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Embryology. A Laboratory Text-book 
of Embryology. By CHARLES S. MINOT, 
S.D., LL.D., Professor of Comparative An- 
atomy, Harvard University Medical School. 
Second Edition, Revised. With 262 Illus. 
xiix402 pages. Cloth, 3.50. 

"Professor Minot is to be congratulated most 
warmly on the success, efficiency, thoroughness, 
and stimulating character of his work." The Lan- 
cet, London. 

"The book is well written and well printed. 
The illustrations are numerous and well executed." 
New York Medical Journal. 




















His Royal Highness, the Grand-Duke of Saxe- Weimar, the 
Rector Magnificentissimus of the University, has graciously 
pleased, after Professor Eucken of Jena had been called to 
Harvard University as Exchange Professor, to express the 
wish that the Harvard Exchange Professor at Berlin this year 
should lecture also in Jena. This wish was communicated to 
Harvard University by the Prussian Ministry of Education. 
After further correspondence the formal invitation was sent 
me to deliver in Jena the six lectures which appear in printed 
form in the following pages. 

It is always a difficult problem to so present new biological 
discoveries that they will be comprehensible to a mixed public, 
and yet lose nothing of their scientific value. The reader 
therefore is requested to exercise a lenient judgment, when he 
finds that the performance leaves much to be desired. It 
seemed desirable to consider the first lecture as an introduc- 
tion which might render it easier for non-biologists to under- 
stand the following lectures. The researches quoted are 
chiefly American. This plan was adopted partly because the 
author was the American Exchange Professor and partly be- 
cause he was informed that his audience in Jena would like 
to hear especially about American discoveries. In the short 
time at command it was impossible to present the evidence for 
all that was said, and the reader must be begged to pardon the 
author if many assertions sound like obiter dicta. 



To their Royal Highnesses, the Grand-duke and the Grand- 
duchess of Saxony, the author expresses his thanks for their 
interest and for the great honor of their presence at one of the 
lectures. He has pleasure in thanking also their Excellencies, 
the Ministers of Education of Saxe-Weimar-Eisenach, 
Altenburg and Meiningen, his Magnificency the Prorektor, 
the Curator of the University and his Colleagues for their 
encouragement and hospitality, by which the visit to Jena was 
made very delightful. 

The lectures were written and have already been published 
in German by Gustav Fischer in Jena. Professor von Bar- 
deleben had the great kindness to revise the original manu- 
script. The translation has been prepared by the author and 
follows the original closely, though now and then a phrase 
has been rendered freely. 















Your Magnificence! 
Gentlemen ! 

To his Royal Highness, the Grand Duke of Saxe- Weimar, 
I wish to express with the highest respect my sincere thanks 
for the interest which his Royal Highness has shown in the 
exchange of professors with America. It is a great honor to 
be the first Harvard professor to come to you, as the official 
representative of the American academical world. The 
University of Jena is as famous and as highly esteemed in 
America as in Germany. When I consider the reputation of 
the Jena professors I cannot venture to hope that the lectures 
I am to deliver will attain that degree of perfection to which 
you are accustomed. Therefore I request you to consider 
my lectures as an expression of my sense of obligation. Not 
merely Harvard University, but the whole United States are 
grateful to you that you have permitted Professor Eucken 
to come to us as exchange professor. I owe your Ministry of 
Education special thanks for the invitation sent me to appear 
here as the guest of your University. 

It is always a difficult task so to present scientific conclu- 
sions that they shall be comprehensible to the public and, at 
the same time, keep their precision and their scientific value; 
but when a branch of science has progressed so far that 



conclusions of wide bearing can be drawn, it becomes desirable 
to communicate the results to wider circles. The new 
achievements of biology are significant and claim the interest 
of all thinkers, and therefore I have decided to attempt to 
make clear to you some of our fundamental conclusions. My 
fellow biologists are requested to excuse the mention of much 
already known to them. 

The general conclusions of biology are formed slowly. 
The phenomena of life are so complicated that they can be 
analyzed only by the most many-sided investigations. If 
one wishes completely to master the science one would have to 
be not only a biologist in the stricter sense, but also a chemist, 
a physicist and a geologist. It has become impossible for a 
single investigator of our time to acquire special knowledge 
in the whole field of biology, and you will certainly not expect 
from me that I attempt to make clear to you all the funda- 
mental conclusions of modern biology. Indeed for this, the 
time at our disposal would not suffice. Therefore I shall 
permit myself to treat only such questions as I have found 
occasion to consider often in the course of my special work. 
We may arrange the subjects to be discussed in the following 
order : 

1. The New Cell Doctrine. 

2. Cytomorphosis. 

3. The Doctrine of Immortality. 

4. The Development of Death. 

5. The Determination of Sex. 

6. The Notion of Life. 

You all know something of cells, which have been described 
often as the units of life. They are small masses of living sub- 
stance, in each of which lies a smaller body, which is desig- 


nated as nucleus. The living sub- 
stance is commonly termed proto- 
plasm. Unfortunately with the 
progress of investigation we have 
become more and more uncertain 
what we can properly designate as 
protoplasm. The nucleus is also a 
living substance, but it is commonly 
not reckoned as protoplasm. Many 
authors apply the term protoplasm 
to the body of the cell, which often 
has a very complicated structure. 
Thus we see spaces which we name 
vacuoles, and which contain only 
fluid. Such a fluid is usually not 
considered part of the protoplasm. 
More frequently we find special en- 
closures, granules, etc., which reveal 

FIG. i. Two blood cells from an embryo duck. 
The protoplasm has a uniform constitution and 
contains the centrosome. In the rounded nucleus 
the material is irregularly distributed and forms 
a larger mass of chromatine. The cells have been 
artificially colored. After M, Heidenhain. 

FIG. 2. Two plant cells 
from the vegetative point of 
a Phanerogam, a, younger; 
6, older stage; k, nucleus; v, 
sap space; cy, protoplasm. 
After Strassburger. 

an entirely different constitution from the rest of the mass, 
which one is inclined to name protoplasm in the stricter 


sense. A further difficulty arises from the observation that 
in the nucleus also a substance can be found with peculiari- 
ties like the protoplasm. Thus it happens that with the 
enlargement of our knowledge we have become more and 
more uncertain what we can properly designate with this 
word "protoplasm." It corresponds better to the present 
condition of science if we say that a cell consists of nucleus 
and a cell body, because we thus restate clearly our direct 
observation. Nevertheless a biologist would hardly like to 
lay aside the word protoplasm, in part because it has such a 
great historic significance. 

As is known, cells were discovered by the botanists, and 
first by the Englishman Hook, and they received from botan- 
ists the name cell, which is completely suitable for the form 
first observed, for in many plants one sees the cells as small 
spaces, which are separated from one another by partitions. 
These spaces were designated simply as cells. Later it was rec- 
ognized that the essential thing was not the arrangement of 
the partitions, but the content of each cell. This content is 
protoplasm mixed with water and containing a nucleus. Two 
eminent German investigators have furnished us with a 
completely new conception of tne cell. Wilhelm Kiihne and 
Max Schulze have proven that the partitions are unessential 
and that we may have a complete cell without them. Thus a 
new conception arose, namely, that a cell consists of proto- 
plasm and nucleus. The great English biologist, Huxley, who 
appreciated the importance of the new views of Kiihne and 
Schulze, has presented them in a lecture to which he gave the 
title, "The Physical Basis of Life." Huxley's presentation is 
so clear and comprehensible that his readers cannot fail to ap- 
preciate the full significance of the views presented. Huxley's 
lecture occasioned great excitement among thinkers in Eng- 


land and America, and also on the European Continent. 
Everybody discussed at that time the question whether proto- 
plasm was really the physical basis of life or not. The solution 
of this problem we have not fully reached even yet. The de- 
scription of the cell which we owe to Max Schulze dominates 
everywhere and yet with the progress of science it has be- 
come insufficient. 

The size of the cell is of the greatest significance to biologists. 
Cells for the most part are rather small, and the size is ex- 
tremely variable. The cells of the human body, according to 
an estimate I have made, have an average diameter of perhaps 
0.014 mm. Variations, however, are considerable; some cells, 
like the blood-corpuscles, are very small; certain nerve cells, 
on the other hand, attain a considerable size. The largest 
cells of all, known to us at present, are eggs. Those of certain 
animals appear as true giants in comparison with other cells. 
The largest eggs occur in birds. The entire yolk of the bird's 
egg corresponds to but a single cell. The albumen which 
surrounds the yolk and the shell do not belong to this cell, but 
are simply layers which are added by the oviduct to the egg 
proper, and which are secretions of the glands of the oviduct. 
Of all the animals now living the ostrich has the largest egg 
and the yolk of the ostrich egg is certainly the largest living 
cell known to us. These enormously enlarged eggs might be 
described as the monsters of the cellular world. They are ex- 
ceptions. By far the majority of cells are of such dimensions 
that they are visible with the microscope alone. The smallest 
organisms which we know are the vegetable germs, which may 
have a diameter of not more than one-tenth of a millimeter. 
As is well known to all, certain of these smallest organisms 
cause diseases which may be extremely dangerous to man. 
The investigators of infectious diseases have made the inter- 


esting discovery that there are disease causers which are in- 
visible even with the microscope. In recent years we hear 
more and more of the so-called invisible organisms. In re- 
gard to this we must express our opinion with reservation, for 
it is by no means demonstrated that we have to deal in this 
case with actually living organisms. It is possible that we have 
to do only with chemical ferments. We have not time, how- 
ever, to enter upon this discussion. For 
the present at least we must hold to 
the opinion that vital phenomena can 
appear only when the amount of living 
substance is so great that it can be 
seen with the microscope. In other 
words, the minimum quantity of chem- 
ical substance which can serve as the 
basis of life is many times greater than 
the minimum quantity of substance 
which suffices for a chemical reaction. 
Here we encounter a fundamental char- 
acteristic of life To permit the activ- 
ities which are characteristic for life to 
go on we must bring together many sub- 
stances which stand in very special 
relations to one another. Hence the 
assertion that life is only possible when these conditions are 
fulfilled, and this requires that the total amount should be 
so much that we can see it with the microscope. 

Cells have been considered for a long time as independent 
bodies. Quite slowly this view has been changing. Many 
years ago botanists made the observation that vegetable 
cells may be united by fine threads of living substance. 
Similar relations have been observed in animals. In the sev- 

FIG. 3. Drawing to 
show the size of bacteria. 
Magnification 1000 (i mm. 
of the picture =0.001). 
A y smallest bacilli (influ- 
enza); 5, streptococcus 
gracilis (round); C, largest 
cocci; D, pus cocci; E, ba- 
cillus megatherium; F, red 
blood corpuscle; G, splenic 
fever bacillus. After H. 


enties of the last 
century J. Heitz- 
mann, a Viennese 
physician who had 
emigrated to New 
York, affirmed that 
cells are not defi- 
nitely separated 
from one another. 
He advanced the 
statement that 
protoplasm is con- 
tinuous and has 
scattered nuclei. 
The opinions ex- 
pressed by Heitz- 
mann 1 remained in 
their time almost 
without notice. 
Very gradually his 
view met with 
wider acceptance. 
The botanist Sachs 
has contributed 
much to develop 
our interpretation. 
For the zoologists 
the writings of the 
American Whit- 
man 2 have been of 
the greatest im- 
portance. Whit- 


+* 3 

O bO 



man and many others have greatly advanced the recogni- 
tion of the actual relations. We know now that when an 
ovum begins its development it must be regarded as a 
complete cell. This cell divides, the process being usually 
termed the segmentation of the ovum. When the ovum 
divides there arise two new cells which then divide again. 
If we investigate the relations of such cells in vertebrates 
we may observe without difficulty that the cells are com- 
pletely isolated from one another. They have no direct 
communication between themselves. They live alongside 
one another, but the living substance of one cell is nowise 
united with the living substances of the neighbor cell. In the 
course of the further development, however, the relation 
changes because the cells begin to unite with one another. 
This occurs chiefly in two ways. Consequently we obtain 
two kinds of tissues which we regard as the primitive tissues of 
the body, since from them all the tissues of the adult are slowly 


FIG. 5. Epithelium (epidermis) of a chicken embryo of the second day of incu- 
bation. The nuclei are mostly oval and lie scattered. The protoplasm forms a 
network. There are no intercellular partitions present. Eph, epitrichial layer; 
Ba, basal layer. 

differentiated. In one form we find the cells completely fused 
with one another and they build a continuous layer which we 
designate as epithelium. In such a primitive epithelium, Fig. 
5, there are no limits between the single cells, but on the 
contrary one has a continuous layer of protoplasm in which 
the nuclei are scattered, though generally rather close to- 


gether. When such an epithelium grows the nuclei multiply 
by division which is in itself a complicated process. The pro- 

FIG. 6. Mesenchyma of a chicken embryo of the third day of incubation. 
Every nucleus is surrounded by a thin layer of protoplasm from which run out the 
strands that form the intercellular network. Cell boundaries are not present. 

toplasm also grows. We have in this case, therefore, a sub- 
stance which, though living, does not, strictly speaking, con- 


FIG. 7. Adult epithelium. Epidermis of Lumbricus venetra. jchl. z, mucous 
cells; Cu, cuticula; J.z., cylinder cells; m.f, muscle fibers below the epithelium. The 
single cells are separated by partition walls from one another. After M. Heidenhain. 

sist of cells. The second form of tissue is called mesenchyma. 
In mesenchyma, Fig. 6, one observes nuclei which are found 


at more or less regular distances from one another, and also 
protoplasm which forms an open network. The meshes of this 
net contain a fluid, which is usually not interpreted as a part 
of the tissue proper, just as the fluids, for example, which we 
find in the articular cavities or in the body cavity of the adult 
are not reckoned as tissues of the body. In vertebrates, in 
which the protoplasm of the network of the-mesenchyma has 
been chiefly studied, we find that the network is at first 
extremely irregular; but early, as development progresses, the 
protoplasm accumulates in parts around the single nuclei and 

; ',* S 


FIG. 8. Hyaline cartilage of a human embryo. Between the cells the firm basal 
substance of the cartilage is developed in large quantities. After J . Sabotta. X 280. 

forms, so to speak, a court of protoplasm around every nucleus. 
From each court radiate the threads of protoplasm, which 
establish the connection with the neighboring courts, and thus 
the mesenchyma remains a network still. These two forms 
of tissue, which are characteristic for the connection or fusion 
of cells, we call syncytium. On tracing the development 


further we learn that alterations occur so that we can observe 
the progressive separation of the single cells; thus, for example, 
in epithelium there arise partition walls, Fig. 7, separating the 
cells finally and completely from one another. In mesen- 
chyma the connections may become interrupted by which the 
protoplasmic masses around the single nuclei are joined 
together, Fig. 8. In this way the cells become completely 
isolated. When we encounter cells which have been separated 
in this way we have to do not with a primitive but with a 
secondary condition. 

The descriptions just given lead us to one of the chief con- 
clusions of the new cell doctrine. We have learned that the 
relations are much more complicated than was previously 

We turn to the discussion of protoplasm, or, as we have 
termed it before, of the cell body. It is necessary to direct at- 
tention to the fact that in the living world we know two chief 
types of cells; first, such cells as exist alone, the so-called uni- 
cellular organisms. Of such cells there are very many species 
which have been grouped into numerous genera. Each genus 
and each species has its special peculiarities which we learn 
chiefly through the microscope. When a cell of any of the 
just-mentioned species is observed for a longer period few al- 
terations in its structure can be observed. The chief changes 
we can observe are, first, an enlargement of the cell, and sec- 
ond, the inner alterations which are usually specially notice- 
able in the nucleus, which lead gradually to the division of the 
cell. The two new daughter cells remain extremely similar to 
the original mother cell in all peculiarities. Such an organism 
propagates itself in this manner endlessly and without essen- 
tially changing its structure. 

Very different are the conditions in the second type of 


cells, which we find only in the multicellular organisms, that is, 
in the higher plants and animals. In them we observe different 
cells which take over the function of propagation. In the case 
of animals such cells are called ova and spermatozoa. A sper- 
matozoon unites with an ovum, which we then designate as 
fertilized. A fertilized ovum is a complete cell which divides 
and continues dividing until the number of cells for the con- 
struction of an animal body has been produced. This number 
may be enormous. The ovum, or egg-cell, proliferates by 
division precisely as does the cell of a unicellular organism. 
The cells of the latter do not change, but the cells which arise 
from the ovum do change. The cells of the multicellular or- 
ganisms through several or many early generations retain a 
relatively similar structure, but later there follows a transform- 
ation which with the succeeding generations progresses, and at 
the same time becomes multifarious. In this manner the tis- 
sues of the adult arise gradually and in accordance with fixed 

In consequence of these conditions it has come about that 
we have derived our conception of protoplasm and in part also 
of the nucleus chiefly from studies which investigators have 
made on the developing ova, for in the early generations of 
these cells we have relatively simple relations. Fortunately, 
however, there occur among the unicellular organisms species 
which are comparatively simple in structure, and which are 
therefore favorable for the study of protoplasm. If we wish 
to summarize the result of numerous investigations in brief 
form we may say that we have learned to recognize three 
conditions of protoplasm; that is, one condition of which 
we know as yet little, but which is of 'the greatest significance 
and which is characterized by the fact that the protoplasm 
appears to us under the miscroscope absolutely homogeneous. 


Homogeneous protoplasm is of the greatest rarity and as yet 
has been studied chiefly by the American, E. B. Wilson. 3 
It claims our highest interest because it represents apparently 
the simplest condition of the living substance which we 
know. In the second state we find the protoplasm consists 
of two fluids which exhibit a foam structure, that is to say, 
the two fluids are so mixed together that one, apparently 
the more fluid, forms droplets and the other holds these 
droplets apart and separates them from one another com- 
pletely. As is well known, Professor Butschli has specially 
studied protoplasm in this condition, and has founded the 
theory, which he has further defended, that we encounter in 

FIG. 9. Striated muscle fibers of a rabbit, colored by Bielschowski's method 
and then teased so as to demonstrate the single muscle nbrillse. After a preparation 
of Prof . Poll's. 

this foam structure the essential true fundamental structure 
of living substance. For this view much may be said. 
Whether, however, we may assume that protoplasm, which 
is apparently homogeneous, also really possesses a foam 
structure, although it escapes our present observation, must 
remain undecided. In its third condition protoplasm is no 
longer simple because new structures have arisen in it which 
are probably also living, but which differ from protoplasm 


in appearance and behavior; thus, for example, if we study 
the development of muscles, we find at first cells with the 
usual so-called undifferentiated protoplasm. In this appear 
fine fibers which we name fibrillae, and which are no longer 
simple protoplasm, but really something new, Fig. 9. These 
fibrils effect the contraction of the muscle. They develop 
themselves, clearly in order to take over this special function 

of the muscle cells. Accordingly we 
designate the third condition of pro- 
toplasm as the differentiated. 

We must now turn to a consider- 
ation of the nucleus. It appears in 
the majority of cases as a body with 
definite limits, completely surrounded 
by protoplasm and with special sub- 
stances in its interior. Usually one 
can distinguish without difficulty a 
network, and in the meshes of this 
network the nuclear sap. The net- 
work varies extraordinarily in the 
single nucleus, but has one striking 
peculiarity, namely, that it may be 
easily artificially colored. On account 

of this peculiarity the substance has been named chromatin. 
Nucleus differs in one respect very noticeably from protoplasm, 
for the nuclei develop no new structures comparable to those 
which we may observe in protoplasm. A nucleus, to be sure, 
changes during the development of tissues more or less, but 
we cannot observe new structures in the nuclei. This fact is 
of special significance for the considerations which are to be 
presented in the next following lecture. For this reason 
attention is now directed to this peculiarity of the nucleus. 

FIG. 10. A vesting nucleus 
after ordinary preservation 
and staining with iron hasma- 
toxyline. From a cell of the 
intestinal epithelium of a sala- 
mander. After M. Heiden- 
hain. Magnified 2300. 


