PROGRESS OF NEUROLOGY. 
BY 
LEWELLYS F. BARKER, M.B., Tor., 
OF BALTIMORE, MD. 
FROM 
THE PHILADELPHIA MEDICAL JOURNAL, 
1899. [Reprinted from The Philadelphia Medical Journal, January 28, 1899.] 
By LEWELLYS F. BARKER, M.B., TOR., 
PROGRESS OF NEUROLOGY.1 
of Baltimore, Md. 
Associate Professor of Anatomy, Johns Hopkins University, Assistant Patholo- 
gist to the Johns Hopkins Hospital. 
When invited by the President of the Association to deliver 
a lecture before its members upon some subject pertaining 
to the nervous system, I must confess that, while I appre- 
ciated deeply the honor conferred upon me, the prospect of 
such a lecture 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 that could 
justify his appearance before them. On turning the matter 
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 
profession that they support and attend each year a course 
of lectures upon scientific subjects related to medicine, a 
brief review of the methods that 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 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 labor- 
1 An address delivered before the Yale Medical Alumni Association, December 
15, 1898. 2 
ious analysis of the details of individual original investiga- 
tions. 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 suc- 
cinctly as possible the broad lines of development and ex- 
pansion of neurological technic, to point out the relation of 
modifications of old and inventions of new methods to the 
successive discoveries in neural morphology and physiology, 
and, possibly, 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 association of well-organ- 
ized laboratories, in which anatomical and physiological re- 
searches 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 with a glance at the conception 
of structure and function entertained by investigators at 
present, and afterward 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 
physiological 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 certain parts of the world. Between 
the most complex of animals 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 that, for want of a better 
name, we call protoplasm. Equally common throughout 
the animal kingdom are certain fundamental activities—the 
capacity to assimilate foodstuffs; to get rid of excrementi- 
tious products ; to react to stimuli emanating from the envi- 
ronment; 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 enormously in 
different animals; it is also a matter of everyday experience 
that the fundamental properties of protoplasm are by no 8 
means identical in their manifestations in the different spe- 
cies of organisms. Morphological differences are constantly 
correlated with physiological distinctions. In the lowest 
forms of animals the protoplasm exists as a simple continu- 
ous mass—a cell—containing within it certain more differ- 
entiated and apparently more solid masses, the so-called 
nucleus, centrosome 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 containing within it nucleus, centro- 
some and archiplasm. This unicellular condition does not, 
however, last long; for by a process of repeated division the 
single protoplasmic mass becomes broken up into, first, 2 
cells, then 4, then 8, and so on, until, ultimately, in an ani- 
mal 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 manifoldly 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 I shall simply remind you that, as the 
subdivision proceeds, groups of the masses that result begin 
to exhibit structural peculiarities that distinguish them from 
one another, and that are markedly different from those of 
the common mother-cell. 
The body, as we are accustomed to say, becomes differen- 
tiated 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 inti- 
mate contact with the external world than others; some are 
closer to the supply of crude food; some are exposed di- 
rectly to light and air, etc. Cavities form, intercellular sub- 
stances, 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 4 
of a higher order. The life of the higher unit “ is not, how- 
ever, an indivisible unitary archeus, dominating, from its 
central seat, the parts of the organism, but a compound re- 
sult of the synthesis of the separate jives of those parts,” i. e., 
of the separate lives of the organic individualities of a lower 
order. 
The cells of a higher organism, though individuals, are 
not, in a sense, as independent as are free unicellular organ- 
isms. 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 that constitute the state. 
The reciprocal influences vary enormously according to the 
position and the 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 distant 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, every 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 inde- 
pendent 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 activity. The whole multicell- 
ular organism, on the other hand, can maintain a normal 
existence only when each individual group of workers func- 
tions in its proper time, place and intensity, so that the sum- 
total of the activities of the various specialized groups of 
workers is just sufficient for the “continuous adjustment of 
the internal to the external relations ” of the organism; in 5 
other words, all goes well only so long as the activities of the 
various parts maintain collectively a certain equilibrium. 
It is not, however, 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 fundamental properties of protoplasm. On the con- 
trary, each of the specialized individualities retains the 
power to assimilate food, to give off excrementitious sub- 
stances, 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 
foodstuffs; 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. Often, doubt- 
less, 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 
ail of you. The great group of cells of hypoblastic origin 
have been set apart for purposes of digestion and respira- 
tion. They build zymogens, acids and alkalies, and pour 
them out into the alimentary canal, where they mix with 
the food and prepare parts of it for absorption and utiliza- 
tion by the’other cells of the body; or, as in the lungs, they 
mediate the gas-interchange between the air in the pulmon- 
ary alveoli in contact with their distal surfaces and the cor- 
puscles and fluids of the blood situated proximal to them. 
