chemists, when they enter into the general con-
sideration of the laws of conjugated acids have to trust more or less
to hypotheses ; and it would scarcely be in accordance with our
views to follow their track. We shall,, however, be compelled to
devote some attention to these hypotheses when we treat of the
acids of this class, pertaining to zoo-chemistry ; and we will here
only remark that we will subsequently treat of those combinations
of organic acids with organic oxides in which all acidity has disap-
peared, and which have been named by Berzelius haloid salts,
whilst other chemists of the present day have included them in the
category of conjugated compounds.
Most of the known conjugated acids are formed by the action
of sulphuric or nitric acid on organic substances. In the following
group, picric acid is the only one we will consider in any detail,
partly by way of general illustration, and partly because it occurs
more frequently than the others as a product of the decomposition
186 CONJUGATED ACIDS.
of different nitrogenous substances by nitric acid. The other acids
of this class, to which reference may be made in zoo-chemistry,
will be considered under the head of the substances from which
they are derived.
There are but few of the pure organic acids whose adjunct can be
determined with much probability. It necessarily arises from the
nature of these substances, that conjugated organic acids can be de-
composed into acids and their adjuncts with much less facility than
the conjugated mineral acids, and that their proximate constituents
cannot be ascertained without difficulty. We have ventured in the
following pages to enumerate nitrogenous organic acids in the group
of conjugated acids, not that the composition of each one can with
certainty be referred to a nitrogenous adjunct and an acid, but
because the study of the products of decomposition of such bodies
renders it tolerably evident that all nitrogenous acids, more especially
on account of their high atomic weight, are composed of proximate
constituents, of which the nitrogenous one scarcely at all contri-
butes to the acidity of the combination.
This, however, is pure conjecture ; but, at the same time, in
considering the nitrogenous acids, we should have to adopt an arbi-
trary classification, if we were to consider those in which the con-
jugate constitution has to any extent been proved, distinct from
those in which no evidence of this nature has been obtained.
Between these two classes there exist so many analogies that it
would be of no practical utility to attempt such a separation.
PICRIC ACID.— C12H2N3O13.HO.
Properties. — This acid, which was formerly known as carbo-
nitric acid, carbazotic acid, and Welter's bitter, crystallises in
yellow, glistening plates or prisms, fuses when carefully heated,
and admits of being sublimed undecomposed, but when rapidly
heated decomposes with explosions ; it is devoid of odour, has a
very bitter taste, and dissolves slightly in cold and readily in hot
water, the solution being of a yellow colour ; it dissolves freely in
alcohol and ether, and reddens litmus ; when heated with phos-
phorus or potassium it decrepitates violently ; it is not decomposed
by chlorine, nitric or hydrochloric acids, or by aqua regia.
Composition. — According to the above formula this acid con-
sists of:
PICRIC ACID. 187
Carbon 12 atoms .... 31*44
Hydrogen 2 „ .... 0'87
Nitrogen 3 „ .... 1834
Oxygen 13 „ .... 45'42
Water 1 „ .... 3'93
100-00
The atomic weight of the hypothetical anhydrous acid= 2750*0;
and its saturating capacity = 3*636. Chemists are not agreed
regarding the rational formula of this body; they unite in regarding
it as a conjugated nitric acid, but there is much difference of opi-
nion regarding the nature of the adjunct. Berzelius writes this
acid as= (C12H2NO3.NO5) +NO5.HO, but there is little to support
the view of a salt-like adjunct such as is here assumed. We know,
for instance, that the group of atoms NO4 is substituted in aniline
and certain other bodies for an equivalent of hydrogen, and it is
now pretty generally assumed that such substitutions of more nega-
tive matters in the place of hydrogen for the most part only extend
to the hydrogen contained in the adjunct ; if, therefore, we assign
to picric acid only a hypothetical formula, it will at all events not
be an irrational one, if we consider that in the adjunct C12H4,
2 atoms of hydrogen are replaced by 2 atoms of NO4, arid write the
acid as = C12(H2.2NO4).NO5.HO. Laurent regards picric acid, not
as a conjugated acid, but as carbolic acid (C12H5O) in which 3
atoms of hydrogen are replaced by 3 atoms of NO4, and hence he
writes it as = C12(H2.3NO4)O.HO.
Combinations. — The picrates are crystallisable, yellow, and for
the most part soluble in water ; when rapidly heated they decrepi-
tate with much violence.
Pier ate of potash is one of the most insoluble salts of this acid;
it crystallises in long, glistening, yellow, iridescent prisms, and
dissolves in 260 parts of cold, and 14 parts of hot water. With
alkaline earths and metallic oxides this acid has a tendency to form
basic and very insoluble salts.
Preparation. — This acid is formed by the action of concentrated
nitric acid on many vegetable and animal substances. Thus, for
instance, in heating salicin with nitric acid, we obtain crystals of
pure picric acid. It is likewise produced in large quantity on
decomposing silk with nitric acid ; it is, however, most commonly
obtained by boiling indigo with nitric acid.
188 CONJUGATED ACIDS.
HIPPURIC ACID.— C1SH8NO5.HO.
Chemical Relations.
Properties. — Hippuric acid, known also as uro-benzoic acid,
separates from hot solutions on cooling, in the form of minute
spangles, or of larger, obliquely-striated, four-sided prisms, termi-
nating at the ends in two flat surfaces. The elementary form of
the crystals is a vertical rhombic prism, which is best studied in
microscopical crystals obtained by the slow evaporation of a solu-
tion of hippuric acid, which are similar to those of phosphate of
ammonia and magnesia, even in their most varied combinations.
(C. Schmidt.*) This acid is devoid of smell, has a slightly bitter
but not an acid taste, dissolves in 400 parts of cold water, and
very freely in hot water ; it is moreover readily soluble in alcohol,
but difficult of solution in ether. Even the cold aqueous solution
reddens litmus powerfully.
When gently heated, hippuric acid fuses, without loss of water,
into an oily liquid, which, on cooling, solidifies into a crystalline
milk-white mass ; on the application of a stronger heat, there is
produced a crystalline sublimate of benzoic acid and benzoate of
ammonia, while a few oily drops are at the same time formed,
which evolve an odour of cumarin (the oil of the Tonka bean,)
or fresh hay, solidify on cooling, and are soluble in alcohol and
ammonia, but not in water. On exposing the acid to a more rapid
and stronger heat, an intense odour of hydrocyanic acid is developed,
and a porous coal is left as a residue.
Hippuric acid is unaffected by chlorine, chlorous, and dilute
mineral acids ; but when heated with concentrated hydrochloric or
nitric acid, or even with oxalic acid, it becomes decomposed (as
already mentioned in page 152,) into benzoic acid and glycine
(Dessaignef). When heated with peroxide of manganese and sul-
phuric acid it is decomposed into carbonic acid, ammonia, and
benzoic acid (Pelouze) ; boiled with freshly prepared peroxide of
lead it yields benzamide, carbonic acid, and water (Fehling) ; and
finally, if it be dissolved in nitric acid, and a stream of nitric oxide
gas be passed through the solution, there is a development of
ammonia, whilst there remains in solution a new non-nitrogenous
acid which = C18H7O7.HO. (Strecker.)
* Entwurf u. s. w. S. 36—40.
t Compt. rend. T. 21, pp. 1224-1227.
HIPPURIC ACID. 189
Heated with hydrate of lime or caustic potash, hippuric acid
yields benzine and ammonia, while the residue consists solely of
carbonate of [lime or] potash, without a trace of cyanide of [calcium
or] potassium. In fermenting and putrefying fluids this acid
becomes decomposed into benzoic acid and other yet unknown
products.
Shortly after Liebig's discovery of hippuric acid, while preparing
it in large quantities from the urine of horses, I obtained one iso-
lated crystal of hippuric acid half an inch in length, in which the
vertical rhombic prism of the elementary form <x> P was combined
with 2 microdiagonal horizontal prisms, whereby the combining
corners were truncated by the brachydiagonal horizontal prism.
I have never again succeeded in obtaining crystals of such size and
thickness.
Composition. — According to the above formula hippuric acid
consists of :
Carbon 18 atoms .... 60-335
Hydrogen .... 8 „ .... 4'469
Nitrogen 1 „ .... 7«82l
Oxygen 5 „ .... 22'347
Water 1 „ .... 5-028
100-000
The atomic weight of the hypothetical anhydrous acid=2125'0;
and its saturating capacity =4*706.
From the various modes in which hippuric acid may be disin-
tegrated, corresponding views have been taken of its constitution ;
all, however, agree in the opinion that in hippuric acid there must be
concealed the radical benzoyl, C14H5, which is common to benzoic
acid, volatile oil of bitter almonds, and benzamide. From the
behaviour of hippuric acid with peroxide of manganese and sul-
phuric acid, and from the composition of formobenzoic acid, which, as
may be shown, consists of formic acid and oil of bitter almonds,
(hydride of benzoyl,) Pelouze* concluded that hippuric acid was a
kind of formobenzoic acid, which had assimilated hydrocyanic acid,
so that it consisted of 1 equivalent of hydrocyanic acid, 1 equivalent
of hydride of benzoyl, and 1 equivalent of formic acid, and
=H.C2N + H.C14H5 + C2HO3.HO.
This view of the composition of hippuric acid also finds some
support in the circumstance that amygdalic acid, according to the
recent investigations of W6hler,t seems most probably to be formic
* Ann. de Chim. et de Pharm. T. 26, pp. 60-68.
t Ann. d. Ch. u. Pharm. Bd. 66, S. 238-242.
190 CONJUGATED ACIDS.
acid, with oil of bitter almonds and sugar as an adjunct. If hippuric
acid were actually composed in this manner, the products of
decomposition with peroxide of manganese, could be hardly dif-
ferent from what they are, for hydrocyanic acid is very readily
decomposed into formic acid and ammonia, and the oxygen yielded
by the manganese converts the formic into carbonic acid, and the
hydride of benzoyl into benzoic acid — both being processes of very
frequent occurrence. But independently of the circumstance that,
at least in analogous processes, some formic acid remains undecom-
posed, this view is also opposed by the fact that other oxidising
agents do not decompose hippuric acid in the same manner which
they undoubtedly would do if the acid actually had this composition.
On this account Fehling,* influenced by the behaviour of hippuric
acid with peroxide of lead, regarded it as fumaric acid conjugated
with benzamide, and=r:H2N.C14H5O2 + C4HO3.HO. If benzoic
acid existed preformed in hippuric acid, it would be very unlikely
that, by the action of an oxidising agent, as peroxide of lead, a
substance so poor in oxygen as benzamide should be formed.
Dessaigne's remarkable discovery must lead to the conclusion
that glycine exists preformed in hippuric acid, and is conjugated
with benzoic acid, so that 1 atom of anhydrous glycine with 1 atom
of benzoic acid forms hydrated hippuric acid, since C4H4NO3 +
C14H5O3=C18H8NO5.HO ; but if we are not altogether opposed to
Streckei^s formula for the formation of conjugated compounds from
their constituents with the loss of certain atoms of water, yet it ap-
pears to us simple and natural that we should only compare with one
another the formulae of anhydrous combinations, and that certain
atoms of water should not be arbitrarily abstracted; anhydrous
glycine and anhydrous benzoic acid yield 1 atom of hydrogen and
1 atom of oxygen more than anhydrous hippuric acid contains : if
now, notwithstanding this, we assume that glycine exists preformed
in hippuric acid, with however only a small quantity of water, we
should proceed just as irrationally as if we assumed that ammonia
existed in oxamide or in benzonitrile, because these bodies, when
they assimilate water, yield ammonia. All, therefore, that we can
maintain is, that in hippuric acid we find, in addition to benzoic
acid, an adjuncts C4H3NO2, which, on its separation, has a strong
tendency to be transformed into glycine — a substance which is as
readily formed as urea in the decomposition of nitrogenous matters,
(see pp. 152 and 158.) It is in the changes which the adjunct under-
goes in its intimate constitution by the action of stronger agents, that
* Ann, d. Ch. u. Pharm. Bd. 28, S. 48.
HIPPURIC ACID. 191
we must seek to ascertain the reason why the fixed acid is freed from
the adjunct. This adjunct of hippuric acid might be regarded, in
reference to its composition, as an amide of fumaric acid (C4H3NO2=r
H2N.C4HO2), and we should thus arrive at the reverse of Fehling's
view of the subject. The question therefore now remains — Ts it
more probable that in hippuric acid benzamide is combined with
fumaric acid, or fumaramide with benzoic acid ? or is it more pro-
bable that in the action of peroxide of lead the benzoic acid is
converted into benzamide by the oxidation of the fumaramide, or
that by the action of concentrated acids the benzamide is decom-
posed and fumaramide formed ? No satisfactory answer to these
questions can be deduced either from the laws of stoichiometry or of
affinity; since most unquestionable observations show in both cases
the remarkable fact of the alternating substitution of 1 atom of amide
and 1 atom of oxygen, (for in the conversion of benzoic acid into
benzamide the former takes in exchange 1 equivalent of amide for 1
atom of oxygen, and a similar substitution occurs in the conversion
of fumaric acid into fumaramide.) If, however, we regard benzoic
acid as existing preformed in hippuric acid, we are by no means
constrained to assume that the adjunct is fumaramide, or indeed
any amide-compound. If we represent the formula of hippuric acid
=C4H3NO2.C14H5O3.HO, this view is supported in the first
place by the circumstance that hippuric acid has many physical and
chemical properties in common with benzoic acid, which lead to
the assumption that benzoic acid exists preformed in it, but afford
no presumption in favour of the pre-existence of benzamide or
fumaric acid in it. Secondly, we are indebted to the labours of
Strecker for our knowledge of another conjugated acid, in whose
analogous decomposition by acids glycine is also separated, which
here also can only be produced by the assimilation of water ; this
acid being the biliary acid presently to be considered, where the
same adjunct is combined with the cholic acid which we have
already described. Thirdly, the fact discovered by Wohler that
benzoic acid, in its passage through the animal organism, is con-
verted into hippuric acid, affords a certain amount of support to
this view.
Recently, however, Strecker* has been led to yet another view
regarding the constitution of hippuric acid from its behaviour with
nitric oxide, and from the formation of the acid whose formula
= C18H7O7.HO. He looks upon hippuric acid as an amide-com-
pound of this acid, and=H2N.C18H7O7 ; but the amides never
have acid properties (besides which this only represents the
* Ann. d. Ch. u. Pharm. Bd. 68, S. 53.
192 CONJUGATED ACIDS.
hydrated hippuric acid) ; if Strecker had not ascertained that the
silver-salt was accurately represented by AgO.C18H7O7, we might
have regarded its composition as expressed by the formula
C9H3O3.HO, and therefore have considered hippuric acid as ana-
logous to oxamic, lactamic, tartramic, and aspartic acids, and as a
compound of this acid with its amide (H2N.C9H3O2 + C9H3O3.HO —
C18H8NO5.HO). The view, in accordance with which benzoic acid
exists preformed, is, however, still the most probable.
Combinations. — With alkalies and alkaline earths hippuric acid
forms crystallisable salts soluble in water and having a bitter taste;
its combinations with metallic oxides are difficult of solution in cold
water, but dissolve somewhat more freely in hot water. All the
crystallised salts contain water of crystallisation. Schwartz* has
analysed the following salts :
Neutral hippurate of potash, KO.Hi + 2HO, occurs in micro-
scopic, oblique rhombic prisms, which part with their water at 100°.
The acid salt KO.Hi + HO.Hi + 2HO, crystallises in broad, satiny
plates.
Hippurate of soda, 2NaO.Hi + HO, is crystalline, and dissolves
readily in water and alcohol.
Acid hippurate of ammonia, H4NO.Hi + HO«Hi + 2HO, occurs
in very minute, four-sided, square prisms ; it behaves, when thrown
upon water, like butyrate of baryta.
Hippurate of baryta, BaO.Hi + HO, is obtained in microscopic,
square prisms, and loses its water at 100°.
Hippurate of strontia, SrO.Hi+5HO, occurs in broad plates,
difficult of solution in cold water, or in microscopic, four-sided
prisms, with large terminal planes.
Hippurate of lime, CaO.Hi + 3HO, occurs in oblique rhombic
prisms ; it parts with all its water at 100°.
Hippurate of magnesia, MgO.Hi + 5 HO, crystallises in wart-like
masses, is readily soluble, and at 100° loses only 4 atoms of water.
Hippurate of cobalt, CoO.Hi + 5HO, occurs in rose-coloured
wart-like masses, consisting of microscopical, flat, four-sided prisms ;
at 100° it loses all its water, and it is perfectly insoluble in alcohol.
Hippurate of nickel, NiO.Hi + 5HO, forms apple-green crusts,
dissolves in warm spirit, and at 100° loses all its water.
* Ann. d. Ch. u. Pharm. Bd.54, S. 29-51. [Schwartz has published another
memoir on this acid during the last few months (in Ann. d. Ch. u. Pharm. Bd. 75,
S. 190.)— o. E. D.]
HIPPURIC ACID. 193
Hippurate of copper, CaO.Hi+3HO, occurs in blue, oblique
rhombic prisms, and at 100° is anhydrous.
Hippurate of lead., PbO.Hi, crystallises from hot solutions with
2 atoms of water in fine silky tufts of needles; from cold solutions,
by slow evaporation, in broad four-sided tablets, with 3 atoms of
water. At 100° it is anhydrous.
Hippurate of silver, AgO.Hi + HO, occurs as a curdy preci-
pitate, which dissolves in boiling water, and, on cooling, separates
in beautiful silky needles.
Hippurate of iron occurs as a dingy, voluminous precipitate,
which does not dissolve, but fuses in boiling water ; it dissolves in
warm alcohol, but falls as an amorphous precipitate on cooling ; it
crystallises from the cold solution in oblique rhombic prisms.
Hippurate of oxide of ethyl, C4H5O.C18H8NO5, forms long,
white, silky needles, with a greasy feeling, devoid of odour, of an
acrid taste, slightly soluble in cold, but more so in hot water; it
fuses at 44°, solidifying again at 32°, and on exposure to a stronger
heat it decomposes.
Products of its metamorphosis. — The non-nitrogenous acid,
C18H7O7.HO, obtained from hippuric acid by the action of nitrous
acid, is, according to Strecker, readily soluble in ether, yields with
baryta a salt, crystallising in silky needles, and readily soluble in
water, and with oxide of silver a salt, AgO.C18H7O7, \vhich dis-
solves in boiling water, and on cooling crystallises in delicate
needles ; and which, on exposure to heat, developes hydride of
benzoyl. The production of this acid from hippuric acid is shown
in the equation C18H8NO5 + 3HO-H3N=C18H7O7.HO.
Preparation. — Hippuric acid is very easily obtained from the
urine of horses, but there is some difficulty in separating it from
the colouring matter. Fresh urine, obtained from horses, is
evaporated to -J-th of its volume, and then treated with hydrochloric
acid ; after it has cooled, the acid which has separated, and is
usually much discoloured, is dissolved in ten times its bulk of
boiling water, and boiled with milk of lime ; the solution is filtered,
a solution of alum is added till there is an -Acid reaction, and the
alumina is then precipitated by bicarbonate of soda. The boiling
with milk of lime destroys a portion of the pigment adhering to the
hippuric acid, while another portion of the pigment is precipitated
with the alumina. The acid precipitated by hydrochloric acid from
the filtered fluid is again dissolved in boiling water, boiled with
animal charcoal, and filtered while hot; on cooling, the acid now
o
194 CONJUGATED ACIDS.
separates in a colourless state. Moreover, by mere, but often
repeated, boiling of horses5 urine, and of the hippuric acid separated
from it with milk of lime, we may obtain it free from colour.
Perfectly fresh urine must be used, since horses' urine, even at
an ordinary temperature, very soon begins to decompose ; and it
then no longer yields hippuric but benzoic acid.
Tests. — Hippuric acid presents such characteristic properties,
that if it be once pretty well freed from other substances, it can
scarcely be confounded with any other acid, except, perhaps, ben-
zoic acid, if the latter be contaminated with organic colouring, and
nitrogenous matters ; since in the pure state, the two acids act so
differently when exposed to heat that it is impossible to confound
one with the other.
When they occur in an impure state, they may be distinguished
from one another by attention to the following points.
Hippuric acid, which is far less soluble in ether than benzoic
acid, crystallises from hot saturated solutions in needles or prisms,
while benzoic acid crystallises in scales. The latter often causes
such a solidification of the whole fluid, that the vessel after cooling
may be inverted without the escape of a single drop. Further, on
the addition of acids to solutions of their salts, hippuric acid is at
once precipitated in needles or spangles, while benzoic acid gives
rise to a milky turbidity before it crystallises. On rapidly evapo-
rating an acid fluid in a basin covered over with paper, delicate
glistening scales may be observed on its lower surface if benzoic
acid be present, but not if hippuric acid alone be present in the
fluid. The microscope, however, affords the best means of dis-
tinguishing these acids from one another, by comparing their crys-
talline forms in accordance with the directions given in pp. 83, and
188. With such an examination, it is impossible that these acids
can be confounded.
In order to detect small quantities of hippuric acid in animal fluids,
we must be especially careful that such fluids are fresh, since if this
be not the case, the hippuric acid will have become changed into ben-
zoic acid, which on evaporation for the most part escapes with the
aqueous vapour; if, however, the animal fluid be still perfectly un-
decom posed, it must be evaporated to almost the consistence of a
syrup and then extracted with alcohol of specific gravity, 0.83 ; a
little oxalic acid must be added to the alcoholic extract during its
evaporation, which must be continued till it assumes a syrupy con-
sistence ; the residue must then be extracted with ether to which
|th of its volume of alcohol has been added. This extract must
HIPPURIC ACID. 195
now be carefully evaporated, and the residue which, besides free
acids, also contains fatty matters, must be treated with water in
in order to remove the latter. It sometimes happens that on the
addition of the water, crystals of hippuric acid at once separate
from the above extract-like mass; but whether this be the
case or not, this ethereal extract must be warmed with water, and
allowed to percolate through a previously well moistened filter ;
the filtered acid fluid may then either be gently concentrated by
warmth, or, if its quantity be very small, it may be left to sponta-
neous evaporation in a watch-glass ; crystals of hippuric acid very
soon separate, whose form must be determined by the microscope.
If much hippuric acid be present, it will sometimes separate from
the syrupy residue by the mere addition of hydrochloric acid, and
can be distinguished from uric acid and other crystalline substances
by the microscope.
Physiological Relations.
Occurrence. — Hippuric acid was first recognised by Liebig as an
independent acid in horses3 urine where it had previously been mis-
taken for benzoic acid; it has been subsequently found in the urine of
many graminivorous animals, as, for instance, oxen, elephants, goats,
hares, sheep, &c. It is, however, singular that, according to Wohler,
it is entirely absent in the urine of calves while suckling, although the
fluid contains allantoine, uric acid, and urea, (see p. 176.) In the
urine of the pig neither Boussingault,* nor von Bibra,f could
discover any hippuric acid. Liebigf was the first who recognised
its presence in healthy human urine, in which it principally occurs
after the use of vegetable food : according to him it exists in human
urine, in about the same quantity as uric acid, while according to
Bird,§ the hippuric acid most commonly stands to the uric acid
in the ratio of 1 : 3.
I have already remarked in p. 83. that benzoic acid never occurs
in fresh horses5 urine, and that it is merely a product of the
decomposition of that fluid ; I can, however, perfectly confirm the
observation of Schmidt, || that hippuric acid is occasionally, although
* Ann. de Chim. et de Phys. 3 Ser. T. 15, pp. 97-104.
f Ann. de Ch. u. Pharm. Bd. 53, S. 98-112.
$ Ibid. Bd. 37, S. 257.
§ London Medical Gazette, vol. 34, p. 685: [In his Urinary Deposits, &c.
3rd edit., p. 96, this opinion is considerably modified. We there find that " its
quantity in health is not constant, and always, unless after the ingestion of benzoic
or cinnamic acid, very much less than has been stated." — G. E. D.]
U Entwurf u. s. w. S. 39.
o 2
196 CONJUGATED ACIDS.
very rarely, entirely absent, and that in its place there is found an
oily matter which when heated with caustic alkalies yields ben-
zine.
Attempts have been made to refute Liebig^s assertion that hip-
puric acid always exists in human urine, at least after the use of
vegetable food ; but although I formerly did not succeed in detect-
ing this acid in my own urine during a purely vegetable diet, I
have since very frequently convinced myself, both from experi-
ments both on large and on small quantities of urine, that this
acid is constantly present during the use of a mixed diet. The
presence of hippuric acid may, however, readily escape our notice
if we evaporate the acid urine too rapidly, after the acid has been
converted into benzoic acid ; on the other hand, we need be under
no apprehension that the hydrochloric acid which is added will
decompose the hippuric acid, as in order to effect any change on it,
a very concentrated acid and prolonged boiling are required.
Hippuric acid is not found in the urine of carnivorous animals,
but it has probably not been sought for with sufficient care and
attention. In the urine of tortoises neither J. Miiller and Magnus,*
nor Marchandf could detect hippuric acid ; I have, however, con-
vinced myself with the greatest certainty, and on many occasions,
that hippuric acid is present in addition to uric acid in the urine
of Testudo grceca.
Magnus was unable even to find uric acid in the urine of Tes-
tudo nigra s. elephantopus, while Marchand found uric, but no hip-
puric acid in the urine of T. tabulata ; I probably worked with
much larger quantities, and certainly always used fresh urine. My
specimens of Testudo graca were fed with lettuce and other vegeta-
bles. The urine may be easily collected by placing the animal on
its back in a dish; when the bladder is moderately filled, the
animal very soon spontaneously passes its urine, which, besides
alkaline urates and hippurates, contains free hippuric acid. Without
the preliminary addition of a stronger acid, we may obtain the
hippuric acid in a crystalline state by the addition of water to the
ethereal extract, and sufficiently pure to admit of our accurately
studying its behaviour when exposed to heat, its solubility, &c. ;
if, however, oxalic or hydrochloric acid were used in the process, in
the manner which has been already explained, we should obtain
much larger quantities of hippuric acid.
In morbid human urine I have almost always been able to detect
* Mailer's Archiv. 1835. S. 214.
t Journ. f. pr. Ch. Bd. 34. S. 244-247.
HIPPURIC ACID. 197
hippuric acid; it especially occurs in large quantity in acid febrile
urine, whether the fever be typhus or be associated with pneumonia
or any other pathological process. Before hippuric acid was dis-
covered in healthy human urine, I detected its presence in diabetic
urine,* in which it is more easily recognised than in other forms of
urine which abound in extractive matters.
In diabetic urine I have found hippuric acid in every instance in
which I have sought for it ; Ambrosiani, Hiinefeld, and others have
also found it in the urine during this disease ; Bouchardat found it in
a case of what is called diabetes insipidus; Pettenkoferf found it in
large quantity in the urine of a girl with chorea. In the case of a
drunkard with a contracted, probably a hob-nail, liver, Birdj ob-
served a sediment consisting of hippuric acid, on the addition of
hydrochloric acid to the concentrated urine. In the strongly acid
urine which is sometimes passed in fevers, the acid reaction is in a
great degree dependent on the hippuric acid ; from the ethereal
extract of urine of this nature, and without the preliminary addition
of any acid, we often obtain the most beautiful crystals of hippuric
acid. Such urine is, however, by no means so common as is gene-
rally supposed ; for this febrile urine is much more rapidly rendered
acid by lactic acid, (which is not formed till after the emission of
the urine,) than the normal secretion, and hence, unless it be
examined when perfectly fresh, we usually find that febrile urine
is more acid than the normal fluid. 1 have not been able to
establish any relation between certain morbid processes or groups
of symptoms and the amount of the hippuric acid contained in the
urine.
Hippuric acid has as yet been found nowhere but in the urine.
[Its recent discovery in the blood of oxen, by Verdeil and Doll-
fass,§ is noticed in the second volume, in the article on " The
Blood/'— G. E. D.]
Origin. — Notwithstanding the many points which seem to
elucidate the inquiry, the formation of hippuric acid in the animal
body still remains unexplained. All views regarding the chemical
constitution of hippuric acid coincide in the belief that it contains,
hidden within it, a benzoyl-compound (C14H5O2 + H or + O or +
H2N) ; it is an established fact that benzoic acid, oil of bitter
* Journ. f. pr. Ch. Bd. 6, S. 113.
t Ann. d. Ch. u. Pharm. Bd. 57, S. 128.
£ London Medical Gazette, vol. 34, p. 686.
§ [Compt. rend. T. 29, p. 789 ; and more fully in the Ann. d. Ch. u. Pharm,
Bd. 74, S 214.]
198 CONJUGATED ACIDS.
almonds, and cinriamic acid, which is very similar to benzoic acid,
are transformed in the animal body into hippuric acid. Now, since
the benzoyl-compounds are almost entirely confined to the vege-
table kingdom, we might believe that this constituent of hippuric
acid principally arises from vegetable food, and the abundance
of this acid in the urine of many herbivorous animals is in favour
of this view. We might therefore be led to regard one constituent
of hippuric acid as an immediate product of decomposition of
certain constituents of food, namely, of the vegetable portion ; but
this view is opposed by several positive experimental results ; thus
in the urine of patients on an antiphlogistic diet, who for several
days have scarcely taken any food, the amount of hippuric acid is
actually increased.
The urine of tortoises, which had been kept fasting for more
than six weeks, still contained hippuric acid ; and it occurred in
the urine of diabetic patients who were restricted to a purely
animal diet. In the urine of granivorous birds, as well as in that
of the larva of Sphinx Cossus, and of several other herbivorous
insects, I have found, after careful examination, larger or smaller
quantities of uric acid, but no hippuric acid. Hence we may con-
clude in the first place that the formation of uric acid is not depen-
dent on the use of animal food; or that of hippuric acid on the use
of vegetable food, and secondly, that the latter acid must derive its
nitrogenous constituent from the retrograde metamorphosis of the
animal tissues. This is, moreover, not opposed to our chemical
facts in relation to the production of the benzoyl-compounds, for
there is every reason to believe that the nitrogenous tissues which,
according to the admirable investigations of Guckelberger, when
treated with oxidising agents, yield benzoic acid and benzonitrile,
yield a like product of decomposition during the gradual oxidation
which they undergo in the animal body.
In reference to the nitrogenous constituent of hippuric acid we
may regard it as fumaramide, or as glycine; it is undoubtedly
derived from the animal albuminous substances, and probably
from effete tissue. It would, however, certainly be rash to attri-
bute it principally to the decomposition of the gelatigenous tissues,
simply because it is chiefly formed from them in artificial experi-
ments ; but independently of the circumstance that this product
into which the nitrogenous adjunct of hippuric acid becomes con-
verted, may also be obtained from albuminous substances, we
must bear in mind that the metamorphosis going on in the gelati-
genous tissues is certainly too insignificant to account for the
URIC ACID. 199
quantity of hippuric acid found in the urine, (as, for instance, after
the ingestion of from two drachms to half an ounce of benzoic
acid,) and that the same substance is separated even more abun-
dantly from the liver. Glycine must therefore be regarded in the
same light as urea, as a common product of decomposition of
nitrogenous substances.
We cannot therefore find any very immediate source from
which either of the proximate constituents of this acid can be
derived, since neither physiological nor pathological relations
elucidate the process by which it is formed in the animal body.
This much, however, is certain, that hippuric acid is to be
regarded merely as a product of excretion, and consequently that
it can have no special uses in the animal organism.
It is to be regretted that benzoic acid is so rarely prescribed
by the physician ; and that, even in those cases, it is usually order-
ed on most irrational principles. It deserves to be thoroughly
tested in a pharmacological point of view; it certainly possesses
one great advantage over all the other officinal acids in its property
of rendering the urine strongly acid. Ure attaches great importance
to this circumstance, but it does not appear to have been turned to
much account in actual practice.
URIC ACID.— C5HN2O2.HO.
Chemical Relations.
Properties. — Pure uric acid occurs either in a glistening white
powder, or in very minute scales, which under the microscope are
seen to consist of irregular plates, whose crystalline form (see our
remarks on the crystals, in the consideration of the "Tests/5)
cannot very well be made out : it is a substance devoid of odour
and taste ; it requires 1800 or 1900 parts of hot, and 14000 or 15000
parts of water at the ordinary temperature of 20°, to dissolve it ; it
is insoluble in alcohol and ether, and does not redden litmus. It
dissolves in concentrated hydrochloric acid somewhat more readily
than in water ; it dissolves tolerably freely> and without decompo-
sition, in concentrated sulphuric acid, but is again precipitated on
the addition of water. It dissolves readily in the alkaline carbo-
nates, borates, phosphates, lactates, arid acetates, since it abstracts
some of the alkali from these salts, and is thus rendered more
soluble. Uric acid is expelled from all its salts by acetic as well as
200 CONJUGATED ACIDS.
by other acids, and on its separation at first forms a gelatinous
mass, (according to Fritzsclie,* a hydrates C5HN2O2. HO + 4HO)
which, however, soon changes into small glistening plates.
Uric acid belongs to the weakest class of acids ; thus, as in the
case of the fatty acids, it does not directly expel carbonic acid from
carbonate of potash, but urate of potash and bicarbonate of pota'sh
are formed, if a sufficient amount of uric acid be added ; if the
solution of potash be concentrated, the urate of potash remains
un dissolved ; the behaviour of uric acid to the alkaline borates and
phosphates is similar, with the exception of this difference, that
the solution of phosphate of soda, which has an alkaline reaction,
reddens litmus when an excess of uric acid has been added to it,
in consequence of the formation of biphosphate of soda.
Uric acid, when submitted to dry distillation) is converted into
urea, cyanic acid, cyamelide, hydrocyanic acid, and a little carbo-
nate of ammonia, leaving, as a residue, a brownish-black coal, rich
in nitrogen.
On fusing uric acid with hydrated potash, carbonate and
cyanate of potash, with cyanide of potassium, are formed. On
boiling uric acid with 20 parts of water, and adding peroxide of
lead as long as the brown colour of the oxide continues to dis-
appear, there are formed oxalate of lead, urea, and allantoine,
( 2C5HN202.HO + 20 + 3HO = C2H4N2O2 + 2C2O3 + C4H3N2O3) .
Moist uric acid, placed in chlorine gas, intumesces, and, giving
off carbonic and cyanic acids, is converted into oxalic acid and
hydrochlorate of ammonia ; dry uric acid in dry chlorine gas yields
much cyanic acid, chloride of cyanogen, and hydrochloric acid,
leaving only a small carbonaceous residue. Uric acid dissolves
with considerable readiness in dilute nitric acid, developing equal
volumes of nitrogen and carbonic acid, and yielding to the solution
several of the different products of decomposition which we shall
presently describe. On evaporating to dryness a solution of uric
acid in nitric acid, there is left a red amorphous residue, which,
especially if we expose it to the vapour of ammonia, assumes a very
beautiful purple tint ; on moistening the red mass (murexide) with
a little caustic potash, a beautiful violet tint is developed (Schloss-
berger.f)
Composition. — According to the above formula, deduced by
BenschJ from his analyses of the urates, uric acid consists of:
* Bull, scient. de St Petersb. T. 1, Nos. 79 et 107.
t Arch. f. physiol. Heilk. Bd. 8, S. 294.
$ Ann. d, Ch. u. Phann. Bd. 51, S. 189-20&
URIC ACID. 201
Carbon .... .... 5 atoms .... 35*714
Hydrogen 1 „ .... 1-191
Nitrogen 2 „ .... 33'333
Oxygen 2 „ .... 19'048
Water 1 „ .... 10714
100-000
The atomic weight of the hypothetical anhydrous acid = 937*5,
and its saturating capacity = 10 '65 6. There is hardly any
other organic acid, whose products of decomposition have been
so accurately and so generally examined as those of uric acid, and
yet chemists have been unable to establish for it any rational
formula. Bensch's discovery of the true atomic weight of uric
acid has tended to weaken the views which were previously held
regarding the intimate constitution of this acid. If we choose
to double the atoms, and if we so far extend the idea of conju-
gation, that the conjugating substances may, in their union, lose
certain atoms of hydrogen and oxygen, (so that we might regard
oxamide as a body composed of oxalic acid and ammonia, and
benzanilide as composed of benzoic acid and aniline,) then indeed,
much might be explained at which we could not arrive by a strict
logical induction. Taking into consideration those substances
which for a long time have been regarded as conjugated, it seems
that we should only consider as true conjugated bodies those
compounds in which two organic bodies unite with one another,
the union being accompanied with a loss of water ; which, however,
in some cases may be shewn by direct experiment, and in others,
may be assumed with great probability, to lie without the true
atomic group, and may therefore be regarded as a basic, acid, or
saline atom of water. Many of the substances which have been
recently regarded as conjugated bodies, undoubtedly contain certain
atoms of oxygen and hydrogen less than the anhydrous substances
from which they are produced, or maybe supposed to be produced;
but this view does not coincide with the original idea of a conju-
gated body ; especially when it is probable that in this union one
of the substances has contributed the oxygen and the other the
hydrogen for the formation and separation of the water.
It would be equally injudicious, were we not to facilitate the
recognition of the metamorphosis or transposition of the atoms of
organic substances, by some general remarks on the connection
and separation of atoms.
Such remarks, however, are not based on anything more than a
fiction, and do not rest on a conclusion obtained by induction.
202 CONJUGATED ACIDS.
That such hypotheses are not always to be rejected in the natural
sciences, is shown by Newton's hypothesis of emanating rays
of light, which now, indeed, is entirely displaced by the undu-
latory theory. In this light we must consider the view re-
garding the composition of uric acid, put forth some years
ago by Liebig and Wohler. From the decomposition of uric
acid by peroxide of lead, they deduced, for uric acid, the hypo-
thetical formula, C2H4N2O2 + 2C4NO2; that is to say, they
regarded urea as existing preformed in it, together with an acid
incapable of isolation in an undecomposed state, to which they
applied the name of urilic acid. Now that the substratum of this
hypothesis has been more than shaken by the discovery of the
true atomic weight of uric acid, we may yet make use of this
fiction in order to be able to represent the formation of the pro-
ducts enumerated by Liebig and Wohler in their classical investi-
gations regarding uric acid. Thus we may conceive, that on the
decomposition by peroxide of lead, 2 equivalents of hydrated uric
acid contain 1 equivalent of urea, which is isolated, while the 2
equivalents of urilic acid are, in the first place, decomposed into
C4O4 and C4N2, of which the former assimilates 2 atoms of oxygen,
and forms oxalic acid, while the latter assimilates 3 atoms of water,
and produces allantoine. In a similar way we can elucidate the
mode of formation of those numerous products which result from
the action of nitric acid on uric acid.
Combinations. — It is only with the fixed alkalies that uric acid
forms salts which possess even a moderate degree of solubility ;
the lithia-salt is especially soluble, while urate of ammonia is
almost insoluble. Potash and soda are the only bases with which
uric acid forms neutral salts ; with ammonia and all other bases it
forms only acid and insoluble salts. On passing carbonic acid
into a potash-solution of uric acid, an acid potash-salt is precipi-
tated.
Neutral urate of potash, KO.C5HN2O2, is obtained on mixing
alcohol with a solution of uric acid in potash (free from the car-
bonate) and concentrating the solution. It crystallises in needles
free from water, dissolves in 30 or 40 parts of boiling water, slightly
in alcohol, and not at all in ether, has a strong alkaline reaction, and
attracts carbonic acid -from the atmosphere.
Bi-urate of potash, KO.C5HN2O2 + HO.C5HN2O,y is precipi-
tated by carbonic acid from the solution of the neutral salt ; it
crystallises in needles, dissolves in 70 or 80 parts of boiling water,
and in 700 or 800 parts of water at 20°. The solution does not
URIC ACID. 203
exhibit an alkaline reaction, and is precipitated by hydro-chlorate of
ammonia and the alkaline bicarbonates.
Neutral urate of soda, NaO.C5HN2O2-f HO crystallises in wart-
like masses, dissolves in 80 or 90 parts of boiling water, is slightly
soluble in alcohol, and insoluble in ether; at 100° it loses its water
of crystallisation.
Bi-urate of soda, NaO.C5HN2O2+HO.C5HN2O2 + HO crys-
tallises in short hexagonal prisms, or in thick six-sided (microscopic)
tablets, which commonly arrange themselves in star-formed masses
in which the individual crystals are larger and can be more
distinctly made out than in the microscopic aggregations of the
ammonia-salt ; it begins to lose its water of crystallisation at 1 70°,
and is soluble in 124 parts of boiling and 1150 parts of cold
water.
Bi-urate of ammonia, H4NO.C5HN2O2 + HO.C5HN2O2, may
be obtained crystallised in extremely delicate needles, but it also
forms under the microscope, globular opaque masses, from some
points of which extremely delicate spikelets may be seen to
project.
Almost all the other salts of uric acid occur as amorphous
precipitates, and consist of 1 atom of base and 2 atoms of uric
acid, of which 1 atom always retains its basic atom of water;
hence we cannot well assume that the atomic weight of uric acid
should be doubled, (that is to say=C10H2N4O4) for if, with such
an atomic weight, these salts were all neutral salts, they, or at all
events, some of them, would certainly lose this 1 atom of water at
a higher temperature.
The salts of baryta, strontia, and lime, are represented by the
formula RO.C5HN2O2+ HO.C5HN2O2 + HO.
Bi-urate of magnesia, MgO.C5HN2O2 + HO.C5HN2O2 + 6HO,
crystallises in delicate needles, loses 5 of its 6 atoms of water at
1700, and dissolves in 160 parts of boiling water, but in not less
than 3800 parts of cold water.
Bi-urate of lead, PbO.C5HN2O2+HO.C5HN2O2+HO, is a
white powder, which loses its water of crystallisation at 160°.
Bi-urate of copper, CaO.C5HN2O2H-HO.C5HN2O2 + 5HO, is
a green powder which, at 140°, loses 3 atoms of water of crystal-
lisation.
Sulphate of uric acid, HO.C5HN2O2 + 4 (HO.SO3), is formed
by dissolving uric acid in warm concentrated sulphuric acid, from
which, on cooling, it separates in colourless crystals, which fuse at
70°, in cooling again solidify in a crystalline mass, and become
204 CONJUGATED ACIDS.
decomposed at 170°; it attracts water from the atmosphere,, and
thus becomes decomposed into its proximate constituents in the
same manner as if water were added to it.
Products of its metamorphosis. — The products of decomposition
of uric acid are of extreme interest, insomuch as they afford us a
deep and general insight into the various transpositions of atoms
and atomic groups.
Alloxan, erythric acid, C8H4N2O10, is produced when 1 part of
dry uric acid is gradually introduced into 4 parts of nitric acid of
1.42 to 1.53 specific gravity, when the whole finally solidifies and
becomes crystalline. A better method of preparing this body is by
mixing 4 parts of uric acid with 8 parts of moderately strong
hydrochloric acid, and then gradually introducing 1 part of chlorate
of potash into the fluid ; in the latter case, urea and alloxan are
formed without any development of gas, while in the former case,
nitrogen and carbonic acid are evolved in consequence of the decom-
position of the urea by nitrous acid. (Compare p. 154.)
Alloxan crystallises in large colourless rhombic octohedra (which
at first have a diamond-like lustre, but soon effloresce) with
6 atoms of water of crystallisation from hot but not perfectly
saturated solutions ; while from saturated solutions it crystallises
in anhydrous four-sided prisms: it has a faintly saline taste, a
sickly odour, reddens litmus, and communicates a purple red
colour to the skin.
It is easy to see that in accordance with the above fiction
respecting urilate of urea, urilic acid assimilates 4 atoms of water
and 2 atoms of oxygen, and thus forms alloxan, (C8N2O4-f4HO
+ 20=C8H4N2010.)
Alloxanic acid, C4HNO4.HO, is formed by digesting alloxan
with caustic alkalies, and by decomposing the baryta-salt by sul-
phuric acid. It crystallises in concentrically grouped needles,
which are unaffected by exposure to the atmosphere, have an acid,
(but subsequently leave a sweetish) taste, dissolve readily in water,
less in alcohol, and very slightly in ether ; this acid reddens litmus
strongly, decomposes carbonates and acetates, and oxidises zinc and
cadmium, hydrogen being at the same time developed; in an aqueous
solution it becomes decomposed at a temperature above 60°. Its
alkaline salts are soluble in water and crystallisable ; its other
neutral salts are difficult of solution : like uric acid it has a strong
tendency to form acid salts, all of which are soluble (Schlieper.)*
Alloxanic acid is produced by the abstraction of 2 atoms of
water from alloxan.
* Ann. d. Ch. u. Pkarm. Bd. 55, S, 251-297.
URIC ACID. 205
If a solution of alloxanic acid be submitted to prolonged ebulli-
tion, it evolves carbonic acid, and is decomposed into an acid
insoluble in water, leucoturic acid, C6H3N2O6, and into a soluble
indifferent body, diffluan; C6H4N2O5 (Schlieper.)
Two atoms of alloxan yield 1 atom of this new acid, and 1 atom
of diffluan, besides 4 atoms of carbonic acid and 1 atom of water,
for C16H8N4020=C6H3N206 + C6H4N2O5 + 4CO2 + HO.
Mesoxalic acid, C3O4, is produced together with urea, when a
solution of alloxan is added by drops to a boiling solution of acetate
of lead : it is crystallisable, and reddens litmus.
Alloxan becomes simply decomposed into 1 equivalent of urea
and 2 equivalents of mesoxalic acid, for C2H4N2O2+2C3O4—
C8H2N20I0.
Mykomelinic acid, C8H5N4O5, is formed when an excess of
dilute nitric acid is added to a supersaturated solution of alloxan,
and boiled for some time with ammonia; in its moist state it occurs
as a yellow gelatinous mass ; when dried, it is a yellow powder,
which is soluble in water, reddens litmus, and decomposes car-
bonates.
This acid is formed from 1 atom of alloxan and 2 atoms of
ammonia with the separation of 5 atoms of water ; C8H4N2O10 +
2H3N - 5 HO =± C8H5N4O5.
Parabanic acid, C6N2O4-f 2HO, is prepared by digesting 1 part
of uric acid or of alloxan, with 8 parts of moderately diluted nitric
acid, and evaporating the solution to the consistence of a syrup ;
after some time there is a separation of small plates or minute prisms
of parabanic acid ; it is unaffected by exposure to the atmosphere,
has an acrid, sour taste, dissolves readily in water, fuses when
heated, and partially sublimes without decomposition.
Parabanic acid is produced in the following manner from uric
acid and nitric acid : the urea of the uric acid is decomposed as
usual by the nitrous acid which is formed, but 2 atoms of water
and 4 atoms of oxygen enter into combination with the urilic acid
with which they form 2 atoms of carbonic acid, and 1 atom of
parabanic acid, for C8N2O4 + H2O2 + 4O-C2O4=C6N2O4 + 2HO.
Alloxan with 2 atoms of oxygen becomes decomposed into
2 atoms of carbonic acid, 4 atoms of water, and 1 atom of
parabanic acid, for C8H4N2O10 + 2Or=C2O4 + H4O4 + C6N2O4.
Hydrurilic acid, C12H3N3O9 -f 2HO, is formed at the same time
with alloxan under certain conditions not yet accurately under-
stood ; it occurs as a white flocculent powder, consisting of delicate
needles; it is difficult of solution in cold, but dissolves more
206 CONJUGATED ACIDS.
readily in hot water ; it is insoluble in alcohol ; with the alkalies it
forms acid and neutral salts ; this acid may be regarded as a com-
bination of the above mentioned hypothetical urilic acid with water;
3 atoms of urilic acid and 1 0 atoms of water forming 2 atoms of
hydrurilic acid. By nitric acid, this acid is converted into nitro-
hydrurilic acid, C8H2N3O14.
Oxaluric acid. CfiHoN0O7.HO : if a solution of uric acid in
> O O ^ /
dilute nitric acid be supersaturated with ammonia and evaporated,
the ammonia-salt of this acid separates in needles ; on separating the
acid from the salt by means of a more powerful acid we obtain it
as a glistening white crystalline powder with an acid taste ,and an
acid reaction ; when heated it becomes decomposed into 2 atoms
of oxalic acid and 1 atom of urea, for C6H3N2O7.HO==2C2O3 +
C2H4N2O2.
Crystallised oxaluric acid may therefore be regarded as a
combination of 2 atoms of oxalic acid and 1 atom of urea, for
C406+C2H4N202=C6H4N208.
Parabanic acid when boiled with ammonia takes up 3 atoms of
water, and forms oxaluric acid, for C6N2O4 + H3O3 = C6H3N2O7.
Thionuric acid^ C8H7N3S2O14, is formed by mixing a solution
of alloxan with an excess of aqueous sulphurous acid, supersa-
turating with ammonia and boiling for some time ; as the solution
cools, thionurate of ammonia separates in nacreous crystalline
scales ; on combining the acid of this salt with lead, decom-
posing the lead-salt by sulphuretted hydrogen, and evaporating
the filtered fluid, we obtain thionuric acid in the form of a white
crystalline mass with an acid taste, which is unaffected by exposure
to the air, dissolves readily in water, and is decomposed both by
simple boiling and on the addition of acids. The salts of this acid
saturate 2 atoms of base ; on the addition of concentrated sulphuric
acid, sulphurous acid is developed.
Thionuric acid may be regarded as a combination of 1 atom of
alloxan with 1 atom of ammonia and 2 atoms of sulphurous acid,
for C8H4N2010+ H3N+ S?O4=C8H7N3S2OI4.
Uramile, C8H5N3O6, is produced either by simply exposing
thionuric acid to ebullition, or by treating thionurate of ammonia
with an excess of hydrochloric acid; it forms minute, silky, glis-
tening needles, and on exposure to the atmosphere and to warmth,
assumes a rose-red tint. It is insoluble in cold water and only
dissolves slightly in boiling water ; the caustic alkalies and concen-
trated sulphuric acid dissolve, but do not decompose it : by simple
ebullition, however, its solutions become decomposed. The alkaline
URIC ACID. 207
solution of uramile on exposure to the air assumes a purple red
tint, and deposits green crystals with a metallic lustre.
On simply boiling thionuric acid, 2 atoms of sulphuric acid are
ghen off, and uramile is formed; for C8H7N3S2O14-2SO3.HO=:
C8H5N306.
Uramile may be regarded as uric acid in which the urea is re-
placed by 1 atom of ammonia and 2 atoms of water ; it is, therefore,
hypothetically composed of 1 atom of urilic acid, 1 atom of ammonia,
and 2 atoms of water, for C8N2O4 + H3N + 2HO = C8H5N3O6.
Uramilic acid, C16H10N5O15, is formed by boiling uramile either
with a solution of potash or with dilute acids ; it crystallises in
colourless, four-sided prisms, or silky, glistening needles, is soluble
in water, faintly reddens litmus, dissolves without the development
of gas, or the communication of colour, in sulphuric acid; is decom-
posed by nitric acid, and forms soluble salts only with the alkalies.
Acids and alkalies expel 1 atom of ammonia from 2 atoms of
uramile, which, in its place, receive 3 atoms of water ; C16H10N6O12
-H3N + 3HO=CI6H10N5015.
Alloxantin, C8H5N2O10, is formed by boiling 1 part of uric acid
with 32 parts of water, then gradually adding dilute nitric acid, and
finally evaporating the fluid to one third of its volume: after some
time crystals of alloxantin separate themselves. It is prepared
from alloxan by the action of reducing bodies, as for instance, sul-
phuretted hydrogen, or hydrochloric acid and zinc. It crystallises
in oblique four-sided prisms, which at first are colourless, but on
exposure to the air become yellowish, and if acted on by the
vapour of ammonia, become red. It is slightly soluble in cold, but
dissolves readily in hot water, it reddens litmus, and is converted
by chlorine into alloxan ; with baryta-water it gives a violet-
coloured precipitate.
When very dilute nitric acid acts on uric acid, the urilic acid
takes up 1 atom of oxygen from the nitric acid and 5 atoms of
water in order to form alloxantin (C8N2O4 -f O -f 5HO=
C8H5N2O10), while the hyponitric acid which is formed, becoming
decomposed into nitrous and nitric acids, partly combines with and
partly decomposes the urea of the uric acid.
On treating alloxan with sulphuretted hydrogen, the sulphur
separates, while the hydrogen unites with the alloxan, and forms
alloxantin, C8H4N2O10 + H = C8H5N2O10.
Mureocide,Cie2R^£)s,purpurate of ammonia, may be obtained
by several very different methods. The most simple means of
preparing it is by boiling equal parts of uramile and red oxide of
208 CONJUGATED ACIDS.
mercury with 40 parts of water and a very small quantity of am-
monia; the purple-red fluid which is thus obtained must be
filtered, and after standing some time will deposit crystals of
murexide. This body may also be prepared by dissolving uric
acid in dilute nitric acid, and evaporating the fluid till it assumes
a reddish tint ; after it has cooled to 70° it must be saturated with
dilute ammonia, diluted with half its volume of water, and allowed
to stand.
Murexide crystallises in, short four-sided prisms, twro of whose
surfaces present a cantharides-green, glistening appearance : in
refracted light these crystals present a garnet-red tint; when
pulverised it is of a brownish-red colour, and under the burnishing
rod presents a green, metallic lustre ; it is insoluble in alcohol and
ether, slightly soluble in cold, but freely in hot water, and it dis-
solves in a solution of potash, communicating an indigo-blue
colour to the fluid. It is decomposed by all the mineral acids.
In the preparation of murexide from uramile and red oxide of
mercury , 2 atoms of uramile take up 3 atoms of oxygen from the
mercury, and form 1 atom of murexide, 1 atom of alloxanic acid
and 3 atoms of water ; (C16H10N6O12 + 3O = C12H6N5O8 +
C4HNO4 + 3HO.)
When uric acid is dissolved in dilute nitric acid, the principal
product is alloxantin, which by the action of the nitric acid during
evaporation is in part converted into alloxan, from which murexide
is formed on the addition of ammonia ; for 1 atom of alloxan, 2
atoms of alloxantin, and 4 atoms of ammonia, yield 2 atoms of
murexide and 14 atoms of water; (C8H4N2O10 + C16H10N4O20
+ H12N4= C24H12N10016 + H14014.)
Murexan, C6H4N2O5, purpuric acid, is prepared by dissolving
murexide in a solution of potash, boiling, and supersaturating with
dilute sulphuric acid ; it crystallises in silky, glistening scales, is in-
soluble in water and in dilute acids, but dissolves unchanged in
concentrated sulphuric acid ; it likewise dissolves in the alkalies,
without, however, neutralising them.
On treating murexide with alkalies or with acids, 2 atoms of
murexide take up 1 1 atoms of wafer, and are converted into 1 atom
of alloxan, 1 atom of alloxantin, 1 atom of murexan, 1 atom of
urea, and 2 atoms of ammonia; (G24H1.2N10O16-|-H11O11 =
C8H4N2010+ C8H5N2010 + C6H4N205 + C2H4N2O2 + H6N2.)
Preparation. — The best method of preparing uric acid is that
given by.Bensch. The excrements of serpents or birds, or calculi
of uric acid, are boiled in a solution of I part of hydrate of potash
URIC ACID. 209
in 20 parts of water till ammoniacal fumes cease to be evolved. A
current of carbonic acid is now passed through the solution till the
fluid almost ceases to have any alkaline reaction ; the precipitated
urate of potash is washed with cold water till it begins to dissolve ;
on now dissolving this potash-salt in a solution of potash, warming
it, arid pouring it into an excess of warmed hydrochloric acid, we
obtain a precipitate of pure uric acid.
Tests. — Uric acid possesses such characteristic properties, and
differs in so many respects from all other substances occurring in
the animal body, that it can hardly be confounded with any other
substance, unless possibly with xan thine and guanine (see p. 169 and
p. 171) ; and from these it may be distinguished with extreme
readiness and certainty, by the relation of its alkaline salts towards
carbonic acid and the alkaline bicarbonates. Uric acid is, how-
ever, principally distinguished from all other organic substances
(except perhaps from caffeine) by the murexide test, that is to say.
by the purplish red residue which its solution in nitric acid leaves
on evaporation ; the further addition of caustic potash should,
however, never be omitted, by which a yet more distinct reaction
—the development of a splendid violet tint — is induced.
All chemical means would, however, frequently fail, and the
presence of uric acid would remain undetected, where the quantity
of matter to be examined is so small as to afford very slight traces
of uric acid, if we were not in possession of the microscope, whose
use in physiological chemistry is inestimable. No substance
presents such characteristic and so easily determinable crystalline
forms under the microscope as uric acid, or crystallises so readily.
Hence it may be detected with ease and certainty by all who are
moderately familiar with the use of the microscope, and with the
various forms which the crystals of uric acid present. Although,
to beginners, the form of the crystals of uric acid appears truly
protean, yet with some knowledge of crystallography one form
may very readily be deduced from another. We must, however,
here refer to the admirable analysis of the crystallogenesis and
crystallography of uric acid, as given by Schmidt.* For those who
are acquainted with crystallography, it is sufficient to give the
symbols for the perfect combination of the crystal of uric acid :
oo P2. ooP. oo P2. ooPoo. OP.
For the benefit of those who are unlearned in crystallography,
we will remark that uric acid when it gradually and spontaneously
* Entwurf, u. s. w. S. 28-34.
210 CONJUGATED ACIDS.
separates from urine, appears in most cases in the whet-stone
form, that is to say it forms flat tablets, which resemble sections
made with the double knife through strongly bi-convex lenses, or
rhombic tablets whose obtuse angles have been rounded. As the
urinary pigment adheres very tenaciously to the uric acid, it is only
rarely that these crystals are devoid of colour ; and if we see a
crystal presenting an extraordinary form and of a yellow colour,
the probability is that it is a crystal of uric acid. On artificially
separating uric acid from its salts it often appears in perfect
rhombic tablets, and even oftener in six-sided plates (resembling
those of cystine) ; when uric acid crystallises very slowly it forms
elongated rectangular tablets or parallelepipeds, or rectangular
four-sided prisms, with horizontal terminal planes ; the latter are
often grouped together in clusters ; we also have barrel-shaped or
cylindrical prisms, which are composed of the more rarely occurring
elliptic tablets ; and finally saw-like or toothed crystals, and many
derivatives of these forms. If we cannot decide with certainty
regarding the presence of uric acid from the form of a crystal, we
must dissolve it in potash, place it under the microscope, and add
a minute drop of acetic acid ; we shall then always obtain one of
the more common forms.
A quantitative determination of the uric acid* in urine is
best made from the residue not taken up by alcohol ; by simply
treating it with dilute hydrochloric acid, the earths, &c., are got rid
of, and nothing but uric acid and mucus remains; their separation
may be effected by dissolving them in a dilute solution of potash,
from which the uric acid may be precipitated by acetic or hydro-
chloric acid. The pigment adhering to the uric acid exercises no
appreciable influence on the quantitative determination of this
substance (Heintz).t
To institute a quantitative determination of the uric acid in the
blood or any other albuminous -riuid is a more difficult and far
more precarious operation. For this purpose we take the clear
serum and evaporate it to dryness, without previously removing the
coagulated albumen by filtration ; for if we filtered, the whole process
would be very prolonged, as the coagulated serum would become
little more than a solid mass of moist coagula, whose thorough wash-
ing, even by the addition of much water, would be impossible (see
the observations in a future page " on the quantitative determination
of albumen.") We now extract the solid residue of the serum
* Journ. f. pr. Ch. Bd. 25, S. 17.
t M iiller's Archiv. 1846. S. 383-389.
URIC ACID. 211
with alcohol, and afterwards with hot water; as the uric acid in
alkaline fluids, and consequently also in the serum, must be com-
bined with an alkali, it is in the aqueous extract that we must
always search for it ; during the evaporation of the aqueous extract
membranes usually form on the surface of the fluid, which must
be removed, but whose removal must slightly affect the accuracy of
the analysis ; when the aqueous extract has been concentrated to
a very small volume, it must be treated with an excess of acetic
acid. The uric acid, if its quantity be small, separates very
gradually, and unless the acetic acid has been added in great
excess, it is usually accompanied with the deposition of a little
protein-compound, of whose presence among the crystals of uric
acid we can readily convince ourselves by the microscope. It
must then be passed through a filter, whose weight has been pre-
viously ascertained; and, after careful drying, must be weighed.
When the blood is examined qualitatively for uric acid, we must
proceed in precisely the same way.
Physiological Relations.
Occurrence. — Uric acid always occurs in the urine of healthy men,
in the ratio of about one to a thousand parts of urine, as appears
from the mean of numerous experiments instituted under different
conditions. While living on a mixed diet, the average amount of
uric acid which I excreted in 24 hours was 1*183 grammes; accor-
ding to BecquerePs observations made on 8 different persons, the
quantity excreted by healthy men in 24 hours, did not amount to
more than from 0*495 to 0*557 of a gramme.
I regret that I must here remark, that the laborious analyses
which I made of my own urine cannot altogether serve as standards
of comparison for other urines, as when I instituted those obser-
vations I was affected with softening of the tissue of the left lung.
Uric acid also occurs in the urine of carnivorous mammalia,
although generally in far less quantity than in that of man. In
the urine of omnivora, as, for instance, in that of the pig, neither
Boussingault* nor Von Bibraf succeeded in detecting uric acid.
In the urine of graminivorous mammalia this acid has never been
found, except by Bracket [and by Fownes§ G. E. D.], although
according to Wohler it occurs in considerable quantity in the urine
* Ann. de Chim. et de Phys. 3 Se'r. T. 15, pp. 97-114.
t Ann. d. Ch. u. Pharra. Bd. 53, S. 98-112.
J Journ. f. pr. Ch. Bd. 25, S. 254.
§ Phil. Mag. vol. 21, p. 383.
P 2
212 CONJUGATED ACIDS.
of calves, while still sucking, (compare p. 195.) The peculiar
urine of birds, both carnivorous and granivorous, and of ser-
pents, (which, as is well-known, is generally discharged with the
solid excrements, although in snakes it is often unmixed with the
latter,) consists almost entirely of urates. In the urine of tortoises
uric acid has been found by Marchand* and myself, and Taylorf has
discovered it in urinary calculi from the Iguana. That the red
excrement of butterflies consists essentially of alkaline urates, and
that the excrement of many beetles contains the same substances,
has been long known ; I have, however, not only found uric acid
in the excrements of many larvce%, but also in large quantities in
those vessels of larvae, to which comparative anatomists have applied
the name of biliary vessels.
It is well-known that the substance called guano is produced
from the excrements of sea-birds ; and that it is found not only in
the islands of the South Sea (especially in the neighbourhood of
Chili,) but also on the coast of Africa and even in England.
In the urine of the lion, Hieronymi§ found only 0'022$ of uric
acid, and Vauquelin could find none whatever.
The nature of the food exerts far less influence on the amount
of the uric acid which is secreted than on that of the urea. While
living on a mixed diet I|| discharged on an average 1*1 gramme of
uric acid in 24 hours, while during a strictly animal and a strictly
vegetable diet, the respective amounts were 1*4 and TO grammes.
As the activity of the skin can to a certain degree replace that of
the kidneys, it is easy to understand how an increased activity of
the skin may cause a diminution of the uric acid in the urine ;
hence it was that Fourcroy^f found that the urine of a man con-
tained more uric acid in winter than in summer, and that Marcet**
was led to the conclusion that the uric acid diminishes in the urine
after severe perspiration. Schultensft found that in Holland,
where, in consequence of the great humidity of the atmosphere, the
cutaneous transpiration is diminished, the amount of uric acid varied
from 0'21 to 0*67£; for a similar reason, in tropical countries,
lithiasis is altogether unknown. These observations, however,
* Journ. f. pr. Ch. Bd. 35, S. 244-247.
t Phil. Mag. vol. 28, pp. 36-46.
£ Jahresb. d. phys. Ch. 1844. S. 25.
§ Jahrb. de Ch. u. Phys. Bd. 3, S. 322.
|| Journ. f. pr. Ch. Bd. 25, S. 254.
IF Syst. de Connaiss. chim. T. 10, p. 236.
"* An Essay on Calculous Disorders, 1817, p. 176.
tt N. Gehlen's Journ. Bd. 3, S. 4.
URIC ACID. 213
merely show it is impossible to lay down numerically any general
standard of comparison.
Generally, I have only examined the morning urine, in which
I have even found as much as 0'878-g- of uric acid ; investigations
regarding the relative qualities of the excreted urinary constituents,
can only lead to any useful results when they are instituted on one
and the same person, and on the whole urine passed in 24 hours
for several days in succession. I have endeavoured to arrive at
results, in accordance with the above principles, respecting the
amount of urine discharged under different conditions, but I have
failed in discovering anything further than that in winter more
water is certainly discharged through the urinary bladder, but that
in summer, during continuous perspirations, the solid constituents,
and especially the uric acid, are neither more nor less than in
winter. It is unnecessary to give the numerical results from which
these conclusions were drawn.
There are however other conditions which give rise both to an
absolute and a relative augmentation of the uric acid on the urine,
and in the first place amongst them we must notice disturbed or
imperfect digestion.
Thus, I have observed both in myself and in several other
persons, that if indigestible food or spirituous liquors not suffi-
ciently spiced be taken shortly before bed-time, the morning urine
always deposited a considerable sediment. While in the normal
state the ratio of the uric acid to the urea=l : 28 to 30, I found
that in urine passed after indigestion, the ratio=l : 23 to 26, and
that the ratio of the uric acid to the other solid constituents,
which is ordinarily about = 1 : 60 was now= 1 : 41 to 52, so that the
amount of uric acid is here not only increased at the expense of
the urea, but also at that of the other solid constituents of the
urine. In the most marked case, I found in 100 parts of solid
residue 2'4 of uric acid, 35*2 of urea, and 62.4 of other solid con-
stituents: hence the latter were absolutely increased in this
urine.
Consequently it is easy to understand why there is an augmen-
tation of the uric a,cid in the urine, in many of those cases which
the older physicians regarded as stases of the portal circulation,
haemorrhoids, and arthritis.
An augmentation in the amount of uric acid in the urine
always accompanies the group of symptoms which we are in the
habit of designating as fever, the uric acid either separating or
remaining dissolved ; for no conclusions can be drawn regarding
214 CONJUGATED ACIDS.
the quantity of uric acid in a specimen of urine, from the formation
of a sediment.
I can fully confirm BecquerePs* observations on this point by
my own experience.
The sediment which is deposited from acid urine in fever, and
in almost all diseases accompanied with severe fever, has long been
misunderstood in reference to its chemical composition. Originally
it was regarded as a precipitate of amorphous uric acid, and subse-
quently (and almost to the present time) it was regarded as urate
of ammonia. It has, however, been fully demonstrated both by
myselff and HeintzJ, that this sediment consists of urate of soda
mixed with very small quantities of urate of lime and urate of
ammonia. It may be very easily and quickly distinguished from
any other urinary sediment, both by the microscope and by the
application of a gentle warmth : under the microscope it certainly
shows little that is characteristic ; it forms fine granules which are
sometimes aggregated in irregular heaps, sometimes conglomerated
so as to resemble granular cells, and in some instances uniformly
distributed over the field of the microscope : as the characteristic
forms of uric acid almost immediately appear on the addition of a
stronger acid, it is impossible that it can be confounded with any
other urinary sediment. An even more simple method of ascer-
taining that this sediment consists of urate of soda, is afforded by
the circumstance that it dissolves at 50°, so that urine rendered
turbid by it, when raised to that temperature, becomes clear and
limpid.
It would be both superfluous and wearisome to recapitulate the
arguments adduced by Becquerel, myself, and Heintz, against the
opinion of Bird, who maintains that this sediment is always urate
of ammonia, as the actual nature of the deposit has been so com-
pletely established. I will here only remark that, as I long ago
found, and as Liebig has since confirmed, scarcely any ammonia
occurs in urine, and that, according to the direct analysis of the
sediment made by Heintz, scarcely 1^ of ammonia could be found
in it.
Much has also been written to prove that uric acid does not
exist free in the urine, but in a state of combination with alkalies ;
but it requires only a moderate knowledge of the properties of uric
* SeWiotique des Urines, pp. 51 and 249, or pp. 40-50 and 126-180 of the
German Translation.
t Jahresber. d. phys. Ch. 1844. S. 2G.
J Muller's Arch. 1845. S. 230-261.
URIC ACID, 215
acid and its salts to perceive that there is nothing wonderful in the
presence of an acid urate in an acid fluid, and that the occurrence
of acid urate of soda is perfectly natural. Ure* and Lipowitzf
were the first to direct attention to the circumstance which was
afterwards very prominently brought forward by Liebig, that
phosphate of soda might be one of the solvents of uric acid, and
that thus an acid urate of soda and an acid phosphate of soda
might be produced. BerzeliusJ, however, has remarked that there
are very few solutions of alkaline salts in which uric acid does not
dissolve more readily than in water, and that it, for the most part,
separates from these solutions as uric acid, and not as an acid
alkali-salt. I have, however, especially remarked (Op. cit.) that
uric acid may extract soda from alkaline lactates, and from com-
pounds of the alkalies with other organic acids, and that the acid
salt thus formed communicates an acid reaction to the previously
neutral fluid; the urate of soda then separates from a pure mixture
in a crystalline form, but from a solution containing extractive
matter, as the urine, in an amorphous state, and dissolves again
very readily when heated to 50°.
The appearance of this sediment of urate of soda (Prout's
amorphous and impalpable yellow sediment) is by no means to be
regarded as a pathological symptom ; it is nothing more than an
augmentation of a salt normally existing in the urine, induced by
simple physiological relations. Hence we especially observe the
formation of such sediments, when, for any reason, the due inter-
change of the gases in the lungs does not take place, or when, from
disturbances of the circulation, the blood does not readily permeate
the pulmonary vessels. Thus a sediment of this nature may be
noticed in men and animals when there is an insufficiency of
proper exercise ; carnivorous animals, which in their natural state
secrete so little uric acid, after long confinement frequently pass a
sedimentary urine, especially when they have been reared in cages,
and have been attacked by osteomalacia. In fully developed
emphysema, or even when only a part of the lung has lost some of
its elasticity, a sedimentary urine is one of the most common
symptoms. Heart-diseases, enlargements of the liver, &c., are
associated with disturbances of the circulation, and hence give rise
to a sedimentary urine. It is to such diseases as these that
illogical, ontological names — such as hemorrhoids, gout, &c. —
* Medical Gazette, vol. 35, p. 188.
-1- Ann. d. Ch. u. Pliann. 13d. 38, S. 350.
1 Jaliresber. Bd. 26, S. 873.
216 CONJUGATED ACIDS.
have been applied. Large masses of secreted urate of soda are
found in no disease, except in the true granular liver, which ob-
viously can never exist without considerable disturbance of the
circulation. In fever also, the due relation between respiration
and circulation is no longer maintained, and hence there is an
augmentation of the uric acid in the urine ; for none but mere
chemists could be led to the erroneous idea, that in fever too
much oxygen is conveyed to the blood — in short that fever is at-
tended by too rapid a process of oxidation. Becquerel's extended
observations on urine in diseases, may be profitably compared with
the above results of my own experience.
Bird* and many others maintain that in gout there is an in-
creased secretion of uric acid ; my own experience, however, per-
fectly confirms that of Garrod,f who found that there was a con-
stant and well-marked diminution of the uric acid in the urine
before the paroxysm in acute gout, and always in chronic gout,
(a term which applies only to those cases in which the disease is
accompanied by depositions in the joints ;) while, on the other
hand, in rheumatism, especially in acute articular rheumatism, the
amount of uric acid in the urine is very much increased — a point
in which all observers coincide.
It is extremely seldom that free uric acid is found in freshly
discharged urine, and its presence there may generally be regarded
as a sign of some extremely severe morbid process.
I have never been able to find separated crystals of uric acid in
urine immediately after its emission, although they may often be
found when it has stood for an hour or more. In the great majority
of cases the uric acid is formed from the urate of soda after the
exposure of the urine to the atmosphere, by the process of acid
urinary fermentation which has been so carefully studied by
J. Scherer.J
Healthy and febrile urine only differ in this point, that the one
contains additional elements by which the formation of lactic acid
is excited and promoted. We shall return on a future occasion
to this beautiful investigation of Scherer's. I have never seen free
uric acid discharged directly from the bladder with the urine except
in cases of the calculous diathesis or of pre-existing gravel.
Even in alkaline urine it is very seldom that urate of ammonia
occurs as a sediment ; in these cases it is found in white opaque
* Urinary Deposits, 3rd. edit., p. 134.
t Medico-Chin Trans. Vol. 31, p. 86.
$ Untersuch. S. 1-17.
URIC ACID. 217
granules, which, as has been already stated, when seen under the
microscope, appear as dark globules, studded with a few acicular
crystals. It scarcely ever occurs except in urine which, by long
exposure to the air, has undergone the alkaline fermentation. Even
in the alkaline urine of patients with paralysis of the bladder
dependent on spinal disease, it is very rarely that I have found
these clusters of urate of ammonia. In the alkaline urine that is
sometimes passed in other conditions of the system, it is never
found.
Uric acid, like urea, also exists in the blood; it has been found
there in healthy as well as in diseased states, and especially after
extirpation of the kidneys by Strahl and Lieberkiihn,* as well as
recently by Garrod,f who observes that in arthritis (but not in
acute articular rheumatism,) it is invariably, and in Brighfs dis-
ease it is very often, increased in the blood.
My own observations for the most part confirm those of Garrod.
I first happened to convince myself of the presence of uric acid in
the blood of carnivora in examining the blood of a very large mas-
tiff who died in consequence of an artificial gastric fistula which I
had established. The serum was freed from its albumen by boiling
and with the aid of acetic acid ; the strongly evaporated filtered
fluid was extracted with alcohol in order that urea might be sought
for ; the residue, insoluble in alcohol, exhibited, under the micro-
scope, most unquestionable crystals of uric acid ; my attention
being thus drawn to the subject, I examined the blood of two
other dogs by the same mode of analysis, and convinced myself of
the presence of uric acid, not only by the microscope, but also by
the murexide test. Garrod asserts that he has often found uric
acid in the blood of healthy men, while Strahl and Lieberkiihn
failed equally in detecting it in the blood of men and of birds ; once
only they found uric acid in the blood of a dog; they recognised
it however with great distinctness, and on many occasions, in the
blood of frogs, dogs, and cats, after the extirpation of the kidneys.