Although the nucleus changes comparatively little during 

the progressive division of the cell, yet during the division of 

the cell matters are 

very different, for 

during every cell Hsa*w "?M^W 

*- ** - t&> 

cleus passes 
through wonderful 
t r a nsf ormations. * 
During these 
transform ations 
the sharp limits of 
the nucleus disap- 
pear, and the nu- 
clear substance 
gathers together 
in small masses to 
which we apply 
the name chromo- 
somes. Each 
chromosome di- 
vides, and one 
piece of each 
tributes to 
formation of one of 

FIG. ii Red blood cells of an embryo duck in vari- 
ous stages of division. The pictures show the origin, 
COn- division and migration of the chromosomes, the spindle, 
the t ^ ie reconst ^ tutlon f tne daughter nuclei after the division 
of the cell bodies. After M. Heidenhain. Magnified 


the new nuclei; the 

other piece to the formation of the other nucleus. This process 

may now be found exactly described in the text-books. Every 

* Reference to the so-called direct division of cells, or amitosis, is intentionally 
omitted. This form of division is rare, and the consideration of it is unessential 
for our present purposes. 


student of medicine, or of biology, has opportunity in his prac- 
tical laboratory work to see for himself the formations of the 
dividing nucleus, and I may therefore allow myself to omit 
a detailed description of this phenomenon. But there is 
something else I should like to say to you concerning the 
nuclei. It is now established that the nucleus has an entirely 
different chemical composition from the protoplasm. In 
protoplasm and in nucleus we have to do cheifly with proteids, 
for they are the chief components of both structures. The 
proteids in the nucleus are, however, in certain respects 
simpler than those in protoplasm. For this and other reasons, 
it is believed that the nutritive material must first reach the 
nucleus in order to be worked over in the nucleus and to be 
later returned from the nucleus to the protoplasm. The 
chemical relations between the nucleus and the protoplasm 
are of the greatest significance. I must ask you to consider 
that I am not a competent biological chemist. In recent 
years chemical biology has made many beautiful and im- 
portant discoveries. It is understood that we must seek the 
explanation of most vital phenomena in the chemical altera- 
tions which occur in the body. If we should ever get so far 
as completely to understand life it will be only when chemists 
are in a position to explain vital phenomena chemically. We 
incline to the belief that the nucleus is absolutely necessary 
to the functions of life. It is besides instructive to learn that 
in certain lower organisms, in which we can distinguish no 
definite nucleus, such as we usually observe, nevertheless 
nuclear substance occurs scattered in the protoplasm. From 
such observations we draw the conclusion that for the main- 
tenance of life it is necessary to have not only the complicated 
protoplasm, but also the presence of the differently compli- 
cated nuclear substance. We cannot hope to reach a basis 


for the explanation of life until we shall know how the 
chemical alterations go on in the living substance, which 
is a highly complicated mixture of many organic combina- 
tions of various sorts, all carried by great quantities of 

A good example 
of the complica- 
tion of the phe- 
nomena is offered 
us by the condition 
of the nucleus in 
certain unicellular 
organisms. In the 
cells of the highest 
plants and ani- 
mals the nucleus is 
always a simple 
unit, but there are 
many species of 
protozoa known in 
which the nucleus 
is double, so that 
there appear to be 
two nuclei of un- 

equal size, Fig. 12. FIG. 12. A unicellular animal, an infusorium (Nassala 
T, i r _j. elegans). Natural length o.i mm. 9, Macronucleus; 

10, micro nucleus. After Schewiakojf, from Lang's 
Covered that the VergUichende Anatomic. 

larger nucleus 

plays a role in the nutrition and growth of the cell while 
the smaller nucleus has assumed exclusively the functions 
which lead to the division of the cell. Nature makes here 
for us an experiment in that she has separated in space the 



two functions of the nucleus, which are usually carried out by 
a single unitary nucleus. 

Vital phenomena rest on chemical processes by which 
energy is set free to show itself through the activities of the 
living being. 

The first thing which the beginner learns is that chemical 
change, or metabolism, plays the chief role in all biological 
phenomena. The biologists describe the intake and excre- 
tion of the nutritive material, and attempt to trace the change 
to which this material is subjected in the cell. Cells possess, 
of course, no mouth. They can absorb material only through 
their surfaces. Therefore the surface of every cell is of the 
utmost importance for the continuation of its life, and the 
investigation of this surface and its tension has been eagerly 
pursued of late. Important results have already been pro- 
duced; as, for example, it has been discovered that the surface 
tension during the impregnation of the ovum must be changed 
if the spermatozoon is to enter, and after the spermatozoon 
is in the interior of the egg the surface tension is again changed. 
The gifted German- American investigator, Jacques Loeb, 4 
has advanced the hypothesis that the egg has a superficial 
layer of lipoid substance which at the time of impregnation 
passes into a soluble condition. This hypothesis has since 
been confirmed by the experiments of Ralph L. Lillie. 5 

The egg of the sea urchin, after remaining some time in 
sea water, becomes more resistant so that the spermatozoon 
cannot penetrate the eggs as easily as when they were fresh. 
If such resistant eggs are treated with sea water, to which one 
has added 0.3 per cent, of ether, by which supposedly lipoid 
substances are dissolved, it is found that the eggs are more 
easily fertilized. But even if Loeb's hypothesis is not ab- 
solutely correct, the phenomenon itself remains extremely 


significant because we must assume that almost incredibly 
small quantities of material occasion alterations in the ovum. 



FIG. 13. Muscle nuclei of the giant salamander (Necturus) in various stages. 
A, nucleus of 7 mm. larva before differentiation; B, from a 26 mm. larva at the 
beginning of differentiation; C, from the adult animal, 23 mm. long, after comple- 
tion of the differentiation. After A. C. Eycleshymer. 

So soon as one spermatozoon penetrates the ovum, as is found 
in the case of most eggs, no spermatozoa can follow. If we 


study the phenomena with the microscope we are unable to 
observe that anything is given off from the spermatozoon to 
the ovum. The changes in the ovum, therefore, by which 
other spermatozoa are excluded depend upon minimum 

Teleology, or the adaptation to an end, rules all living 
bodies. Accordingly we must assume a priori that the 
limited size of cells is a purposeful adaptation. It is probable 
that the size of the cells is favorable to the metabolism which 
occurs chiefly in protoplasm. It depends on the one side 
upon the surface of the cell, and on the other upon the nucleus, 
which must itself be nourished and also supply material to 
the cell body. Therefore it is important that the distances 
remain small. As an example of the relation of the nucleus 
to the differentiation of protoplasm, I wish to cite the investi- 
gations of Eycleshymer 6 on the development of muscle fibers. 
The work was done in my laboratory. He observed that the 
mass of chromatin increases in the nucleus of very young 
muscle fibers, and that thereafter the formation of the muscle 
fibrils begins. As the development of the fibrils progresses, 
the amount of chromatin in the nuclei diminishes, Fig. 
13. It is clear that the chemical combinations are distrib- 
uted through the protoplasm chiefly by diffusion, a slow 
process. Hence the great importance of the small dis- 
tances. A more exact conception of this we may gain from 
the investigations on the early development of pigeons, 
which have been carried out at the University of Chicago, 
at the suggestions of Professor Whitman. 7 The egg of the 
pigeon, like most other eggs, is fertilized by a single spermato- 
zoon. The influence of this does not at first stretch very far 
in the ovum, so that the territory which we may designate as 
saturated is small. All around this territory we have, so to 


speak, non-saturated protoplasm, into which a number of 
spermatozoa make their way and maintain themselves for 
some time, disappearing, however, in a few hours, and ap- 
parently in the same measure as the influence of the fertiliza- 
tion proper expands. In animals, which have relatively 
small eggs, the whole becomes more rapidly saturated by 
fertilization, so that only one spermatozoon can go in. 

We spoke before of the great influence of small quan- 
tities upon the protoplasm. It is certainly the greatest ad- 
vance of modern physiology that we have become better 
acquainted with the significance of this phenomenon. We 
have here to consider especially a new kind of action at a 
distance which takes place constantly in our own bodies. 
When, forty years ago, I made my first physiological experi- 
ments, the nervous system was the only means known to us 
to effect action at a distance within the animal body. We 
studied industriously nerve fibers, sensations in the brain, 
and the stimuli which passed from the central nervous system 
to the various organs of the body. Since then we have dis- 
covered the phenomenon of so-called internal secretion. The 
glands form secretions which are further used in the body. 
The majority of glands have a duct which carries off the se- 
cretion; thus, for example, in the case of the liver we have the 
ductus hepaticus which conducts the secretion of the liver 
to the intestinal canal. It is known now, however, that there 
are glands which have no duct, Fig. 14. Nevertheless, these 
form secretions which are delivered immediately to the blood 
and then are distributed by means of the circulation through 
the entire body. It has been learned that each internal secre- 
tion, which is formed in very small quantities, exerts a sur- 
prisingly great influence on other parts of the body which 
may be quite remote from the gland. I may mention as in- 



ternal secretions the products of the thyroid gland, the hy- 
pophysis and the suprarenal bodies. The thyroid gland in- 
fluences the condition of the muscles; the hypophysis, the 
growth of bones; and the suprarenal capsule the activity of 
nerves. In passing it should be remarked that the phenom- 
ena are not simple, but complicated. In all cases, however 
we see that many cells of one kind depend as to their structure 


FIG. 14. Section of a thyroid gland. The organ consists of closed cavities, 
each of which is bordered by a layer of epithelial cells. Since the gland has no 
duct, the secretion can be carried off only by the blood. After Koelliker. 

and their activity upon the influence of these internal secre- 
tions. It is not the case of a single cell, but always of many 
which have the same constitution. 

The brilliant investigations of Ehrlich and others have 
founded the new doctrine of immunity. In this case we 
have to do with the phenomenon similar to that of in- 
ternal secretion. An animal becomes poisoned by patho- 
genic organisms, and then forms itself a contra-poison, or so- 


called antitoxin. That the toxins and antitoxins occur has 
been demonstrated with certainty, but the quantities are so 
small that we have not yet succeeded in isolating them. 
From these and other similar phenomena we learn that the 
condition, composition and structure of the living substance 
is of fundamental significance, and is, strictly speaking, more 
important for the comprehension of vital phenomena than the 
fact that the physical basis of life shows a strong tendency to 
form cells. 

We may now put into words the deduction which we may 
draw from to-day's lecture. Our conclusions may be ex- 
pressed as follows: 

The new cell doctrine still recognizes the importance and 
significance of cells. Cells remain the units of morphology, 
but from the physiological standpoint they appear as adap- 
tations which, especially by their size and proportions, create 
favorable conditions for metabolism. The living substance 
is more important to biologists than its tendency to form cells. 
Hence we consider the chief problem of biology to be the 
investigation of the structure and chemical composition not 
of cells, but of the living substance. The new conception has 
won its way gradually. It corresponds to so fundamental a 
change of our views that we are justified in .describing the 
new conception as the new cell doctrine. 



Your Magnificence! 

We endeavored in yesterday's lecture to familiarize our- 
selves with the new cell doctrine, according to which a much 
greater importance is attributed to the composition of the 
living substance than to the fact that this substance has a 
strong tendency to form cells; all the same, cells remain the 
most convenient units of biological research, although they 
can by no means be found always completely separated from 
one another. But even if the cells are not separated, it is 
practical and convenient to designate each nucleus, together 
with its surrounding protoplasm, as a cell. Every fully 
formed tissue of the animal body has at least one character- 
istic kind of cells, or in other words the cells of a tissue exhibit 
among themselves similar relations and similar structure. 
Hence we can direct our attention to the single cell which we 
value as the paradigma. 

In man, as in the great majority of multicellular ani- 
mals, development begins with simple cells which arise by the 
segmentation of the ovum. From the simple cells the tissues 
of the adult develop gradually. As I told you yesterday, we 

* The term cytomorphosis was proposed by me in 1901. The corresponding 
conception- was first definitely propounded in the Middleton Goldsmith Lecture, 
published in 1901. This lecture has recently appeared in the German translation in 
my book "Die Methode der Wissenschaft" (Gustav Fischer, Jena). My book 
"The Problem of Age, Growth and Death" (New York, Putnam's, 1908), treats of 
cytomorphosis in some detail, although in somewhat popular form. 



observe no similar developmental processes in unicellular 
organisms. The transformation of cells which leads to the 
formation of tissues is designated, as differentiation. In the 
earliest stages of the embryo the cells are remarkably like 
one another, Fig. 15, but in the course of their further develop- 
ment they become unlike or different; hence the designation 
differentiation. How these differentiations arise is an ex- 
tremely interesting question about which we know very 
little, because as yet we have become acquainted almost 

FIG. 15. Section through the posterior part of a rabbit embryo of seven and 
a half days, to show the three germ layers, each of which consists of undifferentiated 
cells. Magnification 250. 

exclusively only with such alterations as are visible with the 
microscope. The visible alterations, however, we must 
assume, are the consequence of chemical processes which we 
still have to discover. The visible alterations have been 
studied with the utmost care by many eminent biologists, 
and we are able to say that they follow strict laws. It is 
convenient to have for the complete transformation of cells a 
short, scientific term. As such I propose "cytomofphvsis" 
We are now to occupy ourselves with the laws of cytomor- 
phosis so far as these have been determined. The develop- 
ment of simple cells into differentiated we call progressive 


development. The first question which we have to answer 
is: Does a regressive development also occur? The pro- 
gressive is well known to us and we know much about it. I 
incline strongly to the opinion that it is the only kind of 
development, but there are not lacking investigators who 
have come to the belief that under certain conditions develop- 
ment may be reversed. 

My point of view is determined in part by the fact that 
it has been possible in cases where a regressive development 
had been assumed to make sure by careful investigation that 
opinion had been misled by appearances and that in reality 
the development was progressive in these cases also. I may 
mention three examples; first, the nerve fibers. If one cuts 
through a nerve, the fibers in its peripheral part degenerate 
quite rapidly. After several days, however, under favorable 
conditions, newly formed nerve fibers appear in the peripheral 
part. Many investigators have eagerly advanced the view 
that these nerve fibers rise in their place and that they have 
been newly formed in the degenerating nerve. More careful 
research has made it certain that the newly formed fibers 
have simply grown out upon the ends of the healthy fibers, 
left in the central part of the nerve. If one cuts off the roots 
of a tree, the roots which are separated from the trunk 
decay; but if the tree is left one can find later in their place 
living roots, which, however, have not arisen from the dying 
roots, but have grown out from the central healthy parts. 
The fundamental experiments of Harrison 8 make it sure 
that nerve fibers in all cases are formed only in the way 
mentioned. About the origin of nerve fibers there has been 
a long controversy. My countryman, Harrison, has occupied 
himself for several years with this question, and has supported 
his conclusion by the most varied investigations. Four 


years ago he invented a new method to keep isolated cells 
and pieces of tissue living in vitro. Utilizing the new method, 
he subjected young nerve cells, neuroblasts, to observation 
and was able to see under the microscope nerve fibers grow 
out from the living cell. Cultures in vitro are now made 
frequently, and we expect from the application of Harrison's 
ingenious method many valuable discoveries. From time 
to time we find the paradox justified which says: "New 
methods are more important for science than new thoughts. 77 






J t 


1 ' 


FIG. 1 6. Degenerating muscle fibers after experimental injury, a, b, after 
3 days; c, after 8 days; d, 26 days; e, 10 days; /, 21 days; g, 43 days. 4f/er Erws* 

The second example we get from muscles. If the fibers of 
a skeletal muscle are mechanically injured they degenerate 
quickly; later, however, we find new formed muscles. Here 
the processes are of quite a peculiar sort. Every muscle 
fiber consists chiefly of muscular substance which we can 
easily demonstrate by the contractile fibrils. It is the 


muscular substance which breaks down after the injury. 
The muscle fibers, however, contain also the so-called muscle 
corpuscles, which are nothing more than little accumulations 
of undifferentiated protoplasm, containing the nucleus, 
Fig. 16. After the injury these corpuscles do not degenerate, 
so that undifferentiated protoplasm remains from which the 
new formation starts. The differentiated part of the muscle 
disappears and there is in this case no question of a regressive 

FIG. 17. ^Longitudinal section of the regenerating extremity of a young lobster 
one day after amputation. There is formed at first a blood clot (bd) under which 
the epithelial cells e, e', grow across to form the commencement of the new part. 
Magnification 240. After V. E. Emmel. 

The third example we will take from the lobster. If the 
extremities of the larvae of this animal are* cut off, the ex- 
tremities will be newly formed. It was formerly assumed 
that we had to do in such a case with a new regressive develop- 
ment. The investigation made by Emmel 10 in my laboratory 
has rendered the real history clear. The cells of the outer- 
most layer of the skin in these larvae are undifferentiated cells, 
which after the injury grow and spread over the wounded 
surface. They then multiply and by their steady growth 


create the new extremity. Afterward they differentiate 
themselves in part in order to form the various tissues which 
are characteristic for the limbs of Crustacia, Fig. 17. The 
nerves and probably the blood-vessels penetrate subsequently 
into the newly formed extremity. To conclude: Until it is 
shown in at least one case with absolute certainty that 
regressive development occurs it must remain very improbable 
in the minds of earnest biologists that such a development 
occurs at all, or can occur. 

Cytomorphosis defines comprehensively all structural 
relations which cells or successive generations of cells undergo. 
It includes the entire period from the undifferentiated stage 
to the death of the cell. The differentiations which occur in 
the body are very different among themselves, and as is 
well known these differences are much greater in the higher 
than in the lower animals. Hence it is by no means easy to 
recognize at once what is common to these changes, but some 
important results have already been won. First of all it is 
to be stated that the differentiation in all cases shows itself by 
visible new functioning structures in the protoplasm. There 
exists here between the protoplasm and the nucleus a marked 
contrast, for, as you have learned, the nucleus acquires, strictly 
speaking, no new structures, although it also changes with the 
progressive development. 

We know that the visible alterations in protoplasm are 
initiated by invisible ones. Various experiments afford the 
proof of this. The first rudiment of the fore-leg of the 
larva of an amphibian may be cut off and then grafted into 
another part of the body, where the rudiment will develop 
further. 11 The rudiment, or anlage, at the stage which is 
specially suited to this experiment, is a little bud on the 
surface of the larva. Microscopic examination shows that 


its cells are simple and more or less similar to one another.^ 
Tissues in the stricter sense are not present. In spite of the 
fact that these cells attain their further development under 
unnatural conditions they in themselves form muscle fibers, 
connective tissue and bone. In spite of the fact that the 
microscope shows us nothing in these cells by which we can 
recognize their future development, we must assume that 
the specification already exists. Professor Harrison, as I 
have already mentioned, devised a method to cultivate tissues 
in vitro. One can cut out from an embryo chick little pieces 
at will and cultivate them artifically in vitro and bring them 
to further development. In this manner W. H. Lewis has 
succeeded in studying the specific cell formation. The 
cells of the mesenchyma grow in the manner of mesenchyma ; 
the cells of epithelium as epithelium. Neither in the nucleus 
nor in the protoplasm in these cells can we demonstrate 
peculiarities which we can regard as the causes of the unlike- 
ness of their growth, but surely there exist in these cells 
peculiarities which are not visible to us and which determine 
the performances of the cells. It is not going too far to 
assume that in all cases the invisible alterations of protoplasm 
precede the visible. 

The young cells in an undifferentiated vertebrate embryo 
have little protoplasm. The first thing that must happen is 
that the protoplasm grows, a phenomenon which one may 
easily observe with the microscope. After the protoplasm 
has grown, differentiation proper may begin. It is always 
gradual and consists essentially in this, that something new 
becomes visible in the protoplasm. In part, especially in the 
so-called epithelium, we have to do with the formation of 
superficial membranes around each cell. More important 
probably are the new formations in the protoplasm, Fig. 18. 


The developing nerve fibrils I have already mentioned. In 
nerve cells there appear very fine fibers which develop grad- 
ually, making a network in the cell, Fig. 19. There also appear 
deposits of a substance which reacts to stains differently from 
the protoplasm and the fibrils, Fig. 18, k, k'. The deposits in 
question have received the somewhat fantastic name of "tig- 


FIG. 18. Motor nerve cells from the spinal cord of a rabbit, ke, nucleus; den, 
dendrite; Ax, nerve fiber, and x, its origin; k, k f , Nissl bodies. After K. C. Schneider. 

roid substance." We notice also peculiar cavities which form 
a net- work in the protoplasm of the cell, and are filled with 
fluid. In the gland cells one sees the material distributed in 
the protoplasm which is utilized later for the execution of the 
specific activities of the gland cells, Fig. 20 This material is 
not the secretion proper, but a primary stage. In quite 
another wise do the intervening supporting tissues develop, 
for in them the cells show a strong tendency to separate from 
one another and to produce special structures in the inter- 

3 2 


cellular spaces. It is not practicable to lay further illustra- 
tions before you. 

Progressive development is closely connected with another 

phenomenon. The 
embryonic tissues 
grow with immense 
rapidity, the differen- 
tiated tissues on the 
contrary grow slowly. 
If we investigate the 
conditions more care- 
fully we learn that the 
cells gradually lose 
the power of division 
as they are differen- 
tiated. If the differ- 
entiation progresses 
far, then probably the 
capacity of division is 
lost to the cells alto- 
gether. Formerly we 
had no exact concep- 
tion of the rapidity of 
growth in embryos. 
This is a question 
about which I have 
been greatly interested 
for many years. In 
the book " The Prob- 
lem of Age, Growth 
and Death," which I 
published in 1908, I 

FIG. 19. Nerve cell from the spinal cord of 
man. The Nissl bodies have been dissolved out 
and the cell so colored that the neurofibrils are 
brought out. fi, fibrils; x, fibrils in a dendrite; ax, 
nerve fiber; lu, space left by the dissolving of the 
Nissl bodies; ke, nucleus. From K. C. Schneider, 
after Bethe. 



have discussed more fully the alterations of the rapidity of 
growth with age and its relation to the increase of differentia- 
tion. The development of a mammal begins with an extra 
power of growth. How gradual the increase is it is not yet 
possible to determine exactly, but certainly the original daily 
increase is not less than 1000 per cent. This holds true for 
man also. 

Immediately after birth one finds the highest rapidity in 
the rabbit to be not quite 18 per cent, per day; in the chick 
not quite 9, and in the sc h s .i 

guinea pig about 51/2 per 
cent. The relations for 
man are similar. It is 
therefore clear that the 
animals mentioned and 
man also have lost at the 
time of their birth 99 per 
cent, of their original 
growth capacity. In fact, 
from the biological stand- 
point we are really old by 
the time we are born and 
the alterations which make 
us old have for the most 
part already occurred. The further losses which we suffer 
from birth to old age are comparatively small, and we live 
long only because these losses take place slowly. If the 
progress of alteration after birth should be even only 
approximately as swift as before birth we should live only 
a very short time. And in fact the microscope shows us 
that the multiplication of cells after birth is by no means so 
great as before, and that it goes on slowly. 