The mesoblastic cells build intercellular substances and form 
the framework of the body upon which the soft parts are 
hung. Some of the intercellular substances become calci- 
fied, 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 fibers of various sorts—long, 
tough, non-extensile fibrils, as in tendon, aponeurosis, and 
ligament—elastic fibrils, as in areolar tissue, or the extremely 6 
delicate meshwork of finest fibrils, such as those met with in 
the fine-meshed reticulum supporting the parenchymatous 
elements cf the various organs. In the muscle-cells we see 
the embodiment of a special function of high dignity—con- 
tractility. In the protoplasm of these cells are laid down 
certain longitudinal structures—plasma-products—which 
look like fibrils, often with curious cross-markings—struc- 
tures that are undoubtedly associated in some way, though 
we are yet ignorant how, with the approximation of the two 
ends of the fiber when the latter is stimulated. The cells of 
ectoblastic origin become divided into various groups, some 
of them forming a superficial covering for the body and cer- 
tain 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 secret- 
ing glands that 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 system, the axis-cylinders of the peri- 
pheral 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 bloodvessels, with the 
tissue immediately surrounding them in the central nervous 
system, and the connective tissue, bloodvessels and lymph- 
vessels and neurilemma-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 em- 
bryo 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: (l) 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 un- 
ravelled, and it is to an epitome of our knowledge concern- 7 
ing 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 
subdivision of the peripheral parts of the protoplasmic mass, 
with the formation of cell-processes, does occur in several 
tissues of the body, nowhere else is this subdivision so pro- 
nounced; 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 long delicate pro- 
cesses were not known to constitute integral parts of nerve- 
cells, and it was not until they became recognized as such 
that the cell-doctrine could be satisfactorily applied to the 
nervous system. To distinguish the whole nerve-cell, inclu- 
sive of all its processes, from the torso recognized by the 
older observers as the nerve-cell, Waldeyer has introduced 
the term neurone, a designation that 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 incompar- 
able with 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 performed has to do with the functions of irritability 
and conductivity; in the glaud-cell the most manifest func- 
tional 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 
yet 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: (1) 
much-branched processes never extending to great distances 
from the main mass of protoplasm of the cell, processes that 8 
come off by a rather thick wedge of origin from the main 
protoplasmic mass, branch manifoldly soon after leaving the 
cell, and soon exhaust themselves by multiple division ; and 
(2) longer slender processes, each arising from the principal 
protoplasmic mass by a narrow wedge of origin, and ex- 
tending for a shorter or longer distance, maintaining 
or nearly maintaining its original caliber on the way and 
giving off in its course only a few delicate side fibrils or col- 
laterals. Ultimately, the fiber, 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,Jusually multiple, the term “dendrites” is ap- 
plied ; 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 consider the elabor- 
ate nomenclatures that have been introduced for conven- 
ience in the description of certain peculiarities of number, 
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 short, extending for perhaps 
only a few millimeters or even for a fraction of one milli- 
meter from the cell-body, others are much longer, extending 
even to many centimeters, and in extreme instances for a 
distance 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 II. They are, perhaps, better designated with von Len- 
hossek as inaxones and dendraxones. The classification is 
merely a matter of convenience, as transitional forms exist. 
It is interesting to note that the long axones become sur- 
rounded during development 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 cellu- 
lar sheath, the neurilemma, while the sympathetic axones 
are devoid of myelin-sheaths, but retain a partial cellular 
covering. The axis-cylinder of every nerve-fiber 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 9 
of a neurone, that is, the main protoplasmic mass containing 
the nucleus, and its dendrites, do not become surrounded by 
myelin-sheaths, but in certain instances, at any rate, are en- 
closed 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-ramifica- 
tions, constitute then a single nerve-cell, or neurone, that is, 
the particular form of individuality of the lower order met 
with in nervous tissues. It is estimated by Donaldson, of 
Chicago, that of the 26£ billions of cells in the human body, 
some 3,000 millions are nerve-cells, an estimate that, as I 
have suggested 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 the cell-body, afford 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 
workers belonging to one colony, when the colony contains 
thousands of millions of individuals, there is further special- 
ization, division of labor, and accordingly formation of 
multiple sub-groups), one meets with structural peculiarities 
that permit a skilled histologist to decide even from the ex- 
ternal form as to the particular group to which a given 
neuron belongs. Thus, in the diagram no difficulty is en- 
countered in distinguishing 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 
neurones and their processes, have added a wealth of detail 
