ON THE 
PROGRESS OF NEUROLOGY. 
BY 
LEWELLYS F. BARKER, M.8., Tor., 
Associate Professor of Anatomy, Johns Hopkins University, Assistant 
Pathologist to the Johns Hopkins Hospital. Baltimore, Md. 
[.Reprinted from YALE MEDICAL JOURNAL for January, iSgg. ] ON THE PROGRESS OF NEUROLOGY 
Lewellys F. Barker, M.8., Tor., 
Associate Professor of Anatomy, Johns Hopkins University, Assistant 
Pathologist to the Johns Hopkins Hospital.* 
\Reprinted from Yale Medical Journal, February, iBgg ] 
Mr. President and Gentlemen:—When invited by the Presi- 
dent of this Association to deliver a lecture before its members 
upon some subject pertaining to the nervous system, I must con- 
fess that, while I appreciated deeply the honor conferred 
upon me, the prospect was associated with a certain degree 
of anxiety and trepidation. Unless a man is confident that 
what he has to say to an audience composed in large part 
of busy practitioners, will interest and encourage as well as 
instruct his hearers, I can conceive of no possible excuse which 
could justify his appearance before them. On turning the mat- 
ter over in my mind, however, it seemed to me that to a body of 
men so interested in the more purely scientific side of our pro- 
fession that they support and attend each year a course 
of lectures upon scientific subjects related to medicine, a brief 
review of the methods which have been and are being employed 
in neurological investigation, together with an epitome of the 
main results thus far achieved from their application, could 
scarcely fail to be entertaining and helpful. 
Indeed, on further consideration, and especially in the 
attempt to arrange the available matter in a more or less orderly 
fashion, it has struck me that the marked technical progress made: 
and the enormous widening of knowledge concerning structure- 
*An address delivered before the Yale Medical Alumni Association,. 
December 15, 1898. 2 
and function with regard to the nervous system more than any 
other part of the human or animal body are peculiarly fitted to 
arouse enthusiasm and compel the admiration of the practical 
man. 
In the brief time at my disposal it would be folly to attempt 
any minute description of technical methods or any laborious 
analysis of the details of individual original investigations. 
Such circumstantialities find a suitable repository in the special 
journals and reference volumes, not in a general lecture. I 
shall rather attempt, therefore, to indicate as succinctly as pos- 
sible the broad lines of development and expansion of neuro- 
logical technique, to point out the relation of modifications of 
old and inventions of new methods to the successive discoveries 
in neural morphology and physiology, and, possibty, to make 
some references to the probable lines of advance in the future. 
In the course of my remarks I shall have something to say with 
regard to the combination of instruction with investigation in 
the study of the nervous system, the importance of division of 
labor and co-operative activity, and the desirability of the asso- 
ciation of well organized laboratories in which anatomical and 
physiological researches are undertaken with well-equipped 
hospitals and asylums manned with clinicians thoroughly 
trained in the modern methods of investigating disease. 
It will be simplest to begin by a glance at the conception of 
structure and function entertained by investigators at present, 
and afterwards to consider briefly some of the methods by 
which this conception has been gained. 
The human individual as a member of modern society and 
the product of civilization is an animal manifesting physiolog- 
ical activities more complex and diversified than those of any 
other member of the animal series, and far more intricate and 
varied than those of the primitive tribes still to be met with in 
certai .i parts of the world. Between the most complex of ani- 
mals and the simplest Protozoan species extends a series of 
organisms representing a scale of complexity of form and 
function most delicately graded. Common to every member of 
the series, though varying in constitution, is the substance 
which for want of a better name we call protoplasm. Equally 
common throughout the animal kingdom are certain funda- 
mental activities—the capacity to assimilate food stuffs, to get 
rid of excrementitious products, to react to stimuli emanating 
from the environment, to give rise to other organisms of the 
same kind. As every one knows, however, the amount of 
protoplasm and the way in which it is distributed varies enor- 3 
mously in different animals; it is also a matter of every day 
experience that the fundamental properties of protoplasm are 
by no means identical in their manifestations in the different 
species of organisms. Morphological differences are constantly 
correlated with physiological distinctions. In the lowest forms 
of animals the protoplasm exists as a simple continuous mass— 
a cell—containing within it certain more differentiated and 
apparently more solid masses—the so-called nucleus, centro- 
some and archiplasm. In all higher animals the protoplasm, at 
the beginning of the animal’s life, is also met with in the form 
of a continuous mass, the fertilized ovum, a single cell, con- 
taining within it, nucleus, centrosome and archiplasm; this 
unicellular condition does not, however, last long, for by a re- 
peated process of division the single protoplasmic mass be- 
comes broken up into, first, two cells, then four, then eight, and 
so on until ultimately in an animal like man, according to the 
estimate of Francke, there are as many as 26% billions of cells. 
The original relatively simple minute microscopic lump of 
protoplasm has by assimilation of suitable food under favorable 
conditions grown into a divided mass of protoplasm 
and protoplasmic derivatives weighing say 150 pounds or more. 
I shall not stop to discuss the factors, external and internal, 
which are operative in this gradual process of protoplasmic 
growth and subdivision, interesting as such a discussion could 
be made, but shall simply remind you that as the subdivision 
proceeds groups of the masses which result begin to exhibit 
structural peculiarities which distinguish them from one 
another, and which are markedly different from those of the 
common mother-cell. 
The body, as we are accustomed to say, becomes differ 
entiated into a number of groups of cells—the cells of the indi- 
vidual groups resembling one another closely, but differing 
strikingly in microscopical appearance from those of other 
groups. As a result of this manifold subdivision of the living 
substance, certain of the cells have come to be in more intimate 
contact with the external world than others, some are closer to 
the supply of crude food, some are exposed directly to light 
and air, etc. Cavities form, intercellular substances, solid and 
fluid, are manufactured and the organism is now a multicellular 
mass, of which the individual cells or individualities of a lower 
order are so related to one another and so co-ordinated in their 
activities that the whole animal appears to act as a unit—is 
indeed a unit or individuality of a higher order. The life of 
the higher unit “is not, however, an indivisible unitary archeus 4 
dominating, from its central seat, the parts of the organism,, 
but a compound result of the synthesis of the separate lives of 
those parts,” i. e. of the separate lives of the organic individ- 
ualities of a lower order. 
The cells of a higher organism, though individuals, are 
not, in a sense, as independent as are free unicellular organisms. 
They represent, on the contrary, individual members of a great 
cell-state, in which the principle of physiological division of 
labor holds, and in which each individual to a greater or less 
extent affects and is in turn affected by every other individual 
of the billions which constitute the state. The reciprocal influ- 
ences vary enormously according to the position and nature of 
the individual cells; some cells touch one another, some are 
directly united with adjacent cells by means of protoplasmic 
bridges, others are brought into relation with widely dis- 
tant cells by means of extremely long protoplasmic processes 
or with the help of delicate fibrils the product of the activity of 
the protoplasm of the cells; while through the lymph and 
blood, which can carry chemical substances in solution, eveiy 
cell is placed in a position to act upon or to be acted upon by 
any other cell in the body. 
Though in the physiological division of labor each of the 
individualities of the lower order sacrifices in a certain degree 
its independence, yet it is in this way alone that it is possible 
for it to attain to a specialization of function, and had it to care 
for all the exigencies of the life of an independent isolated 
organism it could not long continue its existence in its peculiar 
condition. It is only by virtue of its membership in a well- 
organized state composed of a multitude of individuals divided 
into groups of workers of various sorts that it can with safety 
follow, as it were, “its own bent” and attain to a high degree of 
perfection in its own specialized physiological activit}r. The 
whole multicellular organism, on the other hand, can maintain a 
normal existence only when each individual group of wmrkers 
functions in its proper time, place and intensity so that the 
sum total of the activities of the various specialized group of 
workers is just sufficient for the “ continuous adjustment of the 
internal to the external relations” of the organism; in other 
words, all goes well only so long as the activities of the various 
parts maintain collectively a certain equilibrium. 
