The Physiology of Secretion. 
ANNUAL ADDRESS, 
Medical and Chirurgical Faculty 
DELIVERED BEFORE THE 
OF MARYLAND, 
e APRIL 9TH, 1879. » 
Prof. H. Newell Martin, A. M., &c. 
OF THE 
JOHNS HOPKINS UNIVERSITY. 
Reprint from Transactions of 1871). Annual Address. 
THE PHYSIOLOGY OF SECRETION. 
PROF. H. NEWELL MARTIN, M. A., D. SC., M. 8., OF JOHNS HOPKINS 
UNIVERSITY, BALTIMORE, MD. 
Mr. Vice-President, and Members of the Medical and Chirurgical 
Faculty of Maryland 
When your Executive Committee did me the honor of asking 
me to address you to-day my first impulse was to decline the 
responsibility. Nor indeed from any want of good will to your 
organization, but because I have always some sort of shame in 
meeting a number of medical men, collected together as such ; 
being myself one who has put his hand to the plough and not 
only looked back but gone back from the laborious course of the 
physician or surgeon, into what seemed the more pleasant bye 
paths which tempted me on the road. As a consequence of this 
I am but little acquainted with the problems which are of 
prominent interest to you at this moment; ignorant to a 
great extent of what they are, and still more of any details con 
cerning them, and so am but little fitted to take the place of the 
distinguished member of your profession, whose untimely death 
has prevented his standing to-day in the position towards you, 
which I now occupy. 
Still I have never lost entirely my early love, nor ceased to 
regard the practice of medicine as among the noblest of all the pur- 
suits in which men are engaged ; and am always fain to look upon 
myself as a sort of camp follower in your army, who though not 2 
THE PHYSIOLOGY OF SECRETION. 
destined himself to bear the brunt of the fight with disease and 
all its attendant human miseries, yet is glad to believe that he 
may be so fortunate as to succour at times those who fight in the 
outposts. 
Looking around the field of combat it seemed possible that a 
discussion of some one of the newer problems of physiology 
might be of interest to you ; since the toilsome life of the medical 
man eaves him but little time to learn more of the advances of 
that science than such brief abstracts as are found in the medical 
periodicals. Of all the current subjects of physiological inquiry 
it seemed that there were at present none of greater importance 
than those relating to the physiology of secretion ; a subject 
which I might hope would have a special interest to you, as being 
calculated to throw light not only on cell life in general, but as 
serving well to bring into prominence the relative influence of 
the nervous and vascular systems upon the mode of life of the 
various tissues of the body ; and so having some importance with 
reference to pathological problems. 
With your permission I propose to occupy a few minutes with 
a sketch of some common phenomena of cell life, before pro- 
ceeding to secreting cells in particular. Not, that I suppose the 
fundamental points to which I am about to refer, are unknown to 
you ; but as I wish to look at the mode of life of a gland cell in 
relation to the modes of life of animal cells in general, it will be 
advantageous to have the main facts with respect to the latter 
fresh in mind. 
Among the simplest elements entering into the composition of 
the human body are such cells as the lymph or pale blood cor- 
puscles ; minute granular protoplasmic nucleated masses, with no 
definite cell wall. Each of these simple bodies exhibits of itself, 
certain properties which are distinctive of all living things as 
compared wi-th inanimate objects. 
In the place it can take up new materials from the outside 
and build them up into its own peculiar living substance, the new 
material not being deposited (at least necessarily or always) on 
the surface of the cell, but laid down in its mass between the H . NEWELL MARTIN. 
3 
already existing molecules. Moreover the chemical bodies 
received from outside are either uncombined elements, as oxygen, 
or elements combined in a different manner from that in which 
they exist in the living protoplasm. They only become part and 
parcel of the cell, “ flesh of its flesh,” after it has wrought chemi- 
cal changes in them. 
By this reception from the exterior the cell grows, but the 
increase of size which may be brought about in that manner is 
not indefinite, being limited in two ways. Alongside of the 
reception and deposit of new material there occurs always in the 
living cell a breaking down and removal of the old ; and when 
this disintegration equals the accumulation of new material, as it 
does in all the cells of the body when they have attained a certain 
size, groxvth of course ceases. The disintegration is due to the 
chemical metamorphoses by which energy is liberated for the 
performance of such work in the cell as is necessary for its vital 
maintenance ; and as the necessary work increases dispropor- 
tionately fast, growing with increase of bulk as the cube of the 
diameter, while the receptive powers, primarily dependent on the 
area of the surface of the cell, increase only as the square, at 
last a size is attained at which chemical degradation and elimina- 
tion equal the reception and chemical construction going on in 
the cell, and growth ceases. 
The second limitation to indefinite growth is connected with 
the power of the cell in one way or another to give rise to new 
cells like itself. Under certain circumstance1, as yet imperfectly 
known, the pale blood corpuscle becomes narrowed at one zone ; 
the constriction deepens until the parts on each side of it are 
merely connected by a slender band which finally gives way and 
two independent cells are formed. Commonly the nucleus 
divides before the rest of the cell and so the result of the process 
is a pair of cells, each like the original one but for their smaller 
size. These grow as the mother cell did and may in turn multi- 
ply in the same manner. 
These two faculties, that of taking in and working up into their 
own substance materials derived from outside, or assimilation, 4 
THE PHYSIOLOGY OF SECRETION. 
and that of in some way giving rise to new beings like themselves, 
or reproduction, are possessed by all living beings whether animals 
or plants. There is however an important difference between 
them ; assimilation is necessary for the maintenance of each 
individual cell, plant, or animal, in order to replace its never 
ceasing wastes, but the power of reproduction is necessary only 
for the maintenance of the kind or race, and need be and often 
is, possessed only by some of the individuals composing it. 
Working bees for example cannot reproduce their kind, that duty 
being left to the queen-bee and drones of each hive. 
The breaking down of already existing chemical compounds 
into simpler ones, is as invariable in living things as that building 
up of new complex molecules referred to above. Reception, 
chemical construction, chemical degradation and removal of the 
products of the latter, form a series of correlated phenomena of 
cell life which-we sum up under the name of nutrition. From 
this series of nutritional phenomena, however we may convenient- 
ly separate those implying chemical changes under the name of 
metabolism, and it is this part of cell life that has the more imme- 
diate interest for us in connection with the present subject. 