concerning 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 impos- 10 
sible that all nerve-cells contain these peculiarly differentiated 
structures. In nearly all nerve-cells, after treatment with fix- 
ing reagents, the protoplasm of the dendrites and of the 
perikaryon can be seen to be made up of at least two sub- 
stances (aside from the so-called pigment met with in many 
nerve-cells): (1) a substance, consisting of minute granules, 
arranged in masses that 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-substance, in the fresh condi- 
tion, and by some methods of preparation almost homoge- 
neous 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 distribution in nerve-cells of different groups 
when studied by a particular 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 con- 
tinuous 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 disappear entirely from 
the nerve-cell for awhile, to return again some time after 
the cause of the disturbance has been removed. No direct 
relation, however, between the symptoms manifested by the 
animal as the 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 substance, and on the other the 
alterations in the substance may continue for a relatively 
long period after the unusual symptoms have disappeared. 11 
The structure of the second substance, that which we have 
spoken of as the ground-substance of the nerve-cell proto- 
plasm, and sometimes referred to as the “ unstainable sub- 
stance of Nissl,” is as obscure as is that of protoplasm in 
general. In the perlectly 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 different reagents that 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 quite different from that 
of the axone. In such vacuolized preparations, certain par- 
ticles, 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 
neurosomes, and they also differ much in number and 
arrangement in the various parts of the neurone, being most 
abundant apparently in the protoplasm of the terminal ram- 
ifications 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, 
definite fibrillary appearances have been demonstrated inside 
the neurones of both invertebrate and vertebrate animals, 
and it would appear that these represent special morpho- 
logic entities differentiated 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 net- 
works. In human nerve-cells similar fibrils can, by a some- 
what different method, be demonstrated 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 den- 
drite to another dendrite of the same neurone. It is even 12 
stated that a fibril running for some distance toward the peri- 
karyon 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 ex- 
planations 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. While the latter can 
be markedly disintegrated or even obliterated from the nerve- 
cell structure, and yet complete recovery follow, any pro- 
nounced general alteration in the ground-substance is inevi- 
tably followed by complete degeneration and death of the 
whole neurone. 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 greund-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 that re- 
mains 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-func- 
tions 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 physio- 
logical significance than the more homogeneous parts, the 
data at our disposal do not permit us to decide. Some in- 
vestigators have been tempted, naturally I think, to assume 
that the fibril-like structures in the ground-substance repre- 
sent the essential conducting substance, but, however plausi- 
ble, this is not yet satisfactorily proved, and even if such 
structures were shown to be particularly suited for conduc- 
tion, a similar function for other parts of the nerve-cell pro- 
toplasm 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 elements actually concerned 
in conduction in the nervous system, such establishment would 
refer to only one feature of neuronal function, and the 
capacities other than those of mere conduction would have 
to be considered subsequently. Time will not permit me 13 
to enter into a discussion of the morphological and physi- 
ological facts that have been accumulated with regard to the 
nucleus. It will be sufficient to say that they are probably 
just as important as those of the protoplasm, if not more 
important, 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 
investment of the perikaryon and dendrites. That the blood- 
capillaries give off a nutrient fluid that 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 addition to this lymph and the products of the 
neuroglia and ependyma, there are, besides the perineuronal 
myelin and the reticular investment, any formed cellular 
substances derived from the neurones, we do not know. The 
majority of investigators at present are opposed to the as- 
sumption. 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 gray matter of the central nervous system of vertebrates, 
and especially of man, similar extraneuronal fibrils exist in 
large numbers, and are accountable for the peculiar stamp 
that the gray 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 incom- 
prehensible ; nor would the demonstration of their presence 
be a matter of surprise. Thus far, however, this demonstra- 
tion is lacking, and we need scarcely worry ourselves con- 
cerning the possible function of such hypothetical substances 
before their existence has been proved. That the bringing 
of such proof could fundamentally alter our general concep- 
tion of the structure of the nervous tissues or of the body as 
a whole, I find difficult to realize, for as every histologist who 
has worked with the tails of rats, the ligamentum nuchse 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 con- 14 
sists of a mass of cells or individuals 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-fibers. 