Garrod found 0-005-J, 0'004-J, and, m one case, even 0'0175£ of
uric acid in the serum of the blood of gouty patients. In acute
articular rheumatism he could only discover traces of uric acid in
the blood ; in Bright's disease the uric acid of the blood occurred
in very variable quantities ; (from 100 parts of serum he obtained
the following quantities, 0'0037, 0'0055, 0-0012, and 0*002? parts.)
In Germany we have few opportunities of repeating Garrod's
* Harnsaure im Blut, u. s. w. Berlin. 1848.
t Medico-Chir. Trans. Vol. 31, pp. 8?-92.
218 CONJUGATED ACIDS.
experiments regarding the quantity of uric acid in the blood of
gouty patients, for in this country we should certainly hesitate
before abstracting such masses of blood as he employed in his
analyses ; he never operated on less than two pounds of blood.
Urate of soda is very often found in gouty nodules or concre-
tions, as is shown by the analyses of Wollaston, Laugier, Wurzer,
Pauquy, and Bor. My own limited observations entirely accord
with the statements of these chemists. The concretions form,, for
the most part, yellowish white, soft masses, speckled here and there
with red spots ; on exposure to the atmosphere they harden ;
examined under the microscope they present the most beautiful
tufts of crystals of urate of soda.
Wolf* asserts that he has discovered uric acid in the sweat of
arthritic patients ; I have made many attempts to detect it in
such cases, but have never yet been successful.
Unfortunately the idea of gout in medicine is so vague that it
would be well, if, for the present, it were altogether expelled from
science. The pathologists are wont to refer to the chemist for the
elucidation of this singular disease, but they should rather consider
that it is their place to furnish the chemist with more exact ideas
regarding this mysterious affection before seeking for an explana-
tion. It must, moreover, be observed that, notwithstanding their
assertions to the contrary, pathologists have not yet taught us to
distinguish any appreciable difference between gout and rheuma-
tism ; while we find from pathological anatomy that the group of
symptoms which has generally been regarded as characteristic of
the former of these diseases may yield very different results in
reference to alterations in the tissues as revealed after death. We
most commonly meet with diseases of the osseous system, with
osteomalacia in young persons and adults, an affection in which
the bones become poorer in earths, and consequently more flexible,
than in their natural state, or with osteoporosis or osteospathy-
rosis, where there is resorption of the cartilage as well as of the
earths, as resulting from gout : but the essential principle of the
disease cannot lie in this resorption, since often in one and the
same bone we find sclerosis and porosis ; the change which
the bone undergoes is solely dependent on the nature of the
exudation which is thrown out ; if the latter be very consistent
(fibrinous ?) it puts on an appearance of callus, deposits an excess
of bone-earth, and the affected part becomes sclerotic ; if, on the
other hand, it be fluid, resorption takes place, and the result is
* Diss. siiit. casum Calculositatis. Tub. 1817-
URIC ACID. 219
osteoporosis ; if it exhibit a tendency to decomposition and become
ichorous, caries as well as pyaemia may ensue. Unfortunately,
however, these alterations in the osseous system are not peculiar
to gout, but occur both from purely local causes, and from other
general diseases, especially from syphilis. The diseased condition
of the osseous system, however constantly it may be observed in
gout, when we adhere to the strictest definition of the term, affords
us no firm starting-point ; we must, consequently, have recourse
to the nodules and concretions, but these earthy deposits may
exist independently of gout, and there remains no characteristic of
the nature of gout excepting the concretions of urate of soda ; yet
how seldom do even these occur ; and how far advanced must be
the malady before we can base our diagnosis on their presence !
The accumulation of great quantities of uric acid in the blood, in-
dependently of other symptoms, is also devoid of importance, since,
according to Garrod, this may likewise occur in Bright's disease.
In a word, we know not the nature of arthritis ; and if this ever
be elucidated by physiologico-chemical investigations, I believe
that the sole method which will conduce to this end will be
that of ascertaining the relation in which the chemical constitution
of the blood and urine stands to the above-named diseases of the
osseous system, and to osteomalacia in particular.
It seems to us still more inappropriate and still less in accord-
ance with a rational natural inquiry, if, basing our views on a pre-
conceived and misunderstood proposition, we philosophise on the
analogy of " gout, gravel, and stone" ; a priori explanations of
morbid processes such as have been attempted in the organico-
chemical department of medicine, have usually failed in yielding
any results, from the misconception that, without physiology and
pathological anatomy, medicine might be established in accordance
with subjective chemical views. The pretended oxidation of the
constituents of the blood, which was supposed to explain phthisis
as well as gout and stone, is not the simple method by which alone
specific diseases or individual well -characterised processes can be
explained with scientific accuracy. For there are no acute and but
few chronic diseases in which the oxidation of the constituents of the
blood is not diminished or impeded. The proof of the assertion will,
in a future part of this work, be made as evident as the fact that
there is no disease characterised by a too sudden or rapid oxidato n
of the blood.
Origin. — Since we have already (see p. 168) mentioned that urea
is in part derived from uric acid, there can be no doubt that the latter,
220 CONJUGATED ACIDS.
like the former, must rank amongst the excrementitious matters.
Although we have no numerical proof that in human urine the urea
stands in an inverse ratio to the uric acid, that is to say, that with an
augmentation of the uric acid there is a corresponding diminution of
the urea, yet the numerical results of Becquerel and others show that
there is at least such an approximate ratio. The recent experiments
of Wohler and Frerichs,* in which the introduction of uric acid
into the organism by the primae vies or by the veins, was followed
by an augmentation of the urea and oxalate of lime in the urine,
afford tolerably strong evidence that the uric acid in the animal
organism undergoes a decomposition into urea and oxalic acid pre-
cisely similar to that which can be artificially induced by peroxide
of lead. Now, if the urea be produced from the uric acid by the
partial oxidation of the latter, anything impeding this process must
cause less urea and more uric acid to be separated by the kidneys,
and hence we see why the amount of uric acid in the urine must be
increased in fevers and other disturbances in the circulation and
respiration ; we have seen that in like states oxalate of lime and
lactic acid increase for a precisely similar reason, and without
wishing to introduce rude chemical views into the science of general
life, nothing seems more simple, and in accordance with nature,
than this explanation of the origin and augmentation of uric acid.
We regard uric acid as a substance which stands one degree higher
in the scale of the descending metamorphosis of matter than urea.
The present condition of science does not admit of our specially
indicating the substances from which it is first produced, or the
locality in which it is formed.
Sediments of urate of soda are commonly ranked amongst the
critical discharges. A rational system of medicine can no longer,
in accordance with the doctrines of Hippocrates, regard these
excretions as true crises of diseases, but must rather consider
them only as incidental symptoms, or as necessary consequences
of certain processes. In the present day we regard the crises
merely as very abundant eliminations of excrementitious matters
which must occur when the substances rendered effete during the
fever, and which have accumulated in the blood while the functions
of the excreting organs were more or less impeded, are fit for
simultaneous secretion, and are thus given off to the outer world by
their ordinary channels.
Ann. d. Ch. u. Pharm. Bd. 65, S. 338-342.
INOSIC ACID. 221
INOSIC ACID. — C10H6N2O10. HO.
Chemical Relations.
Properties. — This acid is not crystallisable ; it forms a syrupy
fluid, which is converted by alcohol into a solid, hard mass; it dis-
solves readily in water, but is insoluble in alcohol and ether ; it
reddens litmus strongly, possesses an agreeable taste of the juice
of meat, is decomposed by heating, and in part, if its solution be
boiled.
Composition. — According to the above formula, which Liebig,*
the discoverer of this acid, deduced from his analysis of the baryta-
salt, this acid consists of:
Carbon lOatoms .... 32*787
Hydrogen 6 „ .... 3'279
Nitrogen 2 „ .... 15'300
Oxygen .... .... 10 „ .... 43'716
Water 1 „ .... 4'918
lOO'OOO
The atomic weight of the hypothetical anhydrous acid ==21 75'0,
and its saturating capacity =4*5 97. This acid is unquestionably
no simple oxide of a ternary radical, but contains certain prox-
imate constituents ; its products of metamorphosis have, however,
as yet been so little studied that we cannot even form any conjecture
regarding the adjunct or the peculiar acid contained in it. Liebig
remarks that it may be regarded as composed of 1 equivalent of
acetic acid, 2 equivalents of oxalic acid, and 1 equivalent of urea.
Combinations. — The alkaline inosates are soluble in water,
are crystallisable, and, when heated on a platinum spatula, diffuse
a powerful and agreeable odour of roasted meat.
Inosate of potash, KO.C10H6N2O10 + 7HO, occurs in long,
delicate, four-sided prisms ; on the addition of alcohol to a concen-
trated aqueous solution, this salt separates in fine nacreous
scales.
Inosate of baryta, BaO.C10H6N2O10 + 7HO, crystallises in
long four-sided scales of a nacreous lustre, which, when dry, have the
aspect of polished silver ; it effloresces readily, dissolves freely in
hot, very slightly in cold water, and not at all in alcohol. If a
solution, saturated at ?0,° be heated to boiling, a part of the salt
is deposited in the form of a resinous mass.
* Ann. d. Ch. u. Pharm. Bd. 62, S. 325-335.
222 CONJUGATED ACIDS.
Inosate of copper forms a light blue, amorphous powder,
insoluble even in acetic acid,
Inosate of silver is amorphous, white, and slightly soluble in
pure water.
Preparation. — If the mother-liquid of the juice of flesh, after the
creatine has crystallised and been removed, (see p. 136,) be gradu-
ally treated with alcohol till the whole become milky, it deposits^
in the course of a few days, yellow or white granular, foliated, or
acicular crystals of the inosates of potash and baryta, mixed with
creatine. Chloride of barium must be added to the hot aqueous
solution of these crystals ; on cooling there is a deposition of crys-
tals of inosate of baryta, which, by recrystallisation, are rendered
perfectly pure. By decomposing this salt with sulphuric acid, or
the copper-salt with sulphuretted hydrogen, the acid is obtained in
a state of purity.
Tests. — So little is yet known regarding the properties of this
acid, that the only test we can rely upon is the ultimate analysis.
Physiological Relations.
Liebig has hitherto only found this acid in the fluid of flesh.
The few facts which we at present possess regarding this acid
throw no light on its mode of formation. From the great quan-
tity of oxygen which it contains, it must be regarded as a product
of the decomposition of effete tissues.
GLYCOCHOLIC ACID. — C52H42NOn.HO.
Chemical Relations.
Properties. — This acid, which has been named, par excellence.,
bilic or cholic acid, forms extremely delicate needles, which
remain unchanged at 136°; it has a bitterish-sweet taste, dissolves
in 120*5 parts of hot, and 303 parts of cold water ; is readily soluble
in spirit, but only slightly in ether; it does not crystallise on
evaporating the alcoholic solution, but separates as a resinous mass ;
but it crystallises from the spirituous solution, mixed with water
and exposed in the air to gradual evaporation. The aqueous solu-
tion of this acid reddens litmus strongly. It dissolves without
change in concentrated acetic acid, cold sulphuric acid, and hydro-
chloric acid.
The aqueous solution of this acid is not precipitated by acids,
neutral acetate of lead, corrosive sublimate, or nitrate of silver ;
GLYCOCHOLIC ACID. 223
in alkalies it dissolves freely, being precipitated from them by
acids, in a resinous form ; on standing, especially after the addition
of a little ether, the resinous precipitate becomes crystalline. A
solution of the acid in combination with an alkali yields no preci-
pitate with chloride of barium ; but there are precipitates on the
addition of the salts of the oxides of lead and copper and peroxide
of iron; nitrate of silver, when added to very dilute solutions,
yields a gelatinous precipitate, which, on warming, again dissolves,
and on cooling gradually assumes a crystalline form. By prolonged
boiling with a solution of potash, or still better, with baryta- water,
this acid becomes resolved into the non-nitrogenous cholic acid and
glycine (seep. 152). When boiled with concentrated sulphuric or
hydrochloric acid, it is resolved into choloidic acid and glycine.
(Strecker.*)
With sulphuric acid, and either sugar or acetic acid, glycocholic
acid yields the same reaction as cholic acid (see p. 123.)
If glycocholic acid be submitted to prolonged ebullition in water,
it becomes perfectly insoluble, and breaks up into fragments of six-
sided tablets. To this modification the name ofparacholic acid has
been applied by Strecker.
Composition. — From numerous analyses of glycocholic acid and
its salts, Streckert has deduced for it the above formula, according
to which it consists of :
Carbon .... .... 52 atoms ....
Hydrogen .... 42 ,,
Nitrogen.... .... 1 „
Oxygen .... 11 „
Water .... .... 1 „
100-000
The atomic weight of the hypothetical anhydrous acid =5 700;
and its saturating capacity =1*75 4.
Hardly a doubt can remain that this is a conjugated acid, when
we consider, on the one hand, that we are acquainted with another
acid (hippuric acid) from which the same nitrogenous body, glycine,
may be separated by acids, and that, on the other hand, there is
another acid from which the same non -nitrogenous acid, cholic
acid, is liberated by acids, another body, taurine, being simul-
taneously produced; (this taurine in the taurocholic acid
taking the place of the glycine in the glycocholic acid.) In glyco-
* Ann. d. Ch. u. Pharm. Bd. 66, S. 1-43.
t Ibid. Bd. 65, S. 1-37.
224 CONJUGATED ACIDS.
cholic acid we cannot, however, consider glycine, as we know it in
its isolated state, to be the adjunct of cholic acid, but must rather
assume that the true adjunct of cholic acid, as in the case of hip-
puric acid, undergoes a change during its separation, by which it
forms the body known to us as glycine. If, as in hippuric acid,
we regard this adjunct as a group of atoms isomeric with
fumaramide, the rational formula of glycocholic acid will be=
C4H3N02.C48H3909.HO.
Combinations. — With alkalies and alkaline earths, glycocholic
acid forms very soluble salts ; its compounds with the oxides of
the heavy metals are, however, insoluble ; the glycocholate of silver
alone being soluble in boiling water.
Glycocholate of soda, NaO.C52H42NOn, separates from its
alcoholic solution, on the addition of ether, in large, glistening,
white clusters of radiating needles, resembling wavellite ; it is
not crystallisable from its watery or spirituous solutions ; it
dissolves very readily both in water and in spirit (1 part dissolving
in 2*56 of spirit at 15°); when heated it melts, burns with a
smoky flame, and leaves an ash containing cyanides. Glyco-
cholate of potash behaves in a similar manner.
Glycocholate of ammonia, H4NO.C52H42NO115 occurs in crys-
tals precisely similar to those of the soda-salt, when it is gradually
separated from an alcoholic solution by ether ; it dissolves readily
in water, yields ammonia on boiling, and then has a faintly acid
reaction.
Glycocholate of baryta, BaO. C52H42NOn, is amorphous, has
a strongly sweet and slightly bitter taste, is soluble in water and in
alcohol, and is not decomposed by carbonic acid.
Preparation. — This acid occurs in the bile of most animals, but
it is best prepared from the bile of the ox by one of the two fol-
lowing methods. — The bile first carefully dried in the water-bath,
and subsequently in vacuo, must be extracted with cold absolute
alcohol, and ether must be gradually added to the filtered solution,
which is thus rendered turbid, and soon deposits a brownish, tough,
resinous mass. If the fluid be now only slightly coloured, we
must decant it from the semi-fluid precipitate into another vessel,
and again gradually add ether; the fluid again becomes milky, and
deposits more resinous matter ; after a time, however, glistening
star-like tufts of crystals are deposited, which must be washed with
alcohol to which a tenth part of ether has been added, and then
rapidly placed in vacua, because the crystals, when moist with
ether, rapidly deliquesce into a varnish -like mass ; after drying they
GLY£OCHOLIC ACID. 225
cease to be acted on by the atmosphere. These crystals are a mix-
ture of the glycocholates of potash and soda. On precipitating the
aqueous solution of these crystals with acetate of lead, decomposing
the precipitate with carbonate of soda, evaporating the solution of
glycocholate of soda, re-dissolving in alcohol, and again (in the
same manner as before) crystallising by means of ether, we obtain
a tolerably pure glycocholate of soda, which, when dissolved in
water and treated with dilute sulphuric acid, after a time deposits
crystals mingled with oily globules. The latter may be removed
by washing with water, leaving the glycocholic acid in a state of
purity.
The following is a shorter method of obtaining this acid. The
yellowish precipitate thrown down by sugar of lead from fresh bile
must be extracted with boiling spirit of 85^ and sulphuretted
hydrogen passed through the solution. If water be added to the
filtered fluid and the mixture be allowed to stand for a considerable
time, the acid will separate in a crystalline form ; in this case,
however, it is better to decompose the lead-salt by carbonate
of soda, and then to proceed in accordance with the former
method.
Crystallised bile, which is a mixture of the glycocholates of
potash and soda, was first prepared by Platner.*
Tests. — In attempting to determine the amount of bile in an
animal fluid, it is always necessary that the albuminous matters,
the substances soluble in water only, and the fats, should be as
completely as possible separated. We consequently, in the first
place, obtain an alcoholic extract of the substance to be investi-
gated, and ascertain by Pettenkofer's test whether any derivative of
the bile be present in it. This point being decided, we can only
determine whether one of the acids contained in fresh bile — glyco-
cholic or taurocholic acid, or one of their derivatives, cholic or
choloidic acid — be present, when we have a considerable amount
of matter to work upon. To pursue this inquiry, we must
gradually add from 8 to 12 times its volume of ether to the extract
obtained by strong alcohol, and allow the mixture to stand for from
24 to 48 hours; by this time the turbidity of the fluid will have
disappeared, and a sediment will have formed, which is either
flocculent and viscid, so as to adhere to the walls of the vessel, (in
which case it consists for the most part of albuminous or extrac-
tive matter,) or is a resinous, semi-fluid, tough mass (alkaline
taurocholates or choloidates), or consists of tufts of well-formed
* Ann. d. Ch. u. Pharm. Bd. 51, S. 105 ; Journ. f. pr. Ch. Bd.40, S. 129-133.
Q
226 CONJUGATED ACIDS.
crystals of various sizes, visible to the naked eye, and composed
either of cholate or glycocholate of soda. It is worthy of remark
that even the smallest quantities of the alkaline glycocholates crys-
tallise from their solution in this way. (From a solution of about
O07 of a gramme of glycocholate of soda in 150 parts of alcohol,
I obtained most beautiful crystals of the salt on the addition of
560 grammes of ether.) These crystals must, however, always be
examined microscopically, or at all events with a lens, as many
other salts (acetate of soda for instance) separate in a crystalline
form under this mode of treatment : they form six-sided prisms
with a single very oblique plane of truncation, and as their aqeous
solution reacts with Pettenkofer^s bile-test, no doubt can remain
regarding the presence of glycocholic acid. If the crystals be
obtained either in a state of purity or surrounded by syrupy
matter, we must separate the acid from the alkali by a little sul-
phuric acid, and extract with ether, in which the conjugated cholic
acids as well as choloidic acid are almost insoluble ; if the crystalli-
sable cholic or glycocholic acid be thus isolated, we can determine
regarding the presence or absence of one or other of them by boil-
ing with a solution of potash, when, if glycocholic acid be present,
ammonia is developed ; moreover, the cholate of baryta is a crystal-
lisable salt, while the glycocholate of baryta is amorphous. Gly-
cocholate acid resembles choloidic acid in being only slightly
soluble in ether ; they may, however, generally be distinguished by
the crystallisability of the former acid and of its salts fromethereo-
alcoholic solutions ; the glycocholate of baryta, indeed, resembles
the choloidate in being uiicrystallisable, but it differs from the
latter in being soluble in water. We shall point out the means of
distinguishing between glycocholic and taurocholic acids in our
observations on the latter acid.
Physiological Relations.
Occurrence. — As far as our investigations have hitherto extended,
this acid has been found in the bile of all animals, with the excep-
tion of the pig. In reference to its occurrence in other parts and
fluids of the animal body, we have only to repeat what has already
been said in pp. 124-5 regarding cholic acid. We meet with such
minute quantities of biliary matter in the intestinal canal, in the
blood, and in exudations, that until recently they have been, for the
most part, entirely overlooked, and it is only by means of Petten-
kofer's admirable test that we can now detect them. Important as
it would be in a physiological point of view to ascertain whether
GLYCOCHOLIC ACID. 227
cholic acid or the conjugated biliary acids occur in the blood,
and whether these or choloidic acid occur in the intestine, we must
for the present leave these questions altogether undecided.
Kunde, one of my pupils, has very distinctly recognised the pre-
sence of biliary matters by means of Pettenkofer's test in the fluid
from the hydrocele of an otherwise healthy man. By the same
test he was able to demonstrate the presence of biliary matters in the
blood of frogs, whose livers he had extirpated. (Of six frogs on
which he operated, only two survived.)
Origin. — We have already (see p. 126) attempted to show the
probability that cholic acid obtains its essential elements from the
fats, and that, in short, it is oleic acid conjugated with a non-
nitrogenous body. But in glycocholic acid we again meet with
the same nitrogenous adjunct which we have already encountered
in hippuric acid, and which, consequently, seems to be an ordinary
product of decomposition of nitrogenous bodies. We have already
remarked (see p. 197) that we are not in ac ondition to name the
proximate source of this adjunct, which is, however, isomeric with
fumar amide.
This is not the most appropriate place for entering into the
physiological reasons for showing the part which the fat takes in
the formation of the principal constituents of the bile, or for
balancing the reasons for or against the formation of bile within the
hepatic cells. These are subjects pertaining to the second depart-
ment of our work, in which we shall consider the bile in general as
an animal secretion. We may, however, be permitted to remark
that the possibility of the primary formation of this acid in the
blood is indicated partly by the above-mentioned experiments of
Kunde, and partly by the not unfrequent occurrence of icterus
independently of any hepatic affection (Virchow), that is to say,
without infiltration of the parenchyma of the liver and of the
hepatic cells with bile- pigment.
Uses. — As we are not at present accurately acquainted with the
changes which glycocholic acid undergoes in the intestinal canal,
we are unable to state whether this acid exerts any special action
in the process of digestion.
Q 2
228 'CONJUGATED ACIDS.
HYOCHOLIC ACID. — C54H43NO10.HO.
Chemical Relations.
Properties. — This acid, discovered and accurately examined by
Gundelach and Strecker*, forms a white resinous mass, which melts
in water at 100° and, like choloidic acid, maybe drawn out in long
threads ; when perfectly dry it does not melt at a temperature
under 1 20° ; it is only slightly soluble in water, dissolves readily
in alcohol, and not at all in ether ; it reddens litmus. It dissolves
unchanged in cold concentrated nitric and sulphuric acids; but
when boiled for some time in either of those acids it yields, like gly-
cocholic acid, glycine and a resinous acid similar to choloidic acid ;
with concentrated sulphuric acid and either sugar or acetic acid;, it
yields, like the other biliary acids, a purplish -violet solution ; it is
only decomposed by a solution of caustic potash, when the mix-
ture is so concentrated as to solidify on cooling. It is unchanged
by digestion in moderately concentrated sulphuric acid and peroxide
of lead; putrefaction of the bile seems to exert no influence on it ;
when treated with fuming nitric acid, or decomposed by chromic
acid, it yields the same products as choloidic acid, namely choles-
teric acid, butyric acid, caproic acid, &c.
Composition. — According to Gundelach and Strecker, this acid
may be obtained in an anhydrous state, so as in its combination
with bases to lose no water. From their analyses of the free acid,
as well as of its salts, these chemists have deduced the above
formula, in accordance with which the free anhydrous acid
consists of:
Carbon 54 atoms .... 70*28
Hydrogen .... 43 „ .... 9'33
Nitrogen 1 „ .... 3'04
Oxygen 10 „ .... 17'35
100-00
The atomic weight =5 762*5, and its saturating capacity =1*73 5.
This acid contains 2 atoms of carbon and 1 atom of
hydrogen more, but 1 atom of oxygen less, than glycocholic acid ;
the fact that, when treated with concentrated mineral acids, it
likewise yields glycine, tends to confirm the hypothesis, that
hyocholic acid also contains the gly cine-yielding adjunct isomeric
with fumaramide, and that so much plus of carbon and hy-
* Ann. d. Ch. u. Pharm. Bd. G2, S. 205-232.
HYOCHOLIC ACID. 229
drogen, and minus of oxygen, are respectively added to, and
deducted from the non-nitrogenous acid, that the rational formula for
this acid would be — C4H3NO2.C50H40O8. But as hyocholic acid
when decomposed with nitric acid yields the same volatile fatty
acids and cholesteric acid, the non-nitrogenous acid, contained in
hyocholic acid, may be presumed to have a constitution analogous
to cholic acid (see p. 126), and besides the group of atoms C12H6O6
which yields the cholesteric acid (C8H4O4) to contain another fluid
fatty acid of the formula CnHn_3O3 in place of the oleic acid in the
cholic acid ; and this in point of fact admits of being calculated by
subtracting the group of atoms C12H8O8fromthehydrate of the non-
nitrogenous hyocholoidic acid ; C50H41O9 - C12H6O6==C38H35O3,
which is exactly the formula of doeglic acid (see p. 116).
That this calculation is a mere fiction is sufficiently obvious,
but we believe that such fictions should not be altogether unnoticed,
since they stimulate us to further enquiry, even if it were only to
determine whether an acid isomeric or identical with doeglic acid
existed in the fat of the pig.
Combinations. — The alkaline hyocholates are not crystallisable ;
they are soluble in water and alcohol, but not in ether, which com-
pletely precipitates them from their alcoholic solutions. Their
taste is bitter without any sweet after-taste, and they redden litmus ;
like soaps, they are precipitated from their aqueous solutions by
alkaline salts, the precipitate containing the base of the salting added
in excess ; they melt and are inflammable when heated ; with the
salts of baryta, lime, and magnesia, they yield white precipitates
soluble when the mixture is raised to the boiling temperature.
Their aqueous solutions are precipitated by most of the metallic
salts, but their alcoholic solutions are not affected by these re-
agents. On the addition of an acid to the aqueous solution, the
hyocholic acid is entirely precipitated. Neutral acetate of lead yields
a white precipitate which does not cake on boiling.
Hyocholate of potash, KO.C54H43NO10, is in its moist state a
white amorphous mass which melts in the water-bath, and dissolves
as long as it contains either water or spirit. It does not dry at
a temperature under 120°,
Hyocholate of soda, NaO.C54H43NO10, forms when dry a
brownish mass, which when finely triturated, becomes of a snow-
white colour ; it has a persistent bitter taste without any sweet
after-taste, Its solutions are neutral, and are not rendered turbid
by carbonic acid. It is precipitated from its alcoholic solution
by ether, and from its aqueous solution by soda-salts ; it melts.
230 CONJUGATED ACIDS.
when heated, dissolves, and burns with a bright but smoky
flame.
Hyocholate of ammonia, H4NO.C54H43NO10, is a white crys-
talline powder. Its solutions become turbid on boiling, and
assume an acid reaction. It may be dried over sulphuric acid
without loss of ammonia.
Hyocholate of baryta, BaO.C54H43NO10, is a gelatinous sub-
stance, freely soluble in spirit, moderately soluble in hot water,
and slightly so in cold water.
Hyocholate of lime, CaO.C54H43NO10, is white, amorphous,
and rather more soluble in water than the baryta-salt ; it is preci-
pitated from its spirituous solution by water and by carbonic
acid.
Hyocholate of lead is a white powder, which neither cakes when
boiled with water nor when dried ; it is slightly soluble in water,
but freely in spirit, from which it (like all the other salts of this
acid) is precipitated by ether. Red litmus is turned blue by the
alcoholic solution.
Hyocholate of silver, AgO.C54H43NO10, occurs as a gelatinous
precipitate, which, on boiling^ becomes flocculent; it dissolves
freely in spirit, slightly in cold, but somewhat more easily in
hot water.
Preparation. — The precipitate caused by the addition of a solu-
tion of sulphate of soda to fresh swine's bile is dissolved in abso-
lute alcohol, decolorised by a little animal charcoal, and the soda-
salt of the acid precipitated by ether from the alcoholic solution ;
this is decomposed by dilute sulphuric acid, and the precipitate is
dissolved in alcohol, from which the hyocholic acid is thrown down
by the addition of water.
Tests. — It is only with glycocholic and choloidic acids that this
acid can possibly be confounded. From the former it may easily
be distinguished by the circumstance that neither it nor its salts can
be obtained in a crystalline state by the addition of ether to alco-
holic solutions. It is, however, not so readily distinguishable from
the latter, because, without an elementary analysis, it is impos-
sible to determine its nitrogen; and because, further, when treated
with concentrated hydrochloric acid it yields too little glycine to be
recognised with certainty, unless, indeed, we have a very large
supply of the material to be investigated. The fact that hyocho-
late of lead neither cakes when dried nor when boiled with water,
while the opposite is singularly the case with the glycocholate,
affords a tolerably characteristic test. Other differences are for
TAUROCHOLIC ACID. 231
the most part only gradual, and are inapplicable as tests to enable
us to distinguish between small quantities of these acids.
Physiological Relations.
This acid has hitherto only been found in the bile of the pig,
where it exists in combination with soda, potash, and a little
ammonia. Our remarks on the origin and uses of glycocholic
acid are equally applicable to hyocholic acid.
TAUROCHOLIC ACID.
Chemical Relations.
Properties. — This acid, which has also been named choleic acid>
and was formerly known as bilin, has not yet been obtained in a
state of perfect purity, that is to say, free from glycocholic acid ;
it cannot be obtained in a crystalline state, and it is more soluble
in water than glycocholic acid, while its acid properties are far
weaker. It dissolves fats, fatty acids, and cholesterin in large
quantities, and is thus the cause why glycocholic acid is not precipi-
tated from fresh ox-bile by acetic or the mineral acids. On expo-
sure to the air, as well as on evaporating a solution of the free
acid, decomposition ensues. When boiled with mineral acids it
becomes resolved into taurine and choloidic acid ; when boiled with
alkalies, into taurine, and cholic acid ; and when treated with sul-
phuric acid and sugar, it gives the same reaction as the other essen-
tial acids of the bile. The characters of its salts are, however, very
distinct from those of the other biliary acids.
Composition. — As this acid, like glycocholic acid, becomes
resolved, when acted on by mineral acids and by alkalies, into cho-
loidic or cholic acid, while in place of glycine it yields taurine,
Strecker,* to whom we are especially indebted for our know-
ledge of this acid and of its properties, correctly argues that
its composition is perfectly analogous with that of glycocholic
acid, the only difference being that the adjunct in this case is
taurine. Abstracting from the formula for taurine 1 atom of
water, he assumes that the empirical formula of this acid
= C52H45NS2°i4> and the rational formula^ C4H6NS2O5.C48H39O9.
We must therefore regard taurocholic acid as containing an adjunct
rich in sulphur, which, on its separation from the cholic acid,
* Ann. d. Ch. u. Plmnn. Bd. 66, S. 43-61.
232 CONJUGATED ACIDS.
becomes converted into taurine, whose properties we have already
described at p. 179. By elementary analyses of a mixture of pure
alkaline glycocholates and taurocholates, obtained directly from
fresh bile, Strecker has further confirmed his view regarding the
composition of this acid. Pure taurocholic acid must, therefore,
contain 6*213$ of sulphur, while its atomic weight must= 6437*5
and its saturating capacity be 1'553.
Combinations. — The alkaline taurocholates dissolve readily in
water and in alcohol, but are perfectly insoluble in ether; they
have no reaction on vegetable colours, and attract water from the
atmosphere, but do not deliquesce ; when kept for a long time in
contact with ether they crystallise ; their aqueous solutions have a
sweet taste with a bitter after-taste, and do not decompose when
evaporated, or when exposed to the air, provided they be pure.
These salts when heated melt and burn with a bright smoky
flame. Carbonic acid does not decompose their alcoholic solution ;
their aqueous solution is not precipitated by acids, nor by the
alkaline sulphates or chlorides (like the alkaline hyocholates), but
by concentrated alkaline solutions; it is not precipitated by
the salts of baryta, lime, or magnesia, even on the addition of
ammonia, or by neutral acetate of lead ; but on the addition of
basic acetate of lead, there is a plastery precipitate which dissolves
in boiling water, and even more freely in boiling alcohol, and is
also soluble in an excess of acetate of lead. Nitrate of silver, even
after the addition of ammonia, does not precipitate the tauro-
cholates, neither does corrosive sublimate, but precipitates are
induced by nitrate of suboxide of silver, and protochloride of tin.
Nitrogenous substances, mucus for instance, set up a process of
decomposition in solutions of the alkaline taurocholates, which
may be readily ascertained by the circumstance that the solutions
then become precipitable by dilute acids. The products which are
formed are taurine, alkaline cholates or choloidates, and probably
certain combinations of these substances with taurocholic acid that
has escaped decomposition. In aqueous solutions of pure alkaline
taurocholates, these decompositions are not observed to occur.
Preparation. — We have already remarked, that this acid has
never yet been prepared in a state of complete purity. In order
to separate it as thoroughly as possible from the glycocholic acid
which always accompanies it, we in the first place remove from
the purified ox-bile the greater part of the glycocholic acid and of
the fatty acids by means of neutral acetate of lead, and then pre-
cipitate by basic acetate of lead, to which we may add a little
TAUROCHOLIC ACID. 233
ammonia. This precipitate must be decomposed with carbonate
of soda, and we must extract the solid residue of the filtered fluid
with alcohol. On the addition of ether to the alcoholic solution, a
tolerably pure taurocholate of soda is immediately precipitated in
the form of a resinous, semifluid, yellow mass. If this be dissolved
in a small quantity of water, and all that is precipitable by acetate
of silver be thrown down, and if the fluid after filtration be pre-
cipitated with basic acetate of lead, and the precipitate, after being
thoroughly diffused in a little water, be treated with sulphuretted
hydrogen, we obtain tolerably pure taurocholic acid after evapo-
rating in vacua.
Tests. — No great weight can be attached to any of the differ-
ences in the reaction of the salts of glycocholic and taurocholic
acids, when the quantity of the substance presented to us for exa-
mination is very small. If, however, we have sufficient material,
we must obtain the acids from the alcoholic extract with precisely
the same precautions as we have indicated in the preceding pages
in reference to each of these acids ; from the ratio of the precipi-
tate caused by the sugar of lead to that caused by the acetate of
lead, we must draw our conclusions regarding the relative quan-
tities of the two acids, and then, by treating the alcoholic solution
of the soda- salt with ether, we can determine this point with cer-
tainty ; indeed, we shall always be most decisively convinced of
the presence of taurocholic acid by the exhibition of the taurine,
which, even if obtained in only very small quantities, may be
recognised with certainty by crystallometric examination under the
microscope. Unfortunately, however, the quantities of taurine are
so minute, unless when we are acting directly on bile, that it cannot
be distinguished and recognised with certainty either by the above
means or by its relation towards nitrate of silver and other metallic
salts. Nothing further remains for us but to determine the pre-
sence of sulphur; having ascertained by Pettenkofer's test that
biliary matter is present in the substance under examination, we
must extract the spirituous extract with cold absolute alcohol, con-
centrate this solution, and treat it with ether. A precipitate then
falls, which cannot contain any other known sulphurous substance,
and which we must fuse and deflagrate with nitrate of potash and
caustic potash free from sulphuric acid; if sulphuric acid be found
in the residue, we may regard the presence of taurocholic acid as
almost certain.
Unfortunately, substances in which it is of interest to detect
small quantities of taurocholic acid, are seldom obtained in a state
234 CONJUGATED ACIDS.
of perfect freshness, and the little taurocholic acid that was origi-
nally present is decomposed before we commence our investiga-
tions. When we suspect that this acid is present, and have detected
biliary matter by Pettenkofer's test in the alcoholic extract, we
may hope to find taurine in the aqueous extract, which, however,
contains it in such small quantity, and often so intermingled with
other substances, that its recognition, even under the microscope,
is extremely difficult. We must not attempt to determine the
presence of sulphur as a test for taurocholic acid or taurine in the
aqueous extract, for this contains both sulphates and other
sulphurous organic bodies.
Physiological Relations.
Occurrence. — From the determinations of the amount of sulphur,
instituted by Bensch* and others, we may conclude that taurocholic
acid exists not only in the bile of the ox, but in that of the fox,
bear, sheep, dog, wolf, goat, and certain birds and fresh-water fish ;
it has been found in the bile of the frog by Kunde and myself ; and
that it exists in human bile can hardly be doubted, since, as Gorup-
Besanez was the first to prove, taurine may be exhibited from it.
It might almost be inferred, from the numerical results obtained by
Schlieperf- in his analysis of the purified bile of a Boa Anaconda,
that the liver of this serpent secretes taurocholic alone, and none
of the other known biliary acids. That this acid is almost entirely
absent in the bile of the pig, as shown by the investigations of
Strecker, has been already mentioned.
Unchanged taurocholic acid has not yet been found in any
other animal fluid ; but from the experiments of Kunde to which I
have already referred (p. 227), it is not improbable that it also
occurs in the blood.
Origin. — We have very little to say in the present place re-
garding the production of taurocholic acid : what has been already
stated respecting the formation of cholic acid (p. 126), of taurine
(p. 182), and of glycocholic acid (p. 227), is equally applicable
to the acid under consideration. As it has not yet been found in
the blood, it is impossible to decide chemically whether it be
primarily formed in the liver from its proximate constituents, or
whether it proceeds from the general metamorphosis of the non-
nitrogenous and nitrogenous animal matters.
Uses. — Since we are as ignorant of the chemical changes which
* Aim d. Ch. u. Pharm. Bd. 65, S. 194-203.
t Ibid. Bd. CO, 8. 109-112.
HALOID BASES AND SALTS. 235
taurocholic acid undergoes in the intestinal canal, as we are regard-
ing those of glycocholic acid, we are unable to express by a
chemical equation, the part which it takes in the process of
digestion ; and until this can be done, we cannot give a satisfactory
explanation of the chemical action of the bile. The consideration
of the physiological relations, from which we judge of the import-
ance of the biliary secretion, in reference to the metamorphosis of
the animal tissues and to animal life, and which is based on the
chemical substratum we have here laid down, will be found in
another part of this work.
HALOID BASES AND HALOID SALTS.
The consideration of the above series of organic acids has made
us become acquainted with a number of bodies, which, in oppo-
sition to the ordinary rules of chemistry, enter into combination
with acids without depriving them of their most essential chemical
characters. There is, however, also a series of substances which
can so combine with organic and mineral acids, that they per-
fectly neutralise their acidity, and can form with them true salts,
both neutral and acid, without deserving,, on account of their con-
taining no nitrogen, to be classed among the alkaloids.
This class of salts has recently been referred to the conjugated
compounds (by Gerhardt and Laurent,* and Strecker,f) since the
idea of bodies of this nature has become tolerably firmly established ;
but the property of these non-nitrogenous bases, perfectly to satu-
rate the strongest mineral and organic acids, appears to us a very
stringent reason why these bodies should be separated from the
true adjuncts, and why their neutral and acid combinations with
acids should be separated from the true conjugated acids. Ber-
zeliusj has applied the name of Haloids to these salt-like combina-
tions of acids with non-nitrogenous bodies. If we attempt to apply
the highly probable (but not indubitably established) hypothesis of
* Ann. d. China, et de Phys. 3 Se'r. T. 24, pp. 163-208.
t Ann. d. Ch. u. PJiarm. Bd. 68, S. 47-55,
% Jahresber. 27, S. 425.
236 HALOID BASES AND SALTS.
conjugated ammonia, to explain the basicity of the true nitrogenous
alkaloids, we shall find such a mode of explanation perfectly inap-
plicable to these non-nitrogenous bases. These haloid bases may
be classed as analogous bodies to oxide of ammonium. For as,
according to the ammonium-theory of Berzelius, we assume, in the
so-called ammonia-salts, the existence of the oxide of a combination
of nitrogen and hydrogen, H4N, in which this in some degree simu-
lates a metal, so also we are equally justified in seeking for the
basicity of these substances in the oxide of a carbo-hydrogen ; and
more especially since we are already acquainted with pure carbo-
hydrogen s possessing decided basic properties, as, for instance, the
non-oxygenous ethereal oils. This assumption is not in the least
opposed by the circumstance that the carbo-hydrogen s, like the
ammonium, combine with oxygen to form basic oxides. It is true
that such a mode of viewing the subject leads us back to the
frequently attacked, but by no means perfectly controverted or
exploded theory of organic radicals ; but, in a department of
science so young as chemistry still is, that is the most satisfactory
mode of contemplating the subject, which enables us to represent
and explain, in the simplest manner, the largest number of analogous
phenomena.
These oxides of the carbo-hydrogen radicals are, however, in
their isolated state, so different from the known mineral bases and
organic alkaloids, and exhibit such weak basic properties, that for
a long period it was altogether denied that they possessed the cha-
racter of a base. It is with difficulty that they combine either with
acids or with water. Even their hydrates differ so greatly from the
anhydrous oxides, that they were formerly regarded as perfectly
different bodies, and ether was carefully distinguished from alcohol,
oxide of amyl from fusel oil, and oxide of methyl from pyroxylic
spirit. Moreover, it is only with difficulty, and in certain instances,
that we can separate the water from these hydrates. In the same
way, their combinations with acids, although most of them are per-
fectly neutral, bear very little resemblance in their character to
salts, and hence most of them have received trivial names, as,
naphthas, fats, &c.
As has been already mentioned, the haloid bases form neutral
as well as acid salts ; in the former the acidity of the stronger acids
is, for the most part, far more perfectly neutralised than in the
salts of the nitrogenous alkaloids ; for the neutral salts, with a
few exceptions, exert no action on litmus; they are, however,
essentially distinguished from the salts of almost all other known
HALOID BASES AND SALTS. 237
bases by the circumstance that they cannot be so readily separated
from their acids by simple or double elective affinity. The haloids
cannot be decomposed by stronger acids, nor yet by stronger
bases ; it requires a more considerable time and a more prolonged
action of heat to resolve them into their proximate constituents,
than is necessary for ordinary salts.
In these decompositions of the haloid salts we constantly find
that the base, during its liberation, combines with water, and is
thus separated as a hydrate (for instance, not as oxide of ethyl but
as alcohol, not as oxide of methyl but as pyroxylic spirit, not as
oxide of lipyl but as glycerine). Conversely the haloid bases in
uniting with acids give off all their water, so that they always
form perfectly anhydrous salts — a fact of which chemists have
long availed themselves, in order to ascertain the composition of
organic acids in the anhydrous state ; (the combinations of such
acids with oxide of ethyl or oxide of methyl, being submitted
to examination.)
We should fall into a great error if we were to conclude from
the peculiar relations of the haloids that organic bodies are consti-
tuted on entirely different principles from mineral bodies ; for the
chemical laws deduced from pure inorganic compounds meet with
their fullest application in these compound organic matters ; it is,
however, inorganic chemistry which teaches us, that the smaller
the chemical attraction between two substances, with so much the
more difficulty can they combine with one another, but when once
combined, they often resist the most powerful decomposing agents ;
we need only refer by way of illustration, to the relations of silicic
and phosphoric acids to alumina and zirconia. A natural law
admits of no exceptions, and if the principles taking their origin
in inorganic chemistry be true natural laws, they must be applied
in their fullest extent to the chemical combinations of organic
matters.
The true nature of the acid salts of the haloid bases was also
for a long period not recognised ; these substances were regarded
as peculiar acids, whose consideration led indeed very materially to
the theory of conjugated acids and conjugation ; but there is an
essential difference between an acid haloid salt and a conjugated
acid. We have already seen that in the conjugated acids, the true
acid has lost none of its saturating capacity, while in these acid
haloids half of the acid is always saturated by the haloid base : we
know, for instance, that sulphovinic acid cannot, by any possibility,
be regarded as a conjugated acid, since only half of the sulphuric
238 HALOID BASES AND SALTS.
acid contained in it is in a state to saturate a base, just as in
bisulphate of potash only half of the acid can be engaged in satu-
rating the base. Notwithstanding this very striking difference,
many of the acid haloid salts are, unfortunately, still ranked
amongst the conjugated acids.
Moreover, these acid salts are distinguished from the other
known acid salts of other bases by the difficulty with which the
true base can be separated from the compound ; indeed, the sepa-
ration is here, for the most part, more difficult to accomplish by
strong affinities than in the neutral haloid salts. The acid haloids
have, however, very many properties in common with one another;
they are either solid and crystallisable, or liquid, and, like most of
the acid salts in mineral chemistry, always contain 1 atom of water
from which they cannot be separated without total decomposition,
except by means of a base ; further, however volatile the acid and
the base may be, these acid salts cannot be distillled or sublimed
undecomposed ; and, lastly, it is worthy of remark that their com-
binations with bases are almost without exception soluble in
water, even though the acid in question formed ever so insoluble a
salt with a base, (as, for instance, in the case of sulphate of oxide
of ethyl and baryta.)
Amongst the haloid bases there is a series of homologous
bodies of high interest in relation to theoretical chemistry, but
scarcely falling within the sphere of zoo-chemistry. These are the
bodies already mentioned in p. 40, possessing the general formula
CnHn+ jO, and standing in a definite relation to the acids of the first
group.
There is, however, another haloid base of more importance in
zoo-chemistry, but homologous to no other body with which we
are acquainted, the oxide of lipyl, which, in combination with the
fatty acids, constitutes the fats which hold so prominent a place in
physiological chemistry. There are many other haloid bases, but
for the most part only some of their combinations, namely, their
acid salts, have been examined ; and in their isolated as well as in
their hydrated state they are yet unknown. Hence, we have here
only to consider oxide of lipyl and its combinations, and oxide of
cetyl, which is homologous to the group of ethers.
OXIDE OF LIPYL. 239
OXIDE OF LIPYL. — C3H2O.
On boiling one of the common fats or fatty oils with a caustic
alkali, with the hydrate of an alkaline earth, with hydrate of mag-
nesia, or oxide of zinc or of lead, the fat, without assimilating
oxygen, or giving off hydrogen, is decomposed into one or more
fatty acids, which combine with the base that has been employed,
and form soaps, and a peculiar sweet matter, glycerine. On com-
paring the weight of the resulting products of decomposition with
that of the fat which was employed, we find that an increase of
weight has taken place in consequence of an assimilation of water.
In order to explain the nature of this process, it was assumed
that the fats are combinations similar to the salts of oxide of ethyl,
and that glycerine, represented by the formula C3H2O, constituted
the base of the fats ; but the constitution of glycero-sulphuric acid
proves that glycerine must be represented by the formula C6H7O5,
and that consequently it cannot be regarded as the base of the
neutral fats. Hence it is probable that the fats contain, in addi-
tion to the fatty acid, the oxide of a radical, having the composition
which was formerly ascribed to glycerine ; and that this oxide in
its separation from the fatty acid assimilates water, and is con-
verted into another body, as in the case of oxide of ethyl when it
is expelled by an acid from its combination. To this hypothetical
radical, Berzelius has applied the name of lipyL
That the base in the fats is not glycerine seems obvious also
from the circumstance that hitherto no neutral fat has been pre-
pared from glycerine and the fatty acids. Whether the butyrin
that has been artificially formed from glycerine and butyric acid
has the same composition with that contained in butter has not yet
been ascertained. Acrolein, which is polymeric with oxide of
lipyl, and is a product of distillation of glycerine, cannot, any more
than glycerine, be the base of the fats, since it cannot be made ta
combine even with strong acids.
This conversion of the fats into acids and glycerine, may be in-
duced by other bases than those we have already mentioned, namely,
by the soluble carbonates and borates, if they be digested with the
fats for a sufficiently long period.
In the case of the carbonates we must, however, suppose that
in this process the alkaline carbonate is first resolved into alkaline
bicarbonate and free alkali, and that it is the latter only which takes
part in the saponification ; and that, on further boiling, the alkaline
240 HALOID BASES AND SALTS.
bicarbonate loses 1 atom of carbonic acid, and becomes converted
into a simple salt, which again acts on the fat in the above de-
scribed manner.
Ammonia and its carbonate only form soaps after a more pro-
longed action.
GLYCERINE.— C6H7O5.HO.
Chemical Relations.
Properties. — Glycerine is a faintly yellow fluid with an agreeable,
sweet taste ; it attracts water from the atmosphere, dissolves
readily in water and alcohol, but not in ether, and exerts no reaction
on vegetable colours. It dissolves alkalies and several of the
metallic oxides (for instance, oxide of lead) in large quantities ; in
a concentrated state, it admits of being distilled with only partial
decomposition, but when rapidly heated, it is entirely decomposed ;
if its watery solution be exposed to evaporation, decomposition
immediately commences : when heated in the air, it becomes in-
flammable, and burns with a blue flame. If heated with anhydrous
phosphorus in a tube from which fresh air is excluded, it yields
acrolein. If glycerine be dissolved in a large quantity of water,
mixed with yeast, and exposed to a temperature of between 20°
and 30°, it developes a small quantity of gas, and is converted
into metacetonic acid (C5H7O5-2HO = C6H5O3 ; Redtenbacher.*)
Treated with spongy platinum, glycerine also becomes converted
into an acid (Dobereinerf). By concentrated nitric acid it is con-
verted into carbonic acid, oxalic acid, and water ; with hydrochloric
acid and peroxide of manganese, it yields a large quantity of formic
acid.
Composition. — In accordance with the above formula deduced
by PelouzeJ from his analyses of pure glycerine and its acid salts,
this substance consists of :
Carbon 6 atoms .... 39'130
Hydrogen 7 « .... 7'609
Oxygen 5 „ .... 43-478
Water 1 „ .... 9'783
100-000
The atomic weight of anhydrous glycerine =103 7*5.
* Ann. d. Ch. u. Pharm. Bd. 57, S. 174-177-
t Journ. f. pr. Ch. Bd. 29, S. 451.
J Compt. rend. T.21, pp. 718-722.
GLYCERINE. 241
Glycerine cannot be regarded as a hydrate of oxide of lipyl,
because in its combinations it always contains 3 atoms of water
more than a double atom of oxide of lipyl ; and we know that no
haloid base retains its hydrate-water when it combines with
acids.
Combinations. — No neutral salts of glycerine have yet been
exhibited, but we are acquainted with several of its acid salts,
which, like the acid salts of the oxides of ethyl and methyl, unite
with bases, and form a series of compounds.
Bisulphate of glycerine (glycero-sulphuric acid] C6H7O5.SO3 +
HO.SO3, is formed by the direct union of glycerine with sulphuric
acid ; the excess of sulphuric acid is removed by saturating with
carbonate of lime or baryta ; the sulphate of glycerine-lime or gly-
cerine-baryta is decomposed with oxalic acid and the filtered fluid
evaporated in vacuo.
This acid salt forms a colourless fluid, which, on evaporation
even in vacuo, is readily decomposed into glycerine and sulphuric
acid; it has a strongly acid taste, reddens litmus, and forms easily
soluble double salts, even with baryta and lime. These salts readily
yield glycerine when boiled, and even more readily when treated
with an excess of base ; the dry salts when heated carbonise and
develope a vapour (containing acrolein) with an extremely disagree-
able odour, and irritating to the eyes. The lime-salt crystallises in
colourless needles, and=CaO.SO3 + C6H7O5.SO3.
Acid phosphate of glycerine , (glycero-phosphoric acid,)
C6H7O5.2HO + PO5, is obtained by the direct action of syrupy
glycerine on pulverised glacial phosphoric acid, which developes
much heat, the temperature even rising to 100°. The excess of
phosphoric acid is removed by baryta, and the baryta-salt decom-
posed by sulphuric acid. When in a concentrated state the body
in question forms a colourless fluid, which even in vacuo cannot
be very strongly concentrated without undergoing decomposition ;
it does not crystallise, has a strongly acid taste, and dissolves
freely in water and alcohol; with bases it forms double salts,
which dissolve readily in water, but so very slightly in alcohol that
this fluid precipitates them from their aqueous solutions. Phosphate
of glycerine-lime, 2CaO + C6H7O + PO5, crystallises in white, glis-
tening scales, and dissolves in cold water ; it is, however, so slightly
soluble in hot water that it is precipitated from its aqueous solution
by boiling. The baryta-salt contains I atom of tribasic phosphoric
acid, 2 atoms of baryta, and 1 atom of glycerine.
Bitartrate of glycerine, C6H7O5.C4H2O5+HO.C4H2O5, is pro-
242 HALOIDS AND HALOID BASES.
duced, according to Berzelius,* on heating 1 part of glycerine, dried
at 120°, with 2 parts of dry tartaric acid; it is a semi-solid trans-
parent body, which is solid at 0°, but at 25° admits of being drawn
out in long threads ; it deliquesces in the air, does not dissolve in
alcohol, and with bases forms soluble uncrystallisable double salts,
which are readily decomposed by an excess of base. The relations
of biracemate of glycerine are similar to those of this salt.
Products of its metamorphosis. — Acrolein, C6H4O2, discovered
by Redtenbacher,t is obtained from glycerine by submitting it to dry
distillation with a little anhydrous phosphoric acid in a stream of
dry carbonic acid gas ; the distillate, consisting of a thick oil, of
an acid fluid swimming on it, and of acrolein floating on the
latter, must be digested with oxide of lead and distilled at 52° into
a receiver containing carbonic acid, by which means we obtain the
acrolein. It is an oily fluid, which strongly refracts light, has an
acrid, burning taste, irritates the eyes and respiratory organs, and
forms a neutral solution in water devoid of air, which, however, very
soon assumes an acid reaction on exposure to the atmosphere.
It instantly reduces oxide of silver, and it decrepitates b h with
nitric acid and with potash.
Acrylic acid, C6H3O3 + HO, is formed when acrolein is
oxidised either by exposure to the air or by oxide of silver ;it is a
limpid fluid, with an odour resembling that of very strong acetic
acid, and a pure, acid taste ; nitric acid converts it into acetic and
formic acids ; it forms soluble, crystallisable salts with bases.
Disacrone, disacryl, C10H7O4, is gradually deposited from acro-
lein exposed to the atmosphere ; it is idio-electric, devoid of
odour and taste, and insoluble in all menstrua.
Preparation. — Glycerine is formed, as we have already men-
tioned, during the saponification of the fats, from the oxide of
lipyl contained in them combining with 4 atoms of water. It is
usually prepared from the aqueous fluid which separates during the
preparation of lead- plaster, and contains it, together with oxide of
lead, in solution. After the removal of the lead by sulphuretted
hydrogen we concentrate the solution first in the water-bath and
subsequently in vacuo. We may also obtain it from the mother-
liquid yielded in ordinary saponification by the alkalies, on satu-
rating the alkali of the ley with sulphuric acid, then heating it with
carbonate of baryta, evaporating the filtered fluid, and extracting
with alcohol. It may be obtained very readily, and in a state of
* Jahresber. Bd. 27, S. 438.
t Ann. d. Ch. u. Pharm. Bd. 47, S. 113-148.
GLYCERINE. 243
purity, by dissolving castor-oil in absolute alcohol, and passing
hydrochloric acid gas through the fluid ; at the end of the opera-
tion the compounds of the fatty acids with oxide of ethyl, which
have been produced, must be separated by means of water. The
aqueous fluid, on evaporation, leaves glycerine, which may be
entirely freed from adhering traces of the fatty ethers by being
shaken in ether.
Tests. — Glycerine could not be readily detected in animal
fluids unless we were able to obtain it in sufficient quantity to
admit of its being subjected to an elementary analysis; but this
would be hardly possible, since it would be difficult to obtain the
glycerine in a state of purity from the animal fluids. Fortunately,
however, acrolein is a substance with so intense and characteristic
an odour that this product of the decomposition of glycerine may
be employed as a test of its presence. The glycerine, separated in
as pure a state as possible, must be rapidly heated either alone or
with a little anhydrous phosphoric acid, when, if the glycerine be
much diluted, the peculiar and very disagreeable odour, not unlike
that developed by the wick of an expiring oil-lamp, is evolved with
sufficient distinctness.
Physiological Relations.
Occurrence. — Glycerine has been recently discovered by Gobley*
in animal bodies. He first detected it in the yolk of the egg of the
common fowl in the form of phosphate of glycerine-ammonia, and
subsequently f in the same state of combination in the fats of the
brain.
Origin. — Regarding the source of the glycerine in the organism,
there can be no doubt that, in addition to the true fats — the stearate,
margarate, and oleate of oxide of lipyl — there are many fatty acids,
either free or in combination with alkalies, occurring in the animal
body. Since the combinations of the fatty acids and oxide of lipyl
are introduced into the animal body from without, we need not
wonder that glycerine, which is formed from oxide of lipyl during
the decomposition of the fats, is not found in far larger quantity
in this or that animal fluid. We have already directed attention
to the possibility (p. 56 and p. 103) that in the consumption and
gradual oxidation of the neutral fats, the oxide of lipyl, separated
as glycerine, is probably converted into lactic or even into metace-
tonic acid. Further investigations are, however, necessary before
* Compt. rend. T. 21, pp. 766-769, et 988-992.
t Journ. de Pharm. 3 Ser. T. 11, pp. 409-417, et T. 12, pp. 5-13.
244 HALOIDS AND HALOID BASES.
we can decide whether this conjecture is of any real value. The
uses of fatty articles of food would thus assume a new aspect, since
they would in this way contribute to the formation of the free acids
which act so important a part in many of the processes of animal
chemistry.
How the glycerine in the yolk of egg and in the brain becomes
associated with the phosphoric acid, we cannot specially explain,
but, considering the frequency with which phosphorus occurs, both
in its unoxidised state and as phosphoric acid, there is nothing
singular or inexplicable in such a combination.
SALTS OF OXIDE OF LIPYL. — FATS.
Chemical Relations.
General Properties. — It is especially worthy of remark that the
properties of these haloids are almost entirely influenced by the
acids contained in them ; while in the salts of oxide of ethyl, most of
the properties, including those of the most general character,
appear to depend principally on the base, and to be altogether in-
dependent of the nature of the acid. Hence we find the properties
of the neutral fats to be extremely similar to those of the fatty acids
already described (from p. 105 to p. 116.)
Most of the animal fats are soft and greasy at an ordinary
temperature, although some are firm and waxy, and a few liquid ;
they almost all correspond, however, in the following points. When
exposed to strong cold, especially when in solution in alcohol, they
may be obtained in white scales or minute plates of a peculiar
lustre ; when perfectly pure, they are for the most part colourless
and transparent, they swim on water, render paper and linen trans-
parent, are bad conductors of electricity and heat, melt for the most
part below the boiling point of water, are altogether decomposed
when distilled, unless the process be conducted in vacuo, and are
devoid of smell and taste when they are pure and fresh ; they are
insoluble in water, but most of them dissolve in boiling alcohol,
from which they again separate on cooling ; they are all soluble in
ether and in volatile oils ; when perfectly pure they exert no re-
action on vegetable colours, but on exposure to the air many of them
readily become rancid and acid from the absorption of large
quantities of oxygen. When exposed to a strong heat, and free
access of oxyen is admitted, they are inflammable, and burn with
a clear flame.
FATS. 245
There are certain ferments which resolve the fats into glycerine
and the corresponding fatty acid, in the same manner as sugar is
resolved into alcohol and carbonic acid, or salicin into saligenin
and sugar, or amygdalin into sugar, hydrocyanic acid, and oil of
bitter almonds. Albuminous substances which have already under-
gone a certain degree of decomposition (putrefaction) act in this
manner as ferments to the fats.
If we mix putrid fibrin, which forms an albuminous fluid, with
water, or putrid casein with fat, so as to form an emulsion, and
digest the mixture for some time at a temperature of 37°> the cor-
responding fatty acids separate from the oxide of lipyl, which very
soon undergoes further alterations. In the fermentation of milk,
where sugar is present, it appears from my investigations* that the
fats are decomposed in precisely the same manner as if merely the
putrefying protein-compounds were acting as ferments, and as if no
sugar were present. Cl. Bernardf on digesting fats with pancreatic
fluid observed that they were decomposed into fatty acids and gly-
cerine, from which he concluded that during the act of digestion
the fats are constantly decomposed into glycerine and fatty acids —
a conclusion, however, still admitting of considerable doubt.
By dry distillation certain fats yield other fatty and inflammable
substances, and leave a little charcoal ; others are in part converted
into peculiar fatty acids. When very rapidly heated or thrown on
incandescent bodies, they carbonise and develope olefiant gas.
The fats are decomposed by prolonged contact with chlorine,
bromine, and iodine ; while, on the other hand, they take up sul-
phur, selenium, and phosphorus, without undergoing any change ;
with the former, they only undergo decomposition on the appli-
cation of heat.
By concentrated mineral acids they are for the most part con-
verted into fatty acids, and on the application of sulphuric acid,
they yield acid sulphate of glycerine.
S tear ate of oxide of lipyl, stearin, occurs as a pure white sub-
stance ; it separates on cooling from its alcoholic solution in snow-
white, glistening scales ; under the microscope it appears chiefly in
the form of quadrangular tablets, which although almost square are,
according to Schmidt, J rhombs with angles = 90° 5', but sometimes
in the form of short rhombic prisms (thick rhombic plates,) whose
surfaces, according to Schmidt, are inclined to one another at
* Simon's Beitr. Bd. 1, S. 63-76.
t Arch, ge'iie'r. de me'd. 4 Se'r. T. 19, p. 73,
t Entwurf u. s. w. S. 84.
246 HALOIDS AND HALOID BASES.
angles of 67° 40X and 52° 40. It melts at +62°, solidifies, but
does not become crystalline on cooling, is brittle, when dry is not
a conductor of galvanic electricity, is insoluble in cold and only
slightly soluble in hot alcohol, but dissolves very readily in
ether. On dry distillation it yields stearic and margaric acids, and
the products of decomposition of glycerine ; on saponifi cation it
yields stearic acid and glycerine.
Margarate of oxide of lipyl, margarin, is white and solid ; it
crystallises from alcohol as a flocculent white powder, which under
the microscope appears in the form of very delicate and often
curved needles, which are so grouped as to radiate from one point
as a nucleus, and thus to form a whorl of fine, capillary threads ;
it melts at +48°, and dissolves slightly in alcohol but readily in hot
ether ; it separates from either solution on cooling in nacreous scales,
and on saponifi cation yields glycerine and margaric acid.
Oleate of oxide of lipyl, olein* or elain, is a colourless oil which
solidifies at a low temperature, is not a conductor of galvanic
electricity, becomes rancid on exposure to the air, is never entirely
free from margarin and stearin, and on saponification yields, in
addition to glycerine and oleic acid, a much larger quantity of mar-
garic acid than can be supposed to be derived from the decompo-
sition of the margarin.
Preparation. — The above fats may be obtained in various ways,
although seldom in a state of perfect purity, from the fat contained
in cellular tissue, by repeated melting and purification with water.
Usually we dissolve the fat in boiling alcohol, from which, on
cooling, the stearin, and a great part of the margarin, separate
in crystalline scales, while the olein is almost the only substance
remaining dissolved in the cold alcohol. Margarin is obtained in
the greatest purity from the hot alcoholic solution of those fats,
which, like human fat and the vegetable fats, contain no stearin ;
moreover, by strong pressure between the folds of filtering paper,
the olein may be tolerably effectually separated from the stearin
and margarin, since, above a certain temperature, it penetrates the
paper. Tolerably pure olein may be obtained by digesting a fat
with half the quantity of potash required for its complete saponifi-
cation ; in this case the stearin and margarin are saponified, while
the olein remains unchanged. The corresponding acids may be
obtained in a similar way, but in a state of much greater purity.
Tests. — Cases sometimes present themselves in which it is not
easy to ascertain whether the substance to be examined contains
salts of oxide of lipyl, or the corresponding fatty acids. In dealing
FATS. 247
with small quantities,, we obviously cannot rely on the acid reaction,
or on the formation of glycerine ; in such cases the simplest method
is to obtain an ethereal extract of the alcoholic extract to which a
little acetic acid had been added, and then, by digestion with water,
to separate the residue of the ethereal solution from other sub-
stances. The remaining fat is then to be dissolved in alcohol, and to
be treated with an alcoholic solution of acetate of lead. If the
addition of ammonia give rise to no precipitate, it is a proof that
the solution contains no free fatty acids, but only salts of oxide of
lipyl.
Free fat in the animal fluids, tissues, and cells, is most commonly
and, indeed, most satisfactorily detected by the microscope ; the
vesicles in which fat ordinarily appears, present so characteristic
an appearance, that when they have been seen for a few times under
the microscope, they can hardly be confounded with anything else;
the more consistent fat, containing little olein, sometimes, however,
occurs in nodular, sausage-shaped, and only faintly-transparent
clumps, which cannot so readily be recognised as fat. In these
cases, chemistry must come to the aid of microscopic investigation,
as, for instance, where the fat-vesicles in cells are so minute, that,
with the highest magnifying powers, they appear as mere dark
points or granules. Many histologists now maintain that these
points and aggregate granules may be very readily distinguished
under the microscope, by their solubility in ether ; but the extrac-
tion of the fat from the cells by ether, is by no means easy, for its
rapid evaporation under the microscope, renders it very difficult, if
not impossible, to observe the individual cells. Before making
our observations we must, therefore, repeatedly pour a little ether
on the object, and allow it again to run off, or if we have fine
sections of tissue, we may digest them in ether. Unfortunately
however, the cells and other histological elements are often so
distorted by ether, that even after long maceration in water, an
accurate observation is no longer possible ; and it is nearly the
same in most cases with alcohol, by which, however, well-prepared
sections of many parts, as, for instance, nerve-fibres, may often
have their fat thoroughly removed. Moreover, alkalies cannot be
advantageously applied to the partial saponification of these fats,
since they often dissolve albuminous parts much sooner than the
fats. We shall see, in a future part of this work, that some
histologists believe that they have found fat-granules in tissues
which have been hitherto regarded as utterly devoid of fat : and
248 HALOIDS AND HALOID BASES.
have been too hastily led, by imperfect experiments, to form
theories regarding the fatty degeneration of cells and tissues.
Physiological Relations.
Occurrence. — Fats occur, not only in the animal world, but also
in vegetables, especially in seeds and the kernels of fruits, from
which we chiefly obtain the fatty oils and certain butter-like fats,
as for instance, cacao butter, palm oil, &c. Fats have been found
in almost all parts of all animals, and it is only in the lowest classes
of animals that fat is entirely absent. It is in the higher organ-
isms that we find most fat, where it exists as a mixture of the
above-named salts of oxide of lipyl, and is deposited in the
cellular tissue in oval or polyhedric cells.
It is very rarely that we find one of the above-named fats
unmixed with the others, and in the few cases of this nature which
have been observed, the character of the fat has been recognised
by the microscope only, and not by chemical means; thus C.
Schmidt (according to Bergmann*) and Vogt-f- found distinct
crystals of stearin in the ovum of the frog, and of the accoucheur
toad, (Bufo obstetricans,) and I have frequently, although not
invariably, found delicate masses of acicular crystals in the albumen
of eggs that had been sat upon from three to six days, which from
the few tests that I could attempt, seemed to consist of margarin.
When we consider the occurrence of fat in the different parts
of the human body in a normal condition, we, in the first place,
discover large accumulations of fat, which, when constituting an
integral constituent of certain organs, rarely disappear entirely,
even in the latest stages of wasting diseases ; in the next place we
observe, that there are parts of the body in which the quantity of
fat varies considerably, being either extraordinarily small or very
large ; and finally, that there are some organs in which accumula-
tions of fat are of very rare occurrence. The orbit of the eye and
the heart appear to be the most constant seats of fat, for although
we observe that the fatty matters surrounding the different parts of
the eye diminish in all forms of disease, causing the eye-ball to
sink in the orbit, the socket of the eye is never found entirely free
from fat. A similar remark applies to the fat surrounding the
heart, and penetrating between its bundles of fibres ; and it would
likewise appear that fat is never entirely absent from the muscles
* Muller's Arch. 1841. S. 89.
t Entwickelung der Geburtshelferkrotc. Solothurn. 1842. Einl.
FATS. 249
of the face, for everyone who has dissected these muscles must
have noticed how largely the human face is furnished with fat.
Large quantities of fat, not constituting so essential and integral a
part of the organs, and often almost entirely disappearing, are prin-
cipally found under the cutis and in the cellular tissue, investing the
muscles, in the interstices of several of the larger muscles, about the
gluteei, on the soles of the feet, and in the inner surface of the hands.
Fat is frequently fo und deposited insacs around different tendons
projecting between the ends of the bones into the joints, where they
form special accumulations of fat, known by the name of the
Haversian glands. Large deposits of fat are generally found in
the omentum, and surrounding the kidneys, constituting the
folliculus adiposus renum, which usually contains a harder fat, having
a larger quantity of margarin, than occurs in other parts of the
body.
The female breast is always so largely interspersed with masses
of fat, that full prominent breasts frequently yield a small quantity
of milk, being enlarged solely by the deposition of fat.
The marrow of the bones consists, for the most part, of fat,
which not only remains undiminished, but is even not unfrequently
largely augmented in various diseases of the bones, as, for instance,
in osteomalacia. This bone-fat is perfectly identical with the
ordinary fat of the cellular tissue, excepting that it contains some-
what more olein, especially where there is osteomalacia.
All other parts of the animal and more especially of the human
body, are penetrated by fat. The smallest quantity, and indeed,
occasionally, not a trace of fat is to be found in the pulmonary
tissue, in the glans penis and the clitoris, and, if we except the
so-called non-saponifiable fats, in the brain.
We have already spoken of the occurrence of fat in the animal
fluids. The amount of fat in the blood does not vary much in a
normal condition, and is, according to Boussingault's numerous
investigations,* wholly independent of the amount of fat contained
in the food. The blood contains from 0'14 to 0'33£ of fat in a
normal condition. Boussingault found from 0'2 to 3'0§ of fat in
the blood of dogs, whether they had partaken of food deficient or
abounding in fat, and 0'4£ in that of birds. Tiedemann and Gmelin
always found the chyle very rich in fat ; and its milky turbidity, as
well as that of the lymph, is owing to the fats which it holds in
suspension.
I was unable to discover any trace of Boudet's serolin in the
* Ann. de Chirn. et de Phys. 3 Ser. T. 24, p 460.
250 HALOIDS AND HALOID BASES.
chyle of a dog. The fat which was extracted with ether was oily,
was not precipitated from boiling alcohol on cooling, and was for the
most part saponifiable.
This seems to confirm Schultz's observation,* that the fat of
the blood is more consistent than that of the chyle, and it may
further be remarked that the fats of the blood are mostly saponi-
fied or incapable of saponification, wrhile those of the chyle corres-
spond to the ordinary salts of oxide of lipyl.
The excellent investigations recently instituted by Cl. Bernardf
have afforded the most striking proof that the fats are digested
by the pancreatic fluid ; i. e., that the fats are not reduced to an
emulsive state, either by the gastric juice, or (as BrodieJ believed
that he had found) by the bile, and thus fitted for resorption. But
the conclusion which Bernard would draw from an experiment in
which he found that fat had been converted into fatty acids and
glycerine by the action of the pancreatic juice, viz., that all fats are
converted by the process of digestion into glycerine and the corres-
ponding fatty acids, is controverted by the fact above referred to,
that the chyle contains, in comparison with the blood, much unsa-
ponified and but little saponified fat.
Marchand and Colberg found oily and crystalline fat in the
lymph.
The quantity of fat in the human body varies considerably at
different periods of life. Thus in the foetus we generally find no
fat, except a few small masses in the omentum and in the loins.
Infants prematurely born are rounder in form immediately after
birth than at a subsequent period, for as their organism is not fully
prepared for an atmospheric life, they soon become emaciated, and
lose much fat through the intestinal canal. The muscular tissues
of the heart and face are found to be copiously furnished with fat
even at this early period. New bom children are in general tolerably
plump and roundish, and have a considerable quantity of fat de-
posited under the skin. The organism is most rich in fat during
childhood, but this deposition of adipose matter diminishes with
the development of the sexual functions, although it again increases
at a more mature period of life, and then occasionally acquires an
excess never observed at any other age. Extreme old age gradually
arrests this tendency to adiposity until it is completely destroyed
by marasmus senilis.
* System der Circulation, 1836. S. 131.
t Arch, gener. de rae'd. 4 Se'r. T. 19, pp. 60-81.
£ Quart. Journ. of Science. Jan. 1823.
FATS. 251
A merely superficial comparison of the sexes shows that the
female organism contains more fat, and has a greater tendency to the
deposition of fatty matter than the male, as indeed is most evident
from the rounded outlines and symmetrical curves of the female
figure, which cannot be entirely destroyed even by influences
most inimical to the deposition of fat.
We find that special physiological relations give rise in some
cases to an increase, and in others to a diminution of the fat in the
animal organism. Thus an excessive activity of the sexual functions
prevents the increase of fat, and even induces considerable emacia-
tion where the sexual activity is of a morbid character. Men and
animals that have been castrated, are, on the contrary, much dis-
posed to become fat, as are also women who have ceased to con-
ceive. Many male animals, according to Haller, lose the marrow
from their bones in the season of heat.
It is well known that great muscular activity not only impedes,
but even utterly arrests the deposition of fat. Thus the flesh of
the Arabs, and that of all nations living in a state of nature, as well
as of most wild animals, contains a very small quantity of fat, while
civilized nations and the domestic animals reared for purposes of
food are, in general, much fatter, owing to their inconsiderable
muscular activity. Most persons are familiar with the fact that
horses become much leaner in summer even when better fed, and
that they soon grow fat in the winter. The whole art required in
fattening domestic animals consists in suffering them to have little
exercise and good feeding.
We have daily opportunities of noticing the influence exercised
by food alone on the deposition of fat ; and the degree to which
the temperament and conditions of the mind affect the corpulency
or meagreness of the human body is too obvious to require further
notice here.*
Every physician is familiar with the marvellous rapidity with
which fat disappears from the animal body in acute as well as in
chronic diseases, and we would here only refer to the fact which
undoubtedly is well known to many physicians, that tuberculosis
very frequently induces very little or no emaciation, even where
the pulmonary tissue is already in a great measure destroyed, if
the disease be accompanied with certain forms of hepatic disease,
as fatty or nutmeg liver. The emaciation is often so inconsi-
derable in these cases, that any one not acquainted with the physical
* We may refer to the first volume of Haller's Elementa Physiologies for
the most copious accumulation of facts bearing on this subject.