In addition to the phenomena of nutrition, the pale blood cor- 
puscles present certain other phenomena which though not so 
absolutely diagnostic are yet very characteristic of living things. 
Examined carefully with the microscope on a warm stage they 
exhibit the well known amoeboid movements. They undergo 
changes of fojm independent of any pressure which might 
distort or otherwise mechanically alter their shape. The faculty 
of the cell upon which these form changes depend is known as 
contractility, a word which in a physiological connection is of 
course something quite different from the contractility of a 
stretched india-rubber band, which tends merely to reassume a 
form from which it has previously been forcibly removed. 
Another important property of such cells is their irritability. 
An amoeba coming into contact with a sclid particle calculated 
to serve it as food, will throw out around it processes of its sub- 
stance and gradually convey the foreign mass into its own body, H . NEWELL MARTIN. 
5 
the amount of energy expended by the animal in so doing being 
altogether disproportionate to the.force of the external contact. 
The foreign particle does not actively push-in the surface of the 
amoeba and burrow into it, but the mere touch arouses in the 
amoeba an activity quite incommensurable with the exciting force, 
and comparable to that liberated by a spark falling upon gun- 
powder, or by a slight tap upon a piece of gun cotton. It is this 
disproportion between the excitant, (or stimulus) and the result, 
which is the essential characteristic of physiological irritability. 
In this regard observation shows that pale blood corpuscles may 
behave exactly like amoebae, taking up into their own substance 
in a precisely similar way, minute solid particles injected into a 
vein. In this way, as in others, for example their contraction into 
rigid spheres under the stimuli of electrical shocks, they show 
that they too are endowed with irritability. 
Further when an amoeba or one of these pale corpuscles, 
coming into contact with a foreign object, proceeds to draw it into 
its own substance the activity aroused is not merely displayed by 
the parts actually touched. Distant parts of the cell also 
cooperate, the influence of the stimulus is not local alone, but as 
a result of it a change is brought about in remote parts of the 
cell. In other words the cell substance is physiologically con- 
ductive. 
Finally the movements exerted are not random, but are 
adapted to attain an end. They are so combined as to bring the 
external mass into the interior of the cell. This faculty of all the 
parts to work together in definite strength and sequence to attain 
a particular result, is what we know as co-ordination. 
These four powers or faculties, irritability, conductivity, con- 
tractility and coordination, which, with nutrition and reproduction, 
we may call the fundamental physiological properties, are also 
possessed in a high degree by our bodies as a whole. To take a 
trite but excellent example, having which to hand it is not worth 
while to seek further, we all know that if the interior of the nose 
be tickled by a feather a sneeze usually results. The feather- 
touch or “ stimulus,” calls forth movements which are mechani- 6 
THE PHYSIOLOGY OF SECRETION. 
cally altogether disproportionate to the energy spent in the contact. 
The body is then highly irritable. The resulting movements, 
themselves a manifestation of contractility, are not exhibited at 
the point touched but at more or less distant parts in abdomen, 
chest, and face, so our bodies are physiologically conductive ; and 
finally the movements resulting, are not random convulsions, 
but are so combined as to produce a current of air through the 
nose, calculated to remove the irritating object. In this we have 
a manifestation of co-ordination. 
Speaking broadly these four properties are more obvious in 
animals than in plants, but they are by no means confined to the 
former. In the sensitive plants, touching one leaflet will excite 
regular movements of the whole leaf, and similar phenomena are 
exhibited by the Venus's fly-trap and other plants. 
On the other hand no one of these properties is characteristic 
of living things in the way that their mode of growth (by 
intussusception) and power of reproduction are. Irritability is 
but a name for unstable equilibrium and is as manifest in 
nitro-glycerine as in an amoeba or a muscle; in a telephone the 
influence of the voice is conducted as a molecular change along 
a wire and produces results at a distance, and innumerable 
inanimate machines afford examples of the coordination of move- 
ments to attain a definite end. 
There is however another phenomenon presented by many 
living cells in which they appear at first to differ fundamentally 
from not-living objects. This is their apparent spontaneity or 
automatic power. Lymph corpuscles frequently change their 
form independently of any observed external cause or stimulus ; 
while a dead mass at rest, and unacted upon from outside remains 
at rest. Closer examination however, leads to the conviction that 
th is difference is only superficial ; it depends in fact, not upon a pe- 
culiar spontaneity of the living cell, but upon its nutritive powers. 
Any system of material particles in equilibrium and at rest will for- 
ever remain so if unacted upon by any external force. Under certain 
conditions such a system can carry out a series of changes when 
once a start has been given ; but it cannot initiate them itself. H. NEWELL MARTIN. 
7 
Every living- cell being in the long run a complex system of 
molecules, composed in their turn of chemical elements, if we 
suppose the whole set of atoms in equilibrium at any moment 
no chmge can be started in the cell from inside ; in other words 
it will have no real spontaneity. When, however, we take into 
account the irritability of amoeboid cells, or in other words their 
unstable molecular structure, it is clear that a very slight external 
agency, such as may completely elude our present methods of 
observation, may set going in them a great series of changes, just 
as a slight shake will upset a card house. 
Once the equilibrium of the molecules has been disturbed, 
movements of some or of all will continue until the atoms con- 
stituting the cell have again settled down into a stable state. But 
in living cells the re-attainment of this state may be, and frequently 
is. indefinitely postponed by the reception of new substances, 
food in one form or another, from outside ; and by the metabolic 
powers of the cells. The nearest approach to a complete equili- 
brium in living matter is probably exhibited by the resting state 
into which some of the lower animals, as the wheel animalcules, 
pass, when dried slowly at a low temperature. The removal of 
water checks their metabolism, that is to say those nutritive pro- 
cesses by which the attainment of molecular equilibrium would 
otherwise have been prevented. 
