Remarks on the Scope and Organization 
OF THE 
PATHOLOGICAL INSTITUTE 
OF THE - 
NEW YORK STATE HOSPITALS. 
BY 
Ira T. Van Gieson, M. D., 
Director of the State Pathological Institute. 
[Reprint from the State Hospitals Bulletin.] REMARKS ON THE SCOPE AND ORGANIZATION 
OF THE PATHOLOGICAL INSTITUTE OF 
THE NEW YORK STATE HOSPITALS.* 
By Ira T. Van Gieson, M. D., 
Director of the State Pathological Institute. 
Gentlemen: 
Surely there is no chapter in the history of all medical 
science more replete with the record of difficult and intri- 
cate research than that which relates to the development 
of our knowledge of the nervous system, the noblest and 
most marvelously organized tissue of the body. And 
yet, notwithstanding the supremacy of the nervous system 
over all of the other organs and tissues of the body, 
in its wonderfully intricate organization, nowhere else in 
the body can we localize and establish the nature of the 
lesions with such fascinating accuracy as in the neural dis- 
eases. And this great mass of knowledge whereby the 
physical basis of the symptoms in neural diseases can be 
premised so accurately has been sought out by the clin- 
ician. In no department of medical science has the ob- 
servation of the keen, alert practitioner been of such ines- 
timable service to the anatomist and physiologist as in the 
nervous system. 
However important animal experimentation and labora- 
tory work may have been in the elucidation of questions 
in structure and function in the nervous system it has ever 
been the experiments which nature has evoked in man, in 
the diseases of the nervous system, that have been crucial 
and brilliantly decisive in the development of neuro-path- 
* By invitation. Dr. Van Gieson was invited to meet in regular monthly con- 
ference, the Medical and General Superintendents of the State Hospitals and 
the State Commission in Lunacy and to outline the probable future work of the 
Institute, and its relation to the several hospitals. The Editorial Committee 
consider his address of value to those members of the medical staffs who were 
not present at the conference, and by Dr. Van Gieson’s permission his address 
is herewith published, with the understanding that it shall be received as in- 
formal as was its presentation. Ed. Com. 2 
VAN gieson: pathological institute. 
ology, of the localization of function, architecture of the 
fibre systems, and many other phases of neurology. It has 
been the practitioner of medicine in the rush of his 
humane and trying duties who has again and again found 
such opportunities to play the role of the scientific patholo- 
gist as has led to the utilization of rare and decisive cases 
of human brain and cord lesions for the building up of our 
knowledge of these supreme organs so baffling to research 
in their intricate structure. 
It would be most interesting, had we time, to review 
the slow, patient development of our conceptions of the 
structure and function of the nervous system, and trace 
the studies at the bedside, in the asylum, hospital and dis- 
pensary, and in the laboratory, which have contributed 
each in their measure, each indispensable, to the building 
up of this knowledge of the structure of the human nerv- 
ous system and of the nature of its diseases. 
It seems to be a tendency of the mind to dwell on results 
rather than to enquire how they were brought about. And 
the younger generation of pure scientists, in medicine 
especially, in these days of the revolutionizing achieve- 
ments of the pathological and bacteriological laboratories, 
do not fully realize that it is to the clinician that we owe 
the great bulk of our knowledge of disease processes and 
much of physiological science. And this is especially true 
in regard to our insight into the structure, functions, and 
pathology of the nervous system. The pathologist de- 
scribed changes, but it remained for the clinician to inter- 
pret them; and where clinical data and pathological findings 
seemed at variance the clinician has given the crucial 
decision. 
The clinicians like Tiirck, Duchenne, Westphal, Leyden, 
Erb, Broca, Charcot and Gudden have built up the knowl- 
edge of the diseases of the nervous system and have con- 
tributed much indeed to our understanding of its functions 
and their localization, as well as the pathways of the fibre 
systems. Clinicians like these explained the significance 
of the findings of the autopsy table; they guided the VAN gieson: pathological institute. 
3 
work of the pathologist who followed the footsteps of these 
pioneers in the pathways of the knowledge of the human 
nervous system and its diseases. 
At the present time, however, work along the older 
lines of research in the pathology of the nervous system is 
well-nigh exhausted. The limitations of the previous 
methods of investigation, whereby so much has been ac- 
complished by the clinician and the pathologist in explain- 
ing so well causes and morbid processes underlying many 
nervous diseases, have been growing painfully evident in 
the past few years. The great method of Golgi, the ad- 
vances in minute anatomy of the cell, has given the labora- 
tory an unexpected power and prominence in penetrating 
far beyond the barriers of the previous decade in elucida- 
ting neuro-pathological problems. 