But it is not to be thought that in the differentiation of the 
multicellular organism into organs and tissues, each cell in 
developing a special function loses entirely the general funda- 
mental properties of protoplasm; on the contrary, each of the. 5 
•specialized individualities retains the power to assimilate food, 
to give off excrementitious substances and often the capacity 
of reproducing its like; the difference in capacity is one of 
degree rather than of kind. The specialized cell may not be 
capable of digesting crude food stuffs; it may require that its 
nutriment be especially prepared for it by other cells or even 
by a whole series of other cells of different varieties. Again, 
the excrementitious products of a specialized cell may not 
consist of substances that can be directly eliminated by the 
body; very often doubtless other cells have to carry the process 
of combustion and analysis further; indeed, the excrementitious 
product of the former cell may constitute a suitable article of 
■diet for the latter. 
The various groups of cells in the human body so curiously 
differentiated morphologically in correspondence with their 
specific physiological activities are already well known to all of 
you. The great group of cells of hypoblastic origin have been 
set apart for purposes of digestion and respiration; they build 
zymogens, acids and alkalies and pour them out into the alimen- 
tary canal, where they mix with the food and prepare parts of 
it for absorption and utilization by the other cells of the body, 
or, as in the lungs, they mediate the gas-interchange between 
the air in the pulmonary alveoli in contact with their distal sur- 
faces and the corpuscles and fluids of the blood situated prox- 
imal to them. The mesoblastic cells build intercellular sub- 
stances and form the framework of the body upon which the 
soft parts are hung. Some of the intercellular substances 
become calcified and in the form of bone supply “ struts and 
ties for the bearing of thrusts and tensions;” in other instances 
the intercellular substances are firm but elastic and supply the 
resilient material suitable for the articular surfaces of joints. 
Other mesoblastic cells build fibres of various sorts—long, tough, 
non-extensile fibrils as in tendon, aponeurosis, and ligament— 
elastic fibrils as in areolar tissue or the extremely delicate 
mesh-work of finest fibrils such as those met with in the fine 
meshed reticulum supporting the parenchymatous elements of 
the various organs. In the muscle cells we see the embodiment 
of a special function of high dignity—contractility. In the 
protoplasm of these cells are laid down certain longitudinal 
structures—plasma products—which look like fibrils often with 
curious cross-markings—structures which are undoubtedly asso- 
ciated in some way, though we are yet ignorant how, with the 
approximation of the two ends of the fibre when the latter is 
stimulated. The cells of ectoblastic origin become divided into 6 
various groups, some of them forming a superficial covering for 
the body and certain appendages of that covering as hair and 
nails, others entering the orifices to provide them with a lining, 
still others dipping down beneath the surface to build the 
secreting glands which elaborate the milk, the sweat and the 
sebum. 
A very large proportion of the ectoblastic cells—brothers or 
sisters of the epidermal cells—become especially differentiated 
along the lines of irritability and response and go to form the 
central nervous the axis cylinders of the peripheral 
nerves, and the true nervous elements of the various sense- 
organs. 
The nervous system, as we know it to-day, consists like all 
the other tissues of the body of an aggregation of cells and of 
intercellular substances derived from the cells. Aside from the 
covering membranes and the blood vessels with the tissue im- 
mediately surrounding them in the central nervous system, 
and the connective tissue, blood and lymph vessels and neuri- 
lemma sheaths of the peripheral nervous system, all the cellular 
elements and intercellular substances of the nervous tissues are 
believed to be derived from this ectoderm or outermost of 
the three layers of which the embryo is composed at an early 
stage. 
These cells and intercellular substances of ectoblastic origin 
in the nervous system may be divided into two great classes: 
(i) that including the true nerve cells and their derivatives, 
and (2) that including all the other cells in the central nervous 
system and their derivatives, namely, the elements classed as 
neuroglia and ependyma. Thanks to the newer investigations 
the form relations to be met with in connection with these two 
groups are gradually being unravelled, and it is to an epitome 
of our knowledge concerning these that I wish to direct your 
attention particularly this evening. 
One of the most striking differences between a nerve cell 
and most other cells of the body is the curious distribution in 
space of parts of the protoplasm composing it; while a subdivi- 
sion of the peripheral parts of the protoplasmic mass with for- 
mation of cell processes does occur in several tissues of the 
body, nowhere else is this subdivison so pronounced, nowhere 
are cell processes so long, so complex, and so manifoldly 
branched and so ultimately delicate as in the nervous system. 
Indeed, for a long time these intricate subdivisions of processes 
and many of the very long delicate processes were not known to 
constitute integral parts of nerve cells, and it was not until 7 
they became recognized as such that the cell doctrine could he 
satisfactorily applied in the nervous system. To distinguish the 
whole nerve cell, inclusive of all its processes from the torso 
recognized by the older observers as the nerve cell, Waldeyer 
has introduced the term neurone, a designation which has met 
with almost general adoption. While I shall speak of the 
specialized cell-individuals in the nervous system as neurones, 
I do not mean to imply that we meet here with structures 
incomparable to other cells in the body; on the contrary, the 
neurones or complete nerve cells are individualities of a lower 
order quite comparable with other individualities of the same 
order, e.g. with gland cells, smooth muscle cells, tendon cells 
and the like. In the case of the neurones, the special labor per- 
formed has to do with the functions of irritablity and conduct- 
ivity; in the gland cell the most manifest functional capacity is 
secretion; in the muscle cell, contractility; in the tendon cell, 
the manufacture and nutrition of firm fibrils for mechanical 
purposes. In every instance we may assume that the structural 
peculiarities met with correspond to the physiological functions 
to be performed, although as 5ret we may be unable to correlate 
all the details of structure with their corresponding details of 
function. 
Nearly all the nerve cells or neurones possess more than one 
process; indeed, in most there are many processes, though in 
some cells only two exist. In the cells with many processes the 
latter are found as a rule to consist of two sorts: (i) much 
branched processes never extending to very great distances 
from the main mass of protoplasm of the cell, processes 
which come off by a rather thick wedge of origin from the 
main protoplasmic mass, branch manifoldly soon after leav- 
ing the cell and soon exhaust themselves by multiple division, 
and (2) longer slender processes, each one arising from the prin- 
cipal protoplasmic mass by a narrow wedge of origin and 
extending for a shorter or longer distance, maintaining or 
nearly maintaining its original calibre on the way and giving 
off in its course only a few delicate side fibrils or collaterals. 
Ultimately it, like each of the side fibrils, divides several times 
and exhausts itself in delicate terminal arborizations the 
so-called telodendrions. To the first set of processes, usually 
multiple, the term “dendrites” is applied; to the second set 
of processes usually, however, single for one nerve-cell, the 
name “axones” has been given. That there are neurones free 
from dendrites, and that there are others entirely devoid of 
axones need not detain us here, nor need we at this time con- 8 
sider the elaborate nomenclatures which have been introduced 
for convenience of description of certain peculiarities of num- 
ber, distribution and function of neurones in various parts. 
One important point, however, must be mentioned, viz., the 
axones of the various neurones differ enormously in length. 
Thus, whereas some axones are very short, extending for per- 
haps only a few millimetres, or even for a fraction of one mil- 
limetre from the cell-body, others are much longer, extending 
even to many centimetres, and in extreme instances for a dis- 
tance greater than half the whole length of the human body. 
The neurones with long axones have been called by Golgi cells 
of Type I, and those with short axones cells of Type 11. They 
are, perhaps, better designated with von Lenhossek as inaxones 
and dendraxones. The classification is merely a matter of con- 
venience, since transitional forms exist. It is interesting to 
note that the long axones become surrounded during develop- 
ment by a myelin sheath, while the short axones are not thus 
enveloped. Outside the central nervous system, the axones of 
the cerebrospinal neurones are surrounded, not only by a myelin 
sheath, but also by a cellular sheath, the neurilemma, while the 
sympathetic axones are devoid of myelin sheaths, but retain a 
partial cellular covering. The axis cylinder of every nerve 
fibre is in reality but the axone of some neurone, that is, a long 
drawn out process of the protoplasm of a nerve cell. The 
perikaryon of a neurone, that is, the main protoplasmic mass con- 
taining the nucleus and its dendrites, does not become surrounded 
by myelin sheaths, but, in certain instances, at any rate are 
enclosed in an external reticular covering of peculiar structure, 
resembling, as has been suggested, a stocking drawn over the 
protoplasmic mass. 