If therefore we employ the terms “ spontaneity ” or “ automat- 
icity ” to signify a power in a resting system of particles of 
initiating changes in itself, then they are applicable to neither 
living or not living things. But if we simply use the word 
“ automatic ” to designate changes the starting cause of which we 
do not recognize, and vvhich in many cases acted long antecedent- 
ly to the changes which we do see, then the term is unobjection- 
able and convenient; as it serves to express briefly a phenomenon 
presented by many living cells ; but it then designates no longer 
a property peculiar to them. A steam engine with its furnace 
lighted and water in its boiler may be set in motion by opening 
a valve, and the movements then started will continue automat- 
ically in the above sense until the coals or water are used up. 8 
THE PHYSIOLOGY OF SECRETION, 
The essential difference between it and the living cell is to be 
sought in the nutritive powers of the latter which enable it to 
replace continually what answers to the coals and water of the 
engine. 
Now as you all know at a very early stage of its development, 
the body of each of the higher animals consists solely of an 
aggregation of such nucleated cells as those which we have been 
considering. I mean when it exists as the mulberry mass or 
morula. At that time the constituent units of the body are all 
alike; no different tissues, and still les> any organs, being recog- 
nizable. 
For some time the cells of the morula simply multiply by 
division, but soon new processes appear which ultimately give 
rise to the adult body with its many tissues and organs. Groups 
of cells ceasing to grow and multiply as their parents did, begin 
to grow in ways peculiar to themselves, and so they come to 
differ from the cells of the original morula and from the cells of 
other groups. By peculiar growth a varied wh Die is developed 
from a homogeneous one ; as we say the tissues are differentiated. 
With the differences in structure appear differences in property, 
and then it becomes evident that the cell aggregate is not to give 
rise to a number of nearly independent living things but to a 
single animal, in which each cell, while primarily looking after 
its own interests, shall have duties to perform for the good of the 
whole. A single compound individual is to be formed by the 
union and cooperation of a number of simple ones. 
As differentiation goes on, we find the fundamental physiolog- 
ical properties, originally possessed by all the cells of the morula, 
distributed between the modified cells which form the tissues, 
much in the same way as different employments are distributed 
in a civilized state. For the d fference between the fully de- 
veloped human body and the colh ctiou of amoeboid cells which 
represented it in the morula stage. is essentially I lie same a.-, that 
between a number ot wandering savages and a civilized nat'on, 
As a nation is mor>: a vanced m c \ hzation has its necessary 
work carried on belt r and more • '>n enicaily—the go aicr the H. NEWELL MARTIN. 
9 
division of employments in it, so is an animal higher or lower 
in the scale according to the degree in which it exhibits a distri- 
bution of physiological duties between its tissues. 
Ultimately in the human body we find specially irritable, 
specially contractile, specially receptive, specially metabolic and 
specially eliminative tissues, united by supporting and connective 
tissues. 
It is clear however, that such a collection of living tissues 
would not make a man any more than a chance collection of a 
million persons would make a nation. In order that all shall 
cooperate and produce as the resultant of their individual lives 
one living animal, some bond of union is necessary; some 
arrangement of tissues by which the activities of all shall be 
subordinated to the welfare of the whole. 
Primarily this bond is furnished by the nervous system which, 
highly conductive, places the irritable tissues of the sense organs 
in connection with the coordinating nerve centres, and through 
these, with the contractile, metabolic and certain other tissues; 
so that these may make changes responsive to the changes of 
external conditions which have stimulated the sense organs. To 
properly understand the activity of any tissue we must then know 
not only its special physiological property, but also its dependence, 
if any, upon the nervous system. 
Secondly we find another great integrating bond in the blood 
and lymph. An animal composed of one or few cells and so with 
a large surface in proportion to its bulk may re quire no circula- 
ting liquid. P'ach cell can carry on its own changes directly with 
the environment, getting food from it in one form or another, 
and passing out its waste. But in a more complex organism 
consisting of millions of cells, and moreover, like man, living in 
the air, which necessitates a dense superficial covering to prevent 
excessive evaporation, the great majority of the tissues cannot be 
supplied directly from the surrounding medium. Between it and 
them must intervene something which shall convey excess of 
new materials from receptive cells in the lung or alimentary canal 
to others lying far from a free surface, and shall carry in turn the THE PHYSIOLOGY OF SECRETION 
waste products of these to excretory cells, also in direct com- 
munication with the exterior. 
This medium is afforded by the lymph primarily, which as it 
oozes through the serous canaliculi of the body is in contact 
with the tissues directly. But, more remotely, the blood forms 
the internal medium ; in its circuit it takes up new materials from 
the richly charged lymph in the neighborhood of receptive cells ; 
and wastes from the lymph in the neighborhood of working cells, 
o carry these latter products to the lymph about excretory cells. 
So that while the lymph is really the internal medium m which 
the cells directly live, yet the blood is a sort of resultant of all 
the interchanges between the tissues and the lymph, undergoing in- 
terchanges with the latter by dialysis and filtration in all parts of 
the body; so that it is practically correct, as well as convenient, 
to speak of it as the internal medium. 
Through the circulating blood every cell may react upon every 
other cell. What each takes alters the blood, as well as what 
each gives, and so each cell may act upon distant parts ; and the 
blood comes to form a second bond uniting all the cells into one 
living animal. 
It is clear then that the mode of life of any cell in the body 
will or may depend upon three things; First, upon what we may 
call the physiological character or specialized property of the 
cell itself. Secondly, upon its connections with the nervous 
system and the influence exerted by this upon it; and thirdly, 
upon the nutritive medium. 
Disease, which is, fundamentally, abnormal tissue life, may 
depend on any of these factors ; and at different periods one or 
the other has most engaged the attention of pathologists. The 
humorists looked mainly at the medium ; the nervous school 
ascribed to the nervous tissues a great control on cell life; 
and then of late years, under Virchow’s influence mainly, the 
cellular pathology, brings the individuality of cell itself 
into prominence in the production of disease. It is mainly as 
tending to throw light upon the influence of each of these factors 
on the physiological life of cells, and so upon their pathological, tt. NEWELL MARTIN, 
that t have selected secretion as the topic of this discourse. 