The whole scope of neuro-pathological laboratory work 
is upon an entirely different plane than ten years ago; it 
has an hundredfold more scrutinizing channels of investi- 
gation and rests upon a broader and more philosophical 
basis. Ten years ago nothing could be expected to be 
attained in seeking for the physical basis of mental dis- 
eases. The methods were too coarse; they revealed abso- 
lutely nothing of the wonderful microcosm in the internal 
organization of the ganglion cell and consequently the 
most minute and delicate but none the less definite and 
significant changes in the ganglion cells were completely 
ignored; and it is to some of these new conceptions of 
investigating neuro-pathological problems, bom of new 
methods and precise knowledge of the normal anatomy of 
the nervous system, that I would invite your attention. 
A consideration however of the fields of application 
of the recently inaugurated Pathological Institute of the 
State Hospitals of New York involves such a broad 
and philosophical presentment of the whole scope of 
modem neurology, as well as the course of its progress 
for the next two or three decades, that in addressing you 
upon this almost limitless subject, I may well ask for the 
freedom of an informal speaker, rather than the attitude 4 
van gieson: pathological institute. 
of the elaborate writer. A review of the scope of the 
Institute would embody not only a discussion of the 
biology of the nervous system but also of the pathology 
of mental and nervous diseases, both in regard to what 
has been accomplished in the investigation of their causes, 
as well as what remains to be attained along the lines of 
the comparatively recently discovered and powerful meth- 
ods of research. We may, then, merely sketch in out- 
line, rather than attempt to present a complete view of the 
prospective lines of work of the Institute. 
It is certainly fundamentally important to point out at the 
very beginning that no investigations of the highest order 
of scientific value, of the permanent and philosophical order, 
can be brought out of the Institute without a development 
that grows from a comprehensive basis. The only way 
to advance the knowledge of mental pathology is to study 
this department of neurology hand in hand with all of the 
other branches of neurology and to be ever mindful that 
it is governed by the same laws as morbid processes else- 
where in the body. Mental pathology is, therefore, to be 
studied in the light of general pathological anatomy. 
The Institute should have a staff of scientists each of 
whom should be especially trained in one or the other of 
the specialized departments of modem neurology, for it is 
only by the correlation of all of these departments that 
the proper and valuable kind of investigation toward the 
solution of the causes of nervous and mental diseases can 
be attained. And while, of course, the chief aim of the 
Institute is to study the physical basis of insanity, this is to 
be carried out by a knowledge of the nervous system from 
all its standpoints, and of the general laws of pathology. 
If the work of the Institute, however, be restricted to the 
field of mental pathology and lacks the broader conception 
of its problems conferred by the knowledge of the other 
departments of neurology, the results will be comparatively 
useless to science for they can not be intelligently 
interpreted. 
The pathological problems of insanity must be studied vangieson: pathological institute. 
5 
"hand in hand with general pathology, general pathology of 
the nervous system exclusive of the insanities, experimental 
pathology, physiological chemistry and normal neural anat- 
omy, comparative anatomy and biology of the nervous 
system, the physiology, cytology, and cytological chemistry 
of the nerve cell, and bacteriology especially in its relation 
to the production of toxaemias of the nervous system. To 
this must also be added a most valuable factor of experi- 
mental pathology, namely, the effects on the nervous system 
of toxaemias and intoxications produced experimentally in 
animals. Now the intimate association of all of these de- 
partments of science is so imperative for the elucidation of 
the complex problems of neuropathology, that we cannot 
hope to make any real or lasting headway in explaining the 
physical basis of insanity without a reciprocal relation be- 
tween them in the practical work of the laboratory. 
Specialization is a valuable factor in scientific research, 
but its value is practically shown only in its fraction of the 
whole subject of pathology of which its specialty is but a 
ramifying branch. While specialization, therefore, is valu- 
able for details, for the discovery of new facts and methods 
and extending the knowledge of any one of the head sciences, 
if pursued without reciprocity of associate branches, it cannot 
always be trusted to properly interpret these facts or obtain 
the ultimate goal desired of establishing causes and their 
laws. Hence, the Institute must not be expected, to focus 
its energies upon the study of mental pathology to the ex- 
clusion of other branches of neurology. It must study 
mental pathology, with the broad conception to be gained 
by investigation from the correlation of all of the sub- 
branches of neurology. There should be a division of all 
the special departments of neurology, among the permanent 
staff of the Institute, and the staff should be thus selected 
with a view of diversifying the character of its studies. 