252 HALOIDS AND HALOID BASES.
diagnosis of the disease, would be completely deceived as to its
character and the amount of danger.
It appears scarcely necessary to remark that milk contains a
larger quantity of fat than any other animal fluid. An average of
2*9£ of fat has been found in woman's milk. This subject we shall
however consider more fully in the second volume of this work,
when we purpose treating of the increase arid diminution of the
fat contained in the milk of different animals under different
physiological and pathological relations.
Since Giiterbock's observations, attention has been directed to
the quantity of fat contained in pus, which has frequently been
found to amount to 5-g-.
As we have already remaiked, the fat in the blood is mostly in
a state of saponificaticn ; but in many diseases, the blood has been
observed to contain large quantities of unsaponified fat. Since we
purpose entering more fully into this subject when we proceed to
the consideration of the morbid conditions of the blood, we will
here only observe, that although, as is generally supposed, the blood
of drunkards frequently presents large accumulations of free fat, this
only occurs where there is already some hepatic disease, as for
instance, granular liver, whether this be a mere secretion of colloid-
like exudation accompanied with decrease of size in the liver, or
that species of granular disease in which some of the hepatic
lobules present scattered cells infiltrated with fat.
Pathological depositions of fat, either free or enclosed in cells,
occur most frequently in the liver, but also in the kidneys, the
spleen, in paralysed muscles, in the heart, and other organs, and
occasionally (enclosed in a capsule) in encysted tumours. This fatty
metamorphosis (as it is termed) of some of the organs, will be spe-
cially considered in the third volume of this work, in our remarks
on the individual tissues and organs. It will be sufficient at present
to remark that these so-called fatty degenerations of organs occur
either without any previous exudation, by the direct deposition of
fat in the tissues, the cells, or the areolar tissue, or, (as indeed is
more frequently the case,) after resorption of the physiological
or pathological tissues or exudations, are deposited in their place.
The latter case occurs in paralysis of muscles, where they have
undergone fatty degeneration, and in osteoporosis and osteomalacia,
where the bones, rendered porous by the resorption of their mineral
and organic parts, are found, as it were, swimming in fat ; a similar
process may occur in the fatty degeneration of the spleen and the
kidneys, which many have attempted to explain as the third stage,
FATS. 253
or indeed, as the essential character of Bright's disease. The
endeavour to explain such pathological processes by a perfect
metamorphosis of albuminous and fibrinous exudations into fat,
(that is to say, by a direct metamorphosis of the protein-compounds
into fat,) is purely chimerical and unsupported by the slightest
proof.
It is further an undoubted fact that in many cells, whether
they be constituents of physiological tissues, or products of patho-
logical exudations, fat occurs accumulated in large quantities,
appearing under the form of vesicles, or more frequently of granules,
as in the hepatic cells, in the granular cells in old apoplectic
cysts, and in the analogous cells in the expectoration in confirmed
chronic catarrh ; but it is incorrect to suppose that all strongly
tinged, punctuated granular cells, contain much fat : we will, how-
ever, postpone all further consideration of this subject to the third
volume.
We have no accurate observations regarding the quantity of fat
contained in the fasces in different diseases ; and I will here only
remark, that I have always found fat in the normal excrements,
but more especially in the stools in diarrhoea ; in most of the cases,
in which observations have been made regarding an excess of fat
in the fseces, we are unable to determine whether its increase be
owing to the food, or to fatty medicines.
A firm margarin-like fat, has been frequently noticed as present
in the excrements of diabetic patients (Simon,* Heinrichf)? but I
have never observed any decided increase in the quantity of fat in
the feeces in diabetes ; and the discharge of fat by the intestines,
cannot therefore be regarded as a constant symptom.
It is equally difficult to form a correct opinion of the quantity
of fat in the urine. No reliance is to be placed on the older obser-
vations, since the presence of fat in the urine was at that period
often diagnosed, whenever, in consequence of an alkaline reaction,
the urine was covered with a pellicle ; this was regarded as fat,
although consisting in reality of nothing more than earthy mat-
ters. Where the microscope shows fat-globules in the urine, they
frequently, in women, arise from the external genitals. It is only
in slow fevers that I have been able to confirm the old view, and
often, but not invariably, to detect fat-globules. In the urine of
pregnant women, which contains the so-called kyestein, If have,
* Beitr. Bd. 1,8.408.
t Haser's Arch. Bd. 6, S. 306.
t Handworterb. der Physiol. Bd. 2. S. 9.
254 HALOIDS AND HALOID BASES.
however, always observed a soft buttery fat. I have never met
with true milky, or chylous urine, where the turbidity and colour
were owing to the presence of fat ; for this species of urine seemed
to owe its peculiar character to a large quantity of pus-corpuscles,
held in suspension, which in all the cases I examined, originated in
the kidneys, and were not dependent on vesical catarrh. Where
milky urine has been found to contain a large quantity of fat, it
may be owing, as in Raver's case*, to milk that had been purposely
added, in order to deceive the physician.
It would be very important, in reference to the diagnosis of
Bright's disease, if we could confirm the conjecture advanced by
Oppolzer, that in this disease, at any rate when there is fatty
degeneration of the kidneys, the urine contains fat. I have, unfor-
tunately, hitherto been unable to confirm this conjecture, for even
where a post mortem examination showed decided fatty degenera-
tion of the kidneys., the urine exhibited no microscopic fat-globules,
nor did the ether extract any trace of fat. In one case only, where
the urine removed from the bladder after death, contained the
well-known epithelium cylinders, could I discover fat-globules. I
cannot concur with Virchow in his opinion, that the strongly
tinged epithelium of the tubes of Bellini contains fat, or that such
cells are to be regarded as evidences of the existence of fatty
degeneration.
Origin. — When we consider that vegetable food contains a
greater or lesser quantity of fat, and that we find large quantities of
the most ordinary vegetable fats accumulated in the animal organ-
ism, we might be disposed to infer that a vegetable diet was fully
adequate to the nourishment of animals, since it has been discovered,
or rather demonstrated, that it contains sufficient quantities of
albuminous substances to compensate for the waste of the nitro-
genous tissues. This view is daily confirmed by anatomical as well
as purely physiological observations and experiments. Every
farmer is well aware that cows will yield more butter when kept
upon food abounding in fat, than when kept on fodder deficient
in that ingredient, and that in rainy seasons, when plants contain
less fatty matter, cows, although yielding large quantities of milk,
give less butter than in dry seasons, although their food may be
rich and good. If two organisms, similar in all respects, and under
similar relations, partake of food differing in its quantity of fat,
there will be a difference in the deposition of fat. It cannot be
doubted that a large portion of the fats passes from the food into
* L' Experience, 1838. No. 42.
FATS. 255
the blood ; we need only observe the chyle when the food has been
of a fatty character, to convince ourselves, by the presence of fat-
vesicles, that it has been converted into a perfect emulsion, whilst
it will present only a slight turbidity from the presence of lymph-
or colourless blood-corpuscles, when the food has contained but
little fat. Boussingault* even succeeded, by a series of ingenious
experiments, in showing that only certain quantities of fat passed
in a given time from the intestinal canal into the general system,
and that the excess of fat was discharged unchanged with the excre-
ments. Thus he observed in the case of ducks, that a duck, when
kept on the fattest food, could not assimilate more than 19'2 gram-
mes of fat in twenty-four hours (or 0'8 of a gramme in one hour),
from the primes vice.
A sharp contest has been obstinately maintained during the last
ten years in reference to the question whether the animal organism
does not possess the capacity of generating the requisite quantity of
fat from other nutrient substances besides preformed fat. Dumas,
Boussingault,t and some other French enquirers,! have endea-
voured to show by direct experiments, that herbivorous animals
take up sufficient fat with their food, and that the animal organism
has therefore no need of generating fat; while Liebig and his
school§ have arrived at a totally different conclusion from observa-
tions of a precisely similar character. For as they found that cer-
tain animals contained more fat, and discharged a larger quantity
in their milk and excrements, than they had obtained by their
food, they were led to the conclusion that the animal body must
possess the property of forming fat from other organic substances.
The contested point unfortunately long remained undecided, since
the two parties differed in their idea of that which they termed fat
in the food ; the French enquirers regarding as fats all the matters
that can be extracted from plants by ether, and Liebig reasonably
enough considering those matters only as fats which possessed all
other properties of fats besides that of solubility in ether. Liebig
appealed in support of his views to the experiments first made by
Huber, and afterwards repeated by Gundelach, and which appeared
to prove that bees, when fed on pure sugar, are capable of gene-
rating wax. Subsequently, Dumas, in conjunction with Milne
* Ann. de Chim. et de Phys. 3 Se'r. T. 19, pp. 117-125, et T. 25, pp. 730-733.
f Ibid. T. J2,p. 153.
$ Persoz, in Compt. rend. T. 18, p. 245 ; Payen and Gasparin, in Compt.
rend. T. 18, p. 797 ; Letellier, in Ann. de Chim. et de Phys. 3 Se'r. T. 11, p. 433.
§ Pkyfair, in Phil. Mag. Vol. 22, p. 281.
256 HALOIDS AND HALOID BASES.
Edwards,* found reason to believe that bees cannot be fed for any
length of time on pure cane-sugar ; but that when fed upon the
honey yielded by this sugar, which contains a very little wax, they
were able to produce that substance. Boussingault,t Persoz,i and
others, have since that period convinced themselves, by repeated
experiments on pigs, ducks, and cows, of the correctness of Liebig's
view, and therefore this long-contested question may now be
regarded as at rest.
But it must not be forgotten that these experiments have only
been conducted on the statistical method (that is to say, by a com-
parison of the quantity discharged and the quantity taken up by
the organism) ; and that they cannot therefore afford more than
the general demonstration that under many relations, fat must be
formed within the animal body. But the following questions still
remain unanswered : Does the animal body continue to exercise
its property of generating fat, when a sufficient supply has been
conveyed to it by food ? What is the true seat of the formation
of fat ? And finally, how, and by what process, and in what che-
mical proportion, is fat formed from starch or nitrogenous
substances ?
The first question, as to whether the organism constantly exer-
cises its power of forming fat, does not admit of a solution in the
present state of our knowledge, nor until a satisfactory answer
can be given to the two other questions. If Boussingault's view
be correct, that the ordinary vegetable substances contain suffi-
cient fat to compensate for what has been lost through the func-
tions of the animal body, we might infer that fat would only be
generated from other substances when the food is deficient in fatty
matters, or when the supply of fatty food is inadequate. It may,
however, be argued against this teleological view, that if the con-
ditions for the formation of fat are once present in the animal
organism, this process will probably continue in operation without
reference to the plus or minus supply of fat. But many patholo-
gical phenomena appear to show that this process may in some
cases be abnormally excessive.
According to the views of Liebig and Scherer, in which most
observers now concur, the seat of the formation of fat is to be
sought in the prima vice. This hypothesis is not, however, based
on strict proof, and its value greatly depends upon the origin we
* Ann. de Chim. et de Phys. 3 Ser. T. 14, p. 400.
t Compt. rend. T. 20, p. 1720.
J Ibid. T. 21, p. 20.
FATS. 257
attribute to fat, namely, whether we derive it from albuminous,
and therefore nitrogenous substances, or from starch, sugar, and
other non-nitrogenous matters. Liebig's authority has given
currency to the latter view, although it is opposed by many physio-
logical facts. For if fat were formed in the primes vice from the
starch of vegetables, the chyle would contain more fat after a
vegetable than a fatty animal diet ; but the contrary has invariably
been noticed in all the observations made on this subject since the
experiments of Tiedemann and Gmelin. Boussingault* moreover did
not observe any instance in his recent experiments on ducks, in
which the fat contained in the intestinal contents, was increased
by feeding the birds on starch or sugar, although such must have
been the case if a metamorphosis of these substances into fat
occurred in this part of the system. Thomsonf was also led by
his experiments on the influence of different kinds of food on
the production of milk and sugar, to adopt the opinion that sugar
had no part in the formation of fat. The occurrence of hydroge-
nous gases in the intestines, and the well-known fact of the
reduction of alkaline sulphates into sulphides during the process
of digestion in the intestinal canal, might indeed seem to afford
some grounds for the possible reduction of the substances con-
taining carbon and the elements of water, to which we apply the
term carbo-hydrates, viz., starch, sugar, &c. ; but until supported
by some conclusive evidence, this view must be regarded as
scarcely tenable in opposition to the facts referred to. H. MeckelJ
was indeed led to believe, from some experiments made on the
subject, that sugar was thrown into a sort of fermentation by the
bile, and was thus converted into fat ; but it had escaped the
attention of Meckel, who regarded every substance that dissolved
in ether as a fat, that his etherial extract contained not only fat,
but all the products of decomposed bile soluble in ether; and the
reason of his obtaining a larger quantity of ether-extract when the
bile was decomposed by sugar, than when digested without sugar,
was simply in consequence of the presence of the sugar, which very
much promotes the decomposition of the bile, and the formation
of products easily soluble in ether (namely free biliary acids.)
It does not, therefore, appear from the facts already established,
that fat is generated in the intestinal canal from sugar and starch,
more especially as these substances would appear from Bous-
* Compt. rend. T. 20, p. 1726.
t Ann. d. Ch. u. Pharm. Bd. 61, S. 228-243.
t De genesi adipis in animalibus. Diss. inaug. Hal. 1845C
258 HALOIDS AND HALOID BASES.
singault's experiments,, to be too rapidly absorbed from the
intestinal canal to allow of their being subjected to a fatty
fermentation.
Liebig has advanced an hypothesis, that fat may also be formed
from nitrogenous elements of food; and this view would appear to
acquire support from the experiments made by Boussingault on
ducks. For the latter observer found that when these birds had
been fed on albumen and casein, containing little or no fat, there
was always more fat in their intestinal contents than when they
had fasted for any length of time, or been fed only on clay, starch,
or sugar. Unless, therefore, we would assume (which, indeed, we
have no authority for doing,) that fat is secreted in the intestinal
canal after the use of nitrogenous substances, we must admit, from
the above experiments, that a portion of fat may be generated in
the primce via from albumen containing no fat. It must, however,
be observed, on the one hand, that the increase of the fat in the
intestinal canal, after the use of albuminous food, is very incon-
siderable, and on the other, that the experiments are so few in
number, that we have not sufficient data for the satisfactory solu-
tion of so important a question. But it is very possible that the
digestion of nitrogenous food may be accompanied by a greater
secretion of bile than that of non-nitrogenous substances, and that
the fats and products of decomposition of the bile, may have
increased the ether-extract of the contents of the intestine, in the
above experiments, after the use of nitrogenous food. As has
been already observed, the solid excrements presented scarcely
any residua of the bile except those which are soluble in ether.
Since the above facts do not, as yet, justify us in assuming that
the seat of the formation of fat must be sought in the prima via,
we must turn to the processes at work in the blood, unless, indeed,
we freely confess that nothing definite can, at present, be advanced
on this subject.
The third question, as to how fat is formed from other sub-
stances, would next engage our attention, if the preceding consider-
ations did not show that we are entirely deficient in the materials
necessary for affording a satisfactory answer. For, so long as we
are ignorant of the grounds on which a process is based, although
we may be acquainted with its individual factors, we must
defer all idea of a scientific explanation ; there is, however, no
deficiency of imaginary schemes to explain the formation of fat
from sugar or protein. Support has been borrowed from the
somewhat irrelevant fact of the butyric fermentation of sugar
FATS. 259
and starch ; but, as we have already observed, (p. 333) there are
no grounds for reckoning butyric acid among the fats, and the
formation of metacetonic, acetic, and formic acids, may just as well
be regarded as processes of the formation of fat, as that of butyric
acid. We are, therefore, for the present, constrained to regard
this view as a mere fiction, illustrated by chemical symbols, since,
whatever corroboration it may acquire from future experiments, it
is at present wholly devoid of all scientific support.
Uses. — We may regard the application of fat in the animal
body as conducive to mechanico-anatomical, to physico-physiolo-
gical, and chemico-physiological objects.
The uses of the fat deposited in the areolar tissue of the animal
body are almost entirely of a strictly physical nature. If we reflect
that fat is mostly found in a fluid state during life, we shall per-
ceive some of the most useful properties which this condition im-
parts to the animal body. For although fat is enclosed in separate
layers and cells, it possesses so great a degree of mobility as to
propagate pressure equally in all directions in the same manner as
water. Every physicist knows that a bladder perfectly filled with
water cannot be brought to assume any given form without burst-
ing ; but we know that pressure applied to any part of such a
body will be equally propagated in all directions. If, therefore, we
suppose a number of such bladders to be laid side by side, enclosed
in a larger space, and that we press one of them, the pressure thus
applied will be propagated to all the others ; and here we have an
illustration of the uniform diffusion of external pressure through the
whole adipose tissue. But besides the protection thus afforded the
body from external shocks, it is further guarded in leaping and
falling by the Haversian glands, which penetrate into the joints, and,
receiving the shock, propagate it over a larger surface, by which
its violence at each individual point must be very much diminished.
Such was the object of nature in placing layers of fat on the soles
of the feet, and the tuberosities of the Ischium ; and thus the
depositions of fat were made to answer the purpose of water-cushions
and other inventions of man's ingenuity, for the promotion of his
ease and comfort.
Haller was the first who drew attention to the extreme
utility of fat in filling up those interstices which must unavoidably
exist between muscles, bones, vessels, and nerves. The bodies
of children and women principally own their rounded forms
to the deposition of fat in the subcutaneous cellular tissue. The
extreme mobility of the separate organs and parts of organs is
s 2
260 HALOIDS AND HALOID BASES.
mainly owing to the same cause ; and in every part of the body in
which greater or less deposits of fat are met with, nature appears
to have had a similar object in view. Hence fat is found to
remain the longest in the parts where it is most needed, as in the
heart and in the orbit of the eye. How could so complicated a
muscular structure as the heart move with freedom, ease, and
regularity, if the interstices formed by the muscular bundles often
contracting in opposite directions were not filled with fat, and if
the vessels proceeding from them were not completely enclosed in
fat? How would the muscles of the eye, and indeed the eye itself,
act, if we could remove all the fat from the orbit of the living
subject ? Deprived of this protection, the muscles would become
unable to discharge their functions, the optic nerve would be com-
pressed, and sight utterly destroyed. Thus, too, we find in the
rounded abdominal cavity, which is traversed by the cylindrical
intestinal canal, that every fissure and interstice is filled up with
fatty masses ; in the great omentum, in the mesentery, and the
appendices epiploicae, — wherever there is an interstice — we find fat ;
and it is most evident, that by these means all friction, and every
violent shock, are diminished, while a free peristaltic movement is
afforded to the intestinal canal. The lower part of the pelvis is
especially furnished with fat of so yielding a nature as to permit
of the organs of excretion contained in it, being dilated at will. How
different would be the appearance of the face if all the fat were re-
moved from the muscles and from below the skin! The fat which
smooths the bony corners and angles, and the narrow muscles of the
face, is the cosmetic employed by nature to stamp the human coun-
tenance with the incomparable impress which exalts it far above all
the lower animals. A similar physical use seems to be equally
apparent in the deposition of fat on the extremities, although its
presence may there be subservient to other purposes.
Although we find but little fat in the extremities of persons
who are accustomed to exercise their muscles strongly, the
quantity present is yet sufficient to effect the purposes already
indicated.
Fat, when in a fluid state, is moreover a very bad conductor of
heat. This property of fat has been most wonderfully employed
by nature for the protection of the animal body from the injurious
effects of excessive heat or cold, and of rapid alternations of tempe-
rature. Every one acquainted with the propagation of heat in
fluid bodies, will easily perceive, that by the distribution of fat in
small cells and layers, by which the rising and falling of the heated
FATS. 261
or cooled fluid is impeded, nature has most perfectly effected the
object in view. We surround our stoves with stagnant air, in order
to retain the heat as much as possible ; but this object would be
far more perfectly attained, if we could enclose the air in the sub-
jacent and superimposed layers of so bad a conducting medium as
the cellular tissue. When we consider the enormous quantity
of cells filled with fat which are frequently deposited under the
skin of corpulent persons, we can scarcely comprehend how an
otherwise healthy individual could die from the effects of excessive
cold.
Thus we find that the whole abdomen is filled and covered with
fat, for the purpose of maintaining that equable temperature
which is requisite for the due performance of its various chemico-
physiological processes, the adipose tissue of the omentum
acting as a special protection to the abdominal viscera. In fur-
therance of a similar end, the female breasts are largely supplied
with fat, since, from their exposed position, these organs might,
without such a protection, readily become unfitted for their normal
functions. The testicles, on the other hand, contain no fat, and
the scrotum very little, because these organs must be kept cool, as
we learn from the bad results following the non-descent of the
testicles. Animal heat could not be maintained in so equable a
condition in the body, if all the organs — every part in which a
metamorphosis of tissue occurs — were not enveloped in fat. Do
we not observe how eagerly phthisical patients, convalescents, and
old persons, seek the warmth of the sun, and how emaciated ani-
mals delight in basking in its rays? We should probably also take
into consideration the fact that, next to water, fat possesses the
greatest capacity for heat, and hence a very considerable quantity
of heat will be required to transmit warmth through the fatty
investment of the body. As a proof that fat possesses these useful
properties, we may refer to the practice common alike to the
nations of the extreme north, and to the inhabitants of many
tropical lands, of anointing the skin with fat, in order to guard in
the one case against intense cold, and in the other against extreme
heat.
The various uses arising from the low specific gravity of fat
scarcely require comment. It would be almost impossible to
swim without fat, and although it might be advanced that swimming
is not a necessary faculty of the human body, we shall readily be
disposed to admit the utility of fat in this respect when we con-
sider that, if the muscles of only an arm were encompassed with
262 HALOIDS AND HALOID BASES.
pure water instead of fat, the force of the muscles, which is, more-
over, better adapted to rapid movement than to overcome a
resisting power, would undoubtedly be very considerably dimi-
nished ; for there can be no doubt that in hy drops anasarca the
muscular weakness does not depend alone on the tension, and on
the morbid diminution of the muscular activity, but likewise on the
altered condition of gravity of the whole extremity, depending on
the accumulation of water and diminution of fat.
One of the best known properties of fat, is that of its rendering
other bodies supple, and diminishing as much as possible the brittle-
ness of bodies, and the friction of parts moving on one another.
This use is made most apparent in the movement of the muscles,
and the free action of the joints. In this point of view, the utility
of fat is nowhere more conspicuous than in the bones. Fat, un-
doubtedly, gives great flexibility to the earthy bones, as we perceive
from their brittleness when macerated ; and as is made most appa-
rent in the disease of the bones inaptly termed osteomalacia, for,
while there is so extraordinary a loss of osseous matter, that the
bones appear, when macerated, to consist of a mere gauze-like
tissue, most of the interstices are entirely filled with fat, as if the
vis nature medicatrix would in some degree compensate, by an
excessive accumulation of fat, for that property of the bones which
has been destroyed by this disease.
I found, in the ribs of a patient who had died in a state of
extreme osteomalacia, 56'92§ of fat together with 24'665% of other
organic matters, 15 '881$ of phosphate, and 2' 534% of carbonate of
lime.
The utility of fat, considered in a mechanical point of view, is
so evident from what has been already said, that it would seem
superfluous to add any further remarks on the subject. If negative
evidence were admissible, we might observe that fatty deposits are
rarely or never found in the brain and lungs, where their presence
would occasion mechanical injury, since external pressure, and even
a slight increase of heat, would prove injurious to these organs. In
the glans penis again we find no fat, because its presence would,
undoubtedly, contribute to increase the irritability of this organ.
Before we proceed to the consideration of the chemico-physical
uses of fat, we will cursorily advert to the view which has long pre-
vailed in physiology, that the fat deposited in the areolar tissue is
nothing more than a stored-up nutriment. This proposition, advanced
in accordance with the earlier views of natural philosophy, appeared
to derive a considerable degree of corroboration from a general con-
FATS. 263
sideration of the fatness and leanness of men and animals, under
different physiological or pathological relations ; but such a method
of observation is too vague and general any longer to maintain its
ground in the present position of science. We have ceased to believe
in the existence of a special administrator of the economy of the
living organism, who, under the title of vital force, prepares, in times
of plenty, for a season' of scarcity ; and we now know that the
process of the deposition of fat in the areolar tissue is not so simple,
and that its resorption does not admit of so ready a solution as was,
at one time, believed to be the case. Thus, it must not be supposed
that fat simply collects in the interstices of the cellular tissue, from
which it may be as easily removed as the water which occasionally
accumulates therein in hy drops anasarca. Fat is not contained in
a free state within the interstices of the areolar tissue, but is
contained in special cells, enclosed by an albuminous wall., and
provided originally with a nucleus, the so-called cytoblast. Fat,
therefore, only collects in the cellular tissue by means of a cell-
formation, and hence it is, in many cases, extremely difficult to
explain how fat can so rapidly disappear from the areolar tissue.
It has not even been clearly determined whether the whole cell is
resorbed with the fat, or whether, as Gurlt* maintains, the cell
remains, and is filled with serum instead of fat. We must remember,
in considering the observations made on the increase or diminution
of fat in men and animals in a healthy as well as a diseased con-
dition, that fat-cells, like most other animal cells, stand in a con-
stantly alternating relation to the other fluids, more especially the
blood. The constitution of the blood is reflected in all parts of
the animal body, and endosmotic and counter currents must be
established as soon as one of the fluids in question is subjected to any
alteration. It is not necessary that we should assume with Mascagni
that each fat-cell is provided with an artery and a vein, for the relations
of endosmosis with which we are at present acquainted sufficiently
explain the different results of this mutual action between the
nutrient fluid and the fat- cell. In rapid emaciation, and more
particularly in those conditions of the body which are usually
termed anaemic, (as, for instance, after repeated blood-letting and
other losses of the animal fluids, and after typhus and other severe
diseases,) fat is often accumulated in the blood, while it disappears
from the sub-cutaneous cellular tissue. Conversely, the formation
of fat- cells often appears to be more rapid than the reproduction of
other tissues after anaemic conditions, when the blood has not
* Physiol. S. 20.
264 HALOIDS AND HALOID BASES.
quite recovered its normal character ; hence we frequently observe
a very abundant deposition of fat after typhus and other diseases
resulting in ansemia. We shall enter more fully into the consider-
ation of this subject, when we proceed, at the close of the phy-
siological chemistry, to treat of the general phenomena of nutrition.
We now enter upon what may be termed the physico-physi-
ological uses of fats. Liebig has shown; with his characteristic
ingenuity, that the fats mainly contribute to the excitement and
maintenance of animal heat. One of the most ingenious of
Liebig^s deductions is his classification of the elements of nutrition
into true plastic nutrient substances and food for the respiration,
to the latter of which he especially ascribes the functions of main-
taining animal heat. But as, in our observations on the processes
of respiration and nutrition (in the third volume), we shall enter
more fully into the examination of Liebig's views on this subject,
we shall here only observe that, however paradoxical and apodictic
many of his deductions may appear, he has founded a new era in
physiological chemistry, and has been the means of throwing a
clearer light over the whole economy of the organism. Owing to
his aphoristic mode of representation, his views have often been
misunderstood and erroneously interpreted, and many persons
have even supposed that they must assume that fat is simply
transferred into the blood, where it is burned like the oil in a lamp,
or the coke in a steam-engine. A more attentive examination of
Liebig's writings shows, however, that he did not entertain so
crude a view of the subject. But we must admit that we do not
consider as wholly groundless the objection which has been
advanced against Liebig, that he regards animal heat as too inde-
pendent of other processes. Animal heat can only be considered
under one of two points of view ; that of being an incidental
phenomenon and the mere result of certain vital processes, or as
being necessary to the maintenance of definite animal processes and
functions. If the latter view be even partially correct, we must recol-
lect that animal life is not generally dependent upon a definite high
temperature, and that numerous cold-blooded vertebrate animals
perform the processes of digestion, respiration, blood-formation, and
of the nervous system, as well at a low temperature, as warm-blooded
animals do at 37°*5. If, on the other hand, animal heat were a
mere incidental phenomenon, the fats would appear to be most
uselessly expended in serving no other purpose than that of deve-
loping heat. The fat of the living body therefore probably conduces
to other ends in the animal economy.
FATS. 265
I was long since led, from theoretical grounds, to regard the fat
as one of the most active agents in the metamorphosis of animal
matter ; and this subjective conviction has since been converted
into objective proof by numerous experiments and observations.
After having found by experiments regarding the fermentation of
milk,* that this process cannot be excited by albuminous bodies in
saccharine or amylaceous fluids, excepting with the cooperation of
fat, I next ascertained that a certain, although small quantity of
fat, was indispensable to the metamorphosis and solution of nitro-
genous articles of food during the process of gastric digestion.
Elsasserf has confirmed the fact by the observation that, in expe-
riments on artificial digestion, the solution of articles used as food
is considerably accelerated by means of fat. It is easy to ascer-
tain by means of artificial openings in the stomachs of dogs, that
flesh containing only little fat, and especially albuminous sub-
stances which have been designedly deprived of their fat, remain
longer in the stomach, and therefore require a longer period for
their metamorphosis, than the same substances when mixed or
impregnated with a little fat. An excess of fat appears, on the
other hand, at least in persons of weak digestion, to exert an in-
jurious action. The pancreatic juice most probably owes a portion
of its utility in promoting digestion to the quantity of fat which
it contains.
The pancreatic juice, like pus, deposits, according to Cl. Ber-
nard,J fine crystalline bundles of margarin and margaric acid during
its spontaneous decomposition at a high temperature.
Although we are unable fully to demonstrate the special agency
of fat in the further metamorphosis of the digested food, namely, in
the formation of chyle and blood, yet we need only observe the
intestinal villi during the process of digestion, and see their indi-
vidual cells filled either with clear fat or dilated by a grumous
matter — we need only institute a microscopic and chemical compa-
rison of the fat in the chyle found in the finest lacteals with the con-
tents of the thoracic duct, in relation to the different quantity and
character of the fat in both fluids — in order to perceive that fat is
not only resorbed, but that it also influences the metamorphosis of
the albuminous constituents of the nutrient fluid. Is it probable that
fat would so tenaciously adhere, even under different modifications,
to some of the constituents of the blood, unless it exercised some
* Simon's Beitrage. Bd. 1,8. 63-77-
t Magenerweichung dcr Kinder. S. 112.
J Arch. gen. do Me'd. 4 Ser. T. 10, p. 71.
266 HALOIDS AND HALOID BASES.
influence on their origin or metamorphosis ? Or are we to suppose
that the fat, which we can extract from the animal nerves by boiling
them with alcohol, or digesting them with ether, and whose removal
leaves the separate nerve-fibres like hollow cylinders with thick walls,
is deposited there for no useful end, and that it can be wholly free
from all cooperation in the function of the nervous system ?
However opposed we may be to teleological explanations, we
cannot deny the importance of an enquiry into the grounds and
aims of obscure subjects, since it is by such means that natural
enquiry has ever been guided into those paths which lead to the
investigation of causes, and the final comprehension of pheno-
mena.
We have already become acquainted with two species of animal
cells, in which fat is the main constituent, viz., true fat-cells and
certain kinds of granular cells (the so-called inflammatory globules)
found in milk, (Corps granuleux, Colostrum-corpuscles,) in the
sputa in chronic catarrh, in old apoplectic cysts, &c. Fat, how-
ever, would appear from some of the latest investigations of the
most distinguished physiologists, to play a very important part in
every kind of cell-development ; indeed most enquirers agree in
regarding it as affording the primary foundation in the formation of
a cell. Acherson* was undoubtedly the first to direct attention to
this subject by his discovery that albumen always coagulates
around a fat-globule placed in an albuminous solution ; and although
the question may not be so simple as Acherson would make it
appear, the presence of fat in the cell during its formation, and its
importance in affording the predisposing cause of cellular for-
mation, is no longer denied by any physiologist, whether he adhere
to the old theory of cell-development established by Schwarm
and maintained by Kolliker, or advocate the views of Henle, or
of Reichert. According to Hiinefeld, Nasse, and others, the
nucleoli invariably consist of fat. The newly secreted or recently
formed plasma always contains more free fat than after the nuclei
or cells have been deposited, — a fact that is clearly demonstrated
in H. Miiller'sf excellent memoir on the chyle and its histologi-
* Miiller's Arch. 1840. S. 49. [In connexion with this subject, I may refer
to a Memoir on " the Structural Relation of oil and albumen in the animal eco.
nomy," read by Professor Bennett before the Royal Society of Edinburgh, and
published in the " Monthly Journal of Medical Science," Vol. 8, p. 166 ; a Lecture
published by myself in the " London Medical Gazette," for May, 1848, New
Series, vol. 6, p. 140 ; and v. Wittich,, Ueber die Hymenogonie des Eiweisses.
Konigsberg, 1850. — G. E. D.]
t Zeitschr. f. rat. Med. Bd. 2, S. 233.
FATS. 267
cal elements, who shows that the cloudy turbidity of the chyle which
depends on the presence of the fat, disappears in proportion as
the isolated granules, the aggregated granules, and the cells are
developed. The serum of pus moreover contains much less fat
than pus-corpuscles. In the blood we find that fat is especially
deposited in the cells and in the fibrin, the granular contents of
many of the blood-corpuscles consisting of this substance. All
plastic exudations contain more fat than the non-plastic ; for the
latter, as dropsical fluids and tubercular masses, although occa-
sionally containing much cholesterin, usually contain very little
true fat; while on the other hand exuberant, highly cellular
cancers abound in this ingredient.
In pus, the pus-corpuscles often sink some lines below the
level of the fluid; on comparing the amount of fat in the
supernatant serum with that in the pus beneath it in which the
corpuscles were suspended, I observed, in two experiments con-
ducted with different pus, that in one there was only 7*13^ of fat
in the solid residue of the serum (which should have contained most
of the fat since it was taken from the surface of the pus after it had
stood a long time,) while the thick purulent sediment contained
18*4 1§; in the other case there was 9'084^ in the residue of the
serum, and 17'14§ in that of the pus. The difference between the
amount of fat in the serum of the pus and in the pus-corpuscles
is most plainly apparent when both the sediment and the serum
of good pus are suffered to remain in well closed vessels. Both
fluids become acid, and fats and fatty acids are separated from
them; in the former these changes are but slightly developed,
whilst the acid purulent sediment exhibits, under the microscope, an
innumerable quantity of the most beautiful crystallisations of mar-
garic acid and of margarin, with cholesterin.
The fats of the blood are also principally deposited in the cells
or blood-corpuscles. I found in 100 parts of well dried blood-
corpuscles taken from the blood of the ox, and whose mode of
preparation I shall explain in the second volume of this work,
2-214% of fat in one experiment, and 2'284£ in another; the
fibrin of the same blood contained in the one instance 3*2 18£, in
the other 3'189£ of fat; while 100 parts of the solid residue of
the serum yielded 1-821, and 1'791 parts of fat. The blood-
corpuscles have, unfortunately, scarcely ever been examined with
reference to their amount of fat ; in other respects, however, a
comparison with the analyses instituted by other observers on the
blood, leads to the same result.
268 HALOIDS AND HALOID BASES.
It may be observed, in reference to the small quantity of fat
contained in tubercles, that many fat-vesicles are often discovered
under the microscope in recent tubercular deposits, as, for
instance, in gelatinous tubercles, but that gray, solid tubercles,
when submitted to a chemical analysis, after the separation of the
cholesterin, which although not belonging to the fats is always
reckoned amongst them, are found to contain very little fat. In
a gray tubercular mass, I once discovered only 3"54$ in the well-
dried substance, although almost every other tissue contained far
more fat. Becquerel and Rodier* found, moreover, that in tuber-
culosis the saponified fats were far more diminished in the blood
than in any other fluid.
We may here, perhaps, find some explanation of the mode of
action of cod-liver oil, whose utility cannot be wholly denied even
by that spirit of scepticism which has of late been so prevalent in
medicine ; and we have always been of opinion that cod-liver oil
acts upon certain stages of disease more by its true fatty nature
than by the small quantity of iodine which it contains. In con-
firmation of this view we may observe that many experienced prac-
titioners (Oppolzer among the number) have found that almond
oil and other similar oils are as efficacious as the loathsome cod-
liver oil. But the idea that cod-liver oil, considered (according to
the misconception of Liebig's viewsf) as a mere material of com-
bustion, should be of benefit in a disease where the lungs are so
entirely clogged or degenerated that an extensive oxidation of the
blood is impossible, can only be entertained by persons wholly
ignorant of the character of tuberculosis or of pulmonary consump-
tion. No chemical analysis is needed to show that cellular cancer
(encephaloid) and sarcoma abound in fat, and every one who has
examined one or two of such tumours microscopically will be able
to confirm the truth of this ordinary observation.
When we consider all these facts we shall be almost involuntarily
led to the conclusion that fat takes a highly important share in
the most important, and at the same time the most mysterious pro-
cesses in the formation of cells and tissues. We cannot believe
that fat is a mere incidental agent in all these processes, but we
must rather regard it as of essential aid in the process of converting
nitrogenous nutrient substances into cells and masses of fibres, in
like manner as it cooperates in the processes of lactic fermentation
and digestion ; and it is probable that whenever a chemical equa-
* Gaz. m^d. 1844. No. 51.
t Ann. d. Ch. u. Pharm. Bd. 58, S. 84-89.
FATS. 269
tion representing the formation and function of certain cells can be
established, fat will constitute one of the integral factors. Indeed it
is impossible to believe that in the vital activity of cellular action, fat
should be without influence on the metamorphosis of the substances
which it accompanies, and that without reference to them, it should
obey only its own affinities towards oxygen or an alkali.
In considering fat as an important agent in the various phases
of the metamorphosis of animal matter, we cannot, however, refer
its action solely to mere contact or a catalytic force, but we are
constrained to assume that it cooperates in the metamorphic action,
and experiences metamorphoses, combinations, and decompositions.
None but those chemists, who, imagining they comprehend Liebig^s
views, have framed and illustrated a physiology of their own, in the
same manner as speculative natural philosophers have attempted
a priori to construct the laws of the natural sciences, could have
regarded the animal body as a furnace, and fat as a simple and crude
material of combustion. It is, however, the province of physiological
chemistry to trace the chemical phenomena of the animal body and
its various substances in their separate phases of metamorphosis, and
from the knowledge thus obtained, to sketch the grand and univer-
sal features of chemical action in the living body. It would be
equally unphysiological and unscientific to suppose that the require-
ments of physiology would be fully satisfied by our proving that fat
becomes finally decomposed into carbonic acid and water. The
province of physiological chemistry is rather to show whether fat,
or rather the fatty acids, always gradually and successively lose two
atoms of carbo-hydrogen, that is to say, whether remaining in accor-
dance with the general formula, they become converted into acids of
the first group, and are then finally decomposed into carbonic acid
water ; or whether fats contribute by their metamorphosis in the
animal body to form other known animal substances. As, how-
ever, in the present state of our positive knowledge, we are unfor-
tunately not in a position to answer this question with certainty, it
is better to confess our ignorance, than to indulge in vague conjec-
ture, although many chemical and physiological experiments afford
some support to the hypothesis, that the fats take a part in the
formation of other substances which cannot be regarded as mere
products of their oxidation.
Since we find so large a quantity of saponified fats in the blood
and other animal fluids, as for instance in the bile, it is not impro-
bable that the first step in the alteration of the fats consists in their
decomposition into glycerine and the corresponding fatty acids.
270 HALOIDS AND HALOID BASES.
If we assume that the fats are subjected to so gradual an oxidation
that their carbo-hydrogen radical gradually diminishes by 2 atoms
of carbo-hydrogen, it is singular that we should find the fatty
acids which mark the gradations from capric to margaric acid in
plants, but not in animals ; for while the formation of fatty acids
with a high atomic weight is very gradual in plants, a similar law
does not prevail in reference to their regressive formation in
animals, for here we meet with no acids besides margaric and
stearic having a fat-radical of the formula, CnHn_1. It would
appear, therefore, that the fatty acids, when separated from glyce-
rine (to which reference has already been made at p. 243) enter
into complicated combinations and metamorphoses, in which it is
not easy to recognise or detect their presence. We have already
(at p. 126) noticed the probability that the principal acid contained
in the bile, cholic acid, is a conjugated fatty acid ; chemical experi-
ments giving evidence of the presence of oleic acid in it, although
it cannot actually be separated.
The hypothesis, that a portion of the fat takes part in the forma-
tion of bile, is further confirmed by numerous physiological and
pathological experiments.
The following physiological facts in some degree confirm this
view. A close observation of the development of the chick
within the egg, leads us almost irresistibly to the opinion, that
towards the close of the period of incubation, a portion of the fat
in the yolk-sac (when it is drawn into the abdominal cavity
and adheres to the liver) is converted into biliary matter ; and
every physiological enquirer, who has occupied himself with this
subject, must have observed the greenish tint which is often,
although not always, very distinctly visible in the yolk-sac, and
especially along the course of the veins. On one occasion I found
this colour so intense, that I was induced to treat the whole of the
yolk-sac and its contents with boiling alcohol, and examine it for bile,
according to the method described at p. 123 ; when the ordinary
bile-reaction was obtained by Pettenkofer's test. The veins of the
yolk-sac pass into the liver, and it is well known that the vessels of
the yolk-sac for the most part resorb the yolk, and transfer it into the
liver; for the earlier view that the yolk passes through the ductus
vitello-intestinalis\r\to the intestine, and is carried from thence into
the liver by the biliary ducts, is incorrect. The liver at this period
serves mainly, as E. H. Weber,* and Kollikerf have shown, to
* Zeitschr. f. rat. Med. Bd. 4, S. 160-164.
t Ibid. Bd. 4,8. J 12-160.
FATS. 271
form colourless and coloured blood- corpuscles, and not to produce
or secrete bile, for I have frequently convinced myself by obser-
vations on human and animal embryos, that at this period the
gall-bladder contains no bile.
The blood of the portal vein, from which the bile is principally
formed, differs from all other blood, whether venous or arterial, by
its large quantity of fat, as was noticed by Simon and Schultz, and
has been corroborated more recently by the exact quantitative
analyses of Fr. Chr. Schmid,* who found that the blood of
the portal vein contained so much more fat than that of the
jugular vein, that he was led to regard this as the most
essential difference between these two kinds of blood.
Moreover he observed that the fat from the blood of the portal
vein was of a dark brown colour, and that it was always richer
in olein, and consequently more greasy, than the fat of other
venous blood, which is white and crystalline. When animals are
starved for any length of time it is well known that they rapidly
become emaciated ; the urine still exibits nitrogenous constituents,
corresponding in amount to the products of effete tissue; whilst
the gall-bladder is perfectly full, and the liver constantly pours
forth bile into the intestine, as I have convinced myself by a
repetition of Magendie's experiments.f The above fact seems to
explain the cause of the bitter taste of which persons suffering
from starvation very frequently complain. Whence can the liver
extract the materials necessary to the formation of bile ? The urine,
although poorer in solid constituents, always contains a consider-
able quantity of urea ; and the animal body contains few or no highly
carbonaceous substances, with the exception of fat, which we
here observe disappearing very rapidly, while at the same time
there is an abundant secretion of bile.
In disease the diminution or increase of fat is inversely pro-
portional to the secretion of bile. Polycholia, which seldom occurs
in adults, but which in children constitutes the affection known as
Icterus neonatorum, is always accompanied with rapid emaciation.
In acute diseases, emaciation generally occurs in conjunction with
critical symptoms, that is to say, when the organs of excretion
resume their activity, and eliminate the materials that have become
effete ; hence the copious semi-solid faeces. In all acute or chronic
diseases of the liver, the fat accumulates either merely in the blood,
or in the blood and in the cellular tissue. The obesity observed
* Heller's Arch. Bd. 3, S. 487-521, and Bd. 4, 8. 15-37, and S. 97-132.
t Journ. de Physiol. T. 8, p. 171.
272 HALOIDS AND HALOID BASES.
in habitual drunkards is not in consequence of their taking too
much combustible material into their bodies, (brandy drinkers
moreover generally take only small quantities of solid food,) but
in consequence of the disturbed hepatic action, which the invariably
abormal condition of the liver, found in after death in these cases,
proves to have existed.
Traill* and Lecanu have found the blood extremely rich in fat
in inflammation of the liver ; and Lassaigne,t and more recently
Becquerel and Rodier, found the quantity of the fat in the blood
more increased in icterus than in any other disease. Dobson,
Rollo, and Marcet, observed so large a quantity of fat in the blood of
diabetic patients that it resembled an emulsion ; but I have myself
only on two occasions found the blood to be largely charged with
fat in diabetes, and here the disease was complicated with an
affection of the liver, and the excrements of the patients were pale,
and almost of a grayish-white tint.
All these facts render it difficult to deny the existence of a
connexion between fat and the formation of bile.
It is not, however, wholly impossible that fat should contribute
in some measure to the formation of other substances, but we will
here simply observe that facts subsequently to be noticed give some
probability to the opinion that fat likewise cooperates in the for-
mation of the blood-pigment.
We trust that the above remarks will lead to a more careful
enquiry into the metamorphoses and function of fat in the healthy
and diseased body, and be the means of assigning a higher degree
of importance to this substance, than has hitherto been awarded
to it in the animal economy.
HYDRATED OXIDE OF CETYL. — C32H33O.HO.
Chemical Relations.
Properties. — This substance, to which its discoverer, Dumas,
gave the name of ethal, forms white, solid, crystalline plates, melts
at about 56°, again solidifies at48°, and volatilises readily either alone
or with aqueous vapour, when heated ; it is devoid of smell and taste,
is insoluble in water, but dissolves in all proportions in hot alcohol
and ether, has no action on vegetable colours, and when ignited
burns like wax. It is decomposed when heated with nitric acid ;
* Annals of Philos. 1823, vol. 5, p. 199.
t Journ. de Chim. med. T. 2, p. 264.
FATS. 273
heated to 220° with hydrated potash, it hecomes converted
(see p. 72,) into cetylic acid (C32H33O + 2HO + KO = 4H +
KO.C32H31O3). When warmed with concentrated sulphuric acid
it forms an acid haloid salt.
Composition. — According to the above formula, deduced from
the analyses of Dumas and Peligot,* this body consists of:
Carbon 32 atoms .... 79'339
Hydrogen .... 33 „ .... 13'636
Oxygen 1 „ .... 3.306
Water .... 1 3-?19
100-000
The atomic weight of the hypothetical anhydrous substance
= 2912-5.
This body, like glycerine, is the hydrate of a fatty base ; but its
composition and its relations of combination indicate that it is
much more closely allied to the hydrated ethers or alcohols; in
common with them it is included in the formula CnHn+1O.HO,
it loses the one atom of water in combining with acids, and is
converted by oxidation into an acid of the formula CnHn_1O3.
Oxide of cetyl or cetylic ether in an anhydrous state has not been
obtained.
Combinations. — Very little is known of the acid sulphate of
oxide of cetyl in its isolated state. Its combination with potash,
which = C32H33O.SO3 + KO.SO3 is obtained in minute, thin,
nacreous plates.
Cetylate of oxide of cetyl, C32H33O.C32H31O3 (Smithf) ex-
ists preformed, under the name of cetin or spermaceti, princi-
pally in the cavities of the skull, but also in the fat of other
parts, of the Physeter macrocephalus. To obtain it in a state
of purity, we must repeatedly crystallise it from hot spirit, of
0'816 specific gravity. It separates in minute, nacreous, white
plates, devoid of smell and taste ; it fuses at 49°, but on cooling
solidifies in a crystalline form ; it volatilises at 360° without decom-
position, dissolves in 40 parts of boiling spirit, of 0'821 specific
gravity, and more readily in anhydrous alcohol and ether ; when
submitted to dry distillation it yields no pyroleic acid, and when
digested v.'ith nitric acid it yields adipic but no suberic acid. When
heated with hydrated potash it is resolved into hydrated oxide of
Cetyl and cetylic acid.
* Ann. d. Chim. et de Phys. T. 72, p. 5.
t Ann. d. Ch. u. Phavm. Bd. 42, S. 40-51.
T
274 LIPOIDS.
Preparation. — In order to obtain hydrated oxide of cetyl, pul-
verised hydrated potash must be added to melted spermaceti, and
the mixture be continuously stirred ; when the mass has become
solid it must be digested with water, and the soap which is thus
produced must be treated with hot dilute hydrochloric acid ; after
the oily stratum has been again fused with caustic potash, and
digested with hydrochloric acid in order to ensure the perfect
decomposition of the cetin, the mixture of cetylic acid and oxide of
cetyl must be digested with milk of lime and evaporated. From this
mixture we can take up the hydrated oxide of cetyl by cold alcohol,
which does not dissolve the cetylate of lime.
Tests. — It is impossible to recognise this substance with cer-
tainty unless by an elementary analysis.
Physiological Relations.
Hydrated oxide of cetyl has not yet been found in an isolated
form ; spermaceti, however, occurs in several parts of the Cachalot,
mixed with ordinary fat ; in greatest quantity, however, in the head,
not in the actual cavity of the cranium, but in a large excavation on
either side of the upper part of the head and lying external to the
nostrils. Regarding the formation and uses of this substance,
we can only offer the same opinions as respecting the fats in
general.
The doeglic oxide of Scharling is too hypothetical a body to
be entitled to be yet classed among the haloid bases. Compare
p. 11(5.
LIPOIDS.
Under this head we place what are termed the non-saponifiable
fats, that is to say, such bodies as have many physical properties
in common with the salts of oxide of lipyl, but do not resemble
them in their composition or in their products of decomposition, and
consequently cannot be placed amongst the true fats. In this class
we place cholesterin, serolin, casiorin, and ambrein.
CHOLESTBRIN. 275
OHO LE3TERIN. C37H32O.
Chemical Relations.
Properties. — This body, formerly known as biliary fat, separates
from its solutions in nacreous scales containing 2 atoms of water ;
examined under the microscope, these crystals appear in very thin
rhombic tablets, whose obtuse angles = 100° 30", and whose acute
angles = 7^°30'; it fuses at 145°, solidifying again, and becoming
perfectly crystalline at 135°; it may be distilled in vacuo at 360°
without undergoing decomposition ; it becomes electrical on fric-
tion, is perfectly insoluble in water, but dissolves in 9 parts of
boiling alcohol, from which the greater part again separates on cool-
ing ; it is also slightly soluble in soap-water, and more freely
in the fatty oils and taurocholic acid ; it is inflammable, arid
burns with a smoky flame. Treated with concentrated sulphuric
acid it assumes a red tint at 60°, and is converted, with the
loss of water, into three probably polymeric carbo-hydrogens, which
their discoverer, Zwenger,* has named cholesterilins. If choles-
terin be heated with concentrated phosphoric acid to its melting
point, there are formed two carbo-hydrogens, isomeric with
the cholesterilins, to which Zwengerf has applied the name
of cholesterones. By prolonged boiling with concentrated nitric
acid, it becomes first converted into a resinous mass, which, by pro-
longed digestion, is resolved (RedtenbacherJ) into acetic, butyric,
caproic, oxalic, and cholesteric acids (see page 122). A portion
of the hydrogen may be abstracted from cholesterin by chlorine or
bromine, of which an equivalent quantity takes the place of the
hydrogen thus removed. It is riot decomposed by concentrated
alkalies, even when the mixture is submitted to prolonged heat.
On dry distillation it leaves a charcoal, and yields an oily distillate,
which after rectification with water evolves an agreeable odour,
resembling that of the Geranium.
Composition. — Cholesterin has been analysed by Marchand,§
Schwendler and Meissner, and subsequently by Payen,|| with toler-
ably similar results, which have led to the establishment of the
above formula, C37H32O. As we have not yet succeeded in com-
* Ann. d.Ch. u. Phann. Bd. 66, S. 5-13.
t Ibid. Bd. 69, S. 347-354.
J Ibid. Bd. 57, S. 162-170.
§ Journ. f. pr .Ch. Bd. 16, S. 37-48.
II Ann. de Chim. et de Phys. 3 Ser. T. 1, p. 54.
276 LIPOIDS.
bining cholesterin with any other body, we have no means of con-
trolling this formula and of determining its atomic weight. Zwenger
has very recently analysed the cholesterilins, of which he was the
discoverer, and found them composed in a tolerably uniform man-
ner. He assumes, however, that there are differences between them,
and that they may be respectively represented by C32H26, C22H18,
and C27H22 ; and he believes that cholesterin consists of these
three carbo-hydrogens and 3 atoms of water, its formula being,
according to his views, C81H69O3. Taking into consideration the
limited accuracy which we are capable of attaining in our elemen-
tary analyses, and the method by which we deduce a formula from
empirical results, we must regard Zwenger's view as, at present,
very hypothetical.
We give the composition of cholesterin according to both
formulas :
Carbon 37 atoms 84'733 81 atoms 83-93
Hydrogen 32 „ 12'214 69 „ 11.91
Oxygen 1 „ 3'053 3 „ 4'16
100-000 100-00
Notwithstanding its extraordinarily high numbers, Zwenger's
formula accords more closely than the simpler one with the empi-
rical results.
Products of decomposition. — «. Cholesterilin, C32H265 is earthy,
amorphous, insoluble in water, and slightly soluble in alcohol ; it
differs from the two other carbo-hydrogens by its insolubility in
ether; it crystallises from a hot oil of turpentine solution, and
melts and is decomposed at 240°.
b. Cholesierilin, C22H18, crystallises in minute, strongly glisten-
ing plates or delicate needles, which are insoluble in water and
alcohol, but soluble in ether; it fuses at 255°, and on cooling soli-
difies in a crystalline form.
c. Cholesterilin, C27H22, is a yellow, amorphous, resinous mass,
freely soluble in ether, slightly so in alcohol, and insoluble in water ;
it fuses at 127°. Both this and the preceding variety are decom-
posed by heat. The formulae must be regarded as entirely hypo-
thetical, since the per-centage composition, both as found and as
calculated, approximates to 88$ of carbon, and 12£ of hydrogen for
all three of them.
a. Cholesterone is obtained by extracting with spirit the resi-
due of cholesterin, heated with phosphoric acid to 137°; it
crystallises in right rhombic, bilaterally acuminated prisms ; is
CHOLESTERIN. 277
colourless, transparent, very lustrous, lighter than water, and
melts at 68° into a colourless fluid, which very slowly reassumes
the solid form ; it can be distilled for the most part undecom-
posed, and burns with a smoky flame. It is insoluble in water,
but dissolves freely in alcohol and ether, and in the volatile and
fatty oils.
b. Cholesterone is extracted by ether from the residue insoluble
in alcohol ; it occurs in fine white needles, melts at 175°, cannot be
distilled without partial decomposition, is lighter than water, is
devoid of taste and smell, and burns with a smoky flame. Both
varieties of cholesterone are devoid of oxygen, but contain about
12 parts hydrogen to 88 of carbon.
Preparation. — The best method of preparing cholesterin is by
boiling gall-stones, containing this substance, with alcohol, and
filtering the solution while hot; by recry stall isation from hot alco-
hol it is easily obtained in a state of purity.
Tests. — The recognition of cholesterin in the animal fluids is
by no means so easy as might be supposed from the distinctive
characters of this body ; if, however, it has been once separated in
a crystalline form, nothing is easier than to diagnose its presence
with certainty. If, by its insolubility in water, acids, and
alkalies, and by its solubility in alcohol and ether, it has been
recognised as a fatty substance, it may be readily distinguished
from all other similar substances by a measurement of the angles
of the rhomb. It is only necessary to remark that the tablets
are often so thin that their contour may be easily overlooked in a
microscopic examination, if other morphological substances are
simultaneously present in the field of the microscope : we must
then slightly shade the field by a lateral or central diaphragm to
make the outline stand forth more distinctly. In all this there is
no difficulty ; but it is, on the other hand, often very troublesome
to obtain this substance in a crystalline form from oily fluids
containing bile, or from soapy solutions. If we saponify with an
alkali the fat which holds the cholesterin in solution, it also
dissolves in the soap-water, and on the addition of an acid is
again converted into the fatty acid; hence, when dealing with
very small quantities of cholesterin, it is necessary to combine
the fatty acid with oxide of lead, and to extract with boiling
alcohol; the small quantity of dissolved margarate of lead is
usually deposited previously to the separation of the cholesterin,
which frequently does not crystallise, so as to be recognised by
the microscope, until the fluid has been submitted to evaporation.
278 LIPOIDS.
Physiological Relations.
Occurrence. — Small quantities occur in most of the animal
fluids. It was originally discovered by Gren in biliary calculi,
and has since been recognised as a constant ingredient of the
bile. In the normal condition cholesterin is dissolved in the bile,
and hence cannot be recognised under the microscope : even in
the bile removed from the dead body we rarely find tablets of
cholesterin (Gorup-Besanez*) and in these cases we cannot tell
whether it depends on an augmentation of the cholesterin or
on its separation in consequence of the decomposition of tauro-
cholic acid. Frerichsf found no cholesterin in several examina-
tions which he made of the bile in cases of fatty liver.
Cholesterin was first distinctly recognised as a normal con-
stituent of the blood by Lecanu, Denis, Boudet, and Marchand ;
while Becquerel and RodierJ have especially directed attention to
its augmentation and diminution in diseased conditions of the
blood. According to these authors the amount of cholesterin
in 1000 parts of normal blood ranges from 0*025 to 0*200 (the
mean being O'OSS). There is an augmentation of the cholesterin
in the blood in old age, and in most acute diseases soon after
the occurrence of febrile symptoms, especially in inflammations
and in icterus. They have not discovered any physiological or
pathological condition in which there is a constant diminution of
this substance.
Cholesterin always occurs in the brain, where it was first
discovered by Couerbe. Many subsequent observers have con-
firmed his observations.
It also appears to be an integral constituent of pus ; at least
whenever I have allowed pus to become sour I have found tablets
of cholesterin in the decomposed mass ; moreover, Caventou,
Giiterbock, Valentin, and many others have detected it in fresh pus.
Cholesterin is also very frequently found in dropsical exuda-
tions, especially in cysts ; I have recently, on two occasions, ana-
lysed the fluid of hydrocele discharged by incision ; both specimens
were semi-solid rather than fluid, and when stirred, formed beau-
tiful glistening bands. Their only morphological element was cho-
lesterin.
Obsolete (chalky) tubercle, old echinococcus-cysts, such as
* Untersuchungen iib. Galle. Erlangen, 1846. S. 58.
t Hannov. Ann. Bd. 5, H. I.
T Gaz. me'd. 1844, No. 47. '
SEROLIN. 279
are often found in the liver, and degenerated ovaries and testicles,
often contain a large amount of cholesterin.
I once found the choroid Plexus in the brain perfectly en-
crusted with cholesterin.
In encysted tumours, (especially in meliceris) as well as in car-
cinomatous and other tumours, we often meet with cholesterin.
In the solid excrements we may generally recognise traces of
cholesterin; and in the meconium this substance is present in
very considerable quantity.
In pulmonary expectoration I have only found cholesterin in
the cheesy concretions ejected in advanced phthisis, and when
vomicae are already present.
In the urine, as far as I know, no cholesterin has yet been
found.
[Moller states that he has twice discovered cholesterin in the
pellicle which forms on the urine during pregnancy, but I know
nothing of his character as an observer. See Casper's Wochenschr.
1845, N. 2, 3 ; or my translation of Simon's Animal Chemistry,
vol. 2, p. 333. G. E. D.]
Origin. — In regard to the origin of cholesterin, which is
never found in the vegetable kingdom but only in the animal body,
we cannot offer even a probable conjecture. Judging from the
mode of its occurrence, we must regard it as a product of decom-
position ; but from what substances and by what processes it is
formed, it is impossible even to guess. Notwithstanding the
similarity which many of its physical properties present to those of
the fats, we can hardly suppose that it takes its origin from them,
since the fats, for the most part, become oxidised in the animal
body, whereas in order to form cholesterin, they must undergo
a process of de-oxidation.
SEROLIN.
This body, which as yet has been very little studied, was dis-
covered by Boudet,* in the solid residue of the serum of the blood.
At an ordinary temperature it appears in nacreous, glistening
flocculi, which are very slightly soluble in cold, but dissolve pretty
freely in hot alcohol, and in ether, and do not form an emulsion
with water. This body has no reaction on vegetable colours, melts
at +36°, and apparently may be distilled with only partial change.
* Ann. de Chim. et de Phys. T. 52, p. 337.
280 NON-NITROGENOUS NEUTRAL BODIES.
The ammoniacal vapours and the very peculiar smell which it
developes during distillation indicate that it contains nitrogen. It
is not saponified by the alkalies.
Serolin is obtained by extracting, with hot alcohol, blood which
has been dried, then boiled with water, and again dried. As the
alcohol cools the serolin separates in flocculi.
CASTORIN.
This body occurs in castoreum ; it crystallises from boiling
alcoholic solutions in small, four-sided needles, is pulverisable when
dried, melts at a temperature exceeding 100°, is not saponifiable,
and is converted by concentrated nitric acid into nitrogenous,
crystallisable, castoric-acid.
AMBREIN.
Ambrein is the principal constituent of amber ; it crystallises
in white needles grouped in stars or wart-like shapes, melts at 37°5
cannot be saponified, and is converted by nitric acid into ambreic
/, C21H18N5O3, which is crystallisable, and forms yellow salts.
NON-NITROGENOUS NEUTRAL BODIES.
Most of the substances belonging to this class closely resemble
one another in their empirical composition, and hence some of them
have received the name of " carbo-hydrates " ; for most of them
contain hydrogen and oxygen in the same ratio as these elements
are contained in water, so that if we suppose that they were com-
bined into water, carbon would be the only remaining element of
these bodies ; indeed, even the number of atoms of carbon in them
appears to be in accordance with a general rule, since in all the
formulae which as yet have been well established it is divisible
by 6.
Considering their extremely analogous composition, it is naturally
to be expected that these bodies should present many chemical
properties in common with one another, various as their physical
GLUCOSE. 281
characters may be. They are so indifferent that it is only with few
other bodies, and in these cases with considerable difficulty, that they
can be made to combine, and then they enter into combination in
multiple proportions, so that it is always difficult to determine their
atomic weights with any degree of certainty. Almost the only
physical properties which they have in common are deficiency in
colour and smell. They are all decomposed by heat, and yield
acid products of distillation. By digestion with dilute mineral
acids, they are for the most part converted into glucose or grape-
sugar. When decomposed by nitric acid, they yield oxalic acid,
saccharic acid and mucic acid, and, perhaps, also, conjugated nitric
acids. When treated with concentrated sulphuric acid these bodies
become brown or black, and in addition to humin-like substances,
form conjugated sulphuric acids.
The only substances of this group of any zoo-chemical importance
are glucose or grape-sugar, milk-sugar, [inosite* or muscle-sugar]
and cellulose.
GLUCOSE. — C12H12O12.
Chemical Relations.
Properties. — Glucose, which is the name applied to grape-sugar
by the French chemists, is identical with diabetic sugar* and crys-
tallises with 2 atoms of water in wart-like masses consisting of
minute plates arranged in a cauliflower form ; these plates are rhombic
and not square (as Saussure believed) ; when this substance separates
rapidly from a solution, we may observe under the microscope that
it occurs in irregularly striated, roundish masses, and not in
plates ; it is white, devoid of odour, and not so sweet as cane-
sugar but sweeter than milk-sugar ; it is only half as soluble in
water as cane-sugar, but more soluble than milk-sugar ; it is only
slightly soluble in alcohol, and insoluble in ether; its aqueous
solution turns the plane of polarisation of a ray of light to the
right, and is devoid of action on vegetable colours.
At a few degrees below 100° it begins to cake together, but it
melts perfectly at 100° with the loss of its 2 atoms of water ; at 140° it
becomes converted into caramel, and developes a sweetish odour;
at a higher temperature it becomes frothy, grows brown, developes
a pungent vapour, and leaves a voluminous charcoal.
In contact with nitrogenous bodies, and especially with casein,
* [Inosite or muscle-sugar has been discovered by Scherer since the original
Publication of this volume. Its formula is C12H16016. It will be noticed in a future
^art of this work. G. E. D.]
282 NON-NITROGENOUS NEUTRAL BODIES.
it undergoes the lactic, and subsequently the butyric fermen-
tation ; with common yeast it passes into the state of vinous
fermentation. Digested with concentrated nitric acid, it developes
nitric oxide gas, and is converted into oxalic and saccharic acids ;
while chlorine gas converts it into hydrochloric and saccharic acids.
When digested with dilute sulphuric acid, its solution does not so
rapidly become brown as that of cane-sugar, and it is only on eva-
poration that we observe the formation of a blackish brown residue;
but its solution, when boiled with potash, very quickly assumes a
fine brownish-red tint, and at the same time evolves a pungent,
sweetish odour ; it may be evaporated with lime-water without the
development of any brown colour, the lime arid the sugar forming
a syrupy compound with a bitter taste. On treating an aqueous
solution of glucose with caustic potash, and then adding a salt
of oxide of copper, no precipitate is formed, but the solution
assumes a beautiful azure tint : after some time, this gradually
changes to a green colour, and finally a red powder is deposited ;
if the fluid be boiled, it at once assumes a yellow tint, and sub-
oxide of copper is separated as a yellow or yellowish red powder.
Glucose is distinguished by its property of forming a beautiful
crystalline compound with chloride of sodium.
Composition. — According to the above formula, glucose consists
of:
Carbon 12 atoms .... 40'000
Hydrogen .... 12 „ .... C'666
Oxygen 12 „ .... 53-334
100-000
Its atomic weightz=2250. (Peligot,* Erdmann and Lehmann.f)
Combinations. — The compound of glucose and potash, 2KO +
CI2H12O12, is obtained by adding an alcoholic solution of caustic
potash to an alcoholic solution of glucose ; it occurs in the form of
white floccuii which, on exposure to the air, soon become tenacious
and moist, and at length perfectly deliquescent ; when dissolved in
water they exhibit an alkaline reaction, and attract carbonic acid
from the atmosphere.
The compound of glucose and lime, 2CaO -j-C12H12O12, is formed
when a solution of glucose is mixed with an excess of lime, and
the filtered fluid treated with alcohol ; it forms a white mass, which
on exposure to the atmosphere attracts water and becomes transpa-
rent. .
It is not easy to obtain a combination of glucose with oxide of
* Ann. do Ch. et de Phys. T. 60, p. 110, and Compt. rend. T. 6, p. 232.
t Journ. f. pr. Ch. Bd. 13, S. 113.
GLUCOSE, 283
lead in definite proportions : its aqueous solution takes up a large
quantity of this oxide ; an insoluble compound is obtained from
glucose and a solution of acetate of lead treated with ammonia.
The combination of glucose with chloride of sodium, C12H12O12
+ 2HO + C12H12O12.NaCl, may be obtained by the direct mixture
of the solutions of the two constituents and by spontaneous eva-
poration, in very large, colourless, four-sided, double pyramids.
These crystals are hard, easily^, pulverisable, of 1*5441 specific
gravity, transparent, unaffected by the atmosphere, of a saline
and sweetish taste, soluble in 3*685 parts of cold water, and
difficult of solution in alcohol. At 100° the powdered crystals
begin to cake together, and lose 4f of water ; when rapidly heated
to 120° they melt in their water of crystallisation, and begin to
become brown at + 160°. The crystals contain 13'3^ of chloride of
sodium.
Preparation. — This sugar is not only, as is well known, widely
diffused throughout the vegetable kingdon, but may be formed
from other kinds of sugar and from carbo-hydrates (starch, wood-
fibre, &c.) by digestion with dilute acids; hence it may be pre-
pared in many different ways. On the large scale it is commonly
obtained from starch ; but all that concerns us here is its mode of
preparation from diabetic urine. The following is the ordinary
mode of proceeding. Diabetic urine is treated with basic acetate of
lead, and the excess of lead removed from the filtered fluid by
sulphuretted hydrogen ; the fluid is then evaporated, and extracted
with alcohol, from which the sugar crystallises ; but sugar thus
obtained always contains acetates. In order to obtain the sugar I
am in the habit of evaporating the urine to nearly the thickness of
a syrup ; provided it has not been too powerfully evaporated, the
whole residue, after a variable time, becomes converted into a solid
yellowish white mass, which must be extracted with absolute
alcohol and subsequently with hot spirit. The sugar dissolved in
the latter is removed, after it has crystallised, by filtration, while
the spirit is submitted to evaporation, and then treated with a little
water in order to facilitate further crystallisation. In this way we
obtain the sugar in a state of greater purity than by the ordinary
method.
In order to obtain diabetic sugar in a state of chemical purity, I
prepared the chloride of sodium compound by saturating the
aqueous solution of the alcoholic extract with chloride of sodium,
and by repeated crystallisation obtained it in perfectly transparent
crystals, which I dissolved in water, and cautiously precipitated with
284 NON-NITROGENOUS NEUTRAL BODIES.
sulphate of silver ; the fluid freed by filtration from the chloride of
silver was evaporated., and the sugar was obtained in a state of
chemical purity by extraction with alcohol ; in order to remove
any traces of this fluid, it must be recrystallised from distilled
water.
Tests. — The methods of testing for sugar are not merely of
importance in enabling the physician to establish his diagnosis in
cases of diabetes mellitus, but likewise in consequence of the
physiological relations of sugar to the general metamorphosis of
tissue. Many chemists (amongst whom may be enumerated
Golding Bird*, Gairdnerf, BudgeJ, and myself,§) have turned
their attention to the most accurate methods of discovering sugar.
There has been much discussion regarding Trommer's|| admirable
test for sugar; but if this test be not admitted, equal objections
may be advanced against all the reagents employed in mineral che-
mistry ; for these also require to be used with proper care and circum-
spection ; the application of most of them demanding more precaution
and skilful manipulation than this test. It may be regarded as infal-
lible for the recognition of the presence of sugar in diabetic urine ;
although a person utterly ignorant of chemical reagents may also
here fall into error. In true Diabetes mellitus, the urine is free
from those substances which may interfere with the reaction on
which this test is founded, or rather with the judgment we form
regarding this reaction; diabetic urine presents this difference from
other saccharine urine, that the former with sulphate of copper
and potash gives the reaction almost as readily as a pure solution of
grape-sugar would do, even when there is but little sugar present,
whilst the more normal urine in which sugar is a mere incidental
constituent, gives a less distinct reaction ; and the latter moreover
precipitates other substances with the suboxide of copper, by
which the colour of the precipitate is considerably modified.
The question here arises — what precautionary measures ought
to be observed in the application of Trommer's test ?
The fluid to be examined is treated with caustic potash, and.
filtered if necessary, that is to say, if there be too great a precipi-
tate ; an excess of caustic potash is productive of no harm, as it
* Monthly Journal of Medical Science, vol. 4,,p. 423, [and " Urinary Deposits,*'
3rd Ed. p. 352. — G. E. D.]
t Ibid. p. 564.
$ Arch. f. physiolog. Heilk. Bd. 3, S. 385.
§ Schmidt's Jahrb. Bd. 45, S. 6-10.
|| Ann. d. Ch. u. Pharm. Bd. 39, S. 360.
GLUCOSE. 285
should be present in more than sufficient quantity to decompose
the sulphate of copper ; the latter, which must be added gradually,
and in a diluted state, usually gives rise to a precipitate, which dis-
appears when the fluid is stirred ; as the quantity of the oxide of
copper which is soluble is proportional to the quantity of sugar which
is present, very little sulphate of copper must be added at a time,
if we suspect that only a little sugar is present in the fluid. On
allowing the azure solution thus obtained to stand for some
time, there is usually formed a more pure red or yellow powder
than the precipitate which is at once thrown down on boiling the
fluid. Moreover, very prolonged heating is improper, for there are
several substances which by prolonged boiling separate suboxide of
copper from alkaline solutions of oxide of copper ; amongst them we
may especially name the albuminous substances, which with oxide
of copper and potash yield very beautiful azure-blue, or somewhat
violet solutions, and by very prolonged boiling, separate a little
suboxide of copper, although without the aid of heat they have
not this property.
If a specimen of urine contain very little sugar, or if we are
searching for sugar in some other fluid, it is advisable to extract the
solid residue with alcohol, to dissolve the alcoholic extract in water,
and to apply the potash and sulphate of copper to this solution.
By preceding in this manner we usually obtain the reaction in its
most distinct manner. If, however, we are seeking for very small
quantities of sugar, as for instance in chyle, blood, or in the egg, we
must neutralise the aqueous fluid, previously to its evaporation,
with dilute acetic acid, in consequence of the solubility of albu-
minate of soda or of casein in alcohol, thus preventing any albu-
minous body from remaining in solution. If the reaction do not
properly manifest itself in the alcoholic extract thus obtained, or if
wre would carry the investigation further, we must precipitate the
sugar from the alcoholic solution by an alcoholic solution of potash,
dissolve the compound of sugar and potash in water, and now apply
the sulphate of copper ; if only a trace of sugar be present, we ob-
tain a most distinct and beautiful reaction.
The fermentation-test has been much extolled as a means of
discovering sugar; but independently of the circumstance that the
process is very tedious, it yields, to an inexperienced experiment-
alist and observer, far less certain results than Trommer's test.