As regards the medium, it is clear that any cause cutting off 
the blood supply, and preventing the arrival of food and the 
removal of waste from a cell will lead to the alteration or cessa- 
tion of its activity; an embolism will produce aphasia by pre- 
venting the renewal of the lymph around certain brain cells and 
fibres. On the other hand the absence of certain normal consti- 
tuents of the blood or the presence in it of noxious bodies may 
also influence the cells for evil, as in asphyxia and poisoning. 
But apart from this the question remains over, how far an abund- 
ant or excessive blood supply, can affect the nutrition of cells, or 
their activity. Can you or can you not make a cell feed or work, 
simply by placing plenty of material within its reach. 
Then as to nervous influences, which gained for some time a 
prominence, there is still much obscurity. The observation of 
cutaneous eruptions along the lines of certain nerves, and the 
ulceration of the cornea and parts of the buccal mucous membrane 
following section or injury of the trigeminal nerve, have been 
put forward as indicating a direct influence of the nervous system 
upon cell nutrition; but later work has in large measure weak- 
ened the potency of such arguments, brought forward in support 
of this view. On the one hand the results following section of, 
the trigeminal have been accounted for in other ways than a 
direct loss of tone, if I may so call it, in the cornea cells; w'hile 
the discovery of the vaso-motor nerves has rendered it possible 
that the phenomena of Herpes Zoster and similar diseases are 
only indirectly due to the nerves ; these latter not governing 
directly the cell metabolism, but merely, through the blood ves- 
sels, their food supply. On this point Heidenhain’s recent work 
on the salivary glands is of great importance. 
As I have already pointed out a certain amount of nutritive 
metabolism goes on in every living cell. No matter how spe- 
cialized its functions in other points, it must ultimately take up 
from outside and build up for itself new materials to replace those 
broken down. The Chinese mandarin described by Robinson 
Crusoe had servants to lift the food to his mouth, but even he, had 12 
THE PHYSIOLOGY OF SECRETION, 
to swallow and digest it for himself; and so for all living tissues. 
Apart, however, from this general necessary metabolism of all 
the tissues, we find in the human body certain sets of cells which 
are metabolic par excellence : whose distinctive characteristic is 
the working of chemical metamorphoses, just as the physiological 
character of a muscular fibre is its contractility. 
Such cells are found in glands, the products of which are true 
secretions as distinct from transudata; a transudation being a 
liquid such as that of the pericardium or beneath the arachnoid, 
which contains no chemical bodies but such as exist in the blood , 
while a true secretion contains some specific element, some body 
(as mucin or ptyalin) which does not exist in the blood or lymph, 
and which must therefore have been made in the gland itself 
If we take a survey of the organic world, and study the activity 
of cells in general, it becomes clear that a secreting cell might 
produce the specific element of a secretion in either one of two 
ways. It might as a bye result of its living play of forces pro- 
duce changes in the surrounding medium, or it might build up 
certain substances in itself and then set them free as the specific 
elements. Yeast for example in a saccharine solution causes re- 
arrangement into carbon dioxide, alcohol, glycerine and succinic 
acid of many atoms of carbon, hydrogen and oxygen which 
previously existed as sugar and which during the metamorphosis 
were not passed through the living cell. How the latter acts we 
do not know with certainty, but most probably by picking certain 
atoms out of the sugar molecule, and leaving the rest to fall down 
with simpler compounds. 
On the other hand we find cells forming and storing up in 
themselves large quantities of substances, which they afterwards 
liberate—starch for instance being formed and laid by, in many 
fruit cells; and afterwards rendered soluble and passed out to 
nourish the young plant. 
Gland cells might give rise to the specific elements of secretions 
in either of these two ways and the first question which calls for 
decision is, in which manner do they work. Do they simply act 
as ferments (however that is) upon the surrounding medium, or H . NEWELL MA R TIN . 
13 
do they form the special bodies which characterise their secretion, 
first, within their own substance and then liberate them; either 
disintegrating or not, themselves, at the same time. 
At present there is a large and an increasing body of evidence 
in favor of the second view. There is no doubt some reason to 
believe that every living cell can act more or less as a ferment 
upon certain solutions should they come into contact with it. 
Not always of course as an alcoholic ferment, though even as 
regards that one fermentative power it seems very generally 
possessed by vegetable cells, and there is some evidence that 
alcohol is normally produced in small amount (and presumably 
by the fermentation of glucose) under the influence of certain of 
the living tissues of the Human Body. 
As regards, however, distinctively secretory cells the evidence, 
is all the other way. In many cases we can see the specific ele- 
ment collecting in the gland cells before it is set free in the secre- 
tion. 
In the mammary gland towards the end of pregnancy fatty 
degeneration of the cells occurs ; and the oil of the milk consist- 
ing mainly of butyrine, a fat which does not exist in the blood, is 
thus formed. In the colostrum of the first few days after parturi- 
tion we find many gland cells floating, still tolerably intact, and 
loaded with oil drops. But later, when lactation is more fully 
established, the fatty metabolism of the cells is more complete 
and they break down entirely, so that only the butyrine and casein 
resulting from their destruction are found in the milk ; as a sort 
of detritus of the secreting cells. 
In other cases the liberation of the specific element is not at- 
tended with the destruction of the cell. Take for instance the 
pancreas. As you know, its secretion, besides the power of con. 
verting starch into glucose and of breaking up neutral fats, is 
able to digest albuminous substances in an alkaline medium ; 
turning them into dialysable peptones quite similar to those pro- 
duced by the gastric juice. This albumen digesting or “ proteo- 
lytic ” ferment is called trypsin ; and its formation in the gland 
cells can be followed with the microscope. the physiology of secretion. 
The pancreas, like the majority of the glands connected with 
the alimentary canal, has an intermittent activity determined by 
the presence or absence of food in various parts of the digestive 
tract. If the organ be taken from a dog which has fasted four 
and twenty or thirty hours and put into alcohol, and after harden- 
ing, thin sections be prepared, stained with carmine and examined, 
we get specimens of what we may call the “ resting gland,” a 
gland which has not been secreting for some time. In these it 
will be seen that the cells lining the alveoli present two very 
distinct zones : an outer, next the lumen, which is granular, and 
does not combine with carmine ; and an inner, which is non- 
granular, and picks up the coloring matter. The granules are 
indications of the presence of a trypsin yielding substance formed 
in the cells. 