Among the contemplated number of five associates in the 
Institute, one should have a special training in haematology, 
another in biology and embryology of the nervous system, 
another in physiological chemistry, still another should 6 
vangieson: pathological institute. 
have a special training to conduct and plan out work in 
toxaemias and intoxications of the nervous system with a 
special reference to the induction of these conditions ex- 
perimentally in animals, and finally another associate should 
he a trained bacteriologist. 
It is obvious then, that to conduct the investigations of 
the Institute along such diversified and specialized lines 
as these, its staff should not be entirely removed from 
the influences of the great centres of medical learning, 
namely, the laboratories, chemical, physiological and 
pathological of the medical colleges. It is here that the 
advanced methods, ideas and work invariably come out 
first. These institutions govern the scientific world, they 
make the discoveries and are foremost in the ranks of ad- 
vancing science. The Institute, therefore, by maintaining 
relations with such institutions, receives the advantages of 
all the other departments of pathology necessary for this 
specialized department, without maintaining its equivalent 
in the Institute proper. If the State laboratory, therefore, 
is to reap the greatest possible advantages its officers 
should be in sufficient touch with one or more of the centres 
of medical learning to absorb the benefits of their diversi- 
fied specialties, and apply such knowledge as an ally to the 
specialized work of the Institute in its broadest application. 
While the State laboratory will have certain advantages 
in its systematic organization over the medical collegiate 
laboratories, it can never provide for the enormous divers- 
ity and specialization of study in force at the university 
centres of medical learning. This the State laboratory can 
never hope to attain; it can not become a university; it 
can not maintain a perfectly equipped physiological labora- 
tory, for instance, with all of its apparatus as well as four 
or five men prominently identified with physiology, who 
are devoting their life-work to the elucidation of physio- 
logical problems and the teaching of this branch. Neither 
can it maintain laboratories of the same kind in physio- 
logical chemistry, bacteriology, general pathology, and 
photography. vangieson: pathological institute. 
7 
The Institute, it is hoped, therefore, may avail itself of 
the benefits of the perfectly equipped departments which 
are in force at the medical colleges. It would seem wholly 
unnecessary to duplicate work the results of which can 
be so readily obtained by a neighborhood of laboratories. 
It is entirely appropriate to emphasize the importance 
of the collegiate associations of the Pathological Institute, 
for it is a matter of fundamental value to conduct neuro- 
logical investigations on a broad basis and to prevent the 
Institute from drifting into one specialized field of investi- 
gation at the expense of other departments of modem neu- 
rology. The fact has always asserted itself, and still does, 
that the real progress of science has been made in the uni- 
versity centres of learning, or in such institutes as have 
been more or less closely associated with the university, and 
medical laboratories isolated or excluded from university 
influences have invariably failed to make any signal mark 
on the pages of science. 
The inauguration of the Pathological Institute of the 
.State Hospitals occurs at a most felicitous period in the 
science of neurology for the prosecution of its work. The 
marvelous precision which the anatomy of the nervous sys- 
tem has reached within the last ten years has really been a 
renaissance period in the history of neurology. The pres- 
ent day marks an epoch in the history of the evolution of 
the nervous system. Our knowledge of its construction, 
the development and ramifications of the central nerve fibre 
and their connections is definite and accurate and free 
from the controversial obscurity of the past fifty years. It 
would be interesting to glance over the history of neurol- 
ogy for the past fifty years and pass over the great land- 
marks which have made our conceptions of the nervous sys- 
tem so precise and logical, both in its anatomy and phys- 
iology. It will be sufficient, at the present time however, 
to merely emphasize the precise basis of the anatomy and 
physiology of the nervous system, for when once the anat- 
omy and physiology of an organ or tissue is clear or une- 
quivocal, we are then in a position to build up knowledge 8 
vangieson: pathological institute. 
of its abnormal conditions which is lasting and useful. 
Thus the day is at hand to begin anew the study of 
the abnormal conditions of the nervous system on a clear 
and permanent basis, and in the next two decades, or per- 
haps in less time, with the rapid increase in the ranks 
of investigators, we shall see an epoch in neuro-pathology 
fully as striking as is the present one in the normal anat- 
omy and physiology of the nervous system. 
The methods of Weigert, Golgi and Nissl, together with 
the researches of His, Golgi, Retzius, Kolliker, Lenhossek, 
Cayal and their colleagues have been the prominent fac- 
tors in revolutionizing our knowledge of neurology, and 
have opened the way for the new era in neuro-pathology. 