FIG. 20. Cell from the pancreas of the 
larva of Salamandra maculosa. sec. k, 
sec. k f , secretory granules; x, formative 
focus of the same; fi, secretory fibrils; ke, 
nucleus; schs. i, closing plate. After K. C. 


Cytomorphosis includes more than differentiation proper. 
By continuing it leads to the degeneration of the cell. De- 
generation appears in many cases to depend upon the trans- 
formation of the entire protoplasm so that no more true 
protoplasm remains in the cell. Under such conditions the 
cells do not remain viable. A good example of this process 
is afforded by the epidermis, the outer skin, the lowest layer 
of which consists of undifferentiated cells, which can grow and 
multiply, Fig. 22. Some of these cells liberate themselves 
from their parent layer and migrate toward the surface. 
During their migration their protoplasm is gradually changed 
into horny substance, and when this change is complete the 
cells have completed their cytomorphosis and are dead. The 
surface of our body is covered by dead cells. In this case as 
in all similar cases degeneration leads to the death of the cell. 
We can accordingly distinguish four chief stages of cytomor- 

1. Undifferentiated or embryonic condition. 

2. Differentiation. 

3. Degeneration. 

4. Death. 

Only in this succession can alterations of cytomorphosis 
occur, but it must be added that if regressive development 
should occur it would form an exception to this rule. 

The red blood- corpuscles afford us an excellent example of 
a complete cytomorphosis. They begin their development 
as simple cells, with a well formed nucleus but little proto- 
plasm. Next we observe that the protoplasm grows. Not 
until it has grown sufficiently does it acquire its character- 
istic color through the formation of hemoglobin, thus be- 
coming a young red blood-corpuscle which may still grow a 


little, although the nucleus at the same time begins to 
grow smaller. After the nucleus has become considerably 
smaller it is separated from the body of the corpuscle. As to 
how this separation occurs authorities are still disputing. The 
part left without the nucleus is the so-called mature blood- 
corpuscle which, however, is not able to maintain its own 
but soon breaks down. Every day in each of us numberless 
millions of blood-corpuscles are disappearing. The car- 
tilaginous cells also pass through a complete cytomorphosis 
which, when the cartilage is replaced by bone, terminates with 
the dramatic disappearance of the cells. Cartilage is devel- 
oped from embryonic mesenchymal cells. The cells enlarge 
and there appears between them the basal substance which 
imparts to cartilage its characteristic physical consistency, 
Fig. 8. The so-called ossification of cartilage begins with the 
completion of the chondral cytomorphosis, during which the 
cells pass through rapid degenerative hypertrophy, Fig. 21, 
which involves the destruction of the basal substance, and 
which closes with the disintegration, or autolysis, of the cell. 
Thereupon bone is ; formed in the place of the cartilage which 
has disappeared. ( The nerve cells, at least in vertebrates, 
pass through their cytomorphosis in a special tempo. Their 
differentiation advances quite early to the high point at 
which the cells long remain. The degenerative alterations 
follow very slowly, so that we usually do not encounter mental 
weakness in man until advanced age, the weakness being 
caused by senile atrophy of the brain cells. We are in- 
debted to the peculiar course of the cytomorphosis of the 
brain for the extraordinarily long-lasting functional capacity 
of this organ. The leaves of plants offer us an excellent 
example of cytomorphosis. The leaf bud consists of em- 
bryonic cells which grow and differentiate themselves to 


form the leaf. Later the cells degenerate and die. The leaf 
becomes dead and falls. It would be easy to lay before 


FIG. 21. 

FIG. 22. 

FIG. 21. Cytomorphosis of the cartilage cells. From a section of the vertebral 
arch of a pig embryo, a-e, successive stages; in e, the letters kn refer to the limit of 
the cavity which is no longer filled by the degenerating cell. 

FIG. 22. Epidermis from the sole of the domestic cat. Ba. Schi, basal germ 
layer; Hor. La, hor. z, hor. z', horny layer formed by dead cells; ker. k, layer of cells 
which are being cornified; Ml. La, middle layer of cells which are migrating upward 
and at the same time enlarging; Pa, site of a hypodermic papilla. After K. A . Schnei- 


you many other examples of completed cytomorphosis of the 
most various cells. It might, however, be better to pass 
over to other considerations. 

Death and subsequent removal of cells play a great role 
in our lives. Even in early developmental stages we find cells 
dying and even whole organs which maintain themselves only 
for a certain period and then disappear almost or completely. 
Thus there is an embryonic kidney in which only small re- 
mains can be found in the adult. It is therefore clear that 
there must be some arrangement provided to make good the 
loss of cells. Nature accomplishes this by not bringing all 
cells to further development and by preserving a stock of less 
differentiated cells in the body. Of these I have already 
mentioned an example, the epidermis, the cells of the under 
layer of which preserve an embryonic character. Only by the 
presence of these cells which keep the essential embryonic 
type is the continual renewal of the epidermis made possible. 
For every hair there remains a special group of embryonic cells 
upon the hair papilla, which provide for the growth of the 
hair. Since these cells are not differentiated, they can multi- 
ply and thus furnish cells for the formation of the hair. The 
cells of the hair complete their cytomorphosis, but their sister 
cells remain on the papillae undifferentiated. We thus see 
that while cytomorphosis can go on only in the one direction, 
it remains true that the cytomorphosis can be arrested and 
that it may go on in the different tissues with unequal rapidity. 
Thus it comes that we encounter cells in the adult animal in 
every possible stage of cytomorphosis. There arise in every 
one of us every day cells which complete their cytomorphosis, 
and there are others which have hardly begun it. We cannot 
understand the relations in the adult animal if we do not 
consider at once both the daily dying off of old cells and 


also the daily multiplication of cells which have remained 

We recognize that the embryonic cells are of great impor- 
tance not only during the embryonic period, but also in the 
adult. How great this importance is is revealed in the inves- 
tigation of regeneration. Very many animals, if parts of 
their body are removed, will form the missing parts anew. If, 
for example, we break off the tip of the tail of a lizard, there 
will arise a new tip which is formed by the growth of undif- 
ferentiated tissues. There are worms which multiply by 
forming in the middle of their bodies the so-called budding 
zone. Karl Semper 13 has studied the process in annelids, 
and discovered that in them the budding zone consists of cells 
of the embryonic type. Gradually these cells advance in 
their cytomorphosis, and so there arises a new tail for the 
anterior part of the worm and a new head for the posterior 
part, and thereupon the two parts separate and two complete 
works have arisen from the single animal. We are accustomed 
to designate those animals which have a more complicated 
structure as the higher. Now it is clear that if an animal is 
composed of relatively few cells great complexity of structure 
is impossible. Further we observe that when a highly formed 
animal is to be produced, nature takes care that a large 
number of embryonic cells is produced. In the lower animals 
development is of the so-called larval type. From the little 
ovum there arises quickly a young animal which lives free 
and must take care of itself. Such a larva must possess, even 
if only in simple form, all the principal organs, and since the 
cells must be so far differentiated that they can take over the 
various functions, they necessarily lose in part their capacity 
to multiply, and, what is still more important, the capacity 
to produce other kinds of cells. We see always that when 


a cell has begun to develop in one direction it cannot start 
out to develop in any other direction. In the higher animals, 
on the contrary, we find a relatively large egg which has become 
large through the storing up in it of yolk or nutritive material. 
The developing ovum can nourish itself for a long time from 
this yolk. In this type of development we encounter not 
larvae but embryos which are characterized thereby that they 
contain many cells of the embryonic or undifferentiated type. 
These cells assume definite groupings to form the rudiments 
or anlages of the various organs. So that we may say that 
the anatomical development progresses without there being 
a corresponding alteration in the structure of the single cells. 
Thus we observe in the human embryo the stomach, or other 
organ, which shows the essential characteristics of its total 
form and of its relations to other parts of the body, and yet 
consists of cells not differentiated. In my opinion we are 
justified in regarding the embryonic development as a con- 
trivance to make the postponement of a cytomorphosis pos- 
sible, in order that the total number of cells available for 
differentiation shall be larger. Of the great importance of 
the number of cells we can get some notion by considering the 
cortex of the brain. The number of pyramidal cells in the 
cerebral cortex of man is over 4,000,000,000. This number 
is not astonishing; a cubic millimeter of blood contains be- 
tween four and five million corpuscles. 

The purpose of differentiation is known. Every living 
cell certainly carries on all the essential functions of life. In 
the higher organisms we encounter a division of labor. 
Each organ takes over as its special task one or another 
function, which the organ performs to the advantage of the 
whole. These functions are not new; they are always such 
as are common to the living substance in general, and in 


each single organ there comes about, so to speak, an exaggera- 
tion of a single function. Protoplasm is sensitive and 
irritable. In our case, our sense organs take care of the 
sensations to the advantage of the whole body. Protoplasm 
has contractility, and this function is assumed by the muscles 
again to the advantage of the whole body. Similarly, the 
glands take over the formation of secretions the excretory 
organs, the elimination of urea, etc. Now we know that the 
various structures which we can see in protoplasm, and which 
are characteristic for the sense organs, muscles, gland cells, 
etc., determine in each case the special performances of their 
respective cells. Briefly expressed, the whole meaning of 
differentiation is physiological. The peculiarities which we 
can recognize with the microscope in differentiated cells exist 
in order to render it possible for the cells to accomplish 
their special activity. It would be superfluous to linger over 
this conception, to amplify, or even to justify it by a rounda- 
bout demonstration. I wish, however, to specially emphasize 
the fact that the entire doctrine of cytomorphosis renders 
it clear that structure in living substance is the essential 
thing. This has become clear to us from the phenomenon of 
differentiation. We may probably go still further and say 
that even in those cases in which we as yet cannot recognize 
any microscopic structure, structure is still present. The 
conception of the significance of structure of organization, 
which we win from the investigation of differentiated cells, 
applies also to protoplasm. It is well known, as I have 
already mentioned, that protoplasm is chemically extremely 
complicated, but the chemical combinations are not simply 
mixed together as in a simple solution, but are in part sepa- 
rated spatially. When we state that the living substance 
has organization we base our view not only on the application 


of that notion of structure which we derive from the study of 
differentiated cells, but also on direct observation. Such 
investigation has not yet brought us very far. It teaches us 
that protoplasm is not completely uniform, but usually 
contains fine granules which are unlike among themselves. 
Micro-chemistry is a nascent science from which we may 
expect much, although she has presented us yet with but little. 
It is the science which investigates the chemical substances 
and processes in cells with the help of the microscope. We 
have already succeeded in proving that granules, chromidia, 
fatty substances, lipoids and various proteids exist in 
protoplasm in a visible form. We have also learned through 
micro-chemistry something of the distribution of iron and 
phosphorus in the cell. We have not yet got very far, but 
far enough to be justified in saying that the organization of 
living substance is known in part by direct observation. 

We are acquainted with another structure in the proto- 
plasm of many cells, the so-called centrosome which we can 
only allude to here, although its occurrence again demon- 
strates the importance of organization. 

A word more concerning the nucleus. In the nucleus 
organization can be observed easily and without exception, 
and since the nucleus also belongs with the living substance, 
its peculiarities also serve to strengthen us in the belief in 
the importance of organization. Whoever knows the won- 
derful history of the chromosomes by his own observation, 
must be convinced that the nucleus has a very complicated 

Now to the conclusion. Cytomorphosis is the funda- 
mental conception of the entire development of all multi- 
cellular organisms, and is the foundation at once of morph- 
ology and physiology. It explains to us many processes 


which we otherwise could not understand. It includes the 
whole doctrine of the normal and pathological differentiation 
of cells. The principal conclusion which we may deduce from 
this doctrine is that all living substance possesses an organiza- 
tion, and that probably without organization life is impossible. 



Your Royal Highnesses! 

To your Royal Highnesses I wish to express my profound 
and respectful thanks for the honor of your presence, which 
has for me a great and unforgetable significance. The partici- 
pation of your Royal Highnesses in to-day's lecture is a high 
distinction not only for me but for my university, which we 
gratefully acknowledge. 

Everything living arises only from the living. The phe- 
nomenon of propagation of animals and of plants has always 
excited the interest of mankind. The ancients recognized 
that only living parents could have a living progeny, and it 
was said "Omne vivum ex vivo." But for a long time the 
opinion prevailed that life might continually arise anew. We 
know now, however, with certainty that a new generation of 
this kind does not occur, and assume that under present con- 
ditions a new generation of life is improbable, perhaps impos- 
sible. We know too little to venture a positive opinion. 
Schaefer, 15 the gifted physiologist of Edinburgh, has expressed 
a supposition that new generation still occurs upon our earth 
and escapes our observation because we do not know the con- 
ditions which render such generation possible. This is an 
interesting speculation, but with this possible exception we 
must attribute to the saying, " omne vimim ex vivo" absolute 

With the progress of our knowledge we have made interest- 
ing discoveries concerning the manner in which the uninter- 



rupted continuation of the living substance is assured in 
various organisms. The simplest cases occur in the lower 
organisms, in bacteria, etc., in unicellular plants and ani- 
mals. In these the single individual, or the single cell, 
grows up to a certain size and then divides. In this man- 
ner the two daughter cells come to have part of the same 
substance as the mother cell, and so it goes on. This 
substance, so far as we can observe, does not change 
essentially with time. In the higher plants and animals 
we have in each case to do with many cells and we observe 
that the functions are unequally distributed among these 
cells. For the execution of various functions the cells become 
unlike among themselves. This is the phenomenon of dif- 
ferentiation of which we have already spoken. The majority 
of the cells are destined for the care of the whole, and perform 
their special functions. Some of the cells, however, are not 
utilized in this manner, but serve for propagation. When 
a flower unfolds in our garden we find in it certain special cells 
which have to do with the propagation. These do not show 
such differentiation as we may find in other cells of the plant, 
but remain at first relatively simple in their structure. The 
propagating cells mentioned separate themselves from the 
mother plant and form the seed. As essential in this case 
it appears that two cells are necessary for the process, one of 
which we designate as the egg cell and the other as the seminal 
cell. Two such cells unite and form a new cell, with which 
the further development begins. The mother plant may 
then die. We note in this case that the fate of the cells is 
extremely unlike, in that some of them are given over to death, 
while others remain permanently alive and serve for the 
propagation of the species. In the next lecture, in which we 
shall investigate the development of death, we shall occupy 


ourselves with the consideration of the phenomenon of death. 
At present we shall devote our attention to the propagating 
of cells. 

The kind of propagation which we find in the plant is 
called sexual and occurs also in animals. It is, however, by 
no means necessary that the propagation should occur by 
sexual means. Of the methods which nature applies for the 
multiplication of living individuals, I should like to mention a 
few to you briefly. 

Many methods of asexual reproduction are known to us. 
The art of increasing plants in this way is practiced by every 
gardener, and nature also makes use of the possibilities. 
Among animals we often find a multiplication of individuals 
effected by simple division. The zoologist describes to us 
the column-like growth of certain jelly-fish and the following 
transverse division of the column, so that a number of discs 
arise, each of which becomes a jelly-fish. Asexual reproduc- 
tion occurs among invertebrates in various forms. The pecu- 
liar division of certain annelids has been already mentioned. 
The budding zone is formed, and produces a new head and a 
new tail. In a parasitic tapeworm we have discovered a 
vesicular stage in the life cycle. At certain spots upon the 
wall of the vesicle arise new heads, each of which initiates the 
formation of a new tapeworm. Specially interesting are the 
cases of precocious division, which we have learned about 
recently, and in which we encounter the division of an egg 
before the embryo proper has developed. Thus Kleinenberg 16 
observed in certain earthworms that two individuals develop 
regularly from one egg, an observation which has been con- 
firmed by the American investigator, E. B. Wilson. 17 Still 
more remarkable are the occurrences in certain parasitic 
hymenoptera, in which not merely two but many individuals 


are created from a single egg. This phenomenon is termed 
polyembryony. It was surprising to discover recently that 
polyembryony occurs in a mammal. In the year 1885 Von 
Jhering observed that the armadillo regularly produces four 
embryos in one sac, and he expressed the supposition that they 
arise from a single ovum. Professor Patterson 18 of the Uni- 
versity of Texas has studied the phenomenon carefully in a 
species which occurs in Texas. The development of ordinary 
mammals begins with the formation of a small vesicle. At 
one pole of this vesicle there accumulate a small number of cells 
in which no differentiation is recognizable. The accumula- 
tion is termed the germinal disc and produces the embryo. 
Patterson obtained eggs of the armadillo in- the vesicular stage, 
and found upon each vesicle four distinct germs discs. Each 
disc forms an embryo. Thus it becomes certain that in this 
mammal four embryos, always of the same sex, arise from 
one ovum. 

It is also possible to cause artificial polyembryony with 
certain eggs. When an egg begins its development, it divides 
and when the egg is small the division usually produces two 
cells alike in size. Driesch 19 was the first to make the interest- 
ing experiment so to shake an egg in the two-called stage 
that the two cells were separated from one another. Under 
favorable conditions each of the separated cells forms an 
embryo. The original experiment was made with the eggs of 
sea urchins. The artificial polyembryos do not attain a nor- 
mal size, and therefore do not develop quite as do the natural 
embryos. The experiments of Driesch have been repeated by 
many Americans and much extended, and indeed with such 
eagerness that for a certain period we ^termed our embryolo- 
gists " egg Shakers. " You know probably that the Shakers are 
a Quaker sect, dedicated to celibacy. 


A special form of division is budding, which plays an im- 
portant role, especially among the hydroids. The process is 
described in all text-books, and need therefore be mentioned 
merely. A little superficial group of cells begins to grow and 
forms finally a new polyp. 

In the cases considered thus far, a number of cells partici- 
pate in the propagation. In the case of the so-called partheno- 
genesis the creation of a new individual starts from a single 
cell. This cell is an egg, which develops without being fer- 
tilized. Great interest was excited by the discovery of artifi- 
cial parthenogenesis by A. C. Mead. 20 In the artificial devel- 
opment we utilize chemical action which replaces fertiliza- 
tion proper, and so excites the ovum that it develops further. 

In all these cases the propagation is effected by the separa- 
tion of living material from the body of a living individual. 
The separated substance remains continuously alive. The 
substance may be comprised of many, several, or only one 
cell. The number of cells is unessential; essential is only 
that the substance is alive and remains alive. 

The separated substance inherits the primitive organiza- 
tion, or, more exactly expressed, has the parental organiza- 
tion, because it is unaltered parental substance. We come 
up against a question which we unfortunately cannot yet 
answer : How is the organization regulated ? It seems a matter 
of indifference how the asexual propagation is accomplished. 
Each time the development proceeds, until the original 
organization is completed. When the budding zone of anne- 
lids forms a new tail in the anterior part of the animal and a 
new head for the posterior part, we can only say that a regula- 
tion of the organization is shown. There is no means for 
determining more exactly the process. It seems to be clear that 
this regulation is not to be sought only in the developing cells 


themselves but also in part at least in an influence exerted by 
the rest of the body. In the case of polyembryony, the rudi- 
ment, or anlage, possesses the capacity of forming all tissues 
and organs. During regeneration also, which in many animals 
may go very far, we see that the complete structure is produced 
anew and we recognize here again the phenomenon which we 
call regulation. The physiological explanation of regulation 
we do not yet possess, although we have learned already a 
little concerning it. 

The sexual propagation plays a greater role than the 
asexual, and is often the exclusive method of progagation, 
especially in the higher plants and animals. We learned in 
yesterday's lecture that the cells of the animal body dif- 
ferentiate themselves, that is to say, that their protoplasm 
acquires new qualities and that their power of division 
diminishes. Differentiated cells are not suited for propaga- 
tion. If it should occur that all the cells of an animal or a 
plant should pass through a complete cytomorphosis, they 
would all die off, the organism would reach its end, and could 
produce no progeny. As a matter of fact, however, all the 
cells do not become differentiated. Of the undifferentiated 
cells, the necessary number in each species is reserved for 
the formation of the sexual cells. In phanerogams we find 
undifferentiated cells in the buds. When the bud forms a 
flower and sexual cells are developed in connection with it, 
we learn that some of these undifferentiated cells are made 
use of. It is entirely unknown to us how the transformation 
of undifferentiated cells into sexual cells is caused. We can 
observe with the microscope alterations in the structures of 
the cells, but the cause of these alterations remains hidden 
from us. In lower animals we find relations which to a 
certain extent resemble those prevailing in the phanerogams, 



since in them also there occur slightly differentiated cells 
which are applied for the formation of sexual cells. The 
other cells, which constitute by far the majority, we name 
the somatic cells, and therefore say that every animal body 
consists of many somatic and a few sexual cells. It we pass 
from the lower to the higher animals, we find that the separa- 


FIG. 23. Section through the posterior part of an embryo of the dog-fish, Squalus 
acanthias. Germ cells designates the group of sexual cells which have united in one 
group, which still lies far from the position of the future sexual gland. Ect, ectoderm ; 
Md, spinal cord; Nch, axis of the body (notochord); Mes, mesoderm; Ent, entoderm; 
Yolk, yolk-mass. 

tion of the two classes of cells, the names of which we have 
just heard, becomes sharper. We have succeeded recently in 
observing the precocious separation, or isolation, of the sex 
cells in vertebrates. Their number is very small in propor- 
tion to the number of somatic cells. In the young embryo 



of the dog-fish there lies at either side in the neighborhood of 
the developing intestinal canala group of cells, Fig. 23, germ 



FIG. 24. 

cells, which resemble one another closely, and which may be 
easily distinguished from the other cells of the body. They 




Roof End. 
Sub- germ Cav 

Sub-cerm. End., 

\Periph. End. \Vit End. 