The main mass of protoplasm or perikaryon with its con- 
tents, together with all its dendrites and their subdivisions, the 
axone with its side fibrils, collaterals and end ramifications con- 
stitute, then, a single nerve cell, or neurone, that is, the particu- 
lar form of individuality of the lower order met with in ner- 
vous tissues. It is estimated by Donaldson, of Chicago, that of 
the billions of cells in the human body, some three thou- 
sand millions are nerve cells, an estimate which, as I have sug- 
gested elsewhere, if, of necessity, not quite accurate, is rather 
below than above the truth. 
While the nerve cells or neurones are strikingly uniform in 
general external morphology, still microscopic examination 
shows that the length, mode of branching and size of the 
cell processes, together with the relation in which they stand to 9 
the cell body, affords ample opportunity for the production of 
varied appearances, and in the different groups of nerve cells 
(for as might be easily imagined even among specialized work- 
ers belonging to one colony, where the colony contains thou- 
sands of millions of individuals, there is further specialization, 
division of labor, and accordingly formation of multiple sub- 
groups), one meets with structural peculiarities which permit a 
skilled histologist to decide, even from the external form alone, 
as to the particular group to which a given neurone belongs. 
Thus, in the diagram, no difficulty is encountered in distinguish- 
ing a pyramidal cell of the cerebral cortex, from a Purkinje cell 
in the cerebellum, a motor cell from the ventral horn of the 
spinal cord, or a cell from a spinal ganglion. 
The researches of the cytologists, in addition to supplying 
us with data concerning the form of the outside of the neu- 
rones and their processes, have added a wealth of detail con- 
cerning the internal structure. Each neurone, like every other 
cell individual of the same order, contains a nucleus with one 
or more nucleoli embedded in the protoplasm. In addition, in 
many nerve cells the existence of centrosome and archiplasm 
has been demonstrated, and it is not impossible that all nerve 
cells contain these peculiar differentiated structures. In nearly 
all nerve cells, after treating with fixing reagents, the proto- 
plasm of the dendrites and of the perikaryon can be seen to be 
made up of at least two substances (aside from the so-called 
pigment met with in many nerve cells); (i) a substance consist- 
ing of very minute granules, arranged in masses which have 
the form of dots, rods, spindles, wedges or cones, the so-called 
Nissl bodies, tigroid masses, or chromophile corpuscles; these 
show an especial affinity for certain dyes, contain iron and 
phosphorus, and are soluble in alkalies, and (2) a ground sub- 
stance, in the fresh condition, and by some methods of prepara- 
tion almost homogeneous in appearance, stainable by an entirely 
different set of dyes, resistant to weak alkalies, but digestible 
in artificial gastric juice. 
There is a good deal of evidence that the first substance, 
that corresponding to the Nissl bodies or tigroid, is present in the 
living cell in solution, that it is allied in composition to the 
nucleo-albumins, and that it represents in large part the food 
supply of the nerve cell. The fact that it is present in about 
the same quantity and distribution in nerve cells of the same 
group, and that it varies considerably in quantity and distribu- 
tion in nerve cells of different groups, when studied by a par- 
ticular method, makes it of high importance for the anatomy and pathology of the nerve cell. This substance is present in 
the perikaryon and dendrites, but no ascertainable amounts of 
it exist in the axone or in the portion of the perikaryon directly 
continuous with the axone, the so-called axone hillock. It must 
be extremely labile, for the quantity and distribution can be 
speedily and remarkably altered by insults of various kinds, 
mechanical, chemical or thermal, applied to any part of the 
neurone. It may even be made to entirely disappear from the 
nerve cell for a while, to return again some time after the cause 
■of the disturbance has been removed. No direct relation, how- 
over, between the symptoms manifested by the animal as a 
result of the insult and the change in this tigroid substance can 
at present be made out, for on the one hand the symptoms may 
be out of all proportion to the changes recognizable in this sub- 
stance, and on the other the alterations in the substance may 
continue for a relatively long period after the unusual symp- 
toms have disappeared. 
The structure of the second substance, that which we have 
spoken of as the ground substance of the nerve cell protoplasm 
.and sometimes referred to as the “unstainable substance of 
Nissl,” is as obscure as is that of protoplasm in general. In the 
perfectly fresh condition it seems to be under the highest oil 
immersion lenses quite homogeneous, but that it is not entirely 
homogeneous is rendered likely by a consideration of the effects 
of certain reagents upon it. Thus it is easily vacuolized, and 
the vacuoles when formed, though varying in size with the dif- 
ferent reagents which can be employed, tend to recur in the 
-same variety of nerve-cell constantly in the same arrangement. 
Thus the character of the vacuolization differs in the dendrites 
from that in the main protoplasmic mass, and the vacuolization 
in both dendrites and perikaryon is again very different from 
that of the axone. In such vacuolized preparations, certain 
particles, sometimes lying in the vacuoles, more often lying in 
the protoplasmic walls intervening between the vacuoles, can 
be stained by suitable dyes. These are the so-called neuro- 
somes, and they also differ much in number and arrangement 
in the various parts of the neurone, being most abundant appar- 
ently in the protoplasm of the terminal ramifications of the 
axones and collaterals. 
By special methods of fixing and staining, fibrils have been 
observed from time to time inside the ground substance; some 
of these are doubtless identical with the walls of the vacuoles 
seen in other preparations. Recently, however, very definite 
fibrillary appearances have been demonstrated inside the neu- rones of both invertebrate and vertebrate animals, and it would 
appear that these represent special morphological entities dif- 
ferentiated from the rest of the nerve cell protoplasm. In 
invertebrates coarser fibril-like structures running through the 
axones and dendrites of neurones are described as breaking up 
in the perikaryon into a relatively large number of simpler 
fibrils, which anastomosing freely with one another unite to 
form intricate intracellular networks. In human nerve cells, by 
a somewhat different method, similar fibrils can be demon- 
strated in the processes, and in the perikaryon, but, it is said, 
without the formation of anastomoses or networks. Single fibrils 
can be traced through the perikaryon from a dendrite to an 
axone or from one dendrite to another dendrite of the same 
neurone; it is even stated that a fibril running for some dis- 
tance toward the perikaryon in one branch of a dendrite, may 
before reaching the perikaryon turn back into another branch 
of the same dendrite and run in the opposite direction. 
With regard to the ground substance of the nerve cell pro- 
toplasm, morphological knowledge is far in advance of explana- 
tions of physiological significance. Certain it is that this 
ground substance is of the highest importance for the nerve 
cell functions—certainly of infinitely greater importance than 
the stainable substance of Nissl. For while the latter can be 
markedly disintegrated or even obliterated from the nerve cell 
structure, and yet complete recovery follow, any pronounced 
general alteration in the ground substance is inevitably fol- 
lowed by complete degeneration and death of the whole neu- 
rone. Certain portions of the ground substance may, it is true, 
be destroyed without necessarily causing the death of the whole 
nerve cell; indeed, disintegration of all the ground substance 
forming that portion of an axone distal to the lesion when an 
axone be cut need cause no permanent injury to the neurone; 
the portion of the neurone which remains may regenerate the 
part removed. 
We feel tolerably certain from recent experience, that the 
ground substance of the nerve cell protoplasm is the portion of 
the neurone more especially concerned in the nerve functions 
proper, but whether it acts as a whole, or whether, as would 
seem more likely, the structures differentiable in it, such as the 
neurosomes and fibrils, are of different physiological signifi- 
cance than the more homogeneous parts, the data at our dis- 
posal do not permit us to decide. Some investigators have been 
tempted, very naturally, I think, to assume that the fibril-like 
structures in the ground substances represent the essential con- 12 
ducting substance, but, however plausible, this is not yet satis- 
factorily proven, and even if such structures were shown to be 
particularly suited for conduction, a similar function for other 
parts of the nerve cell protoplasm would be by no means 
excluded. In passing it may not be superfluous to remark that,, 
lucky as we should be to establish clearly the element or ele- 
ments actually concerned in conduction in the nervous 
such establishment would refer to only one feature of neuronal 
function, and the capacities other than those of mere conduc- 
tion would have to be subsequently considered. Time will not 
permit me to enter into a discussion of the morphological and 
physiological facts which have been accumulated with regard to 
the nucleus; it will be sufficient to say that they are probably 
just as important, if not more important, than those of the pro- 
toplasm, and that as yet our knowledge of them is even less 
complete. 