The older data in this field must be revised and the new 
data are now capable of intelligent interpretation. Of all 
of the new discoveries in method, however, which have 
been the real factors in gaining this new knowledge of the 
nervous system, Nissl’s method is destined to be of untold 
importance, in solving new problems in neuro-pathology 
and interpreting the older ones. The importance of Nissl’s 
procedure is not so much due to its innovation as a method, 
but that it premises exact fixation of the nerve cells, and 
the application of staining methods to satisfy the searching 
glance of modern cytology into the delicate and extremely 
complicated protoplasmatic and nuclear organization of the 
nerve cell. 
Within the past ten or fifteen years the knowledge of 
minute cell anatomy has made vast strides, so that it is well 
dignified to the status of a separate science, namely, that of 
cytology or cellular biology. 
Singularly enough, during all this time of the accumula- 
tion of marvelously searching results in the knowledge of 
cell anatomy, the general pathologist neglected to apply 
this accumulated knowledge to the solution of his own 
problem. He was rather more concerned with the gross 
and topographical distribution of lesions and the grouping of 
diseased cells than with the changes in the cells themselves. 
It is precisely, however, to these tiny units of the organs vangieson: pathological institute. 
9 
of the body that attention must be directed in studying 
many of the great groups of disease which are still at the 
present day obscure, and due to the presence in the 
body of some form of poison whether it be due to the 
product of bacteria or to the presence of excretions or 
secretions produced by some of the organs of the body, or an 
abnormal condition of the blood, or even to a poison from 
an extrinsic course. Many of these poisons may at 
times leave coarser or grosser lesions in the body, 
which may be recognized by the older and less searching 
methods of the pathologists, which leave entirely out of 
view the scrutiny of very minute and delicate changes in 
the anatomy of the cells as individuals. Yet, in very 
many cases these subtle poisons frequently leave but 
little trace of their action, except in the organization of 
the individual cells of the organs or tissues of the body. 
The cells are not destroyed or changed in large groups or 
clusters and if viewed by methods which are not especially 
adapted to the cell itself, there appears to be no striking 
change in either the protoplasm or nucleus. If however, 
we take a case of death from many of these poisons, which 
seem to leave no visible trace of their action, fix and 
stain the cells with all of the delicate and complicated 
technique of the modern cellular biologist, we shall be able 
to bring out hidden changes of the most minute and delicate 
character in the parenchyma cells of the viscera. The 
nervous system is especially sensitive from the complex 
organization of the ganglion cell to the action of these 
several poisons, which are the cause of so many mani- 
festations of disease, and the ganglion cells show most 
exquisitely the traces of many of them whether they be 
of extrinsic character or in the nature of toxaemias or 
intoxications. 
While it has probably always been suspected that by far 
the larger majority of diseases has been due to the circulation 
in the body of intrinsic poisons, yet the evidence assuring 
this belief has been the gradual accumulation of very recent 
years. Long before pathology had begun to make any van gieson: pathological institute. 
advances the continued fevers, the exanthemata, syphilis, 
tuberculosis, rabies, tetanus, hydrophobia, in fact all the 
infectious and contagious diseases were naturally thought 
to be the manifestations of poisons which either gained 
access to the body or which were elaborated within the body. 
When the study of pathology made advances, evidences of 
these diseases being due to a poison were found in the 
occurrence of more or less extensive necroses of the tissues 
or organs. When bacteriology gained ground, definite 
micro-organisms were shown to have a causal relationship 
to several of these diseases, which could be induced experi- 
mentally in animals, and furthermore when it was proved 
that certain poisons attending the development of these 
organisms were absorbed by the body and were responsible 
for many of the symptoms, the evidence was complete 
and final for many individual examples of these diseases. 
Then a definite explanation was given for the occurrence 
of necroses of the tissues or organs, or the degenerations 
or cell proliferations which had been observed in the study 
of the lesions attending these diseases. Diphtheria is a 
most brilliant example of the perfection of our understand- 
ing of how the toxine or toxalbumen, as these poisons are 
termed, associated with the growth of bacteria, acts in 
producing the symptoms of the disease. 
It now remains for pathologists to trace out much more 
accurately than they have hitherto attempted the actions of 
these toxines, upon the delicate organization of the cells as 
individuals. Some general laws must be established of the 
action of these toxines, not upon masses of cells in the later 
stages of their action, but of the initial action of the toxine 
upon all of the detailed structures of the protoplasm and 
nucleus. As studies of this kind accumulate, from the 
standpoint of the cytologist, we shall find traces of the 
actions of poisons in many of the obscure diseases of the 
present day which seem to leave no clue of their action, 
and have until recently been regarded by both the clinician 
and the pathologist as diseases sine materia. Thus, at the 
present day, inasmuch as the cell knowledge accumulated VAN gieson: pathological institute. 