FIG. 24. Diagrams to show the migration of sexual cells in four different verte- 
brates. Arch, primitive intestine (archenteron) ; Int, intestine; Lat. Mes, lateral 
mesoderm; Mes, mesothelium, or wall of the body cavity; Meson, embryonic kidney 
(mesonephros); Myo, anlage of the muscle (myotome); Noto, primitive axis (noto- 
chord); S.C, sexual cells in migration; W.D, renal, or Wolffian duct. After Bennett 
M. Allen. 


are the sexual cells and they accomplish during the later 
development a wonderful migration, for they move through 
the wall of the digestive canal and then through the mesen- 
tery until they reach the spot where the sexual gland arises. 
We known this interesting history through the investigations 
of F. A. Woods, 21 which were made in my laboratory. For- 
merly one assumed that the sexual cells arose in the gland, 
but this is probably not the case in any vertebrate. Another 
American, B. M. Allen, 22 has greatly enlarged our knowledge 
of the history of the sex cells in vertebrates. By the re- 
searches of this investigator, we now know that also in the 
turtle, the frog, and in two fishes, Amia and Lepidosteus, the 
sexual cells may be recognized very early. They lie at 
first far from the sexual gland into which they later migrate. 
The paths which these cells take during their migration 
differ for the species mentioned, Fig. 24. Several European 
investigators have also occupied themselves with the history 
of the sexual cells in vertebrates. In spite of the fact that 
much remains to be cleared up, we may nevertheless assert 
that vertebrates have special germinal paths, as they are 
called. In other words sexual cells are held apart. They pass 
through their development by themselves and have nothing 
in common with the somatic cells. They do not participate 
in the structure of the body, but remain almost like guests 
which are cared for by the other cells. When the proper 
time comes the sexual cells change themselves, as the case 
may be, into male or female elements. Since we know the 
history of these cells exactly in several cases, we are able to 
assert that in sexual as in asexual propagation the living 
substance continues uninterruptedly. This continuation up 
to the origin of the sexual elements we have actually ob- 



In insects also a special germinal path has been discovered. 
The small egg of these animals is usually oval in form. The 
French anatomist, Charles Robin, reported in 1862 that a 
special group of cells appears soon after the conclusion of the 
segmentation of the ovum. Balbiani showed twenty years 
later that these pole cells, which are not to be confused with 
the so-called polar globules or directive corpuscles, afterward 


FIG. 25. Preparations from the egg of a beetle, Leptinotarsa. A, the whole 
egg after completion of segmentation, at the posterior end one sees the accumulation 
of the superficial sexual cells, p.z, Xso; B, two cells, X85o; bl.c, ordinary somatic or 
blastodermiccell; p.c, sexual cell (pole cell). C, section through an egg, Xio5',Bl, 
blastodermic layer of somatic cells; p.c, sexual cells which migrate into the interior 
of the egg, in order to enter the sexual gland proper. After R. W . Hegner. 

pass into the sexual gland. The investigation of R. W. Heg- 
ner 23 of Wisconsin University offers us the most exact account 
of the history of these cells which we possess as yet. From 
his paper the pictures in Fig. 25 have been taken. The pole 
cells of Robin are sexual cells which separate precociously 
from the somatic cells, and after they have completed their 
migration, change in the sexual gland into sexual elements. 
We know for animals as for plants a physiological cause 


for the remarkable alterations which produce from a sexual 
cell, as the case may be, an ovum or a spermatozoon. In 
the fifth lecture we shall return to the consideration of the 
visible alterations during this transformation. 

Let us now assume that we have eggs and spermatozoa, 
and occupy ourselves with their further history. Science has 
acquired correct notions of ' these elements very gradually. 
A hundred years have not yet passed since the publication of 
the discovery of the eggs of mammals by Carl Ernst von Baer. 
Eighty years ago one considered the spermatozoa as parasites, 
although they had been known since 1628. The investiga- 
tions of Koelliker first demonstrated the true significance of 
spermatoza. That the semen acted to fertilize ova has been 
long known, but so long as one did not know the male and 
female sexual elements of the higher animals one could have 
no clear conception of reproduction. During the period of 
ignorance all sorts of wonderful theories arose, which, how- 
ever, had no value because precisely that which they should 
explain was, in its essentials, unknown. We must express a 
warning against theories of this sort, because even to-day we 
are much inclined to make up for lacking knowledge by 
theories. It was not until the seventies of the previous 
century that it became possible to understand the role of 
sexual elements in reproduction through the epoch-making 
investigations of the gifted Oskar Hertwig. Hertwig was at 
that time Privatdozent in Jena, and I rejoice that it is 
permitted me to express here the admiration which all biolo- 
gists bestowed on his discovery. Hertwig showed that 
fertilization consists essentially in the union of one spermato- 
zoon with one ovum. Since the ovum is very large in pro- 
portion to the male element we are accustomed to describe 
this union as the penetration of the spermatozoon into the 


ovum. Her twig investigated various species of eggs and 
observed the same fundamental phenomena in them all. 
Out of the head of the entering spermatozoon there arises a 
nucleus-like structure or pronucleus. Before or during 
impregnation the nucleus of the ovum loses a portion of its 
contents by a process which we call the phenomenon of 
maturation. The part of the nucleus of the ovum which 
remains forms the female pronucleus. The two pronuclei 
unite and form a new complete nucleus. The fertilization 
is now accomplished, and further development begins. The 
fertilized ovum divides, and so does also the so-called segmen- 
tation nucleus, which owes its origin to the fusion of the two 
pronuclei. We see therefore that substances from the mater- 
nal side and from the paternal side are employed for the act 
of propagation. A new individual obtains its life from both 
parents. In this case also the history is uninterrupted. 

W. H. Moenkhaus, 25 Professor in the University of 
Indiana, has furnished us the most brilliant proof of the 
accuracy of the assertion just made. He reared the hybrids 
of two fishes, Menidia and Fundulus. The chromosomes of 
Menidiaare noticeably smaller than those of Fundulus. In 
the hybrids Moenkhaus discovered both forms of chromo- 
somes appearing clearly at the time of cell division. This 
extremely interesting case teaches us by direct observation 
that living substance from both parents propagates itself in 
the progeny in visible form. 

At the beginning of today's lecture we cited the Latin 
saying " omne vivum ex vivo." It required the prolonged 
researches of many investigators to reveal to us the ways 
which living substance adopts in order to continue without a 
break. The relations may be easily recognized in asexual 
reproduction, but in the case of sexual reproduction we must 


ascertain the history of the sexual cells, the occurrence of 
sexual elements in all animals, and the internal processes 
during fertilization, in order to establish the necessary founda- 
tion for the modern doctrine of immortality. From the 
numerous researches made, we draw the safe conclusion that 
living beings consist of protoplasm and nucleus which have 
arisen from earlier living protoplasm and earlier living nuclei. 
The animals and plants of today exist only because protoplasm 
in itself is immortal. Only when protoplasm changes itself 
or is destroyed by external influences does it die. To us the 
verse "omne vivum ex vivo" means the immortality of 

This fact procures us a better insight into heredity. It is 
well known to us all that every living species maintains 
itself with slight alteration. This phenomenon signifies to 
us that protoplasm possesses the capacity, when supplied 
with food material, to produce more protoplasm of the same 
constitution as itself. We can offer no further explanation 
of this wonderful capacity. For us it is merely a fact which; 
however, offers us a theory of heredity, namely that the 
progeny are similar to their parents because they are developed 
from the same protoplasm. The creation of a new generation 
appears to us merely as the continuation of the activity and 
growth of the previous generations. 

There has been no lack of theories of heredity. The best 
of the older theories in my opinion is that of Darwin, which 
he termed "pangenesis." He assumed that the cells give 
off little granules or atoms which circulate freely through 
the whole body and which, when they are supplied with the 
proper nutrition, multiply themselves by division and then 
may later develop into cells. Darwin for the sake of 
clearness has named these granules "cell gemmules," or 


simply "gemmules." He assumed that they pass over 
from the parents to the descendants, and usually develop 
themselves in the first generation. Darwin's pangenesis 
explains heredity. It is the hypothesis of a master, and as a 
succinct and comprehensive explanation of the facts of heredity 
must always command admiration. Since Darwin's time 
many modifications of the doctrine of pangenesis have been 
proposed. These modifications, however, possess for us 
merely historical interest, for with the progress of science they 
have become superfluous. 

The new doctrine of heredity is due to Professor Moritz 
Nussbaum, who laid special stress upon the discovery of 
the germinal paths in animals, for he recognized in these an 
arrangement to separate special germinal cells from the 
somatic cells. He concluded that a portion of the germ-plasm 
is withheld from the developing ovum, kept comparatively 
unaltered, and employed for the formation of sexual elements, 
so as to become directly the germ-plasm of a new generation. 
It is clearly superfluous to still employ the expression germ- 
plasm which corresponds to speculative needs, and which we 
may now leave out of consideration. It is simpler to speak 
merely of living substance. Nussbaum's theory has in the 
course of time become, strictly speaking, the only theory of 
heredity which we value. 

If the time at our disposal permitted, it would be interesting 
to analyze carefully some of the theories of heredity which 
have arisen in association with Nussbaum's doctrine. The 
majority of these theories search for a special germ-plasm, to 
use Weissmann's expression. Nageli speaks of idioplasm. 
Some authorities have sought to bring heredity into relation 
with visible parts of the protoplasm or of the nucleus. Oskar 
Hertwig was the first to interpret the nucleus as the organ of 


heredity, a view which many eminent investigators have 
since defended. We must today admit that the nucleus plays 
a part in heredity, but not an exclusive role. The investiga- 
tions of two Americans, Conklin 26 and Lillie, 27 furnish the 
proof that in certain cases distinct regions can be distin- 
guished in the protoplasm of the undeveloped ovum. When 
the development proceeds each of these regions plays a special 
role in the formation of the body. It is possible to alter the 
normal distribution of the substances, which are character- 
istic for the regions, without killing the ovum. This is 
accomplished by the centrifuge. Conklin has succeeded in 
observing in centrifuged eggs that the substances, which have 
acquired a new position in the ovum, nevertheless form the 
same structures as before. From these observations he draws 
the just conclusion that organ-forming substances are present 
in these ova from the beginning. That which arises in the 
course of the development of the new individual is, in these 
cases, certainly determined at least in part by the protoplasm 
of the ovum. Hence we must admit that the protoplasm also 
participates in heredity. I do not see how we can accept 
the theory that the nucleus is exclusively the organ of heredity. 
On the contrary we must say that the essence of reproduction 
is the continuation of the growth of immortal protoplasm. 
The history of protoplasm is uninterrupted, and therefore we 
say : the immortality of the protoplasm and of the nucleus is 
also the explanation of heredity. 


Mortality was formerly regarded as the necessary end- 
phenomenon of life. It was not until our own times that 
it appeared probable to us that so-called natural death does 
not occur with all organisms. 

The development of the higher plants and animals begins 
with the fertilized ovum. By continued division such an egg 
produces the cells which form the plant or animal, as the case 
may be. Many years ago Huxley defended the thesis that 
all cells which arise from a single ovum belong together and 
constitute a cycle. He further proposed to regard all the 
cells of a single cycle as constituting the individual proper. 
The problem of individuality, however, which formerly 
often occupied thinkers, has lost much in interest and signifi- 
cance, owing to the progress of biology. In the higher animals 
as in the unicellular, we encounter real individuals , but in the 
lower multi cellular animals we recognize on the contrary no dis- 
tinct individualities. Thus, for example, in the case of corals 
and sponges, we cannot speak of individuals. Under these 
conditions Huxley's conception of the cycle was very seduc- 
tive to biologists. It could apparently be very well applied 
to the unicellular organisms because in many of them con- 
jugation had been observed. Conjugation is a phenomenon 
closely related with sexual reproduction. It was assumed 
that conjugation served to excite the cell division of unicellu- 
lar organisms. If conjugation and the fertilization of the ovum 
are homologous phenomena, then we are justified in regard- 


ing in both cases the exciting of cell division as the immediate 
consequence alike of conjugation and fertilization. In both 
cases there would arise homologous cycles of cell generations. 
Thus we should have to deal in both types of organisms with 
individuals in Huxley's sense. The only difference between 
the two types, which from our present point of view must be 
regarded as important, is that the cells in the lower type sepa- 
rate from one another, while in the higher, on the contrary, 
they unite to form a plant or animal. Death, as we ordinarily 
observe it, is the breakdown of a multicellular organism, and 
natural death is a consequence of old age. This considera- 
tion leads us directly to the question: Do old age and natural 
death occur in unicellular organisms? Weissmann, who has 
written several times concerning death, has not conceived 
the problem rightly, so that his discussions of death go 
astray in several essential respects. 

The first serious experiments to determine by direct ob- 
servation whether old age occurs in unicellular animals were 
carried out by the French investigator, Maupas. 28 " He 
reared Protozoa through many generations. Of each genera- 
tion he took a few individuals, allowed them to propagate 
themselves and noted the rapidity with which the divisions 
followed upon one another. He found that the rapidity 
diminished until a new conjugation occurred, whereupon the 
animals recovered. Later tests of these results have shown 
that the experiments of Maupas were open to criticism, in 
part because at that time the great influence of external con- 
ditions upon Infusoria was unknown, so that the possibility 
remains that the retardation of the division he observed was 
conditioned not by internal but by external causes. Further, 
in order to bring about conjugation, he introduced into his cul- 
tures newly captured, wild individuals. His cultures, there- 


fore, were not kept strictly pure. In America a long series of 
researches on the rapidity of division in Protozoa has been 
made, largely upon the instigation of G. N. Calkins, 29 who 
discovered that Infusoria may suffer "depression" a result 
which has been confirmed by further investigations of his own, 
of his pupils, and of other American investigators. The de- 
pression arises gradually, the animals become inert, nourish 
themselves poorly, and divide slowly or even not at all. If 
the depression lasts too long the animals may die off Calkins 
considered the depression" to be senescence, or a growing 
old. (He has since himself questioned the justness of this 

Our conception of senescence is based on the observation 
of the higher animals and plants, and comprises not merely 
the increasing weakness, but also alterations in structure 
which go far and are very striking. The Infusoria during 
their depression show no corresponding alterations of their 
organization; hence in my belief we cannot homologize this 
phenomenon in the Protozoa with the senescence of higher 
animals. In this belief we are confirmed by the fact that the 
newer investigations of conjugation make it improbable that 
it serves to renew and hasten the growth and division of 
unicellular organisms. Indeed, it is possible that conjuga- 
tion does not have this function at all. Significant here are 
the studies of the very talented investigator, H. S. Jennings, 30 
which demonstrate that conjugation serves to increase varia- 
bility. Jennings observed that Paramaecium exhibit consid- 
erable variability. During ordinary division the individuals 
remain more alike, but after conjugation their variation in- 
creases. His careful statistics leave no doubt as to his results. 
It is probable that sexual reproduction also has the purpose 
of maintaining the variability of the forms. The interperta- 


tion that impregnation has the purpose of increasing varia- 
bility in order to offer room for the play of natural selection 
originated with Weissmann. (It is said that Treviranus had 
previously expressed this view, but I have as yet been unable to 
personally confirm this statement.) Impregnation has also 
certainly to care both for heredity and for the initiation 
of further development. We know now that these functions 
may be separated experimentally. If sexual reproduction be 
conceived as a modification of conjugation, then we may assume 
that the function of initiating development was acquired later. 
Returning to the Infusoria we encounter in them, so far as the 
available observations go, a so-called depression indeed, but 
no senescence in the strict sense. (Quite conclusive as to 
the absence of senescence are the experiments of L. L. Wood- 
ruff,* who has maintained a pedigreed race of Paramecium 
for five years without conjugation. If all the possible indi- 
viduals had survived, they would have made a volume of 
protoplasm many million times the volume of the earth). 
Calkins, as said above, originally interpreted depression 
as a true senescence and declared the diminution of metab- 
olism to be the essential characteristic of old age. This view 
has been adopted by C. M. Child 31 and E. G. Conklin. 32 Pro- 
fessor Child has made experiments with a simple worm, Plana- 
ria. He treated these animals with alcohol by placing them 
in water to which i per cent, of alcohol had been added. 
The results he obtained are interesting and valuable. He 
seems to me, however, to go too far when he asserts that if 
the metabolism diminishes the animals become old. It is 
true that in the higher animals, when they become old, met- 

* L. L. Woodruff: Biologisches Centralblatt, XXXIII, p. 34, 1913. Professor 
Woodruff has informed me that on April 3, 1913, he had the 36501!! generation of 
the mentioned Paramecium colony. 


abolism becomes slower, but certainly one cannot therefore 
assert that every lessening of the metabolism implies a becom- 
ing old. According to the sum total of our knowledge we 
must regard organization as the cause of function. This is 
the only interpretation which a physiologist may admit. 
When therefore an organization is so altered that the metabo- 
lism diminishes, this diminution has to be considered a conse- 
quence and not a cause. Metabolism, however, is influenced 
by many factors, as every practicing physician experiences 
daily. If we accept Child's opinion we are led logically to 
the conclusion that each one of us may become alternately 
young and old according as his metabolism increases or 
diminishes. We should have to say, for example, that a 
man who performs strenuous and muscular work was reju- 
venated, while on the contrary one carrying on mental work, 
during which the metabolism is less, might become older. It 
seems to me clear that we cannot interpret the diminution of 
the metabolism as a characteristic of age in the sense of Cal- 
kins. In other words, we cannot view the depression in proto- 
zoa as senescence. Thus we reach the conclusion that natural 
death, so far as we know at present, does not occur in unicellu- 
lar organisms, and as a consequence of this we mention the 
corollary that natural death first appeared in the world as the 
higher multicellular plants and animals were evolved. 

We pass now to the examination of senescence in the 
higher animals, a theme which has claimed my active interest 
for many years. If we consider the phenomena as they are ./ 
known to us all, we recognize at once that a diminution of the 
rapidity of growth is characteristic of age, and thus we are 
induced to investigate growth. Obviously we must determine 
how the rapidity of growth alters with advancing age. For 
such an investigation it is important to exclude the influence 

6 4 


of temperature, which is known to have a great influence upon 
growth. Nature makes this exclusion for us in the case of 
warm-blooded animals. I selected for my own experiments on 
warm-blooded animals guinea pigs for various practical reason 
and I maintained a colony of these animals for many years. 
Every animal of the colony was weighed at definite intervals of 
age. After many thousands of determinations of the weight 

~JfLSi{Jvir ( 



FIG. 26. Graphic representation of the increase of weight in children of the Boston 

schools. After H. P. Bowditch. 
(Knaben, boys. Madchen, girls. Jahre, years.) 

had been collected, they were worked over statistically. 33 
My first problem was to invent a method which permitted 
the representation of the rate of growth. Formerly investi- 
gators were satisfied to represent growth graphically in a very 
simple way. Curves were constructed in which the abscissae 
corresponded to the age, and the ordinates to the weight, 
Fig. 26. Such a curve, however, although it represents the 


increase of weight, does not show the rate of growth. The 
real rate can be represented in the following manner with 
approximate accuracy. From the weight which an animal 
has on a given day and that which is found at the next weigh- 
ing, I reckoned the average daily increase during the period 
between the two weighings, and then changed these increases 
into the per cent, value of the weight at the beginning of the 
period. This method may be modified by calculating instead 
of the daily, the monthly or yearly percentage increases. 

51117232935 ^5 60 75 90 105 120 135 150 165 180 195 210 days 
FIG. 27. Curve of the daily percentage increase in weight of male guinea-pigs. 

The method is of course mathematically not exact, since the 
weight is constantly changing. It suffices, however, for our 
purposes. It is easy after one has calculated a series of per- 
centage increments in weight to construct a curve. The 
results obtained in this way I wish to lay before you. When 
guinea-pigs are born, they suffer in consequence of the great 
sudden disturbance of their conditions of living a temporary 
inhibition of their development. They recover within two 
or three days, and thereupon we observe that they may 
increase their weight over 5 per cent, in one day, Fig. 27. 



By the time they are seventeen days old, they grow only 
only about 4 per cent, and at forty-five days only a little 
more than i per cent, and from this age on the rate of growth 
sinks slowly until at the end of the first year it becomes 
almost zero. The general process is the same in females, 
Fig. 28, as in males, although certain inequalities occur. 
It is obvious that if we consider the curves, Figs. 27 and 28, 
carefully, we can distinguish in them two chief periods, which, 
however, pass into one another without definite boundaries. 

5 Tl 17 23 2933 tf 60 75 90 105 120 135 150 165 180 195 210 days 
FIG. 28. Curve of the daily percentage increase in weight in female guinea-pigs. 