If another dog be kept fasting until he has a good appetite and 
be then allowed to eat as much meat as he will, he will commonly 
take so much that his stomach will only be emptied at the end of 
about twenty hours. Now Bernstein’s observations show that 
this period of twenty hours may, so far as the pancreas is con- 
cerned, be divided into two. From the time the food enters the 
stomach and on or about ten hours the gland secretes abundant- 
ly, after that the secretion dwindles, and by the end of the second 
ten hours has nearly ceased. We have then a time during which 
the gland is working hard, followed by a period in which its ac- 
tivity is very little, but during which it is abundantly supplied 
with food materials. The pancreas taken from an animal at the 
end of the first digestion period and prepared for microscopic ex- 
amination in the way above described, will be found very different 
from that taken from a dog, killed at the end of the second diges- 
tion period, and also from the resting gland. 
Towards the end of the period of active work, the gland cells 
are diminished in size, and the proportions of the granular and 
non-granular zones are quite altered. The latter now occupies 
most of the cell, while the granular non-staining zone is greatly 
diminished. Dur ng secretion, there is a growth of the non- 
granular, and a destruction of the granular zone, and the latter H. NEWELL MARTIN. 
15 
process rather exceeding the former, the whole cell is diminished 
in size. 
During the second digestive period, when secretion is languid, 
exactly a reverse process takes place. The cells increase in size, 
so as to become larger than those of the resting gland ; and this 
growih is almost entirely due to the granular zone, which now 
occupies most of the cell. 
These facts suggest that during secretion, the granular part of 
the cells is used up ; but that simultaneously the deeper non- 
granular zone is formed from materials yielded by the blood ; 
and gradually gives rise to the granular. But during active secre- 
tion, the breaking down of the latter to yield the specific elements, 
occurs faster than its regeneration. In a later period, however, 
when the secretion is ceasing, the whole cell grows, and at the 
same time, the granular zone is formed faster than it is disinte- 
grated, and hence the great increase of that part of the cell. 
If this be so, then we ought to find some relationship between 
the digestive activity of an infusion or extract of the gland and the 
size of the granular zones of the cells, and Heidenhain has shown 
that such exists. The quantity of trypsin, which can be obtained 
from a pancreas being proportionate to the size of the granular 
zone of its cells. The trypsin, however, does not exist in these 
latter ready formed, but only a body which yields it under certain 
circumstances, and which Heidenhain calls the zymogen. 
If a perfectly fresh pancreas be divided into halves, and one 
portion immediately minced and extracted with glycerine, while 
the other is laid aside for twenty-four hours in a warm place and 
then similarly treated, it will be found that the first glycerine 
extract has no proteolytic power whatever, while the second is 
very active. In other words, the gland does not contain trypsin, 
but only something which can yield it. The inactive glycerine 
extract, however, is rich in zymogen, and if a little acetic acid be 
added to it, this is converted rapidly into trypsin, and the extract 
becomes powerfully digestive. 
We may then sum up the life of pancreas cell in this way: It 
grows by materials derived from the blood, and first laid down 16 
THE PHYSIOLOGY OF SECRETION. 
in the non-granular zone. This latter, in the ordinary course of 
the cell life gives’ rise to the granular zone ; and in this is a store 
of zymogen. When the gland secretes the zymogen is converted 
into trypsin and set free in the secretion ; but in the resting cell 
this transformation does not occur. During secretory activity 
the chemical processes, (the metabolisms of the cell,) are different 
from chose at other periods, and we have next to consider how 
this metabolic or trophic change in the life of the cell’s is brought 
about. 
When the gland is active we know that it is fuller of blood 
than when at rest; the arteries are dilated and its capillaries 
gorged so that it gets a pink color ; and this extra blood supply 
might be the primary cause of the altered metabolism. 
On the other hand the activity of the pancreas is under the 
influence of the nervous system, as evinced not only by the re- 
flex secretion called forth when food enters the stomach ; but, 
also by the fact that electrical stimulation of the medulla ob- 
longata will cause the gland to secrete. The nervous system 
may, however, only act by governing the calibre of the gland 
arteries and so but indirectly on the secretory cells ; but, on the 
other hand, it is possible that nerve fibres act directly upon the 
gland cells and control their nutritive processes. 
To decide the relative importance of these possible agencies 
we must pass to the consideration of other glands ; since the 
position of the pancreas and the difficulty of getting at its nerves 
without such severe operations as upset the physological condi- 
tion of the animal, furnish obstacles to its study which have not 
yet been overcome. 
In certain other glands however, we find conclusive evidence 
of a direct action of nerve fibres upon the secreting elements. 
If the sciatic of a cat be stimulated the balls of its feet will 
sweat. Under ordinary circumstances they become at the same 
time red and full of blood, but that this congestion is a factor of 
subsidiary importance as regards secretion is proved by the facts 
that stimulation of the nerve is still able to cause sweating in a 
limb which has been amputated ten or fifteen minutes, and in rt. neweLl Martin. 
Which therefore no circulatory changes can occur ; and also by 
the cold sweats, with a pallid skin, of phthisis and the death 
agony. 
It is however with reference to the sublingual and parotid 
glands that our information is most precise; thanks mainly to 
Bernard, Ludwig, and of late years especially to Haidenhain, 
whose contributions to the physiology of secretion are of the 
highest Value. 
When the mouth is empty and the jaws at rest the salivary- 
secretion is little abundant; but a sapid substance placed on the 
tongue will cause a copious how. The phenomenon is closely 
comparable to the production of a reflex movement. A stimulus 
acting upon an irritable tissue excites through it certain efferent 
nerve fibres ; these excite a nerve centre, which in turn stimulates 
efferent fibres, going to a muscle in the one case, to a gland in 
the other. It will be useful to consider for a moment the case 
of a muscle, taking account only of the efferent fibres and the 
parts they act upon. 
When a muscle in the body is made to contract reflexly of 
otherwise, through its nerve, two events occur in it. One is the 
shortening of the muscular fibres ; the other is the dilatation of 
the muscular arteries, so that more blood flows through the organ. 