11 
by the cellular biologist within the past twenty years is 
being applied by the pathologist to his problems, it may 
be well to speak of pathological cytology in contradistinc- 
tion to normal cytology, and Virchow’s term “cellular path- 
ology” used so many years ago will commence at the present 
time to take on a deeper meaning. By normal cytol- 
ogy we mean a description of all of the minutiae of the cells 
of the human body, followed out to an extent indicated by 
the specialized terminology of the modem cytologist; and 
by pathological cytology as applied to the human body, any 
and all of the changes which may affect any of these minute 
details of cell organization under the influence of disease 
or abnormal conditions. 
If the cytologist has pursued his studies of the cell to 
such a marvelous depth as to premise a physical basis for 
heredity in the chromatin of the cell, the pathologist of the 
present day certainly has an encouraging stimulus to search 
out clues for the causes of the unexplained diseases. An 
example always makes a general statement forcible, and 
the history of the pathology of hydrophobia is so interest- 
ing in showing the treasures of knowledge unearthed by 
the application of cytological studies, that it is well worth 
glancing at. Until two years ago practically nothing had 
been found to explain the symptoms of this disease. Yet 
here was a disease which gave the most dramatic evidence 
of the extreme irritation, and even destruction, of the ele- 
ments of the central nervous system. Yet, when exam- 
ined by the coarser methods of general topographical 
patholology, practically nothing was found to give any real 
explanation of the symptoms. At times hemorrhages and 
leucocytosis about the vessels of the spinal cord and medulla 
were found, but the ganglion cells were found in place, 
properly arranged, and the impression was that here was a 
poison which, although it acted most violently on the gan- 
glion cells, left no changes in them; and this is probably 
the impression given by most of the text-books on pathology 
up to within a very recent period. Now, if the nervous 
system from a case of hydrophobia is studied from a stand- van gieson: pathological institute. 
point of pathological cytology, a brilliant chapter can be 
written, which gives step by step the impress of a subtle, 
invisible poison on the ganglion cells, and explains with 
most interesting clearness just why and how the symptoms 
arise. 
In applying the methods and knowledge of advanced 
cell studies to the study of hydrophobia, a perfectly 
definite series of changes can be observed in both the 
nucleus and cell body, which are almost entirely hidden 
from view in the coarser and older technical methods of 
pathology which were subservient to a topographical view 
of the constituents of an organ or tissue, rather than an 
elaborate view of the cellular microcosms composing 
them. By these methods the insight into the ganglion cell 
organization is so scrutinizing that within six hours after 
the onset of the symptoms when the rabid animal exhibits 
nothing more than fine general tremors, changes can be 
found in the cerebellar ganglion cells. Golgi, also, in 
applying his own method to the study of hydrophobia, al- 
though it certainly has not the advantages, in many respects 
of the application of aniline dyes to sublimate hardened 
material, found initial dissolution of the ganglion cell 
nucleus, occurring at a very early period of the disease, and 
simultaneously with karyokineses of the endothelial cells of 
the capillaries in the nervous system. Thus, we can see 
how cytological investigation has cleared up the manifesta- 
tions of hydrophobia, and given us very positive evidence 
of the progressive destruction of the ganglion cells from the 
action of a poison. Just where this poison comes from, or to 
what extent a disorganized condition of thejfiood in hydro- 
phobia, acts as a poison, we do not know; but it certainly 
is a positive gain to have discovered the action of this poison 
on the ganglion cells. As Golgi remarks, it is not to be 
supposed that these changes in the ganglion cells are posi- 
tively characteristic or peculiar to hydrophobia. Undoubt- 
edly, a variety of poisons may produce the same set of 
changes in the ganglion cell. The point, however, is to in- 
vestigate the great mass of obscure nervousTliseases, and VAN gieson: pathological institute. 
13 
ascertain by these cytological methods the evidence of the 
action of the poison, whether it be acute, intermittent, or 
slow and protracted in its exhibition. It can be seen there- 
fore, that we stand on the threshold of a new conception of 
investigating nervous diseases, namely, by applying meth- 
ods which give us exact information about the damage which 
occurs to ganglion cells in diseases, and the action of poisons 
on constituent elements of the nervous system. Formerly 
we could obtain no such data as these. 