In the first, shorter period, the rate diminishes rapidly. This 
period lasts about one and a half months. The second period 
exhibits a much slower decrease and lasts perhaps ten months. 
The result was unexpected. If we accept the rate of growth 
as the measure of senescence, we must say that young animals 
grow old enormously faster than old animals. Since alter- 
ations in the rate of growth of guinea-pigs progress as de- 
scribed, it was to be expected that in still younger stages of 
development the rate of growth would be found still greater. 
Now chickens when they enter the world are not so far 


6 7 

developed as guinea-pigs, and much less far developed are 
newborn rabbits. I have determined the rate of growth in 
both of these animals, and found that chickens, as soon as 

3> 2 13 U 33 <t6566677 90 106 130 197 days 3^2 

FIG. 29. Curve of the daily percentage increase in weight in male chickens. 

y/i 13 22 33 465666 77 90 106 130 197 days 3 

FIG. 30. Curve of the daily percentage increase in weight of female chickens. 

they have recovered from their hatching, may grow as much as 
9 per cent, per day, which is much quicker than the guinea- 
pigs grow. The values for the two sexes are practically equal, 




6 9 

Figs. 29 and 30. Even more striking is the rate in rabbits, 
which immediately after birth may reach for the males almost 
1 8 per cent, per day, and for the females 16 per cent., Fig. 
31, A and B. 

We encounter similar phenomena in man, but since man 
grows much more slowly than the three species of animals, 



Years! 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 

FIG. 32. Curve of the yearly percentage increase in weight of boys. Reckoned 
from H. H. Donaldson's table. 

the growth of which we have studied, I have reckoned the 
increases as yearly percentages, Fig. 32 represents the rate of 
growth for boys, Fig. 33 for girls. The curves fall at first 
with great rapidity, later much more slowly. Fig. 34 shows 
the alterations in the rate of growth in another form. The 
curve corresponds to the observed average weights in the male 





Years 1 


8 9 10 11 12 13 H 15 16 17 18 19 20 21 22 23 

FIG 33. Curve of the yearly percentage increase in weight of girls. Reckoned 
from E. H. Donaldson's table. 

FIG. 34. Curve of human growth in weight, with vertical lines to mark the dura- 
tion of loper-cent. increases. 



sex up to the age of forty years. The vertical lines indicate 
by their distance from one another what interval is required to 
permit each time a lo-per-cent. increase of the weight. 

We may proceed further and study growth during the 
embryonic period. Unfortunately this has not yet been done 
so thoroughly and exactly as for the development after birth. 
Nevertheless we can assert now that 
the growth of embryos proceeds faster, 
Fig. 35, in younger embryos, and that 
in very young embryos the daily in- 
crease is simply enormous. For, as I 
have demonstrated on a previous occa- 
sion, it may reach in very young em- 
bryos the value of at least 1000 per 
cent. Professor Donaldson 38 of the 
Wistar Institute has already published 
more exact data as to the weight of 
embryos of the white rat. He has 
collected further data, and we may 
expect from him a detailed memoir on 
embryonic growth. He has completely 
confirmed my result that there occurs 
an enormous decrease in the rate of 
growth during embryonic life. These 
investigations lead us to the conclusion 
that the diminution in the rate of 
growth occurs chiefly during the first 
developmental periods, and that the 

diminution after birth is very gradual. Hence if we 
seek for the cause of this diminution, the facts indi- 
cate that we should investigate the conditions during 
embryonic life because this is the period of loss We 






01 23^56789 10 
FIG. 35. Curve of the 
monthly increase in weight 
of the human embryo. 


may therefore expect that the changes which cause the 
diminution wll be more noticeable in embryos than in older 

I have not succeeded in determining with absolute cer- 
tainty the cause of the inhibition of growth. We find, 
however, a close correlation between the alterations which 
occur in the cells of the embryo and the inhibition, which 
renders it probable that the alterations of the cells are at 
least one essential cause of the diminution of the growth. 
The alterations which here come into play are those of differ- 
entiation, and in fact differentiation proceeds in young 
embryos with extraordinary rapidity and in older embryos 
more slowly. At the time of tiirth the differentiation is for 
the most part far advanced, and thereafter continues extraor- 
dinarily slowly. Up to the present at least it has been im- 
possible to express our observations of the rapidity of differ- 
entiation in statistical form because we do not yet know how 
to measure differentiation quantitatively. We can merely 
estimate the degree of differentiation. In spite of the 
incomplete reliability of this method, I believe that the es- 
timate which has been made answers to the truth. That a 
causal relation exists between the diminution of differentia- 
tion and the rate of growth is confirmed by the fact that 
direct observation teaches us that undifferentiated cells 
may divide rapidly and that differentiated cells divide more 
slowly, and finally that the most completely differentiated 
cells do not divide at all. The indicated considerations have 
led me to the conclusion that differentiation is to be con- 
sidered the essential cause of senescence. 

I have already asked you to give heed to the fact that 
differentiation occurs principally as a transformation of proto- 
plasm. At the same time we learn that in order to render the 


differentiation possible the protoplasm must grow in order 
to furnish the basis for the differentiation. Hence I should 
/like to give the above conclusion the following form: 
Senescence is caused by the increase and differentiation of pro- 

The correctness of this conclusion is strengthened by the 
fact that we find the opposite relations in young cells which 
have characteristically a nucleus with little undifferentiated 
protoplasm. During the development of the ovum there 
arise at first relatively large cells which develop further, and 
through numerous generations became steadily smaller. 
Since the ovum usually contains a nutritive yolk, the cells grow 
by assimilating the yolk. The brilliant investigations of 
Conklin 32 have shown that during the segmentation of the 
ovum not only is the total amount of nuclear substance in- 
creased, but also the total amount of protoplasm in the strict 
sense. It comes about, however, that the increase of the 
nucleus is relatively greater than the increase of protoplasm. 
Conklin determined in Crepidula that in the two-celled stage 
the nuclei form only 0.0117 of the total volume of the ovum, 
but in the twenty-four-celled stage they form 0.0255 of the 
volume. Soon there follows a stage with really young cells, as 
I have above defined them . We distinguish two chief periods 
of development. The first is much the shorter and is char- 
acterized by the preponderating increase of the nuclei. The 
second is much longer and is marked by the growth and dif- 
ferentiation of the protoplasm. The first is the period of 
rejuvenation, the second the period of senescence or growing 

A remark must be here intercalated. The rate of growth 
and of the division of the cells does not depend solely upon the 
organization of the cells itself for the time being. The degree 


of potential capacity to grow and to divide is presumably 
fixed by the organization of each cell, but there occur in the 
body inhibiting influences, perhaps also exciting. Thus it 
may happen that a cell potentially capable of division cannot 
divide, or that a cell which has long remained inactive may 
be excited to division by special newly arisen influences. The 
phenomena are by no means simple. 

The theory of senescence which I have expounded to you 
was proposed, as you have heard, by myself. All achieve- 
ments of science originate in this way. They are at first 
purely personal. Afterward when they have been tested they 
acquire general validity. And so with regard to my theory, 
until the discussion is concluded we must wait in order to 
decide whether this theory or some other which may be 
brought forward is to be finally adopted. 

Some of the theories of senescence we may now discuss 
briefly. That of Conklin has been previously mentioned. I 
have already indicated to you the reasons which lead me to 
designate these theories as insufficient. There are besides a 
number of theories which have been conceived from a purely 
medical point of view, and which are little adapted to satisfy 
a biologist. First of all must be named the theory of Mets- 
chnikoff, of which probably all cultivated men have heard. 
The Russian investigator, who has been working for many 
years in the Pasteur Institute in Paris, published in the year 
1903 a peculiar book with the title, "La nature de Fhomme." 
With the views of life presented therein, we have at present 
nothing to do. We restrict ourselves to the discussion of the 
theory of disharmonies presented in this book. According to 
Metschnikoff, a disharmony arises whenever the structure 
of an organ is incompletely adapted to the needs of the body. 
The disharmonies he mentioned do not seem to me very 


important, for they refer for the most part to structures whose 
physiological significance we do not know. It is venturing 
much to conclude from our ignorance that a disharmony 
exists. To one physiological disharmony, which he be- 
lieves he has discovered, our author attributes the very 
greatest importance. He is of the opinion that our large 
intestine is too large, and that there occur in it fermentations 
which produce toxic substances which then act to poison the 
body. He believes further that these unfavorable conditions 
become very serious in man with increasing age, and he 
attributes especially to them the difficulties of the very old. 
In order to avoid these weaknesses he recommends a treatment 
which, according to him, is adapted to the suppression of the 
fermentations in the large intestine. The treatment is 
simple, for it consists in drinking sour milk. According to his 
theory the germs pass with the milk into the intestine, where 
they inhibit the toxic fermentations. It has become in the 
highest degree improbable that the fermentations in the 
large intestine have the significance ascribed to them by 
Metschnikoff, but even if he is right his discovery brings no 
explanation of senility, as indeed senescence is a very wide- 
spread phenomenon and occurs also in animals and plants 
which have no large intestine. 

With how little seriousness Metschnikoff has fomulated 
his theory will be clear to anyone who reads an article by 
the American physiologist, C. A. Herter. 34 Herter, whose 
early death means a heavy loss for science, showed that we 
have as yet no proof that sour milk has any influence whatever 
on the bacterial flora of the large intestine, and also no proof 
that such an influence would be rather beneficial than injurious 
to man. The problem of intestinal fermentations is ex- 
ceedingly complicated. 


A similar criticism may be directed against the current 
medical theory of growing old which seeks to explain the 
observed weaknesses and difficulties of old men by the 
condition of their blood-vessels, especially of their arteries. 
Thus Osier has said a man is as old as his arteries. This view 
rests upon clinical experiments, for in fact the disturbances 
in the case of senile weakness, which are occasioned by the 
altered structure of the walls of the vessels, are especially 
noticeable and yield valuable symptoms for the diagnostician. 
We have, however, to do with the consequences, not with the 
causes, of senility. 

Professor Mlihlmann has also written repeatedly concerning 
extreme old age and his memoirs contain many interesting 
and valuable statements. He offers us also an explanation 
of senility. The latest memoir of Miihlmann 35 of which I 
know, and which must be here considered, appeared in the 
year 1910. In it he discusses my theory. The present 
opportunity does not appear to me suited to discuss Miihl- 
mann's critic fully and to answer it. Permit me to direct 
your attention to it, because quiet discussion leads to the 
settlement of scientific problems. I venture to add that 
I am still convinced that my view can be successfully defended 
against Miihlmann's attack. Miihlmann writes, strictly 
speaking, from the medical point of view, or in other words 
from an anthropomorphic point of view. He is concerned 
with rendering the phenomena in man more comprehensible 
without having regard to the corresponding phenomena as 
they occur in living organisms in general. Investigations 
which are conducted by such thoughts as we know from 
experience lead to valuable results. They can, however, 
only exceptionally bring forth results which are com- 
pletely satisfying to biologists. Miihlmann attributes 



special importance and meaning to the outer surfaces of the 
body, and to the consequences involved in the greater or less 
remoteness of the single parts of the body from the outer 
surfaces. It is very possible that these results have signifi- 
cance for the physiological activities of the body, and it is 
not improbable that with the increasing age the proportion of 
the outer surfaces to the rest of the body becomes unfavor- 
able. This interpretation with other related suppositions 
is presented by Miihlmann. He believes further that the 
mentioned results act to the disadvantage of the central 
nervous system by which the gradual destruction of this 
system is caused, a destruction which progresses until it 
brings about natural death. Miihlmann's demonstration is 
not convincing to me, but even if we should grant that he is 
right, and accept his conclusion that natural death in man is 
directly caused by degenerative alterations of the nerve cells, 
we should still not have won a general biological theory of 
death. As we have already heard, the death of cells plays a 
great role during development as well as in the adult. Any 
theory of death must reckon with these facts and cannot be 
sufficiently valid if it does not explain both the natural death 
of the whole body and also the natural death of the cells 
which are continually dying off. It is a merit of the theory of 
cytomorphosis that it maintains its 'value as an explanation 
of all forms of death. 

We owe to Alexander Gotte 36 another theory which I 
wish to mention briefly. According to this theory, natural 
death is closely connected with the phenomena of sexual 
reproduction, for it assumes that the maternal organism is 
exhausted by the effort of reproduction, which thus causes the 
appearance of old age. We must pay attention to the fact 
that it was not until after the appearance of Gotte's article 


* ,. 

in the year 1883 that we have become acquainted with the 
history of the germ cells. Since these cells, properly speaking, 
develop independently of the somatic cells, it becomes very 
doubtful whether they can exert any such influence on the 
body as Gotte's theory requires. Moreover, the fact that a 
man may live long in health after the reproductive capacity 
.is lost speaks against the theory. The theory of Hansemann 37 
may be considered to a certain extent as a modification of 
Gotte's. Hansemann seeks the immediate cause of physio- 
logical death in the atrophy of the germ plasm, but, as we 
know, senescence is not a phenomenon which begins at the 
end of life, but a continuous one which proceeds in young 
individuals also. It is therefore clear that we cannot explain 
becoming old by an event which does not occur until the 
individual is already old. 

The various hypotheses which we have just discussed have 
this in common, that they seek to explain only the death of the 
whole body, and do not investigate the question of death as a 
phenomenon of cell life. The theory of cytomorphosis differs 
from the mentioned theory precisely therein that it regards 
death as a phenomenon which occurs in single cells. It is, if 
I am right, the only theory which we possess up to the present 
time which answers to the demands of biology. 

As to the development of death we know little as yet. 
Naturalists assume that unicellular organisms were developed 
in the world earlier than the multicellular, or in other words, 
that they are more primitive and older. We must therefore 
assert that the first living cells were potentially immortal, as is 
at present the case for their existing representatives. From 
this it follows that natural death appeared later. It seems to 
me probable that death as we now know it in the human race 
was evolved gradually. In sponges and ccelenterates we find 


no individualities as in the higher animals. A part of a 
sponge or of a coral may die and the other part continue living, 
because the correlation of the parts has not advanced so far, 
but in these animals preservation of the whole is independent 
of the preservation of the correlation. In the higher animals 
the correlation is much more intimate, and therefore individ- 
uality more marked, until we reach an animal whose parts 
work together and must reach definite proportions in order 
that the working together may be properly carried out. An 
organism which has attained higher development in this way 
cannot continue its life if an essential part or an essential 
organ becomes incapable of functioning. We know that the 
single organs must have their specific differentiation, and we 
know further that these differentiations in the majority of 
cases increase with age, and that it may go so far that the cells 
of a special organ cannot function any longer. Now if an 
organ which is essential for the maintenance of the whole 
body gives out, the entire animal must die. It is a priori 
improbable that in all cases natural death is a consequence of 
the alterations of the same organ. Thus we know that in 
certain insects and worms death occurs almost suddenly after 
the discharge of the sexual products, yet their nervous system 
may be intact. We may admit that physiological death in 
man is caused by the breakdown of the nervous system, and 
yet the practicing physician sticks to his opinion that death 
in extreme old age occurs more frequently through failure of 
the blood vessels. We must heed the fact that even in the 
highest animals, just as in sponges and coelenterates, parts of 
the body may break down without causing physiological 
death. Permit me again to direct your attention to the fact 
that in man not merely single cells but even entire organs may 
die off. In its essence the phenomenon in these cases is the 


same as that which we meet on a larger scale in the ccelen- 

Has death a purpose? Weissmann has expressed the 
interesting thought that death is advantageous to organisms. 
If an organism lived forever it would become, through acci- 
dents, more and more injured. By death this is avoided, and 
at the same time by continuous reproduction the creation of 
new healthy individuals is provided for. I am, however, not 
inclined to regard death in itself as advantageous, but rather 
as a consequence of differentiation. The higher plants and 
animals have arisen through differentiation to it we are 
indebted for our organization which makes us men; to it we 
owe the possibility of knowing our earth, its inhabitants, and 
ourselves; to it we owe all advantages of our existence; to it 
we owe the possibility of carrying on our physiological work 
much better than the lower organisms; to it we owe the possi- 
bility of those human relations which are the most precious of 
our experiences. These advantages and many others do we 
owe to differentiation, the price of which is death. The price 
is not too high. None of us would like to return to the condi- 
tion of a lower organism which might be capable of continuing 
its species, and which had to suffer death only through acci- 
dent. We pay the price willingly. Natural death comes, as 
we now know, when an essential part of the body yields. It 
may be the brain; it may be the heart; it may be another 
organ, in which the cytomorphosis goes so far that the organ 
can no longer perform the work assigned to it, and when it 
fails it brings the whole to rest. Thus the conception of 
death shapes itself in our minds. The mystery remains. The 
biologist knows the essence of death no better than the essence 
of life. We say of certain bodies that they live, of others 
that they are dead. Science at present is incapable of telling 


us what the difference between these two conditions is, but 
we are learning every year more about life and more about 
death, and we hope that with coming years our biological 
science will so grow that she will make both life and death 


Your Excellency! 

There is probably no phenomenon which has always 
seemed to mankind at once so interesting and so mysterious 
as sex. A history of the opinions, speculations, and customs 
which have arisen in the course of time in connection with the 
question of sex would be instructive. The progress of science 
has recently made us acquainted with the material basis of the 
phenomenon. The most important notion we have acquired 
is that of the difference between sex and sexuality. We 
derive our notion of sex from our repeated experiences in 
connection with man and with domestic animals. We know 
from our daily life that male individuals possess many pecul- 
iarities which the females do not have, and vice versa. By the 
application of the microscope we have discovered sexuality 
proper, which is not characteristic for the male or female 
body, but is peculiar exclusively of the sexual products. An 
animal or plant is a male or female according as the individual 
in question produces ova or spermatozoa (pollen grains). 
We note often that secondary peculiarities have been devel- 
oped in connection with this fundamental difference. The 
secondary peculiarities are pronounced in man and the higher 
animals. One of the most interesting books which we owe to 
Darwin deals brilliantly with the problem of the origin of the 
so-called secondary sexual characteristics. They are really 
secondary and without doubt a consequence of the sexual 



difference, the essence of which consists in the production of 
eggs or spermatozoa. 

By no means seldom do we find animals or plants which 
are hermaphroditic organisms and produce both sexual 
elements. Biologists very commonly hold the opinion that 
hermaphroditism represents the primitive relation. Analysis 
of the relations, however, seems to me not to lead to this 
conclusion, and I propounded in 1892 the hypothesis 39 that 
originally every animal individual is sexually indifferent. 
Expressed in this form the hypothesis is not exact. It may 
be more correctly expressed thus: This sexually indifferent 
condition is primitive. We learned in the third lecture the 
history of the sexual cells. These cells, however, are not sex- 
ual elements, but every one of them must pass through a 
very complicated and remarkable transformation in order to 
become a sexual element. This fact in my opinion renders it 
certain that the primitive condition was an indifferent one. 
After it ensue the alterations which transform a sexless into 
a sexual individual. 

When a cell divides the nucleus usually passes through a 
so-called mitotic change which leads to the division of the nu- 
cleus. During this change chromosomes appear. Each chro- 
mosome is a separate granule which is formed by the concen- 
tration of a small part of the nucleus, Fig. n. After the divi- 
sion is completed the chromosomes become indistinct and are 
at the same time utilized for the restoration of the normal 
structure of the resting nucleus. Hence the chromosomes are 
visible only during the process of division. It has been ascer- 
tained that the number of chromosomes in each species is con- 
stant,* although in different species their number may vary 

* This statement is not exact, for in certain cases, ascaris, etc., the number 
of chromosomes varies with the period of life, and it is probable that in somatic cells 


between wide limits. We have also discovered that the num- 
ber of chromosomes in the sexual elements in every species 
which has been adequately investigated is about half the num- 
ber of chromosomes occurring in the somatic cells. When 
sexual products arise from the sexual cells, each cell divides 
twice in rapid sequence, so that four sexual elements arise. 
When male elements arise all four cells normally develop. 
An interesting and instructive exception will be considered 
presently. In the case of four female elements, on the con- 
trary, only one cell enlarges and becomes an ovum. The 
three other cells, which have long been known by the name of 
polar globules, break down. If we count the chromosomes 
which appear during this double division, we find in typical 
cases that their number is reduced one half, so that at the 
close of the process we have cells, the so-called sexual elements, 
which contain only half as many chromosomes as the cells 
of the body, and the original sex cells. More careful in- 
vestigations have taught us further that the reduction in 
the number of chromosomes is not always exactly to one- 
half. We find in certain cases one or several extra chromo- 
somes. The origin and significance of these extra, or ac- 
cessory, chromosomes has been studied especially in America. 
American investigations have yielded the very important 
result that the accessory chromosomes stand in immediate 
relation to the determination of sex. To collect the facts 
has cost many years of difficult labor. These facts have 
made it clear that in all higher plants and animals we 
encounter two fundamentally different species of cells; first, 
ordinary cells with the full number of chromosomes; second, 
special cells which we know as sexual elements, or sexual 

the number of chromosomes is subject to minor variations. Compare H. L. Wieman's 
article in the number for May, 1913, of the American Journal of Anatomy. 


products, which are characterized by the reduced number of 
chromosomes. We are now in a position to distinguish sexual 
elements and body cells by a visible microscopic character- 
istic, and hence to define the two fundamental, forms of cells. 
A cell is only, then, a sexual element when it has the reduced 
number of chromosomes. The sexual cells have sexuality. 
The body in which the sexual elements are brought to develop- 
ment may have sex. The basis of all clear thinking in 
regard to the questions of sex is the difference between sex and 

How is sex determined? As yet we cannot explain the 
relations in hermaphrodites at all. We know only that they 
have indifferent sexual cells, out of which may be formed male 
and female elements either at one time, or from time to time, or 
at different periods of life. We assume that the occurrences 
are regulated by internal conditions of the hermaphroditic 
organism. We have also discovered that external conditions 
may under certain conditions influence the sexual develop- 
ment of hermaphrodites, thus, for example, in melons, which 
normally produce male and female flowers on the same plant, 
under the influence of higher temperature only male flowers 
develop, and under the influence of shade only female. How 
these results come about is completely unknown. 

