MODERN PROBLEMS OF BIOLOGY
MI N OT
BY THE SAME AUTHOR
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-
"The book is well written and well printed.
The illustrations are numerous and well executed."
New York Medical Journal.
P. BLAKISTON'S SON & CO.
MODERN PROBLEMS OF BIOLOGY
LECTURES DELIVERED AT THE UNIVERSITY OF JENA,
CHARLES SEDGWICK MINOT
LL. D., YALE TORONTO AND ST. ANDREWS; D. SC., OXFORD; DIRECTOR
OF THE ANATOMICAL LABORATORIES, HARVARD MEDICAL
SCHOOL; EXCHANGE PROFESSOR. AT THE UNIVER-
SITIES OF BERLIN AND JENA, IQI2-I3.
WITH FIFTY-THREE ILLUSTRATIONS
P. BLAKISTON'S SON & CO.
1012 WALNUT STREET
COPYRIGHT, 1913, BY P. BLAKISTON'S SON & Co.
THE. MAPLE. PRESS. YORK. PA
UNIVERSITY OF JENA
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.
CHARLES S. MINOT.
1. THE NEW CELL DOCTRINE i
2. CYTOMORPHOSIS 24
3. THE DOCTRINE OF IMMORTALITY 43
4. THE DEVELOPMENT OF DEATH . . . 59
5. THE DETERMINATION OF SEX 82
6. THE NOTION OF LIFE
PROBLEMS IN BIOLOGY
THE NEW CELL DOCTRINE
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
2 THE NEW CELL DOCTRINE
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
1. The New Cell Doctrine.
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-
THE NEW CELL DOCTRINE
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.
an entirely different constitution from the rest of the mass,
which one is inclined to name protoplasm in the stricter
4 THE NEW CELL DOCTRINE
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-
THE NEW CELL DOCTRINE 5
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-
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-
THF NEW CELL DOCTRINE
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.
THE NEW CELL DOCTRINE
enties of the last
century J. Heitz-
mann, a Viennese
physician who had
emigrated to New
York, affirmed that
cells are not defi-
from one another.
He advanced the
protoplasm is con-
tinuous and has
The opinions ex-
pressed by Heitz-
mann 1 remained in
their time almost
Very gradually his
view met with
The botanist Sachs
much to develop
For the zoologists
the writings of the
man 2 have been of
the greatest im-
8 THE NEW CELL DOCTRINE
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-
THE NEW CELL DOCTRINE
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
10 THE NEW CELL DOCTRINE
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
THE NEW CELL DOCTRINE II
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
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
12 THE NEW CELL DOCTRINE
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.
THE NEW CELL DOCTRINE 13
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
THE NEW CELL DOCTRINE
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.
THE NEW CELL DOCTRINE 15
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&>
t r a nsf ormations. *
the sharp limits of
the nucleus disap-
pear, and the nu-
in small masses to
which we apply
the name chromo-
vides, and one
piece of each
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.
1 6 THE NEW CELL DOCTRINE
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
THE NEW CELL DOCTRINE
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
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.
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
1 8 THE NEW CELL DOCTRINE
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
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
THE NEW CELL DOCTRINE
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
20 THE NEW CELL DOCTRINE
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
THE NEW CELL DOCTRINE 21
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-
THE NEW CELL DOCTRINE
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-
THE NEW CELL DOCTRINE 23
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
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.
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
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
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-
cellular spaces. It is not practicable to lay further illustra-
tions before you.
Progressive development is closely connected with another
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-
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,
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
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.
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. 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.
THE DOCTRINE OF IMMORTALITY.
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
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-
44 THE DOCTRINE OF IMMORTALITY
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
THE DOCTRINE OF IMMORTALITY 45
ourselves with the consideration of the phenomenon of death.
At present we shall devote our attention to the propagating
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
46 THE DOCTRINE OF IMMORTALITY
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
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.
THE DOCTRINE OF IMMORTALITY 47
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
48 THE DOCTRINE OF IMMORTALITY
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,
THE DOCTRINE OF IMMORTALITY
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;
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
THE DOCTRINE OF IMMORTALITY
of the dog-fish there lies at either side in the neighborhood of
the developing intestinal canala group of cells, Fig. 23, germ
cells, which resemble one another closely, and which may be
easily distinguished from the other cells of the body. They
THE DOCTRINE OF IMMORTALITY
Sub- germ Cav
\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
52 THE DOCTRINE OF IMMORTALITY
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-
THE DOCTRINE OF IMMORTALITY
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
54 THE DOCTRINE OF IMMORTALITY
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
THE DOCTRINE OF IMMORTALITY 55
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
56 THE DOCTRINE OF IMMORTALITY
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
THE DOCTRINE OF IMMORTALITY 57
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
58 THE DOCTRINE OF IMMORTALITY
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.