It is rather singular that the very striking and complex 
arrangement of the minute structures should have escaped 
attention until such a recent date. The explanation, how- 
ever, is that the unravelling of the nerve fibre pathways, 
together with their origins and connections with ganglion 
cells, entirely engrossed the attention of investigators 
for the past fifty years. The use of bichromate fluids 
in the hardening of the nervous system, upon which 
the methods for the solution of these problems depended, 
renders the ganglion cell entirely unfit for cytological 
study, and for this reason until Nissl, by using such 
a fixative as alcohol in 1885, the wonderful details 
of cellular structure remained unknown. Up to this 
time and also until quite recently, observers who de- 
voted their attention to neuro-pathology also used these 
same fluids, and were completely ignorant of a host of 
minute changes which may take place in the ganglion cell 
under the influence of disease, and yet apparently leave 
the cell in a normal condition when viewed by Muller’s fluid 
hardening, which entirely shuts out of view cytological 
alterations. Thus, we can readily understand how com- 
paratively little progress has been made in the study of 
neuro-pathology, and especially mental pathology, except 
in regard to changes in the nerve fibres, when the gan- 
glion cell microcosm was entirely ignored. 
In brief, until very recently only the outward morphology 
of the ganglion cell, both in the normal and abnormal nerv- 
ous system was studied, and the work of the next two or 
three decades will be the most brilliant in clearing up the 14 
van gieson: pathological institute. 
great number of misconceived problems of neuro-pathol- 
ogy, when conducted along the lines of studying the cell, 
not from its outward form, but by its internal organization. 
Two reasons, apparently, have retarded this most fruitful 
application of cell methods and cell knowledge to the prob- 
lems of both neural and general pathology. In the first 
place, the extremely specialized training, and the unfor- 
tunately complicated terminology of the cellular biologist, 
requires a distinct course of study on the part of the pathol- 
ogist. In the second place, the cells of the human body 
are not as favorable objects for cytologic study as those of 
the lower forms of animals. One has, therefore, to attain a 
broad and comprehensive insight into the elaborate internal 
arrangement of the cells of the human body, especially 
the ganglion cell, and to guard against hasty or erro- 
neous interpretations of the cytological elements, whether 
under normal or abnormal conditions, to devote much time 
to the study of general cellular biology. An investigator 
who desires to apply the broadening conceptions of cytol- 
ogy to the problems of the human body, either under nor- 
mal or abnormal conditions, and to plan out work in pathol- 
ogy from a cytological standpoint, should visit the marine 
or university biological laboratories, preferably the former, 
and become practically familiar with all of the complicated 
methods of the cytologist. He should study fertilization 
and cleavage of the ovum in the most favorable examples 
among the invertebrates and lower vertebrates. The cytolo- 
gist for years has spent the greatest amount of time in this 
field, and in it has achieved his most brilliant results. Such 
an investigator should also study some of the lower forms 
of life which have very large cells, such, for instance, as 
necturus salamandra or amphiuma. The cells in such forms 
as these have thrown a great deal of light on general 
cytology, and show many features or detailed cell organ- 
ization much more plainly than man and the higher 
vertebrates. 
When familiar in this way with the introductory princi- 
ples of the science of the cell, he may then to advantage VAN gieson: pathological institute. 
begin researches in the pathological cytology of many 
human diseases, which are so much in need of these investi- 
gations. Thus, the work of the succeeding years, in writ- 
ing out the normal and pathological cytology of the human 
body, cannot be done by investigators who expect to plunge 
at once into the complicated cellular details of any particular 
set of cells of the body, as the various classes of ganglion 
cells, for instance, without much preparatory and compre- 
hensive work, in general cellular biology. This warning 
is the more forcible in studying very delicate changes in 
cells under abnormal or diseased conditions, for the field 
is almost developed in the light of the most modem ideas, 
and may contain many pitfalls of error for the cell anato- 
mist who has not studied the cell in the lower form of life 
and with absolute perfection of technique. 
Even the chemistry of the various minutiae of the nuclear 
and cytoplasmic organization is approaching a surprisingly 
accurate basis. This cytological chemistry must also be 
thoroughly mastered as well as the detailed structures of 
the internal cell structure. Malfatti and Lillienthal have 
shown that a series of chemical reactions, definite and 
concise in their graduations exist between certain basic 
and acid aniline dyes, and the materials composing the 
nuclear and cytoplasmic network. These exquisitely del- 
icate reactions, indicating differences in the constitution, 
as well as in the location of certain granules or portions of 
the nuclear or protoplasmic reticulum must not be ignored 
in studying the problems of general or neural cell physiology 
and pathology. Finally, to consider the application of 
cytology to the cell which interests us most, namely, the 
ganglion cell, both under normal and abnormal conditions, 
it will be seen that these topics require investigation, with 
much training in general cellular biology, and should be 
investigated by observers who combine a thorough knowl- 
edge of minute cell anatomy with training in both general 
pathology and neuro-pathology. The most valuable and 
perfectly ideal kind of work in analyzing the complicated 
internal arrangement of ganglion cell structure should 16 
van gieson: pathological institute. 
come from men like Fleming, Boveri, the Hertwigs, Fol, 
Gnignard, Van Beneden, Pfnitzner, Biitchli, Verworn and 
their colleagues, and Wilson and Watase in this country. 