Every muscular nerve in fact contains two sets of fibres, one 
motor and one vaso-dilator and normally both act together. In 
this case however, it is clear that the activities of both, though 
correlated, are essentially independent. The contraction is not 
due to the greater blood flow, for not only can an excised muscle, 
entirely deprived of blood, be made to contract by stimulating 
its nerve; but in an animal to which a small dose of curari 
has been given, stimulation of the muscular nerve will cause the 
vascular dilatation but no contraction; the curari paralyzing the 
motor fibres, but unless in large doses, leaving the vaso-dilators 
intact. The muscular fibres themselves are quite unacted upon 
by the poison, as evinced by their ready contraction when direct- 
ly stimulated. 
Now let us return to the salivary glands and see how far the THE PHYSIOLOGY OF SECRETION. 
facts are comparable. If the chorda tympani nerve of a dog be 
divided and a canula placed in Wharton’s duct no saliva will be 
found to flow. But on stimulating the peripheral end of the nerve 
an abundant secretion takes place. At the same time, as Bernard 
showed, there is a great dilatation of the arterioles of the gland, 
much more blood than previously flowing through it in a 
given time ; the chorda obviously contains vaso-dilator fibres. 
In this case it might very well be, that the process was different 
from that seen in a muse'e. It is conceivable that the secretion 
might be but a filtration due to the increased pressure in the gland 
capillaries, consequent on dilatation cf the arteries supplying 
them. If a greater filtration into the lymph spaces of the gland 
took place this liquid might then merely ooze on through the 
secreting cells into the commencing ducts, and as it passed 
through dissolve out and carry on from the cells the specific 
organic elements of the secretion. Of these, in the submaxillary 
of the dog at least, mucin is the most important and abundant. 
That, however, the process is quite different, and that there are 
in the gland true secretory fibres, in addition to the vaso-dilator, 
just as in the muscle there are true motor fibres, has been proved 
by Ludwig and Haidenhain. 
If the flow of liquid from the excited gland wrere merely the 
outcome of a filtration dependent on increased blood pressure in 
it, then it is clear that the pressure of the secretion in the duct 
could never rise above the pressure in the blood-vessels of the 
gland. Now experiment shows that the gland can be made to 
secrete in a recently decapitated animal, in which of course there is 
no blood pressure ; and that when the circulation is going on, the 
pressure in the duct can rise far beyond that in the gland arteries. 
Since arterial pressure constantly diminishes from the heart to 
the capillaries, that in the carotid trunk must be greater than 
that in the twigs from its facial branch which supply the gland, 
and Ludwig has shown that if a manometer be connected with 
the carotid on one side of the neck, and another with Wharton’s 
duct on the other side, then by continued stimulation of the 
chorda, the pressure of the secretion in the duct can be raised ti . NfiWELL MARTIN. 
19 
far above that exhibited by the blood in the carotid. Obviously 
then the secretion is no question of mere filtration, since a liquid 
cannot filter against a higher pressure. 
Finally Haidenhain completed the proof that the vascular dila- 
tation is quite a subsidiary phenomenon. He showed that we 
could produce all the increased blood flow through the gland 
without getting any secretion. That just as m a muscle nerve 
we can by curari paralyze the motor fibres and leave the vaso- 
dilators intact, so we can by atropia get similar phenomena in the 
gland. In an atropised animal stimulation of the chorda will 
produce vascular dilatation but not a drop of secretion, so that 
something more than increased blood flow is wanted. Bringing 
blood to the cells abundantly, will not make them drink. We 
must seek something else in the chorda besides the vaso- 
dilator fibres, and this something else must be secretory fibres. 
That the poison acts upon them and not upon the gland cells, 
is shown, as in the muscle, by the fact that the cells still are 
capable of activity when stimulated otherwise than through the 
chorda tympani. For example by stimulation of the sympathetic 
fibres going to the gland. 
So far then we seem to have good evidence of a direct action 
of nerve fibres upon the gland cells. But that is not the whole 
matter. Haidenhain has recently shewn, to my mind conclm 
sively, that there are two sets of secretory fibres in the gland 
nerves ; a set which so acts upon the cells as to make them pass 
on abundantly the transudation elements of the secretion, the 
water and mineral salts; and another, quite different, which 
governs the chemical transformations of the cells, so as to make 
them produce mucin from matters previously stored in them ; in 
a comparable way to the production of trypsin from zymogen 
in the active pancreas. These latter fibres he calls “ trophic,” 
since they directly control the cell metabolism ; while the former 
he calls “ secretory fibres ” proper. 
Some of the evidence which leads to this conclusion is a little 
complex. In the first place, about eleven years ago, he shewed 
that on stimulation of the chorda of an unexhausted gland (that 20 
THE PHYSIOLOGY OF SECRETION. 
is a gland not over-fatigued by previous work) the following 
points could be noted :—With increasing strength of the stimulus 
the quantity of the secreticn, that is of the water, poured out in 
a unit of time increases ; but at the same time the mineral salts 
also increase, but more rapidly, so that their percentage in a 
rapidly formed secretion is greater than in a more slowly formed, 
up to a certain limit. At the same time the per centage of organic 
constituents of the secretion also increases up to a limit, but soon 
ceases to rise or even falls again, while the water and salts still 
increase. This of course is readily intelligible ; since the water 
and salts can be derived continually from the blood, while the 
specific elements, coming from the gland cells, may be soon 
exhausted. So far then the experiment gives no evidence 
of the existence of distinct nerve fibres for the salts and 
water, and for the specific elements ; both vary together with the 
strength of the stimulus applied to the nerve. But under slightly 
different circumstances their quantities do not run parallel. The 
proportion of specific elements in the secretion is largely de- 
pendent on whether the gland has been previously excited or not. 
Previous stimulation, not carried on of course to exhaustion, 
largely increases the per centage of organic matters in the 
secretion due to a subsequent stimulation ; but has no effect 
whatever on the quantity of water or salts. These are governed 
entirely by the strength of the second stimulation. 