A word as to intercellular or interneuronal substances 
inside the central nervous system. I have already spoken of 
the periaxonal myelin, and have referred to the reticular invest- 
ment of the perikaryon and.dendrites. That the blood capilla- 
ries give off: a nutrient fluid which bathes the nerve cells there 
can be no doubt; that the neurones throw off excrementitious- 
substances into the lymph is just as certain. Whether in addi- 
tion to this lymph, and the products of the neuroglia and epen- 
dyma, there are besides the perineuronal myelin and reticular 
investment any formed intercellular substances derived from 
the neurones, we do not know. The majority of investigators at 
present are opposed to the assumption. For the neuropilum of 
invertebrates, however, it is asserted that fibrils similar to the 
intraneuronal fibrils exist entirely free, and a well-known 
German neurologist has recently made a strong plea in favor of 
the view that in the grey matter of the central nervous system 
of vertebrates, and especially of man, similar extraneuronal 
fibrils exist in large numbers, and are accountable for the pecu- 
liar stamp which the grey matter bears. From what we know of 
other tissues in the body, and from what we have learned of. the 
fibril-building power of neuroglia cells, the existence of such 
intercellular substances in the nervous tissue is not incompre- 
hensible, nor would the demonstration of their presence be a 
matter of surprise. Thus far, however, this demonstration is 
lacking and we need scarcely worry ourselves concerning the 
possible function of such hypothetical substances before their 
existence has been proved. That the bringing of such proof 
could fundamentally alter our general conception of the struc- ture of the nervous tissues or of the body as a whole, I find dif- 
ficult to conceive, for as every histologist who has worked 
with the tails of rats, the ligamentum nuchae of the ox, a piece 
-of hyaline cartilage, or a mass of bone, knows, the occurrence 
of an intercellular substance is no strange phenomenon and 
•exercises no restraining influence on the formation of the idea 
that the body essentially consists of a mass of cells or individ- 
uals of a lower order, united and co-ordinated into a single 
individual of a higher order—the whole organism. 
It would take too long to review even briefly the main 
facts concerning glia cells, ependyma cells and glia fibres. 
An epitome of the changes which the nerve cells undergo 
in the body of the embryo and after birth before they 
bave assumed the form met with in the adult must also be 
omitted. That in early stages the nerve cells are devoid of 
processes, are motile, and multiply by karyokinesis are now well- 
known facts. Independent of one another and wandering from 
their birth-places, the neurones gradually develop their 
wonderful processes, first the axones, later the dendrites and 
finally come to occupy, some of them sooner, others later, the 
localities in which they are destined to spend the remainder of 
their lives. 
So much for the modern conception of the histological units 
in the nerve tissues. The neurologist is in possession, how- 
ever, in addition to the special knowledge which concerns these 
units or individuals, of much valuable information bearing 
upon the inter-relations of the units, the way in which they 
are grouped, the possibilities of reciprocal influence not only 
among members of a single group, but among the groups them- 
selves, in short, the architecture of the central and peripheral 
nervous organs. He sees how that among an enormous num- 
ber of individuals, of the order of body cells in the process of 
physiological integration which leads in normal animals to a 
united functioning as a higher and more complete vital unit, a 
series of units morphologically and physiologically interme- 
diate have arisen. Neuronal mechanisms are combined to make 
neurone-group mechanisms, neurone-group mechanisms are 
combined in turn to give rise to mechanisms of still higher 
orders, until finally the whole nervous system is included. 
The latter, constantly acting upon the rest of the body and the 
environment, and in turn being influenced continuously by the 
rest of the body and its environment, we stand face to face 
with the organism as personality. 
It would take many lectures of the time allotted to this to deal 
with the features of this organization with which we are already 14 
familiar. For we should have to consider the gradual transition 
in the organismal series from unicellular animals, in which the 
response to a stimulus has to be made by the same cell which 
receives it, through a long chain of ever increasing complexity 
in which there is dissociation of the primary stimulus from the 
ultimate response and the intercalation between the two of one, 
two, one hundred or perhaps many thousands of neural activi- 
ties. In multicellular organisms with the increase of func- 
tional complexity there is corresponding increase in the num- 
ber of special laborers, and progressive dissociation of the 
function with distribution of special tasks among these labor- 
ers. A brain appears, a general movement center in' con- 
nection with one or more organs of special sense (Steiner). In 
the highest of animals, consisting as he does of a large number 
of partially fused segments, each segment fitted out with a 
relatively independent sensori-motor apparatus formed archi- 
tecturally of a set of receptive neurones closely related to 
another set of discharging neurones, the individual segments 
in turn being manifoldly united by commissural and associa- 
tion neurones with one another and with higher groups of neu- 
rones, we meet with the acme of dissociation of neural function 
combined with the highest known order of complex unitary 
neural capacity. 
We are learning to recognize the anatomical mechanisms 
which account for the fact that the application of sensory 
stimuli to the skin or tissues belonging to a primitive segment,, 
while primarily influencing byway of neural channels, the mus- 
culature or the secreting glands of the same primitive segment, 
may secondarily excite similar tissues of adjacent or even 
widely removed segments; for the fact that the same sensory 
stimulus which sets free reflexes can also play a part in the 
origin of an instinctive reaction or even enter as an important 
component into the genesis of a voluntary act; for the fact that 
groups of elementary sensations resulting from stimuli origi- 
nating in the body itself or in the external world can be united 
into physiological units of higher orders, into feelings or emo- 
tions, into more clean-cut perceptions and even into abstract 
ideas and conceptions; and also for the fact that subconscious 
afferent impulses, strong feelings and mature reasoning can all 
excite motor discharges, in the one case suddenly as an imme- 
diate and necessary response to the stimulus applied, in the 
second instance less promptly perhaps and modified by inter- 
current factors, and in the last event more slowly with the mani- 
festation of all the characteristics of a deliberate choice. I say we are learning to understand these anatomical mechan- 
isms, for I do not mistake the beginning for the end. What 
we know is but the threshold to that more complete knowl- 
edge, the treasures of which contemporary neurologists are 
beginning to catch a glimpse. Fortunately for medicine and 
for mankind this threshold is that of an “ open door,” entrance 
to which is barred by no political constitution or jealous state 
enactment; portions of the wealth beyond are available to any 
one who possesses natural aptitude, and who, approaching it with 
reverence, interest and industry, is willing to make his apti- 
tude of value by submitting for a time to that rigorous training 
by which alone it is possible to acquire the necessary;- technical 
skill. 
This brings me naturally to the discussion of the methods 
of neurological investigation that have led to that knowledge 
of the nervous system which we already possess, and that 
together with new methods, sure to be discovered as we con- 
tinue to work conscientiously with the old ones, are destined to 
expand our views, to open up new neurological vistas and to 
illuminate those now seen only in the dawn. 
On examination it is, perhaps, not surprising to find that 
these methods can be divided into two groups which stand in 
intimate relation to the two aspects of function which we have 
learned to distinguish in our study of the nervous system. We 
have seen in this system how through the subdivision of the 
labor among a large number of individuals there has arisen a 
marked dissociation of functions, and how through fusions of 
the activities of dissociation-mechanisms the higher and higher 
unitary physiological activities are to be accounted for. In the 
study of the nervous system, also, methods of dissociation or 
analysis have to be combined with methods of integration or 
synthesis in order that the most satisfactory results in either 
morphology or physiology can be reached. It is a universal 
experience that in the progress of acquiring knowledge analyti- 
cal methods precede the synthetical. There must be differen- 
tiation before integration. Now, while a whole series of analy- 
tical methods have been in use for a long time and have of late 
been wonderfully refined and rendered extremely delicate, it is 
striking that there are but few synthetical methods, and those 
that have been employed have been relatively crude, the better 
methods having been used only by a limited number of investi- 
gators. 
I shall not be so inconsiderate as to detain you by describing, 
even briefly, the technique of the various methods which have been and are still helpful, but shall be content with recalling to 
mind the special advantages of the principal ones and, perhaps, 
the names of the investigators deservedly associated with some 
of them. What I shall say in this connection will bear solely 
upon morphological studies. 
The earliest workers occupied themselves mainly with de- 
scribing the gross form relations of the central and peripheral 
nervous systems as revealed on simple exposure by removal of 
the bony and membranous coverings or by cutting into the or- 
gans. The shape of the principal masses and cavities, the 
existence of white and grey substance, the distinction of the 
cerebrospinal and sympathetic nervous systems and certain 
gross pathological alterations were early known and described. 