If such masters in cell anatomy combine also the training 
of the pathologist, and could join the two branches of 
research, especially in the ganglion cell, we should gain an 
enormous amount of knowledge that neither of the two 
branches of science single-handed could ever hope to attain, 
except in a superficial or even unreliable way. 
It will be seen, therefore, that one of the most essential 
factors in the Pathological Institute will be to conduct 
these two branches of research hand in hand, and it will, 
therefore, be especially necessary to have one of the 
associates of the Institute a profound student of cytology, 
in order that he may direct work in the pathology and 
normal anatomy of the nervous system from this standpoint. 
After having emphasized the value of the methods which 
display the minute anatomy of the ganglion cells to gain 
evidence of the action of the subtle body poisons, we may 
resort to a more specific consideration of these poisons. 
One particular group of these poisons was spoken of 
specifically, namely, the poisons which are associated with 
the development of bacteria within the body, and the 
circulation within the body of such a bacterial toxine, 
with its resultant effects, is known as toxaemia. 
Now, hand in hand with the accumulation of the knowledge 
which resulted in the establishment of a group of certain 
poisons associated with the development of bacteria, another 
class of poisons has been very definitely grouped together, 
which are due to the retention in the body of more than the 
normal amount of certain secretions, or on the other hand, of 
an over-production of certain secretions, and these are 
somewhat loosely grouped together under the familiar name 
of intoxicants. The studies which have led up to the more 
definite knowledge of some of these intoxications are cer- 
tainly among the most interesting experiments of the 
present century. The experimental work of the last several 
years on the thyroid gland, shows that it exerts a most VAN gieson: pathological institute. 
powerful influence upon the general nutrition of the body. 
If the thyroid be removed in dogs, a very intense poisoning 
occurs, and death seems to be due to the action of the 
poison on the nervous system. Incidentally it may be re- 
marked that the action of this form of intoxicant on the 
nervous system can only be thoroughly appreciated by 
Nissl’s method. Not only does a deficiency beyond a 
certain degree of the thyroid give rise to an intoxication, 
as in myxoedema, but an over-production or disturbance 
of the thyroid gland secretion may also give rise to an in- 
toxication manifested by that puzzling and hitherto unex- 
plained complexity of symptoms known as exophthalmic 
goitre. The precise nature of the investigations clearing 
up these two forms of thyroid intoxication, and explaining 
the cause of the clinical manifestations resultant from 
their actions, is certainly a most brilliant achievement of 
the past decade of medicine, and has been worked out quite 
entirely in the physiological and pathological laboratories. 
We are led from such results to seek a similar explana- 
tion in several other obscure nervous diseases and inquire if 
they may not also be due to abnormal conditions of others 
of the ductless glands. We might expect to find in many 
nervous manifestations which have hitherto entirely baffled 
us in the search for the clue of a poison, especially with 
Nissl’s method, evidences in the ganglion cells of intoxica- 
tions like myxoedema, thyropravia and exophthalmic goitre. 
Undoubtedly epilepsy is the manifestation of a temporary 
intoxication, which, if examined searchingly, and with a 
careful selection of an appropriate case for cytological study, 
will show traces of a poison which acts on the cortex 
similarly to those found in experimental thyropravia. 
Unfortunately, however, we cannot expect to find any 
changes in the details of the ganglion cell organization, so 
that a series of changes due to toxaemia could be distin- 
guished from an intoxication. We should not, for instance, 
expect to find in the pathological cytology of the ganglion 
cell any set of changes which would indicate specifically 
the changes due to rabies, or the changes due to thyro- 18 
van gieson: pathological institute. 
pravia. In cases of each of these diseases, the changes 
might be quite identical, and this is the result which the 
speaker has found in an extended set of researches in each 
of these sets of poisonings produced experimentally. The 
nervous manifestations in Addison’s disease may also be 
regarded as an intoxication produced by deficiency of the 
suprarenal capsules. In fact, all of these hsematopoetic or- 
gans which some years ago were grouped together as the 
ductless glands, the terra incognita of both the physiologist 
and pathologist, have to-day, as well as the marrow, become 
very important organs for investigation to both the general 
pathologist and neuro-pathologist, for we know that the 
exquisitely delicate maintenance of the normal conditon of 
the blood depends upon these organs, and if through 
disease of any of these haematopoetic organs, the in- 
gredients of the blood fall out of harmony, the blood itself 
becomes a poison and may affect the nervous system very 
profoundly. For instance, in Addison’s disease and the 
various anaemias the nervous system often manifests symp- 
toms of poisoning, which ought to be recognizable from 
cytological study. It is interesting to note that Lichtheim 
pointed out some years ago that even such extensive changes 
in the nervous system as sclerosis of the spinal cord had 
been found associated with several of the blood diseases. 