An epitome of the changes that the nerve-cells undergo in 
the body of the embryo and after birth, before they have 
assumed the form met with in the adult, must also be omit- 
ted. That in early stages the nerve-cells are devoid of pro- 
cesses, are motile and multiply by karyokinesis, is now well 
known. Independent of one another and wandering from 
their birthplaces, the neurones gradually develop their won- 
derful processes, first the axones, later the dendrites, and 
finally they 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, 
however, in addition to the special knowledge that concerns 
the units or individuals, of much valuable information bear- 
ing upon the interrelations 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 themselves—in short, the architecture of the central 
and peripheral nervous organs. He sees how that, among 
an enormous number 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 intermediate have arisen. Neuronal 
mechanisms are combined to make neurone group mechan- 
isms ; neurone-group mechanisms are combined in turn to 
give rise to mechanisms of still higher orders, until, finally, the 
whole nervous system is included. In 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 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 familiar. For we should have to consider the gradual 
transition in the organismal series from unicellular animals 15 
in which the response to a stimulus has to be made by the 
same cell that 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 inter- 
calation between the two of one, two, one hundred or perhaps 
many thousands of neural activities. In multicellular organ- 
isms there is, with the increase of functional complexity, cor- 
responding increase in the number of special laborers and 
progressive dissociation of the function, with distribution of 
special tasks among these laborers. A brain appears, a 
general movement-center in connection 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 indepen- 
dent sensori-motor apparatus formed architecturally of a set 
of receptive neurones closely related to another set of dis- 
charging neurones, the individual segments in turn being 
manifoldly united by commissural and association neurones 
with one another and with higher groups of neurones, we 
meet with the acme of dissociation of neural function, com- 
bined with the highest known order of complex unitary 
neural capacity. 
We are learning to recognize the anatomical mechanisms 
that account for the fact that the application of sensory 
stimuli to the skin or tissues belonging to a primitive seg- 
ment, while primarily influencing, by way of the neural chan- 
nels, the musculature and 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 that 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 sensa- 
tions resulting from stimuli originating in the body itself or 
in the external world can be united into physiological units 
of higher orders, into feelings or emotions, into more clean- 
cut perceptions and even into abstract ideas and concep- 
tions; 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 immediate 
and necessary response to the stimulus applied, in the 
second instance less promptly perhaps and modified by 16 
intercurrent factors, and in the last event more slowly, with 
the manifestation of all the characteristics of a deliberate 
choice. I say we are learning to understand these anatomical 
mechanisms, for I do not mistake the beginning for the end. 
What we know is but the threshold of that more complete 
knowledge of the treasures of which contemporary neurol- 
ogists 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 anyone who possesses natural aptitude, and 
who, approaching it with reverence, interest, and industry, is 
willing to make his aptitude 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 that we already possess, and that, together with new 
methods that are sure to be discovered as we continue to 
work conscientiously with the old ones, are destined to 
expand our views, to open up new neurological vistas, and to 
illuminate those that are 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 that we 
have learned to distinguish in our study of the nervous sys- 
tem. We have seen in this system how, through the sub- 
division of the labor among a large number of individuals, 
there has arisen a marked dissociation of functions, and how 
through fusion 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 analytical methods precede 
the synthetical. There must be differentiation before in- 
tegration. Now while a whole series of analytical methods 
have been in use for a long time, and have of late been won- 
derfully refined and rendered extremely delicate, it is striking 
that there are but few synthetical methods, and those that 17 
have been employed have been relatively crude, the latter 
methods having been used only by a limited number of in- 
vestigators. 
I shall not be so inconsiderate as to detain you by describ- 
ing even briefly the technic of the various methods that 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 
describing the gross form-relations of the central and periph- 
eral nervous systems as revealed on simple exposure by 
removal of the bony and membranous coverings, or by cut- 
ting into the organs. The shape of the principal masses and 
cavities, the existence of white and gray substance, the dis- 
tinction of the cerebro-spinal and sympathetic nervous sys- 
tems, 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, Vesa- 
lius, Monro, Sir Charles Bell, Lockhart Clarke, Reil, Rolando, 
Burdach, and Stilling, we cannot but marvel at the accuracy 
of the observation and the faithfulness of portrayal that they 
manifested. 
The introduction of hardening fluids facilitated the study 
of gross material and, by preserving the tissue from decom- 
position, permitted the prolongation of the examination of a 
single specimen indefinitely. Thick slices of the hardened 
tissue yielded in many respects more satisfactory informa- 
tion than that derivable from slices of the fresh soft organs. 
Alcohol hardening permitted of successful manipulation with 
fingers and forceps, and the newer conceptions gained with 
the aid of the Abfaserungsmethode were at the time justly 
lauded. In this connection the work of Burdach, Reil, Fo- 
ville, Stilling, and Meynert deserves especial mention. 
Late in the last century and early in the present the 
method of isolation of parts was pushed farther, 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 that soften or dissolve out certain 18 
of the substances that ordinarily prevent dissociation were 
introduced, and the knowledge of the nervous organs be- 
came, within a relatively short time, enriched to an unpre- 
cedented degree. The details made out concerning isolated 
nerve-cells and their processes, and separated single nerve- 
fibers and their coverings by these relatively simple manipu- 
lations were truly remarkable. The histologists of the time 
attained to a degree of skill in this field that would give the 
blush to the modern histologist did he attempt to imitate 
them. In this connection Wagner, Deiters, Max Schultze, 
and von Kolliker are the names one thinks of. The student 
of neurology to-day will do well if he do not despise or neg- 
lect a form of examination that affords pictures of the parts 
obtainable by no other means. 