Coincident with the increased study of human material and 
greater skill in the use of the scalpel the descriptions become 
gradually more accurate until in the records left behind them 
by such men as Sylvius, Vesalius, Monro, Sir Charles Bell, 
Lockhart Clarke, Reil, Rolando, Burdach and Stilling, we can- 
not but marvel at the accuracy of observation and the faithful- 
ness of portrayal which they manifested. 
The introduction of hardening fluids facilitated the study of 
gross material and by preserving the tissue from decomposition 
permitted the prolongation of the examination of a single speci- 
men indefinitely. Thick slices of the hardened tissue yielded 
in many respects more satisfactory information than that 
derivable from slices of the fresh soft organs. Alcohol harden- 
ing permitted of successful manipulation with fingers and for- 
ceps and the newer conceptions gained with the aid of the 
Abfase7'imgsmethode were at the time justly lauded. In this 
connection the work of Burdach, Reil, Foville, Stilling and 
Meynert deserve especial mention. 
Late in the last century and early in the present the method 
of isolation of parts was pushed further, especially when the 
microscope came into more general use and methods of teasing 
with needles and of loosening the parts from one another by 
means of fluids which soften or dissolve out certain of the sub- 
stances which ordinarily prevent dissociation were introduced, 
and the knowlege of the nervous organs became within a rela- 
tively short time enriched to an unprecedented degree. The 
details made out concerning isolated nerve cells and their pro- 
cesses and separated single nerve fibres and their coverings by 
these relatively simple manipulations were truly remarkable. 
The histologists of the time attained to a degree of skill in this 
field which would give the blush to the modern histologist 17 
-did he attempt to imitate them. In this connection Wagner, 
Deiters, Max Schultze and v. Kdlliker, are the names one 
thinks of. The student of neurology to-day will do well if he 
do not despise or neglect a form of examination which affords 
pictures of the parts obtainable by no other means. 
As early as 1824, Rolando had cut sections of the nervous 
system and examined them under the microscope. It was in 
1842, however, that Stilling, having cut a frozen section of the 
spinal cord and recognized the ease of the study of relations 
inside it, exclaimed “eureka ” and caught a gimpse of the great 
possibilities of the application of the method of the study of 
serial sections. Since then microtomes have been invented and 
wonderfully improved, satisfactory methods of embedding have 
been devised, and now it is possible to cut the whole brain of 
an adult man into faultless serial sections in any one of the 
three dimensions of space without loss of a single section. 
Recentty Flatau has shown that it is possible also to divide the 
whole spinal cord into longitudinal serial sections. By means 
of absorption, embedding, serial sections of one or a fewT nerve 
cells can be obtained as thin as one micron or even less. 
Next in importance to mechanical subdivision of the ner- 
vous system Into its morphological elements and into extremely 
thin slices, was the invention of the method of differentiation 
by means of the application of coloring matters of various sorts. 
The carmine method of Gerlach in connection with bichromate 
hardening of the tissues not only differentiated the nuclei of 
the nerve cells from the protoplasm in which they were con- 
tained, but by showing a special affinity for the axis cylinders 
of the nerve fibres rendered them easily distinguishable in sec- 
tions from investing sheaths and from neuroglia elements The 
impregnation with chloride of gold also revealed minute nerve 
fibrils and processes of nerve cells which must have appeared 
most remarkable to those who, studying tissues, prepared them 
in this way for the first time. 
Of even greater importance was the introduction of Weigert’s 
stain for myelin sheaths which made it possible to follow bands 
of medullated fibres or even single medullated fibres for long 
distances in the central nervous system and in the peripheral 
nervous system. The method is valuable not alone for the 
study of the adult nervous system of man and animals in health, 
but because in diseased conditions it also gives information of 
the very highest import, since in areas in which the medullated 
nerve fibres have undergone degeneration from any cause and 
have been absorbed, the absence of bundles of myelin sheaths from positions in which they normally exist is demonstrated in 
a superb manner. And while the extremely delicate method of 
Marchi will indicate the existence of degenerated nerve fibres 
at a much earlier period than that corresponding to the total 
absorption of these fibres, and is accordingly a boon to the 
experimental investigator, it can never entirely replace Wei- 
gert’s method for the study of degenerations. Indeed, in 
human pathological anatomy the two methods supplement one 
another most conveniently. 
As a special application of Weigert’s myelin sheath stain 
may be mentioned Flechsig’s studies of the developing nervous 
system. The discovery of the fact that the bundles of medul- 
lated nerve fibres which exist in the adult nervous system do 
not all receive their myelin sheaths at the same time, but get 
them rather at successive intervals corresponding more or less 
accurately in serial appearance to the successive manifestation 
of more and more complex functional activities, gave the clue 
to the embryological analysis of the medullated tracts, which 
having thrown and still throwing so much light upon the archi- 
tectural characters of the spinal cord and brain, will always be 
associated with Flechsig’s name. 
The latest results of this application of this method has 
resulted in Flechsig’s hands in the better localization of the 
primary sensory motor areas in the cerebral cortex, in the 
demonstration of the fact that the projection fibres connecting 
these various areas with lower parts of the central nervous 
system are medullated at different periods and in the discovery 
of the existence and topographical distribution of the secondary 
centers of a higher and fundamentally different significance— 
the so-called association centers of the cerebral cortex. 
Through improvements in the compound microscope,, 
especially by devices for increasing the illumination and for 
the elimination in large part of the spherical and chromatic 
aberration, it has been possible to obtain a clear definition of 
microscopic objects, even when magnified 1,000 or 2,000 diam- 
eters. The extension of the powers of the human retina 
thus made possible, together with the advances in staining, 
clearing and mounting, have revolutionized the science of histo- 
logy and microscopic anatomy, and the old-time six weeks’ 
course given in these subjects has been replaced by one of as 
many months. Cytology in general has made enormous strides, 
and with it cytology in particular, although curiously enough 
the nervous system, owing to the peculiar character of its 
cellular elements, did not reap the benefits quite so soon as did the other organs of the body. But when once results began to 
be attained in the nervous system by these methods or by par- 
ticular modifications of them suited to the special structure of 
the nervous organs, they came with a rush, and during the past 
two decades the world has been flooded with books and original 
articles in morphological journals dealing with the results of 
research into the histology and architecture of the nervous 
system. To Golgi, of Padua, belongs the credit of devising a 
form of metallic impregnation which better than any other 
procedure outlines the external form of the nerve cell and its 
processes, especially in embryonic tissues. Utilized by many 
students in many countries, this method has taught us how 
complicated the various processes of the nerve cell really are; 
it has shown us the external morphological differences between 
dendrites and axones, the varying appearance of these struc- 
tures in the same part and in different parts of the central 
nervous system, and has given us an insight into the various 
inter-relations which exist among the cellular units of which 
the system is made up. Very recently, by slight modifications 
of the method, Golgi has shown that it can be utilized to demon- 
strate not only the reticular investment of the perikaryon and 
dendrite, but also certain curious network-like appearances 
inside the nerve cell protoplasm. The objection, therefore, 
that Golgi’s method affords no information with regard to the 
interior of the neurones can no longer with justice be urged. 
The method of vital staining with methylene blue or thionin, 
invented by Ehrlich, not only confirmed in large part the find- 
ings arrived at with Golgi’s method, but also extended them. 
A special advantage of Ehrlich’s vital staining lies in the fact 
that with it the axones of medullated fibres can be stained; 
whereas, with Golgi’s method the impregnation of an axone 
usually ceases as soon as the myelin sheath is reached. By 
means of the method of fixation which we owe to Bethe, the 
transitory pictures obtainable by the vital staining may be 
caught at the acme of development and rendered permanent. 
Among the host of cytological methods which are suitable 
for the investigation of the interior of the nerve cell that intro- 
duced by Nissl has been extensively followed up. It consists 
of alcohol fixation, sectioning without embedding, staining 
with the methylene blue and soap mixture, differentiating with 
aniline oil and alcohol and mounting in benzine colophonium. 
It is especially valuable for the examination of the neurones 
under normal and pathological conditions with respect to the 
amount of the stainable substance of Nissl present in them 20 
and its distribution in the cytoplasm. Other similar methods, 
such as thionin staining, tolnidin blue staining or double stain- 
ing with methylene blue and erythrosin, offer special advan- 
tages for certain purposes. 