THE EVOLUTION OF DEATH.
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-
60 THE EVOLUTION OF-BEATH
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-
THE EVOLUTION OF DEATH 6 1
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-
62 THE EVOLUTION OF DEATH
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.
THE EVOLUTION OF DEATH 63
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
THE EVOLUTION OF_J1EATH
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
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
THE EVOLUTION OF DEATH 65
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.
THE EVOLUTION OF DEATH
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
THE EVOLUTION OF DEATH
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,
THE EVOLUTION OF DEATH
THE EVOLUTION OF DEATH
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
THE EVOLUTION OF DEATH
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.
THE EVOLUTION OF DEATH
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.
72 THE EVOLUTION QF_PEATH
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
THE EVOLUTION OF DEATH 73
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
74 THE EVOLUTION OF DEATH
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
THE EVOLUTION OF DEATH 75
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-
76 THE EVOLUTION OF DEATH
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
THE EVOLUTION OF DEATH 77
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
7 8 THE EVOLUTION OF DEATH
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
THE EVOLUTION OF DEATH 79
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
8o THE EVOLUTION OF DEATH
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
THE EVOLUTION OF DEATH 8 1
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
THE DETERMINATION OF SEX.
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
THE DETERMINATION OF SEX 83
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
84 THE DETERMINATION OF SEX
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.
THE DETERMINATION OF SEX 85
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
86 THE DETERMINATION OF SEX
important generalizations. How great the variations are is
shown by the following table:
PER CENT. OF MALES.
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
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
THE DETERMINATION OF SEX 87
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
88 THE DETERMINATION OF SEX
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
THE DETERMINATION OF SEX 89
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.
THE DETERMINATION OF SEX
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
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
THE DETERMINATION OF SEX 91
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
THE DETERMINATION OF SEX
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
THE DETERMINATION OF SEX
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.
THE DETERMINATION OF SEX
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-
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,
THE DETERMINATION OF SEX 95
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-
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
96 THE DETERMINATION OF SEX
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
THE DETERMINATION OF SEX
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
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.
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
THE DETERMINATION OF SEX
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-
THE DETERMINATION OF SEX
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-
TOO THE DETERMINATION OF SEX
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
THE DETERMINATION OF SEX IOI
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.
102 THE DETERMINATION OF SEX
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 !
THE SCIENTIFIC CONCEPTION OF LIFE.
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
104 THE CONCEPTION OF LIFE
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
THE CONCEPTION OF LIFE 105
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
106 THE CONCEPTION OF LIFE
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.
THE CONCEPTION OP LIFE 1 07
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
08 THE CONCEPTION OF LIFE
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
THE CONCEPTION OF LIFE 1 09
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-
110 THE CONCEPTION OF LIFE
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-
THE CONCEPTION OF LIFE III
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
112 THE CONCEPTION OF LIFE
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,
THE CONCEPTION OF LIFE 113
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
114 THE CONCEPTION OF LIFE
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
THE CONCEPTION OF LIFE 115
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
Of such phenomena I take the privilege of enumerating
2. The teleological mechanism.
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
Il6 THE CONCEPTION OF LIFE
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
THE CONCEPTION OF LIFE 1 17
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
Il8 THE CONCEPTION OF LIFE
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.
I 20 NOTES
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.
22. B. M. Allen has determined the history of the sexual cells in four verte-
" 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.
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,
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
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."
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,
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
Fr. C. Paulmier, 1899, Journal of Morphology, XV, Suppl.
E. B. Wilson, 1905, Journal Exp. Zoology, II
E. B. Wilson, 1907, Science, XXV, 631.
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.
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.
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.
BOOKS FOR STUDENTS OF BIOLOGY.
KINGSLEY. Comparative Anatomy of Vertebrates. A text-book
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STOHR. Text-book of Histology. Arranged upon an Embryological
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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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UNIVERSITY OF CALIFORNIA IvIBRARY