On adding yeast to a fluid, the phenomena of fermentation are
simply dependent on the development of bubbles of carbonic acid;
if this development of gas from a fluid, as, for instance, from dia-
286 NON-NITROGENOUS NEUTRAL BODIES.
betic urine, be not very active after the addition of yeast, we must
not draw any conclusions regarding the presence of sugar, for yeast
promotes the decomposition of the animal fluids — a process which
is often accompanied with the development of a little gas. If,
however, no yeast be added to the urine, but we wait for spon-
taneous fermentation, as has also been recommended, the de-
velopment of carbonic acid proceeds very slowly, unless an ex-
tremely large quantity of sugar be present; moreover, in this
case, there is this additional difficulty in observing the
formation of the gas, that the sugar for the most part undergoes
the lactic and not the vinous fermentation. As the detection
of the alcohol, which is formed during this process, is by no
means easy, attention has been drawn to the formation of the
yeast-fungus (Torula cerevisice) as a characteristic indication of
vinous fermentation. For those who are accustomed to the use of
the microscope, and are well acquainted with the appearance of
the Torula^ this is unquestionably an easy and certain test ; but it
must be borne in mind, that when normal urine has been allowed
to stand for a long time, especially at a high temperature, fungi
of a precisely similar shape are formed in it, probably, for the most
part, from the mucus. These fungi, which are by no means
dependent on the decomposition of sugar, may exist in urine still
preserving a decidedly acid reaction, although they more frequently
occur in neutral urine ; the individual cells, which, like the yeast-
cells, (Torula cerevisice,) contain distinct nuclei, are mostly about
one-half (in diameter) smaller than the true yeast-cells ; but inde-
pendently of the circumstance that under the microscope apparent
magnitudes afford a very relative criterion, the yeast-cells which
are first and spontaneously formed, are always much smaller than
those which are subsequently produced by gemmation from pre-
viously formed yeast-fungi.
A very good means of discovering sugar, and of determining-
its quantity with considerable accuracy in a clear solution, isaffordea
by Biot and Soleil's polarising apparatus; its expense will, how-
ever, always stand in the way of its general application.
We have already shown (p. 124) that Pettenkofer's test is not
available for the detection of sugar.
All other tests which were formerly employed for the discovery
of sugar (evaporation with hydrochloric or sulphuric acid, treat-
ment with chromic acid, boiling with caustic potash, &c.) are open
to so many sources of fallacy, as compared with the methods we
have already indicated, that we may pass them over in silence.
GLUCOSE. 28-f
Trommer's test may also be successfully employed in the quan-
titative determination of the sugar in diabetic urine ; Barreswil,*
Falck,t and Scharlau,t have recommended different methods of
applying it with this view ; the most generally applicable one,
however, is that of Fehling.§ As a test he uses a solution of
40 grammes of crystallised sulphate of copper in 160 grammes of
water ; this is mixed with a concentrated solution of 160 grammes of
tartrate of potash and 560 grammes of a solution of caustic-soda
(specific gravity =1*1 2), and water is then added till the volume of
th e fluid at + 15° amounts to 1 litre. ll'5c.c. of a saccharine solution
containing 5 grammes of dry sugar(=i C12H12O12) in a litre, are neces-
sary to cause the perfect reduction of the oxide to the suboxide of
copper in lOc.c. of the test-fluid. Hence it follows that 100 parts
of oxide of copper are completely reduced to the state of suboxide
by 45*25 parts of sugar, or 10 atoms of oxide of copper by 1 atom
of sugar. In order to determine with the greatest certainty the
weight of the sugar from the volumetric measurement, and to render
the errors of observation as small as possible, Fehling recommends
that the urine to be examined for sugar should be diluted with
water to 10 or 20 times its volume, that is to say, that 50 grammes
of urine should be treated with 450 or 950 of water : 10 c.c. of
the test-fluid are then to be diluted with about 40 c.c. of water,
boiled, and so much of the diluted urine (which must be kept in a
burette or graduated tube in order that we may be able to estimate
the quantity used) added to it, as to effect as nearly as possible the
complete decomposition of the sugar and of the oxide of copper.
If any uridecomposed oxide of copper be contained in the fluid
after the removal of the suboxide by filtration, it may be recog-
nised by the blue tint, and by its reaction with sulphuretted
hydrogen : if, on the other hand, too much urine be added, the
filtered fluid appears yellow from the action of the caustic alkali on
the sugar. The point of thorough mutual decomposition is easily
attained by a few repetitions of the experiment. As 10 c.c. of the
test-fluid require 0'0577 of a gramme of sugar for the reduction of
the oxide of copper contained in them, there must be exactly that
amount of sugar in the quantity of urine used in the experiment,
and hence the proportion of sugar in any given quantity of urine
may be easily calculated.
Those who are not in the habit of using French weights an:l
* Journ. de Pliarm. T. 6, p. 301.
f Oesterlen's Jahrb. f. pr. Heilk. Bd. 1, S. 501).
£ Die Zuckerharnruhr. Berlin, 1846.
§ Arch. f. phys. Heilk. Bd. 7, S. (J4-73.
288 NON-NITROGENOUS NEUTRAL BODIES.
measures may prepare Fehling's test solution as follows : — Dissolve
69 grains of crystallised sulphate of copper in five times their weight
of distilled water, and add to it, first, a concentrated solution of
268 grains of tartrate of potash, and then a solution of 80 grains of
hydrate of soda in one ounce of distilled water. Put the solution
into an alkalimeter tube, and add distilled water so as to make
1000 grain-measures of the liquor. This solution will be nearly
double the strength of that made according to the above directions,
and every 100 grain-measures of it will be equivalent to 1 grain
of grape sugar. [G. E. D.]
By SoleiFs polarising apparatus the quantity of sugar may be
determined with more rapidity than by the preceding method,
and with equal accuracy. Many precautions are, however, requi-
site in its application, as has been especially shown by Dubrunfaut,*
Clerget,t and Lespiau.J We refer, therefore, to their communi-
cations on this subject ; especially as SoleiPs apparatus, in so far
as its application to saccharine urine is concerned, is still deficient
in many respects.
Fermentation was formerly employed to determine the quan-
tity of sugar in fluids, the carbonic acid being determined, and the
quantity of sugar calculated from it. This mode of determination
is deficient in accuracy, in the first place, because all animal
fluids, and especially the urine, contain free carbonic acid, and,
secondly, because other constituents of the urine are simultaneously
decomposed during the process of fermentation, and also yield
carbonic acid. This method serves, however, very well for approxi-
mate and comparative determinations, if we allow a weighed
quantity of diabetic urine to ferment at 37° in Fresenius'sf alka-
limetrical apparatus, and, as in alkalimetrical processes, determine
the carbonic acid by the loss of weight.
This is the best means of determining the amount of sugar for
ordinary medical purposes, Fehling's method being applicable
rather to technology than to clinical medicine. If the apparatus
be allowed to stand for about 48 hours at the above-mentioned
temperature, all the sugar will have been converted into spirit ; if
we even omit to remove the carbonic acid by drawing a little air
through the apparatus, previously to weighing, we shall still obtain
results at all events sufficiently accurate for purposes of
comparison.
* Ann. d. Chim. et de Phys. 3 Ser. T. 18, p. 101.
t Compt. rend. T. 22, p. 200, and pp. 256-260.
t Ibid. T. 26, p. 306.
§ Neue Verfahrungsweisen zur Prufung der Soda, &c. Heidelb. 1843.
GLUCOSE. 289
Physiological Relations.
Occurrence. — In a normal condition of the system this form of
sugar may always be recognised in the primce vice, especially in the
contents of the small intestine after the use of vegetable, that is to
say, of amylaceous and saccharine food. We shall subsequently see,
when treating of digestion, that it is principally through the influence
of the pancreatic juice that starch is gradually converted, in the in-
testinal canal, into sugar. It is only in small quantity that it exists
in the contents of the small intestine, partly because the change
effected in the starch proceeds very gradually, and partly because
the sugar which is formed is very rapidly absorbed.
Trommer* was the first who detected traces of sugar in the
chyle; I have several times most distinctly recognised the pre-
sence of sugar in the chyle of horses which., a few hours before they
were killed, had taken either pure starch or strongly amylaceous
food.
Sugar cannot generally be recognised in the blood; Magendief
however, asserts that he found considerable quantities of sugar,
together with dextrin, in the blood of a dog, which for several days
had been fed solely on boiled potatoes.
In a normal state it is probable that no sugar finds its way into
the urine ; at least after living for two days solely on fat and sugar,
I was as unsuccessful in the search for sugar in my urine, as
Magendie had been in the case of the dog in whose blood he found
sugar.
It is only seldom that we meet with saccharine urine in other
diseases than diabetes. Prout has sometimes found sugar in the
urine of a gouty and dyspeptic persons," and BudgeJ in " abdo-
minal affections and hypochondriasis,." I§ once met with sugar
in the urine of a puerperal woman, in whom, on the fifth day after
delivery, the secretion of milk was suddenly suspended. I was
led to the discovery that it contained sugar by observing the forma-
tion of yeast-cells in it ; the sugar only continued in the urine of
this woman for four days.
Although I have myself || once found sugar in the saliva, in a
case of acute rheumatism, in which spontaneous salivation ensued,
* Ann. d. Ch. u. Pharm. Bd. 39, S. 360.
t Compt. rend. T. 30, p. 191-192.
S Arch. f. physiol. Heilk. Bd. 3, S. 413.
§ Jaliresb. d. physiol. Ch. 1544, S. 2?.
I) Ibid. S. 20.
U
290 NON-NITROGENOUS NEUTRAL BODIES.
and this secretion was discharged in great abundance, I cannot
venture to conclude from this isolated instance that sugar ever
exists in the saliva of non-diabetic persons, since in this case it is
possible that the sugar might in some way have accidentally got into
the vessel containing the saliva. So many heterogeneous substances
find their way into the saliva, as we shall subsequently see, that there
is nothing extravagant in the assumption that sugar may some-
times occur in morbid saliva. Wright places a sweet saliva
amongst his numerous varieties ; unfortunately, however, he did
not proceed to ascertain whether the sweetness of this saliva was
dependent on the presence of sugar, or whether it was a mere
subjective sensation of the patient.
F. L. Winkler* found 8 grains of sugar in two softly-boiled
eggs, which had been sat upon for some time, and whose white
had a singularly sweet taste. I have recently convinced myself
that small quantities of sugar are constantly present both in the
yolk and in the white of fresh eggs.
I may remark that I experimented upon 30 eggs, in order to
obtain evidence of the existence of small quantities of sugar. I have
repeatedly, and with much care, repeated Winkler's experiment,
in which he found so large a quantity of sugar (milk-sugar) in
incubated eggs, but I cannot confirm his statement. I examined
eggs that had been sat upon for 3, 7? and 15 days.
Bernard and Barreswilf have found sugar in the tissue of the
liver even of animals that do not subsist on saccharine or amyla-
ceous food.
[Experiments conducted in the G lessen laboratory have con-
firmed this statement, both in reference to the livers of graminivorous
and carnivorous animals. See Liebig and Kopp's Annual Report,
£c., for 1847-8, Vol. 2, p. 175, note 6.— G. E. D.]
At present I can only confirm this statement with reference to
the liver of the frog; the extract obtained by cold alcohol from
from frogs' livers was treated with double its volume of ether, in
order to remove a portion of the biliary matters; the fluid decanted
from the separated taurocholate of soda was treated with an alco-
holic solution of potash. The great turbidity which was first
induced was shortly replaced by a considerable precipitate of a re-
sinous appearance, (the glucose and potash compound) which was
dissolved in water and treated with a little potash and sulphate of
copper, due attention being paid to the precautions we have already
* Buchn. Repert. Bd. 42, S. 46.
t Comp. rend. T. 27, p. 514.
GLUCOSE. 291
indicated ; after boiling, and especially after long standing, there was
a very considerable yellow sediment of suboxide of copper. From
the result of this experiment I believe that with from 15 to 20 frogs'
livers the presence of sugar in this tissue may be distinctly demon-
strated. Moreover, I regard this substance as glucose, and not
milk-sugar, in consequence of its reducing the oxide of copper far
more slowly than is usually the case with milk-sugar.
Sugar has been sought for in all the fluids in cases of Diabetes,
and has been so generally found that it is unnecessary to quote
authorities on the subject. It has been found not merely in the
urine, blood, and all serous fluids, but also in the saliva, in vomited
matters, in the solid excrements, and even in the sweat.
In a person suffering from well-developed diabetes, and who
at the same time perspired very freely, (a combination not often
observed,) it was only in the sweat that I failed to detect sugar.
Origin. — The origin of the small quantities of glucose which
normally occur in the animal fluids, is so obvious, as hardly to
require notice. I will here only remark that little or nothing
in the wray of conclusion can be deduced in reference to the meta-
morphosis of starch or dextrin within the animal organism from
experimental attempts to convert starch into sugar by means of
saliva, the serum of the blood, renal tissue, &c. ; for any other
nitrogenous substance acts just as efficiently, if it be digested for a
sufficiently long time with water and starch-paste, in converting a
portion of the latter into sugar. The actual substance which, in all
probability, effects the conversion of starch into sugar, is, as we have
already mentioned, the pancreatic juice. Magendie's experiment,*
in which starch was converted into sugar in the circulating blood
of a living animal, proves little in relation to the physiological
process, since starch does not normally pass into the blood. We
shall enter more fully in the consideration of the digestion of starch
and of the experiments bearing on this point which have been
instituted by Bouchardat and Sandras, Jacubowitsch, Strahl, and
others, in a future part of the work.
But whence originates the enormous quantity of sugar which,
in diabetes, is often discharged with the urine ? While no one can
doubt that it is for the most part, at all events, derived from vege-
table food, it is still a contested question whether the nitrogenous
constituents of the animal body may not also contribute to the
formation of this substance. Many have assumed it as beyond all
* Compt. rend. T. 30, pp. 189-192.
U 2
292 NON-NITROGENOUS NEUTRAL BODIES.
question (Budge,*) that in diabetes sugar is formed from protein, but,
on examining the grounds on which such a view is based, we find
that the facts adduced in support of them are of a very doubtful
character. In the first place it has been alleged that diabetic
patients, living on a highly nitrogenous diet, discharge far more
sugar than could be formed from the sugar-yielding, non-nitro-
genous substances, which have constituted a portion of their
food; but unfortunately no accurate observations on this point,
based on numerical results, have been brought forward; for,
although Pfeuffer and Lowigf have instituted one experiment of
the kind, it led to no result. Moreover, we are still so ignorant
regarding the internal constitution of albuminous and gelatinous
substances, that we can adduce no chemical grounds in support of
such an assumption. Berzelius,J founding his hypothesis on the
fact that protein, like sugar, when treated with hydrochloric acid,
yields formic and humic acids, and, with nitric acid, yields oxalic
and saccharic acids (which, however, has not been decisively
proved), indicates the possibility that protein (like amygdalin,
salicin, &c.) may contain sugar, and that a portion of the diabetic
sugar may therefore proceed from the albuminous substances.
The supposition is, also, by no means at variance with the admi-
rable investigations of Guckelberger on the products of decompo-
sition of nitrogenous animal tissues by sulphuric acid and chro-
mate of potash ; since by this means of oxidation, aldehyde§ is
developed from these nitrogenous matters, just as it is produced
from milk-sugar when similarly treated. These facts, however,
simply indicate the possibility that sugar may be formed from the
protein-compounds; they do not prove that it is so formed;
Liebig|| merely regards it as " conceivable" that in the metamor-
phosis of tissue, sugar may be produced from gelatinous
substances.
Notwithstanding the numerous hypotheses that have been
advanced by physicians regarding the reason why, in diabetes, the
sugar does not undergo the ordinary change in the organism, we
are still utterly ignorant on this point. As we shall return to this
subject in the second volume, in our observations on " the urine/5
* Arch. f. physiol. Heilk. Bd. 3, S. 391.
t Zeitsch. f. rat. Med. Bd. 1, S. 451.
I Jahresber. Bd. 19, S. 655.
§ Ann. d. Ch. u. Pharm. Bd. 64, S. 99.
jj Geiger's Pharm. Bd. 1, S. 796.
GLUCOSE. 293
it will suffice if we here mention the following facts, which may
subsequently influence our judgment in reference to this matter.
I* injected two drachms of cane-sugar dissolved in water into
the veins of a dog ; the dog, who had lost very little blood during
the operation, drank a great deal, and discharged a large quantity
of sweet-tasting urine, which contained unchanged cane-sugar;
and Kerstingf arrived at a similar result with other kinds of
sugar. BernardJ injected a solution of cane-sugar into the veins of a
dog and a rabbit; the urine of the animals remained acid, and con-
tained unchanged cane-sugar; but, on repeating the experiment on
another dog and rabbit with a solution of glucose, he failed to
detect this substance in the urine, which had now become alkaline.
[The admirable experiments and observations of Dr. Percy on
this subject are apparently unknown to Professor Lehmarm. See
the "Medical Gazette," Vol. 32, pp. 19, 591, and 640.— G.E.D,]
If we were to attempt to draw any conclusion from these few
experiments, it would be that in diabetes the glucose formed
from the vegetable substances in the intestine is not, as in the
normal state, metamorphosed in the blood. We have been in the
habit of referring the alkaline reaction of the urine in graminivo-
rous animals to the decomposition of the salts formed by organic
acids and the alkalies into carbonates, but from Bernard's experi-
ment it would appear as if the alkalescence were dependent on
other relations connected with the nature of the vegetable food :
at all events I found that, when for two entire days I took nothing
but sugar, fat, and starch, and consequently food devoid of nitrogen
and free from alkalies, my urine had an extremely weak acid
reaction.
More accurate investigations, or a more detailed account of his
mode of procedure are requisite, before we can form an opinion
regarding certain experiments performed by Bernard,§ or can
attempt to explain them on physiological grounds. He maintains
that he has found sugar in the urine and the blood after irritating
one definite spot in the base of the fourth ventricle of the brain.
This experiment, if it should receive further confirmation, will
apparently strengthen Scharlau's hypothesis that diabetes is essen-
tially a disease of the spinal cord, unless Bernard associates it with
* Jahresber. d. phys. Ch. 1844. S. 47.
t Diss. inaug. med. Lips. 1844.
£ Compt. rend. T. 22, pp. 534-537.
§ Ibid. T. 28, p. 393, and Arch. g6n. de Me'd. 4 Se'r. T. 18.
294 NON-NITROGENOUS NEUTRAL BODIES.
the function of the pneumogastric nerves ; for when they have
been divided he has also found sugar.
Uses. — Since glucose, which, as we have already seen, is
principally formed in the intestinal canal from the starch of the
vegetable food, appears, from the results of all physiological enqui-
ries, to be a true element of nutrition, (see "Nutrition,") the
question that remains to be considered is — how it is applied, or
what is its use in the animal organism ? It belongs, according to
Liebig, to the food for the respiration ; and if we regard it purely
in this light, its object is easily understood ; it undergoes a process
of combustion by combining with the inspired oxygen, its final
products being water and carbonic acid, and tends to support the
animal heat, if we regard this as an independent process. If,
however, we entirely concur in this view, we have still to enquire
whether the sugar does not previously undergo other changes and
serve other objects, before it yields carbonic acid and water as the
final products of its combustion.
It must excite our surprise that in diabetes, where, in refer-
ence to the respiration, the saccharine and amylaceous elements of
food appear to be entirely lost, the respiration and the animal heat
are so well supported ; for although pulmonary tuberculosis is a
frequent complication of diabetes, this is by no means invariably
the case; and it may occur without any affection of the lungs. It
certainly seems very remarkable that such a mass of the respira-
tory food can be lost without inducing any symptom of a dis-
turbed respiration or of a diminished animal heat.
We have already referred (p. 257) to the hypothesis of the
conversion of sugar in the intestinal canal into/iz/, and shown that
it is unsupported by facts ; but we do not deny that in some part
of the animal body (at least under certain relations) sugar may be
metamorphosed into fat. Moreover, we are still so ignorant
regarding the different changes which the sugar undergoes in the
blood, that, to a certain degree, we must content ourselves with
the consideration of questions that may lead us on the true path
of inquiry. We have already pointed out the probability that
the lactic acid occurring in the animal body is formed from sugar
(p. 101) ; under special relations butyric acid may also be produced
from it (p. 59). The alkalescence of the urine observed by Ber-
nard after the injection of glucose would almost seem to indi-
cate that the sugar in the blood is converted into an acid, which,
combining with the alkali of the blood, yields carbonated alkali as
MILK-SUGAK. 295
a product of combustion, which passes into the urine and renders
it alkaline. This experiment undoubtedly shows that the principal
metamorphosis of the sugar occurs primarily in the blood, and not
in the intestinal canal.
That the sugar undergoes vinous fermentation in the intestinal
canal is a view that is now entirely rejected ; for the yeast-cor-
puscles which we sometimes find in the contents of the intestines,
and which might lead to the suspicion of such a fermentation, may
take their origin from the food, as, for instance, from bread.
Does the sugar take any part in the formation of bile ? We
have already attempted (see p. 126 and p. 270) to show the proba-
bility that the bile is in part formed from fat, and that cholic acid
should be regarded as conjugated oleic acid with the adjunct
C12H6O6. Can this adjunct take its origin from the sugar ?
Those who assume that sugar exists preformed in nitrogenous
animal substances, whether gelatinous or albuminous, (as for
instance it does in amygdakn,) need feel no difficulty in believing
that in the animal body protein is primarily formed from nitro-
genous matters and sugar. In the case of chitin, however, (to
which further reference will be made in a future page,) we appear
rather to have a combination of vegetable fibre with a nitrogenous
substance.
We can hardly entertain a doubt that in the female mammalia
the milk-sugar is derived from the glucose, but by what means this
change is accomplished is a point on which we are entirely ignorant.
MlLK-SuGAR. C10H8O8.
Chemical Relations.
Properties. — This substance forms white, opaque, overlying
prisms or rhombohedra containing 2 atoms of water, is hard,
craunches between the teeth, has a very faintly sweet, almost
floury taste, is devoid of smell, dissolves slowly in cold but more
readily in hot water, and is insoluble in absolute alcohol and ether ;
the aqueous solution which moreover turns the plane of polarisation of
a ray of light to the right, may be evaporated to a very considerable
extent without any separation of the sugar in a crystalline form.
When heated, milk-sugar melts, swells up, developes a sweetish
pungent odour, and burns with a flame.
Digested with dilute sulphuric or hydrochloric acid, or with
296 NON-NITROGENOUS NEUTRAL BODIES.
acetic or citric acid, it becomes converted into glucose ; it ab-
sorbs large quantities of chlorine, hydrochloric acid, and ammo-
niacal gases. Nitric acid converts it into mucic acid with a little
oxalic, saccharic, and carbonic acid; with sulphuric acid and bichro-
mate of potash it yields not only formic acid but aldehyde.
In contact with the caustic fixed alkalies it becomes converted
at 225° into oxalic acid ; boiled with dilute alkalies or oxide of lead
and water it becomes yellow or brown ; at 50° it yields several
compounds with oxide of lead. It reacts with sulphate of copper
and potash exactly in the same manner as glucose. It was for
a long time classed among the non- fermentable kinds of sugar, till
Schill* and Hessf almost simultaneously remarked that milk-sugar
only required a longer period in order to pass into a state of vinous
fermentation under the influence of yeast, sour dough, gelatin, or
albumen. H. RoseJ has confirmed SchilPs observations, that the
formation of dextrin must precede the vinous fermentation of the
milk-sugar, as indeed Payen had previously observed in reference to
the sugar of the dahlia, and Rose in reference to cane-sugar. Like
the other varieties of sugar, it can undergo lactic and butyric fer-
mentation when the necessary ferments are added to it.
Composition. — In its crystalline state milk-sugar has exactly the
same empirical formula as anhydrous glucose, so that it there-
fore contains equal equivalents of carbon, hydrogen, and oxygen.
But as, when warmed, it loses 11 '9$ of water, that is to say, 1 atom
of water to 5 atoms of carbon, its formula must either = C5H4O4 or
a multiple of it. As milk-sugar cannot be combined with any body
in a definite proportion, its true atomic weight is unknown. Its
relation to nitric acid, with which, as we have already mentioned,
it yields mucic acid, shows that its constitution must in some
respects be different from that of the other fermentable sugars.
Preparation. — Milk-sugar is obtained on the large scale by
evaporating whey, and allowing the concentrated fluid to stand for
a long time in a cool place. The crystalline incrustations which
are then formed are purified by recrystallisation. Simon recom-
mends that the milk should be evaporated to ^th of its volume, and
that the casein should be precipitated by alcohol ; the filtered fluid
must be then further evaporated and treated with strong alcohol ;
the milk-sugar, which is precipitated with the water-extract, is then
* Ann. d. Ch. u. Pharni. Bd. 31, S. 152.
t Pogg. Ann. Bd. 31, S. 194.
J Ibid. Bd. 52, S. 293.
MILK-SUGAR. 297
rinsed with a little water, dissolved in pure water, and left to
spontaneous evaporation.
According to Haidlen* the milk should be boiled with £th its
weight of pulverised gypsum, which coagulates the casein ; the
filtered fluid is then to be evaporated to dryness, and after the fat
has been removed by ether, the milk-sugar may be extracted from the
residue by boiling alcohol, which yields it in a state of perfect purity.
Tests. — If it be shown by Trommer's test that some kind of
sugar is contained in the alcoholic extract of an animal fluid, we
may readily distinguish milk-sugar from other kinds of sugar (if
we have a sufficient amount of material to examine,) by its difficult
solubility in alcohol, by the slowness with which it ferments in the
presence of yeast, and by its property of yielding the insoluble
mucic acid when boiled with nitric acid. It may be estimated
quantitatively with tolerable accuracy by Haidlen's method given
above ; but when extreme accuracy is required we must use Barres-
wil's or Fehling's test-fluid, in the manner described for grape-sugar
(see p. 287) 5 Poggiale has in this way determined the sugar in cow's
milk by a test-fluid (consisting of 10 parts of crystallised sulphate
of copper, 10 of bitartrate of potash, 30 of caustic potash, and 200
of distilled water), but his results were obviously in excess ; for
although he attempted to remove the casein previously with acetic
acid, a portion of this substance must have remained in solution
and cooperated with the sugar in decomposing the oxide of copper-
A better method of proceeding is to remove the casein by boiling the
milk with sulphate of magnesia or chloride of calcium, precipitating
any excess of the earth from the filtered fluid with potash, and then
applying Fehling's test-fluid ; while perhaps the best is to proceed
according to Haidlen's plan, and then to apply Fehling's method to
determine the quantity of milk-sugar in the alcoholic extract.
Physiological Relations.
Occurrence. — This substance appears to be an integral consti-
tuent of the milk of all mammalia. In woman's milk its amount
ranges from 3'2 to 6'24% (Fr. Simon,f Haidlen,J Clemm,§) ; in
cows' milk it is stated to average from 3 -4 to 4'3&; but by an im-
proved method of analysis I have always found rather a larger
amount of sugar in good cows' milk; but the average (= 5'28g)
* Ann. d. Ch. u. Pharm. Bd. 45, S. 275.
t Frauenmilch. S. 35.
$ Ann. d. Ch. u. Pharm. Bd. 45, S. 275.
§ Handworterbuch d. Phys. Bd. 2, S. 464.
2S8 NON-NITROGENOUS NEUTRAL BODIES.
assumed by Poggiale* is obviously too high ; in that of the ass it
constitutes 4*5^; in that of the mare, 8*7^ m tnat °f tne goat> 4.4&
and in that of the sheep, 4*2^; indeed, it was even found in the milk
of a he-goat. (Schlossberger.t) DumasJ thought that he had ascer-
tained that the milk of bitches restricted entirely to an animal diet
contained no milk-sugar, but it was subsequently ascertained by
Bensch§ that even then traces of milk-sugar were present ; its
quantity is however perceptibly increased under the use of a vege-
table diet.
In the colostrum Simon found 7^? and in the milk six days
after delivery only 6*24£ of milk-sugar ; his investigations show
that it diminishes according to the length of time after delivery at
which it is secreted, and that neither an abundant nor an insuffi-
cient diet influences its quantity, although differences in the food con-
siderably affect the amount of butter. The observations of Donne, ||
Meggenhofen,^[ and Simon** concur in showing that diseases,
especially syphilis, do not modify the amount of sugar in the milk.
Milk-sugar has been sought for in the blood by Mitscherlich,
and Tiedemann and Gmelin, but hitherto without success.
[Braconnotft believes that he has demonstrated that milk-sugar
exists in the cotyledons of the seeds of vegetables. — G. E. D.]
Origin. — The positive experiments of Dumas arid Bensch
which prove that the amount of milk-sugar increases during a
vegetable diet, give great probability to the opinion that this sub-
stance is principally formed from glucose or from the starch of
the food ; but notwithstanding the apparently affirmative observa-
tions of Bensch, the question whether it may not also be formed
from nitrogenous matters, must for the present remain undecided.
Where and by what means this conversion of glucose within the
organism occurs, are subjects of which we are entirely ignorant.
Uses. — No doubt can be entertained that the milk-sugar which
the infant at the breast receives in its food serves the same purposes
in the economy that starch and other carbo-hydrates serve in the
more matured organism.
* Compt. rend. T. 28, pp. 505-7.
t Ann. d Ch. u. Pharm. Bd. 51, S. 431.
J Compt. rend. T. 21, pp. 708-717.
§ Ann. d. Ch. u. Pharm. Bd. 61, S. 221-227.
II Du lait et en particulier de celui des noun-ices. Paris, 1830.
*|J Diss. inaug. sist. iiidagationem lactis muliebris. Fraiicof. a. M., 1816.
** Die Fraiicnmilch. Berlin, 1838.
ft Ann. de Chim. et de Phys. 4 Ser. T. 27, p. 399.
H^EMATIN. 299
A carbo-hydrate has been found in some of the lower classes of
animals whose composition and properties are very similar to those
of the vegetable principle, cellulose. C. Schmidt* discovered it in
the mantel of Phallusia mammillaris, one of the mollusca belonging
to the Tunicata ; and Lowig and Kollikerf have subsequently recog-
nised it in the cartilaginous capsule of the simple Ascidiee, in the
leathery mantle of the Cynthiae, and in the outer tube of the Salpee.
The relation which this substance bears to chitin as well as to the
animal organism generally, will be noticed in our remarks on chitin.
COLOURING MATTERS.
Unfortunately, even less is known of the chemical nature of
the animal than of the vegetable pigments, so that we must still
retain the irrational system of arranging them according to colour.
H^MATIN.— C44H22N3O6Fe.
Chemical Relations.
Properties. — This substance is regarded as the peculiar red
pigment of the blood-corpuscles ; but unfortunately it is by no
means certain whether it is a product of metamorphosis of the true
colouring matter of the blood, or whether the substance prepared
by us only bears the same sort of relation to that which exists in
the blood-corpuscles as coagulated albumen bears to that principle
in its fluid state. We cannot isolate it in its soluble state from
the globulin of the blood-corpuscles ; hence we are only acquainted
with it in its coagulated (and essentially modified) condition. In
a state of purity it occurs as a dark brown, slightly lustrous mass,
which, on trituration, adheres to the pestle ; it is devoid of taste and
smell, and is insoluble in water, alcohol, ether, acetate of oxide of
ethyl, and fatty and volatile oils : Mulder, however, regards it as
slightly soluble in fatty and ethereal oils.
Hsematin dissolves very readily in weak alcohol to which sul-
* Zu vergl. Physiol. der wirbellosen Thiere. 1845. S. 62 [or Taylor's Scientific
Memoirs, vol. 5, p. 34. — G. E. D.]
f Ann. de Scienc. Nat. 3 Se'r. T. 5, pp. 193-232.
300 COLOURING MATTERS.
phuric or hydrochloric acid has been added, forming a brown
solution, which, on saturation with an alkali, assumes a blood-red
colour. Water, acidulated with the same acids, exerts no solvent
power on hsematin, and consequently a precipitation is induced by
the addition of water to alcoholic solutions of this substance. Con-
centrated sulphuric and hydrochloric acids do not dissolve heematin,
but they abstract a little of the iron. After trituration with sul-
phate of soda, it dissolves for the most part in wrater. Even very
dilute solutions of the caustic alkalies or their carbonates in water
or alcohol dissolve hsematin in almost every proportion. A potash-
solution, boiled and then saturated with an acid, yields a form of
heematin which is no longer soluble in a mixture of alcohol and
ammonia. The potash-solution, on boiling, assumes first a dark
red, and subsequently a green tint. The ammoniacal solution
gives off its ammonia during evaporation ; moreover, heematin does
not absorb ammoniacal gas. The colour of the ammonia- solution
of hsematin is not affected by carbonic acid, oxygen, or nitric oxide ;
sulphurous acid gives it a bright red tint, and sulphuretted hydrogen
makes it slightly darker.
Haematin is completely precipitated from its ammonia-solution
by the salts of oxide of silver, of lead, and of copper ; if the solu-
tion of hsematin in alcohol, acidulated with sulphuric acid, be
boiled with oxide of lead, it becomes entirely decolorised.
When heated in an enclosed space, hsematin puffs up, and,
without melting, yields empyreumatic ammoniacal vapours and a
reddish brown oil, and leaves a rather small porous charcoal, which
on combustion yields a red ash. Phosphorus and sulphate of prot-
oxide of iron may be boiled with heematin without in any way
affecting it.
Treated with concentrated nitric acid in the cold, it dissolves
into a brown fluid, and developes nitrous acid ; when boiled with
this acid it is entirely destroyed.
If chlorine be allowed to act on hsematin mixed with water, all
the iron of the hsematin dissolves as perchloride of iron, and there
is a deposition of white flocculi, which are soluble in alcohol and
ether but not in water, develope a little chlorous acid when dried
(at 100°), and then form a light straw-coloured powder. This
powder is unaffected by hydrochloric acid, but dissolves in
alkalies, forming a reddish solution ; according to Mulder, it consists
of chlorous acid arid hsematin freed from its iron. If chlorine gas
be passed over dry hsematin, they unite and form a dark green
compound which is soluble in alcohol, exerts no action on vegetable
HJEMATIN. 301
colours, is unaffected by acids and alkalies, but which, when warmed
with hydrosulphate of ammonia, assumes a red colour.
On passing dry hydrochloric acid gas over dry hsematin,
there is formed a violet mass, which is soluble both in water and
alcohol, communicating to those fluids a red colour and an acid
reaction.
If hsematin be allowed to remain for some time in contact with
pure concentrated sulphuric acid, and the fluid be then diluted with
water, there is a development of hydrogen gas, and sulphate of
protoxide of iron is taken up in solution. By a repetition of this
process the whole of the iron, with the exception of a mere trace,
may be removed from the hsematin, without depriving it of its
properties and without altering its elementary composition, as far
as the relative amounts of the carbon, hydrogen, nitrogen, and
oxygen are concerned.
We are indebted to Mulder and van Goudoever* for the pre-
paration of hsematin free from or poor in iron; Sanson and
Schererf had, however, previously observed that concentrated
sulphuric acid could extract all the iron from the clot or the
residue of the blood- corpuscles, without affecting its dark brown
colour.
Composition. — MulderJ has calculated, from his analyses, the
formula we have given for haematin, according to which it contains :
Carbon 44 atoms .... 65'347
Hydrogen 22 „ .... 5*445
Nitrogen 3 „ .... 10'396
Oxygen 6 „ .... 11-881
Iron 1 „ .... 6-931
100-000
Mulder's analyses of hsematin free from iron coincide with the
formula C44H22N3O6. From the chloride of hsematin Mulder cal-
culates that the atomic weight of hsematin is 5175.
Chloride of hce matin, formed from dry chlorine gas and hsematin,
consists of 1 equivalent of hsematin, and 6 equivalents of chlorine ;
how this combination may be supposed to be formed, is a point on
which at present we can offer no conjecture. The compound
obtained from dry hydrochloric acid gas and hsematin consists,
according to Mulder, of 2 equivalents of hsematin and 3 equivalents
of hydrochloric acid; on exposing this substance to a heat of 100°,
* Journ. f. pr. Ch. Bd. 325, S. 186, ff.
t Ann d. Ch. u. Pharm. Bd. 40, S. 30.
J Journ. f. pr. Ch. Bd. 28, S. 340.
302 COLOURING MATTERS.
it loses half its acid, and then consists of 4 atoms of haematin and
3 atoms of acid. In the combinations of haematin with metals it
appears from an experiment of Mulder's that 1 atom of haematin
is combined with 1 atom of base.
The question — in what condition does the iron exist in the blood,
or on what iron-compound is its red colour dependent ? is one that
has long engaged the attention of chemists and physiologists.
Without considering that, with an equal right, we might inquire
into the causes of the colour of indigo, carmine, or peroxide of iron,
it was universally believed that the blood's colour must depend on
the last named substance, and consequently, all experiments on the
subject were instituted with the view of ascertaining in what state
of combination the peroxide of iron lay concealed. It would be
superfluous for us to notice the different views regarding the
combinations in which the peroxide of iron has been supposed to
exist in the blood. We must not, however, omit all notice of the
circumstance, that a discovery of Engelhardt's showed the fallacy of
these views, for he ascertained that the iron of the blood might be
precipitated by alkalies and liver of sulphur, if chlorine gas had
been previously, and for some time, passed through the blood ; and
this led him to the somewhat illogical conclusion that the iron
could not be oxidised, but must exist in a metallic state in the
blood ; for Rose's discovery that the precipitation of peroxide of
iron and other metallic oxides may be prevented by all the non-
volatile organic acids, shows that notwithstanding Engelhardt's
experiment, the iron may be contained in the blood in the state of
peroxide. Finally, Lecanu discovered the true colouring matter of
the blood, the haematin ; and as almost all the iron of the blood is
contained in this substance, attempts were again made to refer the
colour of this pigment to peroxide of iron. But we know, from
the experiments of Scherer, San son, and Mulder, that the iron
must be contained in some other combination than in direct com-
bination with oxygen, and that the iron may be abstracted from
the red blood-pigment without affecting its colour. That the iron
is directly combined with the group of atoms constituting hsematin,
is not a probable view ; at present, however, we are in possession
of no facts throwing any additional light on the nature of the iron-
compound.
The white body formed by the action of chlorine and water on
haematin, was found by Mulder to be devoid of iron, and to be
composed in accordance with the formula C44H22N3O6 + 6C1O3.
Preparation. — We treat blood with about eight times its volume
HjEMATIN. 303
of a solution of sulphate of soda or chloride of sodium, filter it, and
wash the residue on the filter as thoroughly as possible with the same
saline solution ; the residue thus almost completely freed from serum,
or, in other words, the mass of the blood-corpuscles, is dissolved
in water, and coagulated by the application of heat ; the washed,
dried, and finely triturated coagulum is now boiled with spirit con-
taining sulphuric acid, till the fluid passes through a filter in a
decolorised state. This filtered fluid, which in the mass presents
a brownish-red tint, after being saturated with ammonia, deposits
sulphate of ammonia and a little globulin; these being removed
by filtration, the fluid is evaporated to dryness ; the solid residue is
extracted with water, alcohol, and ether, and in order to effect the
complete removal of any adhering globulin, is again dissolved in
spirit containing ammonia; the solution is then filtered, evapo-
rated, and the residue extracted with water.
Tests. — If from any suspicion of the presence of blood we wish
to examine a fluid for hsematin, it is by far the best plan to employ
the microscope, and by its means to endeavour to detect blood-
corpuscles, or their fragments. It only rarely happens, in certain
exudations or saturated masses in which blood-corpuscles are no
longer present, that we can with certainty recognise the red pigment
of the blood, since its quantity is so small, that we can scarcely
obtain enough, by the methods we have given, to apply any tests
to it.
That the hdematoidin discovered, or at least first accurately
investigated by Virchow,* (the same substance which has also been
named xanthose) is not perfectly identical with hsematin is obvious
from Virchow's experiments ; but the occurrence of this substance
in sanguineous extravasations, whose metamorphoses have been
most admirably traced out by Zwicky, Bruch, and Virchow, denotes
as decidedly as chemical experiments could do, that it is formed
from hsematin ; moreover, several of its properties indicate its close
affinity with the last named substance.
H&matoidin occurs in an amorphous condition in granules,
globules, and jagged masses, as well as in perfectly formed crystals
of the monoclinometric system ; these latter are oblique rhombic
prisms, not unlike crystals of gypsum, but frequently are almost per-
fect rhombohedra ; they are strongly refractive and transparent, are
of a yellowish-red, red, or ruby colour, and are insoluble in water,
alcohol, ether, acetic acid, dilute mineral acids, and alkalies. I
have sometimes seen the smaller and less deeply coloured crystals
* Arch. f. pathol. Anat. u. s. w. Bd. I, S. 383-415.
304 COLOURING MATTERS.
dissolve in alcohol containing sulphuric acid or ammonia, and be
again precipitated by neutralisation of the fluid ; this is, however,
not invariably the case. Virchow has very carefully examined the
behaviour of this body with concentrated alkalies and mineral acids ;
these agents, however, do not act in precisely the same manner on
all specimens of this pigment ; on the addition of hydrate of potash,
a fiery red tint is developed, the mass becomes gradually loosened
in its texture, and becomes disintegrated into red granules which at
length dissolve ; on neutralising the alkali the substance is, how-
ever, not again precipitated. When a concentrated mineral acid,
sulphuric acid, for example, acts on it, it causes the sharp outlines
of the crystals to disappear ; and the colour of the roundish frag-
ments, after first becoming brownish-red, passes through successive
shades of green, blue, and rose-tint, till it finally terminates in a
dirty yellow. Iron may sometimes, but not always, be detected
in the acid fluid containing the decomposed heematoidin.
Hsematoidin may always be found in the sanguineous extrava-
sations occurring in consequence of the bursting of the Graafian
vesicles at the periods of menstruation or conception, and frequently
occurs in old extravasations in the brain, in obliterated veins,
hsemorrhagic infarctus of the spleen, in subcutaneous sugillations,
and in purulent abscess of the extremities. (Virchow.) It appears
from Virchow's observations that these crystals may form from
seventeen to twenty days after the occurrence of the extravasation.
Kolliker* has observed the formation of crystals of this nature
within the corpuscles in the blood of certain fishes ; these crystals
were however, soluble in acetic acid, potash, and nitric acid.
Although every care and precaution have been taken, both
Virchow and I have failed in obtaining these crystals of modi-
fied hsematin either from solutions of blood or of heematin
itself; but yet those who still assign an important part in the
animal body to vital forces, must grant that under the necessary
conditions, haematoidin may be produced out of the body from
haematin, since this kind of metamorphosis occurring in extravasa-
tions in all respects exhibits the character of a disintegration, that
is to say, of a purely physical and chemical process. Moreover,
Kolliker's observation gives us room to hope that we may be able
to obtain crystallisable hsematin or hsematoidin from the blood of
the lower animals, — fishes, for example, — so as to submit it to an
accurate chemical examination.
* Zeitschr. f. wiss. Zoologie. Bd. I, S. 266.
H/EMAT1N. 305
Physiological Relations.
Occurrence. — Haematin has hitherto only been found in the
blood-corpuscles of the higher animals. Intimately united with
globulin, it forms the viscid, fluid contents of the coloured blood-
cells.
Berzelius found 0*3 8$ of metallic iron in the dried blood-corpus-
cles of man or the ox; now as Mulder has found 6*64§ of iron in
hoematin, a simple calculation shows thatin the blood-corpuscles there
are contained 5'/2f of hsematin, independently of fat, globulin, salts,
and biliary matter : hence, in fresh blood in which the red blood-
corpuscles on an average =12-8$, there would be contained 0'732-J-
of hcematin. If we calculate from Becquerel's results, according
to which 1000 parts of blood contain 0'565 parts of iron and 141-1
of blood-corpuscles, we obtain a very similar result, namely, that
100 parts of blood-corpuscles contain 6'02 of hsematin. It is
obvious that such calculations can only lead to approximate
results ; attempts have certainly been made to effect a direct deter-
mination of the amount of hsematin in the blood ; but the method
of separating it is as yet too uncertain to admit of our placing much
reliance on the numbers which have been obtained. The amount
found in the blood by Lecanu, namely 0'227f, was obviously too
small, while Simon's number, 0'7l8f, approximates closely to the
calculated quantity.
By treating defibrinated calves' blood with chloride of sodium,
Schmidt obtained the corpuscles in a state of purity; and after
incineration, found in them 1'1/9-g- of peroxide of iron, hence,
(according to Mulder's analysis of hsematin,) they would contain
12'41-J of this ingredient; in repeating Schmidt's experiment with
ox-blood I obtained 9*076 and 10'94& of peroxide of iron — results
which corresponded tolerably well with that which he found. The
great difference which presents itself between these results of direct
experiment,, and the results of pre-indicated calculations, admits of
an easy explanation ; in the latter case, the blood-corpuscles are
calculated more or less in accordance with their true constitution
in the blood, while in our experiments, the process by which we
purify the blood-corpuscles — their treatment with a solution of
chloride of sodium or sulphate of soda — abstracts from them a
portion of their globulin, and all the soluble salts ; when treated
with saline solutions, the corpuscles lose, in accordance with the laws
of endosrnosis, not only water, but also a part of their soluble
globulin ; while the treatment of the coagulated corpuscles with
306 COLOURING MATTERS.
water, alcohol, and ether, abstracts from them all soluble salts,
and the fat, which in itself amounts, according to my investigations,
to at least 2%.
The ratio of the hsematin to the blood varies in diseases for the
most part with the number of the blood-corpuscles ; but whether
the ratio of the hsematin to the globulin of the blood-corpuscles
be constant, or whether the hsematin be liable to greater variations
than the globulin, are questions which in the present state of organic
analysis it is impossible to answer.
Origin. — There is nothing in the chemical constitution of
hsematin which throws any light on the mode of its formation ;
we do not know whether it is directly formed from the constituents
of the food or from the products of metamorphosis of effete tissue ;
and we have no certain knowledge regarding the part of the organism
in which it is produced. The chyle certainly contains iron, and
hsematin exists in the thoracic duct ; but iron is not hsematin, and
the small quantity of the last-named substance may have passed
from the blood through the mesenteric glands into the chyle, or may
have arisen from the blood-corpuscles which have passed with the
splenic lymph into the chyle. If the formation of hsematin took
place in the chyle it would not be after prolonged fasting that we
should find it richest in this substance. Chemistry, as we have
already observed, affords us no assistance in reference to the for-
mation of this body; we must, therefore, at present, confine our
attention to physiological facts, in order that we may obtain a safe
starting-point for further chemical enquiries.
Most physiologists of the present day coincide in the opinion
that the red blood-corpuscles are developed from the colourless
ones ; but whether they regard the former as nuclei of the latter, or
as independent cells produced from them — whether they adopt the
views of H, M tiller,* of Gerlach,f or of Kollikei J — they must in any
case admit that the red pigment of the blood is primarily formed
within the enveloping membrane of the cell. Further, physiological
enquiry demonstrates, almost beyond a doubt, that the blood pig-
ment is first formed in the perfected cells, and, moreover, affords
us some indication, however indistinct, of the source from whence
this pigment may possibly have been produced. Nasse, Hiinefeld,
and others, have proved that the granular matter visible in many
of the coloured blood-corpuscles is merely fat ; indeed in the yolk-
* Zeitschr. f. rat. Med. Bd. 3, S. 204-278.
t Ibid. Bd. 7, S. 70-90.
J Ibii. Bd. 4, S. 112-1CO.
HE. MATIN. 307
cells, in the young blood-corpuscles of the amphibia [in their
embryonic state] we find not only roundish but also angular
granules soluble in ether, which can hardly be anything else than
stearin. Henle and H. M tiller refer the primary origin of the
colourless blood-corpuscles to the fat which is recognisable as a
fine granular (almost cloudy) matter in the minutest lacteals. We
have already mentioned that the fat stands in a certain relation to
the functions of the liver; the beautiful investigations of E. H.
Weber and Kolliker have, however, now demonstrated that large
quantities of blood-corpuscles are always formed in the liver in the
foetal state, and during the hybernation of certain animals, and
therefore at periods when this organ secretes little or no bile, but
when fat is accumulated in it.
Moreover, an unprejudiced examination of the development of
the chick within the egg leads to the assumption that the fat takes
a part in the formation of haematin ; and if physiological facts can
be adduced in favour of this hypothesis, there are at all events no
chemical objections to it. As it is obvious that the colouring
matter can only be formed when there is free access of oxygen,
namely in the vessels, and as the oxygen doubtless contributes
materially to its production, we cannot suppose that it is formed
from protein, which is a substance rich in oxygen, or from sugar ;
hence there is hardly any other substance than the fat from which
a process of oxidation could yield haematin.
Our present assumption of the formation of haematin from fat
is to be regarded merely as an hypothesis based on one or two phy-
siological facts, which may possibly admit of a very different inter-
pretation ; it is only intended to serve as a means of directing our
attention in a definite direction in the investigation of this subject.
Uses. — The constant occurrence of haematin in the blood-
corpuscles indicates that this body takes an important part in the
metamorphosis of the animal tissues. All sorts of conjectures have
been hazarded regarding its function in the blood, and it has been
especially supposed to be connected with the process of respiration.
In point of fact, however, it is unnecessary to consider any hypo-
thesis, until it has been satisfactorily ascertained whether the
hsematin in question actually stands in the same relation to the true
pigment of the blood as coagulated to non-coagulated albumen, or
whether artificially prepared haematin is altogether a product of
decomposition of the actual pigment. If hsematin has the same
composition as that which we prepare artificially, and if the only
difference be that it exists in a soluble form in the blood- corpuscles,
x 2
308 COLOURING MATTERS.
there is at once an end to all those very imaginative hypotheses
which assume that the iron takes a great share in the process of
respiration, and that it is the conveyer of oxygen to the blood.
The experiments of Bruch* on the action of gases on the colour
of the blood, and the observations of Harless,f regarding the
gradual destruction of the corpuscles of frogs' blood, certainly
indicate that there is a chemical action between the blood-corpuscles
and their contents on the one hand, and the inspired oxygen on the
other, in which action the hsematin doubtless participates.
The observations of Hannover, t which show that persons whose
blood is very deficient in red corpuscles (chlorotic persons) exhale
as much carbonic acid as healthy persons, seem on the other hand
to contra-indicate a direct relation between the blood-corpuscles or
blood-pigment, and oxidation in the blood. We must, therefore,
give up for the present all attempts at understanding the function
of the blood-pigment.
The question as to what becomes of the hsematin when the
blood-corpuscles and their contents undergo disintegration, is one
which for a long time was enshrouded in perfect obscurity, but on
which some light has now been thrown by Virchow's admirable
investigations on haematoidin. The occurrence, in a crystalline form,
of this substance, which is undoubtedly derived from the blood-
pigment, and its different behaviour towards the same reagents,
indicate that, notwithstanding its crystalline arrangement, it con-
tinues to undergo changes which give rise to a substance perfectly
similar to, if not identical with, bile-pigment or melanin. Although
the subject is still far from being satisfactorily settled, Virchow was
the first who by his pathologico-histological and chemical investiga-
tions prominently brought forward definite facts which have afforded
the first solid groundwork for the hypothesis which was long since
propounded, that hsematin might be transformed into cholepyrrhin.
In reference to this point we would specially direct attention to
Virchow's ingenious treatise, in which he endeavours to strengthen
the view regarding this metamorphosis by means of a simple induc-
tion based on direct observation. It has unfortunately hitherto
been found impossible to separate hsematoidin in so pure a state
and in sufficient quantities as to admit of its being subjected to a
* Zeitschr. f. rat. Med. Bd. 3, S. 300,
t Ueber den Einfluss der Gase auf die Blutkorperchen von Rana tonipor.
Krlangen, 1846.
$ De quantitate acidi carbonic! ab homine sano et aogroto exlialati.
I84a.
MELANIN. 3()(J
rigid chemical investigation. From Virchow's investigations it is,
however, apparent that the physician must also lend his help for
the advancement of pathological and physiological chemistry ; for
without the aid of pathological histology, — without a judicious appli-
cation of the microscope, — the chemist could not have succeeded in
discovering hsematoidin any more than in detecting oxalate of lime
in normal urine ; without such aid the chemist could never have con-
ceived an idea of the metamorphosis of the pigments in the
animal body. As long as the physician contents himself with
borrowing mere hypotheses from chemists, without being himself
practically familiar with chemical science, he can never hope to
gain the advantages which it is capable of affording ; in this respect
he resembles the agriculturist, who can never expect to raise his
pursuit to the dignity of a science until he has learned the practical
application of the principles of chemistry.
MELANIN.
Chemical Relations.
Properties. — Melanin forms either a black, cohesive mass, or a
blackish-brown powder ; it is devoid of smell and taste ; when
stirred in water it continues to float for some time, but is insoluble
both in water and in alcohol, in ether, in dilute mineral acids, and
in concentrated acetic acid ; it dissolves, after prolonged digestion,
in a dilute solution of potash, from which it is again precipitated
with a light brown colour by hydrochloric acid ; it is decom-
posed when boiled with concentrated nitric acid, but it is not
affected even by the very prolonged action of chlorine. It is a
conductor of electricity, is incapable of fusing, may be ignited in
the air, and burns with a vivid light, the charcoal continuing to
smoulder till it is reduced to a whitish-yellow ash consisting of
chloride of sodium, lime, bone-earth, and a little peroxide of iron.
By dry distillation it yields an empyreumatic substance, and
carbonate of ammonia. According to Gmelin this pigment is
rendered paler, and is partially dissolved by chlorine- water, the
undissolved portion becoming again of a dark brown colour on the
addition of potash.
Whether the black crystals which have been found by Macken-
zie,* Guillot,t and Virchow,J in melanotic masses are or are not
* A Practical Treatise on Diseases of the Eye. Lond. 1835. p. 663.
f Arch. gen. de Me'd. 4 St-r. T. 7, p. 166.
£ Arch. f. pathol. Anat. u. s. w. Bd. 1 , S. 399.
310 COLOURING MATTERS.
identical with melanin, is a question which, with our present very
imperfect knowledge of this pigment, must still remain undecided.
Virchow found these crystals to be flat rhombic tablets with
extremely acute angles.
Composition. — Scherer* gives the following as the mean result
of three analyses of this body :
Carbon 58'084
Hydrogen 5*917
Nitrogen 13768
Oxygen 22-231
100-000
As we are neither acquainted with the atomic weight of this
body, nor with any of the products of its decomposition, we cannot
attempt to construct a hypothetical formula for it. In the pigment
from the choroid coat of the eye 1 found 0*254^ of iron.
The black pigment which is often deposited as a morbid product
in the lungs presents great differences of composition. In two
different cases which C. Schmidtf analysed he found :
Carbon 72-95 6677
Hydrogen 475 7'33
Nitrogen 3'89 8'29
Oxygen 18'41 17'6l
100-00 100-00
Preparation. — The best method of obtaining this body is from
the eye, by removing the retina, and detaching the choroid coat
from the sclerotic. The choroid coat must be placed in a clean
rag, and the colouring matter washed out with pure water, just as
the starch-granules in the preparation of gluten are washed out
through linen bags; the pigment remains for a long time suspended
in the water, from which, however, it may be readily removed by
filtration, or the fluid may be evaporated and the residue extracted
with water.
Tests. — The physical properties of this body are so character-
istic, that it is easy to recognise and to separate it; generally,
however, it only occurs in such small quantities that it is impos-
sible to distinguish whether the object in question is identical with
the melanin of the eye, especially as we still know comparatively
little regarding the chemical characters of this last-named sub-
stance. No conclusions regarding the presence of black pigment
can be drawn from mere colour and insolubility in different men-
* Ann. de Ch. u. Pharm. Bd. 40, S. 6.
*fr Vogel's pathol. Anat. S. 161 [or English Translation, p. 192.]
MELANIN. 311
strua, since as Jul. Vogel* was the first to observe, the tissues
may be infiltrated with sulphide of iron, from which, however, the
black pigment may very readily be distinguished by means of acids.
Physiological Relations.
Occurrence. — This pigment exists as a thick investment on the
choroid coat of the eye. Whether it also occurs in other parts of
of the animal organism, is a point which cannot be decided, since
the other pigments of the same colour in morbid depositions either
have not been accurately analysed, or from their very small quan-
tity do not admit of analysis ; as for instance, the pigment of the
black bronchial glands, of the rete mucosum sen malpighianum of the
negro, of melanotic tumours, of the black serum which has been
occasionally observed, and of pulmonary tissue in certain cases.
In the choroid coat the melanin is enclosed in peculiar hex-
agonal cells, but in the coats of the blood-vessels of frogs and
other amphibia it is found in jagged ramifying cells. In other
parts of the animal body — in melanotic tumours for instance — it
occurs, however, merely scattered among other cells or tissues.
Whether granular cells, when becoming obsolete, (such for example
as we find in old exudations,) contain actual melanin, is a question
which must still remain undecided. Sanguineous extravasations
are, however, not unfrequently converted into a mass, which is
coloured perfectly black by black pigment.
Origin. — The large quantity of iron contained in this pigment
indicates that it takes its origin from the hsematin. We cannot
recognise such a conversion by chemical means, till we are able to
demonstrate that pathological depositions of pigment contain true
melanin. Whatever view we may adopt regarding the production
of the black-coloured inflammatory globules, we must at all events
agree with Bruchf that they contain blood-pigment and the rudi-
ments of blood-corpuscles, even if we do not, like HasseJ, H.
Muller, and Pestalozzi§, see true blood-corpuscles in these cells ;
if we examine the expectoration in a case of pneumonia in which
resolution is very gradually progressing, we find, on making a
perfectly unprejudiced observation, very many of these cells which
have the exact colour of blood -corpuscles. VirchowlJ has very
* Pathol. Anat.S. 163 u. 311 [or English Translation, pp. 194 & 396.]
t Untersuch. zur Kenntniss des kornigen Pigments derWirbelthiere. Zurich,
1844. S. 42 ff, and Zeitschr. f. rat. Med. Bd. 4, S. 24 ff.
$ Zeitschr. f. rat. Med. Bd. 4, S. 1-15.
§ Ueber Aneurismata spuria der kleinen Hirnarterien u. s. w. Wurzb. 1849.
II Arch. f. pathol. Anat. u. s. w. Bd. 1. 8. 401.
312 COLOURING MATTERS.
accurately traced, by microscopical examination, the conversion of
isolated coagula in obliterated veins into amorphous and crystalline
pigment, and from these morphological investigations it can hardly
be doubted, that at all events the melanin of morbid products is
formed from the hsernatin. Kolliker* has moreover convinced
himself that in the blood- corpuscles enclosed in the enveloping
membrane, the haematin affords the matter from which the black
pigment in the granular cells is formed. Hence it only remains
for the chemist to continue his investigations on this subject, in
order to obtain perfectly satisfactory scientific proof of this meta-
morphosis.
Uses. — That the use of pigment in the choroid coat is princi-
pally to render the eye achromatic, is sufficiently obvious from the
principles of physics. We are ignorant of the uses which it serves
in the walls of the blood-vessels in the amphibia.
BiLE-PlGMRNT.
Chemical Relations.
Properties. — This substance, like so many of the pigments,
belongs to that vast group of bodies, whose chemical properties
have never been thoroughly investigated ; this is partly dependent
on the circumstance that we can only procure it in very small
quantity, and partly on its extreme instability, for not only does it
occur in the animal organism under various modifications, but it is
at once changed by the simplest chemical treatment. The most
frequent modification which the primary substance of the bile-
pigment in the higher animals appears to present, is the brown
pigment, the cholepyrrhin of Berzelius, and the biliphain of
Simon. It occurs as a reddish brown, non-crystalline powder,
devoid of taste and smell ; it is insoluble in water, very slightly
soluble in ether, and more so in alcohol, to which it communicates
a distinct yellow tint ; it is more soluble in caustic potash than in
caustic ammonia, the alkaline solutions being at first of a clear
yellow colour, but on exposure to the air gradually changing to a
greenish brown tint. It is on this modification of the bile -pigment
that the well-known changes of colour which occur in some of the
animal fluids are dependent. The yellow solution of this pigment
when gradually treated with nitric acid (and especially, according
* Zeitschr. f. iviss. Zoologie. Bd. 1, S. 260-267-
BILE-PIGMENT. 313
to Heintz*, when this reagent contains a little nitrous acid,) first
becomes green, then blue (which, however, can hardly be detected
in consequence of its rapid transition into violet,) and red ; after
a considerable period the red again passes into a yellow colour; by
this time, however, the bile-pigment is entirely changed. On the
addition of hydrochloric acid to a potash-solution, the pigment is
precipitated with a green tint; this precipitate forms a red solution
with nitric acid, and a green solution with the alkalies, and appears
to be perfectly identical with the green modification of bile-pigment.
The colouring matter contained in fresh bile is coloured green by
acids ; as Gmelin found that this coloration did not take place
without the free access of oxygen, it is highly probable that most
of these changes of colour are dependent on a gradual oxidation.
Chlorine gas acts on this pigment in the same manner as nitric
acid, but rather more rapidly ; large quantities of chlorine com-
pletely bleach the pigment, and precipitate it in a white flocculent
deposit.
This brown pigment has a strong tendency to combine with
bases, — not merely with alkalies, but also with metallic oxides and
alkaline earths. It forms insoluble compounds with the alkaline
earths — a circumstance which has often led to the idea that this
substance is insoluble.
The green pigment, the biliverdin of Berzelius, is a dark green
amorphous substance, devoid of taste and smell, insoluble in water,
slightly soluble in alcohol, but dissolving in ether with a red
colour ; it dissolves in fats, hydrochloric acid, and sulphuric acid with
a green colour, and in acetic acid and the alkalies with a yellowish
red tint. On exposure to heat, this body undergoes decomposition
without fusing, and without giving off any appreciable quantity of
ammonia, leaving a little charcoal. Berzelius regards this sub-
stance as perfectly identical with the chlorophyll of leaves, and
believes that he has found all three modifications of this substance
in different specimens of bile. This green pigment no longer
undergoes changes of colour on the addition of nitric acid, although
we occasionally meet with green bile-pigment still possessing this
property. On treating bile-pigment with alkalies or acids, its
properties are usually at once changed, partly on account of its
entering into various combinations with these substances, and
partly from the extreme facility with which it becomes decomposed.
Hence it is that the statements regarding the properties of this
substance present such striking differences, as may be seen by a
* Mtiller's Arch. 1840, S. 399-405.
314 COLOURING MATTERS.
comparison of the writings of Berzelius*, Schererf, HeinJ,
Platner§, and others.
Berzelius also found in the bile a substance occurring in small
reddish yellow crystals, soluble in alcohol, to which he has given
the name of bilifulmn. I have obtained it in solution, but have
never succeeded in isolating it in the solid state ; singularly enough,
I have often found it in the bile precipitated with neutral and basic
acetate of lead ; hence it appears either not to be precipitated by
these metallic salts, or (which is more probable) to redissolve in
an excess of the basic salt.
Composition. — With our present ignorance of bile-pigment in
its pure unchanged state, it is not to be wondered at that its
elementary composition is still unknown. Bile-pigment has been
analysed both by Scherer and Hein, but it is obvious from their
analyses that they have examined very different substances, and
Scherer has especially shown that the pigment which he examined
loses much carbon and hydrogen by the action of air, alkalies, and
acids. From 7 to 9^- of nitrogen has been found in bile-pigment.
Preparation. — Till recently the ordinary mode of preparing
bile-pigment consisted in the extraction, by water and ether, of
biliary calculi, consisting for the most part of this constituent ; the
residue thus obtained does not, however, generally possess the
power of dissolving in alcohol, for (as Bramson|| has very cor-
rectly shown, and as any unprejudiced observer may easily con-
vince himself) it exists in a state of insoluble combination with
lime, even in those concretions which for the most part consist of
cholesterin.
The mode of investigation which Brarnsom adopted, and which
I. have often repeated, appears to me to leave no doubt regarding
the correctness of his views, which moreover receive further con-
firmation from the analyses of biliary concretions made by Schmid^f
and Wackenroder.**
Berzelius prepares biliverdin from ox-gall by precipitating the
alcoholic extract with chloride of barium; the precipitate is first
washed with alcohol, and afterwards with water, and then de-
* Lehrb. d. Ch. Bd. 9, S. 281-286.
t Ann. d. Ch. u. Pharm. Bd. 53, S. 377-
t Journ. f. pr. Ch. Bd. 40, S. 47-56.
§ Ann. d. Ch. u. Pharm. Bd. 51, S. 115.
Jl Zeitschr. f. rat. Med. Bd. 4, S. 193-208.
f Arch, der Pharm. Bd. 41, S. 291-293.
** Ibid. S. 294-296.
BILE-PIGMENT. 315
composed with hydrochloric acid, which extracts the baryta ; the
fat is removed by ether from the residue, which is then dissolved
in alcohol.
Platner precipitates the bile- pigment by digesting the bile with
hyclrated protoxide of tin ; the light green deposit which is
formed, after being well washed with water, is shaken with spirit
containing sulphuric acid, and filtered; the pigment is thrown
down in the form of a green flocculent precipitate on the addition
of water to the filtered green solution.
Scherer separated the bile-pigment from urine containing large
quantities of it by means of chloride of barium, in the two following
ways : he either decomposed the baryta-compound with carbonate
of soda, threw down the pigment with hydrochloric acid from the
soda-solution, and purified it by solution in alcohol containing
ether, by washing with water, &c. ; or the baryta-compound was
extracted with alcohol containing hydrochloric acid, the solution
evaporated, extracted with water, and then treated in the manner
above described.
Tests. — Unless the amount of bile-pigment in a fluid be not too
minute, nitric acid, especially if it contain a little nitrous acid,
gives the very characteristic play of colours which we have already
described. When, however, the colouring matter is present in
small quantity, or when it has already undergone a partial modi-
fication, nitric acid often fails to give any appreciable reaction.
Schwertfeger's* method in such cases is to precipitate the fluid
with basic acetate of lead, and to extract the precipitate with
alcohol containing sulphuric acid : if any of the pigment be
present, the alcohol assumes a green tint. Heller^ recommends
that a little soluble albumen should be added to the fluid to be
examined (unless, indeed, it be already albuminous), which must
be precipitated by an excess of nitric acid; if any pigment be
contained in the fluid, it will communicate a bluish or greenish
blue tint to the coagulated albumen. Heller observes that if am-
monia be carefully poured upon urine which contains unchanged
bile-pigment, the surface of the fluid assumes a red colour.
Physiological Relations.
Occurrence. — Bile-pigment usually occurs in fresh bile in a
state of solution ; often, however, it is in a state of suspension.
It almost always constitutes the nuclei of gall-stones ; and we some-
* Jahrb. f. prakt. Pharm. Bd. 9, S. 375.
t Arch. f. Chem. u. Mikrosk. Bd. 2, S. 95.
316 COLOURING MATTERS.
times find ramifying nodular concretions in the gall-bladder and in
the biliary ducts, consisting almost entirely of bile-pigment. This
pigment is found, not only in the bile of man and of the ox, but
also in that of other carnivorous and herbivorous animals; it
presents, however, the most varied modifications, as we find from
the difference of colour exhibited by the bile not only of different
genera but even of different individuals of tbe same species ; thus,
the bile of a dog is of a yellowish brown tint, that of the ox is
brownish green, while that of birds, fishes, and amphibia is usually
of an emerald green.
The bile-pigment which mixes with the contents of the
intestines becomes very rapidly modified, and ceases to present the
ordinary reaction with nitric acid ; the change which it here very
rapidly undergoes, appears to be the same which we can induce
artificially by nitric acid. It is in this form that it occurs in the
solid excrements, unless when diarrhrea is present, in which case
unchanged pigment is found in the alvine dejections. It is only
rarely that the excrements assume a green tint from the green
modification of the pigment ; the green coloration more frequently
depending on an admixture of partially decomposed blood. Bile-
pigment is never entirely absent in the excrements except in the
rare cases of icterus, which are accompanied with a complete
stoppage of the biliary secretion.
Bile-pigment occurs in the blood and in serous fluids in all
forms of icterus ; sometimes however it is absent, or at all events,
cannot be detected in the blood in certain forms of inflammation,
while cholic acid or its conjugated acids may be recognised ; the
converse case, namely, the presence of bile-pigment and the absence
of cholic acid in the blood is, however, more frequently observed.
We shall return to this subject in the second volume.
In diseases the bile-pigment is especially deposited in the fluids
of the cellular tissue, in the aqueous humour, the vitreous humour,
the crystalline lens, and above all in the sclerotic ; cases have even
occurred in which the saliva and the sweat have been coloured
yellow ; sometimes the organism may so long endure this impure
condition of the blood, that the pigment saturates even the car-
tilages, ligaments, and bones,* and may actually be recognised in the
nerves.
Schererf often discovered decided traces of bile-pigment in the
urine of healthy persons, especially during the hot months. In
* Kerkring, Spicil. anat. obs. 57, p. 118.
t Ann. d. Ch. u. Pharm. Bd. 57, S. 181- IU5.
BILE-PIGMENT. 317
disturbances of the function of the liver this pigment very frequently
presents itself in the urine, and may usually be recognised by a
brownish red or cinnamon brown, dark colour, which sometimes,
if the urine be allowed to stand till it become acid (Scherer), passes
into a dark green tint. Sometimes, however, it is also absent in
this fluid while other biliary constituents are present in it. Occa-
sionally, in perfect suppression of the biliary secretion — as for
instance in true granular liver, when the urine throws down an
intense scarlet sediment— no trace either of bile-pigment or of
cholic acid can be detected.
Origin. — As we are still unable to obtain an empirical formula
for the composition of bile-pigment, chemistry affords us no infor-
mation regarding the origin of this substance. The opinion has
certainly long been advanced that bile-pigment was formed from
haematic in consequence of the greenish shades of colour which
extravasated blood usually exhibits, as for instance under the skin
after contusions, in the sputa of patients with pneumonia, and
sometimes in typhous stools. However plausible this view may
appear when we examine the blood-corpuscles of portal blood
and find the colouring matter essentially changed in them, yet
physiological facts are still wanting to support it. Virchow,*
by his physiological investigations, has with much ingenuity pointed
out the way which the chemist must proceed in order to decide the
question in reference to this pigment. He was the first to draw
attention to the red crystals which are found within the animal
organism and which evidently arise from stagnating bile, and to show
that in their reactions they take an intermediate place between
heematoidin and bile -pigment., forming a transition stage between
these two pigments.
Uses. — Whether the bile-pigment takes any part in the process
of digestion, and what are its uses in the intestinal canal, are
questions which for the present must remain altogether undecided.
The fact that it undergoes so decided an alteration in the intestinal
canal leads us ideologically to infer that it fulfils some special
object.
These crystals, which are possibly identical with the bilifulvin
found by Berzelius in bile which had already undergone change
(Pel tauri inspissatum), have been found on the wall of echinococcus-
sacs, which, in consequence of ruptures and partial resorption of the
walls, communicated with the biliary ducts.
The facts now in our possession seem to indicate that the liver
* Arch. f. pathol. Anat. u. s. w. Bd. 1, S. 427-431.
318 COLOURING MATTERS.
is not the part of the organism in which the bile- pigment is formed;
we shall, however, discuss this question in the second volume, when
treating generally of the origin of the bile.
URINE-PIGMENT.
Considered either in a chemical or in a physiological point of
view, there is scarcely any substance in the whole range of physio-
logical chemistry regarding which our knowledge is in so unsatis-
factory a state as the urine-pigment.
Experiments have often been commenced upon this substance,
but the difficulties which present themselves in the investigation are
so numerous that most experimentalists have soon resigned it, and
directed their labours to some more productive department of
chemistry. It unfortunately happens that no certain chemical
differences can be detected between urines presenting the most
striking difference of colour to the eye of the clinical physician.
The difficulties of this investigation are dependent on the fol-
lowing circumstances.
The amount of this substance in the urine is extremely minute ;
a very small quantity of the pigment giving a colour to an extremely
large amount of other matters.
It begins to decompose even during the most cautious evapora-
tion of the urine : to be convinced on this point we need only com-
pare urine concentrated by evaporation, with a spec'.men from which
a great part of the water has been removed by congelation.
Even on exposure to the air, or under the air pump, the decom-
position of this substance commences.
Like many other pigments, it adheres tenaciously to other
substances, sharing their solubility or insolubility.
Besides the pigment, there are other substances in the urine
which have the same degree of solubility, which do not crystallise,
and are not volatile ; as they neither combine in definite propor-
tions with other bodies, nor differ in solubility from the pigment,
they cannot be separated from it.
The pigment occurs in the urine under various modifications,
on which are dependent the different tints presented by morbid
urine and its sediments.
Finally, this pigment is very readily acted on by chemical
reagents, especially by acids and alkalies.
Scherer's* investigations on this subject especially show that this
* Ann. d. Ch. u. Plianti. Bd. 57, S. 180, 195.
URINE-PIGMENT, 319
pigment is in a state of constant change, that it is decomposed by
neutral and basic acetate of lead into two substances, differing in
their respective amounts of carbon and hydrogen; and that in a
healthy condition of the system it is poorer in these two elements
than when there are diseased conditions of the organism impeding
the pulmonary or cutaneous transpiration, or the secretion of bile.
That portion of the colouring matter which is richest in carbon,
forms, as has been found by Scherer and Heller,* a dark blue
powder, which when dried, possesses a coppery lustre similar to
indigo, and dissolves in alcohol with a splendid purple colour.
This latter variety of pigment is especially frequent in Bright's
disease. Heller distinguishes three such pigments, uroxanthin,
uroglaucin, and urrhodin.
It is a matter of common experience in science generally, and
in chemistry more particularly, that the most circumstantial details
are given in reference to the more obscure and less investigated
departments, and that deficiencies of knowledge are concealed by
an enumeration of unconnected or inaccurately observed facts, or
by the most illogical deductions. For ourselves, however, we
prefer to confess our ignorance, and to spare our readers from the
accumulation of individual features which are incapable of afford-
ng a characteristic representation of the subject we would illustrate.
Chemists still reckon the urine-pigments amongst what they term
extractive matters, and may be said by this arrangement to make a
candid avowal of their ignorance in reference to these substances.
Those who may be desirous of attempting to elucidate this
obscure subject experimentally, may derive considerable advantage
from the study of the older writings of Prout, Berzelius, and
Duvernoy, and the more recent memoirs of Heller and Scherer.
EXTRACTIVE MATTERS.
The above observations on the colouring or extractive matters
of the urine, lead us to the consideration of extractive matters in
general, and of those of the blood in particular. The term ex-
tractive matter is applied by chemists to those bodies which,
* Arch. f. Chem. u. Mikrosk. Bd. 2, S. 1C1 17^-
320 EXTRACTIVE MATTERS.
whether they are chemically produced, or exist preformed in an
animal fluid, exhibit few distinguishing properties (that is to say,
are uncrystallisable, incapable of entering into any crystallisable or
stoichiometrically constituted combinations with other substances,
are not volatile at a certain degree of temperature, &c.,) and
cannot therefore be separated, or exhibited in a pure state.