So 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 rela- 
tions inside it, exclaimed “ eureka ” and caught a glimpse 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 pos- 
sible 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. Recently Flatau has shown 
that it is possible also to divide the whole spinal cord into 
longitudinal serial sections. By means of absorption, em- 
bedding, serial sections of one or a few nerve-cells can be ob- 
tained as thin as one micron, or even less. 
Next in importance to mechanical subdivision of the 
nervous system into its morphological elements and into ex- 
tremely thin slices was the invention of the method of differ- 
entiation by means of the application of coloring-matters of 
various sorts. The carmine method of Gerlach, in connec- 
tion with bichromate hardening of the tissues, not only dif- 
ferentiated the nuclei of the nerve-cells from the protoplasm 
in which they were contained, but by showing a special 
affinity for the axis cylinders of the nerve-fibers rendered them, 
in sections, easily distinguishable from investing sheaths 
and from neuroglia-elements. The impregnation with gold 
chlorid also revealed minute nerve-fibrils and processes of 19 
nerve-cells that must have appeared most remarkable to 
those studying tissues prepared in this way for the first time. 
Of even greater significance was the introduction of Wei- 
gert’s stain for myelin-sheaths, which made it possible to fol- 
low bands of medullated fibers or even single medullated fibers 
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 
of animals in health, but because in diseased conditions it 
yields information of the highest import, as in areas in which 
the medullated nerve-fibers 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. While 
the extremely delicate method of Marchi will indicate the 
existence of degenerated nerve-fibers at a much earlier period 
than that corresponding to the total absorption of these 
fibers, and is accordingly a boon to the experimental investi- 
gator, it can never entirely replace Weigert’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 medullated nerve-fibers that exist in the adult nervous 
system do not all receive their myelin sheaths at the same 
time, but get them rather at successive intervals correspond- 
ing more or less accurately in serial appearance to the suc- 
cessive manifestations 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 architectural characters of the spinal 
cord and brain, will always be associated with Flechsig’s 
name. 
The latest results of this application of this method have 
resulted in Flechsig’s hands in the better localization of the 
primary sensori-motor areas in the cerebral cortex, in the 
demonstration of the fact that the projection-fibers connect- 
ing these various areas with lower parts of the central nervous 
system are medullated at different periods, and in the dis- 
covery of the existence and topographical distribution of the 20 
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 
diameters. The expansion of the powers of the human retina 
thus made possible, together with the advances in staining, 
clearing, and mounting, has revolutionized the science of his- 
tological and microscopic anatomy, and the old-time 6 weeks’ 
course given in these subjects has had to be replaced by one 
of as many months. Cytology in general has made enor- 
mous strides and with it cytology in particular, although 
curiously enough the nervous system, owing to the peculiar 
character of these cellular elements, did not reap the benefits 
quite so soon as did the other organs of the body. When 
once results began to be attained in the nervous system by 
these methods or by particular 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 morpholo- 
gical 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 that better than any other procedure outlines 
the external form of the nerve-cell and its processes, espe- 
cially 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 it has given us an insight into the va- 
rious interrelations that exist among the cellular units of 
which the system is made up. Recently, by slight modifica- 
tions of the method, Golgi has shown that it can be utilized 
to demonstrate not only the reticular investment of the para- 
karyon and dendrite, but also certain curious network-like 
appearances inside the nerve-cell protoplasm. The ob- 
jection, therefore, that Golgi’s method affords no information 21 
with regard to the interior of the neurones can no longer be 
urged with justice. 
The method of vital staining with methylene blue or 
thionin, invented by Ehrlich, not only confirmed in large 
part the findings 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 
fibers can be stained ; whereas with Golgi’s method the im- 
pregnation of an axone usually ceases as soon as the myelin- 
sheath is reached. By means of the method of fixation that 
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 that are suitable 
for the investigation of the interior of the nerve-cell, that 
introduced by Nissl has been extensively followed up. It 
consists of alcohol-fixation, sectioning without embedding, 
staining with the methylene-blue-and-soap mixture, differ- 
entiating with aniline-oil and alcohol, and mounting in ben- 
zine-colophonium. It is especially valuable for the exam- 
ination of the neurones under normal and pathological 
conditions with respect to the amount of the stainable sub- 
stance of Nissl present in them and its distribution in the 
cytoplasm. Other similar methods such as thionin staining, 
toluidin-blue staining or double staining with methylene- 
blue and erythrosin, offer special advantages for certain 
purposes. 