To demonstrate the neurosomes, fixation in a neutral solu- 
tion and staining with iron haematoxylin (Held) serves admir- 
ably. Fibrillary appearances are discoverable in tissues fixed 
in chrom-osmo-acetic acid and stained in saffranin (Fleming). 
They are exquisitely stainable in invertebrate tissues by a sub- 
limate gold method and by a haematein stain (Apathy); while 
in vertebrate tissues they are most easily demonstrable in cells 
which have been treated first with ammonia, afterwards with 
hydrochloric acid, then with molybdic acid and finally with 
tolnidin blue (Bethe). The action of alkalies, acids and digest- 
ive agents of various kinds should also be mentioned 
Concerning the synthetic methods there is but little to say, 
inasmuch as the sole procedure which has been employed by 
the majority of neurological investigators is the mental fusion 
of the pictures obtained by isolation and sectioning into more 
or less vague ideas of solidity. Actual reconstruction in tangi- 
ble form of the solid bodies in the nerve tissues from a fault- 
less series of sections has been carried out only by a limited 
number of workers. 
This method originated with the embryologists and grew 
out of the desire felt by investigators to reproduce exactly in 
three dimensions the magnified details of external and inter- 
nal form as studied in microscopic sections. If an embryo be 
cut into serial sections, and section after section be studied, the 
exact relations in the individual sections can be easily made 
out. But even anatomists endowed most liberally with what 
may be termed the spatial sense find difficulty in uniting 
a long series of sections through several bodies as seen through 
the microscope into an integrated, accurate conception of the 
solid bodies thus magnified. My experience teaches me that 
a relatively large number of students are almost absolutely 
devoid of this power of integration, or as it is sometimes ex- 
pressed, of thinking in three dimensions when studying a 
series of sections. For the purpose of coming to more accurate 
■conclusions himself, and especially with the object of making 
■certain form conceptions clear to students, Wilhelm His, of 
Leipzig, many years ago introduced his method of graphic 
reconstruction from serial sections. His procedure is so gen- 
erally known that I need not take the time to describe it in 
full. He used, it will be recalled, paper ruled at distances cor- 21 
responding to the thickness of the sections multiplied by the 
magnification employed. The outline drawing of the whole 
object over these lines thus permitted the introduction on the 
parallel lines of the paper the limits of any desired object in 
the various sections. In this way extremely valuable flat pro- 
jections of the various internal organs and tissues could be ob- 
tained, and the method is a favorite one at present with many 
embryologists. 
From a series of projections of the organs as viewed from 
different aspects it is possible for an artist to model them in 
clay or wax. Thus there arose through the combined activ- 
ities of His and Ziegler the exquisite models illustrating vari- 
ous stages of development of the embryo chick which are 
nowadays a feature of so many anatomical museums. 
Not all investigators, however, are gifted with the mathe- 
matical knowledge and artistic talent necessary for the success- 
ful application of the method. Somewhat later reconstruction 
with the help of wax plates, permitting the making of wax 
models directly, from the specimens, was introduced by Born. 
In the 22 years which have elapsed since he first employed the 
method many improvements have been made, so that a number 
of technical difficulties with which he had to contend can be 
avoided. It is this method, of reconstruction modified and 
improved which Dr. Mall has used so successfully in the study 
of the anatomy of his series of human embryos. It is also 
this method which Miss Sabin, with the aid and counsel of Dr. 
Mall, has employed in the construction of the model of the 
medulla oblongata, pons and mid-brain which I here show you. 
The prerequisites to the work are (x) the possession of fault- 
less serial sections of the objects to be studied stained in a 
suitable manner; (2) an intelligent idea of the general relations 
and significance of the contents of the sections as seen through 
the microscope; (3) suitable mechanism for the production on 
paper or directly on the wax plates of the magnified picture 
of the section (camera lucida or Zeiss projection apparatus); (4) 
wax plates of proper dimensions and consistence; (5) the guid- 
ance of an experienced workman; (6) patience, industry, enthu- 
siasm and a certain amount of spatial sense and mechanical 
skill. 
We are fortunate enough to possess in the anatomical labora- 
tory at Baltimore several sets of serial sections cut in various 
directions through the brain stem and cerebral hemispheres of 
human foetuses and babies of different ages illustrating accord- 
ingly different stages of development. 22 
The early form relations of the human nervous system have 
been worked out by His, and his results are embodied in his 
well known series of models. Last year Mann, of Edinburgh, 
presented at the anatomical society reconstructions of single 
nerve cells. Thus far, however, no one, to my knowledge, has 
published the results of reconstruction of the medullated tracts 
in the human nervous system. It has occurred to us that the 
analysis of tracts rendered possible by the embryological method 
of Flechsig offers a most suitable field for the application of the 
reconstruction method. A number of students may, we believe, 
conduct such investigation satisfactorily, and without interfer- 
ence with their regular medical studies. The task of making 
such reconstructions was accordingly assigned and a number 
of models are now in progress. The first fruits of the work are 
represented by this model upon which Miss Sabin has been 
engaged in the time she could spare from her regular studies 
since one year ago last March. 
The portion of the brain represented by the model is that of 
a human foetus near full term. It was cut into horizontal serial 
sections and stained by the method of Weigert-Pal by Dr. John 
Hewetson in the anatomical laboratory of the University of 
Leipzig. Circumstances preventing Dr. Hewetson from con- 
tinuing his work with the specimens, he was kind enough to 
place them at the disposal of instructors and students at Balti- 
more. 
After some preliminary study of a series of transverse sec- 
tions through the medulla, Miss Sabin made a more careful study 
of the series of horizontal sections until she was sufficiently 
well oriented with regard to the principal medullated tracts 
and grey masses to proceed with the actual work on the model. 
Every other section, by means of the Zeiss apparatus and elec- 
tric illumination, was projected, magnified 14% diameters in a 
dark room upon a sheet of white paper, and the outlines of the 
tracts and nuclei were drawn in accurately with lead pencil. 
This outline drawing was subsequently made entirely accurate 
with regard to certain details by control studies with higher 
powers of the microscope. After all the drawings had been 
made and corrected each one was accurately transferred by 
means of carbon paper to wax plates, numbered to correspond, 
each wax plate, of course, representing in thickness 29 times 
the thickness of the individual sections. To facilitate subse- 
quent manipulations the areas on the wax plates were painted 
in various colors. 
The wax plate sections once completed, it was necessary to 
cut out the various areas and to begin piling the sections of the 23 
different tracts and nuclei upon one another so as to repro- 
duce the exact form magnified times in the three dimen- 
sions. Here the investigator meets with his greatest difficulty, 
and it is just at this juncture that natural mechanical skill, as 
well as experience, count for much. In order to pile the pieces 
correctly the worker is helped enormously by (1) a knowledge 
of the external form of the whole object before it was cut into 
serial sections, and (2) a knowledge of one or more localizable 
perpendiculars or curves which can be used as a guide. There 
need be no trouble about the external form if an accurate draw- 
ing from three aspects or photographs of the object have been 
made to scale before the sections are cut. Unfortunately in the 
present instance no such drawing or photograph was obtained, 
and Miss Sabin had to resort to a method discovered independ- 
ently by Selenka and Mall, which obviates the difficulty. Sev- 
eral brain stems of foetuses of the same age were studied in 
the gross with particular reference to the external form. The 
drawings of the sections were then cut out (whole) of the wax 
plates and piled repeatedly until the type form as learned 
from the study of other specimens was approximated as nearly 
as possible. Then the waste of the wax plates, that is, the 
boundaries of the holes after the drawings of the sections were 
cut out, were piled up in an exactly similar manner. A cast of 
the holes was then made with plaster of paris, the wax picked 
off, and the external form permanently preserved as a guide. 
As to the establishment of perpendiculars and curves, the 
middle line of the sections of the symmetrical nervous system 
serves admirably in the one dimension; for the other two 
dimensions the curves of the external form were followed, 
helped out of course by the known distances of the individual 
structures from one another in the different sections. The 
stratum interolivare lernnisci and lemniscus medialis were first 
modelled and the other structures built up about these. 