Modern science has indeed made considerable advance, by learning
on the one hand to avoid as far as possible the formation of such
substances, and on the other, to separate some of them, and render
them more accessible to accurate chemical investigation. We will
here observe that substances such as albuminate of soda, Mulder's
binoxide and teroxide of protein, creatine, the inosates, &c., have
been reckoned among the extractive matters; and as many better
known substances (as urate of soda, hippurate of soda, and others)
are impeded in their crystallisation, and are enveloped or con-
cealed as it were by the extractive matters, they also have been
embraced under the same head, and have likewise been regarded in
the light of extractive matters, and have been calculated as such
in analyses. When we consider that the matters circulating in the
blood are, on physiological grounds, engaged in an almost constant
metamorphosis, we shall easily comprehend the difficulties that
beset the chemist in his attempt to seize them at any definite
stage of their metamorphosis, especially as they only circulate
through the blood in small quantities for the purpose of being
deposited in some tissue, or of being eliminated from the organism
by the organs of excretion.
The extractive matters must, therefore, be likewise regarded as
important factors in the metamorphosis of animal tissue. In
accordance with the views of Berzelius, these bodies were con-
sidered for the most part as products of the metamorphosis of
tissues which, having become unfitted for further purposes, after ful-
filling their function, are elaborated in the blood in the better known
form of excrementitious matters. But to regard these substances
as of a purely excrementitious nature, was taking too circumscribed
a view of their importance. Since the blood contains the products
of the metamorphosis of the tissues no less than the elements
necessary for their formation, it is not only possible but probable
that plastic and useful matters, as well as the products of re-
gressive formation, may have been comprehended under the head
of extractive matters ; for, as we have already observed (p. 27,) the
idea of the progressive and regressive metamorphosis of matter
cannot be followed through an unbroken series of sequences.
NITROGENOUS HISTOGENETIC SUBSTANCES. 321
Albuminate of soda, fibrin itself, and Mulder's protein-oxides,
cannot assuredly be regarded in the light of excrementitious sub-
stances, but must rather be considered to constitute the transitions
from albuminous to gelatigenous substances.
When we reflect that the different stages of metamorphosis of
such non-nitrogenous bodies as the fats and carbo-hydrates increase
the number of the extractive matters, it seems worthy of notice
that their sum in the blood should not be greater than we generally
find it to be. But this circumstance proves that very small quan-
tities of the substances which must necessarily occur in the blood,
appear simultaneously ; and hence the difficulties of the inquiry
are considerably increased. The reasons why we are thus unfortu-
nately constrained to continue the use of the term extractive matters,
are sufficiently clear, but yet we cannot refrain from expressing
our surprise that, considering the present condition of our science
in this respect, chemists can venture to speak of different erases
of the blood, or attempt to make them serve as the foundation of
a presumed exact humoral pathology.
NITROGENOUS HISTOGENETIC SUBSTANCES.
The substances belonging to this class present, like the fats
and carbo-hydrates, such great similarities in their composition,
and in their most essential properties, that chemists, even if they
were unacquainted with their occurrence in the animal body, and
with their great physiological importance, would naturally have
placed them in one group, seeing that the following properties are
common to all of them.
In the dried state they occur in a solid mass, or in powder,
or form gelatinous, brittle, translucent plates; when moist they are
either translucent and yellowish, opaque and white, solid and
elastic, soft, tough, and adhesive, or, finally, jelly-like and slippery.
All these substances are uncrystallisable, and, unless when an in-
termixture of other substances is present, are devoid of taste and
smell. By far the greater number of them are insoluble in water,
322 NITROGENOUS HiSTOGENETIC SUBSTANCES.
and the few which are soluble in it can readily undergo a conversion
into a modification insoluble in that fluid ; although their physical
properties are essentially dependent on and modified by water, and
although when dried they condense water with very great rapidity
from the atmosphere (and are therefore highly hygroscopic), yet they
show little tendency to form definite hydrates, that is to say, che-
mical combinations with water; they are insoluble in alcohol,, ether,
and in all neutral menstrua; none of them are volatile: many of them
certainly fuse when heated, but not until decomposition has already
commenced ; at a higher temperature, after the loss of water, they
develope a large number of nitrogenous and non-nitrogenous, basic
and neutral products, in addition to ammonia, evolving at the same
time an unpleasant odour, which is usually compared to that of
burnt horn.
A very large number of the substances belonging to this group
dissolve unchanged in acetic and other organic acids, as well as in
common phosphoric acid; and also partially in other mineral acids
in a state of extreme dilution. On the other hand, almost all of
them are decomposed by concentrated mineral acids; many of
them swell and assume a gelatinous appearance in sulphuric and
in hydrochloric acid ; after prolonged digestion, they form, together
with ammoniacal salts, brown humus-like substances, which consist
mainly of leucine and tyrosine, (see pp. 142-3,) and a cry stalli sable
stinking volatile substance, which has not yet been accurately
investigated. All, more especially when they are heated, assume
a more or less intense yellow colour when treated with concentrated
nitric acid.
They are all metamorphosed by prolonged boiling with water ;
and the metamorphoses they thus experience from being heated
with water, have led to their classification into albuminous and
gelatigenous substances.
The alterations experienced by these bodies from the action of
oxidising substances, as for instance, chromic acid or manganese
and sulphuric acid, have been most accurately studied during the
last few years by Schlieper* and Guckelberger ;t and it is worthy
of remark that the non-nitrogenous products of this process of
oxidation belong to the butyric acid group, embracing all the acids
from formic to caproic acid and their aldehydes ; besides these we
must also reckon benzoic acid and hydride of benzoyl; but except-
ing ammonia and hydrocyanic acid, there are only very few nitro-
* Ann.'d. Ch. u. Pharm. Bd. 59, S. 1-32.
t Ibid. Bd. 64, S. 39-100.
NITROGENOUS HISTOGENETIC SUBSTANCES. 323
genous products, namely the nitriles of some of the acids of the
butyric acid group.
Some few of these substances are dissolved by the caustic
fixed alkalies in such a manner, that they can be again precipi-
tated by acids in a perfectly unchanged condition ; but the
majority can only be dissolved in a concentrated alkaline solution,
and with the continued application of heat, by means of which they
become perfectly decomposed. Since the greater number of the
bodies belonging to this group contain sulphur in addition to the
ordinary elements of organic substances, the first effect produced
by the action of heated dilute alkaline solutions is the abstraction
of the sulphur by the formation of liver of sulphur and of alkaline
hyposulphites. There is always a development of ammonia,
although this is most considerable when concentrated alkaline solu-
tions are used; carbonic and formic acids volatilise with the ammonia,
while new bodies appear in the decoction, having either an acid,
or a nitrogenous basic, or indifferent character, as for instance,
leucine, glycine, protide, &c. If these substances be mixed with
alkalies and gently fused, there will appear a large quantity of
cyanide of potassium, leucine, tyrosine, &c., besides the ordinary
products of the dry distillation of nitrogenous substances.
It is worthy of remark that these substances have the property
of being reduced to the humid condition of putrefaction without any
apparent or recognisable agency of other matters, and solely by the
influence of atmospheric agents. While it is proved that other
organic substances admitting of ready decomposition, as, for
instance, urea, are not decomposed by the atmosphere even under
the most favourable conditions, if they are in a chemically pure
condition, the connexion of the elementary molecules of these
bodies is so easily disturbed by the most ordinary atmospheric
influences, that in the presence of water, and at an ordinary tem-
perature, they begin to decompose in the course of a few hours,
or, at all events, in a day or two. The period during which they
can resist these influences, that is to say, the commencement of
decomposition, depends greatly on the state of cohesion in which
the molecules occur. The substances deposited in comparatively
dense and insoluble masses in the animal tissues, pass far more
slowly into a state of putrefaction than the more finely distributed
substances, or those which are dissolved in water. The substance
of the tendons putrefies less rapidly than cellular tissue and coagu-
lated albumen, and the latter less rapidly than soluble albumen.
The products of the putrefaction of these substances have not yet
Y 2
324 NITROGENOUS HI.STOGENETIC SUBSTANCES.
been sufficiently investigated; but among them are always to be
found carbonate, butyrate, and valerianate of ammonia, sulphide of
ammonium, leucine, and tyrosine.
It is further worthy of observation that all histogenetic sub-
stances are invariably accompanied with fats., alkalies, and salts of
lime, from which it is impossible or very difficult to separate them
without decomposition. It is not improbable that in the majority
a portion of these admixtures is chemically combined with them ;
and although but few of these chemical combinations, as that of
casein and phosphate of lime, admit of actual demonstration, many
chemists are disposed to regard a part of these adhering matters
as chemically combined, since the most ordinary indifferent
solvents are unable to separate them, while the more powerful
agents exert a decomposing or at least a metamorphic action on the
main substance ; and this applies more especially to the mineral sub-
stances accompanying these matters. Rose's investigations* re-
garding the mineral substances, have recently given greater weight
to the idea that they may in part at least be combined in a non-
oxidised condition with nitrogenous bodies, as has long been
conjectured, in accordance with Mulder's views, to be the case with
the sulphur, and in part also with the phosphorus of these substances.
Rose has advanced very satisfactory grounds for believing that a
portion of the alkalies and alkaline earths is contained in these
matters in a metallic condition, and combined with radicals con-
taining phosphorus and sulphur. We purpose, however, reverting
to this subject under the head of " the mineral substances of the
animal body."
It may easily be inferred from the abovenamed properties, that
it is extremely difficult or perhaps quite impossible to exhibit these
bodies in a chemically pure condition.
By their not crystallising, and by their not volatilising without
decomposition, we are deprived of two most important means of
readily isolating them from other substances ; while the readiness
with which they are decomposed, has hitherto prevented us from
ascertaining which of the above mineral substances are chemically
combined, and which are simply mixed with them. This refers spe-
cially to the soluble bodies of this class, as albumen, casein, &c., none
of which have as yet been exhibited in a chemically pure soluble
form. We are still more in doubt in reference to the insoluble
substances deposited in the tissues ; for even if we succeed (which
we rarely can) in extracting from them all mineral substances, we
* Ber. d. Akad. d. Wiss. zu Berlin. Decbr. 1848, S. 455-462.
NITROGENOUS HISTOGENETIC SUBSTANCES. 325
yet have no guarantee that there is only one simple, organic sub-
stance deposited in the remaining mass of tissue ; and both micro-
scopic and microscopico-chemical investigations have rendered it
probable that several chemical substances are mechanically depo-
sited by the side of one another in many of the animal tissues,
as quartz, mica, and feldspar, occur together in granite, and
cellulose and the incrusting matter, in vegetable cellular tissue.
It is often impossible to determine whether, after treating animal
tissues with the more powerful solvents, the dissolved matter was /
originally only mixed with the undissolved, or whether it must be
regarded as the product of decomposition of a body having a more
complicated composition.
We might perhaps succeed in exhibiting these substances in a
chemically pure condition, and in acquiring a more accurate know-
ledge of their chemical constitution, if they could only be united
with other substances in definite proportions, and admitted, if
possible, of a single neutral combination ; but such, unfortunately, in
very few instances is the case. Many, it is true, obviously enter into
chemical combination with alkalies, with the oxides of heavy metals,
and even with acids, but as these combinations are mixed with other
bodies and other compounds, we are hindered from establishing by
analysis any definite relation between any two of these substances.
Moreover, putting out of the question the alkaline and earthy salts
that are blended with them, we find that no definite conclusions can be
formed from the combinations of such animal matters with oxide of
lead ; for this oxide (which, with oxide of silver, we prefer to
the other metallic oxides, since it almost always forms anhydrous
compounds with organic substances, or compounds that can be
readily deprived of their water) is found to combine with these
bodies in more than one proportion ; these compounds are then
simultaneously formed^ and cannot be separated from one another.
The analysis exhibits more or less oxide of lead, according as
the neutral compound is mixed with more or less of the basic
compound. Hence we can readily understand the cause why
chemists have succeeded in so few instances in determining with
any certainty the saturating capacity and the atomic weights of
these animal substances.
In the arrangement of these bodies we are again compelled to
have recourse to a physiological principle of classification, which
is the more admissible from the circumstance that chemistry here
affords us no assistance. Our deficient knowledge regarding the
chemical properties of the bodies included in this class, does not
326 PROTEIN-COMPOUNDS.
enable us to establish a purely chemical basis on which to ground
their arrangement. But physiology so far aids us, that it indicates
which of these substances are to be regarded as original and pro-
togenic in the animal body, and which are to be regarded as origi-
nating from these by a zoo-chemical process, and constituting their
derivatives. The protogens or aborigines of these substances,
which are, in part, found in the embryo, bear so striking a
resemblance to one another, that chemists have discovered only very
slight, fluctuating, and often merely relative differences between
them. We cannot wonder, therefore, that chemists should have
conjectured that these, which had previously been termed albu-
minous bodies, possessed one common radical.
Mulder believed that he had discovered this radical, which, from
its great importance, he designated as protein, whilst he regarded
the ordinary albuminous substances as combinations of this protein
with sulphur and phosphorus, or simply with sulphur, and there-
fore called them protein-compounds. Although great doubt has
recently been thrown on Mulder's view of protein and its com-
pounds, we yet retain these names for the sake of facilitating our
comprehension and general examination of these combinations. We
purpose considering the protein-compounds or albuminous bodies
in the first group of histogenetic substances. As, however, phy-
siological chemistry has shown, with great appearance of proba-
bility, that all other nitrogenous animal substances are derived
from these protein-compounds, we will comprise, under the second
group, all those more generally diffused substances of the animal
body, which may be regarded as proximate or remote derivatives
of these compounds.
PROTEIN-COMPOUNDS.
The bodies belonging to this group occur not only in animals,
but also to a certain extent in plants. They were for a long time
regarded as merely different isomeric modifications of one and the
same compound ; but subsequently, as already observed, they have
been considered by Mulder to be combinations of one and the
same atomic group with sulphur and phosphorus. The difficulty
PROTEIN-COMPOUNDS. 327
of solving this question will be made apparent on comparing the
properties of these substances, and considering the observations
already made (at pp. 29-30) on the determination of the atomic
weights. It must rather excite our surprise that chemists should
have hazarded any theory of their composition, than that nothing
positive should as yet have been ascertained regarding their com-
position and mutual relations. Although we have the most accu-
rate analyses of the protein-compounds, it is impossible to form
any decisive conclusion regarding their internal constitution ; for
although the exactness of Mulder's analyses is undoubted, their
accuracy must yet be only commensurate with the present com-
paratively imperfect state of analytical chemistry; that is to say, the
empirical results of the analyses of these bodies do not admit of
our deciding with scientific certainty on their composition. Hence
a formula deduced from these analyses must be simply hypothe-
tical, since several formulae may frequently be derived with equal
correctness from one and the same analysis. In making choice of
one of these formulas we must therefore adopt that which appears
to guide us in the best direction, bearing in mind that we have to
deal with hypotheses only, and not with facts.
Keeping this consideration in view, we have, in the following
remarks, adhered to Mulder's recent hypothesis, in accordance with
which albuminous substances are regarded as combinations of a
purely hypothetical substance, incapable of being exhibited in an
isolated form, with different quantities of sulphamide and phospha-
mide. We only follow this hypothesis, because from the want of a
safer guide, it seems the best adapted to lead us in our advance
through this obscure department.
The following properties are common to all the protein-com-
pounds. Most of them occur in two conditions, namely in a soluble
and in an insoluble or scarcely soluble state ; in the former condition,
we find them naturally existing in the animal fluids, while they are
principally obtained in the latter form by boiling. The soluble
modification forms in a dry condition a faint yellow, translucent,
friable mass, having no smell or peculiar taste ; it dissolves in water,
but is insoluble in alcohol and ether; it is precipitated by alcohol from
the aqueous solution, after which it is usually insoluble in water ;
the aqueous solution may have either a slightly alkaline or a slightly
acid reaction, which depends, however, more on the alkali or acid
mixed with it than on the substance itself. The aqueous solution
is precipitated by most metallic salts, and the precipitate generally
contains the acid and base of the salt employed in addition to the
328 PROTEIN-COMPOUNDS.
protein-compound. The greater number cannot be precipitated
from their aqueous solution by alkalies or by most of the vegetable
acids, but they are precipitated by mineral acids (with the exception
of ordinary phosphoric acid) and by the tannic acids.
Most of them are transformed into their insoluble state by
boiling, some by acetic acid, and almost all by the mineral acids ;
with the latter they usually form compounds soluble in pure water
but insoluble in water to which an acid has been added, and inca-
pable of being restored to the soluble modification by saturating
the acid with a base. The protein-compounds, when precipitated
by salts, usually assume the insoluble form.
The insoluble compounds, when dried, are white and pulver-
isable ; when newly precipitated they are usually of a snow-white
colour, flocculent or in small clots, or else tough and gelatinous,
without taste or smell, without reaction on vegetable colours, and
insoluble in water, alcohol, ether, and all indifferent menstrua;
they are all more or less readily dissolved by alkalies, from which
they can be precipitated by mere neutralisation with acids. They
behave very differently towards different acids ; they are dissolved
by concentrated acetic acid and other organic acids, as well as by
ordinary phosphoric acid, and are precipitated from these solutions
by yellow as well as red prussiate of potash. They do not
dissolve in moderately concentrated mineral acids, although they
combine with them, and these compounds have the property of
being insoluble in water to which an acid has been added, although
they dissolve in pure water, after having first swelled and assumed
a gelatinous appearance. They swell in the same manner in con-
centrated sulphuric acid, but they assume at the same time a
brownish colour, and become decomposed. Their relation to con-
centrated nitric and hydrochloric acid is highly characteristic ; the
former acid giving them when heated a deep lemon-coloured tint,
while concentrated hydrochloric acid causes them to assume a
gradually increasing intensely blue colour, when exposed to a mode-
rate warmth and to a sufficient supply of air. A fluid obtained by
the solution of 1 part of mercury in 2 parts of nitric acid containing
4f equivalents of water, forms the most delicate test for the protein-
compounds, (Millon,*) whether they are dissolved in a fluid or
simply interspersed in a tissue. The fluid, or the tissue that has
been moistened with it, is then heated to from 60° to 100°, when an
intense red colour is observed, which does not disappear either on
prolonged boiling or exposure to the atmosphere.
* Compt.rend. T. 27, p. 42-44.
PROTEIN- COMPOUNDS. 329
The protein-compounds, when submitted to dry distillation,
when allowed to putrefy, and when decomposed by oxidising agents,
behave precisely in the manner of the histogenetic substances gene-
rally, which has been already described (pp. 322-3) ; giving rise to
the above-named products of decomposition, although in different
relations of quantity.
All protein-compounds contain sulphur, which can be very rea-
dily detected in these substances both in their natural state, and when
boiled, either by heating them with a little alkali on silver foil (when a
yellowishbrown spot of sulphide of silver will be formed,) or by boil-
ing their alkaline solution for some time with strong acids, when sul-
phuretted hydrogen will be developed, or with acetate of lead, when
sulphide of lead will be precipitated. It is, however, worthy of notice
that the protein-compounds may contain sulphur under conditions in
which its presence cannot be detected, as Mulder has shown, by the
ordinary tests. These were the bodies which were at one time re-
garded by Mulder as protein, or the non-sulphurous constituents of
albuminous matters, but he has subsequently discovered* that the
substance formerly termed protein contains sulphur. On treating
albuminous substances with a dilute solution of potash as pre-
scribed for the preparation of this supposed protein, they lose the
property of indicating the presence of sulphur by the ordinary
tests. Mulder endeavours to explain this phenomenon by suppos-
ing that those compounds which yield a sulphur-reaction, con-
tain sulphur combined with amide, and therefore as sulphamide
H2NS ; and further, that on treating them with potash, 2 atoms
of sulphamide by assimilating 2 atoms of water, are decom-
posed into ammonia which escapes, and also into hyposulphurous
acid, which combines with the non-sulphurous atomic group
to form those compounds which yield no sulphur-reaction
on silver foil. It certainly is true that all these compounds on
being digested with caustic fixed alkalies, develope ammonia, and
that those yielding the sulphur-reaction contain more nitrogen
than those which do not exhibit it. The assumption of the
presence of sulphamide in these substances, must, however, still
be regarded as a somewhat hazardous hypothesis, in the first place,
because we are as yet wholly unacquainted with this sulphamide,
whether in an isolated or combined state; secondly, because a
combination of hyposulphurous acid with an organic, scarcely basic
substance, is as unlocked for a phenomenon, as that it should not
be separable by stronger acids from its combination with the protein ;
* Chem. Untersuch. ubers. v. Volcker. H. 2, S. 179-272.
330 PROTEIN-COMPOUNDS.
and lastly, because the hyposulphites yield a most evident sulphur-
reaction when heated with organic substances on silver foil.
Mulder in like manner assumes that the phosphorus contained in
albumen, exists in the state of phosphamide, H2NP, a purely
hypothetical body, and totally different from Gerhardt's phospha-
mide, whose amide nature is moreover very doubtful, These are
some of the grounds on which we have been led to regard Mulder's
view as a mere scientific fiction. By subtracting the elements of
hyposulphurous acid from the composition of those albuminous
substances which do not yield the sulphur-reaction, and the
elements of sulphamide from those yielding such a reaction,
Mulder obtained a group of atoms of carbon, hydrogen, nitrogen,
and oxygen, which in all these compounds exhibited perfectly
identical relations, or only a slight increase of oxygen. This com-
plex atomic group contained in 100 parts 54*7 of carbon, 6- 8 of
hydrogen, 14*2 of nitrogen, and 24*3 of oxygen. For this complex
group Mulder has calculated the formula C36H25N4O104-2HO,
which expresses, according to him, the true composition of the
perfectly non-sulphurous protein.
The sulphur which is not detected by the above named reac-
tions can only be discovered and quantitatively determined by the
dry method ; fusing the dry, organic substance with a mixture of
alkaline nitrates and carbonates or caustic alkalies in a silver
crucible till the fused mass becomes perfectly white, when the
sulphuric acid which has been thus formed, can be determined from
the residual saline mass.
ALBUMEN.
Chemical Relations.
Properties. — Albumen, the principal representative of the pro-
tein-compounds, is distinguished amongst these bodies by its
occurrence in very different modifications, which are however not
to be sought in a different arrangement of the atoms of this sub-
stance, that is to say, in a polymerism or metamerism, but depend
alone on the substances mixed with it, as alkalies and salts. Hence
the albumen of the blood differs in several points of view, not
only from that of the hen's egg, and the latter from that of a dove's
egg, but it is even found that the albumen of the blood differs in
different persons, and that the albumen of the albuminous fluids
of the same individual does not exhibit precisely similar reactions.
ALBUMEN. 331
This is one of the causes that has given rise to the various and
frequently contradictory statements abounding in chemical litera-
ture, in reference to the individual properties of albumen. Albu-
men obtained indiscriminately from various sources ought, there-
fore, not to be employed for qualitative chemical experiments,
but we should first obtain albumen in a state of the greatest pos-
sible chemical purity, and we may then ascertain the modifications
experienced in its properties and reactions by the admixture of
different substances in different proportions ; for striking differences
are produced in albumen, not merely by the presence of another body,
but by the different proportions in which it occurs. Scherer* and
myselff were the first to investigate the properties of albumen in
this point of view, but although we may have succeeded in eluci-
dating some few individual points, no perfect and scientifically
conclusive results have been attained; and notwithstanding our in-
vestigations, experiments have been subsequently made on albumen,
containing various admixtures and taken at random from any
sources. We shall in this place limit our remarks to the most
important and general relations of albumen, lest, by introducing
too many details, we should obscure and confuse our general
survey. If even slight admixtures are capable of modifying the pro-
perties of albumen, we may readily comprehend how much more
powerfully they may be affected by chemical changes, even if
small, in the grouping or arrangement of the atoms. We know
that some kinds of albumen vary in the quantity of sulphur
they contain, and others again in their saturating capacity, but
these are relations which require further investigation for their
complete solution.
We purpose adhering to the old classification, and considering
albumen in its soluble and coagulated states.
Soluble albumen, dried in the air, forms a pale yellowish,
translucent mass, which may be easily triturated and reduced to
a white powder. The specific weight of the albumen of the hen's
egg, from which the salts had not been removed, was found by C.
Schmidt} to be 1*3144 ; after calculating for the elimination the salts,
the density of pure albumen was found to be 1-2617. It becomes
positively electric by friction, and is devoid of smell, taste, and reac-
tion on vegetable colours. It swells in water, assuming a gelatinous
appearance, does not dissolve freely in pure water, but very readily
* Ann. d. Ch. u. Pharm. Bd. 40, S. 1-65, and Untersuch. zu Pathol. S/82 ff.
t Arch. f. physiol. Heilk. Bd. 1, S. 234.
J Ann. d. Ch. u. Pharm. Bd. 61. S. 156-167.
332 PROTEIN-COMPOUNDS.
in water containing chloride of sodium or any alkaline salt. It is
insoluble in alcohol and ether.
After being dried in vacuo, or at a temperature below 50°, it
can be heated to 100° without passing into the insoluble condi-
tion ; the aqueous solution, however, becomes turbid at 60°, coa-
gulates perfectly at 63°, and separates in flakes at J5°. When
excessively diluted, no turbidity can be perceived below 90°, and
coagula will only separate after it has been boiled for a considerable
time.
Albumen may be precipitated from an aqueous solution by
diluted alcohol; the precipitate, however, is not coagulated ; but
when a large quantity of strong alcohol is added, it is converted into
the insoluble or coagulated form. It behaves very differently
towards ether free from spirit; it is generally asserted that the
albumen of the serum of blood is not coagulated, while that of eggs,
on the other hand, is coagulated by ether ; but as this observation
is not constant, this supposed variation may be dependent on the
degree of concentration of the albuminous solution.
Fatty and volatile oils neither dissolve nor coagulate albumen.
It is coagulated by creosote and aniline.
Albumen is converted into the insoluble state by most acids,
but it is not precipitated by the mineral acids (except by tribasic
phosphoric acid) unless when they are added in excess. The
organic acids, with the exception of the tannic acids, do not pre-
cipitate albumen.
Alkalies do not precipitate albumen, but they convert it into
the insoluble modification.
The greater number of the metallic salts precipitate albumen ;
the precipitate containing either a combination of a basic salt with
albumen, or a mixture of two compounds, one of which consists of
the acid of the salt and albumen, and the other of the base of the
salt and albumen. The albumen generally passes into the inso-
luble state in these combinations.
Albumen is not usually found isolated in solution in the normal
animal fluids, but in combination with a small proportion of alkali,
whose quantity does not admit of exact determination on account of
the salts which are also mixed with the albumen. In some experi-
ments conducted by myself on the albumen of hens5 eggs, I found
that 1'58 parts of soda were directly combined with 1 00 parts of albu-
men, calculated as devoid of salts. This albumen has a slightly alkaline
reaction, is more readily soluble in water than pure albumen, from
which it differs mainly in the form in which it coagulates when the
ALBUMEN. 333
aqueous solution is heated (Scherer) ; for it does not separate in
flakes like pure albumen, but forms a white, almost gelatinous mass,
or simply gives rise, if the fluid is more or less diluted, to a
milky or only whitish opalescent turbidity. The alkaline reaction
of the fluid is more strongly marked after boiling, which proves
that at least a portion of the alkali must be separated from the
albumen on its coagulation. The liberated alkali combines with a
small portion of the albumen to form albuminate of soda, which
remains dissolved. This albumen, separated by coagulation, passes
however, in part, through the filter, and very soon clogs its pores.
On saturating the solution of albuminate of soda with acetic acid,
or some other organic acid, it will coagulate on being heated, like
pure albumen, into flakes that may be readily collected on the filter.
An albuminous solution, after being thus neutralised, is rendered
turbid when diluted with a large quantity of water (about twenty
times its own volume) ; a large portion of the albumen, poor in
salts and free from an alkali, being precipitated from the solution.
This phenomenon is dependent upon the circumstance that the
albumen, freed from the alkali by acetic acid, is held in solution by
the salts, which, however, when strongly diluted, lose their solvent
power, and cause the gradual separation of the albumen.
On treating this albuminate of soda with dilute alcohol, there is
a precipitation of albumen free from alkali and poor in salts ; whilst
another portion combined with more alkali remains in solution and
represents the true albuminate of soda, which we are now going
to consider. This precipitate dissolves only slightly in pure water,
but readily in aqueous saline solutions.
A further addition of alkali to the normal albumen contained
in the animal fluids gives rise to an essential difference in its
properties. When the solution has been highly concentrated, it
yields, on being heated, a translucent jelly, almost insoluble in water,
and containing, according to my observations, 4'69 parts of
potash or 3'14 of soda to 100 parts of albumen free from salts.
On diluting the solution with water, it no longer yields this colour-
less jelly or any precipitate whatever, on being heated. The albumen
even appears entirely to have lost its coagulability, but such is not
the case, for when treated with an excess of alkali, it becomes con-
verted into the coagulated state even without the application of
heat ; for if the solution be neutralised with some acid that does
not ordinarily precipitate albumen, (as acetic acid, tartaric acid, or
tribasic phosphoric acid), albumen is separated in a coagulated
334 PROTEIN-COMPOUNDS.
state. The solution of this true alkaline albuminate is distinguished
by the circumstance that, on boiling, numerous vesicles are formed
at the bottom of the vessel, which adhere so tenaciously as to im-
part a brown colour to this organic substance in process of forma-
tion ; its surface also becomes covered on evaporation with a trans-
parent film of coagulated albumen (Scherer), which has frequently
caused this albuminate of soda in the animal fluids to be mistaken
for casein. This alkaline solution yields, however, on boiling, a
perfect coagulum in the form of flakes or masses, if any neutral
alkaline salt (such as sulphate of soda, chloride of sodium, or
hydrochlorate of ammonia) either in the form of a saturated solu-
tion, or in the dry state, has been added to it, previously to its
being boiled.
Acids and metallic salts behave to these alkaline solutions of
albumen, nearly in the same way as to those of pure albumen ; but
the quantity of the metallic salt which is added, often induces modi-
fications, the newly formed albuminates being in some cases soluble
and in others insoluble in an excess of the metallic salt or of the
albuminate of soda. The greater number of these compounds
are however soluble in alkalies.
Organic acids added in excess to albuminous solutions, behave
in the same manner as alkalies added in excess, causing the albu-
men to remain dissolved on boiling; if, however, neutral alkaline
salts, such as sulphate of soda, chloride of sodium, or hydrochlorate
of ammonia be added to these solutions, the albumen separates on
boiling into flakes or clots. Further, these acid solutions on being
evaporated are covered with a membrane similar to that which is
formed by casein in acid or alkaline milk.
Coagulated or boiled albumen possesses all the properties which
we have already noticed as exhibited by the insoluble protein-com-
pounds in general. We will, therefore, simply observe that the
albumen in its transition from the soluble to the insoluble state,
losesa portion of its sulphur; for sulphuretted hydrogen is developed
in appreciable quantity: with acids it enters into combinations that
are insoluble in water containing acids, but swell and assume a gela-
tinous form in pure water, before undergoing solution in it. It may be
so perfectly combined with caustic alkalies, as to cause their alkaline
reaction entirely to disappear. When heated with concentrated
hydrochloric acid it dissolves and assumes a blue colour which in-
clines more to purple than is the case with any other of the protein-
compounds. If albumen be boiled for a long time in water, atmo-
ALBUMEN. 335
spheric air being not excluded, it gradually dissolves, forming a non-
gelatinising fluid which contains Mulder's* teroxide of protein.
Finally, albumen when treated with strong oxidising agents, as for
instance, chromate of potash and sulphuric acid, or binoxide of
manganese and sulphuric acid, yields more acetic acid, benzoic acid,
and hydride of benzoyl, and less valerianic acid, than the other
protein-compounds.
Composition. — Albumen, after being coagulated and extracted
with water, alcohol, and ether, has been so repeatedly analysed, that
we shall rest satisfied with giving the mean results of five analyses
made by Scherer,f and subjoining an analysis recently made by
Mulder,J and regarded by him as the most exact.
Scherer. Mulder. Ruling.
Carbon .... 54*883 .... 53'5 .... 53'4
Hydrogen .... 7*035 .... 7'0 .... 7*0
Nitrogen .... 15'675 .... 15'5
Oxygen \ 22'0
Sulphur I 22-365 .... T6
Phosphorus J 0'4
100-000 100-0
Riiling§ found in the albumen of the blood-serum (after sub-
tracting the ash, in accordance with the mean of several experi-
ments) 1-3255. of sulphur, and in that of hens' eggs, 1'748£,
while Mulder found on an average only l'3% in the former, and
1'6# in the latter. Albumen always retains chloride of sodium
with so much tenacity, that it is almost impossible to separate it
by washing. The quantity of phosphate of lime which it contains
is very remarkable, for, although variable, it usually amounts to
about I'6%. Mulder found from its combination with oxide of
lead that the atomic weight of albumen is 2 2483 '9, while from
the oxide of silver compound he calculated it at 22190-2. For
the reasons already advanced, (at p. 324) we are as yet unable to
establish an empirical formula for albumen ; but Mulder calculates,
according to the above hypothesis, that the albumen of eggs is
composed of 96'2£ of protein, 3'2£ of.sulphamide, and 0'6£ of
phosphamide; and deduces from these numbers the very hypo-
thetical formula, 20(C36H25N4O10.2HO) + 8H2NS + H2NP.
* Ann. d. Ch. u. Pharm. Bd. 47, S. 300, and Bullet, de Ne^rlande, 1839,
p. 404.
t Ann. d. Ch. u. Pharm. Bd. 40, S. 36.
| Scheik. Onderz. D. 3, p. 385.
§ Ann. d. Ch. u. Pharm. Bd. 58, S. 310.
336 PROTEIN-COMPOUNDS.
Combinations. — Albumen-protein contains, according to Mulder,
53'74- of carbon, 7'0£ of hydrogen, 14'2£ of nitrogen, 23- 5% of
oxygen, and 1 *6£ of sulphur. He prepares it by dissolving pure
coagulated albumen in a solution containing from -r^th to T^th
of caustic potash, and exposing it for the space of an hour to a
temperature of from 60° to 80°. The presence of sulphide of
potassium in the solution may then be proved by the ordinary
reagents. If we were at once to neutralise the fluid with acetic acid,
there would be a danger that the precipitate would contain an
admixture of sulphur, since, in 'addition to the sulphide of potas-
sium, the fluid must also contain hyposulphite of potash, which
on the addition of an acid, deposits sulphur, and forms sulphurous
acid ; this sulphurous acid again, as is well known, yields sulphur
with the sulphuretted hydrogen which is developed ; hence the
fluid must be exposed to the air, and at the same time frequently
stirred till it ceases to yield any further indication of the presence
of sulphide of potassium ; then, and not till then, we may precipi-
tate the desired body by acetic acid.
When newly precipitated, albumen-protein is of a snow-white
colour, and in the form of minute flakes ; when dried, it assumes a
pale yellow tint, is hard and brittle, swells in water into a jelly,
but is insoluble in that fluid as well as in all indifferent menstrua,
and for the rest behaves like coagulated albumen, with this excep-
tion only, that after the treatment with potash, it yields no indi-
cation of the presence of sulphur, either with the salts of lead or
on silver foil.
Preparation. — We have already shown that soluble albumen
cannot be obtained perfectly free from mineral constituents. The
soluble modification may be obtained in the greatest purity by
neutralising serum or the white of egg dissolved in water with a little
acetic acid, arid extracting with from 20 to 30 times the quantity
of distilled water, or with dilute spirit. It is however usually
prepared by evaporating the serum of the blood, or the white of egg
in platinum vessels, either in vacua or at a temperature not ex-
ceeding 50°, pulverising the yellow residue, and extracting it with
ether, and finally with alcohol.
Coagulated albumen is obtained in a perfectly pure state by
washing the precipitate yielded on the addition of hydrochloric
acid to solutions of white of egg, with dilute hydrochloric acid, in
order to remove the salts, and especially the phosphate of lime;
by dissolving the hydrochlorate of albumen in pure water, and
precipitating it with carbonate of ammonia. The precipitate
ALBUMEN. 337
is then dried, pulverised, and freed from fat by boiling alcohol and
ether.
Wurtz* obtained a soluble albumen which, however, contained
acetic acid, by treating the albumen of hens' eggs with basic acetate
of lead, and removing the lead from the albumen by means of car-
bonic acid and sulphuretted hydrogen. This albumen reddens
litmus.
Hruschauerf likewise obtained an albumen that reddened
litmus by precipitating albumen with sulphuric acid. After being
washed for a period of six weeks it reddened litmus; it was,
however, free, from sulphuric acid.
Tests. — The presence of albumen is in general very easily shown,
since the coagulability of a fluid by heat is usually regarded as a
proof of its presence; but when we consider that several other
substances (to be treated of in the sequel) likewise coagulate when
boiled, we must not adopt this property of albumen as the sole
means of its recognition, since, as has already been noticed, albu-
men under some relations either does not coagulate, or presents a
scarcely perceptible turbidity. We have already indicated the
methods by which the presence of albumen may be detected in
very acid or very alkaline fluids ; we either neutralise the fluid, or
we treat it with a strongly saturated solution of hydrochlorate
of ammonia, and then boil it. Many methods were formerly
recommended for indicating the presence of albumen, especially
when occurring only in very small quantities, among which we
may particularly notice nitric acid, corrosive sublimate, bi-chro-
mate of potash to which a small quantity of sulphuric acid has
been added, and tannic acid ; but these methods were only of value
when applied in addition to the coagulation test, since the greater
number of the protein-compounds are precipitated by them ; they
are, therefore, only regarded as conclusive when they yield re-
actions in a fluid in which no other protein-compound but albumen
is generally found. Thus, for instance, when urine coagulates on
being heated, and is likewise precipitated by nitric acid, corrosive
sublimate, chromic acid, and other means, we entertain no doubt of
the presence of albumen, although these tests yield the same
reactions with most of the other protein-compounds. As, however,
all these reagents collectively yield only a relative proof of the
presence of albumen, we can trust but little to the evidence
afforded by the mere coagulation of a fluid by heating, since animal
* Compt. rend. T. 18, p. 700.
t Ann. d. Ch. u. Pharm. Bd. 46, S. 348.
Z
338 PROTEIN-COMPOUNDS.
fluids, as for instance urine, not unfrequently deposit, on heating,
a dense, amorphous precipitate, showing no trace of albumen, and
consisting only of phosphates. This is often the case when the
urine is very slightly acid, but the precipitate may be distinguished
from coagulated albumen by the addition of a mineral acid, which
readily dissolves the earths, or by acidulating the urine, before
boiling, with a little acetic acid, when no precipitate will any
longer be obtained by boiling, if its presence were dependent
on the earthy salts of the urine.
In testing animal fluids, and especially those of a pathological
nature, we must particularly observe the form in which the
albumen coagulates, for on this, as has already been observed,
numerous other relations depend ; thus, a flocculent coagulum that
admitted readily of being collected on the filter, would show that
the albumen is not combined with an alkali, and that the latter
must have been extracted from it by an acid, since, in the normal
state all the albuminous fluids of the body contain albumen in
combination with an alkali, and coagulate like milk, or in a white,
opaque jelly. Again, if, on evaporation, an animal fluid from
which the albumen has previously been removed by boiling, become
covered with a thin, colourless membrane, we have no right to
conclude, as is so frequently assumed, that casein is present, but
simply that the fluid still contains sufficient alkali to prevent
the ordinary coagulation of the albumen, and, in short, that
although a portion of the alfiumen may have been removed by
boiling, the fluid yet contains the so-called albuminate of soda or
potash.
Morbid blood and exudations frequently contain pure albumen
that has been dissolved merely by salts ; from these fluids the
greatest part of the albumen may be precipitated by dilution with
large quantities of distilled water, first as a milky turbidity, and
finally in flakes, as was first shown by Scherer.
In the determination of albumen it must always be recollected that
we are unable to distinguish it from the similar protein-compounds
with that scientific accuracy with which we are able to recognise
most other organic substances. We may, indeed, indicate the
differences presented by the individual reactions in similar sub-
stances; but albumen unfortunately occurs in several modifications,
sometimes resembling one and sometimes another protein-compound,
while neither the determination of the saturating capacity nor the
elementary analyses of these bodies present any marked differences.
Our determination of the albumen in an animal fluid must there-
ALBUMEN. 339
fore at best exhibit only a relative certainty, and this is specially
the case where we attempt to discover coagulated albumen; fortu-
nately, however, it rarely or never occurs in this condition in the
animal organism ; and from what has already been said (at p. 328)
in relation to the properties common to the coagulated protein-
compounds, it must be apparent that in the present state of science it
is useless to attempt drawing distinctions between them. Since the
determination of the atomic weight and the elementary analysis
are here unable to throw any light on the subject, we might be
disposed to take the quantity of sulphur contained in a substance
known to be a protein-compound (see p. 329) as a means of ascer-
taining its identity with coagulated albumen, fibrin, casein, &c., but
it unfortunately happens that the quantity of sulphur contained in
one and the same body, as for instance in albumen, is not constant.
We must for the present relinquish all hope of distinguishing from
one another the different coagulated protein-compounds of the
animal body, and hence it is utterly absurd to enquire whether it be
coagulated fibrin or albumen that exists in tubercles or in carci-
noma; and yet this is a point which many adherents of the
pathologico-anatomical school believe that they have satisfactorily
settled without the aid of chemistry.
The method usually recommended for the quantitative determina-
tion of albumen in the animal fluids is simply to coagulate it by heat,
to collect it on a filter, and to dry and weigh it. At the first glance
this method seems to be highly practical, but as soon as we attempt
to prosecute it, we find our course impeded by unexpected diffi-
culties, unless we would rest content with such deficient and
inexact analyses as unfortunately are too common in pathological
chemistry. In the first place, it should be observed that the
albumen commonly contained in slightly alkaline animal fluids
cannot be regarded as capable of being collected on a filter after
its coagulation ; for while, on the one hand, some portion always
passes through the filter in consequence of its gelatinous or milky
character, the filter becomes on the other hand so quickly clogged
with the coagulated albumen as to preclude the possibility of
washing it out ; or the fluid passes so slowly through the filter,
that the albumen has time to putrefy. Those who suppose that
these evils can be remedied by the use of linen or woollen
materials as a filter, can have no idea of the degree of exactness
required in a chemical analysis; and we cannot refrain from
observing that the greater number of analyses of animal albumi-
minous fluids have been conducted in this manner, without any
z 2
340 PROTEIN-COMPOUNDS.
reference being made to these difficulties. Scherer is the only
chemist who has directed attention to these obstacles in the way
of an exact determination of the albumen, and given instructions
regarding the manner in which they may be avoided. In order to
determine with exactness the quantity of albumen in a weak
alkaline fluid, we must neutralise or slightly acidulate it with
dilute acetic acid previously to coagulating it ; on the application
of heat, the albumen will then coagulate in flakes, and may be
both perfectly and rapidly collected on the filter, through which
the fluid will pass in a state of perfect clearness. By this method
another error incident to the ordinary mode of determining
albumen is avoided, for as we have already observed, some alkali
is always liberated on boiling any normal albuminous fluid, the
fluid exhibiting a stronger alkaline reaction than it did before the
boiling. This alkali forms, with a small quantity of albumen,
the so-called alkaline albuminate, which, notwithstanding the
boiling, remains perfectly dissolved. A portion of albumen
must therefore be lost in the ordinary method, even when the
coagulated albumen can be collected on a filter, for, as already
observed, some of the albumen actually passes through the filter
in a dissolved form. Scherer's method entirely obviates this cause
of error; care must, however, be taken not to run into an opposite
extreme in treating the albumen with too large a quantity of
acetic acid, which would equally occasion a loss of the albumen
by its solution in that fluid, and its consequent passage through
the filter. Hydrochlorate of ammonia may be employed instead
of acetic acid, but in this case a longer boiling is requisite, in
order completely to precipitate the albumen from the fluid, and to
render it capable of being collected on a filter. It depends entirely
on the other steps of the analysis whether acetic acid or carbonate
of ammonia be the best suited for the purpose.
This is, perhaps, the most fitting place for drawing attention to
a point of the greatest importance in the quantitative analysis of
animal fluids, as well as of organic parts; we allude to the manner of
thoroughly drying substances to be weighed. The thorough drying
of animal substances which are in themselves hygroscopic, or which
contain admixtures of protein-compounds, extractive matters, &c., is
by no means so easy as that of already dry substances, which, in order
to be submitted to elementary analysis, have been exhibited in a per-
fectly pure state, and have been reduced to a pulverised con-
dition before weighing. It is obvious that dessication must be
effected with the same care as for an analysis with the combustion-
ALBUMEN. 341
tube, if we would not injure the result of the whole analysis ; but
the circumstance that the substances must here be weighed on
filters (whose weight in a dry condition must be predetermined,
and which are, moreover, hygroscopic), and that the substances to
be weighed cannot be pulverised beforehand, very much increases
the difficulty of our forming accurate determinations. Animal
substances mostly form horn-like masses on heating, and become
covered during dessication by a crust of dry matter, which is
impervious to the water contained in the interior ; hence it is fre-
quently impossible to remove all the water contained in such sub-
stances without exposing them to a high temperature in vacuo and
employing sulphuric acid. We must therefore, when it is possible,
simultaneously employ high temperatures, air pumps, and hygro-
scopic bodies. As analytical chemistry indicates the numerous
methods in which these three agents for the removal of water may
be employed, we will here simply observe that the two following
methods appear to us% to constitute the most expeditious means of
attaining a perfect dessication. We either heat a small and con-
venient sand-bath under the receiver of the air-pump to about
110°, and then place upon it the watch-glass or vessel on which
the substance to be dried, together with its filter, has already been
laid, and then place the sand-bath with the substance under the
air-pump over sulphuric acid, and form a vacuum ; or we place the
substance to be weighed, together with its filter, in a weighed test-
glass, which is surrounded by hot sand, and connected with a hand air-
pump provided with a chloride of calcium tube, and the air is then
abstracted exactly as in the manner directed by Liebig* in preparing
bodies for elementary analyses. In either case the dessication
should be continued as long as the substance is found to ex-
perience any loss of weight on being weighed. If the air-pump
be dispensed with, and the drying be conducted solely by means of
heat, as, for instance, by Rammelsberg's-f- or Liebig^sJ,' admirable
air-bath, the temperature must first be raised to 110° or 115°, and
the substance then allowed to cool in vacuo, for if this precaution
were not adopted, the filter and the animal substance would, during
their cooling, abstract water from the air, and thus increase in
weight. The method proposed by Becquerel and Rodier for
weighing substances, while still hot, seems even less to be relied on ;
for it is well known that by the heating of one of the scales of the,
* Handworterb. d. Chemie. Bd. I, S. 360.
t Anleit. zur quant, min. Analyse. S. 50.
% Anleit. zur quant, chem. Analyse. S. 37,
342 PROTEIN-COMPOUNDS.
balance, the rising current of air renders the substance to be
weighed apparently lighter, and analytical chemistry shows us that
hygroscopic substances, after being dried at a high temperature,
must be cooled in a closed space over sulphuric acid before their
weight can be ascertained with certainty. It is therefore here even
more necessary than in the preceding method to repeat the process
of weighing, until it yield a constant result.
When we consider that all the results of the analysis of organic
bodies are entirely dependent on the completeness of the drying
process, it is obvious that we can attach very little certainty to
many of the published analyses of pathological products. Bec-
querel and Rodier, who, next to Scherer, have undoubtedly insti-
tuted the best analyses of morbid blood, deem it necessary to
observe, as something worthy of special notice, that they have
devoted the same attention to the quantitative analysis of the
blood that is required for an elementary analysis ; although we do
not see any reason why less exactness is allowable in the far less
controllable analyses of animal fluids, than in elementary analyses.
In every analysis, but especially in organic analyses, the utmost
care is demanded on the part of the experimenter; and where this
is not afforded, the labour will result in nothing better than a loss
of time and trouble, and a detriment to science. Indeed most of
the analyses made in the department of pathological chemistry
have been conducted by chemical dilettanti, who deluded them-
selves with the false idea that they were enriching science, and
contributing to the establishment of exact medicine by their
approximative estimates. It were better for the cause of science,
had it never been weighed down by the unprofitable and crude
burden of these analyses.
Physiological Relations.
Occurrence. — Albumen occurs in all those animal substances
which supply the whole body, or individual parts of it, with the
materials necessary for nutrition and the renovation of effete
matters. Hence albumen is a principal constituent of the blood,
the lymph, and chyle, as well as of all serous fluids. It also occurs
in the fluids of the cellular tissue, in the white of egg, in the
Graafian vesicles, &c. It is especially worthy of notice, however,
that it is only in the uncoagulated state that albumen is found
these parts ; for, as we have already observed, it would be an
impossibility, scientifically considered, to distinguish coagulated
ALBUMEN. 343
albumen from other insoluble protein-compouds in the animal
body.
As we purpose in the second volume entering fully into the
quantitative relations of the albumen in the blood, it will be suffi-
cient here to observe, that the recent investigations of Becquerel
and Rodier,* with the older ones of Lecanu,f Denis^J Simon,
Nasse, and others, are tolerably agreed in stating that the quantity
of albumen in normal blood fluctates between 6'3 and 7'1£ and in
normal blood-serum between 7*9 and 9'8% ; Scherer's§ is undoubt-
edly the best method that has yet been proposed for the analysis of
the blood, which, according to his results, contains in healthy men
from 6-3 to 7'0f of albumen. Nasse|| and Poggiale^f found on
an average less albumen in the blood of most animals than in that
of man, the highest quantity being 6*7$. The blood of men
appears from the concurrent observations of experimentalists to
contain rather less albumen than that of women.
The chyle contains less albumen than the blood, but the quan-
tity is variable, as may readily be conjectured from the nature of
this fluid ; according to Nasse** it averages from 3 to 6$.
Marchand and Colbergft found only 0'434£ of albumen in
human lymph, while in that of horses NasseJJ found only 0*391$,
including some fibrin, and Schlossberger and Geiger§§ only 0'62£.
The white of hens' eggs contains, according to Berzelius,|||| from
12 to 13'8f of albumen.
The serous fluids of the animal body, physiological as well as
pathological, contain much less albumen than the serum of the
blood, as indeed might be inferred a priori from their density ; they
are however never wholly free from it.
The animal tissues are almost all surrounded by albuminous
fluid ; but the large quantity of albumen found in many of these
tissues depends upon the numerous capillaries by which they are
intersected ; as we specially observe in such organs as the liver,
kidneys, brain, and muscles.
* Gaz. meU 3 Ser.^T. 1, p. 503, &c.
t Etudes chim. sur le sang hum. Paris, 1837.
J Arch. gen. de He'd. 3 Se'r. T. 1, p. 171.
§ Haeser's Archiv. Bd. 10, S. 191.
|| Journ. f. pr. Chem. Bd. 28, S. 146.
If Compt. rend. T. 25, pp. 198-201 .
** Handworterb. d. Physiol. Bd. 1, S. 233.
tt Pogg. Ann. Bd. 43, S. 625-628.
Jt Simon's Beitr. z. phys. u. pathol. Chem. Bd. 1, S. 449-455.
§§ Arch. f. physiol. Heilk. Bd. 5, S. 391-396.
III! Lehrb. d. Chem. Bd. 9, S. 650.
344 PROTEIN-COMPOUNDS.
In the normal condition no albumen seems to pass into the
secretions, as for instance the saliva, gastric juice, bile, mucus, &c., for
although they do indeed exhibit traces of protein-compounds, these
latter differ from ordinary albumen. The pancreatic juice contains,
however, in its normal state a substance extremely similar to albu-
men, which coagulates on being heated, and perfectly solidifies the
fluid (as in the white of hens1 eggs). This substance may, however,
occur in any of these fluids in morbid conditions of the secreting
organ; and Jul. Vogel* has especially shown that the mucous
membranes may secrete albumen in addition to the ordinary mucus-
corpuscles, when abnormally excited ; (hence the presence of
albumen in a fluid resembling pus is no evidence of the presence of
true pus, or rather of a suppurating surface.)
Bernardf found that the albuminous substance of the pan-
creatic juice exhibited the same behaviour in reference to acids,
metallic salts, and to heat, as ordinary albumen, and that it was
not coagulated by acetic or lactic acid. Bernard instances as a cha-
racteristic difference, that the substance of the pancreatic juice is
soluble in water after its precipitation by alcohol, but this as we
have already observed, is likewise the case with albumen when
dilute alcohol is used. Concretions taken from the pancreatic
duct, and for which I am indebted to the kindness of Professor
Hasse, dissolved almost entirely in water and exhibited the ordinary
reactions of albumen.
Mack,J Vogt, and Scherer,§ have found albumen in the liquor
amnii} and the two latter enquirers ascertained from their observa-
tions that the amniotic fluid is richer in albumen in the earlier than
in the later periods of fcetal life.
Vogt found in the fluid of a foetus at the fourth month 10*77^
and in that of one at the sixth month 6*67$ albumen. Scherer,
however, in that of one at the fifth month, found 7'6J%. and only
0'82g in the fluid at the ordinary period of delivery.
In the physiological or normal condition no albumen is con-
tained in the excretions, and its appearance indicates either disease
of the excreting organ or a complete alteration in the composition
of the blood.
The occurrence of albumen in the urine may be coincident
with very different pathological conditions, although its presence was
* Untersuch. lib. Eiter, Eiterung u. s. w. Erlangen. S. 75.
t Arch. gen. de He'd. 4 Ser .T. 19, p. 68.
I Heller's Arch. f. Chem. u. Mikrosk. Bd. 2, S. 218.
$ Zeitschr. f. wissenschaftl. Zool. Bd. 1, S. 88-92.
ALBUMEN. 345
formerly made to constitute a special disease. Simon even asserts
that he has often found albumen in the urine of persons, at all
events, apparently healthy. In many acute and chronic diseases^
unconnected with affections of the kidneys, albumen not unfre-
quently appears for a short time in the urine, as, for instance, in in-
flammations of the thoracic organs, acute articular rheumatism, inter-
mittent fevers, typhus, measles, cholera, insufficiency of the valves
or contraction of the orifices of the heart, also in chronic affections
of the liver, and in pulmonary and peritoneal tuberculosis, espe-
cially towards the fatal termination of these diseases. The transi-
tory passage of albumen into the urine appears to depend in these
conditions on a change in the character of the blood, in conse-
quence of which the albumen is able to penetrate through the tissue
of the kidneys. It is, however, in affections of the kidneys, whether
acute or chronic, that albumen appears most constantly in the urine.
Bright's disease, is, as is well known, a term of very wide signifi-
cance, but if we limit it as much as possible, and merely include
under the term a degeneration of the tissue of the kidney, more
especially of the cortical substance, whether of a fatty or other
character, we may regard the presence of albumen in the urine as
a constant symptom of this disease. But in transitory renal catarrh,
such, for instance, as occurs in erysipelas nearly as frequently as
after scarlatina, albumen, together with the well known epithelial
cylinders of Bellini's ducts, is found as constantly in the urine as
in inflammatory affections of the kidneys, where it is associated
with the fibrinous plugs from the same ducts, and as in true
Bright's disease. It is almost unnecessary to observe that the
presence of pus or blood in the urine necessitates that of albumen,
but it is worthy of notice that a little albumen, together with mucus-
corpuscles is always found in uncomplicated severe catarrhs of the
mucous membrane of the bladder.
The observations already made in reference to the occurrence of
albumen in the urine apply almost equally to its appearance in the
solid excrements. Albumen is always found in the excrements in
diarrhoea depending upon intestinal catarrh, and in diseases compli-
cated with this affection ; the quantity of the albumen increases,
moreover, in proportion to the degree in which the blood becomes
altered during the diarrhoea; hence, we find, that not only in
dysentery and cholera, in which so much stress has been laid on the
discharge of albumen, but also sometimes in Bright's disease, albu-
men, together with entire patches of cylindrical epithelium, (in some
cases the entire thimble-like coverings of the intestinal villi) is dis-
charged in masses by the rectum.
346 PROTEIN-COMPOUNDS.
Origin. — We have at present very little definite knowledge
regarding the origin of albumen from the nitrogenous food. No
doubt can be entertained that the chief source of the albumen of
of the blood is to be sought in the protein-compounds contained in the
food ; for independently of the circumstance that direct experiments
prove that animals cannot exist on food containing no protein-
compounds, we find from comparative statistics of the food which
has been taken, and of the nitrogenous matters expended in the
metamorphosis of tissue, (See " Nutrition " in the third volume,)
that the animal organism derives more than a sufficient supply of
protein-compound from the ordinary vegetable food. Although we
are not yet able to decide with absolute certainty on the incapability
of the animal organism to generate albumen from other sources than
protein-compounds, it yet appears highly probable that such is the
case. We are not even acquainted with the mode of origin of the
albumen of the blood from the allied protein-compounds contained
in the food, as casein, vitellin, fibrin, legumin, &c.: all we know is
that these bodies are converted by the process of digestion into
substances differing very much in their physical properties from the
above protein-compounds but resembling one another in their solu-
bility in water, their insolubility in alcohol, and their incapability of
coagulating. How and where these peptones become converted
into the normal albumen of the blood, are points on which we are
entirely ignorant, neither can we understand by what process
the albumen acquires its due quantity of sulphur, since these
peptones, as I have convinced myself, for the most part contain
exactly as much sulphur as the substances from which they
originate.
Uses. — After what has been said of the occurrence of albumen,
it seems scarcely necessary to adduce any further proof of its
utility in forming and renovating the nitrogenous tissues of the
animal body. In fact the whole theory of nutrition rests on this
postulate. It is a question that has been much contested and
variously answered, whether albumen directly cooperates in the
formation of cells and the elements of tissues. Jul. Vogel* is an
especial supporter of the view that fibrinous exudations are alone
adapted for the formation of cells and tissues ; basing his opinion
on pathologico-anatomical experiments on exudations, and on the
fact that a small quantity of fibrin is contained in the lymph for the
* Path. Anat. S. 80 ff. [or p. 107, &c., of the English Translation. Vogel's
opinion is'not quite fairly stated in the text. His remarks apply solely to morbid
developments. — G. E. D.]
ALBUMEN. 347
reproduction of effete materials. The absence of fibrin in the fluids
of the egg, must also be considered as opposing VogePs view, since
these fluids exhibit the highest degree of plasticity ; yet it must be
admitted on the other hand, that this counter-proof is less worthy
of attention from the circumstance that vitellin, which is the true
germ of the egg, has been found by the most careful investigation
to be more similar to fibrin than any other protein-compound, having,
indeed, an almost perfectly identical composition with it. But
independently of the peculiar relations of the germ of the egg, a
careful consideration of plastic exudations will in itself lead us to
doubt the correctness of VogePs view, for how can the small quantity
of fibrin in the plasma (see " Fibrin") give rise to the frequently
large accumulations of fibrinous exudations that are passing into an
organised condition, rapidly as the resorption of the serous portions
of these exudations may be effected ? We cannot suppose that
Vogel intends to assert that it is only the fibrin of the exudations
which is converted into cells and fibres. The following mode of
considering the subject appears to correspond most closely with
the facts before us. We shall in a subsequent part of the work
enter upon the consideration of fibrin, as a link or transition stage
in the metamorphosis of nitrogenous matters ; we agree therefore
so far with Vogel as to assume that all albumen passes through a
transition stage, which we term fibrin, before it can be converted
into cells and the elements of tissues: hence this intermediate
link in the metamorphosis of tissue appears in very small quan-
tity or not at all, because at this stage the metamorphosis is
stationary for only a short time. If we regard fibrin as a body
whose specific gravity is ever changing with its chemical changes,
as, for instance, is the case with the aldehydes, it would scarcely
remain for any appreciable length of time at a given stage of
metamorphism, and would therefore be as little appreciable to our
senses as the aldehyde of acetic acid, in the process of acid fer-
mentation. We therefore believe that in the organisation of the
exudations, fibrin is formed from the albumen of the transuded
plasma, but that it rapidly undergoes further metamorphosis.
It still remains, however, for us to determine why cells and
fibres are not formed from serous exudations, that is to say, from
albuminous solutions containing no fibrin. This question might
perhaps be answered by supposing that the presence of fibrin is
only required to form the point of crystallisation for the deposi-
tion of plastic matter, and this view seems to derive support from
the fact, that a portion of coagulated fibrin when thrown into an
348 PROTEIN-COMPOUNDS.
uncoagulated plasma, perceptibly accelerates the coagulation of the
fibrin ; but so simple an explanation is probably not admissible, and
it would rather seem that the serous exudations possess no tendency
to become organised, in consequence of their never being pure
plasma minus fibrin, but of their frequently containing less albu-
men, and in all cases more salts and extractive matters, than the
serum of the blood ; although we are unable to determine the
manner in which salts are able to arrest the metamorphosis of
albumen into cells, we yet know that other metamorphoses of
albumen, as for instance, putrefaction, are hindered or modified by
the agency of these bodies.
FIBRIN.
Chemical Relations.
Properties. — We must distinguish between numerous modifi-
cations of fibrin, if we would attempt to specify the various sub-
stances to which this term has been applied. We purpose, there-
fore, only to consider fibrin, in the first place, in its naturally dis-
solved form ; next, in a spontaneous state of coagulation ; and,
lastly, when it is coagulated by heat, or boiled.
In the natural solution of fibrin, we can distinguish only a few
of its properties, since it is here mixed with albumen and other
matters of the serum of the blood ; and we are acquainted with
few reagents by which to distinguish dissolved fibrin in filtered
frogs' blood (i. e. in blood deprived of its corpuscles), from
the albumen contained with it in solution. We at present know
nothing more of dissolved fibrin than the facts long ago advanced
by Joh. Miiller*. Neither acetic acid or caustic ammonia
induces a precipitate in the fluid of frogs5 blood; but a concen-
trated solution of caustic potash will precipitate fibrin as well
as albumen (see p. 333); ether causes fibrin to coagulate, while
it allows the albumen of frogs' blood to remain dissolved. The
spontaneous coagulation of the fibrin from the plasma of all verte-
brate animals may be greatly retarded by dilute solutions of the
alkaline sulphates, nitrates, hydrochlorates, carbonates, and ace-
tates, and may even be entirely prevented by concentrated solutions.
As we purpose treating somewhat fully of the spontaneous coagu-
lation of fibrin in the second volume of this work, when we enter
upon the consideration of the blood, we will now merely observe, that
* Lehrb. d. Phys. Bd. 1, S. 117 [or vol. 1, p. 124 of the second Edition of
the English Translation.]
FIBRIN. 349
the liquor sanguinis (after the removal of the blood-corpuscles) will
frequently assume a thick fluid and gelatinous character within two
minutes after its removal from the living body; in a short time some
drops of fluid appear on the tolerably consistent jelly, and speedily
augment, until they form an entire stratum of serum over the now
fully developed coagulum ; this coagulum now begins to contract,
becoming more or less tenacious, tough, elastic, and resistent,
according to certain accompanying conditions (as we shall more
fully explain when treating of the blood). If we trace this tran-
sition of the fibrin from the dissolved fluid condition into the
solid state under the microscope, a careful observation shows us
that the fresh liquor sanguinis exhibits nothing morphological
beyond some few colourless blood-corpuscles ; when it begins to
gelatinise, separate points or molecular granules appear at various
spots, from which arise extremely fine straight threads in radiating
lines, although they do not form star-like masses as in crystallisa-
tion; these threads becoming elongated cross those springing from
other solid points until the whole field of view appears as if it were
covered with a delicate, but somewhat irregular cobweb. This
net- work finally becomes so dense that the colourless blood-cor-
puscles imbedded in it can scarcely be distinguished.
It is scarcely necessary, at the present day, to offer any refuta-
tion of the older views, according to which, on the one hand,
fibrin arose from the bursting of the colourless or even of the red
blood-corpuscles, while, on the other, it was simply deposited from
the blood in which it was originally only suspended. The former
view has long ceased to be held by physiologists, while microscopic
observations affords ample evidence of the untenability of the latter
hypothesis.
As yet no satisfactory solution has been afforded to the question
which has been frequently raised regarding the means by which the
fibrin is held in solution in the circulating blood, and by which it
is disposed to coagulate on the removal of the plasma from the living
body. Various facts prove, indeed, that the access of the air (that is
to say, of the oxygen,) greatly influences the coagulation of the fibrin ;
but it is doubtful whether this is the only cause of coagulation,
since the same process goes on within the vessels of the living
organism, as soon as the blood ceases to circulate. This question
cannot be answered chemically, since we are at present acquainted
only with the product of this process, while it is requisite for a
correct judgment of it that we should know not only the end, but
350 PROTEIN-COMPOUNDS.
the beginning, that is to say, the substance originally held in solu-
tion in the blood. We must, therefore, still limit ourselves to the
assertion that the blood of vertebrate animals holds a substance in
solution, which, by its metamorphosis, generates a substance not
soluble in the serum of the blood, and which we call fibrin.
The view that formerly prevailed, namely, that the fibrin was
held in solution in the blood by alkalies and alkaline salts, and that
its coagulation was owing to the decomposition of the combination
of the fibrin and the alkali by the carbonic acid of the air, has been
thoroughly refuted by Nasse*; indeed, blood containing much
carbonic acid coagulates very slowly, and on the other hand, the
carbonated alkalies retard, and may even wholly prevent the coagu-
lation of the fibrin. If, therefore, we are determined upon seeking an
explanation of this phenomenon, we must rest satisfied with mere
fiction based upon analogy. Thus we may conceive that the
albumen of the blood, while undergoing a process of metamor-
phosis, is disposed to assume a metamorphosed and insoluble form
by the agency of the minutest quantity of oxygen, in the same
manner as the juice of the grape, according to Gay Lussac's expe-
riments, is brought into a condition of vinous fermentation by
means of the minutest quantity of oxygen. But when so distin-
guished an enquirer as Nasse, while* he declares this process to be
a chemical one, regards the substance that undergoes the metamor-
phosis, as endowed with vitality, we are bound to reject his expla-
nation as mere fiction ; for, independently of the fact that if a pro-
cess be chemical it must be capable of chemical explanation, it
seems to us wholly at variance with all preconceived ideas of life
to attribute life to a simple organic substance.
Spontaneously coagulated fibrin is a yellowish, opaque, fibrous
mass, which becomes hard and brittle on drying ; it is without smell
or taste, and is insoluble in water, alcohol, and ether; after being
dried it merely swells in water, and becomes again soft and flexible ;
it readily decomposes peroxide of hydrogen ; it dissolves more easily
in acetic acid and alkalies than many other protein -compounds ; it
decomposes rapidly and putrifies in the air, dissolving, if sufficient
water be present, and becoming converted into a substance which,
like albumen, is coagulable by heat ; during this process it attracts
a considerable quantity of oxygen, gradually developes ammonia,
carbonic acid, butyric acid, and sulphuretted hydrogen, and leaves
a residue consisting principally of leucine and tyrosine (Scherer,f
* Handwbrterb. d. Physiol. Bd. 1, S. 109 ff.
t Ann. d. Ch. u. Pharm. Bd. 40, S. 35.
FIBRIN. 351
Marchand,* Wurtz,f BoppJ). It is generally supposed that
spontaneously coagulated fibrin will dissolve in solutions of cer-
tain alkaline salts ; but we should greatly err if we were to regard
a fluid thus obtained as a simple solution ; for fibrin not only re-
quires a longer period to dissolve in a saline fluid than is
necessary for the solution of a simple substance in an indifferent
menstruum, but also a higher temperature, and the saline fluid
must always be kept for one or more hours at a temperature approxi-
mating to the hatching heat (between 30° and 40°), before any
considerable quantity of fibrin will be dissolved. Moreover, the
fibrin should not be too long exposed to the action of the air, if we
wish to effect its solution. Denis,§ who first noticed this solubility
of fibrin, Scherer,|| and Polli,^" used for this purpose a solution of
3 parts of nitrate of potash in 50 parts of water. Zimmermann** has
however shown that solutions of the alkaline sulphates, phosphates,
carbonates, and acetates, as well as the chlorides, bromides and
iodides, might be employed for the same object. The solution thus
obtained, which is always imperfect, and contains undissolved por-
tions requiring to be removed, is viscid, and at about 73° coagulates
in flakes. It differs from an albuminous solution in being strongly
precipitated by acetic acid (which is only the case to a slight degree
with albumen when carefully neutralised) ; it is not coagulated by
ether, in which respect it differs from the naturally dissolved sub-
stance which forms fibrin. When the fibrin has been digested for
a sufficient length of time, the solution is not rendered turbid by
dilution with water, as is the case after digestion for only a short
period. At an ordinary temperature, the clear solution remains for a
long time unaffected by the atmosphere, only depositing solid par-
ticles after it has absorbed oxygen, when it has passed into a state
of putrefaction, and exhibits vibriones.
Scherer thought that he had proved that the fibrin from arterial
blood or from venous blood in inflammatory diseases could not be
converted into this albuminous substance by saline solutions. This
view has been contradicted by Zimmermann, but the subject has
not yet been fully investigated. My own experiments tend to
show that the fibrin of the venous blood of the ox very speedily
* Lehrb. d. physiol. Chem. 8. 69.
t Ann. de Chim. et de Phys. T. 11, p. 258.
t Ann. d. Ch. u. Pharm. Bd. 69, S. 16-37-
$ Arch. g&i. de M&J. 3 S&-. T. l,p. 171.
|| Op. cit.
IT Ann. univ. di med. 1839. Apr. pp. 25-33.
** Casper's Wochenschr. No. 30, 1843.
352- PROTEIN-COMPOUNDS.
loses these properties, while that of the arterial blood of the same
animal does not dissolve in a solution of nitrate of potash. In man
I found that fibrin, whether from venous, arterial, or inflammatory
blood, was soluble, excepting in two cases of inflammatory blood ;
the arterial and venous fibrin from pigs' blood dissolved equally
well, and with great rapidity in water containing nitrate of potash.
Boiled fibrin possesses almost all the properties common to
coagulated albumen, from which it is extremely difficult to dis-
tinguish it. C. Schmidt* found the specific weight of dry fibrin
extracted with water, alcohol, and ether to be =1*2678 after de-
ducting the influence of the ash-constituents. The influence of
heat deprives this fibrin of the property of decomposing peroxide
of hydrogen, and of being converted into a soluble, albumen-
like substance by digestion in solutions of alkaline salts. With
acids and alkalies it reacts in the same manner as coagulated
albumen ; it dissolves in alkalies, and forms with them compounds
having no reaction on vegetable colours ; with acids it also forms
combinations which are insoluble in water to which an acid has
been added, but dissolve freely in pure water. Concentrated hydro-
chloric acid communicates an indigo-blue colour to it. By pro-
longed boiling in water, it becomes decomposed into a soluble and an
insoluble compound, to the former of which Mulderf has given the
name of teroxide, and to the latter, binoxide of protein. When
decomposed by chromic acid, or by peroxide of manganese and sul-
phuric acid, it yields a larger quantity of butyric acid than any of
the other protein- compounds or their derivatives; it yields, however,
less acetic and benzoic acid than albumen, although more than
gelatin (Guckelberger.J)
Composition. — Before we can consider the chemical constitution
of a body, it is always necessary to inquire whether we have to
deal with a pure and simple substance, with a chemical compound,
or, as is often the case, with a body with which several substances
are mixed. The question is more imperative in reference to fibrin
than to any other animal substance, for both microscopico-mechan -
ical investigations and many chemical experiments seem to indicate
that the ordinary, so-called purified fibrin is not a chemically
simple substance. Whether fibrin be separated from the blood
or from the lymph, it is invariably found to be mixed with hetero-
geneous morphological elements, especially with the colourless
* Ann. d. Ch. u. Pharm. Bd. 61, S. 156-167.
t Ibid. Bd. 47, S. 300 328.
t Op. cit.
FIBRIN.
blood-corpuscles, and what are termed the fibrin-discs, which are
found associated with molecular granules of various kinds, and
usually even with blood- pigment. A microscopic examination
of coagulated and perfectly washed fibrin will readily prove that
the mass under consideration is not of a homogeneous nature. It
is a chemical fact that pure fibrin (even that of the pig, which
dissolves so readily in a saline solution,) is incapable of complete
solution, and always leaves a quantity of insoluble flakes. Even if
Bouchardafs* statement is erroneous, as asserted by Dumas,
Cahour,f and MulderJ, that he has decomposed fibrin into epider-
mose and albuminose, Mulder's experiments undoubtedly tend to
show that more than one substance must lie concealed in fibrin ;
and this seems further proved by the above mentioned difference
in the fibrin in different classes of animals, as well as by its different
character in diseases, (the molecular fibrin of Zimmermann,§ the
parafibrin and bradyfibrin of Polli.||) Microscopical examination
furnishes us, however, with the chief proof that fibrin is not a simple
body.
In considering the elementary composition of this body, we
must therefore always bear in mind that the results of the analyses
refer to a mixed substance.
We will therefore content ourselves with giving the results of
Scherer's and Mulder's analyses, in order to present some idea of
the proportion of the various elements constituting fibrin.
Scherer. Mulder.
Carbon 53-571 .... 52'7
Hydrogen 6-895 .... 6'9
Nitrogen 15'720 .... 15*4
Oxygen .... ) ...i ( 23-5
Sulphur .... V .... 22-814 1'2
Phosphorus J .... I °'3
100-000 100-0
RiilmgH found 1-319$ of sulphur in the fibrin of the blood of
the ox, while Verdeilt gave it as 1'593£. Most of the later
elementary analyses of fibrin agree in the view that there is rather a
larger quantity of oxygen contained in it than in albumen ; Mulder
* Compt. rend. T. 14, p. 962.
t Ibid. p. 995.
J Ann. d. Ch. u. Pharm. Bd. 47, S. 303-305.
§ Zur Analysis und Synthesis der pseudoplast. Processe. Berlin. 1844. S. 1 10 ff.
II Gazeta med. di Milano, 1844, p. 118.
H Ann. d. Ch. u. Pharm. Bd. 58, S. 312 u. 318.