It is rather difficult at present to classify these different 
poisons of intrinsic origin, for the simple reason that we 
have not as yet definite enough knowledge of them except 
the bacterial toxines and the intoxicants from deficient or 
disturbed thyroid gland secretion. Probably at the present 
time it cannot be stated precisely whether in thyropravia 
the poison is due to a failure to eliminate certain materials 
from the blood, or whether the blood is deprived of certain 
additions from the thyroid, although the former hypothesis 
seems the more probable. It is again difficult to know 
whether to classify the poisonous action of the blood in the 
several anaemias and leucocythemias under the head of 
intoxicants. The absorption or failure to eliminate noxious 
materials from the gastro-intestinal tract certainly comes VAN gieson: pathological institute. 
under the head of intoxicants. The disturbed condition 
of the nutrition attending insufficient food or in starva- 
tion, gives rise to a condition of the body fluids which is 
practically equivalent to the condition of poison. Now, 
it will be seen that it is exceedingly important to investi- 
gate the effects of all these forms of poisoning upon the 
nervous system, both for the study of pathology of in- 
sanity and ordinary nervous diseases, It is equally im- 
portant to have a more precise classification of these 
intrinsic poisons. We might, perhaps, for our purposes 
of studying their effects upon the nervous system, divide 
these poisons in an entirely tentative classification in order 
to gain a working basis, as follows: 
No. i. Bacterio-toxines—These accompany or are asso- 
ciated with the development of bacteria within the body. 
No. 2. Haemato-toxines—Poisons due to abnormal con- 
dition of the blood as in the several anaemias and leuco- 
cythemias. 
No. 3. Intoxicants, subdivided into (a) haematopoetic 
intoxicants, for instance, such intoxicants as evince the 
manifestations of myxcedema, thyropravia, Basedow’s 
disease and Addison’s disease, and (b) intestinal intoxi- 
cants, such, for example as cephalalgias and epilepsy (?); and 
(c) Renal intoxicants. These comprise the several materials 
which were not properly eliminated by the kidneys, acting 
as poisons: for example, cerebral symptoms of uraemia; 
(d) pancreatic intoxicants, which cause the accumulation 
in the system of the materials which produce diabetes and 
its cerebral manifestations. (?) 
The condition associated with starvation, if it can be 
likened to a poison, also that of acromegaly or other 
nutritional diseases wherein lesion of the pituitary body 
has been suspected, as well as malaria, are difficult to classify 
in any of these divisions. These last three conditions per- 
haps had best be classified among the haemato-toxines, 
unless we wish to speak of the poison of malaria as being 
a hematozoon toxine, a word, however, which is quite un- 
justifiable, for we do not know positively whether the 20 
van gieson: pathological institute. 
hematozoon malaria induces the poisonous effect of 
malaria by damaging the red blood corpuscles, or whether, 
this red blood cell destruction is associated with the pro- 
duction of a toxine. The word cachexia is at the best a 
loose one, and what is indicated by cachexia and the poison 
producing a cachetic condition might well be placed in any' 
of these classifications. For instance, the cachetic condition 
accompanying extensive tumor growths might be classed 
possibly as an intoxicant, a haemato-toxine. The cachexia of 
marasmus would again be a haematone-toxine. The cachexia 
dependent upon a chronic suppurative condition might pos- 
sibly be classed as a bacterio-toxine or haemato-toxine. It 
is certainly appropriate to speak in detail of these various 
forms of intrinsic poisons, and even to attempt their 
unsatisfactory classification; for it will remind you of the 
very many ways indeed which the nervous system may be 
subjected to those changes which might ultimately lead to 
the several forms of insanity. The period at which the 
nervous system has been poisoned acutely by these poisons 
may be a long time in advance of the appearance of men- 
tal symptoms—so far in advance that it may have been 
overlooked, and yet be the direct cause in preparing the 
ground for insanity in later years, while leaving a stigma 
on the ganglion cells so that they are weakened against 
succeeding inroads of poisons. 
(To be continued.)