To demonstrate the neurosomes, fixation in a neutral 
solution and staining with iron-hematoxylin (Held) serves 
admirably. Fibrillary appearances are discoverable in tissues 
fixed in chrom-osmo-acetic acid and stained in saffranin 
(Flemming). They are exquisitely stainable in invertebrate 
tissues by a sublimate-gold method and by a hematein stain 
(Apathy); while in vertebrate tissues they are most easily 
demonstrable in cells that have been treated first with 
ammonia, afterwards with hydrochloric acid, then with 
molybdic acid and finally with toluidin-blue (Bethe). The 
action of alkalies, acids and digestive agents of various kinds 
should also be mentioned. 
Concerning the synthetic methods there is but little to say, 
inasmuch as the sole procedure that has been employed 
by the majority of the neurological investigators is the 22 
mental fusion of the pictures obtained by isolation and sec- 
tioning into more or less vague ideas of solidity. Actual 
reconstruction in tangible form of the solid bodies in the 
nerve-tissues from a faultless 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 internal 
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 expe- 
rience teaches me that a relatively large [number of students 
are almost absolutely devoid of this power of integration, or, 
as it is sometimes expressed, “ of thinking in three dimen- 
sions,” 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 Leipsic, 
many years ago introduced his method of graphic recon- 
struction from serial sections. His procedure is so gener- 
ally known that I need not take the time to describe it in 
full. He used, it will be recalled, paper ruled at distances 
corresponding to the thickness of the sections multiplied by 
the magnification employed. The outline drawing of the 
whole object over these lines thus permitted the introduc- 
tion on the parallel lines of the paper the limits of any 
desired object in the various sections. In this way extremely 
valuable flat projections of the various internal organs and 
tissues could be obtained, 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 ac- 
tivities of His and Ziegler, the exquisite models illustrating 
various 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- 23 
matical knowledge and artistic talent necessary for the suc- 
cessful application of the method. Somewhat later recon- 
struction with the help of wax-plates permitting the making 
of wax-models directly from the specimens was introduced 
by Born. In the 22 years that 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, that Dr. Mall has used so success- 
fully in the study of the anatomy of his series of human 
embryos. It is also this method that Miss Sabin, with the 
aid and counsel of Dr. Mall, has employed in the construc- 
tion of the model of the medulla oblongata, pons and mid- 
brain which I here show you. The prerequisites to the work 
are (1) the possession of faultless serial sections of the object 
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) a suit- 
able mechanism for the production on paper or directly on 
the wax-plates of the magnified picture of the section (cam- 
era lucida or Zeiss projection-apparatus); (4) wax-plates of 
proper dimensions and consistence; (5) the guidance of an 
experienced workman; (6) patience, industry, enthusiasm 
and a certain amount of spatial sense and mechanical 
skill. 
We are fortunate enough to possess in the anatomical 
laboratory at Baltimore several sets of serial sections cut in 
various directions through the brain-stem and cerebral hemis- 
pheres of human fetuses, and babies of different ages, 
illustrating accordingly different stages of development. 
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 to the Anatomical Society reconstruc- 
tions of single nerve-cells. Thus far, however, no one has, 
to my knowledge, published the results of reconstruction of 
the medullated tracts in the 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 
certain number of students may, I believe, conduct such in- 
vestigation satisfactorily and without interference with their 24 
regular medical studies. 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 March, 
1897. 
The portion of the brain represented by the model is that 
of a human fetus 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 Leipsic. Circumstances preventing Dr. Hewet- 
son from continuing his work with the specimens, he was 
kind enough to place them at the disposal of instructors and 
students at Baltimore. After some preliminary study of a 
series of transverse sections through the medulla Miss Sabin 
made a more careful study of a series of horizontal sections 
until she was sufficiently well oriented with regard to the 
principal medullated tracts and gray masses to proceed with 
the actual work on the model. Every other section of the 
series by means of the Zeiss apparatus and electric illumina- 
tion was projected, magnified 14£ diameters in a dark room 
upon a sheet of whitepaper, and the outlines of the tracts 
and nuclei were drawn in accurately with leadpencil. 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 corre- 
spond, each wax-plate of course representing in thickness 29 
times the thickness of the individual sections. To facilitate 
subsequent 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 different tracts and nuclei upon one another so as to re- 
produce the exact form magnified 14J times in the three 
dimensions. Here the investigator meets with his greatest 
difficulty, and it is just at this juncture that natural mechani- 
cal skill, as well as experience, counts 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, that can 25 
be used as a guide. There need be no trouble about the ex- 
ternal form if an accurate drawing 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 independently by 
Selenka and Mall, which obviates the difficulty. Several 
brain-stems of fetuses 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 approxi- 
mated 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 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 sys- 
tem serves admirably in the one dimension; for the other 
two dimensions the curves of the external form were fol- 
lowed, helped out, of course, by the known distances of the 
individual structures 'from one another in the different sec- 
tions. The stratum interolivare lemnisci and lemniscus 
medialis were first modeled, and the other structures gradu- 
ally built up about these. 