The various ingenious contrivances which had to be invented 
to work out successfully many of the details of the structure 
may be passed over at this time without mention. They will 
doubtless be described by Miss Sabin in full in her publication. 
After the various parts had been reconstructed and the edges 
smoothed with a hot iron the medullated bands of fibres were 
painted white, the motor nuclei blue, the nuclei terminales of 
the sensory nerves red, and other grey masses yellow. 
At first glance the gross relations represented by the model 
are clear—the upper extremity of the spinal cord, the medulla 
oblongata, the pons and the mid-brain. The remarkable curves 24 
made by the central cavity (i) at the junction of the central canal 
of the cord with the fourth ventricle and (2) in the region of the 
aqueductus cerebri are illustrated. The medullated tracts of 
the cord can be followed upward into the rhombencephalon. 
The division of the nervus acusticus into its two components,, 
and their relations to the corpus restiforme, and their nuclei 
terminales are observable. It is seen that the nucleus nervi 
cochleae ventralis forms a continuous mass with the nucleus 
nervi cochleae dorsalis lying lateral from the corpus resti- 
forme. The situation of the striae medullares is indicated. 
At the isthmus the nervus trochlearis of one side undergoes 
decussation with its fellow of the opposite side. 
On removal of the nervus acusticus and the corpus resti- 
forme, the course of the ascending and descending limbs of 
bifurcation of the fibres of the nervus vestibuli can be studied 
as well as the relations of these to the various terminal vesti- 
bular nuclei—the medial, the superior, the lateral nucleus, and 
that of the descending root. 
The modelling of the nervus trigeminus with its motor 
nuclei of origin and sensory nuclei of termination has been 
particularly instructive. The course of the tractus spinalis 
nervi trigemini, the division into a larger lateral and a smaller 
medial portion, the relations of these bundles to the substantia 
gelatinosa, the descending mesencephalic root, the minor motor 
nuclei and the principal motor nucleus and the relations of the 
motor nuclei to the portio minor of the peripheral nerve—all 
are evident. The fibres of the nervus glossopharyngeus and of 
the nervus vagus now come into view, and it is seen how large 
a mass of the glossopharyngeal fibres go to form the tractus, 
solitarius. The relations of the motor fibres to the nucleus 
ambiguus and of the sensory fibres to the nucleus alae cinereae 
are demonstrated. 
These two large masses of grey matter painted yellow, fit- 
ting so accurately into these irregular cavities in the white 
matter which represents the medullary continuation of the 
dorsal funiculi of the spinal cord, are the nucleus funiculi 
gracilis and the nucleus funiculi cuneati respectively. The dif- 
ference in the distribution of internal arcuate fibres derived 
from the two nuclei is obvious. 
Removing the last mentioned structures the funiculus 
lateralis, and the bundle of fibres going into it from Deiters’ 
nucleus can be better examined. The motor nuclei of the 
medulla are now well exposed, and the division into a lateral 
group and a medial group is seen. The nucleus ambiguus and the nucleus nervi facialis are evidently members of the lateral 
group, while this long curved nucleus nervi hypoglossi and the 
nearly spherical nucleus nervi abducentis are more medially 
placed. The old bugbear of the raw student in neurology—the 
course of the nervus facialis inside the medulla—has lost its 
terrors, for here pars prima, genu, and pars secunda are all seen 
at once, the excursion around the sixth nucleus is evident, and 
the final plunge through the corpus trapezoideum to the outside 
can be readily followed. Higher up the motor nuclei of the 
nervus trigeminus, the nervus trochlearis, and the nervus ocu- 
lomotorius are seen. The inclined plane formed by these upper 
eye muscle nuclei is rarely understood from the study of trans- 
verse sections alone, although in sagittal sections of course the 
inclination is obvious. 
Let me call your attention to the plastic representation of 
the lateral lemniscus and the medial lemniscus. The relations 
of the lateral lemniscus to the corpus trapezoideum, to the supe- 
rior olivary complex, and to this long drawn out nucleus lem- 
nisci lateralis which lies in a trench on its lateral surface, as 
well as the intimate connection of a large part of the bundle 
with the colliculus inferior of the lamina quadrigemina, are 
prominent features of the model. No less instructive is the 
illustration of the origin, course and distribution of the fibres of 
the medial lemniscus or fillet. Starting below as a vertical mass 
of fibres—the stratum interolivarelemnisci—formed in large part 
of internal arcuate fibres which have crossed the raphe from 
the opposite side of the medulla, it is continuous dorsally in 
the first part of its course with the fasciculus longitudinalis 
medialis or so-called posterior longitudinal bundle. Higher up 
the two bundles are separated by masses of grey matter and 
from the corpus trapezoideum on, the medial lemniscus, now 
much increased in volume, alters its position and direction, 
spreading out as you see into this large curved fan-shaped mass. 
Miss Sabin’s model of the brachium conjiyictivum supports 
very conclusively the view that the ventral part of the decussa- 
tion of the brachia of the two sides represents a vestibular 
commissure. The pocket between the ventral and dorsal por- 
tions of the decussations is here visible, and is very satisfactory 
to note that the portion of the brachium conjunctivum on 
each side corresponding to the ventral decussation is related 
directly with the antero ventral extremity of the nucleus 
nervi vestibuli superior or Bechterew’s nucleus. The results 
which concern the fasciculus longitudinalis medialis, the for- 
matio reticularis alba et grisea, the decussationes tegmento- 26 
orum, the nucleus ruber and the bundles of white fibres near 
it, the fasciculus retroflexus of Meynert, and the substantia 
nigra are of interest, but to fully appreciate them or indeed 
any part of the model it is necessary to study the serial sections 
along with the reconstructed parts. It is in this, way alone 
that the value of blending the areas met with in the individual 
sections into the solid wax bodies can be fully appreciated, and 
a real mental coalition effected. 
One can hardly fail, I think, to be interested in the appear- 
ance of the nucleus olivaris inferior, here for the first time, I 
believe, accurately reproduced in three dimensions. To me it 
is one of the most instructive parts of Miss Sabin’s work. 
Every one who has studied the olive in sections knows that the 
grey matter is repeatedly depressed and elevated on the sur- 
face, and each of us probably has formed some vague idea of 
the wrinkled shell corresponding to the whole structure. But 
who would have guessed that the olive presents the remarkable 
appearance we see here ! It is obvious on examination that the 
lateral surface is divided by deep fissures into lobes, and that 
each of these lobes is further subdivided by shallower sulci 
into gyri. That these sulci and gyri are no accident, but toler- 
ably constant features, is clear from the reconstructed olive of 
the opposite side, which is almost the exact counterpart of its 
fellow. Since the gyri and sulci are as definite and character- 
istic as those of the cerebral cortex, Miss Sabin will, I have no 
doubt, name them for convenience of description. If the medi- 
cal student of the future had to learn by rote the new lists of 
names which such studies are constantly thrusting upon us, he 
would indeed need to be commiserated, but fortunately instruct- 
ors and examiners are becoming more sensible than their pred- 
ecessors in what they demand of their students. 
This method of wax reconstruction, then, represents the most 
accurate of the integrative methods at present at our command. 
In the solution of morphological problems connected with 
organs the most complex in architectural arrangement in ex- 
istence on this planet it is capable, I believe, of wide application. 
That it will, sooner or later, have served its purpose and be 
replaced by more delicate and accurate integrative methods yet 
to be discovered, there can be but little doubt, for while on the 
one hand those who are familiar only with the mental arith- 
metic reconstruction in general employed, are much impressed 
when they first become acquainted with the wax plate method, 
with the beauty and accuracy of the spatial concepts attainable 
through it; on the other hand, those who know it best and are 27 
familiar with the history of technical procedures in the past, are 
conscious of its crudeness and aware of its limitations, and they 
are prepared for, and will welcome the time when we shall be 
presented with three dimension reproductions of the nervous 
organs as much superior to these wax plate models as the latter 
are to the less accurate, but at the time of their production 
extremely valuable schematic models of an Aeby or a Cazeaux. 
Before closing this lecture, Which I fear has already made 
too great claims upon the graciousness and patience of some of 
you, I must beg your indulgence still further for a moment in 
order to refer briefly to the importance of more systematic 
neurological instruction in our medical schools, the value of 
combining such instruction with neurological investigation, the 
necessity, in order to accomplish this end, of the development 
of better teachers and more perfect laboratories and laboratory 
organization, and finally of the benefits derivable from a better 
understanding of one another’s aims among laboratory investi- 
gators and clinicians, and from such co-operation among these 
as may, while in no wise interfering with individual liberty, 
permit of the direction of their specialized activities along the 
lines of a more or less co-ordinated plan. 