The investigation of forms of separated sex has proved 
more valuable. Investigators have long endeavored to dis- 
cover influences which might determine the sex of an ovum 
during its development. For some time it was hoped to learn 
something from the investigation of the proportion of the 
sexes in various species. The sexual relation is usually cal- 
culated by setting the number of females as = 100, and then 
expressing the number of males in percentage of the number 
of females. These investigations have as yet yielded no 


important generalizations. How great the variations are is 
shown by the following table: 


Loligo 16.6 Man 106.9(105.3?) 

Octopus 33-3 Domestic dog 138.0 

Horse 98.3 Cottus 188.0 

Songbirds 100.0 Lophius 385.0 

Herring 101.0 Latrodectus 819.0 

Cat 105.0 

There are two series of cases known in which the sex 
is determined in advance. The first series comprises several 
species of animals of various classes which produce two sorts 
of eggs, differing in size. Such eggs occur for example in 
the worm Dinophilus, in many rotifers, as, for instance, 
Hydatina, in daphnids, in Phylloxera, and other forms. The 
large eggs produce only females, the smaller only males. 40 
Oskar Schultze was induced by these facts to maintain that 
sex is determined in the ovum. More recent discoveries have 
rendered Schultze's theory superfluous. 

The second series of cases is afforded by the eggs especially 
of various insects which may be developed parthogenetically, 
as occurs, for example, in Phylloxera. The fertilized ova 
produce females only, the unfertilized on the contrary, 
according to conditions, either males or females. For a long 
time it was hoped, though in vain, to secure the explanation of 
the determination of sex by the exact study of such ova. 

Naturalists have long directed their efforts toward dis- 
covering external conditions, the action of which determines 
sex. It appears now to be established that under certain 
conditions the proportions of the sexes may be altered by ex- 
ternal conditions. The experiments of Richard Hertwig, 
which he published in 1907, excited great interest. They have 
been extended by his pupil, Kuschkakewitz. 41 Hertwig 


demonstrated that delayed fertilization of frogs' eggs produces 
an excess of males. Unfortunately it is not clear how this 
result is brought about. An American lady, Miss King, has 
made extensive investigations 42 upon the influence of external 
conditions on the determination of sex in toads' eggs. Nutri- 
tion and temperature are apparently without effect, but if the 
eggs lose water then more females develop. Even if we should 
pass in review the entire literature upon the determination of 
sex through external conditions we should not get much 
further than we could from the examples I have presented to 
you. We are safe in saying that external conditions are prob- 
ably not of great importance, and at the most are merely fav- 
orable or unfavorable for the development of one sex or the 
other. The essential conditions must be sought in the cells 
themselves, and this view has had brilliant confirmation 
through recent researches. 

It is very pleasant for me as exchange professor to have 
the privilege of reporting a series of American investiga- 
tions which are of the highest value because they have pro- 
cured for us entirely new views of the determination of sex. 
Only recently have similar investigations been entered upon 
in Europe. The new doctrine arose from the observation of 
the developmental processes which lead to the formation of 
the male elements in certain insects. The founder of the doc- 
trine is Professor C. E. McClung, 43 who, after serving many 
years at the University of Kansas, became last autumn 
Professor of Zoology at the University of Pennsylvania in 
Philadelphia. His first memoir upon the spermatogenesis of 
insects appeared in the year 1900, and contains the results of 
his investigations on the process in the Acrididse. McClung's 
most important discovery was that one chromosome during 
the evolution of the sexual elements behaves quite differently 


from the rest. It appears when a sexual cell begins its trans- 
formation. At this time the chromosomes arise in the reduced 
number and it is easy then to distinguish the one chromosome 
which McClung has named the accessory. When the sexual 
cell has formed the reduced number of chromosomes it is called 
a spermatocyte. The spermatocyte divides, and at the same 
time all the chromosomes, including the accessory, also divide. 
The two daughter cells quickly divide again and so also do 
the ordinary chromosomes, but this time the accessory chromo- 
some does not divide, but passes undivided into one of the daughter 
cells of the second generation. In this way four cells arise as 
always in spermatogenesis, and of these four cells two have 
each an accessory chromosome and two have none such. The 
four cells pass through further changes in order to become 
mature spermatozoa. Thus it comes about that we have in 
these insects two kinds of spermatozoa, for half of them con- 
tain a piece of the accessory chromosome and the other half 
do not. From these facts McClung drew the conclusion that 
the two kinds of spermatozoa determine the sex, and since he 
found the accessory chromosomes in the cells of the male body, 
he further supposed that the accessory chromosomes have to 
do with the creation of the male sex. The observations of 
the Kansas zoologists have been repeatedly confirmed by 
other Americans. They are so easily made and are so signifi- 
cant that we have demanded for several years past that our 
medical students at Harvard should study the spermatogenesis 
of grasshoppers. That the accessory chromosome stands in 
immediate relation to the production of sex must be considered 
as established, but I must immediately call your attention to 
the fact that McClung's theory acquired an essential further 
development through E. B. Wilson, 44 who, in the investigation 
of the relations of chromosomes in female insects, was able 


to demonstrate that the accessory chromosome does not 
determine the formation of males but of females. The ac- 
cessory chromosome was first seen by a German, Henking, 
and was afterward studied by the American, Montgomery. 
McClung was the first to recognize its true nature and import- 
ance, and to him belongs the honor of having first brought the 
investigation of the determination of sex upon the proper road. 

The formation of the sexual elements is full of meaning 
and interest, but it cannot be made clear by words alone. 
On account of the importance of the phenomenon I wish now 
to show you certain pictures which are suited to clarify your 

The sexual cells, like all cells, are little adapted in their 
natural state to microscopic observation. Special methods 
have been invented to overcome this difficulty. In most cases 
thin sections are made of the organ or tissue which it is de- 
sired to investigate. The sections are artificially colored. 
We should have been able to learn little of the structure of 
cells without this method. The pictures which I have to 
present to you have been made from artificially colored prepa- 
rations. The chromosomes which we wish specially to ob- 
serve are colored almost black, while most of the rest of the 
cell appears gray. Our pictures are all, except Fig. 44, draw- 
ings for the most part from photographs. In the drawings 
only the black parts have been put in, and in most of them 
only the chromosomes are represented. When a sexual cell 
begins to transform itself into a sexual element the nucleus 
passes through a series of changes during which the chromo- 
somes assume wonderfully irregular forms, which, however, 
quickly change again. Our first picture* is a drawing by a 

* The picture mentioned was projected on the screen for the lecture, and is not 
reproduced here. The conditions are similar to those represented in Fig. 52. 


student of the sexual cells of a grasshopper such as all our 
students are given opportunity to see. In every nucleus one 
finds a single round, dark body, the ac- 
cessory chromosome. The remaining 
chromosomes are all drawn out and have 
irregular outlines, so that the accessory 
chromosome is conspicuous. 

Our next pictures, Figs. 36-40, are 
taken from Anasa tristis, and are after 
drawings by Miss Pinney. Anasa tristis 
is a species of Hemiptera very common 
with us. The spermatogenesis of this 
insect has been investigated by many 
Americans: by F. C. Paulmier 1899, by E. 
B. Wilson 1905 and 1907, by Miss Foote 
and Miss Strobell 1907, by Professor 
Lefevre and Miss McGill 1908, by C. V. 
Morril 1901, and by Professor McClung 
and Miss Pinney 1911. Anasa has become, 
so to speak, a classic animal. As the statements of earlier in- 
vestigators did not completely agree, Professor McClung and 
Miss Pinney made a careful reinvestigation. They had at 
their disposal in part the material used by their predecessors. 

FIG. 36. A n a s a 
tristis. A section of a 
spermatogoneal cyst. 
The peculiar arrange- 
ment of the spindle is 

FIG. 37. Anasa tristis. Successive stages in the transformation of the nucleus of 
a sexual cell (spermatogonium). The transformation is the preparation for the 
development of the sexual element. After Edith Pinney. 

Their memoir is excellent, and I present a selection of their 
pictures. We will consider first the commencement of the 


transformation of the sexual cells. Fig. 36 shows a group of 
cells, the nuclei of which have assumed the spindle form. We 
see clearly the fibers of the spindle and the chromatine col- 
lected in the middle of each spindle. The chromatine con- 
sists of chromosomes which lie crowded together. The re- 
maining pictures which we have to consider represent merely 
the nuclei. Fig. 37 shows the successive alterations which the 

FIG. 38. Anasa tristis. Spermatocyte nucleus in preparation for the first 
division, x, the accessory chromosome; p, the plasmasome, a transitory structure 
which does not belong to the chromosomes, but soon dissolves. 

nucleus of a sexual cell passes through when it begins to trans- 
form itself into a sexual element. Soon an accessory chromo- 
some becomes distinct, especially in the stages shown in 
Fig. 38, during which the chromosomes become again dissolved 
except the accessory, which behaves independently and main- 
tains its integrity. The accessory chromosome has no ab- 
solute constant form, but varies greatly. Many of these 
variations have been pictured by Miss Pinney. Fig. 39 
leads us to the first development of the sexual cell (first 
spermatocyte). We recognize easily the spindle figure. 
Out of the dissolving skein of chromatine complete chromo- 
somes have arisen. The accessory chromosome lies always 
at the side of the others. All the chromosomes divide, and 
we can observe readily in the figures how the two groups of 
chromosomes diverge and move toward the poles of the 
spindle. In each group there is one chromosome which has 
been formed by the division of the accessory. The four draw- 
ings in the lower part of Fig. 39 from right to left illustrate the 

9 2 


progressive division of the cell. We notice that in each of the 
daughter cells there is an accessory element. In ordinary 
cell division the chromosomes form in the daughter cells a new 
nucleus which assumes the resting form, in which we can no 
longer distinguish the single chromosomes. In the case of the 
developing sexual elements, however, no resting nucleus is 
produced because the cell at once proceeds to a second division. 

FIG. 39. Anasa tristis. Division of the first spermatocyte. a, b, m, ordinary 
chromosomes; x, accessory chromosomes. 

Fig. 40 shows us the successive stages of the second division. 
During it all the chromosomes divide with the exception of the 
accessory, which does not divide at all, but migrates into one 
of the cells. From the original sexual cell there have now 
arisen four cells, two of which have an accessory chromosome. 
The four cells change themselves into spermatozoa. In this 





FIG. 40. Anasa tristis. Second spermatocyte division, during which the acces- 
sory chromosome remains undivided and partakes itself to one of the daughter cells. 
x, the accessory chromosome; 9, two groups of chromosomes; 19, single accessory 
chromosomes, each from a cell in the stage of Nr. 18; 30, three daughter nuclei with 
the accessory chromosome; 31, later stages of the same (each daughter cell forms a 
spermatozoon). After Edith Pinney. 



way there arise two kinds of spermatozoa. When an egg is 
fertilized by a spermatozoon that contains an accessory ele- 
ment, a female is produced. 

Miss Stevens 46 has published a series of papers on the devel- 
opment of the sexual elements. Fig. 41 represents the alter- 

'- X 

FIG. 41. Diabrotica. a-d, D. vittata; e-f, D. soror; a, dissolution of the con- 
tracted chromosome (first stage after synizesis); b-d, transformation of the nucleus 
of the first spermatocyte; x, the accessory chromosome; e-f, division of the nucleus 
of the first spermatocyte. After N. M. Stevens. 

ations as found by her in a beetle, Diabrotica. b, c, d show 
the accessory chromosome clearly, e and / show us the 
first division. Half of the daughter cells of the first division 
have an accessory chromosome, which, however, divides at 
the second division. The process differs from that in Anasa, 


but the final result is the same, for there are formed two sexual 
elements which have and two which have not an accessory 
chromosome. Miss Stevens has investigated many insects, 
as also has E. B. Wilson. 44 Both have made similar dis- 
coveries, and they have been able to demonstrate that the 
accessory chromosome is not always single but may appear 
in certain eggs as consisting of two, three, four, or even five, 
parts. They have also observed in some species a second 
accessory chromosome, which they have designated as the 
Y-chromosome, and which perhaps also plays a role in the 
determination of sex;- but it must not be confused with the 

FIG. 42 A. FIG. 42B. FIG. 43. 

FIG. 42. Protenor belfragei. Chromosome groups. -4, from a cell of a female; 
B, from a cell of a male. The accessory chromosomes are-much larger than the ordi- 
nary ones. 

FIG. 43. Protenor belfragei. Second division of a spermatocyte. The large 
accessory chromosome is moving undivided toward one pole. 

true accessory. Professor Wilson has had the kindness to 
place at my disposition a number of photographs* of his 
beautiful preparations, and from these Figs. 42-51 have been 
sketched. In Fig. 42 the chromosomes are very distinct. In 
Fig. 42 A, we can count very easily twelve ordinary chromo- 
somes and two accessory. Fig. 42 B is similar. It also shows 
twelve ordinary chromosomes, but only one accessory. The 

* During the lecture the original photographs were projected by the lantern. I 
use this opportunity to express roy very sincere thanks to Professor Wilson, both for 
the loan of the photographs and for his generous permission to make drawings from 


first of the two pictures is from the cell of a female, the second 
from the cell of a male. In these cases we recognize at once 
that the female cells are distinguished from the male by having 
two accessory chromosomes. Wilson was able to demonstrate 
that the eggs of these insects always contain one accessory 
chromosome. When such an egg is fertilized by a spermato- 
zoon that contains an accessory chromosome, then the egg 

FIG. 44. FIG. 45. 

FIG. 44. Protenor belfragei. Photogram of a group of young spermatozoa with 
and without the accessory chromosome. (See text.) 

FIG. 45. Alydus pilosulus. Second division of the spermatocyte. The acces- 
sory chromosome lies separated from the others, does not divide, and is going toward 
one of the poles. 

develops with two accessory chromosomes in its nucleus, and 
there arises a female, but if such an egg is fertilized by a sper- 
matozoon that contains no accessory chromosome then a male 
is produced. Fig. 43 is a somewhat incomplete picture, but 
shows clearly that during the second division the accessory 
chromosome has migrated undivided toward one pole. An 
extremely interesting photograph, Fig. 44, shows a group of 
spermatozoa. The so-called heads are circular. Half of 



them contain a still distinct accessory chromosome, which in 
the other half of the heads cannot be seen. This picture 
affords unquestionable proof that there really are two kinds 
of spermatozoa. The next picture, Fig. 45, is from Alydus, 
and demonstrates to us again the second division and the 
wandering of the accessory chromosome. Next follows a 
drawing of Pyrrochoris, Fig. 46, which represents the second 


FIG. 46. FIG. 47. 

FIG. 46. Pyrrochoris apterus. Division of the 
second spermatocyte. 

FIG. 47. Anasa tristis. 6 Two views of dividing 
female nuclei (oogonia). -* 

FIG. 48. Anasa tristis. 6 The second spermatocyte division. The 
chromosome is lodged at one pole and is lacking at the other. 

FIG. 48. 


division almost completed. Both cells are clearly recogniz- 
able, but only one of them contains an accessory chromosome. 
Next follows a drawing from Anasa, Fig. 47, which is shown 
because it presents to us two views of the cell division. In 
the upper cell we have a side view of the spindle, and we notice 
at once the so-called equatorial plate which is formed by the 
collocation of all the chromosomes in the equatorial plane. 
The lower cell is a view of an equatorial plate seen from the 
spindle pole. Next comes a picture from Anasa, Fig. 48, 
which shows us the second division nearly completed. The 
wandering of the accessory chromosome is very clear. We 
pass now to the consideration of Galgulus, Fig. 49. The 

9 8 


picture shows us a polar view of an equatorial plate of the 
second division. The ordinary chromosomes form a circle; 
in the center we see the accessory chromosome, which in this 
genus is not simple but quadripartite. Fig. 50 is a drawing 
from Syromastes, offering a polar view of the first division. 
Wilson discovered in this genus a double accessory chromo- 
some which does not lie in the center of the equatorial plate 
but outside the circle of the remaining chromosomes. Quite 
similar is the last photograph of our series, Fig. 51, which is 

FIG. 49. FIG. 50. FIG. 51. 

FIG. 49. Galgulus oculatus. Polar view of A the equatorial plate of the second 
spermatocyte division. The accessory chromosome is quadripartite, and lies in the 

FIG. 50. Syromastes marginatus. First spermatocyte division. The accessory 
chromosome is bipartite and lies peripherally. 

FIG. 51. Metapodius terminalis. First spermatocyte division. The accessory 
chromosome lies peripherally, and alongside it is a Y-chromosome. 

taken from Metapodius. In this case the accessory chromo- 
some is simple and lies outside, while near it occurs a Y- 
chromosome which is very similar in appearance to the acces- 
sory, but differs from it in its further development. In the 
center of the equatorial plate lies a minute chromosome, the 
meaning and history of which is not yet completely cleared up. 
The photographs from which these drawings were made are 
very beautiful and render the relations perfectly clear. 

Miss Stevens was a gifted and eager investigator, whose 
early death brings a heavy loss. In the year 1911, she pub- 



lished the discovery of an accessory chromosome in the guinea- 
pig. 47 Her pictures are reproduced in Fig. 52, and show the 
unquestionable accessory chromosome indicated by the letter 
x. Guyer, 48 also an American, has described the accessory 

FIG. 52. Guinea-pig. Spermatocyte nucleus in the preparatory stage (imme- 
diately after the synizesis), in which the accessory chromosome becomes distinct. 
After Miss Stevens. 

chromosome in birds and in man, and it has been found in 
other animals also. 

That the spermatozoa really determine sex has been con- 
firmed by a capital investigation of T. H. Morgan. 49 Phyl- 
loxera"and Aphis lay eggs which develop parthenogenetically. 

FIG. 53. The unequal spermatocyte division, a-c, in Phylloxera; d-f, in Aphis 
solicola. After T. H. Morgan. 

After several generations, and under conditions which are in 
part known to us, the females deposit eggs, which are fertil- 
ized. All fertilized eggs develop into females. This phenom- 
enon does not contradict the new doctrine of sex determina- 


tion, but on the contrary agrees with it fully. Morgan dis- 
covered that when the sexual cells in the male develop in order 
to produce spermatozoa, they form at their second division 
two elements of unequal size. Fig. 53 reproduces two series 
or Morgan's original pictures. In the first series, a-c, and 
also in the second, d-f, the peculiar division is represented. 
The big accessory chromosome moves into the larger of the 
two elements, whech then develops further and becomes a 
spermatozoon. The small element, meanwhile, shrivels up. 
Thus there arise in these animals only spermatozoa with the 
extra chromosome, and accordingly the fertilized ova become 

American investigations, both those mentioned and others 
related to them, lead us to the conclusion that sex is determined 
by peculiarities of the cells, and not by external conditions. 
If an external factor influences the proportion of the sexes, 
this must happen, according to our new interpretation, by 
interfering with the development of one or the other sex. In 
the case of hermaphrodites, interference may act by favoring 
the transformation of indifferent germ cells in one direction or 

That the determination of sex dwells in the cells is made 
probable also by the phenomenon of polyembryony. We 
have already learned that four embryos arise from a single 
Armadillo egg. They are always of the same sex. So also 
in the case of small insects, the parasitic Chalcidae. Accord- 
ing to the investigations of Bugnion, Marshall and Silvester, 
many embryos arise from each single egg, and they are all of 
the same sex. We can explain this wonderful phenomenon 
only by the assumption that the sex of the egg is determined 
from the start. 

It must be mentioned that, according to the investigations 


of Baltzer, the sex of Echini is determined not by the spermato- 
zoa but by the egg. According to him, the Echini have two 
kinds of eggs which differ in their chromosome relations. 

The investigation of the determination of sex must be 
pursued much further. It is above all important to ascertain 
whether the conditions which have been discovered in insects 
recur in all animals and plants. We ask at the same time, 
what are the relations in hermaphrodites? We cannot at 
present even guess the answer to this question. 

It must also be distinctly emphasized that the causal 
relations are not clear. We have learned through the 
memoirs which have been cited that the nuclei of a female in 
a considerable number of animal species contain more chroma- 
tine than the nuclei of a male. We are unable, however, to 
bring this peculiarity into causal relation with the difference 
of sex. It is quite possible that the excess of chromatine is 
only the expression of more essential peculiarities, although 
the greater probability remains that the accessory chromo- 
some is the material cause and basis of sex. 

Mortiz Nussbaum considered the two sexual elements as 
homologous. He wrote in 1880: "Es treten somit bei der 
Befruchtung nicht zwei heterogene Elemente zusammen, die 

einander erganzen und es treffen sich vielmehr 

zwei homologe Zellen, von denen die eine zum Zweck der 
^Conjugation sich in eine beweglichere Form umgegossen hat." 
The homology of the mature ovum with a spermatozoon has 
been generally accepted. The new investigations make this 

We know at present four different species or types of cells. 
Two types are diploid, that is to say, they have the full num- 
ber of chromosomes; and two types are haploid, that is to 
say, they possess the reduced number of chromosomes. 


A. Diploid cells. 

1. Cells of the female bcdy. 

2. Cells of the male body. 

B. Haploid cells. 

3. The female elements (mature ova and polar 

4. The male elements (spermatozoa). 

We suspect besides that there is a fifth kind of cell, the 
indifferent, which we shall perhaps later learn to recognize 
in hermaphrodites and lower organisms. 