Here then we find that under similar circumstances the trans- 
udatory and specific elements of the secretion do not vary 
together; and are therefore probably dependent upon different 
causes. And the facts led to Haidenhain to conclude that there 
were in the chorda, besides the vaso-dilator, two other sets of 
fibres : one governing the salts and water, and the other the 
specific elements of the secretion. 
The evidence was not however, conclusive, but his more recent 
experiments upon the parotid gland of the dog, have put the 
matter beyond a doubt. 
The submaxillary gland gets not only fibres from the facial 
nerve through the chorda, but also fibres from the sympathetic. H . NEWE I. L M ARTIN. 
21 
Stimulation of either nerve causes a secretion, that due to the 
chorda being in the dog abundant, comparatively poor in or- 
ganic constituents, and accompanied by vascular dilatation; 
while the “ sympathetic saliva ” as it is called, is less abundant, 
very rich in mucin, and accompanied with constriction of the 
gland arteries. According to Haidenhain’s view the chorda con- 
tained many secretory and few trophic fibres, and the sympathetic 
many trophic and few secretory. 
It was still, however, possible to object that the greater richness 
in organic bodies of the sympathetic saliva was really due to the 
small quantity of blood reaching the gland, when that nerve was 
stimulated. This might alter the nutritive phenomena of the 
cells and cause them to form mucin in unusual abundance, in 
which case the trophic influence of the nerve would be only in- 
direct. 
Experiments on the parotid, however, preclude this explana- 
tion. That gland, like the submaxillary, gets nerve fibres from Iwo 
sources ; a cerebral and a sympathetic. The latter enter the gland 
along its artery, while the former originating from the glosso- 
pharyngeal, run in its tympanic branch (the nerve of Jacobson), to 
the large superficial petrosal, and thence through the otic ganglion 
and the facial nerve to the gland. Stimulation of the nerve of 
Jacobson causes an abundant secretion, rich in water and salt, 
but with hardly any organic constituents. At the same time it 
causes dilatation of the gland arteries. 
Stimulation of the sympathetic causes contraction of the gland 
arteries but no secretion at all. Nevertheless it causes great 
changes in the gland cells ; it contains many trophic fibres, but 
no secretory. If it be stimulated for a while, and then the nerve 
of Jacobson, the resulting secretion may be ten times as rich in 
organic bodies as that obtained without previous stimulation of 
the sympathetic. And a similar phenomenon is observed if the 
nerve of Jacobson and the sympathetic be stimulated simultane- 
ously. So that the latter nerve, though unable of itself to cause 
a secretion, brings about great chemical changes in the gland 
cells. 22 
THE PHYSIOLOGY OE SECRETION, 
This conclusion is confirmed by histology. Sections of the 
gland after prolonged stimulation of the sympathetic show its 
cells quite altered in appearance and in their relations to carmine, 
when compared either with those of the resting gland, or of the 
gland which has been made to secrete by stimulating the nerve 
of Jacobson alone. 
We have still, however, to meet the objection that the sym- 
pathetic fibres may be only indirectly trophic, governing the 
metabolism of the cells through the blood vessels. If this be so, 
then cutting off or diminishing the blood supply of the gland in 
any way ought to have the same result as stimulation of its 
sympathetic fibres. Experiment shows that such is not the case 
and reduces us to a direct trophic influence of the nerve. 
Haidenhain ligatured both subclavians in a dog and then ex- 
posed the carotids so that they could be clamped or left open at 
will. When they were closed of course the blood supply to the 
gland was very nearly (but, in the dog, not quite) cut off. On 
then stimulating the nerve of Jacobson he found the per centage 
of organic constituents in the secretion was as low as usual, and 
was almost exactly the same whether the carotids were open or 
closed or had been previously open or closed. We must conclude 
the peculiar influence of the sympathetic does not depend upon 
its vaso constructor fibres. These observations make it clear that 
the views until recently commonly held as to the theory of secre- 
tion must be considerably modified, at least for the salivary glands, 
and presumably for others ; and they also throw considerable light 
upon the relationships of the nervous system to cell metabolism. 
Time forbids me to enter upon a full discussion of the question, 
and I must confine myself to briefly stating Haidenhain’s con- 
clusions. 
Let us suppose in the resting gland cells a quantity of material 
to be formed which has a considerable attraction for water; that 
this is the product of the nutritive processes of the resting cells. 
These will, as a result, absorb through the membrana propria a 
quantity of water from the surrounding lymph sinuses; and this 
will accumulate in each cell until its tension equals the endos- H . NEWELL MARTIN. 
23 
motic force which tends to bring it in. The cell will then be in 
equilibrium and thus will last as long as the gland is at rest. 
The water is at a high tension in the cell, but its passage out into 
the duct and its replacement by more from the lymph, is pre- 
vented by the limiting layer of the cell protoplasm; the layer 
bounding it next the lumen of the alveolus. If now a secretory 
fibre acts upon the cell the molecular arrangement of this 
limiting layer is altered, its resistance to filtration or osmosis 
being diminished. That this is no extravagant supposition is 
evident from the fact that a nerve fibre can we know bring about 
entirely new molecular arrangements in other tissues, as for 
instance in a muscular fibre. In consequence of the diminished 
resistance, some of the water accumulated in the cell will flow 
into the duct; the cell perhaps actively contracting at the 
same time and forcing it out, for Kuhne has observed active 
contractions in the cells of the living pancreas of the rabbit. 
The passage of water from the cells will lower the tension 
within them, and the cell will again supply itself through its 
deeper side from the lymph. The lymph in turn will recuperate 
its losses from the blood ; and so long as the gland is secreting 
a transference of water from the blood to the gland duct will go 
on. When the stimulation ceases the molecules of the limiting 
layer of protoplasm will reassume their original arrangement, 
and again oppose a great resistance to filtration. The cell will 
again fill up with water until equilibrium is attained, and so 
return to its resting state. 
By such means we would obtain a secretion the quantity of 
which would be quite independent of the per centage of organic 
matters in it; these, by supposition, existing in such condition 
within the cells that they remain behind when the water passes 
out through the limiting layer. In this way also the secretion 
would be independent of the blood pressure. The pressure which 
it could attain would depend upon the endosmotic equivalent of 
the cell substance, the force with which it tended to take 
up matters from the lymph, and then to pass them out by 
contraction or otherwise into the gland ducts. To explain 24 
THE PHYSiOLOGY OF SECRET iON. 
the increased per centage of salts in the more abundant 
secretion following a more powerful stimulus, we must sup- 
pose also that the molecular rearrangements brought about 
are such as to rendet more easy the passage of saline particles. 