2 A
354 PROTEIN-COMPOUNDS.
therefore regards it as a higher stage of oxidation of his hypo-
thetical protein, combined with sulphamide and phosphamide, and
assigns to it the hypothetical formula, (C36H25N4On.2HO) +
H2NS + H2NP. Fats are always associated with fibrin; and
although they have not been thoroughly investigated, they would
appear to consist principally of soaps of ammonia and lime. (Berze-
lius*, Virchowf.) Dry fibrin contains about 2.6% of these fats.
Like all protein-compounds, fibrin contains mineral substances,
of which the principal is phosphate of lime. Mulder found
1'7§, but Virchow only Q'66% of this salt mixed with a little
carbonate of lime.
Compounds. — Fibrin-protein, binoxide of protein, correspond-
ing, according to Mulder's hypothesis, to the formula
6(C36H25N4O11.2HO)+S2O2, occurs, as we learn from the
same observer,;]: in most animal fluids, associated in larger or
smaller quantity with fibrin. It may be obtained from boiled
fibrin or vitellin, precisely in the same manner as albumen-
protein from albumen, or by boiling the fibrin for a long time in
water exposed to the air, or lastly by treating hair or horn with a
solution of potash, filtering the boiled fluid, and precipitating
with acetic or hydrochloric acid. It may be purified by repeat-
edly dissolving it in caustic potash, and precipitating it with acetic
acid.
This body forms a light yellow, lumpy, tough precipitate,
which, when dried in the air, cakes together into a blackish green,
shining, resinous mass, and on trituration, forms a dark yellow
powder ; it becomes very viscid in warm water, and admits of
being drawn into long, silky, shining bands and threads ; it renders
water in which it is boiled only slightly turbid, and is perfectly
insoluble in alcohol and ether ; in dissolves in dilute acetic acid
and in dilute mineral acids ; nitric acid does not communicate to
it so well marked a yellow colour as to the other albuminous
substances ; when dissolved in acids it may be precipitated by
yellow and red prussiate of potash, by tannic acid, and by ace-
tate of lead ; it is readily soluble in alkalies, from which it may
again be precipitated by acids, it fuses on being heated, and finally
carbonises, with the evolution of a horn-like odour.
Preparation. — The method first adopted by Joh. Miiller is
generally employed for obtaining the natural solution of the fibrin-
* Lehrb. d. Chem. Bd. 9, S. 88.
t Zeitschr. f. rat. Med. Bd. 4, S. 269 ff.
t Untersucb. libers.' v. Volcker. H. 2, S. 253.
FIBRIN. 355
yielding substance, viz., diluting frogs' blood with sugared water,
(1 part of sugar to 200 of water,) and filtering it.
The best means of obtaining frogs' blood for this experiment is
to amputate both thighs, and allow the blood, with which a consi-
derable quantity of lymph is mixed, to flow into sugared water,
which not only dilutes the liquor sanguinis, but retards the coagu-
lation of the fibrin ; the blood-corpuscles of the frog, like those of
most of the other amphibia, are, as is well known, much larger than
those of mammalia and birds, and therefore pass less easily through
the filter.
A considerable quantity of the natural solution of fibrin may
be obtained from human blood (the corpuscles of which have the
property of sinking very rapidly), by pouring off the very slowly
coagulating fluid which collects above the blood-corpuscles.
A single drop of fresh blood, when laid on the object stage and
covered with a piece of glass, is sufficient to exhibit the coagulation
of the fibrin under the microscope : on account of the mass of red
corpuscles the coagulation is however not so well seen as when we
employ a drop of fluid from the surface of blood, in which the red
corpuscles have sunk below the upper level.
In preparing spontaneously coagulated and boiled fibrin, the
blood-clot must be cut into fine pieces, and then washed in water
until it appears perfectly white. The fibrin obtained in this manner
is more readily washed than when obtained from whipped blood.
The process of whipping consists either in shaking the blood, as it
flows from the veins, in a bottle with shot, or rapidly stirring it
with small twigs or rods ; the blood-corpuscles remain suspended
in the serum, while the fibrin separates in delicate but dense flakes;
the greater density of the small coagula renders it difficult, how-
ever, to wash away the blood-corpuscles enclosed in these flakes, or
to obtain the fibrin as free from hsematin as that which is obtained
from the blood-clot. In order to cleanse the fibrin as much as
possible, it is necessary, first to knead it for some time in water,
and then to hang it in water in a bag of linen, by which means the
salts and the pigment gradually dissolve, and the particles of the
fluid rendered thus heavier sink to the bottom of the vessel, while
pure water rises in their place.
In order to obtain boiled fibrin in the greatest possible purity,
we must dry it after it has been boiled in wrater ; it should be then
pulverised and extracted with alcohol containing sulphuric acid,
in order to remove any remains of pigment, and finally with ether
for the removal of the fat.
2 A 2
356 PROTEIN-COMPOUNDS.
Tests. — It is only seldom that a case occurs in which any ques-
tion can arise, as to whether the substance separated from an
animal fluid is, or is not fibrin ; thus, by way of illustration, the
plasma surrounding the organs of insects coagulates on exposure to
the air, and we may term this substance fibrin ; yet it is by no
means identical with the fibrin of vertebrate animals ; for it does
not separate under the microscope into threads, and it is insoluble
in saline solutions., and even in solutions of the alkaline carbonates.
Pathological fluids, on exposure to the air, occasionally deposit a
sediment. But here the form of the coagulum as well as the
microscopic texture of the sediment must decide whether or not the
substance which is separated is fibrin ; and the action of salts upon it
may be observed in the further investigation. In many cases of
this kind the separated substance is not fibrin, but consists of
albuminous products, which appear under the microscope as minute
masses or molecular granules, and whose chemical characters may
be recognised by their behaviour with hydrochloric and nitric acids
and other reagents ; or finally it often consists of fatty or earthy
matters that can easily be distinguished by the ordinary tests from
true fibrin.
It is often perfectly impossible to distinguish coagulated fibrin
from other protein-compounds; and we are therefore not justified
in regarding every insoluble mass contained in an exudation as
fibrin : the fibrin has, in these cases, already assumed an or-
ganised condition, and exhibits the elements of tissues under the
microscope ; or we find an unorganised, amorphous mass, which is
usually not fibrin, although it may be a derivative of that body, and
exhibits no property of fibrin that is not common to all the protein-
compounds, as we see, for instance, in tubercular deposits. Many
obvious reasons conspire to render a quantitative analysis imprac-
ticable in determinations of this kind. It is therefore unchemical,
to say the least, for pathological anatomists to designate every
unorganised exudation as fibrin ; nor shall we learn to distinguish
the chemical substrata of these exudations until we shall have
thoroughly investigated, in a chemical point of view, the actual
constitution of the protein-compounds.
The quantitative determination of fibrin in animal fluids has
probably been more frequently attempted than that of any other
substance ; but we nevertheless are still without any method that
fulfils the requirements of a good analysis. The usual method of
determining fibrin quantitatively is by pressing the clot and
washing out the blood, or more frequently by shaking or whipping
FIBRIN. 357
blood before it has coagulated, and drying and then weighing the
fibrin thus separated. In the former case, notwithstanding the most
careful washing, the membranous cell- walls arid the nuclei (if indeed
they exist) of the red blood-corpuscles remain mixed with the coagu-
lum ; and there are also technical reasons why this method of treating
the blood-clot should occasion a loss of fibrin ; hence the second
method is generally preferred. We have already seen that fibrin
obtained by whipping always contains fragments of some of the
red corpuscles and most of the colourless corpuscles ; indeed the
fibrin thus obtained is far more difficult to wash, and much less
compact in its texture than that which is obtained from the blood-
clot ; it becomes somewhat reddish on exposure to the air, and
often begins to putrefy before it has been freed from all soluble
substances. The fibrin determined in quantitative analyses of blood
and lymph is never or very rarely free from the fat which adheres
most tenaciously to it. Moreover, in some forms of disease, and
in certain animals, the blood when allowed to stand deposits a floc-
culent fibrin, which on washing passes to a greater or less degree
through the filter.
If the separated fibrin were always of the same consistence, and
if one and the same relation existed in every specimen of blood
between the fibrin, the fats, and the colourless corpuscles, we
might regard the analyses of different specimens of blood, in refer-
ence to the amount of fibrin, as always admitting of comparison ;
but we know that even under strict physiological relations, the
quantity of the lymph-corpuscles suspended in the blood is
extremely variable, and thus, for instance, we cannot strictly
compare analyses of the blood after repeated venesections (when
the blood always contains a very large number of colourless cor-
puscles) with those of blood not thus modified by venesection.
Physiological Relations.
Occurrence. — The substance which on coagulation forms fibrin
occurs principally in the blood, in the lymph, and in the chyle.
Its amount in normal venous blood scarcely reaches 0.3£; accord-
ing to most observers it fluctuates between CM 9 and 0'28&. In
the blood of healthy men Scherer* found from 0-203 to 0'263£.
This substance has, however, a higher importance than from its
small amount we should at first suppose, seeing that, in different
physiological and pathological conditions, its quantity is liable to
greater variations than that of any other constituent of the blood.
* Haeser's Arch. Bd. 10, S._50.
358 PROTEIN-COMPOUNDS.
Even in different vessels the blood contains different quantities of
fibrin, although the question whether venous or arterial blood con-
tain the greater quantity is still unanswered; at all events the blood
of the portal vein contains a far less quantity of fibrin than that of
the jugular veins; according to the numerous investigations of
Schmid*, it is at least three times smaller in the former than in the
latter. From some observations of Zimmermann/f it appears that
the blood in the veins remote from the heart is richer in fibrin
than that in the veins nearer to the central organ of circulation.
Sex appears to induce no difference in reference to the amount
of fibrin in the blood, although the quantity of this constituent is
affected both by the period of life and by pregnancy. According
to the experiments of Nasse and the more recent investigations of
PoggialeJ, the blood of new-born infants contains less fibrin than
that of adults, the augmentation in the amount of fibrin being
especially striking at the period of puberty. In pregnancy, as
appears from the researches of Andral and Gavarret, it is princi-
pally in the last three months that the quantity of fibrin increases.
During an animal diet, I found that my blood contained a larger
amount of fibrin than during a vegetable diet; and Nasse§ has
made experiments on dogs with a similar result. There are more-
over many corroborative proofs of the correctness of Nasse's obser-
vation that the quantity of fibrin in the blood is increased during
prolonged fasting.
The results independently obtained by Nasse || and Poggiale
agree in showing that the blood of herbivorous animals generally
contains more fibrin than that of the carnivorous (dogs and cats), and
that the blood of birds contains even more than that of the herbivora.
The results of the quantitative determination of the fibrin in
the blood in different forms of disease are very numerous, and on
the whole tolerably accordant. The most constant and the most
decided augmentation occurs in inflammatory diseases, and espe-
cially in acute articular rheumatism ; in the last-named disease the
fibrin has been found to reach 1*1 8£, and in pneumonia 1'01£.
It is moreover worthy of remark that inflammation in which
no fever is present, and likewise mere fevers without inflammation
augment the quantity of fibrin in the blood.
* Heller's Arch. f. Chem. u. Mikrosk. Bd. 4, S. 97-132.
t Arch. f. phys. Heilk. Bd. 6, S. 586-600.
t Compt. rend. T. 25, p. 198-201.
§ Handworterb. d. Physiol. Bd. 1, S. 148.
II Journ. f. pr. Ch. Bd. 28, S. 146 ff.
FIBRIN. 359
In other diseases, as for instance, in chlorosis, typhus, tuber-
culosis, Bright's disease, and carcinoma, there seems only to be an
augmentation of the fibrin when an inflammatory complication
supervenes ; in carcinoma however, certain observations of Popp
and Heller appear to indicate that there is a decided augmentation
of the fibrin independently of any inflammatory fever.
There are no diseases in which we find a constant and certain
diminution of the fibrin ; and whenever we find any diminution of
the fibrin it is always very slight.
It is however true that in diseases where a constant diminution
of the fibrin has been supposed to exist, we have only rare oppor-
tunities of analysing the blood.
In the lymph of man Marchand and Colberg* found 0*05 2%
and in that of the horse Geiger and Schlossbergerf found 0'04£
of fibrin.
In the chyle of a horse Simon found 0'075§, and in that of a
cat Nasse found 0'13f of fibrin.
The fibrin in the muscles is by no means perfectly identical
with spontaneously coagulated fibrin ; it is one of the many species
embraced under the generic name of fibrin. J
We shall return to the consideration of the fibrin of the mus-
cles (muscle-fibrin) when we treat of chemical histology ; since, in
order correctly to understand its relations, we must have an accu-
rate knowledge of the histological elements of muscular tissue.
The remarks which have been already made on the manner of
recognising fibrin, include all that need be stated in reference to
the views advanced regarding the coagulated fibrin assumed to be
deposited in tissues or exudations.
In the preceding description of fibrin, a criticism might pro-
bably have been expected on the several varieties of this substance,
which have been described by different writers as occurring in
morbid fluids ; we have, however, made no reference to Nasse's
fibrin-discs, to Zimmermann's molecular fibrin, to Rokitansky's
pseudofibrin, or to the fibrin of later coagulation, to which
Virchow attaches much importance, because we regard discussions
on such points as out of place in the department of strict zoo-
chemistry; for it is only after the principles of zoo-chemistry
* Fogg. Ann. Bd. 43, 8. 625-628.
t Arch. f. phys. Heilk. Bd. 5, S. 392-396.
$ [Liebig has recently published a memoir on the fibrin of muscular fibre, in
which he indicates several points in which it distinctly differs from the fibrin of
the blood. See Ann. d. Ch. u.'Pharm. Bd. 73, S. 125.— G. E. D.]
360 PROTEIN-COMPOUNDS.
have been fully discussed, and when we enter on the theory of the
animal juices, that we can form a sound judgment on such subjects.
Origin. — Taking into consideration everything connected with
the occurrence of fibrin, we can scarcely entertain a doubt that it
is formed from albumen, and not directly from the protein-con-
taining food ; for its occurrence in the chyle is not opposed to this
view, partly because, as Henle has shown, fibrin may be conveyed
to this fluid by the lymphatics and blood-vessels, and partly be-
cause, as I have fully convinced myself, all the juices of the animal
body not only contain free carbonic acid but also free oxygen. It
was formerly supposed that the formation of fibrin from albumen
might very easily be accounted for ; since, according to the older
analyses of Mulder, fibrin contained one half less sulphur than the
albumen of serum, nothing seemed more simple than to assume
that the oxygen conveyed by the respiration to the blood, converted
half of the sulphur of the albumen into sulphuric acid, and that
this combined with its alkali, so that fibrin was now evolved. These
and all similar views have become untenable since more recent analyses
of albumen and fibrin have been made. If we would at present
start an hypothesis regarding the formation of fibrin, it can only
rest on the slight excess of oxygen which fibrin contains over albu-
men. The indication afforded by this fact has led, however, to
serious error in reference to the increase of the fibrin in inflam-
mations : since it was concluded that, although we may not know
how the oxygen finds its way to the albumen to form fibrin, it is at
all events incontestable that the latter is formed by a process of oxi-
dation or eremacausis; and it was further very erroneously concluded
that the augmentation of the fibrin in inflammation is dependent
on an increased rapidity of the process of oxidation, and that con-
sequently inflammation is nothing more than an actual process of
combustion. This hypothesis originally propounded by chemists,
was for a long period accepted by physicians, without any doubts
occurring as to its correctness. In accordance with chemical prin-
ciples, an excessive supply and absorption of oxygen might indeed
be regarded as the cause of an increase of fibrin ; but even this is
by no means proved ; for how would it then be possible that in
pneumonia, where a greater or lesser part of the lungs is hepatised,
that is to say, is rendered impermeable to air, a greater quantity of
fibrin should be found in the blood than during other inflammatory
affections ? This has lately been referred to the greater frequency
of the respirations, but independently of the circumstance, that in
inflammation of other parts, the number of the fibrin should then
FIBRIN. 361
attain at least the same height as in pneumonia, we know that fever,
notwithstanding it is often accompanied by an increased frequency
in the respirations, by no means gives rise to an augmentation of
the fibrin. Physiological facts lead us to exactly the opposite hypo-
thesis that the augmentation of the fibrin in inflammatory blood is
to be referred to a diminution in the supply of oxygen. The frequent
but short and incomplete respirations which occur only in febrile
(and not in non-febrile) inflammations, are only sufficient to convey
to the blood sufficient oxygen to convert certain substances into
fibrin but not to oxidise them further; this is the reason why the
amount of fibrin attains its maximum in pneumonia and pieuritis,
and why the blood in the former disease is most rich in carbonic
acid, for this gas is scantily excreted in proportion as oxygen is
scantily received by the lungs. The physiological importance of
fibrin affords arguments altogether in favour of this view.
Uses. — The phrases, progressive and regressive metamorphosis,
of whose import we have spoken in an early part of this volume,
(see p. 27 J have led to a long contest regarding the physiological
importance of fibrin. On the one hand, it has been correctly
maintained that this substance must be necessary to the formation
of tissues, since as a general rule, the only exudations which are
capable of organisation are those which contain fibrin ; on the other
hand, stress is laid upon the circumstance that an augmentation of
the fibrin coincides with those states in which nutrition and reno-
vation are most affected, and on the incontestable fact that the
fibrin in the blood is found to be increased when more albuminous
matters have been taken as food than could be applied to the repa-
ration of effete tissue. We regard it, however, as superfluous to
enter into the detailed arguments for and against these two opinions.
The bearing of the whole case is simply this. It is pretty well
established that fibrin is formed by a process of oxidation from albu-
minous matters ; now we know that almost all the tissues are richer
in oxygen than fibrin, and on the other hand, that the effete mate-
rials of tissue and the excess of nutrient matter can only be removed
from the system, that is to say, be converted into ordinary excreta,
by oxidation. Hence, the simplest view is to regard fibrin as
representing a transition stage. If an albuminous body in the
animal organism be more highly oxidised, it cannot altogether
exceed the transition stage which is represented by fibrin, although
indeed, the formation and increase of the latter may not always be
evident. An analogous instance from pure chemistry will elucidate
this view ; we know, from Licbig's celebrated investigations on fer-
362 PROTEIN-COMPOUNDS.
mentation, the intermediate stages which during the process of acid
fermentation present themselves between the two extremes of spirit
of wine and acetic acid. We know that by a gradual process of
oxidation, aldehyde and aldehydic acid are formed from the spirit,
although these two substances may not become apparent : the beau-
tiful investigation of Mulder regarding the Mycoderma aceti affords an
almost more analogous illustration; its cellulose can onlybeproduced
by a process of oxidation from the alcohol ; moreover, in the forma-
tion of this cellulose from the alcohol there must first be formed an
aldehyde-like substance poorer in oxygen than cellulose ; hence al-
dehyde may just as well be produced during the oxidation of alcohol
into acetic acid, as during its oxidation into cellulose. In a per-
fectly analogous manner we may regard the fibrin as representing
one of the stages in the oxidation of the albumen, wrhich is transferred
either into the tissues or into the secreted substances. There seems
to us to be no discrepancy between the above observations on the che-
mical importance of fibrin, if we will only leave nature unfettered with
divisions into progressive and regressive metamorphoses. For, if we
assume the formation of tissue to be the highest stage of animal
metamorphosis, fibrin pertains to the ascending or progressive
series, inasmuch as it yields the proximate stratum for the develop-
ment of cells and the formation of tissues ; on the other hand, it
must be classed in the descending or regressive series, in so far as
its quantity in the blood is found to be increased in diseases, or
after the excessive use of albuminous food, when it does not be-
come converted into tissue but is changed by oxidation into the
ordinary excreted matters. For we cannot believe that, as in the
percussion-apparatus of Physicists, a given quantity of fibrin will
repel and displace a corresponding amount of tissue. In short, we
seem to be nearest the truth in regarding fibrin as representing one
of the most common stages in the metamorphosis of albuminous
substances.
We must not conclude our observations on fibrin without
noticing a very common error that has crept into pharmacology from
the misunderstanding of a chemical fact. Many physicians believe
that the antiphlogistic power of nitrate of potash is explained by
the chemical fact that spontaneously coagulated fibrin dissolves in
a solution of nitre. Without entering into the question whether this
salt actually possesses the power ascribed to it, we assert that this
mode of explanation is altogether untenable, for it is difficult to
draw the conclusion that nitre can prevent the formation or aug-
mentation of fibrin in inflammatory blood, simply because coagu-
FIBRIN. 363
lated fibrin is soluble in a solution of this salt. According to
Scherer, the fibrin of inflammatory blood appears to be insoluble
in this saline solution ; how then can a solution of nitre prevent
the augmentation of fibrin in inflammatory blood through a
solvent power which, in relation to this inflammatory fibrin, it
actually does not possess ?
There would be much more probability in the assumption that
a solution of nitre hindered the coagulation of highly fibrinous blood,
or that it redissolved already coagulated fibrin. The most simple
arithmetical example will illustrate this view. Scherer asserts that
1 part of nitre is required to dissolve 1'5 parts of fibrin; as-
suming that the quantity of the blood amounts to twenty pounds,
and that it contains only 0'3f of fibrin, the whole amount of fibrin
would be not less than 300 grains, and to dissolve this quantity
200 grains of nitre should be at once taken ; physicians, however,
usually prescribe about 10 grains every two hours, so that in 24
hours 100 or 120 grains are at most all that is taken to act upon
the fibrin. But the amount of nitre in the blood can never rise
even to this insufficient height, partly because the salt becomes
distributed from the blood-vessels into the juices of the body
generally ; and partly because it is much too rapidly carried off by
the urine to admit of its accumulating in great quantity in the
blood. Even if it were possible to prove that nitre possesses this
power, it would be very singular and inexplicable why we never
class amongst the special antiphlogistic medicines other salts, as,
for instance, the alkaline carbonates, which possess a much greater
power of dissolving fibrin, and of preventing its coagulation.
In this pharmacological digression, we cannot help remarking
that if inflammation were actually a process of oxidation or com-
bustion, it is very strange that we have not found the alkaline
salts of the vegetable acids, the amylacea, and the fats, to be the
most efficient antiphlogistics. It is true that we attack severe in-
flammation with tartar emetic, but even when given according to
Rasori's method, it communicates to the blood so little combustible
material as to be inappreciable, especially when combined with an
antiphlogistic diet. If inflammation were a process of combustion,
the antiphlogistic diet must be exactly the reverse of that which
we understand by the term. Moreover, direct experiments on
patients, to whom large doses of acetate and tartrate of potash
might safely be administered, have proved that these salts exert no
action either of a beneficial or of an injurious character, on the
inflammatory process. Even the most zealous adherents of the
364 PROTEIN-COMPOUNDS.
chemico-pathological theory of combustion would hardly attempt
to regard the fat in the emulsion as an antiphlogistic, since it has
been already proved by Nasse and others that the fibrin of in-
flammatory blood, and of the crusta inflammatoria, contains nearly
twice as much fat as ordinary fibrin, unless, indeed, he would
attempt to trace to this fact the digitus index medicatricis naturae,
protecting the fibrin from the action of the oxygen through the
agency of combustible fat.
VlTELLIN.
Chemical Relations.
Properties. — This is the albuminous body of the yolk of egg ;
it is so similar to albumen that, until recently, it has been con-
founded with the albumen of the white of egg ; like the latter, it
exists both in a soluble and in an insoluble modification ; the former
is not precipitated from its aqueous solution by organic acids or by
ordinary phosphoric acid, but is thrown down by' sulphuric and
hydrochloric acids ; at 60° its solution begins to become opalescent,
and at from 73° to 76° there is a deposition of larger or smaller
flakes. It is only distinguished from soluble albumen by the cir-
cumstances that (without the addition of acetic acid or of salts)
when heated, it forms flakes and clots, that it is not precipitated by
the salts of oxide of lead or of copper, and that it is thrown down
by ether.
Coagulated vitellin has the same properties as coagulated
albumen, and the similar modifications of the other protein-com-
pounds. Moreover, in its reactions it coincides with Mulder's
binoxide of protein or fibrin-protein.
Composition. — Dumas was the first who analysed this body,
and discovered that it differed from albumen; according to this
analysis, with which that subsequently made by Gobley* very well
agrees, vitellin contains 3 atoms of water more than albumen;
according to Gobley it also contains phosphorus and sulphur.
Mulder, and especially v. Baumhauerf, have subsequently made
accurate analyses of this body, and regard it as a combination of
oxide of protein with sulphamide, so that its theoretical formula
would somewhat resemble that of fibrin. According to v. Baum-
hauer, the phosphorus contained in vitellin exists in it solely in the
* Journ. de Pharm. T. 11, pp. 410-17, et T. 12, pp. 5-12.
t Scheik. Onderzoek. D. 3, p. 272, or Arch, der Pharm. Bd. 45, S. 193-220, and
Unters. II. 2, S. 80.
VITELLIN. 365
form of phosphate of lime; moreover his amount of sulphur is
obviously too small, since he only determines this substance in the
moist way.
To give a general idea of the composition* of this body, we
append the mean numbers obtained by Gobley and by v.
Baumhauer.
Gobley v. Baumhauer.
Carbon 52-264 .... 52'72
Hydrogen 7*249 .... 7'09
Nitrogen 15-061 .... 15'47
Sulphur 1-170 .... 0-42
Phosphorus .... .... 1-020 .... —
Oxygen 23'236 .... 24'30
100-000 100-00
Berzelius conjectures that we are here not dealing with a
simple substance, but with an admixture of substances, as is unfor-
tunately the case with most of the protein-compounds. Vitellin,
extracted with indifferent menstrua, contains 4 '043$- of phosphate
of lime.
Preparation. — Soluble vitellin, in a pure state, that is to say,
free from yolk-fat and from yolk-globules, has not yet been exhi-
bited. Gobley has only attempted to ascertain its reactions after
stirring the yolk of egg with water and allowing the emulsive con-
stituents, as much as possible, to deposit themselves. In its coa-
gulated form we can obtain it in a far purer state ; boiled and
triturated yolk of egg is extracted with ether, alcohol, and water,
then dissolved in acetic acid, and precipitated therefrom by
ammonia, with, however, such precaution that the fluid remains
sufficiently acid to retain the phosphate of lime in solution ; the
gelatinous precipitate is then dried and extracted with water and
alcohol.
Tests. — The methods of recognising and quantitatively determin-
ing vitellin are sufficiently obvious from our description of the pro-
perties of this body.
Physiological Relations.
Occurrence. — Hitherto vitellin has only been recognised in the
yolk of egg, of which, according to Berzeliusf, it constitutes about
17^-, or, according to the most recent investigations of Gobley,
* [Vitellin has also been recently analysed by Noad. See the Chemical
Gazette, vol. 5, p. 409. G. E. u.]
t Jahrb. d. Ch, Bd. 9, S. 650.
366 PROTEIN-COMPOUNDS.
15*76^. No eggs but those of the common hen have as yet been
examined.*
Origin. — It is very easy to conceive that vitellin may be formed
from albumen or fibrin, but in the yet imperfect state of our know-
ledge regarding albumen and fibrin as well as vitellin, we cannot
chemically trace out this metamorphosis. Since, however, it is
poorer in carbon, and somewhat richer in oxygen, than albumen, it
may, like fibrin, be regarded as one of the first stages of the meta-
morphosis of albumen by the action of oxygen, and as a certain
form of non-spontaneously coagulating fibrin.
Uses. — From the position in which vitellin occurs and from its
analogy with other albuminous substances, it is obviously one of
those nutrient substances which are employed in the formation
of the animal tissues. We are however entirely ignorant of the
chemical equations representing these changes ; from the admirable
work of Baudrimont and Martin St. Angef we may however at
least draw the conclusion that this substance loses a portion of its
nitrogen and assimilates oxygen in its conversion into tissue. (See
the " History of Development " in the third volume.)
GLOBULIN.
Chemical Relations.
Properties. — This body, which has also received the name of
crystalling occurs naturally in the soluble state, but becomes inso-
luble on boiling. Soluble globulin, when dried at 50°, forms a
yellowish, transparent mass, which may be easily triturated, and
then yields a snow-white powder ; it is devoid of smell and taste,
swells like albumen in water, and gradually dissolves, forming a
viscid solution containing merely a few flakes ; after precipitation
by alcohol from this solution, it is insoluble in water, but, like
casein, is partially soluble in boiling alcohol ; on cooling, however,
it again separates from this solution. The aqueous solution of
globulin is coagulated by ether. When dried, the soluble modifi-
cation may be heated to 100° without passing into the insoluble
state. It is distinguished from albumen and vitellin, which are
very similar to it, by the following properties ; its solution does
not become opalescent at a lower temperature than 73° ; at 83° it
* [Gobley has recently examined the eggs of the carp, which in their chemical
composition seem very similar to those of the common hen. Journ. de Chim.
meU T. 6, p. 67.— G. E. D.]
t Ann. de Chim. et de Phys. T. 21, pp. 195-257.
GLOBULIN. 367
assumes a milky turbidity, and at 93° separates as a globular mass
(if it be still mixed with hgematin) or as a milky coagulum which
never becomes clear on filtration, and from which neither small
quantities of acetic acid or ammonia separate flakes capable of
being removed by filtration ; it is only when neutral alkaline
salts are added, and the solution is then boiled, that the fluid
becomes perfectly clear and flakes and small clots are depo-
sited. The following reaction is very characteristic of globulin ;
its solution is not precipitated either by acetic acid or by ammonia,
but it becomes strongly turbid when the fluid treated with acetic
acid is neutralised with ammonia, or conversely when after the
addition of ammonia it is neutralised with acetic acid. Its behaviour
simply with acetic acid is, however, also different from that of
albumen. On the addition of a little dilute acetic acid, the solu-
tion of globulin becomes opalescent, and when heated to 50° a
milky coagulum separates ; the fluid rendered turbid by a little
acetic acid, becomes clearer when more of the acid is added, but
always remains opalescent; this fluid does not coagulate till
heated to 98° ; it is only when a very great excess of acetic acid
has been added that the globulin ceases to be coagulable by heat.
The behaviour of globulin towards mineral acids and metallic salts
is precisely the same as that of albumen. It is also coagulated by
creosote ; it decomposes and becomes putrid much more readily than
the other protein-compounds ; when boiled it developes ammonia.
Lecanu regarded this body as identical with albumen, Simon
with casein; we would rather place it by the side of vitellin, if the
elementary analyses were not opposed to this view ; but it appears
to us by no means advantageous to science, to group together
several ill-defined substances merely on the strength of a few
reactions, and without any definite proof of their similarity.
Berzelius ascribes to the globulin, united in the blood with
hsematin, the singular property of dissolving in water containing
albumen and little or no salts, but not in water which holds in
solution large quantities of alkaline salts. He was in error in re-
garding the sediment of the blood-corpuscles which he named hsema-
toglobulin, as a simple mixture of globulin and hsematin ; for
we shall shew, in the second volume (in the section on " the blood"),
that this hsematoglobulin is composed of blood-corpuscles which
by the law of endosmosis become so distended in pure water as
scarcely to be visible under the microscope, but which (unless the
blood-corpuscles have burst from too great an addition of water)
again become apparent when we add a salt to the fluid in which
368 PROTEIN-COMPOUNDS.
they are immersed, and thus render it denser ; in which case the
blood-corpuscles again contract, become denser and flatter, and
are again visible.
No properties have yet been detected in coagulated globulin
by which it may be distinguished from other boiled protein-
compounds.
Composition. — Globulin has been subjected to even fewer
analyses than vitellin ; as that which is contained in the blood can
never be perfectly freed from haematin, no accurate analysis can be
made of it. Dumas* has however analysed a specimen containing
hsematin, while both Mulderf and Ruling have analysed this sub-
stance as obtained from the crystalline lens.
Ruling.
54-2
Carbon
Hydrogen ....
Mulder.
54-5
6.9
Nitrogen ....
Oxygen 1
Sulphur J
16-5
22-1
1-2
lOO'O lOO'O
Although Berzelius assumed that phosphorus as well as
sulphur was contained in this substance, Mulder found only the
latter, which averaged O265$ : this sulphur was however determined
in the moist way ; in the dry way, I determine the sulphur in
globulin from the crystalline lens of the calf (as a mean of three
experiments) at 1*134?, and RiilingJ in globulin similarly obtained
from the ox at 1*227?-. Mulder, at present, regards globulin as a
combination of his hypothetical protein with sulphamide.
The globulin of the crystalline lens contains only a very small
amount of insoluble ash-constituents; I found only 0*241$ of
phosphate of lime.
In globulin from the crystalline lens of a calf I found 1*548$ of
soluble salts consisting of metallic chlorides, sulphate of soda
( = 30-37? of the soluble salts) and alkaline phosphates ( = 7'77? of
the soluble salts), but containing no alkaline carbonates. On the
other hand, on evaporating the fluid filtered from the coagulated
globulin (which besides 92*095$ of coagulated globulin yielded
7*905$ of soluble residue) I obtained on the incineration of this
residue an ash which contained only 13*166$ of phosphate of lime,
* Compt. rend. T. 22, p. 904.
t Journ. f. pr. Ch. Bd. 19, S. 189 ; and Bullet, d. Ne'er!. 1839, p. 196.
£ Ann. d. Ch. u. Pharm. Bd. 58,'S. 313.
GLOBULIN. 369
while the soluble salts contained a large quantity of alkaline car-
bonates, namely 1671^.
Now as the ash of non-coagulated globulin contains no alkaline
carbonate, we may conclude that in soluble globulin soda is com-
bined with an organic substance — either with the globulin itself or
with an organic acid, — and that after the destruction of the globulin
this free alkali combines with the sulphuric acid produced from the
globulin, which would account for the circumstance that the ash of
the collective globulin contains no alkaline carbonate ; if, on the
other hand, the soluble salts are separated from the globulin on
its coagulation (in the same manner as albumen on coagulation
loses its alkali) they contain much alkaline carbonate after the
combustion of the organic substance not separated with the coagu-
lated globulin, for here there is no formation of sulphuric acid to
decompose the alkaline carbonates. No alkali occurring in the ash
as a carbonate, can, according to my view, be combined with the
globulin previously to its coagulation, for the following reason.
The solution of globulin from the crystalline lens has a distinct,
although a very faint alkaline reaction; during the process of
coagulation we may easily show that it developes ammonia, and
afterwards the fluid does not, as in the case of albumen, exhibit a
stronger alkaline reaction, but on the other hand is now acid ; this
phenomenon cannot be more simply explained than by the assump-
tion that there is phosphate of soda and ammonia in the fluid, for the
solution of this salt has an alkaline reaction, loses ammonia on
boiling, and finally assumes an acid reaction when the salt is thus
converted into acid phosphate of soda. Now if globulin were con-
tained in this fluid, no acid reaction could ensue after its coagula-
tion, because the soda separated from the globulin would take the
place of the ammonia that escaped from the phosphate. Hence
this soda which is combined with carbonic acid in the ash of the
residue from which all globulin has been removed, must have been
previously in combination with an organic acid. If for the present
we regard this organic acid as lactic acid, until the subject can be
more accurately investigated, we can scarcely be charged with
adopting too bold an hypothesis, since this acid cannot at all events
be one of the volatile acids of the animal body. We are unfortu-
nately still compelled to rest upon such deductions as these in our
endeavour to investigate the nature of the salts held in solution in
association with animal substances, since as we shall subsequently
see (when treating of " the mineral constituents of the animal
2 B
370 PROTEIN-COMPOUNDS.
body/5) the constituents of the ash unfortunately afford very
little information regarding the actual constitution of the salts that
existed previously to the calcination of the residue. 1 must more-
over remark, that the boiling must be continued for some time, in
order that the acid reaction after the coagulation of the globulin
may manifest itself.
Preparation. — As in the case of soluble albumen, it is impos-
sible to prepare soluble globulin in a perfectly pure state. Globulin
presenting the reactions which we have already indicated, may be
obtained by neutralising with acetic acid the fluid of the crystalline
lens, evaporating it to dryness at a temperature not exceeding 50°,
and extracting the residue with ether and dilute alcohol. The
globulin of the blood, which cannot be separated without decom-
position of the hsematin, presents, with the exception of its colour,
exactly the same relations as the globulin obtained in the above
manner from the crystalline lens.
Mulder prepared coagulated globulin by simply extracting with
alcohol and ether globulin which had been precipitated by boiling.
The coagulated globulin which I examined was precipitated with
hydrochloric acid, washed with the same acid, then dissolved in
water, again precipitated by carbonate of ammonia, and finally
washed with water, alcohol, and ether, after which it left no per-
ceptible ash.
Tests. — In the preceding remarks we have mentioned the
reactions by which globulin may be distinguished from the similar
protein-compounds : we will here merely add that no other soluble
protein-compound is precipitated both from its acid and its alkaline
solution by neutralisation, although almost all the insoluble
protein-compounds possess this property — a circumstance which
affords a proof that globulin is reduced to the coagulated state both
by an excess of alkali and by an excess of acid. In our observa-
tions on casein, we shall point out how it may always be distin-
guished from that substance. It will always be difficult— indeed
at present it is impossible — to recognise globulin with certainty
when it is mixed with albumen or casein. Here, unfortunately,
elementary analysis affords us no assistance, since it so closely
approximates in its ultimate constitution to other protein-com-
pounds.
In attempting a quantitative determination of globulin we must
adopt the same precautionary measures as in the determination of
albumen 5 indeed, as we have already shown, there are even greater
GLOBULIN. 371
difficulties in reducing globulin to a condition in which it can be
easily and thoroughly collected on a filter, than are presented by
albumen. We must acidify with acetic acid and apply heat ; then
saturate the acid with ammonia, and boil strongly and for a con-
siderable time, in order to obtain the globulin in a state admit-
ting of its being readily collected on a filter. Even if we succeeded
in distinguishing globulin from any similar body, as for instance,
albumen, by its relation to acetic acid, and by noticing its be-
haviour when heated to 50° (see p. 370,) or by observing that it was
precipitated by the neutralisation either of its acid or its alkaline
solution, we could not by these means separate it from that
body ; for it would not be in a state fit for filtration, that is to say,
it would either pass through the filter in a turbid condition, or
it would stop up the pores of the filter and could not by any
possibility be washed off.
Physiological Relations.
Occurrence. — Globulin occurs in the cells of the crystalline lens
in a very concentrated solution. In the human lens Berzelius*
found 35-9J of dry globulin.
Globulin is one of the principal constituents of the blood,
since, with hcematin, it forms the viscid fluid contents of the blood-
corpuscles.
We can form no definite and certain idea regarding the quantity
of globulin contained in the blood-corpuscles, for even if we are
able to form an approximative idea of the amount of heematin
contained in the corpuscles (see p. 305) we have no means of
deciding how much of the remainder of them (amounting to 94'28%)
is to be ascribed to fat, to the enveloping membrane, and to glo-
bulin. Hence it is not possible to make any accurate statement
regarding the quantity of globulin contained in the blood generally.
We shall, however, return to this subject in the second volume,
when treating of " the blood-corpuscles."
Globulin has not yet been found in any other parts of the
animal body. In the present state of organico-analytical chemistry
we are unable to attempt to seek it in its coagulated state.
Origin. — In regard to the seat of the formation of globulin, no
reasonable doubt can be entertained that it at present has only
been found in cells and cell-like bodies like the blood-corpuscles.
Whichever view we adopt regarding the mechanical mode of
formation of the red from the colourless corpuscles (see p. 306) and
* Lehrb. d. Ch. Bd. 9, S. 528.
2 B 2
372 PROTEIN- COMPOUNDS.
the remarks " on the blood-corpuscles/' in the second volume) we
must arrive at the conclusion, that the globuloid is formed within a
cell or a vesicle or a closed saccule, which is bathed in an albumi-
nous fluid. If albumen lies without the enveloping membrane and
globulin exists within it, we are almost compelled to assume that the
globulin is produced by the cellular action from the albumen, but we
cannot give the chemical equation, representing how this transform-
ation takes place, for the simple reason that we are ignorant of the
rational composition both of albumen and globulin. From a com-
parison of the analyses of albumen and globulin, we can, however,
perceive that the latter contains a little less carbon and sulphur, but
rather more oxygen than the former. (Little weight can be attached
to the amount of phosphorus in albumen, in consequence of the un-
certainty connected with our modes of determining that element.)
Hence globulin appears to be albumen modified by oxidation, so
that it is allied to fibrin, or perhaps more correctly should be
placed between this substance and albumen. Moreover, the phy-
siological hypothesis, according to which the blood-corpuscles are
to be regarded as nothing more than laboratories in which the
ordinary nutrient matter, crude albumen, is first prepared, in order
to become applicable to the formation or reparation of tissues in
different organs, corresponds with this view. Whether globulin
be directly converted into fibrin, is a question which at present
is unanswerable ; we shall, however, return to this subject in a
future part of this work.
Uses. — The object of nature in depositing globulin in the
cellular fibres of the crystalline lens is too obvious to require
comment. It is, however, interesting to observe that nature, in
producing a refractive fluid, aimed at rendering the lens achromatic,
not merely by anatomical structure, but also by filling its middle
layers with a concentrated fluid which is always attenuated toward
the capsule.
Chenevix is the first to whom we are indebted for this observar
tion ; he found that the specific gravity of a lens weighing 30 grains,
taken from the eye of the ox, was 1*0765, while, when he had peeled
off the outer layers, the nucleus, weighing 6 grains, had a specific
gravity of T194.
But how nature, to carry out this object, effects the separation
or secretion of pure globulin, free from albumen and hsematin, in
the crystalline lens, from the minute capsular artery, will probably
never be understood.
From the above observations it is manifest that we can never
CASEIN." 373
understand the importance and the uses of the globulin in the
blood until we have obtained an accurate knowledge both of its
chemical constitution, and of the function of the blood-corpuscles.
CASEIN.
Chemical Relations.
Properties. — In its dry state soluble casein occurs as an amber-
yellow mass, devoid of odour, insipid and viscous when tasted, and
having neither an acid nor an alkaline reaction ; it dissolves in
water, forming a yellowish viscid fluid, which on evaporation
becomes covered with a white film of insoluble casein which may
be readily drawn off. If a concentrated solution of casein be exposed
for a long time to the air, it rapidly passes into a state of putrefac-
tion^ developing a very large quantity of ammonia, and yielding
leucine, tyrosine, and similar substances.
Alcohol renders casein opaque, and gives it the appearance of
coagulated albumen ; a part, however, of the casein dissolves in
alcohol, and on evaporation can be again obtained in an unchanged
state ; in boiling alcohol it dissolves more freely, but on cooling, the
greater part of the casein again separates ; this casein thus treated
with alcohol dissolves tolerably readily in water, especially with the
aid of heat, and has all the properties of non-coagulated casein. If
we add a little alcohol to a concentrated aqueous solution of casein,
a precipitate is thrown down which, however, dissolves again readily
in water ; if, however, the precipitation be effected by the free addi-
tion of strong alcohol, the casein is then difficult of solution or
even insoluble in water. By boiling it is not coagulated from its
solutions.
Acids precipitate casein from its aqueous solution, and partially
combine with it, but they do not reduce it to the coagulated state,
for on neutralisation with alkalies or metallic oxides, the casein
again dissolves ; these combinations of casein with acids are readily
soluble both in pure water and in alcohol. Casein is especially
distinguished from albumen by the circumstances that it is preci-
pitated from its aqueous solutions by acetic and lactic acids, the
precipitate not being an acetate or a lactate, but pure casein. The
precipitate is only slightly soluble in an excess of acetic acid;
like all the other combinations of this class with acids, it is preci-
pitated by ferrocyanide of potassium. The alcoholic solution of
casein is not only not precipitated by acids, but alcohol even
possesses the property of dissolving those combinations of casein
374 PROTEIN-COMPOUNDS.
with acids, which are insoluble in water. When treated with
concentrated nitric, hydrochloric, or sulphuric acid, casein yields
the same products of decomposition as albumen and fibrin.
Tannic acid precipitates it from very dilute aqueous and alcoholic
solutions.
Casein combines very readily with bases, turbid solutions of
this substance becoming clear on the addition of caustic alkalies;
alkaline earths dissolve in solutions of casein, and can only with
difficulty be separated from that body ; with larger quantities of
these earths casein forms insoluble compounds. Hence its solutions
are precipitated by chloride of calcium and sulphate of lime, as well
as by sulphate of magnesia, on the application of heat, which thus
afford a reaction very characteristic of casein. It resembles albu-
men in being precipitated by metallic salts, and forming with them
two combinations, namely, one of casein and the acid, and the other
of casein and the metallic oxide. Ferrocyanide of potassium does
not throw down casein from alkaline solutions, and only induces a
slight turbidity in neutral solutions.
These are the properties of casein, as it occurs in its ordinary
state of solution in the milk ; if, however, we obtain it perfectly
free from alkaJi, according to Rochleder's* method, which we shall
presently give, it presents some characters different from those
which we have just described. For instance, it dissolves only very
slightly in pure water, rather better in hot water, and not at all in
alcohol 5 it reddens blue litmus without, however, communicating
this property to water, but it forms solutions with carbonate and
phosphate of soda, which no longer exhibit an alkaline reaction ; it
dissolves very readily in solutions of hydrochlorate of ammonia,
nitrate of potash, and other neutral alkaline salts, does not coagulate
on boiling, like albumen, but forms on evaporation a film of casein
as we have already described. It dissolves in dilute mineral acids,
but is precipitated on the addition of an excess of the acid ; the
solutions of casein in dilute acids become covered on evaporation
with this colourless, transparent, and somewhat tough membrane ;
the solution of this substance in acids or in alkalies is completely
precipitated by neutralisation, and mineral acids throw it down
from its acetic acid solution. The precipitated hydrochlorate of
casein is, like the hydrochlorate. of albumen, soluble in pure water ;
before dissolving, however, it swells, like the latter, into a jelly-like
mass ; both acids and alkalies precipitate it from this solution ; the
deposit thrown down by hydrochloric acid swells and finally
dissolves in alcohol, but is precipitable from this fluid by ether, this
* Ann. d. Ch. u. Fharm. Bd. 45, S. 253.
CASEIN. 375
precipitate being again soluble in water. The mere boiling of a
solution of casein, under no circumstances,, induces a precipitation.
On the other hand, we may be readily led to believe that it is con-
verted into a coagulable substance when we have dissolved it in a
solution of carbonate of potash, or of nitre to which a little potash
has been added ; on neutralising this solution with an acid, a transi-
tory precipitate ensues on stirring or shaking the mixture, and if we
now boil the fluid, there is formed an abundant thick coagulum ; I
have not been able to persuade myself to regard this as a modification
of casein coagulable by mere heat (such as sometimes appears to be
contained in the milk) but I rather incline to the belief that the
acid has converted only a part of the caseate of soda occurring in
solution, and of the simple carbonate of soda, into acid salts, and
that on the application of heat it is only the acid salts remaining in
solution which are decomposed and evolve carbonic acid, while the
casein is precipitated.
From the above observations it follows that casein is not
reduced to its coagulated state by the same means as albumen and
globulin. We have long been acquainted with the fact that the
casein in milk is coagulated by the mucous membrane of the
stomach of the calf; our knowledge is, however, by no means clear
regarding the peculiar condition under which this coagulation
ensues. We have seen that soluble casein, on the evaporation of
its solution, is partially transformed into the insoluble modifica-
tion ; cases, however, occur, in which the whole of the casein in
milk is rendered insoluble by evaporation. Even on prolonged
exposure to the air, it is well known that milk coagulates ; the
casein thus separated reacts in the same manner as the preci-
pitate obtained from a solution of pure casein by means of lactic
acid, that is to say, after treating it with carbonate of lime or
baryta, it is only slightly soluble in water, most of it having been
transformed into the insoluble modification. Simon* and Liebig
explain the coagulation of casein by the calf's stomach (rennet)
by assuming that the latter primarily acts as a ferment, converting
the sugar in the milk into lactic acid, which precipitates the casein;
Simon moreover maintains that he has observed that solutions of
casein free from milk-sugar are not coagulated by rennet. Certain
experiments, instituted by Selmit, are, however, opposed to this
view ; he found that alkaline milk could be coagulated by rennet
in the course of ten minutes, and that, after the coagulation, it still
had a decidedly alkaline reaction ; the same was observed when
* Fraucnmilch. S. 29.
t Journ. de Pharm. T. 0, pp. 265-267-
376 PROTEIiN-COMPOUNDS.
milk, artificially rendered alkaline by the addition of soda, was
exposed to the action of rennet. Conversely, casein dissolved in
an excess of acetic or oxalic acid, coagulated, like the alkaline solu-
tion, at a temperature of from 50° to 56°. The true cause of coa-
gulation is still entirely unknown. It appears, however, from the
observations of Scherer*, that casein cannot coagulate in the form
of a membrane, unless in the presence of oxygen.
From the large number of individual facts which we have
mentioned in relation to casein, it may be inferred that our know-
ledge of this substance is still very defective ; for otherwise we
could have embraced in a few paragraphs the most essential points
in relation to this body ; our difficulties are increased by the pro-
bability that casein is not to be regarded as a simple organic body,
but as a mixture of at least two different substances. Mulderf
and SchlossbergerJ have especially directed attention to this cir-
cumstance. If freshly washed casein be digested for a couple of
days with dilute hydrochloric acid, it is found to be perfectly dis-
solved ; by neutralisation with carbonate of ammonia there is pre-
cipitated from this fluid a white, viscid body, difficult to separate
by filtration ; but in the neutralised fluid there still remains in
solution another substance which may be thrown down by an
excess of hydrochloric acid ; and the hydrochloric acid even now
holds in solution a protein-like body. The first of these bodies
was found by Schlossberger to contain sulphur, and the second to
be free from that element.
Here, however, it might be supposed that the prolonged diges-
tion of the original casein with the dilute hydrochloric acid had
decomposed it into several substances. Another and an earlier
experiment of Mulder, however, supports the view that casein con-
sists of several substances. To milk which had been as thoroughly
as possible freed from butter- globules by chloride of sodium, Mulder
added dilute hydrochloric acid, which yielded the ordinary preci-
pitate ; there remained, however, in solution, a similar body,
which was not precipitated till this mixture was boiled.
It is very difficult to arrive at a definite opinion on this point;
for any one repeating the experiments on casein which have been
described by different authors, will find that all the statements
regarding this substance confirm one another to a certain degree,
but that on often repeating the same experiment differences present
themselves which thus explain the discrepancies in the statements of
* Ann. d. Ch. u. Pharm. Bd. 40, S. 36.
**• Berzelius Jahresbr. Bd. 26, S. 910.
t Ann. d. Ch. u. Pharm. Bd. 58, S. 92-95.
CASEIN. 377
different observers. Casein appears to us to be a highly transmut-
able substance, often undergoing change on the application of the
mildest reagents. In a word, a method of preparing casein, which
would exclude all suspicion of its being changed by the process, is
still a desideratum. The circumstance that the elementary ana-
lyses of the separated matters give such slightly different results,
adds very much to our difficulty of ascertaining whether the con-
stitution of casein is simple or complicated.
Casein, when thoroughly coagulated by rennet, and purified,
is hard, and presents a yellowish translucent appearance; it softens
and swells in water, but is insoluble both in that fluid and in
alcohol. Like its soluble modification it combines with adds and
alkalies ; but on separating the inorganic part from the casein, the
latter is insoluble in water. In its relation to the stronger mineral
acids it in every respect resembles coagulated albumen ; it is as
difficult of solution in acetic acid as its soluble modification ;
alkalies dissolve it very readily, and, if concentrated, decompose it
like the other protein-compounds on the application of heat. On
heating casein, it softens, may be drawn out in threads, and becomes
elastic; and at a higher temperature it fuses, swells up, carbonises,
and developes the same products of distillation as albumen and
fibrin ; when strongly heated in the air it burns with a flame, and,
unless carefully washed with acidulated water, leaves an ash con-
taining carbonate and phosphate of lime, but no alkali.
The investigations of lljenko* show that casein during its putre-
faction, (even when perfectly freed from fat) developes at first
carbonate of ammonia and hydrosulphate of ammonia, but that,
after a space of from two to five months, its principal products are
ammonia, valerianic acid, butyric acid, and leucine, and to these
substances Boppt adds a white, crystallisable, sublimable body,
having a very strong feecal odour, and an acid which, when decom-
posed with a mineral acid, yields a brown substance together with
tyrosine, and ammonia. On fusing casein with hydrated potash, it
developes a very large quantity of hydrogen and ammonia, leaving
much valerianic acid in combination with the potash, and likewise
leucine and tyrosine. (Liebig.^:) When decomposed with chromic
acid, or with sulphuric acid and binoxide of manganese, casein yields
much more acetic acid, oil of bitter almonds, and ben zoic acid, but
much less valerianic acid and butyric acid than fibrin ; in reference
to the quantities of these products of decomposition it most nearly
* Ann. d. Ch. u. Pharm. Bd. 55, S. 78-95, and Bd. 58, S. 264-273.
t Handworterb. der Chemie v. Liebig, Wohler u. Fogg. Bd. 3, S. 220.
± Ann. d. Ch. u. Pharm. Bd, 57, S. 127-129.
378
PROTEIN-COMPOUNDS.
resembles album en, although it yields a larger amount of acetic
acid. (Guckelberger.*)
Simon has directed attention to certain differences presented by
casein from women's milky cows' milk, and the milk of the bitch.
Casein from women's milk is white or yellowish, friable, becomes
moist on exposure to the air, is insoluble in alcohol, but dissolves
in water, forming a turbid, frothy fluid, from which it is completely
thrown down by tannic acid, acetate of lead, and corrosive subli-
mate, and imperfectly precipitated by acetic acid and alum.
Casein from cows' milk is not so freely soluble in water, and, when
dry, is tough and horny ; while that from the milk of the bitch is
not tough and horny, and is difficult of solution in water. Dumas
has, however, ascertained that the composition of these three kinds
of casein is perfectly identical. There is much here that requires
explanation. Simon's observations are certainly correct ; and
can not only confirm his statements from my own experience, but
also those of Elsasser, according to which the cheesy coagulum of
women's milk is always loose and jelly-like in its texture, while
that of cows' milk is very firm and clotty. These differences may,
however, be found to depend on many external relations, on the
admixture of various substances, &c. Thus, for instance, I believe
that the jelly-like coagula of women's milk are more dependent on
the alkaline state of the fluid than on any peculiarity in the casein;
at all events, I have found that women's milk, when acid, yields a
much thicker coagulum than when alkaline, and cows' milk, when
alkaline, a much looser coagulum than when acid ; — facts of the
highest interest and value in relation to dietetics.
Composition. — Casein, like albumen, has very often been ana-
lysed, but all these analyses have led to no perfectly certain empi-
rical formula, and far less to a rational one. We give as examples,
analyses by
Carbon ....
Hydrogen
Nitrogen
Oxygen ....
Sulphur ....
Mulder.t
53-83
7'15
15-65
23-37
100-00
Scherer.J
54-665
7'465
15-724
22-146
100-000
and Dumas.§
53-7
7*2
16-6
22-5
lOO'O
* Ann. d. Ch. u. Pharm. Bd. 64, S. 39-100.
t Bullet, de Nrferl. 1839, p. 10.
£ Ann. d. Ch. u. Pharm. Bd. 40, S. 40.
§ Compt. raid. T. 21, p. 715.
CASEIN. 379
According to more recent investigations purified casein contains
0'85% of sulphur.
In casein, precipitated by acetic acid, and washed with alcohol
and ether, Ruling* found 1'015^ of sulphur; but in casein which
had been precipitated by acetic acid, dissolved in carbonate of
soda, and again precipitated by the acid, the quantity was only
0-850-JS- ; Waltherf found 0'933£, and VerdeilJ 0'842£ of sulphur in
casein, which had been treated with hydrochloric acid and car-
bonate of soda.
According to Mulder, casein is nothing more than his hypo-
thetical protein combined with sulphamide. No formula for
casein can, however, be established till the question is definitively
settled whether it be a simple or a compound body.
Casein that has not been treated with acids contains about 6£
of phosphate of lime ; more, consequently, than is contained in any
of the protein-compounds we have hitherto considered.
Preparation. — We obtain soluble casein by evaporating skimmed
milk, extracting the residue with ether, and dissolving it in
water ; we then throw down the casein from the aqueous solution
by the addition of alcohol, with which we must also carefully wash
the precipitate.
Berzelius precipitates the casein from skimmed milk by sul-
phuric acid, rinses the white coagulum with water, and decomposes
the sulphate of casein with carbonate of lime, or (which s better)
with carbonate of lead; the casein which is dissolved in water
always contains a little lead, which, however, may be removed from
the solution by sulphuretted hydrogen.
Simon removed the fat, by means of alcohol and ether, from
casein precipitated by sulphuric acid, before decomposing it with
carbonate of lime.
Mulder prepared casein for elementary analysis by precipita-
ting it from skimmed milk, by warming it with acetic acid, washing
and thoroughly rinsing the precipitate with water, separating the
fat by boiling alcohol, and finally, by drying at 130°.
According to Rochleder's§ method skimmed milk is coagulated
with dilute sulphuric acid, (acetic acid or hydrochloric acid may
however be used in its place;) the precipitate is then duly pressed
and again dissolved in a dilute solution of carbonate of soda ; this
* Ann. d. Ch. u. Pharm. Bd. 38, S. 309.
f Ibid. Bd. 37, S. 316.
% Ibid. Bd. 38, S. 319.
§ Ibid. Bd. 45, S. 253-256.
380 PROTEIN-COMPOUNDS.
solution is allowed to stand for some time in a shallow vessel,
when there gradually forms on its surface a layer of fatty matter,
which we must remove as completely as possible with a spoon, or
else we must decant the subjacent fluid with a syphon. The fluid
is now again precipitated with an acid, and the previous steps are
repeated. After the casein has been thrice dissolved in carbonate of
soda, and the fat as often skimmed off, the last trace of fatty matter
may then be easily removed by alcohol and ether, which otherwise is a
very difficult task. Casein thus prepared may moreover be rendered
entirely free from acid by repeated boiling in water ; so that if, for
instance, it has been precipitated with sulphuric acid, chloride of
barium does not excite the slightest turbidity when added to its
acid solution. Bopp* adopts a modification of Rochleder^s method;
he precipitates a solution of casein in carbonate of soda with hydro-
chloric acid, and repeatedly washes this precipitate with water con-
taining 2^ or 35. of hydrochloric acid ; it is then mixed with pure
water, in which it swells and gradually dissolves, especially if the
temperature be raised to about 40° ; the solution contains hydro-
chlorate of casein, from which the casein must be thrown down by
careful neutralisation with an alkali, and the precipitate then
washed.
Tests. — It is now ascertained that no reliance is to be placed
on certain properties of casein which were formerly regarded as
characteristic indications of its presence, and it is unfortunately
the case that recent investigations have only shown us the fallacy
of our former tests, without affording us better and more certain
means of detecting it. There were three especial properties by
which it was generally believed that casein might be recognised.
In the first place the capability of an animal fluid to form a mem-
brane on evaporation, was regarded as the most certain sign of the
presence of casein ; we have however already shown (p. 334) that
both alkaline albuminates and acid solutions of albumen equally
possess this property, and, indeed, that the fluid filtered from
ordinary coagulated albumen always contains such an albuminate,
and consequently has a tendency to form such a membrane ; the
tendency of an albuminous fluid to form a membrane on evapora-
tion, is directly proportional to the amount of alkali or albuminate
which it contains, and it is this circumstance that has led some
very accurate observers to believe that they have found casein in
the blood and in fluid exudations, where in reality not a trace of
this substance occurs.
* Ann. d. Ch. u. Pliarm. Bd. 69, S, 16-37.
CASEIN. 381
[Since the publication of this volume in German, two memoirs
on the assumed discovery of casein in the blood have appeared,
one by Guillot and Leblanc,* the other by Panum.f G. E. D.]
This error would be further promoted by a second mode of
testing for casein, namely, by its property of being precipitated by
acetic acid; this was regarded as a means of distinguishing between
casein and albumen ; but if the slight turbidity which affects albu-
minous solutions (see p. 333), when they are neutralised or very
much diluted with water, occasionally gave rise to a confusion
between these substances, this must have occurred far more fre-
quently when it was believed that the albumen had been removed by
boiling from albuminous fluids; for there then remains, as we
have already seen, a little coagulated albumen with soda or potash
in solution ; by the addition of acetic acid the albumen is precipi-
tated from this solution in precisely the same manner as casein,
which is not the case with the unboiled albuminate of potash.
Every accurate experimenter must have thus been led (till these
facts were ascertained) to believe that he had always found a little
casein in the fluid filtered from coagulated albumen.
The third means of discovering casein is the only one now left
us ; and even this, by its incorrect application, has already given
rise to false conclusions. We refer to the coagulability of casein by
rennet, — a test by which some have supposed that they have
detected casein in the blood : but in order that the casein may be
separated by this means, the rennet must be tolerably fresh, or at
all events must not have become putrid, when it is placed in the
fluid which is to be examined; the mixture should then digest,
at a temperature of 40°, for a period not exceeding two hours ; if
no coagulum is then formed, we are not justified in assuming that
casein exists in the fluid ; for if we allow the rennet to remain for
twenty-four hours or longer in the fluid at that temperature, putrefac-
tion ensues, with the development of vibriones,and the fluid becomes
turbid by the products of putrefaction, but not by coagulated
casein. Blood in which, for instance, some chemists fancy that
they have thus detected casein, putrefies, on the addition of rennet,
after a considerable time, but I have never succeeded in obtaining
from it a true coagulum of casein.
Sulphate of magnesia and chloride of calcium have been
recently recommended as very good tests for the presence of casein;
the casein separating on boiling in combination with magnesia or
* Compt, rend. T. 31, p. 585.
t Arch. f. pathol. Anat. Bd. 3, S 251.
382 PROTEIN-COMPOUNDS.
lime ; but unfortunately albuminate of soda (which, as we know,
does not coagulate on boiling) possesses this property in common
with casein.
At an earlier period of organic chemistry, many other reactions
by which casein was characterised used to be described, as,
for instance, sulphurous acid, its difficult solubility in acetic
acid, &c. ; but all these means yield no definite result. More-
ver, during the last few years, much attention has been devoted
to the behaviour of casein and of the protein-compounds gene-
rally with tests of the most varied kind; but however deserv-
ing of notice such endeavours may be, they have not produced
any great results, nor indeed could they be expected to do so,
or independently of the fact that an endeavour to discover
any decisive reactions is mere groping in the dark, when the
investigation is not guided by one uniform leading idea, the results
of these experiments so frequently vary in their individual character
that it is often impossible to bring them into harmony. Any one
who has occupied himself with such investigations, and observed
the action of acids, bases, metallic salts, &c., under various rela-
tions, on the albuminous substances, can confirm the statement
that one and the same substance, under apparently similar rela-
tions, yields the greatest diversity of reactions, sometimes pre-
senting a similarity to one and sometimes to another protein-
compound. The various relations which modify these reactions,
and of whose nature we are still ignorant, render experiments per-
fectly useless, unless these circumstances be taken into account.
In general we may suspect the modifying influence, but in special
cases we are often quite in the dark. A very simple example will
illustrate our meaning. Casein is sometimes very readily soluble
in acetic acid, at other times it is rather difficult of solution, while
again there are other occasions in which it is almost insoluble in
that fluid ; we can only conjecture that the state of cohesion, the
earthy matters contained in it, &c., give rise to this difference; but
in individual cases it is often impossible to say which of these two
conditions, or whether any other, is influencing the result of the
special observation.
I may in this place give another example of the difference
induced by inexplicable circumstances on reactions : on one occa-
sion a turbid acid solution of casein becomes perfectly clear on
the application of heat, on another the casein is entirely sepa-
rated on heating ; and thus acetic acid not unfrequently produces
only a slight precipitation in the milk of cows and other animals,
a true coagulum only separating on boiling.
CASEIN. 383
In order to determine with any certainty whether casein exists
in an albuminous fluid, we should conduct our experiment in the
following manner. The fluid must be boiled for some time, a little
hydrochlorate of ammonia having been first added, to effect the
separation of the albuminate of soda ; we must then filter it, and
ascertain whether sulphate of magnesia or chloride of calcium
yields a precipitate without the aid of heat ; if such a precipitate
be formed, we remove it by filtration, before boiling the fluid, in
order to search for casein. If a precipitate be formed on boiling
the fluid thus prepared, the presence of casein must in this case be
shown by rennet.
Acetic acid was formerly almost the only reagent employed in
the quantitative determination of casein ; but this acid by no means
effects a thorough precipitation of the casein, and when added in
excess it often dissolves a very considerable portion ; — an observa-
tion which formerly led Schiibler to the belief that the milk
contained a peculiar substance, to which he gave a special name,
zieger.* The best method of analysing milk which has yet been
proposed is, unquestionably, that of Haidlen.f On stirring milk
with about one-fifth of its weight of finely pulverised gypsum, and
heating it to 100°, a perfect coagulation ensues, and we obtain on
evaporation a brittle, easily pulverisable residue, from which ether
and alcohol easily remove the fat, milk-sugar, and most of the
salts. The residue is then not pure casein, but the quantity of
that ingredient in a state of purity may be easily calculated by
determining the quantity of fat, sugar, and salts contained in the
milk.
Physiological Relations.
Occurrence. — Casein occurs, as is well known, in the milk of all
the mammalia.
ClemmJ found 3*37^-, and Fr. Simon,§ on an average, 3'5£, of
casein in women's milk ; the latter found 4f in the colostrum, but
only 2*15£ in the milk six days after delivery. In women's milk
of good quality Haidlen|| found 3' If, but in milk of an inferior
character only 2' 7$.
In cows' milk Boussingault^f found the casein to range from 3f
* [Zieger is, literally, a sort of whey.— o. E. D.]
t Ann. d. Ch. u. Pharm. Bd. 45, S. 273 ff.
$ Inquis. chem. etc. Getting. 1845.
§ Frauenmilch. Berl. 1838.
|| Ann. d. Ch. u. Pharm. Bd. 45, S. 273 ff.
IT Ann. de Chim. et de Phys. 3 Ser. T. 8, p. &6.
384 PROTEIN-COMPOUNDS.
to 3'4£, Playfair determined the average at 4*16^, Poggiale* at
3'8%, and Simon at f%.
In the milk of bitches Simon found 14*6$ of casein, Dumasf
from 9'73£ to 13'6£, and BenschJ from 8'34f to W'24% (including
the insoluble salts.) In asses5 milk Peligot§ found 1*95^ and Stiptr.
Luiscius and Bondt|| 2'3&; the latter found 16'2% in mares' milk;
in goats' milk, Payen found 4.52-J, Stiptr. Luiscius and Bondt
9'1 2£, and Clemm 6'03% ; Schlossberger** found 9'66£ in the
milk of a he-goat, and Stiptr. Luiscius and Bondt 15 '3£ in ewes'
milk
According to Dumas and Bensch the milk contains more casein
during an animal than during a strictly vegetable diet.
The nitrogenous substance to which we apply the name of
casein, occurs in the milk, for the most part, in a state of solution,
but a not inconsiderable portion forms the free investing mem-
brane or wall of the milk-globules. The microscope alone affords
us no information regarding the structure of this membrane ; hence
we do not attach much faith to the assertions of Raspail and
Donne,tt wn° were the first to assume the existence of such a
membrane: Simon{{ believed that he had detected fragments of
these membranes in milk which had been evaporated and treated
\vith ether; Henle§§ was the first to demonstrate its existence ; on
examining under the microscope the gradual action of acetic acid on
the milk-globules, he noticed a decided distortion of this membrane.
The best proof of the existence of an investing membrane is, how-
ever, afforded by an experiment instituted by E. Mitscherlich : on
shaking perfectly/res^ milk with ether, it is scarcely at all changed,
the ether merely taking up a little fat ; now, if the milk were a
simple emulsion, it would yield all its fat to the ether, and would be
converted into a transparent, tolerably clear fluid ; as this is not
the case, the separate fat-vesicles must be surrounded by an insolu-
ble substance; if now we add a substance capable of dissolving these
membranes, ether when shaken with milk will act on it precisely
as on an emulsion, that is to say, it will take up the fatty matter ;
* Compt. rend. T. 18, pp. 506-507.
t Ibid. Bd. 21,8.708-717.
$ Ann. d. Ch. u. Pharm. Bd. 61, S. 221-227.
§ Ann. de Chim. et de Phys. T. 62, p. 432.
II Me'moires de la Soc. de Me'd. de Paris. 1787, p. 525.
** Ann. d. Ch. u. Pharm. Bd. 51, S. 431.
ft Cours de Microscopie, p. 356.
Et Medic. Chem. Bd. 2, S. 75, or English Translation, vol. 2, p. 43.
§§ Fror. Notiz. 1839, Nr. 223, and Allgemeine Anatomic, S. 942.
CASEIN. 385
and indeed this is the case if a little caustic or carbonated alkali be
added to the milk before it is shaken with ether. Mitscherlich, by
this beautiful experiment, has removed all doubt regarding the
existence of such a membrane. I have, however, observed the fol-
lowing facts : on placing under the microscope milk shaken with ether
but to which no potash has been added, the surface of the milk-
globules appears of diminished transparency, opaque, and fissured;
in short, the wall presents the appearance of being coagulated. In
place of potash I have used phosphate of soda and sulphate of soda ;
milk, treated with the former, yielded almost all its fat to ether, but
did not become so clear as when treated with potash ; under the
microscope the aqueous fluid exhibited only a few fat-globules,
which were no longer round but corrugated, of a caudate form, &c.
Sulphate of soda has the property of causing the capsules of the
milk-globules to burst, after which the fat can be extracted from
the milk by ether ; the watery fluid, however, remains very turbid,
but no longer exhibits under the microscope either milk-globules,
or shreds of destroyed capsules, but only extremely minute, scarcely
isolable, molecular granules, which are unquestionably the frag-
ments of the destroyed capsules, and do not consist of finely com-
minated fat ; for, on the addition of a little potash, they not only
do not disappear under the microscope, but the fluid which had
previously retained its milky colour becomes perfectly clear and
limpid. Hence we perceive that our ordinary casein not only
contains the protein-compound dissolved in the milk, but likewise
another, which forms the capsule of the milk-corpuscles, so that
we thus also have a microscopico-mechanical proof of the compo-
site nature of ordinary casein.
It was formerly supposed that casein existed in other animal
fluids and solid parts, and indeed it was regarded as a normal con-
stituent of the blood. In our consideration of the means by which
casein may be recognised with certainty, we have, however, shown
that no reliance can be placed on statements of this nature. Hence
we can attach no weight to the assertions that casein occurs in the
urine or in effusions within the peritoneum, the pleura, or the arach-
noid, and the cases where, in consequence of metastasis of the
milk, casein actually occurs in the urine or other fluids, require no
further mention. The same remark holds good in reference to the
supposed occurrence of casein in the saliva, in pus, tubercles, and
other morbid products.
Origin. In our entire ignorance of the true chemical constitu-
tion of casein, we cannot resort to any experiment to elucidate its
2 c
386 PROTEIN-COMPOUNDS.
mode of formation. Although we are unable distinctly to recog-
nise the presence of casein in the blood, there is no doubt that it
is formed there, and that it is merely separated by the mammary
glands. We must clearly understand the differences in the consti-
tution of albumen and casein before we can venture to offer a con-
jecture regarding the conversion of one into the other.
Uses. — The occurrence of casein in the milk, the best of all
kinds of food, leaves no doubt regarding the uses of this substance :
especially since we see how nature provides that more casein is
always supplied for the building up of the bodies of very young
animals, than is required for their future support. Casein not
only yields to the infant body the material by which soft parts are
nourished and caused to grow, but likewise conveys into the system
a sufficient quantity of bone-earth and lime to cause the skeleton of
the infant body gradually to attain its necessary solidity.
We now proceed to notice the chemical relations of certain
substances which, perhaps, strictly speaking, do not belong to
animal chemistry, since they occur only in the vegetable world :
but there are two reasons, a chemical and physiological reason,
why they should be noticed in the present place. In a chemical
point of view they deserve notice, because we thus become
acquainted with new protein-compounds, very similar to those
already described, but yet differing from them, and thus obtain a
more perfect insight into the whole group of this class of bodies ;
and in a physiological point of view they are of at least equal
importance, for it is from them that the animal protein-compounds,
which we have already described, are formed in the organisms of
herbivorous animals, and that the solid substrata of the body are
deposited in the various tissues. The actual physiological im-
portance of these substances will be noticed when we enter upon
the subject of " Nutrition.5'
GLUTEN.
Properties. — This substance, to which the name pJiytocolla has
also been applied, is, when dried, transparent, very hard and diffi-
GLUTEN. 387
cult to pulverise; when moist it is adhesive, viscid,, and elastic; it
is insoluble in cold, and very slightly soluble in hot water ; it dis-
solves readily in boiling alcohol, from which water again precipi-
tates it ; it is also precipitated from its alcoholic solution by corro-
sive sublimate and acetate of lead ; it dissolves imperfectly in acetic
acid, and hence does not seem to be a perfectly pure protein-
compound. In other respects it has all the properties of the pro-
tein-compounds.
Composition. — Gluten from several sources has been submitted
to analysis ; but here, as in the case of all the protein-compounds,
no satisfactory formula has been calculated.
The following are the results of some of the analyses of this
body:
Scherer.* Jones.f Heldt.J Mulder.§
Carbon 54'6 .... 55'22 .... 5626 .... 54-84
Hydrogen .... 74 .... 7'42 .... 7'97 .... 7'05
Nitrogen 15'8 .... 15'98 .... 15'83 .... 15'71
°X/fn ) .... 22-2 .... 21-38 .... 19-94 { 21'8°
Sulphur ) (0-60
100-0 100-00 100-00 100-00
The sulphur in gluten has been accurately determined by
Riilingll and Verdeil ;^[ the former found 1*134^ in wheat-gluten
and the latter 0'985^ in rye-gluten.
It is obvious that the numbers yielded by the above analyses
differ too widely to admit of our attempting to calculate a trust-
worthy formula.