Thus we reach the conclusion of to-day's lecture. We 
advance the hypothesis that sex rests upon a physical basis, 
which we recognize by differences in the proportion of chro- 
matin in the cells of the male and female body. The epoch- 
making discoveries of my American colleagues awake joyful 
excitement among biologists. We are pupils of German 
science, and in carrying out the investigations, the results of 
which I have presented to you today, our investigators have 
striven to equal the German ideal. May our activity express 
to you our gratitude ! 


Your Excellencies! 

Biology is the supreme science from which we still await 
the solution of very many problems. Unfortunately, biology 
has not yet become a united science, but consists of sundry 
disciplines more or less separated from one another. The 
number of species of living beings is enormous, so that it is 
impossible for a single investigator to become familiar with all 
the phenomena. According to a recent estimate of Pratt, 50 
published in 1911, the number of known animal species is 
522,400. The number of species yet to be described is cer- 
tainly also very great, and we have further to reckon with the 
considerable, though smaller, number of species of plants. 

We all know that there are two chief types of naturalists: 
first, of those who incline to observation; and second, of those 
who incline to experiments. It occurs very exceptionally only 
that a naturalist is gifted equally in both directions, and hence 
we see that biologists for the most part are either morpholo- 
gists or physiologists. We divide up biology into single 
sciences merely to adapt it to the capacity of the individual. 
An able savant may perhaps be a zoologist, an embryologist, 
a biological chemist, a physiologist, or a paleontologist, but 
he cannot be a real biologist. We can expect only from the 
future such a fusion of the results of our many and many- 
sided biological investigations as will create a true and real 
biology. To attain this result the work of many men will be 



necessary through many years. The contribution of any one 
man will always be very modest in comparison with the whole 
task, but we shall certainly succeed by our united efforts in 
collecting so many generalizations that we shall ultimately 
possess a unified biological science which will have a much 
higher and farther-reaching significance for us than our present 
biology, which consists of single sciences imperfectly fused. 
This more complete biology of the future will I believe be 
recognized by all as the supreme science. We foresee that it 
will answer many questions which philosopher shave striven for 
thousands of years to solve. Philosophy, strictly speaking, 
is occupied chiefly with biological phenomena. Conscious- 
ness, the relation of the soul to the body, the origin of reason, 
the relations of the external world to psychical perception, and 
most subjects of philosophical thought are fundamentally 
biological phenomena which the naturalist investigates and 
analyzes. If these fundamental problems of human thought 
are ever to be solved, the solution will be presented to us, 
according to my conviction, not by philosophers, but by natur- 
alists. I can express my thought better perhaps by saying 
that the future fusion of philosophy and biology, or the 
inclusion of philosophy in biology, is to be expected. His- 
torically, there is a deep cleft between philosophers and 
naturalists. The philosopher takes existing knowledge, med- 
itates upon it, and endeavors by deep thought to draw from 
his knowledge for his own satisfaction the longed for gen- 
eral conceptions. The naturalist, on the contrary, strives 
to widen his knowledge, and to make new observations. 
He wishes to increase the number of known facts, being con- 
trolled by the conviction that the generalizations will follow 
upon the increased acquaintance with facts. For both the 
philosopher and the biologist the final goal is the same, for 


both desire to win their generalizations. The philosopher 
suffers from the disadvantage that he would like to have a 
complete system, a coordinate and harmonious explanation 
of all existence. The naturalist desires this also, but he has 
more patience and does not expect to reach his goal so 
quickly, but rejoices every time that he advances a small 
distance and is able so to order the facts known to him that 
he can deduce a natural law. The naturalist utilizes hypothe- 
ses as much as the philosopher. The naturalist's hypothesis 
is not intended to complete a system of thought, but merely to 
indicate a way by following which he may discover facts as 
yet unknown. During our present debate it is very important 
not to forget the differences between philosophical thinking 
and scientific investigation. As you might anticipate, I hold 
the scientific method to be the better and more certain, and 
therefore cherish, as stated, the opinion that the solution 
of the great problems of human existence, if it is ever achieved 
by us, will be accomplished through biology. 

The conception of life is very uncertain, but we are able 
to place certain foundation stones for the erection of this 
conception. In other words, biology has already achieved 
some important generalizations, several of which have been 
mentioned in the previous lectures. 

At the start, emphasis must be laid on the fact that life 
is known to us only bound to matter. Only through matter 
can life express itself, only through matter act upon the world, 
and only through matter be influenced by the world. As 
we heard in the first lecture, the minimal amount of living 
substance, which makes life possible, is relatively great, and 
probably so great that we can see it with the microscope. 
I at least regard it as improbable that there are invisible 
living beings. 


The opinion is widespread in unscientific circles that 
life may occur without a material basis. We encounter this 
opinion in almost all religions, for they teach the survival of 
the soul, at least of man. In recent years repeated attempts 
have been made to prove these religious doctrines scientific- 
ally. Thus, the spiritualists assert that they can demonstrate 
the existence of living men without material bodies. It may 
be asserted without overventuring that the majority of biolo- 
gists do not consider this spiritualistic demonstration as sound. 
Exceptions are rare. The most famous of such exceptions is 
Alfred Wallace, co-founder with Darwin of the theory of 
natural selection. He remains even in his extreme old age an 
eager follower of spiritualism. I have conversed with him 
a few times on the subject, and got the impression that he 
keeps the whole field of spiritualism separated from science, 
and that he completely sets aside in the discussion of spiritual- 
ism those criteria which he would inevitably put up in the 
case of scientific investigation. No impression was made 
upon him by the numerous instances in which it had been 
proven that alleged spiritualistic phenomena were due to 
cheating. He demanded that cheating should be proved in 
every case before he could yield his faith. Is not the whole 
doctrine of the spiritualists, properly speaking, a psychical 
phenomenon, which we are not to attempt to explain as a real 
phenomenon of the outer world? 

There has been founded in England a society for psychical 
research. This society includes among its members men of 
good standing, who have carried on very serious investiga- 
tions. The formation of the society was a consequence of 
observations made in Cambridge, from which the conclusion 
was drawn that men may communicate with one another 
directly without using the means previously known to us. 


This mode of communication was named telepathy. When 
the British Association for the Advancement of Science held 
its meeting in Montreal (1886), I made the acquaintance of 
several of the leaders of this Society. At that time it seemed 
possible that telepathy was a real phenomenon, and therefore 
in response to the suggestions of these gentlemen we founded 
a society for psychical research in America. After a number 
of years, the scientific men who had founded the American 
society withdrew, in part because it was found out that the 
alleged phenomena of telepathy, which were first described, 
were produced by cheating. The English society is still 
active, and now defends the doctrine that vital phenomena 
may occur without the usual material body, and that it is 
possible to enter into communication with the spirits of the 
dead, although only under conditions which occur rarely. 
If this doctrine could be scientifically assured, it would con- 
stitute the greatest discovery of our time. The demonstra- 
tion is, however, little convincing. In Germany, so far as I 
know, psychical research has received little attention. In 
England and America one hears and reads much about it. 
Of course, we cannot assert a priori that survival, in the sense 
indicated above, is impossible, yet the biologist is likely to 
stick to his assertion that the presence of the material basis is 
the exclusive substratum for life. 

Where does the living substance come from? So far as 
we know at present it arises only from itself, it propa- 
gates itself, and can be created only by itself. If it should 
once be entirely destroyed, life on our earth would cease. 
Formerly this view did not prevail, for it was believed that 
spontaneous generation occurred in the world. In mediaeval 
times learned men adhered contentedly to the idea that the 
insects which appear in decaying meat arise by spontaneous 


generation from the meat. Francesco Redi's famous experi- 
ments brought the first proof that the insects arise only when 
insect eggs are laid in the meat. For a still longer time it 
was considered possible that the simplest organisms, bacteria, 
etc., could be formed by spontaneous generation. The 
experiments of Pasteur, made not many years ago, brought 
the final proof that this also is impossible. On Pasteur's 
discovery is based the antiseptic treatment of the surgeon, 
which has for its object simply to prevent the entrance of the 
microscopic germs which cause sepsis. We must regard it 
as an assured conclusion of biology that spontaneous genera- 
tion has never been observed, and many naturalists incline 
to assert that it never will be observed by us. 

Thus we come back to the question, where does the living 
substance come from? Helmholtz 51 and, following him, 
Arrhenius have defended a hypothesis according to which 
life reached this earth from outside. This hypothesis assumes 
the occurrence of very small living germs, about of the size of 
the smallest individual germs known to us as occurring on the 
earth, which are driven hither and thither in space, and may 
accidentally hit the earth, or which perhaps are brought on 
meteorites, or, according to the hypothesis advanced by 
Arrhenius, by the beats of waves of light. The hypothesis is 
bold and interesting. If it is correct, the possibility exists 
of our receiving organisms which differ from all species hith- 
erto occurring on the earth, and which therefore might initiate 
a new evolution of living beings. But even if we assume the 
correctness of this hypothesis, it still offers no answer to our 
question, because it assumes the previous existence of living 
substance. Alongside this theory occurs a new hypothesis of 
spontaneous generation. This second hypothesis is, so to 
speak, a side product of the doctrine of evolution. After the 


astronomers had asserted the evolution of our planetary 
system, after the geologists had asserted the evolution of the 
world, followed Darwin, who convinced us of the necessity of 
assuming the evolution of plants and animals. Evolution 
leads us back to a time when the conditions on our earth were 
such that life, as we now know it, must have been impossible. 
Life appeared later. It is therefore clear that somehow living 
substance must have arisen on the earth. Thus it became an 
intellectual necessity for us to assume in this sense the spon- 
taneous generation of life. Those who make this assumption 
have, strictly speaking, only one explanation to offer, namely 
the supposition that proteid molecules could be formed, under 
the then prevailing conditions, and by chance so come together 
and unite in combination with other substances that they 
would produce the first living substance. If we may venture 
to pass judgment on this hypothesis we must bear in mind 
that it is merely the expression of our desire to meet the 
assumed needs of the doctrine of evolution. The hypothesis 
has no further real scientific foundation. Pfliiger 52 has 
endeavored in a clever and interesting memoir to determine 
speculatively the possibility of the origin of proteid sub- 
stances, but he did not get beyond speculation. To be exact, 
we must consider that we have reached the new doctrine of 
spontaneous generation through our inability to conceive the 
origin of life otherwise. I imagine a very interesting and 
instructive book, which is to be on the theme how often the 
scientific man has been led to false conclusions through the 
assumption "it must be so because we cannot conceive it 
otherwise." We may never say in science, it is impossible. 
The time of scientific surprises is not over. A few years ago, 
physicists thought that they had already discovered the basic 
phenomena of their science, and yet they are all today occu- 


pied with so transforming their Tundamental conceptions 
that they will correspond to the discoveries of recent years. 
Some surprises will surely come in biology, and therefore I 
prefer to take an agnostic position in regard to the doctrine of 
spontaneous generation, and to cling to the possibility that the 
final explanation will be found in some unexpected direction, 
or will be given by some phenomenon as yet wholly unknown 
to us. It is much achieved that we can now maintain the 
statement that protoplasm, under which term we include the 
nucleus, is the physical basis of life. 

Let us now pass to the consideration of the general activity 
of protoplasm. First of all, we must regard metabolism which 
we must look upon as the basic phenomenon of life. Very 
many chemical substances are taken up by protoplasm which 
in part are worked over into new chemical combinations, by 
which the growth of the living substance is made possible, and 
at the same time the necessary material is produced for the 
performance of work. In consequence of the performance of 
work simple chemical compounds arise which cannot be fur- 
ther used by the protoplasm, and are therefore discarded, and 
are designated by us as excretes. In order to maintain life, 
the stream of matter through the protoplasm must continue. 
We have no occasion to assume that metabolism is more than 
a series of chemical processes. 

By nourishing itself, protoplasm grows, and as a conse- 
quence thereof follows the multiplication or proliferation of 
cells. We know also that when protoplasm grows, the new 
formed protoplasm is similar to that already present. The 
self-maintenance of its own peculiarities is highly character- 
istic of protoplasm and we recognize in this peculiarity the 
basis of heredity. The question of variations is a very differ- 
ent one. The doctrine of evolution forces us to the assump- 


tion that protoplasm, in spite of the fact that so far as we can 
observe it propagates itself and in this propagation remains 
like itself, nevertheless alters in the course of time. The 
continuous, slowly progressive change of protoplasm which 
has led to the origin of species, we designate as the phylogen- 
etic variation. Many experiments on variation have been 
made in recent years. In one direction our knowledge has 
been greatly extended. The so-called Mendelian variation 
is certainly known to you. It is remarkable that the varia- 
tions which have been found in the investigation of the Men- 
delian law are not new variations, but on the contrary in 
such cases as have hitherto been analyzed with certainty, we 
have to do with the dropping out of a character. This is 
illustrated by the beautiful experiments of Professor Morgan 53 
of Columbia University on Drosophila. The eyes of this 
small fly vary in their color. Morgan has succeeded in prov- 
ing by his experiments that four factors determine the color 
of the eye, and that all variations in the color are caused by 
the dropping out of one or more of these factors. The varia- 
tions arise by the exclusion of a character which is present in 
normal individuals. We still have to discover the origin of 
new variations, although we have already some indications of 
the answer to this problem. I should like to discuss the mat- 
ter if time permitted, but I must restrict myself to a single 
example. Professor Stockard 54 has made experiments at the 
Biological Station at Woods Hole, which led him to the fine 
discovery that the addition of minute quantities of magnesium 
chloride to ordinary sea water creates some wonderful modi- 
fications in the development of bony fishes. He employed 
for his experiments Fundulus heteroclitus, a species of minnow 
very common at Woods Hole. Eggs which are kept in the 
magnesium water produce embryos which appear normal in 


most respects. They show, however, a tendency toward 
fusion, in the median line, of the two eyes which normally are 
lateral. The fusion may go so far that a fish is produced 
which has only one eye in the median line of the head. Such 
an embryo is called a Cyclops. It is thus shown that an alter- 
ation in the chemical conditions produces an extraordinary 
alteration of the development. In this connection we may 
mention also the interesting discovery of artificial parthen- 
ogenesis by A. D. Mead, 20 which has been confirmed by 
Loeb, 56 Matthews 55 and others. These investigators have 
demonstrated that eggs may be excited to further develop- 
ment through various chemical means without being fertil- 
ized in the normal manner. An egg which has remained 
unfertilized and does not receive the chemical excitation will 
break down. The fate of the egg may be completely altered 
by a relatively small chemical treatment. In all these cases 
we must ascribe the striking alterations of the vital processes 
to chemical action. 

The immediate microscopic observation of cells during their 
physiological activity teaches us that the phenomena of 
life depend upon their material substratum. We know, for 
example, in muscles, which have been recently carefully inves- 
tigated by Meigs, 57 very instructive relations. There are 
two kinds of muscle fibers, the so-called smooth and the stri- 
ated. The smooth muscles occur chiefly in the internal 
organs. When they contract they give off water which may 
be found between the single fibers. When they expand they 
take up the water again. The striated muscles are for the 
most part connected with the skeleton. Their fibers are much 
larger than the smooth muscle fibers, and have in their interior 
very fine contractile fibrils, Fig. 9, which I have already had 
occasion to mention. When the striated muscles contract, 


water is taken up by the fibrils, to be given up by them again 
when the muscles elongate. The movement of water in the 
two types occurs in opposite senses during contraction. In 
smooth muscles it moves out from the fibers, in striated, into 
the fibrils. Meigs' investigation was carried out in part in 
my laboratory, and I have been able to confirm his results 
by the inspection of his preparations. The contraction of 
muscles thus appears to depend on the movements of fluid 
within the muscle, and muscular contraction is a chemical- 
physical phenomenon. Nerve cells contain in their ncrmal 
condition small mases, commonly designated as Nissl's bodies. 
When a nerve cell functions these masses are used up during 
its activity. The observations of C. F. Hodge 58 of Clarke 
University are very convincing. He investigated the central 
nervous system of swallows. He collected some birds in the 
morning when they were fresh, and again others at the end of 
the day when they were exhausted by many hours of flight. 
He found it easy to demonstrate that the content of the nerve 
cells was used up during the day, and that the exhausted 
cells showed clearly the loss which they had suffered. He 
also found that certain nerve cells in a very old man have a 
permanently exhausted appearance and were therefore no 
longer capable of functioning. (Mention should be added of 
the very extensive investigation of the exhaustion of nerve 
cells by Dr. Crile, an account of which he presented to the 
American Philosophical Society in April, 1913.) When we 
consider that our highest performances are functions of our 
nerve cells, we must admit that our psychical activity also de- 
pends upon the activity and the using up of living substance. 
If we pass to the organs of the so-called vegetative life we 
find similar conditions. The secretion of glands, as we first 
learned through the investigations of R. Heidenhain, is formed 


usually from substances which we can easily see under suitable 
conditions in the gland cells. When the gland functions, 
these substances, which often may be seen as granules in 
the protoplasm, are metamorphosed chemically, in order to 
form the secretion which is given off by the gland. Very 
exact recent investigations of these processes have been made 
by the American, Bensley. 59 As we heard in the fifth lecture, 
we can distinguish in the nuclei of sexual cells in many animals 
a so-called chromosome which differs from the remaining 
chromosomes. It claims our special interest because it 
occurs in the cells of the female body, but on the contrary is 
not found in the cells of the male body; hence, as we heard, 
the hypothesis that these chromosomes determine the sex. 
As we have already considered these relations, it will suffice 
merely to mention the chromosomes. In conclusion let me 
again direct your attention to the fact that always as we 
grow old we can observe visible modifications of the cells. 

The phenomenon of metabolism and the phenomenon of 
the visible alterations which can be observed in cells, lead to 
the conclusion that the life processes are explicable by the 
chemical properties and the structure of protoplasm and 

This explanation is called the mechanistic theory of life, 
and has found acceptance with the majority of biologists. 
It cannot be doubted that the mechanistic explanation is 
stringently sufficient for most vital processes. Whether it is 
sufficient to explain all the phenomena of life is a question 
in regard to which opinions diverge. On one side there are 
the Monists and their friends, and on the other the Vitalists 
and Dualists. There are biologists who make a dogma of the 
mechanistic theory and defend their doctrine with a vehe- 
mence which recalls the theological discussions of the Middle 


Ages. They express their opinions with limitless certainty 
and listen unwillingly if one does not agree with them. We, 
however, must consider the question more quietly and remain 
remote from over-eagerness, and this chiefly because there 
are important vital phenomena known to us which up to 
the present at least cannot be made comprehensible by the 
mechanistic theory. 

Of such phenomena I take the privilege of enumerating 
three : 

1. Organization. 

2. The teleological mechanism. 

3. Consciousness. 

Organization is characteristic of life, but exactly what 
the organization of living substance is, is by no means clear 
to us. We have already discussed this. We only know 
that organization is created by uniting various chemical 
substances, some of which form small masses which remain 
separate from one another. We know also that the living 
substance always contains in solution certain salts. Water 
is of course indispensable. We possess no knowledge how this 
mixture arises, or how it is capable of maintaining and increas- 
ing itself. We may indeed say that we must assume that this 
organization is to be explained mechanistically, but then we 
really merely say that we have hit on no better explanation 
hitherto and that properly speaking we cannot give a real 
explanation at all. So long as the essence of organization is 
completely unknown, we must refuse with decision to admit 
the complete sufficiency of the mechanistic theory. 

One of the most wonderful properties of life is the tele- 
ology, with which the vital functions are carried out. The 
changes in a living animal or in a living plant progress as if the 


organism was working conscious oFIFs aim. How did this 
vital teleology arise; how has it maintained itself? That 
teleology is to be explained by the mechanistic theory is 
again an assumption, the justification of which we still 

Consciousness is the most obscure problem of biology. 
Hitherto, the philosophers, and more recently, the psycholo- 
gists, but not the biologists, have occupied themselves with 
the study of consciousness, and they have, it seems, only got 
so far that they can make it clear to us that consciousnes is 
an ultimate conception, that is to say, a conception which 
cannot be further analyzed. In an address, 60 which I delivered 
in the year 1902, as President of the American Association 
for the Advancement of Science, I endeavored to make clear 
the importance of consciousness in the evolution of animals. 
I adhere today to the opinion then expressed that the phylo- 
genetic development, especially of vertebrates, was dominated 
by the evolution of consciousness. If this is the case, it offers 
an important proof of the great importance of consciousness 
in animal life, and in fact we are forced to ascribe to conscious- 
ness the leading role in evolution. It can have importance 
only if it influences the life of animals. Consciousness is 
active. In the address mentioned above I stated that accord- 
ing to my conviction it is impossible to avoid the conclusion 
that consciousness stands in immediate causal relation to 
physiological processes. What is consciousness? There are 
so far as I know only three possible explanations from 
which we must choose. According to one view, consciousness 
is not a real phenomenon, but a so-called epiphenomenon, 
something that accompanies the physiological processes with- 
out exerting any influence upon them. As a celebrated psy- 
chologist expressed it to me, consciousness is merely the other 


side of the alterations in the protoplasm of the brain cells. 
According to a second view, consciousness is a special form of 
energy. This view, strictly taken, I believe to be purely 
metaphysical. No observations or experiments are known to 
me which even suggest that energy can be transformed into 
consciousness. As you have doubtless already perceived, I am 
not inclined to regard consciousness as a condition of the pro- 
toplasm or as a form of energy. If we admit, as according to 
my interpretation we must admit, that consciousness plays 
an important role in life, then it must be able to act in some 
way upon the body. Such an action can reveal itself only by 
the transformation of energy somewhere in the body. Thus 
we are led directly to the hypothesis that consciousness may 
cause the transformation of energy, and that it is itself not 

I acknowledge the great significance and importance of 
the mechanistic theory of life. A pupil of CarlLudwig may 
not turn away from this theory, for it has proven of the 
highest value in science, and has guided many investigations 
to fortunate termination. But must we carry our enthusiasm 
for this view, for which we are indebted chiefly to the great 
Leipzig physiologist, so far that we become immediately 
converts to the dogma that this theory suffices for all the phe- 
nomena of life? I do not belong to those who wish to establish 
monism as the definite and final philosophy. On the con- 
trary the possibility still remains that we must accept a dual- 
istic philosophy as the desired solution. According to this 
philosophy we recognize in the universe energy and conscious- 
ness. We biologists, however, are not philosophers. We 
make no assumption to offer you final explanations. The 
conception of consciousness which I have laid before you is 
not a philosophical speculation, but a scientific hypothesis 


which is brought forward because it makes the totality of 
vital phenomena more comprehensible. It would be sup- 
remely interesting to know and we hope that in the future it 
will be known what consciousness is. But the first question 
for the biologist is: Is consciousness a true cause? 