A supposition which is quite in acdord with well known physical 
facts. The quantity of a salt dialysing through a membrane 
under given conditions in a certain time, being largely dependent 
upon the molecular structure of the membrane. On this view 
then the secretory fibres are regarded as simply causing physical 
molecular rearrangements in the cell; but no important chemical 
changes. 
Turning now to the trophic fibres, we have seen that under 
their influence soluble organic bodies arise in the gland cells ; 
substances which can be carried out by the water and salines 
passing through them under the influence of the proper secretory 
fibres , and which then form the specific elements of the secretion. 
The histological and microchemical comparison of the gland 
which has and that which has not had its trophic fibres stimu- 
lated shows that quite different substances accumulate in the 
cells in two cases. The resting parotid cells do not form mucin ; 
but when the sympathetic fibres are stimulated new nutritive 
processes occur by which mucin is formed abundantly. The action 
of these fibres is essentially one on the chemical metabolism of the 
cells—on the very inner processes of cell life. Haidenhain 
believes that the change effected by the trophic fibres is so pro- 
found that on subsequent or simultaneous secretion, the whole 
cell goes to the ground, being disentegrated as the mammary 
gland cells are in the formation of milk; while at the same time 
other more peripheral cells at points in the alveoli, multiply rap- 
idly and form new secreting cells. This does not, however,, 
appear to be conclusively established ; if it be correct we would 
have a state of things answering to that in the beehive where 
certain individuals doing the work of the community, have lost 
the power of reproduction. 
In either case we have evidence of a profound and direct in- 
fluence exerted by the nervous system upon the nutritive phe^ H . NEWELL MARTIN. 
nomena of cell life ; a point which I venture to think has a great 
pathological importance. If we can directly prove that the 
chemical phenomena of any one group of cells are controlled by 
trophic nerve fibres, we establish an a priori probability of a 
similar action in other cases. And the views recently promul- 
gated as to thermal nerves, that is fibres which independently of 
the blood vessels, can control the oxidation and heat devel- 
opment going on in cells, acquire a considerable collateral support. 
Should further investigation bring to light more facts similar to 
those which I have had the honor to lay before you, the whole 
cellular pathology as at present understood must, I think, undergo 
very considerable modification. Fundamentally of course the 
mode of life of the cell will be determined by what I have called 
its physiological character; but We shall have also to take largely 
into account its possible control by an immediate action of the 
nervous system. 
In another way the physiology of secreting cells seems to me 
to have important pathological significance. It seems to show 
how absolutely, one might almost say, the activity of a cell is 
independent of the circulation in its neighborhood. The presence 
of an abundant blood supply, a congestion of a muscle or a 
gland will not throw either organ into activity. One may of course 
starve a cell by cutting off its blood, or poison it by noxious 
bodies in that liquid ; but apart from such extreme influences 
plenty of food will not make a cell work in the absence of some 
other stimulus to exertion, any more than it will make the whole 
man. 
In its ultimate results I believe there has been no more per- 
nicious error than that made when Davy experimenting with 
impure gases, he stated that inhalation of pure oxygen, in other 
words richly supplying the tissues with that element caused 
mental exhilaration, febrile phenomena and other signs of in- 
creased bodily metabolism. In spite of the most conclusive 
proof to the contrary the statement is only just beginning to go 
out of some of the common text books of physiology; and it 
is hard to say when it will cease to be a popular belief. 26 
THE PHYSIOLOGY OF SECRETION. 
So long as that belief holds ground the influence of the circu- 
lation upon the life of the tissues must be ever liable to be over- 
rated. and will find its pathological outcome in such beliefs for1 
instance as that active cerebral congestion will cause mental ex- 
citement. Speaking as a physiologist, and therefore subject to cor- 
rection from those who have made pathology a special subject of 
study, I can only say that the belief has no physiological basis 
whatever; is even directly opposed to all that we know of cell life ' 
There is no evidence that such congestion is the cause of the 
delirium any more than that of a digesting pancreas or a con- 
tracting muscle is the cause of the activity of either; all that we 
do know as physiologists goes to show that the vascular dilata- 
tion is a purely collateral and subsidiary phenomenon in each 
caselt may have secondary results, and of course pathological 
congestion often has, and very serious ones; but the primary 
and immediately acting excitant of the increased tissue activity 
is. in each case, to be sought elsewhere. 
It is possible, indeed probable, that many of you here present, 
concerned in the daily observation of disease are in possession of 
facts which are beyond my reach, and will lead you to dissent 
from the opinions I have just expressed. If however I can lead 
you to accept, supposing any of you previously doubted it. the, 
belief that physiological experiment affords at least suggestive 
material for pathological work and thought, I shall have largely 
gained an end which is naturally very dear to me. The science of 
physiology is the child of the medical profession; and if in late 
years it, with its growth and development, tends to assert its 
claims to existence as an independent science it is in no spirit of 
arrogance or self seeking. Its gains are in the long run your 
gains, and handed over to you in no grudging spirit. In return 
you can do much for physiology, not only by close pathological 
observation but in other ways, and the debt of honor has 
hithcrto been njbly paid. 
(. A fewl:years ago the medical men of England, by their united 
action, saved English physiology from extinction. But a com- 
bined attack, based in part upon benevolent ignorance, in part 2 7 
H, NEWELL MARTIN. 
uron fanatic misrepresentation (I nearly said lying), and largely 
upon a passionate hatred of science, especially biological science, 
which possesses a large section of the English public, led to leg- 
islation which must tend to make English speaking physiology 
find its future home and centre on this side of the Atlantic. 
Should similar circumstances arise here, it rests with you, exert- 
ing that vast influence upon public opinion and enlightenment 
which the medical man possesses, to secure the freedom and ad- 
vance of physiology, the triumph of reason over prejudice—of 
knowledge over ignorance.