Preparation. — As this body especially occurs in the seeds of the
cereals, the best method of obtaining it is by sufficiently knead-
ing their flour under water, boiling the residue with alcohol in
order to effect a perfect removal of the starch, and filtering while
hot ; on cooling and evaporating the solution, it is precipitated in
white flocculi.
LEGUMIN.
Properties. — This body forms either a white, nacreous, iridescent
precipitate, or else is thrown down in a flocculent form ; when dry, it
* Ann. d. Ch. u. Pharm. Bd. 40, S. 7.
f Ibid. S. 65-70.
J Ibid. Bd. 45, S. 191.
§ Versuch einer allg. phys. Ch. 1844. S. 308.
|| Ann. d. Ch. u. Pharm. Bd. 58, S. 310.
IF Ibid. 8. 318.
2 C 2
388 PROTEIN-COMPOUNDS.
has a yellow, transparent appearance, and is brittle. It coagulates
like albumen from its aqueous solution, but is precipitated from it
by acetic and phosphoric acid like casein, from which, however, it
differs, in the first place, in not dissolving in concentrated acetic
acid, and, secondly, in the circumstance that when it is precipitated
by an acid, the precipitate does not dissolve when digested with
carbonate of lime or of baryta. It is coagulated by rennet. It dis-
solves readily in ammonia and other alkalies.
Composition. — No definite results have as yet been obtained
from the analyses of legumin. The following numbers have
been found by the chemists whose names are attached to each
analysis :
Dumas & Cahours.* Jones.-]- Rochleder.!}! Ruling.§
Carbon ........ 50'50 .... 55-05 .... 56'24 .... 50'59
Hydrogen ........ 6'78 .... 7'59 .... 7'97 .... 6'83
Nitrogen ........ 18'17 .... 15'89 .... 15'83 .... 16- 54
25'5?
.... 24-55 .... 21-47 .... 19-96
Sulphur I 0-47
100-00 100-00 lOO'OO 100-00
The differences presented by these analyses are so great that
it is obvious that we have not yet succeeded in obtaining this sub-
stance in a state of purity, and fit for elementary analysis.
Preparation. — This body is chiefly found in peas and beans,
and other leguminous seeds, from which it may be easily obtained ;
the watery extract of these seeds has an acid reaction, and on
neutralisation the legumin is precipitated ; it is purified by solution
in ammonia, from which it is again precipitated by an acid, and
finally by extraction with alcohol and ether.
Besides these substances, there are in the vegetable kingdom,
and especially in seeds, other substances which approximate more
or less closely to the protein-compounds of the animal kingdom.
In the first place there is vegetable albumen, which Liebig calls
vegetable fibrin ; it is insoluble in water, and similar in its com-
position to coagulated animal albumen ; it remains undissolved,
when we have separated the starch from flour by washing, and the
gluten by alcohol. Of the diastase or mucin which is formed
during the germination of grain, and which is a product of the
metamorphosis of the previous substances, we know even less, both
* Ann. de Chim. et de Phys. T. 6, p. 409.
t Ann. d. Ch. u. Pharm. Bd. 40, S. 67.
I Ibid. Bd. 46, S. 155.
§ Ibid. Bd. 58, S. 301-315.
TEROXIDE OF PROTEIN. 389
in reference to its composition and its properties. It appears from
the investigations of Ortloff* and Buckland W. Bullf that the
emulsin or synaptase obtained from almonds is not a protein-
compound ; indeed this is sufficiently obvious from the large
quantity of oxygen (26'56£) which it contains.
There are several animal substances pertaining to the protein-
compounds of which we have no more accurate knowledge than
we have of the above named vegetable substances ; in this category
we may place keratin, the substance deposited in horny tissue,
(which, according to Mulder, is the same oxide of protein as exists
in fibrin, but combined with a far larger quantity of sulphamide,)
the substance termed mucin, peculiar to mucus, and the pyin,
existing in pus and morbid tumours, of which full notice will be
taken when we treat of the chemical theory of the tissues and
juices. In the same manner we shall treat of pepsin and the
peptones when we enter into the special consideration of the
digestive process.
TEROXIDE OF PROTEIN (PROTEINTRITOXYD.)
Chemical Relations.
Properties. — When dried, this substance is brittle, and easily
pulverisable, but when moist it is tough, viscid, capable of being
drawn out in threads, and when warmed has an odour resembling
that of gelatin ; it is soluble in water, but insoluble in alcohol and
ether, and in the fatty and volatile oils ; it has no reaction on
vegetable colours. It is precipitated from its solution by dilute
mineral acids, chlorine water, tannic acid, corrosive sublimate, the
salts of the oxides of lead, silver, zinc, and iron, but not by ferro-
cyanide of potassium, the alkaline salts, or chloride of barium.
With alkalies it forms neutral compounds, from which it is also
precipitated by metallic salts. When boiled with caustic alkalies
it developes ammonia, and becomes converted into a substance,
which, according to Mulder, is the true teroxide of his protein,
in accordance with his latest formula, C36H25N4O10 + 3O + 3HO.
Composition. — This body was discovered and analysed by
* Arch.d. Pharra; Bd. 48, S. 12-27.
t Ann. d. Ch. u. Pharm. Bd. 69, S. 145-162.
390 PROTEIN-COMPOUNDS.
Mulder* ; from the mean of five analyses it was found to
contain :
Carbon 51'«9
Hydrogen 6-64
Nitrogen 15*09
Oxygen 26'58
100-00
In his most recent memoir Mulder regards this substance as a
combination of true teroxide of protein with ammonia, in accord-
ance with the formula H4NO + 2 (C36H25N4O13) +3HO.
Preparation. — Mulder originally obtained this substance by treat-
ing his albumen-protein with chlorine, whereby he obtained the body
which he then termed chlorite of protein ; this substance when
decomposed with ammonia yielded the body in question.
He subsequently ascertained that he could obtain it by the pro-
longed boiling of fibrin or albumen in water, if freely exposed to
the air ; the solution which is thus obtained is filtered and eva-
porated, and the residue extracted with alcohol ; the portion inso-
luble in alcohol is again dissolved in water and precipitated by
basic acetate of lead ; the precipitate after being thoroughly washed
is then decomposed by sulphuretted hydrogen, the sulphide of lead
removed by filtration, and the solution evaporated.
Tests. This body has so few characteristic properties, that in
the present state of our knowledge it is extremely difficult, if not
impossible, to distinguish it with perfect certainty from those
substances which frequently occur, although only in small quan-
tities, which have been hitherto named extractive matters soluble in
water.
The peptones, ptyalin, pyin, and other little investigated
animal matters are very similar to this substance, but differ from
it in some of their characters, and hence must not be regarded as
identical with it, although many of the differences may be dependent
on the admixture of other matters with them. Hence organic ana-
lytical chemistry has here a great blank to fill up in order to eluci-
date the actual conditions under which this substance occurs.
Unfortunately it cannot be obtained in a state of purity from the
animal fluids, so that we cannot have recourse to an elementary
analysis to confirm our diagnosis.
* Journ. f. pr. Ch. Bd. 22, S. 340 ; Bull, de Neerlande, 1839, p. 404 ; Ann. d.
Ch. u. Pharm. Bd. 47, S. 300-320.
TEROXIDE OF PROTEIN. 391
Physiological Relations.
According to Mulder this body exists in normal blood and in
all fluid exudations, and hence also in pus ; and its quantity is very
considerably increased in the blood in inflammatory diseases. He
regards the pyin discovered by Guterbock in pus as altogether iden-
tical with this substance ; but if for the reasons we have already
given in reference to testing for teroxide of protein, we cannot re-
gard it as positively decided that this substance occurs in all these
animal fluids, yet it is probable from the mode in which it is arti-
ficially prepared, that a substance which is formed from albumen or
fibrin in warm water exposed to the air, also occurs in the blood
where the above named substances which yield it, are exposed to
similar influences. If more accurate investigations confirm the
existence of this teroxide of protein in the manner that Mulder
supposes, we shall then acquire a knowledge of an important inter-
mediate link in the metamorphoses of the animal tissues, and in
particular we shall have considerably approximated to the yet un-
solved problem of the conversion of albuminous bodies into bodies
yielding gelatin, or of fibrin into tissue.
DERIVATIVES OF THE PROTEIN-COMPOUNDS.
The bodies of this group present very great differences in their
physical and chemical properties ; except that they all contain
nitrogen, and that they occur only in the animal body, where they
form the chief groundwork of the tissues, there is scarcely a point
of general resemblance between them ; in their behaviour towards
acetic acid and ferrocyanide of potassium, and towards concentrated
hydrochloric and nitric acids they exhibit none of the essential
characters of the protein-compounds. Only four of these sub-
stances have as yet been accurately studied, although regarding even
their intimate chemical constitution there is as much doubt as in
the case of the protein-compounds.
392 DERIVATIVES OF THE PROTEIN-COMPOUNDS.
ANIMAL, GELATIN.
Under the term gelatin we comprehend those animal sub-
stances which do not exist ready formed in that state in the
animal organism, but are produced from certain animal parts by
mere boiling with water, so that the still undescribed substance
from which this body is so easily obtained, may be regarded as
the organic substratum of most of the animal fluids. All these
very similar bodies, to which we give the common name of gelatin,
are especially distinguished by the following properties; they swell
and become very translucent in cold water; they dissolve in hot
water; on cooling they separate as translucent, lubricous masses, and
are precipitated from the most dilute solutions by chlorine, tannic
acid, and most of the salts of the earths and metals.
There are two principal varities of gelatin to be considered,
namely, bone-gelatin, carpenter's glue, or glutin, and cartilage-
gelatin or chondrin, although here, as in the case of protein, there
appear to be several modifications of each variety.
GLUTIN.
Chemical Relations.
Properties. — In a state of purity, glutin appears in colourless,
transparent pieces, which are hard, horny, brittle, heavier than
water, devoid of taste and smell, and exhibit no reaction on vege-
table colours ; on trituration it does not adhere to the pestle like
the protein-compounds.
Glutin immersed in cold water, becomes soft, swells, and loses
its transparency ; in warm water it dissolves, forming a colourless,
viscid solution, from which, on cooling, it separates as a jelly ;
Bostock^s experiments show that good hard glutin will separate in
this manner when diluted with 100 times its bulk of water. After
being repeatedly dissolved in hot water, it loses the property of
gelatinising. Gelatinised glutin gradually becomes acid on exposure
to the air, and then loses its property of fixing and binding. It is
perfectly insoluble in alcohol, ether, fats, and volatile oils ; on the
addition of alcohol to its warm solution, it coagulates into a white,
tenacious, almost fibrous mass, which, however, readily dissolves
again when warmed in pure water.
Acids and alkalies throw down no precipitate from aqueous
GLUTIN. 393
solutions of gelatin ; the latter in a dilute state precipitate a little
bone-earth. Of the organic acids, tannic add is the only one
which throws down a precipitate from a solution of glutin ; the
precipitate is white and cheesy, and is observable even if the glu
tin be dissolved in 5000 times its weight of water.
The only earthy and metallic salts which precipitate glutin are
corrosive sublimate, bichloride of platinum, and sulphate of
bin oxide of platinum. Ferrocyanide of potassium does not affect
either its neutral or its acid solution Chlorine, bromine, and iodine,
on the other hand, act very powerfully on a solution of glutin ;
chlorine causes the separation of a coagulum which is partially
thready, and after prolonged action, compounds are formed of
chlorous acid and undecomposed glutin. Creosote gives a milky
appearance to the clear solution ; the salts of alumina, suboxide
of mercury, the oxides of silver, copper, and lead, and of protoxide
and peroxide of iron, exhibit no reactions when added to a solu-
tion of glutin, or, at most, cause only a very slight turbidity ; and
the same is the case with basic acetate of lead. Basic sulphate of
binoxide of iron when added to a solution of glutin, causes a bulky
precipitate, which, when dried, is of a deep red colour.
Moist glutin exposed to the air soon undergoes putrefaction ;
it first becomes sour, but afterwards developes a large quantity of
ammonia ; according to Gannal,* the gelatigenous tissues are the
first of the solid animal structures to become putrid.
Dry glutin when heated softens, swells up, evolves an odour of
burned horn, does not easily catch fire, and after burning for a very
short time, leaves a voluminous, blistered, glistening coal, which
after perfect combustion, yields a somewhat varying amount of
phosphate of lime. The products of its dry distillation are those
of the animal tissues generally ; it yields, however, a preponderat-
ing quantity of carbonate of ammonia.
When boiled with concentrated nitric acid, glutin becomes
gradually converted into oxalic and saccharic acids, and into two
substances resembling suet and tannic acid. It dissolves in con-
centrated sulphuric acid, forming a colourless fluid, which on
boiling gradually yields leucine, glycine, and other substances. If
however it be treated with sulphuric acid and peroxide of manganese
or bichromate of potash, it yields, according to Schlieperf and
GuckelbergerJ, most of the non-nitrogenous acids of the firs
* Hist, de 1'embaumement, etc. Paris, 1838
t Ann. d. Ch. u. Pharm. Bd. 59, S. 1-32.
% Ibid. Bd. 64, S. 39-100.
394 DERIVATIVES OF THE PROTEIN-COMPOUNDS.
group (CnHn_1O3), and not only these but valeronitrile, hydrocyanic
acid, hydride of benzoyl, benzoic acid, and certain aldehydes, and
consequently precisely the same products of decomposition as the
protein-compounds ; it is however, distinguished from them in
yielding even less acetic acid than fibrin, very little benzoic acid
and hydride of benzoyl, but on the other hand more valerianic acid
than any of the protein-compounds.
When boiled or fused with hydrated potash glutin developes
ammonia, and is for the most part decomposed into leucine and
glycine.
Composition. — Glutin has been analysed by Mulder*, Schererf*
and Goudoever J. They found it to contain :
Mulder. Scherer. Goudoever.
Carbon 50'40 .... 50'76 .... 50'00
Hydrogen 6'64 .... 7'15 .... 672
Nitrogen 18'34 .... 18-32 .... -—
Oxygen 24'62 .... 2377 .... —
10-000 10-000
No chemical formula that can be depended upon, has been
deduced from these analyses. Mulder originally calculated
C13H10N2O5, and Liebig C52H40N8O20, as the most correct for-
mula. The calculations were for the most part based on its com-
binations with chlorous acid.
Schlieper§ has found 0*12 to 0*145. of sulphur in glutin obtained
from bones and ivory.
Preparation. — In order to prepare glutin in the purest possible
form from common glue, (which is obtained by boiling skins,
tendons, &c., and the swimming-bladder of certain kinds of fish,)
Berzelius used to soften it in water, to expose it repeatedly to
strong pressure, and then to suspend it in a linen bag in cold water
till everything soluble in that fluid was removed. The softened
glutin contained in the bag is then heated to 50°, when it becomes
perfectly fluid, and must be rapidly filtered. The albuminous and
mucous portions remain on the filter, while the hot solution of
glutin passes through, and very soon again gelatinises.
In order to prepare glutin from bones, we must digest them
for a considerable time in dilute hydrochloric acid, in order to
* Bullet, de N^erlande. T. 1, p. 23 ; Ann. d. Ch. u. Pkarni. Bd. 46, S.
205-207.
t Ann. d. Ch. u. Pharm. Bd.40, S. 46-49.
t Ibid. Bd. 45, S.62-6?.
§ Ibid. Bd. 58, S. 379-38 J.
GLUTIN. 395
extract the bone-earth, allow the remaining cartilage to lie for some
time in pure water in order to remove any adhering hydrochloric
acid, and finally boil it with water. Glutin obtained from bones,
skins, and tendons, has always a slightly yellow colour.
Pure, colourless glutin can only be obtained from cellular
tissue, shavings of hartshorn, calves' feet, and the swimming-
bladder of certain fishes, by boiling them till they are thoroughly
dissolved, filtering them while hot, and removing from them all
foreign substances by the method recommended by Berzelius,
which has been already described.
Combinations. — On passing chlorine gas into an aqueous solu-
tion of glutin, each bubble of gas becomes enveloped in a glutinous
capsule ; the fluid itself becomes milky ; white flakes are observed
on its surface, and at the bottom of the vessel we observe a deposit
of a semi-transparent jelly. The substance which separates at the
surface has a frothy, snow-white appearance, is tough and elastic,
has a decided odour of chlorous acid, and can be dried at a tempe-
rature below 40° without becoming coloured ; after it has been
partially dried, it may be deprived of all its water at 100°, and then
no longer evolves any odour of chlorous acid. In this state the
body is white, easily pulverisable, and insoluble both in water and
in alcohol. When ammonia is poured over it, nitrogen is deve-
loped, and hydrochlorate of ammonia and unchanged glutin are
left.
Mulder* found that the action of chlorine and water on the
organic substance gives rise to the formation of hydrochloric and
chlorous acids, the latter of which enters into combination with
the unchanged glutin, the compound consisting of 1 equivalent of
acid and 4 equivalents of glutin.
Assuming that the composition of this substance is represented
by the formula C52H40N8O20 + C1O3, its atomic weight^ 8544-26.
Mulder has found two other combinations of glutin with chlorous
acid in the above mentioned gelatinous deposit of the solution of
glutin ; one consisting of 1 atom of glutin with 1 atom of chlorous
acid=C13H10N2O5 + ClO3, and the other of 3 atoms of glutin and
2 atoms of acid=C39H30N6O15 + 2C!O3.
The action of acids on glutin has on the whole been as yet
little examined ; with dilute mineral acids it appears to enter into
combinations, which, however, on cooling, gelatinise in the same
manner as pure glutin. Concentrated acetic acid dissolves glutin
* Bull. de. N«ferl. T. 2, p. 162.
396 DERIVATIVES OF THE PROTEIN-COMPOUNDS.
which has been softened in water, and deprives it of the property
of gelatinising on cooling.
The only compound which has been carefully studied is that
which it forms with tannic acid. This has been done by Mulder,
who finds that, when freshly precipitated, it is white and curdy,
when dried it is hard, brittle, and pulverisable, and that it is inso-
luble in water and alcohol. If the glutin is precipitated with an
excess of tannic acid, we obtain a combination of equal equivalents
of glutin and tannic acid^C^H^N^ + CigHyOn ; if, on the
other hand, there be an excess of glutin, the precipitate consists
of 3 equivalents of glutin and 2 equivalents of tannic acid
=C39H30N60I5 + C36H14022.
No combinations of glutin with alkalies, earths, and pure
metallic oxides are as yet known. Caustic lime dissolves in a solu-
tion of glutin. Glutin can, however, combine with several basic
salts; a very considerable quantity of freshly precipitated bone-
earth dissolves in a solution of glutin. Solutions of glutin, when
treated with alum and with sulphate of peroxide of iron, do not
yield a precipitate, except on the addition of an alkali ; the preci-
pitate in this case consists of glutin and a basic salt=Al2O3.SO3
or Fe2O3.2SO3. The precipitate obtained with sulphate of the
binoxide of platinum appears to contain basic sulphate of binoxide
of platinum=PtO2.SO3.
Physiological Relations.
Occurrence. — Haller's remark : Dimidium corporis humani gluten
est, now requires to be modified to the assertion that half of the
solid parts of the animal body are convertible, by boiling with tvater,
into gelatin; for actual gelatin is not contained in the animal
organism. It has been for a long time maintained that gelatin is
an actual constituent of the swimming bladder of certain fishes ;
but even this is by no means probable.
The tissues of the human body have been divided into the
gelatigenous and the albuminous. Appropriate as such an arrange-
ment might at first sight appear, it is opposed by the experience
both of chemists and anatomists ; Berzelius and E. H. Weber
assert that as the permament cartilages are not converted by
boiling with gelatin, and as moreover they cannot be regarded as
albuminous, cartilages must be divided into the gelatigenous and
non-gelatigenous, and thus these observers abandon the old division
of the tissues. Miiller has subsequently devoted much attention
to the structure and constitution of cartilage, and he finds that the
GLUTIN. 397
permanent and fibrous cartilages which were previously regarded
as non-gelatigenous, may be converted by very prolonged boiling
into a gelatinising and gluing substance ; but at the same time he
ascertained that in many of its other properties, this substance did
not coincide with ordinary gelatin ; hence he named it cartilage-
gelatin^ or chondrin.
Bone-gelatin or glutin is obtained from the following tissues,
by boiling them for a longer or shorter time with water ; from the
cartilages of bone (after ossification), from tendons, the skin,
calves' feet, hartshorn, isinglass, the scales of fish, and from the
permanent cartilages, when they become ossified by disease. The
conversion of these animal parts into glutin proceeds without any
development of gas or absorption of air; acids promote this meta-
morphosis, just as they facilitate many similar transformations in
organic chemistry, which can take place by mere boiling without
their cooperation, but yet are hastened by their presence, as, for
instance, in the case of starch.
We shall revert to this subject when treating of the individual
tissues, and of their relation to gelatin.
Origin. — We have already referred to the production of gelatin
from the gelatigenous tissues ; a comparison of the analyses of
pure gelatin with those of the tissues yielding it, will (in a future
part of the work) show us that there is no chemical difference
between the two, or that at most they only differ by a few atoms
of water. Hence it appears that in the formation of gelatin,
the material of the tissues only undergoes a re-arrangement of its
atoms, or a metamerism, or at most that it only assimilates water,
just as occurs when starch, inulin, and lichenin are converted by
prolonged boiling into dextrin or glucose.
We shall have occasion to refer in considerable detail to the
production of gelatigenous from albuminous matters, when we treat
of cell-formation and the history of development.
UseSi — From what has been already said, it follows that we are
unable at present to discuss the uses of gelatin in the animal
body. The consideration of the tissues from which we obtain
gelatin by boiling, pertains solely to histology, and the tissues
themselves have as yet hardly fallen within the scope of chemical
investigation. We learn from a very superficial consideration of
the animal body that the gelatigenous tissues belong for the most
part to the lower class of tissues, which are only of use through
their physical properties ; they frequently afford strong points of
attachment for muscles, and furnish strong investments for impor-
398 DERIVATIVES OF THE PROTEIN-COMPOUNDS.
tant but easily injured organs ; they give uniformity to the move-
ments of the body through their elasticity, and protect it from the
injurious effects of severe concussions ; from being bad conductors
of heat, they guard the body against rapid changes of temperature ;
and sometimes, as in the cornea, they are useful as refracting media,
in consequence of their transparency.
CHONDBIN.
Chemical Relations.
Properties. — Chondrin or cartilage-gelatin, when dry, appears
as a transparent, horny, glistening mass, which is generally more
colourless than glutin ; it is not rendered electric by friction ; its
behaviour towards indifferent solvents, towards heat, corrosive
sublimate, tannic acid, and chlorine, is precisely the same as that
of glutin ; but its relations to acids and most metallic salts are quite
different. It was shown by Miiller* that acetic acid throws down a
considerable precipitate from a solution of chondrin, and that this pre-
cipitate does not dissolve even in concentrated acetic acid. Simonf
and VogelJ have subsequently proved that most acids throw down
a precipitate from a solution of chondrin, but that this precipitate
easily escapes notice in consequence of the facility with which it
dissolves in a slight excess of the acid. Alum, the sulphates of the
protoxide and peroxide of iron, sulphate of copper, neutral and basic
acetate of lead, and the nitrates of silver, and of suboxide of mercury
throw down copious precipitates. The precipitates thrown down
by the salts of alumina occur in white, compact flocks, which on
drying, cake very much together ; they are insoluble in water, but
dissolve in an excess of the earthy salt, as well as in solutions of
chloride of sodium and of alkaline acetates. The precipitate thrown
down by sulphate of peroxide of iron is not soluble in an excess of
that salt, but dissolves on boiling. In its relations towards ordi-
nary atmospheric influences as well as towards alcohol, creosote,
chlorine, bromine, iodine, and ferrocyanide of potassium, chondrin
perfectly resembles glutin. Its combinations with other bodies and
its products of decomposition have not yet been accurately studied.
Composition. — Mulder§ was the first who made an elementary
* Pogg. Ann. Bd. 38, S. 295.
t Medicin. Chemie, Bd. 1,8. 108.
J Jonrn. f. pr. Ch. Bd. 21, S. 426.
§ Natuur en Schcik. Arch. 1837, p. 450, and 1838, p. 160.
CHONDRTN. 399
analysis of chondrin ; he found that besides the ordinary elements
of animal substances it contains a little free sulphur, and that it
yields more than 4£ of an ash consisting chiefly of bone-earth. It
has subsequently also been analysed by Scherer* and Schroderf.
The following are the results of their analyses :
Mulder. Scherer. Schroder.
Carbon
.... 49-97
.... 50-754 ....
49-88
Hydrogen...,
.... 6-63
6-904 ....
6-61
Nitrogen ....
.... 14-44
.... 14-692
Oxygen
Sulphur ....
.... 28-59
.... 0-38
} 27-650
—
100-00 100-000
From these results Mulder constructs the formula C32H26N4O14
and Scherer, C48H40N6O20.
Preparation. — Chondrin is most readily obtained by boiling the
cartilages of the ribs, larynx, or joints, for from 18 to 24 hours in
water ; to purify it we must adopt the same means as are recom-
mended for glutin, and we must extract the dried residue with
alcohol.
Physiological Relations.
Occurrence. — The remarks which have been already made re-
garding the occurrence of glutin in the animal organism, are equally
applicable in relation to chondrin. Chondrin does not occur ready
formed in the organism, but is produced by the prolonged boiling
of certain tissues in water ; all permanent cartilages in a healthy
state yield chondrin on boiling. Mullens discovery that bone-
cartilage not only yields chondrin before ossification, but also some-
times after it has undergone morbid changes, is very remarkable,
and shows that chondrin and glutin, notwithstanding their perfectly
different constitution, stand in a definite relation to one another ;
but what that relation is, we cannot at present conjecture.
There are, further, in the animal organism, several bodies which
yield a gelatin distinct both from chondrin and glutin. Thus,
Miiller has shown that in osteomalacia where there is sometimes a
considerable diminution of the phosphate of lime, the bones yield
neither glutin nor chondrin ; that the elastic tissue of the arteries,
by prolonged boiling, yields a kind of gelatin which only differs from
chondrin in yielding no precipitate with sulphate of peroxide of
iron ; that the bones of cartilaginous fishes are converted by boiling
* Ann. d. Ch. u. Pharm. Bd. 40, S. 40-51.
t Ibid. Bd. 45, S. 52-58.
400 DERIVATIVES OF THE PROTEIN-COMPOUNDS.
into a substance which does not gelatinise but which glues very well,
and which, moreover, resembles chondrin in its behaviour to acetic
acid and metallic salts, but is not precipitated by the salts of the
oxides of platinum, silver, and gold ; and, finally, that ossified
fish-cartilage when boiled, yields a non-gelatinising fluid which is
precipitated by tannic acid, but not by acetic acid and the salts of
alumina, and consequently, approximates in its character to glutin.
Origin. — In our observations on glutin we pointed out that we
are still perfectly ignorant of the mode of origin of chondrin. The
experiments of Miiller render it highly probable that glutin is
formed from chondrin. But how ? This must be decided by future
researches.
Uses. — The animal tissues which yield chondrin are of the same
use through their physical properties as those which yield glutin ;
their most important character being their elasticity.
FIBROIN.
Chemical Relations.
Properties. — It is a white, amorphous mass, devoid of odour
or taste, insoluble in water, alcohol, and ether, but dissolving in
concentrated sulphuric, nitric, and hydrochloric acids, from which
solutions, if diluted with water, it is precipitated by tannic acid ;
it is insoluble in acetic acid and in ammonia ; it dissolves in a con-
centrated solution of potash but at the same time undergoes decom-
position. This substance becomes decomposed, when heated ;
developing ammonia and empyreumatic vapours.
Composition. — This body was discovered and has been analysed
by Mulder* ; it consists (taking the mean of four of his analyses) of:
Carbon 48-61
Hydrogen 6*50
Nitrogen' 17-34
Oxygen 27*55
100-00
From these numbers Mulder calculated the formula
C39H31N6O17 according to which fibroin may be regarded as 3
atoms of glutin which have assimilated 1 atom of oxygen and 1
atom of water, for 3(C13H10N2O5) + HO + O=C39H31N6O17.
Mulder and Croockewitf moreover found that the common sponge
* Natuur en Scheik. Archief. D. 3, p. 93, D. 5, p. 281.
t Scheik. Onderz. D. 2, p. 1.
CI1ITIN. 401
contains the same substance in combination with iodine, sulphur,
and phosphorus; and Mulder considers from the analyses of
Croockewit that the compound consists of 20 atoms of fibroin, 1
atom of iodine, 3 atoms of sulphur, and 5 atoms of phosphorus ;
for there were found in sponge l'08% of iodine, 0'50J of sulphur,
and 1-90^ of phosphorus, besides the elements of fibroin.
Preparation. — Silk or gossamer threads are boiled with water
and strong acetic acid till all albuminous and gelatinous matters are
dissolved. The remaining fibroin is then purified in the ordinary
manner.
Physiological Relations.
This substance has hitherto been only found in the above
mentioned secretions of silk-worms and spiders ; physiological
investigations show us that it is originally a viscid fluid which is
secreted by the spinning vessels of those animals, and hardens on
exposure to the air. Under the microscope the fluid mass appears
perfectly amorphous.
Sponge is, as is well known, the dry skeleton of an animal
belonging to the Porifera (Grant; and named Sponaia qfficinalis
(Linn.) Its chemical constitution affords one of the arguments
why the Sponaia should be classed amongst animals and not
amongst plants, since in the vegetable kingdom we nowhere meet
with a substance in the slightest degree resembling fibroin.
The physiology of these lower animals has been so little inves-
tigated that it is impossible for us to set up an hypothesis regarding
the formation of this substance, for notwithstanding the very
accurate analyses of Mulder we cannot be regarded as knowing
anything of its intimate chemical composition. Mulder's compa-
rison of the composition of this body with that of gelatin, can
indicate nothing more than the analogy in relation to the physio-
logical value of both substances, that is to say, that nature produces
in these lower animals a similar group of atoms in order to construct
their solid groundwork of tissues possessing little or even no vita-
lity The use of this substance is therefore purely mechanical,
CHITIN.
Chemical Relations.
Properties. — This substance, to which Lassaigne gave the name
of Entomaderm, is a white, amorphous body, which usually retains
402 DERIVATIVES OF THE PROTEIN-COMPOUNDS.
the form of the tissue from which it is prepared ; it is insoluble in
water, acetic acid, and alkalies, but dissolves in concentrated nitric
and hydrochloric acids without communicating any colour to those
fluids ; after neutralisation with ammonia, tannic acid throws down
a precipitate from these solutions. In concentrated sulphuric acid
it swells up and becomes dissolved without communicating any
change of colour to the acid ; it gradually however again separates
as a black mass, while acetic acid and acetate of ammonia remain
in solution ; no sulphurous or formic acid is however formed. It
is not decomposed by the most concentrated solution of potash,
even at a boiling heat ; heated to 280° with water in closed tubes,
it becomes brown and brittle without undergoing any change of
structure that can be detected by the microscope. There are two
points worthy of notice in connexion with the dry distillation of
this substance ; it does not fuse, but leaves a charcoal which on
microscopic investigation always exhibits the form of the original
tissue ; and further, notwithstanding that it contains nitrogen, it
yields acid products of distillation in which not only water and
acetic acid are found, but also acetate of ammonia and a little
empyreumatic oil.
Composition. — This body has been analysed by Lassaigne* and
Payen?f and has been most carefully studied by C. Schmidt^.
Payen found much too little nitrogen. The results of various
analyses and experiments which I have made with chitin exactly
correspond with those of Schmidt. The following are the results
of our analyses.
Schmidt. Lehmann.§
Carbon 46-64 46734
Hydrogen 6-60 6*594
Nitrogen 6'56 6-493
Oxygen 40-20 40-179
100-00 100-000
Schmidt regards C17H14NOH as the simplest formula express-
ing this composition. He directs especial attention to the peculiar
relations of this substance when acted upon by heat and by acids, and
arrives at the very interesting result that this body which so closely
* Journ. de Chim. meU T. 9, p. 379.
t Compt. rend. T. 17, p. 227-
% Zur vergleichend. Physiol. der wirbellos. Thiere, 1845, S. 32-C9 [or Tay-
lor's Scientific Memoirs, vol. 5, pp. 14-28. — o. E. D.]
§ Jahresber. d. ges. Med. 1844, S. 7.
CHITIN. 403
resembles vegetable bodies and especially vegetable fibre, may be
regarded as composed of a carbo-hydrate similar to cellulose, and
of a nitrogenous body which has the composition of the muscular
fibre of insects. The latter is represented, according to his ana-
lyses, by the formula C8H6NO3; and C17H14NOn -C8H6NO3=
C9H808.
Preparation. — The best method of obtaining this body is by
boiling the elytra of the cockchafer with water, alcohol, ether,
acetic acid, and alkalies ; the body always perfectly retains the
structure of the elytrum, or of the other insect-tissues from which
it is prepared.
Physiological Relations.
This body forms the true skeleton of all insects and Crustacea.
It constitutes not merely their external skeleton, the scales, hairs,
&c., but also forms their tracheae, and thus penetrates into the
minuter portions of the organs ; indeed even one of the layers of
the intestinal canal of insects consists of chitin ; hence we can
very well prepare all these parts by treating insects with a solution
of potash and then microscopically examine the finest parts, as for
instance, the valves of the tracheal openings.
If Schmidt's hypothesis regarding the constitution of chitin be
confirmed by further observations, it would be easy to understand
how this substance is formed from the food of insects.
In reference to its application in the insect organism, chitin is
at most entitled to be regarded as a histogenetic substance.
Before concluding our remarks on the organic substrata of the
animal organism we would briefly review the mode of arrangement
in which these substances have been considered. We observed in
our remarks introductory to the subject of Zoo-Chemistry that the
physiological and chemical classifications of animal substances
must perfectly coincide with one another ; and now in our conclu-
ding observations we are constrained to admit that our knowledge
of the organic substrata of the animal body is still very deficient,
and that we have been provisionally compelled to adopt a practical
classification and arrangement, in which, passing from the simpler
2 D 2
404 PRINCIPLES OF CLASSIFICATION.
to the more complex bodies, we have attempted to group together
substances presenting chemical similarities with those of equal
physiological importance. The deficiency of our knowledge on
many points to which allusion has frequently been made, must
plead as an apology for the deficiencies in our mode of arrange-
ment. The laborious accumulation of properties, which are only
slightly connected or are even altogether inapplicable, has grievously
oppressed the science of chemistry, and has reduced it to a mere
task of the memory. We have as yet no logical ideas in relation
to chemistry ; that is to say, although we have perfectly clear per-
ceptions regarding most bodies and processes, we have no distinct
ideas (in the logical sense). There is an utter absence of those
principles of unity around which, as around a nucleus, the indi-
vidual properties of bodies can crystallise, and thus stand in the
same mathemathical relation to one another, as the edges and angles
of crystal.
It is not till chemistry shall have shown us the close mutual
connexion that exists between the properties of all individual sub-
stances, and shall have taught us to unite them into one organic
whole, that we can regard it as coequal in scientific rank with the
different branches of physics, — that it will fully admit of the appli-
cation of the higher mathematics, — or that the sole rational principle
of classification as well as a scientific theory of chemical substances
will be discovered. The beautiful investigations of Kolbe and
others regarding the numerical ratio existing between the densities
and boiling points of the haloid bases, the volatile acids, and the
haloid salts, as also the comparisons of the coefficients of density
of the constituent elements with the other properties of the com-
pound substance, may form a small beginning towards the attain-
ment of logical ideas and the realisation of such a degree of chemical
knowledge. When we have once attained logical ideas regarding
the different animal substrata, — when we are in a position to foretell
the chemical properties of a body from its composition, or its com-
position from a certain number of its properties, — we shall then not
only possess the true principle of classification in physiological
chemistry, but we shall also have attained the means of investi-
gating and comprehending the vital processes of nutrition and
secretion with a degree of certainty at present limited to the most
exact sciences.
MINERAL CONSTITUENTS OF THE ANIMAL BODY. 405
MINERAL CONSTITUENTS OF THE ANIMAL BODY.
The chemistry of inorganic bodies has been so much more fully
investigated than that of organic substances, that it might naturally
be expected that our knowledge of the mineral constituents of vege-
table and animal bodies would far exceed that of the organic
constituents ; but, in truth, the reverse is the case, for we are far
less acquainted with these substances than with many organic
bodies. This circumstance is, however, not consequent on our
having paid less attention to the mineral constituents of organic
bodies, but is especially owing to the difficulty of separating these
substances, in an unchanged state, from organic matters, and of
ascertaining the conditions and combinations in which they actually
existed preformed in the organic substance. The fixed products
of the incineration or combustion of organic substances do not
afford us any information as to the combinations in which they
occurred in the organic substance. Nor can any reflecting chemist
for a moment suppose that the oxides and salts of the ash are con-
tained as such in the juices and tissues of living bodies.
From a deficiency in the means of investigating or even of
conjecturing the true constitution of these substances in organic
parts, a higher value has been attached to the determinations of
the ash and its constituents than it merited, and the results of
these analyses have been more highly estimated than they deserve,
when we consider the agents cooperating in the incineration. It
has, moreover, frequently been forgotten that the quantity and
constitution of many of the constituents of the ash are in a great
measure dependent on the height of the temperature at which the
process of incineration was conducted ; that a great portion of the
substances has been volatilised by the simultaneous action of heat
and carbon ; and that the individual constituents of the ash have
entered into perfectly different combinations from what they had
done in the organic substance.
We will here indicate only some few of the changes which the
mineral constituents of organic substances must necessarily undergo
when exposed to strong heat with a free admission of air. The
sulphur and phosphorus which were not contained in the organic
substance as sulphuric and phosphoric acids, must necessarily be
found in the ash as sulphuric and phosphoric acids combined with
406 MINERAL CONSTITUENTS OF THE ANIMAL BODY.
bases ; and although this necessary change has not been over-
looked, the consequences have too often been neglected. When
in the first place we direct our attention to the sulphuric acid, we
shall find that the number representing this acid as found in the
ash, can scarcely ever correctly express the quantity of sulphuric
acid existing preformed in the organic substance, or the sulphur
contained in it. For if we suppose all the sulphur converted by
combustion into sulphuric acid, and united to the bases that had
previously been combined with organic substances or with carbonic
acid, a great portion of the sulphur must be lost, even when these
bases are sufficient for the saturation of the sulphuric acid that is
formed (which is not always the case, as, for instance, in the bile)
in consequence of the sulphates in contact with the nitrogenous
charcoal, which is so difficult of incineration, being converted into
metallic sulphides, of which a larger or smaller quantity will escape
as sulphurous acid during the prolonged process of calcination.
Under the action of a strong glowing heat common phosphate of soda
removes a part of the base, not only from the carbonates, (see p. 97,)
but also from sulphates of the alkalies, as well as from the metallic
chlorides of the ash, so that not only does all the alkaline carbonate
disappear from the ash, but a portion of the hydrochloric or sul-
phuric acid may be also lost. Where the ash contains acid phos-
phate of soda, as occasionally happens in urine devoid of lactic
acid, a portion of the phosphoric acid must necessarily be lost; for
we know with what difficulty carbon burns in the presence of
fusible salts, and it must be recollected that a portion of the phos-
phoric acid of the acid salts will be reduced by the carbon and
volatilised. These few remarks may suffice to show how little
atttention was formerly directed to the reciprocal decompositions
experienced by the mineral salts that occur in vegetable or animal
substances, under the influence partly of a simple glowing heat,
partly of heat in the presence of unconsumed carbon, and partly
of a glowing heat in oxygen gas.
I have endeavoured in some degree to evade these obstacles in
the way of the determination of the mineral constituents of animal
bodies, by isolating organic substances as much as possible,
according to their solubility (as I have done in the case of blood,*
for instance,) and then determining the constituents of the ash of
each separate extract ; by which means we may be justified in
expecting that the soluble salts that are preformed in the blood
will be contained in the aqueous and alcoholic extracts, and that
* Berichte der k. sachs. Gesellsch. d. Wiss. Bd. 1, S. 98.
MINERAL CONSTITUENTS OF THE ANIMAL BODY. 407
the presence of organic substances, owing to their inconsiderable
quantity in these extracts, will exert less influence on the decom-
position of the salts during incineration. In order as much as
possible to avoid the influence of the carbon and of the phosphates,
during the process of incineration, on the carbonates, I have been
in the habit of not exposing the whole of the carbonaceous residue
originally obtained from the organic substance to entire combustion,
but of reducing it to a small bulk over a gentle fire with free access
of air. The carbonaceous ash is then extracted with water and
hydrochloric acid, and the quantitative determination of the ash is
obtained by weighing and subtracting the residuary charcoal. But,
although I have certainly obtained more correct results by this
method than those yielded by the majority of previous analyses of
ash, it is nevertheless not free from error, nor can it be said to
afford an entirely satisfactory insight into the nature of the mineral
substances existing preformed in animal bodies. Fortunately for
science, H. Rose*, one of the most distinguished analysts of our
day, has entered upon this hitherto unpromising subject, and by a
series of the most carefully conducted investigations has obtained
important results, which are in part of a purely physiological cha-
racter. One of the most important facts ascertained by these
successful researches in analytical chemistry is, that in the animal
or vegetable substance perfectly carbonised by heat, there is usually
a greater or lesser quantity of alkaline and earthy salts, which cannot
be removed from the carbonaceous mass, even by the most pro-
longed extraction either with water or acids. These mineral sub-
stances must therefore be contained in the carbonised residue in a
different condition from those which admit of being removed by
various menstrua. Rose, therefore, concludes that such substances
as alkalies, earths, metals, phosphorus, sulphur, &c., must be con-
tained in the carbonaceous mass in a non-oxidised state, and in
combinations with which we are still unacquainted : he also thinks
that it may be assumed that such combinations of potassium,
sodium, calcium, iron, phosphorus, and sulphur, also exist pre-
formed in organic substances, since on the one hand the carbonisa-
tion of organic substances free from ash (as for instance sugar)
with the ordinary constituents of the ash did not yield any carbo-
naceous residue that could not be perfectly freed by the ordinary
* Pogg. Ann. Bd. 70, S. 449-465, Berichte der Akad. der Wiss. zu Berlin,
Decbr. 1848, S. 445-462, and Pogg. Ann. Bd. 76, S. 305-404. [The last of these
memoirs is translated in the London, Edinburgh, and Dublin Philosophical Maga-
zine. New series, vol. 35, pp. 1, 171, and 271.— G. E. D.]
408 MINERAL CONSTITUENTS OF THE ANIMAL BODY.
menstrua from mineral substances ; and since, on the other hand,
we are already acquainted with some organic bodies in which we
assume that non-oxidised sulphur or non-oxidised iron is present
in a peculiar state of combination. Hence Rose further concludes
that in vegetable and animal substances those mineral constituents
can alone be regarded as preformed, which admit of being extracted
by means of water and acids from the carbonised material, while on
the other hand those substances which cannot be separated until
the carbonaceous mass is entirely burned, are inherent in the ori-
ginal organic substance, as integral constituents in a non-oxidised
condition.
It appears from the numerous investigations prosecuted by
Rose, with vegetable and animal products, that while there are
some, as, for instance, the bones, in which all the mineral consti-
tuents are in a perfectly oxidised state, that is to say, admit of
extraction by the ordinary solvents, (and these he names teleoxidic
organic substances,) the great majority contain the mineral con-
stituents partly in an oxidised and partly in an unoxidised state
(these he terms meroxidic) 9 while none are as yet known that
contain only unoxidised elements (anoxidic.}
In his examination of vegetable substances, Rose found that
the straw of different kinds of grain was almost perfectly teleoxidic,
whilst the seeds of the same plants were meroxidic. In reference
to animal substances, it was to be expected that, as the meroxidic
substances belonging to the vegetable kingdom specially serve as
food for the animal organism, those animal fluids and tissues wliose
chemical constitution approximates to that of vegetable substances,
as the blood, the muscular fibre, milk, and yolk of egg, would be
meroxidic, whilst the excretions, as matters which originated in the
animal body mainly by the process of oxidation, would be teleoxidic.
This supposition has been fully confirmed by the analyses of the
bile, the urine, and solid excrements, instituted by Weber, Fleit-
mann, Weidenbusch, and Poleck. In order to take a general view
of these relations, we will subjoin the numerical results which have
been obtained, according to Rose's method, by investigations on the
mineral constituents of animal substances. In the following table,
A represents the quantity of the salts that can be extracted by
water from 100 parts of the mineral constituents of the organic
substance ; while B represents the quantity of salts dissolved by
hydrochloric acid ; and C, the quantity of the salts which can only
be determined bv the combustion of the carbonaceous residue.
MINERAL CONSTITUENTS OF THE ANIMAL BODY. 409
A.
B.
C.
Ox-blood
60-90
(J.Q4
33.06
Horse-flesh ....
42-81
.... 17-48 ....
39-71
Cows' milk
34-17
.... 31-75 ....
34-08
Yolk of egg ....
40-95
8-05 ....
51-00
White of egg ...
82-19
.... 15-52 ....
2-29
Ox-bile
90-85
.... 4-93 ....
4-22
Urine
90-87
8'54
0*59
Solid excrements
.... 18-55
62-30
19-15
The column C exhibits, therefore, those mineral substances in
the oxidised state which, according to Rose, are not oxidised in the
organic substance.
It must be further observed, that in the solid excrements the
number representing the mineral substances that cannot be ex-
tracted, would not be so strikingly high if sand and the silica
of the vegetable tissue were not mixed with them ; the number
representing the non-oxidised substances is also increased in the
white of egg, the ox-bile, and the urine, by the silica occurring in
them.
Although Rose's investigations have greatly contributed to our
advance towards the knowledge of the inorganic constituents of
animal substances, we dare not flatter ourselves that we have as
yet attained the object in view, for it not only remains for us to
apply this method to the investigation of the mineral substances
contained in different normal and morbid animal juices and tissues,
but also, by further investigation, definitively to determine the
question that has been started against Rose's view of the combina-
tion of radicals containing sulphur and phosphorus with metals; in
other words, it will be necessary to collect a greater number of
facts, in order to illustrate this obscure subject in various points of
view, before we venture to apply it, in all its consequences, to scien-
tific questions. Yet it cannot be denied that no previous method
affords us so good a guide as Rose's, for the correct recognition of
the mineral substances existing preformed in organic bodies.
When, however, we have obtained by Rose's method such an
admixture of mineral bodies as we may assume to exist preformed
in the organic substance, the actual analysis still remains to be
made ; and this, notwithstanding the labours of the most eminent
chemists, has by no means attained to the degree of perfection
which has been generally obtained in mineral analyses. The recent
investigations of Fresenius, Erdmann, Mitscherlich, and more
especially of Rose, have made us acquainted with numerous defi-
ciencies which attached to the former methods of examining the
410 MINERAL CONSTITUENTS OF THE ANIMAL BODY.
ashes of vegetable and animal substances; and notwithstanding
this, we are struck with the great accuracy of many of the earlier
analyses of ashes, although from the methods then employed we
should have expected that their calculations would of necessity
have yielded a minus in the one case and a plus in the other.
We will here only refer to the fact that few observers before
Rose had observed that alkaline as well as earthy salts were con-
tained in the insoluble portion of the ash, and that, conversely, the
presence of carbonate and phosphate of lime in the aqueous extract
of the ash had been very generally overlooked, while the very
imperfect precipitation of the pyrophosphate of magnesia by am-
monia was equally disregarded. The imperfect manner in which
even the simplest relations of this nature have been investigated,
is made apparent by the doubts entertained by Berzelius himself,
in reference to the composition he had ascribed to bone-earth,
which were verified by the investigations of Rose and W. Heintz,*
by whom it was definitely proved that the phosphate of lime in
the bones is represented by 3CaO.PO5, and not as Berzelius had
given it, by 8CaO.3PO5. The difficulty of conducting exact
analyses of ash was, however, mainly increased by the deficiency of
any clear and comparatively simple method of separating phosphoric
acid from its proteus-like salts, and determining it quantitatively.
But this cause of difficulty has likewise been recently obviated by
H. Rose'sf method of thoroughly separating the acids from their
bases by means of mercury and nitric acid.
When we consider these facts in reference to the analysis of the
ash, we shall readily arrive at the conclusion, (without, however,
wishing to animadvert upon those analysts who have engaged in
laborious examinations of the ash of animal bodies,) that most of
these analyses should be used with great caution, and that physio-
logical conclusions should not be too readily drawn from them. It
has, unfortunately too often happened that the empirical results of
analyses of the ash have been applied to the explanation of physio-
logical processes without due consideration, and thus the import-
ance and efficiency of the mineral salts of the animal body have
been extolled before we had any accurate knowledge of the sub-
stances themselves ; and the most rigorous scepticism in reference
to medical experiments has not unfrequently been associated with
a blind confidence in the least reliable of the numerical determina-
tions of chemists.
* Ber. der Ak. d. Wiss. z. Berlin, Febr. 1849, S. 50-53.
t Ibid. S. 42-45.
MINERAL CONSTITUENTS OF THE ANIMAL BODY. 411
Since we have made a practice of incorporating the methods of
qualitative and quantitative analysis in the description of the organic
substrata, it might naturally be expected that we should in like
manner enter into a special consideration of the different methods
for analysing the ash ; but however important this subject may be,
both in itself and in reference to physiology, we have, nevertheless,
been deterred by many reasons from adhering to this rule in the
present case. Thus, for instance, if we were once to enter
thoroughly within the domain of inorganic chemistry, we should
far exceed the limits assigned to this work, more especially if we
were definitely to refer to, and critically to illustrate, the different
methods for the analysis of the ash and the determination of indi-
vidual constituents ; nor could we indicate any one method as the
best, since different objects demand different methods. We, more-
over, entertain the frequently expressed but rarely practised view
that the study of physiological as well as of organic chemistry
generally, should be based upon an exact knowledge of inorganic
chemistry in all its relations, for many of the deficiencies which we
have found occasion to notice in the researches of zealous physio-
logical and pathological chemists are referable to an inadequate
knowledge of inorganic chemistry. We are, therefore, the more
resolved to omit all notice of the analyses of mineral substances,
again referring our readers to the admirable memoirs which have
appeared in recent times on this subject, and for which we are in-
debted to Will and Fresenius,* Mitscherlich,t Knop,{ Erdmann,§
Heintz||, Rose^[, [and Strecker.** — G. E: D.]
If we venture to adopt a physiological classification in our
description of the mineral substances of the animal body (which,
moreover, can refer only to their physiological function,) we adopt
this course simply from a feeling of its great applicability, and
not because we consider ourselves able to indicate the exact
place occupied in this system by each individual mineral substance;
for the remarks we have already made, must sufficiently indicate the
uncertainty and deficiency of our knowledge on this subject. We
therefore attempt to divide the mineral substances of the animal
body in reference to their physiological importance, into :
* Ann. d. Ch. u. Pharm. Bd. 50, S. 363-396.
t Ber. d. Akad. d. Wiss. z. Berlin, 1845, S. 236-252.
t Journ. f. pr. Ch. Bd. 38, S. 14-47.
§ Ibid. Bd. 38, S. 40-69, and Ber. d. Gesellsch. d. Wiss. zu Leipzig, 1847, S. 83-90 .
|| Op. cit.
IF Op cit.
** Ann. d. Ch. u. Pharin. Bd. 73.
412 FIRST CLASS OF MINERAL CONSTITUENTS.
1. Those which are of especial use in the animal body through
their physical properties.
2. Those which are adapted by their chemical properties to
serve definite objects in the animal economy : and
3. Those which are only incidentally conveyed into the animal
body, exert no influence on any special process, and are, therefore,
speedily eliminated from the organism.
FIRST CLASS OF MINERAL BODIES.
WATER.
It would be superfluous to enumerate the uses of this substance
in the animal organism ; we will confine ourselves to the two simple
remarks that water is essential to the establishment of all chemical
activity, and, further, that the functions, or rather the physical
properties, of certain tissues, are dependent on the presence of a
certain quantity of water which is merely in a state of mechanical
combination.
PHOSPHATE OF LIME.
This is the most important of all the mineral substances which,
by their physical properties, are of service in the animal body.
The use of its presence in the bones, where it gives solidity and
strength to the osseous skeleton, is at once apparent. Bones
deficient in this salt are proportionally deficient in firmness: thus
we observe that softening of the bones occurs in those conditions
when the animal organism does not receive a sufficient supply of
phosphate of lime, or when certain physiological processes require
an increased consumption of this salt, as in pregnancy, and
during the dentition of children. We need hardly remark that
rachitis frequently, if not always, occurs simultaneously with the
period of dentition, that the consumption of phosphate of lime
during pregnancy is often so great that scarcely any traces of it
can be found in the urine, and that during this period of woman's
life fractures unite with extreme difficulty, and sometimes do not
PHOSPHATE OF LIME. 413
unite at all. Chossat* was able to induce softening of the bones
artificially in animals, when he restricted them to food containing
little or no phosphate of lime. The permanent cartilages only
ossify in old age, when a superabundance of calcareous salts is
deposited in them. In the dense, cortical portion of bones, we
find more bone-earth deposited than in the spongy parts. The
teeth, whose utility depends entirely on their hardness, contain a
larger proportion of phosphate of lime than any other part of the
animal body; and it exists in still greater quantity in the enamel
than in the dentine.
We have previously had occasion to remark that Berzelius, even
to a recent time, adhered to the formula 8CaO.3PO5 for the phos-
phate of lime of bone-earth, and that on the other hand the inves-
tigations of W. Heintz under Rose's direction, indicate that the
formula for the composition of bone-earth should be 3CaO.PO5.
Berzeliusf has in part given the reason for his formula. It is not
always 8CaO.3PO5 which is precipitated from acid solutions con-
taining lime and phosphoric acid, as he formerly assumed ; but
when there is an excess of lime, and under the prolonged action of
caustic ammonia, the basic salt 3CaO.PO5 is precipitated. Since
the phosphate of lime is for the most part separated in this way,
and the lime which is precipitated after the removal of the phos-
phate is calculated as if it were a carbonate, without any direct
determination of the carbonic acid, there must be some uncertainty
in the ordinary analyses of the earthy constituents of the bones, in
part owing to the not very accurate determination of the magnesia.
Heintz has found that this is the composition of phosphate of lime
not only in normal human bones, but also in those of the sheep and
the ox. In this point of view, however, the investigation of
diseased bones requires a thorough revision ; moreover, von
Bibra'sJ analyses seem to show that in the teeth the ratio of the
phosphoric acid to the lime is not in accordance with either of the
above formulae.
In healthy human bones the phosphate of liaie ranges from
48 to 59£; in softening of the bones it may sink to 30%. It is,
however, singular that in almost all diseases of the bones, whether
the results of osteoporosis, osteomalacia, or osteopsathyrosis, we
find a diminution of the phosphate of lime. Even in consecutive
* Gaz. ni(M. 1842, p. 208.
t Ann. d Ch. u. Pharm. Bd. 53, S. 280-289.
+ Chem. Unters. iib. Knocken u. Zaline. Schweinfurt, 1844, S. 284-287.
414 FIRST CLASS OF MINERAL CONSTITUENTS.
induration (or eburneation) the bones often do not regain their
normal quantity of phosphate of lime.
Von Bibra has very fully investigated the composition of the
different bones of the same individual, and has made the beautiful
observation that those bones which are the most exposed to mecha-
nical influences contain the largest amount of earthy constituents.
The action of this law is manifested even in different families of
the same class of animals ; thus, for instance, in the rasores or
scraping birds, the femur contains the largest quantity of phos-
phate of lime, in the grallatores or waders, the tibia, and in all
other birds, the humerus.
That the phosphate of lime and the earths generally are only
mechanically deposited in the bones, is obvious from the circum-
stance that we can so thoroughly deprive them of all mineral con-
stituents by dilute hydrochloric acid, that they leave scarcely a trace
of ash.
It has for a long time been a matter of discussion whether the
phosphate of lime is, or is not, chiefly deposited in the bone-cor-
puscles and the canalicula chalicophorce. I am however now con-
vinced that the dark colour of these parts in refracted light, and
their white colour in reflected light, essentially depends on their
containing air. Any one may readily convince himself that this is
the case, by treating one thin section of bone with dilute hydro-
chloric acid, so as to remove the earths, and another with a dilute
solution of potash, so as to remove the cartilaginous substance,
and comparing the two under the microscope. Frerichs* attempted
to demonstrate that the earths were uniformly distributed through-
out the bone by showing that osseous laminae from which the car-
tilaginous substance had been removed by a dilute solution of pot-
ash received an uniform yellow tint on the addition of nitrate of
silver, and that the bone-corpuscles were not distinguished by any
special depth of colour.
Phosphate of lime also occurs in many other parts of the
animal body, although in far less quantity than in the bones ;
indeed there is no animal tissue, in whose ash, on incineration, we
do not find phosphate of lime.
Liebigf regards the insolubility of certain tissues, as for
instance, muscular fibre and cellular tissue, as partially due to
the bone-earth which they contain. In the transition of the
* Ann. d. Ch. u. Pharm. Bd. 43, S. 251.
t Ibid. Bd. 50, S. 170.
PHOSPHATE OF LIME. 415
blood into these tissues its protein -compounds part with the soluble
phosphate of soda but retain a large quantity of the phosphate of
lime. It is thus that Liebig accounts for the special power which
hydrochloric acid possesses of dissolving these substances during
the process of digestion.
Well dried muscular fibre contains, according to von Bibra,
from 0-938 to 1'OOSf of bone-earth.
Phosphate of lime is found in solution in all the animal fluids ;
its presence has long been recognised in the blood, the urine,
the fluids of serous membranes, the saliva, gastric juice, milk,
and seminal fluid, but it was for a long time unknown by what
means this insoluble body was retained in solution in alkaline and
neutral fluids. As a general rule phosphate of lime is chemically
combined wtih the protein-compounds and similar organic matters,
and is retained by them in their solutions as well as in their meta-
morphoses into the tissues. Moreover it has been long demonstrated
by Berzelius and Thenard, that phosphate of lime is to a certain
degree soluble in fluids containing much carbonic acid; we know
from analytical chemistry, that it is not altogether insoluble in
fluids containing hydrochlorate of ammonia, and recently Liebig
has shown that a little phosphate of lime is taken up by solutions
of chloride of sodium. The solubility of bone-earth in animal
fluids is thus sufficiently intelligible.
We have already spoken of the solvent power which lactic acid
exerts on phosphate of lime. In opposition to the experiments of
Walter Crumf I will only remark that in my experiments (taking
the mean of six) 68*55 parts of basic phosphate of lime were
dissolved by 100 parts of anhydrous lactic acid, while a fluid
containing 100 parts of anhydrous acetic acid could only dissolve
17'49 parts of the same salt.
The ash of the protein-compounds consists for the most part of
phosphate of lime; BerzeliusJ found 1'8-g- in the albumen from the
serum of ox-blood, while Mulder found 2'03& and Marchand from
2-1 to 2 -5£ in that of the egg; in soluble albumen precipitated by
great dilution and neutralisation, I found l"3% of phosphate of lime ;
in well-washed fibrin from the venous blood of a man, I found only
0-694^. Casein, globulin, chondrin, and glutin also contain phos-
phate of lime as an integral constituent. Casein, according to Mul-
der§ contains 6$ of phosphate of lime, which, when the casein is coag-
* Ann. de Ch. u. Pharm. Bd. 61, S. 128.
t Ibid. Bd. 63, S. 394 ff.
J Lehrb. d. Ch. Bd. 9,8.35.
§ Arcliiv. f. 1828, p. 155.
416 FIRST CLASS OF MINERAL CONSTITUENTS.
ulated, is precipitated with it, even when there is a sufficient quan-
tity of free acid in the fluid. Chondrin, according to Mulder, yields
on incineration 4*09^ of ash, most of which is phosphate of lime.
As chemical compounds of phosphate of lime with albumen and
with gelatin have been prepared, which contain much greater quan-
tities of this salt (in albumen even one -third) there would be nothing
absurd in the supposition that a portion of the phosphate of lime
contained in the bones, is chemically combined with the cartila-
ginous substance, even though it may be removed by hydrochloric
acid.
The constant occurrence of phosphate of lime in the histoge-
netic substances, and especially in the plastic fluids, as well as its
deposition in many pathologically degenerated cells of the animal
body, obviously strengthen the opinion that this substance plays an
important part in the metamorphosis of the animal tissues, and es-
pecially in the formation and in the subsequent changes of animal
cells. This subject must, however, be more fully investigated,,
before we can draw any definite conclusions regarding it.
In connexion with this subject, C. Schmidt* has, however,
made a very interesting observation regarding the folds of the
mantle of Unio and Anodonta. They consist of a middle layer of
fibres of areolar tissue, which on its inner side is covered with
ciliated epithelium and towards the shell with glandular epithelium ;
in these parts he found about 15$ of phosphate of lime, 3£ of car-
bonate of lime and soluble salts, and 82^ of organic matter, — the
quantity of phosphate of lime being very extraordinary, as the
blood of these animals contains only 0*034^ of this salt. The
mucus, lying between the shell and the mantle of these animals,
and secreted by the layer of glandular cells on the mantle for the
consolidation of the shell, consists of a strong basic albuminate of
lime containing only a little preformed carbonate of lime. Schmidt
is of opinion that the function of this glandular epithelium, which
resembles the cells of the liver, is to secrete from the blood
a combination of albumen and lime, decomposable by the carbonic
acid of the air or of water, for the formation of the shell, while it
leaves the phosphate of lime for those organs which require it for
the process of cell-formation (the testicle and ovary.)
The questions now arise, how do such masses of phosphate
of lime find their way into the animal body ? Or how are
they formed in it ? That carnivorous animals receive a more
than sufficient quantity with their food is obvious from the prece-
ding observations. Graminivorous animals likewise receive in their
* Zur vergleiclienden Physiol. S. 56-60.
PHOSPHATE OF LIME. 417
food a sufficient quantity of this earthy salt ; for in the vegetable
kingdom, we find certain nitrogenous bodies which, like the protein-
compounds of the animal organism,, always contain some phosphate
of lime, as for instance, vegetable albumen, legumin, and gluten.
Phosphate of lime, is, however, also formed within the animal
organism. If the experiments of von Bibra, showing that the bones
of young creatures contain relatively more phosphate of ime than
those of older ones, appear to be opposed to the view ttiat the
phosphate of lime is formed from the carbonate, the numerous
analyses of Valentin* prove that newly formed bones, or parts of
bones, always contain a greater quantity of carbonate of lime before
they are provided with their proper quantity of phosphate of lime.
If we review the different substances taking part in the metamor-
phosis of the animal tissues, it appears, as a necessary conclusion,
that phosphate of lime must be formed from its proximate con-
stituents. We know that several animal substances contain phos-
phorus in an unoxidised state, and that they are not removed from
the organism till they are perfectly decomposed, that is to say,
till they are partially oxidised ; in this process the phosphorus
must be converted into phosphoric acid. We further know that very
many animal substances also contain sulphur, and in their decom-
position in the animal body form not only sulphuric acid, but also
uric, hippurie, and other acids, which must partially decompose the
alkaline phosphates that find their way into the body from with-
out, that is to say, by the seeds of the cereals and leguminous plants,
so that the liberated phosphoric acid must combine with the lime
which enters the animal body with the vegetable food or with the
water used as drink. We have an opportunity of almost directly
observing the process of the new formation of phosphate of lime
from its proximate constituents in the development of the chick
within the egg ; for the observations of Front and Lassaigne show
that during incubation, such a quantity of carbonate of lime is
transferred from the shell of the egg to the yolk, that the augment-
ation of the phosphate of lime with the growth of the chick during
incubation, is not more than can be accounted for.
Valentin's opinion is based on the following observations : —
In the carious tibia of a man, aged 38 years, he found 44'12-g-
of ash containing 77'93£ of phosphate, and 15*04£ of carbo-
nate of lime, while the tibia of a healthy man of the same
age yielded 61'98-g- of ash, in which were contained 84£ of phos-
phate, and 12'8£ of carbonate of lime. Hence, in this case, the
* Repert. f. Anat. u. Physiol. 1839, S. 306 ff.
2 E
418 FIRST CLASS OF MINERAL CONSTITUENTS.
amount of ash was diminished almost solely at the expense of the
phosphate of lime. In the callus, as well as in the exostosis of a
horse, he found the carbonate of lime increased in relation to the
phosphate, and hence concluded, that, as a general rule, imperfectly
formed bones always contain more carbonate of lime than normal
bones. Lassaigne's experiments* accord with those of Valentin.
In the osteophyte occurring on the inner layer of the skull during
pregnancy, there is also much carbonate of lime, as was observed
by Kiihn; I found 52'46-g- of organic matter, 30'69-g- of phosphate
of lime, 1'09£ of phosphates of magnesia and iron, 0 98-g- of soluble
salts, and 14'78-g- of carbonate of lime in one of these osteophytes.
Proutf was the first who observed that during the incubation of
the egg the quantity of phosphorus in its contents remains constant,
but that the quantity of lime undergoes a considerable augmentation;
he was almost inclined from this observation to conclude that there
was a formation of lime from other materials, since he did not re-
gard it as probable that the non-vascular membrana putaminis could
transfer lime from the shell to the embryo. But if we take into con-
sideration that during incubation the shell experiences a loss both
in weight and firmness, and that a part of this membrana putaminis
becomes dried, and consequently impermeable, while, however,
the greater part is in contact with the contents and thus remains
moist, it is very easy to perceive that the increase in the amount
of lime within the egg arises from its most proximate source,
namely, from the shell itself. The phosphorus exists chiefly in
the yolk, where it occurs as glycero-phosphoric acid, which during
incubation is gradually decomposed, so that the liberated phos-
phoric acid unites with lime which passes over by endosmosis from
the shell into the egg to form this salt. There is, however, so
much phosphorus contained in the yolk of the egg, that on inci-
neration it forms acid phosphates, or rather metaphosphates
(NaO.KO.PO5), with tlie bases which it there encounters.
CARBONATE OF LIME.
This salt is principally found in the skeletons of invertebrate
animals ; but it always occurs, as has been already mentioned, in
reater or smaller quantities, in the bones of the vertebrata. Its
uses in the animal organism are the same as those of phosphate
of lime
* Journ. de Chim. m^d. T. 4, p. 366.
t Phil. Trans. 1822, p. 365.
CARBONATE OF LIME. 419
There can be no doubt that the carbonate of lime found in
animal substances is very often no educt, but the product of the
incineration to which we have submitted the substance in the
course of the chemical analysis; it not unfrequently, however,
occurs in the bones of the vertebrate animals as true carbonate of
lime, and in the lower classes of this great division we find it deposited
in various places in microscopic crystals. Carbonate of lime in
considerable quantity is found in the urine of graminivorous ani-
mals, in the saliva of the horse, and in many animal concretions.
Numerous experiments have been instituted, especially by
Lassaigne, Fernandes de Barros*, Valentinfs and von BibraJ,
with the view of ascertaining the ratio in which the carbonate of
lime stands to the phosphate in the bones of different men and
animals. According to my own investigations, this ratio in a new-
born child = 1 : 3*8, in an adult male — 1 : 5*9, and in a man
aged 63 years = 1 : 8'1 ; according to Valentin it = 1 : 8 -3 (on
an average) in caries, and = 1 : 5'54 in callus, or 1 : 5*3 according
to Lassaigne ; in an exostosis it = 1:52 according to Valentin,
and 1 : 1*214 according to Lassaigne; according to Barros it — 1 : 3'8
in the lion, 1 : 4' 15 in the sheep, 1 : 8*4 in the hen, 1 : 3'9 in the
frog, and 1 : 1*7 in a fish. According to Lassaigne this ratio
= 1 : 3'6 in the teeth of a new-born child, 1 : 5'3 in those of a
child aged six years, 1 : 6 in those of an adult, and 1 : 6*6 in those
of a man aged 81 years.
Von Bibra, in his numerous analyses of bone, has arrived at
opposite results, since he found that the bones of young creatures for
the most part contained less carbonate of lime than those of older
ones. As we must refer for fuller information to von Bibra's work,
we shall here only give the quantity of carbonate of lime which he
found in the femur in different classes of animals ; in the order glires,
it amounts to 9'48£, in the ruminantia to 9'86-g- , in thepachydermata
to 10'15£, in the cetacea (the dolphin) to 9*99£, in the pinnipedia
(the seal) to 7'23-g-, in the falculata to 6'26-g-, in the pollicata to
9-1 8-g-, and in men to 8'59-g-.
The urine of graminivorous animals often contains so large a
quantity of carbonate of lime as to cause a deposit very soon after
its emission. My investigations tend to show that in the urine of
the horse carbonate of potash and carbonate of lime very frequently
replace one another ; I have usually found that urine rendered
* Journ. de Chira. m^d. T. 4, p. 289.
f Op. cit.
i Op. cit.
2 E 2
420 FIRST CLASS OF MINERAL CONSTITUENTS.
turbid by the presence of much carbonate of lime contains a very
small quantity of alkaline carbonates, and often has only a very
slight reaction on turmeric paper, while clear urine is usually
rich in alkaline carbonates. Hence it is easy to see why urinary
calculi consisting of carbonate of lime are of very common occurrence
in herbivorous animals.
Carbonate of lime sometimes also occurs in human urine with
an alkaline reaction ; and indeed sometimes, although very rarely,
we meet with human urinary calculi, consisting for the most part
of carbonate of lime. Proust* was the first who made this obser-
vation ; but similar calculi have been since found by Cooper,
Prout,f Smith, G6bel,{ and Fromherz.§
In animal concretions, we sometimes find considerable quan-
tities of carbonate of lime deposited with the phosphate. Thus,
Geiger|| found 21'7 of carbonate and 46*7 of phosphate of lime
in a nasal concretion ; I found 24 '3£ of carbonate and 69. 7£ of
phosphate of lime in a phlebolith, and Schlossberger^f 8*3 of carbo-
nate and 50*4 of phosphate of lime in a similar concretion :
Walchner** found 23-g- of carbonate and 50£ of phosphate of lime
in a concretion from the heart of a man with hydrothorax, and
Johnff found 66* 7£ of carbonate and 25% of phosphate of lime in a
concretion taken from a stag's heart. Some stony concretions
from the peritoneum of a man were found by BleyJ J to contain 34-g-
of carbonate and only 19*32^ of phosphate of lime; Lassaigne§§
found 83*36 £ of carbonate of lime in a salivary concretion from a
horse. I need hardly advert to the frequency with which we meet
with tolerably large quantities of carbonate of lime in the micro-
scopico-chemical investigation of indurated or ossified tumours, as
for instance, chalky tubercle.
Carbonate of lime in the crystalline state is very rarely found
in the human organism ; the only place where it constantly occurs
in the normal state is the utriculus of the membranous vestibule || || of
* A. Gehlen's Journ. Bd. 3, S. 532.
t Thomson's Annals of Philos. vol. 15, p. 436.
I Troramsdorf's n. Journ. Bd. 9, S. 198.
§ Schweigg. Journ. Bd. 46, S. 3 29 .
|| Mag. f. Pharm. Bd. 21, S. 247.
1 Ann. d. Ch. u. Pharm. Bd. 69, S. 254.
** Mag. f. Pharm. Bd. 19, S. 152.
ft Chem. Schriften. Bd. 5, S. 155.
£$ Arch. d. Pharm. Bd. 20, S. 212.
§§ Journ. de Chim. meM. 1845. p. 523.
HI) [It occurs also in the sacculus, and is sometimes scattered in the cells lining
the ampulla and semi-circular canals. — o. E. D.]
CARBONATE OF LIME. 421
the inner car, on whose outer and upper walls it is deposited in
minute crystals amongst organic matter. These crystals are usually
so very minute,, that distinct molecular motion may be observed
amongst the smallest of them. The form of the crystals is never
a pure rhombohedron, but always a prism derivable from the
rhombohedron of calc-spar, most frequently resembling the so-
called Kanonendrusen of calc-spar ;* that is to say, they are six-sided
with 3-planed acuminations. Kriegerf has also seen twin crystals
of the scaleno-octahedral form. Crystals of this nature occur
much more frequently and abundantly in the lower animals, both
in the organs of hearing and in other parts; perhaps the best
known and most striking case of the occurrence of such crystals is
in the membrane of the brain of the batrachia, and in the white,
silvery saccules at the intervertebral foramina through which the
spinal nerves emerge. In morbid formations in the human organ-
ism, we not unfrequently meet with crystalline deposits of carbonate
of lime, which however usually appears rather in irregular crystal-
line masses, such as are described by Vogel,J than as perfectly
formed crystals.
There are obviously two ways in which we may account for
the presence of carbonate of lime in the animal organism. It is
well known that spring water holding carbonic acid in solution,
usually contains a considerable quantity of carbonate of lime ; and
this might sufficiently explain the presence of this salt, even if it
were not in a great measure formed within the organism from
other salts of lime, which find their way there in abundant quan-
tity with the vegetable articles of food ; hence it is that the urine
of herbivorous animals is often so rich in carbonate of lime.
The solubility of this salt in the animal fluids, might, at first
sight, seem to be less easily understood than its origin. The free
carbonic acid which, it is almost certain, may be detected in all
the animal fluids, doubtless acts as a solvent for the carbonate of
lime ; and I may remind any who may not be satisfied with this
explanation, that the old experiments of Guiton Morveau, show
that carbonate of lime is also slightly soluble in solutions of the
alkaline salts, as for instance, chloride of potassium. Moreover,
* [The term Kanonendrusen is used in the Hartz to signify a crystalline mo-
dification of calc-spar. Drusen signifies a cluster of crystalline substances. A
crystal is said to be drusy (drusig) when it is coated with a number of minute
crystals of the same kind, so that the new surface acquires a scaly aspect. G. E. D.]
t De otolithis. Berolini, 1840, p. J5.
J Icones histol. path. Tab. 22, fig. 8.
422 FIRST CLASS OF MINERAL CONSTITUENTS.
it is not improbable that there are several animal substances which,
like sugar, exert solvent action on carbonate of lime.
PHOSPHATE OF MAGNESIA.
Phosphate of magnesia always occurs in such small quantity
that we feel scarcely justified in ascribing to it simply a mecha-
nical use in the animal body, and in arranging it in this class of the
mineral substances ; it is, however, so constantly associated with
the corresponding lime-salt that we feel compelled to notice it
in this place. Like the phosphate of lime, it is in the osseous
system that it is chiefly deposited.