The various ingenious contrivances that 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 publica- 
tion. After the various parts have been reconstructed and 
the edges smoothed with a hot iron, the medullated bands 
of fibers were painted white, the motor nuclei blue, the nu- 
clei terminates of the sensory nerves red, and other gray 
masses yellow. 
The gross relations represented by the model are clear at 
a glance—the upper extremity of the spinal cord, the medulla 
oblongata, the pons and the midbrain. The remarkable 
curves made by the central cavity (1) 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 26 
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 cochlearis ventralis forms a con- 
tinuous mass with the nucleus nervi cochlearis dorsalis lying 
lateral from the corpus restiforme. 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 the removal of the nervus acusticus and the corpus 
restiforme, the course of the ascending and descending limbs 
of bifurcation of the fibers of the nervus vestibuli can be 
studied, as well as the relations of these to the various termi- 
nal vestibular nuclei—the medial, the superior, the lateral 
nucleus, and that of the descending root. 
The modeling of the nervus trigeminis, 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 substan- 
tia gelatinosa, the descending mesencephalic root, the minor 
motor nuclei and the principal motor nucleus, and the rela- 
tions of the motor nuclei to the portio minor of the peripheral 
nerve—all are evident. The fibers of the nervus glosso- 
pharyngeus and of the nervus vagus now come into view, 
and it is seen how large a mass of the glossopharyngeal fibers 
go to form the tractus solitarius. The relations of the motor 
fibers to the nucleus ambiguus, and of the sensory fibers to 
the nucleus alae cinereae are demonstrated. 
These two large masses of gray matter painted yellow, fit- 
ting so accurately into these irregular cavities in the white 
matter, which represent the medullary continuation of the 
dorsal funiculi of the spinal cord, are the nucleus funiculi 
gracilis and the nucleus funiculi cuneati respectively. The 
difference in the distribution of internal arcuate fibers de- 
rived from the two nuclei is obvious. 
Removing the last-mentioned structures the funiculus 
lateralis, and the bundle of fibers 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 ambiguous nucleus 27 
and the nucleus of the facial nerve are evidently members of 
the lateral group, while this long, curved nucleus of the 
hypoglossal nerve and the nearly spherical nucleus of the 
abducens are more medially placed. The old bugbear of 
the raw student in neurology—the course of the facial nerve 
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 trapezoid body to the outside can be readily 
followed. Higher up the motor nuclei of the trigeminal 
nerve, the trochlear nerve, and the oculomotor are seen. 
The inclined plane formed by these upper eye-muscle 
nuclei is rarely understood from the study of transverse 
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 rela- 
tions of the lateral lemniscus to the trapezoid body, to the 
superior olivary complex, and to this long-drawn-out nucleus 
lemnisci 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 quad- 
rigemina are prominent features of the model. No less 
instructive is the illustration of the origin, course and distri- 
bution of the fibers of the medial lemniscus or fillet. Start- 
ing below as a vertical mass of fibers—the stratum interolivare 
lemnisci—formed in large part of internal arcuate fibers, 
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 medial longitudinal fasciculus or the so-called pos- 
terior longitudinal bundle. Higher up the two bundles are 
separated by masses of gray matter and, from the trapezoid 
body 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 conjunctivum supports 
most conclusively the view that the ventral part of the 
decussation of the brachia of the two sides represents a 
vestibular commissure. The pocket between the ventral and 
dorsal portions of the decussation is here visible, and it is 
satisfactory to note that the portion of the brachium con- 
junctivum on each side corresponding to the ventral decus- 28 
sation is related directly with the ventral extremity of the 
superior nucleus of the vestibular nerve or Bechterew’s 
nucleus. The results that concern the medial longitudinal 
fasciculus, the formatio reticularis alba et grisea, the decus- 
sationes tegmentorum, the nucleus ruber and the bundles of 
white fibers near it, the fasciculus retrofiexus of Meynert 
and the substantia nigra are of interest, but to fully appreci- 
ate 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 to be interested in the appearance of 
the inferior olivary nucleus 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 gray 
matter is repeatedly depressed and elevated on the surface, 
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 remark- 
able 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 shal- 
lower sulci into gyri. That these sulci and gyri are not acci- 
dental but tolerably constant features, is clear from the 
reconstructed 'olive of the opposite side, which is almost the 
exact counterpart of its fellow. As the gyri and sulci are as 
definite and characteristic as those of the cerebral cortex, 
Miss Sabin will, I have no doubt, name them for convenience 
of description. If the medical student of the future had to 
learn by rote the new lists of names that such studies are 
constantly thrusting upon us he would indeed need to be 
commiserated, but fortunately instructors and examiners 
nowadays are becoming more sensible than their predeces- 
sors 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 con- 
nected with organs the most complex in architectural 
arrangement in existence on this planet it is capable, I 
believe, of wide application. That it will sooner or later have 29 
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 arithmetic ” 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 
familiar with technical procedures of the past, are conscious 
of its crudeness and aware of its limitations, and they are pre- 