It has for several years past seemed to me a striking anomaly 
that so little provision has been made, even in medical schools 
generally recognized for their excellences, for the study of the 
structure and function of the human and animal nervous system, 
especially since everyone prepared to think accurately and who 
has given the subject thought, readily admits that it is precisely 
by virtue of his neural pre-eminence, rather than by marked 
special advantages in other parts of his body, that man ranks 
first among the animals. The difference, too, between individual 
men lies in large part in differences in nervous organization, 
and, indeed, it is owing largely to our knowledge of differences 
in brain morphology and brain capacity that we can, without 
fear of successful contradiction, designate the statement, “ All 
men are born free and equal,” one of the greatest fallacies which 
has ever moved large bodies of men into action. When we 
remember this and recall the large proportion of ailments which 
have a neural or psychic element in them, is it not surprising, to 
use as mild a word as 1 dare, that a more or less extended knowl- 
edge of the anatomy and physiology of the nervous system has 
not been regarded as of essential importance in the training 
of the medical man? It is not long since when even distin- 
guished professors of medicine in our best medical colleges 
were brave enough to admit—indeed, seemed delighted to 28 
jocularly confess—that they “never could understand the 
fillet.” But while at that time knowledge was so limited 
and the means of acquiring the little possessed were so inade- 
quate that such a confession was one of which he who made it 
need not necessarily be ashamed, that period is now happily 
past and we have entered on an era in which neurological facts 
tolerably accessible and of extreme practical usefulness are by 
no means few in number. It is owing to our ignorance of the 
anatomy and physiology and of the nervous sys- 
tem that we are unable as yet to manage as successfully as we 
would that host of so-called functional nervous disorders which 
unhappily are becoming so prevalent among us, and it is in 
large part due to this ignorance that the flora of “ the Garden 
of Cagliostro ” is so rank and luxuriant. Not until medical 
men understand psychology and learn how to recognize and 
cope with the psychic factors of disease and ignorance need we 
hope to prevent the access to “Gloria mundi ” of some disciple 
of the Prince of Quacks. 
A study of the early records which have come down to us 
teaches us that in ancient times the healing of the body was 
entrusted to the priests, who thus ministered to the physical as 
well as to the spiritual needs of their people. Since then the 
science and art of medicine have become separated from the 
priesthood. But is it impossible that at some time in the not 
very distant future, when through the fusion of converging 
lines of research psychology has come to be recognized in its 
normal relations as a department of physiology, psychiatry as 
a department of pathology, a re-distribution of labor should 
take place and the functions of physician of the body and 
physician of the soul come again to be united in a single indi- 
vidual ? 
Two great difficulties at present obstruct progress, (i) The 
lack of trained individuals to serve as teachers and to conduct 
research, and (2) notwithstanding the remarkable multiplica- 
tion of so-called laboratories, the lack of appreciation of the 
importance of suitable laboratory organization. Any one living 
in one of the large centres of medical education, in touch with 
the leaders of medical thought in such places and conversant 
with the extraordinary demand for trained men to undertake 
responsible laboratory and clinical positions, when he sees the 
difficulty of filling such positions, cannot fail to lament the 
gross errors of the system of education responsible for this 
condition. In a country full of young men with great natural 
aptitude and unprecedented adaptability, it is a pity to have to confess a dearth of men with real skill. This is not the 
fault of the men, but the lack of opportunity for adequate train- 
ing-. A wave of educational reform in medicine and in the 
natural sciences is sweeping over this country at present. The 
faults of the older regime are being recognized and the pros- 
pect for the future, I am glad to say, is bright. 
Medical faculties have been too prone to imagine that the 
construction of large lecture halls and magnificent laboratory 
buildings will suffice for the development of a productive de- 
partment and the institution of adequate instruction, but too 
often they are disappointed in the results. A shrewder fore- 
sight and a wider wisdom puts its money into men, the other 
necessaries follow of their own accord. 
That much of the best talent and capable brain is diverted 
from scientific channels in a country where for comfortable 
existence considerable sums of money are necessary, is easily 
understandable when one remembers how meagre the pittance 
so often accorded to the holder of a scientific chair and how 
much greater the same talent and the same brain capacity can 
command in a different market. 
But given a good laboratory and given a good man, the con- 
ditions for successful instruction and investigation are by no 
means fully satisfied. An institution nowadays can no longer 
hope to succeed by taking a scientist into a brick box and say- 
ing to him, “ Robinson Crusoe, here is your island.” The 
director of the laboratory must be accompanied by trained 
assistants, and it is desirable that these assistants, though, 
perhaps on the whole, equally expert, be skilled in somewhat 
different branches of * the same department of knowledge. 
There must be in addition to these assistants provision for the 
execution of purely mechanical labor, for in shame be it spoken, 
fine minds before now have been ruined and fair bodies 
wrecked by being subjected to the iniquitous necessity of 
menial services which could just as well have been performed 
by minds and bodies of ahnuch lower order. 
Apparatus of various sorts, books and journals, collections of 
old material, access to new material, all come into the scheme. 
The division of labor is to be planned; criminal stunting of an 
assistant’s growth by over-demands on his time or in routine 
work is to be avoided; instruction in the known and investiga- 
tion of the unknown, but knowable, have to be arranged for. 
With successful organization, instruction and investigation go 
hand in hand, and students of the better sort, while acquiring 
existing knowledge, can add a necessary prop here or a new beam there to the general mass of knowledge. There is no 
stimulus so great or so beneficial to good students as the feeling 
that by accurate, conscientious work they can contribute some- 
thing, be it ever so little, to the world’s store of facts. The 
time of medical students is usually so limited that only a few 
can possibly undertake long and complicated researches, but in a 
large laboratory, with the sort of organization I have in mind, a 
number of students working on a number of different points in 
one problem, each contributing his mite, can together collect a 
mass of data which, when integrated, make a contribution of 
no mean significance. 
The anatomist, physiologist, or pathologist who directs his 
attention to the special study of neurological problems should, 
of course, have a solid foundation in general pathology and 
clinical medicine before giving himself over to such special 
studies. He should in connection with his work see autopsies, 
and, if possible, a certain number of patients, and should be in 
a position to consult with special workers in pathology and inter- 
nal medicine, helping them, and in turn being helped by them. 
For in the study of the functions of the nervous system espe- 
cially no stable conclusions have been or ever can be arrived at 
with regard to the higher groups of neurones, at least, without 
the rigid control of clinical and pathological observations on 
man. Morphologists working alone tend to become one-sided; 
isolated physiologists cannot fail to focus falsely, and the pathol- 
ogist and the clinician, if out of touch with one another and 
with the students of normal structure and function, are bound 
to arrive at conclusions which are erroneous. 
Let each one work by his own methods and push them as 
far as he can, but let each have reverence for and keep conver- 
sant with the work and results of others. We shall then have 
more facts and fewer hypotheses. Mindful of the fate of our 
speculative predecessors and in awe of the judgment of some 
scientific Dungara, we shall do best to make our sacrifices to 
the God of Things As They Are, rather than pay homage to 
the God of Things as They Should Be. In this way our build- 
ing of knowledge will be slow, but what is lost in rapidity will 
be more than compensated for in solidity. 
I have now d-one. From what I have said it will be clear to 
you that our knowledge of neurology, so slow in acquisition, is 
dependent upon the application of a large number of different 
methods of investigation differentiative and integrative. For 
the proper understanding of form relations the analyses require 
to be synthesized in particular and in general. Owing to the special difficulties in solving problems in the nervous system 
and the increasing complexity of knowledge of structure and 
function and methods of investigation, co-operative activity is 
essential for progress. Such co-ordinated divided labor can be 
most satisfactorily performed in a series of well organized 
laboratories in association with medical schools, hospitals and 
asylums, and in connection with skilled clinical observers. The 
further pursuit of anatomical, physiological, chemical, patholo- 
gical and clinical studies will permit of the recognition of ever 
increasing interrelations among the results with corresponding 
reciprocal benefit.