The bones of carnivorous animals and of man contain very
little phosphate of magnesia ; those of herbivorous animals rather
a larger quantity. Berzelius found 1'16£ in a piece of human bone,
and 2*05^ in the bones of an ox ; Valentin found 1*943^- in a por-
tion of one of the ribs of a horse ; Berzelius 1'5-g- in the enamel of
a human tooth, and 3-g- in that of the tooth of an ox ; in human
dentine he found !-§-, and in that of the ox 2*07-§-. The numerous
analyses of von Bibra afford a general confirmation of these facts ;
he observed, moreover, that the teeth of the pachydermata were
especially rich in phosphate of magnesia. Various physiological
relations (age, &c.), as well as morbid conditions, augment and
diminish the quantity of this salt, which seems, however, to vary in
a direct ratio with the phosphate of lime. We shall return to this
subject in our remarks on "The Bones."
That a little phosphate of magnesia occurs in all the animal
fluids and tissues is demonstrated by the analyses of the ash. The
presence of this salt is very strikingly shown by a microscopic
examination of the tissues of a dead body in which putrefaction has
actively commenced : we observe that it is everywhere studded
with the well-known crystals of the phosphate of ammonia and
magnesia.
Phosphate of magnesia sometimes accumulates in large quan-
tities in certain concretions ; thus Brugnatelli* found a concretion
in a human ovary consisting almost entirely of this earthy salt, and
a similar one in the uterus, which was surrounded by a thin crust
of phosphate of lime. A phlebolith, examined by Schlossbergerf
* Brugn. Giorn. T. 12, p. Ki4.
t Ann. d, Ch. 11. 1'hann. Bd. 69, S. 254.
PHOSPHATE OF MAGNESIA. 423
contained 58'7o of salts of lime, 13'7£ of phosphate of magnesia,
and 20'4-g- of organic matters.
The origin of the phosphate of magnesia is sufficiently obvious;
for this salt occurs in all parts of plants, and particularly in the
common varieties of grain that are used for food. From the ratio
in which, as we have shown, the phosphate of magnesia stands to
the phosphate of lime in the bones and other parts we may conclude
that the animal economy requires far less of this salt than of the
corresponding lime-salt; and this is especially illustrated by the fact
that in different animals it is found that the intestinal canal absorbs
all the phosphate of lime, but only very little phosphate of mag-
nesia ; for the excrements of the carnivora, as well as of the
herbivora, contain an excess of the latter salt.
From these facts, Berzelius* long ago drew the conclusion that
the absorbents of the intestinal canal have less tendency to take up
phosphate of magnesia than phosphate of lime, but that rather
more is always absorbed by the herbivora than by the carnivora ;
this latter fact, however, probably depends upon the circum-
stance that the food of the former contains far more magnesia than
that of the latter class of animals. We should, however, be too
strictly interpreting the meaning of Berzelius if we were to sup-
pose that he considered the absorbents to possess any special
power of selecting and taking up certain substances and rejecting
others. The phenomenon in its whole extent is probably a mecha-
nical one ; the great tendency of the salts of magnesia to form
crystals with the salts of the alkalies, may probably in some mea-
sure impede their free solution and resorption.
Berzelius found 12'9£ of phosphate of magnesia, and 25'8-g- of
phosphate of lime in the ash of the excrements, after the use of
coarse bread and a little animal food. Fleitmannf found that, after
the use, for some days, of a diet consisting of more animal than
vegetable food, the excrements yielded an ash containing 10'67^ of
magnesia.
The common intestinal concretions of horses consist almost en-
tirely of phosphate of magnesia and ammonia, with fragments of
straw, &c. ; in a concretion of this sort, SimonJ found 81-g- of
phosphate of magnesia, but no salt of lime.
Physicians have paid much attention to the crystals of phos-
phate of magnesia and ammonia, which are very strikingly seen
in typhous stools. Although these crystals are often enough to be
* Lehrb. d. Ch. Bd. 9, S. 345.
t Pogg. Ann. Bd. 76, S. 383.
t Buchner's Repertorium. Bd. 16, S. 215.
424 FIRST CLASS OF MINERAL CONSTITUENTS.
found in the faeces in other diseases, it must be granted that their
occurrence is by far the most frequently to be noticed in abdominal
typhus ; indeed, it is well known that the ulcerated patches of the
intestine are usually thickly studded with minute crystals of this
nature.
Phosphate of magnesia is always found in the urine of man and
of carnivorous animals, and its presence is rendered very percep-
tible when the urine becomes alkaline, by the readiness with which
it crystallises in combination with ammonia. As we shall return to
this subject in the second volume, it is sufficient to observe in the
present place, that these crystals are always formed in normal
urine when alkaline fermentation commences. In serious lesions
of the bladder or the spinal cord, we often find whole sediments
consisting of these crystals. These deposits are, for the most
part, either devoid of colour, or of a dirty white tint. In a spe-
cimen of diabetic urine, I once found a glistening white sediment,
consisting entirely of these crystals, and not containing a trace of
lime. Urinary calculi, consisting of pure phosphate of magnesia,
are very rare, although more common than \hefusible calculi which
are composed of a mixture of phosphate of lime with phosphate of
ammonia and magnesia.
FLUORIDE OF CALCIUM.
It is only in very minute quantities that this body occurs in the
animal organism ; it is, however, so integral a part of the enamel of
the teeth, that we are inclined to ascribe to its presence (at least in
part) the polish and the extraordinary hardness of that substance.
The presence of small quantities of fluoride of calcium has been
determined with certainty in the bones of almost all animals.
More fluoride of calcium has been found in the skeletons of fossil
animals than in those of our own time ; and it is worthy of notice,
that human bones found at Pompeii, contain, according to Liebig,*
more fluoride of calcium that recent human bones.
Berzeliusf found 2'1-g- of fluoride of calcium in the dentine and
3'2° in the enamel of a man's tooth, wrhile the dentine and the
enamel of that of an ox contained respectively 5*69-° and 4-{J- of
this constituent. MarchandJ found 1-g- in the femur of a man
aged 30 years, and Heintz§, 2'05-g-.
* Organ. Ch. auf Agricultur u. Physiol. angewendet, 1840, S. 140.
t Alt. Gehlen's Journ. 13d. 3, S. 1.
$ Journ. f. pr. Ch. Bd. 2?,_S. 83.
$ Ber. d. Ak. d. Wiss. z. Berlin. Febr. HUD, S. 51.
FLUORIDE OF CALCIUM. 425
Both Middleton* and von Bibraf have very carefully analysed
the bones of various classes of animals, and have recognised the
presence of fluoride of calcium not only in the bones of the mam-
malia, but also in those of birds, fishes, and reptiles, and even in
the shells of the mollusca. Middleton 's assertion that the bones of
a 6^ months' fretus contain as much fluoride of calcium as those of
an adult, must be regarded as doubtful, till confirmed by further
experiments.
Fluoride of calcium was first discovered in fossil ivory by
MorichiniJ ; it has since been found in all fossil bones by Proust§,
Fourcroy and Vauquelin||, Chevreul^f, Brandes**, Bergemannft,
Marchand, von Bibra, Middleton, and others. Lassaignett found
as much as 15£ in the teeth of an Anoplotherium, and I§§ found
16-g- in the outer portion of one of the ribs of the Hydrarchos.
[The presence of fluorine in blood and milk has been clearly
demonstrated by Dr. George Wilson ||||. G. E. D.]
In regard to the origin of the fluoride of calcium we cannot
doubt that the small quantities found in the animal body may be
easily conveyed into the system with the food; we need only
remember that many mineral waters contain traces of fluorides,
and that plants take up a little fluoride of calcium from micaceous
soils.
Fluoride of calcium was detected by Berzelius in the Carlsbad
water, and has been found in other mineral waters; moreover,
artificially prepared fluoride of calcium is by no means perfectly
insoluble in distilled water. [According to Wilson 16 fluid ounces,
or 7000 grains of water at 60° F, dissolve 0*26 of a grain of fluor
spar. G. E. D.]
Whether the large quantities of fluoride of calcium which have
been found in fossil bones are solely due to infiltration from
without, must remain for the present undecided.
* Philos. Mag. T. 25, p. 14.
f Op. cit.
J A. Gehl. J. Bd. 3, S. 625 ; N. Gehl. J. Bd. 2, S. 177-
§ N. Gehl. J. Bd. 2. S. 187.
|| Ann. d.Chim. T. 57, p. 37.
IT Ibid. p. 45.
** Schweigg. Journ. Bd. 32, S. 505.
ft Ibid. Bd. 52, S. 145.
tt Journ. de Pharm. T. 7, p. 1.
§§ Cams, iiber den Hydrarchos. Dresd. 1846.
HI) Edin. New Phil. Journ. Oct. 1850.
426 FIRST CLASS OF MINERAL CONSTITUENTS.
SILICA.
As the skeleton of the vertebrate animals chiefly owes its
hardness to the phosphate of lime whicli it contains, and the shell
of the invertebrate animals to the carbonate of lime, so the shields
of the lowest classes of animals are rendered hard and firm by con-
taining a large quantity of silica. This substance is so thickly
deposited in these organs that neither decomposition nor incinera-
tion can destroy their form; hence it is that deposits of fossil infu-
soria are so often discovered.
Silica for the most part occurs only as an incidental constituent
of the juices and tissues of the higher classes of animals; Gorup-
Besanez* has, however, shown by numerous experiments that this
body forms an integral constituent of feathers and of hair.
Small quantities of silica have also been found in the blood, in
the white of egg, in the bile, in urine, and in the solid excrements,
and occasionally in certain morbid concretions.
The Bacillarice are the most remarkable of all the infusoria in
relation to the quantity of silica which they contain ; their shields
equally resist the action of fire and of acids. We are indebted to
Ehrenbergf for our first accurate knowledge on this subject, and
for the discovery of fossil infusoria in flint, mountain meal, &c.
Henneberg,J as well as Gorup-Besanez, has determined the
quantity of silica in feathers ; the latter, however, has fully investi-
gated the subject in all its bearings, and extends his enquiry to the
determination of the influence exercised by species, age, food, and
other circumstances on the deposition of silica in the feathers.
Gorup generally found from O'l 1 to 2'4/ir of silica in the feathers
of different birds, and from 6*9 to 65'0£ of silica in the ash. The
last-named quantity, which was the largest he ever found, occurred
in the feathers of Perdix cinerea,but the feathers of Striv flammea,
Gallus domesticus, and Corvus frugilegus, yielded ashes very rich in
silica. The feathers of granivorous birds contained from 1 '69 to
3'7l-§- of silica (and their ash yielded from 25*5 to 50g-) ; the fea-
thers of birds living on fish and aquatic plants contained on an
average 0'23£, and their ash 10'5£ of silica; those of birds living on
flesh and insects yielded, as a mean, 0'64£, and their ash 27£ ; and
* Ann. d. Ch. u. Pharm. Bd. 66, S. 321-342.
t Die Infusionsthierchen u. s. w. S. 143-169.
£ Ann. d. Ch. u. Pharm. Bd. 61, S. 255-61.
SILICA. 427
those of birds living on insects and berries 0'75-g-, and their ash
27$. Gorup usually found about twice as much silica in the feathers
of old animals as in those of the young of the same species.
In newly grown or young feathers only traces of silica were
often to be found. In the pinions of the first order there was
twice as much silica as in the tail-feathers of the second order ;
and in the tail and breast-feathers there was little more than in the
pinions of the second order.
Berzelius found no silica in the bones or teeth of man ; Four-
croy and Vauquelin* have, however, found it in the bones of chil-
dren, and Marchandf in those of Squalus cornubicus ; it has also
frequently been found in fossil bones.
Silica has been found by Chevreulj. in sheep's wool, and by
Vauquelin§, and more recently by Laer||, in the human hair.
Gorup has entered very fully into this part of the enquiry regard-
ing the occurrence of silica. In brown human hair he found
0'22-g- of silica, the ash yielding 13'89£, while in the hair and wool
of various animals he found sometimes rather more and sometimes
rather less of this substance. The quantity of silica in the hair
appears to be altogether independent of the nature of the food.
As silica occurs so constantly in the animal organism, it might
naturally be expected that we should find it in the blood, and
especially in that of birds. Millon^f found it in human blood ;
Weber** found that it amounted to 0'19-g-, in the ash of ox-blood,
and in hens' blood Hennebergft found 0*96£.
PoleckJJ found 7'05-g- in the ash of the white of egg ; silica has
also been found in the bile, urine, and solid excrements. Weiden-
busch§§ found 0'36{7 in the ash of ox-bile; Pleisch|||| and BleyHl" de-
tected it in gall-stones, and Mitscherlich*** found a trace of it in the
saliva. Berzeliusttt was the first who discovered traces of it in
* Ann. de Chim. T. 72, p. 282.
t Lehrb. d. phys. Ch. 8. 97.
I Compt. rend. T. 10, p. 632.
§ Ann. de Chim. T. 58, p. 41.
|| Ann. d. Ch. u. Pharm. Bd. 44, S. 172.
^[ Journ. de Pharra. 3 Ser. T. 13, pp. 86-88.
** Pogg. Ann. Bd. 76, S. 387.
ft Op. cit.
£t Pogg. Ann. Bd. 76, S. 360
§§ Ibid. S. 369.
|||| Kastn. Arch. Bd. 8, S. 300.
flT Journ. f. pr. Ch. Bd. 1, S. 115.
*** Pogg. Ann. Bd. 26, S. 320.
Lehrb. d. Cliem. Bd. 9, S. 433.
428 SECOND CLASS OF MINERAL CONSTITUENTS.
human urine ; Fleitmann* has since found it in the ash of the
urine, and Fourcroy and Vauquelinf > as well as de Koninck and
WurzerJ in urinary calculi. It need cause no wonder that silica
is often found in the contents of the intestines, as it is widely
distributed throughout the vegetable kingdom.
That the quantity of silica occurring in the animal organism
essentially depends on the greater or lesser quantity of silica in the
food, and consequently, that the origin of this body must be prin-
cipally referred to vegetable food and siliceous water (and further,
perhaps, in the case of birds, to the sand which they swallow,) is
rendered sufficiently evident from the experiments of Gorup-
Besanez, if, indeed, any demonstration of the fact were required.
Plants contain far more silica than was formerly supposed ;
in the Equisetacea, for instance, the ash often contains 97-§-.
The best method of exhibiting its presence in the seeds
of the grasses, is by moistening them with a little nitric
acid before incinerating them; in this manner, and with the
aid of the microscope we may, according to Schultz, recognise the
presence of this substance, not only in the husks but also in the
ovaries of many of the monocotyledons. Hence, it is obvious, that
we must receive silica into the system with the bread ; we can thus
readily understand how it was that, after the use of rye-bread, Ber-
zelius§ found l'016£ in the solid excrements, and why it is that the
dung of the herbivora, (whose food consists of those parts of plants
which are richest in silica,) contains so large a quantity of this sub-
stance. In the dung of the cow, Zierl|| found 4'4-g-, in that of the
sheep, 6'0#, and in that of the horse, 4'6£. Hence, large quantities
of silica are often found in the intestinal concretions of herbivorous
animals.
SECOND CLASS or MINERAL BODIES.
HYDROCHLORIC ACID.
As we are convinced by the reasons given in p. 93, that lactic
acid is the essential free acid of the gastric juice, we need devote
* Pogg. Ann. Bd. 76, S. 358.
t Syst. des Connoiss. Chim. T. 10.
4: Schweig. Journ. Bd. 36, S. 321.
§ Lehrb. d. Chem. Bd. 9, S. 346.
II Kastn. Arch. Bd. 2, S. 4?6.
HYDROFLUORIC ACID. 429
no special consideration to this acid. It is sufficient to remind
our readers, that, according to our experiments,* lactic acid can be
replaced by no other acid, except hydrochloric acid, in the process
of digestion.
HYDROFLUORIC ACID.
Brugnatellif believed that he had discovered the existence of
this acid in the gastric juice of birds, when he found that pieces of
agate and rock-crystal, which he introduced by means of tubes into
the stomachs of common fowls and turkeys, were distinctly corroded,
and had lost from 12 to 14 grains in weight, on their removal after
ten days ; and TreviranusJ also believed that, when the contents of
the intestinal canal of fowls were digested in porcelain vessels, the
glazing was attacked.
In reference to the small quantities of this acid which might
possibly occur in the gastric and intestinal juices of these animals,
it is certainly difficult to demonstrate its absence in an unques-
tionable manner ; but as theoretical reasons as well as direct expe-
riments are opposed to Brugnatellr's view, we may, at all events,
with great probability, assume the non- occurrence of this acid.
Tiedemann and Gmelm,§ digested the gastric juice of a duck for
24 hours in a platinum crucible, which was covered with a piece of
glass having a coating of wax through which a few lines were drawn ;
they could, however, detect no corrosion on the glass. I
placed the chyle of a duck which had just been killed, in a
platinum crucible, treated the mass with a little sulphuric
acid, and covered the crucible with a watch-glass coated with
wax except at the centre (the inferior convex part) where its
surface was bare and exposed; at the termination of the experi-
ment, I could not find the slightest corrosion on the watch-glass.
Further, I saturated with potash the fluid obtained by washing the
contents of the crop and stomach of two turkeys with water, eva-
porated it to dryness and burned the residue ; the ash was then
carefully treated with sulphuric acid in a platinum crucible, in the
manner already described, but here also no trace of hydrofluoric
acid was obtained.
If these experiments are not sufficiently stringent to overthrow
* Ber. d. k. sachs. Ges. d. Wiss. z. Leipzig. 1849.
t Crell's Ann. 1787- Bd. 1, S. 230.
J Biologie. Bd. 4, S. 362.
§ Verdammg. Bd. 2, S. 139.
430 SECOND CLASS OF MINERAL CONSTITUENTS.
the observations of Brugnatelli, they at all events serve to explain
how it was that Brugnatelli and Treviranus were led to adopt this
view. For it is very possible that, as we always find small pebbles
and sand in the stomachs of these animals, a purely mechanical
attrition of the finest granules of sand may have apparently cor-
roded the pieces of agate and rock-crystal during their long sojourn
in the stomach, and thus have occasioned their loss of weight.
Moreover, I have never been able to detect any decided corrosion
of the pebbles which we find in the stomachs of ducks and fowls.
It would be strange if nature had here first ordained the secretion of
hydrofluoric acid, in order that it should immediately again disap-
pear through the action of the siliceous pebbles which are swallowed
by birds. Should not the hydrofluoric acid, if it were present,
expel other acids from the salts contained in the gastric juice ?
CHLORIDE OP SODIUM.
In almost every portion of the earth's surface we find this body
in all parts of the animal organism ; and it is not a mere incidental
constituent conveyed into the system with the food and drink, but
it is applied to definite, although highly various ends.
The importance of chloride of sodium in the metamorphosis of
the animal tissues is illustrated by the fact that it always forms the
greatest part of the soluble constituents of the ash of all animal
substances. It is very constantly associated with certain animal
matters, and essentially influences their chemical and physical pro-
perties; thus albumen in part owes its solubility to the chloride of
sodium contained in it, and the differences which it presents in
coagulating are in part dependent on the quantity of this salt that is
present. Chloride of sodium dissolves pure casein, and has a sin-
gular power of impeding the coagulation of the fibrin of the blood.
If it is impossible to prove that chloride of sodium forms definite
chemical compounds with these bodies, the following considerations
at all events render such a view probable ; — namely, the influence
this salt exercises on the above named protein-compounds, the
analogy of the compound of chloride of sodium and glucose, and
finally the impossibility, by mere washing, of perfectly separating
some of the protein-compounds from the chloride of sodium.
We would especially refer the reader to the relation of albumen
towards salts, described in p. 332.
In accordance with these facts we find that the chloride of
sodium, like other important constituents of the animal body, is
CHLORIDE OF SODIUM. 431
not merely constantly present, but also that it is combined in tole-
rably definite proportions in the different constituent parts. For
it is an established law, that the different animal fluids always
strive to attain a similar chemical constitution. This law, to which
we must subsequently recur more in detail, includes the protein-
compounds, which, if they are taken in excess, certainly are decom-
posed in the ordinary manner, but are eliminated as rapidly as pos-
sible by the kidneys under the form of urea and uric acid.
The chloride of sodium in normal human blood stands in a
tolerably constant ratio to its other soluble constituents, the limiting-
ratios being 3 : 1 and 2'4 : 1. Berzelius* found 6 parts in 1000 of
the serum of human blood, and Marcetf 6*6 in 1000 parts of blood,
which corresponds to about 5'5 in 1000 of serum; NasseJ obtained
from 4 to 5 parts of chloride of sodium from 1000 of blood, Denis§
from 3'537 to 3*668 parts, and Becquerel and Rodier|| from 2'3 to
4*2 parts; the mean of 11 analyses of men's blood yielding 3'1, and
of 8 analyses of women's blood 3'5 parts. In 1000 parts of my own
blood in a normal state I found 4' 138 parts of chloride of sodium,
and after the use of very salt food, which caused intense thirst, it
amounted to 4*148; an hour after taking two ounces of salt, and
having in the interval drank about two quarts of water, the quantity
was 4' 181. Hence it seems to follow that the animal organism not
only removes foreign substances with extraordinary rapidity, but
that even useful substances, if they are in excess, are as rapidly as
possible eliminated.
The amount of salt in the blood undergoes great fluctuations
in different diseases ; thus Nasse^f and Scherer** found that there
was a diminution of the chloride of sodium in inflammatory blood ;
O'Shaugnessy, Rayer, and Mulder observed this strikingly in
cholera ; Nasse also observed it in the blood of a diabetic patient,
Lecanu in cases of jaundice, and Jennings and Simon in chlorotic
patients : an augmentation of the salt in the blood has been noticed
by Fremy in sea-scurvy and by Nasse in the rot in sheep. My
experiments have left it very doubtful whether the salts of the
blood are diminished in tuberculosis, since it is not often that we
can obtain the blood of tuberculous patients, except when some
* Lehrb. d. Chem. Bd. 9, S. 98.
t Medico-Chir. Trans. Vol. 2, p. 370.
1 Handworterbuch d. Physiol. Bd. 1, S. 167.
§ Journ. de Chim. m^d. T. 4, p. 111.
|| Gaz. mdd. 1844, No. 48.
TI Das Blut. 1836, S. 28?.
** Haeser's Arch. Bd. 10.
432 SECOND CLASS OF MINERAL CONSTITUENTS.
inflammatory attack gives occasion for the abstraction of blood.
We shall return to this subject more fully in the second volume,
when considering " The Blood."
Even if the well known action of chloride of sodium on the
colour of the blood be entirely dependent on mechanical relations,
the occurrence of almost constant quantities of this salt in the
blood during health, and its considerable variations in different
diseases, and, further, its chemical action on histogenetic sub-
stances, indicate that in all probability it takes some definite che-
mical part in the metamorphosis of the blood. Hofmann* believes
that it increases the capacity of the constituents of the blood for
oxidation, which however, requires proof.
Berzelius was formerly of opinion that the quantity of albumen
contained in the serum of the blood might be the cause why the
blood-pigment which is so readily soluble in pure water did not
dissolve in the serum, but Joh. Muller has shown that the capsules
of the blood-corpuscles dissolve, if they are brought in contact
with an aqueous and not too dilute solution of albumen ; if, how-
ever, we treat the albumen with a little water containing only l-£ of
chloride of sodium, the corpuscles remain unchanged, whereas they
are destroyed by a pure solution of salt containing no albumen.
We shall treat, at some length, of the mode of action of chloride
of sodium and various other bodies on the red colour of the blood,
in the second volume. It is here sufficient to remark that Scherer's
experiments have clearly demonstrated that the bright or dark
colour of the blood principally depends on the form of the blood-
corpuscles, which again is chiefly dependent on the endosrnotic
relations existing between their contents and the surrounding fluid.
For instance, if we add much salt to blood, the corpuscles become
contracted and biconcave ; it is to this biconcave form that Scherer
attributes the brighter colour of the blood.
In those fluids which are secreted from the blood and which
contain a larger quantity of chloride of sodium than the blood
itself, as, for instance, the saliva, gastric juice, inflammatory
exudations, pus, and mucus, this salt doubtless discharges some
important functions. We claim no high importance for it in the
saliva; but if that fluid exercises a function, the chloride of sodium
certainly takes part therein, since its quantity exceeds that of all
he other constituents of the saliva. In the gastric juice
we find, in addition to a little organic matter, scarcely any-
thing but metallic chlorides, and chiefly chloride of sodium.
• * Das Protein u. s. w. S. 19.
CHLORIDE OF SODIUM. 433
From the abundance in which it exists both in the saliva and
the gastric juice we miget be led to infer that it essentially pro-
motes the solution of the food, and its future changes, or at all
events, that it contributes to impede abnormal decompositions
and metamorphoses of the food.
Several observations which I have made, tend to show that the
excess of salt conveyed into the blood is not merely carried off by
the kidneys with the greatest possible rapidity, but also by other
secreting organs, as the salivary glands, the gastric glands, &c.
While the gastric mucous membrane of a dog with a fistulous
opening into the stomach, secreted a juice, when the stomach was
empty and artificially stimulated, which, according to Blondlot,
contained 0*126^ of chloride of sodium, I obtained a gastric juice
in a similar manner from a dog into whose jugular vein I had half
an hour previously injected two ounces of a saturated solution of
salt, which contained 0'385£. These facts are rendered more per-
ceptible by using either of the analogous salts, the iodide of sodium
or of potassium ; iodide of potassium, when injected into the veins,
appears with extreme rapidity in the stomach, although I am not
quite certain whether this is not in a great measure dependent on
its very rapid presence in the saliva, and on its finding its way
into the stomach through that fluid ; for I have convinced myself
that the iodide of potassium passes from the blood in larger quan-
tity, and with more rapidity, into the saliva than into the urine. If
we take a few grains of iodide of potassium in the form of pills, and
at once convince ourselves that no iodine is retained in the buccal
fluids, we can in the course of from 5 to 10 minutes recognise iodine
with certainty in the saliva, although it cannot be then detected in
the urine even if we examine that fluid directly after its secretion
by the kidneys, as it drops from the ureters. Bernard* has made
similar observations with prussiate of potash, lactic acid, and
other substances 5 after injection into the jugular veins of a dog,
they very rapidly appeared in the gastric juice.
Enderlinf found 6l'93% of the chlorides of sodium and potas-
sium in 100 parts of the mineral constituents of saliva.
Proutt found from O'l 2% to 0' 13£ of the chloride of sodium with
a little chloride of potassium in human gastric juice; Braconnot§,
* These soutenue a la faculte de Paris, 1844.
t Ann. d. Ch. u. Pharm. Bd. 50, S. 56.
t Phil. Trans, for 1824, p. 45.
§ Ann. de Chim. et de Phys. T. 59, p. 113.
2 F
434 SECOND CLASS OF MINERAL CONSTITUENTS.
Tiedemann and Gmelin*, and Berzelius agree in stating that the
gastric juice is rich in this salt. I found 0*31 !-§- of chloride of sodium
in the fluid from the crop of a duck which for eight days had been
only fed with barley moistened with distilled water.
That the chloride of sodium, and [the metallic chlorides gene-
rally, which are contained in the gastric juice, contribute at all to
the solution of the histogenetic substances is not probable ; for, not-
withstanding some of my earlier experiments which seemed to sup-
port that view, more recent and more numerous experimentst have
convinced me that any addition of salt, either to natural or well
prepared artificial gastric juice, infallibly retards the changes which
the articles of nitrogenous food undergo. We may presume that
a definite quantity of the metallic chlorides exists in some form of
chemical combination in the gastric juice; this quantity being
exactly sufficient to hinder any abnormal decomposition in that
fluid, without checking its digestive power.
In the exudations we certainly find less chloride of sodium than
in the blood itself, but in relation to the fixed constituents of these
liquids, this salt is always considerably increased. The investiga-
tions of Bracket and Henle§ have proved, almost beyond a doubt,
that this abundant transudation of soluble salts through the walls
of the vessels is dependent on a purely mechanical relation. It is,
however, not improbable that the chloride of sodium cooperates in
the metamorphosis of the exudation $ we find, at least, that pus and
other exudations in which cells become developed, are very rich in
this salt ; and this is especially the case with mucus, as has been
shown by Nasse||. The fluid of cancerous growths always contains
a large quantity of this salt. Whether the chloride of sodium takes
part in the abnormal conversion of the exudation into cells, is a
question that must be at present left undecided. We are almost
led to the belief that every deposition of cells is accompanied by
an increase in the quantity of chloride of sodium, or that this
salt arrests their development at a low stage. We find at
least that the cartilages, which, in their perfectly developed state
abound in cells, contain far more chloride of sodium than occurs
in other parts of the animal body. The cartilaginous bones of the
* Verdauimg. Bd. 1, S. 91.
t Ber. d. k. sachs. Gcs. d. Wiss. 1849.
$ Casper's Wochensch. 1840, No. 21.
§ Zeitschr. f. rat. Med. Bd, 1, S. 122.
|| Journ. f. prakt. Ch. Bd. 29, S. 59.
CHLORIDE OF SODIUM.
435
foetus, before much phosphate of lime has been deposited, contain
far more chloride of sodium than adult bones: and abnormal
depositions of bony matter contain more of this salt than even the
permanent cartilages.
Fromherz and Gugert* found 8' 231% of chloride of sodium in
the ash of the costal cartilages of a man aged 20 years ; I found
11 '236-g- of this salt in the ash of the laryngeal cartilages of an
adult female. From various bones I could only extract from 0'7
to 1*5$. The femur of a six-months3 foetus which I examined
contained 10*13S£ of chloride of sodium, and according to Valentinf
the encrusting exudation, deposited around a carious tibia, con-
tained 13'7-g-.
Nasse, taking the mean of two analyses, found that the chloride
of sodium in the mucus of the air-passages amounted to 0*5 82-(|-,
while two comparative analyses showed that it amounted to 0*46fr
in the serum of the blood, and to 1'26-jJ- in that of pus. Hence in
this respect pus approximates closely to mucus, while the serous
portions of blood and pus are differently constituted.
In order to give a general view regarding the occurrence of
chloride of sodium in the animal fluids, I append the following
table, which is based, in a great measure, on my own analyses •
a signifies the amount of salt in 100 parts of the fluid, b in 100
parts of solid residue, and c in 100 parts of ash.
a.
b.
c.
Human blood
0-421 g
l-931g
57-64 Ig
Blood of the horse
0-510g
2-750g
67-1052-
Chyle
0-531 g
8-313g
67-8842
Lymph (Nasse) ....
0'412§
8-246g
72-9022
Serum of the blood (Nasse)
0-405g
5-2002
59-0902
Blood of the cat (Nasse)
0-537^
2-8262
67-128g
Chyle (Nasse)
o-7JOg
7-529g
62-2863
Human milk
0-087§
0-7262
33-089g
Saliva
0-153S
12-9882
62-195g
Gastric juice of the dog
0-1262
12-7532.
42-0892
Human bile
0-3642
3'353g
30-4042
Urine
0-3322
5'187g
22-972g
Mucus (Nasse)
0'583g
13'IOOJ
70-OOOg
Serum of the blood (Nasse)
0-4602,
4-9192
58-974 g
Serum of pus (Nasse)
1-2608
11-454&
72'330g
Inflammatory exudation in the pleura (Scherer)
0-7502
10- 4 16g
73'529g
Scirrhus of the breast
0-3142.
6-043g
65-391g
* Schweigg. Journ. Bd. 50, S. 187.
t Repertor. 1838, S. 301.
2 F 2
4S5 SECOND CLASS OF MINERAL CONSTITUENTS.
After this general view of the occurrence and uses of salt in the
animal economy, it is hardly requisite to allude to the sources
from which the animal body receives its due supply. Chloride of
sodium is so generally distributed throughout nature, that this
necessary quantity is conveyed into the organism with the ordinary
food and with the water.
The habits of civilized life have elevated salt to the rank of a
positive necessary, but we must by no means conclude from this
circumstance that the salt contained in ordinary food is not suffi-
cient for the support of the animal functions. A simple comparison
of the quantity of salt contained in the animal body, with that
which we are daily taking with the food, at once shows that we
use more salt than is requisite : and if, on the one hand, as several
travellers narrate, certain negro tribes in the interior of Africa
exchange gold-dust for an equal weight of salt, and in want of it
have recourse to the most disgusting substitutes ; we know, on the
other hand, that whole races in the South Sea Islands, and in
South America, flourish without even the knowledge of this sub-
stance. Further, as Liebig has shown, tempests carry salt from
the ocean far into the interior, and thus supply the spring water
with it. A glance at the results of the analyses of the ashes of
plants, is sufficient to show that the ordinary articles of vegetable
food are perfectly sufficient to supply the necessary quantity of salt
to the animal body.
CARBONATE OF SODA.
This salt not unfrequently occurs in the ash of burned animal
matters, but in most cases it is merely the product of the com-
bustion of combinations of soda with organic acids or protein-
compounds. Investigations deserving of the greatest confidence
prove however that carbonate of soda, together with other soda-
compounds, exists in the blood and in the lymph. It is also con-
tained, together with large quantities of the carbonate of potash
and lime, in the urine of herbivorous animals.
The earlier observers assumed the presence of carbonate of
soda in the blood as a recognised fact ; and indeed it was believed to
take an active part in the excretion of carbonic acid ; but certain
later investigations seemed to leave it very doubtful whether
CARBONATE OF SODA. 437
alkaline carbonates exist in the blood. Alkaline carbonates were
always found in the ash of blood, (as for instance, by Berzelius,
Marcet, Mitscherlich, Tiedemann and Gmelin, and more recently
by Nasse, Marchand, and others,) till Enderlin* announced that
blood incinerated according to his method, left an ash which did
not yield a trace of carbonic acid. He examined the ash of the
blood of men, oxen, sheep, and hares, and found that in addition
to the ordinary chlorides and sulphates, the soluble salts consisted
solely of tribasic phosphate of soda. Hence he concludes that as
no carbonates can be found in the ash, it is altogether impossible
that any carbonated alkali can occur in the blood. But it does
not follow that the earlier observers were in error, when they
found carbonate of soda in the blood, (Nassef? for instance, found
from 0'06 to 0'08£, and Marchandt, 0'125-°-,) for we can at pleasure
prepare a blood-ash either with or without carbonates, according
to the degree of heat and the method of incineration we employ.
If we heat common phosphate of soda (2NaO . HO . PO5) with
carbonate of soda, the latter loses its carbonic acid, and as a
necessary consequence there is formed the tribasic phosphate of
soda ; when dissolved in water, this tribasic phosphate of soda very
rapidly absorbs carbonic acid from the atmosphere, and becomes
converted into carbonate and c (common) phosphate of soda.
Hence tribasic phosphate of soda cannot exist in the circulating
blood, since this fluid contains sufficient carbonic acid to ensure
its decomposition.
Assuming that carbonate of soda exists in the blood-ash, this
by no means proves that it is present in fresh blood, for this fluid
contains fatty and other organic acids in combination with alkalies,
which on incineration are converted into carbonates. But if we
consider that fresh blood always has an alkaline reaction, and that,
in consequence of its always containing carbonic acid, caustic soda
can no more occur in it than the above-mentioned tribasic phos-
phate of soda, this reaction can hardly be attributed to any other
body than to carbonate of soda; for the combinations of the fatty
acids with alkalies are contained in the blood in far too small
quantities to account for the alkaline reaction of that fluid, and
the amount of carbonate present in the ash. Liebig§ was the first
* Ann. d. Ch. u. Pharm. Bd. 50, S. 53.
t Handworterb. der Physiolog. Bd. 1, S. 167.
I Lehrb. d. physiol. Chem. S. 226.
§ Ilandwbrterb. der Chem. Bd. 1, S. 001.
438 SECOND CLASS OF MINERAL CONSTITUENTS.
to remark that the carbonate of soda must be contained in the
blood as a bicarbonate. No free acid can be present with common
carbonate of soda. The following experiment favours the view of
the presence of the bicarbonate : if we precipitate the serum of the
blood with alcohol and thoroughly wash the precipitate with
dilute spirit, the albumen on incineration leaves no alkaline ash ; if
soda were chemically combined with album en, the soda must be
precipitated with the albumen, while neutral carbonate of soda and
especially the bicarbonate dissolve readily in spirit. On passing
hydrogen through the fluid from which the albumen has been
removed by nitration, carbonic acid is expelled ; for as Magnus
and Rose formerly proved, and as Marchand* has recently again
demonstrated, hydrogen completely expels the one atom of car-
bonic acid from the bicarbonate of soda, especially if the tempera-
ture be raised to 38°. Liebig also adduces the relation of corrosive
sublimate to the fluid freed from the albumen by spirit of wine, in
evidence of the presence of bicarbonate of soda ; for, on the addi-
tion of corrosive sublimate to this fluid, there is no precipitate,
but after some time there are deposited brown crystals of oxy-
chloride of mercury, precisely as would have occurred if this reagent
had been added to a solution of bicarbonate of soda. By means of
a current of pure hydrogen gas, and by the repeated application of
the air-pump, I so thoroughly removed the carbonic acid from
freshly whipped ox-blood, that a fresh stream of hydrogen passed
through the blood no longer produced the slightest turbidity in
baryta-water ; by means of a special contrivance, so as to exclude
the access of the air, a little acetic acid was forced into the blood
by means of the hydrogen gas, and the latter was again passed in
considerable quantity through the blood; immediately after the
addition of the acetic acid to the blood the baryta-water was ren-
dered turbid by the current of hydrogen. We thus obtain a proof
that a certain quantity of the carbonic acid in the blood exists in
combination with a base, in addition to that which can be expelled
by gases and extracted by the air-pump. Hence there can no
longer be any doubt regarding the presence of carbonate of soda
in the blood. I have found, taking the mean of ten carefully
conducted quantitative analyses,f that ox-blood contains 0*1628$ of
ordinary carbonate of soda, after the expulsion of the free carbonic
acid in the manner which has already been described.
* Journ. f. pr. Chem. Bd. 35. S, 390.
t Ber. d. k. sachs. Ges. d. Wiss. 1847, S. 96-100.
CARBONATE OF SODA. 439
Nasse* found 0*056^ of carbonate of soda in the lymph of a
horse, while Marcetf found 0*1 65£ in the serum of the blood.
Those who regard the kidneys as mere percolators cannot deny the
presence of alkaline carbonates in the blood, since the urine (at
least of herbivorous animals) contains a considerable amount of
carbonates. The parotid saliva of the horse becomes turbid, in
the same manner as lime-water, on exposure to the air, with, how-
ever, this difference, that it almost immediately deposites the most
beautiful microscopic crystals of carbonate of lime.
Liebig was formerly of opinion that the carbonate of soda in the
blood acted an extremely important part in the process of respiration,
in short, that it was the means by which the carbonic acid is con-
veyed from the capillaries into the lungs. The oxygen mixed with
the blood in the lungs there displaces the carbonic acid as completely
as it would be expelled by a current of oxygen or hydrogen from
its state of combination in bicarbonate of soda. As far as our present
knowledge extends, no facts are at variance with this view; indeed,
if the presence of carbonate of soda in the blood be once granted,
no one can wonder that it is converted to the bicarbonate, and on
the other hand, that it must be decomposed on coming in contact
with other gases than carbonic acid. But the question naturally
suggests itself— Is the quantity of carbonate of soda sufficient
to serve as a means of transport for the whole of the carbonic
acid of the blood ? The following calculation supplies the answer :
1000 grammes of blood contain 1*628 grammes of carbonate of
soda, which, to become converted into bicarbonate must take up
0'637 of a gramme of carbonic acid; hence 0'637 of a gramme of
carbonic acid can be extracted from the blood by the air-pump, or
expelled by other gases ; this would amount to 322 cc. according
to volume ; if we assume that the specific gravity of the blood is
1-055, then 1000 cc. of blood would contain 343 cc. of carbonic
acid, capable of being removed by other gases or by the air-pump.
Magnus has, however, succeeded in removing about 300 cc. of
carbonic acid from 1000 cc. of blood by means of hydrogen and a
vacuum ; a method by which a part of the carbonic acid must
always remain in the blood. The coincidence between the empi-
rical result and the calculation is quite as great as could be expected.
It cannot be doubted that the carbonate of soda in the blood
serves as a solvent for the fibrin as well as the albumen ; Bird,
has, however, shown that the bicarbonate is one of the best
* Simon's Beitrage z. phys. u. pathol. Chem. Bd, 1, 8. 449.
t Medico. Chir. Trans, vol. 2, p. 370.
440 SECOND CLASS OF MINERAL CONSTITUENTS.
solvents for albumen. It is well known that large quantities of the
alkaline carbonates have the property of impeding or altogether
preventing the coagulation of the fibrin.
Finally, that the alkali of the blood also contributes to saturate
the acids conveyed into the organism or formed within it, is the
more probable, because nature seems to have provided that the
alkaline carbonates shall be produced as rapidly as possible from
the combinations of potash and soda with vegetable acids. (See
P. 97.)
The origin of carbonate of soda in the animal body is so
obvious, from the preceding observations, that it is unnecessary to
enter further into the subject.
ALKALINE PHOSPHATES.
Important as the alkaline phosphates doubtless are in the meta-
morphosis of animal tissue, we are unable at present to state much
witli certainty regarding them. Before Rose had introduced his
new method of preparing and analysing the ashes of organic bodies,
it must have been concluded from the abundant occurrence of
alkaline phosphates in the ashes of animal substances, that these
salts played an important part in the animal economy. This
conclusion seemed especially to be supported by the peculiar rela-
tions of the saturating capacity of phosphoric acid, and by the
metamerism of the phosphates. For it is almost self-evident that
no salts of any other acid could be so usefully applied in the
metamorphosis of tissue, as those of phosphoric acid, which can
form neutral salts with one, two, and three atoms of base, acid
salts with one and two atoms, and likewise several basic salts.
Moreover it must be recollected that common phosphate of soda
may contain one atom of basic water in place of one atom of fixed
base, and thus by its alkalinity it may serve, like free alkalies or
their carbonates, as a solvent for many animal substances ; — that
it has the property of yielding to the weakest acids, as, for instance,
uric acid, one of the two atoms of fixed base, and of being converted
into an acid phosphate; — and finally, that the ordinary basic phos-
phate of soda (with 3 atoms of fixed base) yields 1 atom of soda to
free carbonic acid, and thus gives rise to two neutral salts both of
which, however, have an alkaline reaction, and a si rung solvent
power.
ALKALINE PHOSPHATES. 441
Taking all these circumstances into consideration, and more-
over recollecting the importance of the earthy phosphates, and
especially of the animal substances containing phosphorus, we might
be disposed to believe the conclusion justified, which, it was
supposed, might be drawn from the abundance with which
alkaline phosphates occur in the ash. But, unfortunately, Rose's
improved analyses of the mineral constituents occurring in animal
bodies have deprived us of the basis on which this conclusion
rests. The earlier ash- analyses of the different animal juices can
no longer be regarded as affording evidence of the importance of
these alkaline phosphates : later and more perfect analyses, in
accordance with Rose's method, do not enable us to form a
decided opinion regarding the occurrence of preformed alkaline
phosphates in the different animal fluids, for it is not only the
alkaline phosphates contained in the aqueous extract of the carbo-
naceous residue of animal bodies which are to be regarded as pre-
formed in the animal body, but also those contained in the
hydrochloric extract, which were retained in the residue with phos-
phate of lime or of magnesia as insoluble double salts (Rose*).
We cannot decide, in reference to these alkaline phosphates,
whether previously to their combining with lime or magnesia, they
existed preformed as basic alkaline phosphates, or rather, as Rose
thinks more probable, as alkaline carbonates or combinations of
alkalies with organic acids ; further, it has never been quite accu-
rately determined to what extent alkaline phosphates are produced
from phosphate of magnesia when decomposed by alkaline carbo-
nates. But putting out of view all these uncertainties, we should
not be too hasty in drawing conclusions from the results of such
analyses of the mineral constituents ; for the principle asserted by
Rose that the mineral bodies which cannot be extracted by hydro-
chloric acid from the carbonaceous residue of animal substances
must be regarded as non-oxidised, and as combinations of phos-
phuretted radicals with metals, is at present only an hypothesis,
although a very probable one. Such are the reasons which deter-
mine us for the present to suppress any consideration of the part
which the alkaline phosphates may take in the general metamor-
phosis of matter, or in individual animal processes. If however,
further investigations demonstrate, with greater certainty, the more
abundant occurrence of these phosphates in the individual animal
juices and in certain processes, our knowledge of the properties of
phosphate of soda, would readily lead us to understand in what
* Pogg. Ann. Bd. 77, S. 208-302.
442
SECOND CLASS OF MINERAL CONSTITUENTS.
manner the alkaline phosphates would act in the different
processes.
In order to give some sort of general idea how, according to
Rose's analyses, the preformed alkaline phosphates should stand
in relation to the other mineral constituents, we have collected, in
the following table, the results of the analyses of several animal
substances, conducted under Rose's superintendence.
Salts which can
There are yielded by 100
parts of the ash of
be extracted
from the carbon-
aceous residue
Alkaline phosphates contained in
100 parts of the soluble salts.
by water.
Ox-blood
60-90
3KO.PO5 .... T58
Horse-flesh
42'81
<2NaO.PO6 .... ITIO
12KO.P05 .... 83-27
Cow's milk
34*17
3KO,POr .... 2T60
Yolk of egg
40-nr,
jKO.PO5 .... 24-57
lNaO.PO5 .... 25-16
White of egg
81'85
O'OO
Ox-bile
Oft'f}^
j3KO.PO5 .... 678
l3NaO-PO5 .... 14-51
Urine
90-87
,2KO.POS .... 16-12
(3KO.PO5 .... 4-55
Solid excrements
18-55
3KO.PO5 .... 20-13
Even these few numerical results promise to throw much light
on the theory of the metamorphosis of animal substances, on the
nature of individual zoo-chemical processes, on the distribution of
the potash and the soda in the different animal fluids, on the phy-
siological importance of phosphorus, &c. Notwithstanding the confi-
dence which we are justified in placing on the accuracy of these
analyses, we avoid entering deeply into the conclusions that might
be deduced from them, for independently of the circumstance that
so few analyses afford us comparatively little means of establish-
ing theories and deductions, we shall find sufficient occasion, when
considering the animal substances named in the above table, to
revert to the data afforded by these experiments, especially as our
observations would extend to too great a length, if we were to
attempt to bring into unison, or to estimate as they deserve, the
often contradictory results of the earlier analyses.
Thus, for instance, in the consideration of the muscular tissue
and of the fluid with which it is saturated, we shall enter into the
IRON. 443
beautiful views which Liebig, with his customary skill, has de-
veloped in his classical memoir on this subject. He has there par-
ticularly directed attention to the different proportions in which
potash and soda exist in the blood and in the muscular fluid ; this
very important difference is less marked in Rose's analyses of the
mineral constituents of both fluids, and taking into consideration
the importance of the subject, it is exceedingly necessary, in order
that we should have a clear insight into these relations, that we
should form a decisive opinion regarding the value of the facts in
our possession.
A glance at the numerous analyses of the ashes of plants, and
especially of their seeds, is sufficient to indicate the source of the
phosphates in the animal body ; the copious discharge of phos-
phates by the urine need scarcely excite our wonder, as it
includes both those which were contained preformed in the food,
and those which are formed during the metamorphosis of animal
tissue, by the oxidation of the phosphuretted organic matters or
radicals.
IRON.
This metal occurs in the animal body, not only in very dif-
ferent parts, but also in different conditions ; in the blood, as we
have already shown in our observations on hcematin, it seems
highly probable that it exists, for the most part, in a non-oxidised
state ; in the gastric juice it exists, according to Berzelius, as a
protochloride, and in other fluids as a phosphate.
According to Rose's method, the ash of ox-blood contains 6'84g
of peroxide of iron, that of horse-flesh 1*00^, that of milk 0*47 8,
that of the yolk of egg 1.85%, that of the white of egg 2'09f , that
of the bile 0-23 % and that of the faeces 2'09f . We have already
noticed the presence of iron in black pigment in our remarks on
melanin. Large quantities of iron are sometimes found in the
ashes of gall-stones, especially of such as consist chiefly of pigment.
There appears to be no relation between the colour of the hair,
and the quality of the iron which it contains. (Lae'r.*)
We are unfortunately perfectly ignorant regarding the special
uses of iron in the animal economy. In reference to the iron in the
blood, we have already seen (p. 308) that it is in some way con-
nected with the function of the corpuscles, but we know nothing
* Ann. d, Ch. \i. Pkarm. Bd. 45, S. 227.
444 THIRD CLASS OF MINERAL CONSTITUENTS.
further. But since the iron is of especial importance in the animal
body, we cannot wonder at its occurrence in the milk and in the
egg. If we find iron in the bile, its occurrence there is easily
explained, if we adopt the view that this fluid is for the most part
produced from the destruction of the blood-corpuscles.
The fluid and solid articles of food contain so much iron that a
portion of it is always thrown off with the solid excrements.
Nature has provided that the animal organism shall receive the
necessary quantity of this essential metal with every kind of food.
THIRD CLASS OF MINERAL BODIES.
ALKALINE SULPHATES.
Sulphates occur in most of the animal fluids, with the excep-
tion of the urine, in extremely small quantities ; and, indeed, in
several, as, for instance, the milk, the bile, and the gastric juice,
they are altogether absent. They are also contained in compara-
tively minute quantities in the blood. Hence it may be concluded
that these salts are of no essential use in the animal organism ;
a view which is confirmed by the fact that as soon as they are
taken into the body, they are as rapidly as possible eliminated
either with the solid or the fluid excrements. On the other hand,
it is worthy of remark, that v. Bibra* found considerable quantities
of soda in the bones of reptiles and fishes.
Berzeliusf and Simon J found no sulphates in the milk, and
Braconnot§ and Berzelius|| also failed to detect them both in the
gastric juice, and in the bile of man and the ox.
If we treat the dry residue of the serum of the blood, milk,
saliva, bile, &c., with spirit, till it ceases to extract anything addi-
tional on boiling, and if we then extract the insoluble residue with
water, precipitate the aqueous solution with a little tannic acid, eva-
* Chem. Unters. liber die Knochen u. Zahne. S. 226 u. 242.
t Lehrb. der Chem. Bd. 9, S. 095.
J Frauenmilch. S. 43.
§ Op. cit.
II Jahresber. Bd. 16, S. 379.
ALKALINE PHOSPHATES. . 445
porate the filtered fluid, again extract with spirit, and dissolve the
residue in water, the aqueous solution only seldom exhibits any traces
of sulphates. That sulphate of soda is frequently found even in con-
siderable quantity in the ash of these animal fluids, and indeed that
it must be found there, is sufficiently explained by the remarks we
have already made regarding the changes which the mineral consti-
tuents of animal substances undergo on incineration. The bile
presents one of the best examples of these changes, for its ash is
very rich in sulphates, while we can hardly discover a trace of them
in the fresh fluid.
The frequent use of the alkaline sulphates in medicine might
almost lead to the presumption, that these salts when conveyed
into the system with the food, are not devoid of use in relation to
the physiological functions of the animal organism, and in particu-
lar to that of digestion. When on the one hand we take into
consideration the changes which the alkaline sulphates undergo in
the process of digestion, and, on the other, the occurrence of highly
sulphuretted organic substances in the animal organism, great prob-
ability seems to attach to this view. The experience of physicians,
and direct physiologico-chemical experiments have clearly proved,
that small quantities of alkaline sulphates are converted in the
intestinal canal during digestion into sulphides. Hence we might
conclude that these salts take part in the production of such highly
sulphuretted animal substances as taurocholic acid, horny tissue,
&c., but as substances which contain sulphur, such as legumin, glu-
ten, &c., enter the animal body with the vegetable food, these highly
sulphuretted substances, peculiar to the animal body, might also
derive this element from the non-oxidised sulphur of the food. In
the absence of any decisive experiments in favour of either of these
views, we must for the present leave this question unanswered.
The experiments of Laveran and Millon* have shown that it
is only when taken in large doses that the alkaline sulphates are
carried off in the stools, small doses being absorbed in the intes-
tinal canal and eliminated by the kidneys. We should, however,
be in error, if we assumed, as Laveran and Millon seem to do, that
this salt is simply absorbed in the intestinal canal; for it is well
known that, after the use of alkaline sulphates, there is an exces-
sive development of intestinal gas, which is especially rich in sul-
phuretted hydrogen.
This conversion of the sulphates into sulphides in the intestine
during digestion is further established by the following facts. L
* Ann. d. Chim. et de Phys. T. 12, p. 135.
446 THIRD CLASS OF MINERAL CONSTITUENTS.
I placed pure gluten, with milk-sugar and a little oil, in a dilute
solution of sulphate of potash, and kept the mixture at a blood-
heat, the mass first underwent the lactic fermentation, very soon
became putrid, and, in the course of 6 or 8 days, unmistakeably
developed sulphuretted hydrogen ; in this way I was enabled, by
the gradual addition of acetic acid, to remove the whole of the sul-
phuric acid from a mixture to which I had added 5 grammes of
sulphate of potash. That the sulphate is, in like manner, de-
oxidised into the sulphide in the intestinal canal, where similar
substances are brought in contact, is obvious from the composition
of the stools which are discharged after the use of mineral waters,
containing (like those of Marianbad) both sulphate of soda and car-
bonate of protoxide of iron.
In these feeces, which are usually green or black, I have recog-
nised with certainty the presence of the sulphide of iron, but not
of the bisulphide, as Kersten* seems to have done.
That the amount of sulphuric acid in the urine is chiefly due
to the decomposition and oxidation of tissues containing sulphur is
obvious from a comparison of the sulphates taken with the food
and of those discharged by the urine.
As a mean of numerous experimentsf, I found that the sul-
phates discharged with the urine amounted daily to 7*026 grammes,
while I was living on an ordinary mixed diet. After a strictly
animal diet for 12 days, the sulphates rose to 10*399 grammes ;
and, after the use of a strictly vegetable diet, they fell to 5*846
grammes. During these experiments I drank nothing to allay my
thirst but common spring water, which, besides a little gypsum,
contained only small quantities of alkaline sulphates ; so that the
striking difference in the amount of the excreted sulphates could
not be traced to that head. Moreover, the extraordinary augment-
ation of the urea in the urine excreted during my animal diet
indicated that this corresponding augmentation of the sulphates
depended on the same cause, namely, on a decomposition and
oxidation of the substances taken as food.
CARBONATE OF MAGNESIA.
This earthy salt occurs only sparingly in the animal organism.
According to BerzeliusJ, it is not improbable that the magnesia in
* Journ. f. Chirtirgie von Walther und Ammon. Bd. 2, S. 2.
t Journ. f. pr. Chem. Bd. 25, S. 2, and Bd. 27, S. 257-
t Lehrb. d. Chem. Bd. 9, S. 545.
CARBONATE OF MAGNESIA. 447
the bones is combined with carbonic, and not with phosphoric
acid, and that the phosphate of magnesia found in the bones is
only formed during the analysis. This view is supported by the
circumstance that carbonate of magnesia is found with carbonate
and phosphate of lime in many pathological concretions. If, how-
ever, the magnesia were combined with carbonic acid in the bones,
it should be taken up with the carbonate of lime by dilute acetic
acid, and neither in my experiments nor in those of von Bibra
has this been the case.
Von Bibra* observes, in opposition to the view of Berzelius,
that far more magnesia exists in the teeth than the carbonic acid
found there can saturate.
Geigerf has published an analysis of a concretion extracted
from the nose; it contained 76*7-3- of mineral substances, of which
8 '3 were carbonate of magnesia. Bleyf found 27'66£ of car-
bonate of magnesia in a stony concretion from the peritoneum of
a man.
A very large quantity of carbonate of magnesia exists in the
urine of herbivorous animals, and hence we often meet with
this salt in the urinary concretions of this class ; it is very seldom
found in human urinary calculi.
The urine of the ox, the camel, the horse, the rhinoceros, the
elephant, the beaver, and the rabbit, deposites carbonate of magnesia
with carbonate of lime. John§ found 10£ of carbonate of magnesia
in the mucous deposit of the urine of a horse suffering from diabetes.
Lassaigne|| found 4'8-g- of this salt, with carbonate of lime, in a
calculus from the bladder of an ox, while Wurzer^f obtained 4'06£,
and Wackenroder** 3*5 22£ of carbonate of magnesia from calculi
obtained from the horse. A calculus from the bladder of a man,
which was analysed by Lindbergsontt? contained, in addition to
the phosphates of lime and magnesia, 2'55£ of carbonate of mag-
nesia, and only 3'14£ of carbonate of lime. In two human calculi
analysed by Bleytt, there were found 5'7£and 6'5-g- of carbonate of
magnesia,
* Op. cit. S. 94 and 287.
f Mag. f. Pharm. Bd."21, S. 24?.
% Arch, der Pharm. Bd. 20, S. 212.
§ Chem. Schriften. Bd. 6, S. 1G2.
|1 Journ. de Chim, meU 2 Se'r. T. 4, p. 49.
Tf Schweig. Journ. Bd. 8, S. 65.
** Ann. der Pharm. Bd. 18, S. 159.
tt Schweig. Journ. Bd. 32, S. 429.
$$ Buchner's Repert. 2. B. Bd, 2, S. 165.
448 THIRD CLASS OF MINERAL CONSTITUENTS.
It is worthy of remark that, while plants, and especially the
grasses, contain almost all their magnesia in combination with
phosphoric acid, the urine of herbivorous animals so frequently
contains carbonate of magnesia. We can hardly suppose that
the phosphate of magnesia in the animal body is robbed of its
electro-negative constituent by a de-oxidation of the phosphoric
acid, which is replaced by the weaker carbonic acid ; it is much
more probable that the combinations of lime with vegetable acids,
conveyed into the animal body with the vegetable food, undergo
such a decomposition with the phosphate of magnesia either in the
blood or in other parts, that bone-earth and a vegetable salt of
magnesia are formed, the latter being subsequently converted into
carbonate of magnesia. The fact that the urine of herbivorous
animals is poor in phosphates seems to confirm this view.
The egg-shell of birds contains not only carbonate of lime, but
also carbonate of magnesia ; both these salts are in part derived
from the embryo during the incubation of the egg. (Prout* and
Lassaignef.)
MANGANESE.
Minute quantities of this metal exist in the animal organism
as elsewhere, in association with iron : manganese, however, seems
to differ from iron in being devoid of influence on the metamor-
phosis of the animal tissues, for it appears in comparatively larger
quantities in the excretions than in any of the fluids that take part
in the vital functions. Like other heavy metals incidentally occur-
ring in the organism, it is principally separated by the liver ; hence
it is found in comparatively large quantity in the bile.
Manganese has been found by VauquelinJ in the hair, and by
Bley§, Wurzer||, and Bucholz^f, in gall-stones and urinary calculi.
Weidenbusch found 0'12£ of proto-sesquioxide of manganese, and
0'23£ of peroxide of iron in the ash of the bile, analysed by Rose's
method.
* Philosophical Transactions for 1822, p. 381,
t Journ. de Cliim. med. T. 10, p. 1U3.
J Ann. de Chim, T. 58, p. 41.
§ Op. cit.
II Op. cit.
1f Op. cit.
ALUMINA. 449
ALUMINA.
This body never occurs in the animal organism ; it has only
been found in certain fossil bones into which it has undoubtedly
entered by infiltration. Its absence in the animal organism is easily
explained; any alumina conveyed into the intestinal canal enters
into insoluble combination with organic substances, especially with
the constituents of the bile, which cannot be resorbed.
After taking 3 grammes of basic sulphate of alumina within
the space of 48 hours, I was unable to find a trace of alumina in
the whole of the collected urine; it was, however, present in the
ash of the solid excrements. The excrements were entirely devoid
of odour for some days after I took this substance.
ARSENIC.
Devergie* and Orfilaf believed that they had found arsenic in
all animal bones, and hence that it should be regarded as an inte-
gral constituent of the animal organism. Subsequent investiga-
tions have, however, shown that there must have been some fallacy
in the method of analysis pursued by these chemists, and that this
view is altogether erroneous.
When positive experiments seemed to show that arsenic existed
in the bones, chemists thought they had found an explanation of
the apparent fact in the circumstance that phosphorus and arsenic
are so frequently associated together; if the discovery of Walchner
and Schafhautl that the sediments of most chalybeate waters con-
tain arsenic had been then known, this would doubtless have been
regarded as strong additional proof of the presence of arsenic in the
animal organism.
Arsenic acts in so noxious a manner on the animal organism,
even in the smallest doses (as we see from experiments on animals),
that nature actively eliminates this deleterious substance as rapidly
as possible from the body.
MeurerJ has made experiments on horses (animals which, as
is well known, can bear large doses of arsenic), and von Bibra§
on rabbits, from whence it appears that most of the arsenic is
* Ann. d'Hygiene publ. Oct. 1839, p. 482.
t Ibid. Juill. 1840, p. 163.
+ Arch. d. Pharm. Bd. 26, S. 15.
§ Untersuch. iiber die Knochen u. s. w. S. 112.
2 G
450 THIRD CLASS OF MINERAL CONSTITUENTS,
carried off with the solid excrements. Both observers also found
the poison in the urine in no inconsiderable quantity. Of the
solid parts of the animal body, the excreting organs, namely the
liver and kidneys, are those in which most arsenic is found ; it has
however also been detected in the heart, lungs, brain, and muscles.
Some of these results are confirmed by the experiments of Duflos
and Hirsch*.
Schnedermann and Knopf could detect no arsenic in the bones
of a pig which had lived for three quarters of a year in the neigh-
bourhood of the silver works at Andreasberg, where cattle and
poultry do not thrive in consequence of the constant evolution of
arsenical vapours.
COPPER AND LEAD.
Both these metals have been found in very minute quantity in
the healthy body by Devergie,{ Lefortier,§ Orfila,|| Dechamps,^[
and Millon,** and were regarded by these chemists as integral con-
stituents of all the soft parts, as well as of the blood ; but it is only
recently that any very decisive experiments on this subject have
been instituted, and they, at all events, prove beyond a doubt that
copper exists in the blood of some of the lower animals and in the
bile of the ox and of man.
Millon believed 'that he had found them in the bloody but Mel-
sensft has brought forward reasons, and even direct experiments
against this view. Since, however, the presence of copper in the
bile of man and the ox has been determined with certainty, the
blood must give traces of this metal, even though they be almost
inappreciable. Moreover, E. HarlessJJ has found copper in the
blood, and more particularly in the liver, of some of the lower
animals, namely, the cephalopoda, ascidice, and mollusca. This
observer found copper in the liver of Helix pomatia ; von Bibra
found it in the liver of cancer payyurus, acanthias, zeus, &c., and
observed that it stood in an inverse ratio to the iron. Copper
* Das Arsenik, seine Erkennung u. s. w. 1842.
t Journ. f. prak. Ch. Bd. 36, S, 471.
J Ann. d'Hygiene publ. Jnill. 1840, p. 180.
§ Ibid. p. 97.
II Me'moires de 1'Acad. de Me'd. T. 8, p. 522.
«fl Compt. rend. T. 27, p. 389.
** Journ. de Pharm. 3 SeY T. 13, pp. 86-88, [also Compt. rend. T. 26, p. 41,
and Ann. de Chim. et de Phys. 3 SeV. p. 372.— G. E. D.]
tt Ann. de China, et de Phys. 3 SeV. T. 23, pp. 358-372.
tt Muller's Arch. 1847, S. 148-157.
SALTS OF AMMONIA. 451
was originally found in the bile and in gall-stones by Bertozzi,* and
subsequently by Heller, t Gorup-Besanez,J Bramson,§ andOrfila.||
I have been equally unsuccessful in demonstrating the presence of
copper either in the human liver, or in the liver of the frog; in
the latter case my experiment was made on 250 livers ; and I have
also failed in obtaining any indication of copper or lead in the
blood, although I followed Millon's instructions.
There can be no doubt that the small quantities of copper
which have been actually found in the fluids of the higher animals
are only to be regarded as incidental constituents, while the expe-
riments of Harless seem to indicate that in the lower animals the
copper stands in an essential relation to the blood-corpuscles.
All the investigations which have hitherto been made, seem to
indicate the liver as the organ in which deleterious substances, and
especially those of a metallic nature, as, for instance, arsenic, lead,
antimony, bismuth, &c., are accumulated, in order that they may
be gradually eliminated with the bile. Hence, even if copper were
constantly found in the blood or in the bile, it would afford no
reason why we should regard this metal as an integral constituent
of those fluids.
As copper has not only been found in many mineral waters, (as,
for instance, by Will,^f Buchner,** Keller,tt and Fischer,! t) but
often in plants, and even in corn (Girardin,§§) there is no difficulty
in accounting for its presence in small quantities in the organisms of
the higher animals.
SALTS OF AMMONIA.
Although many high authorities believe that they have found
these salts in various parts of the animal body, yet if we put out of
the question their occurrence in the excreted fluids, we must re-
gard it as almost undoubted that no salt of ammonia is produced
in the animal organism or found in the living parts.
* Ann. di Chirurg. Milan, 1845, p. 32.
'{• Arch. f. Ghem. u. Mikroskop. Bd. 3, S. 228.
J Unters. uber Galle. Erlangen, 1848, S. 95.
§ Zeitschr. f. rat. Med. Bd. 4, S. 193.
|| Journ. de Chiin. m6d. 3 S^r. T. 3, p. 434.
1 Ann. d. Ch. u. Pharm. T. 55, p. 16.
** Jahrb. f. pr. Pharm. Bd. 15, 8. 20-25.
ft Journ. f. pr. Ch. Bd. 40, S. 442-447.
$+ Arch, der Pharm. Bd. 52, S. 268.
§§ Journ. de Chim. m^d. 3 S^r. T. 2, pp. 443-445.
2 G 2
452 THIRD CLASS OF MINERAL CONSTITUENTS.
In the sweat, especially in that from the axillae, the occurrence
of ammonia is incontestable. In the urine it is assumed to exist in
larger quantities than is actually the case. In the solid excrements
which may be regarded as already in a state of decomposition, and
which very soon develope ammonia when exposed to the atmo-
sphere, Berzelius* believes that there is no carbonate of ammonia.
Important as is the occurrence of ammonia in the vegetable juices
for the renovation of the nitrogenous compounds, the animal
organism appears to stand in little need of this substance. Indeed
the process of decomposition by which the individual constituents
of the organs are reduced to effete nitrogenous matter, by no means
gives rise to the formation of ammonia, for in that case we should
certainly find a far larger quantity of the salts of this alkali in the
excretions. Urea is the principal nitrogenous product of decom-
position which is formed within the body from the nitrogenous
substances.
The blood, chyle, lymph, and milk, the fluids of the egg, and
the secretions of the serous membranes either contain no ammonia
or only extremely small quantities of it. In the pulmonary exha-
lation, on the other hand, small quantities of ammonia may always
be recognised with great certainty.
Almost all histogenetic substances develope ammonia when
treated with dilute acids or alkalies.
Observers have often believed that they had detected hydro-
chlorate of ammonia by the microscope after evaporating the alco-
holic extract of animal fluids, when in reality, they saw the efflo-
rescing forms of chloride of sodium, which, in the presence of cer-
tain organic matters (as, for instance, in the chyle) and especially
when rapidly evaporated, separates in arborescent groups very similar
to those of hydrochlorate of ammonia.
Lecanu and Denis failed in detecting any salts of ammonia in
the blood ; Marchand and Colberg were equally unsuccessful in
reference to the lymph, and Schwartz, and Simon, in reference to
the milk.
Even in the urine the quantity of ammonia is extremely smallr
as is shown by the following experiments. I allowed the greater
quantity of water in the morning urine to freeze, and thus obtained
a very concentrated, almost wine -red urine, in which we might
assume that there was no decomposition of the constituents ; when
carefully treated with caustic potash, it yielded a precipitate which
even after remaining for a long time in contact with the urine, con-
* Lehrb. der Chem. Bd. 9, S. 180.
SALTS OF AMMONIA, 453
tained no uric acid ; if salts of ammonia were contained in the
urine, urate of ammonia would have been precipitated ; but there
was no deposit of this salt till after the addition of hydrochlorate of
ammonia. Scherer and Liebig* have also convinced themselves of
the absence of ammonia in normal urine. Heintz found that the
ordinary urinary sediments consist of urate of soda with a little
urate of lime, and only traces of urate of ammonia.
Marchandf was the first who ascertained with certainty that
ammonia was present in the pulmonary exhalation ; by means of
the colourless heematoxylin discovered by ErdmannJ he could
detect it in the air of each individual respiration ; moreover, when
we employ sulphuric acid for the removal or determination of the
water in experiments on the respiration, it is always found to con-
tain ammonia.
In certain diseased conditions of the system very considerable
quantities of ammonia are often found in the blood as well as in the
urine. Winter§ thought that the presence of ammonia in the blood
explained the phenomena of typhus, but ammonia may be detected
in the blood in all severe cases of acute disease, especially in variola
and scarlatina; there is no more constancy in the presence of ammonia
in the blood during typhus, than there is in the presence of the
crystals of the triple phosphate in the excrements. It is by no
means strange that in this state of the system the urine should
contain ammonia; the urine is, however, richest in ammonia when
it undergoes decomposition within the bladder, as in cases of
inveterate vesical catarrh or diseases of the spinal cord.
HYDROCYANIC ACID.
This acid never occurs preformed in the animal organism; even
in the most varied of the metamorphoses and decompositions which
occur during disease, we never meet with either the free acid or a
metallic cyanide. This is readily accounted for, when we recollect
that hydrocyanic acid, cyanogen, and the metallic cyanides, are only
produced from nitrogenous substances at a high degree of tempe-
rature. But in spite of this, certain physiological chemists have
shown no unwillingness either to assume that hydrocyanic acid,
either in conjugation or in combination, exists preformed in his-
* Ann. d. Ch. u. Pharm. Bd. 50, S. 198.
* Journ. f. pr. Ch. Bd. 33, S. 148, and Bd. 44, S. 35.
+ Ibid. Bd. 27, S. 193-208.
§ Ann. d. Ch. u. Pharm. Bd. 48, S. 329.
454 THIRD CLASS OF MINERAL CONSTITUENTS.
togenetic substances, or to avail themselves of its formation in the
explanation of various chemico-vital processes ; in short, to make
it take a part in the equations by which they pretend to explain
the different stages in the metamorphosis of the animal tissues.
We only mention it here inasmuch as it belongs to the bodies
which are produced during the artificial decomposition of animal
substances, such, for instance, as acetic, valerianic, and oenanthylic
acids; we refer to the decomposition of hippuric acid by mere
heat, and to the decomposition of histogenetic substances by
bichromate of potash or binoxide of manganese and sulphuric acid.
HYDROSULPHOCYANIC ACID.
This acid does not occur in a free state, but only as sulpho-
cyanide of sodium [or potassium.] It was discovered by Trevi-
ranus in the saliva, and has as yet been found in no other fluid.
Treviranus named it haematic acid (Blutsaure) ; and, because he
found that it formed blood-red solutions with the persalts of iron,
he attributed the colour of the blood to sulphocyanide of iron.
For a very long time it has been disputed, whether the ingre-
dient in the saliva, which gives rise to this red colour with the
persalts of iron, is actually sulphocyanogen. There is scarcely any
subject in the whole domain of zoo-chemistry in which so many
experiments have been made with such contradictory results. We
believe, however, that no one who repeats the experiments of
Pettenkofer* can entertain a doubt regarding the presence of sul-
phocyanogen in the saliva. Pettenkofer especially directs attention
to two tests which he discovered for hydrosulphocyanic acid.
Solutions of the acetate and formate of peroxide of iron are per-
fectly decolorised on boiling with alkaline chlorides, while this
treatment has no apparent effect on sulphocyanide of iron : further,
it is known that the persalts of iron do not decompose ferrid-
cyanide of potassium ; but if we heat a solution of sulphocyanide
of iron, hydrocyanic acid is developed, and there is a precipitate of
Prussian blue. Pettenkofer applied this treatment to the alcoholic
extract of the saliva, and thus ascertained the presence of sulpho-
cyanogen. Other chemists had previously made use of a test that
had been discovered for the sulphocyanides, namely, a mixture of
two solutions of sulphate of protoxide of iron and sulphate of oxide
of copper (when sub-sulphocyanide of copper is precipitated) with
the view of detecting this substance in the saliva. The alcoholic
* Buclm. Repert. 2 E. Bd. 41, S. 289-313.
HYDROSULPHOCYANIC ACID. 455
extract of saliva is free from sulphuric acid (for the sulphates are
insoluble in alcohol) ; hence Pettenkofer thought that he might
make a quantitative determination of the sulphocyanogen in the
saliva, by oxidising the alcoholic extract with chlorate of potash
and hydrochloric acid, and precipitating the sulphuric acid that was
formed by chloride of barium.
Sulphocyanogen is almost always present in human saliva ; it
is, however, occasionally absent, without any apparent physiological
or pathological reason. It appears to be wanting in the secretion
during salivation from any cause ; at least, I could never detect it
during the ptyalism following the use of mercury or iodine, or
occurring in the course of typhus or other diseases.
Sulphocyanogen occurs also in the saliva of the dog and the
sheep ; I have examined the saliva of four different horses without
detecting any traces of it ; Wright asserts, however, that it occurs
in the saliva of that animal.
Considering the extremely small quantity in which it occurs,
and that it is often absent without any apparent bad consequence,
it seems hardly probable that the alkaline sulphocyanides take any
definite part in the process of digestion.
I have noticed several healthy, vigorous young men, whose
saliva contained no sulphocyanogen, and yet who enjoyed the best
digestion.
It would be very easy to explain, by chemical formulae, how
sulphocyanogen might be formed from the histogenetic substances ;
but, unfortunately, we as yet possess no facts to confirm us in the
establishment of any particular chemical equation ; it is better,
therefore, frankly to confess that we know absolutely nothing re-
garding the place or the mode in which sulphocyanogen is formed
in the animal organism.
END OF THE FIRST VOLUME.
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