pared for, and will welcome, the time when we shall be pre- 
sented 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 pro- 
duction 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 develop- 
ment 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-investigators and clinicians and from such co-oper- 
ation among these as may, while in nowise 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 anom- 
aly 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 every one, prepared to think 
accurately and who has given the subject thought, readily 
admits that it is precisely by virtue of his neural pre-emi- 
nence, 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-mor- 30 
phology and brain-capacity that we can without fear of suc- 
cessful contradiction designate the statement, “ All men are 
born free and equal,” as one of the greatest fallacies that has 
ever moved large bodies of men into action. When we re- 
member this and recall the large proportion of ailments 
that have a neural or psychic element in them it is surprising 
to use as mild a word as I dare that a more or less extended 
knowledge 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 distinguished professors of medicine in our best medical 
colleges wrere brave enough to admit—indeed seemed de- 
lighted to jocularly confess—that they “never could under- 
stand the fillet; ” but, while at that time knowledge was so 
limited, and the means of acquiring the little possessed 
were so inadequate, that such a confession was one of which 
he who made it need not necessarily be ashamed, that period 
is now happily passed, 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 
pathology of the nervous system 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 that 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 converg- 
ing lines of research psychology has come to be recognized 
in its normal relations as a department of physiology, psy- 
chiatry as a department of pathology, a redistribution of 
labor should take place and the functions of physician of the 31 
body and physician of the soul come again to be united in a 
single individual ? 
Two great difficulties at present obstruct progress: (1) The 
lack of trained individuals to serve as teachers and to con- 
duct research, and (2) notwithstanding the remarkable mul- 
tiplication of so-called laboratories, the lack of appreciation 
of the importance of suitable laboratory-organization. Any- 
one living in one of the large centers 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 posi- 
tions, cannot fail, when he sees the difficulty of filling such 
positions, to lament the gross errors of the system of educa- 
tion 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 training. 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 prospect 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 department and for the institution of adequate 
instruction; but too often they are disappointed in the 
results. A shrewder foresight 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 meager the pit- 
tance 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. 
Given, however, a good laboratory and a good man, the 
conditions for successful instruction and investigation are 
by no means fully satisfied. An institution can nowadays 
no longer hope to succeed by taking a scientist into a brick 
box and saying to him “ Robinson Crusoe, here is your island.” The director of the laboratory must be accompa- 
nied by trained assistants, and it is desirable that these assist- 
ants, 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 have before now 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 a much 
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 investigation of the unknown but knowable 
have to be arranged for. With successful organization, in- 
struction 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 gen- 
eral 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 something, be it never 
so little, to the world’s store of facts. The time of a medical 
student is usually so limited that it is only the exceptional 
man who can undertake a long and complicated research, 
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, that 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 path- 
ology 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 internal medicine, helping them 
and in turn being helped by them; for in the study of the 
functions of the nervous system especially, no stable con- 33 
elusions have been or ever can be arrived at, with regard to 
the higher groups of neurones at least, without the rigid con- 
trol of clinical and pathological observations on man. Mor- 
phologists working alone tend to become one sided ; isolated 
physiologists cannot fail to focus falsely and the pathologist 
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 that 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 con- 
versant with the work and results of others. Objectivity 
must be a watchword; subjective interpretation always mis- 
trusted. We shall then have more facts and fewer hypo- 
theses. 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 building of knowledge 
will be slow, but what is lost in rapidity will be more than 
compensated for in solidity. 
I have now done. From what I have said it will be clear 
. to you that our knowledge of neurology, so slow in acquisi- 
tion, is dependent upon the application of a large number of 
different methods of investigation, differentiative and inte- 
grative. For the proper understanding of form-relations the 
analyses require to be synthetized, in particular and in 
general. Owing to the special difficulties in solving prob- 
lems in the nervous systenl and the increasing complexity 
of knowledge of structure and function and methods of in- 
vestigation, 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 asso- 
ciation with medical schools, hospitals and asylums and in 
connection with skilled clinical observers. The further pur- 
suit of anatomical, physiological, chemical, pathological and 
clinical studies will permit of the recognition of ever-increas- 
ing interrelations among the results, with corresponding 
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