And now for our final conclusion. Life is bound to matter. 
Vital phenomena are alterations of the living substance which 
we describe by saying that they are transformations of energy. 
But there always remains the possibility that consciousness 
cannot be explained mechanistically, that it is neither a con- 
dition of protoplasm, nor a special form of energy, but some- 
thing of its own kind, not comparable with anything else 
that we know, and that it reveals itself by causing transforma- 
tions of energy. 

There still remains for me to thank you for the attention 
with which you have honored me, and for the extreme hospi- 
tality which I have enjoyed here. May the University of 
Jena grow and prosper! Of her I shall carry with me to my 
distant home memories to which I shall always return with 
joy so long as I live. To her I say farewell, and to you, thanks ! 



1. Carl Heitzmann, Microscopical morphology of the animal body in health 
and disease. 8vo. pp., xix, 849. New York, 1885. F. H. Vail and Co. 

2. C. O. Whitman, The inadequacy of the cell theory. 

3. E. B. Wilson, The cell in development and inheritance. Second edition. 
New York, 1900. 

4. J. Loeb, Arch, gesamt. Physiol., 1907, Bd. cxviii, s. 7. 

5. Ralph L. Lillie, Certain means by which star-fish eggs naturally resistant 
to fertilization may be rendered normal and the physiological conditions 
of this action. Biol. Bulletin, XXII, 328-346, 1911. 

6. A. C. Eycleshymer, The cytoplasmic and nuclear changes in the striated 
muscle-cell of Necturus. Amer. Journ. of Anat., Ill, 285310. 

7. Professor Whitman made extensive experiments concerning heredity in 
pigeons, and for this purpose he kept a large flock of these birds. At his 
invitation several students availed themselves of the opportunity to make 
a careful study of the early development of pigeons. The resulting stud- 
ies offer us by far the most exact descriptions of the early development of 
birds which we possess. Compare: 

E. H. Harper, The fertilization and early development of the pigeon's 
egg. Amer. Journ. Anat., Ill, 349-386, 1904. 

Mary Blount, The early development of the pigeon's egg with especial 
reference to polyspermy. Journ. of Morphol., XX, 1-64, 1909. 

J. Thomas Patterson, GaStrulation in the pigeon's egg. A morpholog- 
ical and experimental study. Journ. of Morphol., XX, 65-123, 1909. 

8. R. G. Harrison has published many experiments on the origin of nerve 

1901. Arch.f. mikrosk. Anatomic, Bd. LVII, 354-444. 

1903. Arch. f. mikrosk. Anatomic, Bd. LXIII, 35-149. 

1904. American Journ. of Anatomy, III, 197220. 

1906. American Journ. of Anatomy, V, 121-131. 

1907. Journal of Experimental Zoology, IV, 230-281. 

1907. Anatomical Record, No. 5. 

1908. Anatomical Record, No. 8. 
1908. Anatomical Record, II, 385-410. 

1910. Arch. f. Entwicklungsmechanik, XXX, Tl. 11,15-33. 

1910. The outgrowth of the nerve fiber as a mode of protoplasmic 

movement. Journ. Exp. Zoology, IX, 787-846. 

In the last-nientioned article he describes the observations made upon 
in vitro cultures, and pictures in detail the outgrowth of the axis-cylinders 
(nerve-fibers) of young nerve cells. Harrison has definitely solved the 
problem which has long been disputed. 


9. C. S. Minot, Age, Growth, and Death, p7~2bi, where the literature is also 


TO. V. E. Emmel, A study of the regeneration of tissues in the regenerating 
crustacean limb. Amer. Journ. Anat., X, 109-158. 

1 1. As far as I know, H. Braus was the first to graft rudimentary extremities. 
Compare Verh. Anat. Ges., XVIII and Anat. Anz., XXVI. His experi- 
ments have been repeated and extended by W. H. Lewis and R. G. 

12. W. H. Lewis and Mrs. Lewis conjointly have made experiments upon 
the in vitro cultures of embryonic tissue. Compare The Anatomical 
Record, VI, 195 and 207. 

13. Carl Semper, Die Verwandtschaften der gegliederten Tiere, iii. Sem- 
pers Arbeiten. Zool. Zootom. Institut Wiirzburg, Bd. Ill, 115. 

14. The text deals with the law of genetic restriction, which can be found 
more definitely stated in my "Laboratory Text-book of Embryology," 
2nd ed., p. 14. 

T5. E. A. Schafer, Life: its nature, origin and maintenance. (Presidential 
Address before the British Association for the Advancement of Science, 
Dundee, September, 1912). Longmans, Green & Co., London, 1912. 

1 6. W. Kleinenberg, The development of the earth-worm, Lumbricus trap- 
ezoides. Quart. Journal of Microsc. Science, XIX, 206-244, 1879. 
(Compare also, Zeitschr. wiss. Zool., XLIV, 1886.) 

17. E. B. Wilson, The germ bands of Lumbricus. Journ. of Morphology, 
I, p. 183. 

1 8. J. T. Patterson, A preliminary report on the demonstration of poly- 
embryonic development in the Armadillo. Anat. Anzeiger, XLI, 369- 
381. (Cites also the earlier works of Newman and Patterson, et al.) 

19. Hans Driesch, Entwicklungsmechanische Studien I. Zeitschr. f. wiss. 
Zoologie, LIII, 1 60. 

20. A. D. Mead, Biological Lectures at Woods Hole, Boston, 1898. 

21. F. A. Woods, Origin and Migration of the germ-cells in Acanthias. 
American Journ. of Anat., I, 307. (The so-called "precocious segrega- 
tion" of the sexual cells of fishes was first more exactly described by C. 
H. Eigenmann.) 

22. B. M. Allen has determined the history of the sexual cells in four verte- 
brate types. 

" 1911. Amia, Journal of Morphology, XXII, p. n. 
1911. Lepidosteus Journal of Morphology, XXII, p. 2, 
1907. Rana, Anat. Anzeiger, XXX, 339. 
1906. Chrysemys, Anat. Anzeiger, XXIX, 217. 

23. R. W. Hegner, The origin and early history of the germ-cells in some 
Chrysomelid beetles. Journal of Morphology, XX, 231-296, 4 Taf., 1909. 

NOTES 121 

24. Oskar Hertwig, Beitrage zur Kenntnis der Bildung, Befruchtung und 
Teilung des tierischen Eies. Morphol. Jahrb., I, III, and IV, 1875-1878. 

25. W. G. Moenkhaus, The development of hybrids between Fundulus 
heteroclitus and Menidia notata. Amer. Journ. of Anat., Ill, 39-65, 1904. 

26. E. G. Conklin, Karyokinesis and cytokinesis, etc., of Crepidula and 
other Gastropoda. Journ. Acad. Nat. Sciences, Philadelphia, XII, 1902. 

The organization and cell lineage of the Ascidian egg. Journ. Acad. 
Nat. Sciences, XIII, 1-119, I 95- (See p. 93 ff.) 

27. F. R. Lillie, Embryology of the Uniomidae. Journ. of Morphology, X, 

Differentiation without cleavage in the egg of the annelid Chsetop- 
terus pergamentaceous. Arch, fur Entwicklungsmechanik, XIV, 1902. 

(The works of E. B. Wilson, Arch. f. Entwicklungsmechanik, XVI, and 
Journal of Exp. Zoology, I, may also be compared. Further, the treatise 
of Yatsu's Biol. Bulletin, VI.) 

28. E. Maupas, Recherches experimentales sur la multiplication des In- 
fusoires cilies. Arch. Zool. Experim., 1888. 

' 29. Calkins has caused several students to carry on investigations on the 
life cycle of the Protozoa. The newest one of these is the investigation 
of Miss J. E. Moody, which was published in the Journal of Morphology, 
XXIII, Heft 3 (Sept., 1912), 349-408. Miss Moody cites the earlier 
literature and presents a good discussion of "depression" to the reader. 

30. H. S. Jennings, Assortative mating, variability, and inheritance of size 
in the conjugation of Paramecium. Journ. Exp. Zool., XI, 1-134, 1911. 

31. C. M. Child, A study of senescence and rejuvenation based on experi- 
ments with Planaria dorotocephala. Arch, fur Entwicklungsmechanik, 
XXXI, 537-6i6, 1911. 

32. E. G. Conklin, Cell size and nuclear size. Journ. Exp. Zool., XII, 
1-98, 1912. 

Body size and cell size. Journ. of M or ph., XXIII, 159-188, 1912. 
\ 33. C. S. Minot, Senescence and rejuvenation, ist paper. On the weight 
of guinea-pigs. Journ. of PhysioL, XII, 97-153. 

The results and further conclusions, as well as justification, may be 
found in "The Problem of Age, Growth, and Death," which appeared 
in 1908. 

34. C. A. Herter, Popular Science Monthly, LXXIV, 31 (Jan., 1909). 

35. M. Miihlmann, Das Altern und der physiologische Tod. Samml. anat.- 
physiol. Vortrage (Gaupp u. Nagel), Heft XI, Jena, 1910. 

The earlier works of the author are cited. The criticism of Minot 
may be found on p. 22. Minot's criticism of Miihlmann appears on p. 
28 of the book "Age, Growth and Death." 

122 NOTES 

36. Alexander Goette, Ueber den Ursprung desTodes, 1883. 

37. von Hansemann, Deszendenz und Pathologic, Berlin, 1909. 

38. H. H. Donaldson, The extensive work on the embryonic growth of 
the white rat has not yet appeared. Donaldson's comparison of the 
white rat with man in respect to growth has particular interest. Boas 
Memorial Volume, 1906. 

39. C. S. Minot, Human Embryology, New York, 1892. 

40. Thomas H. Morgan has treated the subject of the relation of egg-size, 
etc., to the determination of sex in an excellent manner in his book, 
"Experimental Zoology," New York, 1907, p. 391-426. 

41. Kuschkakewitz, Richard Hertwigs Festschrift, 1910. The criticism of 
T. H. Morgan should be noticed concerning the experiments of R. Hert- 
wig and Kuschkakewitz. 

42. Helen D. King, Studies on sex-determination in amphibians. 

1907. Biological Bulletin, XIII. 

1909. Biological Bulletin, XVI. 

1910. Biological Bulletin, XVIII, 

1911. Biological Bulletin, XX. 

1912. V. The effects of changing the water content of the egg, etc. 
Journ. Exp. ZooL, XII, 319-336. 

43. C. E. McClung, The spermatocyte divisions of the Acrididae. Kansas 
University Quarterly, January, 1900, 73-100. Pis. XV-XVII. 

The accessory chromosome-sex determinant? Biological Bulletin, III, 
43-84, 1902. 

44. E. B. Wilson has given us two excellent summaries on the results of in- 
vestigations on accessory chromosomes in the year 1909, in Science, 
XXIX, 53-70, and in the year 1911, in the Arch, fiir Mikrosk. Anat., 
Vol. 77, 249-271. His own papers have appeared chiefly under the 
title "Studies on Chromosomes." 

1. 1905. Journal of Experimental Zoology, II, Heft 3. 

2. 1905. Journal of Experimental Zoology, Bd. II, Heft 4. 

3. 1906. Journal of Experimental Zoology, Bd. III. 

4. 1909. Journal of Experimental Zoology, Bd. VI, Heft 2. 

5. 1909. Journal of Experimental Zoology, Bd. VI, Heft 2. 

6. 1910. Journal of Experimental Zoology, Bd. IX. 

7. 1911. Journal of Morphology, XXII, 71. 

45. The following researches on the spermatogenesis of Anasa are known to 
the author. 

Fr. C. Paulmier, 1899, Journal of Morphology, XV, Suppl. 
E. B. Wilson, 1905, Journal Exp. Zoology, II 
E. B. Wilson, 1907, Science, XXV, 631. 

NOTES 123 

Foote and Strobell, 1907, Biological Bulletin, XII. 
Foote and Strobell, 1907, American Journ. Anat., VII, 279-316. 
Lefevre and McGill, 1908, American Journ. Anat., VII, 469-485. 
C. V. Morril, 1909, Biological Bulletin, XIX. 

C. E. McClung and Edith Pinney, An examination of the chromo- 
somes of Anasa tristis. The Kansas University Science Bulletin, V, No. 
20, 349-380. 

To those who would like to acquaint themselves further with this sub- 
ject, this excellent article is especially recommended. It is distinguished 
by its concise, clear and exhaustive pVesentaticn. 

46. Miss N. M. Stevens studied chromosomes in many insects with great 
skill and success. 

1908. Diptera. Journal Exp. Zoology, V, 359. 

1908. Diabrotica. Journ. Exp. Zoology, V, 453. 

1909. Coleoptera. Journ. Exp. Zoology, VI, 101. 
1909. Aphidae. Journ. Exp. Zoology, VI, 115. 

Compare also Biol. Bull., XVIII, 73-75, 1910. 

47. Miss N. M. Stevens. Preliminary note on heterochromosomes in the 
guinea-pig. Biol. Bulletin, XX, 121-122, 1912. 

Heterochromosomes in the guinea-pig. Biol. Bulletin, XXI, 155-167. 

48. Michael F. Guyer,The spermatogenesis of the domestic guinea (Numidia 
meleagris dom.). Anat. Am., XXXIV, 502-513, 1909. 

Accessory chromosomes in man. Biol. Bulletin, XIX, 219-234. 

49. T. H. Morgan, A biological and cytological study of sex determination 
in Phylloxerans and Aphids. Journ. Exp. Zoology, VII, 239-352, 1909. 
(Also several preliminary communications.) 

50. H. S. Pratt, Science, 1912. The author states the following estimations 
of the number of known species of animals: 

Linne 1758 4,236 

Agassiz and Bronn 1859 129,530 

Ludwig (Leuiiis) 1886 272,220 

Pratt 1911 522,400 

51. Helmholz is not the author of the hypothesis that meteorites brought 
life to our earth. As early as 1871 it was introduced by Sir William 
Thompson in his Presidential Address before the British Association. So 
also the hypothesis of Arrhenius, which, according to Schafer, was orig- 
inated by Cohn (1872) and Richter (1875). 

52. E. Pfliiger, Ueber die physiologische Verbrennung in den lebendigen 
Organismen. Pflugers Arch, gesamt. PhysioL, X, 251-367, 1875. (See 

P- 339 #) 

53. T. H. Morgan utilized Drosophila for many experiments on heredity. 

124 NOTES 

The larvae live on fruits and compkte~Eheir metamorphosis in about 
three weeks. Thus one can cultivate many generations of these small 
flies very easily and quickly. The principal investigation on the eyes 
will appear soon in the Journal of the Academy of Sciences, Philadelphia. 
The experiments, however, are still being carried on. Morgan has 
published other researches on Drosophila. See Science, XXXII, p. 
120; XXXII, p. 496; XXXIII, p. 534; XXXIV 5 p. 384. Also, Journal 
Exp. ZooL, XI, 365-411, 1911. (Heredity in eye color, with figures.) 

54. C. R. Stockard, The development of artificially produced Cyclopean 
fish "The magnesium embryo." Journ. Exp. ZooL, VI, 285-337, 1908. 

55. A. P. Matthews, Some ways of causing mitosis in unfertilized Arbacia 
eggs. Amer. Journ. Physiol., 1900, VI, 343-347. 

56. J. Loeb, On the nature of the process of fertilization and the artificial 
production of normal larvae (Plutei) from the unfertilized egg of the sea- 
urchin. Amer. Journ. Physiol., 1900, III, 135-138. 

On the artificial production of larvae from the unfertilized eggs of the 
sea-urchin (Arbacia). Amer. Journ. Physiol., 1900, III, 434-471. 
(Preliminary communication, Ibid., 135-138.) 

Experiments on artificial parthenogenesis in annelids and the nature 
of the process of fertilization. Amer. Journ. Physiol., 1901, IV, 423-459. 
(Compare also Ibid., 178-184). 

57. E. B. Meigs, Zeitschr. f. allgem. Physiologie, 1908, VIII, 81. Amer. 
Journ. Physiol., 1908, XXII, 477. Amer. Journ. Physiol., 1912, XXIX, 


58. C. F. Hodge, Changes in ganglion cells from birth to senile death. Journ. 
of Physiol., XVII, 129-134. 

59. R. R. Bensley, Studies on the pancreas of the guinea-pig. Amer. Journ. 
of Anat., XII, 297-388, 1911. 

60. Charles S. Minot, The problem of consciousness in its biological aspects. 
Presidential address before the American Association for the Advance- 
ment of Science. 

Science, XVI, 1-12, 1902. German translation in the volume, "Die 
Methode der Wissenschaft," published by Gustav Fischer, 1913. 


KINGSLEY. Comparative Anatomy of Vertebrates. A text-book 
arranged upon an embryological basis and prepared especially to meet 
the needs of the under-graduate student. By J. S. Kingsley, Pro- 
fessor 0} Biology in Tufts College. Octavo; 346 Illustrations drawn or 
redrawn expressly for this book. ix+4oi pages. 

Cloth, $2.25. 

DAVISON. Mammalian Anatomy. With Special Reference to the 
Anatomy of the Cat. By ALVIN DAVISON, A. M., PH. D., Professor of 
Biology, Lafayette College, Easton, Pennsylvania. Second Edition, 
Revised. 114 Illustrations. Cloth, $1.50. 

FOLSOM. Entomology with Special Reference to Its Biological and 
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Edition, 4 Plates and 304 other Illustrations. 8vo; 405 pages. 

Cloth, $2.25. 

GALLOWAY. Zoology. A Text-book for Secondary School?, Normal 
Schools and Colleges. .By T. W. GALLOWAY, PH. D., Professor of 
Biology, James Milliken University, Decatur, Illinois. Second Edition, 
Revised. 240 Illustrations. 8vo; 460 pages. Cloth, $2.00. 

Elementary Zoology. A Text-book for Secondary Educational 
Institutions. 160 Illustrations. xx + 4i8 pages. Cloth, $1.25. 

GREEN. Vegetable Physiology, An Introduction to. By J. REYNOLDS 
GREEN, sc. D., F. R. s., Fellow of Downing College, Cambridge. Third 
Edition, Revised. 182 Illustrations. Octavo; 482 pages. 

Cloth, $3.00. 

JOHNSTON. Nervous System of Vertebrates. By JOHN BLACK 
JOHNSTON, PH. D., Professor of Comparative Neurology, University of 
Minnesota. With 180 Illustrations. Octavo; 390 pages. 

Cloth, $3.00. 

SCHEFFER. Zoology. Loose Leaf System of Laboratory Notes. 
Second Edition. Revised and Enlarged. By THEO. H. SCHEFFER, 
A. M., formerly Assistant Professor of Zoology, Kansas State Agricultural 
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BRUBAKER. Text-book of Physiology. Illustrated. Fourth Edi- 
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Students. Including a Section on Physiologic Apparatus. By A. P. 
BRUBAKER, M. D., Professor of Physiology and Medical Jurisprudence at 
Jefferson Medical College. With an appendix giving a brief account of 
some essential forms of apparatus suited to those who have not large 
laboratory opportunities. Fourth Edition. Thoroughly Revised and 
in Parts Rewritten, i Colored Plate and 377 other Illustrations. 
Octavo; xii + 735 pages. Cloth, $3.00. 



HAMAKER. Principles of Biology. Including brief outlines for lab- 
oratory work. By J. I. HAMAKER, Professor of Biology, Randolph- 
Macon Woman's College, College Park, Virginia. With 267 Illustra- 
tions. Octavo X+ 459 pages. Cloth, -$1.50. 

MARSHALL. Microbiology. A Text-book of Microorganisms, General 
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MINOT. Embryology. A Laboratory Text-book of Embryology. By 
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VINAL. A Guide for Laboratory and Field Studies in Botany. By 
WILLIAM GOULD VINAL, A. M. (Harvard) , Salem Normal School, Salem, 
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STEVENS. Plant Anatomy from the Standpoint of the Development 
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152 Illustrations. 8vo; 394 pages. Cloth, $2.00. 

STOHR. Text-book of Histology. Arranged upon an Embryological 
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DR. PHILLIP STOHR, Professor of Anatomy at the University ofWurzburg. 
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CRARY. Field Zoology, Insects and Their Near Relatives and Birds. 
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McMURRICH. The Development of the Human Body. A Manual of 
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PATTEN. The Evolution of the Vertebrates and Their Kin. By 
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